Nitric oxide mediated kisspeptin regulation of steroidogenesis and gametogenesis in the catfish, Clarias batrachus.

Nitric oxide (NO) is a gaseous molecule that regulates various reproductive functions. It is a well-recognized regulator of GnRH-FSH/LH-sex steroid secretion in vertebrates including fish. Kisspeptin is a recently discovered neuropeptide which also regulates GnRH secretion. Nitrergic and kisspeptin neurons are reported in close physical contact in the mammalian brain suggesting their interactive role in the release of GnRH. The existence of kisspeptin and NOS is also demonstrated in vertebrate gonads, but information on their reciprocal relation in gonads, if any, is obscure. Therefore, attempts were made to evaluate the functional reciprocal relation between nitric oxide and kisspeptin in the catfish gonads, if any, by administering the nitric oxide synthase (NOS) inhibitor, L-NAME {N(G)-nitro-L-arginine methyl ester}, which reduces NO production, and kisspeptin agonist (KP-10) and assessing their impacts on the expressions of kisspeptin1, different NOS isoforms, NO and steroid production in the gonadal tissue. The results revealed that L-NAME suppressed the expression of kiss1 in gonads of the catfish establishing the role of NO in kisspeptin expression. However, KP-10 increased the expression of all the isoforms of NOSs (iNOS, eNOS, nNOS) and concurrently NO and steroids in the ovary and testis. In vitro studies also indicate that kisspeptin stimulates the production of NO and estradiol and testosterone levels in the gonadal explants and medium. Thus, in vivo results clearly suggest a reciprocal interaction between kisspeptin and NO to regulate the gonadal activity of the catfish. The in vitro findings further substantiate our contention regarding the interactive role of kisspeptin and NO in gonadal steroidogenesis.

Effectiveness of school oral health programs in children and adolescents: an umbrella review.

AIM: To evaluate the systematic reviews assessing the effectiveness of any type of school-based oral health programs in children and adolescents. METHODOLOGY: A two-staged search strategy comprising electronic databases and registries based on systematic reviews was employed to evaluate the effectiveness of school-based interventions. The quality assessment of the systematic reviews was carried out using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) tool. The Corrected Covered Area was used to evaluate the degree of overlap. RESULTS: Nine reviews were included in this umbrella review. The Critical Covered Area reported moderate overlap (5.70%) among the primary studies. The assessment of risk of bias revealed one study with a high level confidence; one with moderate whereas all other studies with critically low confidence. Inconclusive evidence related to improvements in dental caries and gingival status was reported whereas, plaque status improved in a major proportion of the reviews. Knowledge, attitude, and behavior significantly increased in students receiving educational interventions when compared to those receiving usual care. CONCLUSIONS: The evidence points to the positive impact of these interventions in behavioral changes and clinical outcomes only on a short term basis. There is a need for long-term follow-up studies to substantiate the outcomes of these interventions.

The Rapid Evaluation of Down Syndrome With Quantitative Fluorescence Polymerase Chain Reaction (QF-PCR): A Pilot Study Among the Population in Eastern Uttar Pradesh, India.

Background and objective Down syndrome (DS) is characterized by the presence of an additional chromosome; it is a typical chromosomal disorder causing intellectual disability in individuals. The diagnostic process for DS often involves conventional karyotyping, which can be time-consuming. Trisomy 21 and other chromosomal abnormalities may now be quickly and accurately diagnosed using quantitative fluorescence polymerase chain reaction (QF-PCR). In light of this, this study aimed to investigate chromosomal abnormalities in DS using conventional karyotyping and QF-PCR among the population in eastern Uttar Pradesh, India. Methods Blood samples from 40 individuals with clinically diagnosed DS were collected. Conventional karyotyping involved standard cytogenetic techniques, while QF-PCR utilized DNA extraction and analysis with chromosome-specific short tandem repeat (STR) markers. Results Various distinct physical characteristics were observed in the DS individuals, such as mongoloid slant and low-set ears. Karyotyping and QF-PCR analyses revealed different chromosomal configurations associated with DS trisomy 21, with additional chromosomal abnormalities found in some individuals, including partial monosomy 18 and mosaic trisomy 21. However, in a few cases, neither karyotyping nor QF-PCR revealed any abnormalities. Conclusions The study demonstrated that QF-PCR is a reliable and rapid method for diagnosing DS, providing results within 24 hours. This approach allows for the simultaneous diagnosis of a large number of samples and reduces the time required to obtain results. In the diagnostic procedure for DS, we believe QF-PCR will prove to be a useful tool. Furthermore, therapeutic interventions based on their clinical traits and molecular karyotyping can enhance the quality of life of people with DS.

