Electrostatically Engineered Tetraphenylethylene-Based Fluorescence Sensor for Protamine and Trypsin: Leveraging Aggregation-Induced Emission for Enhanced Sensitivity and Selectivity.

The accurate detection of Protamine and Trypsin, two biomolecules with significant clinical and biological relevance, presents a substantial challenge because of their structural peculiarities, low abundance in physiological fluids, and potential interference from other substances. Protamine, a cationic protein, is crucial for counteracting heparin overdoses, whereas Trypsin, a serine protease, is integral to protein digestion and enzyme activation. This study introduces a novel fluorescence sensor based on a (4-(1,2,2-tris(4-phosphonophenyl)vinyl)phenyl)phosphonic acid octasodium salt (TPPE), leveraging aggregation-induced emission (AIE) characteristics and electrostatic interactions to achieve selective and sensitive detection of these biomolecules. Through comprehensive optical characterization, including ground-state absorption, steady-state, and time-resolved emission spectroscopy, the interaction mechanisms and aggregation dynamics of TPPE with Protamine and Trypsin were elucidated. The sensor exhibits very high sensitivity (LOD: 1.45 nM for Protamine and 32 pM for Trypsin), selectivity, and stability, successfully operating in complex biological matrices, such as human serum and urine. Importantly, this sensor design underscores the synergy between the AIE phenomena and biomolecular interactions, offering a promising alternative for analytical applications in biomedical research and clinical diagnostics. The principles outlined herein open new avenues for the development of other AIE-based sensors, expanding the toolkit available for detecting a wide range of biomolecules using similar design strategies.

Diagnostic accuracy of deep learning in detection and prognostication of renal cell carcinoma: a systematic review and meta-analysis.

Introduction: The prevalence of Renal cell carcinoma (RCC) is increasing among adults. Histopathologic samples obtained after surgical resection or from biopsies of a renal mass require subtype classification for diagnosis, prognosis, and to determine surveillance. Deep learning in artificial intelligence (AI) and pathomics are rapidly advancing, leading to numerous applications such as histopathological diagnosis. In our meta-analysis, we assessed the pooled diagnostic performances of deep neural network (DNN) frameworks in detecting RCC subtypes and to predicting survival. Methods: A systematic search was done in PubMed, Google Scholar, Embase, and Scopus from inception to November 2023. The random effects model was used to calculate the pooled percentages, mean, and 95% confidence interval. Accuracy was defined as the number of cases identified by AI out of the total number of cases, i.e. (True Positive + True Negative)/(True Positive + True Negative + False Positive + False Negative). The heterogeneity between study-specific estimates was assessed by the I 2 statistic. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to conduct and report the analysis. Results: The search retrieved 347 studies; 13 retrospective studies evaluating 5340 patients were included in the final analysis. The pooled performance of the DNN was as follows: accuracy 92.3% (95% CI: 85.8-95.9; I 2 = 98.3%), sensitivity 97.5% (95% CI: 83.2-99.7; I 2 = 92%), specificity 89.2% (95% CI: 29.9-99.4; I 2 = 99.6%) and area under the curve 0.91 (95% CI: 0.85-0.97.3; I 2 = 99.6%). Specifically, their accuracy in RCC subtype detection was 93.5% (95% CI: 88.7-96.3; I 2 = 92%), and the accuracy in survival analysis prediction was 81% (95% CI: 67.8-89.6; I 2 = 94.4%). Discussion: The DNN showed excellent pooled diagnostic accuracy rates to classify RCC into subtypes and grade them for prognostic purposes. Further studies are required to establish generalizability and validate these findings on a larger scale.

A case of COVID-19-associated C-ANCA vasculitis, was successfully treated with rituximab therapy.

Both C-anti-neutrophil cytoplasmic antibody (ANCA) and P-ANCA vasculitis were reported to be associated with COVID-19 infection. The ideal management of COVID-19-associated ANCA vasculitis is unclear, as the experiences were limited to case reports. We presented a case of COVID-19-associated C-ANCA vasculitis, successfully treated with steroids and rituximab therapy without any significant adverse reactions.

