Enteric viruses replicate in salivary glands and infect through saliva.

Enteric viruses like norovirus, rotavirus and astrovirus have long been accepted as spreading in the population through fecal-oral transmission: viruses are shed into feces from one host and enter the oral cavity of another, bypassing salivary glands (SGs) and reaching the intestines to replicate, be shed in feces and repeat the transmission cycle1. Yet there are viruses (for example, rabies) that infect the SGs2,3, making the oral cavity one site of replication and saliva one conduit of transmission. Here we report that enteric viruses productively and persistently infect SGs, reaching titres comparable to those in the intestines. We demonstrate that enteric viruses get released into the saliva, identifying a second route of viral transmission. This is particularly significant for infected infants, whose saliva directly transmits enteric viruses to their mothers' mammary glands through backflow during suckling. This sidesteps the conventional gut-mammary axis route4 and leads to a rapid surge in maternal milk secretory IgA antibodies5,6. Lastly, we show that SG-derived spheroids7 and cell lines8 can replicate and propagate enteric viruses, generating a scalable and manageable system of production. Collectively, our research uncovers a new transmission route for enteric viruses with implications for therapeutics, diagnostics and importantly sanitation measures to prevent spread through saliva.

Design, development and bio-evaluation of a novel radio-ligand 99mTc-THQ-DTPA as a sigma 2 receptor specific breast tumor imaging agent.

Over-expression of sigma-2 receptor in cancer cells provides an opportunity to develop molecular probes for diagnosis, even for non-receptor specific malignancies like triple negative breast cancers. In this work, a novel sigma-2 receptor ligand [THQ-DTPA] has been synthesized and characterized using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THQ) and diethylenetriaminepentaacetic acid (DTPA). The ligand is further chelated with 99mTc for application as metal based radiotracer [99mTc-THQ-DTPA]. Radiolabelling with 99mTc was achieved in an excellent yield of 98.0 ± 0.5% using stannous chloride as a reducing agent. The radioligand was found to be stable in human serum up-to 24 h, bio-compatible with less than 4% hemolysis, and exhibited high binding with sigma receptors isolated from rat liver membrane (Kd of 16.32 ± 4.93 nM and Bmax of 0.5232 ± 0.06 pmol/mg). Bio-distribution studies in triple-negative breast tumor bearing nude mice showed high tumor uptake after 30 min of injection with tumor/muscle (T/M) ratio of 3.58 ± 0.09. At 240 min, the T/M ratio (2.84 ± 0.20) decreased by 35% when administered in sigma blocked tumor bearing mice (1.81 ± 0.16) suggesting the selectivity of the ligand. Tumor imaging in gamma camera indicated a contrast of 3.56 at 30 min p.i. The above findings indicate that the ligand 99mTc-THQ-DTPA binds to sigma-2 receptors with high affinity and has potential for triple-negative breast tumor imaging.

Comparative assessment of immunogenicity of recombinant insulin Aspart from BioGenomics and its originator NovoRapid® in adult patients with type 2 diabetes mellitus.

