Uneven vectorial projection is the best explanation for QRS dispersion, not the asynchronic ventricular activation.

BACKGROUND: It is believed that QRS dispersion (QRSd) is caused by asynchrony of ventricular activation, but there are no studies that prove it. OBJECTIVES: To determine the mechanism that best explains QRSd in surface electrocardiogram (ECG). METHODS: Cross-sectional study in 95 consecutive patients (median age: 31.0 years [25-52], female sex: 66.3%) with atrioventricular nodal reentrant tachycardia. All 12 ECG leads were recorded at once, simultaneously with the intracardiac recordings. QRSd was quantified as the difference between maximum (QRSmax) and minimum QRS duration (QRSmin). QRS was measured firstly at a calibration of 20 mm/mV and a sweep speed of 50 mm/s, enhancement 10× (basic measurement [BM]), and after at sweep speed of 150 mm/s, enhancement 80 - 160×. The interventricular dyssynchrony (IVD) was also quantified. RESULTS: QRSmax increased from BM (98 ms [91-103]) to 80× (102 ms [99-108]; p = 0.029) and 160× (104 ms [101.5-110]; p = 0.027). QRSmin, almost equaled the duration of QRSmax at 160× (103 ms [100-108]). With BM, QRSd was 26 ms [22-35] and was reduced 26-fold (p < 0.001) by magnifying the QRS at 160× (1 ms [0-3]). IVD was weakly correlated with QRSd (r = 0.234, p = 0.023), but strongly with the total QRS at 160× (r = 0.676, p < 0.001). CONCLUSION: When QRS complex is narrow, the best explanation for the origin of QRSd on the surface ECG is the unequal projection of the ventricular depolarization vector in the different axis of the leads.

Vectorial theory surpasses the local theory in explaining the origin of P-wave dispersion.

BACKGROUND: Local theory and the vectorial theory are used to explain the origin of P-wave dispersion (PWD). There are no previous studies that analyze both at the same time. OBJECTIVES: We set out to determine the implication of local and vectorial theories in the origin of PWD. METHODS: Cross-sectional study in 153 randomly selected patients aged 18-70 years, undergoing electrophysiological study. Inhomogeneous atrial conduction was evaluated by atrial electrogram dispersion in terms of duration (EGMdurdis) and morphology (EGMmorph dis). P-distal coronary sinus interval (P-DCS) was also measured. P-wave was measured twice, firstly at a calibration of 20 mm/mV and a sweep speed of 50 mm/s, enhancement 10× (basic measurement [BM]), and second time at sweep speed of 150 mm/s, enhancement 80-160× (high precision measurement [HPM]). RESULTS: PWD with BM was 48 ms [36-54 ms] while with HPM it was 4 ms [0-10 ms], p < 0.001. With BM, maximum and minimum P- wave duration presented a moderate correlation (r = 0.342; p < 0.001), using HPM it becomes strong (r = 0.750; p < 0.001). In cases with P-DCS < 80 ms (r = 0.965; p < 0.001), but not with P-DCS ≥ 80 ms (r = 0.649; p < 0.001), the previous correlation became almost perfect with HPM. EGMdurdis and EGMmorphdis were weak but significantly correlated with PWD. This correlation became moderate in patients with P-DCS ≥ 80 ms and disappeared in those with P-DCS, using BM and HPM. CONCLUSION: Vectorial theory explains almost entirely the PWD phenomenon. Inhomogeneous conduction could be an additional mechanism to explain PWD, but its contribution is small.

New Parameter of the Second Half of the P-Wave, P-Wave Duration, and Atrial Conduction Times Predict Atrial Fibrillation during Electrophysiological Studies.

