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Inflammation is an important driver of atherosclerosis, and the favourable outcomes of the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial revealed the large potential of anti-inflammatory drugs for the treatment of cardiovascular disease, especially in patients with a pro-inflammatory constitution. However, the complex immune reactions driving inflammation in the vascular wall in response to an atherosclerotic microenvironment are still being unravelled. Novel insights into the cellular processes driving immunity and inflammation revealed that alterations in intracellular metabolic pathways are strong drivers of survival, growth, and function of immune cells. Therefore, this position paper presents a brief overview of the recent developments in the immunometabolism field, focusing on its role in atherosclerosis. We will also highlight the potential impact of immunometabolic markers and targets in clinical cardiovascular medicine., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

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]

Ageing is the greatest challenge that health-care systems will have to deal with this century. This is because a wide spectrum of pathological impairments emerge in the later part of the human life course which sharply increase mortality and reduce quality of life. Dysfunction of the immune system with advancing age is of crucial importance to the development of disability in later life and finally death. Understanding immune ageing, immunosenescence, has long been recognised as an essential prerequisite for the delivery of effective interventions which will improve late life health. Ten years ago, the ImAginE consortium undertook a broad ranging series of projects which added significantly to our understanding of how fundamental ageing mechanisms drove immune decline. In the decade which followed, abundant evidence has accumulated from nonhuman model systems that ageing results from the progressive operation of a relatively few common processes which act across the major organ systems. These advances in fundamental understanding both allow better clarification of the potential cross-system dysregulation that occurs in ageing and open new avenues for intervention. Over the course of a 2-day workshop, the original ImAginE participants have considered these issues and present some suggestions for current priority areas in immunosenescence.

The present study was designed to examine, whether, effluents from a modern pulp and paper mill using elemental chlorine-free/total chlorine-free (ECF/TCF) bleaching, exert effects on the immune system of fish and, in addition, to relate these findings to physiological parameters known to be affected by bleached kraft-mill effluents (BKME). Roach (Rutilus rutilus) were exposed in laboratory conditions to primary- or secondary-treated effluent from a pulp and paper mill. In order to study their capability to respond to foreign antigens they were immunised with bovine gamma-globulin (BGG) prior to exposure. The number of anti-BGG antibody-secreting cells (ASC) and the number of immunoglobulin-secreting cells (ISC) in the spleen and blood as well as the level of anti-BGG specific antibodies and concentration of plasma immunoglobulin (IgM) were studied. Phagocytosis and migration of granulocytes of the head kidney were also determined. In addition to the immunological parameters, the activity of hepatic biotransformation enzymes, the carbohydrate metabolism and osmoregulation were examined. Exposure of roach for 21 days to BKME affected several immunological parameters. Both effluents, primary- and secondary-treated, impaired the immunoreactivity of the fish. Sex-related differences in the immune responses were evident in many parameters e.g. in the number of blood ISC and splenic ASC. Sex also had effects on cortisol levels and in the induction of 7-ethoxyresorufin O-deethylase (EROD). These results demonstrate that both primary- and secondary-treated effluent from a pulp and paper mill using ECF/TCF bleaching have effects on fish immune functions. Further, these findings suggest that steroids may contribute to immunomodulation in fish.

The immunotoxic potential of bleached kraft pulp mill effluent (BKME) to cell-mediated immunity in mink (Mustela vison) was investigated October 1993 through May 1994. For 26 weeks, 20 mink were fed a diet based upon fish caught within 6 km downstream of a bleached kraft mill in Saskatchewan, Canada. Water for this group contained 25% softwood-run BKME. Twenty control mink were fed nutritionally matched diets based upon fish from lakes receiving no municipal or industrial effluent and tap water. Using in vitro and in vivo immunotoxicity assays, the proliferative response of mink peripheral blood mononuclear cells (PBMC) to mitogens was optimal, at 72 hr with 10 micrograms/ml Concanavalin A, 1/80 dilution pokeweed mitogen, and 1/80 dilution phytohemagglutinin. Bacterial cell wall Escherichia coli lipopolysaccharide did not stimulate mitosis of the mink PBMC. No difference (P < 0.05) in PBMC proliferation was seen between the control and BKME-exposed mink with any of the mitogens used. Delayed type hypersensitivity (DTH), a cell mediated response, was assessed in mink vaccinated with live bacille Calmette-Guérin (BCG) and then challenged by intradermal toe web injection with 200 micrograms of sonicated BCG approximately 6 weeks later. The DTH response in the BKME-exposed mink was impaired based upon assessment using skin thickness measurements, histopathological assessment and image analyzer technology. This decreased response is evidence for suboptimal immune function associated with BKME exposure, which could affect the competitive fitness of piscivorous mammals naturally exposed to BKME.

