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Staphylococcus chromogenes TA showed significantly lower growth under iron-deprived conditions, and adding an iron supplement (lactoferrin or ferritin) resulted in no improvement in growth; in contrast, growth of S. chromogenes IM was significantly recovered with ferritin iron supplementation. Only Staphylococcus hominis strains originating from quarter milk were able to significantly utilize ferritin as an iron source to reverse the growth inhibition caused by chelating agent 2,2ʹ-bipyridyl in varying degrees. Both S. chromogenes strains (IM and TA) and all S. hominis strains were unable to significantly use lactoferrin as an iron source for growth recovery. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the impact of BMI on uncomplicated pregnancies and healthy births in women who did or did not have medically assisted reproduction (MAR, i.e. ART or hormonal stimulation without manipulation of eggs or embryos) in the Flanders region (Belgium)? SUMMARY ANSWER Women with a higher BMI who use MAR are at the highest risk of pregnancy and birth complications. WHAT WE KNOW ALREADY Medically assisted reproduction (MAR) is used increasingly worldwide and is associated with increased risk of adverse perinatal outcomes. Obesity is also increasing globally and obese women are more likely to seek MAR since obesity is associated with infertility. When obese women undergo MAR, the risk of adverse outcomes may be enhanced but it is not clear to what extent. STUDY DESIGN, SIZE, DURATION We conducted a registry-based study using the data from the Study Centre for Perinatal epidemiology database for years 2009–2015, region of Flanders, Belgium. This included 428 336 women. PARTICIPANTS/MATERIALS, SETTING, METHODS The average age was 30.0 years (SD 4.78), 194 061 (45.31%) were nulliparous, and 6.3% (n = 26 971) conceived with MAR. We examined the association of BMI and MAR with the following composite primary outcomes: 'uncomplicated pregnancy and birth' and 'healthy baby'. We conducted Poisson regression and adjusted for maternal age, parity, gestational weight gain, smoking and previous caesarean section. MAIN RESULTS AND THE ROLE OF CHANCE In our study, 36.80% (n = 157 623) of women had an uncomplicated pregnancy and birth according to the definition used. The predicted probability of having an uncomplicated pregnancy and birth for women with a BMI of 25 kg/m2 who conceived spontaneously was 0.33 (0.32 to 0.35), while it was 0.28 (0.24 to 0.32) for women who used hormonal stimulation and 0.26 (0.22 to 0.29) for women who used IVF/ICSI. This probability reduced with increasing BMI category for both MAR and non-MAR users. For women with a BMI of 30 kg/m2, the predicted probability of having an uncomplicated pregnancy and birth was 0.28 (0.26 to 0.30) for women who conceived spontaneously, and 0.22 (0.16 to 0.29) and 0.20 (0.14 to 0.26) for women who used hormonal stimulation only or IVF/ICSI, respectively. The predicted probability of having a healthy baby for women with a BMI of 25 kg/m2 who conceived spontaneously was 0.92 (0.91 to 0.93), 0.89 (0.87 to 0.92) for women who used hormonal stimulation only and 0.85 (0.84 to 0.87) for women who used IVF/ICSI. LIMITATIONS, REASONS FOR CAUTION The database did not include data on socio-economic status, pre-pregnancy morbidities and paternal BMI. Subsequently, we could not adjust for these factors in the analysis. WIDER IMPLICATIONS OF THE FINDINGS Obese women who use MAR are at the highest risk of pregnancy and birth complications. This increase in interventions also has cost and resource implications which is relevant for funding policies. Weight loss interventions prior to MAR seem plausible but their (cost-) effectiveness needs urgent investigation. STUDY FUNDING/COMPETING INTEREST(S) F.W. received an Erasmus Plus training grant to visit A.B. L.A. and R.D. and conducted this study during this visit. The authors have no competing interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Staphylococcus hominis , a member of the non- aureus staphylococci (NAS) group, is part of the human and animal microbiota. Although it has been isolated from multiple bovine-associated habitats, its relevance as a cause of bovine mastitis is currently not well described. To successfully colonize and proliferate in the bovine mammary gland, a bacterial species must be able to acquire iron from host iron-binding proteins. The aims of this study were (1) to assess the genetic diversity of S. hominis isolated from bovine quarter milk, rectal feces, and teat apices, and (2) to investigate the capacity of bovine S. hominis isolates belonging to these different habitats to utilize ferritin and lactoferrin as iron sources. To expand on an available collection of bovine S. hominis isolates (2 from quarter milk, 8 from rectal feces, and 19 from teat apices) from one commercial dairy herd, a subsequent single cross-sectional quarter milk sampling (n = 360) was performed on all lactating cows (n = 90) of the same herd. In total, 514 NAS isolates were recovered and identified by MALDI-TOF mass spectrometry; the 6 most prevalent NAS species were S. cohnii (33.9%), S. sciuri (16.7%), S. haemolyticus (16.3%), S. xylosus (9.6%), S. equorum (9.4%), and S. hominis (3.5%). A random amplified polymorphic DNA (RAPD) analysis was performed on 46 S. hominis isolates (19 from quarter milk, 8 from rectal feces, and 19 from teat apices). Eighteen distinct RAPD fingerprint groups were distinguished although we were unable to detect the presence of the same RAPD type in all 3 habitats. One S. hominis isolate of a distinct RAPD type unique to a specific habitat (8 from quarter milk, 3 from rectal feces, and 4 from teat apices) along with the quality control strain Staphylococcus aureus ATCC 25923 and 2 well-studied Staphylococcus chromogenes isolates ("IM" and "TA") were included in the phenotypical iron test. All isolates were grown in 4 types of media: iron-rich tryptic soy broth, iron-rich tryptic soy broth deferrated by 2,2'-bipyridyl, and deferrated tryptic soy broth supplemented with human recombinant lactoferrin or equine spleen–derived ferritin. The growth of the different strains was modified by the medium in which they were grown. Staphylococcus chromogenes TA showed significantly lower growth under iron-deprived conditions, and adding an iron supplement (lactoferrin or ferritin) resulted in no improvement in growth; in contrast, growth of S. chromogenes IM was significantly recovered with iron supplementation. Staphylococcus hominis strains from all 3 habitats were able to significantly utilize ferritin but not lactoferrin as an iron source to reverse the growth inhibition, in varying degrees, caused by the chelating agent 2,2'-bipyridyl. [ABSTRACT FROM AUTHOR]

Staphylococcus hominis , a member of the non- aureus staphylococci (NAS) group, is part of the human and animal microbiota. Although it has been isolated from multiple bovine-associated habitats, its relevance as a cause of bovine mastitis is currently not well described. To successfully colonize and proliferate in the bovine mammary gland, a bacterial species must be able to acquire iron from host iron-binding proteins. The aims of this study were (1) to assess the genetic diversity of S. hominis isolated from bovine quarter milk, rectal feces, and teat apices, and (2) to investigate the capacity of bovine S. hominis isolates belonging to these different habitats to utilize ferritin and lactoferrin as iron sources. To expand on an available collection of bovine S. hominis isolates (2 from quarter milk, 8 from rectal feces, and 19 from teat apices) from one commercial dairy herd, a subsequent single cross-sectional quarter milk sampling (n = 360) was performed on all lactating cows (n = 90) of the same herd. In total, 514 NAS isolates were recovered and identified by MALDI-TOF mass spectrometry; the 6 most prevalent NAS species were S. cohnii (33.9%), S. sciuri (16.7%), S. haemolyticus (16.3%), S. xylosus (9.6%), S. equorum (9.4%), and S. hominis (3.5%). A random amplified polymorphic DNA (RAPD) analysis was performed on 46 S. hominis isolates (19 from quarter milk, 8 from rectal feces, and 19 from teat apices). Eighteen distinct RAPD fingerprint groups were distinguished although we were unable to detect the presence of the same RAPD type in all 3 habitats. One S. hominis isolate of a distinct RAPD type unique to a specific habitat (8 from quarter milk, 3 from rectal feces, and 4 from teat apices) along with the quality control strain Staphylococcus aureus ATCC 25923 and 2 well-studied Staphylococcus chromogenes isolates ("IM" and "TA") were included in the phenotypical iron test. All isolates were grown in 4 types of media: iron-rich tryptic soy broth, iron-rich tryptic soy broth deferrated by 2,2'-bipyridyl, and deferrated tryptic soy broth supplemented with human recombinant lactoferrin or equine spleen–derived ferritin. The growth of the different strains was modified by the medium in which they were grown. Staphylococcus chromogenes TA showed significantly lower growth under iron-deprived conditions, and adding an iron supplement (lactoferrin or ferritin) resulted in no improvement in growth; in contrast, growth of S. chromogenes IM was significantly recovered with iron supplementation. Staphylococcus hominis strains from all 3 habitats were able to significantly utilize ferritin but not lactoferrin as an iron source to reverse the growth inhibition, in varying degrees, caused by the chelating agent 2,2'-bipyridyl. [ABSTRACT FROM AUTHOR]

