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This effect was further narrowed down to the secreted cytolysin ShlA and the biologically active pigment prodigiosin. Purified prodigiosin and ShlA from Escherichia coli further supported the role of these factors in activating autophagy in human corneal cells. Additional genetic data indicate a role for flagellin and type I pili, but not the nuclease, S-layer protein, or serratamolide biosurfactant in activation of autophagy. CONCLUSIONS This work identifies specific bacterial components that activate autophagy and give insight into potential host-pathogen interactions or compounds that can be used to therapeutically manipulate autophagy.BACKGROUND Wolcott-Rallison Syndrome (WRS) is a rare autosomal recessive disease that is the most common cause of neonatal diabetes in consanguineous families. WRS is caused by various genetic alterations of the Eukaryotic Translation Initiation Factor 2-Alpha Kinase 3 (EIF2AK3) gene. METHODS Genetic analysis of a consanguineous family where two children were diagnosed with WRS was performed by Sanger sequencing. The altered protein was investigated by in vitro cloning, expression and immunohistochemistry. RESULTS The first cases in Hungary, – two patients in one family, where the parents were fourth-degree cousins – showed the typical clinical features of WRS early onset diabetes mellitus with hyperglycemia, growth retardation, infection-induced multiple organ failure. The genetic background of the disease was a novel alteration in the EIF2AK3 gene involving the splice site of exon 11- intron 11-12 boundary g.53051_53062delinsTG. According to cDNA sequencing this created a new splice site and resulted in a frameshift and the development of an early termination codon at amino acid position 633 (p.Pro627AspfsTer7). Based on in vitro cloning and expression studies, the truncated protein was functionally inactive. Immunohistochemistry revealed that the intact protein was absent in the islets of pancreas, furthermore insulin expressing cells were also dramatically diminished. Elevated GRP78 and reduced CHOP protein expression were observed in the liver. CONCLUSIONS The novel genetic alteration causing the absence of the EIF2AK3 protein resulted in insufficient handling of severe endoplasmic reticulum stress, leading to liver failure and demise of the patients.BACKGROUND Workplace violence against healthcare workers is a global issue that is on the rise, with Chinese healthcare workers facing growing challenges with hospital violence. Attacks on medical staff have increased in recent years with no clear resolution. Prior research focused on policies to improve the doctor-patient relationship and better protect clinicians, but few studies addressed the patient perspective. This paper examines patients’ choices when facing a medical dispute and identifies groups who are more likely to respond to conflict with violence or other serious actions. METHODS Patient survey responses were collected in 12 leading public hospitals in five Chinese provinces with 5556 participants. The survey asked sociodemographic information, patients’ attitudes (e.g., general optimism, trust in their physicians, perceived healthcare quality), and their primary response to a medical dispute. From least to most severe, the options range from “complaining within the family” to “violence.” We useespondents reported mild reactions when facing a medical dispute. Among those who reported the intent of serious reactions, some sociodemographic characteristics and the trust of physicians could be predictive. selleck inhibitor To prevent future hospital violence, this work helps identify the characteristics of patients who are more likely to seek severe approaches to medical dispute resolution, including resorting to violence. From these results, hospitals will be better able to target specific groups for interventions that build patient-provider trust and improve general patient satisfaction.BACKGROUND The mortality risk among cancer patients measured from the time of diagnosis is often elevated in comparison to the general population. However, for some cancer types, the patient mortality risk will over time reach the same level as the general population mortality risk. The time point at which the mortality risk reaches the same level as the general population is called the cure point and is of great interest to patients, clinicians, and health care planners. In previous studies, estimation of the cure point has been handled in an ad hoc fashion, often without considerations about margins of clinical relevance. METHODS We review existing methods for estimating the cure point and discuss new clinically relevant measures for quantifying the mortality difference between cancer patients and the general population, which can be used for cure point estimation. The performance of the methods is assessed in a simulation study and the methods are illustrated on survival data from Danish colon cancer patients. RESULTS The simulations revealed that the bias of the estimated cure point depends on the measure chosen for quantifying the excess mortality, the chosen margin of clinical relevance, and the applied estimation procedure. These choices are interdependent as the choice of mortality measure depends both on the ability to define a margin of clinical relevance and the ability to accurately compute the mortality measure. The analysis of cancer survival data demonstrates the importance of considering the confidence interval of the estimated cure point, as these may be wide in some scenarios limiting the applicability of the estimated cure point. CONCLUSIONS Although cure points are appealing in a clinical context and has widespread applicability, estimation remains a difficult task. The estimation relies on a number of choices, each associated with pitfalls that the practitioner should be aware of.BACKGROUND Dating violence has an alarming prevalence among Brazilian adolescents. School-based preventive programs have been implemented, but remain isolated initiatives with low reach. Health communication strategies based on innovative technologies with a high potential of diffusion are urgent. This study aimed to develop a computer-tailored intervention to prevent victimization and perpetration of dating violence among Brazilian youth. METHODS The intervention, called Dating SOS (SOS Namoro), is based on the I-Change Model and attachment theory and is a comprehensive preventive program targeted to young people with a current partner. The intervention design included the stages of needs assessment; definition of objectives of change; development of the library of messages; elaboration of a questionnaire for tailoring feedbacks according to the relevant variables; integration of the content in the software Tailor Builder; pre-testing; and usability and efficacy evaluation planning. Dating SOS is composed of four online sessions.