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Purpose: This paper outlines the theoretical and empirical basis for compassion focused therapy (CFT) for psychosis, the gaps in the current knowledge and research, as well as some of the challenges for addressing gaps. It will guide the direction of future work and the steps needed to develop and advance this approach. Method: This paper reviews evidence of how evolutionary models such as social rank theory and attachment theory have greatly contributed to our understanding of psychosis and provide a clear rationale and evidence base for the mechanisms of change in CFT for psychosis. It reviews the evidence for outcomes of compassion training more generally, and early feasibility evaluations of CFT for psychosis. Results: The process evidence shows that people with psychosis have highly active social rank and threat systems, and the benefits of switching into attachment and care systems, which can support emotion regulation and integrative mind states. The outcomes evidence shows that compassion training impacts not only psychological outcomes, but also physiological outcomes such as neural circuits, immune system, and the autonomic nervous system. Within the psychosis field, outcomes research is still in the early days, but there are good indications of feasibility and a clear path forward for the next steps. Conclusions: CFT for psychosis is an approach that integrates biopsychosocial processes, an integration that's evidenced across each aspect of the model, from theoretical foundations (evolution‐informed) to interventions (e.g., body/breath training and relational techniques), to evaluation. Future RCTs are required to understand the effects on biopsychosocial outcomes for people with psychosis. [ABSTRACT FROM AUTHOR]

Objective: The level of immunological reactivity of the indigenous inhabitants of the Far North may depend on the extreme-discomfort factors of the climatic environment and genetic traits of the population. Therefore, the aim of this study was to identify the distinctive elements of the immune status of the Kola Saami and Russians living in the Far North (Murmansk Region)., Methods: A complex immunological study of peripheral venous blood composition was performed and involved 67 Saami and 81 Russian inhabitants of the Far North (Murmansk Region) who were aged 21-55. Blood was collected from the cubital vein on an empty stomach in the morning. For the peripheral venous blood, we obtained a hemogram and phagocytic activity of neutrophils, determined the content of lymphocytes with CD4, CD8, CD16, and CD71 phenotypes by indirect immunoperoxidase reaction and flow cytometry using an Epics XL apparatus (Beckman Coulter, United States), obtained concentrations of IL-6, IFN-γ, IL-10, IgA, M, G, E, sCD54, and sCD62L, transferrin, and sCD71 by enzyme immunoassay using the "Evolis" enzyme immunoassay analyzer from Bio-RAD (Germany), and obtained circulating immune complexes by precipitation using 3.5%, 4.0%, and 7.5% PEG-6000. The sIgA content was determined in morning saliva, urine, and gastrointestinal tract secretions. The results were analyzed using descriptive statistics, independent sample t-criterion, and Pearson correlation coefficient., Results: A decrease in the total number of leukocyte cells in the Saami was associated with a high incidence of leukopenia, lymphopenia, and neutropenia. Deficiency in active phagocytes and serum IgA and sIgA concentrations was revealed as well as increased contents of CD4+ and CD8+ receptor lymphocytes, membrane and free adhesion molecules, and transferrin. Leukocytosis, lymphocytosis, neutrophilia, monocytosis, and eosinophilia with increased contents of natural killer cells, IL-6, and IL-10 were recorded more frequently in the Russians. High levels of IgE and IFN-γ, which have the most pronounced cytotoxicity and are indicative of strained immune mechanisms, were characteristic of the Saami and Russians., Conclusion: The distinctive aspects of the immune status of the Kola Saami is related to the deficit in the active phagocyte and serum IgA and sIgA concentrations as well as the increase in the contents of cytotoxic lymphocytes, intercellular adhesion molecules, transferrin, and IFN-γ proinflammatory cytokines. The Russian inhabitants of the Far North are characterized by an adaptive response manifested by an increase in antibody-dependent cytotoxicity, involving IL-6 and IL-10., (© 2023 Wiley Periodicals LLC.)

Plain language summary: A uterine transplant, or womb transplant, provides a potential treatment for women who cannot become pregnant or carry a pregnancy because they do not have a womb, or have a womb that is unable to maintain a pregnancy. This is estimated to affect one in 500 women. Options for those who wish to start a family include adoption and surrogacy, but these are associated with legal, cultural, ethical and religious implications that may not be appropriate for some women and their families. A womb transplant is undertaken when the woman is ready to start a family, and is removed following the completion of their family. Womb transplants have been performed all over the world, with more than 70 procedures carried out so far. At least 23 babies have been born as a result, demonstrating that womb transplants can work. While the procedure offers a different option to adoption and surrogacy, it is associated with significant risks, including multiple major surgeries and the need to take medications that help to dampen the immune system to prevent rejection of the womb. To date there has been a 30% risk of a transplant being unsuccessful. Although the number of transplants to date is still relatively small, the number being performed globally is growing, providing an opportunity to learn from the experience gained so far. This paper looks at the issues that have been encountered, which may arise at each step of the process, and proposes a framework for the future. However, long term follow‐up of cases will be essential to draw reliable conclusions about any overall benefits of this procedure. [ABSTRACT FROM AUTHOR]

The article presents the 2009 issue of the "World Allergy Organization." It discusses the use of sub-lingual immunotherapy (SLIT) in medical care particularly its clinical application for physicains who are focusing on the development of immune system resistance. Moreover, it also provides an overview on the functions of subcutaneous immunotherapy and other routes of immunotherapy administration in treating severe diseases due to allergens.

