Overt Clinical Symptoms Research Articles

Elevation of serum neurofilament light-chain levels disclose possible occult progressive multifocal leukoencephalopathy and immune reconstitution syndrome in a patient receiving ozanimod: a case report

BackgroundWe report the first case of findings suggestive of progressive multifocal leukoencephalopathy and immune restitution syndrome (PML-IRIS) in a patient with multiple sclerosis receiving ozanimod preceded by an unexpected increase in the serum neurofilament light-chain (sNfL) levels.Case reportA 57-year-old-woman treated with ozanimod for the last 8 years presented, during surveillance MRI, with findings compatible with PML-IRIS. Overt clinical symptoms were absent. sNfL levels increased 4 months earlier and peaked at presentation. Lymphocyte count reached nadir of 330/mL at 8 months earlier.ConclusionThe case illustrates the utility of sNfL levels for PML surveillance in patients receiving immunosuppressors.

Acute toxicity assessment of bioactive constituents from Salvia algeriensis (Desf.) extracts: a promising natural agent against clinical bacterial isolates and pathogenic fungi

Salvia species are emerging as promising therapeutic agents due to their diverse bioactivity against various pathologies. This study was conducted to investigate the phytochemical profile, antimicrobial activity, and acute Toxicity of hydromethanolic extracts from Salvia algeriensis (Desf.) leaves, flowers, and roots. Chemical reaction tests and chromatographic analysis were employed to determine the chemical composition, while microdilution was used to determine the tested microorganisms' minimum inhibitory concentration (MIC). The acute Toxicity of the leaf extract was carried out following the rules and guidelines of OECD 425. Toxicity parameters in Swiss albino mice were evaluated after a single dose of 500 mg/kg and 2000 mg/kg. According to the preliminary phytochemical screening results, terpenoids and polyphenols (flavonoids and tannins) were found in all plant parts, but coumarins were only found in the root extract. The HPLC-DAD analysis revealed the presence of 16 phenolic compounds in varying amounts across the three extracts, of which rosmarinic acid, quercetin, caffeic acid, and 3-hydroxybenzoic acid were the most abundant. Selective antimicrobial activity was noticed, with the root extract demonstrating the most substantial effect against the two fungal strains tested. MIC values ranged from 0.3 to 10 mg/mL, and Gram-positive bacteria generally showedgreater susceptibility compared to Gram-negative bacteria. The LD50 was found to be greater than 2000 mg/kg. There were no overt clinical symptoms of Toxicity. Body weights, organ weights, and temperatures were not significantly altered, and hematological analysis showed no significant differences. Salvia algeriensis (Desf.) extracts emerge as potential candidates for natural, non-toxic antimicrobial agents. Keywords: Acute Toxicity; antimicrobial; HPLC-DAD; polyphenols; Salvia

Cardiac magnetic resonance analysis of left atrium function in patients with pre-apical hypertrophic cardiomyopathy.

Patients presenting with unexplained T wave inversion on electrocardiogram combined with thickened left ventricular apex but less than 15 mm had been proposed as a preclinical scope of apical hypertrophy cardiomyopathy (pre-ApHCM). However, analysis of left atrial (LA) function in these patients has not been studied. This study aims to evaluate the LA function in pre-ApHCM patients and compare it with patients with ApHCM using cardiac magnetic resonance (CMR) imaging. In this retrospective case-control study, a total of 3,593 CMR reports from Beijing Anzhen Hospital, Capital Medical University, China were reviewed. Finally, 31 pre-ApHCM patients were identified and 40 ApHCM and 31 normal controls were included for comparison. LA volumetric and strain were analyzed by CMR. Two-tailed one-way ANOVA was used to analyze the difference of three groups. Pearson correlation test was used for correlation analysis. All of the volumetric parameters in pre-ApHCM group were higher than those in control group. LA reservoir (LA total EF, εs) and conduit function (LA passive EF, εe) parameters, were significantly different among the three groups, which were the lowest in the ApHCM group, intermediate in the pre-ApHCM group, and the highest in the control group ((all P<0.001). Compared with the control group, the LA booster pump function, both the booster EF and booster pump strain (εa) in ApHCM were impaired (P=0.003 and P=0.002 respectively). Meanwhile, only the εa was impaired (P=0.016) while LA booster EF was not (P=0.064) in the pre-ApHCM group, neither εa nor the booster EF show difference between the ApHCM and pre-ApHCM (P=0.272 and P=0.518 respectively). LA function features in pre-ApHCM patients were similar to ApHCM but different from the normal controls. In pre-ApHCM and ApHCM patients, LA reservoir and conduit function impaired earlier before left atrium enlarged and decreased progressively as apex thickens. These findings may help to understand the LA functional change from pre-ApHCM to ApHCM, and to detect subclinical changes in patients with pre-ApHCM before overt hypertrophy or clinical symptoms develop.

