Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis.

Chronic kidney disease (CKD) is a highly prevalent disease that has become a public health problem. Progression of CKD is associated with serious complications, including the systemic CKD-mineral and bone disorder (CKD-MBD). Laboratory, bone and vascular abnormalities define this condition, and all have been independently related to cardiovascular disease and high mortality rates. The "old" cross-talk between kidney and bone (classically known as "renal osteodystrophies") has been recently expanded to the cardiovascular system, emphasizing the importance of the bone component of CKD-MBD. Moreover, a recently recognized higher susceptibility of patients with CKD to falls and bone fractures led to important paradigm changes in the new CKD-MBD guidelines. Evaluation of bone mineral density and the diagnosis of "osteoporosis" emerges in nephrology as a new possibility "if results will impact clinical decisions". Obviously, it is still reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will be clinically useful (low versus high turnover-bone disease). However, it is now considered that the inability to perform a bone biopsy may not justify withholding antiresorptive therapies to patients with high risk of fracture. This view adds to the effects of parathyroid hormone in CKD patients and the classical treatment of secondary hyperparathyroidism. The availability of new antiosteoporotic treatments bring the opportunity to come back to the basics, and the knowledge of new pathophysiological pathways [OPG/RANKL (LGR4); Wnt-ß-catenin pathway], also affected in CKD, offers great opportunities to further unravel the complex physiopathology of CKD-MBD and to improve outcomes.

Chemical characterization of PM2.5 from region highly impacted by hailstorms in South America.

The chemical composition of particulate material plays an important role in the atmosphere, providing cloud and ice nuclei for storm development. This study aims to evaluate and infer the sources of ions, metals, and metalloids in the fine atmospheric particulate matter (PM2.5) from triple border Paraná, Santa Catarina (Brazil), and northeastern Argentina, which is among those with the highest hail incidence in the world. Among the ions, the concentrations presented the following sequence in decreasing order: [Formula: see text]> K+> [Formula: see text]> [Formula: see text]> Ca2+> Cl-> Na+> Mg2+. Regarding the metals and metalloid concentrations, the order was of S > Si > Al > Fe > P > Ti, Cr, Cu, and Zn > Br > Mn, and Ni. The main sources, supported by positive matrix factorization results, are soil and agricultural activities, as well as vehicular emissions due to the agricultural machinery and the displacement of residents. Besides, the influence of aerosols from biomass burning and industrial activities was observed, possibly come from long-distance transport. The composition of PM2.5 presents one or more elements considered present ice nuclei (IN) activity, such as Al, Mn, Cu, Co, Ni, and V (in form of oxides), corroborating with other studies, also, with high hail incidence. However, further studies are needed to verify the role of aerosol characteristics in the formation of IN and, consequently, hail.

Diffuse Alopecia and Thyroid Atrophy in Sheep.

Thyroid dysfunction substantially affects the quality of life due to its association with various disorders in different organs. A low intake of selenium and zinc can predispose to thyroid alterations, resulting in hypothyroidism. A deficiency of selenium and zinc causes direct and indirect skin lesions, both by the action of free radicals on the skin and by thyroid dysfunction. The aim of this study was to describe natural cases of diffuse alopecia and thyroid abnormalities in sheep with selenium and zinc deficiency. Five adult sheep presented marked and diffuse alopecia, and the residual hairs were dry and brittle. The skin was thick and crusty, with marked peeling. The triiodothyronine (T3) and thyroxine (T4) serum concentrations were below reference values for the species. Zinc and Se concentrations were low in both the serum and liver. During necropsy, cachexia associated with serous fat atrophy was observed, and the thyroid glands showed marked atrophy. Microscopically, the thyroid presented multifocal to coalescent atrophy, with atrophied and dilated follicles, macrophage infiltration, and the presence of fibrous connective tissue. The skin revealed hyperkeratosis and edema. It is concluded that thyroid atrophy, alopecia, and hyperkeratosis are associated with low serum and liver concentrations of zinc and selenium in sheep.

Mycobacterium tuberculosis and Paracoccidioides brasiliensis Formation and Treatment of Mixed Biofilm In Vitro.