Antiphospholipid Antibodies in Children with Age-Dependent Epileptic Encephalopathy.Purpose:Antiphospholipid antibodies (aPLs) have been found in the serum of patients with several neurologic disorders. Serum aPLs were detected in 19–26% of adult patients both with chronic epilepsy and with newly diagnosed seizure disorders. In children with partial epilepsy, Angelini et al. (1998) found aPLs in 13% of these cases. We studied the serum aPLs in 31 children with age-dependent epileptic encephalopathy: early infantile epileptic encephalopathy with suppression burst (EIEE), West syndrome (WS), and Lennox–Gastaut syndrome (LGS).Methods:Two children with EIEE, 20 with WS, and nine with LGS in the Pediatric Unit of Nihon University Itabashi Hospital were enrolled in the study. Inclusion criteria were (a) reliable diagnosis of age-dependent epileptic encephalopathy, (b) no signs or symptoms consistent with clinical immune system disorders and collagen diseases, and (c) negative for anticardiolipinβ2-glycoprotein I antibodies. Anticardiolipin antibodies (aCLs) of serum immunoglobulin G (IgG class) were measured with the enzyme-linked immunosorbent assay (ELISA) method. A value of aCL<10 U/ml is within normal limits. All of the subjects were classified in two groups. The patients in group A were diagnosed within 3 years, and those in group B were diagnosed beyond 3 years.Results:In the two patient with EIEE, the peak values of aCL were 57.9 and 35.6 U/ml. In patients with WS, the positive rate for the peak aCL levels was 91.7%, and the mean (±SD) level was 40.4± 39.2U/ml in group A, whereas the corresponding figures were 25% and12.7± 17.0 U/ml in group B. In patients with LGS, the positive rate for the peak aCL levels was 100%, and the mean level was 20.3± 6.6U/ml in group A, whereas the corresponding figures were 50% and 11.0± 12.2 U/ml in group B. We divided all the patients into a seizure-free group and a seizure-uncontrolled group. The mean peak value was 15.2± 17.8 in the seizure-free group and 38.8± 35.1 in the seizure-uncontrolled group.Discussion:A high positive rate of aPLs was found among patients with WS, characterized by early onset and long duration of epilepsy. These patients were poor responders to antiepileptic drugs (AEDs). Immunomodulatory therapies (intravenous Igs) have been shown to be effective in some children with this type of intractable epilepsy. Conversely, aPLs were more frequent among patients with localization–related epilepsies than in those with idiopathic generalized epilepsies. Several AEDs such as carbamazepine and phenytoin have been implicated as activators of antinuclear antibody production and drug-induced systemic lupus erythematosus. These antibodies are usually associated with autoimmune disorders such as primary antiphospholipid syndrome in rheumatic and connective tissue disorders. Two main pathogenic mechanisms have been proposed to explain the relationship between positive aPLs and neurologic symptoms (i.e., thrombotic and ischemic events within the CNS, and immune-mediated cellular damage from neuronal synaptic membrane attack). It has been shown that aPLs can disrupt neuronal function by directly acting on nerve terminals and reducingγ-aminobutyric acid-receptor–mediated chloride currents, suggesting a direct and reversible mechanism through which aPLs might lower the seizure threshold. It has also been postulated that antibodies to endothelium frequently coexist with aPLs and may induce apoptosis within the CNS. The high prevalence of positive aPLs in children with epilepsy indicates that immunologic dysfunction is associated with epilepsy, in at least some children. Conversely, aCL may appear after viral infections, and we speculate that some viral infections may be related to the age-dependent epileptic encephalopathyConclusions:The level of aPLs is related to disease severity and seizure frequency in patients with age-dependent epileptic encephalopathy, and aPLs may be useful to indicate prognosis and treatment effect. Regional Hyperperfusion in Temporal Lobe Seizures with Dystonic Posturing, Evaluated by Ictal–Interictal Subtraction SPECT.Purpose:Ictal hyperperfusion areas evaluated by multimodality registration methods may demonstrate anatomic localization of ictal symptoms. Dystonic posturing (DP) is one of the most reliable lateralizing indicators for temporal lobe epilepsy (TLE). Areas of regional hyperperfusion associated with DP in TLE were evaluated by using ictal–interictal subtraction single-photon emission computed tomography (SPECT).Methods:Twenty-three patients were randomly selected from 97 TLE patients who underwent operations between 1988 and 2000 in Shizuoka Medical Institute of Neurological Disorders (National Epilepsy Center). All ictal events were noted by reviewing long-term video-EEG monitoring records (by Y.I. and M.M.). The patients were divided into three groups according to the ictal symptoms: group D with unilateral DP, group H with elevated muscle tonus but without DP, and group N without DP or alternation of muscle tonus. For SPECT (Headtome set-070, Shimazu, Tokyo) sampling, each patient was injected with the same tracer during the ictal and interictal periods. Ictal and interictal SPECT and thin-slice magnetic resonance imaging (MRI; Sierra 1.5-T; General Electric, Milwaukee, WI, U.S.A.) were input into the automatic multimodality registration program (Dr. View/Linux, Asahikasei, Tokyo) to generate ictal–interictal subtraction images of SPECT on MRI for individual patients. Ictal hyperperfusion areas were evaluated by K.M. and M.T.Results:Six patients belonged to group D, nine patients to group H, and eight patients to group N. Statistically significant hyperperfusion was observed in the putamen (five patients in group D, two in group H and group N; p<0.01). Other ictal symptoms (such as autonomic symptoms, oral automatism, ocular or head deviation or both) showed no statistically significant differences except unilateral upper-limb automatism (four patients in group D, one in group H, and none in group N; p<0.01). Other factors such as age, sex, duration of illness, presence of MRI lesion or SPECT tracer (nine patients with[123I]-IMP and 14 with[99mTc]-ECD) were not statistically significant.Conclusions:A strong correlation between DP and putaminal hyperperfusion was demonstrated. Some patients showed a wide hyperperfusion area extending from the mesial temporal lobe to the putamen that may correspond to the propagation of epileptic discharges. Hyperactivity of the putamen is suggested to be associated with contralateral dystonic posturing. Epilepsy with Psychosis: Endocrine Psychic Syndrome.Case 1:A 9-year-old girl has had paroxysmal episodes of microspia and complex partial seizures without aura since age 8 years. She experienced visual hallucinations such as the strange face of an old lady and six moving ballerinas at age 9 years. In addition, she experienced auditory hallucination of a voice, something invisible coming close to her, and the feeling of fear. She broke her sister's comic book in a quick temper. Electroencephalogram (EEG) showed repetitive spikes on the left occipital and posterotemporal regions during both the psychotic state and remission. Brain magnetic resonance imaging (MRI) showed no definite abnormality. Brain single-photon emission computed tomography (SPECT) showed a subtle change in hypoperfusion in the left hemisphere. No definite differences were found during both states in EEG or SPECT. Her psychotic symptoms appeared after a lucid period of 30 min to 2 days and are followed by habitual complex partial seizures. It seemed that the psychotic symptoms of case 1 developed after seizures. We therefore considered that her symptoms correlated with the postictal stage, so-called postictal psychosis. However, her biochemical studies showed hyperthyroidism. Her psychotic symptoms disappeared soon after taking thiamazole.Case 2:A 21-year-old woman experienced complex partial seizures and secondarily generalized tonic–clonic seizures since age 2 years. She was admitted to the pediatrics department for recurrent vomiting. After admission, she complained that a ghost disturbed her eating. She experienced hearing voices of neighbors, delusions of reference and persecution, and delusions of speech with bizarre and grotesque features. In addition, she showed irritation, agitation, and violent behavior to her family. The EEG showed theta waves on bilateral frontocentroparietotemporal regions during psychosis. The same findings of EEG were observed during remission. Brain MRI showed a high-intensity area in the right cingulate gyrus. Brain SPECT showed hypoperfusion in the right mesial and lateral temporal regions during both states. However, hyperperfusion in bilateral frontal cortex were observed during psychosis. No correlation was noted between her psychotic symptoms and seizure activity or medication. We therefore considered that her psychotic symptoms resembled interictal chronic psychosis. However, her biochemistry data and the Ellsworth-Howard test showed pseudohypoparathyroidism type II. Her psychotic symptoms disappeared after treatment with a vitamin D analogue. We were able to discontinue all antipsychotic drugs.Conclusions:More than 150 years ago, von Basedow first described psychotic illness in a patient with exophthalmic goiter. Brownlie et al. reported psychosis associated with thyrotoxicosis. Eight among their 18 patients experienced hallucination, and 10 cases, including two schizophreniform cases, had good prognosis after an adequate treatment. Conversely, Hey et al. reported a case of Capgras syndrome in association with pseudohypoparathyroidism. This patient had mental retardation, epilepsy, and schizophrenia-like symptoms. Because of psychosis, he had a history of electroconvulsive therapy. Pollard et al. reported a 13-year-old Asian girl who showed hysterical paralysis and a rapid-cycling mood disorder. The mood disorder responded to treatment of pseudohypoparathyroidism with a vitamin D analogue.Although endocrine psychic syndrome is not unusual, epileptic psychosis combined with endocrine disease, as in our cases, is confusing as to whether the symptoms mimicked postictal or chronic psychosis. We propose to reconsider the association of psychiatric problems with endocrine disease when we encounter epilepsy patients with psychosis. Single Small Enhancing CT Lesions (SSECTL) in Epilepsy in India.Purpose:Single small enhancing CT lesions (SSECTLs) are extremely common in Indian epilepsy patients seen for the first time with seizures. Various hypotheses exist regarding their etiology, ranging from tuberculomas to neurocysticercosis, on the basis of histology and excisions done in a small percentage of cases. It also has been observed that these lesions disappear spontaneously over a short period after treatment with antiepileptic drugs (AEDs), causing doubts about their etiology and raising questions regarding management. The present study was carried out to observe such patients with SSECTLs with respect to persistence or disappearance of these lesions with AED treatment alone.Methods:All the new patients who attended our neurology clinics, with seizures, generalized or focal, were studied for the purpose of the present study. Apart from historical details and the seizure characteristics, complete neurologic examinations were done and recorded in specified form. Routine blood counts, erythrocyte sedimentation rate, urine examination, blood biochemistry, chest radiograph, and EEG were carried out. Computed tomography (CT) scan was done at the first instance and repeated after≥10–12 weeks of AED wherever possible. All the patients were given AEDs alone.Results:All the patients with first-ever seizures during the study period formed the subjects of this study; 43.5% of the patients had normal scans, whereas in 56.5%, the scans were abnormal. Of the patients, 12.9% had specific abnormalities, which included meningioma (5), gliosis (21), atrophy (21), multiple neurocysticercosis (43), and multiple infarcts (18), among others. 40.4% of patients showed nonspecific abnormalities on their scans such as low attenuation (51), high-attenuation disks (67), high-attenuation rings (241), generalized edema (56), and calcified spots (75). A follow-up scan was possible in 219 cases. Of these, 131 (59.8%) showed complete resolution, whereas 53 (24.2%) had significant resolution, but 35 (16%) remained unresolved.Discussion:The appearing and disappearing CT scan lesions in epilepsy in India have been an enigma. Initially these were thought to be tuberculous granulomas, as tuberculosis is one of the commonest diseases prevalent in this region. Disappearance of these lesions or healing by calcification by antituberculosis therapy (ATT) was taken as evidence for the hypothesis of tuberculosis. When some of these patients had to discontinue ATT because of adverse drug reactions, it was noted that these lesions disappear also without ATT. Subsequently, some histopathologic studies were conducted, with an evidence of neurocysticercosis in some of these patients, which resolved with cysticidal drugs. However, a majority of these patients who neither had ATT nor cysticidal therapy had their lesions resolve spontaneously on follow-up CT scans. Our study also supports the hypothesis. However, a small number of cases were seen in which these lesions either do not resolve or increase on follow-up CT scans. It is probable that these lesions do not represent one single etiology, and they must be managed appropriately.Conclusions:The SSECTL are one of the most common findings on CT in patients of epilepsy in India. These lesions resolve spontaneously without any specific treatment such as ATT or cysticidal therapy in the majority of patients. Therefore, there is an ample justification in treating them initially with AEDs only. A Neuropathological Study on the Limbic System in Dentatorubral-Pallidoluysian Atrophy.Purpose:Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by progressive myoclonic epilepsy (PME), dementia, and cerebellar ataxia. According to the age at onset, DRPLA is classified into juvenile, early-adult, and late-adult types. In the juvenile type, PME is most frequently observed, whereas seizures or PME sometimes and rarely occurs in early- and late-adult types. In general, glutamate transporters and calcium-binding proteins (parvalbumin and calbindin-D28K) are believed to reflect glutamate neurotoxicity and functions of theγ-aminobutyric acid (GABA)ergic inhibitory interneurons in the limbic system, respectively. To investigate epileptogenesis in DRPLA, we examined the expressions of glutamate transporters and calcium-binding proteins in the limbic system in autopsy cases of DRPLA.Methods:Fourteen autopsy cases of clinicopathologically confirmed DRPLA, comprising nine cases of juvenile type with PME and five cases of late-adult type without PME, as well as 10 age-matched controls, were studied. Immunohistochemistry was performed on serial sections of the temporal lobe including the hippocampus, amygdaloid complex, and entorhinal cortex, by using mouse monoclonal antibodies to parvalbumin and calbindin-D28K (Sigma-Aldrich, St. Louis, MO, U.S.A.) and rabbit polyclonal antibodies to excitatory amino acid transporters 1 (EAAT1), EAAT2, and EAAT3 (Wako Pure Chemicals Industries, Japan). The degree of immunoreactivity was evaluated by semiquantitative visual inspection.Results:The number of interneurons immunoreactive for parvalbumin or calbindin-D28K seemed to be lower in cases of the juvenile type of DRPLA with PME compared with that in cases of late-adult type of DRPLA not manifesting PME. Reduction of calbindin-D28K–immunoreactive neurons appeared to be more prominent than that of parvalbumin-immunoreactive neurons. It is noteworthy that four of five cases of the juvenile type, in which seizure occurred before puberty and the amygdaloid complex could be examined, and one case of the adult type completely lacked the amygdaloid immunoreactivity for parvalbumin or calbindin-D28K. The amygdaloid lesion is likely to be related to PME in DRPLA as either a cause or a result. Conversely, the expression of glutamate transporters seemed to be mildly affected. Three cases of juvenile type and one case of adult type showed a reduced expression of EAAT1 or EAAT2 or both in the entorhinal cortex, hippocampus, or amygdaloid complex. The expression of neuronal glutamate transporter EAAT3 was comparatively preserved in most of the remaining neurons in all subjects.Conclusions:An active debate has continued on the subject of whether the cerebral or subcortical lesions are more involved in the epileptogenesis in DRPLA. Neuropathologically, various brainstem changes, such as atrophy of the brainstem tegmentum, have been delineated. Previously we performed neuropathologic analysis of the brainstem in the same subjects and failed to find any PME-specific lesions. The current study showed that the GABAergic