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Aim: Compare the efficacy of triple antibiotic paste (TAP), herbal extracts, and camphorated monochlorophenol (CMCP) as intracanal medicaments against Enterococcus faecalis (E. faecalis) in deciduous molars. Materials and methods: A total of 60 samples were collected from canals of first and second molars of 4-10-year-old children, with more than two-thirds root length, and fitting the inclusion criteria. Samples were collected at three intervals-S1 was collected just after access opening, S2 was collected after biomechanical preparation (BMP) and irrigation, and just before placement of medicament. Randomization was done to place the medicaments into three groups: group I-CMCP, group II-TAP, and group III-herbal combination. Sample S3 was taken 48 hours after removal of medicament from the canals. The collected samples were transported via Amies media to the laboratory, where they were anaerobically incubated for 24 hours. Growth of E. Faecalis was observed, and manual counting of the colony-forming unit (CFU) was done. The change in CFU in all samples was calculated, and the results were statistically analyzed. Results: The results show that there is a change from S1 (TAP = 118.67 ± 122.48, herbal = 109.07 ± 106.43; CMCP = 110.73 ± 120.53) to S2 (TAP = 34.13 ± 63.47; herbal = 27.67 ± 39.39; CMCP = 16.40 ± 26.32) and S3 (TAP = 12.33 ± 24.82; herbal = 4.73 ± 12.78; CMCP = 3.40 ± 7.12). It is seen that there is a significant difference seen from S1 to S2 in all three groups (p ≤ 0.05) using repeated measure analysis of variance (ANOVA) test. This shows that all three medicaments were effective in reducing bacterial counts of E. Faecalis from sample S1 (pre) to S3 (post) significantly after exposure to root canal bacterial flora for 48 hours (2 days). The pairwise comparison of the change in CFU within each group, S1-S3, also shows significant changes. There is a significant decrease in CFU seen from S1 to S2 and S1 to S3 but not from S2 to S3 for all three groups, which was evaluated using the post hoc Bonferroni test. It was also observed that in between the canals, although there was a change from S1 to S3 in terms of the CFU, there was no significant difference in the decrease in the bacterial count when intercanal comparison was made. There was, however, a change that was seen to be significant when values from each canal were compared from S1 to S3. Conclusion: All three medicaments have successfully shown a decrease in the numbers of E. faecalis, which the study aimed at checking. Although the effect varied intergroups, it was mild, so herbal alternatives could be used instead of antibiotics and CMCP. Also, because the local application is effective in controlling interappointment flare-ups, the medicaments can be successfully given without having to prescribe systemic antibiotics. How to cite this article: Tawde MM, Lakade L, Patil S, et al. Comparative Evaluation of Antimicrobial Efficacy of Triple Antibiotic Paste Herbal Combination and Camphorated Monochlorophenol as Intracanal Medicaments against Enterococcus faecalis in Deciduous Molars: An In Vivo Study. Int J Clin Pediatr Dent 2024;17(3):243-254.

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Hurst disease, or Weston-Hurst syndrome, or acute hemorrhagic encephalomyelitis (AHEM), is an infrequent condition that usually gets provoked after a viral infection (respiratory tract infection) or, as reported in many case reports, post-vaccination. Hurst disease is a difficult-to-diagnose condition because it mimics common presentations such as stroke, decreased or loss of consciousness, brain abscess, and seizures, making clinical diagnosis challenging. Radiological imaging, such as magnetic resonance imaging (MRI) of the brain with diffusion-weighted imaging, now serves as the primary modality to identify such conditions, despite its lack of specificity. The treating doctor needs to do an in-depth analysis of the patient's history, as this carries a very high mortality rate. We hereby discuss a case that presented with seizures and deteriorating Glasgow Coma Scale (GCS) score, on imaging revealed posterior circulation acute hemorrhagic leukoencephalitis (AHLE)/AHEM, therein treated with steroids, plasmapheresis resulted in a good outcome implicating, early detection and timely management can reduce the mortality due to this condition.

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Ovarian somatic cells are essential for reproductive function, but no existing ex vivo models recapitulate the cellular heterogeneity or interactions within this compartment. We engineered a novel ovarian somatic organoid model by culturing a stroma-enriched fraction of mouse ovaries in scaffold-free agarose micromolds. Ovarian somatic organoids self-organized, maintained diverse cell populations, produced extracellular matrix, and secreted hormones. Organoids generated from reproductively old mice exhibited reduced aggregation and growth compared to young counterparts, as well as differences in cellular composition. Interestingly, matrix fibroblasts from old mice demonstrated upregulation of pathways associated with the actin cytoskeleton and downregulation of cell adhesion pathways, indicative of increased cellular stiffness which may impair organoid aggregation. Cellular morphology, which is regulated by the cytoskeleton, significantly changed with age and in response to actin depolymerization. Moreover, actin depolymerization rescued age-associated organoid aggregation deficiency. Overall, ovarian somatic organoids have advanced fundamental knowledge of cellular contributions to ovarian aging.

