An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Efficacy of a Brazelton home-visiting program: a single-case subject analysis

The purpose of this current study is to examine the efficacy of a one-year home-visiting Brazelton program to support at-risk families, that is based on the concept of Touchpoints and anticipatory guidance

Evaluación de la ingesta de proteínas en jugadores de rugby de planteles superiores de clubes de Rosario (Argentina)

This study was conducted among 60 first division rugby players from top clubs of the city of Rosario. It was evaluated during February 2012. The rugby players were selected according to their access, availability and willingness to participate in the research, thus being made ?? a convenience sample. As a data gathering method, a self-made food fre- as quency questionnaire was used. In turn, a chemical analysis of a batch of the two most consumed protein supplements was included. The total average of protein intake by respondents was 2.36 g for each kg body weight / day, of which 2.24 came from food proteins, and 0.12 only from protein supplements. The 74.14% (N = 58) of the evaluated players showed a higher consumption than the recom- mended dose (1.7 g protein / kg body weight / day) and 41% (N = 58) reported consuming protein supplements. From the chemical analysis of the two most consumed protein supplements, it was ob- served that only one of them showed the protein content stated on the label, while in the other, there was a total protein value of 47.03% of the value indicated in the label. The results indicate that the average intake of proteins of the players is excessive. On the other hand, from the chemical analysis of the two most consumed protein supplements it can be concluded that the protein content in one of them is inadequate according to the established tolerance levels.El objetivo de esta investigación fue evaluar la adecuación de la ingesta de proteínas, a partir de los diferentes alimentos y de suplementos proteicos, en jugadores de rugby de planteles superiores de clubes de la ciudad de Rosario. Este estudio transversal se realizó en 60 jugadores de rugby del plantel superior de clubes de la ciudad de Rosario, evaluados durante el mes de febrero de 2012. Los mismos fueron elegidos según el acceso, disponibilidad y voluntad de los jugadores de participar en la investigación, quedando de esta manera conformada una muestra por conveniencia. Como método de relevamiento de datos se utilizó un cuestionario de frecuencia de consumo de alimentos de confección propia. A su vez, se incluyó el análisis químico de un lote de los dos suplementos proteicos más consumidos. El consumo de proteínas totales promedio por parte de los encuestados fue de 2,36 g proteínas/kg peso corporal/día; de los cuales 2,24 provinieron de proteínas alimentarias; y sólo 0,12 de suplementos proteicos. El 74,14% (N=58) de los jugadores evaluados registró un consumo superior a la dosis recomendada (1,7 g proteínas/kg peso corporal/día); y el 41% (N=58) indicó consumir suplementos proteicos. Del análisis químico de los dos suplementos proteicos más consumidos, se observó que sólo uno de ellos presentó el contenido de proteínas declarado en el rótulo; mientras que en el otro, se registró un valor total de proteínas del 47,03% del valor indicado en el rótulo. Los resultados señalan que el consumo promedio de proteínas totales de los jugadores es excesivo. Por otro lado, a partir del análisis químico de los dos suplementos proteicos más consumidos se puede concluir que el contenido proteico en uno de ellos es inadecuado de acuerdo a los niveles de tolerancia establecidos

A New Criterion for Fluoroquinolone-Associated Disability Diagnosis: Functional Gastrointestinal Disorders

Background and Objectives: Fluoroquinolones (FQs) are a broad-spectrum class of antibiotics routinely prescribed for common bacterial infections despite recent recommendations to use them only for life-threatening cases. In addition to their antimicrobial properties, FQs act in the central nervous system as GABAA receptor inhibitors, which could potentially affect functionality of the vagus nerve at the forefront of gastrointestinal (GI) tract function. Alterations in neural control of digestion have been shown to be linked to Functional Gastrointestinal Disorders (FGIDs), which are usually diagnosed based on self-reported symptoms. The aim of this study was to assess the incidence of FGIDs following FQ use. Materials and Methods: Self-reports from the FDA Adverse Event Reporting System were analyzed together with ~300 survey responses from a social network derived sample to the Bowel Disease Questionnaire. Results: The results of this study suggested that six different FQs are associated with a wide range of GI symptoms not currently reported in the drugs’ labels. The responses from the survey suggested that ~70% of FQ users scored positive for FGID, with no positive correlation between drug type, duration of administration, dosage and frequency of administration. Conclusions: This study showed that GI disorders other than nausea, vomiting and diarrhea are more common than currently reported on the drug labels, and that FGIDs are possibly a common consequence of FQ use even after single use

Two-layer stratified flows over pronounced obstacles at low-to-intermediate Froude numbers

Two-layer stratified flows over abrupt topographic obstacles, simulating relevant situations in oceanographic problems, are investigated numerically and experimentally in a simplified two-dimensional situation. Experimental results and numerical simulations are presented at low-to-intermediate Froude numbers for two different obstacles: one semicylindrical and the other prismatic. In both cases, four different flow regimes downstream of the obstacles are found: (I) subcritical flow, (II) internal hydraulic jump, (III) Kelvin-Helmholtz instability at the interface, and (IV) shedding of billows. The critical values of the Froude number for the transition between different regimes depend strongly on the shape of the obstacle. In regime (III), we show that the characteristics of the lee wave that appears past the obstacle can be explained with a theoretical stability analysis. Almost independence of the vortex shedding frequency with upstream velocity is observed and explained.</p

Three-Dimensional Printed Models for Preoperative Planning and Surgical Treatment of Chest Wall Disease: A Systematic Review

Introduction: In chest wall reconstruction, the main objectives are the restoration of the chest wall integrity, function, and aesthetic, which is often achieved with the placement of implants. We aimed to evaluate whether 3D printed models can be useful for preoperative planning and surgical treatment in chest wall reconstruction to improve the outcome of the surgery and to reduce the rate of complications. Methods: We conducted a systematic review of literature using PubMed, Scopus, Embase, and Google Scholar databases until 8 November 2021 with the following keywords: (“3D printing” or “rapid prototyping” or “three-dimensional printing” or “bioprinting”) and (“chest wall” or “rib” or “sternum” or “ribcage” or “pectus excavatum”). Results were then manually screened by two independent authors to select studies relevant to 3D printing application in chest wall reconstruction. The primary outcome was morphological correction, and secondary outcomes were changes in operating time and procedure-related complication rate. Results: Eight articles were included in our review. Four studies were related to pectus excavatum correction, two studies were related to rib fracture stabilization, and two studies were related to chest wall tumor resection and reconstruction. Seven studies reported 3D printing of a thorax model or template implants for preoperative planning and implant modeling, and one study reported 3D printing of a PEEK prosthesis for direct implantation. Four studies reported comparison with a conventionally treated control group, and three of them detected a shorter operative time in the 3D printing model-assisted group. Satisfactory morphological correction was reported in all studies, and six studies reported a good implant fitting with minimal need for intraoperative adjustments. There were no major intraoperative or postoperative complications in any of the studies. Conclusions: The use of 3D printing models in chest wall reconstruction seems to be helpful for the production of personalized implants, reducing intraoperative adjustments. Results of morphological correction and postoperative recovery after the 3D printing-assisted surgery were satisfactory in all studies with a low rate of complication. Our literature review suggests good results regarding prosthesis fitting, accuracy of surgical planning, and reduction in operative time in 3D printing-assisted procedures, although more evidence is needed to prove this observation