Brain-based sex differences in schizophrenia: A systematic review of fMRI studies.

Schizophrenia is a chronic psychiatric disorder with characteristic symptoms of delusions, hallucinations, lack of motivation, and paucity of thought. Recent evidence suggests that the symptoms of schizophrenia, negative symptoms in particular, vary widely between the sexes and that symptom onset is earlier in males. A better understanding of sex-based differences in functional magnetic resonance imaging (fMRI) studies of schizophrenia may provide a key to understanding sex-based symptom differences. This study aimed to summarize sex-based functional magnetic resonance imaging (fMRI) differences in brain activity of patients with schizophrenia. We searched PubMed and Scopus to find fMRI studies that assessed sex-based differences in the brain activity of patients with schizophrenia. We excluded studies that did not evaluate brain activity using fMRI, did not evaluate sex differences, and were nonhuman or in vitro studies. We found 12 studies that met the inclusion criteria for the current systematic review. Compared to females with schizophrenia, males with schizophrenia showed more blood oxygen level-dependent (BOLD) activation in the cerebellum, the temporal gyrus, and the right precuneus cortex. Male patients also had greater occurrence of low-frequency fluctuations in cerebral blood flow in frontal and parietal lobes and the insular cortex, while female patients had greater occurrence of low-frequency fluctuations in the hippocampus, parahippocampus, and lentiform nucleus. The current study summarizes fMRI studies that evaluated sex-based fMRI brain differences in schizophrenia that may help to shed light on the underlying pathophysiology and further understanding of sex-based differences in the clinical presentation and course of the disorder.

Statin use and longitudinal changes in quantitative MRI-based biomarkers of thigh muscle quality: data from Osteoarthritis Initiative.

OBJECTIVE: To assess whether changes in MRI-based measures of thigh muscle quality associated with statin use in participants with and without/at-risk of knee osteoarthritis. METHODS: This retrospective cohort study used data from the Osteoarthritis Initiative study. Statin users and non-users were matched for relevant covariates using 1:1 propensity-score matching. Participants were further stratified according to baseline radiographic knee osteoarthritis status. We used a validated deep-learning method for thigh muscle MRI segmentation and calculation of muscle quality biomarkers at baseline, 2nd, and 4th visits. Mean difference and 95% confidence intervals (CI) in longitudinal 4-year measurements of muscle quality biomarkers, including cross-sectional area, intramuscular adipose tissue, contractile percent, and knee extensors and flexors maximum and specific contractile force (force/muscle area) were the outcomes of interest. RESULTS: After matching, 3772 thighs of 1910 participants were included (1886 thighs of statin-users: 1886 of non-users; age: 62 ± 9 years (average ± standard deviation), range: 45-79; female/male: 1). During 4 years, statin use was associated with a slight decrease in muscle quality, indicated by decreased knee extension maximum (mean-difference, 95% CI: - 1.85 N/year, - 3.23 to - 0.47) and specific contractile force (- 0.04 N/cm2/year, - 0.07 to - 0.01), decreased thigh muscle contractile percent (- 0.03%/year, - 0.06 to - 0.01), and increased thigh intramuscular adipose tissue (3.06 mm2/year, 0.53 to 5.59). Stratified analyses showed decreased muscle quality only in participants without/at-risk of knee osteoarthritis but not those with established knee osteoarthritis. CONCLUSIONS: Statin use is associated with a slight decrease in MRI-based measures of thigh muscle quality over 4 years. However, considering statins' substantial cardiovascular benefits, these slight muscle changes may be relatively less important in overall patient care.

Alzheimer Disease Pathology and Neurodegeneration in Midlife Obesity: A Pilot Study.

