A model of hemodialysis after acute kidney injury in rats.

BACKGROUND: Acute kidney injury (AKI) is frequent among critically ill patients. Renal replacement therapy (RRT) is often required to deal with severe complications of AKI. This technique is however associated with side effects such as hemodynamic instability and delayed renal recovery. In this study, we aimed to describe a novel model of hemodialysis in rats with AKI and depict a dialysis membrane performance. METHODS: Eighteen Sprague-Dawley rats received 0.75% adenine-rich diet to induce AKI. After 2 weeks, nine underwent an arterio-venous extracorporeal circulation (ECC) (ECC group) for 2 h without a dialysis membrane on the circuit and nine received a hemodialysis session (HD group) for 2 h with an ECC circuit. All rats were hemodynamically monitored, and glomerular filtration rate (GFR) was measured by transcutaneous fluorescence after the injection of FITC-Sinistrin. Blood samples were collected at different time points to assess serum creatinine and serum urea concentrations and to determine the Kt/V. Sinistrin concentration was also quantified in both plasma and dialysis effluent. RESULTS: After 2 weeks of adenine-rich diet, rats exhibited a decrease in GFR. Both serum urea and serum creatinine concentrations increased in the ECC group but remained stable in the HD group. We found no significant difference in serum creatinine and serum urea concentrations between groups. At the end of experiments, mean serum urea was 36.7 mmol/l (95%CI 19.7-46.9 mmol/l) and 23.6 mmol/l (95%CI 15.2-33.5 mmol/l) in the ECC and HD groups, respectively (p = 0.15), and mean serum creatinine concentration was 158.0 µmol/l (95%CI 108.1-191.9 µmol/l) and 114.0 µmol/l (95%CI 90.2-140.9 µmol/l) in the ECC and HD groups, respectively (p = 0.11). The Kt/V of the model was estimated at 0.23. Sinistrin quantity in the ultrafiltrate raised steadily during the dialysis session. After 2 h, the median quantity was 149.2 µg (95% CI 99.7-250.3 µg). CONCLUSIONS: This hemodialysis model is an acceptable compromise between the requirement of hemodynamic tolerance which implies reducing extracorporeal blood volume (using a small dialyzer) and the demonstration that diffusion of molecules through the membrane is achieved.

Radiographic measurement of the congruence angle according to Merchant: validity, reproducibility, and limits.

PURPOSE: The objective of this study was to analyze the intra- and interobserver variability of this measurement according to a strict methodology and on a representative sample of the general population, as well as to identify the possible difficulties of measurement in case of patellar or trochlear dysplasia. METHODS: This observational study involved radiographic analysis by three independent observers of a total of 50 patients who had a loaded patellofemoral X-ray taken with the knee flexed to 45°. An initial reading was taken to measure the angle of the trochlear sulcus, the Merchant angle, and to classify the knees according to a possible trochlear dysplasia and/or patellar dysplasia according to Wiberg. A second measurement was then performed to analyze intraobserver agreement. Interobserver agreement was measured on all radiographic measurements (n = 100). RESULTS: The Merchant patellofemoral congruence angle showed good intraobserver concordance ranging from 0.925 (95% CI 0.868-0.957) to 0.942 (95% CI 0.898-0.967), as well as interobserver concordance ranging from 0.795 (95% CI 0.695-0.862) to 0.914 (95% CI 0.872-0.942). Poor results were found in terms of interobserver concordance on the measurement of the Merchant angle in case of stage 3 Wiberg patella ranging from 0.282 (95% CI -0.920 to 0.731) to 0.611 (95% CI 0.226-0.892). CONCLUSION: Congruence angle is one of most commonly used measurements for patellar tracking. However, the convexity of the patellar surface makes it difficult to identify the patellar apex on its intraarticular facet, making the measurement of the Merchant congruence angle unreliable and not very reproducible in cases of stage 3 Wiberg patella. Registration N°IRB 2021/139.

The impact of parent history of severe mental illness on schizophrenia outcomes: results from the real-world FACE-SZ cohort.

