bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between anti-diabetes treatments and cardiovascular risk in diabetes patients with and without coronary artery disease
Authors: Gyldenkerne Christine , Olesen Kevin Kris Warnakula , Madsen Morten , Thim Troels , Jensen Lisette Okkels , Raungaard Bent , Sørensen Henrik Toft , Bøtker Hans Erik , Maeng Michael
Published: April 2019

Objective:

We examined the risk of myocardial infarction associated with glucose-lowering therapy among diabetes patients with and without obstructive coronary artery disease.

Methods:

A cohort of patients with type 1 or type 2 diabetes (n = 12,030), who underwent coronary angiography from 2004 to 2012, were stratified by presence of obstructive (any stenosis ⩾50%) coronary artery disease and by type of diabetes treatment: diet, non-insulin treatment and insulin (±oral anti-diabetics). The primary endpoint was myocardial infarction. Adjusted hazard ratios were calculated using diet-treated patients without coronary artery disease as reference.

Results:

In patients without coronary artery disease, risk of myocardial infarction was similar in patients treated with non-insulin medication (adjusted hazard ratio 0.70, 95% confidence interval 0.27–1.81) and insulin (adjusted hazard ratio 0.76, 95% confidence interval 0.27–2.08) as compared to diet only. In patients with coronary artery disease, the risk of myocardial infarction was higher than in the reference group and an incremental risk was observed being lowest in patients treated with diet (adjusted hazard ratio 3.79, 95% confidence interval 1.61–8.88), followed by non-insulin medication (adjusted hazard ratio 5.42, 95% confidence interval 2.40–12.22), and highest in insulin-treated patients (adjusted hazard ratio 7.91, 95% confidence interval 3.51–17.82).

Conclusion:

The presence of obstructive coronary artery disease defines the risk of myocardial infarction in diabetes patients. Glucose-lowering therapy, in particular insulin, was associated with risk of myocardial infarction only in the presence of coronary artery disease.
Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients with combined coronary artery disease and type 2 diabetes mellitus: Sub-study of a randomized control trial
Authors: Zaidi Hani , Byrkjeland Rune , Njerve Ida U , Åkra Sissel , Solheim Svein , Arnesen Harald , Seljeflot Ingebjørg , Opstad Trine B
Published: April 2019

Background:

Adipose tissue produces pro-inflammatory mediators involved in the atherosclerotic process. We investigated whether 12-month exercise training in patients with type 2 diabetes mellitus and coronary artery disease would reduce circulating levels and genetic expression of mediators in the interleukin-18, Caspase-1 and NLR pyrin domain containing 3 pathways. Correlations to glucometabolic variables; fasting glucose, HbA1c, duration of diabetes, insulin, C-peptide, insulin resistance (measured by homeostatic model assessment indexes – insulin resistance) and body mass index at baseline were further assessed.

Methods:

137 patients (aged 41–81 years, 17.2% female participants) were included and randomized to a 12-month exercise programme or to a control group. Fasting blood and adipose tissue samples were taken at inclusion and after 12 months.

Results:

No statistically significant difference in changes of any variable between the intervention and the control group was found. At baseline, a positive correlation between insulin and homeostatic model assessment indexes – insulin resistance, interleukin-18 expression in adipose tissue and an inverse correlation between some glucometabolic variables and leukocyte expression of NLR pyrin domain containing 3 and Caspase-1 were observed.

Conclusion:

No significant effects of long-term exercise training were observed on the inflammasome-related mediators in our patients with combined coronary artery disease and type 2 diabetes mellitus. The observed correlations may indicate a pro-inflammatory state in adipose tissue by overweight and a compensatory downregulation of these mediators in circulating leucocytes.
Mortality and vertebral fracture risk associated with long-term oral steroid use in patients with chronic obstructive pulmonary disease: A systemic review and meta-analysis
Authors: Chang Yu-Ping , Lai Chien-Hao , Lin Chiung-Yu , Chang Ya-Chun , Lin Meng-Chih , Chong Inn-Wen , Sheu Chau-Chyun , Wei Yu-Feng , Chu Kuo-An , Tsai Jong-Rung , Lee Cheng-Hung , Chen Yung-Che
Published: April 2019

Short-term oral steroid use may improve lung function and respiratory symptoms in patients with stable chronic obstructive pulmonary disease (COPD). However, long-term oral steroid (LTOS) use is not recommended owing to its potential adverse effects. Our study aimed to investigate whether chronic use of oral steroids for more than 4 months would increase mortality and vertebral fracture risk in patients with stable COPD. A systemic search of the PubMed database was conducted, and meta-analysis was performed using Review Manager 5.3. Five studies with a total of 1795 patients showed there was an increased risk of mortality in patients using LTOS (relative risk, 1.63; 95% confidence interval (CI), 1.19–2.23; p < 0.0001; I2 = 86%). In addition, four studies with a total of 17,764 patients showed there was an increased risk of vertebral fracture in patients using LTOS (odds ratio, 2.31; 95% CI, 1.52–3.50; p = 0.03; I2 = 65%). Our meta-analysis showed LTOS was associated with increased mortality and vertebral fracture risk in patients with COPD, and this risk may be due to the adverse effects of LTOS and progression COPD.
Progress of Tumor Growth and Metastasis After Inoculation of B16FO Melanoma Cells in Kidney of Female Nude Mice Is Inhibited by a Novel Nutrient Mixture
Authors: Roomi M. Waheed , Bhanap Bilwa , Niedzwiecki Aleksandra , Rath Matthias
Published: April 2019