Obesity and excess adiposity at midlife are risk factors for Alzheimer disease (AD). Visceral fat is known to be associated with insulin resistance and a pro-inflammatory state, the two mechanisms involved in AD pathology. We assessed the association of obesity, MRI-determined abdominal adipose tissue volumes, and insulin resistance with PET-determined amyloid and tau uptake in default mode network areas, and MRI-determined brain volume and cortical thickness in AD cortical signature in the cognitively normal midlife population. Thirty-two middle-aged (age: 51.27±6.12 years, 15 males, body mass index (BMI): 32.28±6.39 kg/m2) cognitively normal participants, underwent bloodwork, brain and abdominal MRI, and amyloid and tau PET scan. Visceral and subcutaneous adipose tissue (VAT, SAT) were semi-automatically segmented using VOXel Analysis Suite (Voxa). FreeSurfer was used to automatically segment brain regions using a probabilistic atlas. PET scans were acquired using [11C]PiB and AV-1451 tracers and were analyzed using PET unified pipeline. The association of brain volumes, cortical thicknesses, and PiB and AV-1451 standardized uptake value ratios (SUVRs) with BMI, VAT/SAT ratio, and insulin resistance were assessed using Spearman's partial correlation. VAT/SAT ratio was associated significantly with PiB SUVRs in the right precuneus cortex (p=0.034) overall, controlling for sex. This association was significant only in males (p=0.044), not females (p=0.166). Higher VAT/SAT ratio and PiB SUVRs in the right precuneus cortex were associated with lower cortical thickness in AD-signature areas predominantly including bilateral temporal cortices, parahippocampal, medial orbitofrontal, and cingulate cortices, with age and sex as covariates. Also, higher BMI and insulin resistance were associated with lower cortical thickness in bilateral temporal poles. In midlife cognitively normal adults, we demonstrated higher amyloid pathology in the right precuneus cortex in individuals with a higher VAT/SAT ratio, a marker of visceral obesity, along with a lower cortical thickness in AD-signature areas associated with higher visceral obesity, insulin resistance, and amyloid pathology.

Central nervous system microstructural alterations in Type 1 diabetes mellitus: A systematic review of diffusion Tensor imaging studies.

AIMS: Type 1 diabetes mellitus (T1DM) is a chronic childhood disease with potentially persistent CNS disruptions. In this study, we aimed to systematically review diffusion tensor imaging studies in patients with T1DM to understand the microstructural effects of this entity on individuals' brains METHODS: We performed a systematic search and reviewed the studies to include the DTI studies in individuals with T1DM. The data for the relevant studies were extracted and a qualitative synthesis was performed. RESULTS: A total of 19 studies were included, most of which showed reduced FA widespread in optic radiation, corona radiate, and corpus callosum, as well as other frontal, parietal, and temporal regions in the adult population, while most of the studies in the juvenile patients showed non-significant differences or a non-persistent pattern of changes. Also, reduced AD and MD in individuals with T1DM compared to controls and non-significant differences in RD were noted in the majority of studies. Microstructural alterations were associated with clinical profile, including age, hyperglycemia, diabetic ketoacidosis and cognitive performance. CONCLUSION: T1DM is associated with microstructural brain alterations including reduced FA, MD, and AD in widespread brain regions, especially in association with glycemic fluctuations and in adult age.

Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis-related outcomes: results from a longitudinal cohort study.

OBJECTIVES: We examined the association between diabetes mellitus (DM) and longitudinal MRI biomarkers for thigh muscle degeneration in patients with knee osteoarthritis (KOA) and their mediatory role in worsening KOA-related symptoms. METHODS: The Osteoarthritis Initiative (OAI) participants with radiographic KOA (Kellgren-Lawrence grade ≥ 2) were included. Thighs and corresponding knees of KOA patients with versus without self-reported DM were matched for potential confounders using propensity score (PS) matching. We developed and used a validated deep learning method for longitudinal thigh segmentation. We assessed the association of DM with 4-year longitudinal muscle degeneration in biomarkers of muscle cross-sectional area (CSA) and contractile percentage (non-fat CSA/total CSA). We further investigated whether DM is associated with 9-year risk of KOA radiographic progression, knee replacement (KR), and symptoms worsening. Finally, we evaluated whether the DM-KOA worsening association is mediated through preceding muscle degeneration. RESULTS: After PS matching, 698 thighs/knees were included (185:513 with:without DM; average ± SD age:64 ± 8-years; female/male:1.4). Baseline DM was associated with a decreased contractile percent of total thigh muscles and quadriceps (mean difference, 95%CI -0.16%/year, -0.25 to -0.07, and -0.21%/year, -0.33 to -0.08). DM was also associated with an increased risk of worsening KOA-related symptoms (hazard ratio, 95%CI 1.70, 1.18-2.46) but not radiographic progression or KR. The decrease in quadriceps contractile percent partially mediated the increased risk of symptoms worsening in patients with DM. CONCLUSIONS: Baseline DM is associated with thigh muscle degeneration and KOA-related symptoms worsening. As a potentially modifiable risk factor, DM-associated longitudinal thigh muscle degeneration may partially mediate the symptoms worsening in patients with DM and coexisting KOA. KEY POINTS: • Diabetes mellitus (DM) is associated with worsening knee osteoarthritis (KOA)-related symptoms. • As a potentially modifiable factor, DM-associated thigh muscle (quadriceps) degeneration partially mediates the worsening of KOA-related symptoms.

