Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1.

Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/µl) and miR-423 (189 copies/µL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents.

[Bilateral ureterocele in single collection system: a particular case]. / Ureterocele bilateral en sistema único: un caso particular.

INTRODUCTION: Ureterocele is an uncommon congenital urinary tract malformation, which consists in a cystic dilation of the vesical portion of the ureter. We present a rare case of ureterocele, reviewing the most important aspects and characteristics that make it so unusual. CASE: Seven year old male admitted for hematuria in the context of afebrile urinary tract infection, the ultrasound revealed a right hydroureteronephrosis (HUN) in a single collecting system and a voiding cystourethogram (VCUG) showed a right ureterocele. A cystoscopy demonstrated the presence of a bilateral orthotopicureterocele in a single collecting system. The patient underwent an endoscopic incision in order to drain the hydronephrotic system. After a month, while performing a check up using ultrasound, we could observe an important reduction in the right HUN, however, it also was acknowledged the presence of dilation of the left distal ureter, reason why it was decided to puncture the left ureterocele. COMMENTS: We present an unusual case: male with a bilateral orthotopicureterocele in a single collecting system and its clinical management. Its particularity is discussed.

2022 SPILF - Clinical Practice guidelines for the diagnosis and treatment of disco-vertebral infection in adults.

These guidelines are an update of those made in 2007 at the request of the French Society of Infectious Diseases (SPILF, Société de Pathologie Infectieuse de Langue Française). They are intended for use by all healthcare professionals caring for patients with disco-vertebral infection (DVI) on spine, whether native or instrumented. They include evidence and opinion-based recommendations for the diagnosis and management of patients with DVI. ESR, PCT and scintigraphy, antibiotic therapy without microorganism identification (except for emergency situations), therapy longer than 6 weeks if the DVI is not complicated, contraindication for spinal osteosynthesis in a septic context, and prolonged dorsal decubitus are no longer to be done in DVI management. MRI study must include exploration of the entire spine with at least 2 orthogonal planes for the affected level(s). Several disco-vertebral samples must be performed if blood cultures are negative. Short, adapted treatment and directly oral antibiotherapy or early switch from intravenous to oral antibiotherapy are recommended. Consultation of a spine specialist should be requested to evaluate spinal stability. Early lifting of patients is recommended.

Association of obesity, diabetes, and hypertension with arsenic in drinking water in the Comarca Lagunera province (north-central Mexico).

Chronic endemic regional hydroarsenicism (CERHA) is a global issue that affects over 200 million people exposed to arsenic (As) in drinking water. This includes 1.75 million individuals residing in La Comarca Lagunera, a region in north-central Mexico. Arsenic levels in this region typically exceeds the WHO guideline of 10 µg L-1. Biochemical alterations related to the human As metabolism may increase the risk of overweight and obesity (O&O), type 2 diabetes (T2D), and hypertension (AHT). In our study, we investigated the role of As in drinking water as a risk factor for these metabolic diseases. We focused on populations with historically moderate (San Pedro) and low (Lerdo) drinking water As levels and people with no historical evidence of As water contamination. The exposure assessment to As was based on measurements of the drinking water (medians 67.2, 21.0, 4.3 µg L-1) and urinary As concentrations in women (9.4, 5.3, 0.8 µg L-1) and men (18.1, 4.8, 1.0 µg L-1). A significant correlation between As in drinking water and urine evidenced the As exposure in the population (R2 = 0.72). Adjusted odds ratios with 95% confidence intervals evidenced higher chances of being diagnosed with T2D (1.7, 1.2-2.0) and AHT (1.8, 1.7-1.9) in individuals living in San Pedro than those in Lerdo. Still, there was no significant association with obesity. Individuals living in CERHA towns were found to have a higher risk of obesity (1.3-1.9), T2D (1.5 to 3.3), and AHT (1.4 to 2.4) compared to those residing in non-CERHA towns. Finally, obesity is more probable in women [inverse of OR and 95%CI 0.4 (0.2-0.7)] compared to men, while men is more likely to be diagnosed with T2D [OR = 2.0 (1.4-2.3)] and AHT [OR = 2.0 (1.5-2.3)] than women, independently of the municipality.

Exposure to indoor air pollutants (polycyclic aromatic hydrocarbons, toluene, benzene) in Mexican indigenous women.

