Effect of high-intensity interval training on obstructive sleep apnea severity: A randomized controlled trial.

Vigorous physical activity has been associated with a reduced risk of developing obstructive sleep apnea (OSA). However, whether high-intensity interval training (HIIT) reduces OSA severity remains unclear. Thus, this study aimed to investigate the impact of 12 weeks of HIIT on the apnea-hypopnea index (AHI) and sleep parameters in participants with moderate-severe OSA. In this randomized controlled trial, 36 adults (19 males; 52.2 ± 9.8 years; body mass index = 34.2 ± 5.8) with moderate to severe OSA (AHI = 42.0 ± 22.9 e/h) were randomly assigned to HIIT [5 periods of 4 min of walking or running on a treadmill at 90-95 % of maximum heart rate (HRmax) interspersed with 3 min of walking at 50-55 % of HRmax performed three times per week for 12 weeks] or a control group (CG; stretching exercises performed two times per week for 12 weeks). Sleep parameters were assessed at baseline and after 12 weeks through overnight polysomnography. Generalized estimated equations assessed differences between groups over time. There was not group × time interaction for body mass index between groups (p = 0.074). However, significant group × time interactions were observed for AHI (CG change = 8.2 ± 3.7, HIIT change = -8.6 ± 4.8; p = 0.005), SaO2 minimum (CG change = -1.6 ± 1.6 %, HIIT change = 0.4 ± 2.3 %; p = 0.030), total sleep time (CG change = -31.5 ± 19.5 min, HIIT change = 33.7 ± 19.3 min; p = 0.049), and sleep efficiency (CG change = -3.2 ± 4.4 %, HIIT change = 9.9 ± 3.5 %; p = 0.026). Moreover, there was a significant time × group interaction for maximum oxygen consumption (VO2max; CG change = -1.1 ± 1.0 mL/kg/min, HIIT change = 4.8 ± 0.9 mL/kg/min; p < 0.001)]. However, In patients with OSA, 12 weeks of HIIT decreases sleep apnea severity, improves sleep quality, and cardiorespiratory fitness. CLINICAL TRIAL REGISTRATION: (Registro Brasileiro de Ensaios Clínicos [ReBec]): # RBR-98jdt3.

First Study of Naturally Formed Fungal Biofilms on the Surface of Intragastric Balloons.

BACKGROUND: Intragastric balloon (IGB) is a medical device used in the endoscopic treatment of pre-obesity and obesity. The involvement of IGB with biofilms has been previously reported; however, little is still known. We determine the frequency of biofilms naturally formed on the external surface of IGB, as well as some variables related to IGB types and patients features, species of fungi involved, and biofilm evidence. METHODS: A retrospective study was conducted based on endoscopies and medical records of patients with explanted IGB between 2015 and 2018, which had masses strongly adhered to the surface of the balloon, suspecting the presence of a biofilm. From 2018, the samples of those masses were investigated seeking biofilm characterization based on mycological and structural aspects. RESULTS: A total of 149 endoscopies were surveyed; 27 IGBs (18.12%) showed signs suggesting biofilm formation. There was no significant difference between biofilm involvement in IGB and the anthropometric and demographic profile of the patients. On the other hand, there was a significant difference regarding the IGB type, 24.05% of the adjustable IGB were compromised by biofilm, while in non-adjustable IGB, it was 11.43% (p = 0.04; OR 2.45; 95% CI, 0.98-6.12). Candida glabrata was the most isolated fungal species from the well-organized fungal biofilm. CONCLUSIONS: The frequency of fungal biofilm naturally formed on the external surface of IGB was elevated. The risk of biofilm formation was increased for the adjustable IGB, but it did not relate to the demographic data and anthropometric patient profile.

Differential responses of dwarf cashew clones to salinity are associated to osmotic adjustment mechanisms and enzymatic antioxidative defense.