Outcomes of Acute Kidney Injury among Hospitalized Patients with Infective Endocarditis: A National Inpatient Sample Analysis.

Background/Objectives: Patients with infective endocarditis (IE) are more susceptible to acute kidney injury (AKI). The presence of AKI increases in-hospital complications in these patients. Methods: The 2016-2020 National Inpatient Sample (NIS) database consisting of adult admissions with IE and AKI was utilized. The primary outcome was all-cause inpatient mortality. Secondary outcomes included fluid and electrolyte disorders, stroke, septic arterial embolism, septic shock, cardiogenic shock, valve surgery, vasopressor support, mechanical ventilation, length of stay (LOS), and total hospital charges. Results: Out of a total of 63,725 adult admissions with IE, 16,295 (25.5%) admissions had AKI. Patients with AKI were more likely to be males (63% vs. 57.6%, p < 0.001) and older (55.8 vs. 50.4, p < 0.001). A higher proportion of these patients were admitted to large hospitals (60.6 vs. 55.3%, p < 0.001) and urban teaching hospitals (81.9 vs. 75%, p < 0.001). Patients with AKI had higher LOS (17 ± 16.1 vs. 11.32 ± 11.7, p < 0.001) and hospital charges (USD 239,046.8 ± 303,977.3 vs. USD 124,857.6 ± 192,883.5, p < 0.001). Multivariable analysis showed higher odds of all-cause inpatient mortality (aOR: 2.22, 95% CI: 1.81-2.73, p < 0.001). They also had higher risk for fluid and electrolyte disorder (aOR: 2.31, 95% CI: 2.10-2.53, p < 0.001), septic arterial embolism (aOR: 1.61, 95% CI: 1.42-1.84, p < 0.001), septic shock (aOR: 3.78, 95% CI: 2.97-4.82, p < 0.001), cardiogenic shock (OR: 3.37, 95% CI: 2.65-4.28, p < 0.001), valve surgery (aOR: 1.52, 95% CI: 1.35-1.71, p < 0.001), vasopressor requirement (aOR: 1.99, 95% CI: 1.52-2.60, p < 0.001), and mechanical ventilation (aOR: 2.75, 95% CI: 2.33-3.24, p < 0.001). The association with stroke was elevated but not statistically significant. Conclusions: This large retrospective analysis demonstrated that patients with AKI and infective endocarditis had increased mortality, adverse hospital outcomes, increased LOS, and hospital costs.

Multi-Facet analysis of analytical and numerical models to resolve sustainable artificial recharge rates in unconfined aquifers.

Managed aquifer recharge (MAR) has emerged as a potential solution to resolve water insecurity, globally. However, integrated studies quantifying the surplus source water, suitable recharge sites and safe recharge capacity is limited. In this study, a novel methodology is presented to quantify transient injection rates in unconfined aquifers and generate MAR suitability maps based on estimated surplus water and permissible aquifer recharge capacity (PARC). Subbasin scale monthly surplus surface runoff was estimated at 75% dependability using a SWAT model. A linear regression model based on numerical solution was used to capture the aquifer response to injection and to calculate PARC values at subbasin level. The available surplus runoff and PARC values was then used to determine the suitable site and recharge rate during MAR operation. The developed methodology was applied in the semi-arid region of Lower Betwa River Basin (LBRB), India. The estimated surplus runoff was generally confined to the monsoon months of June to September and exhibited spatial heterogeneity with an average runoff rate of 5000 m3/d in 85% of the LBRB. Analysis of the PARC results revealed that thick alluvial aquifers had large permissible storage capacity and about 50% of the LBRB was capable of storing over 3500 m3/d of water. This study revealed that sufficient surplus runoff was generated in the LBRB, but it lacked the adequate safe aquifer storage capacity to conserve it. A total 65 subbasins was identified as the best suited sites for MAR which had enough surplus water and storage capacity to suffice 20% of the total water demand in the LBRB. The developed methodology was computationally efficient, could augment the field problem of determining scheduled recharge rates and could be used as a decision-making tool in artificial recharge projects.

Ecological impact of pharmaceutical pollutants and options of river health improvements - A risk analysis-based approach.