UNLABELLED: Indoor air pollution is considered to be a serious public health issue in Mexico; therefore, more studies regarding this topic are necessary. In this context, we assessed exposure to polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds in: (i) women who use firewood combustion (indoor) for cooking and heating using traditional open fire; (ii) women who use firewood combustion (outdoor) for cooking and heating using traditional open fire; and (iii) women who use LP gas as the principal energy source. We studied 96 healthy women in San Luis Potosi, México. Urine samples were collected, and analyses of the following urinary exposure biomarkers were performed by high-performance liquid chromatography: 1-hydroxypyrene (1-OHP), trans, trans-muconic acid, and hippuric acid (HA). The highest levels of 1-OHP, trans, trans-muconic acid, and HA were found in communities where women were exposed to indoor biomass combustion smoke (or products; geometric mean ± s.d., 3.98 ± 5.10 µmol/mol creatinine; 4.81 ± 9.60 µg/l 1-OHP; 0.87 ± 1.78 mg/g creatinine for trans, trans-muconic acid; and 1.14 ± 0.91 g/g creatinine for HA). Our findings indicate higher exposure levels to all urinary exposure biomarkers studied in women who use indoor firewood combustion for cooking and heating (using traditional open fire). PRACTICAL IMPLICATIONS: High mean levels of 1-hydroxypyrene, t,t-muconic acid, and hippuric acid were found in women who use firewood combustion (indoor) for cooking and heating using traditional open fire and taking into account that millions of women and children in Mexico are living in scenarios similar to those studied in this report, the assessment of health effects in women and children exposed to polycyclic aromatic hydrocarbons and volatile organic compounds is urgently needed. Moreover, it is immediately necessary an intervention program to reduce exposure.

Safety of Oral P2Y12 Inhibitors in Interventional Neuroradiology: Current Status and Perspectives.

In the field of interventional neuroradiology, antiplatelet agents are commonly used to prepare patients before the implantation of permanent endovascular materials. Among the available drugs, clopidogrel is the most frequently used one, but resistance phenomena are considered to be relatively common. Prasugrel and ticagrelor were recently added to the pharmacologic arsenal, but the safety of these agents in patients undergoing neurointerventional procedures is still a subject of discussion. The cumulative experience with both drugs is less extensive than that with clopidogrel, and the experience with patients in the neurology field is less extensive than in the cardiology domain. In the present article, we provide a narrative review of studies that investigated safety issues of oral P2Y12 inhibitors in interventional neuroradiology and discuss potential routes for future research.

Effect of silver nanoparticles (AgNPs) exposure on microRNA expression and global DNA methylation in endothelial cells EA.hy926.

The aim of this study was to determine the effect of AgNPs on the epigenome of endothelial cells EA.hy926, including the levels of expression of microRNAs (miRNAs) and global DNA methylation patterns. In addition, evaluation of the expression of inflammatory genes and the levels of VCAM-1 protein (miRNA-126 target) was performed. The expression levels of analyzed miRNAs (microRNAs-126, 155 and 146) were reduced significantly and there were not observed changes in inflammatory gene expression. Regarding the levels of protein vascular cell adhesion molecule 1 (VCAM-1), they increase significantly to 0.5 µM AgNPs at 24 h of exposure. As far as DNA methylation is concerned, we found that AgNPs induce a state of global hyper-methylation. In conclusion, it was demonstrated that direct contact between AgNPs and endothelial cells resulted in the dysregulation of highly enriched and vastly functional miRNAs and DNA hypermethylation, that may have multiple effects on endothelium function and integrity.

Trypanosoma cruzi calreticulin: In vitro modulation of key immunogenic markers of both canine tumors and relevant immune competent cells.

Recombinant calreticulin from Trypanosoma cruzi (rTcCalr), the parasite responsible for Chagas' disease, binds to Canine Transmissible Venereal Tumor (CTVT) cells from primary cultures and to a canine mammary carcinoma cell line. A Complement-binding assay indicated that interaction of the first component C1q with these tumor cells operated independently of the rTcCalr-presence. This apparent independence could be explained by the important structural similarities that exist among rTcCarl, endogenous normal canine and/or mutated calreticulins present in several types of cancer. In phagocytosis assays, tumor cells treated with rTcCalr were readily engulfed by macrophages and, co-cultured with DCs, accelerated their maturation. In addition, DCs maturation, induced by tumor cells co-cultured with rTcCalr, activated T cells more efficiently than DCs, treated or not with LPS. In an apparent paradox, a decrease in MHC Class I expression was observed when these tumor cells were co-cultivated with rTcCalr. This decrease may be related to a down regulation signaling promoting the rescue of MHC I. Possibly, these in vitro assays may be valid correlates of in vivo sceneries. Based on these results, we propose that rTcCalr improves in vitro the immunogenicity of two widely different tumor cell lines, thus suggesting that the interesting properties of rTcCalr to boost immune responses warrant future studies.