Non- aureus staphylococci (NAS) are predominantly isolated from bovine milk samples of quarters suffering from subclinical mastitis. They are also abundantly present on dairy cows' teat apices and can be recovered from bovine fecal samples, as recently described. Differences in ecology, epidemiology, effect on udder health, and virulence or protective traits have been reported among the species within this group. The objectives of this study were (1) to describe the species-specific distribution of NAS in 3 bovine-associated habitats, namely quarter milk, teat apices, and rectal feces, and (2) to evaluate the virulence potential of NAS by comparing their distribution in contrasting milk sample strata and the presence of selected virulence genes. A cross-sectional, systematic sampling procedure was followed in 8 dairy herds that participated in the local Dairy Herd Improvement program in Flanders, Belgium. Quarter milk samples (n = 573) were collected from 144 lactating cows in 8 herds. In 5 of the 8 herds, teat apex swabs (n = 192) were taken from 15 lactating cows, before and after milking, and from 18 dry cows. In the same 5 herds, rectal feces were sampled from 80 lactating cows (n = 80), taking into account that a cow could only serve as the source of one type of sample. In addition, milk samples of all clinical mastitis cases were continuously collected during the 1-yr study period from March 2017 to March 2018 in the 8 herds. In total, 1,676 Staphylococcus isolates were phenotypically identified and subjected to MALDI-TOF mass spectrometry. Thirty-three, 98, and 28% of all quarter milk, teat apex, and rectal fecal samples were NAS-positive, respectively, reaffirming the presence of NAS in rectal feces. The overall predominant species in the 3 habitats combined were Staphylococcus haemolyticus , Staphylococcus chromogenes , and Staphylococcus hominis. Four, 16, and 12% of the healthy quarters (quarter milk somatic cell count ≤50,000 cells/mL of milk), quarters with subclinical mastitis (quarter milk somatic cell count >50,000 cells/mL of milk), and quarters with clinical mastitis, respectively, were NAS-positive, suggesting that the potential to cause (mild) clinical mastitis is present among NAS. This was substantiated by comparing the presence of virulence genes of NAS isolates originating from contrasting milk sample strata (healthy quarters and quarters with clinical mastitis). [ABSTRACT FROM AUTHOR]

Aim: To estimate the economic burden of common health problems associated with pregnancy and childbirth, such as incontinence, mental health problems, or gestational diabetes, excluding acute complications of labour or birth, or severe acute adverse maternal outcomes. Methods: Searches for relevant studies were carried out to November 2019 in Medline, Embase, CINAHL, PsycINFO and EconLit databases. After initial screening, all results were reviewed for inclusion by two authors. An adapted version of a previously developed checklist for cost-of-illness studies was used for quality appraisal. All costs were converted to 2018 Euro using national consumer price indices and purchasing power parity conversion factors. Results: Thirty-eight relevant studies were identified, some of which reported incremental costs for more than one health problem (16 gestational diabetes, 13 overweight/obesity, 8 mental health, 4 hypertensive disorders, 2 nausea and vomiting, 2 epilepsy, 1 intimate partner violence). A high level of heterogeneity was observed in both the methods used, and the incremental cost estimates obtained for each morbidity. Average incremental costs tended to be higher in studies that modelled a hypothetical cohort of women using data from a range of sources (compared to analyses of primary data), and in studies set in the United States. No studies that examined the economic burden of some common pregnancy-related morbidities, such as incontinence, pelvic girdle pain, or sexual health problems, were identified. Conclusion: Our findings indicate that maternal morbidity is associated with significant costs to health systems and society, but large gaps remain in the evidence base for the economic burden of some common health problems associated with pregnancy and childbirth. More research is needed to examine the economic burden of a range of common maternal health problems, and future research should adopt consistent methodological approaches to ensure comparability of results. [ABSTRACT FROM AUTHOR]

The aims of this study were to determine whether non- aureus staphylococci (NAS) are present in rectal feces of healthy dairy cows, and if so, to delineate species to which they belong and to study several phenotypic and genotypic traits as a first step toward determining the potential impact of fecal shedding of NAS on bovine udder health. Fecal samples were aseptically collected from the rectum of 25 randomly selected clinically healthy dairy cows in a commercial dairy herd using an automated milking system. Fecal NAS were isolated and then identified at the species level using transfer RNA-intergenic spacer PCR and sequencing of the 16S rRNA housekeeping gene. Strain typing was performed using random amplification of polymorphic DNA (RAPD)-PCR. The antimicrobial resistance profiles, biofilm formation, and growth and inhibitory characteristics of all NAS isolates were evaluated. Half of the cows were shedding NAS, resulting in 31 NAS isolates belonging to 11 different species. The most prevalent species were Staphylococcus rostri (23%, n = 7), Staphylococcus cohnii (16%, n = 5), and Staphylococcus haemolyticus (13%, n = 4) with all Staphylococcus agnetis , Staphylococcus chromogenes , and Staph. rostri isolates belonging to the same strain according to RAPD banding patterns. Acquired antimicrobial resistance was observed in 28 of the 31 NAS isolates, mainly due to β-lactamase production. Most of the isolates (84%, n = 27) had a weak biofilm-forming potential, but only 2 contained the bap gene. The ica and aap genes were not detected in any of the isolates. In vitro growth of Staphylococcus aureus and Streptococcus dysgalactiae was inhibited by Staph. agnetis isolates, and Staph. chromogenes isolates were able to inhibit the growth of Strep. dysgalactiae and Streptococcus uberis. All fecal isolates were able to grow when oxygen and iron were limitedly available, mimicking the growth conditions in the mammary gland. [ABSTRACT FROM AUTHOR]

Abstract: Chronic obstructive pulmonary disease is a common, preventable and treatable disease. Exercise training programmes (ETPs) improve symptoms, health‐related quality of life (HRQoL) and exercise capacity, but the optimal setting is unknown. In this review, we compared the effects of ETPs in different settings on HRQoL and exercise capacity. We searched (5 July 2016) the Cochrane Airways Group Specialised Register, ClinicalTrials.gov and World Health Organization trials portal. We selected studies, extracted data and assessed risk of bias with two independent reviewers. We calculated mean differences (MD) with 95% CI. We assessed the quality of evidence using Grades of Recommendation, Assessment, Development and Evaluation. Ten trials (934 participants) were included. Hospital (outpatient) and home‐based ETPs (seven trials) were equally effective at improving HRQoL on the Chronic Respiratory Questionnaire (CRQ) (dyspnoea: MD −0.09, 95% CI: −0.28 to 0.10; fatigue: MD −0.00, 95% CI: −0.18 to 0.17; emotional: MD 0.10, 95% CI: −0.24 to 0.45; and mastery: MD −0.02, 95% CI: −0.28 to 0.25; moderate quality) and on the St George’s Respiratory Questionnaire (SGRQ) (MD −0.82, 95% CI: −7.47 to 5.83, low quality). Hospital (outpatient) and community‐based ETPs (three trials) were equally effective at improving HRQoL (CRQ dyspnoea: MD 0.29, 95% CI: −0.05 to 0.62, moderate quality; fatigue: MD −0.02, 95% CI: −1.09 to 1.05, low quality; emotional: MD 0.10, 95% CI: −0.40 to 0.59, moderate quality; and mastery: MD −0.08, 95% CI: −0.45 to 0.28, moderate quality). There was no difference in exercise capacity. There was low to moderate evidence that outpatient and home‐based ETPs are equally effective. See related Editorial [ABSTRACT FROM AUTHOR]

Background: Changes to physiological parameters precede deterioration of ill patients. Early warning and track and trigger systems (TTS) use routine physiological measurements with pre-specified thresholds to identify deteriorating patients and trigger appropriate and timely escalation of care. Patients presenting to the emergency department (ED) are undiagnosed, undifferentiated and of varying acuity, yet the effectiveness and cost-effectiveness of using early warning systems and TTS in this setting is unclear. We aimed to systematically review the evidence on the use, development/validation, clinical effectiveness and cost-effectiveness of physiologically based early warning systems and TTS for the detection of deterioration in adult patients presenting to EDs.Methods: We searched for any study design in scientific databases and grey literature resources up to March 2016. Two reviewers independently screened results and conducted quality assessment. One reviewer extracted data with independent verification of 50% by a second reviewer. Only information available in English was included. Due to the heterogeneity of reporting across studies, results were synthesised narratively and in evidence tables.Results: We identified 6397 citations of which 47 studies and 1 clinical trial registration were included. Although early warning systems are increasingly used in EDs, compliance varies. One non-randomised controlled trial found that using an early warning system in the ED may lead to a change in patient management but may not reduce adverse events; however, this is uncertain, considering the very low quality of evidence. Twenty-eight different early warning systems were developed/validated in 36 studies. There is relatively good evidence on the predictive ability of certain early warning systems on mortality and ICU/hospital admission. No health economic data were identified.Conclusions: Early warning systems seem to predict adverse outcomes in adult patients of varying acuity presenting to the ED but there is a lack of high quality comparative studies to examine the effect of using early warning systems on patient outcomes. Such studies should include health economics assessments. [ABSTRACT FROM AUTHOR]

