Xanthogranulomatous Pyelonephritis in Peritoneal Dialysis.

Introduction: Xanthogranulomatous pyelonephritis (XGP) is a rare illness that consists of a destructive chronic inflammatory process of the renal parenchyma associated with recurrent infection and obstructions of the urinary tract. Peritoneal dialysis (PD) is a form of renal replacement therapy used in advanced kidney disease. PD patients demonstrate a systemic inflammatory state, secondary to the increase in uremic toxins, decreased filtration of proinflammatory cytokines, as well as constant exposure to bioincompatible dialysis solutions or a foreign body reaction from the catheter, among other factors, as peritoneal infections. Case Presentation: We present the clinical case of a 74-year-old woman, with a history of recurrent urinary tract infections associated with nephrolithiasis and stage 5D chronic kidney disease, on a PD program. The patient presented a non-specific 3-month state of progressive asthenia, with increased inflammatory parameters in the analytical controls. After presenting multiple negative urine cultures and peritoneal fluid cultures, she was hospitalized to study the constitutional syndrome. The imaging test revealed bilateral staghorn lithiasis with severe dilatation of the right renal pelvis and great cortical thinning. Given the suspicion of XGP, it was decided to perform right renal nephrectomy, which was confirmed after the anatomopathological study. Prior to the intervention, she was transferred to hemodialysis. Over the following months, significant clinical and analytical improvement was observed. Conclusion: The systemic inflammatory state and the risk of infections in PD can mask the diagnosis of XGP in PD patients. There are no reported cases of XGP in patients in PD.

In Silico Analysis of Glutamate Receptors in Capsicum chinense: Structure, Evolution, and Molecular Interactions.

Plant glutamate receptors (GLRs) are integral membrane proteins that function as non-selective cation channels, involved in the regulation of developmental events crucial in plants. Knowledge of these proteins is restricted to a few species and their true agonists are still unknown in plants. Using tomato SlGLRs, a search was performed in the pepper database to identify GLR sequences in habanero pepper (Capsicum chinense Jacq.). Structural, phylogenetic, and orthology analysis of the CcGLRs, as well as molecular docking and protein interaction networks, were conducted. Seventeen CcGLRs were identified, which contained the characteristic domains of GLR. The variation of conserved residues in the M2 transmembrane domain between members suggests a difference in ion selectivity and/or conduction. Also, new conserved motifs in the ligand-binding regions are reported. Duplication events seem to drive the expansion of the species, and these were located in the evolution by using orthologs. Molecular docking analysis allowed us to identify differences in the agonist binding pocket between CcGLRs, which suggest the existence of different affinities for amino acids. The possible interaction of some CcGLRs with proteins leads to suggesting specific functions for them within the plant. These results offer important functional clues for CcGLR, probably extrapolated to other Solanaceae.

A Comprehensive Review of Patented Antimicrobial Peptides from Amphibian Anurans.

Since the 1980s, studies of antimicrobial peptides (AMPs) derived from anuran skin secretions have unveiled remarkable structural diversity and a wide range of activities. This study explores the potential of these peptides for drug development by examining granted patents, amino acid modifications related to patented peptides, and recent amphibians' taxonomic updates influencing AMP names. A total of 188 granted patents related to different anuran peptides were found, with Asia and North America being the predominant regions, contributing 65.4% and 15.4%, respectively. Conversely, although the Neotropical region is the world's most diversified region for amphibians, it holds only 3.7% of the identified patents. The antimicrobial activities of the peptides are claimed in 118 of these 188 patents. Additionally, for 160 of these peptides, 66 patents were registered for the natural sequence, 69 for both natural and derivative sequences, and 20 exclusively for sequence derivatives. Notably, common modifications include alterations in the side chains of amino acids and modifications to the peptides' N- and C-termini. This review underscores the biomedical potential of anuran-derived AMPs, emphasizing the need to bridge the gap between AMP description and practical drug development while highlighting the urgency of biodiversity conservation to facilitate biomedical discoveries.