Co-infection of Mycobacterium tuberculosis and Paracoccidioides brasiliensis, present in 20% in Latin America, is a public health problem due to a lack of adequate diagnosis. These microorganisms are capable of forming biofilms, mainly in immunocompromised patients, which can lead to death due to the lack of effective treatment for both diseases. The present research aims to show for the first time the formation of mixed biofilms of M. tuberculosis and P. brasiliensis (Pb18) in vitro, as well as to evaluate the action of 3'hydroxychalcone (3'chalc) -loaded nanoemulsion (NE) (NE3'chalc) against monospecies and mixed biofilms, the formation of mixed biofilms of M. tuberculosis H37Rv (ATCC 27294), 40Rv (clinical strains) and P. brasiliensis (Pb18) (ATCC 32069), and the first condition of formation (H37Rv +Pb18) and (40Rv + Pb18) and second condition of formation (Pb18 + H37Rv) with 45 days of total formation time under both conditions. The results of mixed biofilms (H37Rv + Pb18) and (40Rv + Pb18), showed an organized network of M. tuberculosis bacilli in which P. brasiliensis yeasts are connected with a highly extracellular polysaccharide matrix. The (Pb18 + H37Rv) showed a dense biofilm with an apparent predominance of P. brasiliensis and fragments of M. tuberculosis. PCR assays confirmed the presence of the microorganisms involved in this formation. The characterization of NE and NE3'chalc displayed sizes from 145.00 ± 1.05 and 151.25 ± 0.60, a polydispersity index (PDI) from 0.20± 0.01 to 0.16± 0.01, and zeta potential -58.20 ± 0.92 mV and -56.10 ± 0.71 mV, respectively. The atomic force microscopy (AFM) results showed lamellar structures characteristic of NE. The minimum inhibitory concentration (MIC) values of 3'hidroxychalcone (3'chalc) range from 0.97- 7.8 µg/mL and NE3'chalc from 0.24 - 3.9 µg/mL improved the antibacterial activity when compared with 3'chalc-free, no cytotoxicity. Antibiofilm assays proved the efficacy of 3'chalc-free incorporation in NE. These findings contribute to a greater understanding of the formation of M. tuberculosis and P. brasiliensis in the mixed biofilm. In addition, the findings present a new possible NE3'chalc treatment alternative for the mixed biofilms of these microorganisms, with a high degree of relevance due to the lack of other treatments for these comorbidities.

How socio-economic and atmospheric variables impact COVID-19 and influenza outbreaks in tropical and subtropical regions of Brazil.

COVID-19 has been disturbing human society with an intensity never seen since the Influenza epidemic (Spanish flu). COVID-19 and Influenza are both respiratory viruses and, in this study, we explore the relations of COVID-19 and Influenza with atmospheric variables and socio-economic conditions for tropical and subtropical climates in Brazil. Atmospheric variables, mobility, socio-economic conditions and population information were analyzed using a generalized additive model for daily COVID-19 cases from March 1st to May 15th, 2020, and for daily Influenza hospitalizations (2017-2019) in Brazilian states representing tropical and subtropical climates. Our results indicate that temperature combined with humidity are risk factors for COVID-19 and Influenza in both climate regimes, and the minimum temperature was also a risk factor for subtropical climate. Social distancing is a risk factor for COVID-19 in all regions. For Influenza and COVID-19, the highest Relative Risks (RR) generally occurred in 3 days (lag = 3). Altogether among the studied regions, the most important risk factor is the Human Development Index (HDI), with a mean RR of 1.2492 (95% CI: 1.0926-1.6706) for COVID-19, followed by the elderly fraction for both diseases. The risk factor associated with socio-economic inequalities for Influenza is probably smoothed by Influenza vaccination, which is offered free of charge to the entire Brazilian population. Finally, the findings of this study call attention to the influence of socio-economic inequalities on human health.

Risk assessment of temperature and air pollutants on hospitalizations for mental and behavioral disorders in Curitiba, Brazil.

BACKGROUND: Extreme ambient temperatures and air quality have been directly associated with various human diseases from several studies around the world. However, few analyses involving the association of these environmental circumstances with mental and behavioral disorders (MBD) have been carried out, especially in developing countries such as Brazil. METHODS: A time series study was carried out to explore the associations between daily air pollutants (SO2, NO2, O3, and PM10) concentrations and meteorological variables (temperature and relative humidity) on hospital admissions for mental and behavioral disorders for Curitiba, Brazil. Daily hospital admissions from 2010 to 2016 were analyzed by a semi-parametric generalized additive model (GAM) combined with a distributed lag non-linear model (DLNM). RESULTS: Significant associations between environmental conditions (10 µg/m3 increase in air pollutants and temperature °C) and hospitalizations by MBD were found. Air temperature was the environmental variable with the highest relative risk (RR) at 0-day lag for all ages and sexes analyzed, with RR values of 1.0182 (95% CI: 1.0009-1.0357) for men, and 1.0407 (95% CI: 1.0230-1.0587) for women. Ozone exposure was a risk for all women groups, being higher for the young group, with a RR of 1.0319 (95% CI: 1.0165-1.0483). Elderly from both sexes were more susceptible to temperature variability, with a RR of 1.0651 (95% CI: 1.0213-1.1117) for women, and 1.0215 (95% CI: 1.0195-1.0716) for men. CONCLUSIONS: This study suggests that temperatures above and below the thermal comfort threshold, in addition to high concentrations of air pollutants, present significant risks on hospitalizations by MBD; besides, there are physiological and age differences resulting from the effect of this exposure.