Thyroid hormone levels in Alzheimer disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Thyroid hormone (TH) disturbances are perceived to contribute to cognitive impairment and dementia. However, there is no consensus on the association between TH levels and Alzheimer Disease (AD). In this study, we aimed to compare serum and cerebrospinal fluid (CSF) TH levels in AD patients to controls by performing a meta-analysis. METHODS: We systematically searched online databases for papers comparing CSF or serum TH levels in AD patients to controls, and performed a meta-analysis on the extracted data. RESULTS: Out of 1604 records identified, 32 studies were included. No significant difference in serum TSH (standardized mean difference (SMD): -0.03; 95% confidence interval (CI): -0.22-0.16), total T4 (SMD: 0.10; 95% CI: -0.29-0.49), and free T4 (SMD: 0.25; 95% CI: -0.16-0.69) levels were observed. However, there was significantly lower serum total T3 (SMD: -0.56; 95%CI: -0.97 to -0.15) and free T3 (SMD: -0.47; 95%CI: -0.89 to -0.05) levels in AD group compared to controls. Subgroup analyses on studies including only euthyroid patients did not show any significant difference in either of the thyroid hormone levels. Also, no significant difference in CSF total T4 and total T3/total T4 ratios but significantly lower CSF total T3 (SMD: -2.45; 95% CI: -4.89 to -0.02) in AD group were detected. CONCLUSION: Serum total and free T3 and CSF total T3 levels are significantly lower in AD patients compared to controls. The temporality of changes in thyroid hormone levels and AD development should be illustrated by further longitudinal studies.

Longitudinal MRI-defined Cartilage Loss and Radiographic Joint Space Narrowing Following Intra-Articular Corticosteroid Injection for Knee Osteoarthritis: A Systematic Review and Meta-analysis.

Background: Intra-articular corticosteroid injections (IACS) are interventions which provide pain relief in knee osteoarthritis (OA). It remains unclear whether IACS have a deleterious effect on knee cartilage structure. Purpose: To estimate the effect of IACS on cartilage structure in patients with knee OA, using joint space width (JSW) (in radiographic studies), and cartilage thickness (in magnetic resonance imaging). Materials and methods: A literature search was performed to identify randomized control trials and observational studies published from inception to June 15, 2022. Studies were included if patients received IACS for knee OA, with a control arm. Given the different metrics used in reporting continuous variable outcomes among studies, pooled estimates for cartilage thickness change were assessed using standardized mean differences (defined as the difference between the means of the groups divided by a within-group standard deviation) to odds ratio transformation. Sensitivity analyses were conducted based on outcome metric, imaging modality, and number of injections. Results: Six studies (1437 participants) were identified. The estimated effect of IACS on cartilage structure revealed greater odds of cartilage structure worsening (Odds Ratio (OR): 2.01, 95% Confidence Interval (CI): 1.18,3.44). Sensitivity analyses revealed similar trends, with significant results for singular injections with preference to JSW (OR: 2.44, 95%CI: 1.23,4.82), radiographic outcomes with preference to KL grade (OR: 2.03, 95%CI: 1.01,4.10), binary outcomes with preference to KL grade (OR: 2.93, 95%CI: 1.18,7.25) and quantitative measures (Standardized Mean Differences (SMD): -0.34, 95%CI: -0.66, -0.02). Conclusions: IACS use may contribute to imaging features of knee cartilage loss. Further studies are warranted to investigate the underlying pathogenesis.

