A Systematic Review of Community-Acquired Pneumonia in Indian Adults.

This systematic review aimed to consolidate findings on the etiology of community-acquired pneumonia (CAP) among Indian adults. We adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Guidelines 2020 and conducted a comprehensive search across databases including PubMed, Scopus-Elsevier, and hand-searched reference lists using key terms such as "Community-Acquired Pneumonia," "CAP," "Indian," and "adults." Articles published between January 2010 and January 2024 were included, with exclusions for studies involving pediatric populations, non-Indian patients, or those published before 2010. From an initial pool of 344 articles, duplicates were removed and titles and abstracts were screened, resulting in nine studies meeting the inclusion criteria. The analysis of pooled data comprising 1,643 Indian adult participants revealed the following pathogen distribution: Streptococcus pneumoniae was the most common organism, accounting for 33% of the cases. This was followed by Klebsiella pneumoniae at 23%, Staphylococcus aureus at 10%, Mycoplasma pneumoniae and Legionella pneumophila each at 7%, and Chlamydia pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa each at 4%. Notably, the review highlights a rising incidence of K. pneumoniae in CAP cases, which is a significant concern and should be considered when treating CAP patients in India. The findings emphasize the importance of comprehensive diagnostic testing, including advanced methods such as bronchoalveolar lavage, urinary antigen tests, serology for atypical pathogens, and enzyme-linked immunosorbent assays, to improve diagnostic yield and guide targeted antibiotic therapy. This review underscores the need for updated empirical treatment guidelines that account for dominant pathogens. Future research should focus on employing advanced diagnostic methods to enhance understanding of CAP etiology.

A Study on the Etiology and Clinical Manifestations of Community-Acquired Pneumonia in Adults in Western India.

BACKGROUND:  Community-acquired pneumonia (CAP) is an acute lung infection affecting the alveoli in individuals who have not had recent exposure to healthcare settings. It is characterized by newly detected pulmonary infiltration on a chest X-ray or computed tomography scan, accompanied by at least two of the following symptoms: a new or worsening cough, shortness of breath, increased sputum production, fever or hypothermia, pleuritic chest pain, hypoxia, confusion, or an abnormal WBC count (either leukopenia or leukocytosis). It is a major contributor to global mortality and morbidity, especially in elderly populations. This study aims to investigate the etiology of CAP in our region and analyze the clinical characteristics of patients diagnosed with CAP. METHODOLOGY:  This prospective, hospital-based study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, a 2,011-bed multispecialty hospital. The study included 100 patients over 18 years old, diagnosed with CAP, and hospitalized between January 2023 and January 2024. All patients underwent a thorough clinical assessment, and sputum cultures were collected on the day of admission. Patients under 18 years old, those who had been hospitalized within the preceding two weeks, individuals with pneumonia caused by tuberculosis or aspiration pneumonia, patients with compromised immune systems, and pregnant women were excluded. RESULTS:  The study included 100 patients with a mean age of 53.13 years (±18.31). The most common age group was 59-68 years, which included 25 (25%) cases, followed by the 69-78 year age group with 18 (18%) cases and the 18-28 year age group with 15 (15%) cases. The majority were male, with 61 (61%) cases. Common symptoms included fever in 78 cases (78%), chest pain in 69 cases (69%), dyspnea in 65 cases (65%), and cough in 51 cases (51%). Sputum cultures showed growth in 65 cases (65%), with Klebsiella pneumoniae being the most prevalent pathogen in 28 cases (43%), followed by Streptococcus pneumoniae in 18 cases (28%). Together, these two pathogens accounted for 46 out of 65 positive samples (70%). CONCLUSIONS:  This study highlights the clinical profile and rising etiology of K. pneumoniae in CAP in adults in Western India, particularly in the elderly. These findings underscore the need for periodic updates on CAP etiology to inform empirical treatment strategies effectively. Future research should use advanced diagnostics and diverse samples to refine CAP management, with continuous monitoring to update treatment protocols.

Insights into atypical segmental layer thicknesses and phase retardation in thick corneas using ultrahigh-resolution polarization-sensitive optical coherence tomography.