Social inequities in early childhood caries in Australia: A population-based study on statewide public dental services data.

BACKGROUND: Social disadvantage leads to dental caries during childhood. AIM: This study investigated whether dental caries occur earlier in children from households experiencing social disadvantage than those not experiencing social disadvantage. DESIGN: The overall risk of, and relative time to, early childhood caries (ECC) according to sociodemographic characteristics in Victoria, Australia, was quantified. Records for 134 463 children in Victoria, Australia, from 2009 to 2019 were analysed. Time ratios (TR) and hazard ratios (HR) of carious lesion(s) in early childhood were estimated. RESULTS: Compared with reference groups, Indigenous children had an adjusted TR of 0.80 (95% CI: 0.78, 0.82), children from households with languages other than English had an adjusted TR of 0.83 (95% CI: 0.82, 0.84), and dependants of concession cardholders had an adjusted TR of 0.81 (95% CI: 0.80, 0.81); therefore, 20%, 17% and 19% reduced times to the first carious lesion, respectively. The estimated HRs were 1.57 (95% CI: 1.49, 1.67) for Indigenous children, 1.46 (95% CI: 1.42, 1.50) for children from households with other languages and 1.57 (CI: 1.53, 1.60) for dependants of concession cardholders. CONCLUSION: Preventive oral health interventions must be targeted early in children from households experiencing social disadvantage to avoid social inequities in ECC.

Biomaterial-Based Therapeutic Delivery of Immune Cells.

Immune cell therapy is a transformative approach used to treat a wide range of diseases including type 1 diabetes, sickle cell disease, disorders of the hematopoietic system, and certain forms of cancers. Despite excellent clinical successes, the scope of adoptively transferred immune cells is limited because of toxicities like cytokine release syndrome and immune effector cell-associated neurotoxicity in patients. Furthermore, reports suggest that such treatment can impact major organ systems including cardiac, renal, pulmonary, and hepatic systems in the long term. Additionally, adoptively transferred immune cells cannot achieve significant penetration into solid tissues, thus limiting their therapeutic potential. Recent studies suggest that biomaterial-assisted delivery of immune cells can address these challenges by reducing toxicity, improving localization, and maintaining desired phenotypes to eventually regain tissue function. In this review, we highlight recent efforts in the field of biomaterial-based immune cell delivery for the treatment of diseases, their pros and cons, and where these approaches stand in terms of clinical treatment. This article is protected by copyright. All rights reserved.

Optimising Patient Outcomes in Tongue Cancer: A Multidisciplinary Approach.

A multidisciplinary approach to the management of tongue cancer is vital for achieving optimal patient outcomes. Nursing and allied health professionals play essential roles within the team. We developed symposia comprising a series of online lectures offering a detailed perspective on the role each discipline and consumer perspective has in the management of patients with tongue cancer. The topics, including epidemiology and prevention, diagnosis, treatment planning, surgery, adjuvant care, and the management of recurrent or metastatic disease, were thoroughly examined. The symposia highlighted the significance of fostering collaboration and continuous learning through a multidisciplinary approach. This initiative should be relevant to healthcare professionals, researchers, and policymakers striving to enhance patient outcomes in tongue cancer care through innovative collaboration.

