Immunoinflammatory and oxidative alterations in subjects with schizophrenia under clozapine: A meta-analysis.

Clozapine presents immunoregulatory properties not well understood. To address this issue, we performed this systematic review to evaluate the immune alterations induced by clozapine and its relationship with the drug's clinical response and compare it with other antipsychotics. Our systematic review has selected nineteen studies meeting the inclusion criteria, from which eleven were included in the meta-analysis, totalizing 689 subjects distributed over three different comparisons. The results revealed that clozapine treatment activates the compensatory immune-regulatory system (CIRS) (Hedges's g = +1.049; CI +0.62 - +1.47, p < 0.001) but has no effects on the immune-Inflammatory Response System (IRS) (Hedges's g= -0.27; CI -1.76 - +1.22, p = 0.71), M1 macrophage (Hedges's g= -0.32; CI -1.78 - +1.14, p = 0.65) and Th1 (Hedge's g = 0.86; CI -0.93 - +1.814, p = 0.07) profiles. Comparing clozapine-treated patients with other anti-psychotics-treated, plasma levels of interleukin (IL)-6 were greater in the clozapine group (Hedge's g = 0.75; CI 0.35 - 1.15, p<0.001). In addition, higher IL-6 plasma levels after four weeks of clozapine treatment were related to the development of clozapine-induced fever; however, IL-6 levels recovered to baseline in 6-10 weeks due to an unexplained compensatory mechanism. In conclusion, our results show that clozapine treatment causes a time-dependent mixed immune profile characterized by increased IL-6 levels and CIRS activation, which may contribute to this drug mechanism of action and adverse effects. Future studies must be designed to investigate the relationship between clozapine-induced immune alterations and symptom remission, treatment resistance, and adverse effects, given the importance of this drug for treating resistant schizophrenia.

"[I] don't wanna just be like a cog in the machine": Narratives of autism and skilled employment.

LAY ABSTRACT: Autistic people are less likely to be employed than the general population. Autistic people with skilled training (e.g. training for jobs in acting, plumbing, science, or social work) might be even less likely to get a good job in their field. Little is known about the experiences of autistic people in skilled employment or what employment success means to them. We interviewed 45 autistic people with skilled training in a wide range of fields, 11 job supervisors, and 8 topic experts. We asked them about their experiences, what they felt helped them to be successful at work, and what employment success means to them. Participants talked about the high stakes of disclosure, taking unconventional pathways to careers, disconnects with service and support systems, mental health challenges from trauma and burnout, the autistic advantages in the workplace, and complex dimensions of discrimination. Participants said success meant opportunities for growth, good work/life balance, financial independence, sense of community, and feeling valued, accepted, and like their work had meaning. Things that helped them be successful included flexible, accepting workplaces, supportive and respectful supervisors, and direct communication. What we learned suggests that an individualized, wholistic approach to autism employment intervention that considers both employers and employees and employee mental health could be useful. We also recommend more research into disclosure and destigmatizing disability at work.

Advancing Health Equity And Reducing Health Disparities For People With Disabilities In The United States.

Definitions of disability have evolved over time. Consistent with the biopsychosocial model used by the World Health Organization, we conceptualize disability as an interaction between a person's functional impairments or chronic health conditions and the physical and social environment. Having a disability is not synonymous with poor health, and maintaining and improving health is equally important for both people with and people without disabilities. In this article we review estimates of disability prevalence in the US and present evidence of differences in prevalence by race, ethnicity, and sexual orientation; health disparities by disability status and type of disability; and health disparities for people whose disability intersects with other forms of marginalization. We suggest policy changes to advance equity, reduce disparities, and enhance the health and well-being of all Americans with disabilities.

COVID-19 Diagnostics: Past, Present, and Future.

In winter of 2020, SARS-CoV-2 emerged as a global threat, impacting not only health but also financial and political stability. To address the societal need for monitoring the spread of SARS-CoV-2, many existing diagnostic technologies were quickly adapted to detect SARS-CoV-2 RNA and antigens as well as the immune response, and new testing strategies were developed to accelerate time-to-decision. In parallel, the infusion of research support accelerated the development of new spectroscopic methods. While these methods have significantly reduced the impact of SARS-CoV-2 on society when coupled with behavioral changes, they also lay the groundwork for a new generation of platform technologies. With several epidemics on the horizon, such as the rise of antibiotic-resistant bacteria, the ability to quickly pivot the target pathogen of this diagnostic toolset will continue to have an impact.

Malpractice and socioeconomic aspects in neurosurgery: a developing-country reality.

