Induce Pluripotent Stem Cells (iPSC) Technology in Depression.

Induced pluripotent stem cells (iPSCs) are a promising in vitro model for drug-screening and precision-based psychiatry for the treatment of major depressive disorders (MDD). In this chapter, we explore different uses for iPSC technology, three-dimensional (3D) organoids models, and mesenchymal stem cells therapy in MDD, as well their potential and limitations.

Monitoring anomalies on large-scale energy and water balance components by coupling remote sensing parameters and gridded weather data.

The SAFER (Simple Algorithm for Evapotranspiration Retrieving) algorithm was applied with MODIS images and gridded weather data from 2007 to 2021, to monitor the energy balance components and their anomalies, in the Atlantic Forest (AF) and Caatinga (CT) biomes inside the coastal agricultural growing zone, Northeast Brazil. Considering the long-term data, the Rn values between the biomes are not significantly different, however presenting distinct Rn partitions into latent (λE), sensible (H), and ground (G) heat fluxes between biomes. The Rn values annual averages are 9.40 ± 0.21 and 9.50 ± 0.23 MJ m-2 d-1, for AF and CT, respectively. However, for respectively AF and CT, they are respectively 5.10 ± 1.14 MJ m-2 d-1 and 4.00 ± 0.99 MJ m-2 d-1 for λE; 3.80 ± 1.12 MJ m-2 d-1 and 5.00 ± 1.00 MJ m-2 d-1 for H; 0.50 ± 0.12 MJ m-2 d-1 and 0.40 ± 0.10 MJ m-2 d-1 for G, yielding respective mean evaporative fraction (Ef = λE/(Rn - G) values of 0.60 ± 0.12 and 0.50 ± 0.15. Anomalies on λE, H, and Ef were detected through standardized index for these energy balance components by comparing the results for the years 2018 to 2021 with the long-term values from 2007 to each of these years, showing that the energy fluxes between surfaces and the lower atmosphere, and then the root-zone moisture conditions for both biomes, may strongly vary along seasons and years, with alternate positive and negative anomalies. These assessments are important for water policies as they can picture suitable periods and places for rainfed agriculture as well as the irrigation needs in irrigated agriculture, allowing rational agricultural environmental management while minimizing water competitions among other water users, under climate and land-use changes conditions.

Absence of TNFR1 promotes a protective response in the early phase of hepatic encephalopathy induced by thioacetamide in mice.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome with a wide spectrum of cognitive deficits, motor impairment, and psychiatric disturbances resulting from liver damage. The cytokine TNF has been considered the main cytokine in the development and progression of HE, with a pivotal role in the initiation and amplification of the inflammatory cascade. The aim of the present study was to evaluate the involvement of TNF type 1 receptor (TNFR1) in locomotor deficits and in the levels of TNF, IFN-γ, IL-6, IL-10, IL-12p70, CCL2, CX3CL1 and BDNF from the frontal cortex and hippocampus of TNFR1 knockout mice (TNFR1-/-) mice with HE induced by thioacetamide. Wild-type (WT) animals with HE developed locomotor deficit. The absence of TNFR1 absence of TNFR1 in HE animals attenuated the locomotor activity impairment in parallel with a balanced neuroinflammatory environment 24 h after the administration of thioacetamide. Taken together, the data suggests that the absence of TNFR1 promoted a protective response in the early phase of hepatic encephalopathy induced by thioacetamide in mice.

Influence of carbon content and irradiation modes on the antibiotic removal from water using VIS-activated TiO2/expanded graphite composite photocatalysts.

TiO2/expanded graphite (TiO2/EG) composite films were applied to water treatment for sulfadiazine (SDZ) degradation in a continuous flat plate photochemical reactor. The films were synthesized by sol-gel method and deposited on borosilicate glass by airbrush spray coating technique, forming a TiO2/C heterojunction. Increasing the amount of carbon promoted more efficient photocatalytic removal of SDZ under simulated sunlight, which increased from 9.1% in the absence of carbon to 49.8% for the material containing 7.5% C. From the formation of the TiO2/C heterojunction, morphological modifications, changes in the electronic structure and reduction of the band gap energy were observed. Type-II heterojunction formation was observed. Foreground and background irradiation modes were investigated, and a possible photocatalytic mechanism was proposed. TiO2/7.5 %-EG exhibited the best photocatalytic performance, with the possibility of reuse. The films showed good reusability in the SDZ degradation over 4 photocatalytic cycles. The influence of irradiation modes and the role of oxidizing species were discussed. The results showed that TiO2/EG hybrid films are a promising alternative for practical photocatalytic applications under sunlight.