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 purpose of this paper is to present evidence that supports the notion that the primary reason behind marginal bone loss and implant failure is immune-based and that bacterial actions in the great majority of problematic cases are of a secondary nature. Materials and Methods: The paper is written as a narrative review. Results: Evidence is presented that commercially pure titanium is not biologically inert, but instead activates the innate immune system of the body. For its function, the clinical implant is dependent on an immune/inflammatory defense against bacteria. Biologic models such as ligature studies have incorrectly assumed that the primary response causing marginal bone loss is due to bacterial action. In reality, bacterial actions are secondary to an imbalance of the innate immune system caused by the combination of titanium implants and ligatures, ie, nonself. This immunologic imbalance may lead to marginal bone resorption even in the absence of bacteria. Conclusion: Marginal bone loss and imminent oral implant failure cannot be properly analyzed without a clear understanding of immunologically caused tissue responses. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. However, immune-related adverse events (irAEs) and undesired response patterns such as progression after the initial good response in a subset of patients pose a major challenge and drawback to ICIT. This paper provides deep insight into ICIT related bottlenecks and corresponding effective management and combat strategies for very complex complications., Methods: The relevant literatures from PubMed have been reviewed. Based on obtained information, rigorous and exhaustive analyses have been made to present novel methods and strategies against ICIT drawbacks and bottlenecks., Results: The results show that baseline biomarker tests are very crucial to identify suitable candidates for ICIT and frequent assessments throughout ICIT help to recognize possible irAEs at early stages. Equally important are the necessity for mathematical definitions for the ICIT success rate and optimum duration, and the development of combat mechanisms against loss of sensitivity within the tumor microenvironment (TME)., Conclusion: Rigorous management approaches are presented for mostly observed irAEs. Furthermore, for the first time in the literature, a non-linear mathematical model is invented to measure the ICIT success rate and to decide about the optimum ICIT duration. Finally, a strategy against tumor plasticity is introduced., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The paper mulberry (Broussonetia papyrifera) leaf is rich in alkaloids and flavonoids, which has high medicinal and feeding value. We aimed to analyze the effects of B. papyrifera leaf extract on growth performance, antioxidant capacity, immune functions, and fecal microflora of weaned piglets. Thirty healthy, 28-day-old piglets were randomly assigned to three groups and fed with a basal diet supplemented with 0, 150, and 300 g/t B. papyrifera leaf extract for 42 days (control group, group I, and group II) separately. The result revealed that the final weight of piglets in group II was higher than the other groups, and the diarrhea rate in this group was 62.9% lower than in the control group. The feed conversion ratio in group I was significantly lower than the other two groups. Higher blood urine nitrogen concentration was noted in group II, higher glutathione peroxidase and catalase in group II, higher superoxide dismutase in the control group, and higher immune globulins (Ig) IgG, IgA, and IgM in group II. There was no significant difference in community richness and community diversity among the three groups of fecal samples. The relative level of Roseburia was higher in groups I and II, while Lactobacillus was higher in the control group. In conclusion, supplementation with B. papyrifera leaf extract at a certain dosage can increase growth performance and antioxidant capacity of weaned piglets, reduce the occurrence of diarrhea, enhance immune functions and disease resistance, and affect the composition of fecal microflora. [ABSTRACT FROM AUTHOR]

Abstract Background Our current understanding of the pathophysiology and management of sepsis is associated with a lack of progress in clinical trials, which partly reflects insufficient appreciation of the heterogeneity of this syndrome. Consequently, more patient-specific approaches to treatment should be explored. Aims To summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice. A secondary objective is to develop a framework enclosing recommendations on management and priorities for further research. Sources A global search strategy was performed in the MEDLINE database through the PubMed search engine (last search December 2017). No restrictions of study design, time, or language were imposed. Content The focus of this Position Paper is on the interplay between therapies, pathogens, and the host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as targeted antibiotic treatment. Other topics include the disruption of host immune system and the use of biomarkers in sepsis management, patient stratification, and future clinical trial design. Lastly, personalized antibiotic treatment and stewardship are addressed (Fig. 1). Implications A road map provides recommendations and future perspectives. RDTs and identifying drug-response phenotypes are clear challenges. The next step will be the implementation of precision medicine to sepsis management, based on theranostic methodology. This highly individualized approach will be essential for the design of novel clinical trials and improvement of care pathways. [ABSTRACT FROM AUTHOR]