Marine Invertebrates: A Promissory Still Unexplored Source of Inhibitors of Biomedically Relevant Metallo Aminopeptidases Belonging to the M1 and M17 Families.

Proteolytic enzymes, also known as peptidases, are critical in all living organisms. Peptidases control the cleavage, activation, turnover, and synthesis of proteins and regulate many biochemical and physiological processes. They are also involved in several pathophysiological processes. Among peptidases, aminopeptidases catalyze the cleavage of the N-terminal amino acids of proteins or peptide substrates. They are distributed in many phyla and play critical roles in physiology and pathophysiology. Many of them are metallopeptidases belonging to the M1 and M17 families, among others. Some, such as M1 aminopeptidases N and A, thyrotropin-releasing hormone-degrading ectoenzyme, and M17 leucyl aminopeptidase, are targets for the development of therapeutic agents for human diseases, including cancer, hypertension, central nervous system disorders, inflammation, immune system disorders, skin pathologies, and infectious diseases, such as malaria. The relevance of aminopeptidases has driven the search and identification of potent and selective inhibitors as major tools to control proteolysis with an impact in biochemistry, biotechnology, and biomedicine. The present contribution focuses on marine invertebrate biodiversity as an important and promising source of inhibitors of metalloaminopeptidases from M1 and M17 families, with foreseen biomedical applications in human diseases. The results reviewed in the present contribution support and encourage further studies with inhibitors isolated from marine invertebrates in different biomedical models associated with the activity of these families of exopeptidases.

Bufadienolides preferentially inhibit aminopeptidase N among mammalian metallo-aminopeptidases; relationship with effects on human melanoma MeWo cells.

Bufadienolides are steroids that inhibit Na+/K+-ATPase; recent evidence shows that bufalin inhibits the activity of porcine aminopeptidase N (pAPN). We evaluated the selectivity of some bufadienolides on metallo-aminopeptidases. Among the enzymes of the M1 and M17 families, pAPN and porcine aminopeptidase A (pAPA) were the only targets of some bufadienolides. ѱ-bufarenogin, telocinobufagin, marinobufagin, bufalin, cinobufagin, and bufogenin inhibited the activity of pAPN in a dose-dependent manner in the range of 10-7-10-6 M. The inhibition mechanism was classical reversible noncompetitive for telocinobufagin, bufalin and cinobufagin. Bufogenin had the lowest Ki value and a non-competitive behavior. pAPA activity was inhibited by ѱ-bufarenogin, cinobufagin, and bufogenin, with a classical competitive type of inhibition. The models of enzyme-inhibitor complexes agreed with the non-competitive type of inhibition of pAPN by telocinobufagin, bufalin, cinobufagin, and bufogenin. Since APN is a target in cancer therapy, we tested the effect of bufadienolides on the MeWo APN+ human melanoma cell line; they induced cell death, but we obtained scant evidence that inhibition of APN contributed to their effect. Thus, APN is a selective target of some bufadienolides, and we suggest that inhibition of APN activity by bufadienolides is not a major contributor to their antiproliferative properties in MeWo cells.

Diversidad de aves en un gradiente altitudinal en la Reserva de la Biosfera Sierra de Manantlán, México / Diversity of birds along an elevation gradient in the Sierra de Manantlán Biosphere Reserve, Mexico

