N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson\u27s Disease: Preliminary Clinical and Cell Line Data.

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson\u27s disease (PD). METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult with the neurotoxin rotenone. In the clinical study, patients continued their standard of care and were randomized to receive either daily NAC or were a waitlist control. Patients were evaluated before and after 3 months of receiving the NAC with DaTscan to measure dopamine transporter (DAT) binding and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) to measure clinical symptoms. RESULTS: The cell line study showed that NAC exposure resulted in significantly more mDA neurons surviving after exposure to rotenone compared to no NAC, consistent with the protective effects of NAC previously observed. The clinical study showed significantly increased DAT binding in the caudate and putamen (mean increase ranging from 4.4% to 7.8%; p CONCLUSIONS: The results of this preliminary study demonstrate for the first time a potential direct effect of NAC on the dopamine system in PD patients, and this observation may be associated with positive clinical effects. A large-scale clinical trial to test the therapeutic efficacy of NAC in this population and to better elucidate the mechanism of action is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02445651

Estudo comparativo dos efeitos do extrato de Ginkgo biloba L. e Panax ginseng C.A. Meyer na reprodução de ratos machos e fêmeas Wistar

Ginkgo biloba e Panax ginseng são plantas utilizadas na medicina tradicional. O objetivo do estudo foi avaliar a histologia gonadal de ratos machos e fêmeas Wistar submetidos aos tratamentos com o extrato de G. biloba (120 mg kg-1) ou P. ginseng (200 mg kg-1), e avaliar os parâmetros reprodutivos e fetais das ratas tratadas com as plantas. O grupo controle recebeu solução fisiológica 0,9%. Os tratamentos foram efetuados por via oral através de gavage, duas vezes ao dia, durante quinze dias consecutivos. Após este período, machos (n=18) e fêmeas (n=18) foram sacrificados e as gônadas coletadas, pesadas e processadas para avaliação microscópica. Outras fêmeas (n=18) foram acasaladas com machos não tratados para avaliação da fertilidade e produtos da gestação. Os resultados indicaram que o peso dos órgãos reprodutivos masculino e feminino não foi afetado pelos tratamentos. A estrutura gonadal dos machos e fêmeas mostrou o mesmo padrão histológico nos três grupos experimentais. O tratamento materno pré-gestacional com os extratos não promoveu alterações no desempenho reprodutivo das matrizes e nos parâmetros fetais. Concluiu-se que o extrato de P. ginseng ou G. biloba não causou toxicidade reprodutiva em ratos machos e fêmeas.Ginkgo biloba and Panax ginseng are plants used in the traditional medicine. The aim of study was to analyse the gonadal histology of the Wistar male and female rats submitted to the treatments with extract of G. biloba (120 mg kg-1) or P. ginseng (200 mg kg-1), and to evaluate the reproductive and fetal parameters of female rats treated with the plants. The control group received physiological solution 0.9%. The treatments were administered by oral gavage, twice/day, during fifteen consecutive days. After this period, male (n=18) and female rats (n=18) were sacrificed and the gonads collected, weighed and processed for microscopic evaluation. Another females (n=18) were matted with not treated males for evaluation of fertility and pregnancy outcome. The results indicated that the male and feminine reproductive organs weight was not affected by treatments. The gonadal structure of male and female rats showed same histologic pattern in the three experimental groups. The pre-gestational treatment with the extracts not promoted alterations in the reproductive performance of dams and in the fetal parameters. It was concluded that the extract of P. ginseng or G. biloba not presented reproductive toxicity in the male and female rats

Maternal metabolic health conditions and risk of stillbirth in India: evidence from a nationwide survey

Background: Stillbirth, defined by foetal death at or beyond 28 weeks of gestation, represents a significant challenge in India, contributing to approximately 500,000 foetal deaths each year. The country’s stillbirth rate of 12.2 per 1000 births underscores the imperative to address this preventable occurrence. While maternal metabolic conditions diabetes, and hypertension, are widely recognized as established risk factors for stillbirth worldwide, the extent of their impact on India’s stillbirth burden remains inadequately elucidated due to limited evidence. Methods: This cross-sectional study utilized NFHS-5 data to examine stillbirths in the most recent pregnancy outcomes of 204,723 women aged 15–49 years, sampled from all states and union territories of India. The primary exposures assessed were diabetes, and hypertension. Descriptive analyses were conducted to determine the prevalence of diabetes, hypertension and stillbirths. Logistic regression was used to quantify the association between diabetes, hypertension and the risk of stillbirth, indicated by adjusted odds ratios (AOR) with 95% confidence intervals (CI). The study also assessed effect modification by maternal age, education, wealth quintile, and social category. Results: The prevalence of diabetes and hypertension was 1% and 3% respectively, while the stillbirth rate was 1%. diabetes conferred a significantly higher risk of stillbirth with an increase of 74% (AOR 1.74, CI 1.14–2.67) as compared to women without diabetes. The risk was potential among mothers with hypertension with an increase of 50% (AOR 1.50, CI 1.16–1.95) on contrary to women without hypertension. The combined model (i.e. having diabetes or hypertension) also showed a significant risk of stillbirth with a higher risk of 58% (AOR 1.58, CI 1.25–1.99) indicating a synergistic interaction. Stratified analyses revealed the stillbirth risk among mothers belonging to the scheduled caste category (AOR 1.30, CI 1.10–1.53). Conclusion: Diabetes, and hypertension, increase stillbirth risk in India, highlighting the need for better metabolic health management pre- and during pregnancy. Our research highlights the need of integrated care for diabetes and hypertension is crucial. Targeted interventions for high-risk mothers and improved screening are vital to reduce stillbirth rates. More research is needed to understand these risks better. Collaboration across medical fields is essential to save lives and improve pregnancy outcomes

