Clinical Symptomology Research Articles

Clinical health outcomes of Ebola virus disease survivors eight years post recovery: a cross-sectional study in Sierra Leone.

The West African Ebola virus disease (EVD) epidemic that occurred between 2013-2016 resulted in >28,000 confirmed cases and >11,000 fatalities. Thousands of survivors necessitate an understanding of the long-term health effects and future medical needs of these patients. A cross-sectional study of 595 EVD survivors from Sierra Leone and 403 close contacts (n=998). An in-person survey conducted between November 2021 and March 2022 included demographics, clinical health symptomology assessment of each organ system and a reproductive health assessment including sexual dysfunction question sets. The frequency of each disorder was examined and the association of each disorder with EVD survival was assessed. Of 12 number of symptom types, five were reported by >50% of EVD survivors (Ocular, Neurological, Constitutional, Genitourinary, Dermatological), and all but one were reported by >40% of EVD survivors. Symptom types associated with EVD survival included ENT symptoms (AOR: 8.75, 95% CI: 5.63 - 13.60, p < 0.001), ocular symptoms (AOR: 7.18, 95% CI: 5.02 - 10.25, p < 0.001), dermatological symptoms (AOR: 4.16, 95% CI: 3.06 - 5.65, p < 0.001) and cardiovascular symptoms (AOR: 2.96, 95% CI: 2.12 - 4.13, p < 0.001). The West Africa EVD epidemic resulted in a high prevalence of persistent health issues among disease survivors. Continued support for survivor services in West Africa is crucial, and future outbreak response planning should include dedicated funding to ensure adequate care for survivors, both during the acute phase of infection and throughout the post recovery period.

Progressive alterations of resting-state hypothalamic dysconnectivity in schizophrenia

BackgroundThe hypothalamus may be involved in the pathogenesis of schizophrenia. Investigating hypothalamus dysfunction in schizophrenia and probing how it is related to symptoms and responds to antipsychotic medication is crucial for understanding the potential mechanism of hypothalamus dysfunction under the long-term illness. MethodsWe recruited 216 patients with schizophrenia, including 140 antipsychotic-naïve first-episode patients (FES, including 44 patients with 1-year follow-up data), 76 chronically treated schizophrenia (CTS), and 210 healthy controls (HC). Hypothalamic seed-based functional connectivity (FC) was calculated and compared among the FES, CTS, and HC groups using analysis of covariance. Exploratory analysis was conducted between the FES patients at baseline and after 1-year follow-up. Significantly altered hypothalamic FCs were then related to clinical symptomology, while age- and illness-related regression analyses were also conducted and compared between diagnostic groups. ResultsThe FES patients showed decreased hypothalamic FCs with the midbrain and right thalamus, whereas the CTS patients showed more severe decreased hypothalamic FCs with the midbrain, right thalamus, left putamen, right caudate, and bilateral anterior cingulate cortex compared to HCs. These abnormalities were not correlated to the symptomology or illness duration, or not reversed by the antipsychotic treatment. Age-related hypothalamic FC decrease was also identified in the abovementioned regions, and a faster age-related decline of the hypothalamic FC was observed with the left putamen and bilateral anterior cingulate cortex. ConclusionAge-related hypothalamic FC decrease extends the functional alterations that characterize the neurodegenerative nature of schizophrenia. Future studies are required to further probe the hormonal or endocrinal underpinnings of such alterations and trace the precise progressive trajectories.

A non-randomised controlled trial of a community-based accommodation and psychosocial support programme for adults experiencing mental illness and homelessness.

