Derivation of sex and age-specific reference intervals for clinical chemistry analytes in healthy Ghanaian adults.

OBJECTVIES: This study is aimed at establishing reference intervals (RIs) of 40 chemistry and immunochemistry analytes for Ghanaian adults based on internationally harmonized protocol by IFCC Committee on Reference Intervals and Decision Limits (C-RIDL). METHODS: A total of 501 healthy volunteers aged ≥18 years were recruited from the northern and southern regions of Ghana. Blood samples were analyzed with Beckman-Coulter AU480 and Centaur-XP/Siemen auto-analyzers. Sources of variations of reference values (RVs) were evaluated by multiple regression analysis (MRA). The need for partitioning RVs by sex and age was guided by the SD ratio (SDR). The RI for each analyte was derived using parametric method with application of the latent abnormal values exclusion (LAVE) method. RESULTS: Using SDR≥0.4 as threshold, RVs were partitioned by sex for most enzymes, creatinine, uric acid (UA), bilirubin, immunoglobulin-M. MRA revealed age and body mass index (BMI) as major source of variations of many analytes. LAVE lowered the upper limits of RIs for alanine/aspartate aminotransferase, γ-glutamyl transaminase and lipids. Exclusion of individuals with BMI≥30 further lowered the RIs for lipids and CRP. After standardization based on value-assigned serum panel provided by C-RIDL, Ghanaian RIs were found higher for creatine kinase, amylase, and lower for albumin and urea compared to other collaborating countries. CONCLUSIONS: The LAVE effect on many clinical chemistry RIs supports the need for the secondary exclusion for reliable derivation of RIs. The differences in Ghanaian RIs compared to other countries underscore the importance of country specific-RIs for improved clinical decision making.

Prospects of NIR fluorescent nanosensors for green detection of SARS-CoV-2.

The pandemic of the novel coronavirus disease 2019 (COVID-19) is continuously causing hazards for the world. Effective detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can relieve the impact, but various toxic chemicals are also released into the environment. Fluorescence sensors offer a facile analytical strategy. During fluorescence sensing, biological samples such as tissues and body fluids have autofluorescence, giving false-positive/negative results because of the interferences. Fluorescence near-infrared (NIR) nanosensors can be designed from low-toxic materials with insignificant background signals. Although this research is still in its infancy, further developments in this field have the potential for sustainable detection of SARS-CoV-2. Herein, we summarize the reported NIR fluorescent nanosensors with the potential to detect SARS-CoV-2. The green synthesis of NIR fluorescent nanomaterials, environmentally compatible sensing strategies, and possible methods to reduce the testing frequencies are discussed. Further optimization strategies for developing NIR fluorescent nanosensors to facilitate greener diagnostics of SARS-CoV-2 for pandemic control are proposed.

Nanoparticle transfer biosensors for the non-invasive detection of SARS-CoV-2 antigens trapped in surgical face masks.

Detecting SARS-CoV-2 antigens in respiratory tract samples has become a widespread method for screening new SARS-CoV-2 infections. This requires a nasopharyngeal swab performed by a trained healthcare worker, which puts strain on saturated healthcare services. In this manuscript we describe a new approach for non-invasive COVID-19 diagnosis. It consists of using mobile biosensors for detecting viral antigens trapped in surgical face masks worn by patients. The biosensors are made of filter paper containing a nanoparticle reservoir. The nanoparticles transfer from the biosensor to the mask on contact, where they generate colorimetric signals that are quantified with a smartphone app. Sample collection requires wearing a surgical mask for 30 min, and the total assay time is shorter than 10 min. When tested in a cohort of 27 patients with mild or no symptoms, an area under the receiving operating curve (AUROC) of 0.99 was obtained (96.2 % sensitivity and 100 % specificity). Serial measurements revealed a high sensitivity and specificity when masks were worn up to 6 days after diagnosis. Surgical face masks are inexpensive and widely available, which makes this approach easy to implement anywhere. The excellent sensitivity, even when tested with asymptomatic patient samples, along with the mobile detection scheme and non-invasive sampling procedure, makes this biosensor design ideal for mass screening.

Recent advances in sensitive surface-enhanced Raman scattering-based lateral flow assay platforms for point-of-care diagnostics of infectious diseases.