Background. Pelvic girdle pain (PGP) is common during pregnancy and negatively affects women's lives. When PGP persists after the birth, the way it affects women's lives may change, particularly for first-time mothers as they adjust to motherhood, yet the experiences of women with persistent PGP remain largely unexplored. Objectives. The objective of this study was to explore primiparous women's experiences of persistent PGP and its impact on their lives postpartum, including caring for their infant and their parental role. Design. This was a descriptive qualitative study. Methods. Following institution ethical approval, 23 consenting primiparous women with PGP that had started during pregnancy and persisted for at least 3 months postpartum participated in individual interviews. These interviews were recorded, transcribed, and analyzed using thematic analysis. Results. Four themes emerged: (1) "Putting up with the pain: coping with everyday life," in which women put up with the pain but had to balance activities and were grateful for support from family and friends to face everyday challenges; (2) "I don't feel back to normal," in which women's feelings of physical limitations, frustration, and a negative impact on their mood were described; (3) "Unexpected," in which persistent symptoms were unexpected for women due to a lack of information given about PGP; and (4) "What next?," in which the future of women's symptoms was met with great uncertainty, and they expressed worry about having another baby. Conclusion, For first-time mothers, having persistent PGP postpartum affects their daily lives in many ways. These findings provide important information for health care providers, which will improve their understanding of these women's experiences, will enhance rapport, and can be used to provide information and address concerns to optimize maternity care during pregnancy and beyond. [ABSTRACT FROM AUTHOR]

Background: A core outcome set (COS) can address problems of outcome heterogeneity and outcome reporting bias in trials and systematic reviews, including Cochrane reviews, helping to reduce waste. One of the aims of the international Core Outcome Measures in Effectiveness Trials (COMET) Initiative is to link the development and use of COS with the outcomes specified and reported in Cochrane reviews, including the outcomes listed in the summary of findings (SoF) tables. As part of this work, an earlier exploratory survey of the outcomes of newly published 2007 and 2011 Cochrane reviews was performed. This survey examined the use of COS, the variety of specified outcomes, and outcome reporting in Cochrane reviews by Cochrane Review Group (CRG). To examine changes over time and to explore outcomes that were repeatedly specified over time in Cochrane reviews by CRG, we conducted a follow-up survey of outcomes in 2013 Cochrane reviews. Methods: A descriptive survey of outcomes in Cochrane reviews that were first published in 2013. Outcomes specified in the methods sections and reported in the results section of the Cochrane reviews were examined by CRG. We also explored the uptake of SoF tables, the number of outcomes included in these, and the quality of the evidence for the outcomes. Results: Across the 50 CRGs, 375 Cochrane reviews that included at least one study specified a total of 3142 outcomes. Of these outcomes, 32 % (1008) were not reported in the results section of these reviews. For 23 % (233) of these non-reported outcomes, we did not find any reason in the text of the review for this non-report. Fifty-seven percent (216/375) of reviews included a SoF table. Conclusions: The proportion of specified outcomes that were reported in Cochrane reviews had increased in 2013 (68 %) compared to 2007 (61 %) and 2011 (65 %). Importantly, 2013 Cochrane reviews that did not report specified outcomes were twice as likely to provide an explanation for why the outcome was not reported. There has been an increased uptake of SoF tables in Cochrane reviews. Outcomes that were repeatedly specified in Cochrane reviews by CRG in 2007, 2011, and 2013 may assist COS development. [ABSTRACT FROM AUTHOR]

Abstract: In this study we aimed to determine and elucidate the effect of ambient air pollution on the foliar antioxidant system and stable carbon and nitrogen isotopes of white willow (Salix alba L.). We grew white willow in uniform potting soil in the near vicinity of sixteen air quality monitoring stations in Belgium where nitrogen dioxide (NO2), ozone, sulfur dioxide and particulate matter concentrations were continuously measured. The trees were exposed to ambient air during six months (April–September 2011), and, thereafter, the degree of lipid peroxidation and foliar content of antioxidant molecules (ascorbate, glutathione, polyphenols, flavonoids), antioxidant enzymes (superoxide dismutase, ascorbate peroxidase, peroxidase) and foliar stable carbon (δ13C) and nitrogen (δ15N) isotopes were measured. We found that lipid peroxidation was caused by air pollution stress, arising from high ambient NO2 concentrations, as shown by an increased amount of malondialdehyde. The antioxidant system was activated by increasing the amount of polyphenols at monitoring stations with a high atmospheric NO2 and low O3 concentration, while no increase of key enzymes (e.g., ascorbate, glutathione) was observed. The δ13C also decreased with increasing NO2 concentrations and decreasing O3 concentrations, probably reflecting a decreased net photosynthesis and/or a concomitant decrease of 13CO2 in the atmosphere. Shade also influenced foliar δ13C and the content of leaf ascorbate and glutathione. [Copyright &y& Elsevier]

Excess Mn2+ in humans causes a neurological disorder known as manganism, which shares symptoms with Parkinson's disease. However, the cellular mechanisms underlying Mn2+-neurotoxicity and the involvement of Mn2+-transporters in cellular homeostasis and repair are poorly understood and require further investigation. In this work, we have analyzed the effect of Mn2+ on neurons and glia from mice in primary cultures. Mn2+ overload compromised survival of both cell types, specifically affecting cellular integrity and Golgi organization, where the secretory pathway Ca2+/ Mn2+- ATPase is localized. This ATP-driven Mn2+ transporter might take part in Mn2+ accumulation/detoxification at low loads of Mn2+, but its ATPase activity is inhibited at high concentration of Mn2+. Glial cells appear to be significantly more resistant to this toxicity than neurons and their presence in cocultures provided some protection to neurons against degeneration induced by Mn2+. Interestingly, the Mn2+ toxicity was partially reversed upon Mn2+ removal by wash out or by the addition of EDTA as a chelating agent, in particular in glial cells. These studies provide data on Mn2+ neurotoxicity and may contribute to explore new therapeutic approaches for reducing Mn2+ poisoning. [ABSTRACT FROM AUTHOR]

As a major Ca2+ pump in the sarcoplasmic reticulum of the cardiomyocyte, SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a) controls the relaxation and contraction of the cardiomyocyte. It is meticulously regulated by adapting its expression levels and affinity for Ca2+ ions to the physiological demand of the heart. Dysregulation of the SERCA2a activity entails poor cardiomyocyte contractility, resulting in heart failure. Conversely, improving cardiac SERCA2a activity, e.g. by boosting its expression level or by increasing its affinity for Ca2+, is a promising strategy to rescue contractile dysfunction of the failing heart. The structures of the related SERCA1a Ca2+ pump and the Na+/K+-ATPase of the plasma membrane exposed the pumping mechanism and conserved domain architecture of these ion pumps. However, how the Ca2+ affinity of SERCA2a is regulated at the molecular level remained unclear. A structural and functional analysis of the closely related SERCA2b Ca2+ pump, i.e. the housekeeping Ca2+ pump found in the endoplasmic reticulum and the only SERCA isoform characterized by a high Ca2+ affinity, aimed to fill this gap. We demonstrated the existence of a novel and highly conserved site on the SERCA2 pump mediating Ca2+ affinity regulation by the unique C-terminus of SERCA2b (2b-tail). It differs from the earlier-described target site of the affinity regulator phospholamban. Targeting this novel site may provide a new approach to improve SERCA2a function in the failing heart. Strikingly, the intramembrane interaction site of the 2btail in SERCA2b shares sequence and structural homology with the binding site of the β-subunit on the a Na+/K+-ATPase. Thus P-type ATPases seem to have developed related mechanisms of regulation, and it is a future challenge for us to discover these general principles of P-type regulation. [ABSTRACT FROM AUTHOR]

To asses self-reported quality of life (QoL) and perception of impact of illness on siblings of children with cystic fibrosis (CF). The Child Health Questionnaire was used to assess QoL. The Sibling Perception Questionnaire was used to assess impact of illness. Siblings of children with CF ( n= 39) rated their QoL higher than siblings of healthy children on most QoL domains (e.g. Physical Functioning, Behavior, Mental Health). Siblings older than the child with CF reported a higher impact of CF than younger siblings. Perceived impact of illness was higher when the child with CF had been hospitalized or was intermittent or chronically infected with Pseudomonas aeruginosa. Siblings of children with CF reported a good QoL. QoL and impact of illness were related to indices of CF severity. Insight into sibling-issues helps CF teams to provide family-oriented care. [ABSTRACT FROM AUTHOR]

