High-Flux versus High-Retention-Onset Membranes: In vivo Small and Middle Molecules Kinetics in Convective Dialysis Modalities.

BACKGROUND: Patients undergoing maintenance hemodialysis (HD) exhibit increased levels of uremic toxins, which are associated with poor outcomes. Recently, new dialysis membranes have allowed clearance of solutes with higher molecular weight, without significant albumin losses high-retention-onset-HD (HRO-HD). METHODS: Prospective crossover trial, in which 16 prevalent patients switched from high-flux HD (HF-HD) to online hemodiafiltration (olHDF) and HRO-HD for 4 weeks. The following variables were evaluated: pre- and post-dialysis serum concentrations of albumin, urea, phosphate (P), beta-2 microglobulin (ß2M), and total mass (TM) extraction and dialyzer clearance of urea, P, and ß2M. RESULTS: Comparing HF-HD, olHDF, and HRO-HD, respectively, there were no differences regarding pre-dialysis serum concentrations of albumin (3.94 ± 0.36, 4.06 ± 0.22, and 3.93 ± 0.41 g/dL, p = 0.495), urea (166 ± 29, 167 ± 30, and 164 ± 27 mg/dL, p = 0.971), P (4.9 ± 2.1, 5.2 ± 1.6, and 4.9 ± 2.1 mg/dL, p = 0.879), and ß2M (31.3 ± 7.1, 32.6 ± 8.6, and 33.7 ± 5.9 µg/mL, p = 0.646). ß2M clearance was significantly lower in HF-HD in comparison to both olHDF and HRO-HD: 43 (37-53) versus 64 (48-85) mL/min, p = 0.013, and 69 (58-86) mL/min, p = 0.015, respectively. Post-dialysis ß2M serum concentration was higher in HF-HD in comparison to olHDF and HRO-HD: 11.6 (9.6-12.4) vs. 5.7 (4.5-7.0) µg/mL, p = 0.001, and 5.6 (5.3-7.6) µg/mL, p = 0.001, respectively. TM extraction of urea, P, and ß2M were similar across the 3 dialysis modalities. CONCLUSIONS: olHDF and HRO-HD were superior to HF-HD regarding ß2M clearance, leading to lower post-dialysis ß2M levels.

The Chelating Mineral on Organic Acid Salts Modulates the Dynamics and Richness of the Intestinal Microbiota of a Silver Catfish Rhamdia quelen.

The aim of this study was to evaluate the influence of the chelating mineral on propionic acid, calcium or sodium on the composition, dynamics and richness of the intestinal microbiota of a native silver catfish Rhamdia quelen through high-throughput sequencing (HTS). A total of 225 fish (8.43 ± 0.18 g) were distributed in tanks, 15 fish per tank in five groups with three replicates each: Control, Ca-propionate 0.25% (Ca0.25%) Ca-propionate 1% (Ca1%), Na-propionate 0.25% (Na0.25%) and Na-propionate 1% (Na1%). The feed was provided four times a day for 60 days. After experimental period, the fish were fasted for 24 h and the intestine was aseptically collected, pooled by treatment, and fixed in pure absolute ethanol for subsequent DNA extraction and HTS. The HTS showed that the supplementation of the propionic acid chelated to the mineral calcium or sodium in the different concentrations increased the operational taxonomic units and richness in comparison to control group. The main phyla found were Fusobacteria, Firmicutes, Proteobacteria and Bacteroides. Both the fusobacteria and the genus Cetobacterium, especially C. somerae, were positively modulated with Ca0.25% and Na1% supplementation. It can be emphasized that supplementation with calcium or sodium propionate at different concentrations changed the natural microbiota of R. quelen.

Early Start Peritoneal Dialysis: Technique Survival in Long-Term Follow-Up.