Resumen Introducción: México concentra alrededor del 11 % de las especies de aves del mundo, de las cuales el 20 % son endémicas del país, concentrándose el mayor número en la región occidental. Objetivo: Analizar la composición, diversidad y distribución de la avifauna a lo largo de un gradiente altitudinal en el occidente de México. Métodos: La investigación se realizó en la Reserva de la Biosfera Sierra de Manantlán. Registramos especies de aves vistas o escuchadas en 28 puntos de conteo fijos a lo largo de un gradiente de elevación de 1 000 m. La comparación de la riqueza y la completitud del muestreo se determinaron con curvas de interpolación y extrapolación. Las franjas se compararon con un Procedimiento no Paramétrico de Permutación Multirespuesta. Se usaron correlaciones y ordenaciones indirectas para analizar cambios en la riqueza y abundancia. Resultados: Registramos 129 especies (estimado: 96 % de completitud): 19 endémicas de México, 13 en alguna categoría de riesgo y 21 consideradas indicadoras. La elevación determinó la distribución y abundancia de las especies, y las franjas altitudinales más bajas, tuvieron los valores más altos de riqueza y abundancia. Conclusión: La mayor riqueza y abundancia de especies se registró a menor altitud, con un cambio significativo en la composición y tipo de especies indicadoras por franja.

Abstract Introduction: Mexico concentrates around 11 % of the world's bird species, of which 20 % are endemic to the country, with the highest number concentrated in the Western region. Objective: To analyze composition, diversity and avifaunal distribution along an elevation gradient in Western Mexico. Methods: The research was done in the Sierra de Manantlán Biosphere Reserve. We recorded seen or heard bird species in 28 fixed count points along a 1 000 m elevation gradient. Comparative richness and sampling completeness were determined with interpolation and extrapolation curves. Belts were compared with Non-Parametric Multi-Response Permutation. Correlations and indirect ordinations were used to analyze changes in richness and abundance. Results: We recorded 129 species (estimate: 96 % completeness): 19 endemics to Mexico, 13 in some risk category, and 21 considered indicators. Elevation determined the distribution and abundance of species, and the lower elevational bands, had the highest richness and abundance values. Conclusion: The highest species richness and abundance were recorded at lower elevations, with a significant change in composition and type of indicator species by belt. The numbers of endemic and at-risk species remained constant with elevation.

Blockade of interleukin-6 as a possible therapeutic target for AA amyloidosis.

INTRODUCTION: AA (secondary) amyloidosis is a severe complication of chronic inflammatory disorders. It is characterized by the systemic deposition of an abnormal protein called amyloid, affecting mainly renal function. IL-6 is a cytokine with a relevant role in this disease development. Interleukin-receptor antagonists, like Tocilizumab (TCZ), have become possible treatment choice for AA amyloidosis. In published reports, TCZ has shown good efficacy for AA amyloidosis, being associated with regression of renal amyloid deposits. METHODS: Retrospective review that included patients with histological diagnosis of AA renal amyloidosis under treatment with TCZ during the years 2018-2019 in our center. We have registered clinical and demographic variables. Renal function was measured by means of CKD-EPI equation to estimate the glomerular filtration rate (FG) and protein/creatinine ratio (IPC) at 3, 6 and 12 months. We define renal response as a decrease by at least 30% of proteinuria and/or stabilization or improvement of FG. We consider that an anti-inflammatory response is a decrease of more than 50% in serum amyloid protein (PSA) and/or C-reactive protein (CRP). RESULTS: We collected 3 cases of patients with histologically proven AA amyloidosis treated with TCZ (2 men; 1 woman; aged 55, 74 and 75 years). The follow-up was 13, 14 and 75 months. FG was stabilized in two patients. The third patient remained on hemodialysis during follow-up, although with excellent control of her underlying inflammatory disease. In all three cases, reduced PSA and CRP were observed. There have been no adverse events. CONCLUSIONS: The TCZ may be an effective and safe option in treatment of AA amyloidosis with renal involvement. Our results position it as an interesting therapeutic option to consider in these cases, although prospective studies would be necessary to evaluate the global role of TCZ in AA amyloidosis.