Unlike other cells in the body, immune cells have to be able to enter and adapt to life within diverse tissues. Immune cells develop within dedicated immune system organs, such as the bone marrow, thymus and lymphoid tissues, but also inhabit other tissues, wherein they not only provide defense against infection and malignancies but also contribute to homeostatic tissue function. Because different tissues have widely divergent metabolic rates and fuel requirements, this raises interesting questions about the adaptation of immune cells in specific tissues. When immune cells take up residence in different tissues, they develop a transcriptional signature that reflects adaptation to life and function within that tissue. Genes encoding metabolic-pathway proteins are strongly represented within these signatures, reflective of the importance of metabolic adaptation to tissue residence. In this Review, we discuss the available data on the metabolic adaptation of immune cells to life in different tissue sites, within the broader framework of how functional adaptation versus maladaptation in the niche can affect tissue homeostasis.

Smartphone detection of Escherichia coli from field water samples is successfully demonstrated using paper microfluidics. A three-channel paper chip is designed and fabricated, with a negative control channel preloaded with bovine serum albumin (BSA)-conjugated beads and two E. coli detection channels preloaded with anti-E. coli-conjugated beads, for low- and high-concentration detection. Field water samples are introduced to the paper chip by dipping or pipetting, and the antigens from E. coli travel through the paper fibers by capillary action while the dust/soil or algae particles are effectively filtered. Antibody-conjugated beads, confined within the paper fibers, immunoagglutinate in the presence of E. coli antigens, while BSA-conjugated beads do not. The extent of immunoagglutination is quantified by evaluating Mie scatter intensity from the digital images taken at an optimized angle and distance using a smartphone. The assay results show excellent agreement with the MacConkey plate results, i.e., the count of viable E. coli. The scatter simulation procedure is introduced to substitute for experimental optimization, such that the proposed method can be easily adapted to the other types of samples. A smartphone application is developed, incorporating the internal gyroscope of a smartphone, to allow the user to position the smartphone at an optimized angle of scatter detection. The detection limit is single-cell-level and the total assay time is 90 s. [ABSTRACT FROM PUBLISHER]

Aging is associated with substantial physiological changes and constitutes a major risk factor for neurological disorders including dementia. Alterations in gene expression upon aging have been extensively studied; however, an in-depth characterization of post-transcriptional regulatory events remains elusive. Here, we profiled the age-related changes of the transcriptome and translatome in the female mouse hippocampus by RNA sequencing of total RNA and polysome preparations at four ages (3-, 6-, 12-, 20-month-old); and we implemented a variety of bioinformatics approaches to unravel alterations in transcript abundance, alternative splicing, and polyadenylation site selection. We observed mostly wellcoordinated transcriptome and translatome expression signatures across age including upregulation of transcripts related to immune system processes and neuroinflammation, though transcripts encoding ribonucleoproteins or associated with mitochondrial functions, calcium signaling and the cell-cycle displayed substantial discordant profiles, suggesting translational control associated with age-related deficits in hippocampal-dependent behavior. By contrast, alternative splicing was less preserved, increased with age and was associated with distinct functionally-related transcripts encoding proteins acting at synapses/dendrites, RNA-binding proteins; thereby predicting regulatory roles for RBM3 and CIRBP. Only minor changes in polyadenylation site selection were identified, indicating pivotal 3'-end selection in young adults compared to older groups. Overall, our study provides a comprehensive resource of age-associated post-transcriptional regulatory events in the mouse hippocampus, enabling further examination of the molecular features underlying age-associated neurological diseases. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigates the short-term and long-term responses of circulating fish phagocytes peritoneal cavity and those found adhered to gills towards paper mill effluent exposure. It uses healthy fishes of Heteropneustes fossils of both sexes, divided into four groups. The three groups of fishes were exposed to different concentrations of paper mill effluent and the fourth group was exposed to zero effluent concentration. The researchers conclude that biological response of circulating fish phagocytes to an environmental pollutant depends on the type of pollutant and the level and duration of exposure.

