Adora2A downregulation promotes caffeine neuroprotective effect against LPS-induced neuroinflammation in the hippocampus.

Caffeine has been extensively studied in the context of CNS pathologies as many researchers have shown that consuming it reduces pro-inflammatory biomarkers, potentially delaying the progression of neurodegenerative pathologies. Several lines of evidence suggest that adenosine receptors, especially A1 and A2A receptors, are the main targets of its neuroprotective action. We found that caffeine pretreatment 15 min before LPS administration reduced the expression of Il1b in the hippocampus and striatum. The harmful modulation of caffeine-induced inflammatory response involved the downregulation of the expression of A2A receptors, especially in the hippocampus. Caffeine treatment alone promoted the downregulation of the adenosinergic receptor Adora2A; however, this promotion effect was reversed by LPS. Although administering caffeine increased the expression of the enzymes DNA methyltransferases 1 and 3A and decreased the expression of the demethylase enzyme Tet1, this effect was reversed by LPS in the hippocampus of mice that were administered Caffeine + LPS, relative to the basal condition; no significant differences were observed in the methylation status of the promoter regions of adenosine receptors. Finally, the bioinformatics analysis of the expanded network demonstrated the following results: the Adora2B gene connects the extended networks of the adenosine receptors Adora1 and Adora2A; the Mapk3 and Esr1 genes connect the extended Adora1 network; the Mapk4 and Arrb2 genes connect the extended Adora2A network with the extended network of the proinflammatory cytokine Il1ß. These results indicated that the anti-inflammatory effects of acute caffeine administration in the hippocampus may be mediated by a complex network of interdependencies between the Adora2B and Adora2A genes.

Musculoskeletal pain during and after SARS-CoV-2 infection and healthcare utilization: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic necessitated the reorganization of health services to cater to the needs of individuals affected by the virus. OBJECTIVE: This study aimed to examine the association between musculoskeletal pain during and after SARS-CoV-2 infection and the utilization of health services among adults in southern Brazil.  METHODS: A cross-sectional study was conducted with individuals aged 18 years and older, who were diagnosed with COVID-19 between December 2020 and March 2021. Questionnaires were electronically collected using tablets through the REDCap platform via phone calls. The health service utilization outcomes assessed included Primary Health Care, general practitioners, private emergency care, and specialized services. The exposure variable was the presence of musculoskeletal pain during and after SARS-CoV-2 infection in different regions, such as cervical, upper limbs, thoracic, lumbar, and lower limbs. Poisson regression analysis was employed to assess the relationship between health service utilization during and after SARS-CoV-2 infection and musculoskeletal pain during and after the infection with SARS-CoV-2 among adults in southern Brazil. Data were analyzed using the Stata 16.1 statistical package.  RESULTS: A total of 2,919 individuals were interviewed. Overall, individuals with musculoskeletal pain were found to utilize health services approximately 15 percentage points higher when compared to those without musculoskeletal pain. In adjusted analysis, individuals who reported musculoskeletal pain during and after SARS-CoV-2 infection were up to twice as likely to use health services. Among them, the emergency care unit was the most frequently used service, particularly in those with pain in the lower limbs (RP=2.19, 95% CI 1.66-2.87) and thoracic region (RP=2.04, 95% CI 1.47-2.84). Notably, the highest magnitudes of association were observed with emergency care units, specialist doctors, and specialized services, especially neurologists, who were two to three times more likely to be sought, followed by pulmonologists.  CONCLUSION: Health service utilization was significantly associated with musculoskeletal pain during and after SARS-CoV-2 infection. All regions, except for the cervical region, showed a correlation with the use of Primary Health Care. The thoracic region featured an association with pulmonologists and emergency room utilization. Additionally, health services like emergency care units, specialist doctors, and specialized services, including cardiologists and neurologists, were commonly utilized across all regions in southern Brazil.

MicroRNA biogenesis machinery activation and lncRNA and REST overexpression as neuroprotective responses to fight inflammation in the hippocampus.