Discovery of tight-binding competitive inhibitors of dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (DPP-IV, EC 3.4.14.5) is an abundant serine aminopeptidase that preferentially cleaves N-terminal Xaa-Pro or Xaa-Ala dipeptides from oligopeptides. Inhibitors of DPP-IV activity are used for treating type 2 diabetes mellitus and other diseases. DPP-IV is also involved in tumor progression. We identified four new non-peptide tight-binding competitive inhibitors of porcine DPP-IV by virtual screening and enzymatic assays. Molecular docking simulations supported the competitive behavior, and the selectivity of one of the compounds in the DPP-IV family. Since three of these inhibitors are also aminopeptidase N (APN) inhibitors, we tested their impact on APN+/DPP-IV+ and DPP-IV+ human tumor cells' viability. Using kinetic assays, we determined that HL-60 tumor cells express both APN and DPP-IV activities and that MDA-MB-231 tumor cells express DPP-IV activity. The inhibitors had a slight inhibitory effect on human HEK-293 cell viability but reduced the viability of APN+/DPP-IV+ and DPP-IV+ human tumor cells more potently. Remarkably, the intraperitoneal injection of these compounds inhibited DPP-IV activity in rat brain, liver, and pancreas. In silico studies suggested inhibitors binding to serum albumin contribute to blood-brain barrier crossing. The spectrum of action of some of these compounds may be useful for niche applications.

Blockade of interleukin-6 as a possible therapeutic target for AA amyloidosis. / La inhibición de la interleucina-6 como posible diana terapéutica en la amiloidosis AA.

INTRODUCTION: AA (secondary) amyloidosis is a severe complication of chronic inflammatory disorders. It is characterized by the systemic deposition of an abnormal protein called amyloid, affecting mainly renal function. IL-6 is a cytokine with a relevant role in this disease development. Interleukin-receptor antagonists, like Tocilizumab (TCZ), have become possible treatment choice for AA amyloidosis. In published reports, TCZ has shown good efficacy for AA amyloidosis, being associated with regression of renal amyloid deposits. METHODS: Retrospective review that included patients with histological diagnosis of AA renal amyloidosis under treatment with TCZ during the years 2018-2019 in our center. We have registered clinical and demographic variables. Renal function was measured by means of CKD-EPI equation to estimate the glomerular filtration rate (FG) and protein/creatinine ratio (IPC) at 3, 6 and 12 months. We define renal response as a decrease by at least 30% of proteinuria and/or stabilization or improvement of FG. We consider that an anti-inflammatory response is a decrease of more than 50% in serum amyloid protein (PSA) and/or C-reactive protein (CRP). RESULTS: We collected 3 cases of patients with histologically proven AA amyloidosis treated with TCZ (2 men; 1 woman; aged 55, 74 and 75 years). The follow-up was 13, 14 and 75 months. FG was stabilized in two patients. The third patient remained on hemodialysis during follow-up, although with excellent control of her underlying inflammatory disease. In all three cases, reduced PSA and CRP were observed. There have been no adverse events. CONCLUSIONS: The TCZ may be an effective and safe option in treatment of AA amyloidosis with renal involvement. Our results position it as an interesting therapeutic option to consider in these cases, although prospective studies would be necessary to evaluate the global role of TCZ in AA amyloidosis.

Radiocesium in Shiitake mushroom: Accumulation in living fruit bodies and leaching from dead fruit bodies.

In this paper, cesium (Cs) accumulation by the saprophytic fungus Lentinula edodes (Shiitake) was investigated to contribute to the elucidation of radiocesium-cycling mechanisms in forest environments. Although the 137Cs in the mushroom bed before culture was bioavailable, the transfer factor (TF) of Cs (133Cs and 137Cs) from the mushroom bed to fruit bodies was low (approximately 1) and the TFs of K (5) and Na (1.5) were higher. Cs and K concentrations in fruit bodies at different maturity stages were almost constant. The concentration ratio of Cs/K is constant in the pileus regardless of the pileus tissues. These results demonstrate that Shiitake non-specifically accumulates Cs while accumulating the essential element K and provide evidence that no selective Cs accumulation (or binding) sites exist within the Shiitake fruit body. Furthermore, the present results show that most accumulated Cs quickly leaches out from the dead fruit body with exposure to water. The leached Cs was largely adsorbable on clay minerals, suggesting that the Shiitake fruit body likely contains Cs in the cation form.