BACKGROUND/AIMS: Peritoneal dialysis (PD) has gained interest over the last decade as a viable option for early start dialysis. It is still unknown if shorter break-in periods and less time for proper patient evaluation and training could influence technique survival in comparison to planned-start PD. METHODS: A prospective and observational study that compared technique survival in a cohort of patients who started either early or planned PD. Early start PD was defined as break-in period from 3 to 14 days with no previous nephrologist follow-up or patient training. RESULTS: A total of 154 patients were included (40 as early start PD), followed by a median time of 381 days. Comparing early vs. planned-start PD, groups were similar concerning age 56 (40; 70) vs. 48 (32; 63) years, p=0.071, body mass index (BMI) 23.3 ± 4.2 vs. 23.8 ± 4.0 kg/m2, p=0.567 and male gender (60 vs. 48%, p=0.201), respectively. Comparing early vs. planned-start groups, there were no differences regarding PD dropout for peritonitis (7.5 vs. 11.4%, p=0.764), catheter dysfunction (12.5 vs. 17.5%, p=0.619) and patient burnout (0 vs. 4.4%, p=0.328), respectively. Less patients in early start group quit PD for peritoneal membrane failure in comparison to planned-start group (2.5 vs. 16.7%, p=0.026). In multivariate cox-regression analysis, the only factors independently associated with technique failure were BMI> 25 kg/m² (p=0.033) and Diabetes Mellitus (p=0.013), whereas no differences regarding early vs. planned-PD start were observed (p=0.184). CONCLUSION: Despite the adverse scenario for initiating dialysis, early start PD had similar outcomes in comparison to planned-start PD in long-term follow-up.

Decision-making process in the pre-dialysis CKD patients: do anxiety, stress and depression matter?

BACKGROUND: The transition from pre-dialysis chronic kidney disease (CKD) to renal replacement therapy (RRT) is a stressful event. Anxiety, depression and stress are frequent conditions in this population, and might play a role on the choice of dialysis modality. METHODS: This is a prospective study that included stages 4-5 CKD patients during a dialysis multi-disciplinary education program. Demographic, clinical, and laboratory data were evaluated. Hospital Anxiety and Depression Scale and a Perceived Stress Scale assessed levels of anxiety, depression and stress, respectively. RESULTS: A total of 67 from 190 recruited patients were included (59 ± 15 years, 54% males). Comparing patients who chose peritoneal dialysis (PD) and hemodialysis (HD), there were no differences on anxiety (p = 0.55), and depression scores (p = 0.467), and stress (p = 0.854). Anxious (p = 0.007) and depressive (p = 0.030) patients presented lower levels of phosphate than those not affected. There was a significant correlation (p < 0.0001) between anxiety and depression scores (R2 = 0.573), anxiety and stress scores (R2 = 0.542), depression and stress scores (R2 = 0.514). At the end of study, 29.8% of patients had already started on dialysis, and scores of anxiety, depression and stress reduced significantly (all p values < 0.0001), from 5.9 ± 3.3 to 1.8 ± 1.8, from 7.7 ± 4.0 to 3.8 ± 2.9 and from 28.6 ± 7.8 to 10.0 ± 6.2, respectively, regardless of which therapy was chosen. CONCLUSION: Depression, anxiety and perceived stress during final stages of CKD do not seem to be related to the choice of dialysis therapy and tend to decrease after dialysis initiation.

Exploring Au Droplet Motion in Nanowire Growth: A Simple Route toward Asymmetric GaP Morphologies.

Here we show a new nanowire growth procedure, exploring the thermally activated motion of Au droplets on III-V surfaces. We show that by setting a single growth parameter we can activate the crawling motion of Au droplets in vacuum and locally modify surface composition in order to enhance vapor-solid (VS) growth along oxide-free areas on the trail of the metal particle. Asymmetric VS growth rates are comparable in magnitude to the vapor-liquid-solid growth, producing unconventional wurtzite GaP morphologies, which shows negligible defect density as well as optical signal in the green spectral region. Finally, we demonstrate that this effect can also be explored in different substrate compositions and orientations with the final shape finely tuned by group III flow and nanoparticle size. This distinct morphology for wurtzite GaP nanomaterials can be interesting for the design of nanophotonics devices.

High Dialysate Calcium Concentration May Cause More Sympathetic Stimulus During Hemodialysis.

