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Dose optimization of sirolimus may further improve outcomes in allogeneic hematopoietic cell transplant (HCT) patients receiving post-transplantation cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD). Sirolimus exposure-response association studies in HCT patients (i.e., the association of trough concentration with clinical outcomes) have been conflicting. Sirolimus has important effects on T-cells, including conventional (Tcons) and regulatory T-cells (Tregs), both of which have been implicated in the mechanisms by which PTCy prevents GVHD, but there is an absence of validated biomarkers of sirolimus effects on these cell subsets. Considering the paucity of existing biomarkers and the complexities of the immune system, we conducted a literature review to inform a quantitative systems pharmacology (QSP) model of GVHD. The published literature presented multiple challenges. The sirolimus pharmacokinetic models insufficiently describe sirolimus distribution to relevant physiological compartments. Despite multiple publications describing sirolimus effects on Tcons and Tregs in preclinical and human ex vivo models, consistent parameters relating sirolimus concentrations to circulating Tcons and Tregs could not be found. Each aspect presents a challenge in building a QSP model of sirolimus and its temporal effects on T-cell subsets and GVHD prevention. To optimize GVHD prevention regimens, phase I studies and systematic studies of immunosuppressant concentration-effect association are needed for QSP modeling.

Abstract This paper uses computational methods to simultaneously investigate the epistemological effects of misinformation on communities of rational agents, while also contributing to the philosophical debate on ‘higher-order’ evidence (i.e. evidence that bears on the quality and/or import of one’s evidence). Modelling communities as networks of individuals, each with a degree of belief in a given target proposition, it simulates the introduction of unreliable mis- and disinformants, and records the epistemological consequences for these communities. First, using small, artificial networks, it compares the effects, when agents who are aware of the prevalence of mis- or disinformation in their communities, either deny the import of this higher-order evidence, or attempt to accommodate it by distrusting the information in their environment. Second, deploying simulations on a large(r) real-world network, it observes the impact of increasing levels of misinformation on trusting agents, as well as of more minimal, but structurally targeted, unreliability. Comparing the two information processing strategies in an artificial context, it finds that there is a (familiar) trade-off between accuracy (in arriving at a correct consensus) and efficiency (in doing so in a timely manner). And in a more realistic setting, community confidence in the truth is seen to be depressed in the presence of even minimal levels of misinformation.

Background and Aims: Ultrasonography (USG)-guided arterial cannulation is a frequently performed procedure in the operating room and intensive care unit. Conventionally, longitudinal/in-plane and transverse/out-of-plane approaches are used for cannulation. Recently, a longitudinal oblique approach has been described with the advantage of wide visualization area. Hence, the present study was designed to compare the success of USG-guided radial artery cannulation in longitudinal oblique axis (LOA) and longitudinal axis (LA). Material and Methods: Seventy patients requiring radial artery cannulation were randomly allocated into two groups: group L (USG-guided radial artery cannulation in LA) and group O (USG-guided radial artery cannulation in LOA). Primary outcome was to assess cannulation success in the first attempt, while the secondary outcomes were to assess the number of attempts, failure rate, total cannulation time, and associated complications. Results: First-attempt success was higher in group O (80%) compared to group L (54.3%), with a P value of 0.022. In group L, 31.4% required two attempts and 5.7% had three attempts, while in group O, 14.3% had two attempts and 2.9% required three attempts. Group L failure rate was 8.6%, while it was 2.9% in group O. The mean total cannulation time (sec) for group L was 146.83 ± 89.37 and group O was 63.89 ± 26.277. No complication was observed with group O, while in group L, 9% had hematoma formation. Conclusion: The LOA approach for USG-guided radial artery cannulation has higher first-pass success rate, total success rate, and requires less cannulation time compared to the LA approach.

Abstract The research delves into the intricate web of linguistic borrowings in trade terminologies between Ancient Indian languages (Sanskrit, Prakrit) and Egyptian languages (Ancient Egyptian Hieroglyphs, Demotic script) spanning from approximately 3300 BCE to 500 CE. Through a meticulous analysis of selected literary texts and inscriptions, including the Hathigumpha Inscription, Rudradaman I Inscription, Junagadh Rock Inscriptions, Nasik Cave Inscriptions, Rosetta Stone, Satirical Papyrus, and Turin Taxation Papyrus, the study unravels the linguistic evolution and cultural exchanges embedded within ancient trade networks. Contextualizing these linguistic borrowings within the historical framework of trade routes, maritime activities, and economic exchanges, the research sheds light on the nuances of communication and adaptation in commercial interactions. By employing rigorous research methodologies and comparative studies, the findings offer a comprehensive understanding of how language served as a bridge for commerce, diplomacy, and cultural exchange between these ancient civilizations. This study not only contributes to the fields of linguistic history and ancient trade studies but also offers valuable insights into the dynamic interplay of language, trade, and cultural connectivity in the ancient world.

