[First Report of a Family with Familial Hypocalciuric Hypercalcemia in Chile: Differential Diagnosis in a Patient with PTH-Dependent Hypercalcemia Post-Parathyroidectomy]. / Primer reporte de familia con hipercalcemia hipocalciúrica familiar en Chile: Diagnóstico diferencial en paciente con hipercalcemia PTH dependiente post-paratiroidectomía.

We report a 45-year-old woman with persistent post-parathyroidectomy PTH-dependent asymptomatic hypercalcemia who, after evaluation in our bone clinic, was diagnosed as having familial hypocalciuric hypercalcemia based on concomitant hypocalciuria and a family history of asymptomatic hypercalcemia. Genetic study shows a variant of uncertain significance in the CASR gene. To our knowledge, this is the first report on a Chilean family with HHF.

[Role of surgery in Saprochaete capitata (S. capitata) sepsis in a patient with acute myeloid leukemia]. / Rol de la cirugía en el manejo de la infección invasora por Saprochaete capitata.

Saprochaete capitata (S. capitata) fungal sepsis is a severe condition with a clinical presentation that is similar to other yeast originated fungal sepsis. It is observed in patients with hematological malignancies such as acute myeloid leukemia and neutropenia. We report a 23 year old male presenting with cough, fever and malaise. A bone marrow biopsy led to the diagnosis of acute myeloid leukemia. During the first cycle of chemotherapy the patient presented fever: blood cultures were positive for Klebsiella pneumoniae. Despite antimicrobial treatment, fever persisted; a computed tomography showed a focal splenic lesion; a left exudative pleural effusion appeared. A Matrix Assisted Laser Desorption Ionization-Time of Flight mass spectrometry identified the presence of S. capitata. After multiple antifungal treatments and pleural cavity cleansing by means of videothoracoscopy and laparoscopic splenectomy, the infection resolved and the patient completed his chemotherapy.

Perfusion-weighted imaging with dynamic contrast enhancement (PWI/DCE) morphologic, qualitative, semiquantitative, and radiomics features predicting undifferentiated pleomorphic sarcoma (UPS) treatment response.

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft tissue sarcomas. This study determined the value of perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE) morphologic, qualitative, and semiquantitative features for predicting UPS pathology-assessed treatment effect (PATE). This retrospective study included 33 surgically excised extremity UPS patients with pre-surgical MRI. Volumetric tumor segmentation from PWI/DCE was obtained at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The surgical specimens' PATE separated cases into Responders (R) (≥ 90%, 16 patients), Partial-Responders (PR) (89 - 31%, 10 patients), and Non-Responders (NR) (≤ 30%, seven patients). Seven semiquantitative kinetic parameters and maps were extracted from time-intensity curves (TICs), and 107 radiomic features were derived. Statistical analyses compared R vs. PR/NR. At PRT, 79% of R displayed a "Capsular" morphology (P = 1.49 × 10-7), and 100% demonstrated a TIC-type II (P = 8.32 × 10-7). 80% of PR showed "Unipolar" morphology (P = 1.03 × 10-5), and 60% expressed a TIC-type V (P = 0.06). Semiquantitative wash-in rate (WiR) was able to separate R vs. PR/NR (P = 0.0078). The WiR radiomics displayed significant differences in the first_order_10 percentile (P = 0.0178) comparing R vs. PR/NR at PRT. The PWI/DCE TIC-type II curve, low WiR, and "Capsular" enhancement represent PRT patterns typically observed in successfully treated UPS and demonstrate potential for UPS treatment response assessment.

n-3 polyunsaturated fatty acids in the regulation of adipose tissue browning and thermogenesis in obesity: Potential relationship with gut microbiota.

BACKGROUND: Obesity is a worldwide public health problem characterized by fat tissue accumulation, favouring adipose tissue and metabolic alterations. Increasing energy expenditure (EE) through brown adipose tissue activation and white adipose tissue (WAT) browning has gained relevance as a therapeutic approach. Different bioactive compounds, such as n-3 polyunsaturated fatty acids (PUFA), have been shown to induce those thermogenic effects. This process is regulated by the gut microbiota as well. Nevertheless, obesity is characterized by gut microbiota dysbiosis, which can be restored by weight loss and n-3 PUFA intake, among other factors. Knowledge gap: However, the role of the gut microbiota on the n-3 PUFA effect in inducing thermogenesis in obesity has not been fully elucidated. OBJECTIVE: This review aims to elucidate the potential implications of this interrelation on WAT browning adiposw sittue (BAT), BAT activity, and EE regulation in obesity models.

Distribution of the HLA class II frequency alleles in patients with leprosy from the mid-west of Brazil.

