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Monascus purpureus, a filamentous fungus known for its fermentation of red yeast rice, produces the metabolite monacolin K used in statin drugs to inhibit cholesterol biosynthesis. In this study, we show that active cultures of M. purpureus CBS 109.07, independent of secondary metabolites, use the mechanism of cholesterol assimilation to lower cholesterol in vitro. We describe collection, extraction, and gas chromatography-flame ionized detection (GC-FID) methods to quantify the levels of cholesterol remaining after incubation of M. purpureus CBS 109.07 with exogenous cholesterol. Our findings demonstrate that active growing M. purpureus CBS 109.07 can assimilate cholesterol, removing 36.38% of cholesterol after 48 h of incubation at 37 °C. The removal of cholesterol by resting or dead M. purpureus CBS 109.07 was not significant, with cholesterol reduction ranging from 2.75–9.27% throughout a 72 h incubation. Cholesterol was also not shown to be catabolized as a carbon source. Resting cultures transferred from buffer to growth media were able to reactivate, and increases in cholesterol assimilation and growth were observed. In growing and resting phases at 24 and 72 h, the production of the mycotoxin citrinin was quantified via high-performance liquid chromatography-ultraviolet (HPLC-UV) and found to be below the limit of detection. The results indicate that M. purpureus CBS 109.07 can reduce cholesterol content in vitro and may have a potential application in probiotics.

To evaluate the efficacy of a femtosecond laser assisted astigmatic keratotomy (AK) nomogram (FemtoAK.com) for correction of astigmatism during cataract surgery. Consecutive patients underwent cataract extraction with AKs and insertion of a non-toric intraocular lens. Eyes with greater than 0.5 D of against-the-rule (ATR) or 1.0 D of with-the-rule (WTR) or oblique (OBL) astigmatism were treated in accordance with the nomogram. Optical biometry and manifest refraction were checked pre- and one-month post-operatively. Outcome measures included correction index (CI), index of success (IOS), and proportion of eyes with less than 0.5 and 1.0 D of astigmatism. Ninety-five eyes from 69 patients were included, of which 41 had ATR, 35 had WTR, and 19 had OBL astigmatism. Corneal CI (ATR = 0.86, WTR = 0.27) indicated a small and large under-correction of ATR and WTR astigmatism, respectively, while refractive CI revealed a near-ideal correction of WTR (ATR = 0.87, WTR = 1.02). The proportion of eyes with less than 0.5 and 1.0 D of refractive astigmatism increased from 28% and 54% pre-operatively to 56% and 92% post-operatively, respectively. The FemtoAK nomogram is effective at reducing corneal astigmatism at the time of cataract surgery. Astigmatic correction was more precise when evaluated by refractive rather than corneal measures.

People admitted to a hospital rehabilitation unit experience high communicative demands. Rarely, however, is an audiological evaluation performed as part of the multidisciplinary assessment of the person. This report will describe the admission diagnosis, overall hearing loss, degree of hearing loss by age, self-perceived hearing handicap, and use of hearing aids for 324 people admitted to an intensive rehabilitation program over a 3-year period. Results highlight the importance of incorporating audiological testing in a comprehensive rehabilitation assessment.

The Times and Jerry Cohen are to be highly commended for the in-depth study \"Racial Tension in Shadow Hills\" (Jan. 3). This situation has never before been presented objectively.

Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

The lung tumor microenvironment plays a critical role in the tumorigenesis and metastasis of lung cancer, resulting from the crosstalk between cancer cells and microenvironmental cells. Therefore, comprehensive identification and characterization of cell populations in the complex lung structure is crucial for development of novel targeted anti-cancer therapies. Here, a hierarchical clustering approach with multispectral flow cytometry was established to delineate the cellular landscape of murine lungs under steady-state and cancer conditions. Fluorochromes were used multiple times to be able to measure 24 cell surface markers with only 13 detectors, yielding a broad picture for whole-lung phenotyping. Primary and metastatic murine lung tumor models were included to detect major cell populations in the lung, and to identify alterations to the distribution patterns in these models. In the primary tumor models, major altered populations included CD324 + epithelial cells, alveolar macrophages, dendritic cells, and blood and lymph endothelial cells. The number of fibroblasts, vascular smooth muscle cells, monocytes (Ly6C + and Ly6C – ) and neutrophils were elevated in metastatic models of lung cancer. Thus, the proposed clustering approach is a promising method to resolve cell populations from complex organs in detail even with basic flow cytometers.

