Probiotic formulations and gastro-intestinal diseases in the paediatric population: a narrative review.

Background/Aim: Probiotics are live microbial supplements that improve the microbial balance in the host animal when administered in adequate amounts. They play an important role in relieving symptoms of many diseases associated with gastrointestinal tract, for example, in necrotizing enterocolitis (NEC), antibiotic-associated diarrhea, relapsing Clostridium difficile colitis, Helicobacter pylori infections, and inflammatory bowel disease (IBD). In this narrative review, the authors aim to evaluate the role of different probiotic formulations in treating gastrointestinal diseases in pediatric population aged 18 years or younger and highlight the main considerations for selecting probiotic formulations for use in this population. Methodology: The authors searched PubMed and Clinicaltrials.gov from inception to 24th July 2022, without any restrictions. Using an iterative process, the authors subsequently added papers through hand-searching citations contained within retrieved articles and relevant systematic reviews and meta-analyses. Results: The effectiveness of single-organism and composite probiotics in treating gastrointestinal disorders in pediatric patients aged 18 or under were analyzed and compared in this study. A total of 39 studies were reviewed and categorized based on positive and negative outcomes, and compared with a placebo, resulting in 25 studies for single-organism and 14 studies for composite probiotics. Gastrointestinal disorders studied included NEC, acute gastroenteritis (AGE), Acute Diarrhea, Ulcerative Colitis (UC), and others. The results show that probiotics are effective in treating various gastrointestinal disorders in children under 18, with single-organism probiotics demonstrating significant positive outcomes in most studies, and composite probiotics showing positive outcomes in all studies analyzed, with a low incidence of negative outcomes for both types. Conclusion: This study concludes that single-organism and composite probiotics are effective complementary therapies for treating gastrointestinal disorders in the pediatric population. Hence, healthcare professionals should consider using probiotics in standard treatment regimens, and educating guardians can enhance the benefits of probiotic therapy. Further research is recommended to identify the optimal strains and dosages for specific conditions and demographics. The integration of probiotics in clinical practice and ongoing research can contribute to reducing the incidence and severity of gastrointestinal disorders in pediatric patients.

Comparing pyridoxine with dopaminergic agonists (cabergoline and bromocriptine): Unveiling the strategy for lactation inhibition - A systematic review of clinical trials.

This systematic review aims to evaluate the efficacy and safety of Pyridoxine compared to Dopaminergic agonists (cabergoline and bromocriptine) in post-partum lactation inhibition. Cochrane Central, PubMed/MEDLINE, Cochrane Central, ScienceDirect, ClinicalTrials.gov, Web of Science, CINAHL and Google Scholar, covering the period from inception to November 2023. Additionally, the bibliographies of included articles and previous meta-analyses were screened for any relevant articles. The systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The outcomes of interest encompassed inhibition of lactation, breast pain/tenderness, breast engorgement, milk secretion, fever, mastitis, prolactin level and adverse events related to pyridoxine, cabergoline and bromocriptine. Methodological quality assessment was conducted using the Cochrane risk of bias assessment tool for rigorous evaluation. Three clinical trials assessed the effectiveness of pyridoxine and dopaminergic agents (cabergoline and bromocriptine) for lactation inhibition. It was assessed by using different assessment methods such as a scale for milk secretion, serum prolactin levels, and questionnaires for assessing breast engorgement, breast pain, and milk leakage. On the global assessment of the therapeutic efficacy of dopaminergic agents, it was found that there was significant inhibition of lactation as compared to pyridoxine (p < 0.001). In conclusion, this systematic review contributes significant insights into lactation inhibition interventions. Dopaminergic agonists, specifically cabergoline and bromocriptine, stand out as more effective and tolerable choices compared to Pyridoxine. These findings provide a foundation for informed clinical decisions and underscore the need for careful consideration of lactation inhibition strategies in diverse clinical contexts.

Unmasking the long-term effects: unravelling neuropsychiatric and neurological consequences of COVID-19.