In an attempt to clarify the issue of genetic predisposition to leprosy, we examined the distribution of class II human leucocyte antigen variants (DR and DQ) in 70 patients from around the city of Goiânia, Brazil. Only two of the patients presented the tuberculoid form of the disease, whereas 17 fell into the lepromatous category; 51 were intermediate. The allele frequencies found were compared with those in a group of 77 healthy controls. We found an increased frequency of the HLA-DRB1*11 allele in patients with lepromatous leprosy compared with healthy controls (P=0.0132; RR=4.130, 95% Cl: 1.338 to 12.747). These results suggest that the DRB1*11 allele could be related with susceptibility to lepromatous leprosy in Brazil.

New insights in the dihydroxybenzenes-driven Fenton reaction: electrochemical study of interaction between dihydroxybenzenes and Fe(III).

It has been reported that the dihydroxybenzene (DHB) driven Fenton reaction is more efficient to degrade recalcitrant substrates than the simple Fenton reaction. The enhanced reactivity of the DHB driven Fenton reaction is not clear, but it could be explained by the formation of oxidant species different from the ones formed by classical Fenton reaction or by the shift of the redox potential of the complex formed by DHB and Fe(III). The redox reaction between Fe(III) and the DHBs 1,2-dihydroxybenzene (catechol, CAT), 2,3-dihydroxybenzoic acid (2,3-DHBA), 3,4-dihydroxybenzoic acid (3,4-DHBA), and 1,2-dihydroxy-3,5-benzenedisulfonate (TIRON) was studied by cyclic voltammetry to better understand the enhanced reactivity of the DHB driven Fenton reaction. It was determined that the amount of Fe(II) produced by the redox reaction between Fe(III) and DHBs was insufficient to explain the enhanced reactivity. Cyclic voltammograms (CV) of the DHBs/Fe(III) systems show a quasi-reversible or irreversible behavior and also shifting and splitting the anodic peaks. This effect can be related to DHBs oxidation by Fe(III), but not to a real interaction.

The Mexican consensus on the diagnosis, treatment, and prevention of NSAID-induced gastropathy and enteropathy. / Consenso mexicano sobre diagnóstico, prevención y tratamiento de la gastropatía y enteropatía por antiinflamatorios no esteroideos.

More than 30 million persons worldwide take nonsteroidal anti-inflammatory drugs (NSAIDs) on a daily basis, and annual consumption is increasing. In addition to their analgesic and anti-inflammatory properties, NSAIDs also produce well-known gastrointestinal adverse events. There is no consensus in Mexico on the diagnosis, treatment, and prevention of NSAID-induced gastropathy and enteropathy, and so the Asociación Mexicana de Gastroenterología brought together a group of experts to establish useful recommendations for the medical community. Thirty-three recommendations were formulated in the present consensus, highlighting the fact that the risk for NSAID-induced gastrointestinal toxicity varies according to the drug employed and its pharmacokinetics, which should be taken into account at the time of prescription. The risk factors for gastroduodenal complications due to NSAIDs are: a history of peptic ulcer, age above 65 years, high doses of NSAIDs, Helicobacter pylori infection, and the presence of severe comorbidities. The symptoms and gastroduodenal damage induced by NSAIDs vary, ranging from an asymptomatic course to the presentation of iron-deficiency anemia, bleeding, stricture, and perforation. Capsule endoscopy and enteroscopy are direct diagnostic methods in NSAID enteropathy. Regarding prevention, the minimum dose of an NSAID needed to achieve the desired effect, administered for the shortest period of time, is the recommendation. Finally, proton pump inhibitors are the gold standard for the prophylaxis and treatment of gastroduodenal effects, but they are not useful in enteropathy.

MHC class I chain-related gene A transmembrane polymorphism in Spanish women with breast cancer.

The NKG2D-major histocompatibility complex class I-related chain A (MICA) system plays a key role in the antitumoral immune response. We studied five alleles of a microsatellite in the MICA transmembrane region; one of which (MICA-A5.1) gives rise to a truncated protein. The MICA-A5 allele was reduced in breast cancer patients compared with healthy controls (P = 0.04). Given the association between the HLA-B7 allele and the susceptibility to breast cancer in our area, we also analyzed the distribution of the frequency of the MICA alleles in human leukocyte antigen (HLA)-B7 patients compared with patients with the other alleles. The MICA-A5.1 allele was increased in HLA-B7 patients (P = 0.0003). These results suggest that the MICA-A5 allele appears to confer protection against human breast cancer and that the MICA-A5.1 appears to increase the susceptibility to breast cancer in HLA-B7 patients in our area.

Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: involvement of resolvins RvE1/2 and RvD1/2.

High-fat diet (HFD)-fed mice show obesity with development of liver steatosis and a proinflammatory state without establishing an inflammatory reaction. The aim of this work was to assess the hypothesis that eicosapentaenoic acid (EPA) plus hydroxytyrosol (HT) supplementation prevents the inflammatory reaction through enhancement in the hepatic resolvin content in HFD-fed mice. Male C57BL/6J mice were fed an HFD or a control diet and supplemented with EPA (50 mg/kg/day) and HT (5 mg/kg/day) or their respective vehicles for 12 weeks. Measurements include liver levels of EPA, DHA and palmitate (gas chromatography), liver resolvins and triglyceride (TG) and serum aspartate transaminase (AST) (specific kits) and hepatic and serum inflammatory markers (quantitative polymerase chain reaction and enzyme-linked immunosorbent assay). Compared to CD, HFD induced body weight gain, liver steatosis and TG accumulation, with up-regulation of proinflammatory markers in the absence of histological inflammation or serum AST changes; these results were accompanied by higher hepatic levels of resolvins RvE1, RvE2, RvD1 and RvD2, with decreases in EPA and DHA contents. EPA+HT supplementation in HFD feeding synergistically reduced the steatosis score over individual treatments and increased the hepatic levels of EPA, DHA and resolvins, with attenuation of proinflammatory markers. Lack of progression of HFD-induced proinflammatory state into overt inflammation is associated with resolvin up-regulation, which is further increased by EPA+HT supplementation eliciting steatosis attenuation. These findings point to the importance of combined protocols in hepatoprotection due to the involvement of cross-talk mechanisms, which increase effectiveness and diminish dosages, avoiding undesirable effects.

The Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD) : characterization of the cohort.

The Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD) was launched in December 2004 aiming to collect data monthly and continuously from a representative cohort, allowing for a continuous snapshot of the peritoneal dialysis (PD) reality in the country. This is an observational study of PD patients comprising follow-up from December 2004 to February 2007 (mean follow-up of 13.6 months-ranging from 1 to 26 months) in 114 Brazilian centers. All centers report data through a central web-based database. After an initial baseline retrospective data collection, all patients are followed prospectively every month until they drop out from the PD program. Total number of patients recruited until February 2007 was 3226 (2094 incident patients). Mean age was 54+/-19 years (37% above 65 years old), with 55% females and 64% Caucasians. The more frequent causes of renal failure were diabetic nephropathy (34%), renal vascular disease associated with hypertension (26%), and glomerulopathies (13%). The most common comorbidities were hypertension (76%), diabetes (36%), and ischemic heart disease (23%). Automated PD (APD) was the modality utilized in 53%. The estimated overall peritonitis rate was 1 episode per 30 patient-months (most frequently due to Staphylococcus aureus). The total dropout rate was 33%, mainly due to deaths, whereas 20% of dropouts were due to renal transplant. The gross mortality was 17.6% and the main causes of mortality were cardiovascular diseases (40%) and infections (15%). The initial results of this first Brazilian PD registry provide a unique opportunity to develop future clinical studies addressing specific PD questions in the Brazilian reality and context.

Microwave properties of ferromagnetic nanostructures.

A review of the dynamic properties of nanostructured ferromagnetic materials at microwave frequencies (1-40 GHz) is presented. Since some confusion has recently appeared between giant magnetoimpedance (GMI) and ferromagnetic resonance (FMR), a detailed analysis is made in order to establish their differences. A brief review of a novel microwave absorption mode, the low-field microwave absorption (LFA) is then presented, together with a discussion about its similarities with GMI. Recent results on high-frequency measurements on nanogranular thin films and FMR in nanowire arrays are finally addressed.

Effect of supplementing sows' feed with alpha-tocopherol acetate and vitamin C on transfer of alpha-tocopherol to piglet tissues, colostrum, and milk: aspects of immune status of piglets.

