An Instructional Module for Functional Dissociative Seizures (FDS) in Hindi: Enhancing Communication and Management in India.

BACKGROUND AND OBJECTIVES: Functional dissociative seizures (FDS) are very common in neurology clinics, they straddle both neurology and psychiatry. In India, scarce resources and guidelines are available for effectively conveying their diagnosis and management, which leads to a substantial gap in care. We aimed to provide an instructional module for FDS, tailored to clinicians, patients, and caregivers in Hindi, to enhance communication of diagnosis and facilitate suitable management strategies. METHODS: The instructional module development process was based on clinical settings and expert opinions. A standard translation process was performed to ensure the linguistic and cultural equivalence. Validation was carried out by a panel of 15 validators, comprising 13 neurologists and two psychiatrists, to identify key psychoeducation components and their significance. They were provided a questionnaire consisting of five questions that were related to completeness, understandability, legibility, clarification, and usefulness of educational material for clinicians, patients, and caregivers. Items were rated using a 5-point Likert scale. RESULTS: There was agreement on four items (Q1, Q3, Q4, and Q5), whereas approximately 85% of the validators agreed on the remaining one item (Q2). The instructional module demonstrated high content validity as indicated by both item level-content validity index (0.98) and scale-level content validity index (0.97), alongside content validity ratio and modified kappa statistics. CONCLUSIONS: The developed Hindi instructional module for FDS serves as a valuable tool to enhance the communication of FDS diagnosis and dispel misconceptions. This offers a comprehensive resource for clinicians, patients, and caregivers in India, potentially bridging gap in FDS care.

Comparative Analysis of Dorsal Onlay Buccal Mucosal Graft and Vaginal Wall Graft Urethroplasty for Female Urethral Stricture at a Tertiary Care Centre.

OBJECTIVE: To compare dorsal onlay Buccal Mucosal Graft (BMG) and Vaginal Wall Graft (VWG) urethroplasty in the management of Female Urethral Stricture (FUS). METHODS: A retrospective analysis was conducted on 33 women undergoing dorsal onlay urethroplasty using BMG (n = 17) and VWG (n = 16) for urethral stricture at a tertiary care centre. Data including patient demographics, comorbidities, stricture characteristics, preoperative, and postoperative Female Sexual Function Index (FSFI) scores and operative outcomes were analyzed. Their preoperative diagnosis was confirmed with uroflowmetry, micturating cystourethrogram, urethral calibration, and urethrocystoscopy. Per urethral catheter was removed after 3 weeks and patients were followed up at regular intervals with urine analysis, uroflowmetry and post void residual urine assessment. RESULTS: The overall mean age was 47 years (range: 21-75) and follow-up was 16 months (range: 6-26). The overall change in American Urological Association (AUA) symptom score was from 18 to 4, maximum flow rate (Q max) from 5 mL/s to 24 mL/s, Post Void Residual Urine (PVRU) from 110 mL to 10 mL, average operative time of 97 minutes (range: 80 to 118 minutes) with no statistical difference between the 2 groups. Other parameters showed no difference. The overall urethral patency rate was 93.9% with no statistical difference in these groups (0.862). None of the patients developed urinary incontinence. CONCLUSION: Dorsal onlay substitution with BMG and VWG shows equivalent outcomes with low complication rate. Substitution urethroplasty elicits a robust and enduring therapeutic response and should be offered to patients presenting with FUS to avoid the adversities of repeated urethral dilatations.

Interference without interferon: interferon-independent induction of interferon-stimulated genes and its role in cellular innate immunity.

Interferons (IFNs) are multifaceted proteins that play pivotal roles in orchestrating robust antiviral immune responses and modulating the intricate landscape of host immunity. The major signaling pathway activated by IFNs is the JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway, which leads to the transcription of a battery of genes, collectively known as IFN-stimulated genes (ISGs). While the well-established role of IFNs in coordinating the innate immune response against viral infections is widely acknowledged, recent years have provided a more distinct comprehension of the functional significance attributed to non-canonical, IFN-independent induction of ISGs. In this review, we summarize the non-conventional signaling pathways of ISG induction. These alternative pathways offer new avenues for developing antiviral strategies or immunomodulation in various diseases.

