A Randomized Study to Evaluate the Efficacy of Oral Tranexamic Acid, Modified Kligman's Formula, and Placebo Cream in Melasma.

Background: Despite the availability of various treatment modalities, the treatment of melasma is often incomplete, with a high recurrence rate. The present study was undertaken to assess the efficacy and safety of oral tranexamic acid (TXA), modified Kligman's formula (MKF), and a placebo cream in melasma. Materials and Methods: Ninety cases of melasma of both sexes were enrolled, and divided into three groups of 30 patients each. The baseline severity of melasma was graded by Melasma Area Severity Index (MASI) score. Group A, B, and C patients were treated with oral TXA 250 mg twice daily, daily MKF cream at night, and daily placebo cream at night, respectively, for 12 weeks. Improvement in MASI score was calculated after 4, 8, and 12 weeks. At each visit, adverse effects, if any, were noted. Statistical analysis was done using Chi-square test. Results: Based on intention to treat analysis, at the end of 12 weeks, the reduction in MASI score in oral TXA, MKF, and placebo groups was 9.94(65.91%), 6.12(54.78%), and 2.07(17.22%), respectively (P = 0.00). The difference in reduction of mean MASI scores after 12 weeks between oral TXA group and MKF group was not significant (P = 0.29). The efficacy of oral TXA and MKB was significantly higher than that of the placebo group (P = 0.01 and P = 0.03, respectively). Adverse effects in all groups were mild and self-limiting. Limitations: A limited sample size, non-blinded design, and absence of dermoscopic evaluation were the study limitations. Conclusion: In view of its excellent safety profile, oral TXA may be considered as a better option for moderate to severe melasma.

Two KaiABC systems control circadian oscillations in one cyanobacterium.

The circadian clock of cyanobacteria, which predicts daily environmental changes, typically includes a standard oscillator consisting of proteins KaiA, KaiB, and KaiC. However, several cyanobacteria have diverse Kai protein homologs of unclear function. In particular, Synechocystis sp. PCC 6803 harbours, in addition to a canonical kaiABC gene cluster (named kaiAB1C1), two further kaiB and kaiC homologs (kaiB2, kaiB3, kaiC2, kaiC3). Here, we identify a chimeric KaiA homolog, named KaiA3, encoded by a gene located upstream of kaiB3. At the N-terminus, KaiA3 is similar to response-regulator receiver domains, whereas its C-terminal domain resembles that of KaiA. Homology analysis shows that a KaiA3-KaiB3-KaiC3 system exists in several cyanobacteria and other bacteria. Using the Synechocystis sp. PCC 6803 homologs, we observe circadian oscillations in KaiC3 phosphorylation in vitro in the presence of KaiA3 and KaiB3. Mutations of kaiA3 affect KaiC3 phosphorylation, leading to growth defects under both mixotrophic and chemoheterotrophic conditions. KaiC1 and KaiC3 exhibit phase-locked free-running phosphorylation rhythms. Deletion of either system (∆kaiAB1C1 or ∆kaiA3B3C3) alters the period of the cellular backscattering rhythm. Furthermore, both oscillators are required to maintain high-amplitude, self-sustained backscatter oscillations with a period of approximately 24 h, indicating their interconnected nature.

Symbiotic and Nonsymbiotic Bacteria Associated With the Entomo-Pathogenic Nematode, Heterorhabditis spp (Rhabditida: Heterorhabditidae) From South India.

Sixteen isolates of bacteria obtained from the entomopathogenic nematode (Heterorhabditis sp.) infected cadavers of Galleria mellonella larvae were identified following phenotypic characterization and molecular analysis of 16S rRNA. Two isolates were identified as the symbiotic bacterium, Photothabdus luminescens, while 14 other isolates were represented by nine species of nonsymbiotic bacteria viz., Stenotrophomonas maltophilia, Alcaligenes aquatilis, Brevundimonas diminuta, Brucella pseudointermedia, Ochrobactrum sp., Brucella pseudogrignonensis, Brucella anthropic, Pseudomonas azatoformans and Pseudomonas lactis. The phylogenetic analysis confirmed the evolutionary relationship between P. luminescens and Pseudomonas spp. The study also found a close relationship among the nonsymbiotic bacteria such as A. aquatilis, B. diminuta, Ochrobactrum sp., and Brucella spp. P. luminescens has been documented for its insecticidal effects against a wide range of insects. The two local isolates obtained in this study may be explored for their biocontrol potential against major pests of the region. Further, the association of nonsymbiotic bacteria with the EPN may be investigated.