The workplace culture, mental health and wellbeing of early- and mid-career health academics: a cross-sectional analysis.

There are reports of poor working conditions for early and mid-career academics (EMCAs) in universities, however, empirical data using validated tools are scarce. We conducted an online, cross-sectional survey using validated tools to assess workplace satisfaction, exposure to workplace abuse, and mental health. Participants included employees of medical and health faculties of two of the largest Australian universities, surveyed between October 2020 and January 2021.Overall, 284 participants responded. Many reported job insecurity: half (50.7%) working on contracts with less than one remaining year. Workloads were considerable, with 89.5% of participants working overtime and 54.8% reporting burnout. Workplace abuse in the forms of bullying (46.6%), sexual harassment (25.3%), sexism (49.8%) and racism (22.5%) were commonly reported. Clinically significant symptoms of depression (28.0%), anxiety (21.7%) and suicidal ideation or self-harm (13.6%) were reported; with a higher prevalence among those working more overtime, and those exposed to workplace abuse. Priorities include providing a stable and safe workplace, increasing accountability and transparency in addressing workplace abuse, and supporting professional development.In summary, EMCAs in our study were commonly exposed to precarious employment conditions and workplace abuse. Our findings provide empirical evidence on where universities and funding bodies should direct resources and change organisational risk factors, to improve workplace culture.

Comprehensive Genomics Investigation of Neboviruses Reveals Distinct Codon Usage Patterns and Host Specificity.

Neboviruses (NeVs) from the Caliciviridae family have been linked to enteric diseases in bovines and have been detected worldwide. As viruses rely entirely on the cellular machinery of the host for replication, their ability to thrive in a specific host is greatly impacted by the specific codon usage preferences. Here, we systematically analyzed the codon usage bias in NeVs to explore the genetic and evolutionary patterns. Relative Synonymous Codon Usage and Effective Number of Codon analyses indicated a marginally lower codon usage bias in NeVs, predominantly influenced by the nucleotide compositional constraints. Nonetheless, NeVs showed a higher codon usage bias for codons containing G/C at the third codon position. The neutrality plot analysis revealed natural selection as the primary factor that shaped the codon usage bias in both the VP1 (82%) and VP2 (57%) genes of NeVs. Furthermore, the NeVs showed a highly comparable codon usage pattern to bovines, as reflected through Codon Adaptation Index and Relative Codon Deoptimization Index analyses. Notably, yak NeVs showed considerably different nucleotide compositional constraints and mutational pressure compared to bovine NeVs, which appear to be predominantly host-driven. This study sheds light on the genetic mechanism driving NeVs' adaptability, evolution, and fitness to their host species.

Functionalized nanowires for miRNA-mediated therapeutic programming of naïve T cells.

Cellular programming of naïve T cells can improve the efficacy of adoptive T-cell therapy. However, the current ex vivo engineering of T cells requires the pre-activation of T cells, which causes them to lose their naïve state. In this study, cationic-polymer-functionalized nanowires were used to pre-program the fate of primary naïve CD8+ T cells to achieve a therapeutic response in vivo. This was done by delivering single or multiple microRNAs to primary naïve mouse and human CD8+ T cells without pre-activation. The use of nanowires further allowed for the delivery of large, whole lentiviral particles with potential for long-term integration. The combination of deletion and overexpression of miR-29 and miR-130 impacted the ex vivo T-cell differentiation fate from the naïve state. The programming of CD8+ T cells using nanowire-delivered co-delivery of microRNAs resulted in the modulation of T-cell fitness by altering the T-cell proliferation, phenotypic and transcriptional regulation, and secretion of effector molecules. Moreover, the in vivo adoptive transfer of murine CD8+ T cells programmed through the nanowire-mediated dual delivery of microRNAs provided enhanced immune protection against different types of intracellular pathogen (influenza and Listeria monocytogenes). In vivo analyses demonstrated that the simultaneous alteration of miR-29 and miR-130 levels in naïve CD8+ T cells reduces the persistence of canonical memory T cells whereas increases the population of short-lived effector T cells. Nanowires could potentially be used to modulate CD8+ T-cell differentiation and achieve a therapeutic response in vivo without the need for pre-activation.