Progesterone-independent endometrial mRNA expression in dairy cows with clinical or subclinical endometritis

Up to 50 % of dairy cows fail to resolve uterine involution and develop chronic clinical (CE) or subclinical endometritis (SE) 21 days after calving. Clinical endometritis is associated with purulent discharge, while SE is not associated with overt clinical signs. Along with numerous knowledge gaps related to its pathogenesis, SE does not allow for a straightforward and effective therapy. Therefore, it is crucial to unravel differences in the expression of genes among healthy, CE, and SE cows. This might contribute to the discovery of new drug candidates and, in consequence, a potentially effective treatment. In the present study, cows between 21 and 28 days postpartum (PP) were examined using vaginoscopy for the presence of vaginal discharge and endometrial cytology for the determination of the endometrial polymorphonuclear cell (PMN) percentage. Next, an endometrial biopsy sample was taken to investigate the expression of 13 selected candidate genes by qPCR. Uterine health status was assigned to healthy (absence of abnormal vaginal discharge and ≤5 % PMN, n = 13), SE (absence of abnormal vaginal discharge and >5 % PMN, n = 30), and CE (mucopurulent or purulent vaginal discharge and >5 % PMN, n = 9). At the same time, a blood sample was collected to assess serum progesterone concentration and to categorize cows as low (≤1 ng/mL) or high (>1 ng/mL) in progesterone. High expression of IL1B, IL6, IL17A, CXCL8, PTGES, PTGS1, PTGS2, and INHBA genes and low expression of FST was noted in the endometrium of CE compared to healthy cows. Increased endometrial INHBA expression was observed in both SE and CE compared to healthy cows. Interestingly, greater expression of PTGES and PRXL2B genes and lower expression of PTGS2 were characteristic of SE versus CE or healthy. Among cows with no overt clinical symptoms of uterine disease (healthy and SE), the endometrial expression of IL1 B, CXCL8, and PTGES was greater in cows with high versus low serum progesterone. Several genes were differentially expressed among healthy, SE, and CE cows indicating different pathways for the development of different uterine diseases. In conclusion, we found progesterone-independent SE markers, which suggests that low endometrial PTGS2 expression may be indicative of an inadequate immune response and thus contribute to the pathogenesis of SE.

Immunotherapy of cytomegalovirus infection by low-dose adoptive transfer of antiviral CD8 T cells relies on substantial post-transfer expansion of central memory cells but not effector-memory cells.

