bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding local ethnic inequalities in childhood BMI through cross-sectional analysis of routinely collected local data
Authors: Murphy Marie , Johnson Rebecca , Parsons Nicholas R. , Robertson Wendy
Published: November 2019

Background

Local-level analysis of ethnic inequalities in health is lacking, prohibiting a comprehensive understanding of the health needs of local populations and the design of effective health services. Knowledge of ethnic disparities in child weight status is particularly limited by overlooking both the heterogeneity within ethnic groupings; and the complex ecological contexts in which obesity arises. This study aimed to establish whether there was variation in childhood BMI across ethnic groups in Coventry, and the influence of individual, school and neighbourhood contexts, using routinely collected local data.

Methods

National Child Measurement Programme data were compiled for the period 2007/8–2014/15 and combined with routinely collected local data reflecting school performance and demographics, and school and neighbourhood physical environments. Multi-level modelling using Monte Carlo Markov Chain methods was used to account for the clustering of children within schools and neighbourhoods. Ethnic group differences in BMI z-score (zBMI) were explored at 4–5 years and 10–11 years for girls and boys alongside individual, school and neighbourhood covariates.

Results

At age 4–5 years (n = 28,407), ethnic group differences were similar for boys and girls, with children from South Asian, White other, Chinese and ‘any other’ ethnic groups having a significantly lower zBMI, and Black African children having a higher zBMI, versus White British (WB) children. Patterns differed considerably at age 10–11 years (n = 25,763) with marked sex differences. Boys from White other, Bangladeshi and Black African groups had a significantly higher zBMI than WB boys. For girls, only children from Black ethnic groups showed a significantly higher zBMI. Area-level deprivation was the only important school or neighbourhood covariate, but its inclusion did not explain ethnic group differences in child zBMI.

Conclusion

This analysis contributes to the existing literature by identifying nuanced patterns of ethnic disparities in childhood adiposity in Coventry, supporting the targeting of early obesity prevention for children from Black African groups, as well as girls from Black Caribbean and Black other ethnic backgrounds; and boys from Bangladeshi and White other ethnic backgrounds. It also demonstrates the utility of exploring routinely collected local data sets in building a comprehensive understanding of local population needs.
Niacin, lutein and zeaxanthin and physical activity have an impact on Charlson comorbidity index using zero-inflated negative binomial regression model: National Health and Nutrition Examination Survey 2013–2014
Authors: Zhao Hantong , Wang Changcong , Pan Yingan , Guo Yinpei , Yao Nan , Wang Han , Jin Lina , Li Bo
Published: November 2019

Background

Combined with the increasing life expectancy, chronic medical conditions have gradually become the dominant cause of death and disability, and multimorbidity became an increasingly serious public health challenge. However, most existing studies have focused on the coexistence of specific diseases or relatively few diseases. Given one person may have multiple diseases at the same time, we applied Charlson Comorbidity Index (CCI) to systematically evaluate one’s 10-year mortality. In this study, we explored the effects of nutrients and physical activity on CCI using National Health and Nutrition Examination Survey (NHANES) 2013–2014 data.

Methods

The study sample consists of one continuous cycle (2013–2014) of NHANES, and 4386 subjects were included in the study. Nutrients intake was measured by dietary recall, and physical activity was evaluated by the Global Physical Activity Questionnaire respectively. Besides, CCI was the sum of the scores assigned for each medical condition. We utilized zero-inflated negative binomial (ZINB) model to investigate the effects in nutrients intake and physical activity on CCI by adjusting for seven sociodemographic characteristics, smoking and drinking.

Results

Among the 4386 participants, 2018 (68.7%) are Non-Hispanic White, over half participants (78.6%) drink. In count part (CCI ≥ 0), holding other variables constant, the expected change in CCI for a one-unit increase in niacin is 1.621(RR = 1.621, p = 0.016), in lutein + zeaxanthin is 0.974 (RR = 0.974, p = 0.031), and in sedentary time is 1.035 (RR = 1.035, p = 0.005). Moreover, those who do not have vigorous work activity would be more likely to have higher CCI than those who have (RR = 1.275, P = 0.045). In logit part (CCI = 0), the log odds of having CCI equals zero would increase by 0.541 and 0.708 for every additional vigorous recreational activity (OR = 0.541, p = 0.004) and moderate recreational activity (OR = 0.708, p = 0.017) respectively.

Conclusions

Lutein and zeaxanthin intake, vigorous work activity, vigorous recreational activity and moderate recreational activity may be good for one’s health. Rather, increasing niacin intake and sedentary activity may be likely to raise 10-year mortality. Our findings may be significant for preventing diseases and improving health, furthermore, reducing people’s financial burden on healthcare.
Ethnic and gender differences in the management of type 2 diabetes: a cross-sectional study from Norwegian general practice
Authors: Tran Anh Thi , Berg Tore Julsrud , Gjelsvik Bjørn , Mdala Ibrahimu , Thue Geir , Cooper John Graham , Nøkleby Kjersti , Claudi Tor , Bakke Åsne , Sandberg Sverre , Jenum Anne Karen
Published: November 2019

Background

Ethnic minority groups from Asia and Africa living in Western countries have a higher prevalence of type 2 diabetes (T2DM) than the general population. We aimed to assess ethnic differences in diabetes care by gender.

