Miracle-dz/UniFAR-FTUs huggingface dataset:
Process and impact of mergers of NHS trusts: multicentre case study and management cost analysis

Abstract Objective: To study the processes involved in and impact of mergers between NHS trusts, including the effect on management costs. Design: Cross sectional study involving in depth interviews and documentary analysis; case study to compare savings in management costs between case trusts and control trusts. Setting: Nine trusts (cross sectional study) and four trusts (case study) in London. Participants: 96 interviews with trust board members, other senior managers, clinicians, service managers, and representatives of health authorities, regional office, community health councils, local authorities, other trusts in the area, and primary care groups and trusts. Main outcome measures: Stated and unstated drivers, and impact of merger on delivery and development of services, management structures, and staff recruitment, retention, and morale. Effects of difference in trust size before and after the merger. Savings in management costs two years after merger. Results: Some important drivers for merger are not publicly stated. Mergers had a negative effect on delivery of services because of a loss of managerial focus on services. Planned developments in services were delayed by at least 18 months. Trusts' larger sizes after mergers had unintended negative consequences, as well as predicted advantages. The tendency for one trust's management team to dominate over the other resulted in tension. No improvement in recruitment or retention of clinical and managerial staff was reported. Perceived differences in organisational culture were an important barrier to bringing together two or more organisations. Two years after merger, merged trusts had not achieved the objective of saving £500 000 a year in management costs. Conclusions: Important unintended consequences need to be accounted for when mergers are planned. Mergers can cause considerable disruptions to services, and require greater management support than previously acknowledged. Other organisations undergoing restructuring, such as primary care groups developing into primary care trusts and health authorities merging into strategic health authorities, should take these findings into account.
Epigenetic Modifications in Th 2 Cells

Functionally polarized CD4 T helper (Th) cells, such as Th1, Th2, and Th17 cells, are essential for the regulation of acquired immunity. Differentiation of naïve CD4 T cells into Th2 cells is characterized by chromatin remodeling and the induced expression of a set of Th2-specific genes, which include Th2 cytokine genes. In the first stage of this differentiation, a Th2-skewing cytokine environment, especially IL-4, induces STAT6 activation. Activated STAT6 increases the expression of GATA3, a master regulator of Th2 cell differentiation, via direct binding to the Gata3 gene locus. This transcriptional induction of Gata3 mRNA during Th2 cell differentiation is accompanied by dynamic changes in the binding patterns of two epigenetic modification proteins such as Polycomb and Trithorax complexes. Consequently, expressed GATA3 epigenetically modifies and upregulates Th2-specific genes to establish Th2 cell identity. This identity is maintained by high-level expression of the Gata3 gene controlled by Menin, which is a member of the Trithorax proteins, after cycles of cultivation in vitro and a long-term resting state in vivo. Thus, the Menin-GATA3 axis handles the Th2-specific gene regulatory network.
Botanicals for Treatment of Babesiosis and Theileriosis

Problems of toxicity, resistance and residues of existing drugs necessitate development of newer drugs against parasitic diseases. Babesiois and theileriosis are the economically most important haemoprotozoan diseases of domestic animals. Drugs of herbal origin are considered safe for use in human and animal medicine as they have less toxicity and are easily metabolized compared to synthetic chemicals. Potential plant extracts and phytochemicals that have antibabesial and antitheilerial activity are discussed in the present communication.
TNF-TNFR2 Interactions Are Critical for the Development of Intestinal Graft-Versus-Host Disease in MHC Class II-Disparate (C57BL/6J→C57BL/6J × bm12)F1 Mice1