Manual mass spectrometry de novo sequencing of the anionic host defense peptides of the Cuban Treefrog Osteopilus septentrionalis.

RATIONALE: Host defense peptides accumulated in the skin glands of the animals constitute the basis of the adaptive and immune system of amphibians. The peptidome of the Cuban frog Osteopilus septentrionalis was established using tandem mass spectrometry as the best analytical tool to elucidate the sequence of these peptides. METHODS: Manual interpretation of complementary collision-induced dissociation (CID), higher energy collision-induced dissociation (HCD), and electron transfer dissociation (ETD) tandem mass spectra recorded with an Orbitrap Elite mass spectrometer in liquid chromatography/mass spectrometry (LC/MS) mode was used to sequence the peptide components of the frog skin secretion, obtained by mild electrostimulation. RESULTS: Although the vast majority of amphibian peptides discovered so far are cationic, surprisingly only anionic peptides were identified in the skin secretion of the Cuban frog Osteopilus septentrionalis. Mass spectrometry allowed the sequences to be established of 16 representatives of new peptide families: septenins 1 and septenins 2. The highest sequence coverage when dealing with these anionic peptides was obtained with CID normalized collision energy 35 and HCD normalized collision energy 28. CONCLUSIONS: Mirror-symmetrical peptides are sequenced using N-terminal acetylation. Acetylated Ser is reliably distinguished from isomeric Glu by the loss of ketene from b-ions containing the corresponding residue. Calculations of the physicochemical and structural properties of the discovered anionic septenins 1 and 2 allowed the mechanism of their interaction with microbe cells to be postulated.

Reporte de caso. Uso de toxina botulínica tipo A para la reparación de hernia ventral gigante planeada / Surgical treatment of diabetic foot based on Wagner classification, Case report

Introducción: La incidencia de eventración post quirúrgica es del 2-20%, se da mayormente en pacientes con factores de riesgo durante los primeros tres años posteriores a la cirugía inicial. La mayoría de las hernias de la pared abdominal pueden ser reparadas fácilmente, sin embargo, las hernias gigantes (>10cm de diámetro) o aquellas con pérdida de domicilio requieren métodos de expansión gradual de la pared abdominal pre y/o transoperatoriamente. Se ha descrito que posterior a la aplicación de toxina botulínica serotipo A (TBA) de forma bilateral en la pared abdominal, los defectos disminuyen clínica y tomográficamente hasta 5.25cm, por su efecto selectivo en terminaciones nerviosas periféricas colinérgicas, provocando atrofia muscular sin fibrosis. El efecto máximo ocurre al mes de la aplicación y dura 28 semanas. Esta técnica permite planear preoperatoriamente la magnitud de la cirugía. Nuestro caso, paciente masculino de 33 años. Quien ingresa por politrauma. Se realiza procedimiento quirúrgico abdominal y posteriormente se eviscera en múltiples ocasiones. Se cierra herida y posteriormente desarrolla hernia ventral gigante con la que egresa. Se realiza TC abdominal evidenciando defecto herniario de 15.9cm, con este resultado se aplica toxina botulínica serotipo A en la pared abdominal bilateral (50 unidades en cada lado) guiado por ultrasonido. 25 días después se realiza TC abdominal control que evidencia defecto herniario de 14.7cm y se decide ingreso para cirugía electiva. Se decide llevar a sala de operaciones donde se realiza hernioplastía con liberación de componentes anteriores mas colocación de malla de polietileno (cuatro semanas posteriores a la aplicación de la toxina), quedando defecto totalmente cerrado y sin tensión. Paciente con adecuada evolución posterior a intervención por lo que egresa. Actualmente sin defecto herniario recurrente. Conclusión: El uso de toxina botulínica serotipo A es un nuevo recurso prequirúrgico para la preparación de pacientes con hernias ventrales gigantes, ya que permite el cierre sin tensión en la mayoría de los casos. Además, ayuda a que transoperatoriamente la separación de componentes se realice de una mejor manera, ya que se da mejor manipulación al momento de desplazar las estructuras musculares. Idealmente se debe de realizar la intervención quirúrgica cuatro semanas posteriores a su aplicación. (AU)