Pharmaceuticals are one of the emerging pollutants (EPs) in river waters across the world. Due to their toxic effects on aquatic organisms, they have drawn the global attention of the scientific community concerned with river ecosystems. This paper reviews the existing occurrence data for various pharmaceutical pollutants (PPs) reported in river waters in some part of the world and their ecological impacts. Using algae, macroinvertebrates (MI), and fish as biotic indicator groups in water to reflect river health conditions, an attempt has been made to assess the ecological risk due to the presence of PPs in the water environment. After ascertaining the predicted no-effect concentration (PNEC) of PPs for selected groups of aquatic organisms, the risk quotient (RQ) is estimated based on their measured environmental concentration (MEC). When MEC > PNEC and RQ > 1 for any of the biotic indicator, ecologically it is 'high risk' condition. The determination of PNEC uses a minimum assessment factor (AF) of 10 due to uncertainty in data over the no observed effect level (NOEL) or lowest observed effect level (LOEL). Accordingly, MEC 10 times higher than PNEC, (RQ = 10) represents a threshold risk concentration (RCT) beyond which adverse effects may start showing observable manifestations. In the present study, a new classification system of 'high risk' conditions for RQ = 1-10 has been proposed, starting from 'moderately high' to 'severely high'. For RQ > 10, the ecological condition of the river is considered 'impaired'. For river health assessment, in the present study, the whole range of physico-chemical characteristics of river water quality has been divided into three groups based on their ease of measurement and frequency of monitoring. Dissolved oxygen related parameters (DORPs), nutrients (NTs), and EPs. PPs represent EPs in this study. A framework for calculating separate indicator group score (IGS) and the overall river health index (RHI) has been developed to predict indicator group condition (IGC) and river health condition (RHC), respectively. Color-coded hexagonal pictorial forms representing IGC and RHC provide a direct visible perception of the existing aquatic environment and a scientific basis for prioritization of corrective measures in terms of treatment technology selection for river health improvements. The analyses indicate that many rivers across the world are under 'high risk' conditions due to PPs having MEC > PNEC and RQ > 1. Up to RCT, (where RQ = 10), the 'high risk' condition varies from 'moderately high' to 'severely high'. In many instances, RQ is found much more higher than 10, indicating that the ecological condition of river may be considered as 'impaired'. Algae is the most frequently affected group of biotic indicators, followed by MI and fish. A review of treatment methods for selection of appropriate technology to reduce the pollution load, especially PPs from the wastewater streams has been summarized. It appears that constructed wetlands (CWs) are at present the most suitable nature-based solutions, particularly for the developing economies of the world, to reduce the concentrations of PPs within limits to minimize the ecological impacts of pharmaceutical compounds on biotic indicators and restore the river health condition. Some suggestive design guidelines for the CWs have also been presented to initiate the process.

A decision support system for localized planning of reclaimed water around wastewater treatment plants.

Exploding population, industrialization, and an increase in water pollution has led to acute shrinkage in freshwater availability. Numerous countries have started exploring municipal wastewater as a new potential source of water to bring a paradigm shift from linearity to obtaining circularity in human water cycle management. This study aims to develop a decision support system for integrated water and wastewater management (DSS_IWWM), targeted towards reuse-focused selection of appropriate wastewater treatment technology, and localized planning around STPs in terms of reclaimed water demand identification, estimation, allocation, and sustainable pricing. The developed DSS_IWWM comprises of a repository of fourteen reuse purposes, reuse quality criteria, and 25 wastewater treatment technologies (WWTTs) in 360 combinations. It is sensitive to local resource scenarios and applies a socioeconomic and technology-focused methodology for addressing the interests of the community and investing agencies and viably. To validate the application of the DSS_IWWM, it is first tested with data from three cities in the state of Uttar Pradesh (India)-Lucknow, Prayagraj, and Agra-and then extended to nine more Indian cities with varying influent quality characteristics, resource inputs, existing STP technologies, and same target quality and decision criteria prioritization, to present a comparison of appropriate WWTTs and associated average prices obtained in different scenarios. It is concluded that influent quality, existing technology, and target quality criteria play significant role in selection of appropriate WWTTs. The traditional technologies such as UASB and ASP are required to be augmented and supplemented with high-performing WWTTs, such as BIOFOR-F with (C + F + RSF) and SBT + WP to obtain desired effluent quality. High-performing advanced oxidation process (AOP)-based systems such as A2O, SBR, and BIOFOR-F require WWTTs with relatively lower average costs (such as SBT and OP). The developed DSS_IWWM may prove to be very useful and beneficial for policymakers, government officials, engineers, and scientific community as it will facilitate rational decision-making for efficient investment planning in reuse focused wastewater treatment towards achieving circular economy in sustainable water resource management.