OBJECTIVES: To assess and compare the immunogenicity of recombinant Insulin Aspart [manufactured by BioGenomics Limited (BGL-ASP)] with its originator NovoRapid® (manufactured by Novo Nordisk) in adult patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: BGL-IA-CTP301 study was a randomized, open label, parallel group, multicenter phase-III clinical study to compare the efficacy and safety of recombinant Insulin Aspart 100 U/mL [manufactured by BioGenomics Limited (BGL-ASP)] with its reference medicinal product (RMP); NovoRapid® [manufactured by Novo Nordisk], in adult patients with Type 2 diabetes mellitus (T2DM). The primary objective of the study was to compare the immunogenicity of BGL-ASP and RMP; NovoRapid® in patient serum samples collected from phase-III clinical study. Immunogenicity was studied as the incidence of patients positive for anti-insulin Aspart (AIA) antibodies, developed against BGL-ASP/RMP at baseline, end of 12 week and end of 24 week of the treatment period. The changes in incidence of patients positive for AIA antibodies post-baseline were also studied to assess and compare the treatment-emergent antibody response (TEAR) between the treatment groups (BGL-ASP and RMP). Statistical evaluation was done by Fisher's exact test to compare the overall incidence of patients positive for AIA antibodies and the TEAR positives observed post-baseline in both the treated groups. An in-vitro neutralizing antibody assay (Nab assay) was also performed to study the effect of AIA antibodies in neutralizing the biological activity/metabolic function of the insulin. The neutralizing potential of AIA was studied by its effect on %glucose uptake. We also evaluated the association between AIA antibody levels and its impact on biological activity by studying the correlation between them. RESULTS: Analysis of immunogenicity data suggested that the percentage of patients positive for AIA antibodies until week 24 was similar and comparable in both the treatment groups, BGL-ASP and RMP; NovoRapid®. The changes in incidence of patients positive for AIA post-baseline in terms of TEAR positives were also similar and comparable between the treatment groups. The results of the Nab assay with confirmed positive AIA samples from BGL-ASP- and RMP-treated groups did not have any negative impact on %glucose uptake by the cells in Nab assay, confirming the absence of neutralizing antibodies in both the treatment groups. The correlation studies also showed absence of association between AIA antibody levels and percentage glucose uptake in both BGL-ASP and RMP-NovoRapid® treatment groups. CONCLUSIONS: The immunogenicity assessment based on the overall incidence of patients positive for AIA, changes in incidence of patients positive for AIA post-baseline, TEAR rates and absence of neutralizing antibodies, were found to be apparently similar and comparable in both the treatment groups (BGL-ASP and RMP). We conclude from our studies that the immunogenicity of BGL-ASP is similar and comparable to RMP and the observed immunogenicity in terms of anti-insulin Aspart antibody levels had no impact on the biological activity of insulin.

Gasless laparoscopy in rural India-registry outcomes and evaluation of the learning curve.

BACKGROUND: A program of gasless laparoscopy (GL) has been implemented in rural North-East India. To facilitate safe adoption, participating rural surgeons underwent rigorous training prior to independent clinical practice. An online registry was established to capture clinical data on safety and efficacy and to evaluate initial learning curves for gasless laparoscopy. METHODS: Surgeons who had completed the GL training program participated in the online RedCap Registry. Patients included in the registry provided informed consent for the use of their data. Data on operative times, conversion rates, perioperative complications, length of stay, and hospital costs were collected. Fixed reference cumulative sum (CUSUM) model was used to evaluate the learning curve based on operative times and conversion rates published in the literature. RESULTS: Four surgeons from three rural hospitals in North-East India participated in the registry. The data were collected over 12 months, from September 2019 to August 2020. One hundred and twenty-three participants underwent GL procedures, including 109 females (88.6%) and 14 males. GL procedures included cholecystectomy, appendicectomy, tubal ligation, ovarian cystectomy, diagnostic laparoscopy, and adhesiolysis. The mean operative time was 75.3 (42.05) minutes for all the surgeries. Conversion from GL to open surgery occurred in 11.4% of participants, with 8.9% converted to conventional laparoscopy. The main reasons for conversion were the inability to secure an operative view, lack of operating space, and adhesions. The mean length of stay was 3 (2.1) days. The complication rate was 5.7%, with one postoperative death. The CUSUM analysis for GL cholecystectomy showed a longer learning curve for operative time and few conversions. The learning curve for GL tubal ligation was relatively shorter. CONCLUSION: Gasless laparoscopy can be safely implemented in the rural settings of Northeast India with appropriate training programs. Careful case selection is essential during the early stages of the surgical learning curve.

Synthesis and in silico studies of some new pyrrolidine derivatives and their biological evaluation for analgesic and anti-inflammatory activity.

BACKGROUND: An array of commercially viable intermediate molecules necessary for the synthesis of a variety of bioactive molecules are chemically synthesized by pyrrolidine and its derivatives, which play a significant role in drug design and development process. AIM: The aim of the present research work was to explore the synthesis of some new pyrrolidine derivatives and to perform their in silico studies and finally evaluation of analgesic and anti-inflammatory activity. OBJECTIVE: The purpose of this study was to synthesis new pyrrolidine derivatives, examine how they affected the COX-1 and COX-2 enzymes computationally, and to screen their in vivo analgesic and anti-inflammatory activity on laboratory animals. METHOD: The new pyrrolidine derivatives were synthesized by condensing N-(3-acetylphenyl)-2-(pyrrolidin-1-yl)acetamide with substituted aniline in ethanol in the presence of catalytic amounts of glacial acetic acid. The structures of novel pyrrolidine derivatives were characterised using IR, NMR, and mass spectroscopy. Several molecular properties of the newly synthesized derivatives were calculated in order to evaluate the nature of the drug-like candidate. A specific reference cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme was used to dock the newly synthesized pyrrolidine derivatives. RESULTS: From the observed data, it was noted that amongst all newly synthesized compounds, A-1 and A-4 exhibited the highest anti-inflammatory and analgesic effects, respectively. CONCLUSION: On the basis of findings of present research, it was concluded that A-1 and A-4 might be utilized as a promising new lead compound for Non-Steroidal Anti-Inflammatory Drug (NSAIDs) development.