ntroduction: The incidence of post-surgical eventration is 2-20%, it occurs mostly in patients with risk factors during the first three years after the initial surgery. Most abdominal wall hernias can be easily repaired, however, giant hernias (>10cm of diameter) or those with the loss of domain require methods of gradual expansion of the abdominal wall pre or intraoperatively. It has been described that after the application of botulinum toxin A bilaterally in the abdominal wall, the defect can decrease clinically and tomographically up to 5.25cm, due to its selective effect on cholinergic peripheral nerve endings, that cause muscle atrophy without fibrosis. The maximum effect occurs one month after the application and lasts 28 weeks. This technique allows to plan preoperatively the magnitude of the surgery. Description of case: A 33 year old male patient, who entered the emergency room due to polytrauma. Abdominal surgical procedure was performed and later he eviscerates on multiple occasions. The wound was closed and later he develops a giant ventral hernia with which it is discharged. An abdominal CT was performed, showing a hernia defect of 15.9cm. With this result botulinum toxin A was applied guided by ultrasound bilaterally in the abdominal wall (50 U on each side). A control abdominal CT was performed after 25 days, which it revealed a hernia defect of 14.7 cms, so admission was decided for elective surgery. The patient was taken to the operating room where a hernioplasty with anterior components separation plus the placement of a polyethylene mesh was performed (four weeks after the application of the botulinum toxin A), the hernia defect was completely close without tension. The patient had an adequate post-surgical evolution for which it was discharge. Currently without a recurrent hernia defect. Conclusion: The use of botulinum toxin A is a new pre-surgical resource for the preparation of patients with giant ventral hernias, since it allows the closure without tension in most cases. In addition, it helps transoperatively with the components separation, since there is a better manipulation at the time of displacing the muscular structures. Ideally, the surgical intervention should be performed four weeks after its application. (AU)

Antidiabetic Activity of Aloe vera Leaves.

This research evaluated the potential of using the methanol extract of Aloe vera (L.) Burm.f (AVM) to prevent the formation of AGEs by means of the BSA/glucose assay, BSA-methylglyoxal assay, arginine-methylglyoxal assay, fructosamine, Nɛ-(carboxymethyl) lysine (CML), thiol groups, and carbonyl protein in vitro. The effect of AVM was also evaluated with regard to inhibiting the enzymes α-amylase, α-glucosidase, and pancreatic lipase. For this, the plant was dried, ground, and subsequently macerated with methanol. Aloe vera methanol extract (AVM) significantly decreased the formation of AGEs, as well as the formation of fructosamine, CML, and carbonyl protein. The concentration of 5 mg/ml of AVM presented the best results. AVM significantly inhibited the α-amylase and α-glucosidase enzymes. As regards the content of thiol groups, a significant increase was observed during the four weeks of the experiment. So, we can conclude that Aloe vera methanol extract decreases the formation of AGEs and may inhibit the increase in postprandial glucose, suggesting that AVM can prevent diabetes complications associated with AGE.

Why do physicians prescribe dialysis? A prospective questionnaire study.

