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Abstract Aims Fluid congestion is a leading cause of hospital admission, readmission, and mortality in heart failure (HF). We performed a systematic review and meta‐analysis to determine the effectiveness of an advanced fluid management programme (AFMP). The AFMP was defined as an intervention providing tailored diuretic therapy guided by intravascular volume assessment, in hospitalized patients or after discharge. The AFMP group was compared with patients who received standard care treatment. The aim of this systematic review and meta‐analysis was to determine the effectiveness of an AFMP in improving patient outcomes. Methods and results A systematic review of randomized controlled trials, case–control studies, and crossover studies using the terms ‘heart failure’, ‘fluid management’, and ‘readmission’ was conducted in PubMed, CINAHL, and Scopus up until November 2020. Studies reporting the association of an AFMP on readmission and/or mortality were included in our meta‐analyses. Risk of bias was assessed in non‐randomized studies using the Newcastle–Ottawa Scale. From 232 retrieved studies, 12 were included in the data synthesis. The 6040 patients in the included studies had a mean age of 72 ± 4 years and mean left ventricular ejection fraction of 39 ± 8%, there were slightly more men (n = 3022) than women, and the follow‐up period was a mean of 4.8 ± 3.1 months. Readmission data were available in 5362 patients; of these, 1629 were readmitted. Mortality data were available in 5787 patients; of these, 584 died. HF patients who had an AFMP in hospital and/or after discharge had lower odds of all‐cause readmission (odds ratio—OR 0.64 [95% confidence interval—CI 0.44, 0.92], P = 0.02) with moderate heterogeneity (I2 = 46.5) and lower odds of all‐cause mortality (OR 0.82 [95% CI 0.69, 0.98], P = 0.03) with low heterogeneity (I2 = 0). The use of an AFMP was equally effective in reducing readmission and mortality regardless of age and follow‐up duration. Effective pre‐discharge diuresis was associated with significantly lower readmission odds (OR 0.43 [95% CI 0.26, 0.71], P = 0.001) compared with a fluid management plan as part of post‐discharge follow‐up. Conclusions An effective AFMP is associated with improving readmission and mortality in HF. Our results encourage attainment of optimal volume status at discharge and prescription of optimal diuretic dose. Ongoing support to maintain euvolaemia and effective collaboration between healthcare teams, along with effective patient education and engagement, may help to reduce adverse outcomes in HF patients.

Abstract Aims Heart failure (HF) readmission commonly arises owing to insufficient patient knowledge and failure of recognition of the early stages of recurrent fluid congestion. In previous work, we developed a score to predict short‐term hospital readmission and showed that higher‐risk patients benefit most from a disease management programme (DMP) that included enhancing knowledge and education by a nurse. We aim to evaluate the effectiveness of a novel, nurse‐led HF DMP in selected patients at high risk of short‐term hospital readmission, using ultrasound‐guided diuretic management and artificial intelligence to enhance HF knowledge in an outpatient setting. Methods and results Risk‐HF is a prospective multisite randomized controlled trial that will allocate 404 patients hospitalized with acute decompensated HF, and ≥33% risk of readmission and/or death at 30 days, into risk‐guided nurse intervention (DMP‐Plus group) compared with usual care. Intervention elements include (i) fluid management with a handheld ultrasound (HHU) device at point of care; (ii) post‐discharge follow‐up; (iii) optimal programmed drug titration; (iv) better transition of care; (v) intensive self‐care education via an avatar‐based ‘digital health coach’; and (vi) exercise guidance through the digital coach. Usual care involves standard post‐discharge hospital care. The primary outcome is reduced death and/or hospital readmissions at 30 days post‐discharge, and secondary outcomes include quality of life, fluid management efficacy, and feasibility and patient engagement. Assuming that our intervention will reduce readmissions and/or deaths by 50%, with a 1:1 ratio of intervention vs. usual care, we plan to randomize 404 patients to show a difference at a statistical power of 80%, using a two‐sided alpha of 0.05. We anticipate this recruitment will be achieved by screening 2020 hospitalized HF patients for eligibility. An 8 week pilot programme of our digital health coach in 21 HF patients, age > 75 years, showed overall improvements in quality of life (13 of 21), self‐care (12 of 21), and HF knowledge (13 of 21). A pilot of the use of HHU by nurses showed that it was feasible and accurate. Conclusions The Risk‐HF trial will evaluate the effectiveness of a risk‐guided intervention to improve HF outcomes and will evaluate the efficacy of trained HF nurses delivering a fluid management protocol that is guided by lung ultrasound with an HHU at point of care.