The COVID-19 pandemic has not only burdened healthcare systems but has also led to a new emerging medical enigma that is post-COVID-19 syndrome or "long COVID." Characterized by persistent symptoms that extend beyond the acute phase of the illness, long COVID has rapidly become a public health concern with ambiguous neurological and neuropsychiatric dimensions. This narrative review aims at synthesizing available research to decode the long-term impacts of COVID-19 on neurological and mental health. Drawing from a multitude of studies, this review synthesizes evidence on various neuropsychiatric and neurological symptoms, including cognitive deficits, mood disorders, and more. The narrative delves into potential pathogenic mechanisms, hoping to fill existing research gaps and offering directions for future inquiry. The objective is not just academic; it has immediate real-world implications. Understanding these long-term effects is crucial for developing effective treatments and interventions, thereby better serving the millions of individuals living with these lingering symptoms. As healthcare systems continue to grapple with the fallout from the pandemic, this review provides much-needed context and insights into an area that demands urgent research and action.

Understanding the impact of structural modifications at the NNAT gene's post-translational acetylation site: in silico approach for predicting its drug-interaction role in anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is a neuropsychological public health concern with a socially disabling routine and affects a person's healthy relationship with food. The role of the NNAT (Neuronatin) gene in AN is well established. The impact of mutation at the protein's post-translational modification (PTM) site has been exclusively associated with the worsening of the protein's biochemical dynamics. METHODS: To understand the relationship between genotype and phenotype, it is essential to investigate the appropriate molecular stability of protein required for proper biological functioning. In this regard, we investigated the PTM-acetylation site of the NNAT gene in terms of 19 other specific amino acid probabilities in place of wild type (WT) through various in silico algorithms. Based on the highest pathogenic impact computed through the consensus classifier tool, we generated 3 residue-specific (K59D, P, W) structurally modified 3D models of NNAT. These models were further tested through the AutoDock Vina tool to compute the molecular drug binding affinities and inhibition constant (Ki) of structural variants and WT 3D models. RESULTS: With trained in silico machine learning algorithms and consensus classifier; the three structural modifications (K59D, P, W), which were also the most deleterious substitution at the acetylation site of the NNAT gene, showed the highest structural destabilization and decreased molecular flexibility. The validation and quality assessment of the 3D model of these structural modifications and WT were performed. They were further docked with drugs used to manage AN, it was found that the ΔGbind (kcal/mol) values and the inhibition constants (Ki) were relatively lower in structurally modified models as compared to WT. CONCLUSION: We concluded that any future structural variation(s) at the PTM-acetylation site of the NNAT gene due to possible mutational consequences, will serve as a basis to explore its relationship with the propensity of developing AN. LEVEL OF EVIDENCE: No level of evidence-open access bioinformatics research.

Better understanding extrapulmonary tuberculosis: A scoping review of public health impact in Pakistan, Afghanistan, India, and Bangladesh.

Background and Aims: South Asian countries, including Pakistan, Afghanistan, India, and Bangladesh, have a high prevalence of pulmonary and extra-pulmonary tuberculosis (EPTB). This prevalence is influenced by various risk factors such as ethnicity, nutrition, socioeconomic disparities, high out-of-pocket healthcare expenses, and specific Mycobacterium Tuberculosis (TB) lineages. The COVID-19 pandemic has likely hindered access to healthcare and led to under-reporting of EPTB cases nationally and internationally. This rapid review aimed to summarize the literature on the prevalence and disease outcomes of EPTB in the mentioned countries, compare the situations across countries, and provide recommendations for future action. Methods: The review utilized PubMed and Google Scholar databases to search for literature on EPTB in South Asian countries. The search string included keywords related to different forms of EPTB and the countries of interest while excluding pulmonary tuberculosis. Results: The results showed that both TB, including drug-resistant TB, and EPTB are prevalent and burdensome in South Asia. In Pakistan, pleural TB was the most commonly reported form of EPTB, followed by lymph node TB, abdominal TB, osteoarticular TB, Central Nervous System TB, and miliary TB. In India, lymph node TB(LNTB) was more common among EPTB cases. Bangladesh reported a high prevalence of EPTB involving lymph node, pleura, and abdomen, while Afghanistan had a higher prevalence of forms such as LNTB and tuberculous meningitis. Conclusion: In conclusion, the prevalence of EPTB in Pakistan, Afghanistan, India, and Bangladesh is alarmingly high and negatively impacts population health. Effective measures are needed for treatment and management of this condition, along with addressing current and future challenges. Strengthening the evidence base through surveillance and research is crucial to understand the patterns and significant factors related to EPTB, requiring investment in these areas.

Panantiviral agents: implications for treating cancers associated with oncoviruses.

Tweetable abstract Panantiviral agents have emerged as a promising class of drugs for cancer therapy, targeting multiple oncoviruses simultaneously. Challenges include drug resistance, safety and developing specific inhibitors. Future research should focus on viral transcription regulators and new panantivirals. #cancer #oncovirus #panantiviral #drugresistance.

