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Background: The NovoSorb® Biodegradable Temporising Matrix (BTM) is a synthetic polyurethane dermal matrix used to reconstruct complex wounds including deep dermal and full-thickness burns, necrotising fasciitis and free flap donor site. We hope to further explore its potential applications in this series., Methods: Patients who received BTM application across four centres over an 18-month period were included. Patients were followed up to assess BTM and graft take, the aesthetic, the return of sensation and complications., Results: A total of 27 patients with 35 wounds were identified with a range of aetiologies. Thirty-three wounds had 100% integration of BTM at the time of sealing membrane removal. Seven wounds had partial graft loss that later healed by secondary intention. In two cases, re-epithelialisation occurred with BTM alone without split-skin graft., Conclusion: BTM offers a safe and reliable reconstructive option in challenging wounds that would otherwise require more complex operations., (© 2021 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Objectives: Changes in brain connectivity have been observed within the default mode network (DMN) in chronic low back pain (CLBP), however the extent of these disruptions and how they may be related to CLBP requires further examination. While studies using seed-based analysis have found disrupted functional connectivity in the medial prefrontal cortex (mPFC), a major hub of the DMN, limited studies have investigated other equally important hubs, such as the posterior cingulate cortex (PCC) in CLBP., Methods: This preliminary study comprised 12 individuals with CLBP and 12 healthy controls who completed a resting-state functional magnetic resonance imaging (fMRI) scan. The mPFC and PCC were used as seeds to assess functional connectivity., Results: Both groups displayed similar patterns of DMN connectivity, however group comparisons showed that CLBP group had reduced connectivity between the PCC and angular gyrus compared to healthy controls. An exploratory analysis examined whether the alterations observed in mPFC and PCC connectivity were related to pain catastrophizing in CLBP, but no significant associations were observed., Conclusions: These results may suggest alterations in the PCC are apparent in CLBP, however, the impact and functional role of these disruptions require further investigation., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background : Myocardial infarction (MI), remains one of the leading causes of death and disability globally but publications on the progression of MI using data from the real world are limited. Multistate models have been widely used to estimate transition rates between disease states to evaluate the cost-effectiveness of healthcare interventions. We apply a Bayesian multistate hidden Markov model to investigate the progression of MI using a longitudinal dataset from Queensland, Australia. Objective : To apply a new model to investigate the progression of myocardial infarction (MI) and to show the potential to use administrative data for economic evaluation and modeling disease progression. Methods : The cohort includes 135,399 patients admitted to public hospitals in Queensland, Australia, in 2010 treatment of cardiovascular diseases. Any subsequent hospitalizations of these patients were followed until 2015. This study focused on the sub-cohort of 8705 patients hospitalized for MI. We apply a Bayesian multistate hidden Markov model to estimate transition rates between health states of MI patients and adjust for delayed enrolment biases and misclassification errors. We also estimate the association between age, sex, and ethnicity with the progression of MI. Results : On average, the risk of developing Non-ST segment elevation myocardial infarction (NSTEMI) was 8.7%, and ST-segment elevation myocardial infarction (STEMI) was 4.3%. The risk varied with age, sex, and ethnicity. The progression rates to STEMI or NSTEMI were higher among males, Indigenous, or elderly patients. For example, the risk of STEMI among males was 4.35%, while the corresponding figure for females was 3.71%. After adjustment for misclassification, the probability of STEMI increased by 1.2%, while NSTEMI increased by 1.4%. Conclusions : This study shows that administrative health data were useful to estimate factors determining the risk of MI and the progression of this health condition. It also shows that misclassification may cause the incidence of MI to be under-estimated.

Objectives: Chronic pain patients often report higher levels of negative emotions, suggesting reduced ability to regulate emotions effectively, however, little is known of the underlying neural cognitive mechanisms. Therefore, the aim of this study was to explore brain activity and connectivity during cognitive reappraisal in chronic low back pain (CLBP)., Methods: This study recruited 24 female participants; 12 with CLBP and 12 healthy controls. Participants completed an emotion regulation task that involved cognitive reappraisal of negative images during functional magnetic resonance imaging. The negative affect following each image and perceived success of the task were reported. Region of interest and seed-to-voxel analyses were conducted using key regions involved in cognitive reappraisal (i.e., amygdalae and dorsomedial prefrontal cortex) as seed regions., Results: During the task, there were no group differences in the behavioural measures and blood oxygen level-dependent (BOLD) brain activation in the seed regions. Functional connectivity analysis showed reduced coupling between the amygdalae and dorsolateral prefrontal cortex, orbitofrontal cortex and inferior parietal cortex in the CLBP group compared to controls. Connectivity between the amygdala and inferior parietal cortex positively correlated with the percent of reduced negative affect during reappraisal in the CLBP group., Conclusions: These preliminary findings demonstrate that individuals with CLBP exhibit similar emotion regulation abilities to healthy controls at the behavioural and BOLD level. However, altered functional connectivity observed in the CLBP group may reduce effective cognitive reappraisal. These results provide evidence for the potential clinical impact of network changes in CLBP., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: There is no previous study that compare skin cancer awareness and photoprotective behaviours between renal transplant recipients (RTR) and patients with glomerular disease (GD)., Objectives/methods: Sixty-one RTR and 51 patients with GD were given a self-reported questionnaire to evaluate skin cancer awareness and photoprotective behaviours in this cross-sectional study. The former group received a formal education on skin cancer and the latter an informal session prior to immunosuppressant use., Results: Ninety-three percent (n = 57) of RTRs and 88% (n = 45) of patients with GD responded to the survey. Majority of participants from both groups were aware that ultraviolet radiation could play a role in the occurrence of skin cancers and the awareness increased in participants with higher education (odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.15-1.95, P = .003). Ninety-eight percent vs 71% were aware that immunosuppressants can increase the risk of developing cancer (P < .001) and higher awareness was noted in younger participants (OR = 0.92, 95% CI = 0.87-0.97, P = .003). Suboptimal photoprotective behaviours (sun avoidance, sunscreen usage and sun-protective clothing) were noted in both cohorts and slightly lower sun protection rates were reported in RTR when compared with patients having GD. The level of sun protective measures in RTR based on high, moderate and minimal use of photoprotective measures were 21%, 46% and 33%, respectively. In terms of patients with GD, the latter practices were 13%, 50% and 37%, respectively (P = .560). Higher educational status was significantly associated with better sunscreen usage in RTR (P = .017) whereas this finding was not observed in patients with GD., Conclusion: Patients with GD and RTR should have formal education on the risks of skin cancers before starting immunosuppressants. Follow-up education and surveillance is required to improve skin protective practices in these patients., (© 2020 Asian Pacific Society of Nephrology.)

Both DNA and RNA can maintain left-handed double helical Z-conformation under physiological condition, but only when stabilized by Z-DNA binding domain (ZDBD). After initial discovery in RNA editing enzyme ADAR1, ZDBD has also been described in pathogen-sensing proteins ZBP1 and PKZ in host, as well as virulence proteins E3L and ORF112 in viruses. The host-virus antagonism immediately highlights the importance of ZDBD in antiviral innate immunity. Furthermore, Z-RNA binding has been shown to be responsible for the localization of these ZDBD-containing proteins to cytoplasmic stress granules that play central role in coordinating cellular response to stresses. This review sought to consolidate current understanding of Z-RNA sensing in innate immunity and implore possible roles of Z-RNA binding within cytoplasmic stress granules., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chiang, Li and Ng.)