Brain Long non-coding RNA (lncRNA) and microRNAs (miRs) play essential roles in the regulation of several important biological processes, including neuronal activity, cognitive processes, neurogenesis, angiogenesis, and neuroinflammation. In this context, the transcriptional repressor, RE1 silencing transcription factor (Rest), acts regulating the expression of neuronal genes as well as of lncRNAs and multiple miRNAs in the central nervous system. Nevertheless, its role in neuroinflammation was less explored. Here, we demonstrate, using an in vivo model of neuroinflammation induced by i.p. injection of LPS (0.33 mg/kg), that neuroinflammation increases gene expression of pro-inflammatory cytokines concomitant with the native and truncated forms of Rest and of non-coding RNAs. Additionally, the increased expression of enzymes Drosha ribonuclease III) (Drosha), Exportin 5 (Xpo5) and Endoribonuclease dicer (Dicer), associated with high expression of neuroprotective miRs 22 and 132 are indicative that the activation of biogenesis of miRs in the hippocampal region is a Central Nervous System (CNS) protective mechanism for the deleterious effects of neuroinflammation. Our results indicate that positive regulation of Rest gene expression in the hippocampal region by neuroinflammation correlates directly with the expression of miRs 22 and 132 and inversely with miR 335. In parallel, the confirmation of the possible alignment between the lncRNAs with miR 335 by bioinformatics corroborates with the sponge effect of Hottip and Hotair hybridizing and inhibiting the pro-inflammatory action of miR 335. This suggests the existence of a possible correlation between the activation of miR biogenesis machinery with increased expression of the transcription factor Rest, contributing to neuroprotection.

Burnout Syndrome in Selectable Athletes for the Brazilian Handball Team-Children Category.

To investigate the presence of burnout syndrome in child athlete tryouts for the Brazilian Handball Team, before and after the National Development and Technical Improvement Camp is of great interest. A correlational study, with longitudinal design of the before-and-after type, carried out with 64 male athletes in the children's category, immersed in the National Camp for Development and Improvement of Handball Technique, in the municipality of São Bernardo do Campo, São Paulo, Brazil, in December 2018. To evaluate burnout syndrome, we used the Athlete Burnout Questionnaire (ABQ). There was a statistically significant increase of the mean scores for burnout and dimensions (Physical and Emotional Exhaustion = 1.5 to 1.6; p-value < 0.001; Reduced Sense of Accomplishment = 2.7 to 2.9; p-value < 0.001; Sports Devaluation = 1.4 to 1.6; p-value < 0.001; and General Burnout = 1.9 to 2.0; p-value < 0.001). The athletes selected for the national team had lower mean scores for general burnout and dimensions (Physical and Emotional Exhaustion = 1.5; Reduced Sense of Accomplishment = 2.7; Sports Devaluation = 1.5; General Burnout = 1.9). The National Camp for Development and Technical Improvement can have a negative impact on the mental health of athletes. This event is important to select the competitors with greater ability to face the pressure and adversities present in the sport environment.

Association between ADHD symptoms and inhibition-related brain activity using functional near-infrared spectroscopy (fNIRS).

Attention deficit hyperactivity disorder (ADHD) is associated with deficits in inhibitory functions including interference control, inhibition of prepotent/automatic responses and suppression of already initiated responses. This study used functional near-infrared spectroscopy (fNIRS) to investigate the neural basis of these three forms of inhibition assessed by a recently developed behavioral protocol combining the Stroop-matching/stop-signal task in twenty-five young adults with inattention, impulsivity and/or hyperactivity symptoms. The severity of ADHD symptoms was measured using the Adult ADHD Self-Report Scale (ASRS). The concentration of oxygenated hemoglobin (HbO) was assessed in the dorsolateral prefrontal cortex (DLPFC), inferior frontal gyrus (IFG) and temporoparietal regions (TP) during the Stroop-matching/stop-signal task. Correlations yielded significant associations between ASRS scores and HbO concentration in frontal regions during blocks with stop-signal tasks, namely the right IFG, the left DLPFC and the left IFG. This study revealed that different types of inhibition involve unique frontal and temporoparietal activities and linked frontal dysfunction during the suppression of ongoing responses to the severity of ADHD symptoms.