Outcome of COVID-19 infection in patients on antihypertensives: A cross-sectional study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) infection frequently have hypertension as a co-morbidity, which is linked to adverse outcomes. Antihypertensives may affect the outcome of COVID-19 infection. AIM: To assess the effects of antihypertensive agents on the outcomes of COVID-19 infection. METHODS: A total of 260 patients were included, and their demographic data and clinical profile were documented. The patients were categorized into nonhypertensive, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), calcium channel blocker (CCB), a combination of ACEI/ARB and CCB, and beta-blocker groups. Biochemical, hematological, and inflammatory markers were measured. The severity of infection, intensive care unit (ICU) intervention, and outcome were recorded. RESULTS: The mean age of patients was approximately 60-years-old in all groups, except the nonhypertensive group. Men were predominant in all groups. Fever was the most common presenting symptom. Acute respiratory distress syndrome was the most common complication, and was mostly found in the CCB group. Critical cases, ICU intervention, and mortality were also higher in the CCB group. Multivariable logistic regression analysis revealed that age, duration of antihypertensive therapy, erythrocyte sedimentation rate, high-sensitivity C-reactive protein, and interleukin 6 were significantly associated with mortality. The duration of antihypertensive therapy exhibited a sensitivity of 70.8% and specificity of 55.7%, with a cut-off value of 4.5 years and an area under the curve of 0.670 (0.574-0.767; 95% confidence interval) for COVID-19 outcome. CONCLUSION: The type of antihypertensive medication has no impact on the clinical sequence or mortality of patients with COVID-19 infection. However, the duration of antihypertensive therapy is associated with poor outcomes.

Molecular Analysis of Classical Swine Fever Virus Associated Field Infections Evidence Novel CSFV Sub Genotype in Tamil Nadu, Southern India.

Classical swine fever (CSF) is an endemic and major viral infection of Indian swine husbandry, contributing to great economic losses with multiple genotypes associated with vast clinical and subclinical outcomes. Molecular detection and genotyping of CSF virus directly from field samples has great application in disease monitoring and control measures hence this study aimed to isolate and characterize CSFV genotypes circulating in southern states of India. Fifty-seven porcine post-mortem tissues (lymph nodes, spleens, livers, lungs, and kidneys) collected from pigs suspected of systemic infections and sudden death with the history of live attenuated CSF vaccination from different regions of Tamil Nadu were used in this study. An NS5B gene based CSFV specific RT-PCR screening confirmed CSFV positivity in 7% (4/57) of samples with a specific amplicon of 449 bp. Further molecular screening for other viral co-infections such as PCV2, PPV and PRRSV done by specific individual PCR assays to all the samples. Non-involvement of above screened three viral pathogens in all four field samples which showed positivity for CSFV confirming CSFV as primary pathogen. Two RT-PCR positive samples (TNI-4 and CHNL-2) selected randomly and sequenced. Aligned contig sequences of both samples were subjected to BLAST homology search and phylogentic characterization. BLAST study of TNI-4 sequence revealed 99% sequence identity with Indian CSFV sequences of genotype 1 and CHNL-2 showed 98% sequence identity with Indian CSFV sequences of genotype 2. Phylogenetic analysis of the TNI-4 and CHNL-2 sequences obtained in this study along with 38 published CSFV sequences consisting of all 5 new genotypes and 14 sub genotypes through the Maximum Likelihood tree method in MEGA 11 revealed that TNI-4 clustering together with 1.7 sub genotypes and CHNL-2 clustering together with 2.2 sub genotypes. TNI-4 and CHNL-2 partial NS5B gene sequences obtained in this study deposited in the GenBank database under accession numbers of MW822568 and MW822569 respectively. The study is the first to report CSF infections associated with the newer 1.7 sub genotype in Tamil Nadu, southern India. It is possible that vaccination could affect the genetic diversity of the CSFV through recombination and point mutations for immune evasion.

