Enterocutaneous fistulas due to stent migration. How reliable is its use on duodenal benign pathology? a case report

Duodenal stenting has been widely used on malignant pathology on selected patients with poor prognosis and advanced disease. In these last years, there has been a clear ampliation of the clinical applications of endoscopy procedures and stents. Its use on benign pathology is spreading but there is a lack of literature about the complications in this context. The incidence of stent migration is about 10-25% in self-expandable metal stent (SEMS), and 2-5% on covered self-expanding metal stents (CSEMS). We reported a clinical case of a 48 years old patient who developed a duodenal ulcer. The patient was submitted to exploratory laparotomy, with duodenal primary closure of the ulcer. Later, the patient developed a enterocutaneous fistula because of the duodenal leak. It was referred to our third level hospital to the hepatopancreatobiliary surgery service. A new exploratory laparotomy with duodenal exclusion was planned, but it was impossible to access due to frozen abdomen. CSEMS was placed in the duodenal bulb resulting in the resolution of leaking, but the stent could not be removed because of migration. The stent trajectory was followed by abdominal x ray and tomography. The patient developed multiple intestinal an fecal enterocutaneous fistulas. It was submitted to multiples endoscopies, colonoscopies and enteroscopy without any success to reaching it. It was decided to perform a right lumbotomy to extract the prothesis. The stent was surgically removed, a planned stoma was left on the right flank on the extraction site

Health-related fitness in medical students:a curricular intervention in Bogota, Colombia

Objective: To evaluate the impact of a curricular intervention to promote health-related fitness (HRF) among medical students in Bogota, Colombia.Method: The study was conducted between May 2014 and December 2015 as part of the medical physiology course, in which 208 medical students were enrolled.The curricular intervention included two lectures on physical activity (PA) and student-led group presentations on the physiological effects of exercise on human physiology. An academic incentive (10% of final grade) was given to students who reported and documented regular PA practice during the semester. This study assessed students’ HRF variables, perceptions of the curriculum intervention, and PA practices using quantitative and qualitative approaches.Results: 55% of the students were female, with a mean age of 19.5 years. Body fat, estimated maximum oxygen consumption (VO2max), handgrip, and sit-up strength showed statistically significant improvements at the end of the intervention. Students reported that PA practice was positively influenced by the curriculum intervention, particularly the academic incentive and the HRF tests. Students reported a wide variety of PA practices, which were mainly done with friends, classmates, or family members. Lack of time was the main reported barrier to PA practice.Conclusion: The curricular intervention was effective in improving HRF and promoting PA. It remains to be investigated whether these gains are sustained over time

Transcriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes

UNLABELLED For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects. IMPORTANCE The confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that the key outcome of these molecular events is evolution of a new, more virulent pathogenic genotype. Our findings provide new understanding of epidemic disease

A first--order irreversible thermodynamic approach to a simple energy converter

Several authors have shown that dissipative thermal cycle models based on Finite-Time Thermodynamics exhibit loop-shaped curves of power output versus efficiency, such as it occurs with actual dissipative thermal engines. Within the context of First-Order Irreversible Thermodynamics (FOIT), in this work we show that for an energy converter consisting of two coupled fluxes it is also possible to find loop-shaped curves of both power output and the so-called ecological function against efficiency. In a previous work Stucki [J.W. Stucki, Eur. J. Biochem. vol. 109, 269 (1980)] used a FOIT-approach to describe the modes of thermodynamic performance of oxidative phosphorylation involved in ATP-synthesis within mithochondrias. In that work the author did not use the mentioned loop-shaped curves and he proposed that oxidative phosphorylation operates in a steady state simultaneously at minimum entropy production and maximum efficiency, by means of a conductance matching condition between extreme states of zero and infinite conductances respectively. In the present work we show that all Stucki's results about the oxidative phosphorylation energetics can be obtained without the so-called conductance matching condition. On the other hand, we also show that the minimum entropy production state implies both null power output and efficiency and therefore this state is not fulfilled by the oxidative phosphorylation performance. Our results suggest that actual efficiency values of oxidative phosphorylation performance are better described by a mode of operation consisting in the simultaneous maximization of the so-called ecological function and the efficiency.Comment: 20 pages, 7 figures, submitted to Phys. Rev.

