Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity.

Multidimensional single-cell analyses of T cells have fueled the debate about whether there is extensive plasticity or 'mixed' priming of helper T cell subsets in vivo. Here, we developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of helper T cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system (CNS) in a model of multiple sclerosis (MS) are distinct. i-T cells were Cxcr6+, and m-T cells expressed P2rx7. Notably, m-T cells infiltrated white matter, while i-T cells were also recruited to gray matter. Therefore, we propose that the definition of helper T cell subsets by their site of priming may guide an advanced understanding of helper T cell biology in health and disease.

Myeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity.

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have been characterized in the context of malignancies. Here we show that PMN-MDSCs can restrain B cell accumulation during central nervous system (CNS) autoimmunity. Ly6G+ cells were recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interacted with B cells that produced the cytokines GM-CSF and interleukin-6 (IL-6), and acquired properties of PMN-MDSCs in the CNS in a manner dependent on the signal transducer STAT3. Depletion of Ly6G+ cells or dysfunction of Ly6G+ cells through conditional ablation of STAT3 led to the selective accumulation of GM-CSF-producing B cells in the CNS compartment, which in turn promoted an activated microglial phenotype and lack of recovery from EAE. The frequency of CD138+ B cells in the cerebrospinal fluid (CSF) of human subjects with multiple sclerosis was negatively correlated with the frequency of PMN-MDSCs in the CSF. Thus PMN-MDSCs might selectively control the accumulation and cytokine secretion of B cells in the inflamed CNS.

Supramolecular complexation of C60 with branched polyethylene.

Fullerene C60 is a ubiquitous material for application in organic electronics and nanotechnology, due to its desirable optoelectronic properties including good molecular orbital alignment with electron-rich donor materials, as well as high and isotropic charge carrier mobility. However, C60 possesses two limitations that hinder its integration into large-scale devices: (1) poor solubility in common organic solvents leading to expensive device processing, and (2) poor optical absorbance in the visible portion of the spectrum. Covalent functionalization has long been the standard for introducing structural tunability into molecular design, but non-covalent interactions have emerged as an alternative strategy to tailor C60-based materials, offering a versatile and tuneable alternative to novel functional materials and applications. In this work, we report a straightforward non-covalent functionalization of C60 with a branched polyethylene (BPE), which occurs spontaneously in dilute chloroform solution under ambient conditions. A detailed characterization strategy, based on UV-vis spectroscopy and size-exclusion chromatography was performed to verify and investigate the structure of the C60+BPE complex. Among others, our work reveals that the supramolecular complex has an order of magnitude higher molecular weight than its C60 and BPE constituents and points towards oxidation as the driving force behind complexation. The C60+BPE complex also possesses significantly broadened optical absorbance compared to unfunctionalized C60, extending further into the visible portion of the spectrum. This non-covalent approach presents an inexpensive route to address the shortcomings of C60 for electronic applications, situating the C60+BPE complex as a promising candidate for further investigation in organic electronic devices.

Role of Inferior Vena Cava Collapsibility Index in the Prediction of Hypotension Associated With Central Neuraxial Block: A Prospective Observational Study.

BACKGROUND: There are only a few studies on perioperative use of inferior vena cava collapsibility index (IVCCI) to predict hypotension after anesthesia. The study aimed to evaluate IVCCI as predictor of hypotension in patients receiving central neuraxial block (CNB) for elective surgery. METHOD: One hundred patients of ASA grade I/II, aged 18-60 years undergoing elective surgery under CNB were enrolled. Ultrasound IVC examination was performed preoperatively and the patients were allocated to Group C (Collapsing group: IVCCI ≥50%) or Group NC (Non-Collapsing group: IVCCI <50%). Thereafter, in the operation theatre, the patient was given CNB and observed for development of hypotension. The hypotension was treated with additional fluid bolus (5 mL kg-1 over 10 minutes) and/or vasopressor (mephentramine 6 mg IV). The primary objective was to compare the incidence of hypotension; the secondary objective was to compare the fluid and vasopressor requirement in the Groups C and NC. RESULT: Six patients were excluded from study due to poor visualization of IVC. The mean IVCCI for Group C (n = 53) was 56.06 ± 4.62% and Group NC (n = 41) was 34.01 ± 8.94%. The incidence of hypotension was 56.60% (20/53) in Group C and 4.87% (2/41) in Group NC (P < .001). The vasopressor and fluid requirement was also statistically significantly higher in Group C compared with Group NC (P < .001). CONCLUSION: Preoperative ultrasound assessment of IVCCI is useful in predicting hypotension after CNB in patients receiving CNB for elective surgery.