BACKGROUND: Accurately assessing corneal structural status is challenging when thickness deviates from the average. Polarization-sensitive optical coherence tomography (PS-OCT) measures tissue-specific polarization changes, providing additional contrast for accurate segmentations and aids in phase retardation (PR) measurements. Previous studies have shown PR's effectiveness in identifying sub-clinical keratoconus (KC) in asymmetric cases. Thus, this study aims to assess PR distribution in thick corneas with and without KC. METHODS: In this retrospective and cross-sectional study, 45 thick corneas from 30 Asian-Indian subjects, categorized into healthy (n = 26) and KC (n = 19) groups were analyzed. All eyes underwent standard clinical evaluations, tomographic assessments, and corneal biomechanics measurements. PR and individual layer thicknesses were measured using custom-designed ultrahigh-resolution PS-OCT. PR en-face maps were generated. Individual layer thicknesses and PR analysis was conducted across multiple zones, extending up to 8-10 mm in diameter. All eyes in the study had not undergone interventions, received topical medications, or had previous corneal disease history. RESULTS: Significant differences were found in spherical and cylindrical powers, keratometry, pachymetry, and biomechanical indices (all P < 0.01). Thickness profiles from PS-OCT showed significant differences in the 4-8 mm zones only. Bowman's layer thickness significantly differed only in the central 2 mm zone (P = 0.02). The median PR values showed marginal differences in the central 2 mm zone (P = 0.0565). Additionally, there were significant differences observed in the 2-4 mm and 4-6 mm zones (P = 0.0274 and P = 0.0456, respectively). KC eyes exhibited an atypical PR distribution and corneal thinning, while normal eyes maintained a uniform Bowman's layer thickness and PR maps with larger areas of higher PR. CONCLUSION: The study revealed distinctive PR distribution in thick corneas among healthy and KC groups. Using an ultrahigh-resolution PS-OCT the significance of Bowman's layer thickness in these groups was also emphasized. The study offered potential improvements in clinical diagnostics by enhancing our understanding of corneal structure and its altered function.

Attenuation of albumin glycation and oxidative stress by minerals and vitamins: An in vitro perspective of dual-purpose therapy.

Nonenzymatic glycation of proteins is accelerated in the context of elevated blood sugar levels in diabetes. Vitamin and mineral deficiencies are strongly linked to the onset and progression of diabetes. The antiglycation ability of various water- and fat-soluble vitamins, along with trace minerals like molybdenum (Mo), manganese (Mn), magnesium (Mg), chromium, etc., have been screened using Bovine Serum Albumin (BSA) as in vitro model. BSA was incubated with methylglyoxal (MGO) at 37 °C for 48 h, along with minerals and vitamins separately, along with controls and aminoguanidine (AG) as a standard to compare the efficacy of the minerals and vitamins. Further, their effects on renal cells' (HEK-293) antioxidant potential were examined. Antiglycation potential is measured by monitoring protein glycation markers, structural and functional modifications. Some minerals, Mo, Mn, and Mg, demonstrated comparable inhibition of protein-bound carbonyl content and ß-amyloid aggregation at maximal physiological concentrations. Mo and Mg protected the thiol group and free amino acids and preserved the antioxidant potential. Vitamin E, D, B1 and B3 revealed significant glycation inhibition and improved antioxidant potential in HEK-293 cells as assessed by estimating lipid peroxidation, SOD and glyoxalase activity. These results emphasize the glycation inhibitory potential of vitamins and minerals, indicating the use of these micronutrients in the prospect of the therapeutic outlook for diabetes management.

Timing of development of osteoradionecrosis post head and neck radiotherapy: does a safe time interval exist for dental extraction?

INTRODUCTION: Risk factors for developing osteoradionecrosis (ORN) are well known, but less is known about factors influencing the interval between radiotherapy and the onset of ORN. Also, it is unknown whether there is any specific period post-radiotherapy with a reduced probability of ORN when irradiated teeth require extraction. PURPOSE: The primary aim of this study was to identify factors influencing the interval in developing ORN in the following subgroups of patients: (1) patients who spontaneously developed ORN, (2) surgical-intervention-related ORN with a particular focus on patients after mandibulectomy. The secondary aim was to attempt to identify a possible time for safer dental intervention after primary treatment. MATERIALS AND METHODS: The authors retrospectively analysed 1608 head and neck cancer (HNC) patients treated in a single centre. Time intervals were measured from the end of radiotherapy to the development of ORN and further analysed in the subgroups listed above. RESULTS: In all, 141 patients (8.8%) developed intra-oral ORN. Median time from radiotherapy to ORN development in the whole cohort was 9 months. Median interval for spontaneous ORN was 8 months, 6.5 months for intervention-related ORN, and 15 months for patients post-mandibulectomy. In patients who required dental extraction preradiotherapy, median interval of ORN onset was 5 months. CONCLUSION: In our study, a slightly higher proportion of patients with intervention developed ORN earlier in comparison with spontaneous ORN. The period from 12-18 months after radiotherapy was identified as having the highest probability of developing ORN in patients after mandibulectomy. A time for safer dental intervention after primary treatment was not identified.

