Comparison of NEWS2 and PSI as mortality predictors in patients with community acquired pneumonia.

In the West, National Early Warning Score 2 (NEWS2) is commonly applied to predict the severity of illness using only bedside variables unlike the extensive Pneumonia Severity Index (PSI). The objective of this study was to compare these scores as mortality predictors in patients admitted with community acquired pneumonia (CAP). This cross-sectional study was conducted in Jinnah Postgraduate Medical Centre, Karachi, Pakistan, for six months in 2020 on 116 patients presenting with CAP. Cases of aspiration pneumonia, hospital acquired pneumonia, pulmonary tuberculosis, pulmonary embolism, and pulmonary oedema were excluded. In-hospital mortality was taken as the outcome of this study. The mean age of the participants was 46.9±20.5 years. The in-hospital mortalities were 45(38.8%). NEWS2 was 97.8% sensitive but only 15.5% specific in predicting the outcome, whereas PSI was less sensitive (68.9%) but more specific (50.7%), which showed that in comparison with PSI, NEWS2 is a more sensitive mortality predicting score among hospitalised CAP patients.

Exploring the Binding Mechanism of 5-HT7 Specific Benzoxazolone alkyl Piperazinium Derivatives: A Comprehensive Analysis Using Spectroscopic and Computational Approaches.

Recently, the 5-HT7 receptor has achieved greater attention in research fraternity due to the involvement of neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in several neurological disorders. Targeting this neuroreceptor, we have synthesized six compounds named as butyl-benzoxazolone substituted piperazinium derivatives (BBOP) derivatives, abbreviated as L1-L6. These compounds have been evaluated for their binding interaction with BSA through photophysical and in-silico approaches. The UV absorption of these compounds with BSA at λmax = 280 nm, showed an optical density (O.D.) in the range of 0.5-0.9, i.e., 21%-53% (L1max = 1.4, L5min = 0.7385) at varied concentrations (17 µM-114 µM). For fluorescence studies, the Ksv value varied inversely with temperature, which confirmed the static mechanism of quenching with L1 showing maximum quenching. The parameters (ΔH, ΔS) obtained from the thermodynamic study for interaction between BSA and L1-L6 were correlated with in-silico (molecular docking) data. The in-silico docking study showed hydrophobic and the Van der Waals forces were the most significant forces. Amino acid residues ARG 217 & TRP 213 (Sudlow Site I) and LYS 116 & GLU 125 (Sudlow Site II) of BSA were primarily involved in H-bonding.Furthermore, the catalytic activity of BSA for hydrolyzingdifferent chemical entities have monitored in the presence of L1-L6 through esterase-like assay with p-NPA as a substrate, to get more insight about the interaction with catalytic residues (LYS 414, LYS 413, and TYR 411) in BSA at site II. These findings showed the potential of these 5-HT7 markers as promising ligands with appropriate drug likeliness characteristics.

Unraveling the Paradox: Can Anticoagulation Improve Outcomes in Patients With Heart Failure and Increased Bleeding Risk?

Heart failure (HF) patients frequently present with comorbidities such as atrial fibrillation (AF) or other cardiovascular conditions, elevating their risk of thromboembolic events. Consequently, anticoagulation therapy is often considered for thromboprophylaxis, although its initiation in HF patients is complicated by concomitant bleeding risk factors. This review explores the paradoxical relationship between HF, increased bleeding risk, and the potential benefits of anticoagulation. Through an examination of existing evidence from clinical trials, observational studies, and meta-analyses, we aim to elucidate the role of anticoagulation in HF patients with increased bleeding risk. Despite guidelines recommending anticoagulation for certain HF patients with AF or other thromboembolic risk factors, uncertainty persists regarding the optimal management strategy for those at heightened risk of bleeding. The review discusses the pathophysiological mechanisms linking HF and thrombosis, challenges in bleeding risk assessment, and strategies to minimize bleeding risk while optimizing thromboprophylaxis. Shared decision-making between clinicians and patients is emphasized as essential for individualized treatment plans that balance the potential benefits of anticoagulation against the risk of bleeding complications. Furthermore, it examines emerging anticoagulant agents and their potential role in HF management, highlighting the need for further research to delineate optimal management strategies and inform evidence-based practice. In conclusion, while anticoagulation holds promise for improving outcomes in HF patients, careful consideration of patient-specific factors and ongoing research efforts are essential to optimize therapeutic strategies in this population.