OBJECTIVE: Neurosurgery occupies a prominent place in medical malpractice, but cases are still underreported in Brazil. This study describes the socioeconomic issues of medical malpractice in neurosurgery procedures and how they culminate in unfavorable outcomes in a developing country. METHODS: The authors analyzed 112 neurosurgical procedures listed in the Brazilian Hospital Information System (Sistema de Informações Hospitalares do Sistema Único de Saúde [SIHSUS]) records in the DATASUS (Departamento de Informática do SUS) database between January 2008 and February 2020. Malpractice data were collected using the JusBrasil platform, with the authors searching the name of each of the 112 neurosurgical procedures plus "medical malpractice" among the jurisprudence records for January 2008 to February 2020. A simple linear regression analysis was performed using appropriate software. Analyses were considered statistically significant at p < 0.05. RESULTS: According to DATASUS, 842,041 neurosurgical procedures were performed by the Brazilian Unified Health System between January 2008 and February 2020. The mean hospitalization cost for neurosurgical procedures was $714.06, and the average amount paid to professionals per procedure was $145.28 with variations according to the type of practice (public or private) in which they were performed, the complexity of the procedure, and the Brazilian region. The mortality rate and mean length of stay for neurosurgical procedures were 11.37% and 10.15 days, respectively. There were 79 medical malpractice lawsuits in the studied period. In these lawsuits, 26.58% of the court decisions were unfavorable to the neurosurgeons, with a mean compensation per procedure 15 times higher than the median value paid for all professionals in a neurosurgical procedure. The spine subspecialty had more lawsuits, and the brain tumor subspecialty had the most expensive compensation.A lack of resources in public healthcare negatively impacts inpatient care. The mortality rate was 1.5 times higher in public practice than in private practice and was inversely proportional to the MTCs paid for the neurosurgical procedure. Patients with the lower educational levels associated with limited access to good medical care could reflect the lower plaintiff motivation in regions with a low gross domestic product and Human Development Index. In most cases, there is no understanding from either the patient or his family about the health-disease process, nor that there was medical malpractice committed by the physician to be sued. CONCLUSIONS: The socioeconomic inequalities and the population's low awareness of their rights could explain the few malpractice cases reported in Brazil. The authors recommend better decisions regarding the investments to be made in neurosurgical procedures to reduce malpractice lawsuits.

Effects of coal ash supplementation on aerobic granular sludge cultivated in a simultaneous fill/draw sequencing batch reactor / Efeitos da suplementação de cinzas de carvão mineral em lodo granular aeróbio cultivado em reator em batelada sequencial de alimentação/descarte simultâneos

ABSTRACT This study aimed to verify if coal ash, a residue from thermal power plants, could act as a granulation nucleus, cations source, and abrasive element to favor granules formation and stability in aerobic granular sludge (AGS) systems. Two simultaneous fill/draw sequencing batch reactors (SBRs) (R1 and R2) were operated with 6-h cycles, i.e., the filling and drawing phases occurred simultaneously, followed by the reaction and settling phases. R1 was maintained as control, while R2 was supplemented with coal ash (1 g·L-1) on the first day of operation. Granulation was achieved in both reactors, and no significant differences were observed in terms of settleability, biomass retention, morphology, resistance to shear, and composition of the EPS matrix. However, the ash addition did not change the settleability, biomass retention, granule morphology, shear resistance, and extracellular polymeric substances (EPS) content significantly. COD removal was high (≥ 90%), while nitrogen (~50%) and phosphorus (~40%) removals were low, possibly due to the presence of nitrate during the anaerobic phase. With granulation, microbial population profile was altered, mainly at the genus level. In general, the operational conditions had a more considerable influence over granulation than the ash addition. The possible reasons are because the ash supplementation was performed in a single step, the low sedimentation rate of this particular residue, and the weak interaction between the ash and the EPS formed in the granular sludge. These factors appear to have decreased or prevented the action of the ash as granulation nucleus, source of cations, and abrasive element.

RESUMO O objetivo deste estudo foi verificar se a cinza de carvão mineral, um resíduo de usinas termelétricas, poderia atuar como núcleo de granulação, fonte de cátions e elemento abrasivo em sistemas de lodo granular aeróbio (LGA) para favorecer a formação e estabilidade dos grânulos. Dois reatores em batelada sequencial (RBS) (R1 e R2) foram operados em regime de alimentação/descarte simultâneos com ciclos de 6 h, ou seja, as fases de alimentação e descarte do efluente ocorreram simultaneamente, seguidas das fases de reação e de decantação. O R1 foi mantido como controle, enquanto o R2 foi suplementado com as cinzas (1 g·L-1) no primeiro dia de operação. A granulação foi alcançada em ambos os reatores, não havendo diferenças marcantes em termos de sedimentabilidade, retenção de biomassa, morfologia do grânulo, resistência ao cisalhamento e conteúdo de substâncias poliméricas extracelulares (SPE). A remoção de DQO foi alta (≥ 90%), enquanto as remoções de nitrogênio (~50%) e fósforo (~40%) foram baixas, possivelmente pela presença de nitrato na fase anaeróbia. Após a granulação, o perfil da comunidade microbiana mudou, especialmente em termos de gênero. Globalmente, as condições operacionais tiveram maior influência sobre a granulação do que a adição das cinzas, possivelmente porque elas só foram adicionadas uma vez e possuem baixa velocidade de sedimentação, bem como devido a uma fraca interação das cinzas com a matriz de SPE formada no lodo aeróbio. Esses fatores podem ter diminuído, ou mesmo impedido, a ação das cinzas como núcleo de grânulo, fonte de cátions ou elemento abrasivo.

Effect of calcium addition on the formation and maintenance of aerobic granular sludge (AGS) in simultaneous fill/draw mode sequencing batch reactors (SBRs).

This work investigated the effect of Ca2+ (100 mg L-1) addition on the formation and maintenance of aerobic granular sludge in a simultaneous fill/draw mode sequencing batch reactor (SBR), operated with a low liquid upflow velocity (0.92 m h-1), in order to verify if Ca2+ presence compensates the low selection pressure imposed. Additionally, carbon and nutrients removals, granules characteristics and microbial community were evaluated. For this, two SBRs (R1, control, and R2, Ca2+-supplemented) were operated (6-h cycle). In general, Ca2+ supplementation affected positively the sludge settleability, although a larger fraction of inert solids was found in the granules. The total extracellular polymeric substances were the same for both reactors, and no remarkable differences were observed between their polysaccharides and proteins contents. Overall, Ca2+ addition in a simultaneous fill/draw mode SBR neither accelerated the granule formation nor improved the operational performance. The microbial community structure, especially in terms of bioactivity, was not affected as well. Therefore, the effect of divalent cations might be more pronounced in conventional SBRs, in which the selection pressure is higher.