Background: Tumor metastasis is a major cause for most cancer-related deaths. Melanoma is a serious cancer that metastasizes to other areas of the body, including the lungs, liver, brain, bones, or lymph nodes. Currently used cancer therapies are ineffective with a high degree of toxicity and patient mortality. Thus, any successful treatment for melanoma must target metastasis. Methods: We studied the effect of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline, green tea extract, quercetin, and others, on the inhibition of melanoma growth and metastasis after inoculation of B16FO melanoma cells into the left kidney of female nude mice. Female athymic mice (n = 10) 8 to 10 weeks of age, were inoculated superficially in the left kidney with 5 × 105 B16FO melanoma cells in 100 µL of media. The right kidney was left untreated. After inoculation, the mice were randomly divided into 2 groups. The control group (n = 5) was fed a regular rodent chow diet, and the test group was given the same diet supplemented with 0.5% NM. The animals in control and the test groups were sacrificed 2 weeks later. Each animal’s abdominal cavity was opened, and the kidneys, lungs, liver, and spleen were excised and examined for tumor growth and metastasis. Results: The kidneys in the control group weighed 25% to 30% more than those in the NM group due to colonization of B16FO melanoma cells. No metastasis to the liver or spleen was observed in either of the groups. However, severe lung metastasis was observed in the control group and mild to moderate metastasis was observed in the NM group. Conclusion: These results show that the NM is effective in mitigating the growth of tumors in the kidney and metastases to the lung.
Risk Analysis Implications of Dose-Response Thresholds for NLRP3 Inflammasome-Mediated Diseases: Respirable Crystalline Silica and Lung Cancer as an Example
Authors: Cox Louis Anthony (Tony)
Published: April 2019

Chronic inflammation mediates an extraordinarily wide range of diseases. Recent progress in understanding intracellular inflammasome assembly, priming, activation, cytokine signaling, and interactions with mitochondrial reactive oxygen species, lysosome disruption, cell death, and prion-like polymerization and spread of inflammasomes among cells, has potentially profound implications for dose–response modeling. This article discusses mechanisms of exposure concentration and duration thresholds for NOD-like receptor protein 3 (NLRP3)-mediated inflammatory responses and develops a simple biomathematical model of the onset of exposure-related tissue-level chronic inflammation and resulting disease risks, focusing on respirable crystalline silica (RCS) and lung cancer risk as an example. An inflammation-mediated 2-stage clonal expansion model of RCS-induced lung cancer is proposed that explains why relatively low estimated concentrations of RCS (eg, <1 mg/m3) do not increase lung cancer risk and why even high occupational concentrations increase risk only modestly (typically relative risk <2). The model of chronic inflammation implies a dose–response threshold for excess cancer risk, in contrast to traditional linear-no-threshold assumptions. If this implication is correct, then concentrations of crystalline silica (or amphibole asbestos fibers, or other environmental challenges that act via the NLRP3 inflammasome) below the threshold do not cause chronic inflammation and resulting elevated risks of inflammation-mediated diseases.
Initial experience and one-year follow-up with Neuroform Atlas Stent System for the treatment of brain aneurysms
Authors: Quintana Eduardo Murias , Valdes Pedro Vega , Deza Edison Morales , García Alberto Gil , Rodríguez María Cadenas , Pérez Jose María Jiménez , Chaviano Juan , Morales Julio Cesar Gutierrez , Batista Kelvin Piña , García Faustino Arias
Published: April 2019

Introduction

The Neuroform Atlas Stent System is a recently introduced modification of the original Neuroform Stent System consisting of a hybrid design with open and closed cells. Initial experience, technical considerations and treatment outcomes including 1-year follow-up using the Atlas stent in combination with coil embolization are reported.

Material and methods

Thirty patients with 30 unruptured aneurysms were treated with stent reconstruction. Immediate, 4-month and 12-month post-treatment angiography and clinical assessment were performed.

Discussion

In 29 cases, the stents were delivered and positioned without difficulty in deployment. Technical complications occurred in one patient related to advancement of the stent during delivery. One procedure-related clinical complication occurred with no permanent neurological deficit. On immediate post-treatment angiography, 29 of 30 aneurysms showed Raymond Class I or Class II occlusion. At 1-year follow-up, all 30 patients were clinically stable and 18 of 30 aneurysms showed Raymond Class I complete occlusion. Retreatment was performed in two patients with residual aneurysm.