Guardians of the Gut: Harnessing the Power of Probiotic Microbiota and Their Exopolysaccharides to Mitigate Heavy Metal Toxicity in Human for Better Health.

Heavy metal pollution is a significant global health concern, posing risks to both the environment and human health. Exposure to heavy metals happens through various channels like contaminated water, food, air, and workplaces, resulting in severe health implications. Heavy metals also disrupt the gut's microbial balance, leading to dysbiosis characterized by a decrease in beneficial microorganisms and proliferation in harmful ones, ultimately exacerbating health problems. Probiotic microorganisms have demonstrated their ability to adsorb and sequester heavy metals, while their exopolysaccharides (EPS) exhibit chelating properties, aiding in mitigating heavy metal toxicity. These beneficial microorganisms aid in restoring gut integrity through processes like biosorption, bioaccumulation, and biotransformation of heavy metals. Incorporating probiotic strains with high affinity for heavy metals into functional foods and supplements presents a practical approach to mitigating heavy metal toxicity while enhancing gut health. Utilizing probiotic microbiota and their exopolysaccharides to address heavy metal toxicity offers a novel method for improving human health through modulation of the gut microbiome. By combining probiotics and exopolysaccharides, a distinctive strategy emerges for mitigating heavy metal toxicity, highlighting promising avenues for therapeutic interventions and health improvements. Further exploration in this domain could lead to groundbreaking therapies and preventive measures, underscoring probiotic microbiota and exopolysaccharides as natural and environmentally friendly solutions to heavy metal toxicity. This, in turn, could enhance public health by safeguarding the gut from environmental contaminants.

Morphometric analysis of sacral corridor in the upper three sacral segments to prevent neurovascular injury.

Although studies of the sacral corridor dimension have been reported in the European population, little attention has been paid to this issue in the Asian population. The purpose of the study is to estimate the safe dimension of the corridor to avoid neurovascular damage during the fixation of the sacral fracture. The study aimed to examine the cephalocaudal (vertical) and the anteroposterior diameter of the bony passage in the upper three sacral segments. The study further examines the effect of age and sex on corridor dimensions at different sacral levels. Three-dimensionally reconstructed sacra from computed tomography of normal subjects were included in the study. Cephalocaudal and anteroposterior diameters were measured in coronal and axial sections using Geomagic Freeform Plus software. Anteroposterior diameter of the sacral corridor at the first, second, and third sacral segments are significantly higher in males (P=0.013, 0.0011, and <0.0001, respectively). The length of the sacrum also revealed sexual dimorphism (P<0.00016). The anteroposterior diameter of the second sacral segment (ap-S2c) correlated moderately with the first sacral anteroposterior diameter (ap-S1c) (R=0.519, P<0.001). The ap-S2c exhibited a moderate correlation to the third sacral segment (ap-S3c) (R=0.677, P<0.001). The sacral corridor at the level of S1 has the largest cephalocaudal (18.25 mm) and anteroposterior diameter (17.11 mm). Placement of the screw in the first sacral corridor may avoid damage to the neurovascular bundle during the fixation of the sacral fracture.

Synchronized cardioversion resolving refractory supraventricular tachycardia in a neonate: a case report with comprehensive analysis.