Analysis of IL28B Variants in an Egyptian Population Defines the 20 Kilobases Minimal Region Involved in Spontaneous Clearance of Hepatitis C Virus

Spontaneous clearance of hepatitis C virus (HCV) occurs in ∼30% of acute infections. Host genetics play a major role in HCV clearance, with a strong effect of single nucleotide polymorphisms (SNPs) of the IL28B gene already found in different populations, mostly infected with viral genotypes 1 and 3. Egypt has the highest prevalence of HCV infection in the world, which is mostly due to viral genotype 4. We investigated the role of several IL28B SNPs in HCV spontaneous clearance in an Egyptian population. We selected nine SNPs within the IL28B genomic region covering the linkage disequilibrium (LD) block known to be associated with HCV clearance in European populations. These SNPs were genotyped in 261 HCV-infected Egyptian subjects (130 with spontaneous clearance and 131 with chronic infection). The most associated SNPs were rs12979860 (P = 1.6×10−7) and the non-synonymous IL28B SNP, rs8103142 (P = 1.6×10−7). Interestingly, three SNPs at the two bounds of the region were monomorphic, reducing the size of the LD block in which the causal variants are potentially located to ∼20 kilobases. HCV clearance in Egypt was associated with a region of IL28B smaller than that identified in European populations, and involved the non-synonymous IL28B SNP, rs8103142

Mapping Bromodomains in breast cancer and association with clinical outcome

A specific family of proteins that participate in epigenetic regulation is the bromodomain (BRD) family of proteins. In this work, we aimed to explore the expression of the BRD family at a transcriptomic level in breast cancer, and its association with patient survival. mRNA level data from normal breast and tumor tissues were extracted from public datasets. Gene set enrichment analysis (GSEA) was performed to identify relevant biological functions. The KM Plotter Online tool was used to evaluate the relationship between the presence of different genes and patient clinical outcome. mRNA level data from HER2+ breast cancer patients sensible and resistant to trastuzumab were also evaluated. The BRD family was an enriched function. In HER2 positive tumors the combined analyses of BRD2, BAZ1A, TRIM33 and ZMYND8 showed a detrimental relapse free survival (RFS). Similarly, the combined analysis of BRD2, BAZ1A, PHIP, TRIM33, KMT2A, ASH1L, PBRM1, correlated with an extremely poor overall survival (OS). The prognosis was confirmed using an independent dataset from TCGA. Finally, no relation between expression of BRD genes and response to trastuzumab was observed in the HER2 population. Upregulation of some BRD genes is associated with detrimental outcome in HER2 positive tumors, regardless trastuzumab treatment

Current professional standing of young medical oncologists in Spain : a nationwide survey by the Spanish Society of Medical Oncology + MIR section

There is a lack of knowledge about the career paths and employment situation of young medical oncologists. The aim of our study was to evaluate the current professional standing of these professionals in Spain. The Spanish Society of Medical Oncology + MIR section conducted a national online survey in May 2021 of young medical oncology consultants (< 6 years of expertise) and final year medical oncology residents. A total of 162 responses were eligible for analysis and included participants from 16 autonomous communities; 64% were women, 80% were consultants, and 20% were residents. More than half of the participants performed routine healthcare activity and only 7% research activity. Almost three quarters (73%) were subspecialized in a main area of interest and almost half of these chose this area because it was the only option available after residency. Half of the respondents (51%) considered working abroad and 81% believed the professional standing in Spain was worse than in other countries. After finishing their residency, only 22 were offered a job at their training hospital. Just 16% of participants had a permanent employment contract and 87% were concerned (score of ≥ 5 on a scale of 1-10) about their job stability. In addition, one quarter of the participants in our study showed an interest in increasing their research activity. The choice of subspecialty in medical oncology may depend on job opportunities after residency rather than personal interest. The abundance of temporary contracts may have influenced the job stability concerns observed. Future mentoring strategies should engage in building a long-term career path for young medical oncologists. The online version contains supplementary material available at 10.1007/s12094-022-02989-3

Transcriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes

For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects. IMPORTANCE The confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that the key outcome of these molecular events is evolution of a new, more virulent pathogenic genotype. Our findings provide new understanding of epidemic disease.Peer reviewe

Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates

Non-Alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant