Staffordlevy1845

with different age of onset differed in the type of trauma experienced prior to the development of PNES. In addition, the younger onset group demonstrated a significantly higher use of avoidance as a stress-coping strategy.

Patients with small intracranial hemorrhage at initial presentation (ICHi) have a relatively uneventful hospital course, as compared with larger ICHi. In this study, we tested the null hypothesis that ICHi does not impact the symptom profile of patients with traumatic brain injury (TBI) after discharge.

In this retrospective study, TBI patients over 18 years of age with a head CT at initial presentation and at least one follow-up visit between 2015 and 2018 were included. Those with vascular risk factors, major psychiatric comorbidities, neurologic disorders, and TBI / CT evidence of ICH within five years were excluded. Patients were stratified based on the presence or absence of ICHi. Symptom profiles were characterized during early (0-3 months post-TBI) and late follow up (4-12 months post-TBI). An adapted 15-question Post-Concussion Symptom Scale and a vestibulo-oculomotor (VOM) exam were assessed by a TBI specialist. We compared the age adjusted clinical symptom profiles between those with and without ICHi.

69 patients met inclusion/exclusion criteria. 26 (37.8%) had ICHi and 43 (62.32%) did not have ICH. The severity of measured symptoms or VOM findings were not more severe in those with ICHi. Age-adjusted analyses did not show any effect on these outcomes.

ICHi does not impact the symptom profile of patients with TBI in either short or long term.

ICHi does not impact the symptom profile of patients with TBI in either short or long term.SARS-CoV-2 testing data in North Carolina during the first three months of the state's COVID-19 pandemic were analyzed to determine if there were disparities among intersecting axes of identity including race, Latinx ethnicity, age, urban-rural residence, and residence in a medically underserved area. Demographic and residential data were used to reconstruct patterns of testing metrics (including tests per capita, positive tests per capita, and test positivity rate which is an indicator of sufficient testing) across race-ethnicity groups and urban-rural populations separately. Selleckchem Reversine Across the entire sample, 13.1% (38,750 of 295,642) of tests were positive. Within racial-ethnic groups, 11.5% of all tests were positive among non-Latinx (NL) Whites, 22.0% for NL Blacks, and 66.5% for people of Latinx ethnicity. The test positivity rate was higher among people living in rural areas across all racial-ethnic groups. These results suggest that in the first three months of the COVID-19 pandemic, access to COVID-19 testing in North Carolina was not evenly distributed across racial-ethnic groups, especially in Latinx, NL Black and other historically marginalized populations, and further disparities existed within these groups by gender, age, urban-rural status, and residence in a medically underserved area.

Akathisia is a neuropsychiatric syndrome that is commonly related to the use of dopamine receptor antagonists/partial agonists. The characteristics of cariprazine-related akathisia, restlessness, and extrapyramidal symptoms (EPS) were investigated in patients with bipolar I depression.

Akathisia-related data from 3 fixed-dose clinical studies of cariprazine 1.5 mg/d and 3 mg/d in bipolar depression were evaluated in pooled post hoc analyses. Outcomes related to treatment-emergent adverse events (TEAEs) included incidence, time to onset, time to resolution, severity, discontinuations, and rescue medication use.

The incidence of akathisia was 7.6% for overall cariprazine (1.5 mg/d=5.5%; 3 mg/d=9.6%) and 2.1% for placebo; acute EPS occurred in 4.5% of cariprazine-treated (1.5 mg/d=3.8%; 3 mg/d=5.1%) and 2.1% of placebo-treated patients. Findings were similar for restlessness. Most TEAEs were mild/moderate (>95%), occurred during the first 3 weeks of cariprazine initiation or dose increase, and resulted in few discontinuations (<3%); median time to resolution of an akathisia or EPS TEAE after the last dose of cariprazine was ~1 week. Rescue medication was used by <3% of patients to manage akathisia/EPS events.

Post hoc analyses; no active comparator.

In patients with bipolar depression, the incidence of cariprazine-related akathisia was higher than acute EPS or restlessness, with lower cariprazine doses associated with lower incidences of events. Akathisia and EPS TEAEs occurred early in treatment and were mild/moderate in severity. Few patients with akathisia or acute EPS discontinued treatment. Cariprazine-related akathisia and EPS can be minimized with conservative dosing and titration strategies.

ClinicalTrials.gov Identifiers NCT01396447, NCT02670538, NCT02670551.