Introduction and importance: Neonatal supraventricular tachycardia (SVT) poses unique challenges in diagnosis and management, with refractory cases requiring synchronized cardioversion being exceptionally rare. This case report explores the presentation and management of refractory SVT in a neonate, emphasizing the significance of sharing such clinical scenarios. Case presentation: A 16-day-old neonate, born via emergency caesarean section, presented with respiratory distress, poor feeding, and vomiting. Initial diagnosis of SVT was made on the basis of electrocardiography (ECG) changes. Initial attempts with adenosine failed, leading to the recurrence of tachycardia. Despite amiodarone administration, the tachycardia persisted, prompting synchronized cardioversion. Post-cardioversion, the neonate was managed with oral medications, showing sustained improvement. Clinical discussion: This case report highlights a neonate with refractory SVT, requiring synchronized cardioversion, presenting a rare and challenging scenario. The report addresses diagnostic challenges, treatment approaches, and potential mechanisms for refractory SVT, such as delayed presentation and resistance to adenosine. Emphasizing individualized care plans and vigilant monitoring, this report is a valuable resource for healthcare professionals, contributing to neonatal cardiology understanding and emphasizing the importance of early recognition and effective interventions. Ongoing follow-up and successful outcomes underscore the need for sustained management strategies. Conclusion: This case report sheds light on the rarity of refractory SVT in neonates, emphasizing the complexities in diagnosis and management. Successful synchronized cardioversion and subsequent oral therapy highlight the need for a multifaceted approach in neonatal SVT cases. The implications for clinical practice underscore the importance of awareness and continued research in neonatal cardiology and emergency medicine.

Biological Evaluation and Binding Mechanism of 5-HT7 Specific Arylpiperazinyl-Alkyl Benzothiazolone: Radiobiology and Photo-physical Studies.

Diversely substituted methoxy derivatives of arylpiperazinyl-alkyl benzothiazolone has been evaluated as specific probe for 5HT7. To determine the best methoxy derivative for 5HT7 receptor affinity, we synthesised a number of 2-benzothiazolone arylalkyl piperazine derivatives. In-vitro/vivo studies with C-2 substituted [11C]ABT showed 5HT7 specific binding. The radiochemical purity of [11C]ABT was found to be more than 99% with radiochemical stability persistence for more than 1.5 hr at 25 °C. The interaction of BSA and ABT has been analysed by photophysical studies for better understanding of properties such as adsortion, distribution, metabolism and elemination (ADME). The interaction between ABT and BSA was analyzed by using the UV-vis and fluorescence spectra. UV-vis spectra analyzed the changes in primary structure of BSA on its interaction with ABT. ABT showed quenched fluorescence emission intensity of tryptophan residues in BSA via static quenching mechanism. This study might help to understand how ABT binds to serum protein or subsequently to know the ADME of this drug candidate.

The Gut-Brain Axis in Autoimmune Diseases: Emerging Insights and Therapeutic Implications.

The gut-brain axis (GBA) is a two-way communication system that is influenced by signals from the nervous system, hormones, metabolism, the immune system, and microbes. The GBA may play a key role in gastrointestinal and neurological illnesses. Signaling events from the gut can regulate brain function. As a result, mounting data point to a connection between autoimmune disorders (AIDs), both neuroinflammatory and neurodegenerative diseases, and the GBA. Clinical, epidemiological, and experimental studies have shown that a variety of neurological illnesses are linked to alterations in the intestinal environment, which are suggestive of disease-mediated inter-organ communication between the gut and the brain. This review's objective is to draw attention to the clinical and biological relationship between the gut and the brain, as well as the clinical importance of this relationship for AIDs, neurodegeneration, and neuroinflammation. We also discuss the dysbiosis in the gut microbiota that has been linked to various AIDs, and we make some assumptions about how dietary changes such as prebiotics and probiotics may be able to prevent or treat AIDs by restoring the composition of the gut microbiota and regulating metabolites.

An experimental setup and segmentation method for CFU counting on agar plate for the assessment of drinking water.

Quantification of bacterial colonies on an agar plate is a daily routine for a microbiologist to determine the number of viable microorganisms in the sample. In general, microbiologists perform a visual assessment of bacterial colonies which is time-consuming (takes 2 min per plate), tedious, and subjective. Some automatic counting algorithms are developed that save labour and time, but their results are affected by the non-illumination on an agar plate. To improve this, the present manuscript aims to develop an inexpensive and efficient device to acquire S.aureus images via an automatic counting method using image processing techniques under real laboratory conditions. The proposed method (P_ColonyCount) includes the region of interest extraction and color space transformation followed by filtering, thresholding, morphological operation, distance transform, and watershed technique for the quantification of isolated and overlapping colonies. The present work also shows a comparative study on grayscale, K, and green channels by applying different filter and thresholding techniques on 42 images. The results of all channels were compared with the score provided by the expert (manual count). Out of all the proposed method (P_ColonyCount), the K channel gives the best outcome in comparison with the other two channels (grayscale and green) in terms of precision, recall, and F-measure which are 0.99, 0.99, and 0.99 (2 h), 0.98, 0.99, and 0.98 (4 h), and 0.98, 0.98, 0.98 (6 h) respectively. The execution time of the manual and the proposed method (P_ColonyCount) for 42 images ranges from 19 to 113 s and 15 to 31 s respectively. Apart from this, a user-friendly graphical user interface is also developed for the convenient enumeration of colonies without any expert knowledge/training. The developed imaging device will be useful for researchers and teaching lab settings.

Crystal Phase Refinement and Optical Features of Highly Efficient Green Light Radiating Ca9Y(VO4)7: Er3+ Nanophosphors for Emerging Solid-state Lighting Applications.

Ca9Y(VO4)7 phosphor activated with Er3+ ions have been developed by the urea-aided solution combustion technique. XRD profiles assisted with Rietveld refinement executed over-developed Er3+-activated Ca9Y(VO4)7 powder, revealed a trigonal phase with the R3c space group. The electron microscope techniques namely TEM and SEM characterize the size and surface-linked qualities of the developed nanopowder, respectively. The uniform distribution of various elements in the nanocrystalline sample is authenticated by an energy-dispersive spectroscopy (EDS) system. The Eg (band gap) value of 3.64 eV for Ca9Y0.9Er0.1(VO4)7 and 3.74 eV for Ca9Y(VO4)7 has been estimated. Upon 382 nm excitation, Er3+: Ca9Y(VO4)7 phosphor gives rise to the bright green emission owing to the 4S3/2 → 4I15/2 transition. The concentration quenching after 10 mol% composition of trivalent erbium ions is attributed to dipole-dipole interlinkages in accordance with Dexter's theory. The radiative lifetime (1.1083 ms), non-radiative rates (0.2079 ms- 1), quantum efficiency (79%), along with colorimetric parameters i.e. CIE x (= 0.2577), y (= 0.4566), and CCT quantities offer Ca9Y0.9Er0.1(VO4)7 as a proficient green radiating nanomaterial for RGB phosphors in solid-state applications.

Hepatitis-E-induced cholestasis in a child: a case report.

Hepatitis E virus (HEV) is a major cause of epidemic water-borne hepatitis in tropical and subtropical countries in areas with poor sanitary conditions. The infection by HEV in children is frequent but typically asymptomatic or manifested only as a very mild disease without jaundice, and usually, it often goes undiagnosed. In this case report, the authors describe a case of hepatitis-E-induced cholestasis in a child. Case presentation: An 8-year-old male child presented to a Pediatrics emergency with fever and features of acute cholestasis. On abdominal examination, there was non-tender hepatomegaly. The rest of the systemic examinations were normal. Ultrasonography findings were suggestive of acute hepatitis. The liver biopsy report showed hepatic cholestasis and hepatitis. The serological test for hepatitis E IgM was positive. The child was managed symptomatically. Conclusion: Although cholestasis is uncommon in children with HEV infection, it should be considered for non-improving clinical status in children with hepatitis. Also, patients with jaundice and Hepatitis E should be followed up by treating physicians until resolution occurs. To the authors' knowledge, this is the first case report from Nepal describing cholestasis in a child due to HEV infection.

Dysentery and leg ulcer as an atypical presentation of systemic lupus erythematosus: A case report.