interneurons were altered more definitively in cases of juvenile type manifesting PME, whereas glutamate transport might not be severely disturbed in the limbic system in DRPLA. Recently, neuroradiologic studies have shown the presence of cerebral cortical atrophy in DRPLA. Furthermore, the extensive involvement of cerebral cortical neurons was demonstrated by immunohistochemistry against mutant atrophin-1, a responsible protein for DRPLA, particularly in the juvenile type. Taking these findings together, we speculate that the occurrence of PME in DRPLA may be related to the lesions of the cerebral cortex, including the limbic system. We also believe that further functional analysis of the cerebral cortex is useful to examine treatment for the usually intractable PME in DRPLA. Prevalence and Localizing Value of Emotional Facial Paresis in Medically Refractory Temporal Lobe Epilepsy.Purpose:The selection of patients with medically refractory temporal lobe epilepsy (TLE) for surgery depends on the concordance of data from clinical, electroencephalographic (EEG), radiologic, and neuropsychological evaluation. Although the clinical examination is often normal, contralateral emotional facial paresis (EFP) has been observed in patients with medically refractory mesial TLE (MTLE). Emotional facial paresis refers to unilateral lower facial weakness during emotional expression such as smiling, along with normal voluntary facial movements. We intended to determine the frequency of occurrence of EFP and its lateralizing significance in identifying appropriate candidates for anterior temporal lobectomy (ATL) with amygdalohippocampectomy.Methods:We investigated the prevalence, predictive value, and associations of EFP among 50 consecutive patients who underwent ATL during the period from November 1999 to July 2001 and satisfied the following criteria: (a) magnetic resonance imaging (MRI) findings consistent with mesial temporal sclerosis (MTS) and concordant interictal and ictal EEG data; and (b) seizure free or≥90% seizure reduction for≥6 months after ATL. Fifty age- and sex-matched normal subjects acted as controls. Facial asymmetry was assessed at rest and during volitional movements. EFP was looked for during conversation, by provoking a smile. The whole examination undertaken during the video-EEG monitoring was available for review. To ascertain observer bias, two investigators (A.J. and J.C.) independently examined the first 20 patients for the presence or absence of emotional facial paresis. The interobserver agreement was 80% with a kappa value of 0.63. Subsequently, one investigator (A.J.) assessed all subjects, and controversies were resolved by reexamination along with J.C. or K.R. We used standard deviation to define the dispersion, andttest (two-tailed) and Fisher's exact test to evaluate the significance of the association of different clinical characteristics between patient and control groups, and between patients with and without emotional facial paresis.Results:The patients comprised 27 male and 23 female subjects. The age at ATL ranged from 14 to 55 years, and the mean duration of epilepsy before ATL was 17.8 years. When compared with eight (16%) of 50 control subjects, 36 (72%) of 50 MTLE patients exhibited unilateral EFP; the difference was highly significant (p<0.0001). The presence of contralateral EFP correctly predicted the side of ATL in 86.1% of patients. Patients with EFP had a longer duration of epilepsy compared with those without this sign (19.2± 8.0 vs. 14.4± 6.1 years; p= 0.048). We did not find any significant association between EFP and the following clinical characteristics: age at epilepsy onset, age at ATL, gender, and antecedent history of febrile seizures. Both the patients and the control subjects had EFP more frequently involving the right side of the face. Of the eight control subjects who had EFP, seven had it on the right. Whereas 13 (54.2%) of 24 patients with right MTLE had EFP (on the left side in 11), 23 (88.5%) of 26 with left MTLE had emotional facial paresis (right side in 20; p= 0.011).Conclusions:Our observations confirm that EFP contralateral to the side of MTS is a valuable localizing sign in correctly predicting the epileptogenic temporal lobe. To our knowledge, the significant association we observed between left MTLE and more frequent occurrence of emotional facial paresis has not been previously documented. The value of EFP in localizing the ictal-onset zone in patients with bilateral MTS is uncertain. We hypothesize that the presence of an intact right hemisphere and pathologic changes more extensive than MTS may be required for EFP to be readily manifest. Convulsive Episodes in Patients with Group A Xeroderma Pigmentosum.Purpose:Xeroderma pigmentosum is an autosomal recessive disease characterized by sunlight hypersensitivity, freckles, and skin cancers. In addition to these skin lesions, patients with group A xeroderma pigmentosum (A-XP) show progressive and severe neurologic complications of unknown causes. However, few A-XP patients with seizure disorders have been reported in the literature (Mimaki et al., 1988), and no systematic search for seizure disorders in A-XP patients has been performed. We aimed to clarify the incidence of convulsive episodes in patients with A-XP.Methods:We investigated the history of convulsive episodes of 33 A-XP patients in our institute by reviewing the medical charts or conducting interviews with caregivers.Results:Five patients had episodes of convulsions at age 12 years (YoT, male), 13 (MA, female), 14 (HM, female), 16 (YY, female), and 19 and 21 (YaT, male) years. YoT and YY were siblings, and they had another healthy brother who had no history of convulsive episodes. Their parents also had no history of convulsions. Among family members of MA, HM, and YaT, no seizure disorder was identified. YoT, MA, HM, and YY exhibited brief episodes of loss of consciousness with cessation of movement. Valproate acid (VPA) was effective for these episodes. YaT had a brief cessation of respiration at age 19 years, which disappeared after phenobarbital (PB) administration. PB was discontinued by the family after 6 months of treatment, and he (YaT) had a generalized tonic seizure with left upper extremity focality at age 21 years. He has been taking PB again, and no further episode appeared for the past 4 years. A few low-voltage theta rhythms were the dominant background activities of drug-induced sleep EEG recordings of these five patients. Except HM, no apparent epileptic discharge was found on interictal EEG recordings. HM showed periodic high-voltage sharp waves at bilateral frontal regions on drug-induced sleep EEG recording when she was 15 years old. Except MA, no A-XP patient had an episode of febrile seizure. MA had a single febrile seizure when she was 4 years old.Conclusions:Because these five patients exhibited recurrent afebrile seizures, we diagnosed them as having epilepsy. However, we could not identify the precise type of epilepsy, in part because of few EEG findings. A-XP patients exhibit marked diffuse brain atrophy after age 5 years (Ohinata et al., 2002), which makes it difficult to obtain apparent epileptic discharges on routine EEG recordings. From the clinical standpoint, YaT is considered to have symptomatic localization-related epilepsy, showing complex partial seizures at age 19 years with secondary generalization at 21 years. The other four patients might exhibit complex partial seizures (due to localization-related epilepsy) or atypical absence seizures (due to generalized epilepsy), but few typical EEG findings, making it difficult to differentiate the types of epilepsy. Nevertheless, we diagnosed five (15%) of 33 A-XP patients as having symptomatic epilepsy. In contrast, we found only one (3%) patient with a history of febrile seizures. In the general population,∼3% of all people living to age 80 years in the United States will be diagnosed with epilepsy (Westbrook, 2000). The cumulative incidence of febrile seizures in Europe and the United States is 2–5%, and that in Japan is 8–10% (Maeda, 2001). Taking these figures together, in comparison with the general Japanese population, Japanese A-XP patients show a lower incidence of febrile seizures, whereas they exhibit a higher prevalence of epilepsy. Neurohumoral Behavior of Epilepsy with Neurocysticercosis in Nepal.Purpose:Epilepsy due to neurocysticercosis (NC) is common in Nepal. The 120 epilepsy cases with NC confirmed by magnetic resonance imaging (MRI),Diagnostic and Statistical Manual of Mental DisordersIV, and International League Against Epilepsy criteria were subjected to enzyme-linked immunosorbent assay (ELISA) testing for comparative study of serum anti-cysticercus antibody levels between epilepsy with various types of NC before and after treatment with antihelminthic, correlation with therapeutic efficacy of cysticide, and identification of a prognostic indicator. Comparative MRI studies of the brain were done with various types of NC before and after treatment to evaluate drug efficacy, resolution rate of the cerebral lesion, and correlation with antibody titer.Methods:Ninety persons with epilepsy with single benign parenchymal NC and 30 with multiple benign parenchymal NC were subjected to ELISA before and 1 month after the unified treatment regimen with albendazole, 15 mg/kg/body wt daily, for 8 days, and oral cortisone. Comparative studies of serum antibody titers and correlation between mean optical density (OD) and therapeutic efficacy of cysticide before and after treatment were done to evaluate the therapeutic efficacy. Assessment of antibody titer was done to understand the efficacy of treatment and to find an indicator of prognosis. MRI scan of the brain was done before and 8 days after the treatment to assess the resolution of the cerebral lesion and correlation with antibody titer.Results:The sensitivity of ELISA for serum anti-cysticercus antibodies in epilepsy with multiple benign parenchymal NC was 93.3%, showing strong positivity in contrast to epilepsy with single benign parenchymal NC, with a sensitivity of 77.8%. Comparative studies of the sensitivity of ELISA between epilepsy with single and multiple benign parenchymal NC before treatment were significant (F= 15.47; p≤ 0.0001). The mean ODs of epilepsy cases with single benign parenchymal NC before and after treatment were mean, 1.387; SD, 0.433; and m, 0.314 SD, 0.102, respectively (F= 430.31; p= 0.0001). In contrast, the ODs of epilepsy with multiple benign parenchymal NC were m, 1.757; SD, 0.321; and m, 0.482; SD, 0.164, respectively (p= 0.0001). The differences between the OD of epilepsy with single (m, 0.314; SD, 0.102) and multiple benign parenchymal NC (m, 0.482; SD, 0.164) before and after treatment were highly statistically significance (F= 43.93; p= 0.0001). MRI study after treatment for epilepsy with various types of NC revealed that of 90 epilepsy cases with single benign parenchymal NC, 94.4% resolved completely, 2.2% resolved partially, and 3.3% showed no change, whereas, of 30 epilepsy cases with multiple benign parenchymal NC, 40% resolved completely, 30% resolved partially, and 30% showed no change. The comparative therapeutic responses to albendazole in epilepsy cases with single benign parenchymal NC and multiple benign parenchymal NC revealed that the former responded better than the latter (i.e., the cure and resolution rate was 94.4% vs. 40% for epilepsy with single benign parenchymal NC vs. multiple benign parenchymal NC). Epilepsy with single benign parenchymal NC having low serum OD showed better response to treatment, in contrast to epilepsy with multiple benign parenchymal NC having higher serum OD.Conclusions:Epilepsy with NC is the biologic marker of poverty and poor sanitation in the community of an undeveloped country. The low serum OD in epilepsy with single benign parenchymal NC showed a better response to the treatment in contrast to epilepsy with multiple benign parenchymal NC having higher serum OD. These results indicate that low serum antibody titer of epilepsy with NC predicts good prognosis and better therapeutic efficacy of antihelminthic treatment. The evaluation of the serum antibody titer of epilepsy with NC may be used for the diagnosis, assessment of therapeutic efficacy of antihelminthic treatment, and prediction of prognosis. Probable Molecular Dysfunction by Autoantibodies Against NMDA-Receptor GluRℇ2 in Epilepsies After Acute Encephalitis.Purpose:Glutamate receptors (GluRs) in the central nervous system play an important role in the excitatory synapse and have been implicated in neurodegenerative diseases and symptomatic epilepsy. After Rogers et al. reported that autoantibodies against GluR3 were involved in some cases of Rasmussen encephalitis, studies focused on other neurologic diseases with a possible causal relation to autoantibodies against GluRs. In 1999, we found autoantibodies against theN-methyl-d-aspartate (NMDA) GluRℇ2 subunit in sera and CSF from patients with chronic progressive epilepsia partialis continua, Rasmussen encephalitis, and other diseases. To elucidate the pathophysiologic mechanisms of intractable epilepsy after acute encephalitis or encephalopathies, we studied the autoantibodies in sera and CSF from such patients.Methods:With the tetracycline-induction system, we established stable NIH3T3 transformant cell lines expressing the NMDA-type GluRℇ2 subunit. Cell extracts of the transformants were transferred to nitrocellulose membranes to detect the presence of antibodies against GluRℇ2. The membrane was exposed to sera from patients and was stained by second antibodies coupled to alkaline phosphatase. Four peptides (an N-terminal, and three C-terminal fragments) were synthesized from GluRℇ2 cDNA by using bacterial fusion protein vectors. Homogenates of the transformants and bacteria were transferred to nitrocellulose membranes, and the membranes were incubated with the patients' sera or CSF, and stained by second antibodies coupled to alkaline phosphatase. Fifteen patients with epilepsies after acute encephalitis (influenza virus; two patients, herpes simplex virus; two, varicella zoster virus; one, others) and three after acute encephalopathies (influenza vaccination, others) were studied. Ages at onset were from 2 to 36 years (0–5 years, eight patients; 6–10 years, four; 11–15 years, three; older than 16 years, three). Cerebral palsy was found in eight patients, and mental retardation (IQ<70) in 11 of 18 patients. Seizure outcome ranged from seizure free (five patients), monthly (four), weekly (five), to daily (three).Results:Immunoglobulin G (IgG) and IgM autoantibodies against the NMDA GluRℇ2 subunit were positive in 13 and 12, respectively, of 18 patients. IgM autoantibodies disappeared in two patients, and IgG autoantibodies changed from absence to presence in three patients evolutionally. Two patients continued to have the autoantibodies even several years after acute encephalitis. Production of autoantibodies against GluRℇ2 was related significantly to episodes of convulsive status epilepticus in the acute stage of encephalitis (p= 0.19; Spearman's correlation coefficient by rank test) and insignificantly to cell counts and protein levels in CSF, duration of unconsciousness, and the latency of first convulsion from onset. Comparing neuropsychological outcomes between patients with and without the autoantibodies, the autoantibodies were causally related to mental retardation (p<0.03, Mann–WhitneyUtest), motor impairment (p<0.03,χ2 for independent test), and seizure frequencies (p<0.03, Spearman's correlation coefficient by rank test). The epitopes of the autoantibodies existed mainly in the c-terminal of GluRℇ2 molecules. In five patients (broader type), both n- and c-terminals were epitopes of the autoantibodies; in eight (narrow type), only c-terminals were epitopes. Comparing the relations between broadness of epitopes and clinical factors, no significant correlation was found for age at onset (p= 0.11, Spearman's correlation coefficient by rank test), concentration of proteins in CSF (p= 0.07, Spearman's test), and latency of convulsion from the onset of illness (p= 0.09, Spearman's test). The broadness of epitopes was not related to neuropsychological outcomes but was related to lower cell counts in CSF. The spectra of epitopes were broader in CSF than in sera.Conclusions:Production of the autoantibodies might be related to destruction of brain tissue by a convulsive status and might contribute to severe neuropsychological outcomes. Relationship Between Clinical Characteristics and Magnetoencephalographic Findings in Typical and Atypical Benign Childhood Epilepsy with Centrotemporal Spikes.Purpose:Benign childhood epilepsy with centrotemporal spikes (BECT) is an electroclinical syndrome characterized by partial sensorimotor seizures (sylvian seizures: SSs) with centrotemporal spikes (rolandic discharges: RDs). Typically the prognosis is excellent with remission