Search

PURPOSE OF REVIEW This article reviews the neurologic complications associated with human immunodeficiency virus (HIV) infection. RECENT FINDINGS Neurologic complications of HIV may be caused by direct virally mediated pathology, immune-mediated phenomena in response to viral infection, or opportunistic infections secondary to depletion of lymphocytes. These neurologic disorders may be influenced by the degree of immunosuppression (ie, CD4+ T-cell lymphocyte count) and stage of infection (early versus late), as well as use of antiretroviral therapy, and may manifest as a variety of central and peripheral neurologic syndromes, including the more commonly encountered HIV-associated cognitive disorders and length-dependent sensorimotor polyneuropathy, respectively. Immune dysregulation underlies the majority of these neurologic phenomena, as well as other HIV-associated conditions including immune reconstitution inflammatory syndrome (IRIS), CD8 lymphocytosis, and potentially the development of compartmentalized infection within the CSF, also referred to as CSF escape. SUMMARY This article reviews a spectrum of clinical syndromes and related neuropathologic states associated with HIV infection.

BackgroundPregnancy is accompanied by immune suppression. We hypothesized that Mycobacterium tuberculosis-specific inflammatory responses used to identify latent tuberculosis infection (LTBI) lose positivity during pregnancy. We also hypothesized that isoniazid preventive therapy (IPT) may revert LTBI diagnoses because of its sterilizing activity.Methods944 women with human immunodeficiency virus infection (HIV) participating in a randomized, double-blind, placebo-controlled study comparing 28 weeks of IPT antepartum versus postpartum, were tested by QuantiFERON-gold-in-tube (QGIT) antepartum and by QGIT and tuberculin skin test (TST) at delivery and postpartum. Serial QGIT positivity was assessed by logistic regression using generalized estimating equations.ResultsFrom entry to delivery, 68 (24%) of 284 QGIT-positive women reverted to QGIT-negative or indeterminate. Of these, 42 (62%) recovered QGIT positivity postpartum. The loss of QGIT positivity during pregnancy was explained by decreased interferon gamma (IFNγ) production in response to TB antigen and/or mitogen. At delivery, LTBI was identified by QGIT in 205 women and by TST in 113 women. Corresponding numbers postpartum were 229 and 122 women. QGIT and TST kappa agreement coefficients were 0.4 and 0.5, respectively. Among QGIT-positive women antepartum or at delivery, 34 (12%) reverted to QGIT-negative after IPT. There were no differences between women who initiated IPT antepartum or postpartum.ConclusionsDecreased IFNγ responses in pregnancy reduced QGIT positivity, suggesting that this test cannot reliably rule out LTBI during pregnancy. TST was less affected by pregnancy, but had lower positivity compared to QGIT at all time points. IPT was associated with loss of QGIT positivity, the potential clinical consequences of which need to be investigated.

ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.

A 24-year-old woman sought care for 2 weeks of disorientation and short-term memory difficulties, as well as diffuse tremor of all extremities. She returned with further decline in memory and new severe headaches. She had intermittent agitation and emotional outbursts of crying or laughing, insomnia, spells consisting of disorganized speech and episodes of intermittent right gaze deviation with facial twitching and lip smacking. She was nearly mute. Her appetite had decreased and she had not had a bowel movement in several days. She was noted to have significant tachycardia and was intermittently febrile. Within several days she became unresponsive to all external stimuli, with nonpurposeful eye movements and frequent dyskinesias observed, and ultimately required ventilator support. Testing of the cerebrospinal fluid showed 236 white blood cells/µL, mildly increased protein concentration of 50 mg/dL, and normal glucose values. Electroencephalography initially demonstrated generalized slowing and generalized periodic epileptiform discharges and was also notable for an extreme delta brush pattern. Bilateral ovarian masses were identified on pelvic ultrasonography, and subsequent computed tomography of the abdomen and pelvis showed bilateral teratomas. An autoimmune encephalitis autoantibody panel was positive for antibodies targeting the N-methyl-d-aspartate receptor in the serum and cerebrospinal fluid, by both cell-based and immunofluorescence assays. The patient was diagnosed with anti- N-methyl-d-aspartate receptor encephalitis. The patient initially received intravenous methylprednisolone, followed by intravenous immunoglobulin. Benzodiazepines and propranolol were used to manage agitation and dysautonomia. Antiepileptic drugs were initiated for seizures. She required mechanical ventilation and parenteral nutrition given her persistent profound encephalopathic state. She underwent left ovarian cystectomy and right salpingo-oophorectomy. This patient’s history highlights the progressive clinical features characteristic of anti- N-methyl-d-aspartate receptor encephalitis and the long but often complete or near-complete recovery.

Background The aims of this study were to evaluate the characteristics of patients and the pattern and rate of use of deep brain stimulation (DBS) for major depressive disorder (MDD) in the United States. Methods Data from the 2012-2014 Nationwide Inpatient Sample (NIS) included 116,890 patients. Patient variables included age, gender, race, median household income, insurance, primary diagnosis, primary procedure, length of stay, and total cost. Hospital variables included ownership, location, teaching status, bed size, and geographic region. Results Patients who received DBS for MDD were primarily high- income White females with private insurance. The mean age was 49.1 years (SD 7.85). The length of inpatient stay was 1 to 1.6 days. Total cost was highest in the West and lowest in the Northeast. Deep brain stimulation was mostly used by private nonprofit urban teaching hospitals in the South region of the United States. Conclusions Deep brain stimulation was used in .03% of the total inpatient population with a primary diagnosis of MDD. If efficacy is established in definitive trials, DBS could fill a need for patients with treatment-resistant depression who do not respond to standard therapeutics or electro-convulsive therapy.