A rare case of perforated jejunal diverticula of an uncommon origin.

Jejunal diverticula are often asymptomatic and rare, so they can go unnoticed until serious complications like obstruction, bleeding, perforation, volvulus, or diverticulitis occur. Elderly people over 60 are more likely to have this condition.

Fluoroquinolones and the risk of aortic aneurysm or aortic dissection: an updated systematic review and meta-analysis including 53,651,283 patients.

INTRODUCTION: The association between fluoroquinolone use and the risk of aortic aneurysm as well as the risk of aortic dissections remains uncertain, primarily due to conflicting findings from observational studies. We sought to conduct a double-systematic review and meta-analysis of all observational studies to assess the existence and extent of both these associations. The aim of our study is to assess the role of Fluoroquinolone on aortic aneurysm and aortic dissection in comparison to other antibiotics. EVIDENCE ACQUISITION: MEDLINE and Cochrane CENTRAL were systematically searched up till June 2021 for observational studies studying the correlation between fluoroquinolone usage and aortic aneurysms and dissections. Random-effects pooling was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals (CI). To assess publication bias, propensity score matching was conducted, and heterogeneity was evaluated by using I2 statistics. EVIDENCE SYNTHESIS: Of 688 potentially relevant articles, 635 titles were screened. Ten studies were included in the systematic review, and 4 observational studies with 53,651,283 participants were eligible to be included in the meta-analysis. Pooled estimates showed that fluoroquinolone use was associated with a higher risk of aortic aneurysm when compared to other Antibiotics (HR 1.84, 95% CI 1.10-2.48; P<0.00001). However, fluoroquinolones had no significant effect on the risk of developing aortic dissection (HR 1.09, 95% CI 0.96-1.25; P=0.19). CONCLUSIONS: The present analysis suggests that fluoroquinolone usage is more strongly linked to aortic aneurysm than other antibiotics. However, there was no statistically significant link between fluoroquinolone and aortic dissection. As a result, clinicians should exercise caution when administering fluoroquinolone to patients who have a history of or are at risk of aortic disease.

Catheter-Related Bloodstream Infection With Femoral Central Access Versus Internal Jugular Access in Patients Admitting to Medical Intensive Care Unit.

Background The current research focused on studying the pattern of catheter-related bloodstream infections (CRBSI) with femoral central access versus internal jugular access in patients admitted to the medical intensive care unit (ICU). Methods A cross-sectional study was conducted at the Department of Emergency Medicine, Shifa International Hospital, between March 4, 2022, and August 4, 2022. All individuals who presented to the ICU who needed a central venous catheter (CVC) for more than 48 hours were included. Catheter insertion was not permitted if the patient had a history of dermatitis or burns at the site of insertion or if the hemodialysis procedure necessitated the insertion of the catheter into a blood vessel. Three groups of patients were created: group A patients had been diagnosed with CRBSI; group B patients had catheter colonization (CC); and group C did not have CRBSI or CC. Standard microbiological methods were used to identify all of the bacteria collected from the cultures. All data was documented in a predefined pro forma. Results Overall, 20 (12.12%) patients had positive CRBSI, 68 (41.5%) had CC, and the remaining 46.3% of cultures were negative. Elderly populations were more prone to acquiring CRBSI showing a significant correlation between older age and CRBSI (p < 0.0001). CC was significantly associated with a longer duration of ICU stay, i.e., 30.3 ± 3.7 (p = 0.003). The absence of both CRBSI and CC was significantly associated with a lower duration of catheterization (11 ± 8.5 days in group C versus 22.1 ± 6.9 and 18.7 ± 7 days in groups A and B, respectively; p < 0.0001). Our study revealed a higher risk of CRBSI when the femoral access was compared to the internal jugular access (58.3% vs. 41.7%; p = 0.0008). The study did not find any significant association of CC with femoral or internal jugular access. Furthermore, a significantly higher rate of negative cultures was reported in patients with internal jugular access as compared to femoral vein access (85.8% vs. 14.2%; p = 0.007). Conclusion The need for routinely monitoring and observing the microbiological spectrum in patients receiving care in intensive care units is highlighted by the current investigation. The patients with internal jugular vein access had a decreased incidence of CRBSI and CC, while those with femoral access experienced CRBSI more frequently. Escherichia coli and Pseudomonas aeruginosa were the most frequently isolated germs, and both were resistant to various drugs that are used today. It is essential to regularly monitor the epidemiology of CRBSI in order to adopt preventative measures for infection prevention and control, such as staff education, strict hygiene standards, and a higher nurse-to-patient ratio.