Rehabilitation Intervention Is Associated With Improved Neurodevelopment and Modulation of Inflammatory Molecules in Children With Cerebral Palsy.

AIM: To evaluate the effects of systematic rehabilitation on both the neuropsychomotor development, and on the peripheral response from immunological and neuroplastic mediators in children with cerebral palsy. METHODS: This is a prospective cohort study with 90 children with cerebral palsy at 18 months of age. Sixty children received rehabilitation for 6 months, and they were compared to 30 children that were placed in the waiting list. Peripheral biomarkers and neuropsychomotor parameters were compared between the Rehab vs the Nonrehab groups at baseline and at 6 months. RESULTS: Results showed higher Bayley III scores in the Rehab group, with significant differences in inflammatory and neurotrophic biomarkers between groups. Rehabilitation was associated to decreased levels of IL-12p70, IL-6, IL-1ß, CXCL8 IL-8, and CXCL9/MIG and increased levels of BDNF and GDNF. Nonrehab children had stable immune molecule levels but decreased BDNF levels over time. CONCLUSION: Rehabilitation improved neurodevelopment parameters and modulated levels of inflammatory (↓) and neurotrophic (↑) biomarkers.

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM).

A new paradigm for energy is underway demanding decarbonized energy systems. Some of them rely on emerging electrochemical devices, crucial in hydrogen technologies, including fuel cells, CO2 and water electrolysers, whose applications and performances depend on key components such as their separators/ion-exchange membranes. The most studied and already commercialized Nafion membrane shows great chemical stability, but its water content limits its high proton conduction to a limited range of operating temperatures. Here, we report the synthesis of a new series of triazinephosphonate derivatives and their use as dopants in the preparation of new modified Nafion membranes. The triazinephosphonate derivatives were prepared by substitution of chlorine atoms in cyanuric chloride. Diverse conditions were used to obtain the trisubstituted (4-hydroxyphenyl)triazinephosphonate derivatives and the (4-aminophenyl)triazinephosphonate derivatives, but with these amino counterparts, only the disubstituted compounds were obtained. The new modified Nafion membranes were prepared by casting incorporation of the synthesized 1,3,5-triazinephosphonate (TPs) derivatives. The evaluation of the proton conduction properties of the new membranes and relative humidity (RH) conditions and at 60 °C, showed that they present higher proton conductivities than the prepared Nafion membrane and similar or better proton conductivities than commercial Nafion N115, in the same experimental conditions. The Nafion-doped membrane with compound TP2 with a 1.0 wt % loading showed the highest proton conductivity with 84 mS·cm-1.

Genetic ablation of the isoform γ of PI3K decreases antidepressant efficacy of ketamine in male mice.

About one-third of major depressive disorder (MDD) patients demonstrate unresponsiveness to classic antidepressants, and even the clinical efficacy of fast-acting drugs such as ketamine varies significantly among patients with treatment-resistant depression. Nevertheless, the lack of suitable animal models that mimic a possible ketamine-resistant phenotype challenges the understanding of resistance to drug treatment. In this study, we showed that PI3Kγ knock-out (KO) mice do not respond to classical doses of ketamine and classical antidepressants. PI3Kγ KO mice were unresponsive to both the rapid and sustained antidepressant-like effects of a single dose of ketamine in the forced swimming test. Additionally, they were unresponsive to the antidepressant-like effects induced by the tricyclic antidepressant imipramine and the selective serotonin reuptake inhibitor fluoxetine. However, acute pharmacological inhibition of PI3Kγ did not block the antidepressant-like effect of ketamine, showing that a chronic deficiency of the PI3Kγ-mediated pathway is necessary for the effects of classic doses of ketamine and antidepressants. Therefore, we propose that PI3Kγ participates in the antidepressant activity and is likely implicated in the neurobiology and phenotype observed in patients with MDD who demonstrate treatment resistance.

Loop diuretic discontinuation in chronic heart failure patients: A retrospective study.