Anaplasmosis and ehrlichiosis are tick-borne rickettsial diseases that cause significant economic losses in the livestock industry worldwide. Although bovine anaplasmosis is known to be endemic in the Philippines, epidemiological data is fragmented. Moreover, little is known about bovine ehrlichiosis in the country. In this study, the prevalence of Anaplasma marginale and Ehrlichia in cattle and water buffalo from provinces in the southern part of Luzon, Philippines, was investigated through PCR. Blood samples from 620 animals comprised of 512 cattle and 108 water buffalo and 195 tick samples were subjected to nested PCR targeting the groESL gene of Anaplasmataceae. Positive samples were further subjected to another nested PCR and conventional PCR to amplify the A. marginale groEL gene and the Ehrlichia dsbA gene, respectively. Selected A. marginale-positive samples were also subjected to nested PCR targeting the msp5 gene. Regardless of the animal host, the overall prevalence in blood samples obtained was 51.9% for Anaplasmataceae, 43% for A. marginale, and 1.1% for Ehrlichia. No water buffalo were positive for Ehrlichia. Meanwhile, 15.9, 6.7, and 2% of the tick samples, all morphologically identified as Rhipicephalus (Boophilus) microplus, were positive for Anaplasmataceae, A. marginale, and Ehrlichia, respectively. Sequence analysis of selected A. marginale msp5 amplicons showed that the isolates from the region share 94–98% identity to reported A. marginale from other countries. The phylogenetic tree showed clustering of isolates in the region and a close relationship with A. marginale isolates from other countries. Sequences of Ehrlichia amplicons from cattle and ticks were 97–100% similar to reported Ehrlichia minasensis isolates. This study showed the high prevalence of A. marginale in Luzon, Philippines, and provided the first molecular evidence of E. minasensis in the country.

International audience

Highlights • Cancer management adapting to the current state of health during COVID-19 pandemic. • Collaborative strategic action plan for cancer management and workflow in a developing country. • Algorithm in cancer center management during COVID-19 in a developing country. • Measures to be adopted in cancer management and workflow after COVID-19 pandemic.

Objective: Pathological vascular remodeling and excessive perivascular fibrosis are major contributors to reduced vessel compliance that exacerbates cardiovascular diseases, for instance, promoting clinically relevant myocardial remodeling. Inflammation plays a significant role in both pathological vascular remodeling and fibrosis. We previously demonstrated that smooth muscle cell–specific PTEN depletion promotes significant vascular fibrosis and accumulation of inflammatory cells. In the current study, we aimed to determine the beneficial role of systemic PTEN elevation on Ang II (angiotensin II)-induced vascular fibrosis and remodeling. Approach and Results: Transgenic mice carrying additional copies of the wild-type Pten gene (super PTEN [sPTEN]) and WT littermates were subjected to Ang II or saline infusion for 14 or 28 days. Compared with WT, Ang II-induced vascular fibrosis was significantly blunted in sPTEN mice, as shown by histochemical stainings and label-free second harmonic generation imaging. The protection against Ang II was recapitulated in sPTEN mice bearing WT bone marrow but not in WT mice reconstituted with sPTEN bone marrow. Ang II-induced elevation of profibrotic and proinflammatory gene expression observed in WT mice was blocked in aortic tissue of sPTEN mice. Immunofluorescent staining and flow cytometry both indicated that perivascular infiltration of T cells and macrophages was significantly inhibited in sPTEN mice. In vitro induction of PTEN expression suppressed Ang II-induced Ccl2 expression in vascular smooth muscle cells. Conclusions: Systemic PTEN elevation mediates protection against Ang II-induced vascular inflammation and fibrosis predominantly through effects in resident vascular cells. Our data highly support that pharmacological upregulation of PTEN could be a novel and viable approach for the treatment of pathological vascular fibrosis.

Background and Purpose: Due to the potential for high mortality and neurologic complications of rheumatoid meningitis (RM), awaiting biopsy confirmation may delay vital treatment intervention. Our aim was to describe the clinical presentations of RM in our population and determine whether meningeal biopsy impacted diagnosis, treatment, and outcomes. Methods: A retrospective chart review was completed for patients at Mayo Clinic with a diagnosis of RM within the last 28 years. Those with identified alternative inflammatory, infectious, or neoplastic causes of pachymeningitis or leptomeningitis were excluded. Results: Fourteen patients meeting inclusion/exclusion criteria were identified. All patients were positive for rheumatoid factor or cyclic citrullinated peptide. All patients had magnetic resonance imaging abnormalities characterized by pachymeningeal and/or leptomeningeal enhancement. Of the 10 patients who underwent biopsy, nonspecific findings were seen in 74%. All patients except one were treated with corticosteroids with subsequent symptomatic improvement. Radiographic improvement or resolution was seen in 10 (83%) of 12. Patients improved with corticosteroid treatment, including those who were diagnosed with RM on clinical basis without undergoing a biopsy as well. Conclusions: This retrospective review displays the myriad of clinical presentations of RM. It also suggests that with appropriate exclusion of infectious, neoplastic, and other autoimmune etiologies, biopsy may not be necessary to initiate treatment.