OBJECTIVE: Several P-wave parameters reflect atrial conduction characteristics and have been used to predict atrial fibrillation (AF). The aim of this study was to determine the relationship between maximum P-wave duration (PMax) and new P-wave parameters, with atrial conduction times (CT), and to assess their predictive value of AF during electrophysiological studies (AF-EPS). SUBJECTS AND METHODS: This was a cross-sectional study in 153 randomly selected patients aged 18-70 years, undergoing EPS. The patients were divided into 2 groups designated as no AF-EPS and AF-EPS, depending on whether AF occurred during EPS or not. Different P-wave parameters and atrial CT were compared for both study groups. Subsequently, the predictive value of the P-wave parameters and the atrial CT for AF-EPS was evaluated. RESULTS: The values of CT, PMax, and maximum Ppeak-Pend interval (Pp-eMax) were significantly higher in patients with AF-EPS. Almost all P-wave parameters were correlated with the left CT. PMax, Pp-eMax, and CT were univariate and multivariate predictors of AF-EPS. The largest ROC area was presented by interatrial CT (0.852; p < 0.001; cutoff value: ≥82.5 ms; sensitivity: 91.1%; specificity: 81.1%). Pp-eMax showed greater sensitivity (79.5%) to discriminate AF-EPS than PMax (72.7%), but the latter had better specificity (60.4% vs. 41.5%). CONCLUSIONS: Left atrial CT were directly and significantly correlated with PMax and almost all the parameters of the second half of the P-wave. CT, PMax, and Pp-eMax (new parameter) were good predictors of AF-EPS, although CT did more robustly.

Gasto catastrófico en salud en México y sus factores determinantes, 2002-2014.

OBJECTIVE: To assess the financial protection of public health insurance by analyzing the percentage of households with catastrophic health expenditure (HCHE) in Mexico and its relationship with poverty status, size of locality, federal entity, insurance status and items of health spending. METHOD: Mexican National Survey of Income and Expenditures 2002-2014 was used to estimate the percentage of HCHE. Through a probit model, factors associated with the occurrence of catastrophic spending are identified. Analysis was performed using Stata-SE 12. RESULTS: In 2014 there were 2.08% of HCHE (1.82-2.34%; N = 657,474). The estimated probit model correctly classified 98.2% of HCHE (Pr (D) ≥ 0.5). Factors affecting the catastrophic expenditures were affiliation, presence of chronic disease, hospitalization expenditure, rural condition and that the household is below the food poverty line. CONCLUSIONS: The percentage of HCHE decreased in recent years, improving financial protection in health. This decline seems to have stalled, keeping inequities in access to health services, especially in rural population without affiliation to any health institution, below the food poverty line and suffering from chronic diseases.

Utility of inline milk fat and protein ratio to diagnose subclinical ketosis and to assign propylene glycol treatment in lactating dairy cows.

The objective was to identify a fat-to-protein ratio (FPR) cut-off to diagnose subclinical ketosis (SCK) and to evaluate the effect of propylene glycol (PPG) treatment of cows with high FPR. The optimized cut-off was > 1.42; sensitivity (Se) = 92%; specificity (Sp) = 65%. A cut-off > 1.5 was selected for the PPG trial for balanced Se-Sp. Fat-to-protein ratio cut-offs > 1.25, 1.35, 1.50, 1.60, and 1.70 resulted in Se-Sp of 100% to 49%, 96% to 59%, 75% to 78%, 33% to 90%, and 8% to 96%, respectively. The proportions of cows with FPR > 1.25, 1.35, 1.42, 1.50, 1.60, and 1.70 were 60%, 50%, 44%, 30%, 14%, and 6%, respectively. Incidences of clinical ketosis and milk yield were similar between cows that received 400 mL of PPG (n = 34) and control cows (n = 38). Prevalence of SCK at enrollment was 29.2%; therefore, FPR > 1.5 is not indicated for treatment. Lower cut-offs should be used for screening.

