Early morphological and neurochemical changes of the bed nucleus of stria terminalis (BNST) in gestational protein-restricted male offspring.

BACKGROUND: The bed nucleus of the stria terminalis (BNST) is a structure with a peculiar neurochemical composition involved in modulating anxietylike behavior and fear. AIM: The 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. METHODS: Dams 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. RESULTS: Serum 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 blot analysis 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.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study.

BACKGROUND: Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries. METHODS: A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months. RESULTS: Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing. CONCLUSION: Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Pathological findings and differential diagnoses of lymph node diseases in slaughtered cattle in Brazil: A study of 2000 samples.

Slaughterhouse inspections play a crucial role in the sanitary control of zoonoses and foodborne diseases. This study aimed to identify and analyze the frequencies of lymph node diseases in cattle slaughtered for human consumption, using the samples sent to the anatomic pathology service of the Federal Laboratory for Agricultural Defense (Laboratório Federal de Defesa Agropecuária), Minas Gerais, Brazil, from January 2015 to September 2022. In total, 2000 lymph node samples were analyzed, and additional information was individually retrieved. Lesions were most frequently identified in thoracic lymph nodes. Bacterial isolation and quantitative polymerase chain reaction (qPCR) were performed using samples suspected of tuberculosis. Tuberculosis cases accounted for 89.3% of the samples. Histopathology was more sensitive than other ancillary tests for diagnosing tuberculosis. Paraffin-embedded tissues from lymphoma cases were subjected to immunophenotyping using anti-CD3 and anti-CD79a immunohistochemistry. Frozen and/or paraffin-embedded tissues from lymphoma cases were used to identify the enzootic bovine leukosis (EBL) retrovirus through qPCR. Other diagnoses included primary (T- and B-cell lymphoma) and metastatic neoplasms (squamous cell carcinoma, pulmonary adenocarcinoma, undifferentiated carcinoma, undifferentiated adenocarcinoma, undifferentiated sarcoma, undifferentiated round cell tumor, mesothelioma, hepatic carcinoid, meningioma, and seminoma), actinogranulomas (pyogranulomatous lymphadenitis [actinobacillosis and actinomycosis]), idiopathic lymphadenitis (neutrophilic and/or histiocytic, granulomatous, and suppurative), and miscellaneous nonspecific lymphadenopathies (depletion/lymphoid atrophy, lymphangiectasia, erythrocyte drainage, parasitic eosinophilic lymphadenitis, follicular hyperplasia, and toxic granulomatous lymphadenitis). The combination of histopathology with complementary techniques is important for successful diagnosis, especially in complex cases of high epidemiological, economic, and zoosanitary importance, such as tuberculosis and EBL.

Association of single and serial measures of serum phosphorus with adverse outcomes in patients on peritoneal dialysis: results from the international PDOPPS.

BACKGROUND: While high serum phosphorus levels have been related to adverse outcomes in hemodialysis patients, further investigation is warranted in persons receiving peritoneal dialysis (PD). METHODS: Longitudinal data (2014-17) from the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS), a prospective cohort study, were used to examine associations of serum phosphorus with all-cause mortality and major adverse cardiovascular events via Cox regression adjusted for confounders. Serum phosphorus levels were parameterized by four methods: (i) baseline serum phosphorus; (ii) mean 6-month serum phosphorus; (iii) number of months with serum phosphorus >4.5 mg/dL; and (iv) mean area-under-the-curve of 6-month serum phosphorus control. RESULTS: The study included 5847 PD patients from seven countries; 9% of patients had baseline serum phosphorus <3.5 mg/dL, 24% had serum phosphorus ≥3.5 to ≤4.5 mg/dL, 30% had serum phosphorus >4.5 to <5.5 mg/dL, 20% had serum phosphorus ≥5.5 to <6.5 mg/dL, and 17% had serum phosphorus ≥6.5 mg/dL. Compared with patients with baseline serum phosphorus ≥3.5 to ≤4.5 mg/dL, the adjusted all-cause mortality hazard ratio (HR) was 1.19 (0.92,1.53) for patients with baseline serum phosphorus ≥5.5 to <6.5 mg/dL and HR was 1.53 (1.14,2.05) for serum phosphorus ≥6.5 mg/dL. Associations between serum phosphorus measurements over 6 months and clinical outcomes were even stronger than for a single measurement. CONCLUSIONS: Serum phosphorus >5.5 mg/dL was highly prevalent (37%) in PD patients, and higher serum phosphorus levels were a strong predictor of morbidity and death, particularly when considering serial phosphorus measurements. This highlights the need for improved treatment strategies in this population. Serial serum phosphorus measurements should be considered when assessing patients' risks of adverse outcomes.