Feasibility study on application of ready mix concrete in construction projects in Nepal.

Ready mix concrete (RMC) is a new concreting concept in the Nepali construction industry introduced before one decade. The paper aims to assess the acceptance of ready mix for residential buildings of Nepal. The relation was developed for average compressive strength with slump value and water cement ratio based on laboratory test nominal mix M20 (1:1.5:3) and M25 (1:1:2) along with questionnaire survey. The result also shows that the compressive strength of RMC is higher in comparison with the SMC (site mix concrete). During questionnaire, more than 60% of users prefer the RMC over SMC. The merit and demerit of construction projects using RMC and SMC are discussed and interpreted.

Holmes-Adie syndrome and vitamin B12 - associated peripheral neuropathy: An association or coincidence?

A 30-year-old male patient presented to the eye department with complaints of blurring of vision of right eye at distance and near for a duration of 1.5 months. Ocular examination revealed Anisocoria with enlarged pupil in the right eye. On instillation of 0.1% pilocarpine, there was a pronounced miosis in the dilated pupil seen at 30 min associated with an improvement in distance and near vision. On slit lamp examination, vermiform movements were seen in the affected pupil on shining the slit from temporal aspect. Fundus examination was within normal limits. Systemic examination revealed absent deep tendon reflexes. Based on the clinical features, a diagnosis of Holmes-Adie syndrome was reached and the patient was started on 0.1% pilocarpine eye drops. This case highlights the importance of thorough systemic examination and investigations in all cases of anisocoria.

Bacteriophages: A possible solution to combat enteropathogenic Escherichia coli infections in neonatal goats.

Due to awareness and benefits of goat rearing in developing economies, goats' significance is increasing. Unfortunately, these ruminants are threatened via multiple bacterial pathogens such as enteropathogenic Escherichia coli (EPEC). In goat kids and lambs, EPEC causes gastrointestinal disease leading to substantial economic losses for farmers and may also pose a threat to public health via the spread of zoonotic diseases. Management of infection is primarily based on antibiotics, but the need for new therapeutic measures as an alternative to antibiotics is becoming vital because of the advent of antimicrobial resistance (AMR). The prevalence of EPEC was established using bfpA gene, uspA gene and Stx1 gene, followed by phylogenetic analysis using Stx1 gene. The lytic activity of the isolated putative coliphages was tested on multi-drug resistant strains of EPEC. It was observed that a PCR based approach is more effective and rapid as compared to phenotypic tests of Escherichia coli virulence. It was also established that the isolated bacteriophages exhibited potent antibacterial efficacy in vitro, with some of the isolates (16%) detected as T4 and T4-like phages based on gp23 gene. Hence, bacteriophages as therapeutic agents may be explored as an alternative to antibiotics in managing public, livestock and environmental health in this era of AMR.

Kidney transplant surgical director training: Urologists represent a functional alternative to general surgeons.

INTRODUCTION: Kidney transplant (KT) directors are general surgeons or urologists. All KT centers must meet established performance standards. However, it has not been established if general surgery and urology led programs have disparate outcomes. METHODS: Transplant outcomes and donor-recipient characteristics by director training were investigated. Organ Procurement and Transplantation Network (OPTN) directory, program websites were analyzed for surgical director demographics. Scientific Registry of Transplant Recipients (SRTR) 1-year kidney survival and deceased donor (DD) wait-time rankings were evaluated. A retrospective analysis of 142 157 KT recipients from 2010 to 2019 was performed using the United Network for Organ Sharing (UNOS) database. RESULTS: One hunderd and seventy three (90.6%) KT programs were led by general surgeons. There were no significant differences in gender, ethnicity, region, credentials, or fellowship completion. Recipients undergoing KT with urology led programs were older (P = .002) and had longer wait-times (P < .001). These centers used higher KDPI (.47 vs. .45, P < .001) and higher HLA mismatch (3.92 vs. 3.89, P = .02) kidneys. Urology led centers utilized living donors less frequently (32.1% vs. 35.8%, P < .001) and had longer CIT (15.44 vs. 12.21, P < .001). Both had similar SRTR ranking of 1-year survival and DD wait-time. CONCLUSION: Most directors were general surgeon. Patient outcomes did not differ by transplant director training. Urologists represent a viable option for KT leadership and recruitment should be encouraged.