Methods

Population-based, cross-sectional study identified 10,161 individuals with T2DM cared for by 282 General Practitioners (GP) in Norway. Ethnicity was based on country of birth. Multilevel regression models adjusted for individual and GP factors were applied to evaluate ethnic differences by gender.

Results

Diabetes was diagnosed at a younger mean age in all other ethnic groups compared with Westerners (men: 45.9–51.6 years vs. 56.4 years, women: 44.9–53.8 years vs. 59.1 years). Among Westerners mean age at diagnosis was 2.7 years higher in women compared with men, while no gender difference in age at diagnosis was found in any minority group. Daily smoking was most common among Eastern European, South Asian and Middle East/North African men. In both genders, we found no ethnic differences in processes of care (GPs’ measurement of HbA1c, blood pressure, LDL-cholesterol, creatinine). The proportion who achieved the HbA1c treatment target was higher in Westerners (men: 62.3%; women: 66.1%), than in ethnic minorities (men 48.2%; women 53.5%). Compared with Western men, the odds ratio (OR) for achieving the target was 0.45 (95% CI 0.27 to 0.73) in Eastern European; 0.67 (0.51 to 0.87) in South Asian and 0.62 (0.43 to 0.88) in Middle Eastern/North African men. Compared with Western women, OR was 0.49 (0.28 to 0.87) in Eastern European and 0.64 (0.47 to 0.86) South Asian women.

Compared with Westerners, the blood pressure target was more often achieved in South Asians and Middle Easterners/North Africans in both genders. Small ethnic differences in achieving the LDL-cholesterol treatment target by gender were found.

Conclusion

Diabetes was diagnosed at a considerably earlier age in both minority men and minority women compared with Westerners. Several minority groups had worse glycaemic control compared with Westerners in both genders, which implies that it is necessary to improve glucose lowering treatment for the minority groups. Smoking cessation advice should particularly be offered to men in most minority groups.
Communication and patient safety in gynecology and obstetrics - study protocol of an intervention study
Authors: Lippke Sonia , Wienert Julian , Keller Franziska Maria , Derksen Christina , Welp Annalena , Kötting Lukas , Hofreuter-Gätgens Kerstin , Müller Hardy , Louwen Frank , Weigand Marcel , Ernst Kristina , Kraft Katrina , Reister Frank , Polasik Arkadius , Huener nee Seemann Beate , Jennewein Lukas , Scholz Christoph , Hannawa Annegret
Published: November 2019

Background

Patient safety is a key target in public health, health services and medicine. Communication between all parties involved in gynecology and obstetrics (clinical staff/professionals, expectant mothers/patients and their partners, close relatives or friends providing social support) should be improved to ensure patient safety, including the avoidance of preventable adverse events (pAEs). Therefore, interventions including an app will be developed in this project through a participatory approach integrating two theoretical models. The interventions will be designed to support participants in their communication with each other and to overcome difficulties in everyday hospital life. The aim is to foster effective communication in order to reduce the frequency of pAEs. If communication is improved, clinical staff should show an increase in work satisfaction and patients should show an increase in patient satisfaction.

Methods

The study will take place in two maternity clinics in Germany. In line with previous studies of complex interventions, it is divided into three interdependent phases. Each phase provides its own methods and data. Phase 1: Needs assessment and a training for staff (n = 140) tested in a pre-experimental study with a pre/post-design. Phase 2: Assessment of communication training for patients and their social support providers (n = 423) in a randomized controlled study. Phase 3: Assessment of an app supporting the communication between staff, patients, and their social support providers (n = 423) in a case-control study. The primary outcome is improvement of communication competencies. A range of other implementation outcomes will also be assessed (i.e. pAEs, patient/treatment satisfaction, work satisfaction, safety culture, training-related outcomes).

Discussion

This is the first large intervention study on communication and patient safety in gynecology and obstetrics integrating two theoretical models that have not been applied to this setting. It is expected that the interventions, including the app, will improve communication practice which is linked to a lower probability of pAEs. The app will offer an effective and inexpensive way to promote effective communication independent of users’ motivation. Insights gained from this study can inform other patient safety interventions and health policy developments.

Trial registration

ClinicalTrials.gov Identifier: NCT03855735; date of registration: February 27, 2019.
Twenty percent better with 20 micrograms? A qualitative study of psychedelic microdosing self-rapports and discussions on YouTube
Authors: Andersson Martin , Kjellgren Anette
Published: November 2019

Background

Psychedelic microdosing is the trending practice of using tiny repeated doses of psychedelic substances to facilitate a range of supposed benefits. With only a few published studies to date, the subject is still under-researched, and more knowledge is warranted. Social media and internet discussion forums have played a vital role in the growing visibility of the microdosing phenomenon, and the present study utilized YouTube contents to improve comprehension of the microdosing practice as well as the social interactions and discussions around microdosing.

