Modeling oceanic sedimentary methane hydrate growth through molecular dynamics simulation.

The crystallization process of methane hydrates in a confined geometry resembling seabed porous silica sedimentary conditions has been studied using molecular dynamics simulations. With this objective in mind, a fully atomistic quartz silica slit pore has been designed, and the temperature stability of a methane hydrate crystalline seed in the presence of water and guest molecule methane has been analyzed. NaCl ion pairs have been added in different concentrations, simulating salinity conditions up to values higher than average oceanic conditions. The structure obtained when the hydrate crystallizes inside the pore is discussed, paying special attention to the presence of ionic doping inside the hydrate and the subsequent induced structural distortion. The shift in the hydrate stability conditions due to the increasing water salinity is discussed and compared with the case of unconfined hydrate, concluding that the influence of the confinement geometry and pore hydrophilicity produces a larger deviation in the confined hydrate phase equilibria.

Predicting chronic kidney disease progression with artificial intelligence.

BACKGROUND: The use of tools that allow estimation of the probability of progression of chronic kidney disease (CKD) to advanced stages has not yet achieved significant practical importance in clinical setting. This study aimed to develop and validate a machine learning-based model for predicting the need for renal replacement therapy (RRT) and disease progression for patients with stage 3-5 CKD. METHODS: This was a retrospective, closed cohort, observational study. Patients with CKD affiliated with a private insurer with five-year follow-up data were selected. Demographic, clinical, and laboratory variables were included, and the models were developed based on machine learning methods. The outcomes were CKD progression, a significant decrease in the estimated glomerular filtration rate (eGFR), and the need for RRT. RESULTS: Three prediction models were developed-Model 1 (risk at 4.5 years, n = 1446) with a F1 of 0.82, 0.53, and 0.55 for RRT, stage progression, and reduction in the eGFR, respectively,- Model 2 (time- to-event, n = 2143) with a C-index of 0.89, 0.67, and 0.67 for RRT, stage progression, reduction in the eGFR, respectively, and Model 3 (reduced Model 2) with C-index = 0.68, 0.68 and 0.88, for RRT, stage progression, reduction in the eGFR, respectively. CONCLUSION: The time-to-event model performed well in predicting the three outcomes of CKD progression at five years. This model can be useful for predicting the onset and time of occurrence of the outcomes of interest in the population with established CKD.

Endoscopic vacuum therapy: management of upper gastrointestinal anastomotic leaks and esophageal perforations.

BACKGROUND AND STUDY AIMS: Upper gastrointestinal tract (UGT) leaks are associated with severe morbidity and mortality. Endoluminal vacuum (EVAC) therapy is a promising approach for repairing effectively these defects. Our study describes the results obtained from a series of cases treated with EVAC for the management of esophageal anastomotic (EA) leak following esophagectomy for cancer, gastroenteric (GE) anastomoses leak after bariatric surgery and esophageal perforation (EP). PATIENTS AND METHODS: We retrospectively analyzed ten patients who had an EA and GE anastomoses leaks and EP treated with EVAC. We described the results of the sample in terms of treatment failure, treatment duration, and number of EVAC replacements. RESULTS: Five patients underwent esophagectomy with neoadjuvant radio-chemotherapy, one patient underwent gastrojejunal bypass bariatric surgery and there were four EP. The median size of mucosal defects was 6,9 mm. The median duration of treatment was thirteen days with 3,6 interventions performed, every three to four days. Treatment success rate was 70%. Treatment failure was 30%: two patients required surgery and in one case an endoluminal prosthesis. CONCLUSIONS: EVAC therapy is an appropriate treatment for the management of postoperative fistulas in the UGT. Longer treatments are associated with neoadjuvant chemoradiotherapy and larger fistulas.

Effective and alternative treatment of anastomotic leak after gastrojejunal bypass: endoluminal vacuum therapy.