Ethnopharmacological Relevance: DG is a herbal formula, containing the root of Salvia miltiorrhiza Bunge (Danshen) and the root of Pueraria lobate (Willd.) Ohwi (Gegen), has a history of usage in China for cardiovascular protection and anti-atherosclerosis., Aim of the Study: The present study aims to determine the beneficial effect of DG on the hind-limb ischemia rat model which mimics peripheral arterial disease (PAD) and its vasodilative effect on isolated femoral artery., Materials and Methods: The vasodilatory effects were assessed by contractile responses to DG in the isolated femoral artery and its underlying mechanisms were evaluated by the involvement of endothelium, potassium channel and calcium channel. For hind-limb ischemia study, treatment outcomes were assessed by evaluating hind-limb blood flow, functional limb recovery, muscle histology and angiogenesis., Results: Our results demonstrated positive dose-dependent vasodilatory response to DG via an endothelium-independent mechanism that involved inwardly rectifying K + channels and Ca 2+ channels. We also demonstrated significant improvement in blood perfusion and micro-vessel density in the ischemic limb and positive effects in functional limb recovery., Conclusion: In conclusion, our study supported the potential use of DG as a novel treatment for symptomatic PAD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Animal cells are used in the manufacturing of complex biotherapeutic products since the 1980s. From its initial uses in biological research to its current importance in the biopharmaceutical industry, many types of culture media were developed: from serum-based media to serum-free to protein-free chemically defined media. The cultivation of animal cells economically has become the ultimate goal in the field of biomanufacturing. Serum serves as a source of amino acids, lipids, proteins and most importantly growth factors and hormones, which are essential for many cell types. However, the use of serum is unfavorable due to its high price tag, increased lot-to-lot variations and potential risk of microbial contamination. Efforts are progressively being made to replace serum with recombinant proteins such as growth factors, cytokines and hormones, as well as supplementation with lipids, vitamins, trace elements and hydrolysates. While hydrolysates are more complex, they provide a diverse source of nutrients to animal cells, with potential beneficial effects beyond the nutritional value. In this review, we discuss the use of hydrolysates in animal cell culture and briefly cover the composition of hydrolysates, mode of action and potential contaminants with some perspectives on its potential role in animal cell culture media formulations in the future., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2021.)

High-throughput glycan analysis has become an important part of biopharmaceutical production and quality control. However, it is still a significant challenge in the field of glycomics to easily deduce isomeric glycan structures, especially in a high-throughput manner. Ion mobility spectrometry (IMS) is an excellent tool for differentiating isomeric glycan structures. However, demonstrations of the utility of IMS in high-throughput workflows such as liquid chromatography-fluorescence-mass spectrometry (LC-FLR-MS) workflows have been limited with only a small amount of collision cross section (CCS) data available. In particular, IMS data of glycan fragments obtained in positive ion mode are limited in comparison to those obtained in negative ion mode despite positive ion mode being widely used for glycomics. Here, we describe IMS TW CCSN 2 data obtained from a high-throughput LC-FLR-IMS-MS workflow in positive ion mode. We obtained IMS data from a selection of RapiFluor-MS (RFMS) labeled N -glycans and also glycopeptides. We describe how IMS is able to distinguish isomeric N -glycans and glycopeptides using both intact IMS and fragment-based IMS glycan sequencing experiments in positive ion mode, without significantly altering the high-throughput nature of the analysis. For the first time, we were able to successfully use IMS in positive ion mode to determine the branching of isomeric glycopeptides and RFMS labeled glycans. Further, we highlight that IMS glycan sequencing of fragments obtained from RFMS labeled glycans was similar to that of glycopeptides. Finally, we show that the IMS glycan sequencing approach can highlight shared structural features of nonisomeric glycans in a high-throughput LC-FLR-IMS-MS workflow.

International governments' COVID-19 responses must balance human and economic health. Beyond slowing viral transmission, strict lockdowns have severe economic consequences. This work investigated response stringency, quantified by the Oxford COVID-19 Government Response Tracker's Stringency Index, and examined how restrictive interventions affected infection rates and gross domestic product (GDP) in China and OECD countries. Accounting for response timing, China imposed the most stringent restrictions, while Sweden and Japan were the least stringent. Expected GDP declines range from -8% (Japan) to -15.4% (UK). While greater restrictions generally slowed viral transmission, they failed to reach statistical significance and reduced GDP ( p = 0.006). Timing was fundamental: governments who responded to the pandemic faster saw greater reductions in viral transmission ( p = 0.013), but worse decreases in GDP ( p = 0.044). Thus, response stringency has a greater effect on GDP than infection rates, which are instead affected by the timing of COVID-19 interventions. Attempts to mitigate economic impacts by delaying restrictions or decreasing stringency may buoy GDP in the short term but increase infection rates, the longer-term economic consequences of which are not yet fully understood. As highly restrictive interventions were successful in some but not all countries, decision-makers must consider whether their strategies are appropriate for the country on health and economic grounds., Competing Interests: The authors declare no conflict of interest.

MicroRNA-200 (miR-200) family is highly expressed in ovarian cancer. We evaluated the levels of family members relative to the internal control miR-103a in ovarian cancer and control blood specimens collected from American and Hong Kong Chinese institutions, as well as from a laying hen spontaneous ovarian cancer model. The levels of miR-200a, miR-200b and miR-200c were significantly elevated in all human cancer versus all control blood samples. Further analyses showed significantly higher miR-200 levels in Chinese control (except miR-429) and cancer (except miR-200a and miR141) samples than their respective American counterparts. Subtype-specific analysis showed that miR-200b had an overall elevated level in serous cancer compared with controls, whereas miR-429 was significantly elevated in clear cell and endometrioid cancer versus controls. MiR-429 was also significantly elevated in cancer versus control in laying hen plasma samples, consistent with the fact that endometrioid tumor is the prevalent type in this species. A neural network model consisting of miR-200a/200b/429/141 showed an area under the curve (AUC) value of 0.904 for American ovarian cancer prediction, whereas a model consisting of miR-200b/200c/429/141 showed an AUC value of 0.901 for Chinese women. Hence, miR-200 is informative as blood biomarkers for both human and laying hen ovarian cancer.

In the study of multiple failure time data with recurrent clinical endpoints, the classical independent censoring assumption in survival analysis can be violated when the evolution of the recurrent events is correlated with a censoring mechanism such as death. Moreover, in some situations, a cure fraction appears in the data because a tangible proportion of the study population benefits from treatment and becomes recurrence free and insusceptible to death related to the disease. A bivariate joint frailty mixture cure model is proposed to allow for dependent censoring and cure fraction in recurrent event data. The latency part of the model consists of two intensity functions for the hazard rates of recurrent events and death, wherein a bivariate frailty is introduced by means of the generalized linear mixed model methodology to adjust for dependent censoring. The model allows covariates and frailties in both the incidence and the latency parts, and it further accounts for the possibility of cure after each recurrence. It includes the joint frailty model and other related models as special cases. An expectation-maximization (EM)-type algorithm is developed to provide residual maximum likelihood estimation of model parameters. Through simulation studies, the performance of the model is investigated under different magnitudes of dependent censoring and cure rate. The model is applied to data sets from two colorectal cancer studies to illustrate its practical value., (© 2019 The International Biometric Society.)