Circular RNAs as prognostic and diagnostic biomarkers in renal cell carcinoma.

BACKGROUND: Circular RNAs (circRNAs) play pivotal roles in proliferation, apoptosis, migration, and invasion of renal cell carcinoma (RCC) cells. This study is aimed to systematically summarize the current evidence regarding the clinical implications of circRNAs in RCC patients. METHODS: A systematic search in PubMed, Embase, and Web of Science was performed until January 1, 2022. The correlation between the expression of circRNAs and clinicopathological, prognostic, and diagnostic features of RCC was evaluated using the meta-analysis. RESULTS: Ultimately, 41 studies with 3485 RCC patients were included in this study: 26 studies for clinicopathological features, 31 studies for prognosis, and eight studies for diagnosis. Altered expression of circRNAs was significantly associated with clinicopathological characteristics of RCC, including tumor size, tumor stage, lymph node metastasis, distant metastasis, and TNM stage. The tumor promoter circRNAs were associated with reduced overall survival (OS) (Hazard Ratio (HR) = 1.98, 95% confidence interval [CI] 1.68-2.34) and disease/progression/recurrence-free survival (DFS/PFS/RFS) (HR = 2.34, 95% CI 1.85-2.97). Contrarily, the tumor suppressor circRNAs were linked with better OS (HR = 0.49, 95% CI 0.40-0.60) and DFS/PFS/RFS (HR = 0.40, 95% CI 0.28-0.59). The pooled sensitivity and specificity of circRNAs for RCC diagnosis in tissue samples were both 0.84. These results in fluid samples (serum and urine) were 0.78 and 0.69, respectively. CONCLUSION: CircRNAs can serve as promising diagnostic and prognostic biomarkers for RCC.

Microstructural white matter alterations associated with migraine headaches: a systematic review of diffusion tensor imaging studies.

The pathophysiology of migraine as a headache disorder is still undetermined. Diffusion tensor imaging (DTI) has significantly improved our knowledge about brain microstructure in this disease. Here, we aimed to systematically review DTI studies in migraine and survey the sources of heterogeneity by investigating diffusion parameter changes associated with clinical characteristics and migraine subtypes. Microstructural changes, as revealed by widespread alteration of diffusion metrics in white matter (WM) tracts, subcortical and cortical regions, were reported by several migraine DTI studies. Specifically, we reported changes in the corpus callosum, thalamic radiations, corona radiata, and brain stem. These alterations showed high variability across migraine cycle phases. Additionally, migraine associated with depressive/anxiety symptoms revealed significant changes in the corpus callosum, internal capsule, and superior longitudinal fasciculus. No significant WM microstructural differences were observed between migraine patients with and without aura. Overall, differences between chronic and episodic migraine showed inconsistency across studies. Migraine is associated with microstructural changes in widespread regions including thalamic radiations, corpus callosum, and brain stem. These alterations can highlight neuronal damage and neuronal plasticity mechanisms either following pain stimulations occurring in migraine cycle or as a compensatory response to pain in chronic migraine. Longitudinal studies applying advanced modalities may shed new light on the underlying microstructural changes in migraine subtypes.

Role of Thigh Muscle Changes in Knee Osteoarthritis Outcomes: Osteoarthritis Initiative Data.