Introduction and aim. In the literature, blood is described as a body fluid that circulates in a closed vascular system that makes up about 10% of the body weight. The morphotic elements of blood are suspended in this fluid, which is why we can define blood as liquid tissue. Blood in the organization helped to play a role, performing a transport, hemodynamic and protective-defensive function. Its main components are red blood cells, white blood cells and platelets. Erythrocytes due to the ability to connect to the source, participate in the delivery from the lungs to the source. Leukocytes include a group of blood cells that include monocytes, lymphocytes and granulocytes that participate in the body's reactions. Platelets are referred to in the literature as thrombocytes, as non-nucleated blood components. The main component of blood samples is participation in hemostatic processes in the composition. They play one key role in the blood clotting process. At some point, when the continuity of the straight line is interrupted, platelets pass to the subendothelial matrix, the formation of a platelet plug, a clot is formed. Until the beginning of the twentieth, blood functions are provided only for hemostatic activities. Recent scientific research that blood cells are involved in non-hemostatic processes. Including the immune system. Collecting information on the role of blood in an independent team, enabling review work. Material and methods. Literature search from 1989 up to 2022 has been conducted on PubMed, Google Scholar databases and the Practical Medicine for Physicians. For the final analysis, 10 research papers and 9 review papers were used. Following keywords were used to search articles: platelets, in- flammation, immune system, hemostasis. The articles were from the years 1989-2022. Results. Platelets are one of the main morphotic elements of blood, when it comes to size, they are the smallest of all components of peripheral blood, but they are very reactive. They participate in the processes of coagulation and maintaining hemostasis in the body. The characteristic properties of platelets are the presence of dense granules δ and α, their compactness during hemostasis or inflammation are released into the body. Platelets, in addition to active participation in hemostasis processes, take part in immune processes. Platelets have been shown to be regulators of immune processes through the presence of TLRs that trigger the initiation of an immune system response. In addition to the regulatory properties, platelets are involved in the innate immunity and inflammation of the body. Platelets with the participation of endothelial cells lead to the recruitment of leukocytes to the site of inflammation. Platelets participate in the recognition of a foreign pathogen that is in the body, the mechanisms that lead to this are presented in the paper. In addition to the function of platelets in the immune system, the topic of autoimmune diseases, where platelets play a role, is discussed. The work deals with the subject of the influence of platelets on the immune system and their role in immune processes. Through the progress of scientific research, platelets have been shown to play a significant role in immune mechanisms. The work is a review of literature dealing with topics related to the immune system and platelets and aims to explain the mechanisms that lead to the active participation of platelets in the immune system. Conclusion. Platelets are involved in the immune system, it has been shown at the same time that platelets perform regulatory functions in the immune system through the CD154 molecule and additionally participate in inflammation. Where are the first cells that are responsible for fighting in the body's non-specific immune response. In addition, TLR receptors that are found on the surface of platelets play a key role in recognizing a threat and initiating an immune response. Through these receptors, platelets recognize pathogens in the body. Scientists continue to study the non-haemostatic functions of platelets and discover their significant role in the body, which is not only based on blood coagulation processes, but to a large extent in the body's immune defense. [ABSTRACT FROM AUTHOR]

In the pursuit of point-of-care systems that present high sensitivity and fast turnaround time, lateral flow is considered a remarkable promising class of in vitro diagnostics, and popularized by the pregnancy tests. A variety of lateral flow tests have emerged able to provide cardiac panels in emergency conditions, infectious disease screening, drug abuse, among others. However, most commercial tests only provide qualitative results, limiting their applicability for quantification thresholds of most biomarkers. In this paper, we propose a novel detection architecture for quantification of biomolecules labeled with magnetic nanoparticles employing two spin valve sensors. The main goal of this paper is to demonstrate that this architecture can detect and monitor MNPs flowing in a LFT strip for detection and quantification of different solutions varying in MNP concentration. In addition, we present preliminary analytical results that support our strategy for achieving biomolecular quantification using the proposed solution. [ABSTRACT FROM AUTHOR]

