Sleep Quality, and Fatigue As Predictive Factors For Mechanical Neck Pain

Aims: The purpose of our study was to investigate the relationship between mechanical neck pain and sleep disorders, mental and physical fatigue, and the rising expectations of people in modern societies regarding their work, families, and social lives. Mechanical neck pain is a common problem that can result in disability. Methods: We included 230 patients with mechanical neck discomfort, with a mean age of 25.62 ± 9.25years, in our study. The Neck Disability Index, Chalder Fatigue Scale, and Pitssburg Sleep Quality Index was applied to all participant.   Results: Multiple linear regression analysis revealed that the overall model explained 22% of the variance of NDI score. Both sleep quality scale and fatigue scale were significantly associated and can predict NDI score (p < 001). Conclusion: sleep quality and fatigue were found among the independent determinants of neck disability. Therefore, physiotherapists who treat patients with mechanical neck pain should advise them to get enough sleep and teach them relaxation techniques to help them feel less stressed and exhausted, which will lower their neck discomfor

Repurposing celecoxib for colorectal cancer targeting via pH-triggered ultra-elastic nanovesicles: Pronounced efficacy through up-regulation of Wnt/β-catenin pathway in DMH-induced tumorigenesis

Celecoxib (CLX), a selective inhibitor for cyclooxygenase 2 (COX-2), has manifested potential activity against diverse types of cancer. However, low bioavailability and cardiovascular side effects remain the major challenges that limit its exploitation. In this work, we developed ultra-elastic nanovesicles (UENVs) with pH-triggered surface charge reversal traits that could efficiently deliver CLX to colorectal segments for snowballed tumor targeting. CLX-UENVs were fabricated via a thin-film hydration approach. The impact of formulation factors (Span 80, Tween 80, and sonication time) on the nanovesicular features was evaluated using Box–Behnken design, and the optimal formulation was computed. The optimum formulation was positively coated with polyethyleneimine (CLX-PEI-UENVs) and then coated with Eudragit S100 (CLX-ES-PEI-UENVs). The activity of the optimized nano-cargo was explored in 1,2-dimethylhydrazine-induced colorectal cancer in Wistar rats. Levels of COX-2, Wnt-2 and β-catenin were assessed in rats' colon. The diameter of the optimized CLX-ES-PEI-UENVs formulation was 253.62 nm, with a zeta potential of −23.24 mV, 85.64% entrapment, and 87.20% cumulative release (24 h). ES coating hindered the rapid release of CLX under acidic milieu (stomach and early small intestine) and showed extended release in the colon section. In colonic environments, the ES coating layer was removed due to high pH, and the charge on the nanovesicular corona was shifted from negative to positive. Besides, a pharmacokinetics study revealed that CLX-ES-PEI-UENVs had superior oral bioavailability by 2.13-fold compared with CLX suspension. Collectively, these findings implied that CLX-ES-PEI-UENVs could be a promising colorectal-targeted nanoplatform for effective tumor management through up-regulation of the Wnt/β-catenin pathway

The Predictive Value of Circulating Anti-Müllerian Hormone in Women With Polycystic Ovarian Syndrome Receiving Clomiphene Citrate: A Prospective Observational Study

CONTEXT:Elevated serum anti-Müllerian hormone (AMH) concentration in women with polycystic ovarian syndrome (PCOS) is known to lower sensitivity of ovarian follicles to circulating FSH. This effect may compromise the outcome of clomiphene citrate (CC) ovulation induction.OBJECTIVE:The objective of the study was to investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS.DESIGN:This was a prospective cohort observational study.SETTING:The study was conducted at the Fertility Unit, Derby, United Kingdom.PATIENTS:Sixty anovulatory women with PCOS participated in the study.INTERVENTIONS:Serum AMH concentrations were measured on cycle day 2 during 187 CC cycles. These concentrations were compared between responders and nonresponders. The receiver-operating characteristic curve was used to evaluate the prognostic value of circulating AMH. The success rates of CC were compared between patients with high vs low AMH levels. The dose of CC required to achieve ovulation was correlated with serum AMH concentrations.MAIN OUTCOME MEASURES:Ovulation and pregnancy rates were measured.RESULTS:Serum AMH concentrations were significantly (P < .001) lower in responders (achieving ovulation) vs nonresponders (mean ± SEM, 2.5 ± 0.1 vs 5.8 ± 0.7 ng/mL, respectively). Similarly, serum AMH concentrations were significantly (P = .046) lower in pregnant (3.0 ± 0.4 ng/mL) vs nonpregnant patients (4.4 ± 0.5 ng/mL). There was a significant (P = .02) gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation. The receiver-operating characteristic curve showed AMH to be a useful predictor of no ovulation (area under the curve, 0.809; P < .001) with a useful cutoff level of 3.4 ng/mL. Ovulation and pregnancy rates were significantly higher (97%, P < .001, and 46%, P = .034) in patients with low AMH (less than 3.4 ng/mL) vs women with AMH 3.4 ng/mL or greater (48% and 19%).CONCLUSION:PCOS women with high circulating AMH (≥3.4 ng/mL) seem to be resistant to CC and may require a higher starting dose