Humoral Immune Responses and Hepatitis B Infection.

BACKGROUND: Chronicity or seroclearance of hepatitis B virus (HBV) antigens is determined by the host immune responses. Current approaches to treat HBV patients are based on inhibition of replication using different antivirals (nucleoside or nucleotide analogs) as monotherapy, or along with immune modulators as combination therapy is being used worldwide for reducing the viral load. Understanding the role of immune cellular therapies with currently available treatments for persistent viral-mediated responses in HBV patients is unexplored. However, the generation of antibodies against a surface (HBs) and envelop (HBe) antigen of hepatitis B remains an issue for future studies and needs to be explored. SUMMARY: Humoral immunity, specifically T follicular helper (TFh) cells, may serve as a target for therapy for HBsAg seroconversion. In this review, we have been engrossed in the importance and role of the humoral immune responses in CHBV infection and vertical transmission. Key Message: TFh cells have been suggested as the potential target of immunotherapy which lead to seroconversion of HBe and HBs antigens of HBV. HBsAg seroconversion and eradication of covalently closed circular DNA are the main challenges for existing and forthcoming therapies in HBV infection.

RelB Deficiency in Dendritic Cells Protects from Autoimmune Inflammation Due to Spontaneous Accumulation of Tissue T Regulatory Cells.

Foxp3+ regulatory T cells are well-known immune suppressor cells in various settings. In this study, we provide evidence that knockout of the relB gene in dendritic cells (DCs) of C57BL/6 mice results in a spontaneous and systemic accumulation of Foxp3+ T regulatory T cells (Tregs) partially at the expense of microbiota-reactive Tregs. Deletion of nfkb2 does not fully recapitulate this phenotype, indicating that alternative NF-κB activation via the RelB/p52 complex is not solely responsible for Treg accumulation. Deletion of RelB in DCs further results in an impaired oral tolerance induction and a marked type 2 immune bias among accumulated Foxp3+ Tregs reminiscent of a tissue Treg signature. Tissue Tregs were fully functional, expanded independently of IL-33, and led to an almost complete Treg-dependent protection from experimental autoimmune encephalomyelitis. Thus, we provide clear evidence that RelB-dependent pathways regulate the capacity of DCs to quantitatively and qualitatively impact on Treg biology and constitute an attractive target for treatment of autoimmune diseases but may come at risk for reduced immune tolerance in the intestinal tract.

Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus.

Stable expression of Foxp3 in regulatory T cells (Tregs) depends on DNA demethylation at the Treg-specific demethylated region (TSDR), a conserved, CpG-rich region within the Foxp3 locus. The TSDR is selectively demethylated in ex vivo Tregs purified from secondary lymphoid organs, but it is unclear at which stage of Treg development demethylation takes place. In this study, we show that commitment to a stable lineage occurred during early stages of murine thymic Treg development by engraving of lineage-specific epigenetic marks in parallel with establishment of a Treg-specific gene expression profile. TSDR demethylation was achieved through an active mechanism and involved enzymes of the ten-eleven-translocation family and hydroxylation of methylated cytosines, a modification that is implicated as an initiating step of mitosis-independent DNA demethylation pathways and has not yet been observed at specific loci during immune cell differentiation. Together, our results demonstrate that initiating TSDR demethylation during early stages of thymic Treg development commences stabilization of Foxp3 expression and guarantees full functionality and long-term lineage stability of Tregs.

Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function.

Numerous reports have demonstrated that CD4(+)CD25(+) regulatory T cells (Tregs) from individuals with a range of human autoimmune diseases, including type 1 diabetes, are deficient in their ability to control autologous proinflammatory responses when compared with nondiseased, control individuals. Treg dysfunction could be a primary, causal event or may result from perturbations in the immune system during disease development. Polymorphisms in genes associated with Treg function, such as IL2RA, confer a higher risk of autoimmune disease. Although this suggests a primary role for defective Tregs in autoimmunity, a link between IL2RA gene polymorphisms and Treg function has not been examined. We addressed this by examining the impact of an IL2RA haplotype associated with type 1 diabetes on Treg fitness and suppressive function. Studies were conducted using healthy human subjects to avoid any confounding effects of disease. We demonstrated that the presence of an autoimmune disease-associated IL2RA haplotype correlates with diminished IL-2 responsiveness in Ag-experienced CD4(+) T cells, as measured by phosphorylation of STAT5a, and is associated with lower levels of FOXP3 expression by Tregs and a reduction in their ability to suppress proliferation of autologous effector T cells. These data offer a rationale that contributes to the molecular and cellular mechanisms through which polymorphisms in the IL-2RA gene affect immune regulation, and consequently upon susceptibility to autoimmune and inflammatory diseases.

Preparation, characterization and evaluation of ranitidine hydrochloride-loaded mucoadhesive microspheres.

BACKGROUND: Mucoadhesion enables localization of drugs to a defined region of the gastrointestinal tract through attractive interactions between polymers composing the drug delivery devices and the mucin layer of the intestinal epithelium. Thus, this approach can be used for enhancement of the oral bioavailability of the drug. OBJECTIVES: The current communication deals with the development of ranitidine hydrochloride-loaded chitosan-based mucoadhesive microspheres. MATERIAL AND METHODS: Microspheres were prepared by water-in-oil emulsion technique, using glutaraldehyde as a cross-linking agent. The effect of independent variables like stirring speed and polymer-to-drug ratio on dependent variables, i.e. percentage mucoadhesion, percentage drug loading, particle size and swelling index, was examined using a 3(2); factorial design. RESULTS: The microspheres were discrete, spherical, free-flowing and also showed high percentage drug entrapment efficiency (43-70%). An in vitro mucoadhesion test showed that the microspheres adhered strongly to the mucous layer for an extended period of time. The RC 4 batch exhibited a high percentage of drug encapsulation (70%) and mucoadhesion (75%). The drug release was sustained for more than 12 h. The drug release kinetics were found to follow Peppas' kinetics for all the formulations and the drug release was diffusion controlled. CONCLUSIONS: The preliminary results of this study suggest that the developed microspheres containing ranitidine hydrochloride could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.

Comparing the Biofilm Removal Capacity of NaOCl, Povidone-Iodine, Chlorhexidine, Curcumin, and Triphala as Endodontic Irrigants.