Assessment of quorum sensing effects of tyrosol on fermentative performance by chief ethnic fermentative yeasts from northeast India.

AIM: Tyrosol, a quorum sensing molecule in yeasts, was reported to reduce lag phase and induces hyphae formation during cell proliferation. However, evidence of any enhancing effect of tyrosol in cellular proliferation within fermentative environment is unclear. In this investigation, selected yeast cells were assessed for their ability to synthesize tyrosol followed by examining the role of the molecule during fermentation. METHODS AND RESULTS: Tyrosols were characterized in four fermentative yeasts viz., Saccharomyces cerevisiae, Wickerhamomyces anomalus, Candida glabrata and Candida tropicalis isolated from traditional fermentative cakes of northeast India. All the isolates synthesized tyrosol while C. tropicalis exhibited filamentous growth in response to tyrosols retrieved from other isolates. Purified tyrosols showed protective behaviour in C. tropicalis and S. cerevisiae under ethanol mediated oxidative stress. During fermentation, tyrosol significantly enhanced growth of W. anomalus in starch medium while C. tropicalis exhibited growth enhancement in starch and glucose sources. The chief fermentative yeast S. cerevisiae showed notable enhancement in fermentative capacity in starch medium under the influence of tyrosol con-commitment of ethanol production. CONCLUSION: The study concludes that tyrosol exerts unusual effect in cellular growth and fermentative ability of both Saccharomyces and non-Saccharomyces yeasts. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of expression of tyrosol by non-conventional yeasts, where the molecule was found to exert enhancing effect during fermentation, thereby augmenting the process of metabolite production during traditional fermentation.

Clinical effectiveness of gasless laparoscopic surgery for abdominal conditions: systematic review and meta-analysis.

BACKGROUND: In high-income countries, laparoscopic surgery is the preferred approach for many abdominal conditions. Conventional laparoscopy is a complex intervention that is challenging to adopt and implement in low resource settings. This systematic review and meta-analysis evaluate the clinical effectiveness of gasless laparoscopy compared to conventional laparoscopy with CO2 pneumoperitoneum and open surgery for general surgery and gynaecological procedures. METHODS: A search of the MEDLINE, EMBASE, Global Health, AJOL databases and Cochrane Library was performed from inception to January 2021. All randomised (RCTs) and comparative cohort (non-RCTs) studies comparing gasless laparoscopy with open surgery or conventional laparoscopy were included. The primary outcomes were mortality, conversion rates and intraoperative complications. SECONDARY OUTCOMES: operative times and length of stay. The inverse variance random-effects model was used to synthesise data. RESULTS: 63 studies were included: 41 RCTs and 22 non-RCTs (3,620 patients). No procedure-related deaths were reported in the studies. For gasless vs conventional laparoscopy there was no difference in intraoperative complications for general RR 1.04 [CI 0.45-2.40] or gynaecological surgery RR 0.66 [0.14-3.13]. In the gasless laparoscopy group, the conversion rates for gynaecological surgery were high RR 11.72 [CI 2.26-60.87] when compared to conventional laparoscopy. For gasless vs open surgery, the operative times were longer for gasless surgery in general surgery RCT group MD (mean difference) 10 [CI 0.64, 19.36], but significantly shorter in the gynaecology RCT group MD - 18.74 [CI - 29.23, - 8.26]. For gasless laparoscopy vs open surgery non-RCT, the length of stay was shorter for gasless laparoscopy in general surgery MD - 3.94 [CI - 5.93, - 1.95] and gynaecology MD - 1.75 [CI - 2.64, - 0.86]. Overall GRADE assessment for RCTs and Non-RCTs was very low. CONCLUSION: Gasless laparoscopy has advantages for selective general and gynaecological procedures and may have a vital role to play in low resource settings.