Abstract: Paper supports were used to develop a simple, inexpensive, fast and sensitive electrochemical immunosensor for the analysis of antibiotic residues in milk samples, where single-walled carbon nanotubes (SWNTs) and a simple dip–dry coating method were employed to prepare the highly sensitive biosensor. Well-dispersed SWNTs were impregnated with an antibody against neomycin to obtain a composite coating solution, followed by dipping the filtration paper in the solution to fabricate the sensitive biosensor which had high electrical conductivity. Based on the impedance change in the entire paper supported biosensor with increased concentrations of neomycin, the limit detection of the optimized method was 0.04ngmL−1 and a linear detection range from 0.2 to 125ngmL−1, well below the European Union regulations for neomycin in this matrix. This paper supported biosensor was applied to determine neomycin in milk samples after a simple sample treatment, with spiked recoveries which ranged from 93.25 to 110.47%. A variety of antibiotic residues in milk samples could be determined following similar sensor preparation. [Copyright &y& Elsevier]

In 2019, the SARS-CoV-2 virus caused one of the biggest virus pandemics called Coronavirus disease-19 (COVID-19). This virus has been responsible for the death of millions of people around the world. The biological function of SARS-CoV-2 and its pathophysiology mechanisms, as well as the host immunity against this virus, has attracted the attention of the scientific community all over the world. The current study reviewed innate and acquired immune responses following COVID-19 infection. These immune responses are probably involved in the severity of the disease and death. Also, the cause and consequence of potential clinical strategies to treat or prevent SARS-CoV-2 infection have been proposed. [ABSTRACT FROM AUTHOR]

The comparison of methylomes from immune cells enables the identification of differentially methylated regions and thereby region-associated gene loci. Those regions can be used to discriminate one immune cell population from the other, as well as help to identify key molecules and major pathways determining the unique phenotypes of immune cell lineages. The combination of bisulfite treatment of genomic DNA and next-generation sequencing provides the basis for studying epigenetic changes in different immune cell populations. Further development of whole-genome bisulfite sequencing resulted in a protocol for sequencing libraries that accept both single- or double-stranded DNA from fixed or nonfixed cells, respectively. Therefore, researchers can include immune cell populations in their methylation studies whose isolation depends on the staining of intracellular molecules.

Over the past decade, solving complex optimization problems with metaheuristic algorithms has attracted many experts and researchers. Nature has always been a model for humans to draw the best mechanisms and the best engineering out of it and use it to solve their problems. The concept of optimization is evident in several natural processes, such as the evolution of species, the behavior of social groups, the immune system, and the search strategies of various animal populations. For this purpose, the use of nature-inspired optimization algorithms is increasingly being developed to solve various scientific and engineering problems due to their simplicity and flexibility. Anything in a particular situation can solve a significant problem for human society. This paper presents a comprehensive overview of the metaheuristic algorithms and classifications in this field and offers a novel classification based on the features of these algorithms. [ABSTRACT FROM AUTHOR]

The objective of the present study is to identify and evaluate informative indicators for the welfare of rainbow trout exposed to (A) a water temperature of 27 °C and (B) a stocking density of 100 kg/m 3 combined with a temperature of 27 °C. The spleen-somatic and condition index, haematocrit and the concentrations of haemoglobin, plasma cortisol and glucose revealed non-significant differences between the two stress groups and the reference group 8 days after the onset of the experiments. The transcript abundance of almost 1,500 genes was modulated at least twofold in in the spleen of rainbow trout exposed to a critical temperature alone or a critical temperature combined with crowding as compared to the reference fish. The number of differentially expressed genes was four times higher in trout that were simultaneously challenged with high temperature and crowding, compared to trout challenged with high temperature alone. Based on these sets of differentially expressed genes, we identified unique and common tissue- and stress type-specific pathways. Furthermore, our subsequent immunologic analyses revealed reduced bactericidal and inflammatory activity and a significantly altered blood-cell composition in challenged versus non-challenged rainbow trout. Altogether, our data demonstrate that heat and overstocking exert synergistic effects on the rainbow trout's physiology, especially on the immune system.

Polyinosinic:polycytidylic acid [poly (I:C)] was administered in vivo to Chinook salmon (Oncorhynchus tshawytscha) post-smolts to determine the immune responses on haematological and cellular functional parameters, including spleen (SP), head kidney (HK) and red blood cell (RBC) cytokine expression, as well as serum metabolomics. Poly (I:C) in vivo (24 h exposure) did not affect fish haematological parameters, leucocyte phagocytic activity and phagocytic index, reactive oxygen species and nitric oxide production. Gas chromatography-mass spectrometry-based metabolomics revealed that poly (I:C) significantly altered the serum biochemistry profile of 25 metabolites. Metabolites involved in the branched-chain amino acid/glutathione and transsulphuration pathways and phospholipid metabolism accumulated in poly (I:C)-treated fish, whereas those involved in the glycolytic and energy metabolism pathways were downregulated. At cytokine transcript level, poly (I:C) induced a significant upregulation of antiviral ifnγ in HK and Mx1 protein in HK, SP and RBCs. This study provides evidence for poly (I:C)-induced, immune-related biomarkers at metabolic and molecular levels in farmed O. tshawytscha in vivo. These findings provide insights into short-term effects of poly (I:C) at haematological, innate and adaptive immunity and metabolic levels, setting the stage for future studies., (© 2020 The Fisheries Society of the British Isles.)