Methods

Microdosing self-disclosure in YouTube videos and their following comments were qualitatively analyzed by inductive thematic analysis. Various software was utilized to enable gathering and sorting relevant data.

Results

Microdosing of psychedelic substances, primarily LSD and psilocybin, was used for therapeutic and enhancement purposes, and predominantly beneficial effects were reported. Many different applications and outcomes were discussed, and therapeutic effects for depression appeared especially noteworthy. Intentions for use were recognized as an influencing factor for the progression and outcomes of microdosing. The function of social interactions was mainly to discuss views on the microdosing phenomenon, strategies for optimal results, minimize risks, and share emotional support.

Conclusions

Potentially, microdosing could provide some of the same benefits (for certain conditions) as full-dose interventions with less risk of adverse reactions related to the sometimes intense experiences of higher doses. Microdosing may well also mean additional benefits, as well as risks, through the repeated exposure over extended periods.
The dynamics of the inflammatory response during BBN-induced bladder carcinogenesis in mice
Authors: Degoricija Marina , Korac-Prlic Jelena , Vilovic Katarina , Ivanisevic Tonci , Haupt Benedikt , Palada Vinko , Petkovic Marina , Karaman Ivana , Terzic Janos
Published: November 2019

Background

Bladder cancer (BC) is the most common malignant disease of the urinary tract. Recurrent high grade non muscle invasive BC carries a serious risk for progression and subsequent metastases. The most common preclinical mouse model for bladder cancer relies on administration of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) to mice. BBN-induced tumors in mice recapitulate the histology of human BC and were characterized with an overexpression of markers typical for basal-like cancer subtype in addition to a high mutational burden with frequent mutations in Trp53, similar to human muscle invasive BC.

Methods

Bladder cancer was induced in C57BL/6J male mice by administering the BBN in the drinking water. A thorough histopathological analysis of bladder specimen during and post BBN treatment was performed at 2, 4, 16, 20 and 25 weeks. RNA sequencing and qPCR was performed to assess the levels of expression of immunologically relevant genes at 2 weeks and 20 weeks during and post BBN treatment.

Results

We characterized the dynamics of the inflammatory response in the BBN-induced BC in mice. The treatment with BBN had gradually induced a robust inflammation in the first 2 weeks of administration, however, the inflammatory response was progressively silenced in the following weeks of the treatment, until the progression of the primary carcinoma. Tumors at 20 weeks were characterized with a marked upregulation of IL18 when compared to premalignant inflammatory response at 2 weeks. In accordance with this, we observed an increase in expression of IFNγ-responsive genes coupled to a pronounced lymphocytic infiltrate during the early stages of malignant transformation in bladder. Similar to human basal-like BC, BBN-induced murine tumors displayed an upregulated expression of immunoinhibitory molecules such as CTLA-4, PD-L1, and IDO1 which can lead to cytotoxic resistance and tumor escape.

Conclusions

Despite the recent advances in bladder cancer therapy which include the use of checkpoint inhibitors, the treatment options for patients with locally advanced and metastatic BC remain limited. BBN-induced BC in mice displays an immunological profile which shares similarities with human MIBC thus representing an optimal model for preclinical studies on immunomodulation in management of BC.
Monocarboxylate transporter 1 promotes classical microglial activation and pro-inflammatory effect via 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3
Authors: Kong Liang , Wang Zehua , Liang Xiaohong , Wang Yue , Gao Lifen , Ma Chunhong
Published: November 2019

Background

Microglia, the resident macrophages of central nervous system, have been initially categorized into two opposite phenotypes: classical activation related to pro-inflammatory responses and alternative activation corresponding with anti-inflammatory reactions and tissue remodeling. The correlation between metabolic pattern and microglial activation has been identified. However, little is known about the mechanism of metabolism-mediated microglia polarization and pro-inflammatory effect.

Methods

Metabolic alteration was analyzed in different phenotypes of microglia in vitro. LPS-induced neuroinflammation and sickness behavior mouse model was used to investigate the effect of lactate on classical microglial activation in vivo.

Results

Glycolysis-related regulators, monocarboxylate transporter 1 (MCT1), MCT4, and pro-glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), were specifically increased in LPS-stimulated primary microglia and microglia cell line BV2. Knockdown of MCT1 suppressed glycolysis rate and decreased LPS-induced expression of iNOS, interleukin-1β (IL-1β), IL-6, and phosphorylation of STAT1 in BV2 cells. Importantly, MCT1 promoted PFKFB3 expression via hypoxia-inducible factor-1α (Hif-1α), and overexpression of PFKFB3 restored the classical activation of BV2 cells suppressed by MCT1 silence. All above strongly suggested that MCT1/PFKFB3 might accelerate LPS-induced classical polarization of microglia probably by promoting glycolysis. Interestingly, additional administration of moderate lactate, which may block the transport function of MCT1, decreased LPS-induced classical activation and expression of PFKFB3 in BV2 cells. Intracerebroventricular injection of lactate ameliorated LPS-induced sickness behavior and classical polarization of microglia in mice.