Anastomotic leak (AL) after with Roux-en-Y gastric bypass (RYGB) has a morbidity rate to 53% and it can be potentially lethal (mortality rate from 0.5 to 10%). In these cases, surgery is usually a challenge, so in recent years minimally invasive endoscopic treatment is gaining ground. Endoluminal vacuum therapy (EVAC) is a promising treatment that is being used in esophagogastric and rectal surgery for the management of AL. We present the case of a patient on his 5th postoperative day of bariatric surgery (RYGB) with an acute abdomen. He was diagnosed of dehiscence of gastrojejunal anastomosis and he needed urgent surgery twice. Subsequently, in control CT, a new anastomotic leak is evidenced. However, given the clinical stability of the patient, it was decided to start EVAC type ESO-Sponge® placed by endoscopy. A total of 4 changes are made every 3-4 days with a total duration of treatment of 15 days. EVAC was removed when the defect presented a 1 mm sized.

Lymphogranuloma venereum: an unusual cause of rectal stenosis.

Lymphogranuloma Venereum (LGV) is a notifiable disease linked to high-risk sexual practices such as cruising, chemsex, or orgies. The anorectal manifestation is associated with receptive anal sex and presents with characteristic symptoms such as proctitis, tenesmus, suppuration, and in advanced cases, anorectal fistulas or stenosis. The case of a 57-year-old man engaging in high-risk sexual practices is presented, showing symptoms such as discharge, fistulizations, rectal stenosis, and a weight loss of 15 kg. Following diagnostic studies, a neoplastic and inflammatory origin was ruled out, confirming the LGV diagnosis. Although the patient responded positively to a three-week course of doxycycline, the stenosis persisted, ultimately necessitating a terminal colostomy. The patient was scheduled to undergo a protectomy to control the inflammatory and infectious process, a procedure that took place months later without significant incidents. The primary treatment for LGV continues to be doxycycline. In cases of complications, such as fistulas, abscesses, or stenosis, surgical interventions, drainage, or pneumatic dilations may be necessary.

[Primary prevention of gender-based violence]. / Prevención primaria de la violencia de género.

Gender-based violence is a serious public health problem and a violation of human rights. The vast scale of the problem indicates that it is necessary to advance in its primary prevention. The health sector has an important role to play, especially Primary Health Care, based on its community orientation and with the involvement of all members of the team. The intervention framework defined by the acronym "RESPECT", promoted by the World Health Organization, shows the 7 strategies that are currently promising to lead to reductions in gender-based violence, based on the best scientific evidence available to date. Using a participatory, life-cycle approach, promoting coordination and partnership across sectors, and implementing combined interventions are some of the guiding principles from which to work today.

Risk Factors Associated with COVID-19 Mortality in the State of Durango, Mexico.

The coronavirus disease 2019 (COVID-19) has caused over six million deaths worldwide since its emergence in Wuhan China, factors associated with COVID-19 mortality, such as comorbidities, age, and observed symptomatology still remain a major subject of study. In the present work, a total of 16,345 SARS-CoV-2 positive cases from Durango Mexico diagnosed from May 2020 to December 2021 were analyzed to establish an association of COVID-19 mortality with clinical and demographic variables in a case-control study. Selected variables include patient age, smoking status, sex, presence of comorbidities such as hypertension, diabetes and obesity, as well as patient symptomatology such as fever, dyspnea, abdominal pain and diarrhea. Results indicate that among analyzed data, the median age was 43 years; 54% were female, with a mortality rate of 5.66%. Multivariate regression analysis indicated that the comorbidities associated with the highest risk factor were advanced age (>60) with an odds ratio of 4.127 (IC 95%, 3.37-5.05), hypertension with 1.961 (IC 95%, 1.57-2.45), diabetes with 1.753 (IC 95%, 1.39-2.20) and obesity with 1.413 (IC 95%, 1.11-1.78) respectively. On the other hand, the symptom associated with the highest risk factor was dyspnea with an odds ratio of 18.369 (IC 95%, 14.42-23.39). Our data suggests an association between hypertension and old age with COVID-19 mortality. Other findings include the prevalence of dyspnea, polypnea and cyanosis as a major predictor for COVID-19 mortality, as well as lower mortality risks among health workers.

Risk factors indicating the need for surgical therapy in patients with pyogenic liver abscesses.