TNF-TNFR2 interactions promote MHC class II-stimulated alloresponses while TNF-TNFR1 interactions promote MHC class I-stimulated alloresponses. The present studies were designed to evaluate whether TNF-TNFR2 interactions were involved in the in vivo generation of CD4+ T cell-mediated intestinal graft-versus-host disease (GVHD) in the (C57BL/6J (hereafter called B6)→B6 × B6.C-H-2bm12 (bm12))F1 GVHD model. Briefly, 5 × 106 splenic CD4+ T lymphocytes from B6.TNFR2−/− or control B6 mice were transferred with 1–2 × 106 T cell-depleted B6 bone marrow cells (BMC) to irradiated MHC class II-disparate (bm12 × B6)F1 mice. Weight loss, intestinal inflammation, and the surface expression of CD45RB (memory marker) on intestinal and splenic lymphocytes were assessed. IL-2 and IFN-α mRNA levels in intestinal lymphocytes were assessed by nuclease protection assays. A significant reduction in weight loss and intestinal inflammation was observed in recipients of the TNFR2−/−CD4+ SpC. Similarly, a significant decrease was noted in T cell numbers and in CD45RBlow (activated/memory) expression on intestinal but not CD4+ T cells in recipients of TNFR2−/−CD4+ spleen cells. IL-2 and IFN-α mRNA levels were reduced in the intestine in the recipients of TNFR2−/− splenic CD4+ T cells. These results indicate that TNF-TNFR2 interactions are important for the development of intestinal inflammation and activation/differentiation of Th1 cytokine responses by intestinal lymphocytes in MHC class II-disparate GVHD while playing an insignificant role in donor T cell activation in the spleen.
Risk factors for injuries in elite female soccer players

Objective: To describe risk factors for injuries in elite female soccer. Methods: A total of 143 female soccer players from the German national league participated in the study. Baseline information on player characteristics—for example, anthropometric measurements and playing position—and medical history were recorded at the start of the study. During one outdoor season, injuries and training and match exposure times were prospectively documented for each player. Results: The risk of a new anterior cruciate ligament (ACL) rupture was significantly increased in players with a previous rupture (odds ratio (OR) = 5.24, p = 0.01). This was not the case for ankle sprain (OR = 1.39) or knee sprain (OR = 1.50). In addition, no significantly increased risk of new sprains or ACL ruptures was found when the injured leg was the unit of analysis. Injury incidence was considerably higher in defenders (9.4 injuries per 1000 hours exposure) and strikers (8.4/1000 hours) than goalkeepers (4.8/1000 hours) and midfielders (4.6/1000 hours). Ten per cent of all players (n = 14) sustained more than three injuries. Most of these were defenders (n = 8) or strikers (n = 4). Significantly more injuries occurred to the dominant leg (105 v 71, p = 0.01); this was particularly true for contact injuries (52 v 29, p = 0.01). Conclusions: Injury risk should be assessed on an individual basis. Therefore it seems appropriate to individualise preventive training programmes, as is recommended for other training content. Evaluating the existing rules of soccer and their appropriate application may also help to decrease injury risk, particularly in contact situations.
The Role of Hypothalamic TriIodothyronine Availability in Seasonal Regulation of Energy Balance and BodyWeight

Seasonal cycles of body weight provide a natural model system to understand the central control of energy balance. Studies of such cycles in Siberian hamsters suggest that a change in the hypothalamic availability of thyroid hormone is the key determinant of annual weight regulation. Uptake of thyroid hormone into the hypothalamus from the peripheral circulation occurs largely through a specific monocarboxylate transporter expressed by tanycyte cells lining the third ventricle. Tanycytes are the principal brain cell type expressing type II and type III deiodinases, so they control the local concentrations of T4, T3, and inactive metabolites. Type III deiodinase mRNA in tanycytes is photoperiodically upregulated in short photoperiod. This would be expected to reduce the availability of T3 in the hypothalamus by promoting the production of inactive metabolites such as rT3. Experimental microimplantation of T3 directly into the hypothalamus during short-days promotes a long-day phenotype by increasing food intake and body weight without affecting the peripheral thyroid axis. Thus, thyroid hormone exerts anabolic actions within the brain that play a key role in the seasonal regulation of body weight. Understanding the precise actions of thyroid hormone in the brain may identify novel targets for long-term pharmacological manipulation of body weight.
Continuous intravenous infusions of lorazepam versus midazolam for sedation during mechanical ventilatory support: A prospective, randomized study