before age 16 years. However, some patients with BECT initially seem to evolve into atypical or complicated types, one of which has been called atypical benign partial epilepsy of childhood (ABPC) by Aicardi. Recently, the search for the predictor of evolution into atypical or complicated types was attempted. In this article, we use the termcomplicated BECT(CECT) to include atypical or complicated types. We report the detailed analysis of the generator of RDs in BECT and CECT by using magnetoencephalography (MEG).Methods:Sixteen children with BECT undertook MEG examination; seven were excluded because of insufficient numbers of RDs for analysis, leaving nine patients. All three patients with CECT were characterized as having frequent atonic seizures (negative myoclonus) or hemifacial or hand twitching, with continuous spike–waves during slow wave sleep in EEG, and also mental deterioration. MEG activity was recorded during sleep by using a whole-head 204-channel neuro-magnetometer (Neuromag-204) with simultaneous EEG recordings. Locations and directions of estimated dipoles of high-amplitude MEG sharp waves were displayed on magnetic resonance images. The data were sampled at 300 Hz with a 160-Hz low-pass filter and analyzed under 45-Hz low-pass filter and 1- to 3-Hz high-pass filter. Analysis of three types of MEG spikes was performed: current dipoles of the first of the highest or lowest peak. Therefore, a uniform pattern of MEG spikes was analyzed individually.Results:In nine (56.3%) of 16 patients with BECT and all three (100%) patients with CECT, sufficient numbers of MEG spikes (>30 spikes in several sampling sequences for about several minutes each) were detected for analysis. Five typical BECT patients had only SSs during sleep, typical unilateral RDs, and over a 2-year seizure-free period, except one patient. These patients had typical MEG spikes characterized by current dipoles showing relatively limited localization and regular directions. The remaining four patients with BECT had clinical characteristics other than SSs, such as refractory SSs, perioral twitching during wakefulness, febrile convulsions after epilepsy onset, and fewer RDs on EEG while remaining significant in number on MEG. These patients showed less concentrated MEG spikes and moderately irregular dipole directions. In all three patients with CECT, current dipoles were scattered widely around rolandic areas, showing more irregular directions.Conclusions:Although we have not developed sequential MEG data of individual patients, our MEG findings may suggest an intermediate type of BECT as a continuum between typical BECT and CECT. Scattering of epileptic foci from the restricted rolandic areas may be due to some immaturity of neuronal systems. Multifocal activated cortical areas, including excessively inhibitory or excitatory neuronal generators, may induce CECT evolution and neuropsychological dysfunction. This kind of mechanism may play a role in the formation of secondary bilateral synchrony, which is considered to cause generalized spike–waves in some cases of BECT. If sequential MEG data in the very early stages of BECT onset are obtainable individually, evolution to complicated BECT may be predictable. Our MEG findings suggest an intermediate type of BECT as a continuum between typical BECT and CECT or ABPC. If current dipoles are scattered and showing more irregular directions, even in the early stage of CECT, MEG study may be a quick predictor of complications. MEG may be able to explain the mechanism of evolution of typical BECT to complicated BECT. Safe Pregnancy in Epilepsy: Registry of Epilepsy and Pregnancy Initiative in India.Background:Care for women with epilepsy (WWE) is suboptimal in most countries. The Government of India has recently eased the legal constraints to marriage for WWE. The proportion of married among WWE is comparable to that in the community, according to a survey in Kerala State. WWE in developing countries face several difficulties. Health services are sparse and expensive. Many of them have malnutrition, anemia, or intercurrent infections. Social stigma is another major handicap.Objective:Indian Registry of Epilepsy and Pregnancy (IREP) is established to monitor reproductive functions in WWE and facilitate their optimal care under prevailing conditions.Methods:The first registry in India was started at Trivandrum (TVM) in 1998. A consensus protocol was developed in a workshop held in Trivandrum in 1998. Preconception management focuses on diagnosis, antiepileptic drug (AED) therapy, if required, and initiation of folate supplementation. We use a higher dose of folate (5 mg daily) to obviate any nutritional deficiency. The early antenatal care includes estimation of serumα-fetoprotein (16 weeks) and malformation-targeted ultrasonography (18 weeks). The couple is provided extensive counseling on the diverse aspects of epilepsy and pregnancy. It is often necessary to counsel close relatives also, as many couples live in joint families. Two intramuscular injections of vitamin K (10 mg) are recommended in the last 6 weeks of pregnancy, as oral vitamin K preparations are not widely available. Three months after delivery, babies are screened for malformations by physical examination, echocardiography and abdominal ultrasonography. We assess development and language at 1 and 3 years, respectively. Similar registries were set up on the east coast (Vishakhapattanam-VZG, 1999) and North India (Ludhiana-LDH, 2000). These registries are following a unified protocol and joined together to form IREP. Three new centers are being established in other parts of India. IREP is now pooling data with the European Registry of Epilepsy and Pregnancy.Results:As of January 2002, 547 WWE (mean age, 24 years) were enrolled (TVM, 386; VZG, 125; LDH, 36), and 320 had completed pregnancies (TVM, 224; VZG, 66; LDH, 30). AEDs included carbamazepine,141; phenytoin, 98; phenobarbitone, 83; valproate, 63; clobazam, 12; clonazepam, seven; and lamotrigine, seven. Preconception or first trimester folate supplementation was high in TVM (83%) but low in VZG (33%) and LDH (17%). There were 38 (11.9%) cases with malformations (including two terminations). Nervous system malformations included spina bifida and meningomyelocele (three). There were 20 cases of cardiac defects, including tetrology of Fallot, coarctation of the aorta, patent ductus, septal defects, and patent foramen ovale; some of latter had closed subsequently. Other malformations involved the skeleton (seven), genitourinary system (four), and anterior abdominal wall (three). Babies from one center (TVM) showed mild delay in motor and mental development at age 1 year, when compared with matched normal babies.Conclusions:The spectrum and prevalence of birth defects observed in this study are comparable to those in reports from elsewhere. Ultrasonography and echocardiography has enabled us to detect malformations like hydronephrosis, cyst in liver, and small septal defects. It is debatable whether patent foramen ovale should be recognized as an anomaly or otherwise, as several of them closed subsequently. This initiative has sensitized the medical fraternity to the special needs of WWE and has contributed to improving the standards of care for them. Wada Test and Interictal[ 18F]FDG-PET in Unilateral Temporal Lobe Epilepsy.Purpose:To investigate the association between regional glucose metabolism obtained with interictal[18F]fluorodeoxyglucose positron emission tomography (18FDG-PET) and material-specific memory measured with the Wada test in patients with unilateral temporal lobe epilepsy.Methods:We investigated 47 consecutive patients with intractable, unilateral temporal lobe epilepsy (26 left and 21 right) who underwent presurgical evaluation including interictal18FDG-PET and the Wada test. Nine patients had non-left dominance for language (one right and eight mixed); the remainder were left dominant. To obtain regional glucose metabolism, we worked with 14 groups of regions of interest (ROIs) in either hemisphere. We calculated the PET asymmetry index (PET-AI) for each group of ROIs by using the formula: (L− R)/(L+ R)× 200, where L or R represents averaged glucose metabolism in each ROI on the left or right hemisphere. In addition, we created a“general asymmetry factor,” which is the mean of all the 14 PET-AIs, to diminish general effects of unilateral hemispheric hypometabolism that are commonly seen in patients with unilateral temporal lobe epilepsy. To estimate unilateral memory, we used recognition memory paradigms in the Wada test based on words, faces, and pictures and obtained three material-specific memory scores for each hemisphere. The memory asymmetry index (memory-AI) for each material was calculated by using the formula: (L− R)/6× 100, where L or R represents material-specific memory scores performed on the left or right hemisphere. In our statistical analysis, we created a linear regression model to predict the memory-AI for each material by combining the PET-AI for each ROI with the general asymmetry factor. The model was compared between subgroups according to the side of focus or the language dominance.Results:The associations between the PET-AI and the memory-AI did not significantly differ between patients with left and right foci. In four combinations of PET-AI and memory-AI, the associations were significantly different between the subgroups according to language dominance. Only patients with non-left language dominance showed positive correlation of PET-AI with memory-AI: PET-AI for the lateral frontal region with memory-AI for words (t=−3.39; p= 0.002) or for pictures (t=−2.29; p= 0.027); PET-AI for the anterior inferior temporal region and memory-AI for faces (t=−2.48; p= 0.017); and memory-AI for words and PET-AI for the anterior superior temporal regions (t=−1.99; p= 0.053).Conclusions:When we analysed the subgroups according to the side of focus, we found no significant associations between the PET-AI in any brain area and the memory-AI for any material. In contrast, when we analyzed the subgroups according to language dominance, we found four significant associations between hypometabolism in certain areas and material-specific memory deficits, and this was observed only in patients with non-left language dominance. Our results suggest that in patients with unilateral, drug-resistant temporal lobe epilepsy, functional anatomy of memory also is influenced by language dominance. Muscle Activity During Non-REM Sleep in Patients with Infantile Spasms.Purpose:Under physiologic conditions, muscle activity is abolished during rapid-eye-movement (REM) sleep but is sustained in non-REM sleep. We found a disturbance of muscle activity during REM sleep in patients with infantile spasms (ISs) (Kohyama et al., 2000). In the current study, we examined muscle activity during non-REM sleep in patients with ISs.Methods:Twelve IS patients (ages, 53–83 postconceptional weeks; mean, 64.1), who had not previously been treated, were enrolled in the study. Nine of 12 patients had a good prognosis on convulsions. One all-night polysomnography was performed for each patient, and the percentage of chin muscle atonia during non-REM sleep (%ATNR) was calculated. Seven neurologically unaffected infants (ages, 55–81 postconceptional weeks; mean, 70.4 weeks) served as age-matched controls.Results:%ATNR in IS patients ranged from 5.5 to 33.4 (mean, 19.0). The mean value was higher than that in the controls (13.8; range, 3.4–29.4), although no significant difference was obtained (p= 0.27).Conclusions:Petre-Quadens (1972) reported the normal %ATNR value in 10 children aged three months to 5 years as 14.7%. In comparison with this value, Fukuyama et al. (1979) reported elevation of %ATNR in IS patients. They also reported that the mean %ATNR value in three patients who showed unfavorable response to adrenocorticotropic hormone (ACTH; 45.3; range, 32.0–63.8) was higher than that in five IS patients with a favorable response to ACTH therapy (37.6; range, 17.7–55.1). Interestingly, Petre-Quadens (1972) also reported elevation of a similar index in children with mental retardation. Brain insults may result in the elevation of %ATNR. In the current study, however, we failed to demonstrate a significant difference in %ATNR between IS patients and age-matched controls. Petre-Quadens (1972) also observed the average %ATNR in young adults (aged 15–25 years) to be 2.4% and hypothesized that this index declines with age progression. However, based on a study with healthy young children, we found no age-related decrease of %ATNR (Furushima et al., 2002). The cited works including the current study were based on visual inspection of muscle activity, and so far, no consistent results have been obtained on %ATNR. Recently, Werth et al. (2002) analyzed chin muscle activity during non-REM sleep by using computer analysis, and found that chin muscle atonia during non-REM sleep appeared at a constant rate of 10–15% throughout the night in healthy young adults. They also examined %ATNR in patients with narcolepsy and observed that the latency to chin muscle atonia during non-REM sleep was shorter in narcoleptics (0.7± 1.1 min) than in normal controls (48.8± 28.9 min). They speculated that atonia during non-REM represents a measurement of REM propensity. The brainstem cholinergic and monoaminergic systems are involved in the state-dependent muscle activity control. Cholinergic agents microinjected into the brainstem elicit muscle-tone suppression, and the disfacilitation of serotonergic system is considered to be involved in the decrease of excitability of the hypoglossal motoneuron. %ATNR is easily measured on routine EEG recordings, with the only addition of the measurement of chin muscle tone. %ATNR is a potentially useful index reflecting the balance between the brainstem cholinergic and monoaminergic activities. Broad clinical application of %ATNR with the development of a computerized analyzing system is expected to provide new insights into the assessment of cholino-monoaminergic activities in the brainstem. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis (IA) is a leading cause of mortality in haematological patients. Appropriate activation of the innate immune system is crucial for the successful clearance of IA. Therefore, we studied the Aspergillus fumigatus-mediated activation of human granulocytes and monocyte-derived immature dendritic cells (DCs), as well as murine bone marrow-derived DCs (BMDCs) from wild type, toll-like receptor (TLR)4-deficient, TLR2 knockout, and TLR2/TLR4 double deficient mice. Aspergillus fumigatus antigens induced the activation and maturation of immature DCs as characterized by CD83 expression, upregulation of major histocompatibility complex and co-stimulatory molecules. Moreover, fungal antigens enhanced the phagocytosis and production of interleukin (IL)-8 in granulocytes. The release of IL-12 by BMDCs in response to A. fumigatus antigens was dependent on the expression of TLR2, whereas the release of IL-6 was dependent on the expression of functional TLR4 molecules. The protein precipitate of A. fumigatus supernatant provided strong stimulation of DCs and granulocytes, indicating that a factor secreted by A. fumigatus might activate innate immune cells. In conclusion, A. fumigatus antigens induced the activation of DCs and granulocytes. Our results indicated that this activation was mediated via TLR2 and TLR4. Future studies are needed to assess the clinical impact of these findings in patients at high risk for IA. [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by the expansion of phosphatidylinositol glycan class A (PIG-A) defective haematopoietic cells, probably due to the immune-mediated alterations of the bone marrow environment selecting PIG-A− stem cells. The present study investigated the presence of alterations of the immune system in a population of 11 PNH patients. The production of interferon- γ (IFN- γ) and interleukin-2 (IL-2), evaluated by intracellular cytokine analysis, and the frequencies of class I and II human leucocyte antigen (HLA) alleles were studied in comparison with healthy human subjects. Similar percentages of lymphocytes produced cytokines in PNH patients and controls after costimulation-independent activation; however, a negative correlation was found between the percentage of IFN- γ producing cells and white cell or platelets counts. PNH patients showed an higher percentage, compared with controls, of IFN- γ producing cells after costimulation-dependent activation. The frequency of HLA-A31 was higher in patients than in controls (27·2% vs. 4%), similarly to that of HLA-B7 (27·2% vs. 6%). With regard to class II alleles, 18% of PNH patients expressed DQB1*04 compared with none of 50 control cases. This study supports the hypothesis that immune alteration are present in PNH and that the immunogenetic background could influence the development of the disease. [ABSTRACT FROM AUTHOR]