Purpose: This paper explores the intersections between community development and youth development in an initiative that mobilized farmers’ children as Rice Crop Manager (RCM) infomediaries (information mediators). RCM is an ICT-enabled nutrient management application. Design/Methodology/Approach: The study engaged 30 farmers’ children in high school level from the provinces of Pangasinan, Isabela, Camarines Sur, Iloilo, Bukidnon, and Davao del Norte from November 2016 to October 2017. They interacted with the research team (the authors) and the RCM-SMS platform that sends text messages regarding fertilizer recommendations. A staff member from the Agricultural Training Institute (ATI) also called the students for some follow-up questions. The research team conducted three rounds of interviews with the students concerning the messages and calls that they received and what they did with the information. Findings: This study finds that farmers’ children can perform infomediary roles quite effectively. Academically excellent children and those involved in farm work performed best. Practical Implications: The study provides guidance on similar initiatives tapping young people in agricultural development. Theoretical Implications: This paper finds that while Community Youth Development (CYD) Theory provides a powerful lens in understanding community and youth development intersections, some identified outcomes may overlap and may not be very easy to observe. Hence, the identified outcomes may be revisited for clarity and to make them more all-encompassing. Originality/Value: The paper documents actual parent-child interaction when the latter is mobilized to serve as an infomediary to access nutrient management-related information on rice.

Introduction Granulomatosis with polyangiitis (GPA) is a vasculitic process that can cause neurological dysfunction in addition to characteristic sinus and pulmonary manifestations. This case report highlights the spectrum of nervous system manifestations and includes rarely reported autonomic and pituitary involvement. Case report A 62-year-old woman presented with orthostatic intolerance, tachycardia, dry mouth, and temperature sensitivity; subsequent autonomic reflex study demonstrated widespread postganglionic sympathetic sudomotor, cardiovagal, and cardiovascular adrenergic impairment reflective of autonomic neuropathy and overall autonomic failure. Additional progressive symptoms included dysarthria, dysphagia, bilateral hearing loss, voice hoarseness, and right-sided facial numbness with multiple cranial neuropathies identified on neurological examination. The diagnosis of central diabetes insipidus was also confirmed. Pachymeningitis was present on brain magnetic resonance imaging. Pathologic review of the dural biopsy specimen revealed necrotizing granulomatous vasculitis consistent with GPA. She was treated with intravenous methylprednisolone and rituximab. Over the next 2 months, she had near-complete resolution of her symptoms with normalization on repeat autonomic testing. Conclusions This is a unique GPA case presenting with autonomic failure and pituitary dysfunction with conclusive objective findings of autonomic dysfunction. Autonomic dysfunction and other disease manifestations were responsive to immunosuppressive therapy.

BACKGROUND A general belief is to consider elderly patients as poor candidates for free flap reconstruction, which does not reflect our 20-year experience for breast reconstruction (BR). The aim of this study was to determine the safety and benefits of BR using deep inferior epigastric perforator (DIEP) free flap in the elderly population. METHODS We conducted a retrospective study of all consecutive BRs using DIEP flaps in patients 65 years or older at the European Georges Pompidou Hospital from January 2011 to December 2019. Postoperative complications were reported as minor or major. We used a descriptive approach to analyze the main characteristics of the patients included. Surgical patient-reported outcomes and quality of life were assessed using the validated BREAST-Q questionnaire. RESULTS Eighty-three DIEP flaps were performed in 79 patients (4 bilateral flaps) for BR. Sixty-six percent of the patients (52/79) did not present any complication. Total flap loss occurred in 3 BR (3.6%), arterial thrombosis in 4 BR (4.8%), and venous thrombosis in 8 BR (9.6%). The average duration of inpatient stay was 9.5 (±2.7) days. Forty-one of 69 eligible patients completed the questionnaire (response rate 59.4%). Patients reported high satisfaction and well-being scores. The mean Q score for psychosocial well-being was 75.4 (±16.7) and 59 (±13.3) for satisfaction with breasts. CONCLUSION In our retrospective cohort, DIEP flap BR in elderly population had similar success and complication rates compared with those in younger patients, as well as high satisfaction scores. The free flap should be encouraged for BR in women over 65 years of age, and personal motivation as well as physiological age considered as main criteria for patient selection.