Persistence of left superior vena cava: a rare cause of hemodialysis tunneled catheter malposition / Persistência de veia cava superior esquerda: uma causa rara de posicionamento inadequado do cateter tunelizado para hemodiálise

Abstract Hemodialysis central venous catheter (CVC) insertion can be complicated in patients with anomalous vessel anatomy. In such cases detailed knowledge of thoracic vessel anatomy is necessary to identify the exact location of the catheter. Central venous placement under ultrasound control has significantly reduced the complications associated with blind puncture and allows an appropriate puncture of the desired vessel, but the CVC can still get misplaced if it follows an anomalous route. Herein, we report a case of dialysis catheter placed into a left sided superior vena cava, only diagnosed after CT scan study.

Resumo A inserção do cateter venoso central (CVC) para hemodiálise pode ser complicada em pacientes com anatomia anômala dos vasos. Nesses casos, o conhecimento detalhado da anatomia do vaso torácico é necessário para identificar a localização exata do cateter. A colocação venosa central sob controle de ultrassom tem reduzido significativamente as complicações associadas à punção às cegas e permite uma punção apropriada do vaso desejado, mas o CVC ainda pode ficar mal posicionado se seguir uma rota anômala. Aqui, relatamos um caso de cateter de diálise colocado em uma veia cava superior esquerda, apenas diagnosticado após estudo de tomografia computadorizada.

SARS-CoV-2 infection in kidney transplant recipients: clinical impact and outcomes - a single center experience / Infecção por SARS-CoV-2 em receptores de transplante renal: impacto clínico e outcomes - uma experiência de centro único

ABSTRACT Introduction: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. Methods: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. Results: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. Conclusion: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

RESUMO Introdução: Receptores de transplante renal são um subgrupo de doentes com maior risco de apresentar formas críticas de infecção por Síndrome Respiratória Aguda Grave pelo Coronavirus-2 (SARS-CoV-2) e piores outcomes devido ao tratamento imunossupressor. Aqui, apresentamos dados de uma coorte de um único centro de receptores de transplante renal com infecção por SARS-CoV-2. Métodos: Num estudo prospectivo, características basais, características clínicas, adaptação da terapêutica antiviral e de imunossupressão foram comparados entre doentes seguidos em ambulatório e doentes hospitalizados durante um período de um ano. Resultados: Foram analisados setenta e sete receptores de transplante renal, incluindo doentes de ambulatório e hospitalizados, com idade média de 57,7 (IIQ 49,7-64,9) anos. Vinte e oito (36,4%) foram tratados em ambulatório enquanto 49 (63,6%) doentes necessitaram de internação hospitalar. Entre os doentes hospitalizados, 18,4% foram admitidos na UTI, 49% apresentaram LRA, e 20,4% morreram. Foram realizados ajustes de imunossupressão em 95,9% dos pacientes hospitalizados, com dose de antimetabólitos ajustada em 83,7%, inibidores de mTOR em 14,3%, inibidores de calcineurina em 12,2%, e terapia com corticosteroides em 81,6%. Conclusão: Entre os pacientes hospitalizados, a optimização da terapêutica imunossupressora incluiu redução ou retirada de antimetabólito e aumento da dose de corticosteroides. A LRA ocorreu em quase metade dos pacientes e a mortalidade em pacientes hospitalizados atingiu 20%, refletindo uma maior gravidade da doença em relação à população em geral.

Geochemical characterization and the assessment of trace element retention in sediments of the Reconquista River, Argentina.

The mineralogical and geochemical characterization of sediments of the Reconquista River allows analyzing the geochemical partition of trace elements in one of the most polluted water courses of Argentina. The low dissolved oxygen and high ammonia contents, together with the high chemical oxygen demand, attest to the poor water quality. Ammonia, Cd and Cu content in surficial water exceeds the maximum guidelines for freshwater in Argentina. The recent sediments of the uppermost bed are enriched in organic matter (OM), sulfur, Zn, Cu and Pb. The enrichment factor is moderate, and the geoaccumulation index (Igeo) for Cu and Pb indicates uncontaminated to moderately contaminated sediments. The positive and significant correlation between As, Cr, Pb and Zn with the iron content suggests that their retention is controlled by the amount of iron oxy (hydr)oxides in the sediments, probably combined with the silt + clay abundance. In comparison with its tributary, the Las Catonas Stream, the Reconquista River, has less OM and trace elements in the sediments and more dissolved trace elements in the interstitial water. We interpret that OM is the main sorbent of the trace element. In the absence of OM, the iron oxy (hydr)oxides and the silt + clay fraction are a less efficient substitute. Consequently, the interstitial waters of the Reconquista River are enriched in these elements. Therefore, minor changes in the environmental conditions may generate significant release of hazardous trace elements from the sediments to the interstitial water and, in turn, to the surficial water of the river. As most of the big cities and the agricultural activities of Argentina are developed on the loessic substrate, the understanding of its interaction with polluted waters is crucial.