Parent history of severe mental illness (PHSMI) may have long-term consequences in adult offspring due to genetic and early environmental factors in preliminary studies. To compare the outcomes associated in subjects with PHSMI to those in patients without PHSMI. The participants with schizophrenia and schizoaffective disorders were recruited in the ongoing FACE-SZ cohort at a national level (10 expert centers) and evaluated with a 1-day-long standardized battery of clinician-rated scales and patient-reported outcomes. PHSMI was defined as history of schizophrenia or bipolar disorders in at least one parent and was included as explanatory variable in multivariate models. Of the 724 included patients, 78 (10.7%) subjects were classified in the PHSMI group. In multivariate analyses, PHSMI patients had a better insight into schizophrenia and the need for treatment and reported more often childhood trauma history compared to patients without PHSMI. More specifically, those with paternal history of SMI reported more severe outcomes (increased childhood physical and emotional abuses, comorbid major depression and psychiatric hospitalizations). PHSMI is associated with increased risk of childhood trauma, major depressive disorder and psychiatric hospitalization and better insight in individuals with schizophrenia. Specific public health prevention programs for parents with SMI should be developed to help protect children from pejorative psychiatric outcomes. PHSMI may also explain in part the association between better insight and increased depression in schizophrenia.

3-year incidence and predictors of metabolic syndrome in schizophrenia in the national FACE-SZ cohort.

AIMS: Metabolic Syndrome (MetS) is a major health epidemic of Western countries and patients with schizophrenia is a particularly vulnerable population due to lifestyle, mental illness and treatment factors. However, we lack prospective data to guide prevention. The aim of our study is then to determine MetS incidence and predictors in schizophrenia. METHOD: Participants were recruited in 10 expert centers at a national level and followed-up for 3 years. MetS was defined according to the International Diabetes Federation criteria. Inverse probability weighting methods were used to correct for attrition bias. RESULTS: Among the 512 participants followed-up for 3 years, 77.9% had at least one metabolic disturbance. 27.5% were identified with MetS at baseline and excluded from the analyses. Among the rest of participants (N = 371, mean aged 31.2 (SD = 9.1) years, with mean illness duration of 10.0 (SD = 7.6) years and 273 (73.6%) men), MetS incidence was 20.8% at 3 years and raised to 23.6% in tobacco smokers, 29.4% in participants receiving antidepressant prescription at baseline and 42.0% for those with 2 disturbed metabolic disturbances at baseline. Our multivariate analyses confirmed tobacco smoking and antidepressant consumption as independent predictors of MetS onset (adjusted odds ratios (aOR) = 3.82 [1.27-11.45], p = 0.016, and aOR = 3.50 [1.26-9.70], p = 0.0158). Antidepressant prescription predicted more specifically increased lipid disturbances and paroxetine was associated with the highest risk of MetS onset. CONCLUSION: These results are an alarm call to prioritize MetS prevention and research in schizophrenia. We have listed interventions that should be actively promoted in clinical practice.

Self-assembly of gold nanoparticles by chitosan for improved epinephrine detection using a portable surface enhanced Raman scattering device.

Surface enhanced Raman scattering (SERS) has become widely used for identification, quantification and providing structural information about molecular structure in low concentrations as it allows signal Raman enhancement using metallic nanoparticles (NPs). Controlling interaction between analyte and NPs is a major point for the optimization of signal exaltation in SERS analysis. The objective of this study is the improvement and the control of SERS analysis by aggregation/self-assembly optimization of AuNPs using quaternized chitosan. The interest of this approach is to allow stable and reliable measurements with a simple and low cost approach compatible with a massive use in the field. In this work, we used design of experiments by Box-Behnken design to fix optimized conditions to increase signal sensibility of epinephrine water solutions. We also tested SERS signal stability in isotonic sodium chloride 0.9% and glucose 5% matrices. Our results demonstrate that globally neutral AuNPs aggregates were stabilized at a nanometric size by the subsequent addition of polyelectrolyte chains and allows for significant Raman signal enhancement of epinephrine. We succeed to prepare the SERS active material and measure a stable signal of epinephrine at a concentration as down as 0.1 µg mL-1 in less than 5 min. The signal remained stable and exploitable for at least 2 h. Our results reveal a strong correlation between intensity and logarithm of the concentration (concentration before dilution from 0.1 to 10 µg mL-1) suggesting a possible quantification. Furthermore, the signal of epinephrine at 10 µg mL-1 were also exploitable and stable in complex media as isotonic sodium chloride 0.9% and glucose 5%. This represents a particularly interesting application that would allow direct analysis of drugs complex media and open the way to analysis in biological samples.