Abstract: The level of T-cell receptor excision circles (TREC), which decline with advancing age in normal individuals, has recently gained interest as a reference marker for studies on premature or early immunosenescence under particular health conditions. In order to facilitate translational studies at population and clinical levels, essential for the understanding of how changes in TREC levels are associated with responsiveness of the immune system, we have developed and optimized a real-time polymerase chain reaction (qPCR) assay which quantifies the TREC ratio from dried blood spot (DBS) samples. The present study considers a fully automated procedure to purify DNA and amplify sequences of interests by means of qPCR from DBS samples collected in healthy adults. Both TREC:PBMC (peripheral blood mononuclear cell) and TREC:T-cell ratios were compared for intra- and inter individual reproducibility. Furthermore, the impact of the length of storage on the quality of the DNA generated was also analyzed. In conclusion we describe a fully automated procedure for extracting DNA and qPCR set up, which offers a high-precision, robust qPCR assay for the quantification of both TREC:T-cell ratio and TREC:PBMC from DBS samples. [Copyright &y& Elsevier]

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]

Simple Summary: Myeloid-derived suppressor cells (MDSCs) are immature cells that expand in the circulation of patients with cancer, sepsis or chronic inflammation, modulate the immune response against cancer (favoring tumor onset and progression) and promote neoangiogenesis. These premises suggest that MDSCs could be involved in the pathogenesis of primary myelofibrosis (PMF) (a myeloproliferative neoplasm characterized by chronic inflammation and extensive neoangiogenesis in bone marrow and spleen). In this paper, we found that (1) MDSCs are increased both in the circulation and in the spleen of PMF patients and strongly correlate with disease progression; and (2) reduced CXCR4 expression on MDSCs along with increased plasmatic SDF-1α can be involved in their mobilization. These findings suggest that circulating MDSCs can be considered a parameter of disease severity and set MDSCs as potential new targets for cancer therapy. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by a chronic inflammatory state that plays a relevant role in the disease pathogenesis (as proven by high levels of inflammatory cytokines with prognostic significance and by a persistent oxidative stress) and by extensive neoangiogenesis in bone marrow (BM) and spleen. Myeloid-derived suppressor cells (MDSCs) are immature cells that expand in patients with cancer, sepsis or chronic inflammation, favoring tumor onset and progression mainly through the decrease in immune surveillance and the promotion of neoangiogenesis. In this paper, we evaluated the presence of circulating MDSCs in PMF patients, the plasmatic factors involved in their mobilization/expansion and the correlations with laboratory, genetic and clinical parameters. The data indicated that MDSCs could have a relevant role in PMF as a new pathogenic mechanism contributing to explaining the phenotypic diversity observed during the clinical course of the disease, or a potential new target for personalized treatment. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a severe psychiatric illness known to be highly complex due to its difficulty in identifying genetic factors and its polygenic nature. While genetic studies and research into epigenetic changes have advanced our understanding of MDD, the precise role of genetics in MDD's manifestation remains elusive. This paper reviews the current state of research on MDD genetics, encompassing findings on MDD's biological blueprint and investigations into epigenetic modifications associated with MDD development. Furthermore, this paper explores the interplay between depression and the immune system and the impact of inflammation on the disorder. Neuroimaging studies have also impacted comprehension of MDD, revealing alterations in brain size and chemistry. These insights shed light on the biological underpinnings of MDD and hold promise for developing more effective treatments and therapies for patients. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) is a highly malignant childhood brain tumor. Group 3 MB (Gr3 MB) is considered to have the most metastatic potential, and tailored therapies for Gr3 MB are currently lacking. Gr3 MB is driven by PRUNE-1 amplification or overexpression. In this paper, we found that PRUNE-1 was transcriptionally regulated by lysine demethylase LSD1/KDM1A. This study aimed to investigate the therapeutic potential of inhibiting both PRUNE-1 and LSD1/KDM1A with the selective inhibitors AA7.1 and SP-2577, respectively. We found that the pharmacological inhibition had a substantial efficacy on targeting the metastatic axis driven by PRUNE-1 (PRUNE-1-OTX2-TGFβ-PTEN) in Gr3 MB. Using RNA seq transcriptomic feature data in Gr3 MB primary cells, we provide evidence that the combination of AA7.1 and SP-2577 positively affects neuronal commitment, confirmed by glial fibrillary acidic protein (GFAP)-positive differentiation and the inhibition of the cytotoxic components of the tumor microenvironment and the epithelial–mesenchymal transition (EMT) by the down-regulation of N-Cadherin protein expression. We also identified an impairing action on the mitochondrial metabolism and, consequently, oxidative phosphorylation, thus depriving tumors cells of an important source of energy. Furthermore, by overlapping the genomic mutational signatures through WES sequence analyses with RNA seq transcriptomic feature data, we propose in this paper that the combination of these two small molecules can be used in a second-line treatment in advanced therapeutics against Gr3 MB. Our study demonstrates that the usage of PRUNE-1 and LSD1/KDM1A inhibitors in combination represents a novel therapeutic approach for these highly aggressive metastatic MB tumors. [ABSTRACT FROM AUTHOR]