The fovea is a depression in the center of the macula and is the site of the highest visual acuity. Optical coherence tomography (OCT) has contributed considerably in elucidating the pathologic changes in the fovea and is now being considered as an accompanying imaging method in drug development, such as antivascular endothelial growth factor and its safety profiling. Because animal numbers are limited in preclinical studies and automatized image evaluation tools have not yet been routinely employed, essential reference data describing the morphologic variations in macular thickness in laboratory cynomolgus monkeys are sparse to nonexistent. A hybrid machine learning algorithm was applied for automated OCT image processing and measurements of central retina thickness and surface area values. Morphological variations and the effects of sex and geographical origin were determined. Based on our findings, the fovea parameters are specific to the geographic origin. Despite morphological similarities among cynomolgus monkeys, considerable variations in the foveolar contour, even within the same species but from different geographic origins, were found. The results of the reference database show that not only the entire retinal thickness, but also the macular subfields, should be considered when designing preclinical studies and in the interpretation of foveal data.

Introduction: Kidney stone disease has a high prevalence worldwide of approximately 10 % of the population and is characterized by a high recurrence rate Kidney stone disease results from a combination of genetic, environmental, and life-style risk factors, and the dissection of these factors is complex. Methods: The Swiss Kidney Stone Cohort (SKSC) is an investigator-initiated prospective, multi-centric longitudinal, observational study in patients with kidney stones followed with regular visits over a period of 3 years after inclusion. Ongoing follow-ups by biannual telephone interviews will provide long-term outcome data up to 10 years. Results: SKSC comprises 782 adult patients (age > 18 yrs) with either recurrent stones or a single stone event with at least one risk factor for recurrence. In addition, a control cohort of 207 individuals without kidney stone history and absence of kidney stones on a low-dose CT-scan at enrolment has also been recruited. SKSC includes extensive collections of clinical data, biochemical data in blood and 24 hr urine samples, and genetic data. Biosamples are stored at a dedicated biobank. Information on diet and dietary habits were collected through food frequency questionnaires and standardized recall interviews by trained dieticians with the Globodiet software. Conclusion: SKSC provides an unique opportunity and resource to further study cause and course of kidney disease in a large population with data and samples collected of a homogenous collective of patients throughout the whole Swiss population.

Marijuana use is common in persons with HIV, but there is limited evidence of its relationship with potential health benefits or harms. The Marijuana Associated Planning and Long-term Effects (MAPLE) study was designed to evaluate the impact of marijuana use on HIV-related health outcomes, cognitive function, and systemic inflammation. The MAPLE study is a longitudinal cohort study of participants living with HIV who were recruited from 3 locations in Florida and were either current marijuana users or never regular marijuana users. At enrollment, participants completed questionnaires that included detailed marijuana use assessments, underwent interviewer-administered neurocognitive assessments, and provided blood and urine samples. Ongoing follow-ups included brief telephone assessments (every 3 months), detailed questionnaires (annually), repeated blood and urine samples (2 years), and linkage to medical records and statewide HIV surveillance data. Supplemental measures related to intracellular RNA, COVID-19, Alzheimer disease, and the gut microbiome were added after study initiation. The MAPLE study completed enrollment of 333 persons between 2018 and 2021. The majority of participants in the sample were ≥50 years of age (200/333, 60.1%), male (181/333, 54.4%), cisgender men (173/329, 52.6%), non-Hispanic Black (221/333, 66.4%), and self-reported marijuana users (260/333, 78.1%). Participant follow-up was completed in 2022, with annual updates to HIV surveillance data through at least 2027. The MAPLE study is the largest cohort specifically designed to understand the use of marijuana and its effects on HIV-related outcomes. The study population has significant diversity across age, sex, gender, and race. The data will help clinicians and public health officials to better understand patterns of marijuana use associated with both positive and negative health outcomes, and may inform recommendations for future clinical trials related to medical marijuana and HIV. DERR1-10.2196/37153.