Human exposure to microplastics through inhalation has been widely reported in recent years. There is a paucity of work focusing on the direct effect of accumulation of microplastics in airways and how it may impact the respiratory function. This study aimed to investigate whether the exposure of microplastic would change the contractility of isolated airway smooth muscle tissue. Microplastics were obtained through milling of high-density polyethylene (HDPE) pellets by using a centrifugal mill. To confirm that the milled microplastic particle size range fell within the definition of microplastic, field-emission scanning electron microscope (FESEM) was employed. The milled microplastics particle size ranged from 44.2 µm to 552.4 µm. The organ bath technique was employed to study the direct change of tissue contractility of rat isolated tracheal rings. Tracheal rings were incubated with polyethylene microplastics of different concentrations (0.3 mg/ml to 10 mg/ml) for a minimum of 18 hours in physiological Krebs buffer, followed by the construction of concentration-response curves to a contractile agent, carbachol (muscarinic agonist). Exposure to all concentrations of polyethylene microplastics enhanced the contractile responses of the tissues to carbachol. However, the effect was only statistically significant in tissues incubated at 3 mg/ml and above (p < 0.05). Findings from this study provide preliminary evidence that exposure to polyethylene microplastics adversely affects airway function. Heightened contractile responses of airways mimic the pathophysiological responses in respiratory diseases such as asthma, chronic cough and chronic obstructive pulmonary disease. Further experiments focusing on the possible mechanism of actions of these microplastics affecting the airway tissue function are now needed.

To determine the contribution of defective splicing in Autism Spectrum Disorders (ASD), the most common neurodevelopmental disorder, a high throughput Massively Parallel Splicing Assay (MaPSY) was employed and identified 42 exonic splicing mutants out of 725 coding de novo variants discovered in the sequencing of ASD families. A redesign of the minigene constructs in MaPSY revealed that upstream exons with strong 5' splice sites increase the magnitude of skipping phenotypes observed in downstream exons. Select hits were validated by RT-PCR and amplicon sequencing in patient cell lines. Exonic splicing mutants were enriched in probands relative to unaffected siblings -especially synonymous variants (7.5% vs 3.5%, respectively). Of the 26 genes disrupted by exonic splicing mutations, 6 were in known ASD genes and 3 were in paralogs of known ASD genes. Of particular interest was a synonymous variant in TNRC6C - an ASD gene paralog with interactions with other ASD genes. Clinical records of 3 ASD patients with TNRC6C variant revealed respiratory issues consistent with phenotypes observed in TNRC6 depleted mice. Overall, this study highlights the need for splicing analysis in determining variant pathogenicity, especially as it relates to ASD.

Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in ~10% of all patients with acute myocardial infarction (AMI), with an over-representation amongst women. Remarkably, it is estimated that as many as 1 in 4 patients with MINOCA experience ongoing angina at 12 months despite having no flow-restricting stenoses in their epicardial arteries. This manuscript presents the rationale behind Randomized Evaluation of Beta Blocker and Angiotensin-converting enzyme inhibitors/Angiotensin Receptor Blocker Treatment (ACEI/ARB) for Post Infarct Angina in MINOCA patients—The MINOCA BAT post infarct angina sub study.Methods: This trial is a registry-based, randomized, parallel, open-label, multicenter trial with 2 × 2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce post infarct angina in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 664 patients will be randomized into four groups; (i) ACEI/ARB with beta blocker, (ii) beta blocker only, (iii) ACEI/ARB only, or (iv) neither ACEI/ARB nor beta blocker and followed for 12 months.Results: The trial is currently recruiting in Australia and Sweden. Fifty six patients have been recruited thus far. Both sexes were equally distributed (52% women and 48% men) and the mean age was 56.3 ± 9.9 years.Conclusions: It remains unclear whether conventional secondary preventive therapies are beneficial to MINOCA patients in regard to post infarct angina. Existing registry-based literature suggest cardioprotective agents are less likely to be used in MINOCA patients. Thus, results from this trial will provide insights for future treatment strategies and guidelines specific to MINOCA patients.