The article presents abstracts of papers presented in the February 1986 issue of the Journal of Cutaneous Pathology. Some abstracts presented are as follows: The paper "An Immunophenotypic Comparison of the Lymphoid Infiltrates in Jessner's Lymphocytic Infiltration of the Skin and Chronic Discoid LE," by J. Ashworth, M.L. Turbutt and R.M. Mackie focuses on a comparative study of Jessner's lymphocytic infiltration of the skin; "Cutaneous Follicular Lymphomas," by C.F. Garcia, R.A. Warnke, A.J. Cox and G.S. Wood discusses 13 cases of cutaneous follicular lymphomas, which were evaluated clinically, histologically and immunologically.

The article presents a list of papers to be published in forthcoming issue of the "British Journal of Haematology." Some of them are: "Pancytopenia in Hereditary Haemorrhagic Telangiectasia," "Acute Lymphoblastic Leukaemia Relapsing With Solid Hepatic Tumours After Bone Marrow Transplantation," "Inhibitors in Congenital Coagulation Disorders," "The Role of Granulocyte Transfusions in Neutropenic Patients," "TAFI Polymorphisms at Amino Acids 147 and 325 are not Risk Factors for Cerebral Infarction."

The article presents several articles published in the February 2006 issue of the journal "The Veterinary Record." One article focuses on the stimulation of the immune system by certain vaccines shown to increase the severity of lesions associated with porcine circovirus type 2 in pig models. Another article is about methicillin-resistant Staphylococcus aureus that is of great concern in human hospitals. The other article tackles hyperlipemia, an increase in serum triglycerides to more than 5-6 mmol/1 that develops when the liver produces triglycerides faster than they can cleared from the plasma.

The article reflects on the Third International Conference on the Neuroendocrine Immune Basis of the Rheumatic Diseases. The conference discusses various topics which ranged from stress and the immune system to sex steroids and its effects on cytokines and certain disease states. This section aims to provide readers an overview of the topics discussed in the international meeting.