Cytomegaloviruses (CMVs) are host species-specific in their replication. It is a hallmark of all CMVs that productive primary infection is controlled by concerted innate and adaptive immune responses in the immunocompetent host. As a result, the infection usually passes without overt clinical symptoms and develops into latent infection, referred to as "latency". During latency, the virus is maintained in a non-replicative state from which it can reactivate to productive infection under conditions of waning immune surveillance. In contrast, infection of an immunocompromised host causes CMV disease with viral multiple-organ histopathology resulting in organ failure. Primary or reactivated CMV infection of hematopoietic cell transplantation (HCT) recipients in a "window of risk" between therapeutic hemato-ablative leukemia therapy and immune system reconstitution remains a clinical challenge. Studies in the mouse model of experimental HCT and infection with murine CMV (mCMV), followed by clinical trials in HCT patients with human CMV (hCMV) reactivation, have revealed a protective function of virus-specific CD8 T cells upon adoptive cell transfer (AT). Memory CD8 T cells derived from latently infected hosts are a favored source for immunotherapy by AT. Strikingly low numbers of these cells were found to prevent CMV disease, suggesting either an immediate effector function of few transferred cells or a clonal expansion generating high numbers of effector cells. In the murine model, the memory population consists of resting central memory T cells (TCM), as well as of conventional effector-memory T cells (cTEM) and inflationary effector-memory T cells (iTEM). iTEM increase in numbers over time in the latently infected host, a phenomenon known as 'memory inflation' (MI). They thus appeared to be a promising source for use in immunotherapy. However, we show here that iTEM contribute little to the control of infection after AT, which relies almost entirely on superior proliferative potential of TCM.

Active role of amino acid metabolism in early diagnosis and treatment of diabetic kidney disease.

Diabetic Kidney Disease (DKD) is one of the significant microvascular consequences of type 2 diabetes mellitus with a complex etiology and protracted course. In the early stages of DKD, the majority of patients experience an insidious onset and few overt clinical symptoms and indicators, but they are prone to develop end-stage renal disease in the later stage, which is life-threatening. The abnormal amino acid metabolism is tightly associated with the development of DKD, which involves several pathological processes such as oxidative stress, inflammatory response, and immune response and is also closely related to autophagy, mitochondrial dysfunction, and iron death. With a focus on taurine, branched-chain amino acids (BCAAs) and glutamine, we explored the biological effects of various amino acid mechanisms linked to DKD, the impact of amino acid metabolism in the early diagnosis of DKD, and the role of amino acid metabolism in treating DKD, to offer fresh objectives and guidelines for later early detection and DKD therapy.

Association of Blood MicroRNA Expression and Polymorphisms with Cognitive and Biomarker Changes in Older Adults

BackgroundIdentifying individuals before the onset of overt symptoms is key in the prevention of Alzheimer’s disease (AD).ObjkectivesInvestigate the use of miRNA as early blood-biomarker of cognitive decline in older adults.DesignCross-sectional.SettingTwo observational cohorts (CHARIOT-PRO, Alzheimer’s Disease Neuroimaging Initiative (ADNI)).Participants830 individuals without overt clinical symptoms from CHARIOT-PRO and 812 individuals from ADNI.MeasurementsqPCR analysis of a prioritised set of 38 miRNAs in the blood of individuals from CHARIOT-PRO, followed by a brain-specific functional enrichment analysis for the significant miRNAs. In ADNI, genetic association analysis for polymorphisms within the significant miRNAs’ genes and CSF levels of phosphorylated-tau, total-tau, amyloid-β42, soluble-TREM2 and BACE1 activity using whole genome sequencing data. Post-hoc analysis using multi-omics datasets.ResultsSix miRNAs (hsa-miR-128-3p, hsa-miR-144-5p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-29c-3p and hsa-miR-363-3p) were downregulated in the blood of individuals with low cognitive performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The pathway enrichment analysis indicated involvement of apoptosis and inflammation, relevant in early AD stages. Polymorphisms within genes encoding for hsa-miR-29c-3p and hsa-miR-146a-5p were associated with CSF levels of amyloid-β42, soluble-TREM2 and BACE1 activity, and 21 variants were eQTL for hippocampal MIR29C expression.Conclusionssix miRNAs may serve as potential blood biomarker of subclinical cognitive deficits in AD. Polymorphisms within these miRNAs suggest a possible interplay between the amyloid cascade and microglial activation at preclinical stages of AD.