Background: Handheld ultrasound could provide sufficient information to satisfy the clinical questions underlying ‘rarely appropriate’ echo requests, but there are limited data about its use as a gatekeeper to standard echocardiography. We sought to determine whether the use of handheld ultrasound could improve the appropriate use of echocardiography. Method: A prospective study comparing handheld ultrasound strategy to standard echocardiography for studies deemed rarely appropriate, using a questionnaire based on appropriate use criteria was conducted across two hospitals, from October 2017 to April 2018. Results: Groups undergoing Handheld ultrasound (n = 76, 58 (46.5–72.5) years, 53 males, 78% outpatients) and standard echocardiography (n = 72, 61 (49.0–71.5) years, 42 males, 76% outpatients) were comparable. There was a significant decrease in the time to scan from just over 1 month in standard group to a median of 12 days in handheld ultrasound group (P < 0.001). This difference was small for inpatients (from 1 day to a median of 10 min in handheld ultrasound, P = 0.014), but prominent in outpatients (from 1.5 months in the standard group to median of 2 weeks in the handheld ultrasound group, P < 0.001). There was no increase in the need for follow-up scan within 6 months and no significant differences in length of hospital stay for inpatients. Conclusion: Handheld ultrasound can be an effective gatekeeper to standard echocardiography for requests deemed rarely appropriate, reducing time to echocardiography significantly and potentially decreasing the need for standard echocardiography by up to 20%.

The aim of this study is to analyze the thermo-magnetic-gravitational convection of a non-Newtonian power law ferrofluid within a circular cavity. The ferrofluid is exposed to the magnetic field of a permanent magnet. The finite element method is employed to solve the non-dimensional controlling equations. A grid sensitivity analysis and the validation of the used method are conducted. The effect of alterable parameters, including the power law index, 0.7 ≤ n ≤ 1.3, gravitational Rayleigh number, 104 ≤ RaT ≤ 106, magnetic Rayleigh number, 105 ≤ RaM ≤ 108, the location of the hot and cold surfaces, 0 ≤ λ ≤ π/2, and the length of the magnet normalized with respect to the diameter of the cavity, 0.1 ≤ L ≤ 0.65, on the flow and heat transfer characteristics are explored. The results show that the heat transfer rate increases at the end of both arcs compared to the central region because of buoyancy effects, and it is greater close to the hot arc. The location of the arcs does not affect the heat transfer rate considerably. An increase in the magnetic Rayleigh number contributes to stronger circulation of the flow inside and higher heat transfer. When the Kelvin force is the only one imposed on the flow, it enhances the heat transfer for magnets of length 0.2 ≤ L ≤ 0.3.

Background Hypertension confers a poor prognosis in moderate or severe aortic stenosis (AS), however, antihypertensive therapy (AHT) is often not prescribed due to the perceived deleterious effects of vasodilation and negative inotropes.Objective To assess the efficacy and safety outcomes of AHT in adults with moderate or severe AS.Design Systematic review and meta-analysis.Data sources The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and grey literature were searched without language restrictions up to 9 September 2019.Study eligibility criteria, appraisal and synthesis methods Two independent reviewers performed screening, data extraction and risk of bias assessments from a systematic search of observational studies and randomised controlled trials comparing AHT with a placebo or no AHT in adults with moderate or severe AS for any parameter of efficacy and safety outcomes. Conflicts were resolved by the third reviewer. Meta-analysis with pooled effect sizes using random-effects model, were estimated in R.Main outcome measures Mortality, Left Ventricular (LV) Mass Index, systolic blood pressure, diastolic blood pressure and LV ejection fractionResults From 3025 publications, 31 studies (26 500 patients) were included in the qualitative synthesis and 24 studies in the meta-analysis. AHT was not associated with mortality when all studies were pooled, but heterogeneity was substantial across studies. The effect size of AHT differed according to drug class. Renin–angiotensin–aldosterone system inhibitors (RAASi) were associated with reduced risk of mortality (Pooled HR 0.58, 95% CI 0.43 to 0.80, p=0.006), The differences in changes of haemodynamic or echocardiographic parameters from baseline with and without AHT did not reach statistical significance.Conclusion AHT appears safe, is well tolerated. RAASi were associated with clinical benefit in patients with moderate or severe AS.