Early-life factors associated with increased risk of disability pension in the national real-world schizophrenia FACE-SZ cohort study.

Among severe psychiatric disorders, schizophrenia has one of the highest impacts on professional and personal functioning with important indirect costs including disability pension allowance for the patients with the more severe forms of schizophrenia. To explore early-life factors associated with disability pension in schizophrenia. 916 patients were consecutively recruited at a national level in 10 expert centers and received a comprehensive standardized evaluation. Their disability pension status and early-life variables were reported from medical records and validated scales. Eight factors were explored: age, male sex, parental history of severe mental illness, childhood trauma exposure, education level, childhood ADHD, early age at schizophrenia onset and duration of untreated psychosis. 739 (80.7%) participants received a disability pension. In the multivariate model, early age at schizophrenia onset and low education level were associated with disability pension independently of age and sex while no significant association was found for parent history of severe mental illness, childhood trauma, childhood ADHD or duration of untreated psychosis. Low education level and early age at schizophrenia onset seem the best predictors of increased risk of disability pension in schizophrenia.

Medical students and the response to COVID-19: Educational preparedness and psychological impact of their involvement in communicating with patients' relatives.

OBJECTIVES: The COVID-19 pandemic has challenged without precedent both healthcare and educational systems worldwide. How medical students could and should be engaged in the response remains unclear. Medical students were asked to help with communicating with patients' relatives in our institution. Authors aimed: to (i) present the rapid implementation and assessment of a teaching/e-teaching lesson in the COVID-19 era; (ii) report an early evaluation of preparedness, mental health and well-being of students involved. METHODS: The lesson was elaborated at lockdown in France. The clinical guidance consisted of a voluntary lesson entitled: "How to communicate with relatives of hospitalized COVID-19 patients?". Students received an anonymous online questionnaire after two weeks. RESULTS: Sixty-six medical students were trained (32% face-to-face). The response rate was 64%. Most students informed relatives about the routine care of the patient (95%). Concerning the lesson, students assured to have had one (95%), considered it relevant (86%), and had used the educational content (81%). 33% were charged with unexpected missions (only 36% felt prepared). Most of them did not report any psychological impact, but some reported anxiety or sleep disorders with no difference between face-to-face/distance training. CONCLUSIONS: This pandemic may last. Communication ability is a key competence in medical curriculum and is more than ever essential. Distance learning technologies may provide a useful and accepted tool for medical students. We report on a rapid feedback on what can be expected or not from students in terms of mission and short-term psychological consequences.

Redefining peripheral inflammation signature in schizophrenia based on the real-world FACE-SZ cohort.

BACKGROUND: Peripheral inflammation is associated with impaired prognosis in schizophrenia (SZ). Highly sensitive C-reactive protein (hs-CRP) is the most used inflammatory biomarker in daily practice. However, no consensual cut-off has been determined to date to discriminate patients with peripheral inflammation from those without. AIMS: To determine if patients with peripheral inflammation between 1 and 3 mg/L had poorer outcomes compared to those with undetectable CRP (<1 mg/L). METHOD: Consecutive participants of the FACE-SZ cohort with a hs-CRP < 3 mg/L were included in 10 expert academic centers with a national geographical distribution between 2010 and 2018. Potential sources of inflammation, socio-demographics, illness characteristics, current illness severity, functioning and quality of life and were reported following the FACE-SZ standardized protocol. RESULTS: 580 patients were included, of whom 226 (39%) were identified with low-grade inflammation defined by a hs-CRP between 1 and 3 mg/L. Overweight and lack of dental care were identified as potential sources of inflammation. After adjustment for these factors, patients with inflammation had more severe psychotic, depressive and aggressive symptomatology and impaired functioning compared to the patients with undetectable hs-CRP. No association with tobacco smoking or physical activity level has been found. CONCLUSIONS: Patients with schizophrenia with hs-CRP level between 1 and 3 mg/L should be considered at risk for inflammation-associated disorders. Lowering weight and increasing dental care may be useful strategies to limit the sources of peripheral inflammation. Hs-CRP > 1 mg/L is a reliable marker to detect peripheral inflammation in patients with schizophrenia.