INTRODUCTION AND OBJECTIVES: The use of loop diuretics is central in managing congestion in heart failure (HF), but their impact on prognosis remains unclear. In euvolemic patients, dose reduction is recommended, but there is no recommendation on their discontinuation. This study aims to assess the impact of loop diuretic discontinuation on the prognosis of outpatients with HF with reduced ejection fraction. METHODS: This retrospective cohort study collected data from medical records of patients followed in an outpatient HF clinic at a university hospital center. Patients were included if they had been on loop diuretics and these were discontinued. Demographic, clinical and laboratory data were collected, and number and type of congestive events during the one-year period after discontinuation were recorded. RESULTS: Among 265 patients on loop diuretics, almost half (129) discontinued them at some point. Patients had optimized medical therapy, low median age, low New York Heart Association class, low B-type natriuretic peptide values, normal blood pressure, controlled heart rate and kidney function within normal limits. Among 122 patients with one year of follow-up, 18 (14.8%) had a congestive event. Fifteen events (83.3%) were low-dose diuretic reinitiation at a scheduled visit. There were only three worsening heart failure events (2.5%) during the one-year period. A significant improvement in kidney function from discontinuation to the one-year follow-up appointment was also observed. CONCLUSIONS: In our cohort, loop diuretic discontinuation was possible and safe in a large proportion of patients. The results should be interpreted with caution and cannot be extrapolated to a broader population of HF patients.

Targeting inflammasome complexes as a novel therapeutic strategy for mood disorders.

INTRODUCTION: Inflammasome complexes, especially NLRP3, have gained great attention as a potential therapeutic target in mood disorders. NLRP3 triggers a caspase 1-dependent release of the inflammatory cytokines IL-1ß and IL-18, and seems to interact with purinergic and kynurenine pathways, all of which are implicated in mood disorders development and progression. AREAS COVERED: Emerging evidence supports NLRP3 inflammasome as a promising pharmacological target for mood disorders. We discussed the available evidence from animal models and human studies and provided a reflection on drawbacks and perspectives for this novel target. EXPERT OPINION: Several studies have supported the involvement of NLRP3 inflammasome in MDD. However, most of the evidence comes from animal models. The role of NLRP3 inflammasome in BD as well as its anti-manic properties is not very clear and requires further exploration. There is evidence of anti-manic effects of P2×R7 antagonists associated with reduction in the brain levels of IL-1ß and TNF-α in a murine model of mania. The involvement of other NLRP3 inflammasome expressing cells besides microglia, like astrocytes, and of other inflammasome complexes in mood disorders also deserves further investigation. Preclinical and clinical characterization of NLRP3 and other inflammasomes in mood disorders is needed before considering translational approaches, including clinical trials.

Physical comorbidities of older age bipolar disorder (OABD) patients: A global replication analysis of prevalence and sex differences.

OBJECTIVES: To compare the prevalence of physical morbidities between older aged patients with bipolar disorder (OABD) and non-psychiatric comparisons (NC), and to analyze sex differences in prevalence. METHODS: OABD was defined as bipolar disorder among adults aged ≥50 years. Outcomes analyzed were the prevalence of diseases affecting the cardiovascular, respiratory, gastrointestinal, genitourinary, renal, musculoskeletal, and endocrine systems. The analysis used cross-sectional data of OABD participants (n = 878; mean age 60.9 ± 8.0 years, n = 496 (56%) women) from the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) dataset and NC participants recruited at the same sites (n = 355; mean age 64.4 ± 9.7 years, n = 215 (61%) women). RESULTS: After controlling for sex, age, education, and smoking history, the OABD group had more cardiovascular (odds ratio [95% confidence interval]: 2.12 [1.38-3.30]), renal (5.97 [1.31-43.16]), musculoskeletal (2.09 [1.30-3.43]) and endocrine (1.90 [1.20-3.05]) diseases than NC. Women with OABD had more gastrointestinal (1.56 [0.99-2.49]), genitourinary (1.72 [1.02-2.92]), musculoskeletal (2.64 [1.66-4.37]) and endocrine (1.71 [1.08-2.73]) comorbidities than men with OABD, when age, education, smoking history, and study site were controlled. CONCLUSIONS: This replication GAGE-BD study confirms previous findings indicating that OABD present more physical morbidities than matched comparison participants, and that this health burden is significantly greater among women.

Nigrostriatal Inflammation Is Associated with Nonmotor Symptoms in an Experimental Model of Prodromal Parkinson's Disease.

Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson's disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage. The current study aimed to characterize the behavioral and cognitive changes in a toxin-induced model of prodromal PD-like syndrome. We also sought to investigate the role of neuroinflammation in prodromal PD-related NMS. Male mice were subjected to bilateral intranasal infusion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline (control group), followed by comprehensive behavioral, pathological and neurochemical analysis. Intranasal MPTP infusion was able to cause the loss of dopaminergic neurons in the substantia nigra (SN). In parallel, it induced impairment in olfactory discrimination and social memory consolidation, compulsive and anxiety-like behaviors, but did not influence motor performance. Iba-1 and GFAP expressions were increased in the SN, suggesting an activated state of microglia and astrocytes. Consistent with this, MPTP mice had increased levels of IL-10 and IL-17A, and decreased levels of BDNF and TrkA mRNA in the SN. The striatum showed increased IL-17A, BDNF, and NFG levels compared to control mice. In conclusion, neuroinflammation may play an important role in the early stage of experimental PD-like syndrome, leading to cognitive and behavioral changes. Our results also indicate that intranasal administration of MPTP may represent a valuable mouse model for prodromal PD.

Post-COVID-19 cognitive symptoms in patients assisted by a teleassistance service: a retrospective cohort study.

Introduction: Four years after the onset of the COVID-19 pandemic, the frequency of long-term post-COVID-19 cognitive symptoms is a matter of concern given the impact it may have on the work and quality of life of affected people. Objective: To evaluate the incidence of post-acute COVID-19 cognitive symptoms, as well as the associated risk factors. Methods: Retrospective cohort, including outpatients with laboratory-confirmed COVID-19 and who were assisted by a public telehealth service provided by the Telehealth Network of Minas Gerais (TNMG), during the acute phase of the disease, between December/2020 and March/2022. Data were collected through a structured questionnaire, applied via phone calls, regarding the persistence of COVID-19 symptoms after 12 weeks of the disease. Cognitive symptoms were defined as any of the following: memory loss, problems concentrating, word finding difficulties, and difficulty thinking clearly. Results: From 630 patients who responded to the questionnaire, 23.7% presented cognitive symptoms at 12 weeks after infection. These patients had a higher median age (33 [IQR 25-46] vs. 30 [IQR 24-42] years-old, p = 0.042) with a higher prevalence in the female sex (80.5% vs. 62.2%, p < 0.001) when compared to those who did not present cognitive symptoms, as well as a lower prevalence of smoking (8.7% vs. 16.2%, p = 0.024). Furthermore, patients with persistent cognitive symptoms were more likely to have been infected during the second wave of COVID-19 rather than the third (31.0% vs. 21.3%, p = 0.014). Patients who needed to seek in-person care during the acute phase of the disease were more likely to report post-acute cognitive symptoms (21.5% vs. 9.3%, p < 0,001). In multivariate logistic regression analysis, cognitive symptoms were associated with female sex (OR 2.24, CI 95% 1.41-3.57), fatigue (OR 2.33, CI 95% 1.19-4.56), depression (OR 5.37, CI 95% 2.19-13.15) and the need for seek in-person care during acute COVID-19 (OR 2.23, CI 95% 1.30-3.81). Conclusion: In this retrospective cohort of patients with mostly mild COVID-19, cognitive symptoms were present in 23.7% of patients with COVID-19 at 12 weeks after infection. Female sex, fatigue, depression and the need to seek in-person care during acute COVID-19 were the risk factors independently associated with this condition.

Attenuation photochemical potential of Pontal of Paranapanema river waters (Brazil) from agrochemicals: geographical and temporal assessment.

Knowledge of the environmental photochemical fate of pesticides is essential to assess their potential impacts. However, there are few studies in the literature focused on the photochemical attenuation of micropollutants in Brazilian rivers. In this context, this study characterized the surface waters of the Pontal of Paranapanema region (region which concentrates more than 80% of Brazilian sugarcane cultivations), in order to determine its photochemical attenuation potential against micropollutants in different seasons. Thus, the steady-state concentrations of the photochemically produced reactive intermediates (PPRIs) (hydroxyl radical, HO•; singlet oxygen, 1O2, and triplet-excited state chromophoric dissolved organic matter, 3CDOM*), formed in the rivers, were simulated by using the APEX model (Aquatic Photochemistry of Environmentally-occurring Xenobiotics), considering the sunlight irradiance, water chemistry, and depth. Based on our simulations, these concentrations vary between 0.35 × 10-15 and 4.52 × 10-14 mol L-1 for HO•, 1.3 × 10-15 and 1.2 × 10--14 mol L-1 for 3CDOM*, and 2.5 × 10-15 and 2.5 × 10-14 mol L-1 for 1O2. Finally, mathematical simulations were used for predicting persistence of pesticides atrazine (ATZ) and diuron (DIR) in Pontal of Paranapanema surface waters and the half-life times (t1/2) of the pollutants ranged from a few hours to one week.