Introduction It is important to ascertain the cost-effectiveness of alternative services to traditional cardiac rehabilitation while the economic credentials of the Smartphone Cardiac Rehabilitation, Assisted self-Management (SCRAM) programme among people with coronary heart disease (CHD) are unknown. This economic protocol outlines the methods for undertaking a trial-based economic evaluation of SCRAM in the real-world setting in Australia.Methods and analysis The within-trial economic evaluation will be undertaken alongside a randomised controlled trial (RCT) designed to determine the effectiveness of SCRAM in comparison with the usual care cardiac rehabilitation (UC) alone in people with CHD. Pathway analysis will be performed to identify all the costs related to the delivery of SCRAM and UC. Both a healthcare system and a limited societal perspective will be adopted to gauge all costs associated with health resource utilisation and productivity loss. Healthcare resource use over the 6-month participation period will be extracted from administrative databases (ie, Pharmaceutical Benefits Scheme and Medical Benefits Schedule). Productivity loss will be measured by absenteeism from work (valued by human capital approach). The primary outcomes for the economic evaluation are maximal oxygen uptake (VO2max, mL/kg/min, primary RCT outcome) and quality-adjusted life years estimated from health-related quality of life as assessed by the Assessment of Quality of Life-8D instrument. The incremental cost-effectiveness ratio will be calculated using the differences in costs and benefits (ie, primary and secondary outcomes) between the two randomised groups from both perspectives with no discounting. All costs will be valued in Australian dollars for year 2020.Ethics and dissemination The study protocol has been approved under Australia’s National Mutual Acceptance agreement by the Melbourne Health Human Research Ethics Committee (HREC/18/MH/119). It is anticipated that SCRAM is a cost-effective cardiac telerehabilitation programme for people with CHD from both a healthcare and a limited societal perspective in Australia. The evaluation will provide evidence to underpin national scale-up of the programme to a wider population. The results of the economic analysis will be submitted for publication in a peer-reviewed journal.Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12618001458224).

Background The association between mitral valve prolapse (MVP) and sudden death remains controversial. We aimed to describe histopathological changes in individuals with autopsy‐determined isolated MVP (iMVP) and sudden death and document cardiac arrest rhythm. Methods and Results The Australian National Coronial Information System database was used to identify cases of iMVP between 2000 and 2018. Histopathological changes in iMVP and sudden death were compared with 2 control cohorts matched for age, sex, height, and weight (1 group with noncardiac death and 1 group with cardiac death). Data linkage with ambulance services provided cardiac arrest rhythm for iMVP cases. From 77 221 cardiovascular deaths in the National Coronial Information System database, there were 376 cases with MVP. Individual case review yielded 71 cases of iMVP. Mean age was 49±18 years, and 51% were women. Individuals with iMVP had higher cardiac mass (447 g versus 355 g; P