Background Longitudinal data on the association of quantitative thigh muscle MRI markers with knee osteoarthritis (KOA) outcomes are scarce. These associations are of clinical importance, with potential use for thigh muscle-directed disease-modifying interventions. Purpose To measure KOA-associated longitudinal changes in MRI-derived muscle cross-sectional area (CSA) and adipose tissue and their association with downstream symptom worsening and knee replacement (KR). Materials and Methods In a secondary analysis of the Osteoarthritis Initiative multicenter prospective cohort (February 2004 through October 2015), knees of participants with available good-quality thigh MRI scans at baseline and at least one follow-up visit were included and classified as with and without KOA according to baseline radiographic Kellgren-Lawrence grade of 2 or higher and matched for confounders with use of propensity score matching. An automated deep learning model for thigh MRI two-dimensional segmentation was developed and tested. Markers of muscle CSA and intramuscular adipose tissue (intra-MAT) were measured at baseline and 2nd- and 4th-year follow-up (period 1) and compared between knees with and without KOA by using linear mixed-effect regression models. Furthermore, in knees with KOA, the association of period 1 changes in muscle markers with risk of KR (Cox proportional hazards) and symptom worsening (mixed-effect models) during the 4th to 9th year (period 2) was evaluated. Results This study included 4634 matched thighs (2317 with and 2317 without KOA) of 2344 participants (mean age, 62 years ± 9 [SD]; 1292 women). Compared with those without, knees with KOA had a decrease in quadriceps CSA (mean difference, -8.21 mm2/year; P = .004) and an increase in quadriceps intra-MAT (1.98 mm2/year; P = .007). Decreased CSA and increased intra-MAT of quadriceps during period 1 was predictive of downstream (period 2) KOA symptom worsening (Western Ontario and McMaster Universities Osteoarthritis Index total score: odds ratio, 0.24 [negative association] [P < .001] and 1.38 [P = .012], respectively). Quadriceps CSA changes were negatively associated with higher future KR risk (hazard ratio, 0.70; P < .001). Conclusion Knee osteoarthritis was associated with longitudinal MRI-derived decreased quadriceps cross-sectional area and increased intramuscular adipose tissue. These potentially modifiable risk factors were predictive of downstream symptom worsening and knee replacement. Clinical trial registration no. NCT00080171 © RSNA, 2022 Online supplemental material is available for this article.

Combination Therapy in Alzheimer's Disease: Is It Time?

Alzheimer's disease (AD) is the most common cause of dementia globally. There is increasing evidence showing AD has no single pathogenic mechanism, and thus treatment approaches focusing only on one mechanism are unlikely to be meaningfully effective. With only one potentially disease modifying treatment approved, targeting amyloid-ß (Aß), AD is underserved regarding effective drug treatments. Combining multiple drugs or designing treatments that target multiple pathways could be an effective therapeutic approach. Considering the distinction between added and combination therapies, one can conclude that most trials fall under the category of added therapies. For combination therapy to have an actual impact on the course of AD, it is likely necessary to target multiple mechanisms including but not limited to Aß and tau pathology. Several challenges have to be addressed regarding combination therapy, including choosing the correct agents, the best time and stage of AD to intervene, designing and providing proper protocols for clinical trials. This can be achieved by a cooperation between the pharmaceutical industry, academia, private research centers, philanthropic institutions, and the regulatory bodies. Based on all the available information, the success of combination therapy to tackle complicated disorders such as cancer, and the blueprint already laid out on how to implement combination therapy and overcome its challenges, an argument can be made that the field has to move cautiously but quickly toward designing new clinical trials, further exploring the pathological mechanisms of AD, and re-examining the previous studies with combination therapies so that effective treatments for AD may be finally found.

Conventional MRI-derived subchondral trabecular biomarkers and their association with knee cartilage volume loss as early as 1 year: a longitudinal analysis from Osteoarthritis Initiative.

OBJECTIVE: To study associations between MRI-derived subchondral trabecular biomarkers obtained from conventional MRI sequences and knee cartilage loss over 12 and 24 months, using the FNIH osteoarthritis (OA) biomarkers consortium. MATERIALS AND METHODS: Data of the 600 subjects in the FNIH OA biomarkers consortium (a nested case-control study within Osteoarthritis Initiative [OAI]) were extracted from the online database. Baseline knee MRI (intermediate-weighted (IW) sequences) were evaluated to determine conventional MRI-derived trabecular thickness (cTbTh) and bone-to-total ratio (cBV/TV). The measurements for medial and lateral volumes of cartilages using baseline, 12-, and 24-month knee MRI were extracted from the OAI database, and cartilage volume loss over 12 and 24 months of follow-up were determined using Relative Change Index. The association between conventional MRI-based subchondral trabecular biomarkers and cartilage volume loss were studied using logistic regression models, adjusted for relevant confounders including age, sex, body mass index (BMI), vitamin D use, Kellgren Lawrence grade (KLG), and tibiofemoral alignment. RESULTS: Higher medial cTbTh and cBV/TV at baseline were associated with increased odds of medial tibial cartilage volume loss over 12 months (ORs: 1.01 [1.00-1.02] and 1.24 [1.10-1.39] per 1-SD change) and 24 months (ORs: 1.01 [1.00-1.02] and 1.22 [1.08-1.37], per 1-SD change). No significant association was observed between medial subchondral trabecular biomarkers and lateral tibial or femoral (medial or lateral) cartilage volume loss over the first and second follow-up years. CONCLUSIONS: Conventional MRI-derived subchondral trabecular biomarkers (higher medial cTbTh and cBV/TV) may be associated with increased medial tibial cartilage volume loss as early as 1 year.