The transition out of inpatient mental health is a crucial time for adults experiencing concurrent mental illness and homelessness, yet evidence regarding effective support options is mixed. Choices is an intensive 3-month psychosocial outreach and crisis accommodation support programme for adults experiencing mental illness and homelessness, delivered by Baptcare in Tasmania, Australia. This study examined the effect of Choices on adults' psychosocial functioning, clinical symptomology and psychiatric readmissions in comparison to standard care only. Participants were adults aged 18-64 years experiencing mental illness and homelessness, recruited upon discharge from a psychiatric admission. Intervention participants (n = 124) received the Choices programme. Control participants (n = 122) received standard care, clinical assessment and treatment from hospital-based Mental Health Services. Outcomes were psychosocial functioning (primary), clinical symptomology, hospital readmission rate and readmission length of stay. Outcomes were assessed at programme commencement and closure (3 months) and 3 months post-closure (intervention group only). Analysis of covariance was used to analyse differences between groups at closure, while controlling for baseline differences. Intervention participants had significantly improved social functioning (encompassing living conditions, social relationships, self-esteem/confidence), overall psychosocial functioning, symptoms of depression and anxiety and shorter hospital readmission length of stay in comparison to the control group. Intervention participants experienced further improvements in social and overall psychosocial functioning 3 months post-closure. The Choices programme is effective in enhancing the psychosocial functioning of adults experiencing concurrent mental illness and homelessness. These findings support the ongoing delivery of this combined accommodation and wrap-around psychosocial model of intensive support.

Tianeptine-involved emergency department visits, fatal overdoses, and substance seizures in Tennessee, 2021–2023

BackgroundTianeptine is an antidepressant that acts as an agonist to the mu-opioid receptor and enhances serotonin reuptake. Tianeptine has been legally sold as an antidepressant in some countries but is not approved for any medical use by the U.S. Food and Drug Administration (FDA). Tianeptine is not a federally controlled substance, but became a schedule II substance in Tennessee on July 1, 2022. This publication aims to describe the prevalence of tianeptine-involved emergency department visits, fatal overdoses, and substance seizures in Tennessee from 2021 to 2023. MethodsWe conducted a study to examine the prevalence of tianeptine-involved emergency department visits and fatal overdoses in Tennessee using data for 2021 to 2023 from the Tennessee Electronic Surveillance System for the Early Notification of Community based Epidemics (ESSENCE) database and the Tennessee State Unintentional Drug Overdose Reporting System (SUDORS). Substance seizure data from National Forensic Laboratory Information System (NFLIS) are included. ResultsOur search of ESSENCE, SUDORS, and NFLIS yielded 50 tianeptine-involved emergency department visits, 6 tianeptine-involved fatal overdoses, and 19 tianeptine substance seizures respectively. Demographic information is provided for the emergency department visits and tianeptine-involved fatal overdoses. Discharge diagnosis and clinical symptomology information are provided for the emergency department visits. ConclusionEmergency department visits and fatal overdoses involving tianeptine have occurred in Tennessee despite tianeptine becoming a schedule II substance. Among emergency department visits, tianeptine use is most commonly associated with gastrointestinal and psychological symptoms. All fatal cases where tianeptine was detected involved other substances, suggesting tianeptine plays a role in polysubstance use.

The Effect of Glycemic Status on P Wave Dispersion.

Background and aim The growing number of people with diabetes mellitus (DM) across the world is a public health concern. The diabetes epidemic involves enormous health costs to the patients, their careers, and society at large. Cardiovascular diseases such as atrial fibrillation (AF) often develop in the diabetic population. An increase in the P wave dispersion (PWD) has been established as an independent risk factor for the occurrence of AF, hence the present study was conducted to establish a possible relationship between PWD and the glycemic status of the individualto predict the occurrence of AF ahead of clinical symptomology. Methodology A comparative cross-sectional study was conducted at a tertiary care hospital after obtaining approval from the institutional ethics committee and written consent of each study subject. The main steps included the selection and categorization of the study population based on their glycemic status, collection of demographic data, performing ECGs calculating PWD using digital calipers, and recording the data systematically for evaluation. Results In this study, 234 patients with a mean age of 53.3 ± 13.1 years were studied, of which 121 (51.7%) were maleand 113 (48.29%) were female. The 234 patients were divided into four groups based on their glycemic status - 74 uncontrolled DM patients (31.62%), 51 type 2 DM (T2DM) patients (21.78%), 56 prediabetespatients (23.93%), and 53 patients in thecontrol group (22.64%; not a known case of diabetes with normal HbA1c and fasting blood sugar (FBS) levels).Minimal correlation was observed between FBS with PWD (r value0.175)and age with PWD (r value0.161), butstatisticalsignificance was observed only between age and PWD (p-value 0.014).The difference in means between the four different study groupswas found to be not statistically significant (p-value- 0.104); hence, no intergroup variation was noted. Conclusion Advancing age and higher fasting blood sugars have shown minimal correlation with widening P-wave dispersion. With further studies involving larger populations, this can be a promising aid in identifying PWD as a probable early predictor of atrial arrhythmias among diabetic patients.

