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ABSTRACTBackgroundThe bed nucleus of the stria terminalis (BNST) is a structure with a peculiar neurochemical composition involved in modulating anxietylike behavior and fear.AimThe present study investigated the effects on the BNST neurochemical composition and neuronal structure in critical moments of the postnatal period in gestational protein-restricted male rats' offspring.MethodsDams were maintained during the pregnancy on isocaloric rodent laboratory chow with standard protein content [NP, 17%] or low protein content [LP, 6%]. BNST from male NP and age-matched LP offspring was studied using the isotropic fractionator method, Neuronal 3D reconstruction, dendritic-tree analysis, blotting analysis, and high-performance liquid chromatography.ResultsSerum corticosterone levels were higher in male LP offspring than NP rats in 14-day-old offspring, without any difference in 7-day-old progeny. The BNST total cell number and anterodorsal BNST division volume in LP progeny were significantly reduced on the 14th postnatal day compared with NP offspring. The BNST HPLC analysis from 7 days-old LP revealed increased norepinephrine levels compared to NP progeny. The BNST blotanalysis from 7-day-old LP revealed reduced levels of GR and BDNF associated with enhanced CRF1 expression compared to NP offspring. 14-day-old LP offspring showed reduced expression of MR and 5HT1A associated with decreased DOPAC and DOPA turnover levels relative to NP rats. In Conclusion, the BNST cellular and neurochemical changes may represent adaptation during development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition alters the BNST content and structure and contributes to already-known behavioral changes.

Background/objective: A high prevalence of fatigue and a positive association between fatigue and post-hemodialysis recovery have been reported in predominantly white populations of maintenance hemodialysis (MHD) patients. The present study evaluates associations between self-reported fatigue by the 11-item Chalder Fatigue Questionnaire (CFQ-11) and the need for post-hemodialysis recovery in a predominantly African-descent MHD population.Methods: A total of 233 patients (94% Black or Mixed-Race) participating in the “Prospective Study of the Prognosis of Patients on Maintenance Hemodialysis” (PROHEMO), Salvador, Brazil were recruited for this cross-sectional study. The CFQ-11 was used to measure fatigue: <4 for absent or mild, ⩾4 for moderate to severe. Patients were also asked if they needed some time to recover after the hemodialysis. Logistic regression was used to estimate odds ratio (OR) of the association with adjustments for age, sex, race, educational level, economic class level, diabetes, hearth failure, and hemoglobin.Results: Mean age was 51.5 ± 12.5 years. Moderate to severe fatigue (⩾4 points) was observed in 70.8% (165/233), and absent or mild fatigue (<4 points) in 29.2% (68/233). Compared to patients with fatigue scores <4 (20.6%), the need for post-hemodialysis recovery was 2.5 times greater in patients with fatigue scores ⩾4 (52.7%). The covariate-adjusted logistic regression OR was 4.60, 95% CI: 2.27, 9.21.Conclusion: This study in MHD patients of predominantly African descent supports self-reported fatigue assessed by the CFQ-11 as a relevant predictor of the need for post-hemodialysis recovery. The results offer a rationale for investigating whether interventions to prevent fatigue reduce the need of post-hemodialysis recovery.

Background:The existing data support the Chalder Fatigue Questionnaire (CFQ-11) as a valid instrument to assess fatigue in maintenance hemodialysis (MHD) patients. The objective of this work was to investigate whether self-reported fatigue can serve as an independent prognostic indicator for mortality in MHD patients. Methods:The data are from 233 adult patients enrolled in the cohort “The Prospective Study of the Prognosis of Chronic Hemodialysis Patients” (PROHEMO) developed in Salvador, BA, Brazil. The Brazilian version of the validated CFQ-11 was used to calculate self-reported fatigue. The CFQ-11 scores may range from 0 to 33; higher scores represent more fatigue. Fatigue categories were created based on proposed cut point: absence or mild degree if CFQ-11 scores <4 and moderate to severe if scores ≥4. Cox models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of associations between fatigue and mortality with adjustments for sociodemographic factors, time on dialysis, education, economic class, hemoglobin concentration, diabetes, heart failure, depression, and other psychiatric disorders. Results:The mean age was 51.5 ± 2.5 years, 58% were male, and 30% were diabetic. Self-reported moderate to severe fatigue was reported by 71% of patients. The mortality rate was 8.6 cases/100 person-years. Patients with moderate to severe fatigue had a more than threefold mortality rate (HR = 3.07, 95% CI: 1.19, 7.93) compared to patients with absent or mild fatigue, after extensive adjustments for covariates. Conclusion:The study provides evidence that self-reported fatigue can help identify MHD patients at higher risk of earlier death.