This study evaluate growth, gas exchange, solute accumulation and activity of antioxidant enzymes in dwarf cashew clones subjected to salinity. Shoot dry mass reduced 26.8% (CCP06) and 41.2% (BRS189) at 16 dS m-1, concerning control. For net photosynthesis, CCP06 and BRS189 presented 69.8% and 34.7% of reduction, respectively. Na+ and Cl- contents increased in leaves and roots, in both clones, although CCP06 leaves presented Na+ concentrations lower than those of BRS189, the first one was the clone that the most accumulated such toxic ion, whereas K+ content remained almost unchanged for both clones. Soluble N-amino was the organic solute that more varied with salinity in cashew seedlings. Salt stress increased the activity of superoxide dismutase in both clones, mainly 16 dS m-1 treatment. Additionally, salinity promoted increases in ascorbate and guaiacol peroxidase activities, and the last enzyme was the main involved in H2O2 removal. Despite the reductions in growth and gas exchange, dwarf cashew seedlings of both clones presented an osmotic adjustment mechanism, and an efficient enzymatic antioxidant system that were able to attenuate the salt and oxidative stress, respectively. Our research suggested that BRS189 clone is more tolerant to salt stress than CCP06.

Guideline on the peri-operative management of patients with sickle cell disease: Guideline from the Association of Anaesthetists.

Sickle cell disease is a multisystem disease characterised by chronic haemolytic anaemia, painful vaso-occlusive crises and acute and chronic end-organ damage. It is one of the most common serious inherited single gene conditions worldwide and has a major impact on the health of affected individuals. Peri-operative complications are higher in patients with sickle cell disease compared with the general population and may be sickle or non-sickle-related. Complications may be reduced by meticulous peri-operative care and transfusion, but unnecessary transfusion should be avoided, particularly to reduce the risk of allo-immunisation. Planned surgery and anaesthesia for patients with sickle cell disease should ideally be undertaken in centres with experience in caring for these patients. In an emergency, advice should be sought from specialists with experience in sickle cell disease through the haemoglobinopathy network arrangements. Emerging data suggest that patients with sickle cell disease are at increased risk of COVID-19 infection but may have a relatively mild clinical course. Outcomes are determined by pre-existing comorbidities, as for the general population.

Long-Term Consequences of Severe Maternal Morbidity on Infant Growth and Development.

OBJECTIVE: Severe maternal morbidity (SMM) is already known to be associated with adverse neonatal outcomes, however, its association with long-term deficits of weight and height, and impairment in neurodevelopment among children was not yet fully assessed. We aim to evaluate whether SMM has repercussions on the weight and height-for-age and neurodevelopmental status of the child. METHODS: A retrospective cohort analysis with women who had SMM events in a tertiary referral center in Brazil. They were compared to a control group of women who had not experienced any SMM. Childbirth and perinatal characteristics, weight and height-for-age deficits and neurodevelopmental impairment suspicion by Denver II Test were comparatively assessed in both groups using RR and 95% CI. Multiple regression analysis was used addressing deficit of weight-for-age, height-for-age and an altered Denver Test, estimating their independent adjusted RR and 95% CI. RESULTS: 634 women with perinatal outcomes available (311 with SMM and 323 without) and 571 children were assessed. Among women with SMM, increased rates in perinatal deaths, Apgar lower than 7 at five minutes, shorter breastfeeding period, preterm birth (49.0% × 11.1%), low birthweight (45.8% × 11.5%), deficits of weight-for-age [RR 3.11 (1.60-6.04)] and height-for-age [RR 1.52 (1.06-2.19)] and altered Denver Test [RR 1.5 (1.02-2.36)] were more frequently found than in the control group. SMM was not identified as independently associated with any of the main outcomes. CONCLUSION: SMM showed to be associated with a negative impact on growth and neurodevelopment aspects of perinatal and infant health. These findings suggest that effective health policies directed towards appropriate care of pregnancy may have an impact on the reduction of maternal, neonatal and infant morbidity and mortality.