Does the Timing of Alzheimer’s Disease vary by Severity of Intellectual Disability in Down Syndrome?

AbstractBackgroundTrisomy 21 causes Down syndrome (DS) and is a recognized cause of Alzheimer’s disease (AD). The triplication of the amyloid precursor protein gene leads to an overexpression of amyloid‐beta (Aβ), which accumulates into extracellular plaques, followed by intracellular neurofibrillary tau tangles (Lott &amp; Head, 2019). However, variability in the age of AD onset in DS spans 25+ years (Iulita et al., 2022). As the DS field moves to AD clinical trials, it is important to identify factors related to this variability, such as premorbid severity of intellectual disability (ID). We compared the age‐trajectory of the AD biomarkers Aβ and tau and cognitive decline across premorbid ID levels (mild, moderate, and severe/profound), in models controlling trisomy type (full, mosaic, translocation) and APOE statusMethodAnalyses involved 361 adults with DS (M = 45.22 years, SD = 9.92) from the Alzheimer’s Biomarkers Consortium‐Down Syndrome. Participants completed measures of memory, mental status, and visuospatial ability. Premorbid ID level was recorded. PET was acquired using [11C] PiB for Aβ, and [18F] AV‐1451 for tau in 162 participants. Aβ was quantified using the centiloid method and tau was quantified as SUVR (reference: cerebellar cortex) in a composite region determined as the volume‐weighted average of select FreeSurfer 5.3, T1 MR‐based components.ResultsGeneral linear models controlling for site, age, trisomy type and APOE status indicated no significant effect of premorbid ID level by age on the cognitive outcomes (Figure 1a‐e). There was not a significant effect of premorbid ID by age on PET Aβ or on tau PET (Figure 2a‐b). There was not a significant difference in age of those with mild cognitive impairment‐DS (MCI‐DS) or dementia by premorbid ID level (Figure 3).ConclusionThis study adds to the characterization of the time course of AD pathology and clinical symptomology in DS. Findings provide robust evidence of a similar time course in AD trajectory across severity of ID, laying the groundwork for the inclusion of individuals with DS with a variety of IQ levels in clinical AD trials. Premorbid IQ may have little effect on AD biomarkers in DS in contrast to findings in neurotypical populations.

711. High Prevalence of Positive Cell Cytotoxicity Neutralization Assay in Symptomatic and Asymptomatic Pediatric Oncologic Patients