A detailed study of the inactivation of Staphylococcus aureus and Yersinia enterocolitica by high-pressure homogenisation was performed at, respectively, 25 and 35 different combinations of process temperature and process pressure covering a range of 5–50 °C and 100–300 MPa. It appeared that in the entire studied pressure–temperature domain, S. aureus was more resistant to high-pressure homogenisation than Y. enterocolitica. Furthermore, the effect of the process pressure on the inactivation of S. aureus was considerably smaller than on the inactivation of Y. enterocolitica. Also, temperature between 5 and 40 °C did not affect inactivation of S. aureus by high-pressure homogenisation, while Y. enterocolitica inactivation was affected by temperature over a much wider range.Different mathematical models were compared to describe the inactivation of both bacteria under the experimental conditions applied. Such pressure–temperature inactivation models form the engineering basis for design, evaluation and optimisation of high-pressure homogenisation processes as a new preservation technique. [Copyright &y& Elsevier]

The speed of contraction of a skeletal muscle largely depends on the myosin heavy chain isoforms (MyHC), whereas the relaxation is initiated and maintained by the sarcoplasmic reticulum Ca[sup 2+]-ATPases (SERCA). The expression of the slow muscle-type myosin heavy chain I (MyHCI) is entirely dependent on innervation, but, as we show here, innervation is not required for the expression of the slow-type sarcoplasmic reticulum Ca[sup 2+]-ATPase (SERCA2a) in regenerating soleus muscles of the rat, although it can play a modulator role. Remarkably, the SERCA2a level is even higher in denervated than in innervated regenerating soleus muscles on day 7 when innervation is expected to resume. Later, the level of SERCA2a protein declines in denervated regenerated muscles but it remains expressed, whereas the corresponding mRNA level is still increasing. SERCA1 (i.e., the fast muscle-type isoform) expression shows only minor changes in denervated regenerating soleus muscles compared with innervated regenerating controls. When the soleus nerve was transected instead of the sciatic nerve, SERCA2a and MyHCI expressions were found to be even more uncoupled because the MyHCI nearly completely disappeared, whereas the SERCA2a mRNA and protein levels decreased much less. The transfection of regenerating muscles with constitutively active mutants of the Res oncogene, known to mimic the effect of innervation on the expression of MyHCI, did not affect SERCA2a expression. These results demonstrate that the regulation of SERCA2a expression is clearly distinct from that of the slow myosin in the regenerating soleus muscle and that SERCA2a expression is modulated by neuronal activity but is not entirely dependent on it. [ABSTRACT FROM AUTHOR]

Garden cress, sesame, radish, and mustard seeds immersed in water were treated with high pressure (250, 300, 350, and 400 MPa) for 15 min at 20°C. After treatment, percentages of seeds germinating on water agar were recorded for up to 11 days. Of the seeds tested, radish seeds were found to be the most pressure sensitive, with seeds treated at 250 MPa reaching 100% germination 9 days later than untreated control seeds did. Garden cress seeds, on the other hand, were the most pressure resistant, with seeds treated at 250 MPa reaching 100% germination 1 day later than untreated control seeds did. Garden cress sprouts from seeds treated at 250 and 300 MPa also took about 1 day longer to reach average sprout length than sprouts from untreated control seeds did, indicating that sprout growth was not retarded once germination had occurred. Garden cress seeds were inoculated with suspensions of seven different bacteria (10[sup 7] CFU/ml) and processed with high pressure. Treatment at 300 MPa (15 min, 20°C) resulted in 6-log reductions of Salmonella Typhimurium, Escherichia coli MG1655, and Listeria innocua, >4-log reductions of Shigella fiexneri and pressure-resistant E. coli LMM1010, and a 2-log reduction of Staphylococcus aureus. Enterococcus faecalis was virtually not inactivated. For suspensions of the gram-positive bacteria, similar levels of inactivation in water in the absence of garden cress seeds were found, but the inactivation of E. coli LMM1010 and S. flexneri in water in the absence of garden cress seeds was significantly less extensive. These data suggest that garden cress seeds contain a component that acts synergistically with high hydrostatic pressure against gram-negative bacteria. [ABSTRACT FROM AUTHOR]

Besides the well-known sarco/endoplasmic-reticulum Ca2+-transport ATPases (SERCA), animal cells contain a much less characterized P-type Ca2+-transport ATPase: the PMR1/SPCA Ca2+/Mn2+-transport ATPase. SPCA is mainly targeted to the Golgi apparatus. Phylogenetic analysis indicates that it might be more closely related to a putative ancestral Ca2+ pump than SERCA. SPCA supplies the Golgi apparatus, and possibly other more distal compartments of the secretory pathway, with the Ca2+ and Mn2+ necessary for the production and processing of secretory proteins. In the lactating mammary gland, SPCA appears to be the primary pump responsible for supplementing the milk with high (60–100 mM) Ca2+. It could also play a role in detoxification of cells overloaded with Mn2+. Mutations in the human gene encoding the SPCA pump (ATP2C1) result in Hailey–Hailey disease, a keratinocyte disorder characterized by incomplete cell adhesion. Recent observations show that the Golgi apparatus can function as a Ca2+ store, which can be involved in setting up cytosolic Ca2+ oscillations. [ABSTRACT FROM AUTHOR]

We have studied sublethal injury in Salmonella enterica serovar Typhimurium caused by mild heat and by different emerging nonthermal food preservation treatments, i.e., high-pressure homogenization, high hydrostatic pressure, pulsed white light, and pulsed electric field. Sublethal injury was determined by plating on different selective media, i.e., tryptic soy agar (TSA) plus 3% NaCl, TSA adjusted to pH 5.5, and violet red bile glucose agar. For each inactivation technique, at least five treatments using different doses were applied in order to cover an inactivation range of 0 to 5 log units. For all of the treatments performed with a technique, the logarithm of the viability reductions measured on each of the selective plating media was plotted against the logarithm of the viability reduction on TSA as a nonselective medium, and these points were fitted by a straight line. Sublethal injury between different techniques was then compared by the slope and the y intercept of these regression lines. The highest levels of sublethal injury were observed for the heat and high hydrostatic pressure treatments. Sublethal injury after those treatments was observed on all selective plating media. For the heat treatment, but not for the high-pressure treatment, sublethal injury occurred at low doses, which were not yet lethal. The other nonthermal techniques resulted in sublethal injury on only some of the selective plating media, and the levels of injury were much lower. The different manifestations of sublethal injury were attributed to different inactivation mechanisms by each of the techniques, and a mechanistic model is proposed to explain these differences. [ABSTRACT FROM AUTHOR]

The resistance of five gram-positive bacteria, Enterococcus faecalis, Staphylococcus aureus, Lactobacillus plantarum, Listeria innocua and Leuconostoc dextranicum, and six gram-negative bacteria, Salmonella enterica serovar typhimurium, Shigella flexneri, Yersinia enterocolitica, Pseudomonas fluorescens and two strains of Escherichia coli, to high-pressure homogenisation (100–300 MPa) and to high hydrostatic pressure (200–400 MPa) was compared in this study. Within the group of gram-positive bacteria and within the group of gram-negative bacteria, large differences were observed in resistance to high hydrostatic pressure, but not to high-pressure homogenisation. All gram-positive bacteria were more resistant than any of the gram-negative bacteria to high-pressure homogenisation, while in relative to high hydrostatic pressure resistance both groups overlapped. Within the group of gram-negative bacteria, there also existed another order in resistance to high-pressure homogenisation than to high hydrostatic pressure. Further it appears that the mutant E. coli LMM1010, which is resistant to high hydrostatic pressure is not more resistant to high-pressure homogenisation than its parental strain MG1655. The preceding observations indicate a different response of the test bacteria to high-pressure homogenisation compared to high hydrostatic pressure treatment, which suggests that the underlying inactivation mechanisms for both techniques are different.Further, no sublethal injury could be observed upon high-pressure homogenisation of Y. enterocolitica and S. aureus cell population by using low pH (5.5–7), NaCl (0–6%) or SDS (0–100 mg/l) as selective components in the plating medium.Finally, it was observed that successive rounds of high-pressure homogenisation have an additive effect on viability reduction of Y. enterocolitica and S. aureus. [Copyright &y& Elsevier]

Examines the relationship between pressure- and nutrient-induced germination of Bacillus subtilis spores. Selection of B. subtilis mutants affected in pressure-induced germination; Effect of different germination stimuli on specific germination mutants; Germination response of H-spores; Impact of inhibitors of nutrient-induced spore germination.