Sialic acids are sugars present in many animal glycoproteins and are of particular interest in biopharmaceuticals, where a lack of sialylation can reduce bioactivity. Here, we describe how α-2,6-sialyltransferase from Photobacterium damselae can be used to markedly increase the level of sialylation of CHO-produced α-1-antitrypsin. Detailed analysis of the sialylation products showed that in addition to the expected α-2,6-sialylation of galactose, a second disialyl galactose motif Neu5Ac-α2,3(Neu5Ac-α2,6)Gal was produced, which, to our knowledge, had never been detected on a mammalian glycoprotein. We exploited this disialyl galactose activity of the P. damselae in a multienzyme reaction to produce a highly sialylated α-1-antitrypsin. The influence of this unique disialylation on the in vitro activity of α-1-antitrypsin was studied, and a toolkit of mass spectrometry methods for identifying this new disialyl galactose motif in complex mixtures was developed.

This study sought to determine patterns of multimorbidity and quantify their impact on use of primary health services in the presence and absence of anxiety and depression among a cohort of urban community-dwelling men in Australia. The analytic sample consisted of men ( n = 2039; age 38-85) from the follow-up wave of a prospective cohort study of all participants of the Florey Adelaide Male Ageing Study (FAMAS; Stage 2 [2007-2010]) and age-matched men from the North-West Adelaide Health Study (NWAHS; Stage 3 [2008-2010]). Self-reported data and linkage with a national universal health coverage scheme (Medicare) provided information on the prevalence of eight chronic conditions and health service utilization information (including annual GP visits). Obesity and cardiovascular disease (CVD) were associated with the highest number of comorbid conditions. Two nonrandom multimorbidity "clusters" emerged: "CVD, Obesity, Diabetes" and "CVD, Obesity, Osteoarthritis." Participants with conditions comorbid with CVD were more likely to have 10 or more annual GP visits, compared to multimorbidity involving other conditions. In comparison to participants without CVD, the presence of CVD increased the chance of having 10 or more annual GP visits (adjusted risk ratio: 3.7; 95% CI [2.8, 4.8]). When CVD was comorbid with anxiety and depression, having 10 or more annual GP visits was more common (adjusted risk ratio: 1.8; 95% CI [1.2, 2.5]). Multimorbidity patterns involving CVD, especially for multimorbidity that includes CVD with comorbid anxiety and depression, should be considered in developing clinical trials to better inform medical decision-making and care for patients with CVD and comorbid conditions.

Background: Renal biopsy is often required to obtain information for diagnosis, management and prognosis of kidney disease that can be broadly classified into acute kidney injury (AKI) and chronic kidney disease (CKD). The most common conditions identified on renal biopsy are glomerulonephritis and tubulo-interstitial disorders. There is a paucity of information on management strategies and therapeutic outcomes in AKI and CKD patients. A renal biopsy registry will provide information on biopsy-proven kidney disorders to improve disease understanding and tracking, healthcare planning, patient care and outcomes., Methods: A registry of patients, that includes biopsy-proven kidney disease, was established through the collaboration of nephrologists from Queensland Hospital and Health Services and pathologists from Pathology Queensland services. The registry is in keeping with directions of the Advancing Kidney Care 2026 Collaborative, established in September 2018 as a Queensland Health initiative. Phase 1 of the registry entailed retrospective acquisition of data from all adult native kidney biopsies performed in Queensland, Australia, from 2002 to 2018. Data were also linked with the existing CKD.QLD patient registry. From 2019 onwards, phase 2 of the registry involves prospective collection of all incident consenting patients referred to Queensland public hospitals and having a renal biopsy. Annual reports on patient outcomes will be generated and disseminated., Discussion: Establishment of the Queensland Renal Biopsy Registry (QRBR) aims to provide a profile of patients with biopsy-proven kidney disease that will lead to better understanding of clinico-pathological association and facilitate future research. It is expected to improve patient care and outcomes.

Background: The minimum effective dose of intramuscular polyvalent immune globulin for prevention of hepatitis A post-exposure is unknown. In Australia current dosing is according to weight category., Methods: The peak concentration and decay of hepatitis A antibodies after intramuscular dosing of immune globulin in adults was modeled utilizing published parameters. Models simulated dosing according to current Australian guidelines, then adjusted the dose in clinically relevant increments to estimate the optimal dose of hepatitis A antibodies for post-exposure prophylaxis of nonimmune individuals. Optimal dosing assumed a target serum concentration of hepatitis A antibodies of the correlate of protection plus a 10% margin of error at an incubation period. The effect of weight on hepatitis A antibody concentration at an incubation period under current guidelines was examined by fixing weight in 5 kg increments., Results: Current dosing guidelines in Australia may underdose people who weigh in excess of 85 kg. The optimal dose of hepatitis A-specific antibodies according to the model was 3.6, 2.5, and 1.9 IU/kg assuming 50%, 75% and 100% bioavailability respectively., Conclusions: For individuals in Australia recommended passive immunization as post-exposure prophylaxis and weighing in excess of 85 kg, conservative management would include dosing between 2.5 and 3.6 IU hepatitis A antibodies/kg.

Background: Laparoscopic and open techniques in rectal cancer are well-published, however, technical challenges remain for mid to low rectal cancer resections in the narrow pelvis. Transanal total mesorectal excision (taTME) has been pioneered to potentially circumvent these challenges. The aims of this study were to evaluate the learning curve associated with our first cases of taTME as well as compare outcomes to that of conventionally performed rectal resections., Methods: This was a single-centre retrospective study with data collated from all elective resections by the colorectal unit from 2015 to 2017. Primary outcome was completeness of total mesorectal excision and secondary outcomes were intra- and post-operative morbidity and mortality., Results: A total of 43 patients were identified. Of which, 20 underwent taTME. Mesorectal completeness was obtained in only 47.4% in the taTME group compared to 78.3% in the anterior resection group (p = 0.115). 5.9% of patients in our taTME group had positive circumferential resection margin compared to nil in the anterior resection. Conversion rates were greater in the taTME group (15% versus 0%; 0.028). Operative time, length of stay and clavien IV and V complications were greater in the taTME group., Conclusion: This study highlights the difficulty in introducing a novel technique given the learning curve. Our results would expect to improve with increased caseload., (© 2020 Royal Australasian College of Surgeons.)

Excessive accumulation of extracellular matrix (ECM) is a hallmark of bone marrow (BM) milieu in primary myelofibrosis (PMF). Because cells have the ability to adhere to the surrounding ECM through integrin receptors, we examined the hypothesis that an abnormal ECM-integrin receptor axis contributes to BM megakaryocytosis in JAK2V617F+ PMF. Secretion of ECM protein fibronectin (FN) by BM stromal cells from PMF patients correlates with fibrosis and disease severity. Here, we show that Vav1-hJAK2V617F transgenic mice (JAK2V617F+) have high BM FN content associated with megakaryocytosis and fibrosis. Further, megakaryocytes from JAK2V617F+ mice have increased cell surface expression of the α5 subunit of the α5β1 integrin, the major FN receptor in megakaryocytes, and augmented adhesion to FN compared with wild-type controls. Reducing adhesion to FN by an inhibitory antibody to the α5 subunit effectively reduces the percentage of CD41+ JAK2V617F+ megakaryocytes in vitro and in vivo. Corroborating our findings in mice, JAK2V617F+ megakaryocytes from patients showed elevated expression of α5 subunit, and a neutralizing antibody to α5 subunit reduced adhesion to FN and megakaryocyte number derived from CD34+ cells. Our findings reveal a previously unappreciated contribution of FN-α5β1 integrin to megakaryocytosis in JAK2V617F+ PMF., (© 2020 by The American Society of Hematology.)