Utilité du ratio de matière grasse et de protéine sur la ligne de traite pour diagnostiquer une cétose subclinique et assigner le traitement au propylèneglycol chez les vaches laitières en lactation. L'objectif consistait à identifier un seuil du ratio de matière grasse et de protéine (RMGP) pour diagnostiquer une cétose subclinique et évaluer l'effet du traitement au propylèneglycol (PPG) chez les vaches présentant un RMGP élevé. Le seuil optimisé était de > 1,42; la sensibilité (Se) = 92 %; la spécificité (Sp) = 65 %. Un seuil de > 1,5 a été choisi pour l'essai au PPG pour des Se-Sp équilibrées. Des seuils de ratios de matière grasse et protéine de > 1,25, 1,35, 1,50, 1,60 et 1,70 ont produit des Se-Sp de 100 % et 49 %, de 96 % et 59 %, 75 % et 78 %, de 33 % et 90 % et de 8 % et 96 %, respectivement. Les proportions des vaches avec un RMGP de > 1,25, 1,35, 1,42, 1,50, 1,60 et 1,70 étaient de 60 %, 50 %, 44 %, 30 %, 14 % et 6 %, respectivement. L'incidence de cétose clinique et la production de lait étaient semblables entre les vaches qui avaient reçu 400 mL de PPG (n = 34) et les vaches témoins (n = 38). La prévalence de cétose subclinique au recrutement était de 29,2 %; par conséquent, un RMGP de > 1,5 n'est pas indiqué pour le traitement. Des seuils inférieurs devraient être utilisés pour le dépistage.(Traduit par Isabelle Vallières).

External validation of a minimal-resource model to predict reduced estimated glomerular filtration rate in people with type 2 diabetes without diagnosis of chronic kidney disease in Mexico: a comparison between country-level and regional performance.

Background: Patients with type 2 diabetes are at an increased risk of chronic kidney disease (CKD) hence it is recommended that they receive annual CKD screening. The huge burden of diabetes in Mexico and limited screening resource mean that CKD screening is underperformed. Consequently, patients often have a late diagnosis of CKD. A regional minimal-resource model to support risk-tailored CKD screening in patients with type 2 diabetes has been developed and globally validated. However, population heath and care services between countries within a region are expected to differ. The aim of this study was to evaluate the performance of the model within Mexico and compare this with the performance demonstrated within the Americas in the global validation. Methods: We performed a retrospective observational study with data from primary care (Clinic Specialized in Diabetes Management in Mexico City), tertiary care (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán) and the Mexican national survey of health and nutrition (ENSANUT-MC 2016). We applied the minimal-resource model across the datasets and evaluated model performance metrics, with the primary interest in the sensitivity and increase in the positive predictive value (PPV) compared to a screen-everyone approach. Results: The model was evaluated on 2510 patients from Mexico (primary care: 1358, tertiary care: 735, ENSANUT-MC: 417). Across the Mexico data, the sensitivity was 0.730 (95% CI: 0.689 - 0.779) and the relative increase in PPV was 61.0% (95% CI: 52.1% - 70.8%). These were not statistically different to the regional performance metrics for the Americas (sensitivity: p=0.964; relative improvement: p=0.132), however considerable variability was observed across the data sources. Conclusion: The minimal-resource model performs consistently in a representative Mexican population sample compared with the Americas regional performance. In primary care settings where screening is underperformed and access to laboratory testing is limited, the model can act as a risk-tailored CKD screening solution, directing screening resources to patients who are at highest risk.

Genomic and Phylogenetic Characterisation of SARS-CoV-2 Genomes Isolated in Patients from Lambayeque Region, Peru.

OBJECTIVE: this study aims to identify and characterise genomic and phylogenetically isolated SARS-CoV-2 viral isolates in patients from Lambayeque, Peru. METHODS: Nasopharyngeal swabs were taken from patients from the Almanzor Aguinaga Asenjo Hospital, Chiclayo, Lambayeque, Peru, which had been considered mild, moderate, and severe cases of COVID-19. Patients had to have tested positive for COVID-19, using a positive RT-PCR for SARS-CoV-2. Subsequently, the SARS-CoV-2 complete viral genome sequencing was carried out using Illumina MiSeq®. The sequences obtained from the sequence were analysed in Nextclade V1.10.0 to assign the corresponding clades, identify mutations in the SARS-CoV-2 genes and perform quality control of the sequences obtained. All sequences were aligned using MAFFT v7.471. The SARS-CoV-2 isolate Wuhan NC 045512.2 was used as a reference sequence to analyse mutations at the amino acid level. The construction of the phylogenetic tree model was achieved with IQ-TREE v1.6.12. RESULTS: It was determined that during the period from December 2020 to January 2021, the lineages s C.14, C.33, B.1.1.485, B.1.1, B.1.1.1, and B.1.111 circulated, with lineage C.14 being the most predominant at 76.7% (n = 23/30). These lineages were classified in clade 20D mainly and also within clades 20B and 20A. On the contrary, the variants found in the second batch of samples of the period from September to October 2021 were Delta (72.7%), Gamma (13.6%), Mu (4.6%), and Lambda (9.1%), distributed between clades 20J, 21G, 21H, 21J, and 21I. CONCLUSIONS: This study reveals updated information on the viral genomics of SARS-CoV-2 in the Lambayeque region, Peru, which is crucial to understanding the origins and dispersion of the virus and provides information on viral pathogenicity, transmission and epidemiology.