Made available in DSpace on 2022-04-28T19:40:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-06-01 Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Background: The hematology of turtles of the Amazon, such as the Arrau turtle (Podocnemis expansa), has not been well described in the literature. Referencing how to collect and analyze blood samples is fundamental for the medical practice of these exotic animals. Objectives: The aim of this study was to evaluate the hematologic parameters of Arrau turtles of the Amazon to determine the best anticoagulant (EDTA, citrate, or sodium heparin) and cytologic stain (Giemsa, Quick Panoptic, or Rosenfeld) for use with this species. Methods: Blood samples from eight turtles were collected. Three blood smears were made using blood without anticoagulant, and the rest of the sample was distributed in three tubes, containing EDTA, citrate, and sodium heparin, for erythrogram and leukogram analyses. Results: All blood samples anticoagulated with EDTA showed marked hemolysis. Blood collected with citrate showed minimal hemolysis, and blood collected with sodium heparin did not have any hemolysis. Some analyses were not performed on blood containing EDTA because of the intense hemolysis. The erythrocyte variables were obtained and showed better results for blood samples in heparin. Blood smears without anticoagulant were appropriate for differential leukocyte counts with the three stain types, while blood with any of the anticoagulants made it difficult to differentiate leukocytes. Conclusions: Sodium heparin showed the best results and should be the anticoagulant of choice for hematologic studies in P expansa. All cytologic stains were efficient, allowing adequate identification of distinct cell groups. Leukocyte differentiation was assured and had better contrast using blood smears made from blood without an anticoagulant. Mestrado em Sanidade e Produção Animal nos trópicos Curso de Medicina Veterinária Universidade de Uberaba Universidade de Uberaba Escola de Medicina Veterinária Instituto Federal Goiano Faculdade de Ciências Agrárias e Veterinárias de Jaboticabal Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Ciências Agrárias e Veterinárias de Jaboticabal Universidade Estadual Paulista Júlio de Mesquita Filho

Background Coccidioidomycosis is often diagnosed with a collection of tests that rely on the patient’s ability to mount an immune response to the fungus (antibody-based diagnostics), making diagnosis of this infection challenging. Here we present an antigen-based assay that detects and quantifies coccidioidal chitinase-1 (CTS1) in human serum. Methods An inhibition-based enzyme-linked immunoassay (ELISA) was developed that utilizes a monoclonal antibody specific for coccidioidal CTS1. CTS1 was quantified in commercial antigen preparations using recombinant CTS1 as a standard. Sera from 192 individuals from an endemic area were tested, which included 78 patients (40.6%) with proven or probable coccidioidomycosis. Results The quantity of CTS1 in diagnostic commercial antigen preparations from different suppliers varied. CTS1 antigenemia was detected in 87.2% of patients with proven or probable coccidioidomycosis. Specificity was determined to be 96.94% using serum from individuals who reside in the Phoenix, Arizona area who did not have coccidioidomycosis. Levels of CTS1 correlated with low- and high-titer serology from patients with a coccidioidomycosis diagnosis. Conclusions Since the CTS1 inhibition ELISA described in this report does not depend on the host immune response, it is a promising diagnostic tool to aid in diagnosis and disease monitoring of coccidioidomycosis., Diagnosis of coccidioidomycosis often relies on the host’s ability to mount an immune response. Here we present an antigen-based assay that detects and quantifies coccidioidal chitinase-1 in human serum to diagnose coccidioidomycosis independent of host immune status.

Opsoclonus myoclonus syndrome (OMS) is a rare immune-mediated paraneoplastic or para/-post-infectious syndrome characterized by “dancing” eye movements, myoclonus, and ataxia. Neuropsychiatric symptoms have also been reported. Without treatment, OMS may progress to further neurological impairment and even death. Autoimmune attack of CNS structures in OMS is most commonly mediated by anti-Ri (also known as ANNA2) IgG antibodies, with additional findings implicating antibodies targeting various neurotransmitter receptors. Prompt immunotherapy and neoplasm treatment may result in improvement. We report a novel association of Contactin-Associated Protein-Like 2 (Caspr2) antibodies occurring in association with paraneoplastic OMS. While breast cancer and small cell lung cancer (SCLC) are more commonly associated with OMS among adults, we characterize a novel association between Caspr2 antibody in a patient with mixed non-small cell and small cell lung carcinoma.

Background Neoplasms of the brain and spine are relatively uncommon compared to breast, lung and gastrointestinal tumours, which occur at higher rates in the Asian population. Updated guidelines in diagnosis and treatment of neuro-oncologic diseases recommend advanced molecular-based precision-medicine; thus the need for increasingly individualised regimens. It is, therefore, necessary to determine whether there are areas of improvement in the provision of care to these patients, especially in low- to middle-income economies like the Philippines. Methods In this study, we identified gaps in the delivery of medical care to Filipino patients with tumours of the central nervous system. We performed a scoping review on the available literature on clinical experience with treatment of neuro-oncologic cases from the Philippines and performed qualitative analysis viewed through the lens of the existing healthcare system. Results The medical practice of neuro-oncology in the Philippines lacks robust local data on epidemiology and treatment outcomes. There are existing legislative frameworks to support adequate healthcare delivery and financing to brain tumour patients. However, inequities in the geographic distribution of infrastructure, manpower and medications are roadblocks for accessibility to neuro-oncologic services like specialised molecular markers, neurosurgical procedures, sustained chemotherapy and radiation therapy centres. Conclusion There are significant treatment gaps in the care of neuro-oncologic patients in the Philippines that need to be addressed. Early detection and initiation of prognosis-changing therapeutics through reduction of out-of-pocket expenses, access to readily available diagnostic tools and sustainability of management regimens are the main areas that necessitate strengthened partnership between the public and private sectors of Philippine society.