Relation between ADHD and COVID-19: A Narrative Review to Guide Advancing Clinical Research and Therapy.

Objective: To cope with the COVID-19 pandemic, national health authorities temporarily closed cultural, religious, and educational institutions such as universities and schools. Children and adolescents with ADHD were challenged with the restrictions caused by the Covid-19 pandemic such as homeschooling and reduced physical activity. The present narrative review aimed to summarize the state-of-the-art regarding associations between COVID-19-related social restrictions and possible psychological and behavioral issues in children and adolescents with ADHD. Additionally, we discussed the underlying possible reasons of the association focusing on the role of parental influence and physical activity, vulnerabilities of individuals with ADHD to Covid-19 infection and to school closure and remote learning. Method: To collect data for the present narrative review, recent publications on these topics between February 1st, 2020 and January 10th, 2021 were retrieved from the most popular search engines (PubMed; Scopus; Google Scholar; Psych Info; Embase) through a comprehensive search using relevant keywords. Results: During confinement, children and adolescents with ADHD reported increased behavioral and ADHD-related symptoms and overall decreased psychological well-being. Factors negatively impacting children's and adolescents' behavioral symptoms and well-being were: less physical activity, adverse parental behavior, difficulties in coping with preventive guidelines, and school closure and remote learning consequences. Conclusion: Children and adolescents with ADHD and their caregivers faced both specific and general psychological issues related to the school lockdowns and homeschooling. Additionally, Individuals with ADHD seem to be more vulnerable to Covid-19 infection which highlights the need for better healthcare adaptation.

Intravenous thrombolysis in ischemic stroke patients with a prior intracranial hemorrhage: a meta-analysis.

BACKGROUND: The history of intracranial hemorrhage (ICrH) is considered a contraindication for intravenous thrombolysis (IVT) among patients with acute ischemic stroke (AIS). Objective: This study aimed at comparing the safety of IVT among patients with and without a history of ICrH. METHODS: We performed a systematic review of the literature. Data regarding all AIS patients with prior ICrH who received IVT were retrieved. Meta-analysis was performed to compare the rate of symptomatic hemorrhagic transformation (sHT), death within 90 days, and favorable and unfavorable 90-day functional outcomes based on modified Rankin Scale (mRS) among stroke patients with and without prior ICrH. RESULTS: Out of 13,032 reviewed records, 7 studies were included in the systematic review and meta-analysis. Quantitative synthesis of data regarding the rate of sHT (5068 patients) revealed no significant difference between the two groups [odds ratio, OR: 1.55 (0.77, 3.12); p = 0.22]. However, a significantly higher risk of death within 90 days [OR: 3.91 (2.16, 7.08); p < 0.00001] and a significantly higher 90-day poor functional outcomes (mRS, 4-6) [OR: 1.57 (1.07, 2.30); p = 0.02] were observed among patients with prior ICrH. Likewise, the percentage of 90-day good functional outcomes (mRS, 0-1) was lower in the prior ICrH group [OR: 0.54 (0.35, 0.84); p = 0.06]. Subgroup analyses in patients with a history of ICrH (based on both patients' medical history and imaging confirmation) revealed no significant between-group differences in rates of sHT. Also, sensitivity analysis consisting of only studies using standard-dose IVT showed no difference in sHT rates and 90-day outcomes between the two groups. There was no evidence of heterogeneity (I 2 >50%) among included studies. CONCLUSION: The results of this study indicated that prior history of ICrH does not increase the risk of sHT post-IVT, but it is associated with a higher risk of death and poor functional outcomes in 90 days.