To evaluate the efficacy of continuous infusions of lorazepam vs. midazolam for sedation in the intensive care unit (ICU). Design:Prospective, randomized study. Setting:Large, urban university hospital. Patients:Twenty adult medical ICU patients receiving mechanical ventilatory support. Interventions:Patients were randomized to receive either lorazepam or midazolam. The infusion rate was adjusted at the bedside by the ICU nurse according to a standardized study protocol to achieve and maintain sedation at Ramsay's sedation level 2 or 3. Measurements and Main Results:Ten patients were randomized to receive lorazepam and ten to receive midazolam. The groups were similar in demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, ICU admission diagnosis, underlying disease processes, and supplemental analgesic administration. The mean time to achieve initial adequate sedation was 124 mins for lorazepam and 105 mins for midazolam. The mean infusion rate at the point of initial sedation was 0.06 mg/kg/hr for lorazepam and 0.15 mg/kg/hr for midazolam. The maximum and mean infusion rates for the entire study period were 0.1 and 0.06 mg/kg/hr, respectively, for lorazepam and 0.29 and 0.24 mg/kg/hr, respectively, for midazolam. The number of infusion rate adjustments per day was 1.9 mg/kg/hr for lorazepam and 3.6 mg/kg/hr for midazolam. Of the surviving patients, the mean time to return to baseline mental status after discontinuation of the benzodiazepine infusion was 261 mins for lorazepam and 1815 mins for midazolam. The mean volume of fluid per day required to deliver the maximum dose of benzodiazepine was 1.2 L for lorazepam (maximum 2.4 L) and 1.3 L for midazolam (maximum 3.6 L). Conclusions:While there was a tendency to a longer time required for return to baseline mental status in patients receiving midazolam, this was not statistically signficant. Findings of interest concerning both midazolam and lorazepam were: a) time to achieve sedation in medical ICU patients is often prolonged; b) actual dose requirements necessary to maintain sedation in this patient population are larger than the current literature describes; c) time to awaken after discontinuation of the infusion was occasionally delayed for >24 hrs; d) large volumes of fluid were required to deliver these doses of drug via this route of administration. (Crit Care Med 1994; 22:1241–1247)
Rationale and design of the EXAMINATION trial: a randomised comparison between everolimus-eluting stents and cobalt-chromium bare-metal stents in ST-elevation myocardial infarction.

AIMS To assess the performance of the everolimus-eluting stent (EES) versus cobalt chromium bare-metal stent (BMS) in the setting of primary percutaneous coronary intervention for treatment of patients presenting with ST-segment elevation myocardial infarction (STEMI). The implantation of a drug-eluting stent in the setting of an acute myocardial infarction is still controversial. In several registries this clinical scenario has been associated with the development of stent thrombosis. The EES has demonstrated to reduce the stent thrombosis rate as compared to paclitaxel-eluting stent in randomised controlled trials, mainly performed in patients in stable clinical conditions. There are however few data regarding the effectiveness of EES in the context of STEMI. METHODS AND RESULTS This is an investigator-driven, prospective, multicentre, multinational, randomised, single blind, two-arm, controlled trial (ClinicalTrials.gov number: NCT00828087). This trial, with an all comer design, randomises approximately 1,500 patients 1:1 to EES or BMS. Overall, any patient presenting with STEMI up to 48 hours who requires emergent percutaneous coronary intervention can be included. The primary endpoint is the patient-oriented combined endpoint of all-cause death, any myocardial infarction and any revascularisation at 1-year according to the Academic Research Consortium. Clinical follow-up will be scheduled at 30 days, six months, one year and yearly up to five years. No angiographic follow-up is mandated per protocol. CONCLUSIONS This trial with broad inclusion and few exclusion criteria will shed light on the performance of the second generation EES in the complex scenario of STEMI.
Rate and indications of cesarean section in the Maternity Teaching Hospital in Erbil City, Kurdistan region, Iraq

Background and objective: Knowing the rate and indications of the cesarean section will help to have an overview of this common type of obstetrical procedure and to plan for the high level of care management. This study aimed to find out the rate of cesarean section and to identify its indications. Methods: A cross-sectional study was conducted at the Maternity Teaching Hospital in Erbil city of Kurdistan Region, Iraq. Data were collected during the period of 20th of March to 30th of December 2015 by an interview with 722 women who were admitted to the hospital and underwent cesarean section out of 11881 cesarean section done during 2015. Results: Results showed the increasing rate of the cesarean section from 28.5% in 2010 to 35.77% in 2015. The main overall indications for cesarean section were a previous cesarean section (70.49%), cephalopelvic disproportion (35.31%) and mother’s request (14.26%). Conclusion: Rate of cesarean section is much higher than the optimal range recommended by the World Health Organization. Finding the appropriate strategies for decreasing the rate of primary and secondary indications is essential.
Perioperative hypertension in patients undergoing carotid endarterectomy: shorter duration under regional block anesthesia.