Radiation therapy for HPV-Positive oropharyngeal squamous cell carcinoma: an ASTRO clinical practice guideline

Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct disease from other head and neck tumors. This guideline provides evidence-based recommendations on the critical decisions in its curative treatment, including both definitive and postoperative radiation therapy (RT) management. ASTRO convened a task force to address 5 key questions on the use of RT for management of HPV-associated OPSCC. These questions included indications for definitive and postoperative RT and chemoradiation; dose-fractionation regimens and treatment volumes; preferred RT techniques and normal tissue considerations; and posttreatment management decisions. The task force did not address indications for primary surgery versus RT. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. Concurrent cisplatin is recommended for patients receiving definitive RT with T3-4 disease and/or 1 node >3 cm, or multiple nodes. For similar patients who are ineligible for cisplatin, concurrent cetuximab, carboplatin/5-fluorouracil, or taxane-based systemic therapy are conditionally recommended. In the postoperative setting, RT with concurrent cisplatin (either schedule) is recommended for positive surgical margins or extranodal extension. Postoperative RT alone is recommended for pT3-4 disease, >2 nodes, or a single node >3 cm. Observation is conditionally recommended for pT1-2 disease and a single node ≤3 cm without other risk factors. For patients treated with definitive RT with concurrent systemic therapy, 7000 cGy in 33 to 35 fractions is recommended, and for patients receiving postoperative RT without positive surgical margins and extranodal extension, 5600 to 6000 cGy is recommended. For all patients receiving RT, intensity modulated RT over 3-dimensional techniques with reduction in dose to critical organs at risk (including salivary and swallowing structures) is recommended. Reassessment with positron emission tomography-computed tomography is recommended approximately 3 months after definitive RT/chemoradiation, and neck dissection is recommended for convincing evidence of residual disease; for equivocal positron emission tomography-computed tomography findings, either neck dissection or repeat imaging is recommended. The role and practice of RT continues to evolve for HPV-associated OPSCC, and these guidelines inform best clinical practice based on the available evidence.

Short-Term Outcomes of Patients With Hyponatremia Presenting to the Emergency Department: An Observational Study.

BACKGROUND: Hyponatremia is the predominant electrolyte imbalance disorder in the emergency department. It can manifest with a diverse array of symptoms, ranging from non-specific and moderate to severe and even life-threatening. There is a scarcity of literature addressing the clinical characteristics and prognosis of patients with hyponatremia presenting to the emergency department in the western part of Rajasthan. The objective of this study was to investigate the impact of hyponatremia on the outcomes of patients presenting to the emergency department. METHODS: In this prospective, cross-sectional, observational study, 200 patients aged more than 18 years who presented to the emergency department with serum sodium < 135 mEq/l were included. The triage of patients was determined by their primary complaints. The primary outcome was to study the clinical profile of patients with hyponatremia presenting to the emergency department. The secondary outcomes were to examine the etiology, i.e., hypovolemic, euvolemic, or hypervolemic, and the outcome of patients on the 7th day (patient admitted to the ward or intensive care unit) and the 28th day (discharged or death) with hyponatremia presenting to the emergency department. The clinical status of the patients was noted by telephonic follow-up in case they were not admitted for this period. RESULTS: Out of 200 patients, 66 (33%) had hypovolemic, 96 (48%) had euvolemic, and 38 (19%) had hypervolemic hyponatremia. We observed that seizures (84.2%), confusion (56%), and coma (77.7%) were the most common clinical features of patients with severe hyponatremia in the emergency, which was statistically significant than mild and moderate hyponatremia (p = 0.03, 0.023, and 0.029, respectively). On the 7th day of hospitalization, out of 181 (90.5%) admissions in the ward, 116 (64.08%) had severe hyponatremia, and out of 19 (9.5%) ICU admissions, 13 (68.4%) had severe hyponatremia. Death was seen in five (2.5%) patients, one (20%) in moderate and four (80%) in severe hyponatremia cases. CONCLUSION: Most cases of hyponatremia in this study were euvolemic. Most patients experienced severe hyponatremia, and seizures, confusion, and coma were the most prevalent symptoms. These disorders must be recognized early to properly diagnose and treat hyponatremia and prevent its morbidity and death.