The interactions between adipose tissue secretions and Parkinson's disease: The role of leptin.

Leptin is a hormone that regulates appetite by acting on receptors in the hypothalamus, where it modifies food intake to maintain equilibrium with the body energy resources. Leptin and its receptors are widely distributed in the central nervous system, suggesting that they may give neuronal survival signals. The potential of leptin to decrease/increase neuronal damage and neuronal plasticity in Parkinson's diseases (PD) is the subject of this review, which outlines our current knowledge of how leptin acts in the brain. Although leptin-mediated neuroprotective signalling results in neuronal death prevention, it can affect neuroinflammatory cascades and also neuronal plasticity which contribute to PD pathology. Other neuroprotective molecules, such as insulin and erythropoietin, share leptin-related signalling cascades, and therefore constitute a component of the neurotrophic effects mediated by endogenous hormones. With the evidence that leptin dysregulation causes increased neuronal vulnerability to damage in PD, using leptin as a target for therapeutic modification is an appealing and realistic option.

Depression, Anxiety and Coping Responses among Iranian Healthcare Professionals during the Coronavirus Disease (COVID-19) Outbreak.

Objective: This cross-sectional study aimed to assess the effects of different coping strategies on the mood states (anxiety and depression) of healthcare providers in the novel coronavirus disease (COVID-19) pandemic. Method : From February to April 2020, we asked medical staff in 4 referral hospitals in Iran to voluntarily complete online questionnaires including: Generalized Anxiety Disorder (GAD-2) questionnaire, Patient Health Questionnaire (PHQ-2) and the Coping Strategies Questionnaire-28. Univariate and multiple logistic regressions were applied to identify the associations of coping strategies and mood states. Results: 258 people filled out the online questionnaire. Of them, 39.9% and 39.1% reported anxiety and depression, respectively, with age as a risk factor. Overall, participants used more emotion-based coping strategies. Anxiety and depression were associated with applying more of emotion-based and less of problem-based coping mechanisms. The findings remained stable even after adjustment for confounding variables including age, gender and direct contact with COVID-19 patients. Conclusion: Providing social support to health workers, planning to reduce their perceived stigma, and educating them about how to use more effective coping mechanisms can be beneficial in reducing the psychological impact on this segment of the population in the event of COVID-19.

White matter changes in drug-naïve Parkinson's disease patients with impulse control & probable REM sleep behavior disorders.

BACKGROUND: According to epidemiological studies, Parkinson's disease (PD) patients with probable REM sleep behavior disorder (pRBD) are more prone to develop impulse control disorders (ICDs), which is shown to be present in drug-naïve PD patients, and vice versa. OBJECTIVES: To investigate white-matter integrity differences, with and without comorbid pRBD and ICDs. METHODS: 149 de-novo PD patients and 30 age- and gender-matched controls from the Parkinson's Progression Markers Initiative were studied. PD subjects were categorized into four groups with and without these comorbidities. We investigated the white matter integrity differences between these groups. RESULTS: PDs with only ICDs manifested greater fractional anisotropy (FA) and lower mean diffusivity (MD) in ipsilateral cerebellar connections when compared to controls and to Parkinson's with both comorbid disorders. In contrast, significantly lower FA and higher MD in the ipsilateral fornix-stria-terminalis was observed in PDs with only pRBD compared to controls and to PDs without either comorbid disorder. Also, PDs with only pRBD manifested greater FA in contralateral putamen when compared to controls. CONCLUSIONS: Our results suggest the presence of an underlying neural network in PDs with ICDs, particularly involving cerebellar connections, which makes the subjects susceptible to pRBD. Lower white-matter integrity in the fornix of PDs with only pRBD suggests a neuropathological pathway specific to sleep behavior disorder, independent of impulse control disorders. Greater white-matter integrity observed in PDs without comorbid ICDs, regardless of their comorbid pRBD status, might reflect compensatory mechanisms. Targeted therapies for this particular neuropathology may help prevent these comorbidities.