Conclusions

Our results demonstrate the key role of MCT1 in microglial classical activation and neuroinflammation in pathological conditions. In addition, lactate administration may be a potential therapy to suppress neuroinflammation by altering microglial polarization.
Power asymmetries in global governance for health: a conceptual framework for analyzing the political-economic determinants of health inequities
Authors: Kentikelenis Alexander , Rochford Connor
Published: November 2019

Background

Recent scholarship has increasingly identified global power asymmetries as the root cause of health inequities. This article examines how such asymmetries manifest in global governance for health, and how this impacts health outcomes.

Results

We focus on the political-economic determinants of global health inequities, and how these determinants operate at different levels of social action (micro, meso, and macro) through distinct but interacting mechanisms. To clarify how these mechanisms operate, we develop an integrative framework for examining the links between global neoliberalism—the currently dominant policy paradigm premised on advancing the reach of markets and promoting ever-growing international economic integration—and global health inequities, and show how these mechanisms have macro–macro, macro–meso–macro, and macro–micro–macro manifestations.

Conclusions

Our approach enables the design of theoretically-nuanced empirical strategies to document the multiple ways in which the political economy entrenches or, alternatively, might ameliorate global health inequities.
Japan: achieving UHC by regulating payment
Authors: Ikegami Naoki
Published: November 2019

The triple goals of Universal Health Coverage (UHC) are to cover the whole population, to reduce patients’ costs, and to expand coverage to all effective services, equitably available to all. This paper analyses the experience of Japan in achieving these goals, focusing on the central role played by the payment system. The payment system, or fee schedule, sets the price of services and pharmaceuticals, as well as the conditions that providers must comply with in order to receive payment. The fee schedule was first introduced following the enactment of social health insurance (SHI) in 1922. Initially, the SHI program covered only manual workers, who comprised a mere 3% of the population. However, the fee schedule of the largest SHI plan was subsequently adopted by all other SHI plans. From 1958, there has been only one fee schedule. Population coverage was achieved in 1961 by mandating all residing in Japan to enroll in SHI, thereby making everyone entitled to all the services and pharmaceuticals listed in the fee schedule. Next, co-insurance was capped to an affordable level by the introduction of catastrophic coverage in 1973. Lastly, extra billing and balance billing were explicitly restricted in 1984. The key to achieving and sustaining UHC goals in Japan lies in being able to contain costs and reallocate resources by revising the fee schedule.
A conceptual framework for capacity strengthening of health research in conflict: the case of the Middle East and North Africa region
Authors: El Achi Nassim , Papamichail Andreas , Rizk Anthony , Lindsay Helen , Menassa Marilyne , Abdul-Khalek Rima A. , Ekzayez Abdulkarim , Dewachi Omar , Patel Preeti
Published: November 2019

Background

In conflict settings, research capacities have often been de-prioritized as resources are diverted to emergency needs, such as addressing elevated morbidity, mortality and health system challenges directly and/or indirectly associated to war. This has had an adverse long-term impact in such protracted conflicts such as those found in the Middle East and North Africa region (MENA), where research knowledge and skills have often been compromised. In this paper, we propose a conceptual framework for health research capacity strengthening that adapts existing models and frameworks in low- and middle-income countries and uses our knowledge of the MENA context to contextualise them for conflict settings.

Methods

The framework was synthesized using “best fit” framework synthesis methodology. Relevant literature, available in English and Arabic, was collected through PubMed, Google Scholar and Google using the keywords: capacity building; capacity strengthening; health research; framework and conflict. Grey literature was also assessed.

Results

The framework is composed of eight principal themes: “structural levels”, “the influence of the external environment”, “funding, community needs and policy environment”, “assessing existing capacity and needs”, “infrastructure and communication”, “training, leadership and partnership”, “adaptability and sustainability”, and “monitoring and evaluation”; with each theme being supported by examples from the MENA region. Our proposed framework takes into consideration safety, infrastructure, communication and adaptability as key factors that affect research capacity strengthening in conflict. As it is the case more generally, funding, permissible political environments and sustainability are major determinants of success for capacity strengthening for health research programmes, though these are significantly more challenging in conflict settings. Nonetheless, health research capacity strengthening should remain a priority.