First report of Aphrialatifrons (Diptera, Tachinidae, Leskiini) in the Canary Islands.

Background: The Canary Islands are an archipelago of volcanic origin, located off north-west Africa comprising eight islands. Fuerteventura and Lanzarote are the oldest (20 and 15 millon years old, respectively) and the easternmost islands. The order Diptera is one of the most relevant taxa in the Canary Islands as they constitute the second highest species richness. Within this order, the family Tachinidae is especially interesting as all species are endoparasitoids of arthropods and most species play a key role as pollinators. In the Canary Islands, the family comprises 52 species, with Fuerteventura and Lanzarote harbouring up to 20 species each. New information: Aphrialatifrons, a Palaearctic tachinid fly, is reported for the first time from the Canary Islands, where it was found on Fuerteventura and Lanzarote. Morphological examination was carried out and the first known barcode of the species is presented. Its potential distribution and source of origin are discussed.

Hypoxia-Inducible Factor 2 Alpha (HIF2α) Inhibitors: Targeting Genetically Driven Tumor Hypoxia.

Tumors driven by deficiency of the VHL gene product, which is involved in degradation of the hypoxia-inducible factor subunit 2 alpha (HIF2α), are natural candidates for targeted inhibition of this pathway. Belzutifan, a highly specific and well-tolerated HIF2α inhibitor, recently received FDA approval for the treatment of nonmetastatic renal cell carcinomas, pancreatic neuroendocrine tumors, and central nervous system hemangioblastomas from patients with von Hippel-Lindau disease, who carry VHL germline mutations. Such approval is a milestone in oncology; however, the full potential, and limitations, of HIF2α inhibition in the clinic are just starting to be explored. Here we briefly recapitulate the molecular rationale for HIF2α blockade in tumors and review available preclinical and clinical data, elaborating on mutations that might be particularly sensitive to this approach. We also outline some emerging mechanisms of intrinsic and acquired resistance to HIF2α inhibitors, including acquired mutations of the gatekeeper pocket of HIF2α and its interacting partner ARNT. Lastly, we propose that the high efficacy of belzutifan observed in tumors with genetically driven hypoxia caused by VHL mutations suggests that a focus on other mutations that similarly lead to HIF2α stabilization, such as those occurring in neuroendocrine tumors with disruptions in the tricarboxylic acid cycle (SDHA/B/C/D, FH, MDH2, IDH2), HIF hydroxylases (EGLN/PHDs), and the HIF2α-encoding gene, EPAS1, are warranted.

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings.

BACKGROUND: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. METHODS: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. RESULTS: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. CONCLUSION: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

PET/MR: primary inferior vena cava leiomyosarcoma.

Positron emission tomography (PET) combined with a magnetic resonance (MR) scanner (PET/MR) with 18F-fluorodeoxyglucose (FDG) tracer is being used in quite a few nuclear medicine centers. The aim of this study is to illustrate two uncommon cases of primary inferior vena cava leiomyosarcoma which were formerly evaluated with anatomical images such as computed tomography and ultrasound. These techniques were inferior in the definition of the tumor and its characteristics. F-18 FDG PET/MR was essential and provided all the necessary information: its origin, local extension, anatomo-metabolic behavior, form of presentation, and distant metastasis in one single diagnostic technique. PET/MR accurately contributed to the diagnosis in a shortened period of time and, therefore, in the prognosis of this disease with greater benefits.