ABSTRACTBackgroundGestational protein intake restriction-induced long-lasting harmful outcomes in the offspring's organs and systems. However, few studies have focused on this event's impact on the brain's structures and neurochemical compounds.AimThe present study investigated the effects on the amygdala neurochemical composition and neuronal structure in gestational protein-restricted male rats' offspring.MethodsDams were maintained on isocaloric standard rodent laboratory chow with regular protein [NP, 17%] or low protein content [LP, 6%]. Total cells were quantified using the Isotropic fractionator method, Neuronal 3D reconstruction, and dendritic tree analysis using the Golgi–Cox technique. Western blot and high-performance liquid chromatography performed neurochemical studies.ResultsThe gestational low-protein feeding offspring showed a significant decrease in birth weight up to day 14, associated with unaltered brain weight in youth or adult progenies. The amygdala cell numbers were unchanged, and the dendrites length and dendritic ramifications 3D analysis in LP compared to age-matched NP progeny. However, the current study shows reduced amygdala content of norepinephrine, epinephrine, and dopamine in LP progeny. These offspring observed a significant reduction in the amygdala glucocorticoid (GR) and mineralocorticoid (MR) receptor protein levels. Also corticotrophin-releasing factor (CRF) amygdala protein content was reduced in 7 and 14-day-old LP rats.ConclusionThe observed amygdala neurochemical changes may represent adaptation during embryonic development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition stress can alter the amygdala's neurochemical content and may contribute to known behavioral changes induced by gestational protein restriction.

Background and objective: Some studies on maintenance hemodialysis (MHD) patients report a longer survival, albeit with poorer health-related quality of life (HRQoL), and more depression symptoms in women than in men. Whether these gender differences vary with age is uncertain. We tested the associations of gender with mortality, depression symptoms, and HRQoL in MHD patients of different age groups.Methods: We used data from 1504 adult MHD patients enrolled in the PROHEMO, a prospective cohort in Salvador, Brazil. The KDQOL-SF was used for the component summaries of the mental (MCS) and physical (PCS) HRQoL scales. Depression symptoms were assessed by the complete version of the Center for Epidemiological Studies Depression Screening Index (CES-D). To test for gender differences, extensively adjusted linear models were used for depression and HRQoL scores, and Cox models for death hazard ratio (HR).Results: Women reported worse HRQoL than men, particularly for ages ⩾60 years. In the age group ⩾60 years, the adjusted difference (AD) in score was −3.45; 95% CI: −6.81, −0.70 for MCS −3.16; −5.72, −0.60 for PCS. Older (⩾60 years) women also had more depression symptoms (AD 4.98; 2.33, 7.64). Mortality was slightly lower in women than in men with an adjusted HR of 0.89 (0.71, 1.11) and consistent across age categories.Conclusions: In a sample of Brazilian MHD patients, women had a slightly lower mortality, albeit with more depression symptoms and poorer HRQoL than men, particularly among older patients. This study highlights the need to investigate gender inequalities for MHD patients across different cultures and populations.

Background: Maternal undernutrition has been associated with psychiatric and neurological disorders characterized by learning and memory impairment.Objective: Considering the lack of evidence, we aimed to analyze the effects of gestational protein restriction on learning and memory function associated with hippocampal cell numbers and neurodegenerative protein content later in life.Methods: Experiments were conducted in gestational low- (LP, 6% casein) or regular-protein (NP, 17% casein) diet intake offspring. Behavioral tests, isolated hippocampal isotropic fractionator cell studies, immunoblotting, and survival lifetime were observed.Results: The birthweight of LP males is significantly reduced relative to NP male progeny, and hippocampal mass increased in 88-week-old LP compared to age-matched NP offspring. The results showed an increased proximity measure in 87-week-old LP compared to NP offspring. Also, LP rats exhibited anxiety-like behaviors compared to NP rats at 48 and 86-wk of life. The estimated neuron number was unaltered in LP rats; however, non-neuron cell numbers increased compared to NP progeny. Here, we showed unprecedented hippocampal deposition of brain-derived neurotrophic factor, amyloid-ß peptide (Aß), and tau protein in 88-week-old LP relative to age-matched NP offspring.Conclusion: To date, no predicted studies showed changes in hippocampal morphological structure in maternal protein-restricted elderly offspring. The current data suggest that gestational protein restriction may accelerate hippocampal function loss, impacting learning/memory performance, and supposedly developing diseases similar to Alzheimer’s disease (AD) in elderly offspring. Thus, we propose that maternal protein restriction could be an elegant and novel method for constructing an AD-like model in adult male offspring.