Using Myelin Water Imaging to Investigate Myelin Damage and its Association with Clinical Outcomes in Radiologically Isolated Syndrome (S27.005)

Using Myelin Water Imaging to Investigate Myelin Damage and its Association with Clinical Outcomes in Radiologically Isolated Syndrome (S27.005)

Plasma and cerebrospinal fluid neurofilament light concentrations reflect neuronal damage in systemic lupus Erythematosus

Neuronal damage in systemic lupus erythematosus (SLE) is common, but the extent and mechanisms are unclear. Neurofilament light (NfL) concentrations rise in plasma and cerebrospinal fluid (CSF) during neuronal damage in various neurological disorders. In this cross-sectional study, plasma and CSF concentrations of NfL were explored as a marker of neuronal damage in SLE. Seventy-two consecutive SLE out-patients and 26 healthy controls, all female, aged < 55 years, underwent magnetic resonance imaging (MRI) and neurocognitive testing. NfL concentrations in plasma from all individuals and in CSF from 32 patients were measured with single-molecule array technology. Patients were assessed by a rheumatologist and neurologist to define neuropsychiatric involvement (NPSLE) according to three attribution models: SLICC A, SLICC B and ACR. Plasma and CSF NfL concentrations correlated strongly (r = 0.72, p < 0.001). Both NPSLE and non-NPSLE patients in all attribution models had higher plasma NfL concentrations compared with healthy controls (log-NfL, pg/ml, mean (SD); healthy controls (0.71 (0.17)); SLICC A model: NPSLE (0.87 (0.13), p = 0.003), non-NPSLE (0.83 (0.18), p = 0.005); SLICC B model: NPSLE (0.87 (0.14), p = 0.001), non-NPSLE (0.83 (0.18), p = 0.008); ACR model: NPSLE (0.86 (0.16), p < 0.001), non-NPSLE (0.81 (0.17), p = 0.044)). Plasma and CSF NfL concentrations did not differ between NPSLE and non-NPSLE patients. Higher plasma NfL concentrations correlated with larger CSF volumes on MRI (r = 0.34, p = 0.005), and was associated with poorer cognitive performance in the domains of simple attention, psychomotor speed and verbal memory. SLICC/ACR-Damage Index ≥1 was independently associated with higher plasma NfL concentrations (β = 0.074, p = 0.038). Higher plasma creatinine concentrations, anti-dsDNA-positivity, low complement C3 levels, or a history of renal involvement were associated with higher plasma NfL concentrations (β = 0.003, p = 0.009; β = 0.072, p = 0.031; β = 0.077, p = 0.027; β = 0.069, p = 0.047, respectively). Higher plasma NfL concentrations in NPSLE and non-NPSLE patients may indicate a higher degree of neuronal damage in SLE in general, corresponding to cognitive impairment and organ damage development. Furthermore, our results may indicate a higher degree of neuronal breakdown in patients with active SLE, also without overt clinical symptoms. NfL may serve as an indicator of neuronal damage in SLE in further studies.

Serum metabolites associate with biofluid neurofilament light chain in Alzheimer’s disease

