Genes encoded in the major histocompatibility complex affecting the generation of peptides for TAP transport

The B cell line 721.174 has lost the ability to present intracellular antigens to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL). This phenotype results from a homozygous deletion in the MHC that includes the peptide transporter genes TAP1 and TAP2, and the proteasome subunits LMP2 and LMP7. Recent work has shown that such cells transfected with TAP genes load their class I molecules with endogenous peptides, and present several viral epitopes to class I-restricted CTL. These data implied that the LMP2 and LMP7 genes were not required for the presentation of most epitopes through class I molecules. By contrast, while confirming the previous reports, we have identified several epitopes that appear to require genes in the MHC in addition to the TAP for their presentation. Further analysis localizes the defect to proteolysis in the cytosol. In one case, presentation could be partially restored by re-expression of full-length LMP7. Control experiments with LMP7, from which the putative pro-region had been removed, failed to restore presentation, and this lack of effect correlated with failure of the shortened LMP7 to incorporate into the proteasome. These results suggest a role for LMP7 in the generation of a viral epitope, but leave open the possibility that additional genes within the .174 deletion are required for full restoration of antigen presentation.     

Comparative evaluation of the Eiken and API 20E systems and conventional methods for identification of members of the family Enterobacteriaceae

To evaluate the accuracy and utility of the Eiken Systek No. 1 (Eiken system; Eiken Chemical Co., Ltd., Tokyo, Japan), we conducted a clinical comparison, with 345 Enterobacteriaceae isolates, of the Eiken System with API 20E (Analytab Products, Inc., Plainview, N.Y.) and conventional methods. The Eiken system is a 21-biochemical-test battery tray stored at 25 degrees C and inoculated in one step. It is similar to the API 20E except that the Eiken system contains malonate, adonitol, and maltose; lacks gelatin, sucrose, melibiose, amygdalin, and arabinose; and uses reagent strips instead of liquid reagents. The API 20E and Eiken systems correctly identified 339 (97.7%) and 276 (79.5%), respectively, and misidentified 3 (0.9%) and 13 (3.7%), respectively, of the isolates. There were no identification codes for 5 (1.4%) organisms with the API 20E and 58 (16.7%) organisms with the Eiken system; of these latter unidentified organisms, 42 were identified as Proteus spp., Morganella sp., and Providencia rettgeri by conventional methods. There was no significant difference between the two rapid systems in total time required for inoculation and reading. Modifications for interpretation of decarboxylase and oxidase tests were needed for the Eiken system, and manipulation of reagent strips required considerable dexterity. However, the Eiken system was easier to inoculate than the API 20E, and, with minor increases in the data base to include more of the Proteus and Morganella spp. and P. rettgeri, the system should be reliable for identification of members of the family Enterobacteriaceae.     

Identifying undiagnosed diabetes: cross-sectional survey of 3.6 million patients' electronic records.

BACKGROUND: Around 1% of the UK population has diabetes that is either undiagnosed or unrecorded on practice disease registers. AIM: To estimate the number of people in UK primary care databases with biochemical evidence of undiagnosed diabetes. To develop simple practice-based search techniques to support early recognition of diabetes. DESIGN OF STUDY: Cross-sectional survey of 3 630 296 electronic records. SETTING: Four hundred and eighty UK practices contributing to the QRESEARCH database. METHOD: Electronic searches to identify people with no diabetes diagnosis in one of two categories (A and B), using the most recently recorded blood glucose measurement: random blood glucose level >or=11.1 mmol/l or fasting blood glucose level >or=7.0 mmol/l (A); either a random or a fasting blood glucose level >or=7.0 mmol/l (B). An additional outcome measure was the proportion of the population with at least one blood glucose measurement in the record. RESULTS: The number (percentage) identified in category A was 3758 (0.10% of the total population); the number in category B was 32 785 (0.90%). Projected to a practice of 7000 patients, around eight patients have biochemical evidence of undiagnosed diabetes, and 68 have results suggesting the need for further follow-up. One-third of people aged over 40 years without diabetes have a blood glucose measurement in the past 2 years in their record. CONCLUSION: People with possible undiagnosed diabetes are readily identifiable in UK primary care databases through electronic searches using blood glucose data. People with borderline levels, who may benefit from interventions to reduce their risk of progression to diabetes, can also be identified using practice-based software.     