Recommendations of the schizophrenia expert center network for the screening prevention and treatment of sleep disorders based on the results from the real-world schizophrenia FACE-SZ national cohort.

BACKGROUND: Sleep disorders associated factors are under explored in schizophrenia while the literature suggests high and heterogeneous frequency. AIMS: The objective of the present study was to determine the prevalence and risk factors of sleep disorders in the real-world FACE-SZ national cohort. METHOD: Stabilized schizophrenic outpatients were recruited in 10 expert centers for schizophrenia. Sleep quality was explored with the Pittsburgh Sleep Quality Index (PSQI) and sleep disorders was defined by a PSQI score > 5. Psychosis severity was measured with the Positive and Negative Syndrome Scale, current major depressive episode with the Calgary Depression Scale for Schizophrenia, verbal aggressiveness with the Buss-Perry Aggression Questionnaire, adherence to treatment with the Medication Adherence Rating Scale, akathisia with the Barnes Akathisia Scale. Current somatic comorbidities and body mass index were reported. Variables with P values <0.20 in univariate analysis were included in a multivariate regression model. RESULTS: Of the 562 included patients, 327 subjects (58.2%, IC95% [54.1% - 62.3%]) reported having sleep disorders. After adjustment, sleep disorders were significantly associated with migraine (adjusted odds ratio aOR = 2.23, p = 0.041), major depressive disorder (aOR 1.79, p = 0.030), poor adherence to treatment (aOR = 0.87, p = 0.006), akathisia (aOR = 1.29, p = 0.042) and verbal aggressiveness (aOR = 1.09, p = 0.002). CONCLUSIONS: More than one on two stabilized real-life outpatients with schizophrenia have been identified with sleep disorders. Combined with the literature data, we have yielded expert recommendations for the treatment and prevention of sleep disorders including treating undiagnosed comorbid depression and migraine and managing antipsychotic treatment to improve adherence and akathisia.

The External Morphology of the Eggs of Culex (Culex) saltanensis (Diptera: Culicidae) Under Scanning Electron Microscopy.

The aim of the present study was to describe the morphology of the eggs of Culex (Culex) saltanensis Dyar that occurs in the Neotropical region. Eggs of the Cx. (Cux.) saltanensis were collected at the Mata Atlântica FIOCRUZ campus, fixed in 1% osmium tetroxide, prepared for mounting on metal supports, observed under a scanning electron microscope, and described morphologically. The eggs had a coniform shape with a length of approximately 0.5 mm (505-510 µm) and a width in the median portion of 117 µm (113-123 µm). Upper portion is lined with tubers of irregular shape and varying sizes (0.64-1.31 µm), located on a cross-linked matrix forming bands observed under optical microscopy. The micropyle is encased in a necklace of approximately 6.6-µm plates arranged in a flower-like shape. Comparing Cx. (Cux.) saltanensis eggs with several species of different genera, important divergent characteristics can be observed. However, this study points to the need for new descriptions of eggs of species belonging to the same subgenus in order to analyze if there will be differences between them. Culex (Cux.) saltanensis eggs have particular characteristics not observed in eggs of other Culicidae genera.

Towards precision medicine: What are the stratification hypotheses to identify homogeneous inflammatory subgroups.

Diverse lines of research testify a link, presumably causal, between immune dysregulation and the development, course and clinical outcome of psychiatric disorders. However, there is a large heterogeneity among the patients' individual immune profile and this heterogeneity prevents the development of precise diagnostic tools and the identification of therapeutic targets. The aim of this review was to delineate possible subgroups of patients on the basis of clinical dimensions, investigating whether they could lead to particular immune signatures and tailored treatments. We discuss six clinical entry points; genetic liability to immune dysregulation, childhood maltreatment, metabolic syndrome, cognitive dysfunction, negative symptoms and treatment resistance. We describe the associated immune signature and outline the effects of anti-inflammatory drugs so far. Finally, we discuss advantages of this approach, challenges and future research directions.