Multiple intra-abdominal splenosis with imaging correlative findings: A case report and review of literature.

We present a case of a 31-year-old male who presented to the emergency department with a history of abdominal pain localized to the lower abdomen. The patient had undergone splenectomy 2 years ago for splenic injury following a road traffic accident. Computerized tomography showed multiple well-defined, homogeneously enhancing soft tissue density nodules of varying sizes distributed throughout the abdomen and pelvis. A diagnosis of splenosis was made based on imaging findings and history. Abdominal splenosis is an uncommon entity of which radiologists need to be aware, and this case serves to shed further light on this condition.

Radiation Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma: An ASTRO Clinical Practice Guideline.

PURPOSE: Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct disease from other head and neck tumors. This guideline provides evidence-based recommendations on the critical decisions in its curative treatment, including both definitive and postoperative radiation therapy (RT) management. METHODS: ASTRO convened a task force to address 5 key questions on the use of RT for management of HPV-associated OPSCC. These questions included indications for definitive and postoperative RT and chemoradiation; dose-fractionation regimens and treatment volumes; preferred RT techniques and normal tissue considerations; and posttreatment management decisions. The task force did not address indications for primary surgery versus RT. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: Concurrent cisplatin is recommended for patients receiving definitive RT with T3-4 disease and/or 1 node >3 cm, or multiple nodes. For similar patients who are ineligible for cisplatin, concurrent cetuximab, carboplatin/5-fluorouracil, or taxane-based systemic therapy are conditionally recommended. In the postoperative setting, RT with concurrent cisplatin (either schedule) is recommended for positive surgical margins or extranodal extension. Postoperative RT alone is recommended for pT3-4 disease, >2 nodes, or a single node >3 cm. Observation is conditionally recommended for pT1-2 disease and a single node ≤3 cm without other risk factors. For patients treated with definitive RT with concurrent systemic therapy, 7000 cGy in 33 to 35 fractions is recommended, and for patients receiving postoperative RT without positive surgical margins and extranodal extension, 5600 to 6000 cGy is recommended. For all patients receiving RT, intensity modulated RT over 3-dimensional techniques with reduction in dose to critical organs at risk (including salivary and swallowing structures) is recommended. Reassessment with positron emission tomography-computed tomography is recommended approximately 3 months after definitive RT/chemoradiation, and neck dissection is recommended for convincing evidence of residual disease; for equivocal positron emission tomography-computed tomography findings, either neck dissection or repeat imaging is recommended. CONCLUSIONS: The role and practice of RT continues to evolve for HPV-associated OPSCC, and these guidelines inform best clinical practice based on the available evidence.

Social Determinants of Health Among American Indians and Alaska Natives and Tribal Communities: Comparison with Other Major Racial and Ethnic Groups in the United States, 1990-2022.