Graphene in 3D Bioprinting.

Three-dimensional (3D) bioprinting is a fast prototyping fabrication approach that allows the development of new implants for tissue restoration. Although various materials have been utilized for this process, they lack mechanical, electrical, chemical, and biological properties. To overcome those limitations, graphene-based materials demonstrate unique mechanical and electrical properties, morphology, and impermeability, making them excellent candidates for 3D bioprinting. This review summarizes the latest developments in graphene-based materials in 3D printing and their application in tissue engineering and regenerative medicine. Over the years, different 3D printing approaches have utilized graphene-based materials, such as graphene, graphene oxide (GO), reduced GO (rGO), and functional GO (fGO). This process involves controlling multiple factors, such as graphene dispersion, viscosity, and post-curing, which impact the properties of the 3D-printed graphene-based constructs. To this end, those materials combined with 3D printing approaches have demonstrated prominent regeneration potential for bone, neural, cardiac, and skin tissues. Overall, graphene in 3D bioprinting may pave the way for new regenerative strategies with translational implications in orthopedics, neurology, and cardiovascular areas.

A Case Report of Simultaneous Intracranial Hemorrhage and Cerebral Venous Sinus Thrombosis in a Young Indian Male: Diagnostic and Therapeutic Challenges.

This case report discusses the intricate diagnostic and therapeutic challenges faced by a 23-year-old Indian male who presented with altered consciousness, a holo-cranial headache, right-sided hemiparesis, and subsequent neurological symptoms. The patient's dietary habits, leading to vitamin B12 and folic acid deficiencies resulting in hyperhomocysteinemia, along with binge alcohol drinking leading to dehydration, were identified as the main causes of cerebral venous sinus thrombosis (CVST) in this case. The case was complicated by an additional cerebral hemorrhage. The patient received a comprehensive treatment regimen involving antiepileptic medications, intravenous fluids, and anticoagulation therapy. A decline in the Glasgow Coma Scale score prompted further interventions. Collaborative decision-making, involving neurologists, neurosurgeons, and the patient's relatives, steered the treatment course, ultimately favoring continued medical management over decompression surgery. Notably, the patient exhibited remarkable progress in mobility, achieving the ability to walk with support by the end. This case report contributes valuable insights to the understanding of CVST, emphasizing the significance of nutritional considerations, especially in vegetarians, and underscoring the importance of thorough diagnostic evaluations in complex clinical scenarios.

Metastatic spinal cord compression: the Spinal Instability Neoplastic Score and early surgical intervention.

OBJECTIVES: To evaluate the value of Spinal Instability Neoplastic Score (SINS) in patients with spine metastasis who subsequently developed or did not develop metastatic spinal cord compression (MSCC). METHODS: In this single institutional retrospective descriptive observational study, of 589 patients with MSCC who were referred for radiotherapy, 34 patients (with 41 compression sites) met the inclusion criteria: availability of diagnostic MRI spine pre-development of MSCC (MRI-1) and at the time of MSCC development (MRI-2) (CordGroup).For comparison, NoCordGroup consisted of 152 patients (160 sites) treated with radiotherapy to spinal metastases. SINS was compared between the two groups. RESULTS: In CordGroup, the median interval between MRI-1 and MRI-2 was 11 weeks. The median SINS was 8 (range: 4-14) and 9 (range: 7-14) on MRI-1 and MRI-2, respectively. In NoCordGroup, the median SINS was 6 (range: 4-10). CONCLUSIONS: Our study showed a trend in difference in SINS value between the two groups. This difference should be a subject of future prospective research in this patient population with poor survival.

Elevated temperature-driven coordinative reconstruction of an unsaturated single-Ni-atom structure with low valency on a polymer-derived matrix for the electrolytic oxygen evolution reaction.

