Is 24/7 remote patient management in heart failure necessary? Results of the telemedical emergency service used in the TIM‐HF and in the TIM‐HF2 trials

Aims: Telemedical emergency services for heart failure (HF) patients are usually provided during business hours. However, many emergencies occur outside of business hours. This study evaluates if a 24/7 telemedical emergency service is needed for the remote management of high-risk HF patients. Methods: and results The study included 1119 patients merged from the TIM-HF and TIM-HF2 trials [age 69 +/- 11, 73% male, left ventricular ejection fraction 37% +/- 13, 557 New York Heart Association (NYHA) II/562 NYHA III]. Patients received a 24/7 physician-guided emergency service provided by the telemedical centre (TMC) in addition to remote management within business hours. During emergency calls, patient status, symptoms, electronic patient record, and instant telemonitoring data were evaluated by the TMC physician. Following diagnosis, patients were referred for hospital admission or instructed to stay at home. Apart from the TMC, patients could place a call to the public emergency service at any time. Seven hundred sixty-eight emergency calls were placed over 1383 patient years (0.56 calls/patient year). Five hundred twenty-six calls (69%) occurred outside business hours. There were 146 (19%) emergency calls for worsening HF, 297 (39%) other cardiovascular, and 325 (42%) non-cardiac causes, with a similar pattern inside and outside business hours. Of the 1119 patients, 417 (37%) placed at least one emergency call. Patients with NYHA Class III, higher N-terminal prohormone of brain natriuretic peptide (>1.400 pg/mL) levels, ischaemic aetiology of HF, implanted defibrillator, and impaired renal function had a higher probability of placing emergency calls. During study follow-up, patients who made an emergency call had a higher all-cause mortality (22% vs. 11%, P = 0.007 in TIM-HF; 16% vs. 4%, P < 0.001 in TIM-HF2) and more unplanned hospitalizations (324 vs. 162, P < 0.001 in TIM-HF; 545 vs. 180, P < 0.001 in TIM-HF2). Of the total 1,211 unplanned hospital admissions, 492 (41%) were initiated by a patient emergency call. Three hundred seventy-nine calls (49%) were placed to the TMC, whereas 389 calls (51%) were made to the public emergency service. Three hundred twenty-six (84%) of the calls to the public emergency service resulted in acute hospitalizations. The TMC initiated 202 (53%) hospital admissions; 177 (47%) patients were advised to stay at home. All patients that remained at home were alive during a prespecified safety period of 7 days post-call. Diagnoses made by the TMC physician were confirmed in 83% of cases by the hospital. Conclusion: A telemedical emergency service for high-risk HF patients is safe and should operate 24/7 to reduce unplanned hospitalizations. Emergency calls could be considered as a marker for higher morbidity and mortality

Indoor air pollution concentrations and cardiometabolic health across four diverse settings in Peru: a cross-sectional study.

BACKGROUND: Indoor air pollution is an important risk factor for health in low- and middle-income countries. METHODS: We measured indoor fine particulate matter (PM2.5) and carbon monoxide (CO) concentrations in 617 houses across four settings with varying urbanisation, altitude, and biomass cookstove use in Peru, between 2010 and 2016. We assessed the associations between indoor pollutant concentrations and blood pressure (BP), exhaled carbon monoxide (eCO), C-reactive protein (CRP), and haemoglobin A1c (HbA1c) using multivariable linear regression among all participants and stratifying by use of biomass cookstoves. RESULTS: We found high concentrations of indoor PM2.5 across all four settings (geometric mean ± geometric standard deviation of PM2.5 daily average in μg/m3): Lima 41.1 ± 1.3, Tumbes 35.8 ± 1.4, urban Puno 14.1 ± 1.7, and rural Puno 58.8 ± 3.1. High indoor CO concentrations were common in rural households (geometric mean ± geometric standard deviation of CO daily average in ppm): rural Puno 4.9 ± 4.3. Higher indoor PM2.5 was associated with having a higher systolic BP (1.51 mmHg per interquartile range (IQR) increase, 95% CI 0.16 to 2.86), a higher diastolic BP (1.39 mmHg higher DBP per IQR increase, 95% CI 0.52 to 2.25), and a higher eCO (2.05 ppm higher per IQR increase, 95% CI 0.52 to 3.57). When stratifying by biomass cookstove use, our results were consistent with effect measure modification in the association between PM2.5 and eCO: among biomass users eCO was 0.20 ppm higher per IQR increase in PM2.5 (95% CI - 2.05 to 2.46), and among non-biomass users eCO was 5.00 ppm higher per IQR increase in PM2.5 (95% CI 1.58 to 8.41). We did not find associations between indoor air concentrations and CRP or HbA1c outcomes. CONCLUSIONS: Excessive indoor concentrations of PM2.5 are widespread in homes across varying levels of urbanisation, altitude, and biomass cookstove use in Peru and are associated with worse BP and higher eCO

