Patient-Derived Induced Pluripotent Stem Cells and Organoids for Modeling Alpha Synuclein Propagation in Parkinson's Disease

Parkinson's disease (PD) is an age-associated, progressive neurodegenerative disorder characterized by motor impairment and in some cases cognitive decline. Central to the disease pathogenesis of PD is a small, presynaptic neuronal protein known as alpha synuclein (a-syn), which tends to accumulate and aggregate in PD brains as Lewy bodies or Lewy neurites. Numerous in vitro and in vivo studies confirm that a-syn aggregates can be propagated from diseased to healthy cells, and it has been suggested that preventing the spread of pathogenic a-syn species can slow PD progression. In this review, we summarize the works of recent literature elucidating mechanisms of a-syn propagation, and discussed the advantages in using patient-derived induced pluripotent stem cells (iPSCs) and/or induced neurons to study a-syn transmission

Auricular acupuncture treatment for insomnia: A systematic review

Objectives: To review trials on the efficacy and safety of auricular acupuncture (AA) treatment for insomnia and to identify the most commonly used auricular acupoints for treating insomnia in the studies via a frequency analysis. Data sources: The international electronic databases searched included: (1) AMED; (2) the Cochrane library; (3) CINAHL; (4) EMBASE; and (5) MEDLINE.® Chinese electronic databases searched included: (1) VIP Information; (2) CBMdisc; and (3) CNKI. Study selection: Any randomized controlled trials using AA as an intervention without using any co-interventions for insomnia were included. Studies using AA versus no treatment, placebo, sham AA, or Western medicine were included. Data extraction: Two (2) independent reviewers were responsible for data extraction and assessment. The efficacy of AA was estimated by the relative risk (RR) using a meta-analysis. Results: Eight hundred and seventy eight (878) papers were searched. Six (6) trials (402 treated with AA among 673 participants) that met the inclusion criteria were retrieved. A meta-analysis showed that AA was chosen with a higher priority among the treatment subjects than among the controls (p < 0.05). The recovery and improvement rates produced by AA was significantly higher than those of diazepam (p < 0.05). The rate of success was higher when AA was used for enhancement of sleeping hours up to 6 hours in treatment subjects (p < 0.05). The efficacy of using Semen vaccariae ear seeds was better than that of the controls (p < 0.01); while magnetic pearls did not show statistical significance (p = 0.28). Six (6) commonly used auricular acupoints were Shenmen (100%), Heart (83.33%), Occiput (66.67%), Subcortex (50%), Brain and Kidney (each 33.33%, respectively). Conclusions: AA appears to be effective for treating insomnia. Because the trials were low quality, further clinical trials with higher design quality, longer duration of treatment, and longer follow-up should be conducted. © Mary Ann Liebert, Inc.published_or_final_versio

(S)-2-(1-Methyl­indolin-2-yl)-1,3-diphenyl­propan-2-ol

The five-membered ring in the the title mol­ecule, C24H25NO, fused with the phenyl­ene ring, is almost planar (r.m.s. deviation = 0.023 Å), with the methyl­ene C atom deviating most from this mean plane [0.031 (1) Å]. The tertiary N atom shows a flattened pyramidal configuration [Σ(angles at N) = 350.3 (6)°]

Statin use and mortality risk in Asian patients with prostate cancer receiving androgen deprivation therapy: A population-based cohort study

Background This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). Methods Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow-up conducted until September 2021. Patients who had received medical castration for <180 days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180 days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180 days concurrent with ADT, while non-users were those who had not used any statins. PCa-related mortality was the primary outcome, while all-cause mortality served as the secondary outcome. Inverse probability treatment weighting was employed to balance the covariates. Results A total of 4920 patients were included, consisting of 2578 statin users and 2342 non-users (mean age 76.1 ± 8.2 years). Over a mean follow-up period of 4.2 ± 3.3 years, it was observed that statin users had significantly lower risks of both PCa-related mortality (weighted hazard ratio [wHR] 0.56 [95% confidence interval (CI) 0.48, 0.65], p < 0.001) and all-cause mortality (wHR 0.57 [95% CI 0.51, 0.63], p < 0.001), regardless of the type of ADT used. Notably, these associations were more pronounced among patients with less advanced PCa, as indicated by the absence of androgen receptor antagonist or chemotherapy usage (p value for interaction <0.001 for both outcomes). Conclusion(s) The use of statins concurrent with ADT was associated with reduced mortality risks among Asian patients with PCa. These findings suggest the need for additional research to explore the potential role of statins in the treatment of PCa patients

Metformin use and hospital attendance-related resources utilization among diabetic patients with prostate cancer on androgen deprivation therapy: A population-based cohort study

Background Androgen deprivation therapy (ADT), used increasingly in the treatment of prostate cancer (PCa), negatively influences glycemic control in diabetes and is associated with an increased risk of diabetes complications where hospitalization commonly ensues. Metformin could decrease the metabolic consequences of ADT and enhance its effect. This study examined the association of metformin use with healthcare resources utilization among diabetic, PCa patients receiving ADT. Methods Diabetic adults with PCa on ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with <6 months of concurrent metformin and ADT use were excluded. All included patients were followed up until September 2021. The outcomes were hospital attendances and related costs. Results In total, 1,284 metformin users and 687 non-users were studied. Over 8,045 person-years, 9,049 accident and emergency (A&E), and 21,262 inpatient attendances, with 11,2781 days of hospitalization were observed. Metformin users had significantly fewer A&E attendances (incidence rate ratio (IRR): 0.61 [95% confidence interval 0.54–0.69], p < 0.001), inpatient attendances (IRR: 0.57 [0.48–0.67], p < 0.001), and days of hospitalization (IRR: 0.55 [0.42–0.72], p < 0.001). Annual attendance costs were lower for metformin users than non-users (cost ratio: 0.28 [0.10–0.80], p = 0.017). Conclusions Metformin use was associated with decreased hospital attendances, days of hospitalization, and associated costs, which could help reduce healthcare resource utilization following ADT in the treatment of PCa