BACKGROUND/AIMS: Acute activation of sympathetic activation during hemodialysis is essential to maintain blood pressure (BP), albeit long-term overactivity contributes to higher mortality. Low heart rate variability (HRV), a measure of autonomic nervous system activity, and abnormal ankle-brachial index (ABI) are associated with higher mortality in patients on hemodialysis. In this study, we assessed HRV and ABI pre and post dialysis in incident patients on hemodialysis using high (1.75mmol/l) and low (1.25mmol/l) dialysate calcium concentration (DCa). METHODS: HRV was measured as the ratio between low frequency and high frequency power (LF/HF). Thirty patients (age 47±16 years, 67% men) were studied in two consecutive mid-week hemodialysis sessions. RESULTS: Mean BP variation was positive with DCa 1.75 and negative with DCa 1.25 [4.0 (-6.0, 12.2 mmHg) vs. -3.2 (-9.8, 1.3 mmHg); p=0.050]. Reduction of ABI from pre to post HD was related to higher sympathetic activity (p=0.031). The increase in LF/HF ratio was higher with DCa 1.75 (58.3% vs. 41.7% in DCa 1.75 and 1.25, respectively, RR 2.8; p=0.026). CONCLUSION: Although higher DCa is associated with better hemodynamic tolerability during hemodialysis, this occurs at the expense of increased sympathetic activity. Higher sympathetic activity was associated with a decrease of ABI during hemodialysis.

Effect of mushroom Agaricus blazei on immune response and development of experimental cerebral malaria.

BACKGROUND: Cerebral malaria (CM) is debilitating and sometimes fatal. Disease severity has been associated with poor treatment access, therapeutic complexity and drug resistance and, thus, alternative therapies are increasingly necessary. In this study, the effect of the administration of Agaricus blazei, a mushroom of Brazilian origin in a model of CM caused by Plasmodium berghei, strain ANKA, was investigated in mice. METHODS: C57BL/6 mice were pre-treated with aqueous extract or fractions of A. blazei, or chloroquine, infected with P. berghei ANKA and then followed by daily administration of A. blazei or chloroquine. Parasitaemia, body weight, survival and clinical signs of the disease were evaluated periodically. The concentration of pro-and anti-inflammatory cytokines, histopathology and in vitro analyses were performed. RESULTS: Mice treated with A. blazei aqueous extract or fraction C, that shows antioxidant activity, displayed lower parasitaemia, increased survival, reduced weight loss and protection against the development of CM. The administration of A. blazei resulted in reduced levels of TNF, IL-1ß and IL-6 production when compared to untreated P. berghei-infected mice. Agaricus blazei (aqueous extract or fraction C) treated infected mice displayed reduction of brain lesions. Although chloroquine treatment reduced parasitaemia, there was increased production of proinflammatory cytokines and damage in the CNS not observed with A. blazei treatment. Moreover, the in vitro pretreatment of infected erythrocytes followed by in vivo infection resulted in lower parasitaemia, increased survival, and little evidence of clinical signs of disease. CONCLUSIONS: This study strongly suggests that the administration of A. blazei (aqueous extract or fraction C) was effective in improving the consequences of CM in mice and may provide novel therapeutic strategies.

Hemodynamic behavior during hemodialysis: effects of dialysate concentrations of bicarbonate and potassium.

BACKGROUND/AIMS: Ultrafiltration that occurs during hemodialysis (HD) promotes profound alterations in a relatively short period of time. The dialysate content of bicarbonate (DBic) and potassium (DK) may have impact over intradialytic hemodynamics, which goes beyond ultrafiltration, and its impact was evaluated in a prospective cohort. METHODS: 30 patients under HD were submitted to hemodynamic assessment (HA) at the beginning and at the end of HD sessions, through a non-invasive method. Serum minus dialysate potassium concentration was expressed as K-Gap. Cardiac index (CI) and peripheral arterial resistance (PAR) variation (post-HD minus pre-HD) were expressed as ΔCI and ΔPAR. Dialysate content of sodium and calcium were expressed as DNa and DCa, respectively. RESULTS: Mean DNa, DK and DBic were, respectively, 136.4 ± 1.1, 2.1 ± 0.6 and 38.2 ± 2.1 mEq/L. In 15 patients, DCa was >1.5 mmol/L and in the other 15 patients ≤ 1.5 mmol/L. The K-Gap ranged from 1.4 to 5.1 mEq/l (median 3.0 mEq/L). There was a reduction in post-HD CI and systolic blood pressure (ΔCI = -0.72l/min/m(2) and -11.3±15.1mmHg, respectively, p<0.001 for both). Conversely, PAR increased (ΔPAR = 272dyn.s/cm(5), p<0.001). Lower post-HD CI was was associated to higher DBic (p=0.0013) and lower K-Gap (p=0.026). In multivariate analysis, ΔCI was dependent on DBic and K-Gap, whereas ΔPAR was dependent on dialysate calcium during HD. CONCLUSION: We confirmed that Na and Ca dialysate content exerts and important role on hemodynamic during HD. In addition, our findings pointed out that higher dialysate concentrations of bicarbonate and potassium promote lower cardiac performance at the end of hemodialysis session.