Conclusions

The Atlas stent is technically safe and simple to implant and has a low thrombogenic potential. We experienced fewer problems associated with deployment and implantation, thromboembolic complications and hemorrhagic events compared with other types of stents, including braided stents. However, because of its low thrombogenic potential, partially occluded aneurysms or those with aneurysm remnants do not progress to complete occlusion.
Stress intensity factors for embedded cracks within torsionally loaded square prismatic bars
Authors: Zhou Ding , Liew Haw Ling , Purbolaksono Judha , Andriyana Andri , Chong Wen Tong
Published: April 2019

The behavior of embedded planar elliptical cracks within square prismatic bars that are commonly used as torque-resisting structural components motivates this work, as the literature for such stress intensity factors is evidently deficient. The stress intensity factors are evaluated using the dual boundary element program of Beasy, and studied by considering the elliptical aspect ratio and the eccentricity in the sense of an offset from the centroid. The variation of shear mode stress intensity factors for a penny crack situated near to the free surface and the square corner is also reported for the first time, complementing the available results for tensile mode.
Study on motion analysis and force/position hydraulic control of a parallel cylinder transmission system of heavy-duty quadruped robot
Authors: Shao Junpeng , Jin Chaohui , Wang Xigui , Wang Yongmei , Jing Jing , Zhou Xue
Published: April 2019

In the article, a heavy-duty quadruped robot was designed. A parallel cylinder transmission scheme for the heavy load torque of the hip joint of heavy-duty hydraulic quadruped robot is proposed, the mathematical model of the parallel cylinder system is derived, the model characteristics of the parallel cylinder system are analyzed, the characteristics of internal force and joint control of parallel cylinders are considered, the force/position hybrid control of parallel cylinder is proposed to eliminate the internal forces and realize the requirement of joint control and the force/position control is decoupled by the design of the force and position signal. According to the characteristics of the servo cylinder force control model, the flow compensation and speed compensation are introduced, the minimum control synthesis controller is used to control the servo cylinder force and the proportional integral controller is applied to control the position of servo cylinder. The compound control strategy is analyzed on the table of parallel cylinder, and the experimental results show that the amplitude attenuation and phase lag of position and force are less than 10% and 18°, respectively, and the efficiency of the proposed control strategy is verified. The research results of this article will be widely used in many fields of robot control in the future.
Is breathing our polluted air a risk factor for stroke?
Authors: Estol Conrado J
Published: April 2019

The conference “Climate change, air pollution and health” was held at the Pontifical Academy of Sciences. The data presented highlighted that air pollution is a major, under-recognized and modifiable risk factor for stroke and heart disease. Air pollution causes 7.6% of all deaths making it the fifth cause of death globally, and this figure is expected to increase by 50% by 2050. Particulate matter causes endothelial dysfunction and induces thrombosis by altering reactive oxygen species, nitric oxide, insulin resistance, and lipid levels. Thirty-three articles published since 2002 were reviewed to assess the relation between air pollution and stroke with age, geographical location, particulate and gaseous matter type, duration of exposure, previous stroke, and comorbidities. It remains to be defined if air pollution has pathophysiological effects that preferentially predispose individuals to ischemic or hemorrhagic stroke. There is ample evidence showing an association between acute and chronic exposure to PM2.5 or gaseous pollutants with stroke. This potentially avoidable scenario and its dramatic consequences are heavily under-recognized by health professionals and the wider public. Preventive measures in people at high vascular risk are warranted. Procrastination in implementing efforts to stop the current worldwide course of worsening air pollution is the seed of a potential global health catastrophe.
Measuring the effects of listening for leisure on outcome after stroke (MELLO): A pilot randomized controlled trial of mindful music listening
Authors: Baylan Satu , Haig Caroline , MacDonald Maxine , Stiles Ciara , Easto Jake , Thomson Meigan , Cullen Breda , Quinn Terence J , Stott David , Mercer Stewart W , Broomfield Niall M , Murray Heather , Evans Jonathan J
Published: April 2019

Background

Cognitive deficits and low mood are common post-stroke. Music listening is suggested to have beneficial effects on cognition, while mindfulness may improve mood. Combining these approaches may enhance cognitive recovery and improve mood early post-stroke.

Aims

To assess the feasibility and acceptability of a novel mindful music listening intervention.

Methods

A parallel group randomized controlled feasibility trial with ischemic stroke patients, comparing three groups; mindful music listening, music listening and audiobook listening (control group), eight weeks intervention. Feasibility was measured using adherence to protocol and questionnaires. Cognition (including measures of verbal memory and attention) and mood (Hospital Anxiety and Depression Scale) were assessed at baseline, end of intervention and at six-months post-stroke.

Results

Seventy-two participants were randomized to mindful music listening ( n = 23), music listening ( n = 24), or audiobook listening ( n = 25). Feasibility and acceptability measures were encouraging: 94% fully consistent with protocol; 68.1% completing ≥6/8 treatment visits; 80–107% listening adherence; 83% retention to six-month endpoint. Treatment effect sizes for cognition at six month follow-up ranged from d = 0.00 ([−0.64,0.64], music alone), d = 0.31, ([0.36,0.97], mindful music) for list learning; to d = 0.58 ([0.06,1.11], music alone), d = 0.51 ([−0.07,1.09], mindful music) for immediate story recall; and d = 0.67 ([0.12,1.22], music alone), d = 0.77 ([0.16,1.38]mindful music) for attentional switching compared to audiobooks. No signal of change was seen for mood. A definitive study would require 306 participants to detect a clinically substantial difference in improvement (z-score difference = 0.66, p = 0.017, 80% power) in verbal memory (delayed story recall).

