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

30-day morbidity and mortality of sleeve gastrectomy, Roux-en-Y gastric bypass and one anastomosis gastric bypass: a propensity score-matched analysis of the GENEVA data

Background: There is a paucity of data comparing 30-day morbidity and mortality of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). This study aimed to compare the 30-day safety of SG, RYGB, and OAGB in propensity score-matched cohorts. Materials and methods: This analysis utilised data collected from the GENEVA study which was a multicentre observational cohort study of bariatric and metabolic surgery (BMS) in 185 centres across 42 countries between 01/05/2022 and 31/10/2020 during the Coronavirus Disease-2019 (COVID-19) pandemic. 30-day complications were categorised according to the Clavien–Dindo classification. Patients receiving SG, RYGB, or OAGB were propensity-matched according to baseline characteristics and 30-day complications were compared between groups. Results: In total, 6770 patients (SG 3983; OAGB 702; RYGB 2085) were included in this analysis. Prior to matching, RYGB was associated with highest 30-day complication rate (SG 5.8%; OAGB 7.5%; RYGB 8.0% (p = 0.006)). On multivariate regression modelling, Insulin-dependent type 2 diabetes mellitus and hypercholesterolaemia were associated with increased 30-day complications. Being a non-smoker was associated with reduced complication rates. When compared to SG as a reference category, RYGB, but not OAGB, was associated with an increased rate of 30-day complications. A total of 702 pairs of SG and OAGB were propensity score-matched. The complication rate in the SG group was 7.3% (n = 51) as compared to 7.5% (n = 53) in the OAGB group (p = 0.68). Similarly, 2085 pairs of SG and RYGB were propensity score-matched. The complication rate in the SG group was 6.1% (n = 127) as compared to 7.9% (n = 166) in the RYGB group (p = 0.09). And, 702 pairs of OAGB and RYGB were matched. The complication rate in both groups was the same at 7.5 % (n = 53; p = 0.07). Conclusions: This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts

30-Day morbidity and mortality of bariatric metabolic surgery in adolescence during the COVID-19 pandemic – The GENEVA study

Background: Metabolic and bariatric surgery (MBS) is an effective treatment for adolescents with severe obesity. Objectives: This study examined the safety of MBS in adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This was a global, multicentre and observational cohort study of MBS performed between May 01, 2020, and October 10,2020, in 68 centres from 24 countries. Data collection included in-hospital and 30-day COVID-19 and surgery-specific morbidity/mortality. Results: One hundred and seventy adolescent patients (mean age: 17.75 ± 1.30 years), mostly females (n = 122, 71.8%), underwent MBS during the study period. The mean pre-operative weight and body mass index were 122.16 ± 15.92 kg and 43.7 ± 7.11 kg/m2, respectively. Although majority of patients had pre-operative testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 146; 85.9%), only 42.4% (n = 72) of the patients were asked to self-isolate pre-operatively. Two patients developed symptomatic SARS-CoV-2 infection post-operatively (1.2%). The overall complication rate was 5.3% (n = 9). There was no mortality in this cohort. Conclusions: MBS in adolescents with obesity is safe during the COVID-19 pandemic when performed within the context of local precautionary procedures (such as pre-operative testing). The 30-day morbidity rates were similar to those reported pre-pandemic. These data will help facilitate the safe re-introduction of MBS services for this group of patients

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

El bajo rendimiento escolar y su relación con la malnutrición y conducta en los niños del primero y segundo año de educación básica de la escuela Zoila Aurora Palacios Cuenca. 2013