Multiple contact zones and karyotypic evolution in a neotropical frog species complex.

Previous studies of DNA sequence and karyotypic data have revealed high genetic diversity in the Physalaemus cuvieri - Physalaemus ephippifer species complex-a group of small leptodactylid frogs in South America. To date, seven major genetic lineages have been recognized in this group, with species delimitation tests supporting four to seven of them as valid species. Among these, only P. ephippifer shows heteromorphic sex chromosomes, but the implications of cytogenetic divergence for the evolution of this group are unknown. We analyzed karyotypic, mitochondrial DNA, and 3RAD genomic data to characterize a putative contact zone between P. ephippifer and P. cuvieri Lineage 1, finding evidence for admixture and karyotypic evolution. We also describe preliminary evidence for admixture between two other members of this species complex-Lineage 1 and Lineage 3 of P. cuvieri. Our study sheds new light on evolutionary relationships in the P. cuvieri - P. ephippifer species complex, suggesting an important role of karyotypic divergence in its evolutionary history and underscoring the importance of hybridization as a mechanism of sex chromosome evolution in amphibians.

Quantifying the impact of non-stationarity in reinforcement learning-based traffic signal control.

In reinforcement learning (RL), dealing with non-stationarity is a challenging issue. However, some domains such as traffic optimization are inherently non-stationary. Causes for and effects of this are manifold. In particular, when dealing with traffic signal controls, addressing non-stationarity is key since traffic conditions change over time and as a function of traffic control decisions taken in other parts of a network. In this paper we analyze the effects that different sources of non-stationarity have in a network of traffic signals, in which each signal is modeled as a learning agent. More precisely, we study both the effects of changing the context in which an agent learns (e.g., a change in flow rates experienced by it), as well as the effects of reducing agent observability of the true environment state. Partial observability may cause distinct states (in which distinct actions are optimal) to be seen as the same by the traffic signal agents. This, in turn, may lead to sub-optimal performance. We show that the lack of suitable sensors to provide a representative observation of the real state seems to affect the performance more drastically than the changes to the underlying traffic patterns.

Detecting cells in intravital video microscopy using a deep convolutional neural network.

The analysis of leukocyte recruitment in intravital video microscopy (IVM) is essential to the understanding of inflammatory processes. However, because IVM images often present a large variety of visual characteristics, it is hard for an expert human or even conventional machine learning techniques to detect and count the massive amount of cells and extract statistical measures precisely. Convolutional neural networks are a promising approach to overcome this problem, but due to the difficulty of labeling cells, large data sets with ground truth are rare. The present work explores an adaptation of the RetinaNet model with a suite of augmentation techniques and transfer learning for detecting leukocytes in IVM data. The augmentation techniques include simulating the Airy pattern and motion artifacts present in microscopy imaging, followed by traditional photometric, geometric and smooth elastic transformations to reproduce color and shape changes in cells. In addition, we analyzed the use of different network backbones, feature pyramid levels, and image input scales. We have found that even with limited data, our strategy not only enables training without overfitting but also boosts generalization performance. Among several experiments, the model reached a value of 94.84 for the average precision (AP) metric as our best outcome when using data from different image modalities. We also compared our results with conventional image processing techniques and open-source tools. The results showed an outstanding precision of the method compared with other approaches, presenting low error rates for cell counting and centroid distances. Code is available at: https://github.com/brunoggregorio/retinanet-cell-detection.

