This review discussed the molecular mechanisms of epitranscriptomic regulation in neurodevelopmental and neuropathological conditions with the goal to identify novel therapeutic targets.The ischemic penumbra defined four decades ago has been the main battleground of ischemic stroke. The evolving ischemic penumbra concept has been providing insight for the development of vascular and cellular approaches as well as diagnostic tools for the treatment of ischemic stroke. rt-PA thrombolytic therapy to prevent the transition of ischemic penumbra to core has been approved for acute ischemic stroke within 3 h and was later recommended to extend to 4.5 h after symptom onset. Mechanical thrombectomy was introduced for the treatment of acute ischemic stroke with a therapeutic window of up to 24 h after stroke onset. Multiple modalities brain imaging techniques have been developed that provide guidance to define ischemic penumbra for reperfusion therapy in clinical practice. Cellular and molecular dissection of ischemic penumbra has been providing targets for the development of neuroprotective therapy for ischemic stroke. However, the dynamic nature of ischemic penumbra implicates that infarct core eventually expands into penumbra over time without reperfusion, dictating relative short therapeutic windows and limiting the impact of current reperfusion intervention. Entering the 5th decade since the introduction, ischemic penumbra remains the main focus of ischemic stroke research and clinical practice. In this review, we summarized the evolving ischemic penumbra concept and its implication in the development of vascular and cellular interventions as well as diagnostic tools for acute ischemic stroke. In addition, we discussed future perspectives on expansion of the campaign beyond ischemic penumbra to develop treatment for ischemic stroke.
  The proportion of tuberculosis (TB) patients who are older adults is increasing worldwide. Nearly 60% of TB patients in Japan are 70 years or older, and the TB incidence rate in Japan is one of the highest among high-income countries. The previous TB treatment guidelines prior to 2018 in Japan recommended excluding pyrazinamide (PZA) from the initial regimen for patients aged over 80 years.
 
  We aimed to examine differences in TB treatment outcomes among different age groups, and between those who received PZA and those who did not.
 
  We performed a retrospective cohort study of patients with pulmonary TB who were managed at a single medical center in Japan. We compared treatment outcomes and adverse events that resulted in treatment interruption across the age groups.
 
  Of 246 patients, 117 (48%) were aged 75 years or older. Compared with patients aged <74years, those ≥75years were less likely to have PZA in the initial regimen (53.0% vs 89.9%; p<0.0001), more likely to die during treatment (38.5% vs 6.2%; p<0.0001), and more likely to experience adverse events (30.8% vs 19.4%; p<0.05). The mortality rate related to TB at 2 months after TB treatment initiation was 28% in those aged ≥84 years. Furthermore, among patients aged ≥84 years, those who did not receive PZA were significantly more likely to die than those who did (65.8% vs 36.8%; p<0.05).
 
  Patients aged ≥75years with pulmonary TB experienced increased mortality related to TB during treatment and more frequent adverse events than younger patients, even though PZA was often avoided among older patients.
 Patients aged ≥ 75 years with pulmonary TB experienced increased mortality related to TB during treatment and more frequent adverse events than younger patients, even though PZA was often avoided among older patients.
  Several medication classes are considered to present risk factors for falls. However, the evidence is mainly based on observational studies that often lack adequate adjustment for confounders. Therefore, we aimed to assess the associations of medication classes with fall risk by carefully selecting confounders and by applying propensity score matching (PSM).
 
  Data from several European cohorts, harmonized into the ADFICE_IT cohort, was used. Our primary outcome was time until the first fall within 1-year follow-up. The secondary outcome was a fall in the past year. Our exposure variables were commonly prescribed medications. We used 11 PSM to match the participants with reported intake of specific medication classes with participants without. We constructed Cox regression models stratified by the pairs matched on the propensity score for our primary outcome and conditional logistic regression models for our secondary outcome.
 
  In total, 32.6% of participants fell in the 1-year follow-up and 24.4% reportedwith fall risk in a relatively healthy population of community-dwelling older persons. However, the treatment effects and risks can be heterogeneous between individuals. Therefore, focusing on identification of individuals at risk is warranted to optimize personalized falls prevention.Pain is a frequent and disabling non-motor feature of Parkinson's disease (PD). The recently proposed PD Pain Classification System (PD-PCS) allows for an association of pain with PD to be determined before being allocated to the main pain mechanism (i.e. nociceptive, neuropathic, and nociplastic). In this article, previous studies on treatments for pain in PD are summarized according to the pain mechanisms. A mechanistic approach to treatment is discussed. We suggest that the first step should be optimizing dopaminergic therapy before other therapy is started. When these treatments remain unsuccessful, further causes of pain must be considered. The role of drugs, invasive treatments, and physiotherapeutic interventions are discussed with a focus on older PD patients and considering polypharmacy, altered pharmacokinetics, and comorbidities.Sevoflurane postconditioning (SPC) has been widely reported to attenuate brain injury after hypoxia-ischemia encephalopathy (HIE) by inhibiting neural necrosis and autophagy. Moreover, recent reports revealed that sevoflurane facilitated hippocampal reconstruction via regulating migration. Yet, it remains unclear whether the promotion of neural migration by SPC repairs the hippocampal injury after HIE. Here, we hypothesize that SPC exerts a neuroprotective effect by ameliorating neuronal migration disorder after HIE and regulating Reelin expression. Furthermore, the downstream Reelin/Dab1 pathway may be involved. The classical Rice-Vannucci model of hypoxia-ischemia was performed on postnatal day 7 rat pups, which was followed by SPC at 1 minimum alveolar concentration (MAC 2.5%) for 30 min.  https://www.selleckchem.com/products/PD-0325901.html  Piceatannol, causing Reelin aggregation in vivo, was used to detect whether Reelin/Dab1 was involved in the neuroprotection effect of SPC. Hippocampal-dependent learning ability tests were conducted to assess the long-term effects on locomotor activity and spatial learning ability.