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Neuroinflammation is a prominent feature of Alzheimer's disease (AD). Activated microglia undergo a reprogramming of cellular metabolism necessary to power their cellular activities during disease. Thus, selective targeting of microglial immunometabolism might be of therapeutic benefit for treating AD. In the AD brain, the levels of microglial hexokinase 2 (HK2), an enzyme that supports inflammatory responses by promoting glycolysis, are significantly increased. In addition, HK2 displays non-metabolic activities that extend its inflammatory role beyond glycolysis. The antagonism of HK2 affects microglial phenotypes and disease progression in a gene-dose-dependent manner. HK2 complete loss fails to improve pathology by exacerbating inflammation, while its haploinsufficiency reduces pathology in 5xFAD mice. We propose that the partial antagonism of HK2 is effective in slowing disease progression by modulating NF-κB signaling through its cytosolic target, IKBα. The complete loss of HK2 affects additional inflammatory mechanisms related to mitochondrial dysfunction.

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OBJECTIVE: This study aimed to compare the clinical endotracheal tube (ETT) depth after initial stabilization of infants with congenital diaphragmatic hernia (CDH) to weight and gestational age-based depth estimates. STUDY DESIGN: This retrospective analysis included 58 inborn infants with left-sided CDH. We compared a standard anatomic ETT depth calculated from initial chest radiographs and the clinical depth of the ETT after adjustments to predicted depths using weight and gestational age-based estimates. RESULTS: The standard anatomic depth was deeper than age (standard deviation 1.29 ± 1.15 cm, p < 0.001) and weight-based (standard deviation 0.59 ± 0.95 cm, p < 0.001) estimates. The clinical ETT depth was also deeper than age (standard deviation 1.01 ± 0.77 cm, p < 0.001) and weight-based (standard deviation 0.26 ± 0.50 cm, p < 0.001) estimates. CONCLUSION: Established strategies to predict ETT depth underestimate the ideal depth in infants with left-sided CDH. These data suggest utilizing caution during initial ETT placement based on standard depth estimates for patients with CDH. KEY POINTS: · CDH patients present unique stabilization challenges.. · Standard ETT depth estimates are too shallow.. · Resuscitation teams should cautiously choose ETT depth..

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Litchi (Litchi chinensis Sonn.) is a tropical fruit with various health benefits. The objective of this study is to present a thorough analysis of the cancer preventive and anticancer therapeutic properties of litchi constituents and phytocompounds. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria were followed in this work. Various litchi extracts and constituents were studied for their anticancer effects. In vitro studies showed that litchi-derived components reduced cell proliferation, induced cytotoxicity, and promoted autophagy via increased cell cycle arrest and apoptosis. Based on in vivo studies, litchi flavonoids and other extracted constituents significantly reduced tumor size, number, volume, and metastasis. Major signaling pathways impacted by litchi constituents were shown to stimulate proapoptotic, antiproliferative, and antimetastatic activities. Despite promising antineoplastic activities, additional research, especially in vivo and clinical studies, is necessary before litchi-derived products and phytochemicals can be used for human cancer prevention and intervention.

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Guillain-Barré syndrome is the most common cause of acute flaccid paralysis in children, but several diseases mimic GBS. We aimed to identify and report the clinical pointers and battery of tests required to differentiate Guillain-Barré syndrome from its observed mimics in the pediatric population admitted to our neuro-critical care unit. We conducted a retrospective record analysis of all pediatric patients admitted over ten years from 2008-2018, whose initial presentation was compatible with a clinical diagnosis of GBS. Eighty-three patients were at first treated as GBS, of which seven (8.4%) were found to have an alternate diagnosis-three cases of paralytic rabies, one case each of acute disseminated encephalomyelitis, cervical myeloradiculopathy, neuromyelitis optica, and a case of community-acquired Staphylococcus aureus pneumonia associated sepsis. Neurophysiological and neuro-virological testing, central nervous system imaging, and sepsis screening helped to confirm the alternate diagnosis. Our case series provides knowledge of subtle clinical differences along with the mindful use of diagnostic testing to facilitate the accurate diagnosis of GBS mimics.

