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Archaeal transcription is carried out by a multi-subunit RNA polymerase (RNAP) that is highly homologous in structure and function to eukaryotic RNAP II. Among the set of basal transcription factors, only Spt5 is found in all domains of life, but Spt5 has been shaped during evolution, which is also reflected in the heterodimerization of Spt5 with Spt4 in Archaea and Eukaryotes. To unravel the mechanistic basis of Spt4/5 function in Archaea, we performed structure-function analyses using the archaeal transcriptional machinery of Pyrococcus furiosus (Pfu). We report single-particle cryo-electron microscopy reconstructions of apo RNAP and the archaeal elongation complex (EC) in the absence and presence of Spt4/5. Surprisingly, Pfu Spt4/5 also binds the RNAP in the absence of nucleic acids in a distinct super-contracted conformation. We show that the RNAP clamp/stalk module exhibits conformational flexibility in the apo state of RNAP and that the enzyme contracts upon EC formation or Spt4/5 engagement. We furthermore identified a contact of the Spt5-NGN domain with the DNA duplex that stabilizes the upstream boundary of the transcription bubble and impacts Spt4/5 activity in vitro. This study, therefore, provides the structural basis for Spt4/5 function in archaeal transcription and reveals a potential role beyond the well-described support of elongation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: The purpose of this study was to develop and validate a generic questionnaire to evaluate experiences and reported outcomes in patients who receive treatment across a range of healthcare sectors., Design: Mixed-methods design including focus groups, pretests and field test., Setting: The patient questionnaire was developed in the context of a nationwide program in Germany aimed at quality improvements across the healthcare sectors., Participants: For the field test, 589 questionnaires were distributed to patients via 47 general practices., Main Measurements: Descriptive item analyzes non-responder analysis and factor analysis (PCA). Retest coefficients (r) calculated by correlation of sum scores of PCA factors. Quality gaps were assessed by the proportion of responders choosing a response category defined as indicating shortcomings in quality of care., Results: The conceptual phase showed good content validity. Four hundred and seventy-four patients who received a range of treatment across a range of sectors were included (response rate: 80.5%). Data analysis confirmed the construct, oriented to the patient care journey with a focus on transitions between healthcare sectors. Quality gaps were assessed for the topics 'Indication', including shared-decision-making (6 items, 24.5-62.9%) and 'Discharge and Transition' (10 items; 20.7-48.2%). Retest coefficients ranged from r = 0.671 until r = 0.855 and indicated good reliability. Low ratios of item-non-response (0.8-9.3%) confirmed a high acceptance by patients., Conclusions: The number of patients with complex healthcare needs is increasing. Initiatives to expand quality assurance across organizational borders and healthcare sectors are therefore urgently needed. A validated questionnaire (called PEACS 1.0) is available to measure patients' experiences across healthcare sectors with a focus on quality improvement., (© The Author 2014. Published by Oxford University Press in association with the International Society for Quality in Health Care.)

We investigate prescription drug use, and information and enrollment intentions for the new Medicare Part D drug insurance program, using a sample of Medicare-eligible subjects surveyed before open enrollment began for this program. We find that, despite the complexity of competing plans offered by private insurers under Part D, a majority of the Medicare population had information on this program and a substantial majority planned to enroll. We find that virtually all elderly, even those with no current prescription drug use, can expect to benefit from enrollment in a Part D Standard plan at the low premiums available in the current market. However, there is a significant risk that many eligible seniors, particularly low-income elderly with poor health or cognitive impairment, will make poor enrollment and plan choices.

Endoscopic sphincterotomy has proven to be a safe alternative to surgery for selected types of biliary disease. Despite a relatively low morbidity, postprocedure complications are well described. This report presents an experience with three patients in whom acute relapsing pancreatitis developed as a possible complication of papillary stenosis after endoscopic sphincterotomy. None of the patients had a previous history of elevations in serum amylase levels before endoscopic sphincterotomy. After procedure, pancreatitis and subsequently acute relapsing pancreatitis with documented stricture of the pancreatic duct orifice developed in all three patients. After surgical transduodenal sphincteroplasty, no new episodes of acute relapsing pancreatitis occurred.

Reported are eight patients with idiopathic chronic pancreatitis and two patients with alcoholic pancreatitis who had near total distal pancreatectomy for disabling pain and underwent simultaneous segmental pancreatic autotransplantation of the body and tail of the gland to the femoral area in an attempt to prevent or delay the onset of diabetes. The median follow-up period was 31 months, and follow-up study in nine patients ranged from 24 to 54 months. Patency of the grafts was determined by angiography and selected percutaneous venous assays for insulin. Islet cell function was determined by oral glucose tolerance tests, intravenous (I.V.) glucose tolerance tests, and I.V. glucagon stimulation studies. Segmental autotransplantation was technically successful in eight patients, only one of whom required insulin (at 2 years after grafting). The other seven patients with technically successful grafts have remained insulin independent, including two patients who later underwent pyloric preserving pancreatoduodenectomy for completion pancreatectomy. Variable pain relief was observed in patients who underwent near total pancreatectomy, but pain was unrelieved in those patients who underwent limited distal resection. Patients with idiopathic pancreatitis appear to have better pain relief and preservation of endocrine function than alcoholic patients. Segmental pancreatic autotransplantation prevents or delays the onset of diabetes mellitus and should be considered as an alternative for those patients who require extensive pancreatic resection for chronic pancreatitis.