Background and Objective: Limited research exists on health inequities between American Indians and Alaska Natives (AIANs), tribal communities, and other population groups in the United States. To address this gap in research, we conducted time-trend analyses of social determinants of health and disease outcomes for AIANs as a whole and specific tribal communities and compared them with those from the other major racial/ethnic groups. Methods: We used data from the 1990-2022 National Vital Statistics System, 2015-2022 American Community Survey, and the 2018-2020 Behavioral Risk Factor Surveillance System to examine socioeconomic, health, disability, disease, and mortality patterns for AIANs. Results: In 2021, life expectancy at birth was 70.6 years for AIANs, lower than that for Asian/Pacific Islanders (APIs) (84.1), Hispanics (78.8), and non-Hispanic Whites (76.3). All racial/ethnic groups experienced a decline in life expectancy between the pre-pandemic year of 2019 and the peak pandemic year of 2021. However, the impact of COVID-19 was the greatest for AIANs and Blacks whose life expectancy decreased by 6.3 and 5.8 years, respectively. The infant mortality rate for AIANs was 8.5 per 1,000 live births, 78% higher than the rate for non-Hispanic Whites. One in five AIANs assessed their physical and mental health as poor, at twice the rate of non-Hispanic Whites or the general population. COVID-19 was the leading cause of death among AIANs in 2021. Risks of mortality from alcohol-related problems, drug overdose, unintentional injuries, and homicide were higher among AIANs than the general population. AIANs had the highest overall disability, mental and ambulatory disability, health uninsurance, unemployment, and poverty rates, with differences in these indicators varying markedly across the AIAN tribes. Conclusion and Global Health Implications: AIANs remain a disadvantaged racial/ethnic group in the US in many health and socioeconomic indicators, with poverty rates in many Native American tribal groups and reservations exceeding 40%.

Effects of Low and High Doses of Aspirin on Inflammatory Markers in Diabesity Patients: A Quasi-Experimental Study.

Introduction The intertwined nature of obesity and diabetes, termed diabesity, is a significant health concern. Aspirin has been recognized for its potential in mitigating inflammation-related health issues, a key concern in managing diabesity. However, the optimal aspirin dosage and its impact on specific inflammatory markers, viz. high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, over time remain a subject of ongoing research. Objective This study investigated the effects of different doses of aspirin (150mg and 300mg) on the levels of hs-CRP and IL-6 over a period of 6 months. Methods This cross-sectional observational quasi-experiment study involved 125 confirmed type-2 diabetes mellitus (T2DM) patients with obesity aged ≥40 years. Blood samples were collected for analyzing hs-CRP and IL-6 levels. Demographics and clinical characteristics, such as BMI, waist-hip ratio, blood parameters, fasting blood sugar (FBS), and hs-CRP, were analyzed. Results At baseline, both the 150 mg and 300 mg aspirin dose groups had similar median levels of hs-CRP. After two months, there was no significant difference (p=0.150). However, by six months, the 150mg dose group had a significantly higher median hs-CRP than the 300 mg dose group (p=0.003). The 150 mg dose group had a significantly higher median level of IL-6 levels at baseline (median; 40.0) compared to the 300 mg dose group (median; 2.27, p<0.0001). After two months, the levels of IL-6 in both groups were similar (median; 2.27 and 2.23 respectively, p<0.0001). By the end of six months, the groups had no significant difference (median; 0.53 and 2.22 respectively, p=0.128). Conclusion The dose of aspirin may significantly impact the levels of hs-CRP and IL-6 over time, with the effects being more pronounced after six months of treatment. These findings suggest that aspirin, a commonly used and cost-effective medication, could potentially be leveraged in a more targeted manner to manage inflammation (CRP and IL-6 levels) in individuals with diabesity.

Assessing the accuracy of pleural puncture sites in patients with pleural effusion as determined by clinical examination versus ultrasound-A single-centre prospective study.

INTRODUCTION: This study aimed to ascertain the accuracy of clinical examination for the determination of pleural puncture sites as compared to the use of ultrasonography in patients with pleural effusion. MATERIAL AND METHODS: A single-centre, prospective, observational study was carried out amongst 115 patients with pleural effusion in a tertiary care hospital in western India. Patients were subjected to clinical assessment for determination of pleural puncture sites and the same were confirmed with ultrasonography. All physicians were blinded to the marking of the previous physician to prevent any influence on their assessment. RESULTS: The study had 345 physician observations. The overall accuracy of the clinical examination was 94.8%. Multivariate logistic regression of the factors responsible for the accuracy of clinical examination demonstrated a significant role of higher body mass index (BMI) (OR-1.19) and lower zone pleural effusions (OR-4.99) when adjusted for age, gender, side of effusion, and experience of examining doctors. When the effusions were classified according to their location, lower zone pleural effusions and loculated pleural effusions had an error rate of 15.9% and 8.33%, respectively. CONCLUSION: An ultrasound is the standard of care to assess all pleural effusions and guide the best point for aspiration.