The Role of Oestrogen Receptor Beta (ERβ) in the Aetiology and Treatment of Type 2 Diabetes Mellitus

Introduction: Challenges facing the treatment of type 2 diabetes necessitate the search for agents which act via alternative pathways to provide better therapeutic outcomes. Recently, an increasing body of evidence implicates the activation of oestrogen receptors (ERα and ERβ) in the development and treatment of underlying conditions in type 2 diabetes. This article summarizes available evidence for the involvement of oestrogen receptors in insulin secretion, insulin resistance as well as glucose uptake and highlights the potential of ERβ as a therapeutic target. Background: Recent studies indicate an association between the activation of each of the isoforms of ER and recent findings indicate that ERβ shows promise as a potential target for antidiabetic drugs. In vitro and in vivo studies in receptor knockout mice indicate beneficial actions of selective agonists of ERβ receptor and underscore its therapeutic potential. Conclusion: Studies are needed to further elucidate the exact mechanism underlying the role of ERβ activation as a therapeutic approach in the management of type 2 diabetes

No Effect of Microgravity and Simulated Mars Gravity on Final Bacterial Cell Concentrations on the International Space Station: Applications to Space Bioproduction

Microorganisms perform countless tasks on Earth and they are expected to be essential for human space exploration. Despite the interest in the responses of bacteria to space conditions, the findings on the effects of microgravity have been contradictory, while the effects of Martian gravity are nearly unknown. We performed the ESA BioRock experiment on the International Space Station to study microbe-mineral interactions in microgravity, simulated Mars gravity and simulated Earth gravity, as well as in ground gravity controls, with three bacterial species: Sphingomonas desiccabilis, Bacillus subtilis, and Cupriavidus metallidurans. To our knowledge, this was the first experiment to study simulated Martian gravity on bacteria using a space platform. Here, we tested the hypothesis that different gravity regimens can influence the final cell concentrations achieved after a multi-week period in space. Despite the different sedimentation rates predicted, we found no significant differences in final cell counts and optical densities between the three gravity regimens on the ISS. This suggests that possible gravityrelated effects on bacterial growth were overcome by the end of the experiment. The results indicate that microbial-supported bioproduction and life support systems can be effectively performed in space (e.g., Mars), as on Earth

Frequent and sex-biased deletion of SLX4IP by illegitimate V(D)J-mediated recombination in childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) accounts for ∼25% of pediatric malignancies. Of interest, the incidence of ALL is observed ∼20% higher in males relative to females. The mechanism behind the phenomenon of sex-specific differences is presently not understood. Employing genome-wide genetic aberration screening in 19 ALL samples, one of the most recurrent lesions identified was monoallelic deletion of the 5′ region of SLX4IP. We characterized this deletion by conventional molecular genetic techniques and analyzed its interrelationships with biological and clinical characteristics using specimens and data from 993 pediatric patients enrolled into trial AIEOP-BFM ALL 2000. Deletion of SLX4IP was detected in ∼30% of patients. Breakpoints within SLX4IP were defined to recurrent positions and revealed junctions with typical characteristics of illegitimate V(D)J-mediated recombination. In initial and validation analyses, SLX4IP deletions were significantly associated with male gender and ETV6/RUNX1-rearranged ALL (both overall P < 0.0001). For mechanistic validation, a second recurrent deletion affecting TAL1 and caused by the same molecular mechanism was analyzed in 1149 T-cell ALL patients. Validating a differential role by sex of illegitimate V(D)J-mediated recombination at the TAL1 locus, 128 out of 1149 T-cell ALL samples bore a deletion and males were significantly more often affected (P = 0.002). The repeatedly detected association of SLX4IP deletion with male sex and the extension of the sex bias to deletion of the TAL1 locus suggest that differential illegitimate V(D)J-mediated recombination events at specific loci may contribute to the consistent observation of higher incidence rates of childhood ALL in boys compared with girl