Conclusions

Mindful music listening is feasible and acceptable post-stroke. Music listening interventions appear to be a promising approach to improving recovery from stroke.
Risk, discretion, accountability and control: Police perceptions of sex offender risk management policy in England and Wales
Authors: Hoggett James , McCartan Kieran , O’Sullivan Jack
Published: April 2019

This article argues that understanding current approaches to sex offender risk management and its operationalization must account for front line situational decision-making practices and the culture from which they develop and operate. The research utilizes a mixed-methods approach, combining an online questionnaire survey ( N = 227) with a series of semi-structured interviews ( N = 27) with members of the police service of England and Wales. Analysis identifies ambivalence about the effectiveness of the current system of categorizing sex offenders and suggests concerns about accountability and a lack of resources results in discretion being used to engage with but also negotiate policy in practice. The article suggests that the task for sex offender risk management is to create classification tools that work with this discretion rather than against it.
Affirmative actions in terms of special rights: Confronting structural violence in Brazilian higher education
Authors: Silva Guilherme Henrique Gomes da , Skovsmose Ole
Published: April 2019

In this article, the authors interpret affirmative actions with reference to structural violence, which is accompanied by legitimizing discourses that tend to make discrimination appear natural and unquestionable. They illustrate the extension of structural violence in Brazilian society with particular reference to access to higher education. It has been common to talk about some groups of students as having special needs. However, the authors see groups of students suffering structural violence as being groups with special rights, and explore affirmative actions through the notion of special rights. The authors find that special-rights terminology establishes the discussion of affirmative actions in higher education in a broader and, at the same time, more profound conceptual framework related to interpretations of social justice. Simultaneously, special-rights terminology brings an educational specificity to the discussion of affirmative actions. Thus, the authors see affirmative actions as being both a general sociopolitical and specific educational challenge.
Development of a national conceptual framework and measuring tool for Organisational Social Responsibility and Accountability for Health (OSRAH)
Authors: Keshavarz Mohammadi Nastaran , Taheri Fereshteh , Motallebi Masoud , Yazdanpanah Ali , Khosravi Yahya , Borhani Jebeli Maryam , Corbin Hope J. , Farshad Ali Asghar
Published: April 2019

Organisations can have a significant impact (positive or negative) on society through their actions and decisions. Given this reality, it is important that they are held responsible and accountable for the consequences of their actions. This concept is often referred to as ‘social responsibility’. However, ‘social responsibility’, as currently conceived in the literature, neglects a specific focus on health as a social goal. Additionally, there are no practical tools to capture this concept in a holistic way to facilitate implementation and monitoring of organisational improvement. This paper reports on the process of developing a more holistic conceptual framework and tool for assessing organisational social responsibility and accountability for health (OSRAH). We conducted a review of the published and grey literature and engaged in expert consultation and focus group discussions. The initial OSRAH framework and the self-assessment tool were finalised for implementation and used by 95 organisations at a national event in Iran in February 2017. The results of the assessment data collected at the event showed organisations scored lowest in the domain of community health and highest in the domain of employee health. The OSRAH framework and assessment tool represents a new understanding of health and its determinants in organisations outside the health sector. It integrates health within the existing Corporate Social Responsibility (CSR) culture of organisations. The process of creating the tool and implementing it at the national festival of OSRAH in Iran created momentum for intersectoral action. This experience can inspire researchers and practitioners in other countries, especially in developing countries, to develop their own local definition and practical assessment framework for responsibility and accountability.
¡Activate Ya! Co-learning about school-based tobacco prevention and physical activity promotion in secondary school students in Uruguay
Authors: Springer Andrew E. , Harrell Melissa B. , Martínez Gomensoro Lucía , Traversa Fresco María , Rogers Shannon , Florines Martina , Moreno Viviana , Lee Joowon , Perry Cheryl L. , Bianco Eduardo , Estol Diego
Published: April 2019

Purpose:

¡Activate Ya! was a group-randomized controlled intervention trial aimed at developing and evaluating the impact of a school-based intervention on preventing cigarette smoking and promoting physical activity (PA) in secondary school students in Uruguay. Secondary aims were to evaluate the program’s impact on students’ smoking- and PA-related psychosocial risk and protective factors.

Methods:

Sixteen schools and n = 654 students participated in the study. The one-year intervention included a classroom-based curriculum, an afterschool program, activity breaks, and final showcase event. A self-administered questionnaire measured outcomes at three time points. Fixed effects regression models tested for differences in outcomes by study condition.

Results:

While positive intervention effects were found for selected psychosocial-related smoking outcomes, no impact on past-year smoking or smoking susceptibility was detected. Past 7-day PA, measured by the PAQ-C, was significantly higher among intervention school students overall ( p = .048) and for girls ( p = .03) at posttest, and intervention girls reported significantly higher athletic identity PA competence, friend and teacher PA support at posttest, and PA enjoyment at follow-up ( p < .05).