INTRODUCTION: The incidence of unplanned dialysis initiation (DI) with consequent increased comorbidity, mortality and reduced modality choice remains high, but the optimal timing of dialysis initiation (DI) remains controversial, and there is a lack of studies of specific reasons for DI. We investigated why and when physicians prescribe dialysis and hypothesized that physician motivation for DI is an independent factor which may have clinical consequences. METHODS: In the Peridialysis study, an ongoing multicenter prospective study assessing the causes and timing of DI and consequences of unplanned dialysis, physicians in 11 hospitals were asked to describe their primary, secondary and further reasons for prescribing DI. The stated reasons for DI were analyzed in relation to clinical and biochemical data at DI, and characteristics of physicians. RESULTS: In 446 patients (median age 67 years; 38% females; diabetes 25.6%), DI was prescribed by 84 doctors who stated 23 different primary reasons for DI. The primary indication was clinical in 63% and biochemical in 37%; 23% started for life-threatening conditions. Reduced renal function accounted for only 19% of primary reasons for DI but was a primary or contributing reason in 69%. The eGFR at DI was 7.2 ±3.4 ml/min/1.73 m2, but varied according to comorbidity and cause of DI. Patients with cachexia, anorexia and pulmonary stasis (34% with heart failure) had the highest eGFR (8.2-9.8 ml/min/1.73 m2), and those with edema, "low GFR", and acidosis, the lowest (4.6-6.1 ml/min/1.73 m2). Patients with multiple comorbidity including diabetes started at a high eGFR (8.7 ml/min/1.73 m2). Physician experience played a role in dialysis prescription. Non-specialists were more likely to prescribe dialysis for life-threatening conditions, while older and more experienced physicians were more likely to start dialysis for clinical reasons, and at a lower eGFR. Female doctors started dialysis at a higher eGFR than males (8.0 vs. 7.1 ml/min/1.73 m2). CONCLUSIONS: DI was prescribed mainly based on clinical reasons in accordance with current recommendations while low renal function accounted for only 19% of primary reasons for DI. There are considerable differences in physicians´ stated motivations for DI, related to their age, clinical experience and interpretation of biochemical variables. These differences may be an independent factor in the clinical treatment of patients, with consequences for the risk of unplanned DI.

Cosegregation of a novel mutation in the sixth transmembrane segment of the luteinizing/choriogonadotropin hormone receptor with two Brazilian siblings with severe testotoxicosis.

PURPOSE: Testotoxicosis is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor (LHCGR) gene. The aim of this study was to describe two Brazilian siblings with testotoxicosis, to confirm the molecular diagnosis, and to perform an in silico analysis of a novel mutation in the hot spot of the LHCGR gene. MATERIALS AND METHODS: Molecular analysis of the mutation on the LHCGR gene was performed by direct Sanger sequencing, followed by an in silico analysis using HOPE bioinformatics tool to predict a functional defect of the mutant. RESULTS: Both patients presented with gonadotropin-independent precocious puberty before the age of four years. Genetic analysis revealed a novel non-maternally inherited p.Asp578Val mutation of the LHCGR gene. An in silico analysis showed that the p.Asp578Val mutation disturbed amino acid physicochemical features regarding its size, charge, and hydrophobicity value. CONCLUSIONS: Clinical and hormonal profile of the siblings here evaluated was not different while compared to those patients previously described. An in silico mutation analysis reinforced the causative role of recurrent activating mutations in the intracellular loop and transmembrane helices of the LHCGR. The segregation of this mutation with the offsprings' phenotype indicated that it is causative.

Comparison between the Reflux Finding Score and the Reflux Symptom Index in the Practice of Otorhinolaryngology

Abstract Introduction The Gastroesophageal Reflux Disease has a prevalence of 12% of the urban population in Brazil. Koufman proposed the term to designate Laryngeal Pharyngeal Reflux (LPR) symptoms, signs or tissue damage resulting from aggression of the gastrointestinal contents in the upper aerodigestive tract. Belafsky et al proposed a score that points to inflammatory laryngeal signs through videolaryngoscopic findings, the Reflux Finding Score (RFS). Moreover, in 2002, they published the Reflux Symptom Index (RSI). Objective The objective of this study is to provide a comparison between the Reflux Finding Score and the Reflux Symptom Index in the practice of Otorhinolaryngology. Methods Our study involved a total of 135 patients who visited the Ear, Nose, and Throat (ENT) clinic Núcleo de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço de São Paulo between April 2014 and May 2015 with suspected LPR.We excluded nine patients and the study group was 126 patients. All patients were ranked by their RSI and RFS scores. Results The study group consisted of 126 patients (88 women and 38 men). Their main complaints were cough (40.4%), globus (21.4%), dysphonia (19.8%), throat clearing (15.8%), postnasal drip (3.17%), snoring (1.5%), dysphagia (1.5%), cacosmia (0.7%), and regurgitation (1.5%). The RSI ranges from 13 to 42 with a mean of 20.7 (SD = 6.67). The RFS ranged from 3 to 19 with a mean of 9.53 (SD = 2.64). Conclusion The RSI and RFS can easily be included in ENT routines as objective parameters,with low cost and high practicality. Based on the clinical index, the specialist can evaluate the need for further tests.