The cells presented in this work are not classified as cells that make up the immune system. They, however, present functions and molecules, which are characteristic of immune cells. These characteristic functions are, for example, sensing threat, performing phagocytosis, presentation of foreign antigens, cytokine release or enhancing immune memory. The enlisted immune response mechanisms are carried out by the possession of molecules such as Toll‐like receptors, receptors for the Fc fragment of IgG, major histocompatibility complex class II molecules, costimulatory CD80/CD86 proteins and molecules needed for NLRP3 (NOD‐like family pyrin domain containing 3) inflammasome activation. Thanks to these properties, the described nonimmune cells play an important role in the local immune response and support of the entire body in the fight against pathogens. They constitute the first line of defense of tissues and organs against pathogens and molecules recognized as harmful. The cells described in this article are particularly important in immunologically privileged places (e.g. the Bowman's capsule in the kidney), where "typical" immune cells normally do not have access. In this paper, we present immune‐like functions and molecule suites of resident kidney cells (podocytes and mesangial cells), cochlear resident cells, fibrocytes and fibroblasts, as well as some stem cells (mesenchymal stem cells and umbilical cord Wharton's jelly–derived cells). [ABSTRACT FROM AUTHOR]

The aim of the present paper is to explore whether seasonal outbreaks of infectious diseases may be linked to changes in host microbiomes. This is a very important issue, because one way to have more control over seasonal outbreaks is to understand the factors that underlie them. In this paper, I will evaluate the relevance of the microbiome as one of such factors. The paper is based on two pillars of reasoning. Firstly, on the idea that microbiomes play an important role in their hosts' defence against infectious diseases. Secondly, on the idea that microbiomes are not stable, but change seasonally. These two ideas are combined in order to argue that seasonal changes in a given microbiome may influence the functionality of the host's immune system and consequently make it easier for infectious agents to infect the host at certain times of year. I will argue that, while this is only a theoretical possibility, certain studies may back up such claims. Furthermore, I will show that this does not necessarily contradict other hypotheses aimed at explaining seasonal outbreaks; in fact, it may even enhance them. [ABSTRACT FROM AUTHOR]

In this paper, we study a delayed HIV infection model with nonmonotonic immune response and perform stability and bifurcation analysis. Our results show that the delayed HIV infection system with nonmonotonic immune response has bistability and stable periodic solution appear. We find that both the uninfected and immune-free equilibria are globally asymptotically stable under certain conditions which are not affected by time delay. However, the time delay makes one immune equilibrium always unstable for τ ≥ 0 and also makes another immune equilibrium appear stability switches; meanwhile, the system will exhibit local Hopf bifurcation, global Hopf bifurcation, and saddle-node-Hopf bifurcation. Numerical simulations are carried out to verify our results. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to review papers that assessed the vitamin D intake of children living in Norway, as research has suggested that it has remained below the recommended daily allowance of 10 μg/day. Methods: This mini review examined the vitamin D status of Norwegian children aged 0–18 years by systematically searching the PubMed, Google Scholar and Scopus databases from 1 January 2009 to 1 July 2020. Results: The review comprised six studies published in English between 2009 and 2020 on native‐born and non‐Western immigrant children. Most studies defined satisfactory vitamin D status as a plasma 25‐hydroxyvitamin D (25(OH)D) concentration of 50 nmol/L, with 25–50 nmol/L being classified as insufficient and below 25 nmol/L being classified as deficient. A study of healthy children found that 21% had insufficient levels and a further 1% were deficient, but this second finding was only among adolescents. Other studies showed that 47% of Norwegian children with a non‐Western immigrant background were deficient, and so were 19% of overweight children, mainly adolescents. Conclusion: Vitamin D concentrations were often insufficient among children living in Norway, particularly adolescents and those with a non‐Western immigrant background. Higher recommended supplements may be needed. [ABSTRACT FROM AUTHOR]

The article lists several papers related to immune system that are to be published in the December 2004 issue of the journal "Immunology." Some of the papers are "Phenotypic and Functional Heterogeneity of Porcine Blood Monocytes and Its Relation With Maturation," by Sonia Chamorro, Concepcion Revilla, Belen Alvarez, Fernando Alonso, Angel Ezquerra, Javier Dominguez; "Influence of Pathological Progression on the Balance Between Cellular and Humoral Immune Responses in Bovine Tuberculosis," Michael Welsh, Rodat Cunningham, David Corbett, R. Martyn Girvin, James McNair, Robin Skuce, David Bryson, John Pollock.

Lists the papers to be published in the forthcoming issues of the periodical "British Journal of Haematology". Immune reconstitution following hematopoietic stem cell transplantation; Perirenal extramedullary hematopoiesis in myelofibrosis demonstrated on computed tomography.

The immune system is a central component of organismic function in humans. This paper addresses self‐organization of biological systems in relation to—and nested within—other biological systems in pregnancy. Pregnancy constitutes a fundamental state for human embodiment and a key step in the evolution and conservation of our species. While not all humans can be pregnant, our initial state of emerging and growing within another person's body is universal. Hence, the pregnant state does not concern some individuals but all individuals. Indeed, the hierarchical relationship in pregnancy reflects an even earlier autopoietic process in the embryo by which the number of individuals in a single blastoderm is dynamically determined by cell– interactions. The relationship and the interactions between the two self‐organizing systems during pregnancy may play a pivotal role in understanding the nature of biological self‐organization per se in humans. Specifically, we consider the role of the immune system in biological self‐organization in addition to neural/brain systems that furnish us with a sense of self. We examine the complex case of pregnancy, whereby two immune systems need to negotiate the exchange of resources and information in order to maintain viable self‐regulation of nested systems. We conclude with a proposal for the mechanisms—that scaffold the complex relationship between two self‐organising systems in pregnancy—through the lens of the Active Inference, with a focus on shared Markov blankets. [ABSTRACT FROM AUTHOR]

Summary: Under the background of "Internet +" and "dual innovation," start‐ups are faced with huge, complex, and diverse growth risks with sudden, dominant, and dynamic characteristics during the growth process. It is significant to identify these risks accurately during the growth and development of new ventures. This paper draws on the theory of biological immune system, combines the ontology with the growth risk of start‐ups, and uses SWRL and Jess engine to build an ontology knowledge base of start‐ups' growth risk to identify various risks in the growth process of start‐up. The results show that the ontology model supports the risk identification based on semantic reasoning and can improve the accuracy of the growth risk identification of start‐ups. What's more, it provides new ideas for the research on the growth risk identification of new start‐ups. [ABSTRACT FROM AUTHOR]

Lists forthcoming papers on immunology published in the October 2005 issue of the journal "Immunology." "Relationship Between SPRY and B30.2 protei domains: Evolution of a Component of Immune Defense?" by David Rhodes, Bernard de Bono and John Trowsdale; "Putting the NK Cell in Its Place," by Geraldine O'Connor, Orla Hart and Clair Gardiner; "Tolerosome Induced Oral Tolerance Is MHC Restricted," by Esbjorn telemo, S. Ostman and M. Taube; Others.

Lists the papers to be published in the forthcoming issues of the periodical "British Journal of Haematology". "Cerebral and pulmonary nocardia in a bone marrow transplant patient," by A. D. Laurence and K. S. Peggs; "Heparin-induced skin necrosis," by R. Patel, Z. Lim, S. Dawe, J. Salisbury and R. Arya; "Psychological complications in sickle cell disease," by K. A. Anie.

Cellular therapy nowadays includes various products from haematopoietic stem cells (HSC) collected from bone marrow, peripheral blood, and umbilical cord blood to more complex adoptive immune therapy for the treatment of malignant diseases, and gene therapy for inherited immune deficiencies. Broader utilization of cellular therapy requires extensive quality testing of these products that should fulfil the same requirements regarding composition, purity, and potency nevertheless they are manufactured in various centres. Technical improvements of the flow cytometers accompanied by the increased number of available reagents and fluorochromes used to conjugate monoclonal antibodies, enable detailed and precise insight into the function of the immune system and other areas of cell biology, and allows cell evaluation based on size, shape, and morphology or assessment of cell surface markers, as well as cell purity and viability, which greatly contributes to the development and progress of the cell therapy. The aim of this paper is to give an overview of the current use and challenges of flow cytometry analysis in quality assessment of cellular therapy products, with regard to basic principles of determining HSC and leukocyte subpopulation, assessment of cells viability and quality of thawed cryopreserved HSC as well as the importance of validation and quality control of flow cytometry methods according to good laboratory practice. [ABSTRACT FROM AUTHOR]

Urban areas face mounting risks from many sources. Cities pursue myriad tactics to resist, recover from and adapt to shocks and stresses, but little is known about how these approaches relate across the scales of a city nor how cities compare in their abilities. Part of the challenge in addressing these gaps is that the risk to cities is typically studied with an emphasis on one or a few hazards or through the lens of a singular sector. This paper proposes a framework, dubbed the Urban Immune System (UIS) to coalesce and expand industrial ecology research on urban risk management. In the same way that Urban Metabolism (UM) is a unifying framework for urban environmental sustainability, UIS can be a unifying framework for urban resilience, especially related to climate change. Herein, UIS is defined, its many capabilities are dissected and linked to disparate studies; and opportunities for application of the concept are provided. The paper concludes by examining the relationship between UIS and climate change and by identifying those attributes of the UIS that are expected to be of increasing importance under climate change. [ABSTRACT FROM AUTHOR]

Background: Sexual dimorphism is observed in the occurrence, course, and severity of human disease. The difference in immune response between males and females can in part be attributed to sexual genotype. However, immunological differences can also be explained by endocrine–immune interactions. Specifically, androgens possess the ability of directly modulating the development and function of immune cells. Although androgens generally contribute to immunosuppressive effects, this is not necessarily always the case. Aim: The aim of the review is to uncover the role of androgens in shaping the innate immune response. Material & Methods: Authors included papers in this review which discussed the impact of androgens on specific innate immune cells. Results: Androgens modulate the innate immune response through various mechanisms. However, there is conflicting evidence in the literature regarding the interplay betwen androgens and the innate immune system. Discussion: Conflicting evidence presented in this review could in part be explained by the limitations present in interpreting results. Conclusion: This review is of great importance for our understanding of occurence and mechanism of human inflammatory disease. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa ( HS) is a chronic inflammatory disabling skin disease consisting of recurrent nodules, sinuses, fistulas and scarring involving the intertriginous regions. HS is often a therapeutic challenge and most treatments are off-label. A better understanding of aetiology and pathogenesis of HS may facilitate the development of effective treatment. Although the clinical presentation is strongly reminiscent of bacterial infection, the role of bacteria remains controversial. Studies have isolated an array of different bacteria specimens. Consistent findings of Gram-positive cocci and Gram-positive rods including Staphylococus aureus, coagulase-negative staphylococci (Co NS) and Corynebacterium species in deep tissue samples have been demonstrated in HS and may constitute a central target for the immune system. Efficacy of antibiotics, that is rifampicin, clindamycin or tetracycline, supports a microbial role in disease pathogenesis. However, these antibiotics also work as immunomodulators of especially T cells, and the underlying mechanisms may therefore be more complex. We performed a systematic review of previous studies investigating the bacterial flora in hidradenitis suppurativa. We searched PubMed, EMBASE, Royal Danish Library and Cochrane library (search date 11 December 2014). A total of 66 papers were identified and nine papers published between 1988 and 2014 matched our inclusion criteria, yielding bacteriological data of a total of 324 patients with HS (mean age 36.8 years and female/male ratio 215/109). This overview of the bacteriology may aid researchers and physicians exploring the potential role of bacteria in HS. Furthermore, to stimulate a broader debate, we also present different viewpoints on the possible role of bacteria in HS. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Biomarkers as common data elements (CDEs) are important for the characterization of biobehavioral symptoms given that once a biologic moderator or mediator is identified, biologically based strategies can be investigated for treatment efforts. Just as a symptom inventory reflects a symptom experience, a biomarker is an indicator of the symptom, though not the symptom per se. The purposes of this position paper are to (a) identify a “minimum set” of biomarkers for consideration as CDEs in symptom and self‐management science, specifically biochemical biomarkers; (b) evaluate the benefits and limitations of such a limited array of biomarkers with implications for symptom science; (c) propose a strategy for the collection of the endorsed minimum set of biologic samples to be employed as CDEs for symptom science; and (d) conceptualize this minimum set of biomarkers consistent with National Institute of Nursing Research (NINR) symptoms of fatigue, depression, cognition, pain, and sleep disturbance. Design and Methods: From May 2016 through January 2017, a working group consisting of a subset of the Directors of the NINR Centers of Excellence funded by P20 or P30 mechanisms and NINR staff met bimonthly via telephone to develop this position paper suggesting the addition of biomarkers as CDEs. The full group of Directors reviewed drafts, provided critiques and suggestions, recommended the minimum set of biomarkers, and approved the completed document. Best practices for selecting, identifying, and using biological CDEs as well as challenges to the use of biological CDEs for symptom and self‐management science are described. Current platforms for sample outcome sharing are presented. Finally, biological CDEs for symptom and self‐management science are proposed along with implications for future research and use of CDEs in these areas. Findings: The recommended minimum set of biomarker CDEs include pro‐ and anti‐inflammatory cytokines, a hypothalamic‐pituitary‐adrenal axis marker, cortisol, the neuropeptide brain‐derived neurotrophic factor, and DNA polymorphisms. Conclusions: It is anticipated that this minimum set of biomarker CDEs will be refined as knowledge regarding biologic mechanisms underlying symptom and self‐management science further develop. The incorporation of biological CDEs may provide insights into mechanisms of symptoms, effectiveness of proposed interventions, and applicability of chosen theoretical frameworks. Similarly, as for the previously suggested NINR CDEs for behavioral symptoms and self‐management of chronic conditions, biological CDEs offer the potential for collaborative efforts that will strengthen symptom and self‐management science. Clinical Relevance: The use of biomarker CDEs in biobehavioral symptoms research will facilitate the reproducibility and generalizability of research findings and benefit symptom and self‐management science. [ABSTRACT FROM AUTHOR]