ClinicalTrials.gov Identifiers NCT01396447, NCT02670538, NCT02670551.The search for antibacterial agents for the combat of nosocomial infections is a timely problem, as antibiotic-resistant bacteria continue to thrive. The effect of indoline substituents on the antibacterial properties of aminoalkylphenols was studied, leading to the development of a library of compounds with minimum inhibitory concentrations (MICs) as low as 1.18 μM. Two novel aminoalkylphenols were identified as particularly promising, after MIC and minimum bactericidal concentrations (MBC) determination against a panel of reference strain Gram-positive bacteria, and further confirmed against 40 clinical isolates (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, and Listeria monocytogenes). The same two aminoalkylphenols displayed low toxicity against two in vivo models (Artemia salina brine shrimp and Saccharomyces cerevisiae). The in vitro cytotoxicity evaluation (on human keratinocytes and human embryonic lung fibroblast cell lines) of the same compounds was also carried out. They demonstrated a particularly toxic effect on the fibroblast cell lines, with IC50 in the 1.7-5.1 μM range, thus narrowing their clinical use. The desired increase in the antibacterial properties of the aminoalkylphenols, particularly indoline-derived phenolic Mannich bases, was reached by introducing an additional nitro group in the indolinyl substituent or by the replacement of a methyl by a bioisosteric trifluoromethyl substituent in the benzyl group introduced through use of boronic acids in the Petasis borono-Mannich reaction. Notably, the introduction of an additional nitro moiety did not confer added toxicity to the aminoalkylphenols.Three near-infrared (NIR-I) optical theranostic systems were synthesized, characterized and studied in vitro and in vivo. These original homo-bimetallic gold(I)-based aza-BODIPY complexes proved to be trackable through near-infrared optical imaging in cells and in mice. They display anti-proliferative properties in micromolar range against human and murine cancer cell lines (4T1, MDA-MB-231, CT26, and SW480). Moreover, the injection of the most promising theranostic agent in CT26 tumor-bearing BALB/c mice induced a significant anti-cancer activity.Duchenne muscular dystrophy is a fatal disease with no cure, caused by lack of the cytoskeletal protein dystrophin. Upregulation of utrophin, a dystrophin paralogue, offers a potential therapy independent of mutation type. The failure of first-in-class utrophin modulator ezutromid/SMT C1100 in Phase II clinical trials necessitates development of compounds with better efficacy, physicochemical and ADME properties and/or complementary mechanisms. We have discovered and performed a preliminary optimisation of a novel class of utrophin modulators using an improved phenotypic screen, where reporter expression is derived from the full genomic context of the utrophin promoter. We further demonstrate through target deconvolution studies, including expression analysis and chemical proteomics, that this compound series operates via a novel mechanism of action, distinct from that of ezutromid.Boron-dipyrromethene (BODIPY) based photosensitizers as porphyrinoids and curcumin as natural product possess exciting photophysical features suitable for theranostic applications, namely, imaging and photodynamic therapy (PDT). Limited aqueous solubility and insufficient physiological stability, however, reduce their efficacy significantly. We have designed a novel strategy to deliver these two unusable cytotoxins simultaneously in cancer cells and herein, report the synthesis, characterization and imaging-assisted photocytotoxicity of three zinc(II) complexes containing N3-donor dipicolylamine (dpa) ligands (L1-3) and O,O-donor curcumin (Hcur) viz. [Zn(L1)(cur)]Cl (1), [Zn(L2)(cur)]Cl (2) and [Zn(L3)(cur)]Cl (3), where L2 and L3 have pendant fluorescent BODIPY and non-emissive di-iodo-BODIPY moieties. Metal chelation imparted remarkable biological stability (pH ∼7.4) to the respective ligands and induces significant aqueous solubility. These ternary complexes could act as replacements of the existing metalloporphyrin-based PDT photosensitizers as their visible-light photosensitizing ability is reinforced by the dual presence of blue light absorbing curcumin and green light harvesting BODIPY units. Complex 2 having emissive BODIPY unit L2 and curcumin, showed mitochondria selective localization in HeLa, MCF-7 cancer cells and complex 3, the di-iodinated analogue of complex 2, exhibited type-I/II PDT activity via inducing apoptosis through mitochondrial membrane disruption in cancer cells while being significantly nontoxic in dark and to the healthy cells.We report the development and extensive structure-activity relationship evaluation of a series of modified coumarins as cannabinoid receptor ligands. In radioligand, and [35S]GTPγS binding assays the CB receptor binding affinities and efficacies of the new ligands were determined. Furthermore, we used a ligand-based docking approach to validate the empirical observed results. In conclusion, several crucial structural requirements were identified. The most potent coumarins like 3-butyl-7-(1-butylcyclopentyl)-5-hydroxy-2H-chromen-2-one (36b, Ki CB2 13.7 nM, EC50 18 nM), 7-(1-butylcyclohexyl)-5-hydroxy-3-propyl-2H-chromen-2-one (39b, Ki CB2 6.5 nM, EC50 4.51 nM) showed a CB2 selective agonistic profile with low nanomolar affinities.

Physical and psychological changes in most postmenopausal women tend to lower their quality of life. Various medical/psychological interventions have been applied to improve the postmenopausal quality of life. This study set out to investigate the effect of Mindfulness Based Stress Reduction (MBSR) training on the Menopause-specific quality of life (MENQOL).

This RCT was conducted on 66 postmenopausal women aged 47-62 in Iran. Participants were randomly assigned to either the MBSR or the control group. The menopause--specific quality of life was assessed in two groups via MENQOL questionnaire prior to, immediately and three months after the intervention.

The findings revealed a significant improvements in MENQOL (P<0.001),as well as physical(P=0.001), psychosocial(P=0.001) and sexual(P<0.001)dimensions of the intervention groups compared to the control group, immediately and 3 months after the intervention.

MBSR program can be safely applied to improve menopausal women's quality of life and curb the postmenopausal symptoms.