A high-temperature pyrolysis-controlled coordination reconstruction resulted in a single-Ni-atom structure with a Ni-Nx-C structural unit (x = N atom coordinated to Ni). Pyrolysis of Ni-phen@ZIF-8-RF at 700 °C resulted in NiNP-NC-700 with predominantly Ni nanoparticles. Upon elevating the pyrolysis temperature from 700 to 900 °C, a coordination reconstruction offers Ni-Nx atomic sites in NiSA-NC-900. A combined investigation with X-ray absorption spectroscopy, X-ray photoelectron spectroscopy, and soft X-ray L3-edge spectroscopy suggests the stabilization of low-valent Niδ+ (0 < δ < 2) in the Ni-N-C structural units. The oxygen evolution reaction (OER) is a key process during water splitting in fuel cells. However, OER is a thermodynamically uphill reaction with multi-step proton-coupled electron transfer and sluggish kinetics, due to which there is a need for a catalyst that can lower the OER overpotentials. The adsorption energy of a multi-step reaction on a single metal atom with coordination unsaturation tunes the adsorption of each oxygenated intermediate. The promising OER activity of the NiSA-NC-900/NF anode on nickel foam was followed by the overall water splitting (OWS) using using NiSA-NC-900/NF as anode and Pt coil as the cathodic counterpart, wherein a cell potential of 1.75 V at 10 mA cm-2 was achieved. The cell potential recorded with Pt(-)/(+)NiSA-NC-900/NF was much lower than that obtained for other cells, i.e., Pt(-)/NF and NF(-)/(+)NF, which enhances the potentials of low-valent NiSAs for insightful understanding of the OER. At a constant applied potential of 1.61 V (vs. RHE) for 12 h, an small increase in current for initial 0.6 h followed by a constant current depicts the fair stability of catalyst for 12 h. Our results offer an insightful angle into the OER with a coordinatively reconstructed single-Ni-atom structure at lower valency (<+2).

Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and, as such, provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may result in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in epigenetic regulation primarily by modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extranuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases, and we will discuss the potential of their inhibitors for lung injury prevention.

Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis.

Diabetes and its complications, Alzheimer's disease (AD), and Parkinson's disease (PD) are increasing gradually, reflecting a global threat vis-à-vis expressing the essentiality of a substantial paradigm shift in research and remedial actions. Protein glycation is influenced by several factors, like time, temperature, pH, metal ions, and the half-life of the protein. Surprisingly, most proteins associated with metabolic and neurodegenerative disorders are generally long-lived and hence susceptible to glycation. Remarkably, proteins linked with diabetes, AD, and PD share this characteristic. This modulates protein's structure, aggregation tendency, and toxicity, highlighting renovated attention. Gut microbes and microbial metabolites marked their importance in human health and diseases. Though many scientific shreds of evidence are proposed for possible change and dysbiosis in gut flora in these diseases, very little is known about the mechanisms. Screening and unfolding their functionality in metabolic and neurodegenerative disorders is essential in hunting the gut treasure. Therefore, it is imperative to evaluate the role of glycation as a common link in diabetes and neurodegenerative diseases, which helps to clarify if modulation of nonenzymatic glycation may act as a beneficial therapeutic strategy and gut microbes/metabolites may answer some of the crucial questions. This review briefly emphasizes the common functional attributes of glycation and gut microbes, the possible linkages, and discusses current treatment options and therapeutic challenges.

DNDI-6174 is a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc1.

New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field are urgently required. Despite concerted efforts over the last several years, the number of new chemical entities that are suitable for clinical development for the treatment of Leishmania remains low. Here, we describe the discovery and preclinical development of DNDI-6174, an inhibitor of Leishmania cytochrome bc1 complex activity that originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required for progression into preclinical development. In addition to good metabolic stability and pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro activity against a variety of Leishmania species and can reduce parasite burden in animal models of infection, with the potential to approach sterile cure. No major flags were identified in preliminary safety studies, including an exploratory 14-day toxicology study in the rat. DNDI-6174 is a cytochrome bc1 complex inhibitor with acceptable development properties to enter preclinical development for visceral leishmaniasis.

Advanced Self-Powered Biofuel Cells with Capacitor and Nanogenerator for Biomarker Sensing.