Modern immunology has seen an apparent revolution with the recognition that human immune defense is not only the responsibility of bone marrow-derived leucocytes, but also dependent on a coordinated network of many cell types including epithelial cells, fibroblasts and neural elements. This classic paper by Alexander Fleming and V.D. Allison (British J of Exp Path, 111, 1922, 252) was largely forgotten for 75 years and describes the discovery that epithelia produce a protein with direct antimicrobial activity. Thus, this paper represents the birth of the field now referred to as innate immunity and first describes an antimicrobial protein ( AMP). [ABSTRACT FROM AUTHOR]

Keywords: algorithm; allergy; atopic; atopic dermatitis; childhood; children; diagnosis; eczema; immune system; medical algorithm; pediatric EN algorithm allergy atopic atopic dermatitis childhood children diagnosis eczema immune system medical algorithm pediatric 403 406 4 01/09/21 20210101 NES 210101 Atopic dermatitis (AD, atopic eczema) is a chronic, relapsing, pruritic, noncommunicable inflammatory skin disease that affects children and adults.1 It almost always has its debut in early life;2,3 therefore, this medical algorithm focuses on diagnosis (part I) and therapy (part II4) of AD in early childhood, which is defined by UNESCO as "the period from birth to eight years old." ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. Algorithm, allergy, atopic, atopic dermatitis, childhood, children, diagnosis, eczema, immune system, medical algorithm, pediatric. [Extracted from the article]

In the first of two papers we described the development in the field of allergy mechanisms as described by Clinical and Experimental Allergy in 2015. Experimental models of allergic disease, basic mechanisms, clinical mechanisms and allergens are all covered. A second paper will cover clinical aspects. [ABSTRACT FROM AUTHOR]

This first paper, in a three-part CE series on the prevention of infection in patients with chronic kidney disease, focuses on infection susceptibility in this patient population and the application of infection control principles to the renal care environment. The second and third papers in this series will focus on specific aspects of infection control including the prevention and management of blood-borne virus and other healthcare-associated infections. [ABSTRACT FROM AUTHOR]

In the past 15 years, it became clear that the symbiotic microbiota has an important impact on the development and regulation of the immune system. Consequently, it is incorrect to interpret a phenotype solely as a direct result of the genotype, without considering the impact of the microbiota. In fact, ignorance of the effects exerted by the microbiota may account for a large part of the "replication issues" found in many studies. In this issue of the European Journal of Immunology, Beller et al. [Eur. J. Immunol. 2020. 50: 783–794] provide data suggesting that eosinophils are not required to maintain IgA‐producing plasma cells in the intestine, contrary to earlier reports. This paper shows that mice lacking eosinophils develop an altered intestinal microbiota, which poorly induces IgA. Normal levels of IgA were obtained in mice lacking eosinophils when these were colonized by microbiota from the WT mice. Therefore, the use of littermate controls carrying the same microbiota, in experiments comparing WT and mutant mice, is necessary to control the potential role of the microbiota. Nevertheless, caution should always be exercised in the interpretation of the results: changes in the microbiota may result from mutations in the host, and thereby, indirectly convey the effect of genotypes on phenotypes. [ABSTRACT FROM AUTHOR]

Summary: In this paper, we propose and analyze an optimal control problem where human immunodeficiency virus treatment and immunotherapy are described by two control functions that are subject to time delays representing pharmacological and absorption delays, respectively. The goal is to propose effective optimal control solutions for the combination of human immunodeficiency virus treatment and immunotherapy, ensuring a functional behavior of the immune system. The incubation period is mathematically represented by a time delay in the virus load, and the local asymptotic and Hopf bifurcation analysis of the CTL‐equilibrium point of the uncontrolled delayed system is studied. We obtain optimal controls of bang‐singular type both for the nondelayed and delayed optimal control problem with and without state constraints. We study boundary arcs of state constraints and junction properties of the control and adjoint variables at entry and exit points of boundary arcs. Moreover, we derive an explicit formula of the multiplier associated with the state constraint. [ABSTRACT FROM AUTHOR]

Monitoring of donor‐specific HLA antibodies (DSA) has become part of the clinical routine in kidney transplantation. This paper gives a brief overview on data from the Collaborative Transplant Study (CTS) and the Heidelberg Transplant Center on the clinical relevance of post‐transplant DSA monitoring in patients undergoing renal transplantation. The obtained findings underline the importance of DSA monitoring in the post‐operative course in immunologically high‐risk patients and patients with deterioration of graft function. Especially in patients with a pre‐activated immune system, a gap in the immunosuppressive therapy appear to lead to persistence, reappearance or de novo occurrence of strong, complement‐activating DSA, resulting in severe antibody‐mediated rejection (AMR) and, without timely intervention, in AMR‐related graft loss. [ABSTRACT FROM AUTHOR]

Immunosenescence, also known as immune aging, refers to the degeneration, compensation, and reconstruction of the immune system with aging. Immune aging is an important factor in the increased susceptibility of the elderly to infectious diseases, malignant tumors, and a variety of chronic diseases and has long been a hotspot in geriatrics and immunology research. In this paper, the characteristics and progression of immune aging are briefly reviewed for clinicians' reference. [ABSTRACT FROM AUTHOR]

In this paper, first the immune system is analyzed in a relatively deeper and all-sided point of view reflecting the fresh research in biology. Second, based on the previous statements, a new optimization method, the immune genetic algorithm (IGA), is presented by simulating the behavior of the biological immune system and is proved to converge to the global optimum with probability 1. Third, a new method on the multi-object optimization that is transformed into a single-object one is proposed based on the joints' best compliance in the redundant robot path planning using IGA. Last, the experiment results show that the method of this article behaves more successfully. © 2004 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The colon is the largest compartment of the immune system, with innate immune cells exposed to antigens in the environment. However, the mechanisms by which the innate immune system is instigated are poorly defined in colorectal cancer (CRC). Here, a population of CD16+ neutrophils that specifically accumulate in CRC tumor tissues by imaging mass cytometry (IMC), immune fluorescence, and flow cytometry, which demonstrated pro‐tumor activity by disturbing natural killer (NK) cells are identified. It is found that these CD16+ neutrophils possess abnormal cholesterol accumulation due to activation of the CD16/TAK1/NF‐κB axis, which upregulates scavenger receptors for cholesterol intake including CD36 and LRP1. Consequently, these region‐specific CD16+ neutrophils not only competitively inhibit cholesterol intake of NK cells, which interrupts NK lipid raft formation and blocks their antitumor signaling but also release neutrophil extracellular traps (NETs) to induce the death of NK cells. Furthermore, CD16‐knockout reverses the pro‐tumor activity of neutrophils and restored NK cell cytotoxicity. Collectively, the findings suggest that CRC region‐specific CD16+ neutrophils can be a diagnostic marker and potential therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

Posttranslational modifications play a crucial role in governing cellular functions and protein behavior. Researchers have implicated dysregulated posttranslational modifications in protein misfolding, which results in cytotoxicity, particularly in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and Huntington disease. These aberrant posttranslational modifications cause proteins to gather in certain parts of the brain that are linked to the development of the diseases. This leads to neuronal dysfunction and the start of neurodegenerative disease symptoms. Cognitive decline and neurological impairments commonly manifest in neurodegenerative disease patients, underscoring the urgency of comprehending the posttranslational modifications' impact on protein function for targeted therapeutic interventions. This review elucidates the critical link between neurodegenerative diseases and specific posttranslational modifications, focusing on Tau, APP, α‐synuclein, Huntingtin protein, Parkin, DJ‐1, and Drp1. By delineating the prominent aberrant posttranslational modifications within Alzheimer disease, Parkinson disease, and Huntington disease, the review underscores the significance of understanding the interplay among these modifications. Emphasizing 10 key abnormal posttranslational modifications, this study aims to provide a comprehensive framework for investigating neurodegenerative diseases holistically. The insights presented herein shed light on potential therapeutic avenues aimed at modulating posttranslational modifications to mitigate protein aggregation and retard neurodegenerative disease progression. [ABSTRACT FROM AUTHOR]