Role of postoperative intact serum PTH as an early predictor of severe post-thyroidectomy hypocalcemia: a prospective study.

BACKGROUND: Post thyroidectomy hypocalcemia is a major sequel of thyroidectomy and continues to trouble the endocrinologists and the endocrine surgeons as there is no ideal predictive marker of hypocalcemia which has the potential to develop into a life-threatening complication. The role of early serum intact parathormone (iPTH) to predict post thyroidectomy hypocalcemia is becoming useful but the literature is still unclear regarding the optimal time of testing and the optimal cut-off value of serum iPTH. PATIENTS AND METHODS: This is a prospective cohort study of 111 patients who underwent total thyroidectomy in a tertiary care endocrine surgery referral unit. Serum iPTH was measured after 20 min and 4 h of surgery. Receiver-Operator characteristic Curve (ROC) was used to find out of the best cut-off value of S. iPTH 20 min and 4 h after surgery in predicting hypocalcemia. RESULTS: Hypocalcemia was noted in 60 (54%) out of 111 subjects who underwent total thyroidectomy. The best cut-off values of Serum iPTH to predict hypocalcemia was found to be 4.28 pmol/l at 20 min post total thyroidectomy with a sensitivity and specificity of 81.7% and 51%, respectively. In addition, patients with malignancy or central lymph nodal dissection were significantly over-represented in the hypocalcemia group with serum iPTH above the threshold level of 4.28 pmol/l. Below the cut off level, parenteral calcium supplementation was required in 23% (17/74) subjects while the rate was only 5.4% (2/37) patients when serum iPTH was above the cut-off level. CONCLUSIONS: The decline of serum iPTH below a specific level after surgery has predictive value together with other factors strictly related to patient, the thyroid disease itself and surgery. The risk of development of hypocalcemia and consequent need for calcium supplementation should be evaluated by clinical assessment along with serum PTH measurement.

The importance of small samples in medical research.

Almost all bio-statisticians and medical researchers believe that a large sample is always helpful in providing more reliable results. Whereas this is true for some specific cases, a large sample may not be helpful in more situations than we contemplate because of the higher possibility of errors and reduced validity. Many medical breakthroughs have occurred with self-experimentation and single experiments. Studies, particularly analytical studies, may provide more truthful results with a small sample because intensive efforts can be made to control all the confounders, wherever they operate, and sophisticated equipment can be used to obtain more accurate data. A large sample may be required only for the studies with highly variable outcomes, where an estimate of the effect size with high precision is required, or when the effect size to be detected is small. This communication underscores the importance of small samples in reaching a valid conclusion in certain situations and describes the situations where a large sample is not only unnecessary but may even compromise the validity by not being able to exercise full care in the assessments. What sample size is small depends on the context.

Ultrasound imaging for the differential diagnosis of periapical lesions of endodontic origin in comparison with histopathology - a systematic review and meta-analysis.

BACKGROUND: Differentiating periapical lesions is important for treatment planning and subsequent treatment outcome. OBJECTIVE: To assess the diagnostic accuracy of ultrasound imaging for the differentiation of periapical lesions in comparison with histopathology. METHODS: PubMed, Scopus, Embase, Web of Science and ProQuest databases were searched for clinical studies published until June 2020 that evaluated the use of ultrasound (US) imaging for differential diagnosis of periapical lesions and used histopathology as the reference standard. Animal studies, laboratory-based studies, reviews and clinical studies not using a reference standard were excluded. Risk of bias (RoB) assessment was performed using a modified Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The random effects model was used for quantitative analysis of the data, and the Deeks test was used for calculating publication bias. Quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Twelve articles were included in the systematic review, out of which ten articles were quantitatively assessed. All the articles had a high RoB and concerns regarding applicability in the patient selection domain. For the index test domain, seven articles had low and the remaining five had unclear RoB and concerns regarding applicability. In the reference standard domain, low RoB and concerns regarding applicability were observed for all the articles. The RoB was low in flow and timing domains in all the articles except for one, where it was high. Summary estimates of sensitivity and specificity of US to diagnose periapical granulomas were 0.94 and 0.98, whereas for periapical cysts it was 0.98 and 0.99, respectively. Area under the curve for diagnosis of both periapical granulomas and periapical cysts was 0.99. All the included articles had inherent publication bias. Quality of evidence using GRADE, for sensitivity, was moderate for periapical granulomas and high for periapical cysts, whereas for specificity, it was high for periapical granulomas and low for periapical cysts. DISCUSSION: The available evidence is considered to be of low quality due to the observational nature of the studies and inherent publication bias. CONCLUSION: Although the sensitivity and specificity for differentiating periapical cysts and periapical granulomas using US were high, taking the quality of evidence into consideration, it can serve as an additional tool in differential diagnosis of periapical lesions.