Endovascular Treatment for Cerebral Venous Sinus Thrombosis: Comparison among Different Endovascular Procedures.

Background: Cerebral venous sinus thrombosis (CVST) is a rare, treatable cause of stroke. Even though CVST has an established medical treatment, 15% of patients remain refractory to treatment. These patients may be candidates for endovascular treatment (EVT), yet the selection of patients remains a challenge. The study aims to understand the profile and outcome of patients treated with EVT and the type of procedure associated with good outcomes. Methods: This is a single-center, retrospective analysis of CVST patients who underwent EVT from 2009 till 2022. Patients who received only medical management were excluded. Modified Rankin Scale (mRS) ≤2 at 3 months was taken as the primary outcome. Secondary outcomes assessed were hospital stay, death, recurrence, mRS ≤ 2 at discharge, and angiographic recanalization. Results: Fifty-two patients were included. Twenty-eight (53.8%) were males; the mean age was 33.3 ± 12.3 years. Headache (n = 44, 84.6%) predominated among the symptoms. The common risk factors were anemia (n = 13, 25.5%) and hyperhomocysteinemia (n = 13, 25.5%). Worsening of sensorium (n = 21, 40.3%) and non-improvement of symptoms (n = 15, 28.8%) were the common indications for the procedure. Twenty-five (48.1%) people underwent in situ thrombolysis (IST). Death occurred in eight (15.3%) patients. Thirty-six (73.5%; 36/49) patients had a good outcome at 3 months. IST had a significantly better outcome (mRS ≤ 2, n = 20, 80%) compared to other procedures (P = 0.04). Hospital stay was lesser in the IST subgroup, but without statistical significance. Midline shift >5 mm (odds ratio [OR] 6.8 [1.5-30.9], P = 0.01) and Glasgow Coma Scale <9 before the procedure (OR 27.2 [3.1-236.4], P = 0.002) predicted bad outcomes at 3 months. Female gender (OR 4.5 [1.07-8.8], P = 0.03), presence of altered sensorium (OR 10.2 [1.2-87.5], P = 0.01), encephalopathic syndrome (P = 0.02), presence of parenchymal bleed (OR 3.7 [0.9-4.5], P = 0.04), and midline shift (OR 4.8 [1.1-20.2], P = 0.03) were associated with poor outcome at discharge. Conclusion: EVT yielded good outcomes in carefully selected, medically refractory patients of CVST. IST performed well compared to other procedures.

Laser power and high-temperature dependent Raman studies of layered bismuth and copper-based oxytellurides for optoelectronic applications.

Layered metal oxychalcogenide materials have gained significant attention in recent years due to their numerous applications in various emerging fields. The bismuth (Bi) based ternary and quaternary oxychalcogenide materials have become popular due to their excellent potential in optoelectronic, thermoelectric, and semiconducting applications. Adding copper (Cu) to these building matrices has enhanced their usefulness in various ways. In this work, Bi and Cu-based ternary and quaternary layered oxytellurides are synthesized using a unique, rarely used "microwave (MW) assisted method," and their temperature and laser power-dependent Raman measurements are carried out. All the samples are prepared at the same MW power and at a fixed irradiation time. Crystallographic studies show that the good crystallinity of the synthesized materials matches well with the phases reported previously. Nanosheet-like morphology was observed for all the prepared samples. The optical properties and band gap energies of these materials were obtained using the diffuse reflectance spectroscopy technique, which are in the range of 1.15-2.52 eV. The photoluminescence spectrum shows broad peaks around orange-red regions, indicating the potential applicability of these materials in various optoelectronic applications. The effect of high temperature and laser power on the Raman spectra of the oxytellurides is demonstrated, where the appearance of different vibrational modes along with a redshift in peak positions with the increase in temperature and power is observed.

