Search

Background: Ultraviolet (UV) radiation from sun, particularly its UVB component (290-320 nm), is considered the major etiological cause of skin cancer that impacts over 2 million lives in the United States alone. Recently, we reported that polydisperse colloidal suspension of silver nanoparticles (AgNPs) protected the human keratinocytes (HaCaT) against UVB-induced damage, thus indicating their potential for prevention of skin carcinogenesis. Here we sought out to investigate if size controlled the chemopreventive efficacy of AgNPs against UVB-induced DNA damage and apoptosis.Methods: Percent cell viability was examined by WST-1 assay after treating the cells with various doses (1-10 μg/mL) of AgNPs of different sizes (10, 20, 40, 60 and 100 nm) for 12 and 24 h. For protection studies, cells were treated with AgNPs of different sizes at a uniform concentration of 1 μg/mL. After 3 h, cells were irradiated with UVB (40 mJ/cm(2)) and dot-blot analysis was performed to detect cyclobutane pyrimidine dimers (CPDs) as an indication of DNA damage. Apoptosis was analyzed by flow cytometry after staining the cells with 7-Amino-Actinomycin (7-AAD) and PE Annexin V. Immunoblot analysis was accomplished by processing the cells for protein extraction and Western blotting using specific antibodies against various proteins.Results: The data show that the pretreatment of HaCaT cells with AgNPs in the size range of 10-40 nm were effective in protecting the skin cells from UVB radiation-induced DNA damage as validated by reduced amounts of CPDs, whereas no protection was observed with AgNPs of larger sizes (60 and 100 nm). Similarly, only smaller size AgNPs (10-40 nm) were effective in protecting the skin cells from UV radiation-induced apoptosis. At the molecular level, UVB -irradiation of HaCaT cells led to marked increase in expression of pro-apoptotic protein (Bax) and decrease in anti-apoptotic proteins (Bcl-2 and Bcl-xL), while it remained largely unaffected in skin cells pretreated with smaller size AgNPs (10-40 nm).Conclusions: Altogether, these findings suggest that size is a critical determinant of the UVB-protective efficacy of AgNPs in human keratinocytes. [ABSTRACT FROM AUTHOR]

We sought to determine the epidemiology and outcomes of Aspergillosis and ABPA in patients with pulmonary CF (pCF) and its outcomes. B CONCLUSIONS: b The incidence of Aspergillosis and ABPA related hospitalizations in pCF patients has been increasing in the United States. B CLINICAL IMPLICATIONS: b Physicians should be aware that nearly one-third of patients with pCF related hospitalizations have Aspergillosis and these patients have worse outcomes. [Extracted from the article]

Patients with primary TP were significantly younger (40.05 + 20.76 years vs 56.01 + 19.89 years, p<0.001), and had lower rates of acute respiratory failure (8.15% vs 21.36%, p<0.001), mechanical ventilation (5.58% vs 11.73%, p<0.001) and inpatient mortality (3.54% vs 5.98%, p<0.001) when compared to secondary TP patients. B CONCLUSIONS: b Patients with primary TP have better outcomes of acute respiratory failure, mechanical ventilation, mortality and lower rates of pleurodesis and thoracoscopy, when compared to patients with secondary TP. Among CLD patients, patients with CF, ILD and Sarcoidosis have higher rates of TP when compared to COPD patients. [Extracted from the article]

Patients with primary SP were significantly younger (35.6 +/- 19.5 years vs 53.6 +/- 21.4 years, p<0.001), lower rates of acute respiratory failure (7.8% vs 22.9%, p<0.001), mechanical ventilation (3.8% vs 10.5%, p<0.001) and inpatient mortality (1.9% vs 5.3%, p<0.001) when compared to secondary SP. Patients with primary SP have better outcomes compared to patients with secondary SP. Patients with SP have higher odds of acute respiratory failure, mechanical ventilation, and inpatient mortality when compared to CLD patients without SP. [Extracted from the article]