Yield estimation of radionuclides from 6,7Li-induced reactions: A comparative analysis for 97,95Ru.

The article reports the production yields of the medically relevant Ru radionuclides and other co-produced radionuclides from 6,7Li-induced reactions on 93Nb target within the 20-45 MeV energy range. The residues were measured employing the activation technique followed by the offline γ-spectroscopy. Statistical model calculations using EMPIRE3.2.2 code are employed to assess the optimized nuclear model parameters and production mechanisms of the residues. As an outcome, new data from 6Li reaction suggests 9720 MBq/C of thick target yield (TTY) for the production of 95Ru with minimal impurities. While 7Li reaction may be relied upon for producing 97Ru, yielding 813 MBq/C TTY within the studied energy range.

Statistical modelling, optimization, and mechanistic exploration of novel ureolytic Enterobacter hormaechei IITISM-SA3 in cadmium immobilization under microbial inclusive and cell-free conditions through microbially induced calcite precipitation.

The study aimed to evaluate the potential of a novel isolated ureolytic Enterobacter hormaechei IITISM-SA3 in cadmium bioremoval through MICP. The optimization and modelling of the biotic and abiotic factors affecting the process of mineralization were also performed. In addition, the underlying mechanism of MICP-driven Cd mineralization under microbial-inclusive and cell-free conditions was revealed and supported through the characterization of the bio-precipitates obtained using various characterization techniques. The results indicated that the isolate could remove 97.18% Cd2+ of 11.4 ppm under optimized conditions of 36.86 h, pH 7.63, and biomass dose of 1.75 ml. Besides, the presence and absence of bacterial cells were found to influence both the morphologies and crystalline structures of precipitates. The precipitates obtained under microbial-inclusive conditions showed typical rhombohedral crystalline structures of the composition comprising CaCO3, CdCO3, and 0.67Ca0.33CdCO3. However, the crystalline nature of the precipitate reduced to a nano-sized granular structure in cell-free media. Unlike the cadmium mineralization process under microbial-inclusive media, where bacterial cells serve as nucleation sites for crystallization, the carbonate precipitation effectively captures Cd2+ through co-precipitation, chemisorption, or alternative mechanisms involving interactions between metal ions and CaCO3 under cell-free conditions. The findings presented suggest that using cell-free culture supernatant enriched with carbonate ions provides an avenue that could be harnessed for sustainable metal remediation.

The effect of informal caring on mental health among adolescents and young adults in Australia: a population-based longitudinal study.

BACKGROUND: Young carers are people aged up to 25 years who provide unpaid care to a relative or a friend living with a long-term condition or a disability. Providing informal care is associated with poor mental health. Longitudinal evidence on this relationship among young people is scarce. To address this gap, we assessed the mental health of people aged 15-25 years when providing informal care compared with when not providing informal care. METHODS: We conducted a population-based longitudinal study using 20 years of data between 2001 and 2020 from the Household Income and Labour Dynamics in Australia (HILDA) survey. We included observations of participants aged 15-25 years with at least two observations across 20 waves of HILDA. Informal care was categorised as 0 h per week, 1-19 h per week, and 20 or more h per week. Mental health was measured using the Mental Health Inventory (MHI-5) from the 36-Item Short Form Survey (SF-36). Multivariate linear fixed-effects regression models were fitted to assess within-person changes in mental health when providing different levels of informal care. FINDINGS: Of 44 663 people with 410 658 observations who participated in HILDA waves 1 to 20, 32 726 were excluded with 351 445 observations. 11 937 young people (with 59 213 observations) were deemed eligible for this study and, of these, 8996 participants with 43 231 observations were included in the complete case analytical sample. When caring for 1-19 h per week, young carers had an MHI-5 score of -1·98 points (95% CI -3·06 to -0·89) compared with when caring for 0 h per week. Mental health was worse when caring for 20 or more h per week, with participants displaying an MHI-5 score of -3·47 points (95% CI -6·02 to -0·92) compared with when caring for 0 h per week. Our findings were consistent across sensitivity tests. INTERPRETATION: Our findings suggest potential mental health effects of informal care in young people, particularly when providing an intense amount of caregiving. Reducing young caring loads could be a possible avenue for intervention. FUNDING: Melbourne Disability Institute Scholarship, University of Melbourne Research Training Program Scholarship, Australian Research Council Discovery Early Career Researcher Award, National Health and Medical Research Council of Australia funded Centre of Research Excellence in Disability and Health.