The aim of this study was to investigate the effects of dietary supplementation of sows with alpha-tocopherol acetate (ATA) and vitamin C on deposition of alpha-tocopherol (AT) in piglet lymphoid organs, such as bone marrow, thymus, and spleen at birth and at weaning, as well as on indicators of immune response in piglets. Sows were given the following treatment diets: control, vitamin C 10 g/day, ATA 500 mg/kg feed, and combined vitamins (ATA 500+Vit-C 10). Supplementation with vitamins started at the beginning of pregnancy and lasted until weaning at 21+/-3 days of age. AT was determined in colostrum, milk, piglet plasma (cord blood) and tissues at birth and on day 21. Immunoglobulins were measured in piglet plasma, milk, and colostrum. Lymphocyte proliferation in response to PHA and ConA was determined in sow and piglet blood. ATA supplementation resulted in a significant increase (P<0.001) in the AT content of colostrum, milk, piglet plasma, liver, thymus, bone marrow, and spleen at weaning. The AT content of colostrum and milk significantly (P<0.001) influenced the AT content of piglet plasma and tissues at weaning (day 21). Total Ig and IgG concentrations in piglet plasma were significantly increased in piglets given the combined vitamin treatment. No effect of AT supplementation was observed on IgG and IgA in colostrum and milk. In sows, vitamin C given alone significantly increased lymphocyte response to ConA and PHA; whereas, in piglets, there was no significant effect of treatments on lymphocyte response to PHA and ConA.

Potent beta-amyloid modulators.

Currently, the potential to interfere with the pathology of beta-amyloid targeting a well-known drugable enzyme, the acetylcholinesterase (AChE), is opened. Peripheral or dual binding site inhibitors of AChE may simultaneously alleviate the cognitive and behavioral deficits in Alzheimer's disease (AD) patients and, more importantly, act as disease-modifying agents delaying amyloid plaque formation. As part of a rational drug design program directed to find dual binding site AChE inhibitors, several families of compounds have been synthesized as potent AChE inhibitors. From these series, several drug candidates were selected based on their potent and selective inhibition of AChE (subnanomolar activity) and their interference with the beta-amyloid aggregation in vitro (IC(50) in the low micromolar range). First in vivo data confirm our initial hypothesis. Oral treatment with NP-61 for 3 months is able to reverse the cognitive impairment (Morris water maze test) and to reduce plaque load in the brains of human amyloid precursor protein transgenic mice (Swedish mutation). These results suggest that NP-61, a potent beta-amyloid modulator, is able to reverse the AD-like neurodegenerative phenotype in transgenic mice, indicating a promising disease-modifying agent for clinical application.

[The experience obtained in a private hospital using endoscopy capsule]. / Experiencia clínica en un hospital del sector privado con el uso de la cápsula endoscópica.

INTRODUCTION AND OBJECTIVES: Capsule endoscopy constitutes a non invasive method used for direct observation of the small bowel's mucosae and for recognizing possible injuries in it, such as the causes of obscure gastrointestinal hemorrhage and inflammatory diseases, for instance. The present study shows the experience obtained in a private hospital using capsule endoscopy for evaluating diverse intestinal pathologies. MATERIALS AND METHODS: Ambulatory patients were evaluated, and the results analyzed in a retrospective, observational and transverse manner. The Given Imaging PillCam was used in all cases. RESULTS: Forty five cases were evaluated; 27 of them (60%) were female, 18 were male (40%). The mean age was 58.16, ranging from 18 to 84 years. Obscure gastrointestinal bleeding constituted the most common indication for undergoing capsule endoscopy; present in 32 patients (71.11% of the cases). Other indications were: chronic diarrhea 5 cases (11.11%), abdominal pain 3 cases (6.67%) and melena 3 cases (6.67%). 18 cases presented no anomaly (40%). The most frequent pathological findings were: erosions 10 cases (22.20%), vascular disorders 8 cases (17.76%) and polyps 6 cases (13.32%). No complications were presented during or after the procedures, although in two of the cases the capsule had to be inserted under endoscopic assistance with sedation. CONCLUSIONS: Capsule endoscopy is an innocuous, safe method, useful in identifying causes of obscure gastrointestinal bleeding, which is the most common indication for the study, and in identifying diverse small bowel pathologies.

Alpha vs. gamma sarcoglycanopathy: DNA tests solve a case from Argentina.

Immunohistochemical and DNA results are described in a patient with sarcoglycanopathy. Immunostaining was comparatively normal for alpha-, attenuated for beta- and delta-, and markedly attenuated for gamma-sarcoglycan, thus sarcoglycanopathy was diagnosed, presumably a gamma-sarcoglycanopathy. Unexpectedly, two alpha-SGP-related pathogenic mutations were identified in compound heterozygosity in the SGCA gene: c.229C > T (p.Arg77Cys) in exon 3 and c.850C > T (p.Arg284Cys) in exon 7. These are discussed together with six additional changes detected in SGCB, SGCG and SGCD.

Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

OBJECTIVES: To determine efficacy and safety of withholding antimicrobials in children with cancer, fever and neutropenia (FN) with a demonstrated respiratory viral infection. METHODS: Prospective, multicentre, randomized study in children presenting with FN at five hospitals in Santiago, Chile, evaluated at admission for diagnosis of bacterial and viral pathogens including PCR-microarray for 17 respiratory viruses. Children positive for a respiratory virus, negative for a bacterial pathogen and with a favourable evolution after 48 h of antimicrobial therapy were randomized to either maintain or withhold antimicrobials. Primary endpoint was percentage of episodes with uneventful resolution. Secondary endpoints were days of fever/hospitalization, bacterial infection, sepsis, admission to paediatric intensive care unit (PICU) and death. RESULTS: A total of 319 of 951 children with FN episodes recruited between July 2012 and December 2015 had a respiratory virus as a unique identified microorganism, of which 176 were randomized, 92 to maintain antimicrobials and 84 to withdraw. Median duration of antimicrobial use was 7 days (range 7-9 days) versus 3 days (range 3-4 days), with similar frequency of uneventful resolution (89/92 (97%) and 80/84 (95%), respectively, not significant; OR 1.48; 95% CI 0.32-6.83, p 0.61), and similar number of days of fever (2 versus 1), days of hospitalization (6 versus 6) and bacterial infections throughout the episode (2%-1%), with one case of sepsis requiring admission to PICU in the group that maintained antimicrobials, without any deaths. CONCLUSIONS: The reduction of antimicrobials in children with FN and respiratory viral infections, based on clinical and microbiological/molecular diagnostic criteria, should favour the adoption of evidence-based management strategies in this population.

Transhiatal versus transthoracic resection for oesophageal carcinoma in Yemen.

INTRODUCTION: Cancer of the oesophagus is a major problem in Yemen, where most of the patients present with advanced disease. Curative oesophageal resection for carcinoma may be carried out by either the transhiatal or transthoracic technique. The aims of this study were to compare the morbidity, mortality, short term outcome and long term survival of the two techniques in the treatment of oesophageal carcinoma. METHODS: From March 1998 to July 2004,118 patients with cancer of the oesophagus were studied. The tumours in 84 patients were resected by transhiatal oesophagectomy (43) and transthoracic oesophagectomy (41). RESULTS: The two groups were comparable in terms of age, sex, location of the tumours, risk factors and stage of the disease. There was no significant difference in the mean intensive care unit stay, blood transfusion and mean hospital stay. Anastomotic leak was higher in the transhiatal oesophagectomy group than transthoracic group (21 percent versus 12 percent, p-value is equal to 0.001). Recurrent laryngeal nerve lesion was present in 18.6 percent of the transhiatal group and absent in the transthoracic group. The overall hospital mortality was 8.3 percent with no significant difference between the two groups (transhiatal 9.3 percent versus transthoracic 7.3 percent, p-value is equal to 0.742). CONCLUSION: Transhiatal oesophagectomy was associated with a higher incidence of anastomotic complications and recurrent laryngeal nerve lesions, but there was no significant difference in the mortality between the two groups.

Phosphorous metabolite and cell cycle kinetic response of two human squamous cell carcinomas to radiation.

Phosphorous metabolism and cell cycle phase kinetics in response to radiation of two perfused human squamous cell carcinoma cell lines, SQ20B (radioresistant) and SQ38 (relatively radiosensitive), embedded in both basement membrane (Matrigel) and agarose gel threads were studied. The findings for these human cancer cells in response to 2- and 50-Gy irradiation are as follows. (a) Well perfused pure cancer cells (both SQ20B and SQ38) in both proliferative (cells embedded in Matrigel) and static (cells embedded in agarose threads) states did not show significant alteration in either phosphorous bioenergetics or membrane metabolites at 24 and 48 h after irradiation, although a large fraction of the population was clonogenically impaired. Previously reported, sensitively detected, metabolite alterations in response to radiation in rodent and human tumors in situ were not seen in these homogeneous cancer cell populations. (b) The radiosensitive squamous cell carcinoma cell lines SQ38 exhibited G1 block (from 54.38 +/- 1.40% in control to 73.93 +/- 1.01% after irradiation; mean +/ SD) in response to low-dose 2-Gy irradiation and G2 block (from 12.98 +/- 2.15% in control to 25.6 +/- 3.15% after irradiation) in response to high-dose 50-Gy irradiation, while the radioresistant cell line SQ20B showed only conventional G2 block in response to both doses. The differential cell cycle phase response may indicate the difference in radioresistance. (c) The membrane metabolites (including phosphomonoesters and phosphodiesters) and phosphocreatine gradually increased from the early passages to late passages, suggesting that cell proliferation rates were increasing as the cells adapted to tissue culture. The results suggest that the radiation-induced metabolite changes observed in solid tumors in situ may not be a direct response to interim changes within the cancer cells but, rather, a consequence of radiation damage either to the vasculature or to other host-mediated factors.