Expression map of entry receptors and infectivity factors for pan-coronaviruses in preimplantation and implantation stage human embryos.

PURPOSE: To predict if developing human embryos are permissive to multiple coronaviruses. METHOD: We analyzed publicly available single-cell RNA-seq datasets of human embryos for the known canonical and non-canonical receptors and spike protein cleavage enzymes for multiple coronaviruses like SARS-CoV, SARS-CoV-2, MERS-CoV, hCoV-229E, and hCoV-NL63. We also analyzed the expression of host genes involved in viral replication, host proteins involved in viral endosomal sorting complexes required for transport (ESCRT), genes of host proteins that physically interact with proteins of SARS-CoV-2, and the host genes essential for coronavirus infectivity. RESULTS: Of the known receptors of SARS viruses, ACE2, BSG, GOLGA7, and ZDHHC5 were expressed in different proportions in the zygote, 4-cell, 8-cell, morula, and blastocysts including the trophectoderm. The MERS-CoV receptor, DPP4, and hCoV-229E receptor, ANPEP, were expressed mainly from the compact morula to the blastocyst stages. Transcripts of the MERS-CoV alternate receptor LGALS1 were detected in most cells at all stages of development. TMPRSS2 transcripts were detected in the epiblast, primitive endoderm, and trophectoderm, while transcripts of the endosomal proteases CTSL, CTSB, and FURIN were expressed in most cells at all stages of development. ACE2 and TMPRSS2 were co-expressed in a proportion of epiblast and trophectoderm cells. The embryonic cells expressed genes involved in ESCRT, viral replication, SARS-CoV-2 interactions, and coronavirus infectivity. The ACE2 and TMPRSS2 co-expressing cells were enriched in genes associated with lipid metabolism, lysosome, peroxisome, and oxidative phosphorylation pathways. CONCLUSION: Preimplantation and implantation stage human embryos could be permissive to multiple hCoVs.

Integrated hydrochemical and ERT approach for seawater intrusion study in a coastal aquifer: a case study from Jafrabad Town, Gujarat State, India.

Hydrochemical and geophysical approach has been adopted to evaluate the seawater intrusion (SWI) in coastal aquifers of Jafrabad Town, Gujarat State, India. Electrical Resistivity Tomography (no. 9) was carried out with spread length of 160-400 m which provided penetration depth of about 23 to 76 m. Very low resistivity zone (0-3 Ω-m range) has been observed in the ERT profiles conducted in the study area. Parameters, namely, TDS, Na, and Cl, have been considered to examine the signature of SWI. The results obtained from ionic ratios, Piper plot, and Chaddha's diagram also confirm the influence of saline water within aquifer. The very low resistivity signature is correlated with the high TDS values in the nearby wells. SWI has been observed up to 9 km from the coast, and it is observed at a depth of 20-22 m in the existing limestone mines near the coast.

The Effect of TLR Agonists and Myokines on Secretory Activity of Adipogenically Differentiated MSC Cultures.

We studied the effect of bacterial pathogen-associated molecular patterns and myokines on the secretion of adipokines by mesenchymal stem cells (MSC) and products of their adipogenic differentiation. The secretion of adiponectin, adipsin, leptin, and insulin by adipogenically differentiated cell cultures was quantitatively determined using multiplex ELISA. MSC obtained from the stromal vascular fraction of human subcutaneous adipose tissue were shown to secrete a known adipokine adipsin. The ability of white adipocytes to secrete significant amounts of insulin (in vitro) has been shown for the first time. Control cultures of white adipocytes secreted much higher levels of adiponectin, leptin, and insulin when compared to other adipocytes cultures. On the other hand, beige and brown adipocyte cultures secreted more adipsin than white adipocyte cultures. The influence of myokine ß-aminoisobutyric acid on the secretion of adipsin in MSC, white, beige, and brown adipocytes was also studied.