Gestational protein restriction alters early amygdala neurochemistry in male offspring.

BACKGROUND: Gestational 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. AIM: The present study investigated the effects on the amygdala neurochemical composition and neuronal structure in gestational protein-restricted male rats' offspring. METHODS: Dams 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. RESULTS: The 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. CONCLUSION: The 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.

Serum biomarkers of iron stores are associated with worse physical health-related quality of life in nondialysis-dependent chronic kidney disease patients with or without anemia.

BACKGROUND: Iron deficiency (ID) is a common condition in nondialysis-dependent chronic kidney disease (NDD-CKD) patients that is associated with poorer clinical outcomes. However, the effect of ID on health-related quality of life (HRQoL) in this population is unknown. We analyzed data from a multinational cohort of NDD-CKD Stages 3-5 patients to test the association between transferrin saturation (TSAT) index and ferritin with HRQoL. METHODS: Patients from Brazil (n = 205), France (n = 2015) and the USA (n = 293) in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps, 2013-2019) were included. We evaluated the association of TSAT and ferritin (and functional and absolute ID, defined as TSAT ≤20% and ferritin ≥300 or <50 ng/mL) on pre-specified HRQoL measures, including the 36-item Kidney Disease Quality of Life physical component summary (PCS) and mental component summary (MCS) as the primary outcomes. Models were adjusted for confounders including hemoglobin (Hb). RESULTS: TSAT ≤15% and ferritin <50 ng/mL and ≥300 ng/mL were associated with worse PCS scores, but not with MCS. Patients with composite TSAT ≤20% and ferritin <50 or ≥300 ng/mL had lower functional status and worse PCS scores than those with a TSAT of 20-30% and ferritin 50-299 ng/mL. Patients with a lower TSAT were less likely to perform intense physical activity. Adjustment for Hb only slightly attenuated the observed effects. CONCLUSIONS: Low TSAT levels, as well as both low TSAT with low ferritin and low TSAT with high ferritin, are associated with worse physical HRQoL in NDD-CKD patients, even after accounting for Hb level. Interventional studies of iron therapy on HRQoL among NDD-CKD individuals are needed to confirm these findings.

Impact of longer term phosphorus control on cardiovascular mortality in hemodialysis patients using an area under the curve approach: results from the DOPPS.

BACKGROUND: Serial assessment of phosphorus is currently recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, but its additional value versus a single measurement is uncertain. METHODS: We studied data from 17 414 HD patients in the Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, and calculated the area under the curve (AUC) by multiplying the time spent with serum phosphorus >4.5 mg/dL over a 6-month run-in period by the extent to which this threshold was exceeded. We estimated the association between the monthly average AUC and cardiovascular (CV) mortality using Cox regression. We formally assessed whether AUC was a better predictor of CV mortality than other measures of phosphorus control according to the Akaike information criterion. RESULTS: Compared with the reference group of AUC = 0, the adjusted hazard ratio (HR) of CV mortality was 1.12 [95% confidence interval (CI) 0.90-1.40] for AUC > 0-0.5, 1.26 (95% CI 0.99-1.62) for AUC > 0.5-1, 1.44 (95% CI 1.11-1.86) for AUC > 1-2 and 2.03 (95% CI 1.53-2.69) for AUC > 2. The AUC was predictive of CV mortality within strata of the most recent phosphorus level and had a better model fit than other serial measures of phosphorus control (mean phosphorus, months out of target). CONCLUSIONS: We conclude that worse phosphorus control over a 6-month period was strongly associated with CV mortality. The more phosphorus values do not exceed 4.5 mg/dL the better is survival. Phosphorus AUC is a better predictor of CV death than the single most recent phosphorus level, supporting with real-world data KDIGO's recommendation of serial assessment of phosphorus to guide clinical decisions.