Persistence of left superior vena cava: a rare cause of hemodialysis tunneled catheter malposition.

Hemodialysis central venous catheter (CVC) insertion can be complicated in patients with anomalous vessel anatomy. In such cases detailed knowledge of thoracic vessel anatomy is necessary to identify the exact location of the catheter. Central venous placement under ultrasound control has significantly reduced the complications associated with blind puncture and allows an appropriate puncture of the desired vessel, but the CVC can still get misplaced if it follows an anomalous route. Herein, we report a case of dialysis catheter placed into a left sided superior vena cava, only diagnosed after CT scan study.

SARS-CoV-2 infection in kidney transplant recipients: clinical impact and outcomes - a single center experience.

INTRODUCTION: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. METHODS: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. RESULTS: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. CONCLUSION: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

Plasmapheresis as an Alternative Treatment of Hypertriglyceridemia-Induced Pancreatitis: A Case Report.

Hypertriglyceridemia-induced pancreatitis is a relatively common form of acute pancreatitis that may represent up to 10% of all etiologies of this condition. Due to its specific pathogenic mechanisms related to high serum triglyceride levels, different treatment options have been proposed, including insulin perfusion, heparin perfusion, and plasmapheresis. Although the superiority of plasmapheresis in this clinical setting has not been demonstrated in randomized clinical trials, many centers have reported its effectiveness and considered this as a possible alternative according to the current guidelines. We report a case of a young patient diagnosed with hypertriglyceridemia-induced pancreatitis that was successfully treated with plasmapheresis. Since complications associated with plasmapheresis are rare and other therapeutic options may not be so effective or safe, we believe that this should be a valid alternative treatment that may be offered to these patients. More studies are still needed to further evaluate its effectiveness and to elucidate if there is a subset of patients in whom treatment with plasmapheresis may be more beneficial.

Asociación entre comercialización de agrotóxicos con prematuridad y bajo peso al nacer al sur de Brasil / Association of Commercialization of Pesticides with Premature and Low Birth Weight in Southern Brazil

Introducción: Brasil expandió el mercado de agrotóxicos y Río Grande do Sul se destaca como mayor comercializador desde 2014. La población rural, factores socioeconómicos, ambientales y la exposición a agrotóxicos pueden ocasionar la prematuridad y bajo peso al nacer. Objetivo: Verificar la asociación entre la comercialización de agrotóxicos y la ocurrencia de prematuridad, bajo peso al nacer y factores socioeconómicos. Métodos: Estudio ecológico con 496 municipios del estado do Río Grande do Sul, Brasil, en los años 2017 y 2018. La población fueron los nacidos vivos por residencia materna, notificados en el Sistema de Informaciones Sobre Nacidos Vivos. La comercialización de agrotóxicos fue obtenida del Sistema Integrado de Gestión de Agrotóxicos. Se clasificaron los municipios en cuatro grupos de orden creciente, con base en cuartiles de comercialización. Se realizaron análisis de estadísticas en el programa IBM SPPS versión 21.0, considerando nivel de significancia de 5 por ciento (p 0,05). Conclusión: El consumo de agrotóxicos, la disminución de acceso a educación, servicios de salud y ambientes inseguros de trabajo, pueden contribuir para surgimiento de recién-nacidos prematuros y con bajo peso(AU)

Introduction: Brazil expanded the pesticide market and Rio Grande do Sul stands out as the largest marketing state since 2014. The rural population, socioeconomic and environmental factors, as well as exposure to pesticides can cause prematurity and low weight at birth. Objective: To verify the association between the commercialization of pesticides and the occurrence of prematurity, low weight at birth and socioeconomic factors. Methods: Ecological study carried out, in the years 2017 and 2018, with 496 municipalities of Rio Grande do Sul State, Brazil. The population was made up of the live births by maternal residence and reported in the Live Births Information System. Information regarding the commercialization of pesticides was obtained from the Integrated System for Pesticide Management. The municipalities were classified into four groups of increasing order, based on marketing quartiles. Statistical analyses were carried out in the program IBM SPPS (version 21.0); considering a significance level of 5 percent (P 0.05). Conclusion: Consumption of pesticides, decrease in access to education and healthcare services, as well as unsafe work settings, can contribute to the occurrence of premature and underweight newborns(AU)

Effects on Ultrastructure, Composition and Specific Surface Area of the Gills of Odontesthes bonariensis Under Subchronic Glyphosate-Based Herbicide Exposure.