Multidimensional assessment of women after severe maternal morbidity: the COMMAG cohort study.

OBJECTIVES: To perform a multidimensional assessment of women who experienced severe maternal morbidity (SMM) and its short-term and medium-term impact on the lives and health of women and their children. DESIGN: A retrospective cohort study. SETTING: A tertiary maternity hospital from the southeast region of Brazil. PARTICIPANTS: The exposed population was selected from intensive care unit admissions if presenting any diagnostic criteria for SMM. Controls were randomly selected among women without SMM admitted to the same maternity and same time of childbirth. PRIMARY AND SECONDARY OUTCOME VARIABLES: Validated tools were applied, addressing post-traumatic stress disorder (PTSD) and quality of life (SF-36) by phone, and then general and reproductive health, functioning (WHO Disability Assessment Schedule), sexual function (Female Sexual Function Index (FSFI)), substance abuse (Alcohol, Smoking and Substance Involvement Screening Test 2.0) and growth/development (Denver Developmental Screening Test) of children born in the index pregnancy in a face-to-face interview. RESULTS: All instruments were applied to 638 women (315 had SMM; 323 were controls, with the assessment of 264 and 307 children, respectively). SF-36 score was significantly lower in the SMM group, while PTSD score was similar between groups. Women who had SMM became more frequently sterile, had more abnormal clinical conditions after the index pregnancy and a higher score for altered functioning, while proportions of FSFI score or any drug use were similar between groups. Furthermore, children from the SMM group were more likely to have weight (threefold) and height (1.5 fold) for age deficits and also impaired development (1.5-fold). CONCLUSION: SMM impairs some aspects of the lives of women and their children. The focus should be directed towards monitoring these women and their children after birth, ensuring accessibility to health services and reducing short-term and medium-term repercussions on physical, reproductive and psychosocial health.

General and reproductive health among women after an episode of severe maternal morbidity: Results from the COMMAG study.

OBJECTIVE: To assess general and reproductive health in women after severe maternal morbidity (SMM). METHODS: A retrospective cohort study was performed at a tertiary maternity hospital. Women with SMM criteria who delivered during 2008-2012 were included in the SMM group. The control group included a random sample of women without SMM delivering in the same year of cases. Both groups were compared regarding sociodemographic/obstetric characteristics, general and reproductive health, using χ2 , Yates χ2 , Fisher exact, and Mann-Whitney tests. RESULTS: There were 315 women in the SMM group and 323 women in the control group. The SMM group was older and had a history of more medical conditions (hypertension, diabetes, obesity), cesarean deliveries, preterm births, and perinatal deaths. Breastfeeding was negatively affected in these women, as was fertility. The SMM group had a non-significant trend of fewer children after index pregnancy, had new complications in subsequent pregnancies, and required specialized medical care, besides higher risk of death. CONCLUSION: Women experiencing SMM are at higher risk of general and reproductive health problems after pregnancy, including risk of death. Therefore, their surveillance and follow-up should continue beyond 42 days postpartum, highlighting the importance of more specialized health care.

Secondary colonic stent insertion in acute large bowel obstruction following primary stent failure.

INTRODUCTION: Colonic stent insertion has been shown to be an effective treatment for patients with acute large bowel obstruction, either as a bridge to surgery or as definitive treatment. However, little is known of the role of secondary stent insertion following primary stent failure in patients considered inappropriate or high risk for emergency surgery. METHODS: Fourteen patients presenting with acute large bowel obstruction who had previously been treated with colonic stent insertion were studied. All underwent attempted placement of a secondary stent. RESULTS: Technical deployment of the stent was accomplished in 12 patients (86%) but only 9 (64%) achieved clinical decompression. Successful deployment and clinical decompression of a secondary stent was associated with older age (p=0.038). Sex, pathology, site of obstruction, duration of efficacy of initial stent and cause of primary failure were unrelated to outcome. No procedure related morbidity or mortality was noted following repeated intervention. CONCLUSIONS: Secondary colonic stent insertion appears an effective, safe treatment in the majority of patients presenting with acute large bowel obstruction following failure of a primary stent.