INTRODUCTION: Due to heterogeneity in the organs involved and a variety of influencing factors, a wide range of clinical manifestations are possible in systemic lupus erythematosus (SLE). In our knowledge, a combination of leg ulcer and dysentery as presenting symptoms of SLE has never been reported previously. PATIENT CONCERNS: A 13-year-old female child presented with a chronic wound over right medial malleolus for 6 months, and passing of watery stool, later mixed with blood, for 4 days. On examination, she had a fever of 38.5°C. Lab reports revealed anemia, thrombocytopenia, proteinuria, and features of urinary tract infection. Renal biopsy showed membranous glomerulonephropathy. She was positive for antinuclear antibodies (ANA) and antidouble stranded DNA (anti-dsDNA). Immunofluorescence revealed reduced C4 and C3 levels. Abdominal ultrasound showed symmetrical circumscribed thickening, and edematous cecum and ascending colon. DIAGNOSIS: The patient was diagnosed with SLE based on the Systemic Lupus International Collaborating Clinics classification criteria. INTERVENTIONS: The patient was treated with prednisolone, hydroxychloroquine, metronidazole, ciprofloxacin, trypsin-chymotrypsin, zinc, calcium, and calcitriol tablets. OUTCOMES: Fever subsided within 3 days of treatment. Gastrointestinal symptoms subsided within 1 week of treatment. On 31 day of treatment, the wound had been reduced and showed features of healing. CONCLUSION: Dysentery and leg ulcers can be the manifestations of SLE. Therefore, SLE should also be considered when a patient presents with such symptoms. Any suspicion of infection in SLE should be treated aggressively with antibiotics.

Benzoxazolone-arylpiperazinyl scaffold-based PET ligand for 5-HT7 : Synthesis and biological evaluation.

Efforts are underway to improve the diagnosis and treatment for neurological disorders like depression, anxiety, epilepsy, and schizophrenia. The G-protein-coupled receptors (GPCRs) 5-HT7   receptor, the most recently identified member of 5-HT receptor family dysregulation has an association with various central nervous system (CNS) disorders and its ligands have an edge as potential therapeutics. Here, we report the synthesis, characterization, and biological evaluation of diversely substituted methoxy derivatives of 2-benzoxazolone arylpiperazine for targeting 5-HT7  receptors. Out of all derivatives, only C-2 substituted derivative, 3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)benzoxazol-2(3H)-one/ABO demonstrate a high affinity for human 5-HT7 receptors. [11 C]ABO was obtained by O-methylation of desmethyl-precursor using [11 C]CH3 OTf in the presence of NaOH giving a high radiochemical yield of 25 ± 12% (decay-corrected, n = 7) with stability up to 1.5 h postradiolabeling. In vitro autoradiography displays binding of [11 C]ABO in accordance with 5-HT7 distribution with a decrease of approximately 80% and 40% activity in the hippocampus and cerebellum brain region when administered with 10 µM cold ligand. Prefatory positron emission tomography scan results in Sprague-Dawley (SD) rat brain revealed fast and high radioactivity build-up in 5-HT7 receptor-rich regions, namely, the hippocampus (2.75 ± 0.16 SUV) and the cerebral cortex (2.27 ± 0.02 SUV) establishing selective targeting of [11 C]ABO. In summary, these pieces of data designate [11 C]ABO as a promising 5-HT7  receptor ligand that can have possible roles in clinics after its further optimization on different animal models.

[99mTc-BBPA]: A possible SPECT agent to understand the role of 18-kDa translocator protein (PBR/TSPO) during neuro-glial interaction.

The translocator protein (TSPO, 18 kDa) is one of the most promising biomarker to understand the role of neuroinflammation in human as well as in different animal species. Here we report a new TSPO-selective ligand 2-(5-(2-(bis(pyridin-2-yl methyl)amino)acetamido)-2-oxobenzo[d] oxazol-3(2H)-yl)-N-methyl-N-phenylacetamide, BBPA, which is supposed to be a potential probe to understand the role of TSPO in neuro-glial interaction through SPECT modality.