Major depression, sleep, hostility and body mass index are associated with impaired quality of life in schizophrenia. Results from the FACE-SZ cohort.

BACKGROUND: Impaired Quality of life (QoL) in schizophrenia has been mostly associated with psychotic and mood symptomatology, insight and functioning so far. AIMS: QoL levels remain unsatisfactory due to other factors we aim to explore. METHOD: We have explored sleep quality with the Pittsburgh Sleep Quality Index, hostility with the Buss&Perry questionnaire, major depression with the Positive and Negative Syndrome Scale depressive factor, functioning with the Global Assessment of Functioning scale and weight gain with body mass index in addition to other classical QoL-associated factors. RESULTS: 559 patients (mean age=31 (SD 9) years, 74% male sex) were included in the national FACE-SZ cohort. Impaired QoL has been significantly associated with respectively major depression, impaired sleep quality, increased hostility, impaired functioning and impaired insight independently of age, sex, treatments, tobacco smoking and body mass index. Major depression was associated with impaired psychological and physical well-being, and impaired self-esteem. Impaired sleep quality has been associated with impaired psychological and physical well-being and sentimental life. Hostility has been associated with impaired psychological well-being and self-esteem, impaired friends' relationships and impaired autonomy. Weight was associated with impaired physical well-being. Tobacco smoking was associated with higher level of friends' relationships. CONCLUSIONS: Major depression, sleep, hostility, and weight gain have been identified as potential targets to improve QoL in schizophrenia and should be implemented in the recommendations for good practice to optimize schizophrenia care.

Confirmations, advances and recommendations for the daily care of schizophrenia based on the French national FACE-SZ cohort.

BACKGROUND: The National FondaMental Centers of Expertise (FACE) for Schizophrenia (SZ) have been created to shorten the gap between research and clinical practice. OBJECTIVES: To synthetize in a review the 10-year findings issued from the FACE-SZ cohort analyses. METHODS: More than 1000 patients were evaluated in 10 expert centers since 2010 with a 2-day long comprehensive standardized battery including neuropsychological testes and physical health assessment and followed-up for 3 years. RESULTS: 1. The phase 0 cross-sectional analyses have confirmed well-known data: over-prescription of first-generation antipsychotics, antipsychotic polytherapy and long-term benzodiazepine and under-prescription of clozapine, 13% of drug-induced parkinsonism, 18% of akathisia, a mean duration of untreated psychosis of 18 months, one third of poorly-adherent patients, 24% of metabolic syndrome and 52% of current tobacco smokers with poor care for physical illnesses; a yearly mean financial cost of 15,000 euro/patient. 2. FACE-SZ also yielded additional data in insufficiently explored area: a half of major depression issues (among them one third of undiagnosed major depression and 44% of treated patients with unremitted depression), major depression having a strong impact on Quality of Life independently of negative symptoms, 22% of moderated to severe untreated physical pain. 3. FACE-SZ has explored emerging fields of research, including development of 4 stages- model of schizophrenia, chronic low-grade peripheral inflammation, latent Toxoplasma infection, hypovitaminosis D, and a model for relapse prediction at 2 years. DISCUSSION: The associated factors and implications for public health programs were discussed. Based on the FACE-SZ findings and literature, the FACE-SZ group has yielded recommendations to improve daily care for schizophrenia and for future research.

Sexual dysfunctions are associated with major depression, chronic inflammation and anticholinergic consumption in the real-world schizophrenia FACE-SZ national cohort.