Conclusion

The model presented is the first framework that focuses on strengthening health research capacity in conflict with a focus on the MENA region. It should be viewed as a non-prescriptive reference tool for health researchers and practitioners, from various disciplines, involved in research capacity strengthening to evaluate, use, adapt and improve. It can be further extended to include representative indicators and can be later evaluated by assessing its efficacy for interventions in conflict settings.
An efficient system composed of maize protoplast transfection and HPLC–MS for studying the biosynthesis and regulation of maize benzoxazinoids
Authors: Gao Lei , Shen Guojing , Zhang Lingdan , Qi Jinfeng , Zhang Cuiping , Ma Canrong , Li Jing , Wang Lei , Malook Saif Ul , Wu Jianqiang
Published: November 2019

Background

Insect herbivory poses a major threat to maize. Benzoxazinoids are important anti-insect secondary metabolites in maize, whose biosynthetic pathway has been extensively studied. However, yet little is known about how benzoxazinoids are regulated in maize, partly due to lack of mutant resources and recalcitrance to genetic transformation. Transient systems based on mesophyll- or cultured cell-derived protoplasts have been exploited in several plant species and have become a powerful tool for rapid or high-throughput assays of gene functions. Nevertheless, these systems have not been exploited to study the regulation of secondary metabolites.

Results

A protocol for isolation of protoplasts from etiolated maize seedlings and efficient transfection was optimized. Furthermore, a 10-min-run-time and highly sensitive HPLC–MS method was established to rapidly detect and quantify maize benzoxazinoids. Coupling maize protoplast transfection and HPLC–MS, we screened a few genes potentially regulating benzoxazinoid biosynthesis using overexpression or silencing by artificial microRNA technology.

Conclusions

Combining the power of maize protoplast transfection and HPLC–MS analysis, this method allows rapid screening for the regulatory and biosynthetic genes of maize benzoxazinoids in protoplasts, before the candidates are selected for in planta functional analyses. This method can also be applied to study the biosynthesis and regulation of other secondary metabolites in maize and secondary metabolites in other plant species, including those not amenable to transformation.
Functional outcomes after total joint arthroplasty are related to the severity of Parkinson’s disease: a mid-term follow-up
Authors: Rong Xiao , Dahal Suraj , Luo Ze-yu , Zhou Kai , Yao Shun-Yu , Zhou Zong-Ke
Published: November 2019

Background

Performing total joint arthroplasty (TJA) in Parkinson’s disease (PD) patients may encounter a higher complication rate or worse functional outcomes compared with common patients. The relationship between PD and clinical outcomes after TJA is not fully understood.

Methods

Retrospectively, we used manual charts to investigate the clinical outcomes in 41 patients including 24 total hip arthroplasty (THA) patients (28 hips) and 18 total knee arthroplasty (TKA) patients (22 knees) with a diagnosis of PD from 2009 to 2016. The stage of PD was confirmed by Hoehn and Yahr scale. Prosthesis survivorship was estimated with revision for any reason as the endpoint.

Result

All the clinical outcomes improved significantly (p < 0.05). Subgroup analysis revealed worse functional outcomes in mid- or end-stage PD patients. Sixteen short-term mild to moderate complications were noted. Two revisions were conducted for hip periprosthetic osteolysis and postoperative knee pain. The prosthesis survivorship at 60 months for TJA, total hip arthroplasty (THA), or total knee arthroplasty (TKA) was 91.6%, 94.1%, and 87.5%, respectively.

Conclusion

Patients with PD who underwent TJA would result in excellent pain relief and gain of function. However, patients at late-stage PD may suffer from functional loss. The effectiveness of TJA in patients with severe PD remains a concern. Physician should help delay the progression of PD which may optimize and stabilize the functional outcomes of TJA.
Supramalleolar osteotomy combined with lateral ligament reconstruction and talofibular immobilization for varus ankle osteoarthritis with excessive talar tilt angle
Authors: Qu Wenqing , Xin Dajiang , Dong Shengjie , Li Wenliang , Zheng Yanping
Published: November 2019

Background

Although supramalleolar osteotomy is the main joint-preserving method for the treatment of varus ankle osteoarthritis, it tends to be ineffective when ankle osteoarthritis presents in combination with an excessive talar tilt angle. The purpose of this study was to present a new surgical technique, supramalleolar osteotomy combined with lateral ligament reconstruction and talofibular immobilization, for the treatment of varus ankle osteoarthritis with an excessive talus tilt angle and to evaluate the clinical and radiological results.

Methods

From January 2013 to October 2016, a total of 17 patients with 17 cases of varus ankle arthritis with excessive talar tilt angles (larger than 7.3°) underwent surgical treatment using our new technique. The American Orthopaedic Foot and Ankle Society (AOFAS) clinical ankle-hindfoot scale and a visual analogue scale (VAS) were used to evaluate ankle function and pain before surgery and at the last follow-up. The medial distal tibial angle (MDTA), anterior distal tibial angle (ADTA), talar tilt angle (TTA), and hindfoot moment arm values (HMAVs) were evaluated on weight-bearing radiographs acquired preoperatively and at the last follow-up.