This review reports the recent advances in surface-enhanced Raman scattering (SERS)-based lateral flow assay (LFA) platforms for the diagnosis of infectious diseases. As observed through the recent infection outbreaks of COVID-19 worldwide, a timely diagnosis of the disease is critical for preventing the spread of a disease and to ensure epidemic preparedness. In this regard, an innovative point-of-care diagnostic method is essential. Recently, SERS-based assay platforms have received increasing attention in medical communities owing to their high sensitivity and multiplex detection capability. In contrast, LFAs provide a user-friendly and easily accessible sensing platform. Thus, the combination of LFAs with a SERS detection system provides a new diagnostic modality for accurate and rapid diagnoses of infectious diseases. In this context, we briefly discuss the recent application of LFA platforms for the POC diagnosis of SARS-CoV-2. Thereafter, we focus on the recent advances in SERS-based LFA platforms for the early diagnosis of infectious diseases and their applicability for the rapid diagnosis of SARS-CoV-2. Finally, the key issues that need to be addressed to accelerate the clinical translation of SERS-based LFA platforms from the research laboratory to the bedside are discussed.

Fraxetin inhibits interleukin-1ß-induced apoptosis, inflammation, and matrix degradation in chondrocytes and protects rat cartilage in vivo.

Osteoarthritis (OA) is a disease characterized by degeneration of the joint complex due to cartilage destruction. Fraxetin, a widely used and studied coumarin compound extracted from a traditional Chinese herb (Qin Pi), has shown anti-inflammatory and antioxidant properties, but its effects on OA have not been studied. In the present study, western blotting, immunofluorescence, and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) were used to evaluate the effects of fraxetin on IL-1ß-induced apoptotic activity, inflammatory responses, and catabolism in rat chondrocytes. The results showed that fraxetin prevented IL-1ß-induced apoptosis of chondrocytes and inhibited inflammatory mediator release by regulating the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB pathway in chondrocytes. Additionally, fraxetin suppressed the upregulation of matrix metalloproteinase 13 (MMP13) and degradation of collagen II in the extracellular matrix (ECM). Moreover, the effects of fraxetin in vivo were assessed in a monosodium iodoacetate (MIA)-induced rat model of OA using hematoxylin and eosin (H&E) and Safranin O-fast green staining and magnetic resonance imaging (MRI). The results showed that fraxetin protected the cartilage against destruction. In conclusion, fraxetin could be a potential therapeutic for OA.

Microbial exposure to dairy farmers' dwellings and COPD occurrence.

Dairy farming is a risk factor for chronic obstructive pulmonary disease (COPD). The aim was to determine predictive markers either in blood samples or in dwelling dust samples by comparing COPD and healthy controls with or without farming activity. Dust was collected and analyzed by real-time quantitative PCR. ELISA and DELFIA® were performed to assay the level of specific IgG and IgE of 10 targeted microorganisms. The dwelling exposure of farmers was higher than in the non-farmers (Especially Eurotium amstelodami and Lichtheimia corymbifera). The IgG response against Wallemia sebi and Saccharopolyspora rectivirgula was more often higher in the farmers than the non-farmers. However, exposure and sensitization to the microorganisms tested cannot explain the occurrence of COPD in the dairy farmers' population. COPD development is probably caused by multiple factors associated with exposure over a period of several years.

The application of self-assembled nanostructures in peptide-based subunit vaccine development.

Peptide based-vaccines are becoming one of the most widely investigated prophylactic and therapeutic health care interventions against a variety of diseases, including cancer. However, the lack of a safe and highly efficient adjuvant (immune stimulant) is regarded as the biggest obstacle to vaccine development. The incorporation of a peptide antigen in a nanostructure-based delivery system was recently shown to overcome this obstacle. Nanostructures are often formed from antigens conjugated to molecules such as polymers, lipids, and peptide, with the help of self-assembly phenomenon. This review describes the application of self-assembly process for the production of peptide-based vaccine candidates and the ability of these nanostructures to stimulate humoral and cellular immune responses.

Production and characterization of lentivirus vector-based SARS-CoV-2 pseudoviruses with dual reporters: Evaluation of anti-SARS-CoV-2 viral effect of Korean Red Ginseng.