"Doctors' Dilemmas

Three British physicians briefly review the final programs in a BBC series, "Doctors' Dilemmas," each consisting of a case history followed by a discussion involving health professionals, administrators, and lawyers. Taylor, an occupational physician, comments on the episode in which a company doctor is asked by management to disclose confidential information about an employee. Psychiatrist Jerram discusses his reactions to the program presenting the dilemmas of treating a patient with anorexia nervosa against her will. Forsythe, a community physician, reviews the final episode, which dealt with resource allocation, the role of health professionals within the National Health Service, and the potential conflict between the NHS and private practice.     

Tackling the frailty burden with an integrative value-based approach: results from a mixed-methods study

Journal of Public Health - The purpose of this paper is to investigate the implementation of value-based care principles in the context of frailty in the perioperative process, highlighting the...     

Universal Mindfulness Training in Schools for Adolescents: a Scoping Review and Conceptual Model of Moderators,Mediators, and Implementation Factors

Prevention Science - There is evidence that universal school-based mindfulness training (SBMT) can have positive effects for young people. However, it is unknown who benefits most from such...     

Dietary Patterns Derived from UK Supermarket Transaction Data with Nutrient and Socioeconomic Profiles

Poor diet is a leading cause of death in the United Kingdom (UK) and around the world. Methods to collect quality dietary information at scale for population research are time consuming, expensive and biased. Novel data sources offer potential to overcome these challenges and better understand population dietary patterns. In this research we will use 12 months of supermarket sales transaction data, from 2016, for primary shoppers residing in the Yorkshire and Humber region of the UK (n = 299,260), to identify dietary patterns and profile these according to their nutrient composition and the sociodemographic characteristics of the consumer purchasing with these patterns. Results identified seven dietary purchase patterns that we named: Fruity; Meat alternatives; Carnivores; Hydrators; Afternoon tea; Beer and wine lovers; and Sweet tooth. On average the daily energy intake of loyalty card holders -who may buy as an individual or for a household- is less than the adult reference intake, but this varies according to dietary purchase pattern. In general loyalty card holders meet the recommended salt intake, do not purchase enough carbohydrates, and purchase too much fat and protein, but not enough fibre. The dietary purchase pattern containing the highest amount of fibre (as an indicator of healthiness) is bought by the least deprived customers and the pattern with lowest fibre by the most deprived. In conclusion, supermarket sales data offer significant potential for understanding population dietary patterns.     

Rare Norovirus GIV Foodborne Outbreak,Wisconsin, USA

We report a norovirus GIV outbreak in the United States, 15 years after the last reported outbreak. During May 2016 in Wisconsin, 53 persons, including 4 food handlers, reported being ill. The outbreak was linked to individually prepared fruit consumed as a fruit salad. The virus was phylogenetically classified as a novel GIV genotype.     

Burden of Providing Informal Care for Patients with Atrial Fibrillation

ObjectivesPatients with atrial fibrillation (AF) have rapid and irregular heart rates, increasing the risk of comorbidities and mortality. Next to formal medical care, many patients receive informal care from their social environment. The objective of this study was to examine the well-being and economic burden of providing informal care to patients with AF in the UK, Italy, and Germany.MethodsCaregivers of patients with AF completed an online survey based on the iMTA Valuation of Informal Care Questionnaire, with questions about their caregiving situation, perceived burden of caregiving, and absence from work due to health problems resulting from caregiving. Care-related quality-of-life utilities were calculated using the Care-related Quality of Life instrument and associated tariffs. Societal costs of caregiving were calculated based on the proxy good method.ResultsA total of 585 caregivers participated in this study. On average, caregivers provided 33 hours of informal care per week to patients (SD 29 hours). On a scale from 0 to 10, their self-rated burden was 5.4. The average Care-related Quality of Life utility was 72. Caregivers primarily indicated problems with daily activities, mental health, and physical health. Still, the vast majority of caregivers (87%) derived fulfillment from providing care. Weekly societal costs of caregiving were on average €636. Comorbidities contributed substantially to the caregiver time and burden.ConclusionsCaring for a patient with AF is associated with substantial objective and subjective burden, but also provides fulfillment from being able to care for a loved one.