Results

The AOFAS score improved significantly from 45.8 ± 2.1 before surgery to 84.8 ± 1.8 after surgery (p < 0.001), and the VAS score decreased from 4.9 ± 0.4 to 1.1 ± 0.2 (p < 0.001). The MDTA, TTA, and HMAV changed from 80.9° ± 0.4° to 90.1° ± 0.4°, 11.7° ± 0.6° to 1.4° ± 0.3°, and 12.6 mm ± 0.8 mm to 4.2 mm ± 0.6 mm, respectively (each p < 0.001). The ADTA showed no obvious change (p = 0.370). The staging of 11 cases (65%) improved. Intramuscular vein thrombosis of the lower limbs occurred in 1 patient 1 week after surgery, and superficial infection occurred in 1 patient.

Conclusions

Supramalleolar osteotomy combined with lateral ligament reconstruction and talofibular immobilization can correct the load of the weight-bearing ankle and effectively improve the ankle function. As the talar tilt angle can be significantly improved after surgery, this technique can be used for the treatment of varus ankle osteoarthritis with an excessive TTA.
RETRACTED ARTICLE: Effect of sagittal femoral component alignment on biomechanics after mobile-bearing total knee arthroplasty
Authors: Koh Yong-Gon , Lee Jin-Ah , Lee Hwa-Yong , Suh Dong-Suk , Kim Hyo-Jeong , Kang Kyoung-Tak
Published: November 2019

Background

Recently, there has been increasing interest in mobile-bearing total knee arthroplasty (TKA). However, changes in biomechanics with respect to femoral component alignment in mobile-bearing TKA have not been explored in depth. This study aims to evaluate the biomechanical effect of sagittal alignment of the femoral component in mobile-bearing TKA.

Methods

We developed femoral sagittal alignment models with − 3°, 0°, 3°, 5°, and 7°. We also examined the kinematics of the tibiofemoral (TF) joint, contact point on the TF joint, contact stress on the patellofemoral (PF) joint, collateral ligament force, and quadriceps force using a validated computational model under a deep-knee-bend condition.

Results

Posterior kinematics of the TF joint increased as the femoral component flexed. In addition, contact stress on the PF joint, collateral ligament force, and quadriceps force decreased as the femoral component flexed. The results of this study can assist surgeons in assessing risk factors associated with femoral component sagittal alignment for mobile-bearing TKA.

Conclusions

Our results showed that slight flexion implantation may be an effective alternative technique because of its advantageous biomechanical effect. However, excessive flexion should be avoided because of potential loosening of the TF joint.
Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial
Authors:   on behalf of the Magic Bullet Working Group WP1, Cisneros José M. , Rosso-Fernández Clara María , Roca-Oporto Cristina , De Pascale Gennaro , Jiménez-Jorge Silvia , Fernández-Hinojosa Esteban , Matthaiou Dimitrios K. , Ramírez Paula , Díaz-Miguel Ramón Ortiz , Estella Angel , Antonelli Massimo , Dimopoulos George , Garnacho-Montero José
Published: November 2019

Background

Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined.

Methods

A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7–14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved.

Results

A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of − 2.16 (− 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015).

Conclusions

This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination.

Trial registration

ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.
Ductal tree ablation by local delivery of ethanol prevents tumor formation in an aggressive mouse model of breast cancer
Authors: Kenyon Elizabeth , Westerhuis Jennifer J. , Volk Maximilian , Hix Jeremy , Chakravarty Shatadru , Claucherty Ethan , Zaluzec Erin , Ramsey Lisa , Madaj Zach , Hostetter Galen , Eagleson Bryn , Shapiro Erik , Moore Anna , Sempere Lorenzo F.
Published: November 2019

Background

Prophylactic mastectomy is the most effective intervention to prevent breast cancer. However, this major surgery has life-changing consequences at the physical, emotional, psychological, and social levels. Therefore, only high-risk individuals consider this aggressive procedure, which completely removes the mammary epithelial cells from which breast cancer arises along with surrounding tissue. Here, we seek to develop a minimally invasive procedure as an alternative to prophylactic mastectomy by intraductal (ID) delivery of a cell-killing solution that locally ablates the mammary epithelial cells before they become malignant.

Methods

After ID injection of a 70% ethanol-containing solution in FVB/NJ female animals, ex vivo dual stained whole-mount tissue analysis and in vivo X-ray microcomputed tomography imaging were used to visualize ductal tree filling, and histological and multiplex immunohistochemical assays were used to characterize ablative effects and quantitate the number of intact epithelial cells and stroma. After ID injection of 70% ethanol or other solutions in cancer-prone FVB-Tg-C3(1)-TAg female animals, mammary glands were palpated weekly to establish tumor latency and examined after necropsy to record tumor incidence. Statistical difference in median tumor latency and tumor incidence between experimental groups was analyzed by log-rank test and logistic mixed-effects model, respectively.

Results

We report that ID injection of 70% ethanol effectively ablates the mammary epithelia with limited collateral damage to surrounding stroma and vasculature in the murine ductal tree. ID injection of 70% ethanol into the mammary glands of the C3(1)-TAg multifocal breast cancer model significantly delayed tumor formation (median latency of 150 days in the untreated control group [n = 25] vs. 217 days in the ethanol-treated group [n = 13], p value < 0.0001) and reduced tumor incidence (34% of glands with tumors [85 of 250] in the untreated control group vs. 7.3% of glands with tumor [7 of 95] in the ethanol-treated group, risk ratio = 4.76 [95% CI 1.89 to 11.97, p value < 0.0001]).