Conclusion:

The positive short-term effects of ¡Activate Ya! on PA and related outcomes for girls support the utility of school-based health promotion in Uruguay. Additional research is needed to determine the most effective strategies to prevent tobacco use among students and promote PA among boys in this setting.
Integrative settings approach to workplace health promotion to address contemporary challenges for worker health in the Asia-Pacific
Authors: Pham Cong Tuan , Lee Chiachi Bonnie , Nguyen Thi Lien Huong , Lin Jin-Ding , Ali Shahmir , Chu Cordia
Published: April 2019

Workplaces in the rapidly industrializing Asia-Pacific region face growing pressures from high-speed development driven by global competition, migration and the aging of the workforce. Apart from addressing work-related injuries, workplaces in the region also have to deal with increasing occupational stress, chronic diseases and their associated socio-economic burden. Meanwhile, interventions in workplace health are still dominated by a narrow behavioral change model. To this end, the integrative workplace health promotion model, initiated by the World Health Organization from successful post-1990 pilot projects, emerges as a timely, comprehensive and appropriate means to manage contemporary workplace health and safety issues in the region. In this paper, we highlight the key workplace health challenges in the Asia-Pacific region and the utility of the integrative workplace health promotion model in addressing them. We provide a brief overview of the pressing challenges confronting workplaces in the region, then explain the why, what and how of integrative workplace health promotion. We illustrate this model by reviewing successful examples of good practice and evidence of their achievements from workplace health promotion programs in Asia-Pacific from 2002 to date, with specific attention to government-led workplace health promotion programs in Shanghai, Singapore and Taiwan. Drawing from these successful examples, we recommend government policies and facilitating strategies needed to guide, support and sustain industries in implementing integrative workplace health promotion. We conclude that consistent supportive government policies, coupled with facilitation by international bodies towards capacity and professional network building, are crucial to developing and sustaining healthy workplaces in the region.
Case Study of a New Engineering Early College High School: Advancing Educational Opportunities for Underrepresented Students in an Urban Area
Authors: Gilson Cindy M. , Matthews Michael S.
Published: April 2019

In response to the pervasive problem of making college more accessible to at-risk and underrepresented populations, the early college high school (ECHS) model has gained popularity. However, limited research exists on engineering-focused ECHSs (EECHS). Given the current demand for diverse and highly qualified engineers in the workforce, further research on EECHSs that potentially support the science, technology, engineering, and mathematics (STEM) pipeline is warranted. We examined the perceptions of six teachers, 10 ninth-grade students, and one principal at a newly formed EECHS. Our qualitative analyses revealed numerous successes and few challenges related to the school’s culture, curriculum, and instructional practices. General findings that might apply to all ECHS programming included the school’s small size, the benefits of developing caring and supportive relationships, and a common focus on preparing students for future academic and career success. We discuss key implications of these findings within the context of replicating an EECHS program or similar school structure.
Echocardiographic assessment of right ventricular function in experimental pulmonary hypertension
Authors: Zhu Zhongkai , Godana Dureti , Li Ailing , Rodriguez Bianca , Gu Chenxin , Tang Haiyang , Minshall Richard D. , Huang Wei , Chen Jiwang
Published: April 2019

Echocardiography, a non‐invasive and cost‐effective method for monitoring cardiac function, is commonly used for evaluation and pre‐clinical diagnostics of pulmonary hypertension (PH). Previous echocardiographic studies in experimental models of PH are fragmentary in terms of the evaluation of right ventricle (RV) function. In this study, three rodent models of PH: a mouse model of hypoxia‐induced PH, a rat model of hypoxia+Sugen induced PH and a rat model of monocrotaline‐induced PH, were employed to measure RV fractional area change (RVFAC), RV free wall thickness (RVFWT), pulmonary acceleration time (PAT), pulmonary ejection time (PET), and tricuspid annular plane systolic excursion (TAPSE). We found that, in these models, RVFWT significantly increased, but RVFAC, PAT, or PAT/PET ratios and TAPSE values significantly decreased. Accurate and complete TAPSE patterns were demonstrated in the three rodent models of PH. The RV echocardiography data matched the corresponding invasive hemodynamic and heart histologic data in each model. This serves as a reference study for real‐time and non‐invasive evaluation of RV function in rodent models of PH using echocardiography.
Acute adrenal haemorrhage in two cats with aldosterone-secreting adenocarcinomas
Authors: Kirkwood Nicolle , Boland Lara , Brunel Laurencie , Wardman Alison , Barrs Vanessa R
Published: April 2019

Case summary

Two 13-year-old domestic shorthair cats were diagnosed with unilateral right adrenocortical carcinomas (ACCs) and primary hyperaldosteronism (PHA). Both had polyuria, polydipsia and weight loss, and developed severe anaemia from an episode of acute adrenal haemorrhage. In one case, this occurred during hospitalisation and treatment of severe muscle weakness with cervical ventroflexion, while the other cat had acute collapse at home. A diagnosis of PHA was confirmed in both cases based on measurement of plasma aldosterone and renin activity. In one case, basal progesterone was also measured and was elevated. On ultrasonography and CT in one case, haemorrhage into the right retroperitoneal space was identified. Unilateral adrenalectomy was performed in both cases and there was no evidence of venous tumoral invasion in either. On histopathology of the excised adrenal glands both were ACCs with tumour necrosis, and one had extensive intratumoral haemorrhage. Both cats were diagnosed with International Renal Interest Society stage 2 or 3 chronic kidney disease postoperatively; one survived for 18 months and the other was well 8 months postoperatively.