Mechanical loading of joint modulates T cells in lymph nodes to regulate osteoarthritis.

OBJECTIVE: The crosstalk of joint pathology with local lymph nodes in osteoarthritis (OA) is poorly understood. We characterized the change in T cells in lymph nodes following load-induced OA and established the association of the presence and migration of T cells to the onset and progression of OA. METHODS: We used an in vivo model of OA to induce mechanical load-induced joint damage. After cyclic tibial compression of mice, we analyzed lymph nodes for T cells using flow cytometry and joint pathology using histology and microcomputed tomography. The role of T-cell migration and the presence of T-cell type was examined using T-cell receptor (TCR)α-/- mice and an immunomodulatory drug, Sphingosine-1-phosphate (S1P) receptor inhibitor-treated mice, respectively. RESULTS: We demonstrated a significant increase in T-cell populations in local lymph nodes in response to joint injury in 10, 16, and 26-week-old mice, and as a function of load duration, 1, 2, and 6 weeks. T-cell expression of inflammatory cytokine markers increased in the local lymph nodes and was associated with load-induced OA progression in the mouse knee. Joint loading in TCRα-/- mice reduced both cartilage degeneration (Osteoarthritis Research Society International (OARSI) scores: TCRα 0.568, 0.981-0.329 confidence interval (CI); wild type (WT) 1.328, 2.353-0.749 CI) and osteophyte formation. Inhibition of T-cell egress from lymph nodes attenuated load-induced cartilage degradation (OARSI scores: Fingolimod: 0.509, 1.821-0.142 CI; Saline 1.210, 1.932-0.758 CI) and decreased localization of T cells in the synovium. CONCLUSIONS: These results establish the association of lymph node-resident T cells in joint damage and suggest that the S1P receptor modulators and T-cell immunotherapies could be used to treat OA.

Mixed organic and inorganic nitrogen sources enhance chitosan yield in novel isolates of Penicillium.

Chitosan, a valuable biopolymer, has traditionally been derived from marine sources. However, exploring fungal alternatives offers a sustainable supply. This research investigates the potential of chitosan production from fungal sources, focusing on the optimization of abiotic factors using two novel Penicillium strains (IITISM-ANK1 and IITISM-ANK2) isolated from dry aged sludge. Box-Behnken model and standard statistical analysis were deployed to develop an equation predicting the effect of carbon and nitrogen sources, pH, and temperature on chitosan production. Batch experiments validate the model's accuracy under optimized conditions. The results indicate that mixed organic and inorganic nitrogen sources in the form of peptone, nitrate, and ammonium salts enhanced chitosan yield in both isolates. At optimal conditions for the chitosan production of IITISM-ANK2 and IITISM-ANK1 were found to be 293.29 mg/L and 325.01 mg/L, with the degree of deacetylation of over 74 % which is a critical parameter for chitosan quality. Thus, these isolates can be used as a potent microbe for industrial chitosan production and contribute to advancing sustainable chitosan production and its potential industrial applications.

Trends in age of tobacco use initiation over time in Bangladesh, India and Pakistan: analysis of cross-sectional nationally representative surveys.

OBJECTIVE: Tobacco use begins at an early age and typically leads to a long-term addiction. The age of initiation for tobacco use is not well studied in South Asia, where 22% of tobacco smokers and 81% of smokeless tobacco (SLT) users reside. METHODS: Data from the nationally representative Global Adult Tobacco Surveys in India, Bangladesh and Pakistan were analysed to examine patterns of initiation among smokers and smokeless tobacco users. RESULTS: Data on 94 651 individuals were analysed, of which 13 396 reported were ever daily smokers and 17 684 were ever SLT users. The proportion of individuals initiating tobacco use before the age of 15 years has increased over time. The rates of SLT initiation among those aged 15-24 years increased markedly in Bangladesh (by 7.8%) and Pakistan (by 37.7%) between 1983 and 1999-2000. Among males, the increase in SLT initiation was higher in individuals aged below 15 years compared with other age groups in India and Bangladesh. Smoking initiation among females aged below 15 years has also significantly increased in India over time. Compared with the initiation of tobacco smoking before the age of 15 years, a greater increase in the proportion of SLT users was observed in urban areas. CONCLUSION: Our findings indicate that the proportion of youth initiating tobacco (both smoking and smokeless) before the age of 15 years has increased over time in all three countries. Moreover, variations in age at initiation for different types of tobacco products across countries, and by rurality, were noticeable. Younger youths (aged up to 15 years) should therefore be a priority population for tobacco control interventions. Strategies such as raising the legal age of tobacco sale and use to 21 years, and, other measures under WHO Framework Convention on Tobacco Control (FCTC), may prevent underage use and avert lifelong addiction to tobacco products.

Deciphering the biochemical regulation of metabolic pathways in abating stress-induced damages during co-exposure of arsenic and fluoride in a non-aromatic and an aromatic rice variety.

The aim of the current work was to decipher the systemic damage and biochemical defense machinery due to combined arsenic (5 mg L-1 Na3AsO4) and fluoride (50 mg L-1 NaF) stress in two rice cultivars viz., IR-64 (non-aromatic) and Gobindobhog (aromatic), grown for 14 days, under 16/8 h light/dark photoperiodic cycle at 32 °C. Higher accumulation of arsenic and fluoride in Gobindobhog generated higher levels of H2O2 that caused higher electrolyte leakage, along with malondialdehyde and methylglyoxal formation. Higher oxidative damages severely compromised seed germination and led to chlorophyll loss, inhibition of root and shoot growth and fresh and dry weight of the seedlings. On the contrary, oxidative damage was less pronounced in IR-64, as compared to that of Gobindobhog, which can be attributed to higher accumulation of protective metabolites, i.e., osmolytes and antioxidants. Higher levels of osmolytes (proline, glycine betaine and amino acids) in IR-64 helped in maintaining the osmotic balance of the cells and the integrity of the cell membrane. Additionally, up regulated activity of enzymatic antioxidants (catalase, superoxide dismutase, ascorbate peroxidase, glutathione peroxidase and glutathione S-transferase) along with elevated levels of non-enzymatic antioxidants (flavonoids, phenolics, xanthophylls and carotenoids) played a pivotal role in controlling oxidative damages and strengthening the defense machinery in IR-64, as compared to that of Gobindobhog where lesser enhancement in the level of the above mentioned protective metabolites was noted. The present work illustrated differential phytotoxicity in rice seedlings and elucidated the yet uncharacterized biohazard associated with arsenic and fluoride co-contamination, with better adaptive features of IR-64, compared to Gobindobhog, which appeared as the sensitive variety.

Pediatric Renal Rickets at a Tertiary Center.

We report clinical and etiological profile of 19 children (10 males) with renal rickets managed in the years 2021-2022. Median (IQR) age of presentation was 60 (18-96) months. The commonest cause was renal tubular acidosis (n=8). Genetic analysis revealed the diagnosis in 83% subjects (5 out of 6 tested).