Conclusions

This preclinical study demonstrates the feasibility of local ductal tree ablation as a novel strategy for primary prevention of breast cancer. Given the existing clinical uses of ethanol, ethanol-based ablation protocols could be readily implemented in first-in-human clinical trials for high-risk individuals.
RegSNPs-intron: a computational framework for predicting pathogenic impact of intronic single nucleotide variants
Authors: Lin Hai , Hargreaves Katherine A. , Li Rudong , Reiter Jill L. , Wang Yue , Mort Matthew , Cooper David N. , Zhou Yaoqi , Zhang Chi , Eadon Michael T. , Dolan M. Eileen , Ipe Joseph , Skaar Todd C. , Liu Yunlong
Published: November 2019

Single nucleotide variants (SNVs) in intronic regions have yet to be systematically investigated for their disease-causing potential. Using known pathogenic and neutral intronic SNVs (iSNVs) as training data, we develop the RegSNPs-intron algorithm based on a random forest classifier that integrates RNA splicing, protein structure, and evolutionary conservation features. RegSNPs-intron showed excellent performance in evaluating the pathogenic impacts of iSNVs. Using a high-throughput functional reporter assay called ASSET-seq (ASsay for Splicing using ExonTrap and sequencing), we evaluate the impact of RegSNPs-intron predictions on splicing outcome. Together, RegSNPs-intron and ASSET-seq enable effective prioritization of iSNVs for disease pathogenesis.
Common DNA sequence variation influences 3-dimensional conformation of the human genome
Authors: Gorkin David U. , Qiu Yunjiang , Hu Ming , Fletez-Brant Kipper , Liu Tristin , Schmitt Anthony D. , Noor Amina , Chiou Joshua , Gaulton Kyle J. , Sebat Jonathan , Li Yun , Hansen Kasper D. , Ren Bing
Published: November 2019

Background

The 3-dimensional (3D) conformation of chromatin inside the nucleus is integral to a variety of nuclear processes including transcriptional regulation, DNA replication, and DNA damage repair. Aberrations in 3D chromatin conformation have been implicated in developmental abnormalities and cancer. Despite the importance of 3D chromatin conformation to cellular function and human health, little is known about how 3D chromatin conformation varies in the human population, or whether DNA sequence variation between individuals influences 3D chromatin conformation.

Results

To address these questions, we perform Hi-C on lymphoblastoid cell lines from 20 individuals. We identify thousands of regions across the genome where 3D chromatin conformation varies between individuals and find that this variation is often accompanied by variation in gene expression, histone modifications, and transcription factor binding. Moreover, we find that DNA sequence variation influences several features of 3D chromatin conformation including loop strength, contact insulation, contact directionality, and density of local cis contacts. We map hundreds of quantitative trait loci associated with 3D chromatin features and find evidence that some of these same variants are associated at modest levels with other molecular phenotypes as well as complex disease risk.

Conclusion

Our results demonstrate that common DNA sequence variants can influence 3D chromatin conformation, pointing to a more pervasive role for 3D chromatin conformation in human phenotypic variation than previously recognized.
Safety and efficacy of PG102P for the control of pruritus in patients undergoing hemodialysis (SNUG trial): study protocol for a randomized controlled trial
Authors: Kim Yong Chul , Park Jae Yoon , Oh Sohee , Cho Jang-Hee , Chang Jae Hyun , Choi Dae Eun , Park Jung Tak , Lee Jung Pyo , Kim Sejoong , Kim Dong Ki , Ryu Dong-Ryeol , Lim Chun Soo
Published: November 2019

Background

Pruritus in patients undergoing hemodialysis is a highly prevalent complication that affects quality of life. Several medications are currently used for the treatment of uremic pruritus, but these are not satisfactory. PG102P, which is prepared fromActinidia arguta, has an immune-modulating effect on pruritus. This trial is designed to assess the antipruritic effect of PG102P compared with placebo.

Methods

This multicenter, randomized, double-blind, placebo-controlled clinical trial will include 80 patients undergoing hemodialysis. The patients will be randomized in a 1:1 ratio to a treatment group (PG102P 1.5 g/day) or a control group (placebo). The treatment will last for 8 weeks, followed by a 2-week observational period. During the observational period, all of the patients will maintain the antipruritic treatment previously used. The primary endpoint will be measured as the difference in visual analog scale between the groups before and after treatment. Secondary outcomes include serum levels of total immunoglobulin E, eosinophil cationic protein, potassium, calcium, phosphorus, intact parathyroid hormone, and blood eosinophil count between weeks 0 and 8. Kidney Disease and Quality of Life and Beck’s Depression Inventory questionnaires will be conducted. Safety assessments and any adverse events that occur will also be evaluated.