Bone scintigraphy outperformed anatomic images in frostbite injuries: a case report.

Frostbite is a localized cold thermal injury, as a result of tissue exposure to temperatures below freezing point for a prolonged period of time. The spectrum of injury is broad; thus, frostbite injuries may have deleterious effects with the possibility of losing part or whole extremities. We aim to present the case of a 38-year-old male patient evaluated with multiphase technetium-99m-methylene diphosphonate bone scintigraphy. This methodology may accelerate clinical management of frostbite injuries because it provides precise clinical-imaging correlation by determining the extent of injury and can accurately predict the level of amputation if required.

Endocrine and Neuroendocrine Tumors Special Issue-Checkpoint Inhibitors for Adrenocortical Carcinoma and Metastatic Pheochromocytoma and Paraganglioma: Do They Work?

Adrenocortical cancers and metastatic pheochromocytomas are the most common malignancies originating in the adrenal glands. Metastatic paragangliomas are extra-adrenal tumors that share similar genetic and molecular profiles with metastatic pheochromocytomas and, subsequently, these tumors are studied together. Adrenocortical cancers and metastatic pheochromocytomas and paragangliomas are orphan diseases with limited therapeutic options worldwide. As in any other cancers, adrenocortical cancers and metastatic pheochromocytomas and paragangliomas avoid the immune system. Hypoxia-pseudohypoxia, activation of the PD-1/PD-L1 pathway, and/or microsatellite instability suggest that immunotherapy with checkpoint inhibitors could be a therapeutic option for patients with these tumors. The results of clinical trials with checkpoint inhibitors for adrenocortical carcinoma or metastatic pheochromocytoma or paraganglioma demonstrate limited benefits; nevertheless, these results also suggest interesting mechanisms that might enhance clinical responses to checkpoint inhibitors. These mechanisms include the normalization of tumor vasculature, modification of the hormonal environment, and vaccination with specific tumor antigens. Combinations of checkpoint inhibitors with classical therapies, such as chemotherapy, tyrosine kinase inhibitors, radiopharmaceuticals, and/or novel therapies, such as vaccines, should be evaluated in clinical trials.

A technology assisted precision ketogenic diet intervention for cardio-renal-metabolic health in overweight or obese adults: Protocol for a randomized controlled trial.

BACKGROUND: The obesity epidemic is a public health concern, as it is associated with a variety of chronic conditions. The ketogenic diet has drawn much scientific and public attention. However, implementation is challenging and its effect on cardio-renal-metabolic health is inconclusive. This study will assess the feasibility, acceptability, and preliminary efficacy of a technology-assisted ketogenic diet on cardio-renal-metabolic health. METHODS: This is a single center, 6-month, stratified, randomized controlled trial. A total of 60 overweight/obese adults (18+ years old) will be enrolled, including 20 without type 2 diabetes (T2D) and without chronic kidney disease (CKD); 20 with T2D, but without CKD; and 20 with early-stage CKD. Participants will be stratified based on health conditions and randomized into a ketogenic diet (n = 30) or a low-fat diet group (n = 30). Health education involving diet and physical activity will be delivered both digitally and in-person. Mobile and connected health technologies will be used to track lifestyle behaviors and health indicators, as well as provide weekly feedback. The primary outcome (weight) and the secondary outcomes (e.g., blood pressure, glycemic control, renal health) will be assessed with traditional measurements and metabolomics. DISCUSSION: Mobile and connected health technologies provide new opportunities to improve chronic condition management, health education attendance, planned lifestyle changes and engagement, and health outcomes. The advancement of bioinformatics technology offers the possibility to profile and analyze omics data which may advance our understanding of the underlying mechanisms of intervention effects on health outcomes at the molecular level for personalized and precision lifestyle interventions.

Increased p wave dispersion in elite athletes.