Background: Pseudotyped virus systems that incorporate viral proteins have been widely employed for the rapid determination of the effectiveness and neutralizing activity of drug and vaccine candidates in biosafety level 2 facilities. We report an efficient method for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus with dual luciferase and fluorescent protein reporters. Moreover, using the established method, we also aimed to investigate whether Korean Red Ginseng (KRG), a valuable Korean herbal medicine, can attenuate infectivity of the pseudotyped virus. Methods: A pseudovirus of SARS-CoV-2 (SARS-2pv) was constructed and efficiently produced using lentivirus vector systems available in the public domain by the introduction of critical mutations in the cytoplasmic tail of the spike protein. KRG extract was dose-dependently treated to Calu-3 cells during SARS2-pv treatment to evaluate the protective activity against SARS-CoV-2. Results: The use of Calu-3 cells or the expression of angiotensin-converting enzyme 2 (ACE2) in HEK293T cells enabled SARS-2pv infection of host cells. Coexpression of transmembrane protease serine subtype 2 (TMPRSS2), which is the activator of spike protein, with ACE2 dramatically elevated luciferase activity, confirming the importance of the TMPRSS2-mediated pathway during SARS-CoV-2 entry. Our pseudovirus assay also revealed that KRG elicited resistance to SARS-CoV-2 infection in lung cells, suggesting its beneficial health effect. Conclusion: The method demonstrated the production of SARS-2pv for the analysis of vaccine or drug candidates. When KRG was assessed by the method, it protected host cells from coronavirus infection. Further studies will be followed for demonstrating this potential benefit.

Breakthrough infections, hospital admissions, and mortality after major COVID-19 vaccination profiles: A prospective cohort study.

Background: Several COVID-19 vaccination rollout strategies are implemented. Real-world data from the large-scale, government-mandated Central Vaccination Center (CVC), Thailand, could be used for comparing the breakthrough infection, across all available COVID-19 vaccination profiles. Methods: This prospective cohort study combined the vaccine profiles from the CVC registry with three nationally validated outcome datasets to assess the breakthrough COVID-19 infection, hospitalization, and death among Thais individuals who received at least one dose of the COVID-19 vaccine. The outcomes were analyzed by comparing vaccine profiles to investigate the shot effect and homologous effect. Findings: Of 2,407,315 Thais who had at least one dose of COVID-19 vaccine, 63,469 (2.75%) had breakthrough infection, 42,001 (1.79%) had been hospitalized, and 431 (0.02%) died. Per one vaccination shot added, there was an 18% risk reduction of breakthrough infection (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.80-0.82), a 25% risk reduction of hospitalization (HR 0.75, 95% CI 0.73-0.76), and a 96% risk reduction of mortality (HR 0.04, 95% CI 0.03-0.06). The heterologous two-shot vaccine profiles had a higher protective effect against infection, hospitalization, and mortality compared to the homologous counterparts. Interpretation: COVID-19 breakthrough infection, hospitalization, and death differ across vaccination profiles that had a different number of shots and types of vaccines. Funding: This study did not involve any funding.

Integrated metabolomics and network analysis reveal changes in lipid metabolisms of tripterygium glycosides tablets in rats with collagen-induced arthritis.

Tripterygium glycosides tablets (TGT) are the commonly used preparation for rheumatoid arthritis (RA). However, the changes in TGT on RA are still unclear at the metabolic level. This study aimed to reveal the biological processes of TGT in collagen-induced arthritis (CIA) rats through integrated metabolomics and network analysis. First, the CIA model in rats was established, and the CIA rats were given three doses of TGT. Then, the endogenous metabolites in the serum from normal rats, CIA rats, and CIA rats treated with varying doses of TGT were detected by UHPLC-QTOF-MS/MS. Next, univariate and multivariate statistical analyses were performed to find the differential metabolites. Finally, differential metabolites, metabolic pathways, and hub genes were analyzed integrally to reveal the biological processes of TGT in CIA rats. The paw diameter, arthritis score, immunoglobulin G (IgG) concentration, CT image, and histological assay showed that TGT had evident therapeutic effects on CIA rats. Untargeted metabolomics revealed that TGT could ameliorate the down-regulation of lipid levels in CIA rats. Four key differential metabolites were found including LysoP(18:0), LysoPA(20:4), LysoPA(18:2), and PS(O-20:0/17:1). The glycerophospholipid metabolic pathway was perturbed in treating CIA with TGT. A total of 24 genes, including PLD1, LPCAT4, AGPAT1, and PLA2G4A, were found to be the hub genes of TGT in CIA rats. In conclusion, the integrated analysis provided a novel and holistic perspective on the biological processes of TGT in CIA rats, which could give helpful guidance for further TGT on RA. Future studies based on human samples are necessary.