BACKGROUND: Percutaneous drainage (PD) and antibiotics are the therapy of choice (non-surgical therapy [non-ST]) for pyogenic liver abscesses (PLA), reserving surgical therapy (ST) for PD failure. The aim of this retrospective study was to identify risk factors that indicate the need for ST. METHODS: We reviewed the medical charts of all of our institution's adult patients with a diagnosis of PLA between January 2000 and November 2020. A series of 296 patients with PLA was divided into two groups according to the therapy used: ST (n = 41 patients) and non-ST (n = 255). A comparison between groups was performed. RESULTS: The overall median age was 68 years. Demographics, clinical history, underlying pathology, and laboratory variables were similar in both groups, except for the duration of PLA symptoms < 10 days and leukocyte count which were significantly higher in the ST group. The in-hospital mortality rate in the ST group was 12.2% vs. 10.2% in the non-ST group (p = 0.783), with biliary sepsis and tumor-related abscesses as the most frequent causes of death. Hospital stay and PLA recurrence were statistically insignificant between groups. One-year actuarial patient survival was 80.2% in the ST group vs. 84.6% in the non-ST (p = 0.625) group. The presence of underlying biliary disease, intra-abdominal tumor, and duration of symptoms for less than 10 days on presentation comprised the risk factors that indicated the need to perform ST. CONCLUSIONS: There is little evidence regarding the decision to perform ST, but according to this study, the presence of underlying biliary disease or an intra-abdominal tumor and the duration of PLA symptoms < 10 days upon presentation are risk factors that should sway the surgeons to perform ST instead of PD.

Giant sigmoid diverticulum.

Unlike acute diverticulitis, giant diverticulum larger than 4 cm is a rare entity with few cases described in the literature. We present a case of a 66-year-old male patient diagnosed with colonic diverticulosis. He presented to the emergency department with symptoms of acute abdomen and was diagnosed by CT scan with a 13x14 cm giant diverticulum showing signs of complication. Given the findings, an urgent surgical intervention was decided, and diverticulectomy at the diverticular neck was performed using an endostapler. The etiology of giant diverticula is related to a mechanism of one-way valve at the diverticular neck. Diagnosis poses a challenge as the clinical presentation is nonspecific. The imaging modality of choice is CT scan, which reveals a large cystic image dependent on the sigmoid colon. Definitive treatment is surgical, either by resecting the affected segment including the lesion or by performing a simple diverticulectomy in uncomplicated cases.

Short series regarding uncontrolled donor after cardiac death: A call for caution.

The authors did not receive any funding for this work.

New technique for abdominal wall procurement. Initial experience.

Difficulty in obtaining adequate abdominal wall closure due to loss of the abdominal domain is a frequent complication of multivisceral, isolated intestinal transplantation and in some cases of liver transplantation. Various methods for primary closure have been proposed, including the use of synthetic and biological meshes, as well as full-thickness abdominal wall and non-vascularized rectus fascia grafts. We describe a novel technique for abdominal wall procurement in which the graft is perfused synchronously with the abdominal organs and can be transplanted as a full-thickness wall or as a non-vascularized rectus fascia graft. We performed six transplants of non-vascularized rectus fascia in three intestinal transplants, one multivisceral transplant, and two liver transplants. The size of the covered abdominal wall defects ranged from 17 cm × 7 cm to 25 cm × 20 cm. Only one patient developed graft infection secondary to enterocutaneous fistula requiring surgical correction and removal of the fascia graft. This patient, as well as two other patients, died due to sepsis. Our procurement technique allows removal of the rectus fascia graft to cover the abdominal wall defect, providing a feasible solution for treatment of abdominal wall defects in recipients after abdominal organ transplantation.

Homogeneous ice nucleation rates for mW and TIP4P/ICE models through Lattice Mold calculations.