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BACKGROUND: Human genetic contribution to HIV progression remains inadequately explained. The type 1 interferon (IFN) pathway is important for host control of HIV and variation in type 1 IFN genes may contribute to disease progression. This study assessed the impact of variations at the gene and pathway level of type 1 IFN on HIV-1 viral load (VL). METHODS: Two cohorts of antiretroviral (ART) naïve participants living with HIV (PLWH) with either early (START) or advanced infection (FIRST) were analysed separately. Type 1 IFN genes (n = 17) and receptor subunits (IFNAR1, IFNAR2) were examined for both cumulated type 1 IFN pathway analysis and individual gene analysis. SKAT-O was applied to detect associations between the genotype and HIV-1 study entry viral load (log10 transformed) as a proxy for set point VL; P-values were corrected using Bonferroni (P < 0.0025). RESULTS: The analyses among those with early infection included 2429 individuals from five continents. The median study entry HIV VL was 14,623 (IQR 3460-45100) copies/mL. Across 673 SNPs within 19 type 1 IFN genes, no significant association with study entry VL was detected. Conversely, examining individual genes in START showed a borderline significant association between IFNW1, and study entry VL (P = 0.0025). This significance remained after separate adjustments for age, CD4+ T-cell count, CD4+/CD8+ T-cell ratio and recent infection. When controlling for population structure using linear mixed effects models (LME), in addition to principal components used in the main model, this was no longer significant (p = 0.0244). In subgroup analyses stratified by geographical region, the association between IFNW1 and study entry VL was only observed among African participants, although, the association was not significant when controlling for population structure using LME. Of the 17 SNPs within the IFNW1 region, only rs79876898 (A > G) was associated with study entry VL (p = 0.0020, beta = 0.32; G associated with higher study entry VL than A) in single SNP association analyses. The findings were not reproduced in FIRST participants. CONCLUSION: Across 19 type 1 IFN genes, only IFNW1 was associated with HIV-1 study entry VL in a cohort of ART-naïve individuals in early stages of their infection, however, this was no longer significant in sensitivity analyses that controlled for population structures using LME.

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Ovarian cancer (OC) is deadly, and likely arises from the fallopian tube epithelium (FTE). Despite the association of OC with ovulation, OC typically presents in post-menopausal women who are no longer ovulating. The goal of this study was to understand how ovulation and aging interact to impact OC progression from the FTE. Follicular fluid released during ovulation induces DNA damage in the FTE, however, the role of aging on FTE exposure to follicular fluid is unexplored. Follicular fluid samples were collected from 14 women and its effects on FTE cells was assessed. Follicular fluid caused DNA damage and lipid oxidation in an age-dependent manner, but instead induced cell proliferation in a dose-dependent manner, independent of age in FTE cells. Follicular fluid regardless of age disrupted FTE spheroid formation and stimulated attachment and growth on ultra-low attachment plates. Proteomics analysis of the adhesion proteins in the follicular fluid samples identified vitronectin, a glycoprotein responsible for FTE cell attachment and spreading.

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Introduction: Immune checkpoint blockade (ICB) with or without chemotherapy has a very modest benefit in patients with small cell lung cancer (SCLC). SCLC tumors are characterized by high tumor mutation burden (TMB) and low PD-L1 expression. Therefore, TMB and PD-L1 do not serve as biomarkers of ICB response in SCLC. CD38, a transmembrane glycoprotein, mediates immunosuppression in non-small cell lung cancer (NSCLC). In this brief report, we highlight the potential role of CD38 as a probable biomarker of immunotherapy response in SCLC. Methods: We evaluated the role of CD38 as a determinant of tumor immune microenvironment in SCLC with bulk and single-cell transcriptomic analyses and protein assessments of clinical samples and preclinical models, including CD38 in vivo blockade. Results: In SCLC clinical samples, CD38 levels were significantly correlated with the gene expression of the immunosuppressive markers FOXP3, PD-1 and CTLA-4. CD38 expression was significantly enhanced after chemotherapy and ICB treatment in SCLC preclinical models and clinical samples. A combination of cisplatin/etoposide, ICB, and CD38 blockade delayed tumor growth compared to cisplatin/etoposide. Conclusion: Our study provides a preliminary but important direction toward exploring CD38 as a potential biomarker of ICB response and CD38 blockade as a combination strategy for chemo-immunotherapy in SCLC.