Presents a systematic memory management methodology for embedded network applications. Network management of modern telecommunication systems; Industrial application of the methodology; Conclusions.

Two commercial antifungal susceptibility testing systems (Fungitest® and Neo-Sensitabs®) were compared with the M27T-NCCLS reference broth microdilution method using one hundred isolates of Candida sp. and Cryptococcus neoformans. Six different antifungal drugs were tested: amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole and miconazole. The overall agreement between the Fungitest and the reference methods was much better than between the Neo-Sensitabs and the reference methods: the agreement for the Fungitest ranged from 100% for amphotericin B to 76.7% for itraconazole whereas for the Neo-Sensitabs, it ranged from 90.4% for amphotericin B to 36% for ketoconazole. For the total number of tests performed with Neo-Sensitabs, there were 37.8% of discrepancies with the reference method whereas for the tests performed with Fungitest, there was only 16.5% of discrepancies. Major discrepancies, defined as results that classified an isolate as susceptible by one method and resistant by another, occurred in 21 cases for the Neo-Sensitabs test and only in four cases with the Fungitest, namely 0.6% of the cases. We conclude that the Fungitest method constitutes a simple and reliable procedure for antifungal drug susceptibility testing. [ABSTRACT FROM AUTHOR]

Presents a study on the pressure-induced germination of Bacillus subtilis (B. subtilis) spores. Germination and inactivation of B. subtilis spores by high pressure; Comparison of the sensitivity of spores germinated at both high and low pressure; In-depth look at the results of the study.

Introduction and hypothesis: Considerable proportions of pregnant and postpartum women experience urinary incontinence, but to our knowledge, there are no national data on the preventative and treatment services available in Ireland's 19 maternity hospitals. Methods: Ethical approval was granted. A national benchmarking survey on the range and type of services on prevention and treatment of urinary incontinence during pregnancy and postpartum was developed. Directors of Midwifery and Nursing in each hospital identified midwives and women's health physiotherapists to complete the survey. Data were analysed descriptively, and results presented as proportions. Results: Responses were received from 17 hospitals. Women were asked about urinary incontinence during their first booking visit in 6 hospitals, during all antenatal visits in 2 and the onus was on women self-reporting symptoms in 9. Pelvic floor muscle exercises were taught in antenatal classes in 14 hospitals and management of urinary incontinence in 9. In hospital postpartum, midwives in 13 hospitals asked women about urinary incontinence. All women were seen by a physiotherapist in 7 hospitals and only those who were referred in 6. Women could access the hospital's physiotherapy services up to 6 weeks postpartum in 3 hospitals, up to 6 months or 1 year in 5 and beyond 1 year in 6. Conclusions: Geographical inequity exists in the services offered to pregnant and postpartum women nationally. This indicates that many pregnant and postpartum women, both continent and incontinent, cannot avail themselves of preventative and treatment services within the maternity hospital system and points to the need to review, reconfigure and resource services. [ABSTRACT FROM AUTHOR]

The article introduces the issue which includes research articles about adenosine triphosphate enzymes (ATPases).

Background: Pregnancy-related Pelvic Girdle Pain (PPGP) is a common complaint. The aetiology remains unclear and reports on risk factors for PPGP provide conflicting accounts. The aim of this scoping review was to map the body of literature on risk factors for experiencing PPGP.Methods: We searched the databases PubMed, Embase, CINAHL, PsycINFO, MIDIRS, and ClinicalTrial.gov (3 August 2020). We selected studies with two reviewers independently. Observational studies assessing risk factors for PPGP were included. Studies examining specific diagnostic tests or interventions were excluded.Results: We identified 5090 records from databases and 1077 from ClinicalTrial.gov. Twenty-four records met the inclusion criteria. A total of 148 factors were examined of which only 14 factors were examined in more than one study. Factors that were positively associated with PPGP included a history of low back or pelvic girdle pain, being overweight/obese, already having a child, younger age, lower educational level, no pre-pregnancy exercise, physically demanding work, previous back trauma/disease, progestin-intrauterine device use, stress, depression and anxiety.Conclusions: A large number of factors have been examined as potential risk factors for PPGP, but there is a lack of repetition to be able to draw stronger conclusions and pool studies in systematic reviews. Factors that have been examined in more than five studies include age, body mass index, parity and smoking. We suggest a systematic review be conducted to assess the role of these factors further in the development of PPGP. [ABSTRACT FROM AUTHOR]

There is a high level of medication usage among people with intellectual disability due to the presence of significant morbidity and co-morbidities. This review sought to explore medication management and administration in intellectual disability settings, identifying frameworks for practice, analysing whether collaborative practice led to better outcomes, identifying key processes associated with practice, locating tools to support practice and describing metrics for outcome measurement. A systematic review was conducted with analysis of 64 sources which remained following screening and appraisal. Limited evidence was identified with some insight into the processes underpinning medication management and administration. No assessment tools were found, but two potential outcome measures, adherence and errors, were noted. The paucity of guidelines and frameworks is concerning as this is a complex area of practice. There is a need for further practice development and research to be undertaken that takes note of the unique issues that can present in intellectual disability settings. [ABSTRACT FROM AUTHOR]

Background: Systematic reviews of randomised trials guide policy and healthcare decisions. Yet, we observed that some reviews judge randomised trials as high or unclear risk of bias (ROB) for sequence generation, potentially introducing bias. However, to date, the extent of this issue has not been well examined. We evaluated the consistency in the ROB assessment for sequence generation of randomised trials in Cochrane and non-Cochrane reviews, and explored the reviewers' judgement of the quality of evidence for the related outcomes. Methods: Cochrane intervention reviews (01/01/2017–31/03/2017) were retrieved from the Cochrane Database of Systematic Reviews. We also searched for systematic reviews in ten general medical journals with highest impact factors (01/01/2016–31/03/2017). We examined the proportion of reviews that rated the sequence generation domain as high, low or unclear risk of selection bias. For reviews that had rated any randomised trials as high or unclear risk of bias, we examined the proportion that had assessed the quality of evidence. Results: Overall, 100 systematic reviews were included in our analysis. We evaluated 64 Cochrane reviews which comprised of 984 randomised trials; 0.8% (n = 8) and 52.2% (n = 514) were rated as high and unclear ROB for sequence generation respectively. We further evaluated 36 non-Cochrane reviews which comprised of 1376 trials; 5.8% (n = 80) and 39.6% (n = 545) were rated as high and unclear ROB respectively. Ninety percent (n = 10) of non-Cochrane reviews which rated randomised trials as high ROB for sequence generation did not report an underlying reason. All Cochrane reviews assessed the quality of evidence (GRADE). For the non-Cochrane reviews, only just over half had assessed the quality of evidence. Conclusion: Systematic reviews of interventions frequently rate randomised trials as high or unclear ROB for sequence generation. In general, Cochrane reviews were more transparent than non-Cochrane reviews in ROB and quality of evidence assessment. The scientific community should more strongly promote consistent ROB assessment for sequence generation to minimise selection bias and support transparent quality of evidence assessment. Consistency ensures that appropriate conclusions are drawn from the data. [ABSTRACT FROM AUTHOR]

Background: Pelvic Girdle Pain (PGP) is an important cause of disability and economic cost worldwide. There is a need for effective preventative and management strategies. Emerging studies measure a variety of outcomes rendering synthesis and translation to clinical practice difficult. A Core Outcome Set (COS) can address this problem by ensuring that data are relevant, useful and usable for making well-informed healthcare choices. The aim of this study is to develop a consensus-based PGP-COS, including agreement on methods (e.g. instruments) for measuring the construct outcomes in the COS for use in research and clinical practice. Furthermore, as there is uncertainty as to whether incorporating stakeholder interviews in addition to conducting a systematic review to determine an initial list of outcomes for the Delphi survey, or, whether using different rating scales in a Delphi survey impacts on the final COS, we propose to embed two methodological studies within the PGP-COS development process to address these questions.Methods: The PGP-COS study will include five phases: (1) A systematic review of the literature and semi-structured interviews with 15 patients (three countries) to form the initial list of outcomes for the Delphi survey; (2) A 3-round Delphi including patients, clinicians, researchers and service providers; (3) A systematic review of methods for measuring the outcomes in the preliminary PGP-COS identified in the Delphi survey; (4) A face-to-face consensus meeting to agree on the final PGP-COS and methods for measuring the COS; (5) Global dissemination. To address the methodological questions, we will assess the number and type of outcomes, in the final PGP-COS, that were exclusively derived from the interviews. Secondly, we will randomise Delphi survey participants to either a 5-point or 9-point importance rating scale, and examine potential differences in 'important' ratings between the groups.Discussion: There is currently no COS for measuring/monitoring PGP in trials and clinical practice. A PGP-COS will ensure that relevant outcomes are measured using appropriate measurement instruments for patients with PGP globally.Core Outcome Set Registration: This PGP-COS was registered with COMET (Core Outcome Measures for Effectiveness Trials) in January 2017 ( http://www.comet-initiative.org/studies/details/958 ). [ABSTRACT FROM AUTHOR]