Comparison between the Reflux Finding Score and the Reflux Symptom Index in the Practice of Otorhinolaryngology.

INTRODUCTION: The Gastroesophageal Reflux Disease has a prevalence of ∼12% of the urban population in Brazil. Koufman proposed the term to designate Laryngeal Pharyngeal Reflux (LPR) symptoms, signs or tissue damage resulting from aggression of the gastrointestinal contents in the upper aerodigestive tract. Belafsky et al proposed a score that points to inflammatory laryngeal signs through videolaryngoscopic findings, the Reflux Finding Score (RFS). Moreover, in 2002, they published the Reflux Symptom Index (RSI). OBJECTIVE: The objective of this study is to provide a comparison between the Reflux Finding Score and the Reflux Symptom Index in the practice of Otorhinolaryngology. METHODS: Our study involved a total of 135 patients who visited the Ear, Nose, and Throat (ENT) clinic Núcleo de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço de São Paulo between April 2014 and May 2015 with suspected LPR. We excluded nine patients and the study group was 126 patients. All patients were ranked by their RSI and RFS scores. RESULTS: The study group consisted of 126 patients (88 women and 38 men). Their main complaints were cough (40.4%), globus (21.4%), dysphonia (19.8%), throat clearing (15.8%), postnasal drip (3.17%), snoring (1.5%), dysphagia (1.5%), cacosmia (0.7%), and regurgitation (1.5%). The RSI ranges from 13 to 42 with a mean of 20.7 (SD = 6.67). The RFS ranged from 3 to 19 with a mean of 9.53 (SD = 2.64). CONCLUSION: The RSI and RFS can easily be included in ENT routines as objective parameters, with low cost and high practicality. Based on the clinical index, the specialist can evaluate the need for further tests.

[Overweight and obesity: review and update]. / Sobrepeso y obesidad: revisión y puesta al día de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (SLAGHN.

Obesity is an epidemic with important health repercussions in addition to high treatment-related costs. Between 2006 and 2007 the WHO developed new assessment tools, which aren't being globally used. In fact, there is no unified problem management across the hemisphere. Objectives: To update obesity epidemiology, to promote application of WHO's standards, to review new findings on physiopathology (i.e., fatty tissue as endocrine organ, intestinal microbiota), to update epidemiological information, and to provide management guidelines that can be integrated in clinical care. Methods: LAPSGHAN called up its members to collaborate in preparing this review article under the direction of an editor/coordinator, who selected the contents and literature with the best evidencetogether with the members. Each member prepared a separate document for each content. The chosen contents were later collated, unified, and edited. Results. This documents highlights the following: 1) Although extreme obesity is increasing in the US, overweight and obesity prevalence has stabilized, while in other countries it is alarmingly increasing; 2) New information regarding role of fatty tissue as endocrine organ and self-regulator of obesity; 3) The promising role of microbiota; and 4) Guidelines for children handling during consultation and follow-up. Conclusions: There is no widespread implementation of standards and guidelines from the World Health Organization (WHO). There is no agreement as to whether z-scores or percentiles should be used, especially regarding children under 2 due to their changing body complexion. The most accepted tool to assess overweight, obesity and severe obesity is the Body Mass Index (BMI). This document provides recommendations on how to approach clinical care with affected children.