Im vierwöchigen Schulpraktikum der Leuphana Universität Lüneburg sollen die Studierenden zum ersten Mal eigenen Unterricht planen und durchführen. Der Schwerpunkt dieser ersten schulpraktischen Erfahrungen liegt auf der Förderung von Klassenführungskompetenzen. Die entsprechenden didaktisch-methodischen Grundlagen werden mit den Studierenden in den vorangegangen Seminaren erarbeitet. Während des Schulpraktikums sollen die eigenen Unterrichtsstunden reflektiert werden und die Studierenden erhalten auf Klassenführung bezogenes Feedback von Mitstudierenden und Dozierenden. Dieses Coaching findet traditionell face-to-face und direkt im Anschluss an die eigene Unterrichtsstunde statt (Live-Coaching). Im Sommersemester 2017 wurde dieses konventionelle Format der Praktikumsbegleitung durch neue online und teilweise videobasierte Formate ergänzt. Studierende der V-Coaching Seminare nahmen sich zweimal in ihrem eigenen Unterricht mit Videokameras auf. Aus diesen Videos wählten sie jeweils eine ca. fünf- bis zehnminütige Sequenz aus, welche sie dann auf der Lernplattform Moodle hochluden. Anhand dieser Videosequenz verfassten die Studierenden eine Selbstreflexion mit dem Schwerpunkt auf Klassenführung und erhielten Feedback von Mitstudierenden und Dozierenden. Studierende der T-Coaching Seminare reflektieren basierend auf ihrer Erinnerung im Textformat ihren eigenen Unterricht. Diese Selbstreflektionen luden sie ebenfalls auf Moodle hoch und erhielten Feedback. Erste empirische Ergebnisse zeigen, dass die Studierenden der V-Coaching Seminare ihre professionelle Wahrnehmung von Klassenführung mehr steigern konnten als Studierende der Live-Coaching Seminare. Zudem wurden insbesondere die V-Coaching Seminare gut angenommen und scheinen einen motivierenden Faktor für Studierende zu haben. Die Konzeptualisierung und Gestaltung neuer online- und videobasierter Coaching Formate im Praktikum scheint somit eine sinnvolle Ergänzung zum konventionellen Live-Coaching darzustellen.

BackgroundThere are conflicting reports on the association of undercarboxylated osteocalcin (ucOC) in cardiovascular disease development, including endothelial function and hypertension. We tested whether ucOC is related to blood pressure and endothelial function in older adults, and if ucOC directly affects endothelial-mediated vasodilation in the carotid artery of rabbits.MethodsIn older adults, ucOC, blood pressure, pulse wave velocity (PWV) and brachial artery flow-mediated dilation (BAFMD) were measured (n = 38, 26 post-menopausal women and 12 men, mean age 73 ± 0.96). The vasoactivity of the carotid artery was assessed in male New Zealand White rabbits following a four-week normal or atherogenic diet using perfusion myography. An ucOC dose response curve (0.3-45 ng/ml) was generated following incubation of the arteries for 2-hours in either normal or high glucose conditions.ResultsucOC levels were higher in normotensive older adults compared to those with stage 2 hypertension (p < 0.05), particularly in women (p < 0.01). In all participants, higher ucOC was associated with lower PWV (p < 0.05), but not BAFMD (p > 0.05). In rabbits, ucOC at any dose did not alter vasoactivity of the carotid artery, either following a normal or an atherogenic diet (p > 0.05).ConclusionIncreased ucOC is associated with lower blood pressure and increased arterial stiffness, particularly in post-menopausal women. However, ucOC administration has no direct short-term effect on endothelial function in rabbit arteries. Future studies should explore whether treatment with ucOC, in vivo, has direct or indirect effects on blood vessel function.

Background: Telemedicine and digital health technologies hold great promise for improving clinical care of heart failure. However, inconsistent and contradictory findings from randomized controlled trials have so far discouraged widespread adoption of digital health in routine clinical practice. We undertook this review study to summarize the study outcomes of the use of exploring the evidence for telemedicine in the clinical care of patients with heart failure and readmissions. Methods: We inspected the references of guidelines and searched PubMed for randomized controlled trials published over the past 10 years on the use of telemedicine for reducing readmission in heart failure. We utilized a modified realist review approach to identify the underlying contextual mechanisms for the intervention(s) in each randomized controlled trial, evaluating outcomes of the intervention and understanding how and under what conditions they worked. To provide uniformity, all extracted data were synthesized using adapted domains from the taxonomy for disease management created by the Disease Management Taxonomy Writing Group. Results: A total of 12 papers were eligible, 6 of them supporting and 6 others undermining the use of telemedicine for improving heart failure readmission. In general terms, those studies not supporting the use of telemedicine were multicentre, publicly funded, with large amount of participants, and long duration. The patients had also better rates of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker and beta-blockers, and telemonitoring and automatic transmission of vital signs were less utilized, in comparison with the studies in which telemedicine use was supported. The analysis of the environment, intensity, content of interventions, method of communication, quality of the underlying model of care and the ability, capability, and interest from health workers can help us to envisage probabilities of success of telemedicine use. Conclusions: A realist lens may aid to understand whom and in which circumstances the use of telemedicine can add any substantial value to traditional models of care. Wider outcome criteria beyond major adverse cardiovascular events, for example, cost efficacy, should also be considered as appropriate for effecting guidelines on care delivery when robust prognostic therapeutics already exist.