Abstract The study was formulated to identify the effect of Mangifera indica leaf extract in inhibiting the growth and metamorphosis of Culex quinquefasciatus larva. Bioassay-guided extraction identified the bioactive fraction, after which GC-MS characterized it. The larvicidal activity was analyzed by administrating extract in various concentrations and then subjecting the mortality rate for probit analysis. The morphological and physiological impact upon larvae was understood by histological analysis and acetylcholinesterase activity assay. The results suggested that the extract possessed a high degree of larvicidal activity, whereas the Dose50 was 225.158 ± 15.168 with a Total Chi-Square of 13.09 and p-value of 0.11. The histological studies revealed notable aberrations among the study subjects compared to the control group due to diminished abdominal tissue integrity. It was also observed that the extract could inhibit the acetylcholinesterase activity, with an LD 50 of 0.9512 µg/ml. The observations made in these studies may be utilized to develop a potential larvicidal agent that could act upon multiple targets.

Abstract Background Takayasu arteritis (TA) is a chronic inflammatory disease of unknown etiology characterized by a large vessel vasculitis involving the aorta and its branches. Myocardial involvement is extremely unusual in TA and is mostly in the form of myocarditis, ventricular hypertrophy, and ventricular dysfunction secondary to coronary ischemia. Submitral aneurysms have been reported in TA and has been attributed to the chronic inflammatory process in TA. Case presentation We report a novel instance of left ventricular apical aneurysm in a 37-year-old lady with TA and normal epicardial coronaries. She was diagnosed with a left ventricular apical aneurysm, moderate aortic regurgitation, and moderate pericardial effusion. The coronary arteries were normal. The patient had concomitant chronic active Epstein–Barr virus infection complicating patient outcome. Conclusions Left ventricular apical aneurysm with normal epicardial coronaries is a rare cause of heart failure in Takayasu arteritis. Concomitant chronic active Epstein–Barr virus infection can potentially accentuate the inflammatory process in Takayasu arteritis and complicate management and patient outcomes.

Introduction: Permanent pacemaker implantation (PPI) in neonates is challenging with respect to indications, device selection, implantation technique, and long-term outcomes. Complex anatomy, the need for long-term pacing with high rates, and a problematic postoperative period are the major problems. Methods: We prospectively followed up 22 newborns who underwent PPI below 28 days of life at our institute. Results: The median age at implantation was 2 days (interquartile range 1–9 days), and 9% were born preterm. The average heart rate before implantation was 46.4 ± 7.2 bpm. Maternal lupus antibodies were positive in 8 (36.4%) neonates, whereas 11 (50.0%) had associated congenital heart disease. Nineteen neonates underwent single chamber (VVI) and three underwent dual chamber (DDD) pacemaker implantation. Over a median follow-up of 46 months (range 2–123 months), the average ventricular pacing percentage was 87.5 ± 24.9%, with a stable pacing threshold. Seven children underwent pulse generator replacement due to battery depletion at a median age of 47 months. Pacing-induced ventricular dysfunction was seen in five children at a median age of 23.6 months, and two underwent upgradation to cardiac resynchronization therapy. Overall mortality was 13.6%, all due to tissue hypoperfusion and lactic acidosis in the postimplantation period. Conclusions: PPI in neonates has a favorable outcome with excellent lead survival. Overall mortality is 13.6%, which is predominantly in the postimplantation period and related to myocardial dysfunction.