Relevance and novel information

Acute adrenal haemorrhage secondary to adrenal neoplasia has been reported in only one other cat, in which tumour type and function were not specified. Acute adrenal haemorrhage can occur as a consequence of tumour necrosis and rupture and can cause severe hypovolaemia and anaemia in cats with primary hyperaldosteronism.
Can Cognitive Bias Modification Simultaneously Target Two Behaviors? Approach Bias Retraining for Alcohol and Condom Use
Authors: Hahn Austin M. , Simons Raluca M. , Simons Jeffrey S. , Wiers Reinout W. , Welker Logan E.
Published: April 2019

This study tested the effectiveness of a cognitive bias modification (CBM) intervention to simultaneously reduce approach biases toward alcohol and increase approach biases toward condoms among high-risk young adults. Participants ( N = 102) were randomly assigned to either a training condition or a sham-training condition. Participants in the training condition were trained to make avoidance movements away from alcohol stimuli and approach movements toward condom stimuli over four training sessions. Approach biases and behavior were assessed at pretest, posttest, and 3-month follow-up. Approach biases changed for both stimulus categories in accordance with training condition. Condom behavior and attitudes also changed as a function of training condition such that participants in the training condition reported fewer instances of condom nonuse and more positive attitudes toward condoms at a 3-month follow-up. Participants in both conditions had significant reductions in alcohol consumption following the intervention and did not differ by training condition.
Ischial tuberosity avulsion fracture nonunions in the adolescent population treated with a posterior column screw: A case series of two patients
Authors: Hughes Jonathan D , Stahl Daniel L
Published: April 2019

Various surgical techniques exist to approach an ischial tuberosity avulsion fracture, including open reduction and internal fixation with screws and suture anchors, augmentation with allograft tendon, and excision of the fragment. However, the majority of these techniques approached acute fractures, and nonunions were not addressed nor studied. This case series describes two adolescent patients treated for ischial tuberosity nonunions with a posterior column screw through a subgluteal approach. Both patients demonstrated radiographic healing of their nonunion sites at 6 months’ follow-up. Each patient reported no pain during activity, had symmetric hamstring strength, and were able to return to pre-injury level of activity by final follow-up. In conclusion, the authors utilized a muscle-sparing approach to the ischial tuberosity nonunion site through a cosmetically appealing incision and introduced a novel approach to nonunion fixation without the use of bone graft, resulting in excellent clinical outcomes.
Targeting of Metabotropic Glutamate Receptors for the Development of Novel Antidepressants
Authors: Chaki Shigeyuki , Koike Hiroyuki , Fukumoto Kenichi
Published: April 2019

Since discovering that ketamine has robust antidepressant effects, the glutamatergic system has been proposed as an attractive target for the development of novel antidepressants. Among the glutamatergic system, metabotropic glutamate (mGlu) receptors are of interest because mGlu receptors play modulatory roles in glutamatergic transmission, consequently, agents acting on mGlu receptors might not exert the adverse effects associated with ketamine. mGlu receptors have eight subtypes that are classified into three groups, and the roles of each mGlu receptor subtype in depression are being investigated. To date, the potential use of mGlu5 receptor antagonists and mGlu2/3 receptor antagonists as antidepressants has been actively investigated, and the mechanisms underlying these antidepressant effects are being delineated. Although the outcomes of clinical trials using an mGlu5 receptor negative allosteric modulator and an mGlu2/3 receptor negative allosteric modulator have not been encouraging, these trials have been inconclusive, and additional trials using other compounds with more appropriate profiles are needed. In contrast, the roles of group III mGlu receptors have not yet been fully elucidated because of a lack of suitable pharmacological tools. Nonetheless, investigations of the use of mGlu4 and mGlu7 receptors as drug targets for the development of antidepressants have been ongoing, and some interesting evidence has been obtained.
NUP98-HBO1–fusion generates phenotypically and genetically relevant chronic myelomonocytic leukemia pathogenesis
Authors: Hayashi Yoshihiro , Harada Yuka , Kagiyama Yuki , Nishikawa Sayuri , Ding Ye , Imagawa Jun , Shingai Naoki , Kato Naoko , Kitaura Jiro , Hokaiwado Shintaro , Maemoto Yuki , Ito Akihiro , Matsui Hirotaka , Kitabayashi Issay , Iwama Atsushi , Komatsu Norio , Kitamura Toshio , Harada Hironori
Published: April 2019