In semi-solid metal high pressure die casting and in conventional high pressure die casting, it is common to find a defect band just below the surface of the component. The formation of these bands is not fully understood. However, there are several theories as how they occur, and it has been suggested that segregation is caused by the migration of aluminium-rich externally solidified crystals. In the present work the formation of these bands is investigated theoretically by reviewing suitable potential mechanisms for the migration of such crystals. Two mechanisms are identified as the most probable: Saffman lift force and the Mukai-Lin-Laplace effect. However, it was not possible to identify which of these two mechanisms acted in the case studies. Further testing is required to identify the mechanism that is causing the migration of the aluminium globules and suitable tests are proposed.

This feature article for the thematic series on congestive heart failure (CHF) readmissions aims to outline important gaps in guidelines for patients with multiple comorbidities and the elderly. Congestive heart failure diagnosis manifests as a 3-phase journey between the hospital and community, during acute, chronic stable, and end-of-life (palliative) phases. This journey requires in variable intensities a combination of multidisciplinary care within tertiary hospital or ambulatory care from hospital outpatients or primary health services, within the general community. Management goals are uniform, ie, to achieve the lowest New York Heart Association class possible, with improvement in ejection fraction, by delivering gold standard therapies within a CHF program. Comorbidities are an important common denominator that influences outcomes. Comorbidities include diabetes mellitus, chronic obstructive airways disease, chronic renal impairment, hypertension, obesity, sleep apnea, and advancing age. Geriatric care includes the latter as well as syndromes such as frailty, falls, incontinence, and confusion. Many systems still fail to comprehensively achieve all aspects of such programs. This review explores these factors.

In the chlorophyll (Chl) biosynthesis pathway the formation of protochlorophyllide is catalyzed by Mg-protoporphyrin IX methyl ester (MgPME) cyclase. The Ycf54 protein was recently shown to form a complex with another component of the oxidative cyclase, Sll1214 (CycI), and partial inactivation of the ycf54 gene leads to Chl deficiency in cyanobacteria and plants. The exact function of the Ycf54 is not known, however, and further progress depends on construction and characterisation of a mutant cyanobacterial strain with a fully inactivated ycf54 gene. Here, we report the complete deletion of the ycf54 gene in the cyanobacterium Synechocystis 6803; the resulting ycf54 strain accumulates huge concentrations of the cyclase substrate MgPME together with another pigment, which we identified using nuclear magnetic resonance as 3-formyl MgPME. The detection of a small amount (~13%) of Chl in the ycf54 mutant provides clear evidence that the Ycf54 protein is important, but not essential, for activity of the oxidative cyclase. The greatly reduced formation of protochlorophyllide in the ycf54 strain provided an opportunity to use 35S protein labelling combined with 2D electrophoresis to examine the synthesis of all known Chl-binding protein complexes under drastically restricted de novo Chl biosynthesis. We show that although the ycf54 strain synthesizes very limited amounts of photosystem I and the CP47 and CP43 subunits of photosystem II (PSII), the synthesis of PSII D1 and D2 subunits and their assembly into the reaction centre (RCII) assembly intermediate were not affected. Furthermore, the levels of other Chl complexes such as cytochrome b6f and the HliD– Chl synthase remained comparable to wild-type. These data demonstrate that the requirement for de novo Chl molecules differs completely for each Chl-binding protein. Chl traffic and recycling in the cyanobacterial cell as well as the function of Ycf54 are discussed.