Leveraging a Phage-Encoded Noncanonical Amino Acid: A Novel Pathway to Potent and Selective Epigenetic Reader Protein Inhibitors.

Epigenetic reader proteins interpret histone epigenetic marks to regulate gene expression. Given their vital roles and the link between their dysfunction and various diseases, these proteins present compelling targets for therapeutic interventions. Nevertheless, designing selective inhibitors for these proteins poses significant challenges, primarily due to their unique properties such as shallow binding sites and similarities with homologous proteins. To overcome these challenges, we propose an innovative strategy that uses phage display with a genetically encoded noncanonical amino acid (ncAA) containing an epigenetic mark. This ncAA guides binding to the reader protein's active site, allowing the identification of peptide inhibitors with enhanced affinity and selectivity. In this study, we demonstrate this novel approach's effectiveness by identifying potent inhibitors for the ENL YEATS domain that plays a critical role in leukemogenesis. Our strategy involved genetically incorporating Nε-butyryl-l-lysine (BuK), known for its binding to ENL YEATS, into a phage display library for enriching the pool of potent inhibitors. One resultant hit was further optimized by substituting BuK with other pharmacophores to exploit a unique π-π-π stacking interaction with ENL YEATS. This led to the creation of selective ENL YEATS inhibitors with a KD value of 2.0 nM and a selectivity 28 times higher for ENL YEATS than its close homologue AF9 YEATS. One such inhibitor, tENL-S1f, demonstrated robust cellular target engagement and on-target effects to inhibit leukemia cell growth and suppress the expression of ENL target genes. As a pioneering study, this work opens up extensive avenues for the development of potent and selective peptidyl inhibitors for a broad spectrum of epigenetic reader proteins.

A Comparative Analysis of Bacterial Adhesion on Different Long-Term Provisional Fixed Prostheses Fabricated by CAD/CAM Milling, 3D Printing, and Heat Cure Technique: An In Vivo Study.

Objectives: This study compares the bacterial susceptibility to three different provisional restorations manufactured with different laboratory techniques, i.e., heat cure, CAD/CAM, and 3D printing. Materials and Methods: Totally, 45 health patients with age group of 30-60 years undergoing complete veneer crown treatment were selected for the study and divided into three groups with 15 samples in each as Group I: the crowns were made from polymethyl methacrylate polymer fabricated by the conventional heat cure method, Group 2: the crowns were made from polymethyl methacrylate fabricated by subtractive manufacturing CAD/CAM method, and Group 3: the crowns were made from oligomers fabricated by additive manufacturing 3D printing. The samples were examined for bacterial adherence at scanning electron microscope. The colony-forming units (CFUs) were calculated, and statistically analyzed. Results: It has been determined that the digitally fabricated provisional restorations prove to be superior in terms of surface topography than to the conventionally fabricated provisional restorations. Conclusion: The study concludes that 3D-printed provisional restorations are more precise with reduced bacterial susceptibility than milled ones.

Adult Onset Orbital Xanthogranuloma, a Variant of Adult Orbital Xanthogranulomatous Disease: An Infrequent Entity.

Adult orbital xanthogranulomatous diseases (AOXGD) present clinically with symmetrical swellings around the eyes and are collectively considered within the broader group of non-Langerhans cell histiocytosis. A 45-year-old female presented with asymptomatic progressive, skin-colored, thick raised lesions around the eyes of 1 year duration. On dermatological examination, large indurated, lobulated, skin-colored thick plaques were seen bilaterally over infraorbital areas, along with a few hard, discrete nodules over the left infraorbital area. Histopathology showed pan-dermal infiltration with foamy histiocytes, non-lipidized histiocytes, a few multinucleate giant cells, lymphocytes, and a few plasma cells, with immunohistochemistry showing CD68 and S100 positivity. Laboratory and imaging studies did not show any abnormality. Based on the above findings and the absence of internal organ involvement, the patient was diagnosed with adult-onset orbital xanthogranuloma (AOX). The patient was treated with three monthly sessions of intralesional corticosteroid injections, along with methotrexate 12.5 mg per week for 8 weeks, resulting in a moderate reduction in the size of the plaques. The patient is under regular follow-up. The present case highlights the rare case of AOX and the importance of prompt recognition and evaluation in view of its potential hematological and systemic associations.

