Anterior abdominal wall swelling as incarcerated Spigelian hernia in an elderly female: A diagnostic dilemma.

Spigelian hernias are difficult to detect and palpate during physical examination due to their deeper location. They can be asymptomatic or present with acute complications such as incarceration, strangulation, or bowel obstruction. Here we present a case of a 58-year-old female with history of palpable swelling over the left iliac fossa region with abdominal distension. A computed tomography with oral contrast revealed features suggestive of incarcerated Spigelian hernia with small bowel obstruction, which was later managed with laparoscopic ventral hernia repair and repair of seromuscular tear of the small bowel. Computed tomography is the gold standard for diagnosing the condition and assessing bowel status. Conservative treatment is not effective due to the high likelihood of complications, and surgery is the mainstay of management. The approach to surgery depends on the patient's characteristics, the type of hernia, and the surgeon's experience. Mesh repair is advocated regardless of approach.

Morphological changes in white blood cells in systemic inflammatory response syndrome (SIRS) with and without sepsis: An observational study.

Background: This is an observational study which aims to research morphological changes of white blood cells in patients with Systemic Inflammatory Response Syndrome (SIRS) with and without sepsis and evaluate morphological changes in white blood cells as predictors of sepsis. Methods: Patients aged 18 years or more with SIRS with sepsis and SIRS without sepsis were included and those with haematological disorders or pregnant patients were excluded. A total of 52 patients with SIRS with sepsis and 32 patients of SIRS without sepsis were included. Peripheral blood smear was prepared from the venous blood sample drawn. The presence of toxic granules, cytoplasmic vacuoles, and Dohle bodies in both cases of SIRS with sepsis without sepsis were assessed and it was compared with culture-positive sepsis and shock. Results: The difference in the presence of toxic granules (55.8% vs. 12.5%; p <0.001), cytoplasmic vacuoles (30.8% vs. 6.3%; p -0.012), and Dohle bodies (17.3% vs. 0%; p = 0.012) was significantly higher in the SIRS with sepsis group, compared to the SIRS without sepsis group. In the subgroup analysis of patients in the sepsis group, it was observed that patients with positive blood culture (9%) had a significantly higher proportion of toxic granules (100% vs. 51.1%; p=0.059), cytoplasmic vacuoles (40% vs. 29.8%; p=0.637) and Dohle bodies (40% vs. 14.9%; p=0.202). However, these differences were not statistically significant. Conclusion: Toxic granules and cytoplasmic vacuoles in the neutrophils of patients with SIRS with sepsis were found more frequently, compared to patients of SIRS without sepsis. Dohle bodies were found only in patients with sepsis and not in those with SIRS without sepsis.

Barriers and enablers of breastfeeding in mother-newborn dyads in institutional settings during the COVID-19 pandemic: A qualitative study across seven government hospitals of Delhi, India.

Introduction: The COVID-19 pandemic disrupted newborn care and breastfeeding practices across most healthcare facilities. We undertook this study to explore the barriers and enablers for newborn care and breastfeeding practices in hospitals in Delhi, India for recently delivered mother (RDM)-newborn dyads during the first wave of the COVID-19 pandemic (2020) and inductively design a "pathway of impaction" for informing mitigatory initiatives during the current and future pandemics, at least in the initial months. Materials and methods: We used an exploratory descriptive design (qualitative research method) and collected information from seven leading public health facilities in Delhi, India. We conducted separate interviews with the head and senior faculty from the Departments of Pediatrics/Neonatology (n = 12) and Obstetrics (n = 7), resident doctors (n = 14), nurses (labor room/maternity ward; n = 13), and RDMs (n = 45) across three profiles: (a) COVID-19-negative RDM with healthy newborn (n = 18), (b) COVID-19-positive RDM with healthy newborn (n = 19), and (c) COVID-19 positive RDM with sick newborn needing intensive care (n = 8) along with their care-giving family members (n = 39). We analyzed the data using grounded theory as the method and phenomenology as the philosophy of our research. Results: Anxiety among clients and providers, evolving evidence and advisories, separation of the COVID-positive RDM from her newborn at birth, providers' tendency to minimize contact duration and frequency with COVID-positive mothers, compromised counseling on breastfeeding, logistic difficulties in expression and transportation of COVID-positive mother's milk to her baby in the nursery, COVID restrictions, staff shortage and unavailable family support in wards and nursery, and inadequate infrastructure were identified as major barriers. Keeping the RDM-newborn together, harmonization of standard operating procedures between professional associations and within and between departments, strategic mobilization of resources, optimization of human resources, strengthening client-provider interaction, risk triaging, leveraging technology, and leadership-in-crisis-situations were notable enablers. Conclusion: The separation of the RDM and newborn led to a cascade of disruptions to newborn care and breastfeeding practices in the study institutions. Separating the newborn from the mother should be avoided during public health emergencies unless there is robust evidence favoring the same; routine institutional practices should be family centered.