Background: To determine whether the insertion of the sternothyroid muscle onto the oblique line of the thyroid cartilage can be used to reliably locate the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy., Methods: This is a prospective descriptive case series. The EBSLN was identified and confirmed with a nerve stimulator during thyroid surgery. The entry point of the EBSLN into the inferior constrictor/cricothyroid muscle was measured in relation to the insertion and anterior border of the sternothyroid muscle. The perpendicular distance from the insertion of the sternothyroid muscle onto the oblique line was designated the vertical distance (VD) of the nerve entry point (NEP), and the perpendicular distance from the anterior border of the sternothyroid muscle was designated the horizontal distance., Results: Ninety patients underwent 130 thyroid lobectomies (60 female, 30 male) (mean age 53.5 years, range, 18-91 years). An attempt to identify the nerve was made in 127 thyroid lobectomies. The EBSLN was identified in 111 cases (87.4%). The mean VD of the NEP from the muscle insertion was 1.1 mm (SD 1.1 mm, range, 0-5 mm) and the mean horizontal distance (HD) was 9.5 mm (SD 3.8 mm, range, 2-21 mm)., Conclusions: The EBSLN muscle entry point usually lies 1.1 mm from the sternothyroid insertion onto the oblique line, and 5-12 mm from the anterior border of the muscle. These useful landmarks allow the nerve to be consistently located, identified and preserved during thyroid surgery prior to ligating the superior thyroid vessels., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs.2020.03.25). The authors have no conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

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There is emerging evidence that hydrogen-rich water (H 2 -water) has beneficial effects on the physiological responses to exercise. However, few studies investigate its ergogenic potential. This randomized controlled trial examined the effects of H 2 -water ingestion on physiological responses and exercise performance during incremental treadmill running. In a double-blind crossover design, 14 endurance-trained male runners (age, 34 ± 4 years; body mass, 63.1 ± 7.2 kg; height, 1.72 ± 0.05 m) were randomly assigned to ingest 2 doses of 290-mL H 2 -water or placebo on each occasion. The first bolus was given before six 4-min submaximal running bouts, and the second bolus was consumed before the maximal incremental running test. Expired gas, heart rate (HR), and ratings of perceived exertion (RPE) were recorded; blood samples were collected at the end of each submaximal stage and post maximal running test. Cardiorespiratory responses, RPE, and blood gas indices were not significantly different at each submaximal running intensity (range: 34%-91% maximal oxygen uptake) between H 2 -water and placebo trials. No statistical difference was observed in running time to exhaustion (618 ± 126 vs. 619 ± 113 s), maximal oxygen uptake (56.9 ± 4.4 vs. 57.1 ± 4.7 mL·kg -1 ·min -1 ), maximal HR (184 ± 7 vs. 184 ± 7 beat·min -1 ), and RPE (19 ± 1 vs. 19 ± 1) in the runners between the trials. The results suggest that the ingestion of 290 mL of H 2 -water before submaximal treadmill running and an additional dose before the subsequent incremental running to exhaustion were not sufficiently ergogenic in endurance-trained athletes. Novelty Acute ingestion of H 2 -water does not seem to be ergogenic for endurance performance. A small dose of H 2 -water does not modulate buffering capacity during intense endurance exercise in athletes.

Epidemiologic and histopathologic findings and the laying hen model support the long-standing incessant ovulation hypothesis and cortical inclusion cyst involvement in sporadic ovarian cancer development. MicroRNA-200 (miR-200) family is highly expressed in ovarian cancer. Herewith, we show that ovarian surface epithelial (OSE) cells with ectopic miR-200 expression formed stabilized cysts in three-dimensional (3D) organotypic culture with E-cadherin fragment expression and steroid hormone pathway activation, whereas ovarian cancer 3D cultures with miR-200 knockdown showed elevated TGF-β expression, mitotic spindle disorientation, increased lumenization, disruption of ROCK-mediated myosin II phosphorylation, and SRC signaling, which led to histotype-dependent loss of collective movement in tumor spread. Gene expression profiling revealed that epithelial-mesenchymal transition and hypoxia were the top enriched gene sets regulated by miR-200 in both OSE and ovarian cancer cells. The molecular changes uncovered by the in vitro studies were verified in both human and laying hen ovarian cysts and tumor specimens. As miR-200 is also essential for ovulation, our results of estrogen pathway activation in miR-200-expressing OSE cells add another intriguing link between incessant ovulation and ovarian carcinogenesis.

Many medical studies yield data on recurrent clinical events from populations which consist of a proportion of cured patients in the presence of those who experience the event at several times (uncured). A frailty mixture cure model has recently been postulated for such data, with an assumption that the random subject effect (frailty) of each uncured patient is constant across successive gap times between recurrent events. We propose two new models in a more general setting, assuming a multivariate time-varying frailty with an AR(1) correlation structure for each uncured patient and addressing multilevel recurrent event data originated from multi-institutional (multi-centre) clinical trials, using extra random effect terms to adjust for institution effect and treatment-by-institution interaction. To solve the difficulties in parameter estimation due to these highly complex correlation structures, we develop an efficient estimation procedure via an EM-type algorithm based on residual maximum likelihood (REML) through the generalised linear mixed model (GLMM) methodology. Simulation studies are presented to assess the performances of the models. Data sets from a colorectal cancer study and rhDNase multi-institutional clinical trial were analyzed to exemplify the proposed models. The results demonstrate a large positive AR(1) correlation among frailties across successive gap times, indicating a constant frailty may not be realistic in some situations. Comparisons of findings with existing frailty models are discussed.