Freezing of water is the most common liquid-to-crystal phase transition on Earth; however, despite its critical implications on climate change and cryopreservation among other disciplines, its characterization through experimental and computational techniques remains elusive. In this work, we make use of computer simulations to measure the nucleation rate (J) of water at normal pressure under different supercooling conditions, ranging from 215 to 240 K. We employ two different water models: mW, a coarse-grained potential for water, and TIP4P/ICE, an atomistic nonpolarizable water model that provides one of the most accurate representations of the different ice phases. To evaluate J, we apply the Lattice Mold technique, a computational method based on the use of molds to induce the nucleus formation from the metastable liquid under conditions at which observing spontaneous nucleation would be unfeasible. With this method, we obtain estimates of the nucleation rate for ice Ih and Ic and a stacking mixture of ice Ih/Ic, reaching consensus with most of the previously reported rates, although differing with some others. Furthermore, we confirm that the predicted nucleation rates obtained by the TIP4P/ICE model are in better agreement with experimental data than those obtained through the mW potential. Taken together, our study provides a reliable methodology to measure nucleation rates in a simple and computationally efficient manner that contributes to benchmarking the freezing behavior of two popular water models.

Cytomegalovirus colitis seems to be colon cancer. HIV debut.

Cytomegalovirus (CMV) infection is very common in immunosuppressed patients. It can y puede afectar a todo el tracto gastrointestinal, presentándose como úlceras o pseudotumores. A 43-year-old male with no personal background of interest, was studied due to constitutional syndrome. The diagnosis was neoplasia of the right colon, reported by colonoscopy and CT scan. A right hemicolectomy was performed with oncologic character. The definitive histology was CMV infectious colitis with positive immunohistochemical staining. Treatment with ganciclovir was started and the patient was diagnosed with HIV infection. The unusual finding of CMV infection as a pseudotumor can simulate, clinically and radiologically, a colonic neoplasm. It has been described in the literature in patients immunocompromised by HIV; however, the absence of risk factors means that it can be confused with a primary neoformative process.

Sigmoid colon Schwannoma simulating colon cancer.

Schwannomas tumours are uncommonly developed in the gastrointestinal tract (2-6%), located in 12% of cases in small and large intestines. An 87-year-old woman was studied due to epigastric pain and dyspepsia. CT scan and colonoscopy showed a neoplastic process in the sigmoid colon. It was performed an oncologic laparoscopic sigmoidectomy. Histological study described a schwannoma and a positive immunohistochemistry to S-100. The diagnostic challenge is that this is a submucosa lesion, therefore, endoscopy biopsy is realized only in the mucosa. This becomes the differential diagnostic very difficult in order to differentiate from another mesenchymal tumor (GIST or leiomyoma). The immunohistochemistry helps in the diagnostic if it is positive to S- 100 and negative to C-KIT, CD-34, actine and desmine (findings of GIST tumors and leiomyoma). In conclusion, schwannoma diagnostic is tough. Those are asymptomatic tumors with nonspecific radiological findings. Diagnostic confirmation is a S-100 positive immunohistochemistry in the histological study.

Incidence and risk factors of primary non-function after liver transplantation using grafts from uncontrolled donors after circulatory death.

BACKGROUND: Graft primary non-function (PNF) is the most severe complication after orthotopic liver transplantation (OLT) and is frequently associated with livers from uncontrolled circulatory death (uDCD). METHODS: We reviewed retrospectively the incidence, risk factors, and outcome of patients showing PNF after receiving uDCD liver grafts. The series comprises 75 OLT performed during 11 years. RESULTS: The incidence of PNF using uDCD livers was 8%. We compared patients who developed PNF (n = 6) vs. patients without PNF (n = 69). Mean pump flow of donors during normothermic regional perfusion (NRP) was significantly lower in PNF (p = .032). Day 1 post-OLT levels of transaminases and the incidence of renal complications and postoperative mortality were also significantly higher in the PNF group, but 5-year patient survival was similar in both groups (66.7% in PNF and 68.5% in non-PNF). All PNF patients underwent re-OLT, and 2 died. PNF incidence has decreased in the last 5-years. Binary logistic regression analysis confirmed final ALT value >4 times the normal value as risk factor for PNF, and median donor pump flow >3700 ml/min as protective effect. CONCLUSIONS: Adequate donor pump flow during NRP was a protective.