Self-powered biofuel cells (BFCs) have evolved for highly sensitive detection of biomarkers such as noncodon micro ribonucleic acids (miRNAs) in the presence of interfering substrates. Self-charging supercapacitive BFCs for in vivo and in vitro cellular microenvironments represent the most prevalent sensing mechanism for diagnosis. Therefore, self-powered biosensing (SPB) with a capacitor and contact separation with a triboelectric nanogenerator (TENG) offers electrochemical and colorimetric dual-mode detection via improved electrical signal intensity. In this review, we discuss three major components: stretchable self-powered BFC design, miRNA sensing, and impedance spectroscopy. A specific focus is given to 1) assembling of sensors for biomarkers, 2) electrical output signal intensification, and 3) role of supercapacitors and nanogenerators in SPBs. We outline the key features of stretchable SPBs and the sequence of miRNA sensing by SPBs. We have emphasized the need of a supercapacitor and nanogenerator for SPBs in the context of advanced assembly of the sensing unit. Finally, we outline the role of impedance spectroscopy in the detection and estimation of biomarkers. We highlight key challenges in SPBs for biomarker sensing, which needs improved sensing accuracy, integration strategies of electrochemical biosensing for in vitro and in vivo microenvironments, and the impact of miRNA sensing on cancer diagnostics. This article attempts a specific focus on the accuracy and limitations of sensing unit for miRNA biomarkers and associated tool for boosting electrical signal intensity for a potential big step further.

Quality of Life of Oral Squamous Cell Carcinoma Patients before and after Primary Treatment.

Background: HNSCC (head and neck squamous cell carcinoma) is a serious global health problem, with estimated more than 550,000 new cases and 300,000 deaths annually. More than 90% of these malignancies are oral squamous cell carcinoma (OSCC). Materials and Methods: Patients selected were asked to fill the detailed structured case history proforma and thorough clinical examination, structured, pre-designed, pre-evaluated (UW-QOL) UW Questionnaire version 4 on quality of life (QOL) of oral squamous cell carcinoma patients containing thirteen subjective questionnaires and three global questionnaires. All the patients of OSCC after one month (1 month) of radiation and chemotherapy were assessed for quality of life by questionnaire. Result: Post-treatment QOL assessment of OSCC patients reveals a number of problems such as chewing, swallowing, saliva, lack of activity, and mood disturbances. Preoperative clinical features including tumor site, tumor stage, and extent of mouth opening have a significant impact on post-treatment problems in different ways. Conclusion: The need to balance clinician's need and use of health-related quality of life (HRQOL) data against patient's burden should be considered in the selection process.

Evaluation of Different Decalcification Agents on Extracted Tooth: A Comparative Study.

Introduction: The pulp is the most negatively impacted tissue during decalcification since it comprises the soft tissue components. The most effective decalcifying agent would be safest for cells and tissues while yet removing all traces of calcium. It has to get the job done quickly and have good staining properties. Aim and Objective: The goal of this research was to identify the most effective decalcifying agent for diagnostic purposes via a qualitative investigation of tissue preservation and a comparison of the efficiency of several decalcifying agents on human permanent teeth, covering both hard and soft tissue components. Materials and Methods: Fifty premolars from people aged 14 to 30 who needed them pulled for orthodontics were included in the research. Participants in the research were divided into five groups of ten. Group A, Group B, Group C, Group D, and Group E make up the total of five groups. In this investigation, we compared the efficiency of five decalcifying chemicals and analyzed their staining patterns and effects on tooth tissue. Fifty premolar teeth from participants aged 14-30 years old were removed for orthodontic therapy. For the research, they were split up into five groups of ten. Group A contains 5% ethylenediaminetetraacetic acid (EDTA), Group B contains 10% formic acid, Group C contains 5% Trichoraticectic acid, Group D contains 5% nitric acid, and Group E contains 5% formalin-nitric acid. Result: Regardless of the specifics of the chosen decalcification solution, all procedures benefit from the inclusion of external stimuli. None of the variables were used in the current investigation; it was conducted only to compare various decalcifying chemicals. Conclusion: When time is not a concern, neutral EDTA may be recommended for preservation and presentation because of its ability to maintain soft-tissue integrity and provide high-quality staining. The formalin-nitric acid solution was one agent that appeared to strike a good compromise between speed and tissue preservation.