Comparative Evaluation and Correlation of Periodontal Status With Inflammatory Markers in Pregnant Women With or Without Chronic Periodontitis: A Clinico-Hematological Study.

Background The research delves into the intricate relationship between periodontal health and specific blood biomarkers in pregnant women during their second trimester. It specifically focuses on the levels of interleukin-6 (IL-6), lactate dehydrogenase (LDH), and C-reactive protein (CRP) in those suffering from chronic periodontitis compared to healthy controls. Methodology A detailed approach was taken involving 60 pregnant women categorized into two groups based on the presence or absence of chronic periodontitis. Out of 60 pregnant women, 30 had chronic periodontitis, while the other 30 served as controls selected from the regular patient population of the college. The study utilized blood sample analysis and advanced statistical tools for data analysis, ensuring precise and reliable results. Levels of IL-6, LDH, and CRP in those suffering from chronic periodontitis compared to healthy controls were checked. Results The findings revealed a notable variance in IL-6, LDH, and CRP levels between the two groups. Women with chronic periodontitis exhibited significantly higher levels of these biomarkers. The statistical analysis reinforced the validity of these differences, highlighting their significance. Conclusions The study underscored a clear link between higher levels of IL-6, LDH, and CRP and the presence of chronic periodontitis in pregnant women. These biomarkers emerge as potential indicators for early detection and monitoring of periodontal health in this demographic.

Expanding the scope of self-assembled supramolecular biosensors: a highly selective and sensitive enzyme-responsive AIE-based fluorescent biosensor for trypsin detection and inhibitor screening.

Trypsin, a pancreatic enzyme associated with diseases like pancreatic cancer and cystic fibrosis, requires effective diagnostic tools. Current detection systems seldom utilize macrocyclic molecules and tetraphenyl ethylene (TPE) derivative-based supramolecular assemblies, known for their biocompatibility and aggregation-induced emission (AIE) properties, for trypsin detection. This study presents an enzyme-responsive, AIE-based fluorescence 'Turn-On' sensing platform for trypsin detection, employing sulfated-ß-cyclodextrin (S-ßCD), an imidazolium derivative of TPE (TPE-IM), and protamine sulfate (PrS). The anionic S-ßCD and cationic TPE-IM formed a strongly fluorescent supramolecular aggregation complex in an aqueous buffer. However, PrS suppresses fluorescence because of its strong binding affinity with S-ßCD. The non-fluorescent TPE-IM/S-ßCD/PrS supramolecular assembly system exhibits trypsin-responsive properties, as PrS is a known trypsin substrate. Trypsin restores fluorescence in the TPE-IM/S-ßCD system through the enzymatic cleavage of PrS, correlating linearly with trypsin catalytic activity in the 0-10 nM concentration range. The limit of detection is 10 pM. This work contributes to the development of self-assembled supramolecular biosensors using charged TPE derivatives and ß-cyclodextrin-based host-guest chemistry, offering an innovative fluorescence 'Turn-On' trypsin sensing platform. The sensing system is highly stable under various conditions, selective for trypsin, and demonstrates potential for biological analysis and disease diagnosis in human serum. Additionally, it shows promise for the screening of trypsin inhibitors.

Sodium-glucose Co-transporter-2 Inhibitors Causing Candida tropicalis Fungemia and Renal Abscess.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a relatively newer class of medications, approved by the U.S. Food and Drug Administration in 2013 to treat type 2 diabetes mellitus. Over the past few years, the indications for SGLT2i have been expanded to decrease the risk of kidney disease and cardiovascular disease. SGLT2i are associated with an increased risk of euglycemic diabetic ketoacidosis, urinary tract infections, and genital mycotic infections. There are a few case reports of severe invasive fungal infections due to Candida in patients using SGLT2i. We present the case of Candida tropicalis fungemia and renal abscess in a patient on an SGLT2i.

Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.

Montelukast Ameliorates 2K1C-Hypertension Induced Endothelial Dysfunction and Associated Vascular Dementia.

BACKGROUND: Declined kidney function associated with hypertension is a danger for cognitive deficits, dementia, and brain injury. Cognitive decline and vascular dementia (VaD) are serious public health concerns, which highlights the urgent need for study on the risk factors for cognitive decline. Cysteinyl leukotriene (CysLT1) receptors are concerned with regulating cognition, motivation, inflammatory processes, and neurogenesis. OBJECTIVE: This research aims to examine the consequence of montelukast (specific CysLT1 antagonist) in renovascular hypertension 2-kidney-1-clip-2K1C model-triggered VaD in experimental animals. METHODS: 2K1C tactics were made to prompt renovascular hypertension in mature male rats. Morris water maze was employed to measure cognition. Mean arterial pressure (MAP), serum nitrite levels, aortic superoxide content, vascular endothelial activity, brain's oxidative stress (diminished glutathione, raised lipid peroxides), inflammatory markers (IL-10, IL-6, TNF-α), cholinergic activity (raised acetylcholinesterase), and cerebral injury (staining of 2, 3, 5- triphenylterazolium chloride) were also examined. RESULTS: Montelukast in doses of 5.0 and 10.0 mg kg-1 was used intraperitoneally as the treatment drug. Along with cognitive deficits, 2K1C-operated rats showed elevated MAP, endothelial dysfunction, brain oxidative stress, inflammation, and cerebral damage with diminished serum nitrite/nitrate. Montelukast therapy significantly and dose-dependently mitigated the 2K1Chypertension- provoked impaired behaviors, biochemistry, endothelial functions, and cerebral infarction. CONCLUSION: The 2K1C tactic caused renovascular hypertension and associated VaD, which was mitigated via targeted regulation of CysLT1 receptors by montelukast administration. Therefore, montelukast may be taken into consideration for the evaluation of its complete potential in renovascular-hypertension-induced VaD.

Synthesis, Photophysical Properties and Self-Assembly of a Tetraphenylethylene-Naphthalene Diimide Donor-Acceptor Molecule.

The development of new π-conjugated molecular structures with controlled self-assembly and distinct photophysical properties is crucial for advancing applications in optoelectronics and biomaterials. This study introduces the synthesis and detailed self-assembly analysis of tetraphenylethylene (TPE) functionalized naphthalene diimide (NDI), a novel donor-acceptor molecular structure referred to as TPE-NDI. The investigation specifically focuses on elucidating the self-assembly behavior of TPE-NDI in mixed solvents of varying polarities, namely chloroform: methylcyclohexane (CHCl3 : MCH) and chloroform: methanol (CHCl3 : MeOH). Employing a several analytical methodologies, including UV-Vis absorption and fluorescence emission spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), and dynamic light scattering (DLS), these self-assembled systems have been comprehensively examined. The results reveal that TPE-NDI manifests as distinct particles in CHCl3 : MCH (fMCH =90 %), while transitioning to flower-like assemblies in CHCl3 : MeOH (fMeOH =90 %). This finding underscores the critical role of solvent polarity in dictating the morphological characteristics of TPE-NDI self-assembled aggregates. Furthermore, the study proposes a molecular packing mechanism, based on SEM data, offering significant insights into the design and development of functional supramolecular systems. Such advancements in understanding the molecular self-assembly new π-conjugated molecular structures are anticipated to pave the way for novel applications in material science and nanotechnology.

A Comprehensive Review on Molecular Mechanism Involved in Arsenic Trioxide Mediated Cerebral Neurodegenerative and Infectious Diseases.