Treatment resistant late-life depression: A narrative review of psychosocial risk factors, non-pharmacological interventions, and the role of clinical phenotyping.

BACKGROUND: Treatment resistant depression (TRD) is a subset of major depressive disorder (MDD) in which symptoms do not respond to front line therapies. In older adults, the assessment and treatment of TRD is complicated by psychosocial risk factors unique to this population, as well as a relative paucity of research. METHODS: Narrative review aimed at (1) defining TRLLD for clinical practice and research; (2) describing psychosocial risk factors; (3) reviewing psychological and non-pharmacological treatments; (4) discussing the role of clinical phenotyping for personalized treatment; and (5) outlining research priorities. RESULTS: Our definition of TRLLD centers on response to medication and neuromodulation in primary depressive disorders. Psychosocial risk factors include trauma and early life adversity, chronic physical illness, social isolation, personality, and barriers to care. Promising non-pharmacological treatments include cognitive training, psychotherapy, and lifestyle interventions. The utility of clinical phenotyping is highlighted by studies examining the impact of comorbidities, symptom dimensions (e.g., apathy), and structural/functional brain changes. LIMITATIONS: There is a relative paucity of TRLLD research. This limits the scope of empirical data from which to derive reliable patterns and complicates efforts to evaluate the literature quantitatively. CONCLUSIONS: TRLLD is a complex disorder that demands further investigation given our aging population. While this review highlights the promising breadth of TRLLD research to date, more research is needed to help elucidate, for example, the optimal timing for implementing risk mitigation strategies, the value of collaborative care approaches, specific treatment components associated with more robust response, and phenotyping to help inform treatment decisions.

Bipolar symptoms, somatic burden and functioning in older-age bipolar disorder: A replication study from the global aging & geriatric experiments in bipolar disorder database (GAGE-BD) project.

OBJECTIVES: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean ± standard deviation age 47.2 ± 13.5, 65% women, 49% aged over 50) dataset. DESIGN/METHODS: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). RESULTS: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p ≤ 0.001, depression p ≤ 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. CONCLUSIONS: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning.

Treatment of Depression in Huntington's Disease: A Systematic Review.

Depression is a common psychiatric disorder among individuals with Huntington's disease (HD). Depression in HD and major depressive disorder appear to have different pathophysiological mechanisms. Despite the unique pathophysiology, the treatment of depression in HD is based on data from the treatment of major depressive disorder in the general population. The objective of this systematic review was to conduct a comprehensive evaluation of the available evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies on the treatment of depression in HD were identified by searching MEDLINE, Embase, and PsycInfo. The initial search yielded 2,771 records, 41 of which were ultimately included. There were 19 case reports, seven case series, three cross-sectional studies, one qualitative study, nine nonrandomized studies, and two randomized trials among the included studies. The most common assessment tools were the Hospital Anxiety and Depression Scale (N=8), the Beck Depression Inventory (N=6), and the Hamilton Depression Rating Scale (N=6). Only 59% of the included studies assessed depressive symptoms with a scoring system. The pharmacological options for the treatment of depression included antidepressants and antipsychotics. Nonpharmacological approaches were multidisciplinary rehabilitation, psychotherapy, and neurostimulation. Limited evidence on the treatment of depression in HD was available, and this literature consisted mainly of case reports and case series. This systematic review highlights the knowledge gap and the pressing need for HD-specific research to determine the efficacy of treatment approaches for depression in HD.

Management of anhedonia after epilepsy surgery.

Anhedonia is clinically defined as difficulty or inability to feel pleasure or to be motivated to perform activities that were previously pleasurable. Anhedonia is a core feature of depressive disorders but can be present in other conditions such as substance use and anxiety disorders. Herein we report the case of a 34-year-old female who developed marked anhedonia after left cortico-amygdalohippocampectomy. Despite optimal seizure control, the person struggled with anhedonia and other depressive symptoms. After ruling out medico-neurologic complications, she was prescribed with a selective serotonin reuptake inhibitor and cognitive-behavioral therapy. Anhedonia can be a challenging neuropsychiatric presentation that requires ruling out the effects of antiseizure medications, neurosurgery, and other drugs before prescribing antidepressants.