Canine distemper outbreak and coinfections in three giant anteaters and in a maned wolf has been described. Three giant anteaters developed respiratory and digestive clinical signs after the introduction of a maned wolf to a Wildlife Rehabilitation Center. The maned wolf and two anteaters died, and one anteater was euthanized. Post mortem and histopathologic exams revealed lesions associated with numerous intraepithelial inclusion bodies, mainly in the respiratory and digestive systems. Infection by distemper virus was confirmed in all animals by RT-PCR and gene sequencing, which revealed the Europe 1/ South America 1 strain, closely related to the strain from Canis familiaris. In addition to distemper, the animals had other comorbidities, such as toxoplasmosis and salmonellosis in the maned wolf and cutaneous candidiasis in an anteater. Considering the chronology of clinical manifestation in both species and the viral characterization, it is possible that the maned wolf was the source of infection to the anteaters. This study demonstrates the importance of implementing biosecurity measures in enclosures that house animals of different species, highlighting the importance of quarantine before introduction of new animals into the same environment.

Background/objective: There is a lack of studies describing the prevalence of vascular calcification (VC) and its association with mortality in maintenance hemodialysis (MHD) patients of African descent. We investigated if a VC score based on the number of calcified vascular beds was associated with mortality in MHD patients.Methods: We analyzed data from 211 MHD patients enrolled from January 2010 to January 2011 in the prospective cohort study, “The Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO),” developed in Salvador, BA, Brazil. VC was evaluated using radiographs of the hands, abdomen, hip, and chest; the score was calculated by the number of calcified sites as 0 (absence of calcification), 1 (one calcified site), 2 (two sites), 3 (⩾3 sites). We used Cox’s regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of associations between VC and mortality with adjustments for age and comorbidities.Results: VC was detected in 114 (54.0%) patients; 37 (17.5%) with a VC score = 1; 21 (10%) with VC score = 2 and 56 (26.5%) with VC score = 3. Compared with VC score = 0, the adjusted hazard of death was 2.67 (95% CI: 1.12, 6.33) for patients with VC score = 1; HR = 2.89 (95% CI: 0.95, 7.63) for VC score = 2; and HR = 3.27 (95% CI: 1.47, 7.28) for VC score = 3.Conclusion: The present study in an African descent MHD population provides support for the VC score based on conventional radiography as a prediction tool for the clinical practice. As shown, the VC score was monotonically and independently associated with mortality.

Purpose: The potential of lowered surface features as well as the application of wear resistant coatings have been known for many years to improve the tribological behavior of forming tools. More recent studies also discuss the capability of protruded microfeatures for adjusting the tribological behavior between contacting surfaces. The demand for a high wear resistance of such structures as well as their economical and reliable production, however, often limits the industrial application. The laser implantation process can overcome these limitations. In contrast to conventional cw-laser dispersing processes, where the formation of uniform metal matrix composite layers is intended, this surface engineering technique aims to improve the tribological behavior of contacting surfaces by a localized dispersing of pre-placed hard ceramic particles. This enables the formation of deterministic textures composed of separated wear resistant dome- or ring-shaped microstructures (implants). Since TaC shows very promising material properties for improving the wear resistance of tools exposed to severe operating conditions, this paper analyzes its suitability for pulsed laser implantation on X38CrMoV5-3 tool steel for the first time. Methods: In the experiments, the influence of the particles and the laser parameters (pulse power, pulse duration and focal diameter) on the material properties of the localized dispersed zones was studied by optical microscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction. The composite’s (micro-) hardness was measured and calculated by using a rule of mixture. Additionally, the influence of the laser parameters and the TaC particles on the geometrical properties of the implants was studied by optical microscopy and white light interferometry. Results: The results showed that defect-free implants with hardness values of ~900 HV1 can be obtained at the focal spot, since a localized dispersing of the TaC particles is possible using a pulsed millisecond laser. However, in dependence of the laser intensity, also a partial dissolution of the initial particles occurs. This leads to the precipitation of new dendritic TaC nanoparticles and to varying contents of retained austenite in the matrix. Both effects have a strong influence on the implant hardness and must be considert by the rule of mixture. Regarding the geometrical response it was pointed out that protruded microfeatures with heights up to 10 μm can be created. In comparison to laser remelted zones, the implanted zones showed significantly altered weld pool profiles due to the influence of the particles on the melt convection. A transition of the implant shape from predominantly dome-shaped to predominantly ring-shaped was observed for intensities >1.7∙106W/cm2due to the onset of the keyhole effect. Conclusions: In conclusion, TaC particles seem to be very suitable for laser implantation on hot-work tool steels. The implants can be used for textures, where flat structures are needed. Since the TaC particles can be dispersed in the LIZ, it may be possible to reduce abrasive and adhesive wear due to the promising material properties of this hard phase and the improved hardness of the implants.