Objective: To report a case series of dysautonomia associated with COVID-19 infection.Methods: This is a retrospective review of patients evaluated in the autonomic clinic at our institution with suspected signs and symptoms of dysautonomia who underwent formal evaluation, including autonomic testing.Results: Six patients were identified with signs and symptoms suggestive of dysautonomia who underwent autonomic testing. All patients had symptoms typical of COVID-19 infection, though none were hospitalized for these or other symptoms. All patients reported symptoms of postural lightheadedness and near-syncope, fatigue, and activity intolerance. Five patients reported the onset of autonomic symptoms concomitant with other COVID-19 symptoms, with the other patient reporting symptom onset 6 weeks following initial COVID-19 symptoms. Autonomic testing demonstrated an excessive postural tachycardia in 4 patients, a hypertensive response with head-up tilt in 3 patients, orthostatic hypotension in 1 patient, and sudomotor impairment in 1 of the patients with excessive postural tachycardia.Conclusions: We present clinical features and results of autonomic testing in 6 patients with a history COVID-19 infection. While all patients reported typical features of orthostatic intolerance, fatigue, and activity intolerance, the results of autonomic testing were heterogenous, with orthostatic hypotension in 1 patient, excessive postural tachycardia typical of postural tachycardia syndrome in 4 patients, and postural hypertension in 3 patients.

[Importance] Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood., [Objective] To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia., [Design, Setting, and Participants] Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244., [Main Outcomes and Measures] Interregional profiles of group difference in cortical thickness between cases and controls., [Results] A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders., [Conclusions and Relevance] In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

Magcale-Macandog DB, Lapitan FRG, Laruya JM, Valerio JIF, Aguila JCD, Mesina CAL, Santos TMF, Cuevas ANT, Baylon KD, Silapan IM, Dimalobot R, Edrial JD, Larida NJA, Natuel FA, Perez MAGLD, Quinones SGL. 2021. Updating of Makiling Biodiversity Information System (MakiBIS) and Analysis of Biodiversity Data. Biodiversitas 22: 211-226. Mt. Makiling is a Philippine biodiversity hotspot listed as one of the 170 conservation priority areas established by the Philippine government. With the vast amount of ecological and biological information about the flora and fauna of Mt. Makiling, the Makiling Biodiversity Information System (MakiBIS) was developed to serve as a repository for these data. MakiBIS may serve as a prototype in the development of a national BIS that will be useful in addressing the need to set a national baseline, measurable targets, and indicators to facilitate the assessment of biodiversity status and as a basis for decision-making.The MakiBIS project started in 2011 and was last updated in 2014. In 2019, a new version of the information system was updated to take advantage of current web technologies in software development. The new MakiBIS’ (MakiBIS 2.0) frontend was written using ReactJS, while its backend functions were coded using NodeJS, and the database tables were compressed and optimized for faster queries. MakiBIS 2.0 was published online and can be accessed at www.makibis.com.The MakiBIS 2.0 database was populated with biodiversity information from published botanical and faunal survey studies conducted in Mt. Makiling. Biodiversity information includes taxonomic classification, botanical description, habitat, mode of reproduction, economic use, endemism, and conservation status. The MakiBIS database was analyzed for patterns, trends, distribution, and potential threats that will be useful towards the conservation and management of these biodiversity resources.

Introduction: Advancing new therapies from discovery to development usually requires proof-of-concept in animal models to justify the costs of continuing the program. While animal models are useful for understanding the mechanism of action (MOA) of a target, limitations of many published colitis models restrict their value to predict clinical efficacy.Areas covered: The authors focused their literature search on published studies of chronic animal models used to evaluate the pre-clinical efficacy of therapeutic molecules subsequently evaluated in clinical trials for UC. The UC therapies evaluated were anti-α4β7, anti-IL13, anti-IL12p40, and anti-IL23p19. The models of chronic colitis evaluating these molecules were: mdra1a-/-, chronic dextran sulfate sodium (DSS), chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the T cell transfer model.Expert opinion: While some models provide insight into target MOA in UC, none is consistently superior in predicting efficacy. Evaluation of multiple models, with varying mechanisms of colitis induction, is needed to understand potential drug efficacy. Additional models of greater complexity, reflecting the disease chronicity/heterogeneity seen in humans, are needed. Although helpful in prioritizing targets, animal models alone will likely not improve outcomes of UC clinical trials. Transformational changes to clinical efficacy will likely only occur when precision medicine approaches are employed.

International audience

Purpose Neuroinvasive West Nile virus (WNV) is rare, occurring in less than 1% of those infected, and may manifest as meningitis, encephalitis, and/or acute flaccid paralysis. Patients may present initially with nonspecific symptoms including fevers. Although rare, neuroinvasive WNV is associated with significant morbidity and mortality. The mainstay of treatment is supportive care. Electroencephalography (EEG) allows for identification of nonconvulsive status epilepticus and other epileptiform and nonepileptiform patterns suggestive of underlying cognitive dysfunction. Our aim was to describe specific EEG patterns observed in WNV neuroinvasive disease. Methods A retrospective chart review was conducted. West Nile virus was confirmed with serum and/or cerebrospinal fluid markers. Patients with a history of abnormal EEG were excluded. Electroencephalography reports were classified into categories based on the presence of epileptiform activity, focal slowing, generalized periodic discharges with triphasic morphology, and frontally predominant generalized rhythmic delta activity. Results In our cohort of 34 patients, 60% of focal EEG abnormalities were anterior-predominant, seen as epileptiform discharges, focal slowing, or frontally predominant generalized rhythmic delta activity. Nonepileptiform EEG patterns included nonspecific slowing and generalized periodic discharges with triphasic morphology. Two patients had electrographic seizures, one arising from the frontocentral head region. Conclusions EEGs are important in the evaluation of WNV infection to rule out seizures or alternative causes of encephalopathy, and because of the risk of nonconvulsive seizures or status epilepticus in encephalitis. Although an anterior predominance of EEG abnormalities was seen in our cohort, this most likely is more correlative to encephalopathy than WNV itself. Although a specific correlative EEG pattern may not accompany all cases of WNV neuroinvasive disease, WNV should be considered as a possible etiology in patients presenting with an encephalitic or meningitic syndrome in the presence of abnormal EEG findings including encephalopathic patterns, particularly those with anterior predominant EEG changes.