Abstract Background Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea in the United States. This burden is more prevalent and severe in the oncologic population and is associated with greater morbidity and mortality. Diagnostic modalities are limited, and misdiagnosis is high with resultant mismanaged care – inappropriate antibiotics, and potentially missed opportunities for appropriate targeted care towards graft-versus-host disease or other etiologies. To date, no large-scale evaluations have been performed to characterize the incidence of true disease in this population or to help delineate predictive markers for true infections (cell cytotoxicity neutralization assay (CCNA) positivity). Methods This is a multi-center, prospective stool banking study from January 2020 to date enrolling pediatric patients with an oncologic diagnosis admitted at Advocate Children’s Hospital and Comer Children’s Hospital. Stool was collected weekly along with relevant clinical histories and symptomology. Isolates of C. difficile were cultured and CCNA performed. Stool was also collected during episodes of PCR diagnosed CDI. Results 65 unique subjects were enrolled over 183 admissions. 11 samples from 10 patients were thought to represent CDI with PCR positivity noted. Five of these specimens were confirmed as CCNA positive while the remainder did not have active toxin presence. Bristol type 4 stools or &amp;gt; 3 stools in 24 hours were significant factors for modeling CCNA positivity, but not for modeling PCR positivity. Notably 26 stool specimens were CCNA positive, and 21 did not have PCR tests done. Among all CCNA positive specimens, no significant difference was noted in symptomatology or antibiotic use. Conclusion Differentiating true CDI can be challenging. However, even in patients with high risk of alternative GI pathology, the frequency of stooling and stool characteristics can be used. Although considered the gold standard for assessment of disease, CCNA positivity in this population was noted in patients who were not evaluated for disease by their primary providers. Underdiagnosis is possible, but potentially less likely given the absence of clinically significant differentiation in symptoms. Host factors predisposing to disease are likely present. Disclosures Larry K. Kociolek, MD, MSCI, Merck: Grant/Research Support

Atypical presentations of primary acquired hypothyroidism – a case series

Primary acquired hypothyroidism in children manifests with a myriad of clinical presentations. Clinical features can be insidious in nature, often under the guise of non-specific presentations to other subspecialties prior to referral to the endocrinologist. Growth failure is a hallmark feature in these children alongside their presenting clinical symptomology which needs to be identified through detailed history, physical examination and analysis of the growth charts. In this case series, we discuss 5 atypical presentations of acquired primary hypothyroidism with multisystemic involvement, including musculoskeletal, hepatobiliary, gynaecological and haematological manifestations. This is of importance as untreated hypothyroidism leads to fatigue, decreased physical activity, suboptimal height gain, disordered puberty and poor neurocognitive development in children with long term detrimental outcomes.

Bilateral anterior corona radiata microstructure organisation relates to impaired social cognition in schizophrenia

ObjectiveThe Corona Radiata (CR) is a large white matter tract in the brain comprising of the anterior CR (aCR), superior CR (sCR), and posterior CR (pCR), which have associations with cognition, self-regulation, and, in schizophrenia, positive symptom severity. This study tested the hypothesis that the microstructural organisation of the aCR, as measured by Fractional Anisotropy (FA) using Diffusion Tensor Imaging (DTI), would relate to poorer social cognitive outcomes and higher positive symptom severity for people with schizophrenia, when compared to healthy participants. We further hypothesised that increased positive symptoms would relate to poorer social cognitive outcomes. MethodsData were derived from n = 178 healthy participants (41 % females; 36.11 ± 12.36 years) and 58 people with schizophrenia (30 % females; 42.4 ± 11.1 years). The Positive and Negative Symptom Severity Scale measured clinical symptom severity. Social Cognition was measured using the Reading the Mind in the Eyes Test (RMET) Total Score, as well as the Positive, Neutral, and Negative stimuli valence. The ENIGMA-DTI protocol tract-based spatial statistics (TBSS) was used. ResultsThere was a significant difference in FA for the CR, in individuals with schizophrenia compared to healthy participants. On stratification, both the aCR and pCR were significantly different between groups, with patients showing reduced white matter tract microstructural organisation. Significant negative correlations were observed between positive symptomatology and reduced microstructural organisation of the aCR. Performance for RMET negative valence items was significantly correlated bilaterally with the aCR, but not the sCR or pCR, and no relationship to positive symptoms was observed. ConclusionsThese data highlight specific and significant microstructural white-matter differences for people with schizophrenia, which relates to positive clinical symptomology and poorer performance on social cognition stimuli. While reduced FA is associated with higher positive symptomatology in schizophrenia, this study shows the specific associated with anterior frontal white matter tracts and reduced social cognitive performance. The aCR may have a specific role to play in frontal-disconnection syndromes, psychosis, and social cognitive profile within schizophrenia, though further research requires more sensitive, specific, and detailed consideration of social cognition outcomes.