IntroductionDuring the COVID-19 pandemic, excess mortality has been reported, while hospitalisations for acute cardiovascular events reduced. Brazil is the second country with more deaths due to COVID-19. We aimed to evaluate excess cardiovascular mortality during COVID-19 pandemic in 6 Brazilian capital cities.MethodsUsing the Civil Registry public database, we evaluated total and cardiovascular excess deaths, further stratified in specified cardiovascular deaths (acute coronary syndromes and stroke) and unspecified cardiovascular deaths in the 6 Brazilian cities with greater number of COVID-19 deaths (São Paulo, Rio de Janeiro, Fortaleza, Recife, Belém, Manaus). We compared observed with expected deaths from epidemiological weeks 12–22 of 2020. We also compared the number of hospital and home deaths during the period.ResultsThere were 65 449 deaths and 17 877 COVID-19 deaths in the studied period and cities for 2020. Cardiovascular mortality increased in most cities, with greater magnitude in the Northern capitals. However, while there was a reduction in specified cardiovascular deaths in the most cities, the Northern capitals showed an increase of these events. For unspecified cardiovascular deaths, there was a marked increase in all cities, which strongly correlated to the rise in home deaths (r=0.86, p=0.01).ConclusionExcess cardiovascular mortality was greater in the less developed cities, possibly associated with healthcare collapse. Specified cardiovascular deaths decreased in the most developed cities, in parallel with an increase in unspecified cardiovascular and home deaths, presumably as a result of misdiagnosis. Conversely, specified cardiovascular deaths increased in cities with a healthcare collapse.

Objective: To investigate associations of sex-age-specific handgrip strength by a dynamometer with all-cause mortality and the percent excess risk explained (%ERE) by comorbidities and nutritional indicators in incident maintenance hemodialysis patients.Methods: Prospective cohort of 413 adult patients (165 women, 248 men, 299 <60 years and 114 ⩾60 years) with <6 months (82% <3 months) on dialysis enrolled in PROHEMO in Salvador, Brazil. Low and high handgrip strength groups were based on sex-age-specific cutoffs (17.8 kg for women <60 years, 13.8 kg for women ⩾60 years, 29.5 kg for men <60 years, and 21.9 kg for men ⩾60 years). We used Cox regression to estimate the mortality hazard ratio. The %ERE was determined by the equation (HR1 – HR2)/(HR1 – 1) × 100, in which HR1 represented the hazard ratio in a model with a smaller number of covariates and HR2 represented the hazard ratio in a subsequent model with the inclusion of new covariates plus the variables included in the previous model.Results: The mortality hazard ratio comparing low and high handgrip strength was 2.58 (95% confidence interval: 1.73, 3.85) in the model with sociodemographic factors and vintage and 2.25 (95% confidence interval: 1.49, 3.43) with addition of comorbidities, corresponding to a %ERE of 21%. The hazard ratio was 1.98 (95% confidence interval: 1.29, 3.06) after addition of nutritional indicators corresponding to %ERE of 38%. Results stratified by age and gender followed similar patterns.Conclusion: These results provide support for the assessment of handgrip strength in all maintenance hemodialysis patients for early identification of those who may require special care to improve nutritional status and survival.