Temporal trends in cardiovascular burden among patients with prostate cancer receiving androgen deprivation therapy: a population-based cohort study

Background Although androgen deprivation therapy (ADT) is associated with cardiovascular risks, the extent and temporal trends of cardiovascular burden amongst patients with prostate cancer receiving ADT are unclear. Methods This retrospective cohort study analyzed adults with PCa receiving ADT between 1993–2021 in Hong Kong, with follow-up until 31/9/2021 for the primary outcome of major adverse cardiovascular events (MACE; composite of cardiovascular mortality, myocardial infarction, stroke, and heart failure), and the secondary outcome of mortality. Patients were stratified into four groups by the year of ADT initiation for comparisons. Results Altogether, 13,537 patients were included (mean age 75.5 ± 8.5 years old; mean follow-up 4.7 ± 4.3 years). More recent recipients of ADT had more cardiovascular risk factors and used more cardiovascular or antidiabetic medications. More recent recipients of ADT had higher risk of MACE (most recent (2015–2021) vs least recent (1993–2000) group: hazard ratio 1.33 [1.11, 1.59], P = 0.002; Ptrend < 0.001), but lower risk of mortality (hazard ratio 0.76 [0.70, 0.83], P < 0.001; Ptrend < 0.001). The 5-year risk of MACE and mortality for the most recent group were 22.5% [20.9%, 24.2%] and 52.9% [51.3%, 54.6%], respectively. Conclusions Cardiovascular risk factors were increasingly prevalent amongst patients with prostate cancer receiving ADT, with increasing risk of MACE despite decreasing mortality

HbA1c variability and cardiovascular events in patients with prostate cancer receiving androgen deprivation therapy

Androgen deprivation therapy (ADT) worsens glycaemic control and cardiovascular outcomes. The prognostic value of visit-to-visit HbA1c variability (VVHV) has been unexplored in prostate cancer (PCa) patients receiving ADT. To explore the effect of ADT on VVHV and the cardiovascular prognostic value of VVHV. PCa patients receiving ADT in Hong Kong between January 1, 1993 and March 31, 2021 were included in this retrospective cohort study. Those with fewer than three HbA1c results available within 3 yr after ADT initiation, <6 mo of ADT, missing baseline HbA1c, prior diagnosis of any component of major adverse cardiovascular events (MACEs), and MACEs occurring within 3 yr were excluded. Patients were followed up until September 31, 2021. The outcome was MACEs (composite of heart failure, myocardial infarction, stroke, and cardiovascular mortality). VVHV was calculated from HbA1c levels within 3 yr after and, separately where available, before ADT initiation using coefficient of variation (CV; standard deviation [SD] divided by mean) and average real variability (ARV; average difference between consecutive measurements). Altogether, 1065 patients were analysed (median age 74.4 yr old [interquartile range 68.3-79.5 yr]). In 709 patients with VVHV available before and after ADT initiation, VVHV increased after ADT initiation (  < 0.001), with 473 (66.2%) and 474 (66.9%) having increased CV and ARV, respectively. Over a median follow-up of 4.3 yr (2.8-6.7 yr), higher VVHV was associated with a higher risk of MACEs (adjusted hazard ratio [per SD] for CV 1.21 [95% confidence interval: 1.02, 1.43],  = 0.029; ARV 1.25 [1.06, 1.48],  = 0.008). Limitations included residual confounding and selection bias. In PCa patients receiving ADT, VVHV increased after ADT initiation. Higher VVHV was associated with an increased risk of MACEs. In prostate cancer patients receiving androgen deprivation therapy (ADT), glycaemic control is less stable after initiating ADT, which was associated with an increased cardiovascular risk. [Abstract copyright: © 2022 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.

2,6-Bis[(4R,5R)-4,5-diphenyl-4,5-di­hydro-1,3-oxazol-2-yl]pyridine

The mol­ecule of the title compound, C35H27N3O2, lies on a twofold rotation axis passing through the pyridine ring. The five-membered ring is approximately flat (r.m.s. deviation = 0.065 Å) and is essentially coplanar [dihedral angle = 4.2 (2)°] with the pyridine ring

(S)-Perillaldehyde azine

The C=N–N=C linkage [torsion angle −172.5 (2)°] in the title azine, C20H28N2, adopts a trans conformation. The six-membered rings adopt sofa conformations

Diaqua­bis­(5-carb­oxy-2-ethyl-1H-imidazole-4-carboxyl­ato-κ2 N 3,O 4)cobalt(II) trihydrate

In the title compound, [Co(C7H7N2O4)2(H2O)2]·3H2O, the CoII cation, located on an inversion center, is N,O-chelated by two 5-carboxy-2-ethyl-1H-imidazole-4-carboxylate anions and further coordinated by two water mol­ecules in a distorted octa­hedral geometry. Only one carboxy group of the anion is deprotonated, and the two carboxyl groups of the same anion are linked via an intra­molecular O—H⋯O hydrogen bond. One of the lattice water mol­ecules is located on an inversion center, its H atom equally disordered over two positions. One of H atoms of another lattice water mol­ecules is also equally disordered over two sites. Water H atoms and the amino H atom all are involved in an inter­molecular hydrogen-bonded network in the crystal