BACKGROUND: Few studies have been performed on P wave indices in athletes. The aim of this study was to determine the behaviour of maximum P wave duration (Pmax), minimum P wave duration (Pmin) and P wave dispersion (PWD) in young high performance athletes, as well as the relationship of PWD with training history, heart rate (HR) and echocardiographic parameters. METHODS: We performed a cross-sectional observational study in 38 athletes of high performance in sports: water polo, distance running and weight lifting compared with 34 sedentary controls. RESULTS: The average age in both groups was 20.6 years. Note that PWD was increased in athletes (57 ± 14 ms vs. 40 ± 12 ms, p <0.001) while Pmin was significantly lower (57 ± 13 ms vs. 72 ± 13 ms, p <0.001), and there was no difference when comparing Pmax (114 ± 9 ms vs. 117 ± 14 ms, p> 0.05). The correlation between the duration of training (r = 0.511) and resting HR (r = 0.461) with PWD was significant (p <0.01). CONCLUSIONS: PWD is increased in young athletes of high performance and was positively correlated with duration of training and baseline HR. The increase in PWD was secondary to a significant decrease in Pmin.

Increased QRS duration and dispersion are associated with mechanical dyssynchrony in patients with permanent right ventricular apical pacing.

BACKGROUND: Permanent right ventricular apical pacing may have negative effects on ventricular function and contribute to development of heart failure. We aimed to assess intra- and interventricular mechanical dyssynchrony in patients with permanent right ventricular apical pacing, and to establish electrocardiographic markers of dyssynchrony. METHODS: 84 patients (46:38 male:female) who required permanent pacing were studied. Pacing was done from right ventricular apex in all patients. We measured QRS duration and dispersion on standard 12-lead ECG. Intra- and interventricular mechanical dyssynchrony and left ventricular ejection fraction were assessed by transthoracic echocardiography. Patients were followed-up for 24 months.  Results: Six months after implantation, QRS duration increased from 128.02 ms to 132.40 ms, p≤0.05. At 24 months, QRS dispersion increased from 43.26 ms to 46.13 ms, p≤0.05. Intra- and interventricular dyssynchrony increased and left ventricular ejection fraction decreased during follow-up. A QRS dispersion of 47 ms predicted left ventricular dysfunction and long-term electromechanical dyssynchrony with a sensitivity of 80% and a specificity of 76%.  Conclusion: In patients with permanent right ventricular apical pacing there is an increased duration and dispersion of QRS related to dyssynchrony and decreased left ventricular ejection fraction. This study shows that QRS dispersion could be a better predictive variable than QRS duration for identifying left ventricular ejection fraction worsening in patients with permanent right ventricular apical pacing. The electrocardiogram is a simple tool for predicting systolic function worsening in these patients and can be used at the bedside for early diagnosis in the absence of clinical symptoms, allowing adjustments of medical treatment to prevent progression of heart failure and improve the patient's quality of life.

Insights into Mechanisms of Pheochromocytomas and Paragangliomas Driven by Known or New Genetic Drivers.

Pheochromocytomas and paragangliomas are rare tumors of neural crest origin. Their remarkable genetic diversity and high heritability have enabled discoveries of bona fide cancer driver genes with an impact on diagnosis and clinical management and have consistently shed light on new paradigms in cancer. In this review, we explore unique mechanisms of pheochromocytoma and paraganglioma initiation and management by drawing from recent examples involving rare mutations of hypoxia-related genes VHL, EPAS1 and SDHB, and of a poorly known susceptibility gene, TMEM127. These models expand our ability to predict variant pathogenicity, inform new functional domains, recognize environmental-gene connections, and highlight persistent therapeutic challenges for tumors with aggressive behavior.

Genotype-Phenotype Features of Germline Variants of the TMEM127 Pheochromocytoma Susceptibility Gene: A 10-Year Update.