Quality of Life after an Episode of Severe Maternal Morbidity: Evidence from a Cohort Study in Brazil.

OBJECTIVE: To assess quality of life (QOL) in women who experienced a severe maternal morbidity (SMM) event and associated factors, in comparison to those who did not. STUDY DESIGN: Retrospective cohort study performed at the maternity of the University of Campinas in Brazil, including 801 women with or without SMM, within 6 months to 5 years after delivery. Women were interviewed by phone and data were electronically stored, using the Brazilian version of the SF36 to assess women's self-perception of quality of life. To analyze a possible relationship between SMM and perceived impairment in quality of life, χ2 and Fisher's Exact tests were used. Multiple analysis using Generalized Linear Models was applied to identify factors independently associated with the general health score. The main outcome measures were general and domain-specific SF36 scores on quality of life. RESULTS: Maternal morbidity conditions were associated with lower scores of patient perceptions of quality of life in the following domains: physical functioning, role-limiting physical, pain, and general health status. A lower level of school education, not having a partner, caesarean section, and history of previous clinical conditions were associated with a worse perception of general health and quality of life. CONCLUSION: Health professionals should know the association between life conditions, previous chronic health conditions, and SMM for women during prenatal care to beyond 42 weeks postpartum. Longitudinal and interdisciplinary actions should be put into practice to provide healthcare for these women, with special emphasis on the effective reduction in health inequities.

Reference ranges of the WHO Disability Assessment Schedule (WHODAS 2.0) score and diagnostic validity of its 12-item version in identifying altered functioning in healthy postpartum women.

OBJECTIVES: To compare scores on the 36-item WHO Disability Assessment Schedule 2.0 tool (WHODAS-36) for postpartum women across a continuum of morbidity and to validate the 12-item version (WHODAS-12). METHODS: This is a secondary analysis of the Brazilian retrospective cohort study on long-term repercussions of severe maternal morbidity. We determined mean, median, and percentile values for WHODAS-36 total score and for each domain, and percentile values for WHODAS-12 total score in postpartum women divided into three groups: "no," "nonsevere," and "severe" morbidities. RESULTS: The WHODAS-36 mean total scores were 11.58, 18.31, and 19.19, respectively for no, nonsevere, and severe morbidity. There was a dose-dependent effect on scores for each domain of WHODAS-36 according to the presence and severity of morbidity. The diagnostic validity of WHODAS-12 was determined by comparing it with WHODAS-36 as a "gold standard." The best cut-off point for diagnosing dysfunctionality was the 95th percentile. CONCLUSION: The upward trend of WHODAS-36 total mean value scores of women with no morbidity compared with those with morbidity along a severity continuum may reflect the impact of morbidity on postpartum functioning.

Validation of the WHO Disability Assessment Schedule (WHODAS 2.0) 12-item tool against the 36-item version for measuring functioning and disability associated with pregnancy and history of severe maternal morbidity.

OBJECTIVE: To validate the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item tool against the 36-item version for measuring functioning and disability associated with pregnancy and the occurrence of maternal morbidity. METHODS: This is a secondary analysis of the Brazilian retrospective cohort study on long-term repercussions of severe maternal morbidity (SMM) among women who delivered at a tertiary facility (COMMAG study). We compared WHODAS-12 and WHODAS-36 scores of women with and without SMM using measures of central tendency and variability, tests for instruments' agreement (Bland-Altman plot), confirmatory factor analysis (CFA), and Cronbach alpha coefficient for internal consistency. RESULTS: The COMMAG study enrolled 638 women up to 5 years postpartum. Although the median WHODAS-36 and -12 scores for all women were statistically different (13.04 and 11.76, respectively; P<0.001), there was a strong linear correlation between them. Furthermore, the mean difference and the differences in variance analyses demonstrated agreement of total scores between the two versions. CFA demonstrated how the WHODAS-12 questions are divided into six previously defined factors and Cronbach alpha showed good internal consistency. CONCLUSION: WHODAS-12 demonstrated agreement with WHODAS-36 for total score and was a good instrument for screening functioning and disability among postpartum women, with and without SMM.