Gills represent one of the major sites of gas exchange of fish, consequently they are in continuous close contact with the aquatic environment and its pollutants. In the present study the effects on gills of pejerrey fish, Odontesthes bonariensis, under glyphosate-based herbicide subchronic exposure were analyzed. Adult animals were exposed to sublethal concentrations of a glyphosate-based commercial formulation (1 and 10 PMG mg L-1, PMG: glyphosate active ingredient) for 15 days, while control group was maintained in rearing water. Ultrastructural changes in gills were observed by scanning electron microscopy (SEM). The composition of the surface epithelium and specific surface area were determined by energy dispersive spectroscopy (EDS) and N2 (g) adsorption-desorption isotherms, respectively. The herbicide exposure induced severe alterations in gill ultrastructure, as shown in the SEM micrographs. Accordingly, an increase in surface area of the gills of exposed animals was determined. These results support that gills parameters of freshwater fish are sensitive morphological biomarkers for glyphosate exposure.

Rethinking palliative care in a public health context: addressing the needs of persons with non-communicable chronic diseases.

Non-communicable chronic diseases (NCCDs) are the main cause of morbidity and mortality globally. Demographic aging has resulted in older populations with more complex healthcare needs. This necessitates a multilevel rethinking of healthcare policies, health education and community support systems with digitalization of technologies playing a central role. The European Innovation Partnership on Active and Healthy Aging (A3) working group focuses on well-being for older adults, with an emphasis on quality of life and healthy aging. A subgroup of A3, including multidisciplinary stakeholders in health care across Europe, focuses on the palliative care (PC) model as a paradigm to be modified to meet the needs of older persons with NCCDs. This development paper delineates the key parameters we identified as critical in creating a public health model of PC directed to the needs of persons with NCCDs. This paradigm shift should affect horizontal components of public health models. Furthermore, our model includes vertical components often neglected, such as nutrition, resilience, well-being and leisure activities. The main enablers identified are information and communication technologies, education and training programs, communities of compassion, twinning activities, promoting research and increasing awareness amongst policymakers. We also identified key 'bottlenecks': inequity of access, insufficient research, inadequate development of advance care planning and a lack of co-creation of relevant technologies and shared decision-making. Rethinking PC within a public health context must focus on developing policies, training and technologies to enhance person-centered quality life for those with NCCD, while ensuring that they and those important to them experience death with dignity.

Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study.

Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, ß2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.

Seasonal variations in the dose-response relationship of acetylcholinesterase activity in freshwater fish exposed to chlorpyrifos and glyphosate.

The herbicide glyphosate [N- (phosphonomethyl) glycine; PMG] and the insecticide chlorpyrifos [O, O-diethyl O- (3,5,6-trichloro-2-pyridinyl) -phosphorothioate, CPF] are widely used in agricultural practices around the world and can reach aquatic environments. Therefore, it is necessary to characterize the toxicity of these pesticides on non-target species. The use of biomarkers as a tool to assess responses of organisms exposed to pollutants requires the understanding of their natural fluctuation and the dose-response relationship. In the present work, the effect of the exposure to PMG and CPF on the acetylcholinesterase activity (AChE, biomarker of neurotoxicity) in Cnesterodon decemmaculatus, a native teleost, was evaluated in different environmental conditions. Semi-static bioassays of acute toxicity were carried out under controlled conditions during the four weather seasons of the year using animals of homogeneous size. Circannual rhythms in the basal levels of AChE activity in homogenates of the anterior section were confirmed. Statistically significant average inhibition of AChE activity (47.1 ±â€¯0.7% for 1 µg CPF × L-1; 69.7 ±â€¯2.5% for 5 µg CPF × L-1; 23.1 ±â€¯1.1% for 1 mg PMG × L-1 and 32.9 ±â€¯3.3% for 10 mg PMG × L-1) was determined during summer, winter and spring weather seasons. Interestingly, animals exhibit an increased susceptibility to exposure during the autumn season (inhibition of 55.4 ±â€¯0.6% for 1 µg CPF × L-1; 81.9 ±â€¯3.3% for 5 µg CPF × L-1; 41.4 ±â€¯1.7% for 1 mg PMG × L-1 and 61.1 ±â€¯0.3% for 10 mg PMG × L-1). A different sensitivity of the enzyme between seasons was evaluated by in vitro tests. The inhibition pattern for chlorpyrifos-oxon (CPF-oxon, the active metabolite of CPF) was not affected when test was performed using homogenates of unexposed specimens of summer or autumn. Otherwise, PMG in vitro inhibitory effect was not observed in a wide range of concentrations. The results confirm that AChE activity is a sensitive biomarker for exposure to CPF and PMG, even at environmentally relevant concentrations. Finally, this work highlights the existence of seasonal variations in the dose-response relationship, which could be due to variations in the metabolism of the pollutants.