Enhanced susceptibility to infections in a diabetic wound healing model

<p>Abstract</p> <p>Background</p> <p>Wound infection is a common complication in diabetic patients. The progressive spread of infections and development of drug-resistant strains underline the need for further insights into bacterial behavior in the host in order to develop new therapeutic strategies. The aim of our study was to develop a large animal model suitable for monitoring the development and effect of bacterial infections in diabetic wounds.</p> <p>Methods</p> <p>Fourteen excisional wounds were created on the dorsum of diabetic and non-diabetic Yorkshire pigs and sealed with polyurethane chambers. Wounds were either inoculated with 2 × 10⁸Colony-Forming Units (CFU) of <it>Staphylococcus aureus </it>or injected with 0.9% sterile saline. Blood glucose was monitored daily, and wound fluid was collected for bacterial quantification and measurement of glucose concentration. Tissue biopsies for microbiological and histological analysis were performed at days 4, 8, and 12. Wounds were assessed for reepithelialization and wound contraction.</p> <p>Results</p> <p>Diabetic wounds showed a sustained significant infection (>10⁵CFU/g tissue) compared to non-diabetic wounds (p < 0.05) over the whole time course of the experiment. <it>S. aureus</it>-inoculated diabetic wounds showed tissue infection with up to 8 × 10⁷CFU/g wound tissue. Non-diabetic wounds showed high bacterial counts at day 4 followed by a decrease and no apparent infection at day 12. Epidermal healing in <it>S. aureus</it>-inoculated diabetic wounds showed a significant delay compared with non-inoculated diabetic wounds (59% versus 84%; p < 0.05) and were highly significant compared with healing in non-diabetic wounds (97%; p < 0.001).</p> <p>Conclusion</p> <p>Diabetic wounds developed significantly more sustained infection than non-diabetic wounds. <it>S. aureus </it>inoculation leads to invasive infection and significant wound healing delay and promotes invasive co-infection with endogenous bacteria. This novel wound healing model provides the opportunity to closely assess infections during diabetic wound healing and to monitor the effect of therapeutical agents <it>in vivo</it>.</p

Effects of a household air pollution intervention using liquefied petroleum gas stoves, continuous fuel distribution and behavioural messaging on dietary and sodium intake of adult women in Puno, Peru: a randomised controlled trial

Abstract Objective: Household air pollution (HAP) is a widespread environmental exposure worldwide. While several cleaner fuel interventions have been implemented to reduce personal exposures to HAP, it is unclear if cooking with cleaner fuels also affects the choice of meals and dietary intake. Design: Individually randomised, open-label controlled trial of a HAP intervention. We aimed to determine the effect of a HAP intervention on dietary and Na intake. Intervention participants received a liquefied petroleum gas (LPG) stove, continuous fuel delivery and behavioural messaging during 1 year whereas control participants continued with usual cooking practices that involved the use of biomass-burning stoves. Dietary outcomes included energy, energy-adjusted macronutrients and Na intake at baseline, 6 months and 12 months post-randomisation using 24-h dietary recalls and 24-h urine. We used t-tests to estimate differences between arms in the post-randomisation period. Setting: Rural settings in Puno, Peru. Participants: One hundred women aged 25–64 years. Results: At baseline, control and intervention participants were similar in age (47·4 v. 49·5 years) and had similar daily energy (8894·3 kJ v. 8295·5 kJ), carbohydrate (370·8 g v. 373·3 g) and Na intake (4·9 g v. 4·8 g). One year after randomisation, we did not find differences in average energy intake (9292·4 kJ v. 8788·3 kJ; P = 0·22) or Na intake (4·5 g v. 4·6 g; P = 0·79) between control and intervention participants. Conclusions: Our HAP intervention consisting of an LPG stove, continuous fuel distribution and behavioural messaging did not affect dietary and Na intake in rural Peru