The impact of hypertension, hemorrhage, and other maternal morbidities on functioning in the postpartum period as assessed by the WHODAS 2.0 36-item tool.

OBJECTIVE: To assess the scores of postpartum women using the WHO Disability Assessment Schedule 2.0 36-item tool (WHODAS-36), considering different morbidities. METHODS: Secondary analysis of a retrospective cohort of women who delivered at a referral maternity in Brazil and were classified with and without severe maternal morbidity (SMM). WHODAS-36 was used to assess functioning in postpartum women. Percentile distribution of total WHODAS score was compared across three groups: Percentile (P)<10, 1090. Cases of SMM were categorized and WHODAS-36 score was assessed according to hypertension, hemorrhage, or other conditions. RESULTS: A total of 638 women were enrolled: 64 had mean scores below P<10 (1.09) and 66 were above P>90 (41.3). Of women scoring above P>90, those with morbidity had a higher mean score than those without (44.6% vs 36.8%, P=0.879). Women with higher WHODAS-36 scores presented more complications during pregnancy, especially hypertension (47.0% vs 37.5%, P=0.09). Mean scores among women with any complication were higher than those with no morbidity (19.0 vs 14.2, P=0.01). WHODAS-36 scores were higher among women with hypertensive complications (19.9 vs 16.0, P=0.004), but lower among those with hemorrhagic complications (13.8 vs 17.7, P=0.09). CONCLUSIONS: Complications during pregnancy, childbirth, and the puerperium increase long-term WHODAS-36 scores, demonstrating a persistent impact on functioning among women, up to 5 years postpartum.

Post-Traumatic Stress Disorder and severe maternal morbidity: is there an association?

OBJECTIVE: To evaluate the occurrence of Post-Traumatic Stress Disorder among women experiencing a severe maternal morbidity event and associated factors in comparison with those without maternal morbidity. METHODS: In a retrospective cohort study, 803 women with or without severe maternal morbidity were evaluated at 6 months to 5 years postpartum for the presence of Post-Traumatic Stress Disorder. Interviews were conducted by telephone and electronic data was stored. Data analysis was carried out by using χ2, Fisher's Exact test, and logistic regression analysis. RESULTS: There was no significant change in the prevalence of Post-Traumatic Stress Disorder related to a previous severe maternal morbidity experience. There were also no differences in diagnostic criteria for severe maternal morbidity (hypertensive syndromes, hemorrhage, surgical intervention or intensive care unit admission required, among other management criteria). Low parity (2.5-fold risk) and increasing age were factors associated with Post-Traumatic Stress Disorder. CONCLUSIONS: A severe maternal morbidity episode is not associated with Post-Traumatic Stress Disorder symptoms within five years of the severe maternal morbidity event and birth. However, a more advanced maternal age and primiparity increased the risk of Post-Traumatic Stress Disorder. This does not imply that women who had experienced a severe maternal morbidity event did not suffer or need differentiated care.

Post-Traumatic Stress Disorder and severe maternal morbidity: is there an association?