Background: The COVID-19 pandemic has affected the delivery of dental care globally. Air contamination during aerosol and splatter-generating procedures is of great concern to dental healthcare provider during these times. Extra oral suction (EOS) apparatus has been shown to be effective in preventing infection by control of aerosol. But very limited data is available regarding the efficacy of the apparatus in preventing splatter contamination. Objectives of the Study: To assess the efficacy of EOS apparatus in reducing frequency and mean intensity of splatter contamination at clinician, assistant, patient sites during lower third molar surgical procedures. Materials and Methods: Patients who required surgical removal of an impacted lower third molar were divided into two groups (EOS and non-EOS) with 20 patients each. Universal indicating paper (UIP) was placed in specific locations on the surgeon, patient, and assistant. Colour changes after the settling of splatter on the UIP were analyzed to calculate the percentage intensity of splatter contamination. Results: The use of an EOS device has shown an overall reduction in the total number of contaminated sites, with a difference of 6.36%. Surgeon, patient, and assistant sites showed reductions of 6.25, 10%, and 1.66%, respectively. The apparatus has showed statistically significant reduction of splatter frequency and intensity at the patient's chest and left shoulder regions respectively, during surgical removal of the impacted 48. Conclusion: The magnitude of splatter contamination during minor dentoalveolar surgical procedures is inevitable. Therefore, to achieve a better working environment, usage of an EOS apparatus is advocated.

Background: Hypocalcaemia following thyroidectomy is a relatively common complication, which is sometimes difficult to correct. Methods: In this cohort study, we assessed the predictive factors for laboratory hypocalcaemia and symptomatic in patients who underwent thyroidectomy between January 2018–June 2019. Results: A total of 170 patients (153 women) were studied. Laboratory hypocalcaemia was found in 91.2% of patients, while 62.7% manifested symptomatic hypocalcaemia. Of the patients with symptomatic hypocalcaemia/(36%) had hypomagnesaemia as well. Univariate analysis revealed that type of disease (P = 0.0001), duration of surgery (P = 0.001), duration of disease (P = 0.005), type of surgery (P = 0.032) and hypomagnesaemia (P = 0.002) were significantly associated with hypocalcaemia. Age did not play a key role in the development of hypocalcaemia. Hypocalcaemia did not respond to supplementation without correcting the hypomagnesaemia. Conclusions: Type of disease, duration of disease, duration of surgery, type of surgery and hypomagnesaemia were risk factors. Age did not play a key role in the development of hypocalcaemia. Hypocalcaemia did not respond to supplementation without correcting the hypomagnesaemia. Adequate intervention can be started earlier to reduce the duration of hospital stay.

Background: This cross-sectional study among dentists in Kerala assessed the COVID-19 prevalence and severity, vaccination status, and medication usage in August 2022. Materials and Methods: A questionnaire was created to assess the impact of COVID-19 on dental surgeons in Kerala. This questionnaire had 19 questions with multiple choices which were converted into Google Forms and distributed among the dentists residing in Kerala. Results: A total of 650 dentists responded to the questionnaire, yielding a response rate of 76.4%. As of August 2022, the prevalence of COVID-19 among Kerala dentists was found to be 33.23%. 60.7% of positive dentists were either asymptomatic or had only mild symptoms. 99% had received at least one vaccine dose, mainly Covishield. The prevalence of COVID-19 positivity was higher among dentists with postgraduate degrees (47.4%) in comparison with participants holding only BDS degrees. Conclusion: The prevalence of COVID-19 among practicing dentists was 33.23%. All dentists were vaccinated and used good preventive measures.

Background: Acute pulmonary embolism (APE) is the third most common cause of vascular death. Data on APE from India and other low-and middle-income countries is sparse. Objectives: Study the clinical characteristics, prognostic factors, in-hospital mortality (IMH) and 12 months mortality of patients with APE in India. Methods: We prospectively enrolled 186 consecutive patients diagnosed with APE between November 2016 and November 2021 in Madras Medical College Pulmonary Embolism Registry (M-PER). All patients had electrocardiography and echocardiography. High risk patients and selected intermediate risk patients underwent fibrinolysis. Results: 75 % of our patients were below 50 years of age. 35 % were women. The mean time to presentation from symptom onset was 6.04 ± 10.01 days. 92 % had CT pulmonary angiography. Intermediate risk category (61.3 %) was the more common presentation followed by high risk (26.9 %). Electrocardiography showed S1Q3T3 pattern in 56 %. 76 % had right ventricular dysfunction and 12.4 % had right heart thrombi(RHT) by echocardiography. 50.5 % received fibrinolysis. Patients with RHT received fibrinolysis more frequently (78.3 % vs 46.6 %; p = 0.007). In-hospital mortality (IHM) was 15.6 %. Systemic arterial desaturation and need for mechanical ventilation independently predicted IHM. Ten patients (5.3 %) were lost to follow up. One year mortality was 26.7 % (47/176). One year mortality of patients discharged alive was similar among high, intermediate and low risk groups(14.8 % vs 1.9 % vs 10.5 %; p = 0.891). Conclusions: Patients with PE are often young and present late in India. The in-hospital and 12 months mortality were high. Low and intermediate risk groups had a high post discharge mortality similar to high risk patients.