BACKGROUND AND AIM: A sessile multicellular organism that is immersed in a self-produced matrix of extracellular polymeric substances and has its cells firmly attached to a surface is referred to as a microbial biofilm. When it comes to pulp and periradicular pathosis, biofilms are crucial. To reduce the number of microorganisms in the root canal and assist in treating periapical pathosis, endodontic therapy must include decontamination of the system of tooth root canals through biomechanical preparation and irrigation of the root canal. This study compares sodium hypochlorite (NaOCl), povidone-iodine, chlorhexidine, curcumin, and triphala as endodontic irrigating solutions regarding their capacity to eliminate biofilm from root canals. MATERIALS AND METHODS: A total of 60 patients were included if they had pulpitis. Two specific samples (samples A and B) were chosen for analysis from a collection of samples so that their bacterial composition is most similar to that of acute pulpitis. The suspensions of bacterial cells from this polymicrobial culture have been collected from frozen stock and then regrown by inoculation on Columbia agar base (Basingstoke, UK) with the addition of vitamin K1, hemin, and 5% (v/v) calf blood. The pureness of the suspensions was assessed using colony morphology and Gram staining. Analytical profile index (API) 20A tests or automated test for bacteria (ATB) ID 32A tests were initially used to identify the isolates. These polymicrobial cultures' in vitro biofilms were developed using membrane filters made of cellulose nitrate. The tested irrigating solutions were as follows: 5.25% sodium hypochlorite, 10% triphala, 0.2% chlorhexidine gluconate, 10% povidone-iodine, and 5% curcumin (CUR). On the other hand, phosphate-buffered saline was taken as a control agent. RESULTS: As the standard of excellence in endodontic irrigation, NaOCl has eliminated all germs in sample A following 15 minutes of culture and in both of the specimens after 40 minutes. Iodine also eliminated all germs after 40 minutes of administration, indicating that it would be worth exploring using iodine as a potential endodontic irrigant. Iodine achieved total bacterial elimination after 40 minutes in both samples; however, it was less effective after 15 minutes. Our findings indicate that iodine solution is the most suitable alternative after the supremely effective NaOCl, although it requires longer contact times to generate the necessary and recognized broad-spectrum antibacterial properties, including in the case of biofilms. Furthermore, curcumin also showed significant results after NaOCl and iodine. CONCLUSION: The antibacterial potency of each studied irrigant was significant, supporting their usage in endodontics. It was observed that NaOCl has the maximum antibacterial activity.

To Evaluate Different Endodontic Instrumentation Systems Regarding Post-Operative Pain After Endodontic Therapy: A Clinical Study.

BACKGROUND: Despite substantial breakthroughs in instrumentation systems and pharmaceutical interventions, pain following endodontic therapy remains a serious concern. The effect of the type of endodontic instrumentation system in post-operative pain after endodontic therapy has been a matter of debate. AIM: To evaluate different endodontic instrumentation systems, namely Reciproc (GmbH, Munich), OneShape® (MicroMega, France), Protaper Gold (Dentsply Sirona, USA), and Hyflex® EDM (Coltène/Whaledent Inc., USA) file systems, regarding post-operative pain after endodontic therapy Methods and materials: The endodontic department treated healthy patients aged 20 to 50 years who were experiencing symptoms of irreparable pulpitis in one or more maxillary molars or mandibular molars. Five hundred was the determined size of the sample. The study participants were divided into five categories, each comprising 100 participants. These categories were: Category 1: Reciproc instrumentation system. Category 2: OneShape® instrumentation system. Category 3: ProtaperGold instrumentation system. Category 4: HyFlex® EDM instrumentation system. Category 5: Control (stainless steel K-files). Following endodontic therapy, these scores were recorded at 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours using the VAS scale. RESULTS: The visual analog scale (VAS) score (mean±SD) in the control group was 0.73± 0.40 (<0.001). The VAS score in the Reciproc group was 0.43± 0.05 (<0.001). The VAS score in the OneShape® group was 0.36±0.09 (<0.001). The VAS score in the Protaper Gold group was 0.41 ±0.08 (<0.001). The VAS score in the HyFlex® EDM group was 0.55 ±0.02 (<0.001). The VAS score in all instrumentation techniques at 72 hours follow-up was lesser in comparison to a control group with meaningful statistical significance (<0.001). However, the post-operative pain among the Reciproc, OneShape®, Protaper Gold, and HyFlex® EDM instrumentation systems was not different clinically when compared among themselves. However, VAS values were greater in OneShape® and HyFlex® EDM compared to Reciproc and Protaper Gold, showing increased post-operative pain in OneShape and HyFlex® EDM compared to Reciproc and Protaper Gold. It was also observed that there was a decline in the VAS score in all instrumentation systems as the follow-up period increased from 6 hours to 72 hours, with maximum post-operative pain at 6 hours of follow-up and minimum post-operative pain at 72 hours of follow-up. However, the decline was lesser in OneShape® and HyFlex® EDM in comparison to Reciproc and Protaper Gold, with increased post-operative pain in OneShape® and HyFlex® EDM in comparison to Reciproc and Protaper Gold. CONCLUSION: Post-operative pain at all follow-ups of endodontic procedures was less in Reciproc, OneShape®, Protaper Gold, and HyFlex® EDM than in the control group. VAS scores were higher in the OneShape® and HyFlex® EDM groups compared to the Reciproc and Protaper Gold groups, indicating increased post-operative pain with OneShape® and HyFlex® EDM instruments in comparison to Reciproc and Protaper Gold.

