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ngle-cell transcriptomic analysis suggests that LDL uptake by endothelial cells is diverted to lysosomal degradation and reverse cholesterol transport pathways. This reduces intimal accumulation of lipid and impacts lesion initiation and growth.Mendelian randomization is an epidemiological approach to making causal inferences using observational data. It makes use of the natural randomization that occurs in the generation of an individual’s genetic makeup in a way that is analogous to the study design of a randomized controlled trial and uses instrumental variable analysis where the genetic variant(s) are the instrument (analogous to random allocation to treatment group in an randomized controlled trial). As with any instrumental variable, there are 3 assumptions that must be made about the genetic instrument (1) it is associated (not necessarily causally) with the exposure (relevance condition); (2) it is associated with the outcome only through the exposure (exclusion restriction condition); and (3) it does not share a common cause with the outcome (ie, no confounders of the genetic instrument and outcome, independence condition). Using the example of type II diabetes and coronary artery disease, we demonstrate how the method may be used to investigate causality and discuss potential benefits and pitfalls. We conclude that although Mendelian randomization studies can usually not establish causality on their own, they may usefully contribute to the evidence base and increase our certainty about the effectiveness (or otherwise) of interventions to reduce cardiovascular disease.Renal toxicity from immune checkpoint inhibitors (ICIs) is an increasingly recognized cause of acute kidney injury among patients with cancer. ICI-associated acute kidney injuries typically present as acute interstitial nephritis and the timing of onset is highly variable. Herein, we present a case of a patient with relapsed metastatic melanoma previously treated with pembrolizumab who developed grade 3 immune-related renal toxicity after reintroduction of the same ICI, secondary to acute interstitial nephritis with accompanying high PR3-antineutrophil cytoplasmic antibody titer. The patient improved after steroid treatment and discontinuation of pembrolizumab. This case highlights the importance of not excluding ICI-related nephrotoxicity as a possible cause of renal failure, including in those who previously tolerated ICI treatment, since it is a treatable entity.Chronic constipation is a complex and multifactorial problem. We present the case of a 53-year-old woman with life-long constipation complicated by a solitary rectal ulcer. In these cases it is always necessary to evaluate the presence of evacuation disorder, both functional (dyssynergic defecation) and anatomical. An exhaustive clinical history and physical examination that includes a dynamic rectal examination are essential. Currently, anorectal manometry is the study of choice for functional anorectal evaluation accompanied by the balloon expulsion test. When the results of both techniques are disagreed, a third diagnostic test is required, such as defecography that will confirm the dyssynergic defecation and/or the presence of important anatomical lesions, as in the case of the patient we present. These cases do not normally respond to conservative treatment only, requiring surgical repair of the prolapsed organs, with the aid of rehabilitative techniques that help to carry out a complete and adequate defecatory maneuver. This case reflects the diagnostic doubts, uncertainty and the complex management of these patients, which must be addressed by a multidisciplinary team.

Objective we conducted a systematic review of the main scientific evidence that associates food insecurity with a higher frequency of obesity and cardiometabolic risks in Mexican women. Design a systematic review. Data sources MEDLINE, Embase, CINAHL Plus, Web of Science, CAB Abstracts and PAIS Index. Selection criteria articles that met the journal quality criteria and integrated food status with health insecurity, in which the situation of vulnerability in the current statistics for cardiometabolic diseases and risks that are associated with food insecurity was shown in women and their homes. Data analysis relevance and quality of the results regarding food security, the presence of overweight and obesity, and socio-environmental indicators in women. Results households headed by women who are at higher risk of having some degree of food insecurity or food assistance associated with the presence of obesity and overweight (RR = 1.28 to 2.97; 95 % CI 1.08-1.44 to 1.52-6.14) as well as the development of carde (diabetes, hypertension), in addition to anemia and vitamin deficiency.Spontaneous intramural small-bowel hematoma is an uncommon cause of acute abdominal pain in anticoagulated patients. Recognition of this pathology is essential, as it is becoming more frequent due to the increase in patients receiving anticoagulant therapy. A suitable diagnosis based on a good anamnesis, the recognition of an abnormal blood test and characteristic findings in the imaging tests would avoid unnecessary procedures. The majority of patients will improve with conservative treatment.Pentameric ligand-gated ion channels (pLGICs), embedded in the lipid membranes of nerve cells, mediate fast synaptic transmission and are major pharmaceutical targets. Because of their complexity and the limited knowledge of their structure, their working mechanisms have still to be fully unraveled at the molecular level. Over the past few years, evidence that the lipid membrane may modulate the function of membrane proteins, including pLGICs, has emerged. NX-5948 in vivo Here, we investigate, by means of molecular dynamics simulations, the behavior of the lipid membrane at the interface with the 5-HT3A receptor (5-HT3AR), a representative pLGIC which is the target of nausea-suppressant drugs, in a nonconductive state. Three lipid compositions are studied, spanning different concentrations of the phospholipids, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine, and of cholesterol, hence a range of viscosities. A variety of lipid interactions and persistent binding events to different parts of the receptor are revealed in the investigated models, providing snapshots of the dynamical environment at the membrane-receptor interface.