Objective To investigate the etiology and longitudinal clinical, neuropsychological, psychosocial, and surgical outcome profile of patients with medication refractory epilepsy and temporal encephaloceles with a view to highlight diagnostic clues and management strategies. Methods The comprehensive epilepsy program databases at two surgical epilepsy centers from January 2000 to October 2018 were reviewed for this observational study, to identify patients with encephaloceles causing temporal lobe epilepsy (TLE) and treated with surgical resection. Their clinical, radiological, neuropsychological, psychiatric, and surgical data were obtained. Body mass index (BMI) data were also reviewed due to possible correlation between idiopathic intracranial hypertension and encephaloceles. Results Thirteen patients (eight female) were identified; only three were recognized on initial magnetic resonance imaging (MRI) report. Temporal encephaloceles were identified on the left in eight patients, on the right in three patients, and bilaterally in two patients. One patient had a strong family history of encephaloceles. The median BMI for patients with seizure onset ≤20 years of age was 22.4, whereas for patients with onset >20 years median BMI was 32.6 (P = .06). Five patients underwent a focal lesionectomy, three patients had limited temporal lobectomy, and five patients had standard anterior temporal lobectomy. Median postoperative follow-up was 5.5 years. All but one patient were free of disabling seizures. Nine of ten neuropsychologically tested patients had no discernable cognitive decline postoperatively. Postoperative psychosocial adjustment features were present in four patients. Significance Genetic factors and a possible association with idiopathic intracranial hypertension (given female predominance and elevated BMI) may contribute to the causation of temporal lobe encephaloceles. It is notable that a targeted surgical approach in the management of patients with TLE associated with encephaloceles has an excellent long-term clinical and neuropsychological outcome. Subtle encephaloceles should be actively searched for in patients with drug-resistant TLE because they significantly change surgical strategy and prognostication.

OBJECTIVE: We investigated the relationship between the interictal metabolic patterns, the extent of resection of 18 F-fluorodeoxyglucose positron emission tomography (18 FDG-PET) hypometabolism, and seizure outcomes in patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) following anterior temporal lobe (TL) resection. METHODS: Eighty-two patients with hippocampal sclerosis or normal magnetic resonance imaging (MRI) findings, concordant 18 FDG-PET hypometabolism, and at least 2 years of postoperative follow-up were included in this 2-center study. The hypometabolic regions in each patient were identified with reference to 20 healthy controls (p < 0.005). The resected TL volume and the volume of resected TL PET hypometabolism (TLH) were calculated from the pre- and postoperative MRI scans coregistered with interictal 18 FDG-PET. RESULTS: Striking differences in metabolic patterns were observed depending on the lateralization of the epileptogenic TL. The extent of the ipsilateral TLH was significantly greater in left MTLE patients (p < 0.001), whereas right MTLE patients had significantly higher rates of contralateral (CTL) TLH (p = 0.016). In right MTLE patients, CTL hypometabolism was the strongest predictor of an unfavorable seizure outcome, associated with a 5-fold increase in the likelihood of seizure recurrence (odds ratio [OR] = 4.90, 95% confidence interval [CI] = 1.07-22.39, p = 0.04). In left MTLE patients, greater extent of resection of ipsilateral TLH was associated with lower rates of seizure recurrence (p = 0.004) in univariate analysis; however, its predictive value did not reach statistical significance (OR = 0.96, 95% CI = 0.90-1.02, p = 0.19). INTERPRETATION: The difference in metabolic patterns depending on the lateralization of MTLE may represent distinct epileptic networks in patients with right versus left MTLE, and can guide preoperative counseling and surgical planning. Ann Neurol 2019; 1-10 ANN NEUROL 2019;85:241-250.

Post-transplantation lymphoproliferative disorder (PTLD) is a complication of solid organ and hematopoietic stem cell transplantation. Cases with isolated central nervous system (CNS) disease are rare. Epstein-Barr virus (EBV) plays a causative role. We present a patient with EBV cerebellitis documented 5 months prior to development of primary CNS PTLD (PCNS-PTLD). This case report demonstrates progression from EBV CNS infection to lymphoproliferative disorder, highlighting the importance of serial clinical and imaging monitoring in transplant patients post-EBV CNS infection. PCNS-PTLD should always be considered in the differential diagnosis for transplant patients presenting with CNS symptoms, even in cases with no evidence of EBV viremia. Earlier diagnosis and appropriate treatment could result in improved outcomes.