Air Pollution and Cognitive Impairment across the Life Course in Humans: A Systematic Review with Specific Focus on Income Level of Study Area.

Cognitive function is a crucial determinant of human capital. The Lancet Commission (2020) has recognized air pollution as a risk factor for dementia. However, the scientific evidence on the impact of air pollution on cognitive outcomes across the life course and across different income settings, with varying levels of air pollution, needs further exploration. A systematic review was conducted, using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Guidelines to assess the association between air pollution and cognitive outcomes across the life course with a plan to analyze findings as per the income status of the study population. The PubMed search included keywords related to cognition and to pollution (in their titles) to identify studies on human participants published in English until 10 July 2020. The search yielded 84 relevant studies that described associations between exposure to air pollutants and an increased risk of lower cognitive function among children and adolescents, cognitive impairment and decline among adults, and dementia among older adults with supportive evidence of neuroimaging and inflammatory biomarkers. No study from low- and middle-income countries (LMICs)was identified despite high levels of air pollutants and high rates of dementia. To conclude, air pollution may impair cognitive function across the life-course, but a paucity of studies from reLMICs is a major lacuna in research.

Impact of incident age-related macular degeneration and associated vision loss on vision-related quality of life.

BACKGROUND: We examined the associations between the 6-year incidence of age-related macular degeneration (AMD) and vision-related quality of life (VRQoL), and the contribution of presenting visual acuity (VA), in an Asian population. METHODS: Fundus images from the Singapore Chinese Eye Study, a population-based cohort study (baseline: 2009-2011; follow-up: 2015-2017), were graded using a modified Wisconsin age-related maculopathy grading system. Incident AMD was defined as no baseline AMD in both eyes and early/late AMD in the worse eye at follow-up. Presenting VA was assessed using the logarithm of the minimum angle of resolution chart at 4 m under standard lighting conditions with habitual correction. Multiple linear regression models determined the associations between AMD incidence with changes in the Rasch-transformed scores of the Reading, Mobility and Emotional VRQoL domains of the 32-item Impact of Visual Impairment (IVI-32) questionnaire, adjusted for traditional confounders. The contribution of presenting VA to changes in VRQoL was also estimated. RESULTS: Of the 2251 participants without AMD at baseline (mean age (SD): 57.7 (9) years, 51.4% women), 101 (4.5%) and 11 (0.5%) developed incident early and late AMD at follow-up, respectively. Incident late AMD was associated with significant 30.3%, 32.5% and 30.9% decrements in Reading, Mobility and Emotional IVI scores, respectively. The contribution of presenting VA ranged between 1.62% and 4.35% of the observed decrements. No significant associations were noted with incident early AMD. CONCLUSION: Incident late AMD had a substantial impact on all aspects of VRQoL, with presenting VA contributing only minimally to this longitudinal relationship.

Synthesis and evaluation of technetium-99m labelled 1-(2-methoxyphenyl)piperazine derivative for single photon emission computed tomography imaging for targeting 5-HT1A.

Quantitative changes in expression level of 5HT1A are somewhere related to common neurological disorders such as anxiety, major depression and schizophrenia. We have designed EDTA conjugated SPECT imaging probe for localization of 5HT1A receptor in brain. For designing SPECT probe we have employed the concept of bivalent approach and a homodimeric system with desirable pharmacokinetics of 5HT1A imaging. 99mTc-EDHT was also evaluated for its stability through serum stability assay and glutathione challenge experiment. Biodistribution study showed the highest accumulation of radioactivity in kidney which depicted the renal mode of excretion from the body. However in brain the uptake of 1.21% ID per gram was observed in initial 5 min of drug administration. On blocking the receptor this percent get decreased to 0.97% ID per gram. The regional distribution in brain was also performed which showed the accumulation of drug in cerebellum, cortex and hippocampus part, which are already known for 5HT1A expression. Dynamic study in rabbit is also in support of results derived from biodistribution and blood kinetics experiment. These finding suggest that 99mTc-EDHT holds promising place for further optimization before nuclear medicine applications in different animal species.