Subpulmonary membrane: A rare cause of right ventricular outflow tract obstruction.

Subpulmonary membrane is a rare cause of right ventricular outflow tract (RVOT) obstruction, and only a few case reports exist with or without associated ventricular septal defect. We report a series of three cases with subpulmonary membrane causing RVOT obstruction. Two of these have been operated (the first case operated after unsuccessful attempt at balloon dilatation), and the third case is on follow-up at present.

Role of real-time polymerase chain reaction in diagnosing Hepatitis E, the commonest cause of acute hepatitis in adult patients seeking institutional care.

Background: This cross-sectional study was performed with the aim of determining the prevalence of hepatitis E virus (HEV) infection among acute hepatitis patients attending a tertiary care teaching hospital in a developing country and to determine the relative performance of prevalent diagnostic assays in establishing its diagnosis. Materials and Methods: A total of 46 adult patients were included in this study, all of whom presented with jaundice of <4 weeks' duration and elevation of AST and ALT above 500 U/L. The prevalence of HEV among patients with acute hepatitis was calculated on the basis of the proportion of recruited patients reacting positively in serum anti-HEV immunoglobulin M (IgM) and real-time polymerase chain reaction (RT-PCR) assays. Results: Among the recruited patients, 11 (23.91%) and 15 (32.6%) patients were positive for anti-HEV IgM and RT-PCR, respectively. The two tests demonstrated poor inter-test agreement, thereby implying the necessity of performing both tests for reliable diagnosis of acute HEV virus infection. We also observed a significant difference in the duration of illness between RT-PCR positive and negative patients (P = 0.008). The mean (±SD) duration of illness in the two groups was 8.6 (±3.50) and 11.66 (± 5.15) days, respectively. Combining the results of IgM ELISA and RT-PCR, we observed that 23 out of 46 patients (50%) had evidence of acute HEV virus infection among our patients. Conclusion: Our study suggests that HEV is the commonest cause of acute hepatitis in adult patients attending a tertiary care teaching hospital and that the diagnostic algorithm for its confirmation should include both IgM ELISA and RT-PCR assays.

Optimization studies on gastroretentive floating system using response surface methodology.

The aim of the present investigation was to develop and optimize gastroretentive floating system of amoxicillin for the efficient treatment of peptic ulcer induced by Helicobacter pylori infection. Floating microballoons were developed using central composite design (CCD), and optimization was done by employing response surface methodology. The selected independent variables were cellulose acetate phthalate, drug-Eudragit S100 ratio, and the ratio of dichloromethane/ethanol/isopropyl alcohol. The selected dependent variables were yield, mean particle size, buoyancy, encapsulation efficiency, and drug release within 8 h. A quadratic polynomial model was generated which had linear, interaction, and quadratic terms to predict and evaluate the independent variables with respect to the dependent variables. Results showed that selected independent variables significantly affect the yield (30.53-82.71%), particle size (31.62-47.03 µm), buoyancy (42.68-95.75%), encapsulation efficiency (56.96-93.13%), and cumulative drug release from the microballoons (34.01-74.65%). The interaction and quadratic terms were also found to affect the process variables. An excellent agreement was found between the actual value and predicted value. In conclusion, it can be said that CCD is a valuable second-degree design to develop and optimize GFS of amoxicillin which in turn provides a basis to localize the drug release in the gastric region for effective treatment of H. pylori-mediated infection.