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OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by chronic systemic inflammation; however, the mechanisms underlying these pathologic consequences are incompletely understood. Our objective was to determine the effects of short- versus long-term exposure to intermittent hypoxia (IH) on pro-inflammatory mediators within vulnerable organs impacted by OSA. STUDY DESIGN: Experimental animal study. METHODS: A total of 8-10 week old C57BL/6J mice were exposed to normoxic or IH conditions for 7 days (short-term) or 6 weeks (long-term) under 12 h light, 12 h dark cycles. After exposure, multiple tissues were collected over a 24 h period. These tissues were processed and evaluated for gene expression and protein levels of pro-inflammatory mediators from peripheral tissues. RESULTS: We observed a global decrease in immune response pathways in the heart, lung, and liver compared with other peripheral organs after short-term exposure to IH. Although there were tissue-specific alterations in the gene expression of pro-inflammatory mediators, with down-regulation in the lung and up-regulation in the heart, we also observed reduced protein levels of pro-inflammatory mediators in the serum, lung, and heart following short-term exposure to IH. Long-term exposure to IH resulted in an overall increase in the levels of inflammatory mediators in the serum, lung, and heart. CONCLUSIONS: We demonstrated novel, longitudinal changes in the inflammatory cascade in a mouse model of OSA. The duration of exposure to IH led to significant variability of inflammatory responses within blood and cardiopulmonary tissues. Our findings further elucidate how inflammatory responses change over the course of the disease in vulnerable organs. LEVEL OF EVIDENCE: NA Laryngoscope, 134:S1-S11, 2024.

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PURPOSE: Infection in the neurocritical care unit ( NCCU) can cause significant mortality and morbidity. Autonomic nervous system plays an important role in defense against infection. Autonomic dysfunction causing inflammatory dysregulation can potentiate infection. We aimed to study the relationship between autonomic dysfunction and occurrence of infection in neurologically ill patients. METHODS: Fifty one patients who were on mechanical ventilation were prospectively enrolled in this study. Autonomic dysfunction was measured for three consecutive days on admission to NCCU using Ansiscope. Patients were followed up for seven days to see the occurrence of infection. Infection was defined as per centre of disease control definition. RESULTS: A total of 386 patients were screened for eligibility. 68 patients satisfied the eligibility criteria and 51 patients were finally included in the study. The incidence of infection was 74.5%. The commonest infection was pulmonary infection (38.8%) followed by urinary tract infection (33.3%), blood stream infection(14.8%), central nervous system infection (11.1%) and wound site infection (3.7%). The degree of autonomic dysfunction (AD) percentage was more in infection group (37.7% (25.2-49.7)) compared to non infection group (23.5% (18-33.5)) and maximal on day 3 (P = 0.02). Patients with increasing trend of AD% from day 1 to day 3 had the highest infection rates. The length of NCCU stay (20(10-23) days and mortality (42.1%) was higher in infection group (p < 0.001). CONCLUSION: AD assessment can be used as a tool to predict development of infection in NCCU. This can help triage and institute early investigation and treatment.

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Free Open-Access Medical Education (FOAMed) has transformed medical education in the past decade by complementing and substituting for traditional medical education when needed. The attractiveness of FOAMed resources is due to their inexpensive nature, wide availability, and user ability to access on demand across a variety of devices, making it easy to create, share, and participate. The subject of nephrology is complex, fascinating, and challenging. Traditional didactic lectures can be passive and ineffective in uncovering these difficult concepts and may need frequent revisions. Active teaching methods like flipped classrooms have shown some benefits, and these benefits can only be multifold with current social media tools. Social media will inspire the involvement of students and allow them to create and share educational content in a "trendy way," encouraging the participation of their peers and thus building an educational environment more conducive to them while promoting revision and retainment. FOAMed also promotes asynchronous learning, spaced learning, microlearning, and multimodal presentation with a meaningful variation. This article discusses the evolution of digital education, social media platforms, tools for creating and developing FOAMed resources, and digital scholarship.

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Microgliosis and neuroinflammation are prominent features of Alzheimer's disease (AD). Disease-responsive microglia meet their increased energy demand by reprogramming metabolism, specifically, switching to favor glycolysis over oxidative phosphorylation. Thus, targeting of microglial immunometabolism might be of therapeutic benefit for treating AD, providing novel and often well understood immune pathways and their newly recognized actions in AD. We report that in the brains of 5xFAD mice and postmortem brains of AD patients, we found a significant increase in the levels of Hexokinase 2 (HK2), an enzyme that supports inflammatory responses by rapidly increasing glycolysis. Moreover, binding of HK2 to mitochondria has been reported to regulate inflammation by preventing mitochondrial dysfunction and NLRP3 inflammasome activation, suggesting that its inflammatory role extends beyond its glycolytic activity. Here we report, that HK2 antagonism selectively affects microglial phenotypes and disease progression in a gene-dose dependent manner. Paradoxically, complete loss of HK2 fails to improve AD progression by exacerbating inflammasome activity while its haploinsufficiency results in reduced pathology and improved cognition in the 5XFAD mice. We propose that the partial antagonism of HK2, is effective in slowed disease progression and inflammation through a non-metabolic mechanism associated with the modulation of NFKß signaling, through its cytosolic target IKBα. The complete loss of HK2 affects additional inflammatory mechanisms associated to mitochondrial dysfunction.