OBJECTIVE: To evaluate the occurrence of Post-Traumatic Stress Disorder among women experiencing a severe maternal morbidity event and associated factors in comparison with those without maternal morbidity. METHODS: In a retrospective cohort study, 803 women with or without severe maternal morbidity were evaluated at 6 months to 5 years postpartum for the presence of Post-Traumatic Stress Disorder. Interviews were conducted by telephone and electronic data was stored. Data analysis was carried out by using χ2, Fisher's Exact test, and logistic regression analysis. RESULTS: There was no significant change in the prevalence of Post-Traumatic Stress Disorder related to a previous severe maternal morbidity experience. There were also no differences in diagnostic criteria for severe maternal morbidity (hypertensive syndromes, hemorrhage, surgical intervention or intensive care unit admission required, among other management criteria). Low parity (2.5-fold risk) and increasing age were factors associated with Post-Traumatic Stress Disorder. CONCLUSIONS: A severe maternal morbidity episode is not associated with Post-Traumatic Stress Disorder symptoms within five years of the severe maternal morbidity event and birth. However, a more advanced maternal age and primiparity increased the risk of Post-Traumatic Stress Disorder. This does not imply that women who had experienced a severe maternal morbidity event did not suffer or need differentiated care.

Viscoelastometry guided fresh frozen plasma infusion for postpartum haemorrhage: OBS2, an observational study.

BACKGROUND: Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. Based on data from trauma studies, empirical infusions of fresh frozen plasma (FFP) are often given during severe PPH if coagulation tests are unavailable. This study observed a cohort of women with moderate/severe PPH in whom FFP infusion was guided by the use of viscoelastometric point-of-care testing (VE-POCT) and clinical assessment. METHODS: Women were enrolled into this observational study when blood loss was measured or suspected to be about 1000 mL. If Fibtem A5 determined by Rotem ® thromboelastometry remained >15 mm, or bleeding stopped, FFP was withheld. If Fibtem A5 was ≤15 mm and bleeding ongoing, women were randomized into an interventional study as previously reported. Clinical and laboratory outcomes were recorded. RESULTS: The study recruited 605 women and 98% had FFP withheld. The median (25 th -75 th centile) total blood loss was 1500 (1300-2000) mL with 300 (50-545) mL occurring after enrolment. Total blood loss was >2500 mL in 40/605 (6.6%) women. RBCs were transfused in 141/605 (23.3%) patients and 11 (1.8%) received ≥4 units. At least one invasive procedure was performed in 283/605 (46.8%) women. Level 3 care was required for 10/605 (1.7%) women. No women developed clinically significant haemostatic impairment. CONCLUSIONS: Restrictive use of FFP guided by clinical assessment of bleeding and VE-POCT is feasible and did not result in clinically significant haemostatic impairment. Studies should compare the clinical and cost effectiveness of empirical FFP infusions, according to current guidelines, with targeted use of FFP based on VE-POCT. CLINICAL TRIAL REGISTRATION: ISRCTN46295339 ( http://www.isrctn.com/ISRCTN46295339 ) (accessed July 24, 2017), EudraCT 2012-005511-11 ( https://www.clinicaltrialsregister.eu/ctr-search?query=2011-005511-11 ) (accessed July 24, 2017).

Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial.

BACKGROUND: Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. We hypothesized that early fibrinogen replacement, guided by viscoelastometric testing, reduces blood product usage and bleed size. METHODS: Women with PPH 1000-1500 ml were enrolled. If Fibtem A5 was ≤15 mm and bleeding continued, subjects were randomized to fibrinogen concentrate or placebo. The primary outcome compared the number of units of red blood cells, plasma, cryoprecipitate and platelets transfused. RESULTS: Of 663 women enrolled 55 were randomized. The adjusted incidence rate ratio (IRR) (95% CI) for the number of allogeneic units transfused in the fibrinogen group compared with placebo was 0.72 (0.3-1.7), P =0.45. In pre-specified subgroup analyses, subjects who had a Fibtem A5 ≤12 mm at the time of randomization and who received fibrinogen concentrate received a median (25th-75th centile) of 1 (0-4.5) unit of allogeneic blood products and had an additional 300 (100-350) ml blood loss whereas those who received placebo also received 3 (0-6) units of allogeneic blood products and had 700 (200-1550) ml additional blood loss; these differences were not statistically significantly different. There was one thrombotic event in each group. CONCLUSIONS: Infusion of fibrinogen concentrate triggered by Fibtem A5 ≤15 mm did not improve outcomes in PPH. Pre-specified subgroup analyses suggest that fibrinogen replacement is not required if the Fibtem A5 is > 12 mm or Clauss fibrinogen >2 g litre -1 , but an effect below these levels cannot be excluded. The raised fibrinogen at term appears to be a physiological buffer rather than required for haemostasis. TRIAL REGISTRATION: ISRCTN46295339 ( http://www.isrctn.com/ISRCTN46295339 , last accessed 5 July 2017), EudraCT 2012-005511-11 ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-005511-11 , last accessed 5 July 2017).