Two alternative anesthetic techniques for use during carotid endarterectomy were studied in a series of 424 procedures. A total of 248 were performed in patients under general anesthesia and 176 patients received regional block anesthesia. Perioperative instability of blood pressure was noted in 108 patients. Hypertension was noted in 17.7% of those under general anesthesia vs 20.5% of those under regional block anesthesia. Intravenous vasodilator agents were used for 19.62 hr (+/- 4.33) in the general anesthesia group vs 1.4 hr (+/- 0.44) in the regional block anesthesia group (p less than .02). Perioperative hypertension correlated best with uncontrolled preoperative hypertension. Under regional block anesthesia the incidence of shunting was 4.5%. The 1 month operative mortality for the entire carotid series was 1.2% (5/424). There were three stroke-related deaths. In addition, two nonfatal major strokes and two minor strokes occurred in patients who received general anesthesia vs one nonfatal major stroke in a patient who received regional block anesthesia.
Psychosocial correlates of benefit finding in breast cancer survivors in China

Breast cancer is number one in incidence and sixth in mortality among all cancers of women in China. Prior work identified positive consequences following diagnosis and treatment, including benefit finding among breast cancer survivors from Western countries. This study evaluated psychosocial correlates of benefit finding in breast cancer survivors in China. A total of 148 participants completed measures of coping, perceived stress, depressive symptoms, social support, and benefit finding. Results indicated that benefit finding was positively related to active coping and negatively related to depression. Future research may evaluate whether interventions to enhance active coping will improve outcomes among Chinese breast cancer survivors.
Collecting Duct Nitric Oxide Synthase 1ß Activation Maintains Sodium Homeostasis During High Sodium Intake Through Suppression of Aldosterone and Renal Angiotensin II Pathways

Background During high sodium intake, the renin‐angiotensin‐aldosterone system is downregulated and nitric oxide signaling is upregulated in order to remain in sodium balance. Recently, we showed that collecting duct nitric oxide synthase 1β is critical for fluid‐electrolyte balance and subsequently blood pressure regulation during high sodium feeding. The current study tested the hypothesis that high sodium activation of the collecting duct nitric oxide synthase 1β pathway is critical for maintaining sodium homeostasis and for the downregulation of the renin‐angiotensin‐aldosterone system–epithelial sodium channel axis. Methods and Results Male control and collecting duct nitric oxide synthase 1β knockout (CDNOS1KO) mice were placed on low, normal, and high sodium diets for 1 week. In response to the high sodium diet, plasma sodium was significantly increased in control mice and to a significantly greater level in CDNOS1KO mice. CDNOS1KO mice did not suppress plasma aldosterone in response to the high sodium diet, which may be partially explained by increased adrenal AT1R expression. Plasma renin concentration was appropriately suppressed in both genotypes. Furthermore, CDNOS1KO mice had significantly higher intrarenal angiotensin II with high sodium diet, although intrarenal angiotensinogen levels and angiotensin‐converting enzyme activity were similar between knockout mice and controls. In agreement with inappropriate renin‐angiotensin‐aldosterone system activation in the CDNOS1KO mice on a high sodium diet, epithelial sodium channel activity and sodium transporter abundance were significantly higher compared with controls. Conclusions These data demonstrate that high sodium activation of collecting duct nitric oxide synthase 1β signaling induces suppression of systemic and intrarenal renin‐angiotensin‐aldosterone system, thereby modulating epithelial sodium channel and other sodium transporter abundance and activity to maintain sodium homeostasis.
Temperature-dependent Modulation of CaV3 T-type Calcium Channels by Protein Kinases C and A in Mammalian Cells*