Background: West Nile virus (WNV) causes a spectrum of human disease ranging from a febrile illness (WNV fever) to severe neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis). Since WNV gained entry into North America in 1999, clinicians caring for WNV survivors have observed persistent neurological symptoms occurring long-after the production of neutralizing antibodies and clearance of the virus. Accordingly, alternative pathogeneses other than direct viral invasion have been hypothesized to explain these post-infectious symptoms. The dominant hypothesis is that antiviral inflammatory responses triggered initially to clear WNV may persist to promote a post-infectious proinflammatory state. Methods: In 4 serologically-confirmed WNV patients with persistent post-infectious symptoms (3 WNV fever, 1 neuroinvasive disease), we ordered a comprehensive cytokine panel at weeks 8, 10, 12, and 36 months post-onset of illness, respectively, to better understand the pathophysiology of the protracted symptoms. Results: All patients had abnormally elevated tumor necrosis factor alpha (TNF-α), a major molecule triggering antiviral cytokines and chronic inflammation in many human autoimmune diseases, but heretofore not reported to be upregulated in human WNV infection. Three patients also had elevations of other proinflammatory proteins. Major symptoms included fatigue, arthralgias, myalgias, generalized or multifocal pain or weakness, imbalance, headaches, cognitive problems, and symptoms of dysautonomia. Conclusion: The findings provide support for an extended post-infectious proinflammatory state that may contribute to chronic inflammation and long-term morbidity in some WNV survivors and further suggest that TNF-α may play a pathogenic role in initiating this inflammatory environment. Clinical trials may be warranted to determine if TNF-α inhibitors or other immunosuppressive agents can improve patient outcomes.

Following acute West Nile virus (WNV) infection in humans, there is upregulation of pro-inflammatory molecules that promote neuroinflammation, including S100 calcium binding protein B (S100B), high-mobility group box-1 (HMGB1), and osteopontin (OPN). The effects of S100B and HMGB1 are transduced by the receptor for advanced glycation end products (RAGE). Interestingly, the same immunoregulatory proteins that fuel neuroinflammation can also promote tumorigenesis. We present 2 cases of glial neuronal tumors, a glioblastoma multiforme and dysembryoplastic neuroepithelial tumor, in patients with severe West Nile neuroinvasive disease (WNND). In these cases, the viral infection was a precursor to the development of the aggressive brain tumors. We describe a potential mechanism where the presence of tumorigenic proteins in the microenvironment induced by WNV, and subsequent RAGE and OPN signaling, may contribute to development or aggressive growth of these tumors. Although it is certainly possible that the occurrence of primary brain tumors following WNND is coincidental, the ability of WNV to alter cellular signaling and increase expression of pro-inflammatory and tumorigenic molecules merits further investigations to determine whether there is an association between these disease processes or implications for brain tumor patients who develop WNV infection.

Worsening renal function (i.e. any increase in creatinine or decrease in the estimated glomerular filtration rate) is common in patients admitted for acute heart failure in the emergency department. Although worsening renal function (WRF) has been associated with the occurrence of dismal outcomes, this only appears to be the case when associated with clinical deterioration. However, if the clinical status of the patient is improving, a certain increase in serum creatinine may be acceptable. This WRF, which is not associated with clinical deterioration or adverse outcomes (e.g. during treatment up-titration), has been referred to as 'pseudo-WRF' and should not detract clinicians from targeting 'guideline-recommended' therapies. This is an important message for emergency physicians to pursue diuretics as long as signs of pulmonary congestion persist to improve the clinical status of the patient. In the present review, we aim to provide clinicians in acute settings with an integrative and comprehensive approach to cardiorenal interactions in acute heart failure.

Rationale: Isoniazid-monoresistant tuberculosis (INH-monoresistant TB) is the most common drug-resistant TB type in the United States; however, its impact on TB treatment outcomes is not clear. Objectives: This study aims to understand 1) factors associated with INH-monoresistant TB and 2) the association between INH monoresistance and response to TB treatment. Methods: We studied all patients with TB (age, ≥15 yr) reported to the Georgia State Electronic Notifiable Disease Surveillance System (SENDSS) from 2009 to 2014. INH-monoresistant TB was defined as a Mycobacterium tuberculosis isolate resistant to isoniazid only. Time to sputum culture conversion was defined as the time (measured in days) from TB treatment initiation to the date of the first consistently negative culture result reported to the SENDSS. Logistic regression and Cox proportional hazard models were used to estimate the odds and hazard rate of sputum culture conversion, all-cause mortality, and poor TB outcome among patients with INH-monoresistant TB. Results: Among 1,141 culture-confirmed patients with available drug susceptibility testing results, 998 (87.5%) were susceptible to TB first-line drugs, and 143 (12.5%) were patients with INH-monoresistant TB. In multivariable analysis, male sex (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 1.01–2.67) and homelessness (aOR, 5.55; 95% CI, 3.38–9.17) were associated with higher odds of INH-monoresistant TB. In the same multivariable model, older age (≥65 yr old) (aOR, 0.21; 95% CI, 0.07–0.55) and miliary disease (aOR, 0.19; 95% CI, 0.01–0.96) were associated with lower odds of INH-monoresistant TB. Among 1,116 patients with pulmonary TB, the median time to sputum culture conversion was 30 days (interquartile range, 13–58). The rate of culture conversion was similar among patients with and without INH monoresistance (adjusted cause-specific hazard ratio, 1.15; 95% CI, 0.95–1.40). INH-monoresistant TB was not significantly associated with poor TB treatment outcomes (aOR, 1.61; 95% CI, 0.67–3.70) or mortality during TB treatment (aOR, 1.72; 95% CI, 0.58–4.94). Conclusions: Our findings suggest that compared with drug-susceptible TB, patients in Georgia with INH-monoresistant TB have a similar response to TB treatment including culture conversion rate, final TB treatment outcome, and all-cause mortality.