OBJETIVO: determinar la relación del bajo rendimiento escolar con la malnutrición y los problemas de conducta de los alumnos de primero y segundo de básica de la Escuela Zoila Aurora Palacios de Cuenca. METODOLOGÍA: se realizo un estudio cuantitativo transversal de prevalencia en estudiantes de Primero y Segundo de básica de la escuela Zoila Aurora Palacios (n=184). Se consideró el bajo rendimiento escolar, tomando como base un puntaje < 7 en el promedio del rendimiento académico del año. El estado nutricional de los niños se evaluó con la antropometría y curvas de crecimiento de la Organización Mundial de la Salud (peso, talla e IMC), y, para la determinación de problemas de conducta se aplicó la Escala de Conners para profesores. Los padres de los niños firmaron el consentimiento para la intervención en el estudio. La tabulación y análisis se realizó en Microsoft Excel 2012 y SPSS 2008 1.7.0.0. RESULTADOS: el 66.3 % de la población estudiada es masculino, el 1.09% tiene bajo rendimiento escolar. La prevalencia de desnutrición crónica es de 6%, de sobrepeso 13.26 %, y de obesidad 2.2 %. Se encontró relación de bajo rendimiento escolar con mal estado nutricional (RP: 0 IC95% -2.33 – 4.33 p: 0,0198) y problemas de conducta (RP: 3.97 IC 95%: 0.71- 1.28 p: 0,0198). CONCLUSIONES: la frecuencia de bajo rendimiento fue del 1.09 %, aunque se encontró significancia estadística entre la relación de bajo rendimiento escolar y nutrición, y bajo rendimiento escolar y problemas de conducta; los pocos casos de bajo rendimiento no pueden concluir esta significancia como dependiente. PALABRAS CLAVES: MALNUTRICIÓN, OBESIDAD INFANTIL, RENDIMIENTO, NUTRICION EN NIÑOS, PROBLEMAS DE CONDUCTA.OBJECTIVE: To determine the relationship of poor academic performance with malnutrition and behavioral problems of students from first and second grades from Zoila Aurora Palacios School. METHODOLOGY: This is a cross-sectional quantitative study of prevalence in all students (n = 184) of the first and second grade from the fiscal school. Poor school performance was considered when the year’s grade point average (GPA) had a score <7. Nutritional status was assessed by anthropometry and tables WHO, and for determining behavioral problems Conners Scale was applied to teachers. Parents of children signed consent for children. The tabulation and analysis were performed in Microsoft Excel 2012 and SPSS 2008 1.7.0.0. RESULTS: The 66.3% of the analyzed population is male, 1.09% have poor school performance. The prevalence of chronic malnutrition is 6 %, 13% overweight and 2.2 % obesity. Poor academic performance with poor nutritional status relationship was found (OR: 3.97 IC: 95%: 0.71 - 1.28 p= 0.0198), together with behavioral problems (IC: 4.33 -2.33 RP 0 p= 0.0198). CONCLUSION: The frequency of poor performance was 1.09 %, although statistically significance relationship between poor school performance with nutrition, and poor school performance with behavioral problems were found; the few cases of poor performance cannot conclude this significance as dependent. . KEYWORDS: MALNUTRITION, CHILDHOOD OBESITY, PERFORMANCE NUTRITION IN CHILDREN BEHAVIOR PROBLEMSMédicoCuenc

A GPU algorithm for tracking yeast cells in phase-contrast microscopy images

When information and measures obtained from sequences of microscopic images are subject to time constraints, suitable fast algorithms must be implemented to process the whole data set. In this work, we deal with sequences of images obtained from time-lapse microscopy in order to detect single yeast cells in a microfluidics chip over time. The underlying idea consists in determining a minimum cost configuration for each couple of frames, which can be expressed by setting up and solving a linear programming (LP) problem. Laboratories seldom have the opportunity to use HPC hardware for such intent. For this reason, we propose an efficient GPU-parallel software implemented in CUDA and based on the simplex method, a common tool for solving LP problems. Our parallel strategy minimizes the threads divergence and maximizes the device occupancy, in order to maximize the overall throughput. Also, memory transfers between host and device have been minimized to exploit data locality. Experimental results on real images sequences highlight a promising speedup with respect to the CPU version suitable for real-time applications