Synthesis of 1H-1,2,3-triazoles and study of their antifungal and cytotoxicity activities.

We report herein the results of antifungal activity of fifteen 1,2,3-triazoles against Candida albicans, Candida krusei, Candida parapsilosis, Candida kefyr, Candida tropicalis, Candida dubliniensis, Tricophyton rubrum, Microporum canis and Aspergillus niger. All of the 1,2,3-triazoles were prepared from 1,3-dipolar cyclizations between aryl azides and alkynes catalyzed by Cu(I), and several of the compounds exhibited antifungal activity with low cytotoxicity. The results demonstrated the potential and importance of developing new 1,2,3-triazoles compounds with antifungal activity.

Neuroglobin is up-regulated in the cerebellum of pups exposed to maternal epileptic seizures.

To evaluate a potential insult in the cerebellum of pups exposed to maternal epileptic seizures during intrauterine life, female rats were subjected to pilocarpine-induced epilepsy. Pups from different litters were sacrificed at 1, 3, 7 and 14 post-natal days (PN) and neuroglobin (Ngb) and gliosis were analyzed in the cerebellum by Western blotting (WB) and RT-PCR. (14)C-l-leucine-[(14)C-Leu] incorporation was used to analyze protein synthesis at PN1. Nitric Oxide (NO) and thiobarbituric acid-reactive substances (TBARS) levels were also measured. Pups from naive mothers were used as controls. The mRNA level of Ngb was increased in experimental animals at PN1 ((**)p ≤ 0.001) and PN3 ((**)p ≤ 0.001), at PN7 ((***)p ≤ 0.0001) and at PN14 ((**)p ≤ 0.001) compared to the respective controls. The protein level of Ngb increased significantly in the experimental pups at PN1 ((*)p ≤ 0.05) and at PN3 ((**)p ≤ 0.001), when compared to the control pups at PN1 and PN3. At PN7 and PN14 no difference was found. The mRNA level of GFAP increased significantly about two times at PN3 ((*)p ≤ 0.05) and PN7 ((*)p ≤ 0.05) in the experimental pups when compared to the respective controls, but was unchanged in the other studied ages. Data showed that experimental pups at PN1 exhibited reduced (about 2 times, (*)p ≤ 0.05) total protein synthesis in the cerebellum when compared to control. No differences were found in the NO and TBARS levels. Our data support the hypothesis that an up-regulation of Ngb could be a compensatory mechanism in response to the hypoxic-ischemic insults caused by seizures in pups during intrauterine life.

Epidural blood patch in Jehovah's Witness: two cases report.

BACKGROUND AND OBJECTIVES: There are reports on epidural blood patch in Jehovah's Witness patients using a closed system which allows blood collection and epidural injection without loss of continuity. This report aimed at presenting two cases of Jehovah's Witness patients with post-dural puncture headache and treated with epidural blood patch in a closed venous blood transfusion system to the epidural space. Cases were reported by two different hospitals in two different cities. CASE REPORTS: One 21 years old male patient and one 32 years old female patient, with post-dural puncture headache after outpatient procedures. Since they were Jehovah's Witnesses, blood patch was performed with a closed system. System was prepared in sterile conditions using the following materials: two serum catheters cut in 60 cm segments, one two-way connection, one three-way tap and one 20 ml syringe. System was assembled to allow one connection to the puncture needle (20G), one connection to the three-way tap and the remaining two ways were connected to a 20 ml syringe and to the other serum catheter segment, which would be connected to the epidural needle. Lumbar region and right upper limb were disinfected with patients in the left lateral position. Epidural puncture was performed at L2-L3 interspace with 17G needle which was maintained fixed and connected to the serum catheter. Then, venous puncture was performed with a needle connected to the other edge of the serum catheter with the three-way tap directed from the vein to the syringe and 15 ml blood were aspirated. Redirecting the tap from the syringe to the epidural needle, the same 15 ml blood were re-injected. CONCLUSIONS: In Jehovah's Witness patients refractory to clinical treatment, autologous blood injection may be performed through the above-described technique after patients informed consent.