Feedback-based Self-improving CNN Algorithm for Breast Cancer Lymph Node Metastasis Detection in Real Clinical Environment.

Digital pathology can be thought of as a model composed of 3 main elements; classification algorithm, Graphical User Interface (GUI) and the pathologists. Currently there is only a one way interaction from the classification algorithm to the pathologist. This paper, proposes an additional backward path which is a new feedback-based method, aimed to improve the performance of the classification algorithms by utilizing the feedback of the pathologists. The GUI developed for this purpose, is aimed to be simple and adaptive to different classification algorithms. The method showed significant improvement in the classification performance of the applied Convolutional Neural Network (CNN) algorithm. The 25% quantile of the probability score of the predictions increased from 0.48 to 0.89 and the median of the data increased from 0.95 to 0.99.

Texture differentiation using audio signal analysis with robotic interventional instruments.

Robotic minimally invasive surgery (RMIS) has played an important role in the last decades. In traditional surgery, surgeons rely on palpation using their hands. However, during RMIS, surgeons use the visual-haptics technique to compensate the missing sense of touch. Various sensors have been widely used to retrieve this natural sense, but there are still issues like integration, costs, sterilization and the small sensing area that prevent such approaches from being applied. A new method based on acoustic emission has been recently proposed for acquiring audio information from tool-tissue interaction during minimally invasive procedures that provide user guidance feedback. In this work the concept was adapted for acquiring audio information from a RMIS grasper and a first proof of concept is presented. Interactions of the grasper with various artificial and biological texture samples were recorded and analyzed using advanced signal processing and a clear correlation between audio spectral components and the tested texture were identified.

Effects of physical exercise on skeletal muscles of rats with cerebral ischemia.

Physical exercise is a known preventive and therapeutic alternative for several cerebrovascular diseases. Therefore, the objective of the present study was to evaluate the motor performance and histomorphometry of the biceps brachii, soleus, and tibialis anterior muscles of rats submitted to a treadmill training program prior to the induction of cerebral ischemia via occlusion of the middle cerebral artery (OMCA). A total of 24 Wistar rats were distributed into four groups: Sham-Sed: sedentary control animals (n=6), who underwent sham surgery (in which OMCA did not occur); Sham+Ex: control animals exercised before the sham surgery (n=6); I-Sed: sedentary animals with cerebral ischemia (n=6); and I+Ex: animals exercised before the induction of ischemia (n=6). The physical exercise consisted of treadmill training for five weeks, 30 min/day (5 days/week), at a speed of 14 m/min. The results showed that the type-I fibers presented greater fiber area in the exercised ischemic group (I+Ex: 2347.96±202.77 µm2) compared to the other groups (Sham-Sed: 1676.46±132.21 µm2; Sham+Ex: 1647.63±191.09 µm2; I+Ex: 1566.93±185.09 µm2; P=0.0002). Our findings suggested that the angiogenesis process may have influenced muscle recovery and reduced muscle atrophy of type-I fibers in the animals that exercised before cerebral ischemia.

Correlation Between Incisional Biopsy Histological Subtype and a Mohs Surgery Specimen for Nonmelanoma Skin Cancer.

BACKGROUND: Histological diagnosis of a clinically suspected nonmelanoma skin cancer (NMSC) is recommended before treatment. For NMSC, concordance between the histological subtype of the preoperative biopsy and the excision specimen of basal cell carcinoma (BCC) has been reported to range from 10% to 81%. No large study on the concordance between NMSC histology seen in a preoperative biopsy with the following tumour specimen from Mohs micrographic surgery (MMS) has been performed in a Latin American population. OBJECTIVE: The aim of this study was to analyse and compare the histological subtype of the incisional biopsies reviewed by the dermatopathologist with the histological subtype of the tumour specimen obtained during MMS interpreted by the dermatopathologist and the Mohs surgeon. METHODS: A retrospective analysis of 320 NMSC was performed. The interobserver correlation was based on kappa values. RESULTS: The mean weighted kappa value between the preoperative NMSC biopsy and intraoperative histological subtype of the tumour specimen from MMS analysed by the Mohs surgeon and the dermatopathologist was 0.22 and 0.24, respectively. The correlation in the histologic subtype of the intraoperative tumour specimen from MMS that was interpreted by the dermatopathologist and Mohs surgeon was 0.58. CONCLUSIONS: Dermatologists need to be aware of the limited value of incisional biopsies to accurately diagnose the histological subtype of a NMSC. The concordance rate in the histological diagnosis of the tumour specimens that were obtained from MMS between the Mohs surgeon and the dermatopathologist is moderate. However, the correlation is low compared with incisional biopsy subtypes.