A specialized DNA extraction method and a SYBR Green quantitative polymerase chain reaction (SyG-qPCR) assay were combined to generate a ready-to-use kit for rapid detection of porcine admixtures in processed meat products. Our qPCR assay utilized repetitive LINE-1 elements specific to the genome of Sus scrofa domesticus (pig) as a target and incorporated internal controls. We improved the genomic DNA extraction method, and reduced extraction times to the minimum. The method was validated for specificity, sensitivity (0.001% w/w) and robustness, and values were compared with those of a commercially available kit. We also tested our method using 121 processed food products and consistently detected amplification only in samples containing pork. Due to its efficiency and cost-effectiveness, our method represents a valuable new method for detecting food adulteration with pork that is superior to existing quality control approaches., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The Breast Size Satisfaction Survey (BSSS) was established to assess women's breast size dissatisfaction and breasted experiences from a cross-national perspective. A total of 18,541 women were recruited from 61 research sites across 40 nations and completed measures of current-ideal breast size discrepancy, as well as measures of theorised antecedents (personality, Western and local media exposure, and proxies of socioeconomic status) and outcomes (weight and appearance dissatisfaction, breast awareness, and psychological well-being). In the total dataset, 47.5 % of women wanted larger breasts than they currently had, 23.2 % wanted smaller breasts, and 29.3 % were satisfied with their current breast size. There were significant cross-national differences in mean ideal breast size and absolute breast size dissatisfaction, but effect sizes were small (η 2  = .02-.03). The results of multilevel modelling showed that greater Neuroticism, lower Conscientiousness, lower Western media exposure, greater local media exposure, lower financial security, and younger age were associated with greater breast size dissatisfaction across nations. In addition, greater absolute breast size dissatisfaction was associated with greater weight and appearance dissatisfaction, poorer breast awareness, and poorer psychological well-being across nations. These results indicate that breast size dissatisfaction is a global public health concern linked to women's psychological and physical well-being., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Concurrent chemoradiotherapy (CCRT) is one of the standard treatments for patients with advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT may lead to decreased quality of life (QoL) and treatment compliance. This study aimed to determine the effects of PG2 (Astragalus polysaccharides) injection on CCRT-associated adverse events (AEs) and patients' compliance with the CCRT course., Methods: In this phase II double-blind randomized placebo-controlled trial, PG2 injection (sterile powder form) or placebo was administrated three times per week in parallel with CCRT to patients with HNSCC. The chemotherapy regimen included 50 mg/m 2 cisplatin every 2 weeks with daily tegafur-uracil (300 mg/m 2 ) and leucovorin (60 mg/day)., Results: The study was terminated prematurely due to the successful launch of a newly formulated PG2 injection (lyophilized form). A total of 17 patients were enrolled. The baseline demographics and therapeutic compliance were comparable between the CCRT/PG2 and CCRT/placebo groups. During CCRT, severe treatment-associated AEs were less frequent in the CCRT/PG2 group than in the CCRT/placebo group. Furthermore, less QoL fluctuations from the baseline during CCRT were noted in the CCRT/PG2 group than in the CCRT/placebo group, with a significant difference in the pain, appetite loss, and social eating behavior. The tumor response, disease-specific survival and overall survival did not differ between the two groups., Conclusion: This preliminary study demonstrated PG2 injection exhibited an excellent safety profile, and has potential in ameliorating the deterioration in QoL and the AEs associated with active anticancer treatment among patients with advanced pharyngeal or laryngeal HNSCC under CCRT. Further research in patients with other cancer types or treatment modalities may widen PG2's application in clinical settings.

Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) that usually portends a poor prognosis with limited therapeutic options available. Currently, only allogeneic stem cell transplantation is curative in those who are candidates, while administration of the JAK1/2 inhibitor ruxolitinib carries a risk of worsening cytopenia. The limited therapeutic options available highlight the need for the development of novel treatments for PMF. Lysyl oxidase (LOX), an enzyme vital for collagen cross-linking and extracellular matrix stiffening, has been found to be upregulated in PMF. Herein, we evaluate two novel LOX inhibitors, PXS-LOX&#95;1 and PXS-LOX&#95;2, in two animal models of PMF (GATA1low and JAK2V617F-mutated mice). Specifically, PXS-LOX&#95;1 or vehicle was given to 15- to 16-week-old GATA1low mice via intraperitoneal injection at a dose of 15 mg/kg four times a week for 9 weeks. PXS-LOX&#95;1 was found to significantly decrease the bone marrow fibrotic burden and megakaryocyte number compared to vehicle in both male and female GATA1low mice. Given these results, PXS-LOX&#95;1 was then tested in 15- to 17-week-old JAK2V617F-mutated mice at a dose of 30 mg/kg four times a week for 8 weeks. Again, we observed a significant decrease in bone marrow fibrotic burden. PXS-LOX&#95;2, a LOX inhibitor with improved oral bioavailability, was next evaluated in 15- to 17-week-old JAK2V617F-mutated mice at a dose of 5 mg/kg p.o. four times a week for 8 weeks. This inhibitor also resulted in a significant decrease in bone marrow fibrosis, albeit with a more pronounced amelioration in female mice. Taking these results together, PXS-LOX&#95;1 and PXS-LOX&#95;2 appear to be promising new candidates for the treatment of fibrosis in PMF.

Mammalian host cell lines are the preferred expression systems for the manufacture of complex therapeutics and recombinant proteins. However, the most utilized mammalian host systems, namely Chinese hamster ovary (CHO), Sp2/0 and NS0 mouse myeloma cells, can produce glycoproteins with non-human glycans that may potentially illicit immunogenic responses. Hence, we developed a fully human expression system based on HEK293 cells for the stable and high titer production of recombinant proteins by first knocking out GLUL (encoding glutamine synthetase) using CRISPR-Cas9 system. Expression vectors using human GLUL as selection marker were then generated, with recombinant human erythropoietin (EPO) as our model protein. Selection was performed using methionine sulfoximine (MSX) to select for high EPO expression cells. EPO production of up to 92700 U/mL of EPO as analyzed by ELISA or 696 mg/L by densitometry was demonstrated in a 2 L stirred-tank fed batch bioreactor. Mass spectrometry analysis revealed that N-glycosylation of the produced EPO was similar to endogenous human proteins and non-human glycan epitopes were not detected. Collectively, our results highlight the use of a human cellular expression system for the high titer and xenogeneic-free production of EPO and possibly other complex recombinant proteins.

Background: Lateral epicondylalgia (tennis elbow) is a common, debilitating and often treatment-resistant condition. Two treatments thought to address the pathology of lateral epicondylalgia are hypertonic glucose plus lignocaine injections (prolotherapy) and a physiotherapist guided manual therapy/exercise program (physiotherapy). This trial aimed to compare the short- and long-term clinical effectiveness, cost effectiveness, and safety of prolotherapy used singly and in combination with physiotherapy., Methods: Using a single-blinded randomised clinical trial design, 120 participants with lateral epicondylalgia of at least 6 weeks' duration were randomly assigned to prolotherapy (4 sessions, monthly intervals), physiotherapy (weekly for 4 sessions) or combined (prolotherapy+physiotherapy). The Patient-Rated Tennis Elbow Evaluation (PRTEE) and participant global impression of change scores were assessed by blinded evaluators at baseline, 6, 12, 26 and 52 weeks. Success rate was defined as the percentage of participants indicating elbow condition was either 'much improved' or 'completely recovered.' Analysis was by intention-to-treat., Results: Eighty-eight percent completed the 12-month assessment. At 52 weeks, there were substantial, significant improvements compared with baseline status for all outcomes and groups, but no significant differences between groups. The physiotherapy group exhibited greater reductions in PRTEE at 12 weeks than the prolotherapy group (p = 0.014)., Conclusion: There were no significant differences amongst the Physiotherapy, Prolotherapy and Combined groups in PRTEE and global impression of change measures over the course of the 12-month trial., Trial Registration: ACTRN12612000993897 .