Spectrum of Autoimmune Liver Disease and Real-World Treatment Experience from a Tertiary Care Hospital.

Background and aims: Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India. Methods: A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC. Results: Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000-1.003], P = 0.034), high albumin (OR 1.91 [1.05-3.48], P = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33-0.91], P = 0.020) predicted complete response. Conclusion: AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response.

Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis - a case series.

Background: The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti-B cell activating factor, belimumab. The first three patients had concomitant Sjögren's disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren's disease. Aims and methods: To retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren's disease treated with the anti-BAFF therapy belimumab at the University Hospital in Bern, Switzerland. Results: In all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren's disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time. Conclusions: Belimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging.

A Case of Hypophysitis Associated With SARS-CoV-2 Vaccination.

Background/Objective: Although SARS-CoV-2 vaccines have been developed with multiple novel technologies and rapidly disseminated worldwide, the full profile of adverse effects has not been known. Recently, there are sporadic but increasing reports of endocrinopathy in relation to SARS-CoV-2 vaccination. Here we report a rare case of hypophysitis with acute onset of diabetes insipidus, immediately after SARS-CoV-2 vaccination. Case Report: A 48-year-old female patient had been in her usual state of health until she received the first SARS-CoV-2 vaccine. Two days after vaccination, she started to have flu-like symptoms, including severe headache and myalgia as well as persistent headache, polydipsia, and polyuria. She was diagnosed with diabetes insipidus, and magnetic resonance imaging revealed thickening of the pituitary stalk. Three months after vaccination, her symptoms had somewhat improved, but she still had pituitary stalk thickening on magnetic resonance imaging. Discussion: Given the timing of the occurrence of diabetes insipidus, we believe that the patient's hypophysitis may be associated with SARS-CoV-2 vaccination. We also found 19 cases of endocrinopathy after SARS-CoV-2 vaccination by literature search. The reported endocrine organs were the thyroid, pituitary, and adrenals. Twelve cases of diabetes were also reported. Among 3 pituitary cases, diabetes insipidus was reported only in our case. Conclusion: We report a rare case of SARS-CoV-2 vaccine-triggered hypophysitis, which led to diabetes insipidus. SARS-CoV-2 vaccine-related endocrinopathy seems, indeed, possible. Endocrinopathy is associated with infrequent complications; however, it may be underestimated in the post-SARS-CoV-2-vaccinated population. Further studies are warranted to better understand SARS-CoV-2 vaccine-related endocrinopathy.

SARS-CoV-2 seroprevalence and social inequalities in different subgroups of healthcare workers in Rio de Janeiro, Brazil.

BACKGROUND: COVID-19 has exacerbated health inequalities worldwide. Yet, such a perspective has not been investigated in specific healthcare workers and their resulting inclusion as a priority group for vaccination have been an important focus of political and social discussion. This study aimed at investigating whether SARS-CoV-2-seropositivity in healthcare workers in a public hospital in Rio de Janeiro, Brazil, was influenced by social determinants of health and the social vulnerability in subgroups of workers. METHODS: A serological survey was conducted in 1,154 healthcare workers in June and July 2020. The association between the serological test results for detection of IgG antibodies to SARS-CoV-2 and socioeconomic, occupational characteristics and transportation used by the workers to commute was assessed using the Pearson´s chi-square test and Cramer's V. FINDINGS: Overall, the serum prevalence for the virus in the healthcare workers was 30% (342/1141). Non-white workers (208/561) with lower income (169/396) and schooling (150/353), as well as users of the mass transportation system (157/246) showed the highest infection rates. Importantly they mostly corresponded to hospital support workers (131/324), in particular the cleaning personnel (42/70). Accordingly, income, schooling and work modality appeared as negative predictors, as ascertained by forest plot analysis. INTERPRETATIONS: The data clearly illustrate the inequality in SARS-CoV-2 infection in the Brazilian population, comprising even healthcare workers of the Brazilian unified health system.

Pre-existing T cell immunity determines the frequency and magnitude of cellular immune response to two doses of mRNA vaccine against SARS-CoV-2.