Arsenic is an environmental toxicant and its toxicity is a global health problem affecting millions of people. Arsenic exposure occurs from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Both cancerous, noncancerous and immunological complications are possible after arsenic exposure. The many other target organs like lungs, thymus, spleen, liver, heart, kidney, and brain. Arsenic-mediated neuro, as well as immunotoxicity, is the main concern of this review. Long-term arsenic exposure can lead to various neurological dysfunctions, which may cause neurobehavioral defects and biochemical impairment in the brain, this might negatively affect one's quality of life in later stages. Arsenic also alters the levels of various neurotransmitters such as serotonin, dopamine and norepinephrine in the brain which produces neurotoxic effects and immunological deficiency. So, it is crucial to understand the neurotoxic mechanism of arsenic trioxide-mediated cerebro neurodegenerative and immunerelated alterations. One of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. This review focuses on the various toxic mechanisms responsible for arsenic-mediated neurobehavioral and immune-related changes. Therefore, this review provides a critical analysis of mitochondrial dysfunctions, oxidative stress, glutamate excitatory, inflammatory and apoptosis-related mechanistic aspects in arsenic-mediated immunotoxicity, neurotoxicity, and neurodegenerative changes.

Spatial distribution of heavy metals in the sediments of River Ganges, India: Occurrence, contamination, source identification, seasonal variations, mapping, and ecological risk evaluation.

Present study analyzed the seasonal and spatial distribution patterns, sources, and ecological risks of seven heavy metals (Cr, Fe, Ni, Cu, Zn, Cd and Pb) in the sediments of River Ganges, finding that the majority of concentrations were lithologic, except for Cd, which was significantly higher than background standards. Elevated values of geochemical indices viz. Igeo, CF, RI, Cd, mCd, HQ, mHQ, and PN suggest moderate to high ecological risk in the benthic environment and its organisms due to the synergistic effect of heavy metals. The PEC-Qmetals revealed 8-10 % toxicity in the upstream and downstream sites, due to the influence of agricultural activities. Multivariate statistical techniques (PCM and PCA) indicated that Cd and Pb predominantly originated from anthropogenic sources, while other metals primarily derived from geological background. These geochemical findings may help to understand the potential risks and recommend strategies to mitigate the effects of metallic contamination in river sediments.

Effect of audio distraction with thermomechanical stimulation on pain perception for inferior alveolar nerve block in children: a randomized clinical trial.

Background: Pain control is a crucial aspect of pediatric dentistry for patient management. Thermo-mechanical devices (Buzzy™ Pain Care Labs, USA) work on the concept of vibration and cooling and have shown promising results in pain control during local anesthesia in pediatric dentistry. On the other hand, audio distraction has also been used for pain management. The amount of pain endured is determined by the patient's perception and attentiveness. Thus, if audio function is added to the thermomechanical device it might increase its efficiency. Hence, the present study aimed to compare pain on injection using a thermo-mechanical device with and without audio during inferior alveolar nerve block (IANB) injection in children aged 5-10 years old. Methods: Twenty-eight children aged between 5 and 10 indicated for IANB were included in this randomized study. Children who were undergoing the dental procedure were divided into 2 groups, with 14 children in each group. The study group was the thermo-mechanical device with audio distraction; the control group was the thermo-mechanical device without audio distraction. IANB was administered. Subjective pain evaluation was performed using the Wong-Baker Faces Pain Rating Scale (WBFPR) and objective pain evaluation was done using the Faces, Leg, Activity, Consolability, Cry (FLACC) scale. Results: The outcome depicted a significant reduction in pain on injection for both objective and subjective evaluations in the thermo-mechanical device with an audio distraction group. Conclusions: Less pain on injection was observed, when a thermo-mechanical device was used with audio distraction for IANB procedures.

Dual functioning by the PhoR sensor is a key determinant to Mycobacterium tuberculosis virulence.