Modified Atkins Diet in Adolescents and Adults with Drug Resistant Epilepsy: A Systematic Review and Meta-Analysis.

Epilepsy is one of the common neurological diseases which affects 65-70 million people worldwide. Modified Atkins diet (MAD) as a therapy is used as one of the treatments to reduce the seizures occurrence in epileptic patients. The purpose of this purpose is to review all evidence regarding the efficacy of the MAD from randomized controlled trials (RCTs) in adolescents and adults with drug resistant epilepsy (DRE). The total of three databases were searched (PubMed, Embase, and Cochrane Library) till 31 January 2023. Only RCTs with MAD as a one of the treatment arms were included in meta-analysis. The proportion of reduction of seizures in patients with epilepsy and relative risk to identify the relationship between MAD (as risk) to decrease the epileptic seizure was used as outcomes. The Jadad score with three domains was used to estimate the quality of RCTs included for meta-analysis. Only three RCTs were included following the stringent inclusion criteria in current meta-analysis. The pooled proportion from 142 patients going through MAD therapy shows the reduction in epileptic seizure ≥50%, by the random effect model was 0.23 (95% confidence interval [CI], 0.10 to 0.37). Our meta-analysis underlines a significant efficacy of MAD compared to the control group in seizure reduction ≥50%, The pooled relative risk was 6.47 (95% CI, 1.60 to 26.14; p-value <0.05). MAD therapy was efficacious and had better compliance for seizure reduction in subjects with DRE.

The impact of COVID-19 on tuberculosis in most populated state of India: A geospatial meta-analysis.

Background: Tuberculosis is one of the major burdens to developing nations. India is among the countries categorized by the World Health Organization (WHO) as experiencing a significant burden of TB, HIV-associated TB, and MDR/RR-TB within the context of low- and middle-income nations. Globally South East Asian and African region alone accounted for 82% of death (HIV negative), where India accounts for 36% of TB fatalities. Materials and Methods: The data was extracted from NIKSHAY web portal on TB notification cases in UP, India. The random effects meta-analysis was performed to estimate pooled proportion of TB cases in public and private notified during both the periods. Spatial analysis was used to display the spread of TB cases across the state, during both the periods. Results: A total 75 districts data on TB notified cases were available for current investigation. The pooled proportion of TB cases were 0.24 (0.21, 0.27) and 0.76 (0.73, 0.79) during COVID-19 period for private and public hospitals, respectively. Similarly, the pooled proportion of TB cases were 0.26 (0.23, 0.29) and 0.74 (0.71, 0.77) post-COVID-19 for private and public hospitals, respectively. Conclusion: The proportion of TB cases were more in public hospital as compared to private hospitals during COVID-19 period. Similarly, result was obtained in post-COVID-19 period.

Mammalian cell expressed recombinant trimeric spike protein is a potent vaccine antigen and confers near-complete protection against SARS-CoV-2 infection in Hamster.

Numerous vaccine candidates have emerged in the fight against SARS-CoV-2, yet the challenges posed by viral evolution and the evasion of vaccine-induced immunity persist. The development of broadly protective vaccines is essential in countering the threat posed by variants of concern (VoC) capable of eluding existing vaccine defenses. Among the diverse SARS-CoV-2 vaccine candidates, detailed characterization of those based on the expression of the entire spike protein in mammalian cells have been limited. In our study, we engineered a recombinant prefusion-stabilized trimeric spike protein antigen, IMT-CVAX, encoded by the IMT-C20 gene. This antigen was expressed utilizing a suspension mammalian cell line (CHO-S). The establishment of a stable cell line expressing IMT-CVAX involved the integration of the gene into the CHO genome, followed by the expression, purification, and characterization of the protein. To gauge the vaccine potential of adjuvanted IMT-CVAX, we conducted assessments in small animals. Analyses of blood collected from immunized animals included measurements of anti-spike IgG, SARS-CoV-2 neutralization, and responses from GC-B and Tfh cells. Furthermore, the protective efficacy of IMT-CVAX was evaluated using a Hamster challenge model. Our findings indicate that adjuvanted IMT-CVAX elicits an excellent immune response in both mice and hamsters. Notably, sera from animals immunized with IMT-CVAX effectively neutralize a diverse range of SARS-CoV-2 variants. Moreover, IMT-CVAX immunization conferred complete protection to hamsters against SARS-CoV-2 infection. In hACE2 transgenic mice, IMT-CVAX vaccination induced a robust response from GC-B and Tfh cells. Based on our preclinical model assessments, adjuvanted IMT-CVAX emerges as a highly efficacious vaccine candidate. This protein-subunit-based vaccine exhibits promise for clinical development, offering an affordable solution for both primary and heterologous immunization against SARS-CoV-2 variants.