Introduction: The use of phosphate binders to control hyperphosphatemia may allow diets less restricted in protein and calories for maintenance hemodialysis (MHD) patients. The study compared intakes of protein, calorie and phosphate among MHD patients with different serum phosphate concentrations, taking into account binder use. The hypothesis was that low serum phosphate would be associated with low intakes of protein and calories only in patients not on binders.Methods: A cross-sectional study of 443 patients enrolled in the Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO) in Salvador, Brazil, with stratified sampling on serum phosphate: ≤3.0 (n = 41), 3.5-5.5 (n = 328) and ≥7.0 mg/dL (n = 74). A 3-day diet diary was used to determine dietary intakes.Results: Approximately 49.0% confirmed binder use. Covariate-adjusted linear regression showed that associations between dietary intakes and serum phosphate were modified by the binder use. In patients not on binders, protein intake was >20% lower for serum phosphate ≤3.0 mg/dL compared to higher concentrations. Also in those not on binders, calorie intake was >30% lower for serum phosphate ≤3.0 mg/dL compared to ≥7.0 mg/dL. Differences in dietary intakes by serum phosphate were virtually absent in patients on binders.Conclusions: The results are consistent with the hypothesis that low serum phosphate is associated with low protein and calorie intake only among MHD patients not on binders. This study supports recommendations to prevent hyperphosphatemia in MHD patients by adequate combination of binder use and selection of foods restricted in phosphors but not severely restricted in protein and calories.

Background Sedentariness, high inflammation status and malnutrition are highly prevalent in end-stage kidney disease patients on maintenance hemodialysis (MHD). This study investigated associations of weekly physical activity energy expenditure (PAEE) with clinical and anthropometric markers of nutrition and inflammation.Methods The analysis was performed using baseline cross-sectional data of 640 patients enrolled in the prospective cohort “The Prospective Study of the Prognosis of Patients Treated Chronically by Hemodialysis” (PROHEMO) developed in Salvador, BA, Brazil. The long version of the International Physical Activity Questionnaire was used to determine a summary measure of PAEE, the metabolic equivalent of task (MET), taking into account physical activities related to occupation, recreation, travel, sports, and housework. PAEE was the predictor variable. To assess associations of PAEE with outcomes, the sex-age-specific median MET was used. The malnutrition-inflammation score (MIS) with range of 0 to 30 (higher is worse), conicity index as indicator of abdominal adiposity and C-reactive protein (CRP) were the nutritional-inflammatory outcomes.Results The mean age of the patients was 48.9 ± 13.8 y, 60.3% were males, 16.7% diabetic, 88.1% nonwhite. In multivariable logistic regression models with adjustments for sociodemographic variables and comorbidities, PAEE =median was associated with MIS =6 (odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.08, 2.29), conicity index =1.3 (OR = 1.52, 95% CI = 1.03, 2.23) and CRP >1.30 mg/dL (OR = 1.69, 95% CI = 1.08, 2.84).Conclusions Greater physical activity assessed by PAEE was associated with indicators of better nutritional and inflammation status. These results indicate opportunities for improving outcomes in MHD patients by counseling and treatment intervention.

The malnutrition-inflammation score (MIS) combines ten components to assess nutritional status. Higher MIS has been associated with higher mortality and poorer health-related quality of life (HRQOL) in maintenance hemodialysis (MHD) patients. It is interesting to investigate associations of each component with mortality and patient-reported outcomes (PROs), that is, HRQOL and depression symptoms, and if MIS associations are generalizable for diverse populations. This study assessed associations of MIS and its components with mortality and PROs in an African descent MHD population.

Esthesioneuroblastoma is an uncommon malignant tumor of the nasal vault. Treatment consists of craniofacial resection. As endoscopic techniques have advanced, this approach has been recommended to avoid morbidity and to reduce costs.

Reactions promoting direct Mannich‐type α‐methylenation of α, β and γ‐ketoesters have been monitored via electrospray ionization mass and tandem mass spectrometric experiments. Key intermediates of the catalytical cycle of this synthetically useful reaction have been intercepted and characterized. The mechanistic information provided by electrospray ionization mass spectrometry/mass spectrometry (ESI‐MS/MS) guided the optimization of reaction conditions, allowing α‐methyleneketoesters to be prepared in high yields (80–95%) and in high‐enough purity for immediate further manipulation. Copyright © 2007 John Wiley & Sons, Ltd.