Mast cells exhibit intracellular microbicidal activity against Aggregatibacter actinomycetemcomitans.

BACKGROUND AND OBJECTIVE: Several studies have demonstrated that mast cells are equipped with versatile tools to combat and kill bacteria. Additionally, mast cells produce and secrete a variety of mediators, which either regulate the host's immune system or directly attack bacteria. In this study, the intracellular microbicidal capacity of mast cells against Aggregatibacter actinomycetemcomitans was evaluated. METHODS: Murine mast cells were challenged in vitro with A actinomycetemcomitans for 3, 5, 10, and 24 hours. Subsequently, the colony-forming units were counted. Additionally, the production and release of nitric oxide and hydrogen peroxide were analyzed by DAF-FM diacetate, the Griess reaction, and the Amplex Red kit, respectively. Cell death was evaluated using FITC Annexin V and propidium iodide staining. RESULTS: Mast cells are able to efficiently eliminate periodontopathogen, with best results after 10 hours of intracellular challenge. The production/release of nitric oxide-and to a lesser extent of hydrogen peroxide-by mast cells was in agreement with its microbicidal capacity. Ninety percent of the mast cells  maintained their cellular viability even after 24 hours of bacterial challenge. CONCLUSIONS: This is-to the best of our knowledge-the first report to describe the intracellular microbicidal activity of mast cells against A actinomycetemcomitans, concerning the production and release of potentially bactericidal substances. Further, the low number of cell deaths confirms that the decreased number of colony-forming units was due to the higher antimicrobial activity of mast cells. The results highlight the importance of these cells in the defense mechanisms of biofilm-induced periodontal disease.

Functional dependence and the mental dimension of quality of life in Hemodialysis patients: the PROHEMO study.

BACKGROUND: Functional dependence is highly prevalent in maintenance hemodialysis (MHD) settings. Also, poor health-related quality of life (HRQoL) and high levels of depressive symptoms have been reported by MHD patients. We investigated associations between functional status and mental aspects of quality of life in Brazilian MHD patients. METHODS: Cross sectional study of 235 patients enrolled in two of the four participating MHD clinics of the Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO) in Salvador, BA, Brazil. Data were collected from September 2016 to August 2017. The Katz's questionnaire was used for basic activities of daily living (ADL) and the Lawton-Brody's questionnaire for instrumental activities of daily living (IADL). ADL and IADL scores were combined to create 3 functional status groups: highly dependent (n = 47), moderately dependent (n = 109) and independent (n = 82). The validated Brazilian version of the Kidney Disease Quality of Life Short Form (KDQOL-SF) was used for scores of two distinct HRQoL measures, i.e., the mental component summary (MCS) and the 5-item mental health inventory (MHI-5). We used linear regression to estimate differences in scores with adjustment for possible confounders: months of dialysis, age, gender, other sociodemographic variables, body mass index, type of vascular access, dialysis dose by Kt/V, laboratory variables (albumin, blood hemoglobin, calcium, phosphorus, urea, creatinine and parathyroid hormone) and nine comorbid conditions. RESULTS: Mean age was 51.2 ± 12.4 yr (median age = 51.0 yr), 59.1% were male, 93.2% were non-White. The prevalence of self-reported functional status differed by age: 54.4% for age < 45 yr, 67.8% for age 45-60 yr and 73.9% for age ≥ 60 yr. Using functionally independent as reference, lower scores were observed for highly dependent patients in MCS (difference: -4.69, 95% CI: -8.09, -0.29) and MHI-5 (difference: -5.97, 95% CI: -8.09, -1.29) patients. These differences changed slightly with extensive adjustments for covariates. CONCLUSIONS: Our results call attention to a high prevalence of functional dependence in younger and older MHD patients. The results suggest that the lower self-reported mental quality of life in functionally dependent MHD patients cannot be explained by differences in age and comorbidities.