Adropin promotes testicular functions by modulating redox homeostasis in adult mouse.

PURPOSE: Adropin is an emerging metabolic hormone that has a role in regulating energy homeostasis. The present study aimed to explore the impact of adropin on redox homeostasis and its possible role in testicular functions in adult mouse testis. METHODS: Western blot, flow-cytometry, and TUNEL assay were performed to explore the impact of intra-testicular treatment of adropin (0.5 µg/testis) on testicular functions of adult mice. Hormonal assay was done by ELISA. Further, antioxidant enzyme activities were measured. RESULTS: Adropin treatment significantly increased the sperm count and testicular testosterone by increasing the expression of GPR19 and steroidogenic proteins. Also, adropin treatment reduced the oxidative/nitrosative stress by facilitating the translocation of NRF2 and inhibiting NF-κB into the nucleus of germ cells. Enhanced nuclear translocation of NRF2 leads to elevated biosynthesis of antioxidant enzymes, evident by increased HO-1, SOD, and catalase activity that ultimately resulted into declined LPO levels in adropin-treated mice testes. Furthermore, adropin decreased nuclear translocation of NF-κB in germ cells, that resulted into decreased NO production leading to decreased nitrosative stress. Adropin/GPR19 signaling significantly increased its differentiation, proliferation, and survival of germ cells by elevating the expression of PCNA and declining caspase 3, cleaved caspase 3 expression, Bax/Bcl2 ratio, and TUNEL-positive cells. FACS analysis revealed that adropin treatment enhances overall turnover of testicular cells leading to rise in production of advanced germ cells, notably spermatids. CONCLUSION: The present study indicated that adropin improves testicular steroidogenesis, spermatogenesis via modulating redox potential and could be a promising target for treating testicular dysfunctions.

Restoration of the soil fertility under Cr(VI) and artificial drought condition by the utilization of plant growth-promoting Bacillus spp. SSAU2.

The study explores the potential of an indigenous halo-tolerant microbe identified as Bacillus spp. SSAU-2 in enhancing soil fertility and promoting plant growth for sustainable agricultural practices under the influence of multiple abiotic stresses such as Cr(VI), high salinity, and artificial drought condition. The study investigated various factors influencing IAA synthesis by SSAU-2, such as pH (5 to 11), salinity (10 to 50 g/L), tryptophan concentration (0.5 to 1%), carbon (mannitol mand lactose), and nitrogen sources (peptone and tryptone). The highest IAA concentration was observed at pH 10 (1.695 mg/ml) and pH 11 (0.782 mg/ml). IAA synthesis was optimized at a salinity level of 30 g/l, with lower and higher salinity levels resulting in decreased IAA concentrations. Notably, the presence of mannitol and lactose significantly augmented IAA synthesis, while glucose and sucrose had inhibitory effects. Furthermore, peptone and tryptone played a pivotal role in enhancing IAA synthesis, while ammonium chloride exerted an inhibitory influence. SSAU-2 showed a diverse array of capabilities, including the synthesis of gibberellins, extracellular polymeric substances, siderophores, and hydrogen cyanide along with nitrogen fixation and ammonia production. The microbe could efficiently tolerate 45% PEG-6000 concentration and effectively produce IAA in 15% PEG concentration. It could also tolerate high concentration of Cr(VI) and synthesize IAA even in 50 ppm Cr(VI). The findings of this study provide valuable insights into harnessing the potential of indigenous microorganisms to promote plant growth, enhance soil fertility, and establish sustainable agricultural practices essential for restoring the health of ecosystems.