Race May Not Impact Endocrine Therapy–Related Changes in Breast Density

Abstract Background: Reduction in breast density may be a biomarker of endocrine therapy (ET) efficacy. Our objective was to assess the impact of race on ET-related changes in volumetric breast density (VBD). Methods: This retrospective cohort study assessed longitudinal changes in VBD measures in women with estrogen receptor–positive invasive breast cancer treated with ET. VBD, the ratio of fibroglandular volume (FGV) to breast volume (BV), was measured using Volpara software. Changes in measurements were evaluated using a multivariable linear mixed effects model. Results: Compared with white women (n = 191), black women (n = 107) had higher rates of obesity [mean ± SD body mass index (BMI) 34.5 ± 9.1 kg/m2 vs. 30.6 ± 7.0 kg/m2, P &amp;lt; 0.001] and premenopausal status (32.7% vs. 16.7%, P = 0.002). Age- and BMI-adjusted baseline FGV, BV, and VBD were similar between groups. Modeled longitudinal changes were also similar: During a follow-up of 30.7 ± 15.0 months (mean ± SD), FGV decreased over time in premenopausal women (slope = −0.323 cm3; SE = 0.093; P = 0.001), BV increased overall (slope = 2.475 cm3; SE = 0.483; P &amp;lt; 0.0001), and VBD decreased (premenopausal slope = −0.063%, SE = 0.011; postmenopausal slope = −0.016%, SE = 0.004; P &amp;lt; 0.0001). Race was not significantly associated with these longitudinal changes, nor did race modify the effect of time on these changes. Higher BMI was associated with lower baseline VBD (P &amp;lt; 0.0001). Among premenopausal women, VBD declined more steeply for women with lower BMI (time × BMI, P = 0.0098). Conclusions: Race does not appear to impact ET-related longitudinal changes in VBD. Impact: Racial disparities in estrogen receptor–positive breast cancer recurrence and mortality may not be explained by differential declines in breast density due to ET. </jats:sec

Conditional Deletion of the Mouse Klf4 Gene Results in Corneal Epithelial Fragility, Stromal Edema, and Loss of Conjunctival Goblet Cells

The Krüppel-like transcription factor KLF4 is among the most highly expressed transcription factors in the mouse cornea (B. Norman, J. Davis, and J. Piatigorsky, Investig. Ophthalmol. Vis. Sci. 45:429-440, 2004). Here, we deleted the Klf4 gene selectively in the surface ectoderm-derived structures of the eye (cornea, conjunctiva, eyelids, and lens) by mating Klf4-LoxP mice (J. P. Katz, N. Perreault, B. G. Goldstein, C. S. Lee, P. A. Labosky, V. W. Yang, and K. H. Kaestner, Development 129:2619-2628, 2002) with Le-Cre mice (R. Ashery-Padan, T. Marquardt, X. Zhou, and P. Gruss, Genes Dev. 14:2701-2711, 2000). Klf4 conditional null (Klf4CN) embryos developed normally, and the adult mice were viable and fertile. Unlike the wild type, the Klf4CN cornea consisted of three to four epithelial cell layers; swollen, vacuolated basal epithelial and endothelial cells; and edematous stroma. The conjunctiva lacked goblet cells, and the anterior cortical lens was vacuolated in Klf4CN mice. Excessive cell sloughing resulted in fewer epithelial cell layers in spite of increased cell proliferation at the Klf4CN ocular surface. Expression of the keratin-12 and aquaporin-5 genes was downregulated, consistent with the Klf4CN corneal epithelial fragility and stromal edema, respectively. These observations provide new insights into the role of KLF4 in postnatal maturation and maintenance of the ocular surface and suggest that the Klf4CN mouse is a useful model for investigating ocular surface pathologies such as dry eye, Meesmann's dystrophy, and Steven's-Johnson syndrome