Differential pathogenesis of SARS-CoV-2 variants of concern in human ACE2-expressing mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic resulting in millions of deaths worldwide. Increasingly contagious variants of concern (VoC) have fueled recurring global infection waves. A major question is the relative severity of disease caused by the previous and currently circulating variants of SARS-CoV-2. In this study, we evaluated the pathogenesis of SARS-CoV-2 variants in human ACE-2-expressing (K18-hACE2) mice. Eight-week-old K18-hACE2 mice were inoculated intranasally with a representative virus from the original B.1 lineage, or the emerging B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta) or B.1.1.529 (omicron) lineages. We also infected a group of mice with the mouse-adapted SARS-CoV-2 (MA10). Our results demonstrate that B.1.1.7, B.1.351 and B.1.617.2 viruses are significantly more lethal than B.1 strain in K18-hACE2 mice. Infection with B.1.1.7, B.1.351 and B.1.617.2 variants resulted in significantly higher virus titers in the lungs and brain of mice compared to the B.1 virus. Interestingly, mice infected with the B.1.1.529 variant exhibited less severe clinical signs and high survival rate. We found that B.1.1.529 replication was significantly lower in the lungs and brain of infected mice in comparison to other VoC. Transcription levels of cytokines and chemokines in the lungs of the B.1.1.529-infected mice were significantly less when compared to those challenged with the B.1.1.7 virus. Together, our data provide insights into the pathogenesis of the previous and circulating SARS-CoV-2 VoC in mice.

Influenza virus-like particle-based hybrid vaccine containing RBD induces immunity against influenza and SARS-CoV-2 viruses

Several approaches have produced an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the influence of immune responses induced by other vaccinations on the durability and efficacy of the immune response to SARS-CoV-2 vaccine is still unknown. We have developed a hybrid vaccine for SARS-CoV-2 and influenza viruses using influenza virus-like particles (VLP) incorporated by protein transfer with glycosylphosphatidylinositol (GPI)-anchored SARS-CoV-2 S1 RBD fused to GM-CSF as an adjuvant. GPI-RBD-GM-CSF fusion protein was expressed in CHO-S cells, purified and incorporated onto influenza VLPs to develop the hybrid vaccine. Our results show that the hybrid vaccine induced a strong antibody response and protected mice from both influenza virus and mouse-adapted SARS-CoV-2 challenges, with vaccinated mice having significantly lower lung viral titers compared to naive mice. These results suggest that the hybrid vaccine strategy is a promising approach for developing multivalent vaccines to prevent influenza A and SARS-CoV-2 infections.