BACKGROUND: Sexual dysfunctions (SD) are frequent in schizophrenia (SZ) and associated with treatment withdrawal, however they remain under-explored and under-treated. To date, most of the studies have focused on SD as antipsychotics' side effects in therapeutic trials. AIMS: The objectives of the present study were to determine the SD prevalence in stabilized SZ outpatients and their clinical, pharmacological and biological correlates. METHOD: Two hundred and thirty-seven participants (61.2% men) were consecutively included and received a thorough 2 days- clinical assessment including the self-reported Sexual Functioning Questionnaire (SFQ). SD was defined by a SFQ score ≥ 8. RESULTS: Two hundred and thirty-seven subjects were recruited in the FACE-SZ cohort, 41% of them reported sexual dysfunctions. In multivariate analyses, SD have been associated with current major depressive disorder (adjusted odd ratio aOR = 2.29[1.08-4.85], p = .03), anticholinergic prescription (aOR = 2.65, p = .02) and chronic low-grade inflammation (aOR = 2.09, p = .03) independently of age, gender, current cannabis use disorder and olanzapine prescription. No antipsychotic has been associated with increased or decreased SD rate. CONCLUSIONS: SD are frequent in SZ subjects. Major depression, anticholinergic prescription and chronic low-grade peripheral inflammation may be the three targets of interest for addressing this specific issue.

Evaluation of two shaping systems and two sonic irrigation devices in removing root canal filling material from distal roots of mandibular molars assessed by micro CT.

AIM: To compare two preparation systems and two sonic irrigation devices during the removal of root filling material from oval distal canals of extracted mandibular molars. METHODOLOGY: The distal canals in 40 extracted mandibular molars were shaped using the ProTaper Next system (Dentslpy Sirona, Ballaigues, Switzerland), filled with Gutta Percha X2 (Dentsply Sirona), along with AH Plus sealer (Dentsply De Trey, Konstanz, Germany) and randomly divided into two groups (n = 20) according to volume of initial filling, preparation diameter and working length. One group was retreated using the Reciproc system (VDW, Munich, Germany), and the other using the 2Shape system (Micro-Mega, Besançon, France). A micro-CT scan was taken after the initial root filling and after retreatment to evaluate the volume of filling material remnants. The teeth were divided into four groups to test the supplementary effect of two sonic irrigation devices on removing filling material: Eddy (VDW) and MM1500 (Micro-Mega). In the first and second groups, 2Shape was followed subsequently by MM1500 and Eddy; in the third and fourth groups, Reciproc was followed by MM1500 and Eddy. A third micro-CT was taken to compare the remaining root filling material in all groups. Wilcoxon's signed rank tests, Mann-Whitney and Kruskal-Wallis tests were used for statistical analysis. RESULTS: No significant difference was found for the volume of filling material removed between the Reciproc and 2Shape in the entire canal (P = 0.355). The volume dropped significantly from its initial value after removing the bulk of the root filling by 95.8% (from 4.71 to 0.22 mm3 ) with the 2Shape (P < 0.001) and by 94.0% (from 5.05 to 0.33 mm3 ) with the Reciproc (P < 0.001). Sonic activation significantly decreased the residual volume of filling material remnants by 3.21% (P = 0.013) in the first group, 1.38% (P = 0.012) in the second group, 1.83% (P = 0.008) in the third group and 1.83% (P = 0.012) in the fourth group. At the end, the percentage of residual material was not significantly different among the groups in the entire canal (P = 0.163). CONCLUSION: In the distal oval canals of extracted mandibular molar teeth, there was no significant difference between the 2Shape and Reciproc systems in removing gutta-percha/sealer. Sonic activation with MM1500 and Eddy significantly improved filling material removal.

Towards an improved access to psychiatric rehabilitation: availability and effectiveness at 1-year follow-up of psychoeducation, cognitive remediation therapy, cognitive behaviour therapy and social skills training in the FondaMental Advanced Centers of Expertise-Schizophrenia (FACE-SZ) national cohort.

Psychosocial Interventions (PIs) have shown positive effects on clinical and functional outcomes of schizophrenia (SZ) in randomized controlled trials. However their effectiveness and accessibility remain unclear to date in "real world" schizophrenia. The objectives of the present study were (i) to assess the proportion of SZ outpatients who benefited from PIs between 2010 and 2015 in France after an Expert Center Intervention in a national multicentric non-selected community-dwelling sample; (ii) to assess PIs' effectiveness at 1-year follow-up. 183 SZ outpatients were recruited from FondaMental Advanced Centers of Expertise for Schizophrenia cohort. Baseline and 1-year evaluations included sociodemographic data, current treatments, illness characteristics and standardized scales for clinical severity, adherence to treatment, quality of life, a large cognitive battery, and daily functioning assessment. Only 7 (3.8%) received a PI before the evaluation, and 64 (35%) have received at least one PI during the 1-year follow-up. Having had at least one PI during the follow-up has been associated in multivariate analyses with significantly higher improvement in positive and negative symptoms (respectively p =0.031; p = 0.011), mental flexibility (TMT B, p = 0.029; C-VF, p = 0.02) and global functioning (p =0.042). CBT and SST were associated with higher cognitive improvements, while CRT was associated with clinical improvement. These results have not been demonstrated before and suggest that the effect of each PI is larger than its initial target. The present study has confirmed the PIs' effectiveness in a large sample of community-dwelling SZ outpatients at 1 year follow-up. Efforts to improve access to PI should be reinforced in public health policies.