Aging & COVID-19 susceptibility, disease severity, and clinical outcomes: The role of entangled risk factors.

The emergence of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) in late 2019 has been associated with a high rate of mortality and morbidity. It has been determined that the old population are not only at an increased risk for affliction with COVID-19 infection, but also atypical presentations, severe forms of the disease, and mortality are more common in this population. A plethora of mechanisms and risk factors contribute to the higher risk of infection in the old population. For instance, aging is associated with an increment in the expression of Angiotensin-Converting Enzyme-2 (ACE-2), the receptor for SARS-CoV-2 spike protein, which precipitates replication of the virus in the old population. On the other hand, immune dysregulation and changes in gut microbiota as a result of aging can contribute to the cytokine storm, one of the main indicators of disease severity. Decrement in sex steroids, especially in women, as well as growth hormone, both of which have crucial roles in immune regulation, is a key contributor to disease severity in old age. Senescence-associated oxidative stress and mitochondrial dysfunction in both pneumocytes and immune cells contribute to the severity of infection in an exacerbative manner. In addition, lifestyle-associated factors such as nutrition and physical activity, which are compromised in old age, are known as important factors in COVID-19 infection. Aging-associated comorbidities, especially cardiovascular diseases and diabetes mellitus, also put older adults at an increased risk of complications, and disease severity.

Effects of Prenatal Methamphetamine Exposure on the Developing Human Brain: A Systematic Review of Neuroimaging Studies.

Methamphetamine (MA) can cross the placenta in pregnant women and cause placental abruption and developmental alterations in offspring. Previous studies have found prenatal MA exposure effects on the social and cognitive performance of children. Recent studies reported some alterations in structural and functional magnetic resonance imaging (MRI) of prenatal MA-exposed offspring. In this study, we aimed to investigate the effect of prenatal MA exposure on brain development using recently published structural, metabolic, and functional MRI studies. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed and SCOPUS databases for articles that used each brain imaging modality in prenatal MA-exposed children. Seventeen studies were included in this study. We investigated brain imaging alterations using 17 articles with four different modalities, including structural MRI, diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and functional MRI (fMRI). The participants' age range was from infancy to 15 years. Our findings demonstrated that prenatal MA exposure is associated with macrostructural, microstructural, metabolic, and functional deficits in both cortical and subcortical areas. However, the most affected regions were the striatum, frontal lobe, thalamus and the limbic system, and white matter (WM) fibers connecting these regions. The findings from our study might have valuable implications for targeted treatment of neurocognitive and behavioral deficits in children with prenatal MA exposure. Even so, our results should be interpreted cautiously due to the heterogeneity of the included studies in terms of study populations and methods of analysis.

Nuclear factor-kappa B (NF-κB) in pathophysiology of Parkinson disease: Diverse patterns and mechanisms contributing to neurodegeneration.

Parkinson's disease (PD), the most common movement disorder, comprises several pathophysiologic mechanisms including misfolded alpha-synuclein aggregation, inflammation, mitochondrial dysfunction, and synaptic loss. Nuclear Factor-Kappa B (NF-κB), as a key regulator of a myriad of cellular reactions, is shown to be involved in such mechanisms associated with PD, and the changes in NF-κB expression is implicated in PD. Alpha-synuclein accumulation, the characteristic feature of PD pathology, is known to trigger NF-κB activation in neurons, thereby propagating apoptosis through several mechanisms. Furthermore, misfolded alpha-synuclein released from degenerated neurons, activates several signaling pathways in glial cells which culminate in activation of NF-κB and production of pro-inflammatory cytokines, thereby aggravating neurodegenerative processes. On the other hand, NF-κB activation, acting as a double-edged sword, can be necessary for survival of neurons. For instance, NF-κB activation is necessary for competent mitochondrial function and deficiency in c-Rel, one of the NF-κB proteins, is known to propagate DA neuron loss via several mechanisms. Despite the dual role of NF-κB in PD, several agents by selectively modifying the mechanisms and pathways associated with NF-κB, can be effective in attenuating DA neuron loss and PD, as reviewed in this paper.