Abstract Titanium dioxide nanoparticles (TiO2-NPs) are a promising anode material for Lithium-ion batteries (LIBs) due to their good rate capability, low cost, non-toxicity, excellent structural stability, extended cycle life, and low volumetric change (∼4%) during the Li+ insertion/de-insertion process. In the present paper, anatase TiO2-NPs with an average particle size of ~ 12 nm were synthesized via a green synthesis route using Beta vulgaris (Beetroot) extract, and the synthesized TiO2-NPs were evaluated as anode material in LIBs. Furthermore, we employed an aqueous binder (1:1 mixture of carboxy methyl cellulose and styrene butadiene) for electrode processing, making the process cost-effective and environmentally friendly. The results revealed that the Li/TiO2 half-cells delivered an initial discharge capacity of 209.7 mAh g−1 and exhibited superior rate capability (149 mAh g−1 at 20 C) and cycling performances. Even at the 5C rate, the material retained a capacity of 82.2% at the end of 100 cycles. The synthesis route of TiO2-NPs and the aqueous binder-based electrode processing described in the present work are facile, green, and low-cost and are thus practically beneficial for producing low-cost and high-performance anodes for advanced LIBs.

Abstract Two types of immunity, humoral and cellular, offer protection against COVID. Humoral protection, contributed by circulating neutralizing antibodies, can provide immediate protection but decays more quickly than cellular immunity and can lose effectiveness in the face of mutation and drift in the SARS-CoV-2 spike protein. Therefore, population-level seroprevalence surveys used to estimate population-level immunity may underestimate the degree to which a population is protected against COVID. In early 2021, before India began its vaccination campaign, we tested for humoral and cellular immunity to SARS-Cov-2 in representative samples of slum and non-slum populations in Bangalore, India. We found that 29.7% of samples (unweighted) had IgG antibodies to the spike protein and 15.5% had neutralizing antibodies, but at up to 46% showed evidence of cellular immunity. We also find that prevalence of cellular immunity is significantly higher in slums than in non-slums. These findings suggest (1) that a significantly larger proportion of the population in Bangalore, India, had cellular immunity to SARS-CoV-2 than had humoral immunity, as measured by serological surveys, and (2) that low socio-economic status communities display higher frequency of cellular immunity, likely because of greater exposure to infection due to population density.

Introduction: Methemoglobinemia is a potentially life-threatening condition characterized by the reduced oxygen-carrying capacity of hemoglobin. With the increasing popularity of natural and herbal biopesticides, there is a growing risk of exposure to substances that can induce this dyshemoglobinemia. This case report highlights the importance of recognizing and promptly treating methemoglobinemia in the context of biopesticide exposure, a concern relevant to various healthcare professionals. Case description: A 70-year-old male presented to the emergency department (ED) in an unresponsive state following suspected ingestion of an unknown quantity of an organic biopesticide labeled ''Bull Fight''. Initial management included fluid resuscitation, endotracheal intubation and mechanical ventilation. The patient developed significant hypoxia and hypotension. Abnormal blood color and a saturation gap raised suspicion of methemoglobinemia, which was confirmed by co-oximetry (68.7 % MetHb). Treatment with methylene blue was initiated, leading to initial improvement. However, the patient experienced rebound methemoglobinemia, requiring additional doses of methylene blue. Despite treatment, the patient ultimately succumbed to pneumonia. Discussion: This case underscores the potential dangers of organic biopesticides and the importance of considering methemoglobinemia in patients with unexplained cyanosis, saturation gap, and abnormal blood color. The increasing use of natural and herbal products in agriculture may expose individuals to undisclosed ingredients capable of inducing methemoglobinemia. Healthcare professionals across various specialities, including emergency medicine, critical care, toxicology, and primary care, must remain vigilant and maintain a high index of suspicion for this condition, especially in cases of biopesticide exposure. Conclusion: Awareness of methemoglobinemia and its association with biopesticide exposure is crucial for all healthcare providers who may encounter such cases. Prompt recognition and treatment can be lifesaving. As natural biopesticide use increases, clinicians should be prepared to diagnose and manage methemoglobinemia effectively. Careful monitoring is crucial to detect and prevent rebound methemoglobinemia. Ongoing education and preparedness are essential to address risks associated with emerging agricultural practices and products.