Analgesic efficacy of ultrasound-guided transversus abdominis plane block for laparoscopic gynecological surgery: a randomized controlled trial.

BACKGROUND: This study aimed to determine whether ultrasound-guided transversus abdominis plane (TAP) block is more effective in reducing postoperative pain and analgesic consumption than local anesthetic infiltration (LAI) at the port site for elective laparoscopic gynecological surgeries. METHODS: Eighty patients with the American Society of Anesthesiologists status I/II undergoing laparoscopic gynecology surgery were enrolled for this randomized control trial. After general anesthesia was administered, patients in group C received LAI at each port site, and patients in group T received bilateral ultrasound-guided TAP. Postoperative pain was assessed at time intervals of 1/2, 2, 4, 6, 8, and 24 h using the numeric pain scale (NPS). Clinical metrics such as postoperative analgesic diclofenac consumption, need for rescue fentanyl, nausea-vomiting scores, and antiemetic requirements were also recorded. RESULTS: Seventy-four patients were included in the final analysis. Postoperatively, patients in group T had significantly lower NPS than those in group C (P < 0.05). The highest difference in the postoperative NPS was observed at 2 h (median [1Q, 3Q]; group C = 3 [2, 4]; group T = 1 [0, 2]; P < 0.001). A statistically significant difference was observed in the frequency of diclofenac (75 mg intravenous) requirement between the groups (P = 0.010). No significant difference was observed between the groups in need of rescue fentanyl or antiemetic and the nausea-vomiting scores. CONCLUSIONS: In patients undergoing laparoscopic gynecological surgery, ultrasound-guided TAP block provided greater postoperative analgesic benefits in terms of lower NPS and reduced analgesic requirements than port site LAI.

Presence of entry receptors and viral markers suggest a low level of placental replication of hepatitis B virus in a proportion of pregnant women infected with chronic hepatitis B.

The transplacental route of vertical transmission of Hepatitis B Virus (HBV) has been known for over a decade. Here we present evidence which suggest HBV can replicate in placenta. Forty-one HBsAg positive and 10 control pregnant women were enrolled in the study after obtaining informed consent. HBV positives were further divided in the High Viral Load (HVL) Group and Low Viral Load (LVL) Group according to INASL guidelines 2018. The Presence of the HBV DNA and expression of NTCP in the placenta was analyzed by qPCR/RT-qPCR and/or immunohistochemistry (IHC). The presence of cccDNA was assessed using Digital Droplet PCR while the presence of pre-genomic (pg) RNA was assessed through qRT-PCR and sequencing. The presence of HBeAg and HBcAg in the placenta was assessed by IHC. Immunostaining of NTCP, HBeAg and HBcAg on trophoblasts along with the presence of total HBV DNA, cccDNA and pgRNA indicated, that these cells are not only susceptible to HBV infection but may also support viral replication. This is further supported by the finding that trophoblasts of the several HBeAg seronegative samples harbored the HBeAg. Although, we did not find any correlation in NTCP expression and viral markers with viral load indicates placental replication may not aping hepatocytes. The presence of the HBV receptor, NTCP along with the presence of cccDNA, pgRNA, and HBeAg in placenta of HBV infected females without circulating HBeAg suggest that placenta act as a replication host.