The Effect of LPS and Flagellin on the Process of Lipolysis in Mesenchymal Stromal Cells during Adipogenic Differentiation.

We analyzed the effects of bacterial pathogen-associated molecular patterns (LPS and flagellin) and adrenergic agonist isoproterenol on the content of total and phosphorylated (Ser552) hormone-sensitive lipase in mesenchymal stromal cells and cell products of their adipogenic differentiation. The expression of hormone-sensitive lipase and an increase in the content of its activated phosphorylated form were demonstrated by Western blotting in cells of all three lines of adipogenic differentiation. Under the influence of flagellin, the content of total and phosphorylated forms of hormone-sensitive lipase increased in brown adipocytes, while LPS induced a decrease in the content of total hormone-sensitive lipase in white adipocytes. We hypothesize that bacterial pathogen-associated molecular patterns can activate lipolysis under pathological conditions associated with slow remodeling of the adipose tissue.

Prevalence of Loss of Smell and/or Taste and other Otorhinolaryngology Symptoms in COVID-19 Patients.

Background Loss of smell and/or taste have been described in COVID-19 patients. Studies have not been conducted to evaluate the loss of smell and/or taste in the context of Nepal. Objective To investigate the prevalence of Ear, Nose and Throat related symptoms and assess smell and taste disorders in laboratory-confirmed SARS-CoV-2 patients. Method This prospective cross-sectional study evaluated patients from September 2020 to March 2021 with preceding COVID-19 diagnosis from a tertiary centre in Kathmandu. COVID-19 positive patients visiting out-patient department, quarantined or admitted were included. Patients were given questionnaire consisting of demographic data, history of smoking and evaluation of presenting symptoms. Loss of smell and taste were subjectively tested and followed up via telephone for ten weeks to evaluate for recovery time and degree of recovery. Result A total of 226 patients participated in the study, 18-92 years old (mean age, 36.77 ± 15.23 years; 53.5% males, 69% non-smokers). Majority of the patients had Myalgia (n = 128, 56.6%) as their presenting symptoms followed by fever (n = 122, 53.9%), loss of smell (n = 117, 51.7%), cough (n = 107, 47.34) and sore throat (n = 102, 45.1%). Loss of sense of smell and taste was reported in 51.8% and 42% respectively. The association between loss of sense of smell and taste was statistically significant (p < .001). All patients had some degree of recovery with 64.1% recovery of smell and 64.2% recovery of taste within 14 days of onset of symptoms. The mean recovery time for sense of smell and taste was 14.34 ± 9.82 days and 15.03 ± 10.06 days, respectively. Conclusion Olfactory and gustatory dysfunctions are cardinal features of COVID-19. They recover spontaneously along with other symptoms within few weeks. The absence of smell or taste in times of pandemic can be suggestive of potential COVID-19 infection and be used as a screening tool for early diagnosis and reduce transmission of the infection.

Establishing core outcome sets for gastrointestinal recovery in studies of postoperative ileus and small bowel obstruction: protocol for a nested methodological study.

INTRODUCTION: Gastrointestinal recovery describes the restoration of normal bowel function in patients with bowel disease. This may be prolonged in two common clinical settings: postoperative ileus and small bowel obstruction. Improving gastrointestinal recovery is a research priority but researchers are limited by variation in outcome reporting across clinical studies. This protocol describes the development of core outcome sets for gastrointestinal recovery in the contexts of postoperative ileus and small bowel obstruction. METHOD: An international Steering Group consisting of patient and clinician representatives has been established. As overlap between clinical contexts is anticipated, both outcome sets will be co-developed and may be combined to form a common output with disease-specific domains. The development process will comprise three phases, including definition of outcomes relevant to postoperative ileus and small bowel obstruction from systematic literature reviews and nominal-group stakeholder discussions; online-facilitated Delphi surveys via international networks; and a consensus meeting to ratify the final output. A nested study will explore if the development of overlapping outcome sets can be rationalized. DISSEMINATION AND IMPLEMENTATION: The final output will be registered with the Core Outcome Measures in Effectiveness Trials initiative. A multi-faceted, quality improvement campaign for the reporting of gastrointestinal recovery in clinical studies will be launched, targeting international professional and patient groups, charitable organizations and editorial committees. Success will be explored via an updated systematic review of outcomes 5 years after registration of the core outcome set.