PhoP-PhoR, one of the 12 two-component systems (TCSs) that empower M. tuberculosis to sense and adapt to diverse environmental conditions, remains essential for virulence, and therefore, represents a major target to develop novel anti-TB therapies. Although both PhoP and PhoR have been structurally characterized, the signal(s) that this TCS responds to remains unknown. Here, we show that PhoR is a sensor of acidic pH/high salt conditions, which subsequently activate PhoP via phosphorylation. In keeping with this, transcriptomic data uncover that acidic pH- inducible expression of PhoP regulon is significantly inhibited in a PhoR-deleted M. tuberculosis. Strikingly, a set of PhoP regulon genes displayed a low pH-dependent activation even in the absence of PhoR, suggesting the presence of non-canonical mechanism(s) of PhoP activation. Using genome-wide interaction-based screening coupled with phosphorylation assays, we identify a non-canonical mechanism of PhoP phosphorylation by the sensor kinase PrrB. To investigate how level of P~PhoP is regulated, we discovered that in addition to its kinase activity PhoR functions as a phosphatase of P~PhoP. Our subsequent results identify the motif/residues responsible for kinase/phosphatase dual functioning of PhoR. Collectively, these results uncover that contrasting kinase and phosphatase functions of PhoR determine the homeostatic mechanism of regulation of intra-mycobacterial P~PhoP which controls the final output of the PhoP regulon. Together, these results connect PhoR to pH-dependent activation of PhoP with downstream functioning of the regulator. Thus, PhoR plays a central role in mycobacterial adaptation to low pH conditions within the host macrophage phagosome, and a PhoR-deleted M. tuberculosis remains significantly attenuated in macrophages and animal models.

Methods of Determining Irritable Bowel Syndrome and Efficiency of Probiotics in Treatment: A Review.

Background: Irritable bowel syndrome (IBS) is a prevalent lifestyle-associated ailment linked to the gut microbiota that significantly influences patients' quality of life. A notable correlation exists between Blastocystis infections and susceptibility to IBS, with infected individuals exhibiting an increased likelihood of developing the condition. Despite promising results from using probiotics to modulate the gut microbiota and manage IBS, the precise mechanisms and potential risks remain unclear. Objective: This review aims to explore the therapeutic potential of probiotics, particularly Saccharomyces boulardii, in the management of IBS, highlighting the role of the gut microbiota and the gut-brain axis in IBS pathophysiology. Methods: A comprehensive literature survey was conducted to examine the association between gut microbiota and IBS, the role of probiotics in managing IBS, the mechanisms of their action, and the potential risks associated with their long-term use. Additionally, this study addresses the influence of Blastocystis infections on IBS susceptibility and evaluates various ongoing clinical trials investigating probiotic use for IBS. Results: S boulardii, a yeast species with probiotic properties, has demonstrated effectiveness in both the treatment and prophylaxis of IBS. Its administration is associated with a decrease in the proinflammatory cytokine interleukin 8 and an increase in the anti-inflammatory cytokine interleukin 10. Probiotics appear to function by inhibiting the growth of pathogenic microorganisms and regulating neurotransmitter activity, influencing the gut-brain axis. However, selecting appropriate probiotic strains and dosing regimens is crucial because of potential adverse effects, such as infections and allergic reactions. Conclusions: Probiotics, specifically S boulardii, offer a promising avenue for IBS management by modulating gut microbiota. However, further research is necessary to delineate the precise mechanisms of action, optimal strains, dosing regimens for IBS treatment, and potential risks associated with long-term use. A comprehensive approach incorporating probiotics, a low-FODMAP diet, and cognitive-behavioral therapy may provide effective management of IBS symptoms.

Role of Sodium-Glucose Co-Transporter 2 Inhibitors in Chronic Kidney Disease, Congestive Heart Failure and Stroke-A Review and Clinical Guide for Healthcare Professionals.

Diabetic kidney disease (DKD) causes a progressive decline in renal function, leading to end-stage kidney disease (ESKD), and increases the likelihood of cardiovascular events and mortality. The recent introduction of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor has been a game changer in managing chronic kidney disease (CKD) and congestive heart failure (CHF). These agents not only slow down the progression of kidney disease but also have cardioprotective benefits, including for patients with congestive heart failure and atherosclerotic cardiovascular disease. Some evidence suggests that they can decrease the risk of stroke as well. This review aims to provide a comprehensive overview of the role of SGLT-2 inhibitors in CKD and CHF and their efficacy in stroke prevention. This review includes a comparison with glucagon-like peptide-1 (GLP-1) agonist and finerenone; focuses on safety data, the potential benefits beyond glycemic control, and a review of significant trials; and provides guidance in clinical practice.