AbstractBackgroundNeurodegeneration is one of the main components of A/T/N (amyloid/ tau/ neurodegeneration) classification. Recently, neurofilament light chain (NFL), a neuronal protein that is expressed in myelinated axons, has been increasingly recognized as a biomarker of neurodegeneration. In this study, we performed large‐scale association analysis of serum metabolites with NFL in Alzheimer’s disease.MethodWe performed cross‐sectional and longitudinal association analysis of serum metabolome with plasma and CSF NFL in Alzheimer’s disease (AD), after adjusting for multiple testing (N=1,317 for 140 metabolites). Subjects who had both NFL and metabolomics panel data were included. Metabolites were measured using a targeted metabolomics approach using the AbsoluteIDQ‐p180 kit.ResultWe identified 70 metabolites including acylcarnitines sphingomyelins, biogenic amines, amino acids, and glycerophospholipids as significantly associated with baseline plasma NFL, where we identified sex‐specific and APOE ε4‐specific metabolites. Of those, eight metabolites (C16:1, C18:1, SM(OH) C14:1, SM(OH) C16:1, SM C20:2, PC.aa.C28.1, PC.ae.C30.2, and PC.ae. C32.2) were also associated with baseline cerebrospinal fluid NFL and 10 metabolites (C9, C10:2, citrulline, creatinine, SDMA, PC.ae.C34.2, PC.ae.C36.2, PC.ae. C36.3, SM C20:2, and SM C16:0) were associated with change rates of plasma NFL in AD. Metabolites with significant associations were related to biological functions including amyloid precursor protein processing, neuroinflammation, nitric oxide production, and renal function. There were two significant interactions between sex and two medium‐chain acylcarnitine metabolites (C8 and C10) on plasma NFL levels.ConclusionOur present study provides insight into the association of serum‐based circulating metabolites with biofluid biomarker evidence of neurodegeneration, which is closely related to overt clinical symptoms in AD. Metabolites found in our study are related to various biological functions or associated with known risk factors of AD.

The Relationship Between Thiamine Intake and Long Sleep Duration: Results From the Korea National Health and Nutrition Examination Survey.

Thiamine is thought to modify sleeping patterns, while alcohol use diminishes internal thiamine levels. We investigated the association between thiamine intake and sleep duration and explored possible heterogeneity in the effect according to alcohol use. In total, 15 384 participants aged 19-64 were obtained from the Korea National Health and Nutrition Examination Survey 2012-2016. Nutrient intake, including thiamine, was measured using a food frequency questionnaire. Sleep duration was measured by a self-reported questionnaire. The highest thiamine intake quartile was set as the reference group. Participants were divided into 3 groups, with 7-8 hours of daily sleep as a reference group and those who slept more or less than that as "oversleeping" and "insufficient sleeping," respectively. Multivariate logistic regression was used, adjusting for socioeconomic, medical, and nutritional factors. Additionally, participants were stratified according to high-risk alcohol use defined by the World Health Organization standards on alcohol use. Low thiamine intake was associated with oversleeping (Q3: odds ratio [OR], 1.06; 95% confidence interval [CI], 0.86 to 1.32; Q2: OR, 1.24; 95% CI, 0.99 to 1.55; Q1: OR, 1.49; 95% CI, 1.16 to 1.91) and showed a significant trend for higher ORs at lower intake levels (p-trend&lt;0.001). The effect was stronger in the high-risk alcohol use group (Q1: OR, 1.78; 95% CI, 1.28 to 2.49). Low thiamine intake was associated with oversleeping, and alcohol use intensified that association. These results were found in a context where overt clinical symptoms due to thiamine deficiency are considered rare. More awareness of the potential relationship of thiamine intake with oversleeping and its related risks should be considered.

Isolation and characterization of two novel serotypes of Tibet orbivirus from Culicoides and sentinel cattle in Yunnan Province of China.

Tibet orbivirus (TIBOV), a new candidate of Orbivirus genus, was initially isolated from mosquitoes in Tibet in 2009 and subsequently from both Culicoides and mosquitoes in several provinces of China and Japan. Little is known about the origin, genetic diversity, dissemination and pathogenicity of TIBOV, although its potential threat to animal health has been acknowledged. In this study, two viruses, V290/YNSZ and V298/YNJH, were isolated from the Culicoides and sentinel cattle in Yunnan Province. Their genome sequences, cell tropism in mammalian and insect cell lines along with pathogenicity in suckling mice were determined. Genome phylogenetic analyses confirmed their classification as TIBOV species; however, OC1 proteins of the V290/YNSZ and V298/YNJH shared maximum sequence identities of 31.5% and 33.9% with other recognized TIBOV serotypes (TIBOV-1 to TIBOV-4) and formed two monophyletic branches in phylogenetic tree, indicating they represented two novel TIBOV serotypes which were tentatively designated as TIBOV-5 and TIBOV-6. The viruses replicated robustly in BHK, Vero and C6/36 cells and triggered overt clinical symptoms in suckling mice after intracerebral inoculation, causing mortality of 100% and 25%. Cross-sectional epidemiology analysis revealed silent circulation of TIBOV in Yunnan Province with overall prevalence of 16.4% (18/110) in cattle, 10.8% (13/120) in goats and 5.5% (6/110) in swine. The prevalence patterns of four investigated TIBOV serotypes (TIBOV-1, -2, -5 and 6) differed from each one another, with their positive rates ranging from 8.2% (9/110) for TIBOV-2 in cattle to 0.9% (1/110) for TIBOV-1 and TIBOV-5 in cattle and swine. Our findings provided new insights for diversity, pathogenicity and epidemiology of TIBOV and formed a basis for future studies addressing the geographical distribution and the zoonotic potential of TIBOV.