Background: As the development of core outcome sets (COS) increases, guidance for developing and reporting high-quality COS continues to evolve; however, a number of methodological uncertainties still remain. The objectives of this study were: (1) to explore the impact of including patient interviews in developing a COS, (2) to examine the impact of using a 5-point versus a 9-point rating scale during Delphi consensus methods on outcome selection and (3) to inform and contribute to COS development methodology by advancing the evidence base on COS development techniques.Methods: Semi-structured patient interviews and a nested randomised controlled parallel group trial as part of the Pelvic Girdle Pain Core Outcome Set project (PGP-COS). Patient interviews, as an adjunct to a systematic review of outcomes reported in previous studies, were undertaken to identify preliminary outcomes for including in a Delphi consensus survey. In the Delphi survey, participants were randomised (1:1) to a 5-point or 9-point rating scale for rating the importance of the list of preliminary outcomes.Results: Four of the eight patient interview derived outcomes were included in the preliminary COS, however, none of these outcomes were included in the final PGP-COS. The 5-point rating scale resulted in twice as many outcomes reaching consensus after the 3-round Delphi survey compared to the 9-point scale. Consensus on all five outcomes included in the final PGP-COS was achieved by participants allocated the 5-point rating scale, whereas consensus on four of these was achieved by those using the 9-point scale.Conclusions: Using patient interviews to identify preliminary outcomes as an adjunct to conducting a systematic review of outcomes measured in the literature did not appear to influence outcome selection in developing the COS in this study. The use of different rating scales in a Delphi survey, however, did appear to impact on outcome selection. The 5-point scale demonstrated greater congruency than the 9-point scale with the outcomes included in the final PGP-COS. Future research to substantiate our findings and to explore the impact of other rating scales on outcome selection during COS development, however, is warranted. [ABSTRACT FROM AUTHOR]

Background: Women's experiences of pregnancy, birth and motherhood extend beyond healthcare provision and the immediate postpartum. Women's social, cultural and political environments shape the positive or negative effects of their experiences through this transition. However, there is limited research concerning the factors that women identify as being protective or promotive of maternal well‐being in the perinatal period and motherhood transition. Objective: To explore women's views on the factors within healthcare, social, cultural, organizational, environmental and political domains that do or can work well in creating positive perinatal experiences. Design, Setting and Participants: A qualitative descriptive study with embedded public and participant involvement (PPI). Participants were 24 women who were maternity care service users giving birth in Ireland. Results: Three themes were developed. The first theme, 'tone of care', related to women's interactions with and attitudes of healthcare professionals in setting the tone for the care they experienced. The second theme, 'postpartum presence and support', concerned the professional postpartum supports and services that women found beneficial in the motherhood transition. The final theme, 'flexibility for new families' addresses social and organizational issues around parents returning to paid employment. Discussion and Conclusion: Women suggested multiple avenues for promoting positive perinatal experiences for women giving birth in Ireland, which may be implemented at healthcare and policy levels. Women identified that maternal health education focuses on supporting informed decision‐making processes as a positive and worry‐alleviating resource. Additionally, women valued being met by healthcare professionals who regard women as the decision makers in their care experience. Exchanges in which healthcare professionals validate and encourage women in their mothering role and actively involve their partners as caregivers left lasting positive impressions. Extended and professional postpartum support was a common issue, and phone lines or drop‐in clinics were suggested as invaluable and affirming assets where women could access personalized support with healthcare professionals who had the knowledge and skills to genuinely approach women's concerns. Social and organizational considerations involved supporting parents to balance their responsibilities as new or growing families in the return to work. Public or Patient Contribution: Maternity care service users were involved in the interviews and manuscript preparation. [ABSTRACT FROM AUTHOR]

Women's postpartum health is a public health issue that has lifelong consequences. Timely recognition and treatment of physical and mental health issues can have positive health consequences while lack of access to effective treatments or health care services can lead to long-term health problems. To advance knowledge of priority health symptoms and trajectories of postpartum recovery from women's health perspectives, we share findings from the Maternal health And Maternal Morbidity in Ireland (MAMMI) study. Data from 3047 first-time mothers recruited to a longitudinal maternal health study in Ireland from 2012 to 2017 reveal the trajectories of maternal health and health problems experienced up to 12 months postpartum. Morbidities explored include urinary incontinence, pelvic girdle pain, and sexual and mental health issues. Viewed together, and over time, the scale and persistent nature of many physical and mental health problems become apparent, yet considerable proportions of women were not asked directly about health problems by health care professionals. When women do not know what is and is not normal postpartum, they may suffer in silence and the consequence is that health problems/issues that are preventable, and treatable, are likely to become chronic. To make positive contributions to women's health, maternity care systems must be truly woman-centered and structured in ways that place emphasis on women's own health needs. In systems where women's voices and concerns are acknowledged and central, women are likely to thrive and flourish in motherhood. [ABSTRACT FROM AUTHOR]

The molecular mechanism underlying the characteristic high apparent Ca2+ affinity of SERCA2b relative to SERCA1a and SERCA2a isoforms was studied. The C-terminal tail of SERCA2b consists of an 11th transmembrane helix (TM11) with an associated 11-amino acid luminal extension (LE). The effects of each of these parts and their interactions with the SERCA environment were examined by transient kinetic analysis of the partial reaction steps in the Ca2+ transport cycle in mutant and chimeric Ca2+-ATPase constructs. Manipulations to the LE of SERCA2bmarkedly increased the rate of Ca2+dissociation from Ca2E1. Addition of the SERCA2b tail to SERCA1a slowed Ca2+ dissociation, but only when the luminal L7/8 loop of SERCA1 was simultaneously replaced with that of SERCA2, thus suggesting that the LE interacts with L7/8 in Ca2E1. The interaction of LE with L7/8 is also important for the low rate of the Ca2E1P → E2P conformational transition. These findings can be rationalized in terms of stabilization of the Ca2E1 and Ca2E1P forms by docking of the LE near L7/8. By contrast, low rates of E2P dephosphorylation and E2 → E1 transition in SERCA2b depend critically on TM11, particularly in a SERCA2 environment, but do not at all depend on the LE or L7/8. This indicates that interaction of TM11 with SERCA2-specific sequence element(s) elsewhere in the structure is critical in the Ca2+-free E2/E2P states. Collectively these properties ensure a higher Ca2+ affinity of SERCA2b relative to other SERCA isoforms, not only on the cytosolic side, but also on the luminal side. [ABSTRACT FROM AUTHOR]

The neonatal isoform of the sarcoplasmic/endoplasmic reticulum Ca ATPase 1 (SERCA1b) is a dominant Ca pump in the young fibers of regenerating muscle. In vivo transfection of about 1% of the fibers with SERCA1b RNAi plasmid resulted in no apparent change in the transfected fibers, but enhanced the increase of fresh weight and fiber size in the whole regenerating rat soleus muscle, until the normal size was reached. Co-transfection of calcineurin inhibitor cain/cabin-1 with SERCA1b RNAi was sufficient to cut down the widespread growth stimulation, but the subsequent transfection of cain into the SERCA1b RNAi transfected muscle did not inhibit muscle growth. The SERCA1b RNAi preferably upregulated the expression of the NFAT reporter lacZ compared to controls when co-transfected into the fibers. Notably, perimuscular injection of interleukin-4 (IL-4) antibody but not that of an unrelevant antibody completely abolished the growth-promoting effect of SERCA1b RNAi. This indicates that silencing SERCA1b in a few fibers stimulates the calcineurin-NFAT-IL-4 pathway and fiber growth in the whole regenerating soleus. These results suggest the presence of an autocrine-paracrine coordination of growing muscle fibers, and put forward a new method to stimulate skeletal muscle regeneration. [ABSTRACT FROM AUTHOR]