Background: There are limited prospective data among overweight and obese individuals on the prevalence of advanced fibrosis, and cirrhosis using advanced MRI-based methods in the USA. The aim of this study was to fill that gap in knowledge by prospectively determining the MRI-based prevalence of steatotic liver disease (SLD) and its subcategories, advanced fibrosis and cirrhosis among overweight and obese individuals residing in the USA., Methods: This is a cross-sectional analysis of prospectively enrolled overweight or obese adults aged 40-75 years from primary care and community-based settings in Southern California. Participants were classified as having SLD if MRI proton density fat fraction ≥5%, and subclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-related liver disease (ALD) consistently with the new nomenclature guidance per AASLD-EASL-ALEH. Advanced fibrosis and cirrhosis were defined as magnetic resonance elastography (MRE) ≥3.63 kPa and MRE ≥4.67 kPa, respectively., Results: The cohort included 539 participants with mean (±SD) age of 51.5 (±13.1) years and body mass index of 32.6 (±6.2) kg/m 2 , respectively. The prevalence of SLD, advanced fibrosis and cirrhosis was 75%, 10.8% and 4.5%, respectively. The prevalence of MASLD, MetALD and ALD was 67.3%, 4.8% and 2.6%, respectively. There was no difference in prevalence of advanced fibrosis and cirrhosis among subcategories., Conclusions: Using advanced MRI methods among community-dwelling overweight and obese adults, the prevalence of cirrhosis was 4.5%. Most common SLD subcategory was MASLD with 67% of individuals, whereas MetALD and ALD were less common. Systematic screening for advanced fibrosis among overweight/obese adults may be considered., Competing Interests: Competing interests: RL serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc, Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics. In addition, his institution received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes and Terns Pharmaceuticals. Cofounder of LipoNexus Inc. CBS reports payment to institution for non-federal research grants from ACR, Bayer, Foundation of NIH, GE, Gilead, Pfizer, Philips, Siemens, V Foundation; payment to institution for lab service agreements from OrsoBio, Enanta, Gilead, ICON, Intercept, Nusirt, Shire, Synageva, Takeda; payment to institution for institutional consulting from BMS, Exact Sciences, IBM-Watson, Pfizer; payment to self for personal consulting from Altimmune, Ascelia Pharma, Blade, Boehringer, Epigenomics, Guerbet, and Livivos; payment to self for royalties and/or honoraria from Medscape and Wolters Kluwer; ownership of stock options in Livivos; unpaid advisory board position in Quantix Bio; executive position for Livivos (Chief Medical Officer, unsalaried position with stock options and stock) through 28 June 2023; Principal Scientific Advisor to Livivos (unsalaried position with stock options and stock) since 28 June 2023; support for attending meetings and/or travel from Fundacion Santa Fe, Congreso Argentino de Diagnóstico por Imágenes, Stanford, Jornada Paulista de Radiologia and Ascelia Pharma; member (no payment) of Data Safety Monitoring board for National Cancer Institute funded Early Detection Research Network; equipment loans to institution from GE and Siemens. BS has been consulting for Ferring Research Institute, HOST Therabiomics, Intercept Pharmaceuticals, Mabwell Therapeutics, Patara Pharmaceuticals, Surrozen and Takeda. B.S.’s institution UC San Diego has received research support from Axial Biotherapeutics, BiomX, ChromoLogic, CymaBay Therapeutics, NGM Biopharmaceuticals, Prodigy Biotech and Synlogic Operating Company. BS is the founder of Nterica Bio. UC San Diego has filed several patents with BS as inventor., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Epidemiologic data suggest an association of obesity with breast cancer (BC); however, obesity's contribution to early onset and risk of diagnosis with specific molecular subtypes by race is uncertain., Objective: To examine the race-specific association of body mass index with early onset and diagnosis of specific molecular subtypes., Design, Setting, and Participants: This retrospective cohort study included patients with BC diagnosed between October 1, 2017, and March 31, 2022, at 3 University of South Alabama Mitchell Cancer Institute clinics. Participants were also prospectively enrolled for serum leptin measurement., Main Outcomes and Measures: The primary outcome was age at BC onset and specific subtype diagnosis. The secondary outcome was race-specific differences. Odds ratios (ORs) for associations of body mass index with age at onset and subtype were estimated using the Fisher exact test. Race was self-reported., Results: Of the 1085 study patients, 332 (30.6%) were Black with a median age of 58 (IQR, 50-66) years, and 753 (69.4%) were White with a median age of 63 (IQR, 53-71) years. A total of 499 patients (46.0%) had obesity, with Black women with obesity receiving more frequent BC diagnosis than their White counterparts (OR, 2.40; 95% CI, 1.87-3.15; P < .001). In addition, Black women had a significantly higher incidence of early-onset disease (OR, 1.95; 95% CI, 1.33-2.86; P = .001) than White women, and obesity increased this risk significantly in Black women (OR, 2.92; 95% CI, 1.35-6.22; P = .006). Black women with obesity also had a significantly higher risk of luminal A BC (OR, 2.53; 95% CI, 1.81-3.56; P < .001) and triple-negative BC (TNBC) (OR, 2.48; 95% CI, 1.43-4.22; P = .002) diagnosis than White counterparts. Black women, with or without BC, had significantly higher serum leptin levels (median [IQR], 55.3 [40.3-66.2] ng/mL and 29.1 [21.1-46.5] ng/mL, respectively, P < .001) than White women (median [IQR], 33.4 [18.9-47.7] ng/mL and 16.5 [10.0-22.9] ng/mL, respectively), which was associated with higher odds of luminal A disease (OR, 5.25; 95% CI, 1.69-14.32, P = .003). Higher odds of early-onset disease (OR, 3.50; 95% CI, 0.43-23.15; P = .33 for trend), and TNBC diagnosis (OR, 6.00; 95% CI, 0.83-37.27; P = .14 for trend) were also seen, although these outcomes were not statistically significant., Conclusions and Relevance: In this cohort study of patients with BC, obesity and high serum leptin levels were associated with an enhanced risk of early-onset BC and diagnosis of luminal A and TNBC subtypes in Black women. These findings should help in developing strategies to narrow the existing disparity gaps.

Prostate cancer incidence and mortality rates are remarkably higher in African-American men as compared to their European-Americans counterparts. Despite these recognitions, precise causes underlying such prevalent racial disparities remain poorly understood. Although socioeconomic factors could account for such differences up to a certain extent, it is now being increasingly realized that such disparity has a molecular basis. Indeed, several differences, including genetic polymorphism, gene mutations, epigenetic modifications, miRNAs alterations, etc . , have been reported in malignant prostate tissues from patients of diverse racial backgrounds. Here, we attempt to provide a molecular perspective on prostate cancer racial disparities by gathering available information on these associated factors and discussing their potential significance in disproportionate incidence and clinical outcomes.

Although known as a major supplier of generic drugs, India has begun to forge new alliances with big US and European pharma companies. Such collaborations are helping to shepherd Indian drug companies into a new era of innovative drug discovery, but regulations governing patents, drug approvals, and clinical trials are still in the process of being updated.