Reduced expression of chlorophyllide a oxygenase (CAO) decreases the metabolic flux for chlorophyll synthesis and downregulates photosynthesis in tobacco plants.

Chlorophyll b is synthesized from chlorophyllide a, catalyzed by chlorophyllide a oxygenase (CAO). To examine whether reduced chlorophyll b content regulates chlorophyll (Chl) synthesis and photosynthesis, we raised CAO transgenic tobacco plants with antisense CAO expression, which had lower chlorophyll b content and, thus, higher Chl a/b ratio. Further, these plants had (i) lower chlorophyll b and total Chl content, whether they were grown under low or high light; (ii) decreased steady-state levels of chlorophyll biosynthetic intermediates, due, perhaps, to a feedback-controlled reduction in enzyme expressions/activities; (iii) reduced electron transport rates in their intact leaves, and reduced Photosystem (PS) I, PS II and whole chain electron transport activities in their isolated thylakoids; (iv) decreased carbon assimilation in plants grown under low or high light. We suggest that reduced synthesis of chlorophyll b by antisense expression of CAO, acting at the end of Chl biosynthesis pathway, downregulates the chlorophyll b biosynthesis, resulting in decreased Chl b, total chlorophylls and increased Chl a/b. We have previously shown that the controlled up-regulation of chlorophyll b biosynthesis and decreased Chl a/b ratio by over expression of CAO enhance the rates of electron transport and CO2 assimilation in tobacco. Conversely, our data, presented here, demonstrate that-antisense expression of CAO in tobacco, which decreases Chl b biosynthesis and increases Chl a/b ratio, leads to reduced photosynthetic electron transport and carbon assimilation rates, both under low and high light. We conclude that Chl b modulates photosynthesis; its controlled down regulation/ up regulation decreases/ increases light-harvesting, rates of electron transport, and carbon assimilation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01395-5.

Widening Disparities in COVID-19 Mortality and Life Expectancy Among 15 Major Racial and Ethnic Groups in the United States, 2020-2021.

Persistent and often widening racial/ethnic and socioeconomic inequalities in health have long existed in the US. Although racial/ethnic disparities in COVID-19 mortality are well documented, COVID-19 mortality risks and resultant reductions in life expectancy during the pandemic for detailed racial and ethnic groups in the US, including Asian and Hispanic subgroups, are not known. We used 2020-2021 US mortality data to estimate age-adjusted COVID-19 mortality rates, life expectancy, and the consequent declines in life expectancy due to COVID-19 overall and for the 15 largest racial/ethnic groups. We used standard life table methodology, cause-elimination life tables, and inequality indices to analyze trends in racial/ethnic disparities. The number of COVID-19 deaths increased from 350,827 in 2020 to 416,890 in 2021. COVID-19 death rates varied 7-fold among the racial/ethnic groups; Japanese and Chinese had the lowest mortality rates and Mexicans and American Indians/Alaska Natives (AIANs) had the highest rates. In 2021, life expectancy ranged from 70.3 years for Blacks and 70.6 years for AIANs to 85.2 years for Japanese and 87.7 years for Chinese. The life-expectancy gap was wide- 22.4 years in 2020 and 23.2 years in 2021. COVID-19 mortality had the greatest impact in reducing the life expectancy of Mexicans (3.53 years in 2020 and 3.78 years in 2021), Central/South Americans (4.86 years in 2020 and 3.50 years in 2021), and AIANs (2.51 years in 2020 and 2.38 years in 2021). Racial/ethnic inequalities in COVID-19 mortality, life expectancy, and resultant reductions in life expectancy during the pandemic widened between 2020 and 2021.