AT(N) biomarker profiles and Alzheimer's disease symptomology in Down syndrome.

Down syndrome (DS) is a genetic cause of early-onset Alzheimer's disease (AD). The National Institute on Aging-Alzheimer's Association AT(N) Research Framework is a staging model for AD biomarkers but has not been assessed in DS. Data are from the Alzheimer's Biomarker Consortium-Down Syndrome. Positron emission tomography (PET) amyloid beta (Aβ; 15 mCi of [11 C]Pittsburgh compound B) and tau (10 mCi of [18 F]AV-1451) were used to classify amyloid (A) -/+ and tau (T) +/-. Hippocampal volume classified neurodegeneration (N) -/+. The modified Cued Recall Test assessed episodic memory. Analyses included 162 adults with DS (aged M=38.84 years, standard deviation=8.41). Overall, 69.8% of participants were classified as A-/T-/(N)-, 11.1% were A+/T-/(N)-, 5.6% were A+/T+/(N)-, and 9.3% were A+/T+/(N)+. Participants deemed cognitively stable were most likely to be A-T-(N)- and A+T-(N)-. Tau PET (T+) most closely aligning with memory impairment and AD clinical status. Findings add to understanding of AT(N) biomarker profiles in DS. Overall, 69.8% of adults with Down syndrome (DS) aged 25 to 61 years were classified as amyloid (A)-/tau (T)-/neurodegeneration (N)-, 11.1% were A+/T-/(N)-, 5.6% were A+/T+/(N)-, and 9.3% were A+/T+/(N)+. The AT(N) profiles were associated with clinical Alzheimer's disease (AD) status and with memory performance, with the presence of T+ aligned with AD clinical symptomology. Findings inform models for predicting the transition to the prodromal stage of AD in DS.

Concussion: Beyond the Cascade.

Sport concussion affects millions of athletes each year at all levels of sport. Increasing evidence demonstrates clinical and physiological recovery are becoming more divergent definitions, as evidenced by several studies examining blood-based biomarkers of inflammation and imaging studies of the central nervous system (CNS). Recent studies have shown elevated microglial activation in the CNS in active and retired American football players, as well as in active collegiate athletes who were diagnosed with a concussion and returned to sport. These data are supportive of discordance in clinical symptomology and the inflammatory response in the CNS upon symptom resolution. In this review, we will summarize recent advances in the understanding of the inflammatory response associated with sport concussion and broader mild traumatic brain injury, as well as provide an outlook for important research questions to better align clinical and physiological recovery.

Actigraphy: An Adjunctive Method to Measure Irritability in Opioid-Exposed Newborns.

Background and purpose: Conventional measures of withdrawal in newborns with prenatal opioid exposure (POE) rely on nursing assessments, including the subjective judgment of infant irritability. This study investigated limb movement actigraphy as a tool for providing an objective, quantifiable measure of underlying distress. Methods: Correlational analyses compared continuous physiological-detected movement actigraphy and clinical intervallic-scored symptomology (modified Finnegan system) obtained from a control cohort of 37 term neonates with POE studied in their crib in the newborn unit (1-8 days). Results: Infants spent 15% crib time in high movement activity (>100 movements/minute; index irritability) and 38% crib time in low activity (0-5 movements/minute; index calm). There was a significant positive association between actigraphy and Finnegan composite score (r = .28, P = .001) and between actigraphy and subcomponent scores (i.e., central nervous system, gastrointestinal, and metabolic-vasomotor-respiratory). Conclusion: Movement activity via actigraphy captures underlying distress and calm not measured by conventional assessments. Such objective, quantifiable measures can serve to promote equitable assessment and treatment of hospitalized newborns with POE.

A Randomized Controlled Trial of Probiotics Targeting Gut Dysbiosis in Huntington's Disease.