Antimalarial Dibenzannulated Medium-Ring Keto Lactams.

We discovered dibenzannulated medium-ring keto lactams (11,12-dihydro-5H-dibenzo[b,g]azonine-6,13-diones) as a new antimalarial chemotype. Most of these had chromatographic LogD7.4 values ranging from <0 to 3 and good kinetic solubilities (12.5 to >100 µg/mL at pH 6.5). The more polar compounds in the series (LogD7.4 values of <2) had the best metabolic stability (CLint values of <50 µL/min/mg protein in human liver microsomes). Most of the compounds had relatively low cytotoxicity, with IC50 values >30 µM, and there was no correlation between antiplasmodial activity and cytotoxicity. The four most potent compounds had Plasmodium falciparum IC50 values of 4.2 to 9.4 nM and in vitro selectivity indices of 670 to >12,000. They were more than 4 orders-of-magnitude less potent against three other protozoal pathogens (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani) but did have relatively high potency against Toxoplasma gondii, with IC50 values ranging from 80 to 200 nM. These keto lactams are converted into their poorly soluble 4(1H)-quinolone transannular condensation products in vitro in culture medium and in vivo in mouse blood. The similar antiplasmodial potencies of three keto lactam-quinolone pairs suggest that the quinolones likely contribute to the antimalarial activity of the lactams.

Depth of Invasion, Lymphovascular Invasion, and Perineural Invasion as Predictors of Neck Node Metastasis in Early Oral Cavity Cancers.

Aims: The present study examines the role of demographic and pathological features of primary tumours in predicting neck metastasis in early oral cavity cancers, which has been a matter of debate. Methods: A single-centre, retrospective, institution review was conducted of all the patients presented to our centre from January 2014 to December 2021. Patient characteristics were compared between the two lymph node groups (lymph node positive and lymph node negative) and significant prognostic factors were determined. Results: A total of 462 oral squamous cell carcinoma (OSCC) patients were included, 407 male and 55 female. Tobacco chewing (59.2%) was a major habit with buccal mucosa (49.5%) and tongue (44.8%) as primary sites. The majority of the patient's histology was of SCC (96.8%) with grade II (moderately differentiated, 74.5%). Univariate logistic regression analysis to predict lymph node metastasis showed pT size (< 0.001), LVI (< 0.001), and PNI (< 0.001) as significant tumor characteristics. On multivariate, pT size (OR-1.58, P - 0.0001) and LVI (OR-19.70, P - 0.0001) were reported to be statistically significant to predict lymph node metastasis. Conclusion: Reporting and studying the clinico-pathological features of primary tumors can give vital information in predicting the neck node metastasis in OSCC patients.

Elevated translationally controlled tumour protein promotes oral cancer progression and poor outcome.

BACKGROUND: Translationally controlled tumour protein (TCTP) is a multifunctional protein elevated in multiple cancers. However, studies on its role in oral carcinogenesis and prognosis are rare. We recently reported the role of its interacting partner, MCL1, in oral cancer progression and outcome. Hence, the present study aimed to assess TCTP expression in oral tumorigenesis and its association with patient outcomes alone and in combination with MCL1. METHODS: TCTP expression was assessed by immunohistochemistry and immunoblotting in oral tissues and cells, respectively. Cell viability post siRNA/dihydroartemisinin treatment was analysed by tetrazolium salt assay. Cell survival, invasion and tumorigenic potential post TCTP knockdown were assessed by clonogenic, Matrigel and soft-agar assays, respectively. The association of TCTP with patient outcome was analysed by Kaplan-Meier and Cox regression. RESULTS: TCTP was significantly overexpressed in oral premalignant lesions (p < 0.0001), oral tumours (p < 0.0001) and oral dysplastic and cancer cells versus normal oral mucosa and also in recurrent (p < 0.05) versus non-recurrent oral tumours. Further, elevated TCTP was significantly (p < 0.05) associated with poor recurrence free survival (RFS) and poor overall survival (OS; hazard ratio = 2.29; p < 0.05). Intriguingly, the high co-expression of TCTP and MCL1 further reduced the RFS (p < 0.05) and OS (p < 0.05; hazard-ratio = 3.49; p < 0.05). Additionally, TCTP knockdown decreased survival (p < 0.05), invasion (p < 0.01) and in vitro tumorigenic potential (p < 0.0001). Dihydroartemisinin treatment reduced TCTP levels and viability of oral cancer cells. CONCLUSION: Our studies demonstrate an oncogenic role of TCTP in oral cancer progression and poor outcome. Thus, TCTP may be a potential prognostic marker and therapeutic target in oral cancers.