Heart failure is the leading cause of death in western countries and is often associated with impaired Ca2+ handling in the cardiomyocyte. In fact, cardiomyocyte relaxation and contraction are tightly controlled by the activity of the cardiac sarco(endo)plasmic reticulum (ER/SR) Ca2+ pump SERCA2a, pumping Ca2+ from the cytosol into the lumen of the ER/SR. This review addresses three important facets that control the SERCA2 activity in the heart. First, we focus on the alternative splicing of the SERCA2 messenger, which is strictly regulated in the developing heart. This splicing controls the formation of three SERCA2 splice variants with different enzymatic properties. Second, we will discuss the role and regulation of SERCA2a activity in the normal and failing heart. The two well-studied Ca2+ affinity modulators phospholamban and sarcolipin control the activity of SERCA2a within a narrow window. An aberrantly high or low Ca2+ affinity is often observed in and may even trigger cardiac failure. Correcting SERCA2a activity might therefore constitute a therapeutic approach to improve the contractility of the failing heart. Finally, we address the controversies and unanswered questions of other putative regulators of the cardiac Ca2+ pump, such as sarcalumenin, HRC, S100A1, Bcl-2, HAX-1, calreticulin, calnexin, ERp57, IRS-1, and -2. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Extracellular agonists increase the cytosolic free Ca2+ concentration ([Ca2+]c) by Ca2+ influx and by stimulating Ca2+ release from intracellular stores, mainly the endoplasmic reticulum and to a lesser extent also later compartments of the secretory pathway, particularly the Golgi. The Golgi takes up Ca2+ via Sarco/Endoplasmic Reticulum Ca2+ ATPases (SERCAs) and the Secretory-Pathway Ca2+ ATPases (SPCAs). The endogenous expression of SERCAs and SPCAs neutrophils was demonstrated by Western blotting and immunocytochemistry. Up till now, all cytosolic Ca2+ transients due to intracellular Ca2+ release have been found to originate from SERCA-dependent stores. We found that human neutrophils also present Ca2+ release from a SERCA-independent store. Changes in [Ca2+]c of neutrophils were investigated during chemokinesis induced by chemotactic factors in Ca2+-free solution with and without the SERCA-specific inhibitor thapsigargin. Using N-formyl-methionyl-leucyl-phenylalanine or interleukin-8 as agonists, Ca2+ release from intracellular stores was observed in respectively about 40% and 20% of the neutrophils pre-treated with Ca2+-free solution and thapsigargin. In the latter condition, 20–30% of the cells preserved migratory behaviour. These results indicate that both SERCA-dependent and SERCA-independent (presumably SPCA-dependent) intracellular Ca2+ stores contribute to Ca2+ signaling during chemokinesis of human neutrophil granulocytes. [Copyright &y& Elsevier]

Abstract: The inactivation of Escherichia coli MG1655 by high-pressure homogenisation (HPH) at pressures ranging from 100 to 300 MPa was studied in buffered suspensions adjusted to different relative viscosities (1.0, 1.3, 1.7, 2.7 and 4.9) with polyethylene glycol 6000 (PEG 6000). The water activity of these suspensions was not significantly affected by this high molecular weight solute. Bacterial inactivation was found to decrease with increasing viscosity of the suspensions, an effect that was more pronounced at higher pressures. To study the effect of water activity, series of E. coli suspensions having a different water activity (0.953–1.000) but the same relative viscosity (1.3, 1.7, 2.7 and 4.9) were made using PEG of different molecular weights (400, 600, 1000 and 6000), and subjected to HPH treatment. The results indicated that water activity does not influence inactivation. Finally, inactivation of E. coli MG1655 by HPH in skim milk, soy milk and strawberry–raspberry milk drink was found to be the same as in PEG containing buffer of the corresponding viscosity. These results identify fluid viscosity as a major environmental parameter affecting bacterial inactivation by HPH, as opposed to water activity and product composition, and should contribute to the development of HPH applications for the purpose of bacterial inactivation. [Copyright &y& Elsevier]

Abstract: The inactivation of Escherichia coli MG1655 was studied at 256 different pressure (150–600 MPa)–temperature (5–45 °C) combinations under isobaric and isothermal conditions in Hepes–KOH buffer (10 mM, pH 7.0) and in fresh carrot juice. A linear relationship was found between the log10 of inactivation and holding time for all pressure–temperature combinations in carrot juice, with R2-values≥0.91. Decimal reduction times (D-values), calculated for each pressure–temperature combination, decreased with pressure at constant temperature and with temperature at constant pressure. Further, a linear relationship was found between log10 D and pressure and temperature. A first order kinetic model, describing log10 D in carrot juice as a function of pressure and temperature was formulated that allows to identify process conditions (pressure, temperature, holding time) resulting in a desired level of inactivation of E. coli. For Hepes–KOH buffer, the Weibull model more accurately described the entire set of inactivation curves of E. coli MG1655 compared to the log-linear or the biphasic model. Several secondary models (first and second order polynomial and Weibull) were evaluated, but all had poor fitting capacities. When the Hepes–KOH dataset was limited to 22 of the 34 pressure–temperature combinations, a first order model was appropriate and enabled us to use the same model structure as for carrot juice, for comparative purposes. The major difference in kinetic behaviour of E. coli in buffer and in carrot juice was that inactivation rate as a function of temperature showed a minimum around 20–30 °C in buffer, whereas it increased with temperature over the entire studied temperature range in carrot juice. [Copyright &y& Elsevier]

Abstract: This study investigates to what extent the expression of the slow myosin heavy chain (MyHCI) isoform and the slow type sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) isoform are co-regulated in fibers of regenerating skeletal soleus muscle. Both overexpression of cain, a calcineurin inhibitor, or partial tenotomy prevented the expression of MyHCI but left SERCA2a expression unaffected in fibers of regenerating soleus muscles. These data complement those from different experimental models and clearly show that the expression of MyHCI and SERCA2a – the major proteins mediating, respectively, the slow type of contraction and relaxation – are not coregulated in regenerating soleus muscle. [Copyright &y& Elsevier]

Cryptococcosis was diagnosed postmortem in a striped grass mouse ( Lemniscomys barbarus) housed in the nocturnal department of Antwerp Zoo. Eight of the remaining mice in the cage were captured. Cryptococcus neoformans was isolated from the lung of one animal. Two mice had an elevated serum cryptococcal antigen titre. On examination of the pooled faecal samples collected from 17 animal species housed in 23 cages of the nocturnal department, the pathogenic yeast was isolated from the faeces of the striped grass mice and a degu ( Octodon degus). Numerous Cr. neoformans colonies were isolated from a tree-trunk, tree-stumps, and decaying wood collected from a hollow tree used to decorate the animals cage. Subsequent examination in four other cages of the nocturnal department revealed that all the sampled tree-trunks were colonized by Cr. neoformans. The fungus was isolated from the air sampled in the cage of the degu. Air samples collected in the public and service corridors remained negative. All the isolated strains were identified as Cr. neoformans var. neoformans serotype A. [ABSTRACT FROM AUTHOR]

The level of active subunit of calcineurin and the calcineurin (Cn) enzyme activity are increased in innervated but not in denervated slow type regenerating skeletal soleus muscle. These nerve-dependent increases were not accompanied by similar increases in the mRNA levels. The changes in the mRNA level of the modulatory calcineurin interacting protein, MCIP1.4, reflected the calcineurin activity and did not increase in denervated regenerating muscles compared to the innervated regenerating controls. The increases in Cn activity and in MCIP1.4 mRNA levels occurred before the switch from fast to slow-type myosin heavy chain isoforms, a phenomenon similarly known to be dependent on innervation. This highlights the role of mediators, acting between the nerve and calcineurin, in the formation of slow fiber identity. [Copyright &y& Elsevier]

Sodium concentrations as low as 2 mM exerted a significant protective effect on the high-pressure inactivation (160–210 MPa) of Rhodotorula rubra at pH 6.5, but not on two other yeasts tested (Shizosaccharomyces pombe and Saccharomyces cerevisiae). A piezoprotective effect of similar magnitude was observed with Li+ (2 and 10 mM), and at elevated pH (8.0–9.0), but no effect was seen with K+, Ca2+, Mg2+, Mn2+, or NH4+. Intracellular Na+ levels in cells exposed to low concentrations of Na+ or to pH 8.0–9.0 provided evidence for the involvement of a plasma membrane Na+/H+ antiporter and a correlation between intracellular Na+ levels and pressure resistance. The results support the hypothesis that moderate high pressure causes indirect cell death in R. rubra by inducing cytosolic acidification. [ABSTRACT FROM AUTHOR]

It has been reported that muscles of myoD−/− mice present a lower potential to regenerate, but there are no reports on the effect of acute interference with myoD expression limited in space and time to only a particular regenerating muscle. Here we relied on antisense inhibition of this factor. Four different oligos were tested. The suppression of regeneration indices (the expression of desmin, the formation of myotubes and the initiation of endplates) was the most pronounced, with the oligomer targeting a region encompassing the translation start site of myoD. A mixed backbone phosphorothioate–phosphate diester oligo (200 μl at 20 μM) was still detectable in the muscles 1 h after its administration and reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the level of the targeted 5′ end of the myoD mRNA was selectively decreased. The level of myoD protein was also lowered. Four hours after the antisense treatment, when the oligos were no longer detectable, the myoD mRNA level was restored and 24 h later it exceeded controls together with that of myf-5 and myogenin. After 4 weeks, the antisense-treated soleus muscles were similar to the control-treated and the untreated regenerated soleus with respect to fiber types and motor endplates, however, they contained smaller fibers which reflected the asynchronity of regeneration. This shows that successfully targeted simple antisense oligonucleotides can be used as selective tools for inhibition of individual factors in studying the process of muscle regeneration. [Copyright &y& Elsevier]