Little is known about the factors associated with lack of T-cell response to mRNA vaccines against SARS-CoV-2. In a prospective cohort of 61 health care workers (HCWs), 21% and 16% after the first dose of mRNA BNT162b vaccine, and 12% and 7% after the second dose, showed lack of CD4+ and CD8+ T-cell response, respectively. Pre-existing T-cell immunity, due to past infection (46%) or cross-reactive cellular response (26%), was significantly associated with T-cell response in frequency (CD4+ T-cell, 100% vs 82% after two doses; p = 0.049) and in the magnitude of T-cell response during follow up. Furthermore, baseline CD4+ T-cell correlated positively with the titer of specific IgG-antibodies after first and second vaccine dose. Our data demonstrate that cross-reactive T-cells correlate with a better cellular response as well as an enhanced humoral response, and we confirm the close correlation of humoral and cellular response after mRNA vaccination.

Evaluation of the health status outcome among inpatients treated for Amphetamine Addiction.

Amphetamine is one of the most abuser drugs in Saudi Arabia. The aim of this study was to evaluate health status outcome at baseline and after detoxification in amphetamine users through the evaluation of the body mass index, renal function tests, cardiac biomarkers, gonadal hormonal levels, and oxidative stress markers. A cross-sectional study was conducted on 90 participants. Sixty participants were hospitalized patients for treatment of addiction and 30 participants were healthy volunteers. This study was performed at a psychiatric and rehabilitation center, in Qassim region, in the Kingdom of Saudi Arabia. Participants were divided into: group I = control; group II = amphetamine users and group III = amphetamine plus cannabis users. Socio-demographic data was collected. The urinary amphetamine level, Severity Dependence Scale (SDS), body mass index (BMI), vital signs; serum levels of troponin T (TnT), immunoglobulin M (IgM), immunoglobulin G (IgG), luteinizing Hormone (LH), testosterone Hormone (TSTS), urea, creatinine, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured on admission and after detoxification. The results showed that the BMI was significantly decreased while, vital signs such as heart rate, blood pressure and respiratory rate were significantly increased in all abusers and returned to normal values after the detoxification period. The cardiac biomarker troponin T was significantly increased and reversed after detoxification. The immune system was evaluated through assessing serum levels of immunoglobulin (Ig) M and IgG. The immune system remained immunocompromised in drug users, and IgM and IgG levels did not reach the level of control group after treatment. Luteinizing and testosterone hormones were evaluated. Both hormones were increased on admission and improved after the detoxification period. Renal function showed no significant differences between drug users and the control group. In the evaluation of the antioxidant system, there was a significant increase in serum MDA, SOD, GPx, and CAT levels compared to healthy controls. After the detoxification phase, these oxidative stress biomarkers still remained elevated. The current results have shown the addiction of amphetamine and cannabis exert detrimental effects on different body organs and the exert major consequences on the health status of drug users. The present study showed that, there was no improvement in the levels of oxidative stress biomarkers, although an improvement was observed in the other parameters after the detoxification phase.

Feasibility of home-based ELISA capillary blood self-testing for anti-SARS-CoV-2 antibodies.

Objectives: Serological assays for the presence of anti-SARS-CoV-2 antibodies are crucially needed for research and monitoring of the SARS-CoV-2 pandemic. Antibodies are reliability detected in capillary blood, a minimally invasive and cost-effective alternative to venous blood testing. However, there is a limited knowledge on feasibility of capillary blood self-sampling. This study compared the feasibility of capillary blood self-testing in people aged less than 65 vs. people aged 65 or more. A secondary aim was to investigate the performance of the Hem-Col® (no additive) device compared to venous blood testing. Design and methods: Data were collected in a prospective study in Switzerland (n = 106). Capillary blood was collected using the Hem-Col® (no additive) device. Feasibility was assessed using 1) collecting the recommended amount of capillary blood and 2) achieving all steps of capillary blood collection. A sample of 5 ml of venous blood was also collected. Results: For the primary objective, 86.2%/62.1% of patients aged less than 65 collected the recommended amount of capillary blood/achieved all steps vs. 62.5%/39.6% of patients aged 65 or more (p = .006/p = .022). For the secondary objective, the correlation between capillary and venous blood was r = 0.992 and kappa = 1. Conclusions: Capillary blood self-testing appeared as a feasible and reliable alternative to venous blood testing. Such alternative would improve access to serological testing and spare health care resources. However, the difference between age groups should be considered when using self-sampling devices. Help should be developed for older people, such as phone counseling or encouraging asking younger family members for help.

Ocular manifestations and full house membranous nephropathy as a rare presentation of secondary syphilis.