In 2008, an outbreak of isoniazid-resistant tuberculosis was identified among residents of homeless shelters in Atlanta, Georgia, USA. When initial control efforts involving standard targeted testing failed, a comprehensive approach that involved all providers of services for the homeless successfully interrupted the outbreak.

International audience

Greenhouse is a structure with walls and roof made chiefly of transparent materials, in which plants requiring controlled climatic conditions are grown. Also, this requires human care and assistance to be able to perform some significant greenhouse processes such as irrigation and ventilation, for continuous operation. In order to achieve such goal to the fullest and minimize manpower support and intervention, it is best to make the greenhouse fully automated. It is provided with an integrated temperature control system for its ventilation to maintain the desired temperature needed by the plant. The watering system has been constructed with submersible pump that pumps water from the water reservoir up to the water piping system and the water flows down to the different vertical plant mount tubings that contain the different plants. Finally, the water returns to the reservoir it came from and it is being conserved. The irrigation system is also provided by a timer for the necessary watering requirement. The greenhouse has an off-grid power system, which is solar, and wind powered, and can stand alone. Finally, it uses vertical farming technology that increases plant production several time for a given land area as compared to the conventional. With the developed system, this improves the quality of crops.

Background Epidemiological transition in the developing world has resulted in a shift from infectious to non-communicable diseases as leading causes of morbidity and mortality, cardiovascular (CV) disease (CVD) is the first cause of death in Africa. However, data regarding the characteristic of patients with CVD are scarce, especially in Sub-Saharan Africa. Purpose We built an observatory recording the characteristics of all patients admitted to hospital in CV departments and hospital care components in Sub-Saharan Africa (FEBRUARY Study). Methods We conducted a transversal and longitudinal study in CV departments of 29 hospitals from 14 African countries. FEBRUARY study was designed by a multidisciplinary collaborative team of epidemiologists, pharmacists and cardiologists from Africa and France. This ongoing observatory included all patients admitted in hospitalization during the month of February every year since 2016 and will continue every year. Data including socio-demographic and clinical characteristics, causes of admission, clinical, biological, complementary examinations, treatments, length of stay and discharge diagnosis were collected by the investigating physicians. Results Overall 2680 patients were admitted to hospital in February 2016 (n=736), 2017 (n=967), and 2018 (n=987) in CV departments from 14 countries: Benin, Burkina Faso, Burundi, Cameroon, Congo, Côte d'Ivoire, Gabon, Guinea, Mali, Niger, Dem. Rep of The Congo, Senegal, Togo and Sudan (figure). Men represented 58,8%. Mean age of age was 54 years and Women 52 years. The mean length of stay was 9 days, and death rate 10,1%. The main cause of admission was cardiac failure (40,3%) followed by acute coronary syndrome (10.1%) and stroke (9,3%). Among CV risk factors, high blood pressure, sedentary behavior, diabetes, active tobacco consumption and dyslipidemia were present in 46%, 19%, 13%, 11% and 6% of patients, respectively. In a longitudinal analysis, hospital admission due coronary syndrome increased from 7% in 2016 to 10.5% in 2018 (p for trend = 0.03). Length of hospital stay and rate of hospital death remain stable. Hospitalizations by country (FEBRUARY) Conclusion The FEBRUARY observatory is an important tool to describe cardiovascular characteristics of patients in transversal analysis, but also the longitudinal evolution over the coming years in Sub-Saharan Africa.

Key points Exercise training effectively improves vascular and skeletal muscle function; however, these effects of training may be blunted in postmenopausal women as a result of the loss of oestrogens. Accordingly, the capacity to deliver oxygen to the active muscles may also be impaired in postmenopausal women. In both premenopausal and recent postmenopausal women, exercise training was shown to improve leg vascular and skeletal muscle mitochondrial function. Interestingly, these effects were more pronounced in postmenopausal women. Skeletal muscle oxygen supply and utilization were similar in the two groups of women. These findings suggest that the early postmenopausal phase is associated with an enhanced capacity of the leg vasculature and skeletal muscle mitochondria to adapt to exercise training and that the ability to deliver oxygen to match the demand of the active muscles is preserved in the early phase following the menopausal transition. Abstract Exercise training leads to favourable adaptations within skeletal muscle; however, this effect of exercise training may be blunted in postmenopausal women as a result of the loss of oestrogens. Furthermore, postmenopausal women may have an impaired vascular response to acute exercise. We examined the haemodynamic response to acute exercise in matched pre- and postmenopausal women before and after 12 weeks of aerobic high intensity exercise training. Twenty premenopausal and 16 early postmenopausal (mean ± SEM: 3.1 ± 0.5 years after final menstrual period) women only separated by 4 years of age (mean ± SEM: 50 ± 0 years vs. 54 ± 1 years) were included. Before training, leg blood flow, O2 delivery, O2 uptake and lactate release during knee-extensor exercise were similar in pre- and postmenopausal women. Exercise training reduced (P