Antifungal activity of Punicalagin-nystatin combinations against Candida albicans.

OBJECTIVES: Oral candidiasis is the most common opportunistic fungal infection of oral mucosa and results from an overgrowth of Candida, especially Candida albicans. The potential anti-C. albicans and cytotoxicity of punicalagin (PCG), isolated from Punica granatum, alone or with nystatin (NYS) were evaluated. METHODS: Activity of compounds alone or in combinations was determined against two C. albicans strains (ATCC 90028 and SC5314). Minimal inhibitory concentration (MIC)-50 and Minimum Fungicidal Concentration (MFC) were assessed by XTT assay and CFU counts, respectively. For combinations, determination of fractional inhibitory concentration index was performed. Ergosterol pathway was investigated as a possible PCG antifungal mechanism. Cytotoxicity assays were undertaken on human primary oral keratinocytes and gingival fibroblasts incubated with antifungal concentrations of PCG and/or NYS for 24 hr. RESULTS: Combination of NYS and PCG increased antifungal efficacy, compared with compounds tested alone. Combinations 4 (PCG-6.25 µg/ml; NYS-3.9 µg/ml) and 5 (PCG-12.5 µg/ml; NYS-1.95 µg/ml) were more effective since they reduced the MIC-50 of PCG (50 µg/ml) by 8 and 4 times, respectively, increased the candidal inhibition and nullified the PCG cytotoxicity for keratinocytes. PCG antifungal mechanism did not involve ergosterol biosynthesis pathway. CONCLUSIONS: The favorable outcomes for combination of PCG and NYS encourage further testing this therapeutic strategy against C. albicans.

Updates on medical management of hyperkalemia.

PURPOSE OF REVIEW: Hyperkalemia is a potentially fatal electrolyte disorder, more commonly present when the potassium excretion capacity is imparied. Hyperkalemia can lead to adverse outcomes, especially due to severe cardiac arrhythmias. It can also impair the cardiovascular effects of renin-angiotensin-aldosterone system inhibitors (RAASis) and potassium rich diets, as hyperkalemia frequently leads to their discontinuation. RECENT FINDINGS: Potassium is a predictor of mortality and should be monitored closely for patients who are at risk for hyperkalemia. Acute hyperkalemia protocols have been revised and updated. Randomized trials have shown that the new anti-hyperkalemic agents (patiromer and zirconium cyclosilicate) are effective hyperkalemia treatment options. The use of anti-hyperkalemic agents may allow for a less restrictive potassium diet and lower RAASi discontinuation rates. SUMMARY: Hyperkalemia should be monitored closely for high-risk patients, as it is associated with adverse outcomes. New therapies have demonstrated effective control, offering hope for potential use in patients that would benefit from diet or medications associated with an increase in serum potassium, indicating that the use of hyperkalemic agents can be associated with better outcomes.

John Henryism and Perceived Health among Hemodialysis Patients in a Multiracial Brazilian Population: the PROHEMO.