SARS-CoV-2 variants of concern infect the respiratory tract and induce inflammatory response in wild-type laboratory mice

The emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern poses a major threat to the public health due to possible enhanced virulence, transmissibility and immune escape. These variants may also adapt to new hosts in part through mutations in the spike protein. In this study, we evaluated the infectivity and pathogenicity of SARS-CoV-2 variants of concern in wild-type C57BL/6 mice. Six-week-old mice were inoculated intranasally with a representative virus from the original B.1 lineage or emerging B.1.1.7 and B.1.351 lineages. We also infected a group of mice with a mouse-adapted SARS-CoV-2 (MA10). Viral load and mRNA levels of multiple cytokines and chemokines were analyzed in the lung tissues on day 3 after infection. Our data show that unlike the B.1 virus, the B.1.1.7 and B.1.351 viruses are capable of infecting C57BL/6 mice and replicating at high concentrations in the lungs. The B.1.351 virus replicated to higher titers in the lungs compared to the B.1.1.7 and MA10 viruses. The levels of cytokines (IL-6, TNF-, IL-1{beta}) and chemokine (CCL2) were upregulated in response to the B.1.1.7 and B.1.351 infection in the lungs. Overall, these data indicate a greater potential for infectivity and adaptation to new hosts by emerging SARS-CoV-2 variants.

Neuroinvasion and encephalitis following intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can cause neurological disease in humans, but little is known about the pathogenesis of SARS-CoV-2 infection in the central nervous system. Herein, using K18-hACE2 mice, we demonstrate that SARS-CoV-2 neuroinvasion and encephalitis is associated with mortality in these mice. Intranasal infection of K18-hACE2 mice with 105 plaque-forming units of SARS-CoV-2 resulted in 100% mortality by day 6 after infection. The highest virus titers in the lungs were observed at day 3 and declined at days 5 and 6 after infection. In contrast, very high levels of infectious virus were uniformly detected in the brains of all the animals at days 5 and 6. Onset of severe disease in infected mice correlated with peak viral levels in the brain. SARS-CoV-2-infected mice exhibited encephalitis hallmarks characterized by production of cytokines and chemokines, leukocyte infiltration, hemorrhage and neuronal cell death. SARS-CoV-2 was also found to productively infect cells within the nasal turbinate, eye and olfactory bulb, suggesting SARS-CoV-2 entry into the brain by this route after intranasal infection. Our data indicate that direct infection of CNS cells together with the induced inflammatory response in the brain resulted in the severe disease observed in SARS-CoV-2-infected K18-hACE2 mice.

The FDA-approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells

SARS-COV-2 has recently emerged as a new public health threat. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Treatment of cells with auranofin resulted in a 95% reduction in the viral RNA at 48 hours after infection. Auranofin treatment dramatically reduced the expression of SARS-COV-2-induced cytokines in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Auranofin has a well-known toxicity profile and is considered safe for human use.

A study of the PfNT3 in Plasmodium falciparum

Previous genetic studies demonstrated that survival and proliferation of Plasmodium falciparum parasites is dependent on salvage of essential purines from the host. Plasmodium falciparum, the causative agent of the most lethal form of human malaria lacks the enzymes required for de novo synthesis of purines. Analysis of the hypothetical nucleoside/nucleobase transporter protein, the gene product of PfNT3 (PF14_0662) gene in P. falciparum parasites was carried out by localisation, in view of a novel chemotherapeutic target. Immunoblotting, immunofluorescent and immunoelectron microscopic localization of PfNT3 was demonstrated using polyclonal antiserum in in vitro cultured Plasmodium falciparum parasites, propagated in human red blood cells. PfNT3 protein, the translated product of PfNT3 gene was detected in intraerythrocytic ring, trophozoite, and schizont stages. PfNT3 was localized primarily to the PPM (Parasite Plasma Membrane). The endogenous PfNT3 putative nucleoside transporter with the predominant location to the parasite plasma membrane may serve not only as routes for targeting of purine analogs/cytotoxic agents into the intracellular parasite but may also serve as drug targets. Being genome encoded the vital transporter protein can be prevented from expression by silencing of the gene, validating it to be a novel drug target.

Prevalence of inflammatory markers (high-sensitivity C-reactive protein, nuclear factor-κB, and adiponectin) in Indian patients with type 2 diabetes mellitus with and without macrovascular complications.