Gastrointestinal obstruction in the course of incarcerated Richter’s hernia in the peritoneal drainage catheter tunnel – a case report

Gastrointestinal obstruction is a condition in which the passage of contents through the intestine is arrested. Thorough physical examination as well as imaging and laboratory diagnosis are needed for a correct diagnosis. Richter’s hernia is a rare form of abdominal hernia in which a part of the intestinal wall is entrapped in the hernial sac. A female patient reported to the Emergency Department (ED) with symptoms of gastrointestinal obstruction. After performing all necessary investigations, Richter-type hernia was found in the peritoneal drainage catheter tunnel, which was surgically treated. Incarcerated abdominal hernias are one of the most common causes of gastrointestinal obstruction. Richter’s hernia, which poses diagnostic difficulty despite overt clinical symptoms, and may be found even in small defects in the abdominal wall, is one of them.

Gut Resistome after Antibiotics among Children with Uncomplicated Severe Acute Malnutrition: A Randomized Controlled Trial.

A broad-spectrum antibiotic, typically amoxicillin, is included in many country guidelines as part of the management of uncomplicated severe acute malnutrition (SAM) in children without overt clinical symptoms of infection. Alternative antibiotics may be beneficial for children with SAM without increasing selection for beta-lactam resistance. We conducted a 1:1 randomized controlled trial of single dose azithromycin versus a 7-day course of amoxicillin for SAM. Children 6-59 months of age with uncomplicated SAM (mid-upper arm circumference < 11.5 cm and/or weight-for-height Z-score < -3) were enrolled in Boromo District, Burkina Faso, from June through October 2020. Rectal swabs were collected at baseline and 8 weeks after treatment and processed using DNA-Seq. We compared the resistome at the class level in children randomized to azithromycin compared with amoxicillin. We found no evidence of a difference in the distribution of genetic antibiotic resistance determinants to any antibiotic class 8 weeks after treatment. There was no difference in genetic macrolide resistance determinants (65% azithromycin, 65% placebo, odds ratio, OR, 1.00, 95% confidence interval, CI, 0.43-2.34) or beta-lactam resistance determinants (82% azithromycin, 83% amoxicillin, OR 0.94, 95% CI, 0.33-2.68) at 8 weeks. Although presence of genetic antibiotic resistance determinants to macrolides and beta-lactams was common, we found no evidence of a difference in the gut resistome 8 weeks after treatment. If there are earlier effects of antibiotics on selection for genetic antibiotic resistance determinants, the resistome may normalize by 8 weeks.