Syphilis is an often-overlooked diagnosis and without timely diagnosis and treatment, can have serious repercussions. Although its prevalence had decreased with the introduction of penicillin, it has had a resurgence over the years. Discerning the proper patient population to test for syphilis should be led by a patient's risk factors. Here, we present a patient diagnosed with secondary syphilis, with initial concern for a possible concomitant lupus diagnosis. He initially presented with visual symptoms and optic nerve inflammation, along with a positive antinuclear antibody (ANA). Due to an unprotected sexual encounter, there was suspicion for a sexually transmitted infection. Testing revealed reactive rapid plasma reagin (RPR) (≥1:256 titer) and reactive treponemal antibody, consistent with active syphilis. He was immediately started on intravenous Penicillin G. Lumbar puncture was consistent with a reactive venereal disease research laboratory test (VDRL). Urinalysis revealed nephrotic range proteinuria, which along with the positive ANA, prompted renal biopsy. This showed membranous nephropathy with full house staining, which is seen primarily in lupus nephritis and further confounded the diagnosis. He completed a two-week course of penicillin and steroids inpatient with clinical improvement. On follow up, his RPR improved (≥1:64 titer), and lumbar puncture showed a non-reactive VDRL. Due to the resolution of proteinuria, decrease of the ANA titer and no further positive testing or symptoms convincing for a concomitant rheumatologic disorder, the presence of lupus was collectively determined to be of low concern. and the sole diagnosis of secondary syphilis was made.

SARS-CoV-2/COVID-19 associated pediatric acute-onset neuropsychiatric syndrome a case report of female twin adolescents.

"Pediatric acute-onset neuropsychiatric syndrome", or PANS, is a rare syndrome characterized by an acute onset of obsessive-compulsive disorder (OCD), and/or severely restricted food intake accompanied by a variety of neuropsychiatric symptoms. To our knowledge, this is the first case report of twin adolescents with COVID-19-associated PANS. Dizygotic twin sisters in late teens, with abrupt and acute onset of severely restrictive food intake, weight loss, OCD, anxiety with intermittent auditory and visual hallucinations, depression, attention deficit, and sleep disturbances, simultaneously accompanied by milder neurologic symptoms such as hand tremor, tinnitus, dizziness, headache, and weakness of proximal muscles, were applied to child and adolescent psychiatry clinic. The only relevant agent underlying those neuropsychiatric and somatic complaints was COVID-19, and it was validated with laboratory testing, such as positive IgG titers of SARS-CoV-2 and negative biomarkers for other possible bacterial or viral agents. Generalized epileptic anomaly and a vermian/folial atrophy in the cerebellum were detected in further evaluations. Treatment options consisted of psychotropic agents, antibiotics, antiepileptic, and intravenous immunoglobulin transfusion finely treated the neuropsychiatric symptoms. Clinicians should consider SARS-CoV-2 as a potential agent, when a child presents with abrupt onset, dramatic neuropsychiatric symptoms also consisting of PANS, even in asymptomatic patients or with mild respiratory symptoms.

A case series sharing novel experience of treating viral pandemic cases of morbid, mid aged, mild, moderate & severe grade with only Ayurvedic Medicines.

In ongoing viral pandemic named as COVID-19 also Severe Acute Respiratory illness (SARI) or Flue Like illness (FLI) reported surging in many cities of India and many of the patients opted for traditional medicine, in spite of they have been given a option of contemporary line of treatment instructed by health authorities, they opted to take traditional indian medicine that is Ayurvedic medicine. Present case series is a same novel experience of early diagnosing and treating mid aged, morbid individuals who took only Ayurvedic treatment and could get out of the disease without any complications. This case series had 10 mid aged, morbid patients with maximum symptoms of COVID-19 disease and their hemogram and CRP was suggestive of moderate to severe type COVID-19/FLI/SARI. They were diagnosed by contemporary methods of pathology and treated with Ayurvedic classical medicines Tamra Sinduradi Yoga and Bhunimbadi Kwath for 20 days along with continuing the medicines for their ongoing morbidities. All 10 patients showed recoveries without any complications, they reduced their all symptoms, drastic reduction in their CRP and corrections in their hemograms were observed and also they showed any complications neither physically nor in their pathological tests. Hence it can be concluded that early diagnosis and treating it with Ayurvedic medicine can manage viral pandemic issue in a very successful way.