Purpose: John Henryism (JH) is a strong behavioral predisposition to engage in high-effort coping with difficult socioenvironmental stressors. We investigated associations between JH and perceived general health (GH) among maintenance hemodialysis (MHD) patients in a multiracial Brazilian population. Design: The 12-item John Henryism Acting Coping (JHAC) Scale was completed by 525 patients enrolled in The Prospective Study of the Prognosis of Hemodialysis Patients (PROHEMO) in Salvador (Bahia) Brazil. JH scores could range from 12 to 60. The low and high JH groups were determined by a median split (<52 vs ≥52). The 36-Item Short Form Health Survey was used to determine GH score (range 0-100; higher means better health). Linear regression with extensive adjustments was used to test associations. Results: Mean age was 48.3±13.7 years; 38.7% were female; 11.4% were White, 29.1% were Black and 59.4% were mixed race. JH was positively associated with higher GH in the whole sample (adjusted difference [AdjDif]=7.14, 95% CI= 2.98, 11.3) and similarly in men and women. A strong positive association between JH and GH was observed in non-Whites but not in Whites; (AdjDif in Blacks =16.4, 95% CI=8.37, 24.4). Also, a strong positive association between JH and GH was observed for patients aged <60 years (AdjDif =9.04, 95% CI = 4.46, 13.6) but not for older patients. Conclusions: The results indicate that MHD patients engaged in high-effort coping with socioenvironmental stressors as demonstrated by high JH tend to feel more positively about their overall health. This seems to be especially the case for non-White and younger patients.

Additional Contribution of the Malnutrition-Inflammation Score to Predict Mortality and Patient-Reported Outcomes as Compared With Its Components in a Cohort of African Descent Hemodialysis Patients.

OBJECTIVE: 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. DESIGN: Prospective cohort for mortality and cross-sectional design for PROs using data of the Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO). SUBJECTS: A total of 632 MHD patients (92% black or mixed race) treated in Salvador, Brazil. PREDICTORS: MIS (range: 0-30, higher worse) and each of its ten components (range: 0-4, higher worse). MAIN OUTCOME MEASURES: Mortality, HRQOL using the KDQOL-SF, and depression symptoms using the 20-item Center for Epidemiological Studies Depression Scale. STATISTICAL ANALYSIS: Linear regression for comparing scores and Cox regression for mortality. RESULTS: After extensive adjustments, MIS ≥6 was associated with 52% higher mortality (hazard ratio = 1.52; 95% confidence interval = 1.13-2.05), higher depression symptoms, and poorer HRQOL, including physical, mental, and kidney disease-targeted HRQOL measures. Weight change, comorbidity, muscle wasting, and albumin were the MIS components indicating associations between poor nutrition and higher mortality. By contrast, gastrointestinal symptoms and functional capacity were the MIS components denoting detrimental associations of poorer nutritional status with PROs. LIMITATION: Causal conclusions are not possible. CONCLUSIONS: The PROHEMO results indicate that MIS components associated with mortality are not the same associated with PROs. However, the MIS showed consistent associations with mortality and PROs. These results in a population that were not the target of previous investigations, add support for using tools combining nutritional components, such as MIS, to predict outcomes in MHD populations.

Estimation of glomerular filtration rate from serum creatinine and cystatin C in octogenarians and nonagenarians.

BACKGROUND: Equations to estimate GFR have not been well validated in the elderly and may misclassify persons with chronic kidney disease (CKD). We measured GFR and compared the performance of the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease-Epidemiology Collaboration (CKD-Epi) and the Berlin Initiative Study (BIS) equations based on creatinine and/or cystatin C in octogenarians and nonagenarians. METHODS: Using cross-sectional analysis we assessed 95 very elderly persons (mean 85 years) living in the community. GFR was measured by iohexol (mGFR) and compared with estimates using six equations: MDRD, CKD-Epi_creatinine, CKD-Epi_cystatin, CKD-Epi_creatinine-cystatin, BIS_creatinine and BIS_creatinine-cystatin. RESULTS: Mean mGFR was 55 (range,19-86) ml/min/1.73 m(2). Bias was smaller with the CKD-Epi_creatinine-cystatin and the CKD-Epi_creatinine equations (-4.0 and 1.7 ml/min/1.73 m(2)). Accuracy (percentage of estimates within 30% of mGFR) was greater with the CKD-Epi_creatinine-cystatin, BIS_creatinine-cystatin and BIS_creatinine equations (85%, 83% and 80%, respectively). Among the creatinine-based equations, the BIS_creatinine had the greatest accuracy at mGFR < 60 ml/min/1.73 m(2) and the CKD-Epi_creatinine was superior at higher GFRs (79% and 90%, respectively). The CKD-Epi_creatinine-cystatin, BIS_creatinine-cystatin and CKD-Epi_cystatin equations yielded the greatest areas under the receiver operating characteristic curve at GFR threshold = 60 ml/min/1.73 m 2 (0.88, 0.88 and 0.87, respectively). In participants classified based on the BIS_creatinine, CKD-Epi_cystatin, or BIS_creatinine-cystatin equations, the CKD-Epi_creatinine-cystatin equation tended to improve CKD classification (net reclassification index: 12.7%, p = 0.18; 6.7%, p = 0.38; and 15.9%; p = 0.08, respectively). CONCLUSIONS: GFR-estimating equations CKD-Epi_creatinine-cystatin and BIS_creatinine-cystatin showed better accuracy than other equations using creatinine or cystatin C alone in very elderly persons. The CKD-Epi_creatinine-cystatin equation appears to be advantageous in CKD classification. If cystatin C is not available, both the BIS_cr equation and the CKD-Epi_cr equation could be used, although at mGFR < 60 ml/min/1.73 m(2), the BIS_cr equation seems to be the best alternative.