Objectives: We propose a data-matching approach to estimate intervention efficacy for randomized controlled trials (RCTs) when there is noncompliance to the allocated treatment with induced selection bias., Study Design and Setting: We considered a large RCT to compare health care costs and hospital length of stay 12 months after randomization. Participants allocated to the intervention group were eligible to receive health-coaching and disease-management services. An opt-out approach was adopted for recruitment. Control-group participants received usual care but were allowed to opt-in to receive the intervention. Using "nearest-neighbor"-matched data, we identified compliant participants in both arms to estimate intervention efficacy. Results were compared with intention-to-treat (ITT), instrumental-variable-adjusted ITT, per-protocol (PP), and as-treated (AT) analyses., Results: The ITT estimated an intervention effect of a 1.5% reduction in cost, but 56.7% of intervention-group participants did not receive health coaching. The PP and AT found an increase in cost of 9.4% and 17.1%, respectively. The matching method estimated a 12.3% reduction in cost. After adjustment for baseline covariates, the intervention group had lower same-day admission cost (13.6%; 95% CI: 7.3%-20.0%; P < 0.001) and shorter hospital stay (11.2%; 95% CI: 2.6%-19.9%; P = 0.021)., Conclusion: Opt-in/opt-out strategies in RCTs misled intervention comparisons and the matching approach improved estimation of intervention efficacy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Qualitative studies have elucidated cancer survivors' experiences of cognitive changes associated with cancer and cancer treatment. This study specifically explored experiences of women treated for breast cancer who were seeking cognitive rehabilitation. The objective was to characterise the frequency and nature of cognitive changes and adaptations to cognitive change reported by these participants to better understand treatment needs of this group., Method: Australian women who had completed primary treatments for breast cancer (surgery, chemotherapy, and/or radiotherapy) and volunteered to participate in one of two cognitive rehabilitation intervention studies were interviewed via telephone. Interview responses regarding cognitive changes and adaptations to cognitive change were transcribed by the interviewers, then coded and analysed by two researchers using content analysis., Results: Among the 95 participants (age M=54.3 years, SD=9.6), the most commonly reported cognitive change was memory (79% of participants) and 61% reported more than one type of cognitive change. Adaptations to change were reported by 87% of participants, with written or electronic cues the most common (51%). Most often, participants reported using a single type of adaptation (48%) with only 39% reporting multiple types of adaptations., Conclusions: Women treated for breast cancer, who were seeking cognitive rehabilitation, most commonly reported memory changes, which were mainly managed through a single type of adaptation. These results suggest that there is considerable scope for increasing the range of cognitive adaptations to improve the quality of life of cancer survivors who experience adverse cognitive changes., (© 2019 John Wiley & Sons, Ltd.)

Distal radius fractures are among the most common fractures encountered in the clinical setting. Of these common fractures, it has been said that up to 60% are intraarticular in nature. Intra-articular or unstable and comminuted fractures represent severe and high energy injuries. Despite a large amount of literature, it is surgeon preference which determines the fixation method employed. There are only a few randomised control trials that report 2-year outcomes. There has yet to be a meta-analysis comparing the long-term outcomes of open reduction internal fixation (ORIF) and external fixation (EF). The aim of this metaanalysis is to identify any difference in the outcomes of either fixation method in the long term. We pooled the data of all the available randomised control trials that followed the patients for a minimum of 2 years and compared outcomes of ORIF against EF of distal radius fractures as per PRISMA guidelines from inception of the databases to December 2016. We then performed our meta-analysis using RevMan 5.3 software. Flexion/extension arcs were significantly improved in ORIF, and 7 of the 10 analysed outcomes supported ORIF, although most not to a significant degree. The meta-analysis indicated that there is no difference in outcomes with either form of treatment. Even though the flexion extension arc was statistically better in the ORIF group, the difference is not clinically meaningful., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest., (©Copyright: the Author(s), 2019.)

Chinese hamster ovary (CHO) cells are the most prevalent mammalian cell factories for producing recombinant therapeutic proteins due to their ability to synthesize human-like post-translational modifications and ease of maintenance in suspension cultures. Currently, a wide variety of CHO host cell lines has been developed; substantial differences exist in their phenotypes even when transfected with the same target vector. However, relatively less is known about the influence of their inherited genetic heterogeneity on phenotypic traits and production potential from the bioprocessing point of view. Herein, we present a global transcriptome and proteome profiling of three commonly used parental cell lines (CHO-K1, CHO-DXB11, and CHO-DG44) in suspension cultures and further report their growth-related characteristics, and N- and O-glycosylation patterns of host cell proteins (HCPs). The comparative multi-omics and subsequent genome-scale metabolic network model-based enrichment analyses indicated that some physiological variations of CHO cells grown in the same media are possibly originated from the genetic deficits, particularly in the cell-cycle progression. Moreover, the dihydrofolate reductase deficient DG44 and DXB11 possess relatively less active metabolism when compared to K1 cells. The protein processing abilities and the N- and O-glycosylation profiles also differ significantly across the host cell lines, suggesting the need to select host cells in a rational manner for the cell line development on the basis of recombinant protein being produced., (© 2019 Wiley Periodicals, Inc.)

Background: While pelvic floor ultrasound is commonly utilised in high-resource locations, our understanding of pelvic floor characteristics in women suffering with obstetric fistula and unrepaired fourth degree obstetric tears in low-resource areas is limited., Aims: This study aimed to assess the pelvic floor ultrasound characteristics of Ugandan women suffering with obstetric fistula, unrepaired fourth degree obstetric tears and pelvic organ prolapse, and determine whether obstructed labour resulting in obstetric fistula causes more levator muscle defects compared to parous women without a history of obstructed labour., Materials and Methods: This was a prospective study in western Uganda assessing 82 women with obstetric fistula, unrepaired fourth degree obstetric tears and pelvic organ prolapse with a pelvic floor ultrasound scan., Results: Demographic characteristics were significantly different, with women suffering pelvic organ prolapse being older and more parous. Hiatal area on Valsalva was significantly smaller in the obstetric fistula group (mean 21.45 cm 2 ) compared to non-obstetric fistula group (unrepaired fourth degree obstetric tears and pelvic organ prolapse; mean 30.44 cm 2 ); a mean difference of 9.0 cm 2 (95% CI: 5.4-12.6 cm 2 , P < 0.001). Overall, levator muscle defects were significantly more common in women with obstetric fistula (66.7%) compared to the non-obstetric fistula group (44.7%) with P = 0.048; however, there were no significant differences in complete levator muscle defects between obstetric fistula (28.6%) and non-obstetric fistula (23.7%)., Conclusions: Increased hiatal area on Valsalva was noted in the non-obstetric fistula group compared to women with obstetric fistula; however, there were no differences in proportions of complete levator muscle defects., (© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Understanding the natural history of childhood OSA can help to determine disease prognosis and to guide risk stratification and management strategies., Methods: To evaluate the natural history of childhood OSA and factors associated with spontaneous remission and persistent and incident OSA from childhood to late adolescence/early adulthood, a longitudinal analysis of a prospective community-based cohort was designed. Subjects from a cohort established for an OSA prevalence study were invited to participate in this 10-year follow-up study., Results: Two hundred and forty-three participants (59% male) took part, and their mean age was 9.8 (SD, ± 1.8) and 20.2 (SD, ± 1.9) years at baseline and follow-up, respectively. The mean follow-up duration was 10.4 (SD, ± 1.1) years. Associations between baseline and follow-up log-transformed obstructive apnea-hypopnea index (OAHI) differed by age; a significant positive association was observed only among participants aged 10 years or older at baseline. Overall polysomnographic remission rate (with OAHI < 1 event/h at follow-up) of childhood OSA was 30%, and 69% had an OAHI < 5 events/h at follow-up. Complete remission of OSA was associated with female sex. Incidence of adolescent/adult OSA with an OAHI ≥ 5 events/h at follow-up was 22%. Male sex and higher baseline BMI z score were associated with incident OSA., Conclusions: A proportion of children with OSA, particularly female children, had complete resolution during transition to late adolescence or early adulthood. Childhood and adolescent OSA are distinct entities, with the latter more likely to persist into adulthood. Obesity and male sex are consistent key risk factors for incident OSA., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