Evaluation of postoperative analgesia of erector spinae plane block in elective laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: Only a few studies have evaluated the analgesic effect of Erector Spinae Plane Block (ESPB) for laparoscopic cholecystectomy surgery. We aimed to evaluate the analgesic effect of ESPB in patients undergoing Laparoscopic Cholecystectomy. METHODS: Seventy-five patients of ASA grade I / II, aged 18-60 years undergoing elective laparoscopic cholecystectomy were enrolled and were randomly assigned to group C or T. Patients in group C were given general anaesthesia alone and patients in group T were given bilateral ultrasound-guided ESPB followed by general anaesthesia. The primary objective was to compare total 24hr postoperative analgesic consumption of tramadol and secondary objective was to indicate the need for rescue analgesia and numeric pain rating scores (NRS) at rest and on movement between the groups. RESULTS: Sixty-six patients were included for final analysis. The total tramadol consumption in 24hr postoperative period for Group T was 105.21 ± 60.18 mg and for group C was 178.12 ± 54.3 mg the difference was statistically highly significant (P = 0.0001). The need for rescue analgesia (fentanyl) was also statistically significantly lower in group T compared to group C (0.91 ± 5.22 mcg vs. 13.64 ± 23.82 mcg, P= 0.002). The postoperative NRS at ½, 2, 4, 6, 8 hr at rest and on movement were statistically lower in group T than group C, although this difference was not of clinical significance. CONCLUSION: In patients undergoing laparoscopic cholecystectomy, bilateral ultrasound-guided ESPB provided effective analgesia as it reduced the total tramadol consumption and the need for rescue analgesia in 24hr postoperative period.

The role and delicate balance of Host Immunity in Coronavirus Disease-19.

Severe Acute Respiratory Syndrome (SARS) associated with SARS-CoV-2, causes a severe form of the respiratory illness known as Coronavirus Disease-19 (COVID-19). COVID-19 has emerged as a worldwide pandemic with a high number of fatalities. Approximately 112,654,202 people have been infected so far with this disease which has led to the death of more than one point seven million (2,496,749) till 24th Feb, 2021. Measures to counter this disease have led to a global economic slowdown. Multiple drug trials are ongoing and several putative candidates for vaccination against the virus have been approved and are in the pipeline. Many studies have also characterized the immunological profile of patients infected with COVID-19. Some studies suggest that the severity of the COVID-19 infection is directly associated with the cytokine storm. In this review, we aim to compile the available knowledge and describe the nature of immune responses in patients infected with COVID-19 in different age groups, comorbidity, and immune-compromised state and their association with disease severity.

Diverse psychiatric presentation associated with child sexual abuse: Case series.

Child sexual abuse (CSA) occurs when a person involves the child in sexual activities for his/her sexual gratification, commercial gain, or both. We report a series of 12 cases of CSA, who presented to the psychiatry department with diverse psychiatric presentations associated with CSA. In most of these cases, the perpetrator was unmarried and known to the child. The presentation was varied with patients being diagnosed with obsessive-compulsive disorder, schizophrenia, acute and transient psychotic disorder, dysthymic disorder, recurrent depressive disorder, acute stress reaction, conversion disorder, borderline personality disorder, and moderate depressive episode with somatic symptoms. Individual and family counseling was an important part of management of these cases along with pharmacotherapy. More vigilance about CSA and mental health in all categories of health-care personnel would help in early detection and timely management of these cases.

Gut Dysbiosis and IL-21 Response in Patients with Severe COVID-19.

BACKGROUND: The disease severity, ranging from being asymptomatic to having acute illness, and associated inflammatory responses has suggested that alterations in the gut microbiota may play a crucial role in the development of chronic disorders due to COVID-19 infection. This study describes gut microbiota dysbiosis in COVID-19 patients and its implications relating to the disease. DESIGN: A cross sectional prospective study was performed on thirty RT-PCR-confirmed COVID-19 patients admitted to the All India Institute of Medical Sciences, Bhopal, India, between September 10 and 20, 2020. Ten healthy volunteers were recruited as the control group. IFN, TNF, and IL-21 profiling was conducted using plasma samples, and gut bacterial analysis was performed after obtaining the metagenomics data of stool samples. RESULTS: Patients with a variable COVID-19 severity showed distinct gut microflora and peripheral interleukin-21 levels. A low Firmicute/Bacteroidetes ratio, caused by the depletion of the fibre-utilizing bacteria, F. prausnitzii, B. Plebius, and Prevotella, and an increase in Bacteroidetes has associated gut microbiota dysbiosis with COVID-19 disease severity. CONCLUSIONS: The loss of the functional attributes of signature commensals in the gut, due to dysbiosis, is a predisposing factor of COVID-19 pathophysiology.