Discrepancies in Gleason score between needle core biopsy and radical prostatectomy specimens with correlation between clinical and pathological staging.

BACKGROUND: The studies have shown that GS given after assessment of the entire prostate gland on the radical prostatectomy specimen may differ from GS given after examination of a small sample from needle core biopsy. We conducted this study to assess discrepancies in the Gleason score between NCB and RP specimens and to find out the correlation between the clinical stage and pathological stage. METHODS: The study included 174 patients with carcinoma prostate which underwent robotic-assisted radical prostatectomy (RARP). Pre-operative Gleason score was determined on 12-core biopsy samples under trans-rectal ultrasound (TRUS) guidance. The Gleason score obtained from the radical prostatectomy specimen was compared with that of the NCB Gleason score to find out differences. RESULTS: The preoperative Gleason score (GS) ranges from 6 to 9 with a mean GS of 6.97 ± 1.02. The post-operative GS ranges between 6 and 10 with mean and GS of 7.5 ± 1.10. On the pre-operative assessment of biopsy specimens, 70 (43.2%) patients had a GS of 6, while 44 patients had a GS of 7 (27.1%) and 48 (29.8%) patients had a GS of more than 7. On the postoperative assessment of specimens, 31 (19.1%) patients had post-operative GS of 6, while 66 (41%) patients had GS of 7 and 74 (41.1%) patients had GS of more than 7. When pre-operative GS and post-operative GS were compared, no changes were observed in the GS of 79 patients, whereas 83 patients showed the difference in GS, with 75 patients showing up-gradation and eight patients marked as down-graded. CONCLUSION: concordance between biopsy and the pathology results directly affects the prognosis of the patient. The results of our study demonstrated the rate of discordance between Gleason scores obtained from transrectal prostate biopsy and RP surgical specimens. This rate brings into question the accuracy of the chosen treatment.

Adropin may regulate ovarian functions by improving antioxidant potential in adult mouse.

The corpus luteum (CL) is a temporary endocrine gland that synthesizes progesterone. The luteal progesterone plays a central role in the regulation of the estrous cycle as well as the implantation and maintenance of pregnancy. Our previous study showed the expression of adropin and its receptor, GPR19, in the luteal cells and its significant role in luteinization. The aim of the present study was to investigate the in vitro effect of adropin on hCG-induced ovarian functions in adult mice. We also evaluated the effect of exogenous treatment with adropin on ovarian steroidogenesis and anti-oxidant parameters, with special emphasis on CL function. Our results demonstrated that adropin acts synergistically with hCG to promote ovarian steroidogenesis and survival by increasing the expression of StAR, 3ß-HSD, and aromatase proteins and decreasing the BAX/BCL2 ratio. Exogenous adropin treatment increased progesterone production by increasing the expression of GPR19, StAR and 3ß-HSD enzymes in the mouse ovary. Also, adropin inhibited the luteal oxidative stress by increasing nuclear translocation of NRF-2 in CL, which resulted in increased HO-1 expression and SOD, catalase activity. Decreased oxidative stress might inhibit the translocation of NF-κB into the nucleus of luteal cells, resulting into increased survival and decreased apoptosis, as evident by decreased lipid peroxidation, BAX/BCL2 ratio, caspase 3, active caspase 3 expression, and TUNEL-positive cells in adropin treated mice. Our findings suggest that adropin can be a promising candidate that can enhance the survivability of the CL.

Incidental detection of rare vascular variation during pyeloplasty and its clinical implication - A case report.