More than 80% of infectious bacteria form biofilm, which is a bacterial cell community surrounded by secreted polysaccharides, proteins and glycolipids. Such bacterial superstructure increases resistance to antimicrobials and host defenses. Thus, to control these biofilm-forming pathogenic bacteria requires antimicrobial agents with novel mechanisms or properties. Pseudomonas aeruginosa , a Gram-negative opportunistic nosocomial pathogen, is a model strain to study biofilm development and correlation between biofilm formation and infection. In this study, a recombinant hemolymph plasma lectin (rHPL OE ) cloned from Taiwanese Tachypleus tridentatus was expressed in an Escherichia coli system. This rHPL OE was shown to have the following properties: (1) Binding to P. aeruginosa PA14 biofilm through a unique molecular interaction with rhamnose-containing moieties on bacteria, leading to reduction of extracellular di-rhamnolipid (a biofilm regulator); (2) decreasing downstream quorum sensing factors, and inhibiting biofilm formation; (3) dispersing the mature biofilm of P. aeruginosa PA14 to improve the efficacies of antibiotics; (4) reducing P. aeruginosa PA14 cytotoxicity to human lung epithelial cells in vitro and (5) inhibiting P. aeruginosa PA14 infection of zebrafish embryos in vivo. Taken together, rHPL OE serves as an anti-biofilm agent with a novel mechanism of recognizing rhamnose moieties in lipopolysaccharides, di-rhamnolipid and structural polysaccharides (Psl) in biofilms. Thus rHPL OE links glycan-recognition to novel anti-biofilm strategies against pathogenic bacteria.

Objective: To assess interobserver agreement and intraobserver reproducibility when assessing the nasopharynx for malignancy under white light and narrow band imaging endoscopy because the decision to biopsy hinges on the examiner's perceived chance of malignancy., Methods: An interobserver and intraobserver agreement study utilizing white light and narrow band endoscopic images of the nasopharynx. The setting was an academic referral hospital. Participants were 156 adults with suspected nasopharyngeal carcinoma who underwent white light and narrow band imaging endoscopy and biopsy. Images of the nasopharynges were subsequently scored for malignancy by four otolaryngologists. The nasopharynx was scored on 4-point scales under white light and narrow band imaging endoscopy for the likelihood of malignancy or abnormality, respectively., Results: Intraclass correlation coefficients for intraobserver agreement for nasopharyngeal malignancy for four observers under white light were 0.86, 0.89, 0.79 and 0.88 (mean 0.855), respectively; and under narrow band imaging they were 0.64, 0.68, 0.64, and 0.66 (mean 0.655), respectively (all P values < 0.001). The coefficient for interobserver reliability under white light was 0.79 (95% confidence interval [CI] 0.76-0.82; P < 0.001), which indicated strong agreement. The coefficient for interobserver reliability under narrow band imaging was 0.56 (95% CI 0.50-0.61; P < 0.001), which indicated moderate agreement., Conclusions: Intraobserver and interobserver agreement for nasopharyngeal malignancy was strong on white light endoscopy but only moderate on narrow band imaging endoscopy. Agreement may be improved by adopting a standard set of assessment guidelines, including an objective detailed morphological analysis under white light and vasculature analysis under narrow band imaging., Level of Evidence: 2a Laryngoscope, 129:1374-1379, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

We present a multilevel frailty model for handling serial dependence and simultaneous heterogeneity in survival data with a multilevel structure attributed to clustering of subjects and the presence of multiple failure outcomes. One commonly observes such data, for example, in multi-institutional, randomized placebo-controlled trials in which patients suffer repeated episodes (eg, recurrent migraines) of the disease outcome being measured. The model extends the proportional hazards model by incorporating a random covariate and unobservable random institution effect to respectively account for treatment-by-institution interaction and institutional variation in the baseline risk. Moreover, a random effect term with correlation structure driven by a first-order autoregressive process is attached to the model to facilitate estimation of between patient heterogeneity and serial dependence. By means of the generalized linear mixed model methodology, the random effects distribution is assumed normal and the residual maximum likelihood and the maximum likelihood methods are extended for estimation of model parameters. Simulation studies are carried out to evaluate the performance of the residual maximum likelihood and the maximum likelihood estimators and to assess the impact of misspecifying random effects distribution on the proposed inference. We demonstrate the practical feasibility of the modeling methodology by analyzing real data from a double-blind randomized multi-institutional clinical trial, designed to examine the effect of rhDNase on the occurrence of respiratory exacerbations among patients with cystic fibrosis., (© 2018 John Wiley & Sons, Ltd.)

Objective: To assess the occurrence of intimate partner violence (IPV) among women seeking surgery for pelvic floor dysfunction (PFD) in a rural African community., Methods: A prospective questionnaire-based study was conducted among women with obstetric fistula, unrepaired obstetric anal sphincter injuries (OASIS), or severe (stage 3 or 4) pelvic organ prolapse (POP) who attended surgical camps at Kagando Hospital in western Uganda between July 15, 2016, and September 14, 2017. The control group comprised women without PFD. Participants completed the Hurt, Insult, Threaten, and Scream (HITS) tool and the Woman Abuse Screening Tool (WAST) to screen for IPV., Results: 117 of the 312 women interviewed reported current IPV: 73/214 (34.1%) in the PFD group and 44/98 (44.9%) in the control group. The PFD group comprised unrepaired OASIS (n=85, 39.7%), obstetric fistula (n=75, 35.1%), and severe POP (n=54, 25.2%). All groups experienced high levels of IPV. The frequency of positive screening results for IPV with WAST (score ≥13.0) and/or HITS (score ≥10.5) were: severe POP (n=17, 31.5%), obstetric fistula (n=28, 37.3%), unrepaired OASIS (n=30, 35.3%), and control group (n=44, 44.9%)., Conclusion: Women in western Uganda experienced high rates of IPV, regardless of whether or not they had PFD. ANZCTR number: ACTRN12617001073392., (© 2018 International Federation of Gynecology and Obstetrics.)

Background: The prevalence of metabolic syndrome (MetS) and its components have been increasing globally; therefore, there is a need for better understanding of MetS components and their risk factors, as well as their development and changes over time. This study was designed to identify the determinants of the changes in the components of MetS in a cohort of Iranian adults from 2001 to 2013., Methods: A total of 6504 adults, ≥35 years of age, were recruited from central Iran in 2001and were followed up in an ongoing longitudinal population-based study for 12 years. Of the total, 3356 subjects were followed between 2001 and 2007 and 1385 subjects were followed between 2001 and 2013. MetS components and its risk factors were measured by standard methods in 2001, 2007, and 2013. Mean changes in the MetS components from 2001 to 2013 were assessed using the Generalized Estimating Equations test with three time points. Multivariate linear regression model was applied to examine the association between socioeconomic and behavioral characteristics and changes in MetS components. Furthermore, multivariate logistic regression analysis was carried out to examine various factors associated with the development of abnormality of MetS components., Results: Examining the biochemical and anthropometric characteristics of individuals from 2001 to 2013 revealed a significant increase in systolic and diastolic blood pressure, fasting blood sugar, waist circumference, and body mass index, and a significant decrease in total cholesterol, triglyceride, and physical activity levels. Results also indicated that age, gender, marital status, education levels, and area of residence were significantly associated with the changes in MetS components., Conclusion: This study concluded that baseline sociodemographic characteristics are important in determining changes of MetS components.