Modulation of low voltage-activated CaV3 T-type calcium channels remains poorly characterized compared with high voltage-activated CaV1 and CaV2 calcium channels. Notably, it is yet unresolved whether CaV3 channels are modulated by protein kinases in mammalian cells. In this study, we demonstrate that protein kinase A (PKA) and PKC (but not PKG) activation induces a potent increase in CaV3.1, CaV3.2, and CaV3.3 currents in various mammalian cell lines. Notably, we show that protein kinase effects occur at physiological temperature (∼30–37 °C) but not at room temperature (∼22–27 °C). This temperature dependence could involve kinase translocation, which is impaired at room temperature. A similar temperature dependence was observed for PKC-mediated increase in high voltage-activated CaV2.3 currents. We also report that neither CaV3 surface expression nor T-current macroscopic properties are modified upon kinase activation. In addition, we provide evidence for the direct phosphorylation of CaV3.2 channels by PKA in in vitro assays. Overall, our results clearly establish the role of PKA and PKC in the modulation of CaV3 T-channels and further highlight the key role of the physiological temperature in the effects described.
Yeasts associated with plums and their potential for controlling brown rot after harvest

Bacterial and yeast antagonists isolated from fruit surfaces have been effective in controlling various post‐harvest diseases, and several microbial antagonists have been developed into commercial products. Our knowledge of the fruit microbial community, with the exception of grapes, apples and some citrus fruit, is rudimentary and the potential of the resident yeasts for biocontrol remains largely unknown. We determined the occurrence of yeasts on plum surfaces during fruit development from the pre‐hardening stage until harvest for 2 years. A total of 16 species from 13 genera were isolated. Species from three genera, basidiomycetes Rhodotorula (29.5%) and Sporidiobolus (24.7%) and the dimorphic ascomycete genus Aureobasidium (24.7%), constituted 78.7% of all isolations and were recovered throughout fruit development, while Cryptococcus spp. constituted only 6.2% of the total plum isolates. The yeast community in the final sampling was significantly different from the first three samplings, reflecting a rapidly changing fruit habitat during the maturation of fruit. For example, Hanseniaspora, Pichia, Zygosaccharomyces and Wickerhamomyces occurred only on the most mature fruit. Screening of the yeasts for antagonistic activity against Monilinia fructicola, a fungus that causes brown rot, revealed a range of biocontrol activities. Several isolates provided complete control of the decay on plums, challenged with a pathogen suspension of 103 conidia/ml and > 90% of control on fruit inoculated with the pathogen at a concentration 10 times higher. Some of the best antagonists included A. pullulans and R. phylloplana. Populations of both of these antagonists increased rapidly by several orders of magnitude in wounds of plums incubated at 24ºC and 4ºC. Our results indicate that plum surfaces harbour several yeast species, with excellent potential for use in biological control of brown rot of stone fruits. Published 2014. This article is a U.S. Government work and is in the public domain in the USA
POLYPHENOLS COMPOUNDS INVESTIGATION OF LEAVES AND CALLUS ARTICHOKES ( CYNARA COLYMUS L . )

Since ancient times humans have adopted herbs and wild plants in the treatment of diseases. Medicinal plants were used more at the beginning of the 20th century to treat many diseases through the extraction of active chemical compounds. It is, therefore, necessary to detect the active substances of medicinal plant extract. Cynara scolymus L. is a medicinal plant mentioned in British and European Pharmacopeia. Artichoke is considered as medicinal plant, due to its nutritional and phytochemical composition, especially high proportion of phenolics compound. The phenolics include phenolic acids such as (Cynarin, Chlorogenic acid, Luteolin Salicylic acid and caffeic acid). The present study included phytochemicals (secondary metabolites) Screening of the crude extracts (leaves, friable and compact callus) and the five major active phenolic compounds were identified from the crude methanolic extracts of leaves, friable and compact callus using high performance liquid chromatography (HPLC) analysis. Two of these compounds, Salicylic acid and 5-o-Caffeoylquinic acid (Chlorogenic) were found to be in high concentration in leaves extract that recorded 526.182 μg/ml and 5222. 421μg/ml, respectively. The other three compounds, 1,3-di-o-Caffeoylquinic acid (Cynarin), Luteolin, and Caffeic acid were found to be in high concentration in friable callus extract that recorded 3205.153 μg/ml, 940.983 μg/ml, 380.437 μg/ml respectively.