Experimental Periodontitis Worsens Dopaminergic Neuronal Degeneration.

AIM: To investigate the hypothesis supporting the link between periodontitis and dopaminergic neuron degeneration. MATERIALS AND METHODS: Adult male Wistar rats were used to induce dopaminergic neuronal injury with 6-hydroxydopamine (6-OHDA) neurotoxin and experimental periodontitis via ligature placement. Motor function assessments were conducted before and after periodontitis induction in controls and 6-OHDA-injury-induced rats. Tissue samples from the striatum, jaw and blood were collected for molecular analyses, encompassing immunohistochemistry of tyrosine hydroxylase, microglia and astrocyte, as well as micro-computed tomography, to assess alveolar bone loss and for the analysis of striatal oxidative stress and plasma inflammatory markers. RESULTS: The results indicated motor impairment in 6-OHDA-injury-induced rats exacerbated by periodontitis, worsening dopaminergic striatal degeneration. Periodontitis alone or in combination with 6-OHDA-induced lesion was able to increase striatal microglia, while astrocytes were increased by the combination only. Periodontitis increased striatal reactive oxygen species levels and plasma tumour necrosis factor-alpha levels in rats with 6-OHDA-induced lesions and decreased the anti-inflammatory interleukin-10. CONCLUSIONS: This study provides original insights into the association between periodontitis and a neurodegenerative condition. The increased inflammatory pathway associated with both 6-OHDA-induced dopaminergic neuron lesion and periodontal inflammatory processes corroborates that the periodontitis-induced systemic inflammation may aggravate neuroinflammation in Parkinson's-like disease, potentially hastening disease progression.

A journey through cannabidiol in Parkinson's disease.

Parkinson's disease is a chronic neurodegenerative disorder with no known cure characterized by motor symptoms such as tremors, rigidity, bradykinesia (slowness of movement), and postural instability. Non-motor symptoms like cognitive impairment, mood disturbances, and sleep disorders often accompany the disease. Pharmacological treatments for these symptoms are limited and frequently induce significant adverse reactions, underscoring the necessity for appropriate treatment options. Cannabidiol is a phytocannabinoid devoid of the euphoric and cognitive effects of tetrahydrocannabinol. The study of cannabidiol's pharmacological effects has increased exponentially in recent years. Preclinical and preliminary clinical studies suggest that cannabidiol holds therapeutic potential for alleviating symptoms of Parkinson's disease, offering neuroprotective, anti-inflammatory, and antioxidant properties. However, knowledge of cannabidiol neuromolecular mechanisms is limited, and its pharmacology, which appears complex, has not yet been fully elucidated. By examining the evidence, this review aims to provide and synthesize scientifically proven evidence for the potential use of cannabidiol as a novel treatment option for Parkinson's disease. We focus on studies that administrated cannabidiol alone. The results of preclinical trials using cannabidiol in models of Parkinson's disease are encouraging. Nevertheless, drawing firm conclusions on the therapeutic efficacy of cannabidiol for patients is challenging. Cannabidiol doses, formulations, outcome measures, and methodologies vary considerably across studies. Though, cannabidiol holds promise as a novel therapeutic option for managing both motor and non-motor symptoms of Parkinson's disease, offering hope for improved quality of life for affected individuals.

Citizenship status and career self-efficacy: An intersectional study of biomedical trainees in the United States.

This study examines the intersectional role of citizenship and gender with career self-efficacy amongst 10,803 doctoral and postdoctoral trainees in US universities. These biomedical trainees completed surveys administered by 17 US institutions that participated in the National Institutes of Health Broadening Experiences in Scientific Training (NIH BEST) Programs. Findings indicate that career self-efficacy of non-citizen trainees is significantly lower than that of US citizen trainees. While lower career efficacy was observed in women compared with men, it was even lower for non-citizen female trainees. Results suggest that specific career interests may be related to career self-efficacy. Relative to US citizen trainees, both male and female non-citizen trainees showed higher interest in pursuing a career as an academic research investigator. In comparison with non-citizen female trainees and citizen trainees of all genders, non-citizen male trainees expressed the highest interest in research-intensive (and especially principal investigator) careers. The authors discuss potential causes for these results and offer recommendations for increasing trainee career self-efficacy which can be incorporated into graduate and postdoctoral training.

Brainstem Modulates Parkinsonism-Induced Orofacial Sensorimotor Dysfunctions.

Parkinson's Disease (PD), treated with the dopamine precursor l-3,4-dihydroxyphenylalanine (L-DOPA), displays motor and non-motor orofacial manifestations. We investigated the pathophysiologic mechanisms of the lateral pterygoid muscles (LPMs) and the trigeminal system related to PD-induced orofacial manifestations. A PD rat model was produced by unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. Abnormal involuntary movements (dyskinesia) and nociceptive responses were determined. We analyzed the immunodetection of Fos-B and microglia/astrocytes in trigeminal and facial nuclei and morphological markers in the LPMs. Hyperalgesia response was increased in hemiparkinsonian and dyskinetic rats. Hemiparkinsonism increased slow skeletal myosin fibers in the LPMs, while in the dyskinetic ones, these fibers decreased in the contralateral side of the lesion. Bilateral increased glycolytic metabolism and an inflammatory muscle profile were detected in dyskinetic rats. There was increased Fos-B expression in the spinal nucleus of lesioned rats and in the motor and facial nucleus in L-DOPA-induced dyskinetic rats in the contralateral side of the lesion. Glial cells were increased in the facial nucleus on the contralateral side of the lesion. Overall, spinal trigeminal nucleus activation may be associated with orofacial sensorial impairment in Parkinsonian rats, while a fatigue profile on LPMs is suggested in L-DOPA-induced dyskinesia when the motor and facial nucleus are activated.