Serine/Threonine Protein Phosphatases 1 and 2A in Lung Endothelial Barrier Regulation.

Vascular barrier dysfunction is characterized by increased permeability and inflammation of endothelial cells (ECs), which are prominent features of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and sepsis, and a major complication of the SARS-CoV-2 infection and COVID-19. Functional impairment of the EC barrier and accompanying inflammation arises due to microbial toxins and from white blood cells of the lung as part of a defensive action against pathogens, ischemia-reperfusion or blood product transfusions, and aspiration syndromes-based injury. A loss of barrier function results in the excessive movement of fluid and macromolecules from the vasculature into the interstitium and alveolae resulting in pulmonary edema and collapse of the architecture and function of the lungs, and eventually culminates in respiratory failure. Therefore, EC barrier integrity, which is heavily dependent on cytoskeletal elements (mainly actin filaments, microtubules (MTs), cell-matrix focal adhesions, and intercellular junctions) to maintain cellular contacts, is a critical requirement for the preservation of lung function. EC cytoskeletal remodeling is regulated, at least in part, by Ser/Thr phosphorylation/dephosphorylation of key cytoskeletal proteins. While a large body of literature describes the role of phosphorylation of cytoskeletal proteins on Ser/Thr residues in the context of EC barrier regulation, the role of Ser/Thr dephosphorylation catalyzed by Ser/Thr protein phosphatases (PPases) in EC barrier regulation is less documented. Ser/Thr PPases have been proposed to act as a counter-regulatory mechanism that preserves the EC barrier and opposes EC contraction. Despite the importance of PPases, our knowledge of the catalytic and regulatory subunits involved, as well as their cellular targets, is limited and under-appreciated. Therefore, the goal of this review is to discuss the role of Ser/Thr PPases in the regulation of lung EC cytoskeleton and permeability with special emphasis on the role of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) as major mammalian Ser/Thr PPases. Importantly, we integrate the role of PPases with the structural dynamics of the cytoskeleton and signaling cascades that regulate endothelial cell permeability and inflammation.

Variable neutralizing antibody responses to 10 SARS-CoV-2 variants in natural infection with wild- type (B.1) virus, Kappa (B.1.617.1), and Delta (B.1.617.2) variants and COVISHIELD vaccine immunization in India: utility of the MSD platform.

For the efficacy of COVID-19 vaccines, emergence of variants accumulating immune-escape mutations remains a major concern. We analyzed the anti-variant (n = 10) neutralization activity of sera from COVID-19 patients infected with Wuhan (B.1), Kappa, and Delta variants and COVISHIELD vaccine recipients with (prepositives) or without (prenegatives) prior antibody positivity using V- PLEX ACE2 Neutralization Kit from MSD. MSD and PRNT50 correlated well (r = 0.76-0.83, p < 0.0001). Despite the least antibody positivity in Kappa patients, anti-variant neutralizing antibody (Nab) levels in the responders were comparable with Delta patients. Vaccinees sampled at 1 month (PD2-1) and 6 months (PD2-6) post-second dose showed the highest seropositivity and Nab levels against the Wuhan strain. At PD2-1, the responder rate was variant-dependent and 100% respectively in prenegatives and prepositives. Nab levels against B.1.135.1, B.1.620, B.1.1.7+E484K (both groups), AY.2 (prenegatives), and B.1.618 (prepositives) were lower than that of Wuhan. At PD2-6, positivity decreased to 15.6%-68.8% in the prenegatives; 3.5%-10.7% of prepositives turned negative for the same four variants. As against the decline in Nab levels in 9/10 variants (prenegatives), a further reduction was seen against the same four variants in the prepositives. These variants possess immune-evasion-associated mutations in the RBD/S region. In conclusion, our data show that the Nab response of patients to multiple variants depends on the infecting variant. We confirm superiority of hybrid immunity in neutralizing multiple variants. Depending on the infecting variant pre- or postvaccination, immune response to different vaccines in different populations will vary and impact protection against emerging variants. The MSD platform provides an excellent alternative to live virus/pseudovirus neutralization tests.