G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells.

Elevated glucagon concentrations have been reported in patients with type 2 diabetes (T2D). A critical role for α cell-intrinsic mechanisms in regulating glucagon secretion was previously established through genetic manipulation of the glycolytic enzyme glucokinase (GCK) in mice. Genetic variation at the glucose-6-phosphatase catalytic subunit 2 () locus, encoding an enzyme that opposes GCK, has been reproducibly associated with fasting blood glucose and hemoglobin A1c.

Assessing and upgrading the cleanliness of the emergency department brief title: upgrading the emergency room's cleanliness.

Objective: To upgrade cleaning and disinfection of patient rooms in a crowded emergency department (ED).

Setting: Tertiary referral hospital.

Design: Prospective, 3-component, before-and-after intervention study.

Nucleosome fibre topology guides transcription factor binding to enhancers.

Cellular identity requires the concerted action of multiple transcription factors (TFs) bound together to enhancers of cell-type-specific genes. Despite TFs recognizing specific DNA motifs within accessible chromatin, this information is insufficient to explain how TFs select enhancers. Here we compared four different TF combinations that induce different cell states, analysing TF genome occupancy, chromatin accessibility, nucleosome positioning and 3D genome organization at the nucleosome resolution.

[EFFECTIVENESS OF SERIAL C-REACTIVE PROTEIN (CRP) MEASUREMENTS IN HOSPITALIZED PATIENTS WITH BLOOD STREAM INFECTION].

Background: C-reactive protein (CRP) is increasingly being used as an inflammatory marker in sepsis. Its main use is for diagnosis, less for prognosis, while it is increasingly used for serial monitoring of response to treatment - with little evidence to support this practice.

Objectives: Assessment of the effectiveness of serial measurements of CRP in the management of patients with blood stream infection (BSI).

Time is encoded by methylation changes at clustered CpG sites.

Age-dependent changes in DNA methylation allow chronological and biological age inference, but the underlying mechanisms remain unclear. Using ultra-deep sequencing of >300 blood samples from healthy individuals, we show that age-dependent DNA methylation changes are regional and occur at multiple adjacent CpG sites, either stochastically or in a coordinated block-like manner. Deep learning analysis of single-molecule patterns in two genomic loci achieved accurate age prediction with a median error of 1.

What should you have in your little black bag? A letter to a young doctor.

Rather than looking at which instruments to put in the traditional physician's black bag, the changing face of medicine suggests that some virtual assets assume prime importance. With a solid background of core knowledge and skills acquired through medical school but continuously developed and updated, several habitual attitudes are advocated-each aiming to address a different facet of concerns in today's time-constrained, often impersonal, fast-changing, information-overloaded, and highly technological practice. They include humility, curiosity, "red flag" identification, and reflexive database consultation-each with myriad, diverse advantages.

Acetaminophen in Pregnancy and Attention-Deficit and Hyperactivity Disorder and Autistic Spectrum Disorder.

Acetaminophen is a common over-the-counter medication that recently gained substantial media attention regarding its use by pregnant individuals. In this clinical perspective, we discuss the strengths and limitations of the published literature on the effect of maternal acetaminophen use in pregnancy on the child's risk of developing attention-deficit and hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). Studies included were specifically selected on the basis of the quality and validity of ADHD or ASD outcome definitions.

Prognosis of Cirrhotic Patients After Osteoporotic Femoral Neck Fracture.

: Osteoporotic hip fractures in cirrhotic subjects are associated with increased post-fracture mortality. Our aim was to identify unfavorable factors that were associated with increased post-fracture mortality. : We employed a retrospective evaluation of the short- and long-term prognosis of cirrhotic patients that were admitted with a hip fracture to our institution.

[INTEGRATING SEX AND GENDER DIFFERENCES/GENDER MEDICINE INTO THE FACULTY OF MEDICINE CURRICULUM].

In recent decades, the recognition of the importance of sex, gender and their interrelationship for health research and for the practice of medicine has grown. Accordingly, the move to include gender medicine in medical school curricula has gained momentum in many countries. This article reviews the challenges of integrating this subject into medical school curricula and details the recent initiative to mainstream gender medicine into the six-year curriculum of the Hadassah-Hebrew University Medical School in Jerusalem, Israel.

Breaking a dogma: orthodontic tooth movement alters systemic immunity.

Background: The prevailing paradigm posits orthodontic tooth movement (OTM) as primarily a localized inflammatory process. In this study, we endeavor to elucidate the potential ramifications of mechanical force on systemic immunity, employing a time-dependent approach.

Materials And Methods: A previously described mouse orthodontic model was used.

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases.

Enteropathogenic (EPEC) is a Gram-negative bacterial pathogen that causes persistent diarrhea. Upon attachment to the apical plasma membrane of the intestinal epithelium, the pathogen translocates virulence proteins called effectors into the infected cells. These effectors hijack numerous host processes for the pathogen's benefit.

Issues Concerning the Mechanisms of Bone Conduction.

Air and bone conduction thresholds are used to differentiate between conductive and sensori-neural hearing losses because bone conduction is thought to bypass the conductive apparatus, directly activating the inner ear. However, the suggested bone conduction mechanisms involve the outer and middle ears. Also, normal bone conduction thresholds have been reported in cases of lesions to the conduction pathway.

Splenic spread and hepatic encephalopathy in metastatic malignant melanoma.

An older adult patient was admitted with epigastric pain and vomiting and found to have an abdominal mass, increased cholestatic liver enzymes and markedly elevated serum lactate dehydrogenase (LDH). Imaging revealed extensive liver metastases of unknown primary but also an unusual splenic metastasis diagnosed by liver biopsy as malignant melanoma. The patient became lethargic and developed mental status changes associated with asterixis, abnormal EEG, and increased serum ammonia levels.

Cryo-tomography and 3D Electron Diffraction Reveal the Polar Habit and Chiral Structure of the Malaria Pigment Crystal Hemozoin.

Detoxification of heme in depends on its crystallization into hemozoin. This pathway is a major target of antimalarial drugs. The crystalline structure of hemozoin was established by X-ray powder diffraction using a synthetic analog, β-hematin.

The Wide Spectrum of Presentations of Cytomegalovirus Infection in Immunocompetent Hosts: An Exhaustive Narrative Review.

CMV is a ubiquitous DNA virus that establishes infection and results in 40-100% seropositivity. Viral replication occurs following an acquired primary infection (or reinfection) or by the reactivation of life-long latency. In immunocompetent patients, CMV infection is mostly asymptomatic or mild and self-limited.

The Autophagic Activator GHF-201 Can Alleviate Pathology in a Mouse Model and in Patient Fibroblasts of Type III Glycogenosis.

Glycogen storage disease type III (GSDIII) is a hereditary glycogenosis caused by deficiency of the glycogen debranching enzyme (GDE), an enzyme, encoded by , enabling glycogen degradation by catalyzing alpha-1,4-oligosaccharide side chain transfer and alpha-1,6-glucose cleavage. GDE deficiency causes accumulation of phosphorylase-limited dextrin, leading to liver disorder followed by fatal myopathy. Here, we tested the capacity of the new autophagosomal activator GHF-201 to alleviate disease burden by clearing pathogenic glycogen surcharge in the GSDIII mouse model .