Glycolysis: The Next Big Breakthrough in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the death of dopaminergic neurons. Its pathogenesis comprises defects in the physiological pathway of mitophagy and mutations in the genes involved in this process's regulatory mechanism. PD manifests itself with multiple motor and non-motor symptoms, and currently, there are multiple pharmacological treatments, and unconventional non-drug treatments available. The mainstay of Parkinson's disease treatment has centered around directly manipulating neural mechanisms to retain high dopamine levels, either by exogenous administration, increasing intrinsic production, or inhibiting the breakdown of dopamine. In this review, we highlight a new potential biochemical modality of treatment, treating PD through glycolysis. We highlight how terazosin (TZ), via PGK1, increases ATP levels and how enhanced glycolysis serves a neuroprotective role in PD, and compensates for damage caused by mitophagy. We also discuss the role of quercetin, a bioactive flavonoid, in preventing the development of PD, and reversing mitochondrial dysfunction but only so in diabetic patients. Thus, further research should be conducted on glycolysis as a protective target in PD that can serve to not just prevent, but also alleviate the non-dopaminergic signs and symptoms of PD.

In silico identification of the rare-coding pathogenic mutations and structural modeling of human NNAT gene associated with anorexia nervosa.

PURPOSE: Increased susceptibility towards anorexia nervosa (AN) was reported with reduced levels of neuronatin (NNAT) gene. We sought to investigate the most pathogenic rare-coding missense mutations, non-synonymous single-nucleotide polymorphisms (nsSNPs) of NNAT and their potential damaging impact on protein function through transcript level sequence and structure based in silico approaches. METHODS: Gene sequence, single nucleotide polymorphisms (SNPs) of NNAT was retrieved from public databases and the putative post-translational modification (PTM) sites were analyzed. Distinctive in silico algorithms were recruited for transcript level SNPs analyses and to characterized high-risk rare-coding nsSNPs along with their impact on protein stability function. Ab initio 3D-modeling of wild-type, alternate model prediction for most deleterious nsSNP, validation and recognition of druggable binding pockets were also performed. AN 3D therapeutic compounds that followed rule of drug-likeness were docked with most pathogenic variant of NNAT to estimate the drugs' binding free energies. RESULTS: Conclusively, 10 transcript (201-205)-based nsSNPs from 3 rare-coding missense variants, i.e., rs539681368, rs542858994, rs560845323 out of 840 exonic SNPs were identified. Transcript-based functional impact analyses predicted rs539681368 (C30Y) from NNAT-204 as the high-risk rare-coding pathogenic nsSNP, deviating protein functions. The 3D-modeling analysis of AN drugs' binding energies indicated lowest binding free energy (ΔG) and significant inhibition constant (Ki) with mutant models C30Y. CONCLUSIONS: Mutant model (C30Y) exhibiting significant drug binding affinity and the commonest interaction observed at the acetylation site K59. Thus, based on these findings, we concluded that the identified nsSNP may serve as potential targets for various studies, diagnosis and therapeutic interventions. LEVEL OF EVIDENCE: No level of evidence-open access bioinformatics research.

Exploring the impact of the COVID-19 pandemic on cardiac surgical services: A scoping review.

Cardiac surgery was severely affected by the COVID-19 pandemic. Reallocation of resources, conversion of surgical intensive care units and wards to COVID-19 facilities, increased risk of nosocomial transmission to cardiac surgery patients, lead to reduced accessibility, quality, and affordability of health care facilities to cardiac surgery patients. Increasing the mortality and morbidity rate among such patients. Cardiac patients are at an increased risk to develop a severe illness if infected by COVID-19 and are associated with a high mortality rate. Therefore, measures had to be taken to reduce the spread of the virus. Various approaches such as the hubs and the spokes centers, or parallel system were enforced. Elective surgeries were postponed while urgent surgeries were prioritized. Use of personal protective equipments and surgeries performed by only senior surgeons became necessary. Surgical trainees were also affected as limited training opportunities deprived them of the experience required to complete their fellowship. Some of the trainees were reallocated to COVID-19 wards, while others invested their time in research opportunities. Online platforms were used for teaching, meetings, and workshops across the globe. Although some efforts have been made to reduce the impact of the pandemic, more research and innovation is required.