Self-reported fatigue by the Chalder fatigue questionnaire and mortality in Brazilian hemodialysis patients: The PROHEMO.

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 (HR) and 95% confidence intervals (CI) 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% diabetics. 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.

Mortality, health-related quality of life, and depression symptoms in younger and older men and women undergoing hemodialysis.

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.

A Survey of Diseases in Different Species of Wild, Captive, and Illegally Traded Birds in Brazil.

Native and exotic avian species can act as reservoirs of pathogens, including bacteria and viruses, with conservation and public health implications. A retrospective study on the diagnosis and frequency of diseases in wild and exotic avian species was conducted. The occurrence of particular diseases was associated with the type of captivity or the bird's origin. The investigation included macroscopic and microscopic descriptions and the molecular determination of the causative agent(s). Additional immunohistochemical (IHC) analysis, PCR, and genetic sequencing were conducted. A total of 243 cases were compiled for the study, mainly consisting of native wild species (39.1%) obtained from illegal trade. Primary infectious diseases, mainly parasitic (18.1%) and viral (17.7%), were the most common, although coinfections were substantial (18.1%) in birds rescued from trafficking. Fractures and neoplasms accounted for 3.7% and 3.3% of the cases, respectively. Parasitic and viral diseases were the most common in both exotic and wild birds. Chlamydia psittaci, a lethal and zoonotic bacterium, was an important cause of death, especially in native Psittaciformes. The recent detection of Psittacid alphaherpesvirus 5 (PsAHV 5) in exotic psittacines and the diagnosis of coinfections in trafficked birds highlight the importance of monitoring avian health to control potential pathogens that may endanger conservation efforts.

Routinely measured cardiac troponin I and N-terminal pro-B-type natriuretic peptide as predictors of mortality in haemodialysis patients.