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Follicular fluid (FF) is a primary microenvironment of the oocyte within an antral follicle. Although several studies have defined the composition of human FF in normal physiology and determined how it is altered in disease states, the direct impacts of human FF on the oocyte are not well understood. The difficulty of obtaining suitable numbers of human oocytes for research makes addressing such a question challenging. Therefore, we used a heterologous model in which we cultured mouse oocytes in human FF. To determine whether FF has dose-dependent effects on gamete quality, we performed in vitro maturation of denuded oocytes from reproductively young mice (6-12 weeks) in 10%, 50%, or 100% FF from participants of mid-reproductive age (32-36 years). FF impacted meiotic competence in a dose-dependent manner, with concentrations >10% inhibiting meiotic progression and resulting in spindle and chromosome alignment defects. We previously demonstrated that human FF acquires a fibro-inflammatory cytokine signature with age. Thus, to determine whether exposure to an aging FF microenvironment contributes to the age-dependent decrease in gamete quality, we matured denuded oocytes and cumulus-oocyte complexes (COCs) in FF from reproductively young (28-30 years) and old (40-42 years) participants. FF decreased meiotic progression of COCs, but not oocytes, from reproductively young and old (9-12 months) mice in an age-dependent manner. Moreover, FF had modest age-dependent impacts on mitochondrial aggregation in denuded oocytes and cumulus layer expansion dynamics in COCs, which may influence fertilization or early embryo development. Overall, these findings demonstrate that acute human FF exposure can impact select markers of mouse oocyte quality in both dose- and age-dependent manners.

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The ovarian microenvironment becomes fibrotic and stiff with age, in part due to increased collagen and decreased hyaluronan. However, the extracellular matrix (ECM) is a complex network of hundreds of proteins, glycoproteins, and glycans which are highly tissue specific and undergo pronounced changes with age. To obtain an unbiased and comprehensive profile of age-associated alterations to the murine ovarian proteome and ECM, we used a label-free quantitative proteomic methodology. We validated conditions to enrich for the ECM prior to proteomic analysis. Following analysis by data-independent acquisition (DIA) and quantitative data processing, we observed that both native and ECM-enriched ovaries clustered separately based on age, indicating distinct age-dependent proteomic signatures. We identified a total of 4,721 proteins from both native and ECM-enriched ovaries, of which 383 proteins were significantly altered with advanced age, including 58 ECM proteins. Several ECM proteins upregulated with age have been associated with fibrosis in other organs, but to date their roles in ovarian fibrosis are unknown. Pathways regulating DNA metabolism and translation were downregulated with age, whereas pathways involved in ECM remodeling and immune response were upregulated. Interestingly, immune-related pathways were upregulated with age even in ECM-enriched ovaries, suggesting a novel interplay between the ECM and the immune system. Moreover, we identified putative markers of unique immune cell populations present in the ovary with age. These findings provide evidence from a proteomic perspective that the aging ovary provides a fibroinflammatory milieu, and our study suggests target proteins which may drive these age-associated phenotypes for future investigation.

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This study evaluates whether implementation of a content expert­developed clinical documentation tool can be beneficial to workflow by reducing time from patient arrival to encounter closure among pediatric patients receiving intestinal rehabilitation.

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of Aß plaques and neurofibrillary tangles, resulting in synaptic loss and neurodegeneration. The retina is an extension of the central nervous system within the eye, sharing many structural similarities with the brain, and previous studies have observed AD-related phenotypes within the retina. Three-dimensional retinal organoids differentiated from human pluripotent stem cells (hPSCs) can effectively model some of the earliest manifestations of disease states, yet early AD-associated phenotypes have not yet been examined. Thus, the current study focused upon the differentiation of hPSCs into retinal organoids for the analysis of early AD-associated alterations. Results demonstrated the robust differentiation of retinal organoids from both familial AD and unaffected control cell lines, with familial AD retinal organoids exhibiting a significant increase in the Aß42:Aß40 ratio as well as phosphorylated Tau protein, characteristic of AD pathology. Further, transcriptional analyses demonstrated the differential expression of many genes and cellular pathways, including those associated with synaptic dysfunction. Taken together, the current study demonstrates the ability of retinal organoids to serve as a powerful model for the identification of some of the earliest retinal alterations associated with AD.

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