Morphobiological, morphometric and ultrastructural characterization of sylvatic Trypanosoma cruzi isolates from Rio de Janeiro state, Brazil / Caracterização morfobiológica, morfométrica e ultraestrutural de isolados silvestres de Trypanosoma cruzi do estado do Rio de Janeiro, Brasil

Abstract Triatoma vitticeps is a triatomine with geographic distribution restrict to Brazil, which exhibits high prevalence of Trypanosoma cruzi natural infection. Of special epidemiologic concern, this species often invades households in the states of Rio de Janeiro, Minas Gerais and Espírito Santo. The objective of this study was to evaluate morphological and ultrastructural parameters on three T. cruzi isolates obtained from wild T. vitticeps specimens. The growth and cell differentiation of the parasite was evaluated through epimastigote and trypomastigote forms obtained in the growth curves for three distinct isolates. The maximum growth showed differences at the 20th day of the curve. Our in vitro results show a heterogeneity, regarding these features for samples cultivated under the same conditions. Morphometric analyzes based on the shape of epimastigotes and trypomastigotes corroborated such differentiation. These results highlight the need of better understanding the meaning of this diversity under an eco-epidemiological perspective.

Resumo Triatoma vitticeps é um triatomíneo com distribuição geográfica restrita ao território brasileiro, apresentando alta prevalência de infecção natural pelo Trypanosoma cruzi. Esta espécie é relevante sob o ponto de vista epidemiológico por invadir domicílios com frequência nos estados do Rio de Janeiro, Minas Gerais e Espírito Santo. O objetivo deste estudo foi avaliar parâmetros morfológicos e ultraestruturais, em três isolados de T. cruzi obtidos a partir de triatomíneos silvestres. O crescimento e a diferenciação celular do parasita foi avaliado através das formas epimastigotas e tripomastigotas obtidas nas curvas de crescimento para os três isolados. O crescimento máximo mostrou diferenças no 20º dia da curva. Nossos resultados in vitro mostram uma heterogeneidade, em relação a essas características para amostras cultivadas nas mesmas condições. As análises morfométricas baseadas na conformação de epimastigotas e trypomastigotes corroboraram essa diferenciação. Estes resultados ressaltam a necessidade de uma melhor compreensão do significado desta diversidade sob uma perspectiva eco-epidemiológica.

Tobacco smoking is associated with antipsychotic medication, physical aggressiveness, and alcohol use disorder in schizophrenia: results from the FACE-SZ national cohort.

Tobacco smoking is common in schizophrenia and is one of the main causes of premature mortality in this disorder. Little is known about clinical correlates and treatments associated with tobacco smoking in patients with schizophrenia. Still, a better characterization of these patients is necessary, in a personalized care approach. Aggressiveness and childhood trauma have been associated with tobacco smoking in general population, but this association has never been explored in schizophrenia. Our study examines the clinical and therapeutic characteristics of tobacco smoking in schizophrenia. 474 stabilized patients (mean age = 32.2; 75.7% male gender; smokers n = 207, 54.6%) were consecutively included in the network of the FondaMental Expert centers for Schizophrenia and assessed with valid scales. Current tobacco status was self-declared. Aggressiveness was self-reported with Buss-Perry Aggressiveness Questionnaire and Childhood Trauma with Childhood Trauma Questionnaire. Ongoing treatment was reported. In univariate analysis, tobacco smoking was associated with lower education level (p < 0.01), positive syndrome (p < 0.01), higher physical aggressiveness (p < 0.001), alcohol dependence (p < 0.001), and First Generation Antipsychotics (FGAs) use (p = 0.018). In a multivariate model, tobacco smoking remained associated with physical aggressiveness (p < 0.05), current alcohol dependence (p < 0.01) and FGA use (p < 0.05). No association was observed with childhood trauma history, mood disorder, suicidal behavior, psychotic symptom, global functioning or medication adherence. Patients with tobacco use present clinical and therapeutic specificities, questioning the neurobiological links between tobacco and schizophrenia. They could represent a specific phenotype, with specific clinical and therapeutic specificities that may involve interactions between cholinergic-nicotinic system and dopaminergic system. Further longitudinal studies are needed to confirm the potential efficacy of second generation antipsychotics (SGAs) on tobacco use in schizophrenia and to develop effective strategies for tobacco cessation in this population.