Total Serum Testosterone Level in Obese Patients with Type -2 Diabetes Mellitus

Both obesity and type 2 diabetes mellitus (T2DM) are independently associated with reduced serum testosterone. The additive effect of obesity and T2DM on reducing testosterone levels need to be investigated. Their combined additive effects may place obese T2DM patients at higher risk of decreased testosterone and the associated increased morbidity and mortality. The aim of this study was to screen obese T2DM patients for biochemical hypogonadism regardless of the presence of overt clinical symptoms to consider testosterone replacement therapy. 152 adult male aged 40 to 68 years with T2DM were recruited through simple random sampling. The study participants were grouped based on their BMI into lean (n=48); overweight (n=57), obese (n=37) and morbidly obese (n=11). Total serum testosterone (TST), BMI and waist circumference (WC) were measured in all patients and luteinizing hormone (LH) was measured in 103 of them. Low TST was defined as TST&lt;9nmol/L and the normal range for LH was 1.7-11.2mIU/ml. Mean TST in lean T2DM patients was 15.61± 6.0 nmol/l. TST levels were significantly lower in obese and morbidly obese groups compared with the lean group (P=0.003 and 0.015 respectively). TST negatively correlated with BMI (r= -0.29, P&lt;0.001) and WC (r= -0.21, P&lt;0.009). Overall, 19.7% of T2DM patients had low TST. The prevalence of low TST increased from 14.9% in lean, to 21.1% in overweight, to 21.6% in obese, to 27.3% in morbidly obese T2DM patients, (P=0.74). LH was inappropriately normal in 95% (19/20) of patients with low TST. Obese T2DM patients had reduced TST levels and a higher prevalence of reduced TST compared to lean patients. TST negatively correlated with BMI and WC. Therefore, screening obese T2DM patients for testosterone deficiency should be considered.

PREVALENCE OF DYSLIPIDEMIA AND ASSESSMENT OF BLOOD PRESSURE IN PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM IN A TERTIARY CARE HOSPITAL - A CASE CONTROL STUDY

Introduction: The THYROID gland has been incriminated to cause a spectrum of diseases that involve almost every system of the human body. Subclinical thyroid disorders can be rightly said to be the forerunners of these clinical scenarios. One pole constitutes subclinical hypothyroidism, the other end being subclinical hyperthyroidism. 'Subclinical hypothyroidism' is dened as a condition with elevated serum TSH and normal serum T3 and T4 in the absence of overt clinical signs and symptoms. It is quite common in the community. Estimation of the prevalence ofAims: dyslipidemia among cases of subclinical hypothyroidism and Estimation of the prevalence of hypertension among cases of subclinical hypothyroidism. The present study was Observational study. This Study was conducted from January 2012 to JuneMaterials And Methods: 2014(18 months) at N.R.S Medical College and Hospital, Kolkata. 100 patients were included in this study. In this study, SH has beenResult: found to be more prevalent among elderly female.81% of total SH cases were female and 61% of the cases were aged above 50 years. Most (70%) of the SH cases had TSH value &gt; 10 micro IU/ml. These ndings correlate with the results of the Wickham survey, although the prevalence of cases with higher TSH value was more than that of the Colorado Thyroid Disease Prevalence Study. Hypertension was more prevalentConclusion: among SH cases than control population. Systolic and diastolic both blood pressure means were higher among SH cases although diastolic blood pressure was more affected. Mean arterial blood pressure was also higher among SH cases than euthyroid control.

New strategies and therapies for the prevention of heart failure in high-risk patients.

Despite declines in total cardiovascular mortality rates in the United States, heart failure (HF) mortality rates as well as hospitalizations and readmissions have increased in the past decade. Increases have been relatively higher among young and middle‐aged adults (<65 years). Therefore, identification of individuals HF at‐risk (Stage A) or with pre‐HF (Stage B) before the onset of overt clinical signs and symptoms (Stage C) is urgently needed. Multivariate risk models (e.g., Pooled Cohort Equations to Prevent Heart Failure [PCP‐HF]) have been externally validated in diverse populations and endorsed by the 2022 HF Guidelines to apply a risk‐based framework for the prevention of HF. However, traditional risk factors included in the PCP‐HF model only account for half of an individual's lifetime risk of HF; novel risk factors (e.g., adverse pregnancy outcomes, impaired lung health, COVID‐19) are emerging as important risk‐enhancing factors that need to be accounted for in personalized approaches to prevention. In addition to determining the role of novel risk‐enhancing factors, integration of social determinants of health (SDoH) in identifying and addressing HF risk is needed to transform the current clinical paradigm for the prevention of HF. Comprehensive strategies to prevent the progression of HF must incorporate pharmacotherapies (e.g., sodium glucose co‐transporter‐2 inhibitors that have also been termed the “statins” of HF prevention), intensive blood pressure lowering, and heart‐healthy behaviors. Future directions include investigation of novel prediction models leveraging machine learning, integration of risk‐enhancing factors and SDoH, and equitable approaches to interventions for risk‐based prevention of HF.