Biliary reconstruction after choledochal cyst resection: a systematic review and meta-analysis on hepaticojejunostomy vs hepaticoduodenostomy.

Choledochal cysts are a rare pediatric biliary pathology. Excision of the extrahepatic cyst and restoration of biliary-enteric continuity through either hepaticoduodenostomy (HD) or Roux-en-Y hepaticojejunostomy (HJ) is the mainstay treatment. This study aims to determine if either method provides an advantage. Following PRISMA guidelines, a systematic review was conducted, identifying studies comparing hepaticojejunostomy to hepaticoduodenostomy in patients with choledochal cysts. Data were analyzed using Review Manager 5.3. Nine studies were included, operative time was shorter - 97.50 [- 172.31, - 22.69] p = 0.01 and bleeding reduced - 48.98 [- 88.25, - 9.71] p = 0.01 in HD. HD was associated with shorter length of stay 2.18 [- 3.87, - 0.50] p = 0.01 and similar cholangitis and reintervention rates. Time to a normal diet was similar between groups. Biliary reflux was seen more frequently in HD 19.14 [2.60, 140.63] p = 0.004. Complications such as leak and cholangitis were similar between groups. HD represents a viable alternative to HJ with various advantages such as shorter operative time, decreased bleeding and shorter length of hospital stay. Bile reflux remains a major limitation.Level of evidence IV.

Identification of relapse-associated gene mutations by next-generation sequencing in low-risk acute myeloid leukaemia patients.

Recommended genetic categorization of acute myeloid leukaemias (AML) includes a favourable-risk category, but not all these patients have good prognosis. Here, we used next-generation sequencing to evaluate the mutational profile of 166 low-risk AML patients: 30 core-binding factor (CBF)-AMLs, 33 nucleophosmin (NPM1)-AMLs, 4 biCEBPα-AMLs and 101 acute promyelocytic leukaemias (APLs). Functional categories of mutated genes differed among subgroups. NPM1-AMLs showed frequent variations in DNA-methylation genes (DNMT3A, TET2, IDH1/2) (79%), although without prognostic impact. Within this group, splicing-gene mutations were an independent factor for relapse-free (RFS) and overall survival (OS). In CBF-AML, poor independent factors for RFS and OS were mutations in RAS pathway and cohesin genes, respectively. In APL, the mutational profile differed according to the risk groups. High-risk APLs showed a high mutation rate in cell-signalling genes (P = 0·002), highlighting an increased incidence of FLT3 internal tandem duplication (ITD) (65%, P < 0·0001). Remarkably, in low-risk APLs (n = 28), NRAS mutations were strongly correlated with a shorter five-year RFS (25% vs. 100%, P < 0·0001). Overall, a high number of mutations (≥3) was the worst prognostic factor RFS (HR = 2·6, P = 0·003). These results suggest that gene mutations may identify conventional low-risk AML patients with poor prognosis and might be useful for better risk stratification and treatment decisions.

Biliary Complications After Liver Transplantation From Uncontrolled Donors After Circulatory Death: Incidence, Management, and Outcome.

The utilization of livers from donation after uncontrolled circulatory death (uDCD) increases the availability of liver grafts, but it is associated with a higher incidence of biliary complications (BCs) and lower graft survival than those organs donated after brain death. From January 2006 to December 2016, we performed 75 orthotopic liver transplantations (OLTs) using uDCD livers. To investigate the relationship of BCs with the use of uDCD OLT, we compared patients who developed BCs (23 patients) with those who did not (non-BC group, 43 patients) after excluding cases of hepatic artery thrombosis (a known cause of BC) and primary nonfunction. The groups had similar uDCD donor maintenance, donor and recipient characteristics, and perioperative morbidity/mortality rates, but we observed a higher rate of hepatocellular carcinoma and hepatitis C virus in the non-BC group. Percutaneous transhepatic biliary dilation, endoscopic retrograde cholangiopancreatography dilation, Roux-en-Y hepaticojejunostomy (HJ), a T-tube, and retransplantation were used for BC management. In the BC group, 1-, 3-, and 5-year patient survival rates were 91.3%, 69.6%, and 65.2%, respectively, versus 77.8%, 72.9%, and 72.9%, respectively, in the non-BC group (P = 0.89). However, 1-, 3-, and 5-year graft survival rates were 78.3%, 60.9%, and 56.5%, respectively, in the BC group versus 77.8%, 72.9%, and 72.9%, respectively, in the non-BC group (P = 0.38). Multivariate analysis did not indicate independent risk factors for BC development. In conclusion, patient and graft survival rates were generally lower in patients who developed BCs but not significantly so. These complications were managed in the majority of patients through radiological dilation, endoscopic dilation, or Roux-en-Y HJ. Retransplantation is necessary in rare cases after the failure of biliary dilation or surgical procedures.