Chronic myelomonocytic leukemia (CMML) constitutes a hematopoietic stem cell (HSC) disorder characterized by prominent monocytosis and myelodysplasia. Although genome sequencing has revealed the CMML mutation profile, the mechanism of disease development remains unclear. Here we show that aberrant histone acetylation by nucleoporin-98 (NUP98)-HBO1, a newly identified fusion in a patient with CMML, is sufficient to generate clinically relevant CMML pathogenesis. Overexpression of NUP98-HBO1 in murine HSC/progenitors (HSC/Ps) induced diverse CMML phenotypes, such as severe leukocytosis, increased CD115+ Ly6Chigh monocytes (an equivalent subpopulation to human classical CD14+ CD16− monocytes), macrocytic anemia, thrombocytopenia, megakaryocyte-lineage dysplasia, splenomegaly, and cachexia. A NUP98-HBO1–mediated transcriptional signature in human CD34+ cells was specifically activated in HSC/Ps from a CMML patient cohort. Besides critical determinants of monocytic cell fate choice in HSC/Ps, an oncogenic HOXA9 signature was significantly activated by NUP98-HBO1 fusion through aberrant histone acetylation. Increased HOXA9 gene expression level with disease progression was confirmed in our CMML cohort. Genetic disruption of NUP98-HBO1 histone acetyltransferase activity abrogated its leukemogenic potential and disease development in human cells and a mouse model. Furthermore, treatment of azacytidine was effective in our CMML mice. The recapitulation of CMML clinical phenotypes and gene expression profile by the HBO1 fusion suggests our new model as a useful platform for elucidating the central downstream mediators underlying diverse CMML-related mutations and testing multiple compounds, providing novel therapeutic potential.
Vitamin D3 supplementation and treatment outcomes in patients with depression (D3-vit-dep)
Authors: Hansen Jens Peter , Pareek Manan , Hvolby Allan , Schmedes Anne , Toft Tomas , Dahl Erik , Nielsen Connie Thurøe
Published: April 2019

Objective

To examine whether vitamin D supplementation in patients with depression would result in a reduction in Hamilton D-17 depression score (primary outcome) at 3 and 6 months compared to controls and to explore the correlations between serum vitamin D and symptoms of depression, wellbeing, systolic blood pressure, and waist circumference. In this outpatient multicentre study conducted between 2010 and 2013, patients, 18–65 years old, diagnosed with mild to severe depression were randomly assigned to receive D supplementation 70 micrograms daily or placebo on top of standard treatment. Participants, care givers and those assessing the outcomes were blinded to group assignment.

Results

At baseline, 23 patients had a normal 25(OH)D level, 22 had insufficiency (< 25 nmol/L), and 17 had deficiency (25–50 nmol/L). No significant reduction in depression was seen after vitamin D supplementation compared to placebo at Hamilton (18.4–18.0; p = 0.73 at 12 weeks). Vitamin D supplementation did not provide a reduction in symptom score among patients with depression.

Trial registration The trial was registered in the National Board of Health (EudraCT: 2011-002585-20) and in ClinicalTrials.Gov (NCT01390662).
Omalizumab in patients with severe asthma and persistent sputum eosinophilia
Authors: Mukherjee Manali , Kjarsgaard Melanie , Radford Katherine , Huang Chynna , Leigh Richard , Dorscheid Delbert R. , Lemiere Catherine , Boulet Louis-Philippe , Waserman Susan , Martin James , Nair Parameswaran
Published: April 2019

Omalizumab, a recombinant humanized monoclonal antibody targeting the IgE molecule, is the first biologic approved for moderate-to-severe allergic asthmatics, who remain uncontrolled despite high dose inhaled corticosteroid and bronchodilators. Steroid-sparing effect of omalizumab has not been demonstrated in asthmatics with persistent airway eosinophilia in a randomised controlled trial till date. From this double-blind, placebo-controlled, multi-centred, randomized parallel group design, we report that omalizumab is possibly inadequate to control sputum eosinophilia, and therefore may not have a steroid-sparing effect, especially in those maintained on oral corticosteroids daily. This needs to be confirmed or refuted in a larger trial, which may be a challenge with respect to recruitment, since there are currently three additional biologics available to prescribe.

Trial registration Clinicaltrials.gov, NCT02049294, Registered 30th January 2014, https://clinicaltrials.gov/ct2/show/NCT02049294
Safety and Efficacy of a Five-Fraction Stereotactic Body Radiotherapy Schedule for Centrally Located Non–Small-Cell Lung Cancer: NRG Oncology/RTOG 0813 Trial
Authors: Bezjak Andrea , Paulus Rebecca , Gaspar Laurie E. , Timmerman Robert D. , Straube William L. , Ryan William F. , Garces Yolanda I. , Pu Anthony T. , Singh Anurag K. , Videtic Gregory M. , McGarry Ronald C. , Iyengar Puneeth , Pantarotto Jason R. , Urbanic James J. , Sun Alexander Y. , Daly Megan E. , Grills Inga S. , Sperduto Paul , Normolle Daniel P. , Bradley Jeffrey D. , Choy Hak
Published: April 2019

PURPOSE

Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC.

MATERIALS AND METHODS

Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it.

RESULTS

One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively.

CONCLUSION

The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.
Transcriptome Analyses Identify a Metabolic Gene Signature Indicative of Dedifferentiation of Papillary Thyroid Cancer
Authors: Ma Ben , Jiang Hongyi , Wen Duo , Hu Jiaqian , Han Litao , Liu Wanlin , Xu Weibo , Shi Xiao , Wei Wenjun , Liao Tian , Wang Yulong , Lu Zhongwu , Wang Yu , Ji Qinghai
Published: April 2019

Context

Metabolic reprogramming is a common feature of tumorigenesis. It remains unknown concerning the expression pattern of metabolism-associated genes in dedifferentiated thyroid cancer (DDTC).