Discussion

The SNUG is a clinical study that aims to investigate the antipruritic effect of PG102P to ameliorate itching in patients undergoing hemodialysis.

Trial registration

Clinical Trials.gov,NCT03576235. Registered on 4 July 2018.
The effects of oral vitamin D supplementation on the prevention of peritoneal dialysis-related peritonitis: study protocol for a randomized controlled clinical trial
Authors: Zhang Yu-hui , Xu Xiao , Pi Hai-chen , Yang Zhi-kai , Johnson David W. , Dong Jie
Published: November 2019

Background

Vitamin D deficiency has been shown to be closely associated with peritoneal dialysis (PD)-related peritonitis. The aim of this study is to examine the feasibility of conducting a large, powered randomized controlled trial to determine the effects of vitamin D supplementation on the risk of PD-related peritonitis in patients who have already experienced an episode of peritonitis.

Methods

This prospective, open-label randomized controlled pilot trial with blinded end-points aims to determine the feasibility of oral vitamin D supplementation and to explore its effects on the risk of subsequent PD-related peritonitis among PD patients who have recovered from a recent episode of peritonitis. Eligible patients will be randomized 1:1 to either oral vitamin D supplementation (2000 IU per day; intervention group) or no vitamin D supplementation (control group) in addition to usual care according to International Society for Peritoneal Dialysis guidelines. The sample size will be 30 patients for both groups. All participants will be followed for 12 months. The primary outcome is the assessment of feasibility (recruitment success, retention, adherence, safety) and fidelity (change in serum 25-hydroxyvitamin D level during follow-up) for a large, powered randomized controlled trial to determine the effects of vitamin D on the risk of PD-related peritonitis in the future. Secondary outcomes include time to peritonitis occurrence, recovery of peritonitis, peritonitis-related transition to hemodialysis, and peritonitis-related death (defined as death within 30 days of peritonitis onset).

Discussion

This is the first randomized controlled trail investigating the effects of vitamin D supplementation on the risk of subsequent PD-related peritonitis among patients on PD. The findings for this pilot study will determine the feasibility of conducting a full-scale randomized controlled trail, which may provide a new strategy for preventing PD-related peritonitis among PD patients.

Trial registration

Clinicaltrails.gov, NCT03264625. Registered on 29 August 2017.
ENACT: a protocol for a randomised placebo-controlled trial investigating the efficacy and mechanisms of action of adjunctive N-acetylcysteine for first-episode psychosis
Authors: Cotton S. M. , Berk M. , Watson A. , Wood S. , Allott K. , Bartholomeusz C. F. , Bortolasci C. C. , Walder K. , O’Donoghue B. , Dean O. M. , Chanen A. , Amminger G. P. , McGorry P. D. , Burnside A. , Uren J. , Ratheesh A. , Dodd S.
Published: November 2019

Background

First-episode psychosis (FEP) may lead to a progressive, potentially disabling and lifelong chronic illness; however, evidence suggests that the illness course can be improved if appropriate treatments are given at the early stages. Nonetheless, the efficacy of antipsychotic medications is suboptimal, particularly for negative and cognitive symptoms, and more efficacious and benign treatments are needed. Previous studies have shown that the antioxidant amino acid N-acetylcysteine (NAC) reduces negative symptoms and improves functioning in chronic schizophrenia and bipolar disorder. Research is scarce as to whether NAC is beneficial earlier in the course of illness. The primary aim of this study is to determine the efficacy of treatment with adjunctive NAC (2 g/day for 26 weeks) compared with placebo to improve psychiatric symptoms in young people experiencing FEP. Secondary aims are to explore the neurobiological mechanisms underpinning NAC and how they relate to various clinical and functional outcomes at 26- and 52-week follow-ups.

Methods/design

ENACT is a 26-week, randomised controlled trial of adjunctive NAC versus placebo, with a 26-week non-treatment follow-up period, for FEP. We will be recruiting 162 young people aged 15–25 years who have recently presented to, and are being treated at, the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The primary outcome is the Total Score on the Positive and Negative Syndrome Scale which will be administered at baseline, and weeks 4, 8, 12, 26 (primary endpoint), and 52 (end of study). Secondary outcomes include: symptomatology, functioning, quality of life, neurocognition, blood-derived measures of: inflammation, oxidative and nitrosative stress, and magnetic resonance spectroscopy measures of glutathione concentration.

Discussion

Targeted drug development for FEP to date has generally not involved the exploration of neuroprotective agents. This study has the potential to offer a new, safe, and efficacious treatment for people with FEP, leading to better treatment outcomes. Additionally, the neuroprotective dimension of this study may lead to a better long-term prognosis for people with FEP. It has the potential to uncover a novel treatment that targets the neurobiological mechanisms of FEP and, if successful, will be a major advance for psychiatry.

Trial registration

Australian New Zealand Clinical Trials Registry, ID: ACTRN12618000413224. Registered on 21 March 2018.