The microbial metabolism of hydrocarbons is increasingly associated with the corrosion of carbon steel in sulfate-rich marine waters. However, how such transformations influence metal biocorrosion in the absence of an electron acceptor is not fully recognized. We grew a marine alkane-utilizing, sulfate-reducing bacterium, Desulfoglaeba alkanexedens, with either sulfate or Methanospirillum hungatei as electron acceptors, and tested the ability of the cultures to catalyze metal corrosion. Axenically, D. alkanexedens had a higher instantaneous corrosion rate and produced more pits in carbon steel coupons than when the same organism was grown in syntrophic co-culture with the methanogen. Since anaerobic hydrocarbon biodegradation pathways converge on fatty acid intermediates, the corrosive ability of a known fatty acid-oxidizing syntrophic bacterium, Syntrophus aciditrophicus was compared when grown in pure culture or in co-culture with a H2-utilizing sulfate-reducing bacterium (Desulfovibrio sp., strain G11) or a methanogen (M. hungatei). The instantaneous corrosion rates in the cultures were not substantially different, but the syntrophic, sulfate-reducing co-culture produced more pits in coupons than other combinations of microorganisms. Lactate-grown cultures of strain G11 had higher instantaneous corrosion rates and coupon pitting compared to the same organism cultured with hydrogen as an electron donor. Thus, if sulfate is available as an electron acceptor, the same microbial assemblages produce sulfide and low molecular weight organic acids that exacerbated biocorrosion. Despite these trends, a surprisingly high degree of variation was encountered with the corrosion assessments. Differences in biomass, initial substrate concentration, rates of microbial activity or the degree of end product formation did not account for the variations. We are forced to ascribe such differences to the metallurgical properties of the coupons.

The Birt-Hogg-Dube disease occurs as a result of germline mutations in the human Folliculin gene (FLCN), and is characterized by clinical features including fibrofolliculomas, lung cysts and multifocal renal neoplasia. Clinical and genetic evidence suggest that FLCN acts as a tumor suppressor gene. The human cell line UOK257, derived from the renal cell carcinoma of a patient with a germline mutation in the FLCN gene, harbors a truncated version of the FLCN protein. Reconstitution of the wild type FLCN protein into UOK257 cells delays cell cycle progression, due to a slower progression through the late S and G2/M-phases. Similarly, Flcn (-/-) mouse embryonic fibroblasts progress more rapidly through the cell cycle than wild type controls (Flcn (flox/flox)). The reintroduction of tumor-associated FLCN mutants (FLCN ΔF157, FLCN 1-469 or FLCN K508R) fails to delay cell cycle progression in UOK257 cells. Additionally, FLCN phosphorylation (on Serines 62 and 73) fluctuates throughout the cell cycle and peaks during the G2/M phase in cells treated with nocodazole. In keeping with this observation, the reintroduction of a FLCN phosphomimetic mutant into the UOK257 cell line results in faster progression through the cell cycle compared to those expressing the wild type FLCN protein. These findings suggest that the tumor suppression function of FLCN may be linked to its impact on the cell cycle and that FLCN phosphorylation is important for this activity. Additionally, these observations describe a novel in vitro assay for testing the functional significance of FLCN mutations and/or genetic polymorphisms.

Avaliou-se o impacto do desmatamento e implantação de pastagens nos estoques de carbono e nitrogênio e na dinâmica da matéria orgânica do solo, em duas cronossequências com florestas e pastagens de 8 e 20 anos em Rondônia. Os conteúdos de carbono e nitrogênio aumentaram na pastagem com 20 anos de implantanção em uma das cronossequências estudadas, mas poucas alterações foram observadas na outra cronossequência. O uso de ð13C permitiu diferenciar e quantificar as duas fontes de carbono no solo sob pastagem, ou seja, o carbono remanescente da floresta e o introduzido pela pastagem. Verificou-se uma tendência de aumento do carbono do solo derivado da pastagem, acompanhado de um declínio do carbono do solo derivado da floresta. Os valores de ð13C do solo na camada de 0-10 cm variaram de -27 o/oo a -28 o/oo na floresta para aproximadamente -20 o/oo na pastagem com vinte anos de implantação, o que confirma a entrada de uma grande quantidade de carbono no solo derivado de plantas C4. As mudanças verificadas nos estoques de carbono e nitrogênio do solo, em áreas de sucessão floresta-pastagem, possuem implicações importantes nas análises dos ciclos biogeoquímicos globais

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021–2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets. [ABSTRACT FROM AUTHOR]