Monoketonic Curcuminoid Lidocaine Co Deliver Using Thermosensitive Organogels From Drug Synthesis to Epidermis Structural Studies

Organogels ORGs are remarkable matrices due to their versatile chemical composition and straightforward preparation. This study proposes the development of ORGs as dual drug carrier systems, considering the application of synthetic monoketonic curcuminoid m CUR and lidocaine LDC to treat topical inflammatory lesions. The monoketone curcuminoid m CUR was synthesized by using an innovative method via a NbCl5 acid catalysis. ORGs were prepared by associating an aqueous phase composed of Pluronic F127 and LDC hydrochloride with an organic phase comprising isopropyl myristate IPM , soy lecithin LEC , and the synthesized m CUR. Physicochemical characterization was performed to evaluate the influence of the organic phase on the ORGs supramolecular organization, permeation profiles, cytotoxicity, and epidermis structural characteristics. The physico chemical properties of the ORGs were shown to be strongly dependent on the oil phase constitution. Results revealed that the incorporation of LEC and m CUR shifted the sol gel transition temperature, and that the addition of LDC enhanced the rheological G amp; 8242; G amp; 8243; ratio to higher values compared to original ORGs. Consequently, highly structured gels lead to gradual and controlled LDC permeation profiles from the ORG formulations. Porcine ear skin epidermis was treated with ORGs and evaluated by infrared spectroscopy FTIR , where the stratum corneum lipids were shown to transition from a hexagonal to a liquid crystal phase. Quantitative optical coherence tomography OCT analysis revealed that LEC and m CUR additives modify skin structuring. Data from this study pointed ORGs as promising formulations for skin deliver

Cohesin complex-associated holoprosencephaly

Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one of the most common human developmental disorders. Despite decades of phenotype-driven research, 80–90% of aneuploidy-negative holoprosencephaly individuals with a probable genetic aetiology do not have a genetic diagnosis. Here we report holoprosencephaly associated with variants in the two X-linked cohesin complex genes, STAG2 and SMC1A, with loss-of-function variants in 10 individuals and a missense variant in one. Additionally, we report four individuals with variants in the cohesin complex genes that are not X-linked, SMC3 and RAD21. Using whole mount in situ hybridization, we show that STAG2 and SMC1A are expressed in the prosencephalic neural folds during primary neurulation in the mouse, consistent with forebrain morphogenesis and holoprosencephaly pathogenesis. Finally, we found that shRNA knockdown of STAG2 and SMC1A causes aberrant expression of HPE-associated genes ZIC2, GLI2, SMAD3 and FGFR1 in human neural stem cells. These findings show the cohesin complex as an important regulator of median forebrain development and X-linked inheritance patterns in holoprosencephaly

Trauma and amyotrophic lateral sclerosis: A case-control study from a population-based registry

Background and purpose: Published reports on the association between amyotrophic lateral sclerosis (ALS) and trauma are controversial suggesting the need for a new case-control study done in a large population. Methods: A case-control study was undertaken in Italy to assess this association. Cases were patients with newly diagnosed ALS from four population-based registries. For each case, two hospital controls were selected, matched for age, sex, and province of residence, one with a neurological (non-degenerative) disease and one with a non-neurological disease (other than orthopedic or surgical). Traumatic events (defined as accidental events causing injuries requiring medical care) were recorded with details on type, site, timing, severity, and complications. The risks were assessed as odds ratios (ORs) with 95% confidence intervals (CI), crude and adjusted for age, sex, education, interviewee (patient or surrogate), physical activity, smoking, alcohol, and coffee. Results: The study population comprised 377 patients in each of the three groups. One or more traumatic events were reported by 225 cases (59.7%), 191 neurological controls (50.7%), and 179 non-neurological controls (47.5%) (P < 0.01) (OR 1.63; 95% CI 1.25-2.14) (P < 0.01). The ORs were 3.07 (95% CI 1.86-5.05) for patients reporting 3+ traumatic events and 2.44 (95% CI 1.36-4.40) for severe traumatic events. The ORs remained significant when the analysis was limited to events that occurred 5+ and 10+ years before ALS onset, to incident ALS, and direct informant. Conclusion: Antecedent trauma, repeated trauma, and severe trauma may be risk factors for AL

Coffee and amyotrophic lateral sclerosis: A possible preventive role

The relation between coffee intake and risk of amyotrophic lateral sclerosis (ALS) was investigated in 377 newly diagnosed ALS patients from 4 Italian population-based registries in the European ALS Consortium (EURALS Group) (2007-2010). For each patient, 2 age-and sex-matched hospital controls were selected, one from a neurology department and one from a nonneurologic department. Two additional healthy control groups were identified from local general practitioners' (GPs') lists (n = 99) and residents of the same area as a cancer cohort (n = 7,057). Coffee intake was defined in terms of status (ever consuming coffee daily for ≥6 months vs. never), duration, and history (never, former, or current). Ever coffee drinkers comprised 74.7% of ALS patients, 80.4% of neurologic controls, 85.6% of nonneurologic controls (P = 0.0004), 88.9% of GP controls (P = 0.0038), and 86.0% of cancer cohort controls (P < 0.0001). Current coffee drinkers comprised 60.2% of ALS patients, 70.2% of neurologic controls (P = 0.0294), 76.4% of nonneurologic controls (P < 0.0001), and 82.3% of GP controls (P = 0.0002); duration of intake was ≥30 years for 62.3%, 67.7%, 74.7%, and 72.6%. ALS patients had lower lifetime coffee exposure: Odds ratios were 0.7 (95% confidence interval (CI): 0.5, 1.1), 0.6 (95% CI: 0.4, 0.8), and 0.4 (95% CI: 0.2, 0.9) in comparison with neurologic, nonneurologic, and GP controls, respectively. In current (vs. never) coffee drinkers, odds ratios were 0.7 (95% CI: 0.5, 1.0), 0.5 (95% CI: 0.3, 0.7), and 0.4 (95% CI: 0.2, 0.8), respectively. These findings provide epidemiologic evidence of an inverse correlation between coffee intake and ALS risk

The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic.

. High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving &gt;230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. . Starting 04/26/2020, up to 14/07/2021 &gt;151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. . Cross-sectional survey, preponderance of non-representative participants. . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics

Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults.

The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score". The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. From &gt;150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex. COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health

Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Correction to: Nature Genetics https://doi.org/10.1038/s41588-021-00973-1, published online 6 December 2021. In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article