Influenza virus polymerase subunits co-evolve to ensure proper levels of dimerization of the heterotrimer.

The influenza A virus RNA-dependent RNA polymerase complex consists in three subunits, PB2, PB1 and PA, that perform transcription and replication of the viral genome through very distinct mechanisms. Biochemical and structural studies have revealed that the polymerase can adopt multiple conformations and form oligomers. However so far it remained unclear whether the available oligomeric crystal structures represent a functional state of the polymerase. Here we gained new insights into this question, by investigating the incompatibility between non-cognate subunits of influenza polymerase brought together through genetic reassortment. We observed that a 7:1 reassortant virus whose PB2 segment derives from the A/WSN/33 (WSN) virus in an otherwise A/PR/8/34 (PR8) backbone is attenuated, despite a 97% identity between the PR8-PB2 and WSN-PB2 proteins. Independent serial passages led to the selection of phenotypic revertants bearing distinct second-site mutations on PA, PB1 and/or PB2. The constellation of mutations present on one revertant virus was studied extensively using reverse genetics and cell-based reconstitution of the viral polymerase. The PA-E349K mutation appeared to play a major role in correcting the initial defect in replication (cRNA -> vRNA) of the PR8xWSN-PB2 reassortant. Strikingly the PA-E349K mutation, and also the PB2-G74R and PB1-K577G mutations present on other revertants, are located at a dimerization interface of the polymerase. All three restore wild-type-like polymerase activity in a minigenome assay while decreasing the level of polymerase dimerization. Overall, our data show that the polymerase subunits co-evolve to ensure not only optimal inter-subunit interactions within the heterotrimer, but also proper levels of dimerization of the heterotrimer which appears to be essential for efficient viral RNA replication. Our findings point to influenza polymerase dimerization as a feature that is controlled by a complex interplay of genetic determinants, can restrict genetic reassortment, and could become a target for antiviral drug development.

Luminescent Lanthanide Metal Organic Frameworks as Chemosensing Platforms towards Agrochemicals and Cations.

Since the first studies of luminescent sensors based on metal organic frameworks (MOFs) about ten years ago, there has been an increased interest in the development of specific sensors towards cations, anions, explosives, small molecules, solvents, etc. However, the detection of toxic compounds related to agro-industry and nuclear activity is noticeably scarce or even non-existent. In this work, we report the synthesis and characterization of luminescent lanthanide-based MOFs (Ln-MOFs) with diverse crystalline architectures obtained by solvothermal methods. The luminescent properties of the lanthanides, and the hypersensitive transitions of Eu3+ (5D0→7F2) and Tb3+ (5D4→7F5) intrinsically found in the obtained MOFs in particular, were evaluated and employed as chemical sensors for agrochemical and cationic species. The limit of detection (LOD) of Tb-PSA MOFs (PSA = 2-phenylsuccinate) was 2.9 ppm for [UO22+] and 5.6 ppm for [Cu2+]. The variations of the 4f⁻4f spectral lines and the quenching/enhancement effects of the Ln-MOFs in the presence of the analytes were fully analyzed and discussed in terms of a combinatorial "host⁻guest" vibrational and "in-silico" interaction studies.