Background: Disease management programmes may improve quality of care, improve health outcomes and potentially reduce total healthcare costs. To date, only one very large population-based study has been undertaken and indicated reductions in hospital admissions > 10%., Objective: We sought to confirm the effectiveness of population-based disease management programmes. The objective of this study was to evaluate the relative impact on healthcare utilisation and cost of participants the Costs to Australian Private Insurance - Coaching Health (CAPICHe) trial., Design: Parallel-group randomised controlled trial, intention-to-treat analysis SETTING: Australian population PARTICIPANTS: Forty-four thousand four hundred eighteen individuals (18-90 years of age) with private health insurance and diagnosis of heart failure, chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD), diabetes, or low back pain, with predicted high cost claims for the following 12 months., Intervention: Health coaching for disease management from Bupa Health Dialog, vs Usual Care., Main Outcome Measures: Total cost of claims per member to the private health insurer 1 year post-randomisation for hospital admissions, including same-day, medical and prostheses hospital claims, excluding any maternity costs. Analysis was based on the intent-to-treat population., Results: Estimated total cost 1 year post-randomisation was not significantly different (means: intervention group A$4934; 95% CI A$4823-A$5045 vs control group A$4868; 95% CI A$4680-A$5058; p = 0.524). However, the intervention group had significantly lower same-day admission costs (A$468; 95% CI A$454-A$482 vs A$508; 95% CI A$484-A$533; p = 0.002) and fewer same-day admissions per 1000 person-years (intervention group, 530; 95% CI 508-552 vs control group, 614; 95% CI 571-657; p = 0.002). Subgroup analyses indicated that the intervention group had significantly fewer admissions for patients with COPD and fewer same-day admissions for patients with diabetes., Conclusions: Chronic disease health coaching was not effective to reduce the total cost after 12 months of follow-up for higher risk individuals with a chronic condition. Statistically significant changes were found with fewer same-day admissions; however, these did not translate into cost savings from a private health insurance perspective.

Purpose: To assess the performance of a system of intraoperative dosimetry and obtain estimates of dosimetry outcomes achieved when utilizing the system in a Phase II clinical trial., Methods and Materials: Forty-five patients undergoing permanent Pd-103 seed implantation for prostate cancer were prospectively enrolled. Seed implantation was performed and dose was tracked intraoperatively using intraoperative registered ultrasound and fluoroscopy (iRUF). Three-dimensional seed locations were computed from X-rays and registered to ultrasound for intraoperative dosimetry, followed by adaptive plan modification to achieve prostate V100 ≥95% and ≥95% D90. Time required for iRUF was recorded. Postoperative CT/MRI scans were performed 1 day after the implantation and used as reference for dosimetric analysis. Dosimetric parameters for the prostate and urethra were compared between standard ultrasound-based dosimetry (USD), iRUF, and postoperative CT/MRI., Results: Mean total time for iRUF was <30 min. A mean of four seeds (0-12) were added per implant to correct cold spots discovered by iRUF. Day 1 CT/MRI prostate V100 was ≥95% for 44/45 patients; 1 patient had Day 1 V100 93%. No patient had rectal V100 exceeding 1 cc. Compared to CT/MRI, iRUF dosimetry had significantly smaller mean differences and higher correlations for all prostate and urethral dosimetric parameters examined than USD. Both USD and iRUF tended to overestimate dose, but with less bias in iRUF than USD., Conclusions: Intraoperative dosimetry utilizing iRUF was associated with acceptable increase in procedure time and enabled very high rates of achieving excellent prostate dose coverage. iRUF intraoperative dosimetry approximated postoperative CT/MRI dosimetry to a greater degree than USD for the prostate and urethra., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: This review aimed to explore the processes that underlie the main and the buffering effect of social support on decreased pain experience., Materials and Methods: The systematic review was conducted according to the PRISMA guidelines. Online databases of PubMed and PsycINFO were searched for peer-reviewed articles using keywords ("social support," OR "interpersonal," OR "social presence," OR "spouse," OR "couple," OR "marriage") AND "pain"). Articles were included if they examined the cognitive or behavioral processes linking social support to any aspects of reduced pain experience., Results: The database search identified 38 studies, of which 33 were cognitive-behavioral studies and 5 were neurobiological. Cognitive-behavioral studies generated a total of 57 findings of the analgesic influence of social support. This effect was further categorized as social support decreasing the adverse influence of pain-related stress (28/44 findings), reappraising pain-related stress (7/9 findings), and facilitating coping attempts (2/4 findings). Of the 5 neurobiological studies, the influence of social support on pain reduction was associated with reduced neural and physiological stress systems in response to painful stimuli., Discussion: This review presents evidence that the stress-buffering effect is more often able to account for the relationship between social support and pain experience. Moreover, findings suggest the critical significance of stress appraisal and attenuated stress systems in linking social support to aspects of reduced pain experience. Findings implicate the role of integrating perceived support and intimacy in support-oriented interventional trials for chronic pain.

Objective: To investigate the relationship between tendon structural changes determined by static ultrasound images (US) and sensory changes using quantitative sensory testing (QST), and clinical measures in lateral epicondylalgia., Materials and Methods: Both elbows of 66 adult participants with a clinical diagnosis of lateral epicondylalgia were investigated. Using a standardised ultrasound image rating scale, common extensor hypoechogenicity, heterogenicity, neovascularity, and bony abnormalities at the enthesis were scored, and tendon thickness (longitudinal and transverse plane) was measured by a trained assessor. Sensory measures of pressure, heat and cold pain thresholds and vibration detection threshold were recorded. Pain and function were assessed using the patient-rated tennis elbow (PRTEE), pain-free grip strength, pain visual analog scale (PVAS) and quality of life (EuroQoL EQ -5D). Univariate and multivariate linear regression analyses were used to explore the association between tendon structural, sensory and clinical variables which were adjusted for age, gender and duration of symptoms., Results: A negative correlation was identified between the presence of neovascularity and cold pain threshold (P = 0.015). Multiple regression analyses revealed that a combination of female gender (P = 0.044) and transverse tendon thickness (P = 0.010) were significantly associated with vibration detection threshold in affected elbows, while gender (P = 0.012) and total ultrasound scale score (P = 0.024) were significantly associated with heat pain threshold and vibration detection threshold in unaffected elbows. Heat pain threshold and gender were significantly associated with pain and disability (PRTEE; P < 0.001), and pain-free grip strength (P < 0.001) respectively, in the affected elbows., Conclusion: Generally, structural and sensory measures were weakly correlated. However, neovascularity and transverse tendon thickness may be related to sensory system changes in LE., Competing Interests: The Authors have declared that no competing interests exist.