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OBJECTIVES Our aim was to analyze the link between hyperandrogenism and early clinical manifestations of osteoarthritis (OA), knee cartilage thickness, and serum cartilage oligomeric matrix protein (sCOMP) levels in patients with polycystic ovary syndrome (PCOS) and to compare them with healthy volunteers.

Fifty-four PCOS patients who met the Rotterdam criteria with phenotypes A, B, and C were included. They were compared with 26 age- and body mass index (BMI)-matched controls. Detailed anthropometric measurements and clinical evaluation for hyperandrogenism were performed for all participants who also filled in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Furthermore, laboratory tests including sCOMP and hormone quantification were performed in a fasting stage. Finally, an ultrasound assessment was carried out in randomly selected 56 study participants.

PCOS women reported more prominent knee-related symptoms (p = 0.035) and more impaired activities of daily living (ADL) (p = ience knee-related symptoms and impaired ADL. They had greater knee femoral cartilage thickness. Although sCOMP levels did not significantly differ between the groups, lower levels of sCOMP may be inherent to PCOS patients with higher testosterone levels. Key Points • Although PCOS patients may experience more prominent knee related symptoms, their femoral cartilage of the knee joint is found thicker than controls. • PCOS patients did not have significantly elevated levels of sCOMP. • Lower sCOMP levels were related to higher testosterone levels.The present study was conducted to formulate ethosomal thermoreversible in situ gel of apixaban, an anticoagulant drug, for nasal delivery. Ethosomes were formed, of lecithin, cholesterol, and ethanol, by using thin-film hydration method. The prepared ethosomes were characterized by Zetasizer, transmission electron microscope, entrapment efficiency, and in vitro study. The selected ethosomal formula (API-ETHO2) was incorporated in gel using P407 and P188 as thermoreversible agents and carbopol 934 as mucoadhesive agent. Box-Behnken design was used to study the effect of independent variables (concentration of P407, P188, and carbopol 934) on gelation temperature, mucoadhesive strength, and in vitro cumulative percent drug released at 12h (response variables). The optimized formulation was subjected to compatibility study, ex vivo permeation, histopathological examination for the nasal mucosa, and in vivo study. API-ETHO2 was spherical with an average size of 145.1±12.3 nm, zeta potential of -20±4 mV, entrapment efficiency of 67.11%±3.26, and in vitro % release of 79.54%±4.1. All gel formulations exhibited an acceptable pH and drug content. The optimum gel offered 32.3°C, 1226.3 dyne/cm2, and 53.50% for gelation temperature, mucoadhesive strength, and in vitro percent released, respectively. Apixaban ethosomal in situ gel evolved higher ex vivo permeation (1.499±0.11 μg/cm2h) through the nasal mucosa than pure apixaban gel. Histopathological study assured that there is no necrosis or tearing of the nasal mucosa happened by ethosomal gel. The pharmacokinetic parameters in rabbit plasma showed that intranasal administration of optimized API-ethosomal in situ gel achieved higher Cmax and AUC0-∞ than unprocessed API nasal gel, nasal suspension, and oral suspension. The ethosomal thermoreversible nasal gel established its potential to improve nasal permeation and prolong anticoagulant effect of apixaban.We built upon a recent study by Rodrigues, Fasoli, Huic, and Lopes (2018) by investigating potential mechanisms driving the dehumanization of consensual non-monogamous (CNM) partners. Using a between-subjects experimental design, we asked 202 Portuguese individuals (158 women; Mage = 29.17, SD = 9.97) to read the description of two partners in a monogamous, open, or polyamorous relationship, and to make a series of judgments about both partners. Results showed the expected dehumanization effect, such that both groups of CNM partners (open and polyamorous) were attributed more primary (vs. secondary) emotions, whereas the reverse was true for monogamous partners. Moreover, results showed that the dehumanization effect was driven by the perception of CNM partners as less moral and less committed to their relationship. However, these findings were observed only for individuals with unfavorable (vs. favorable) attitudes toward CNM relationship. Overall, this study replicated the original findings and extended our understanding of why people in CNM relationships are stigmatized.On January 28 in Nature online, Zheng et al. (Nature, 2021 (Online ahead of print)) reported that they developed an ingenious method of interspecies PSC co-culture system in vitro which unfolded interspecific cell competition. This study paves the way for discovering the mechanism of interspecific chimera and for further interspecific organogenesis between evolutionarily distant species.

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal-dominant disorder with high penetrance characterized by progressive cognitive and motor dysfunction. selleck chemical The objective of the study was to describe a new variant of the colony stimulating factor-1 receptor (CSF1R) gene causing HDLS in a Chinese family.

Physical examinations, laboratory tests, structural neuroimaging studies, and whole-exome sequence analysis were carried out.

Three patients in this family exhibited typical manifestations of HDLS, including progressive cognitive impairment, language and motor dysfunctions, and urinary and bowel incontinence. Genetic analysis identified a heterozygous missense mutation (c.2264T>C, p.L755P) in exon 17 of the CSF1R gene that cosegregated with the HDLS phenotype in an autosomal-dominant pattern. Brain MRI of the proband and her father showed diffuse white matter changes. The proband’s 10-year-old son, a gene carrier, remains clinically asymptomatic at present.

Our findings identify a novel missense mutation, p.L755P, in the CSF1R gene within a Chinese family with autosomal-dominant HDLS and broaden the genetic spectrum of CSF1R-associated HDLS.

Our findings identify a novel missense mutation, p.L755P, in the CSF1R gene within a Chinese family with autosomal-dominant HDLS and broaden the genetic spectrum of CSF1R-associated HDLS.