ABSTRACT: Crossing vessels is one of the important causes of pelviureteric junction obstruction (PUJO). Accessory lower polar vessels are commonly seen with congenital PUJO, but they are not always the cause of obstruction. We incidentally encountered a variation in the lower polar crossing vessel while doing laparoscopic pyeloplasty in a patient with congenital PUJO. We encountered a right accessory lower polar artery and vein along with a right gonadal artery arising from the accessory right renal artery and right gonadal vein draining into the right lower polar crossing accessory renal vein. Knowledge of variations in genitourinary vasculature is important in the current era to prevent inadvertent complications.

Early port site and peritoneal metastasis following robot-assisted radical cystectomy: a rare case report.

Radical cystectomy with pelvic lymph node dissection is the recommended treatment for managing muscle-invasive carcinoma of the urinary bladder. Early recurrence is observed in only about 4.1% of cases. Port-site metastasis following robot-assisted radical cystectomy is extremely rare. We encountered a challenging and a rare case of bladder cancer that manifested with port-site and peritoneal metastasis within 6 weeks of surgery.

From A to E: Uniting vitamins against stroke risk-A systematic review and network meta-analysis.

BACKGROUND AND AIM: Stroke represents a significant public health challenge, necessitating the exploration of preventive measures. This network meta-analysis aimed to assess the efficacy of different vitamin treatments compared to a placebo in preventing stroke. METHODS: A systematic electronic search in databases including PubMed, EmBASE, Web of Science, clinicaltrials.gov, and Google Scholar until 31 May 2023 was conducted, to identify published studies investigating the association between vitamin intake and the risk of stroke. Pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using a frequentist network meta-analysis. Furthermore, we ranked vitamins based on p-scores, facilitating a comparative assessment of their effectiveness in preventing stroke. RESULTS: A total of 56 studies, including 17 randomized controlled trials (RCTs) and 39 cohort studies were analyzed. Direct estimates obtained from network meta-analysis, we found that vitamin A (RR: .81 [.72-.91]), vitamin B-complex (RR: .85 [.74-.97]), vitamin B6 (RR: 79 [.68-.92]), folate (RR: .86 [.75-.97]), vitamin C (RR: .77 [.70-.85]) and vitamin D (RR: .73 [.64-.83]) were significantly associated with a decreased stroke risk. However, no significant association was observed for vitamin B2, vitamin B12, and vitamin E. Subsequent to network meta-analysis, vitamins were ranked in decreasing order of their efficacy in stroke prevention based on p-score, with vitamin D (p-score = .91), vitamin C (p-score = .79), vitamin B6 (p-score = .70), vitamin A (p-score = .65), vitamin B-complex (p-score = .53), folate (p-score = .49), vitamin B2 (p-score = .39), vitamin E (p-score = .28), vitamin B12 (.13) and placebo (.10). CONCLUSION: Our study has established noteworthy connections between vitamin A, vitamin B-complex, vitamin B6, folate, vitamin C, and vitamin D in the realm of stroke prevention. These findings add substantial weight to the accumulating evidence supporting the potential advantages of vitamin interventions in mitigating the risk of stroke. However, to solidify and validate these observations, additional research is imperative. Well-designed clinical trials or cohort studies are needed to further explore these associations and formulate clear guidelines for incorporating vitamin supplementation into effective stroke prevention strategies.

Correlation of urinary continence recovery with various factors after Robot assisted radical prostatectomy.

BACKGROUND: In addition to ensuring cancer control, prevention of incontinence which significantly impact patients' quality of life, is also an important issue in robot-assisted radical prostatectomy (RARP) operations. In this study, we aimed to find the correlation of urinary continence recovery with various factors after Robot assisted radical prostatectomy. METHODS: This study included 162 patients treated with RARP with perioperative data and at least 1 year of follow-up. Also, the preoperative, intraoperative, and postoperative parameters of the patients were analyzed. The continence recovery rate in our study was assessed at 6th week, 3rd month, 6th month, 9th month, and 12th month, post-surgery. Logistic regression analysis evaluated the association between the predictive factors and urinary continence recovery in the early and late stages. RESULTS: The majority of patients with prostate cancer present in sixth decade of life. The majority of our patients (56.7%) were categorized as high risk using D'Amico classification. The continence rate in our study at 6th week, 3rd month, 6th month, 9th month, and 12th month were 40.1%, 72.2%, 85.2%, 89.5%, and 91.4%, respectively. No improvement in continence status was observed after 1 year in our study. There was significant correlation of age with continence status at 6th week, 3rd month, and 6th month. The young age is associated with early recovery of continence. At 3 and 9 months, the non-diabetics cases achieved significantly higher continence rates than diabetics (p < 0.05) which shows that diabetes causes delay in attainment of continence. CONCLUSION: The young age may be associated with early recovery of continence, but further validation requires large number of cases. We attributed good continence recovery rate to meticulous dissection and preservation of good urethral length.