Career self-efficacy disparities in underrepresented biomedical scientist trainees.

The present study examines racial, ethnic, and gender disparities in career self-efficacy amongst 6077 US citizens and US naturalized graduate and postdoctoral trainees. Respondents from biomedical fields completed surveys administered by the National Institutes of Health Broadening Experiences in Scientific Training (NIH BEST) programs across 17 US institutional sites. Graduate and postdoctoral demographic and survey response data were examined to evaluate the impact of intersectional identities on trainee career self-efficacy. The study hypothesized that race, ethnicity and gender, and the relations between these identities, would impact trainee career self-efficacy. The analysis demonstrated that racial and ethnic group, gender, specific career interests (academic principal investigator vs. other careers), and seniority (junior vs. senior trainee level) were, to various degrees, all associated with trainee career self-efficacy and the effects were consistent across graduate and postdoctoral respondents. Implications for differing levels of self-efficacy are discussed, including factors and events during training that may contribute to (or undermine) career self-efficacy. The importance of mentorship for building research and career self-efficacy of trainees is discussed, especially with respect to those identifying as women and belonging to racial/ethnic populations underrepresented in biomedical sciences. The results underscore the need for change in the biomedical academic research community in order to retain a diverse biomedical workforce.

Association Between Residence in Historically Redlined Districts Indicative of Structural Racism and Racial and Ethnic Disparities in Breast Cancer Outcomes.

Importance: Historical structural racism may be associated with racial, ethnic, and geographic disparities in breast cancer outcomes, but few studies have investigated these potential relationships. Objective: To test associations among historical mortgage lending discrimination (using 1930s Home Owners' Loan Corporation [HOLC] redlining data), race and ethnicity, tumor clinicopathologic features, and survival among women recently diagnosed with breast cancer. Design, Setting, and Participants: This cohort study used a population-based, state cancer registry to analyze breast tumor clinicopathology and breast cancer-specific death among women diagnosed from 2008 to 2017 and followed up through 2019. Participants included all primary, histologically confirmed, invasive breast cancer cases diagnosed among women aged at least 20 years and who resided in a HOLC-graded area of New Jersey. Those missing race and ethnicity data (n = 61) were excluded. Data were analyzed between June and December 2021. Exposures: HOLC risk grades of A ("best"), B ("still desirable"), C ("definitely declining"), and D ("hazardous" [ie, redlined area]). Main Outcomes and Measures: Late stage at diagnosis, high tumor grade, triple-negative subtype (lacking estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression), breast cancer-specific death. Results: Among a total of 14 964 women with breast cancer, 2689 were Latina, 3506 were non-Latina Black, 7686 were non-Latina White, and 1083 were other races and ethnicities (non-Latina Asian/Pacific Islander/Native American/Alaska Native/Hawaiian or not otherwise specified); there were 1755 breast cancer-specific deaths. Median follow-up time was 5.3 years (95% CI, 5.2-5.3 years) and estimated 5-year breast cancer-specific survival was 88.0% (95% CI, 87.4%-88.6%). Estimated associations between HOLC grade and each breast cancer outcome varied by race and ethnicity; compared with residence in HOLC redlined areas, residence in HOLC areas graded "best" was associated with lower odds of late-stage diagnosis (odds ratio [OR], 0.34 [95% CI, 0.22-0.53]), lower odds of high tumor grade (OR, 0.72 [95% CI, 0.57-0.91]), lower odds of triple-negative subtype (OR, 0.67 [95% CI, 0.47-0.95]), and lower hazard of breast cancer-specific death (hazard ratio, 0.48 [95% CI, 0.35-0.65]), but only among non-Latina White women. There was no evidence supporting associations among non-Latina Black or Latina women. Conclusions and Relevance: Compared with redlined areas, current residence in non-redlined areas was associated with more favorable breast cancer outcomes, but only among non-Latina White women. Future studies should examine additional factors to inform how historical structural racism could be associated with beneficial cancer outcomes among privileged racial and ethnic groups.

Health professional mobility in the WHO European Region and the WHO Global Code of Practice: data from the joint OECD/EUROSTAT/WHO-Europe questionnaire.

WHO Member States adopted the Global Code of Practice on the International Recruitment of Health Personnel 10 years ago. This study assesses adherence with the Code's principles and its continuing relevance in the WHO Europe region with regards to international recruitment of health workers. Data from the joint OECD/EUROSTAT/WHO-Europe questionnaire from 2010 to 2018 are analyzed to determine trends in intra- and inter-regional mobility of foreign-trained doctors and nurses working in case study destination countries in Europe. In 2018, foreign-trained doctors and nurses comprised over a quarter of the physician workforce and 5% of the nursing workforce in five of eight and four of five case study countries, respectively. Since 2010, the proportion of foreign-trained nurses and doctors has risen faster than domestically trained professionals, with increased mobility driven by rising East-West and South-North intra-European migration, especially within the European Union. The number of nurses trained in developing countries but practising in case study countries declined by 26%. Although the number of doctors increased by 27%, this was driven by arrivals from countries experiencing conflict and volatility, suggesting countries generally are increasingly adhering to the Code's principles on ethical recruitment. To support ethical recruitment practices and sustainable workforce development in the region, data collection and monitoring on health worker mobility should be improved.