Author Correction: Optical Absorption Exhibits Pseudo-Direct Band Gap of Wurtzite Gallium Phosphide.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Optical Absorption Exhibits Pseudo-Direct Band Gap of Wurtzite Gallium Phosphide.

Definitive evidence for the direct band gap predicted for Wurtzite Gallium Phosphide (WZ GaP) nanowires has remained elusive due to the lack of strong band-to-band luminescence in these materials. In order to circumvent this problem, we successfully obtained large volume WZ GaP structures grown by nanoparticle-crawling assisted Vapor-Liquid-Solid method. With these structures, we were able to observe bound exciton recombination at 2.14 eV with FHWM of approximately 1 meV. In addition, we have measured the optical absorption edges using photoluminescence excitation spectroscopy. Our results show a 10 K band gap at 2.19 eV and indicate a weak oscillator strength for the lowest energy band-to-band absorption edge, which is a characteristic feature of a pseudo-direct band gap semiconductor. Furthermore, the valence band splitting energies are estimated as 110 meV and 30 meV for the three highest bands. Electronic band structure calculations using the HSE06 hybrid density functional agree qualitatively with the valence band splitting energies.

Hypokalemia and hyperkalemia in patients on peritoneal dialysis: incidence and associated factors.

BACKGROUND: Hypokalemia is a well-described electrolyte disturbance in patients on peritoneal dialysis (PD). Hyperkalemia, however, is still overlooked, although it also represents a risk factor for mortality. Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (ACE/ARB), diuretics, and proton pump inhibitor (PPI) can interfere with potassium levels in these patients. METHODS: This is a retrospective study that evaluated monthly serum potassium in a 5-year period. Serum potassium disturbances were evaluated as time-average and number of hypo- and hyperkalemia episodes per patient. Prescribed medication such as ACE/ARB, diuretics, and omeprazole were recorded. RESULTS: We evaluated 2025 potassium measurements obtained from 146 patients on PD. Serum potassium ranged from 2.5 to 8.3 mEq/L with an average of 4.72 ± 0.74 mEq/L. Hypokalemia was found in 59 measurements (2.9%) obtained from 35 patients (23.9%) whereas hyperkalemia was demonstrated in 269 (13.3%) measurements obtained from 74 patients (50.7%). Hypokalemia was associated with low albumin (p = 0.022), and omeprazole use (p = 0.024). Black race was a protector factor (p = 0.031). Omeprazole-associated hypokalemia was seen only in non-anuric patients and remained an independent risk factor even after adjustments. Patients who had hyperkalemia were more likely to be anuric (p = 0.001) and in use of furosemide (p = 0.0001). CONCLUSION: Hyperkalemia and hypokalemia are very frequent in patients on PD and should be closely monitored. Interventional studies should address the impact of discontinuing omeprazole in the levels of potassium.

Adherence to Medical Treatment in Inflammatory Bowel Disease Patients from a Referral Center in Bahia-Brazil.

METHODS: Observational, analytical, and cross-sectional studies carried out from June/2017 to July/2018, with questionnaire application and medical record review at a referral center in inflammatory bowel diseases in Salvador, Bahia. The Morisky Green Levine Scale was applied to assess adherence. Mean, standard deviation, and frequency analyses were performed using the statistical package SPSS, and chi-square was used to evaluate the association between categorical variables and adherence degree to treatment. Significant associations were considered with p < 0.05. RESULTS: 302 patients with inflammatory bowel diseases were included. Nonadherence was highlighted in the sample. Most part of the study population was female, declared themselves to be mixed race, claimed to be from urban areas, and married. Nonadherence was more frequent than adherence in most sociodemographic variables of the present study. Nonadherence also stood out among the clinical variables, such as disease activity, drug side effect, and use of more than two additional medications. The association between all studied variables and adherence degree to treatment, considering the general sample, did not show statistical significance. When Crohn's disease and ulcerative colitis patients were evaluated separately, a statistically significant association between nonadherence and female patients with ulcerative colitis was observed. CONCLUSIONS: The high frequency of nonadherence was observed in the studied sample. Female gender was associated to nonadherence in the subpopulation with ulcerative colitis.