Assessing pentafecta outcomes post radical cystectomy: A tertiary care center study.

INTRODUCTION: Bladder cancer is a common and serious disease globally, often requiring radical cystectomy as the preferred treatment. However, this procedure carries substantial risks and complications. To evaluate its success, pentafecta, a five-component measure, was introduced. This study investigates the attainment of pentafecta following radical cystectomy and examines factors that influence its achievement. METHODOLOGY: This retrospective, single-group study was conducted at AIIMS Jodhpur. The study population included 42 patients who underwent radical cystectomy for bladder cancer. Various data, including demographic characteristics, clinical features, surgical techniques, and postoperative outcomes, were collected from medical records. The primary outcome measure was the rate of achieving pentafecta, which comprises five parameters. RESULTS: Out of 42 patients, 26 (61.9%) achieved pentafecta. Age, gender, comorbidities and surgical approach did not significantly affect the attainment of pentafecta. Negative surgical margins were achieved in 95.2% of cases, and adequate lymph node dissection (>16 lymph nodes) was performed in 85.7% of cases. The absence of Clavien-Dindo grade 3-5 complications and recurrence was observed in 80.9% and 90.47% of cases, respectively. Uretero-enteric stricture was absent in 95.2% of cases. CONCLUSION: The study emphasizes the significance of negative surgical margins, thorough lymph node dissection, absence of complications, recurrence, and uretero-enteric strictures in evaluating the success of radical cystectomy as pentafacta outcomes. Patients with higher drain output and wound infections are less likely to achieve pentafacta outcome and indicates poorer outcome. By considering these factors, clinicians can assess patient outcomes and identify areas for improvement.

Adropin, a novel hepatokine: localization and expression during postnatal development and its impact on testicular functions of pre-pubertal mice.

Adropin, a multifaceted peptide, was identified as a new metabolic hormone responsible for regulating gluco-lipid homeostasis. However, its role in the testicular function is not yet understood. We aimed to investigate the localization and expression of adropin and GPR19 during different phases of postnatal development. Immunohistochemical study revealed the intense reactivity of adropin in the Leydig cells during all phases of postnatal development, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells as well as primary and secondary spermatocytes. Western blot study revealed maximum expression of GPR19 in pre-pubertal mouse testis that clearly indicates maximum responsiveness of adropin during that period. So, we hypothesized that adropin may act as an autocrine/paracrine factor that regulates pubertal changes in mouse testis. To examine the effect of adropin on pubertal onset, we gave bilateral intra-testicular doses (0.5 and 1.5 µg/testis) to pre-pubertal mice. Adropin treatment promoted testicular testosterone synthesis by increasing the expression of StAR, 3ß-HSD, and 17ß-HSD. Adropin also promoted germ cell survival and proliferation by upregulating the expression of PCNA and downregulating the Bax/Bcl2 ratio and Caspase 3 expression resulting in fewer TUNEL-positive cells in adropin-treated groups. FACS analysis demonstrated that adropin treatment not only increases 1C to 4C ratio but also significantly increases the 1C (spermatid) and 1C to 2C ratio which demarcates accelerated germ cell differentiation and turnover of testicular cells. In conclusion, adropin promotes steroidogenesis, germ cell survival, as well as the proliferation in the pre-pubertal mouse testis that may hasten the pubertal transition in an autocrine/paracrine manner.

Mucosal SARS-CoV-2 vaccination of rodents elicits superior systemic T central memory function and cross-neutralising antibodies against variants of concern.