PURPOSE: This work aimed to evaluate genotype-phenotype associations in individuals carrying germline variants of transmembrane protein 127 gene (TMEM127), a poorly known gene that confers susceptibility to pheochromocytoma (PHEO) and paraganglioma (PGL). DESIGN: Data were collected from a registry of probands with TMEM127 variants, published reports, and public databases. MAIN OUTCOME ANALYSIS: Clinical, genetic, and functional associations were determined. RESULTS: The cohort comprised 110 index patients (111 variants) with a mean age of 45 years (range, 21-84 years). Females were predominant (76 vs 34, P < .001). Most patients had PHEO (n = 94; 85.5%), although PGL (n = 10; 9%) and renal cell carcinoma (RCC, n = 6; 5.4%) were also detected, either alone or in combination with PHEO. One-third of the cases had multiple tumors, and known family history was reported in 15.4%. Metastatic PHEO/PGL was rare (2.8%). Epinephrine alone, or combined with norepinephrine, accounted for 82% of the catecholamine profiles of PHEO/PGLs. Most variants (n = 63) occurred only once and 13 were recurrent (2-12 times). Although nontruncating variants were less frequent than truncating changes overall, they were predominant in non-PHEO clinical presentations (36% PHEO-only vs 69% other, P < .001) and clustered disproportionately within transmembrane regions (P < .01), underscoring the relevance of these domains for TMEM127 function. Integration of clinical and previous experimental data supported classification of variants into 4 groups based on mutation type, localization, and predicted disruption. CONCLUSIONS: Patients with TMEM127 variants often resemble sporadic nonmetastatic PHEOs. PGL and RCC may also co-occur, although their causal link requires further evaluation. We propose a new classification to predict variant pathogenicity and assist with carrier surveillance.

Atrial conduction explains the occurrence of the P-wave dispersion phenomenon, but weakly.

BACKGROUND: P-wave dispersion (PWD) is believed to be caused by inhomogeneous atrial conduction. This statement, however, is based on limited little solid evidence. The aim of this study was to determine the relationship between atrial conduction and PWD by means of invasive electrophysiological studies. METHODS: Cross-sectional study in 153 patients with accessory pathways and atrioventricular node reentry tachycardia (AVNRT) undergoing an electrophysiological study. Different atrial conduction times were measured and correlated with PWD. RESULTS: Only the interatrial (P-DCS) and left intra-atrial conduction times (ΔDCS-PCS) showed a significant correlation with PWD, but this correlation was weak. Multivariate linear regression analysis determined that both P-DCS (ß = 0.242; P = .008) and ΔDCS-PCS (ß = 0.295; P < .001) are independent predictors of PWD. Performing the multivariate analysis for arrhythmic substrates, it is observed that only ΔDCS-PCS continued to be an independent predictor of PWD. Analysis of the receiver operating characteristic curves showed that regardless of the types of arrhythmic substrates, PWD discriminates significantly, but moderately, to patients with P-DCS and ΔDCS-PCS ≥75 percentile. CONCLUSIONS: Interatrial and intraleft atrial conduction times were directly and significantly correlated with PWD, but only weakly, and were independent predictors of PWD. In general, PWD correctly discriminates patients with high values in interatrial and intraleft atrial conduction times, but moderately. This is maintained in cases with accessory pathways; however, in patients with AVNRT it only does so for intraleft atrial conduction times. Interatrial and intraleft atrial conduction times weakly explains PWD.

Molecular Sexing of the White-Winged Guan (Penelope albipennis) and Other Wild Birds of the North of Peru.

The use of accurate and reliable techniques for sex determination of wild birds is of special importance in captive breeding programs, especially in birds with monogamous, aggressive behavior, with absence of copulation, and with a low hatching rate. Using PCR, we evaluated the relative efficacy of primers HPF/HPR and CHD1Wr/NP/CHD1Zr in the amplification of the chromo-helicase-DNA binding 1 (CHD1) gene for sex determination in Penelope albipennis and 8 other species of cracids, 4 species of falconids, 4 species of accipitrids, and 3 species of psittacines. Primer effectiveness was compared using previously sexed bird samples. The HPF/HPR primer set was found to demonstrate a better performance and reliability. Therefore, these primers should be used to determine the sex of juvenile birds to avoid or minimize incompatibilities during the selection of potential breeding pairs.