Assembly-defective Tembusu virus ectopically expressing capsid protein is an approach for live-attenuated flavivirus vaccine development

Live-attenuated vaccines (LAVs) represent a promising approach for flavivirus vaccine development. In the present study, we demonstrated a method for generating flavivirus LAVs based on breaking spatially and temporally regulated C-prM cleavage to disturb the viral assembly process, using an avian flavivirus (Tembusu virus) as the model. Using reverse genetics technology, we successfully generated two recombinant viruses (CQW1-IRES-mC and CQW1-MINI-mC) with bicistronic genomic RNA in which native capsid genes were deleted and instead expressed in the 3’UTR under the control of an internal ribosome entry site (IRES) or minimum IRES. Both viruses showed a significantly attenuated phenotype in vitro due to impaired viral assembly, and the engineered mutations were genetically stable in vitro within ten passages. Importantly, their virulence was also highly attenuated in ducklings and suckling mice and did not cause any overt clinical symptoms or mortality. In addition, a single dose of immunization with any of these mutant viruses could completely protect ducklings from a lethal challenge, and no viremia was detected after immunization and challenge, even though the viruses induced a relatively moderate immune response in terms of the T-lymphocytes proliferative response and the level of neutralization antibodies compared with that obtained with the wild-type virus. Besides, a recombinant virus ectopically expressing the prM-E protein was also generated in the present study, but this virus was too attenuated with severely decreased proliferation. Our results indicated that the use of a recombinant flavivirus that ectopically expresses structural proteins could be an effective and universal method for flavivirus LAVs development.

Intra-Abdominal Pressure Measurement Devices: A Technologic Analysis.

The purpose of this Technologic Analysis is to review devices designed to measure intra-abdominal pressure (IAP); these devices are used to detect intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). Published literature focusing on devices designed to measure IAP was reviewed, comparing the options available and outlining recommendations for appropriate use. Safety information regarding IAP measurement devices was derived from the Manufacturer and User Facility Device Experience (MAUDE) database. Intra-abdominal hypertension is prevalent among critically ill patients of all ages and is linked to adverse consequences, such as abdominal compartment syndrome. The condition is often unrecognized due to the lack of overt clinical symptoms, supporting the need for devices to accurately measure IAP. Commercially available devices measure IAP indirectly, typically via the bladder or stomach. Additional research is needed to demonstrate the benefits of routine screening, further define risk factors for IAH/ACS development, and evaluate the impact of measures to reduce IAP in an effort to improve patient outcomes.

Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection.

SARS-CoV-2 causes acute respiratory disease, but many patients also experience neurological complications. Neuropathological changes with pronounced neuroinflammation have been described in individuals after lethal COVID-19, as well as in the CSF of hospitalized patients with neurological complications. To assess whether neuropathological changes can occur after a SARS-CoV-2 infection, leading to mild-to-moderate disease, we investigated the brains of four rhesus and four cynomolgus macaques after pulmonary disease and without overt clinical symptoms. Postmortem analysis demonstrated the infiltration of T-cells and activated microglia in the parenchyma of all infected animals, even in the absence of viral antigen or RNA. Moreover, intracellular α-synuclein aggregates were found in the brains of both macaque species. The heterogeneity of these manifestations in the brains indicates the virus’ neuropathological potential and should be considered a warning for long-term health risks, following SARS-CoV-2 infection.