Multivariate and integrative approach to analyze multiple biomarkers in ecotoxicology: A field study in Neotropical region.

Aquatic pollution has dramatically worsened in developing countries, due to the discharge of a mixture of pollutants into water bodies, to the lack of stringent laws, and the inadequate treatment of effluents. In this study, the Neotropical fish Astyanax aff. paranae was sampled from three sites with different pollution levels: 1) a Biological Reserve (Rebio), protected by the Brazilian government; 2) an agricultural area in one of the most productive regions of Brazil, upstream of an urban zone; and 3) a site downstream from urban zone, characterized by the influx of different effluents, including wastes from industry, a sewer treatment plant, and agricultural areas. We assess biomarkers at multiple levels, such as the comet assay, hepatic histopathological analysis, brain and muscle acetylcholinesterase (AChE) and the hepatic enzymes glutathione-S-transferase (GST), catalase (CAT), and lipoperoxidation (LPO), during winter and summer. The interpretation of field results is always a very complex operation, since many factors can influence the variables analyzed in uncontrollable conditions. For this reason, we apply an integrative multivariate analysis. The results showed that the environmental risk of the three sites was significantly different. We can see a gradient in data distribution in discriminant analysis: separating, from one side, the fish of Rebio; in the middle are the fish from agricultural area and, in the other side are the animals from downstream site. Overall, the biomarkers responses were more greatly altered in the downstream site, whereas fish from the agricultural area showed an intermediate level of damage. The greatest changes were likely caused by agriculture, industrial chemical effluents and ineffective sewage treatments, in a synergic interaction in downstream site. In conclusion, the use of multiple biomarkers at different response levels to assess the toxic effects of mixed pollutants in a natural aquatic environment is an important tool for monitoring polluted regions.

Integrated regulation of AMPA glutamate receptor phosphorylation in the striatum by dopamine and acetylcholine.

Dopamine (DA) and acetylcholine (ACh) signals converge onto protein kinase A (PKA) in medium spiny neurons of the striatum to control cellular and synaptic activities of these neurons, although underlying molecular mechanisms are less clear. Here we measured phosphorylation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) at a PKA site (S845) as an indicator of AMPAR responses in adult rat brains in vivo to explore how DA and ACh interact to modulate AMPARs. We found that subtype-selective activation of DA D1 receptors (D1Rs), D2 receptors (D2Rs), or muscarinic M4 receptors (M4Rs) induced specific patterns of GluA1 S845 responses in the striatum. These defined patterns support a local multitransmitter interaction model in which D2Rs inhibited an intrinsic inhibitory element mediated by M4Rs to enhance the D1R efficacy in modulating AMPARs. Consistent with this, selective enhancement of M4R activity by a positive allosteric modulator resumed the cholinergic inhibition of D1Rs. In addition, D1R and D2R coactivation recruited GluA1 and PKA preferentially to extrasynaptic sites. In sum, our in vivo data support an existence of a dynamic DA-ACh balance in the striatum which actively modulates GluA1 AMPAR phosphorylation and trafficking. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.