AIMS: Cardiac troponin (cTn) and B-type natriuretic peptide (BNP) are elevated in haemodialysis (HD) patients, and this elevation is associated with HD-induced myocardial stunning/myocardial strain. However, studies using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS) have shown that these cardiac biomarkers are measured in <2% of HD patients in real-world practice. This study aimed to examine whether routinely measured N-terminal pro-BNP (NT-proBNP) and cTnI (contemporary assay) are more appropriate than clinical models for reclassifying the risk of HD patients who have the highest risk of death. METHODS AND RESULTS: Pre-dialysis levels of cTnI and NT-proBNP at study enrolment were measured in 1152 HD patients (Japan DOPPS Phase 5). The patients were prospectively followed for 3 years. Cox regression was used to test the associations of cardiac biomarkers with all-cause mortality, adjusting for potential confounders. Subgroup analyses were performed to assess potential effect modification of clinical characteristics, such as age, systolic blood pressure, HD vintage, diabetes mellitus, coronary artery disease, and a history of congestive heart failure. At baseline, 337 (29%) patients had elevated cTnI (99th percentile of a healthy population: >0.04 ng/mL) with a median (inter-quartile range) level of 0.020 (0.005-0.041) ng/mL, and 1140 (99%) patients had elevated NT-proBNP (cut-off for heart failure: >125 pg/mL) with a median level of 3658 (1689-9356) pg/mL. There were 167 deaths during a median follow-up of 2.8 (2.2-2.8) years. Higher levels of both cardiac biomarkers were incrementally associated with mortality after adjustment for potential confounders. Even after adjustment for alternative cardiac biomarkers, the overall P value for the association was <0.01 for both biomarkers. However, the prognostic significance of NT-proBNP was moderately diminished when cTnI was added to the model. The hazard ratios of mortality for cTnI > 0.04 ng/mL (vs. cTnI < 0.006 ng/mL) and NT-proBNP > 8000 pg/mL (vs. NT-proBNP < 2000 pg/mL) were 2.56 (95% confidence interval: 1.37-4.81) and 1.90 (95% confidence interval: 0.95-3.79), respectively. Subgroup analyses showed that the associations of both cardiac biomarkers with mortality were generally consistent between stratified groups. CONCLUSIONS: Routinely measured NT-proBNP and cTnI levels are strongly associated with mortality among prevalent HD patients. These associations remain robust, even after adjustment for alternative biomarkers, suggesting that cTnI and NT-proBNP have identical prognostic significance and may reflect different pathological aspects of cardiac abnormalities.

Severe Gestational Low-Protein Intake Impacts Hippocampal Cellularity, Tau, and Amyloid-ß Levels, and Memory Performance in Male Adult Offspring: An Alzheimer-Simile Disease Model?

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.

Utility of a Single Itch-Related Question and the Skindex-10 Questionnaire for Assessing Pruritus and Predicting Health-Related Quality of Life in Patients Receiving Hemodialysis.

Rationale & Objective: Chronic kidney disease-associated pruritus has been linked with poorer mental and physical health-related quality of life (HR-QOL) in patients receiving hemodialysis. We used the Skindex-10 questionnaire and a single itch-related question to evaluate their prediction of HR-QOL. Study Design: Prospective, international cohort. Setting & Participants: We analyzed data from 4,940 patients receiving hemodialysis from 17 countries enrolled in phase 5 (2013) of the Dialysis Outcomes and Practice Patterns Study. Predictors: The responses to the 10 questions of Skindex-10 (0-6 scale) pertaining to itchiness in the past week were summed to create a summary score (range, 0-60). Concurrently, a single question from the Kidney Disease Quality of Life 36-item survey asked "during the past 4 weeks, to what extent were you bothered by itchy skin?" with 5 responses, ranging from "not at all" to "extremely" bothered. Outcomes: Physical component summary (PCS) and mental component summary (MCS) scores of HR-QOL. Analytical Approach: We used separate linear regression models to evaluate the predictive power, based on R2 values, for 3 models: 1 for each predictor and 1 with both predictors. Results: The correlation between the single itch-related question and the Skindex-10 score was 0.72. A 10-point higher Skindex-10 score was associated with a 1.2-point lower PCS score (95% CI, -1.4 to -0.9) and a 1.5-point lower MCS score (95% CI, -1.7 to -1.3) . The R2 value for PCS was 0.065 when the single question was used and only 0.033 when Skindex-10 was used as the predictor; the R2 value for MCS was 0.056 for the single question versus 0.052 for Skindex-10. Limitations: Measurement bias and translation issues in the questionnaires. Conclusions: The single question about the extent to which the patients were bothered by itchy skin was highly correlated with the Skindex-10 score and at least as predictive of key HR-QOL measures. In daily clinical practice, using 1 simple question about the extent to which patients are bothered by itchy skin can be a feasible and efficient method for the routine assessment of pruritus.