Resonant States of H3+ and D2H+.

Vibrational resonances for H(3) (+) and D(2)H(+), as well as H(3) (+) at J=3, are calculated using a complex absorbing potential (CAP) method with an automated procedure to find stability points in the complex plane. Two different CAP functional forms and different CAP extents are used to analyze the consistency of the results. Calculations are performed using discrete variable representation continuum basis elements calculated to high levels of accuracy by diagonalizing large, dense, Hamiltonian matrices. For D(2)H(+), two energy regions are analyzed: the one where D(2)+H(+) is the only dissociation product and the one where HD+D(+) can also be formed. Branching ratios are obtained in the latter case by using different CAPs. It is shown that H(3) (+) and D(2)H(+) support some narrow Feshbach-type resonances but that higher angular momentum states must be studied to model the pre-dissociation spectrum recorded by Carrington and co-workers [J. Chem. Phys. 98, 1073 (1993)].

Kidney injury and other complications related to colonoscopy in inpatients at a tertiary teaching hospital.

OBJECTIVES: To describe clinical complications related to colonoscopy in inpatients with multiple diseases. Among the known complications, acute kidney injury was the primary focus. METHODS: This was an observational retrospective study of 97 inpatients. Data relating to age; gender; comorbidities; current medication; blood tests (renal function, blood glucose and LDL cholesterol levels); length of hospital stay; indication, results, and complications of colonoscopies; and time to the development of kidney injury were collected between June 2011 to February 2012. RESULTS: A total of 108 colonoscopies (9 screening and 88 diagnostic) were conducted in 97 patients. Renal injury occurred in 41.2% of the patients. The univariate analysis revealed that kidney injury was related to the use of diuretics, statins, calcium channel blockers, and angiotensin converting enzyme inhibitor; however, the multivariate analysis showed that only the use of diuretics was associated with kidney injury. The occurrence of kidney injury and the time to its development were independent of the previous glomerular filtration rate as calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. CONCLUSIONS: The use of diuretics was the only independent variable associated with the development of kidney injury in inpatients with multiple comorbidities who underwent colonoscopy. The occurrence of kidney injury and the time to its development were independent of previous CKD-EPI-based assessments of renal function. These results highlight the increased risk of colonoscopy in such patients, and its indication should be balanced strictly and perhaps avoided as a screening test.

Vascular changes in chronic renal disease patients with secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) and its metabolic consequences - high serum phosphate and calcium x phosphate (Ca x P) product - are associated with cardiovascular disease in chronic kidney disease (CKD). We evaluated the relationship between PTH, mineral metabolism, vascular reactivity and arterial stiffness in patients with CKD. METHODS: The study included 31 CKD patients and 12 matched controls. Brachial artery diameter was recorded at baseline and after reactive hyperemia (flow-mediated vasodilation) and 0.45 mg of trinitrate, to analyze the flow-dependent and flow-independent responses. Large vessel stiffness was evaluated on the common carotid artery. RESULTS: Compared with controls, both flow-mediated (5.8% +/- 4.3% vs. 11.6% +/- 5.4%; p<0.001) and flow-independent (11.7% +/- 7.6% versus 23% +/- 7.5%; p<0.001) vasodilation were reduced in CKD. Flow-mediated vasodilation was negatively correlated with PTH (r=-0.416, p<0.05) and age (r=-0.365, p<0.05) and positively with flow-independent vasodilation (r=0.483, p<0.01). Blood pressure, dialysis duration, hematocrit and serum levels of Ca, P, and Ca x P product, lipids, and medications did not influence flow-mediated function. Carotid distension correlated independently and negatively with age (r=-0.681, p<0.01) and Ca x P product (r=-0.496, p<0.01) but was not influenced by PTH. CONCLUSION: In CKD, PTH adversely affects vascular reactivity, possibly by interfering with endothelial function, while large vessel distension is influenced by Ca x P product but not by PTH. This result suggests a dual mechanism of vascular aggression in SHPT: an endothelial effect mediated by PTH and a media/adventitial effect linked to alterations in mineral metabolism.