The innate immune system is the first line of defense against pathogens. Its composition includes barriers, mucus, and other substances as well as phagocytic and other cells. The purpose of the present paper is to compare tissues with regard to their immune response to infections and to cancer. Simple ideas and the qualitative theory of differential equations are used along with general principles such as the minimization of the pathogen load and economy of resources. In the simplest linear model, the annihilation rate of pathogens in any tissue should be greater than the pathogen's average replication rate. When nonlinearities are added, a stability condition emerges, which relates the strength of regular threats, barrier height, and annihilation rate. The stability condition allows for a comparison of immunity in different tissues. On the other hand, in cancer immunity, the linear model leads to an expression for the lifetime risk, which accounts for both the effects of carcinogens (endogenous or external) and the immune response. The way the tissue responds to an infection shows a correlation with the way it responds to cancer. The results of this paper are formulated in the form of precise statements in such a way that they could be checked by present-day quantitative immunology. [ABSTRACT FROM AUTHOR]

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)., (© 2024 the Australian and New Zealand Society for Immunology, Inc.)

Fast-moving, competitive fields often inadvertently duplicate research. In a research environment that values being first over being robust, this results in one manuscript “scooping” ongoing research from other groups. Opportunities to demonstrate the solidity of a result through coincidental reproduction are thus lost. Here, two group leaders, one the scooper and one the scoopee, discuss their experiences under PLOS Biology’s new “complementary research” policy. In this case, submission of the second article followed publication of the first by mere days. Scooper and scoopee discuss how complementary research is good for everyone by expanding the scientific reach of studies that are overlapping but not identical, demonstrating the robustness of related results, increasing readership for both authors, and making “replication” studies cost effective by creatively using resources that have already been spent. [ABSTRACT FROM AUTHOR]

Detection of bacterial colonies in water is a pressing issue in recent times owing to its implications on human health, leading to an urgent need for low cost, disposable sensors. In this work, we report a disposable impedimetric sensor for detection of total bacterial colonies present in water samples. The sensor consists of a polyaniline coated filter paper functionalized with a homo-bi functional crosslinker, glutaraldehyde. Prior to the functionalization step, two Ag electrodes are deposited on the filter paper using conductive silver paste. The aldehyde groups of glutaraldehyde bind with the amine functional groups present on bacterial cell wall resulting in a change in dielectric constant, and consequently, the capacitive effect between the two Ag electrodes. Also, bacterial metabolism affects the medium conductivity and in turn, the medium resistance changes. The combined effect of changes in capacitive effect as well as resistance is reflected as a change in AC impedance measured using a frequency response analyzer (FRA). E. coli and Pseudomonas aeruginosa bacteria are detected in PBS buffer up to ~ 500 cfu/mL. Testing is also carried out by spiking tap water and grey water with known concentrations of bacteria samples. The detection limits obtained are 500 – 1000 cfu/mL with a response time of ~ 20 minutes. The developed sensor provides rapid, moderately sensitive, cost-effective solution for detecting total bacterial load in water samples. [ABSTRACT FROM AUTHOR]