[Tinea nigra palmaris: a clinical case in Argentina]. / Tinea nigra palmaris: presentacion de un caso clínico en la República Argentina.

A clinical case of a female patient with a black spot on the palm of her left hand is presented. The infection was due to a black fungus identified as Hortaea werneckii, the aetiological agent of tinea nigra palmaris. This infection can be easily diagnosed and it is important to establish the differential diagnosis from other skin pathologies. Normally, the treatment has a successful outcome. In this case, the patient was treated with econazole locally applied during one month, with complete remission of the lesions. In conclusion, the early diagnosis of this disease is very important since the mycology procedures are fast and non-invasive and cure is obtained with local treatment.

Affinity and hydrophobic chromatography of Escherichia coli aspartate transcarbamoylase.

Chromatography of aspartate transcarbamoylase from Escherichia coli on agarose-immobilized dyes and alkyl-agaroses of differing carbon length were investigated. The bacterial aspartate transcarbamoylase was bound by Procoin red HE3B-agarose and Cibacron blue F3GA-agarose nearly completely under the conditions chosen relative to other agarose-coupled dyes. The aspartate transcarbamoylase holoenzyme was eluted from the Procion red HE3B-agarose slightly later than from the Cibacron blue F3GA-agarose during salt gradient elution. The catalytic trimer of the enzyme as well as its regulatory dimer were eluted by a lower salt concentration from both dye-agarose gels than the concentration required to elute the holoenzyme. The interaction of the catalytic trimer with the Procion red HE3B-agarose and Cibacron blue F3GA-agarose gels may be a determinant in the holoenzyme being retained on these resins. Of those alkyl-agaroses tested, the ethyl-, propyl- and hexyl-agarose gels bound the majority of aspartate transcarbamoylase activity. Chromatography of aspartate transcarbamoylase on ethyl-agarose found it to be eluted by a low salt concentration. A purification scheme for relatively small amounts of aspartate transcarbamoylase utilizing Procion red HE3B-agarose and ethyl-agarose is presented. This purification scheme is particularly useful for mutant versions of aspartate transcarbamoylase which cannot be purified by literature procedures.

Skeletal muscle regeneration and Trypanosoma cruzi-induced myositis in rats.

Although Chagas' disease is known to provoke severe acute myositis, information on muscle regeneration is missing. The current paper shows that during T. cruzi infection in rats, skeletal muscle parasitism and the consequent inflammatory process are higher in muscle with a high proportion of type-I myofibres (soleus and diaphragm). Immunohistochemistry showed an acute inflammatory process characterized by ED1+ and ED2+ macrophages, CD8+ lymphocytes, and NK cells. Parasite-nest rupture provoked segmental degeneration of myofibres followed by regeneration. These phenomena were observed at both light and transmission electron microscopy levels. Myofibre regeneration involved activation of satellite cells assessed by the expression of MyoD, a muscle-specific transcription factor. Ultrastructural evidence of fusion of myoblast-like cells with the intact segment of degenerating fibres has been provided. At the chronic phase no signs of fibrosis were found, but sparse and small inflammatory foci were found. Our results argue against the relevant participation of autoimmunity phenomena in both acute and chronic phases and furnish a new view for explaining histopathological findings in human patient muscles.

Central administration of mCPP, a serotonin 5-HT(2B/2C) agonist, decreases water intake in rats.

In the present study, we investigated in rats the effect of third ventricle injections of 1-(3-chlorophenyl)piperazine (mCPP), a 5-HT(2) receptor agonist, on water intake induced by three different physiological stimuli: fluid deprivation, acute salt load and hypovolemia. Injections of mCPP in the doses of 80 and 160 nmol/rat were able to decrease water intake in all three conditions studied. Third ventricle injections of mCPP (160 nmol/rat) were no longer able to diminish water intake in the groups of rats pretreated with central injections of an equimolar amount of (+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo[1,7-bc][2,6]-naphthyridine (SDZ SER 082), a selective 5-HT(2B/2C) antagonist. The central administration of mCPP (160 nmol/rat) was not able to modify the intake of a 0.1% saccharin solution. It is suggested that the central activation of a 5-HT(2B/2C) component is able to impair the drive for water intake induced by the physiological stimuli represented by fluid deprivation, acute salt load and hypovolemia. This effect seems not to be consequent on a general nonspecific central nervous system depression or on a locomotor deficit, because saccharin intake is not affected by third ventricle injections of mCPP.