BACKGROUND: COVID-19 vaccines used in humans are highly effective in limiting disease and death caused by the SARS-CoV-2 virus, yet improved vaccines that provide greater protection at mucosal surfaces, which could reduce break-through infections and subsequent transmission, are still needed. METHODS: Here we tested an intranasal (I.N.) vaccination with the receptor binding domain of Spike antigen of SARS-CoV-2 (S-RBD) in combination with the mucosal adjuvant mastoparan-7 compared with the sub-cutaneous (S.C.) route, adjuvanted by either M7 or the gold-standard adjuvant, alum, in mice, for immunological read-outs. The same formulation delivered I.N. or S.C. was tested in hamsters to assess efficacy. FINDINGS: I.N. vaccination improved systemic T cell responses compared to an equivalent dose of antigen delivered S.C. and T cell phenotypes induced by I.N. vaccine administration included enhanced polyfunctionality (combined IFN-γ and TNF expression) and greater numbers of T central memory (TCM) cells. These phenotypes were T cell-intrinsic and could be recalled in the lungs and/or brachial LNs upon antigen challenge after adoptive T cell transfer to naïve recipients. Furthermore, mucosal vaccination induced antibody responses that were similarly effective in neutralising the binding of the parental strain of S-RBD to its ACE2 receptor, but showed greater cross-neutralising capacity against multiple variants of concern (VOC), compared to S.C. vaccination. I.N. vaccination provided significant protection from lung pathology compared to unvaccinated animals upon challenge with homologous and heterologous SARS-CoV-2 strains in a hamster model. INTERPRETATION: These results highlight the role of nasal vaccine administration in imprinting an immune profile associated with long-term T cell retention and diversified neutralising antibody responses, which could be applied to improve vaccines for COVID-19 and other infectious diseases. FUNDING: This study was funded by Duke-NUS Medical School, the Singapore Ministry of Education, the National Medical Research Council of Singapore and a DBT-BIRAC Grant.

Adropin may promote insulin stimulated steroidogenesis and spermatogenesis in adult mice testes.

Adropin is a versatile peptide which was discovered as a novel metabolic hormone that is involved in the regulation of lipid and glucose homeostasis. However, its possible role in the testicular function is not yet understood. The aim of our study was to explore the distribution pattern of adropin and GPR19 in various cell types and its possible role in testicular functions of adult mice. Immunohistochemical study revealed the intense immunoreactivity of adropin in the Leydig cells, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells and primary as well as secondary spermatocytes in mouse testis. Enho mRNA was also found to be expressed in the mouse testis. These findings suggested that adropin-GPR19 signaling may act in autocrine/paracrine manner to modulate testicular functions. Furthermore, to find out the direct role of adropin in the testicular function, in vitro study was performed in which testicular slices were cultured with adropin alone (10 and 100 ng/mL) and in combination with insulin (5 µg/mL). Adropin alone inhibited testicular testosterone synthesis by inhibiting the expression of P450-SCC, 3ß-HSD, and 17ß-HSD while along with insulin stimulated the testicular testosterone synthesis by increasing the expression of GPR19, IR, StAR, P450-SCC, 3ß-HSD, and 17ß-HSD. Adropin alone or in combination with insulin promoted germ cell survival and proliferation by upregulating the expression of PCNA, Bcl2, and pERK1/2. Thus, it can be concluded that adropin-GPR19 signaling promotes insulin stimulated steroidogenesis and germ cell survival as well as proliferation in the mice testes in an autocrine/paracrine manner.

Postradical cystectomy delayed urethral recurrence: a rare presentation posing diagnostic dilemma.

The incidence of urethral recurrence after radical cystectomy is 1% to 8%, with most cases occurring within the first 2 years of surgery. Prophylactic urethrectomy is rarely performed nowadays due to no known survival benefit and increased morbidity due to the procedure. However, we encountered a rare case of delayed urethral recurrence presenting as recurrent urethral collection 4 years after radical cystectomy with ileal conduit diversion, posing a diagnostic dilemma.