N-acetylglucosaminyltransferases and nucleotide sugar transporters form multi-enzyme-multi-transporter assemblies in golgi membranes in vivo.

Branching and processing of N-glycans in the medial-Golgi rely both on the transport of the donor UDP-N-acetylglucosamine (UDP-GlcNAc) to the Golgi lumen by the SLC35A3 nucleotide sugar transporter (NST) as well as on the addition of the GlcNAc residue to terminal mannoses in nascent N-glycans by several linkage-specific N-acetyl-glucosaminyltransferases (MGAT1-MGAT5). Previous data indicate that the MGATs and NSTs both form higher order assemblies in the Golgi membranes. Here, we investigate their specific and mutual interactions using high-throughput FRET- and BiFC-based interaction screens. We show that MGAT1, MGAT2, MGAT3, MGAT4B (but not MGAT5) and Golgi alpha-mannosidase IIX (MAN2A2) form several distinct molecular assemblies with each other and that the MAN2A2 acts as a central hub for the interactions. Similar assemblies were also detected between the NSTs SLC35A2, SLC35A3, and SLC35A4. Using in vivo BiFC-based FRET interaction screens, we also identified novel ternary complexes between the MGATs themselves or between the MGATs and the NSTs. These findings suggest that the MGATs and the NSTs self-assemble into multi-enzyme/multi-transporter complexes in the Golgi membranes in vivo to facilitate efficient synthesis of complex N-glycans.

Haplotype block analysis of an Argentinean hexaploid wheat collection and GWAS for yield components and adaptation.

BACKGROUND: Increasing wheat (Triticum aestivum L.) production is required to feed a growing human population. In order to accomplish this task a deeper understanding of the genetic structure of cultivated wheats and the detection of genomic regions significantly associated with the regulation of important agronomic traits are necessary steps. To better understand the genetic basis and relationships of adaptation and yield related traits, we used a collection of 102 Argentinean hexaploid wheat cultivars genotyped with the 35k SNPs array, grown from two to six years in three different locations. Based on SNPs data and gene-related molecular markers, we performed a haplotype block characterization of the germplasm and a genome-wide association study (GWAS). RESULTS: The genetic structure of the collection revealed four subpopulations, reflecting the origin of the germplasm used by the main breeding programs in Argentina. The haplotype block characterization showed 1268 blocks of different sizes spread along the genome, including highly conserved regions like the 1BS chromosome arm where the 1BL/1RS wheat/rye translocation is located. Based on GWAS we identified ninety-seven chromosome regions associated with heading date, plant height, thousand grain weight, grain number per spike and fruiting efficiency at harvest (FEh). In particular FEh stands out as a promising trait to raise yield potential in Argentinean wheats; we detected fifteen haplotypes/markers associated with increased FEh values, eleven of which showed significant effects in all three evaluated locations. In the case of adaptation, the Ppd-D1 gene is consolidated as the main determinant of the life cycle of Argentinean wheat cultivars. CONCLUSION: This work reveals the genetic structure of the Argentinean hexaploid wheat germplasm using a wide set of molecular markers anchored to the Ref Seq v1.0. Additionally GWAS detects chromosomal regions (haplotypes) associated with important yield and adaptation components that will allow improvement of these traits through marker-assisted selection.