Gastrointestinal symptoms are clinical features of Huntington's disease (HD), which adversely affect people's quality of life. We recently reported the first evidence of gut dysbiosis in HD gene expansion carriers (HDGECs). Here, we report on a randomized controlled clinical trial of a 6-week probiotic intervention in HDGECs. The primary objective was to determine whether probiotics improved gut microbiome composition in terms of richness, evenness, structure, and diversity of functional pathways and enzymes. Exploratory objectives were to determine whether probiotic supplementation improved cognition, mood, and gastrointestinal symptoms. Forty-one HDGECs, including 19 early manifest and 22 premanifest HDGECs were compared with 36 matched-healthy controls (HCs). Participants were randomly assigned probiotics or placebo and provided fecal samples at baseline and 6-week follow-up, which were sequenced using 16S-V3-V4 rRNA to characterize the gut microbiome. Participants completed a battery of cognitive tests and self-report questionnaires measuring mood and gastrointestinal symptoms. HDGECs had altered gut microbiome diversity when compared to HCs, indicating gut dysbiosis. Probiotic intervention did not ameliorate gut dysbiosis or have any effect on cognition, mood, or gastrointestinal symptoms. Gut microbiome differences between HDGECs and HCs were unchanged across time points, suggesting consistency of gut microbiome differences within groups. Despite the lack of probiotic effects in this trial, the potential utility of the gut as a therapeutic target in HD should continue to be explored given the clinical symptomology, gut dysbiosis, and positive results from probiotics and other gut interventions in similar neurodegenerative diseases.

Functional dysconnectivity of anterior cingulate subregions in schizophrenia and psychotic and nonpsychotic bipolar disorder.

Aberrant resting-state functional connectivity (FC) of anterior cingulate cortex (ACC) has been implicated in the pathophysiology of schizophrenia and bipolar disorder (BP). This study investigated the subregional FC of ACC across schizophrenia and psychotic (PBP) and nonpsychotic BP (NPBP) and the relationship between brain functional alterations and clinical manifestations. A total of 174 first-episode medication-naive patients with schizophrenia (FES), 80 patients with PBP, 77 patients with NPBP and 173 demographically matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Brain-wide FC of ACC subregions was computed for each individual, and compared between the groups. General intelligence was evaluated using the short version of the Wechsler Adult Intelligence Scale. Relationships between FC and various clinical and cognitive variables were estimated using the skipped correlation. The FES, PBP and NPBP groups showed differing connectivity patterns in the left caudal, dorsal and perigenual ACC. Transdiagnostic dysconnectivity was found in the subregional ACC associated with cortical, limbic, striatal and cerebellar regions. Disorder-specific dysconnectivity in FES was identified between the left perigenual ACC and bilateral orbitofrontal cortex, and the left caudal ACC coupling with the default mode network (DMN) and visual processing region was correlated with psychotic symptoms. In the PBP group, FC between the left dorsal ACC and the right caudate was correlated with psychotic symptoms, and FC connected with the DMN was associated with affective symptoms. The current findings confirmed that subregional ACC dysconnectivity could be a key transdiagnostic feature and associated with differing clinical symptomology across schizophrenia and PBP.

271 Diagnosis and Detection of Thrombosis in PCOS

OBJECTIVES/GOALS: Identify and stratify clinical presentations of thrombotic pathology in PCOS patients. This will be accomplished by 1) evaluating clinical assays for the detection of hypofibrinolysis, and 2) analyzing clinical symptomology of thrombosis in PCOS via Symptom-Disease Pair Analysis of Diagnostic Error (SPADE). METHODS/STUDY POPULATION: Preliminary study populations include n=3 for each of the following groups PCOS with thrombotic complications, PCOS without thrombotic complications, healthy controls, and healthy control samples treated ex vivo with PAI-1. Coagulation assays include ACL coagulation panel, antiphospholipid antibody assays, viscoelastic testing with TEG and Quantra devices, and global fibrinolytic capacity. Coagulation assays will be performed on three samples taken at 4-week intervals. The SPADE techniques will be used to evaluate symptomology of thrombosis in the study period and patient electronic medical history. Molecular testing will be performed for pro-thrombotic polymorphisms (PAI-1 and Apo E) and mutations (Factor V Leiden and Prothrombin). RESULTS/ANTICIPATED RESULTS: We anticipate PCOS and ex vivo PAI-1 samples to show signs of hypofibrinolysis on TEG and Quantra devices outside of reference ranges and with statistical significance. We also anticipate seeing a statistical significance with ACL coagulation panels, however, these results are expected to still be within the reference ranges, as seen in previous studies. We believe the SPADE method will identify clinical presentations of hypofibrinolysis in PCOS patients coinciding with patterns in laboratory tests that were misdiagnosed due to being within reference ranges. We hope to stratify clinical presentations predictive of thrombosis in PCOS patients with standard clinical assays and with increased precision using viscoelastic assays. DISCUSSION/SIGNIFICANCE: The incidence rate of thrombosis is 40x higher in PCOS compared to healthy populations. However, the mechanisms of thrombosis in PCOS are unknown and are undetectable with current clinical assays. We hypothesize that chronic cellular stress in PCOS disrupts the regulation of interconnected immune pathways, causing hypofibrinolysis.

Recent Developments in Mpox Prevention and Treatment Options.

Human mpox is an emerging epidemic in the world. The monkey pox virus (MPXV) belongs to the same family of zoonotic Orthopoxviridae as that of the smallpox virus and exhibits similar clinical symptomology. Information regarding its diagnostics, disease epidemiology, surveillance, preventive methods, and treatment strategies are being collated with time. The purpose of this review is to trace the recent events in the scientific platform that have defined new preventive and treatment strategies against mpox. A methodological approach has been used to gather data from the latest literature to comprehensively overview the emerging treatment options. The results portion will cover details regarding the prevention of mpox. It will also shed light on a brief description of contemporary vaccines and antiviral agents that have been evaluated for their treatment potential since the emergence of the mpox threat. These treatment options are setting the pace for controlling the widespread monkeypox infection. However, the limitations attached to these treatment strategies need to be tackled quickly to increase their efficacy so that they can be deployed on a large scale for the prevention of this epidemic becoming another pandemic in this decade.

Cumulative Lifetime Violence, Gender, Social Determinants of Health and Mental Health in Canadian Men: A Latent Class Analysis.

Among men, violence is pervasive and associated with poor mental health, but little is known about which men are most vulnerable. Our purpose is to address this gap by exploring mental health and social determinants of health (SDOH) including gender role conflict (GRC) in heterogenous groups of men with distinct patterns of cumulative lifetime violence (CLV) as target and perpetrator. Latent class analysis was conducted using means of 64 indicators of CLV severity collected from a community sample of 685 eastern Canadian men, ages 19 to 65 years. Class differences by SDOH, and depression, anxiety, and posttraumatic stress disorder (PTSD) were explored with Chi-square and analysis of variance. A 4-class solution was optimal. Class 1 had the lowest CLV severity; were more likely to be better educated, employed, and have little difficulty living on their incomes; and had better mental health than other classes. Class 2, characterized by moderate psychological violence as both target and perpetrator, had mean depression and PTSD scores at clinical levels, and more difficulty living on income than Class 1. Classes 3 and 4 were typified by high severity CLV as target but differentiated by Class 4 having the highest perpetration severity, higher GRC, and being older. In both classes, mean mental health scores were above cut-offs for clinical symptomology and higher than Classes 1 and 2. This is the first evidence that distinct patterns of CLV severity among men intersect with GRC and SDOH and are uniquely associated with mental health.

Biomarkers for Osteoarthritis Diseases.

Growing evidence has revealed the pivotal role of inflammatory biomarkers in the pathogenesis of osteoarthritis. There is significant interest in the prognostic value of select biomarkers, given the potential for early identification and treatment of patients at risk of osteoarthritis prior to the development of irreversible clinical disease. Clinical trials of novel therapeutics that disrupt the inflammatory pathways of osteoarthritis are also ongoing. The purpose of this review is to summarize the current literature on key biomarkers within the context of osteoarthritis pathogenesis, clinical symptom development, and treatment capabilities. Multiple recent studies have established biomarkers that signal the existence of osteoarthritis pathology and the development of clinical symptomology. However, prior to implementation in clinical practice, additional research is required to precisely define the prognostic value for numerous biomarkers and standardize their measurement. Biomarker-driven investigations represent a promising avenue for the early diagnosis and treatment of osteoarthritis.

A NOVEL MUTATION OF IL21R IN A PATIENT WITH COMMON VARIABLE IMMUNODEFICIENCY

<h3>Introduction</h3> Interleukin-21 (IL21) and its receptor (IL21R) are involved in activation of the JAK/STAT pathway and are necessary for B-Cell differentiation. Common variable immunodeficiency (CVID) is a disorder where the patient has hypogammaglobulinemia. There is a growing number of mutations associated with this disease, and we present a novel heterozygous IL21R mutation in a patient with CVID. <h3>Case Description</h3> We report a 70-year-old male patient with diagnosed CVID based on clinical symptomology. The patient had diminished serum antibody levels: IgG (383 mg/dL; normal: 600-11450 mg/dL), IgM (36 mg/dL; normal: 50-300 mg/dL), and IgA (43 mg/dL; normal: 70-320 mg/dL) along with abnormal lymphocyte markers showing low CD19 (26 cells/uL; normal: 110-660 cells/uL), CD3 (538 cells/uL; normal: 840-3060 cells/uL), CD4 (425 cells/uL; normal: 490-1740 cells/uL), CD8 (129 cells/uL; normal: 180-1170 cells/uL) levels. Genetic evaluation was performed by Invitae^TM genomic hybridization-based protocol with Illumina sequencing technology. A mutation, a heterozygous mutation of IL21R c.615G>C (p.Met205Ile) on exon 6 was found. A second heterozygous mutation, DOCK8 c.494C>T (p.Ser165Leu), was also found. <h3>Conclusion</h3> IL21R is largely expressed in the spleen and the thymus and are important in adaptive immunity. Mutations in IL21R have been reported prior in patients with CVID, but none on exon 6. We report a novel mutation of the IL21R in a patient with CVID.

A CASE OF PULMONARY EMBOLISM POST COVID-19 INFECTION IN A PATIENT WITH STAT3 MUTATION

<h3>Introduction</h3> Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator that plays an important role in controlling the innate and adaptive immune system. Hyper IgE syndrome, caused by a STAT3 deficiency, is a rare disorder that commonly presents with connective tissue, skeletal, and vascular abnormalities. Known vasculopathies seen in this syndrome include aneurysms and thrombotic events frequently in coronary and cerebral vascular systems. <h3>Case Description</h3> We report a 55-year-old white male with a known STAT3 deficiency based on clinical symptomology and genetic testing. The patient has been on monthly intravenous immunoglobulin therapy. He has refused active and passive immunization to COVID-19 due to religious reasons. Soon after a COVID-19 infection he presented with dyspnea, leg swelling, and chest pain. Worsening symptoms caused him to be admitted to the hospital and a V/Q scan was performed. The result showed a pulmonary embolism of the left lower lobe, he was treated for this condition and then discharged from the hospital. <h3>Discussion</h3> STAT3 deficient patients typically present with a triad of symptoms: eosinophilia, atopic dermatitis, and pulmonary/skin infections. The complication of recurrent vasculopathies, including clots, has been seen in many patients with a STAT3 deficiency. Outside of STAT3 deficient patients, there has been multiple clinical scenarios where pulmonary embolisms have been present in patients after a COVID-19 infection. This is the first published case of a STAT3 deficient patient presenting with a pulmonary embolism due to a COVID infection.