Objective

This study aimed to identify a useful signature to indicate dedifferentiation of papillary thyroid cancer (PTC).

Design and Setting

We used one discovery and two validation cohorts to screen out aberrant metabolic genes in DDTC, and further used The Cancer Genome Atlas (TCGA) cohort to search for independent risk factors for the low-differentiated phenotype of PTC as a signature of dedifferentiation. The prediction of the signature for DDTC was validated in the TCGA cohort and the combined Gene Expression Omnibus cohort. We also analyzed the correlations of the signature risk score with clinicopathological features of PTC. Gene set enrichment analyses were performed in the TCGA cohort.

Results

Significant enrichment of metabolic pathways correlated with differentiation status of PTC. A signature of metabolic genes including LPCAT2, ACOT7, HSD17B8, PDE8B, and ST3GAL1 was discovered and validated across three cohorts. The signature was not only predictive of DDTC but also significantly associated with BRAFV600E mutation (P < 0.001), T3/T4 stage (P < 0.001), extrathyroidal extension (P < 0.001), lymph node metastasis (P < 0.001), and tumor/lymph node/metastasis III/IV stage (P < 0.001) in PTC. Downregulations of LPCAT2 expression (P = 0.009) and ST3GAL1 expression (P = 0.005) increased risks of decreased disease-free survival for patients. Furthermore, the signature was implicated in a number of oncogenic biological pathways.

Conclusions

Our findings suggest that metabolic deregulations mediate dedifferentiation of PTC, and that the metabolic gene signature can be used as a biomarker for DDTC.
Influences of Hypoxia Exercise on Whole-Body Insulin Sensitivity and Oxidative Metabolism in Older Individuals
Authors: Chobanyan-Jürgens Kristine , Scheibe Renate J , Potthast Arne B , Hein Markus , Smith Andrea , Freund Robert , Tegtbur Uwe , Das Anibh M , Engeli Stefan , Jordan Jens , Haufe Sven
Published: April 2019

Context

Aging is a primary risk factor for most chronic diseases, including type 2 diabetes. Both exercise and hypoxia regulate pathways that ameliorate age-associated metabolic muscle dysfunction.

Objective

We hypothesized that the combination of hypoxia and exercise would be more effective in improving glucose metabolism than normoxia exercise.

Design and Participants

We randomized 29 older sedentary individuals (62 ± 6 years; 14 women, 15 men) to bicycle exercise under normobaric hypoxia (fraction of inspired oxygen = 15%) or normoxia (fraction of inspired oxygen = 21%).

Intervention

Participants trained thrice weekly for 30 to 40 minutes over 8 weeks at a heart rate corresponding to 60% to 70% of peak oxygen update.

Main Outcome Measures

Insulin sensitivity measured by hyperinsulinemic-euglycemic glucose clamp and muscle protein expression before and after hyperinsulinemic-euglycemic glucose clamp.

Results

Heart rate and perceived exertion during training were similar between groups, with lower oxygen saturation when exercising under hypoxia (88.7 ± 1.5 vs 96.2 ± 1.2%, P < 0.01). Glucose infusion rate after 8 weeks increased in both the hypoxia (5.7 ± 1.1 to 6.7 ± 1.3 mg/min/kg; P < 0.01) and the normoxia group (6.2 ± 2.1 to 6.8 ± 2.1 mg/min/kg; P = 0.04), with a mean difference between groups of –0.44 mg/min/kg; 95% CI, –1.22 to 0.34; (P = 0.25). Markers of mitochondrial content and oxidative capacity in skeletal muscle were similar after training in both groups. Changes in Akt phosphorylation and glucose transporter 4 under fasting and insulin-stimulated conditions were not different between groups over time.

Conclusions

Eight weeks of hypoxia endurance training led to similar changes in insulin sensitivity and markers of oxidative metabolism compared with normoxia training. Normobaric hypoxia exercise did not enhance metabolic effects in sedentary older women and men beyond exercise alone.
Bacterial mechanosensing: the force will be with you, always
Authors: Gordon Vernita D. , Wang Liyun
Published: April 2019

Whether bacteria are in the planktonic state, free-swimming or free-floating in liquid, or in the biofilm state, sessile on surfaces, they are always subject to mechanical forces. The long, successful evolutionary history of bacteria implies that they are capable of adapting to varied mechanical forces, and probably even actively respond to mechanical cues in their changing environments. However, the sensing of mechanical cues by bacteria, or bacterial mechanosensing, has been under-investigated. This leaves the mechanisms underlying how bacteria perceive and respond to mechanical cues largely unknown. In this Review, we first examine the surface-associated behavior of bacteria, outline the clear evidence for bacterial mechanosensing and summarize the role of flagella, type-IV pili, and envelope proteins as potential mechanosensors, before presenting indirect evidence for mechanosensing in bacteria. The general themes underlying bacterial mechanosensing that we highlight here may provide a framework for future research.