Chronic low-grade peripheral inflammation is associated with ultra resistant schizophrenia. Results from the FACE-SZ cohort.

A high rate of patients with schizophrenia (SZ) does not sufficiently respond to antipsychotic medication, which is associated with relapses and poor outcomes. Chronic peripheral inflammation has been repeatedly associated with schizophrenia risk and particularly to poor responders to treatment as usual with cognitive impairment in SZ subjects. The objective of present study was to confirm if ultra resistance to treatment in schizophrenia (UTRS) was associated to chronic peripheral inflammation in a non-selected sample of community-dwelling outpatients with schizophrenia. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. Current psychotic symptomatology was evaluated by the Positive and Negative Syndrome scale for Schizophrenia (PANSS). UTRS was defined by current clozapine treatment + PANSS total score ≥ 70. Functioning was evaluated by the Global Assessment of Functioning scale. High sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. 609 stabilized community-dwelling SZ subjects (mean age = 32.5 years, 73.6% male gender) have been included. 60 (9.9%) patients were classified in the UTRS group. In multivariate analyses, UTRS has been associated independently with chronic peripheral inflammation (OR = 2.6 [1.2-5.7], p = 0.01), illness duration (0R = 1.1 [1.0-1.2], p = 0.02) and impaired functioning (OR = 0.9 [0.9-0.9], p = 0.0002) after adjustment for age, sex, current daily tobacco smoking, metabolic syndrome and antidepressant consumption. Peripheral low-grade inflammation is associated with UTRS. Future studies should explore if anti-inflammatory strategies are effective in UTRS with chronic low-grade peripheral inflammation.

Inflammatory DEpression Advances in Schizophrenia (IDEAS): A precision medicine approach of the national FACE-SZ cohort.

BACKGROUND: Major Depressive Disorder (MDD) is a therapeutic challenge in schizophrenia (SZ). Untangling different forms of MDD appears as the best current strategy to improve remission to treatment in the so-called precision medicine approach. AIMS: The objectives of the present study were to determine (i) the prevalence of Inflammatory Depression (ID) in stabilized SZ outpatients (ii) if ID was associated with clinical or cognitive profiles that may help clinicians detecting ID (iii) if antidepressants were effective in ID and (iv) the biological correlates of ID that may orientate personalized treatments. METHOD: Participants were consecutively included and received a thorough 2 days- clinical assessment. RESULTS: 785 subjects were recruited in the FACE-SZ cohort. 289 (36.8%) were diagnosed with MDD (remitted or unremitted), of them 57 with ID (19.7%). No clinical or cognitive features were associated with ID (all p > 0.05). ID has been associated with increased abdominal perimeter (aOR = 4.48, p = 0.002) and latent Toxoplasma infection (aOR = 2.19, p = 0.04). While antidepressants were associated with decreased depressive symptoms level in ID, 44% of the subjects remained unremitted under antidepressant, with no association with CRP blood levels. CONCLUSIONS: ID may not differ from other forms of depression by its clinical symptoms but by its aetiologies. ID is associated with increased perivisceral fat and latent Toxoplasma infection that are both potentially related to gut/microbiota disturbances. Specific anti-inflammatory drugs and microbiota-targeted therapeutics appear as promising strategies in the treatment of inflammatory depression in schizophrenia.