Background: Inconsistent reporting of outcomes in clinical trials of women with Pelvic Girdle Pain (PGP) hinders comparison of findings and the reliability of evidence synthesis. A core outcome set (COS) can address this issue as it defines a minimum set of outcomes that should be reported in all clinical trials on the condition. The aim of this study was to develop a consensus-based COS for evaluating the effectiveness of interventions in PGP during pregnancy and postpartum for use in research and clinical practice. Methods: A systematic review of previous studies on PGP and semi-structured interviews with women were undertaken to identify all outcomes that were reported in prior studies and that are relevant to those experiencing the condition. Key stakeholders (clinicians, researchers, service providers/policy makers and individuals with PGP) then rated the importance of these outcomes for including in a preliminary PGP-COS using a 3-round Delphi study. The final COS was agreed at a face-to-face consensus meeting. Results: Consensus was achieved on five outcomes for inclusion in the final PGP-COS. All outcomes are grouped under the "life impact" domain and include: pain frequency, pain intensity/severity, function/disability/activity limitation, health-related quality of life and fear avoidance. Conclusion: This study identified a COS for evaluating the effectiveness of interventions in pregnancy-related and postpartum-related PGP in research and clinical settings. It is advocated that all trials, other non-randomised studies and clinicians in this area use this COS by reporting these outcomes as a minimum. This will ensure the reporting of meaningful outcomes and will enable the findings of future studies to be compared and combined. Future work will determine how to measure the outcomes of the PGP-COS. Core outcome set registration: This PGP-COS was registered with COMET (Core Outcome Measures for Effectiveness Trials) in January 2017 (http://www.comet-initiative.org/studies/details/958). [ABSTRACT FROM AUTHOR]

The incidence of milk leakage (ML) after dry-off (DO) and related risk factors was studied in 1,175 dairy cows from 41 commercial herds in 8 European countries: Belgium, Czech Republic, Denmark, France, Germany, Italy, the Netherlands, and Spain. Milk leakage was assessed twice for 30 s each during 3 visits at 20 to 24 h, 30 to 34 h, and 48 to 52 h after DO. Information related to dry-cow management and udder health was collected at herd and cow level, including individual somatic cell count (ISCC) from test-day controls and occurrence of clinical mastitis cases from DO until 30 d in lactation. Mixed-effect logistic regression analyses were used to identify possible risk factors for ML and to study the association between ML and new intramammary infections. Intramammary infections were defined as clinical mastitis cases during the dry period and in the first 30 d in lactation or a rise in ISCC from before to after the dry period (threshold: 200,000 cells/mL) or both. Milk leakage was observed in 24.5% of the cows between 20 and 52 h after DO, where the herd incidence varied between 0.0 and 77.8%. The reduction in number of milkings in the weeks before DO had statistically significant effect on the ML incidence. When the milking frequency was reduced from 3 times/d to 2 or maintained at twice a day, cows had 11 (95% CI = 3.43–35.46) or 9 (95% CI = 1.85–48.22) times higher odds of leaking milk, respectively, compared with cows where the milking frequency was reduced from twice to once a day. Also, the milk production 24 h before DO was associated with ML incidence. Hence, cows with a milk production between 13 and 21 L or above 21 L had 2.3 (95% CI = 1.48–3.53) and 3.1 (95% CI = 1.79–5.3) times higher odds of leaking milk, respectively, compared with cows with a milk production below 13 L. A higher ML incidence was present in the group of cows with an average ISCC in the last 3 mo before DO ≥200,000 cells/mL (odds ratio = 1.7; 95% CI = 1.13–2.41) compared with cows with an average ISCC <100,000 cells/mL. Quarters with ML tended to have 2.0 times higher odds of developing clinical mastitis compared with quarters not leaking milk. Cows with ML tended to have 1.5 times higher odds of intramammary infections (i.e., an increase of ISCC or clinical mastitis) compared with cows without ML. [ABSTRACT FROM AUTHOR]

Caesarean section (CS) rates throughout Europe have risen significantly over the last two decades. As well as being an important clinical issue, these changes in mode of birth may have substantial resource implications. Policy initiatives to curb this rise have had to contend with the multiplier effect of women who had a CS for their first birth having a greater likelihood of requiring one during subsequent births, thus making it difficult to decrease CS rates in the short term. Our study examines the long-term resource implications of reducing CS rates among first-time mothers, as well as improving rates of vaginal birth after caesarean section (VBAC), among an annual cohort of women over the course of their most active childbearing years (18 to 44 years) in two public health systems in Europe. We found that the economic benefit of improvements in these two outcomes is considerable, with the net present value of the savings associated with a five-percentage-point change in nulliparous CS rates and VBAC rates being €1.1million and £9.8million per annual cohort of 18-year-olds in Ireland and England/Wales, respectively. Reductions in CS rates among first-time mothers are associated with a greater payoff than comparable increases in VBAC rates. The net present value of achieving CS rates comparable to those currently observed in the best performing Scandinavian countries was €3.5M and £23.0M per annual cohort in Ireland and England/Wales, respectively. [ABSTRACT FROM AUTHOR]

Socio-ecological stresses currently affecting the semi-arid regions of equatorial East Africa are driving environmental changes that need to be placed in a proper context of long-term human-climate-landscape interaction. Here we present a detailed reconstruction of past human influences on the landscape of the central Kenya Rift Valley, against the backdrop of natural climate-driven ecosystem dynamics over the past 1300 years. Proxy records of vegetation dynamics (pollen), animal husbandry (fungal spores), biomass burning (charcoal) and soil mobilization (clastic mineral influx) extracted from the continuous depositional archive of Lake Bogoria reveal six distinct phases of human activity. From ca 700 to 1430 CE, strong primary response of savanna woodland ecotonal vegetation to climatic moisture-balance variation suggests that anthropogenic influence on regional ecosystem dynamics was limited. The first unambiguous ecological signature of human activities involves a mid-15th century reduction of woodland/forest trees followed by the appearance of cereal pollen, both evidence for mixed farming. From the mid-17th century, animal husbandry became a significant ecological factor and reached near-modern levels by the mid-19th century, after severe early-19th century drought had substantially changed human-landscape interaction. A short-lived peak in biomass burning and evidence for soil mobilization in low-lying areas of the Bogoria catchment likely reflects the known 19th-century establishment of irrigation agriculture, while renewed expansion of forest and woodland trees reflect the return of a wetter climate and abandonment of other farmland. Since the mid-20th century, the principal signature of human activity within the Lake Bogoria catchment is the unprecedented increase in clastic sediment flux, reflecting widespread soil erosion associated with rapidly intensifying land use. Image 1 • Lake Bogoria sediment record provides a detailed history of past human impacts. • Human influence on this central Kenyan landscape can be traced back ca 600 years. • Intensifying human influence gradually supplants climate-driven ecosystem dynamics. • Anthropogenic environmental disturbance has markedly accelerated since the 1960s. [ABSTRACT FROM AUTHOR]

The Ca2+/Mn2+ transport ATPases 1a and 2 (SPCA1a/2) are closely related to the sarco(endo)plasmic reticulum Ca2+- ATPase (SERCA) and are implicated in breast cancer and Hailey- Hailey skin disease. Here, we purified the human SPCA1a/2 isoforms from a yeast recombinant expression system and compared their biochemical properties after reconstitution. We observed that the purified SPCA1a displays a lower Ca2+ affinity and slightly lower Mn2+ affinity than SPCA2. Remarkably, the turnover rates of SPCA1a in the presence of Mn2+ and SPCA2 incubated with Ca2+ and Mn2+ were comparable, whereas the turnover rate of SPCA1a in Ca2+ was 2-fold higher. Moreover, we noted an unusual biphasic activation curve for the SPCA1a ATPase and autophosphorylation activity, not observed with SPCA2. We also found that the biphasic pattern and low apparent ion affinity of SPCA1a critically depends on ATP concentration. We further show that the specific properties of SPCA1a at least partially depend on an N-terminal EF-hand-like motif, which is present only in the SPCA1a isoform and absent in SPCA2. This motif binds Ca2+, and its mutation lowered the Ca2+ turnover rate relative to that of Mn2+, increased substrate affinity, and reduced the level of biphasic activation of SPCA1a. Abiochemical analysis indicated that Ca2+binding to the N-terminal EF-hand-like motif promotes the activity of SPCA1a by facilitating autophosphorylation. We propose that this regulation may be physiologically relevant in cells with a high Ca2+ load, such as mammary gland cells during lactation, or in cells with a low ATP content, such as keratinocytes. [ABSTRACT FROM AUTHOR]