Immune dysregulation is a pivotal factor in the onset and progression of various diseases. In cancer, the immune system's inability to discern and eliminate abnormal cells leads to uncontrolled tumor growth. When faced with resilient pathogens or harmful toxins, the immune system encounters challenges in clearance and neutralization. Achieving a delicate balance of pro‐inflammatory and anti‐inflammatory signals is essential in managing a range of disorders and diseases. Like in other biomedical research domains, nanotechnology has provided innovative approaches for rebalancing host immunity. Among the plethora of nanotechnology‐based interventions, the concept of cell membrane‐coated nanoparticles holds significant potential for immunomodulatory applications owing to their biomimetic properties that allow for precise interaction with the compromised immune system. This review thoroughly examines the potential of novel nanosystems for immune modulation. The exploration covers crucial elements, including the origins and characteristics of cell membranes, the methods employed for their procurement and coating, physicochemical/biological characterization techniques, and enhancement of their therapeutic efficacy via functionalization. Subsequently, case studies‐based analysis of utilizing these bioinspired nanosystems in tackling different conditions caused by immune disturbance has been comprehensively discussed. [ABSTRACT FROM AUTHOR]

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Regulatory T cells (Tregs) are essential for maintaining immune homeostasis by serving as negative regulators of adaptive immune system effector cell responses. Reduced production or function of Tregs has been implicated in several human autoimmune diseases. The cytokine interleukin 2 plays a central role in promoting Treg differentiation, survival, and function in vivo and may therefore have therapeutic benefits for autoimmune diseases. mRNA‐6231 is an investigational, lipid nanoparticle‐encapsulated, mRNA‐based therapy that encodes a modified human interleukin 2 mutein fused to human serum albumin (HSA‐IL2m). Herein, we report the development of a semi‐mechanistic kinetic‐pharmacodynamic model to quantify the relationship between subcutaneous dose(s) of mRNA‐6231, HSA‐IL2m protein expression, and Treg expansion in nonhuman primates. The nonclinical kinetic‐pharmacodynamic model was extrapolated to humans using allometric scaling principles and the physiological basis of pharmacological mechanisms to predict the clinical response to therapy a priori. Model‐based simulations were used to inform the dose selection and design of the first‐in‐human clinical study (NCT04916431). The modeling approach used to predict human responses was validated when data became available from the phase I clinical study. This validation indicates that the approach is valuable in informing clinical decision‐making. [ABSTRACT FROM AUTHOR]

Despite being some of the most anecdotally well‐known roads to pathogenesis, the mechanisms governing autoimmune rheumatic diseases are not yet fully understood. The overactivation of the cellular immune system and the characteristic development of autoantibodies have been linked to oxidative stress. Typical clinical manifestations, such as joint swelling and deformities and inflammation of the skin and internal organs, have also been connected directly or indirectly to redox mechanisms. The differences in generation and restraint of oxidative stress provide compelling evidence for the broad variety in pathology among rheumatic diseases and explain some of the common triggers and discordant manifestations in these diseases. Growing evidence of redox mechanisms in pathogenesis has provided a broad array of new potential therapeutic targets. Here, we explore the mechanisms by which oxidative stress is generated, explore its roles in autoimmunity and end‐organ damage, and discuss how individual rheumatic diseases exhibit unique features that offer targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

The phenotypes and receptors of the intraepithelial lymphocytes which are a major component of the mucosal immune system are of considerable interest. Intraepithelial lymphocytes, especially those of the intestines, are well documented. The nasal intraepithelial lymphocytes probably play a key role in the immune defense of the entire respiratory tract. However, documentation of these lymphocytes is limited to only a few nondescriptive studies by immunohistological methods. In our previous paper, we examined the subsets of the nasal intraepithelial lymphocytes by two-color flow cytometry after culture with monoclonal antibody against CD3 and PMA. The mucosal immune system, which comprises the lymphoid tissue associated with the mucosal surface, consists of lymphocyte populations from both the epithelium and the lamina propria. In this paper (a sequel to our previous study), we have carried out a comparative study of the intraepithelial lymphocytes and lamina propria lymphocytes of the human nasal mucosa. In the 42 patients (with allergic rhinitis/infectious hypertrophic rhinitis) whom we examined, T lymphocytes were predominant in the epithelium as well as the lamina propria. B lymphocytes were detected only in the lamina propria. CD8 + T cells (suppressor/cytotoxic) and CD4-8 - (double-negative) (DN) comprised the major population of the intraepithelial lymphocytes. The CD4 +/CD8 + ratio was 0.5 ± 0.1. In contrast, the lamina propria showed a predominance of CD4 + T cells (helper/inducer), with a CD4 +/CD8 + ratio of 1.3 &plusmnn; 0.2. CD3 + 4-8 - (double-negative T cells) were comparable in number in the epithelium and the lamina propria. CD8 + T cells of the epithelium were predominantly cytotoxic T cells, and CD4 + T cells were predominantly helper T cells. In the lamina propria, CD8 + T cells were predominantly of the suppressor type. In the analysis of the T-cell receptors of the epithelium and the lamina propria, there was a predominance of the αβ receptor-bearing T cells in both. However, in the double-negative T-cell population of the epithelium, αβ heterodimer predominated over αβ. In order to verify the influence of culture conditions on the percentages of the individual subsets of lymphocytes, we examined the peripheral blood lymphocytes by flow cytometry before and after culture under the same conditions. We found no significant change in the different subsets caused by culture except a slight reduction in the percentage of suppressor T cells as well as a significant increase in activated T cells. We therefore wish to emphasize that the nasal intraepitheial lymphocytes are heterogenous in phenotype, and are dominated by double-negative cells and CD8 + T cells. Moreover, the nasal lamina propria lymphocytes are also heterogenous in phenotype, and differ in proportion from the intraepithelial lymphocytes. What is of utmost interest is the preferential location of the αβ receptor-bearing T cells in the epithelium and their relative absence in the lamina propria. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a disease that has shown a considerable increase in prevalence in recent centuries. Current knowledge about its etiology is incomplete, and therefore it cannot be managed optimally utilizing targeted therapeutic regimens at each stage of the disease. MS progresses in different stages, beginning with a cascade of inflammation. The pivotal spark to initiate this cascade seems to be the migration of Th17 into the central nervous system across the blood–brain barrier (BBB) through the disrupted tight junctions. Coupling of interleukin (IL)‐17 and IL‐22 to their receptors in the BBB layer facilitates this migration. Subsequently, axon degeneration and the various manifestations of nerve–muscle disorders appear. Curcumin, a major component of turmeric, is derived from Curcuma longa, which belongs to the Zingiberaceae family. Numerous properties of curcumin have been identified recently, some of which can be effective in the treatment of MS, particularly the anti‐inflammatory properties via inhibition of secretion of proinflammatory cytokines. In this paper, we will review the various properties and key effects of curcumin for the treatment of MS. [ABSTRACT FROM AUTHOR]

In this paper, we proposed a multidelayed in‐host HIV model to represent the interaction between human immunodeficiency virus and immune response. One delay was considered to incorporate the time required by the virus for various intracellular events to make a host cell productively infective, and the second delay was introduced to take into account the time required for adaptive immune system to respond against infection. We extensively analyzed this multidelayed model analytically and numerically. We show that delay may have both destabilizing and stabilizing effects even when the system contains a single immune response delay. It happens when there exists two sequences of critical values of this delay. If the system starts with stable state in absence of delay, then the smallest value of these critical delays causes instability and the next higher value causes stability. The system may also show stability switching for different values of the virus replication factor. These results demonstrate the possible reasons of intrapatients and interpatients variability of CD4+ T cells and virus counts in HIV‐infected patients. [ABSTRACT FROM AUTHOR]

As the penetration of wind generation increases, the uncertainty it brings has imposed great challenges to power system operation. To cope with the challenges, tremendous research work has been conducted, among which two aspects are of most importance, that is, making immune operation strategies and accessing the power system's capability to accommodate the variable energy. Driven and inspired by the latter problem, this paper will discuss the power system's capability to accommodate variable wind generation in a probability sense. Wind generation, along with its uncertainty is illustrated by a polyhedron, which contains prediction, risk, and uncertainty information. Then, a three-level optimisation problem is presented to estimate the lower probability bound of power system's capability to fully accommodate wind generation. After reformulating the inner max-min problem, or feasibility check problem, into its equivalent mixed-integer linear program (MILP) form, the bisection algorithm is presented to solve this challenging problem. Modified IEEE systems are adopted to show the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Recent empirical contributions highlight the negative impact of pollution on labor supply. This relationship is explained by two mechanisms: first, pollution modifies agents' work–leisure trade‐off as it deteriorates their working conditions (incentive effect); and second, a polluted environment is likely to generate more frequent epidemic outbreaks and to affect agents' immune systems (health effect). Bosi et al. () explore the aggregate consequences of the incentive effect and show that it can generate endogenous fluctuations in the economic activity. The present paper focuses on the health effect as we study a Ramsey model augmented with the spread of infectious disease. We find that industrial pollution may generate limit cycles around an endemic steady state. More precisely, the economic system may undergo a transcritical bifurcation followed by two Hopf bifurcations near this steady state. [ABSTRACT FROM AUTHOR]

ABSTRACT: Acute kidney injury is common and associated with negative renal and patient outcomes. The human kidney has a real but limited regeneration capacity. Understanding renal regeneration may allow us to manipulate this process and thus develop therapeutic weapons to improve patients’ outcome. In the first part of this paper we discuss the clinical factors associated with renal recovery: baseline patient particularities, acute kidney injury characteristics and the medical approach taken in the short and long‐term. In the second part, the cellular and molecular mechanisms underlying renal regeneration are explored. The immune system seems to have an important role, first promoting inflammation and then tissue healing. Other players, such as cellular senescence, mitochondrial dysfunction, renal haemodynamics and metabolic reprogramming also have a role in renal regeneration. We aim to develop a short review of renal regeneration, offering a holistic view of this process. [ABSTRACT FROM AUTHOR]

Osteoporosis disease is caused by hormonal changes, vitamin D, and calcium deficiency. With current technologies, the identification of osteoporosis requires many tests with the support of medications. Bone mineral density is a typical measure implemented using a DEXA scan which can be very costly. Such high technology equipment is usually not accessible for remote people, and thus a low‐cost screening system is very appealing. This article proposes an osteoporosis prediction system that effectively determines its possibility of occurrence based on essential factors such as smoking habits and calcium level so that the people at high risk can be referred to access the DEXA scanner. Our proposed system is implemented by an improved version of the artificial immune system, enabling care providers to take precautionary measures at the right time to avoid the early development of osteoporosis. The experiments demonstrated a promising result of 94% prediction accuracy that proved its usefulness in identifying people with potential osteoporosis in the future. [ABSTRACT FROM AUTHOR]

Introduces articles that focus on the application of microscopic techniques for the analysis of immune cell development and function. Technologies that enable investigators to visualize cognate interactions during immune cell development and activation; Determination of the biochemical events in single cells; Applications and topics which contribute to the understanding of immune system responses.