Cognition in older age bipolar disorder: An analysis of archival data across the globe.

BACKGROUND: Cognitive deficits in bipolar disorder (BD) impact functioning and are main contributors to disability in older age BD (OABD). We investigated the difference between OABD and age-comparable healthy comparison (HC) participants and, among those with BD, the associations between age, global cognitive performance, symptom severity and functioning using a large, cross-sectional, archival dataset harmonized from 7 international OABD studies. METHODS: Data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database, spanning various standardized measures of cognition, functioning and clinical characteristics, were analyzed. The sample included 662 euthymic to mildly symptomatic participants aged minimum 50years (509 BD, 153 HC), able to undergo extensive cognitive testing. Linear mixed models estimated associations between diagnosis and global cognitive performance (g-score, harmonized across studies), and within OABD between g-score and severity of mania and depressive symptoms, duration of illness and lithium use and of global functioning. RESULTS: After adjustment for study cohort, age, gender and employment status, there was no significant difference in g-score between OABD and HC, while a significant interaction emerged between employment status and diagnostic group (better global cognition associated with working) in BD. Within OABD, better g-scores were associated with fewer manic symptoms, higher education and better functioning. LIMITATIONS: Cross-sectional design and loss of granularity due to harmonization. CONCLUSION: More research is needed to understand heterogenous longitudinal patterns of cognitive change in BD and understand whether particular cognitive domains might be affected in OABD in order to develop new therapeutic efforts for cognitive dysfunction OABD.

Risk of MS relapse and deterioration after COVID-19: A systematic review and meta-analysis.

BACKGROUND: Upper respiratory viral infections have long been considered triggers for multiple sclerosis (MS) relapse and exacerbation. The possible effects of SARS-CoV-2 infection on MS relapse and deterioration remain controversial. METHODS: We systematically searched PubMed, Scopus, Embase, Cochrane, and Web of Science databases to find relevant studies assessing changes in relapse rates or Expanded Disability Status Scale (EDSS) following COVID-19 in people with MS. Meta-analyses were performed, and to investigate sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. RESULTS: We included 14 studies in our systematic review and meta-analysis. The meta-analysis demonstrated that COVID-19 was not associated with a rise in relapse rate (risk ratio (RR): 0.97, 95 % confidence interval (CI): 0.67, 1.41, p-value: 0.87) or a rise in EDSS (standardized mean difference (SMD): -0.09, 95 % CI: -0.22, 0.03, p-value: 0.13). The analysis of EDSS changes indicated a significant heterogeneity (I2: 55 %, p-value: 0.01). Other analyses were not statistically significant. CONCLUSIONS: COVID-19 infection was not associated with an increased risk of relapse and clinical deterioration in people with MS.

Effect of smoking on Brain-Derived Neurotrophic Factor (BDNF) blood levels: A systematic review and meta-analysis.

BACKGROUND: Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that plays a crucial role in neuronal survival and plasticity. Previous studies have suggested that smoking may influence BDNF levels, but the findings have been inconsistent. METHODS: A comprehensive search of electronic databases was conducted to identify relevant studies. Inclusion criteria were applied to select studies that investigated the relationship between smoking and blood levels of BDNF. A random-effects model was used to estimate the overall effect size. RESULTS: A total of 23 studies were included. The meta-analysis revealed a significant association between smoking and increased blood levels of BDNF (standardized mean difference [SMD] = -0.38, 95 % confidence interval [CI] 0.15 to 0.62, p = 0.002). Subgroup analyses based on BDNF source showed a significant increase in plasma-derived BDNF levels (SMD = 1.02, 95 % CI 0.50 to 1.53, p = 0.0001), while no significant difference was observed in serum-derived BDNF levels (SMD = 0.02, 95 % CI -0.19 to 0.22, p = 0.87). The pooled analysis revealed a non-significant difference in blood levels of BDNF between former smokers and non-smokers (random-effects model, SMD = 0.21, 95 % CI -0.04 to 0.46, p = 0.1). CONCLUSION: Smokers exhibited significantly higher plasma levels of BDNF compared to non-smokers. Further research is needed to elucidate the underlying mechanisms and explore the potential therapeutic implications of targeting BDNF in smoking.