BACKGROUND: Atherosclerosis is more prevalent in subjects with diabetes mellitus. Recent evidence suggests that diabetic atherosclerosis is not simply a disease of hyperlipidemia, but is also an inflammatory disorder. Our aim was to study the prevalence of inflammatory markers such as high-sensitivity C-reactive protein (hsCRP), adiponectin, and nuclear factor-κB (NF-κB) expression, in peripheral blood mononuclear cells in Indian patients with type 2 diabetes mellitus (T2DM) with and without macrovascular disease (MVD). METHODS: A total of 29 consecutive cases of T2DM with proven MVD (group A), 28 matched cases without MVD (group B), and 14 healthy controls (group C) were evaluated for the clinical parameters fasting blood glucose (FBG), 2-h postprandial blood glucose (PPBG), glycosylated hemoglobin (HbA1c), lipid profile, and the above-mentioned inflammatory markers. RESULTS: Diabetic subjects with T2DM had higher hsCRP and NF-κB expression and lower values of adiponectin compared to healthy controls. Group A had significantly higher serum hsCRP than group B (P=0.0001) despite comparable values of BMI, FBG, 2-h PPBG, HbA1c, and lipid parameters. Group A had significantly higher serum hsCRP and NF-κB expression and significantly lower levels of adiponectin than group C (P=0.0001, 0.007, and 0.02, respectively). In Group A, serum adiponectin negatively correlated with NF-κB expression. In Group B, adiponectin values correlated negatively with both FBG and 2-h PPBG. CONCLUSIONS: Indian subjects with T2DM with or without MVD had higher hsCRP and lower adiponectin values as compared to healthy controls, whereas hsCRP was significantly higher in those with MVD, suggesting that our patients with T2DM were in a proinflammatory state.

Serum total PSA and free PSA in breast tumors.

Now a days measurement of molecular forms of PSA has gained importance in clinical practice. Several studies have demonstrated the production of PSA in female tissues, such as breast. The present piece of work has been undertaken with an objective to estimate the relative proportion of the molecular forms of PSA in serum along with serum testosterone in benign and malignant breast tumor cases and to analyze their association with the severity of the disease process 34 malignant and 26 benign breast disease cases along with 33 healthy controls of same age group were enrolled in this study for evaluation. Serum testosterone was measured by ELISA, whereas serum total PSA (TPSA) and free PSA (FPSA) were estimated by electrochemiluminescence immunoassay. A significant rise of fasting plasma glucose along with prominent dyslipidemia was observed in breast tumor cases. Marked rise in serum testosterone as well as TPSA and FPSA was documented in both benign and malignant breast tumor cases. Serum testosterone revealed a significant positive association with both TPSA and FPSA pointing towards an etiological association between them. However, surgical removal of tumor mass resulted in a marked decline of presurgical value of both TPSA and FPSA with a non-significant fall in serum testosterone revealing tumor tissue as the source of FPSA and TPSA. Thus, estimation of PSA provides prognostic information that may assist in future treatment.

Effect of Metformin on Hormonal and Biochemical Profile in PCOS Before and After Therapy.

Insulin resistance and the resultant hyperinsulinemia exacerbate the reproductive abnormalities of Polycystic Ovarian Syndrome by increasing ovarian androgen productions and decreasing serum sex hormone binding globulin. The present study was conducted to estimate serum insulin and testosterone level in 44 PCOS cases and 32 control patients. Simultaneously the role of metformin (an insulin sensitizing agent) in modulating insulin resistance and serum androgen level was also analyzed. A significant rise in serum insulin and testosterone (P < 0.001) was observed in cases in comparison to control. Fasting Plasma Glucose to insulin ratio, a marker of insulin resistance revealed a significant fall in PCOS group. Follow up of cases with metformin for 3 months revealed a significant fall in serum insulin (P < 0.05) with improvement in insulin resistance along with a nonsignificant fall in testosterone level. Serum insulin registered a significant positive correlation (P < 0.05) with serum testosterone revealing its etiological association. Thus administration of drugs ameliorating insulin levels is expected to provide new therapeutic modality for PCOS.