bluuebunny/crossref_metadata_2025 huggingface dataset:
N‐Acetylcysteine alleviates gut dysbiosis and glucose metabolic disorder in high‐fat diet‐fed mice
Authors: Zheng Junping , Yuan Xubing , Zhang Chen , Jia Peiyuan , Jiao Siming , Zhao Xiaoming , Yin Heng , Du Yuguang , Liu Hongtao
Published: May 2018

Background

N‐Acetylcysteine (NAC), an antioxidative reagent for clinical diseases, shows potential in the treatment of diabetes and other metabolic diseases. However, it is unknown how NAC modulates the gut microbiota of mice with metabolic syndrome. The aim of the present study was to demonstrate the preventive effect of NAC on intestinal dysbiosis and glucose metabolic disorder.

Methods

Mice (C57BL/6J strain) were fed either a normal chow diet (NCD), NCD plus NAC, a high‐fat diet (HFD), or HFD plus NAC for 5 months, after which glucose levels, circulating endotoxins and key metabolism‐related proteins were determined. Fecal samples were analyzed by 16S rRNA sequencing. A novel analysis was performed to predict functional changes in gut microbiota. In addition, Spearman's correlation analysis was performed between metabolic biomarkers and bacterial abundance.

Results

Treatment with NAC significantly reversed the glucose intolerance, fasting glucose concentrations, and gains in body weight and plasma endotoxin in HFD‐fed mice. Further, NAC upregulated occludin and mucin glycoprotein levels in the proximal colon of HFD‐treated mice. Noticeably, NAC promoted the growth of beneficial bacteria (i.e. Akkermansia, Bifidobacterium, Lactobacillus and Allobaculum) and decreased populations of diabetes‐related genera, including Desulfovibrio and Blautia. In addition, NAC may affect the metabolic pathways of intestinal bacteria, including lipopolysaccharide biosynthesis, oxidative stress, and bacterial motility. Finally, the modified gut microbiota was closely associated with the metabolic changes in NAC‐treated HFD‐fed mice.

Conclusions

N‐Acetylcysteine may be a potential drug to prevent glucose metabolic disturbances by reshaping the structure of the gut microbiota.
Warfarin, but not rivaroxaban, promotes the calcification of the aortic valve in ApoE−/− mice
Authors: Rattazzi Marcello , Faggin Elisabetta , Bertacco Elisa , Nardin Chiara , Pagliani Leopoldo , Plebani Mario , Cinetto Francesco , Guidolin Diego , Puato Massimo , Pauletto Paolo
Published: May 2018

Introduction

Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma‐carboxylation of Matrix‐Gla‐Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification.

Aims

To compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice.

Results

42 ApoE−/− mice fed with Western‐type Diet (WTD) were randomized to treatment with warfarin (n = 14), rivaroxaban (n = 14) or control (n = 14) for 8 weeks. Histological analyses were performed to quantify the calcification of aortic valve leaflets and the development of atherosclerosis. The analyses showed a significant increase in valve calcification in mice treated with warfarin as compared to WTD alone (P = .025) or rivaroxaban (P = .005), whereas no significant differences were found between rivaroxaban and WTD (P = .35). Quantification of atherosclerosis and intimal calcification was performed on the innominate artery of the mice and no differences were found between the 3 treatments as far as atherogenesis and calcium deposition is concerned. In vitro experiments performed using bovine interstitial valve cells (VIC) showed that treatment with rivaroxaban did not prevent the osteogenic conversion of the cells but reduce the over‐expression of COX‐2 induced by inflammatory mediators.

Conclusion

We showed that warfarin, but not rivaroxaban, could induce calcific valve degeneration in a mouse model of atherosclerosis. Both the treatments did not significantly affect the progression of atherosclerosis. Overall, these data suggest a safer profile of rivaroxaban on the risk of cardiovascular disease progression.
The Core Challenges of Financial Regulation
Authors: Price Edward
Published: May 2018

Financial regulation is characterised by policy challenges. These illustrate both specific challenges facing policy makers after the global financial crisis and the general uncertainty involved in the design and implementation of coherent economic policy.
China's Crowding Out Effect on East Asian Exports: Gross Value and Domestic Value‐Added Analysis
Authors: Nguyen Son Thanh , Wu Yanrui
Published: May 2018

This paper aims to revisit the debate about China's crowding out effect on other East Asian exporters using both gross value and domestic value‐added export data. The results show that in gross value terms, the crowding out effect is evident in most product categories, and particularly strong in the textile, leather and footwear. In value‐added terms, the analysis did not find evidence of the crowding out effect on other East Asian exporters. The results suggest that (i) while China's exports compete fiercely with other East Asian countries’ exports, this competition does not necessarily worsen the competitors’ economic welfare; and (ii) there are new opportunities for East Asian developing countries to join the regional production network, rather than merely filling in the product categories left vacant by the more developed countries as suggested by the flying geese pattern.
Recruitment of extravascular fluid by hyperoncotic albumin
Authors: Zdolsek M. , Hahn R. G. , Zdolsek J. H.
Published: May 2018

Background

Although hyperoncotic albumin may be used to recruit oedema, its effectiveness remains unclear. Therefore, this issue was studied during infusion experiments in healthy volunteers.

Method

Fifteen healthy volunteers (mean age 31 years) received an infusion of 3 mL/kg of 20% albumin over 30 minutes. Their urinary excretion was recorded, and venous blood samples were taken to measure blood haemoglobin (Hb), haematocrit, colloid osmotic pressure as well as plasma albumin and sodium concentrations on 15 occasions over a period of 300 minutes. Plasma volume expansion was taken as the inverse of the fluid‐induced dilution of venous plasma, as given by the blood Hb concentration. Mass balance calculations were used to estimate the mobilisation of fluid from the tissues.

Results

Maximum plasma volume expansion was reached 20 minutes after completing an infusion of 20% albumin. Urinary excretion was effectively increased, and the mobilised fluid from the tissues at 300 minutes amounted to 3.4 ± 1.2 mL for each infused mL of 20% albumin, of which 19% was of intracellular origin. The urinary excretion correlated strongly with the amount of recruited fluid (R2 = 0.87) and inversely with the plasma volume expansion (R2 = 0.53).

Conclusion

The infusion of 20% albumin significantly increases the plasma volume by recruiting interstitial fluid. After completing the infusion, there is a delay of 20 minutes until maximum plasma dilution is reached, and the duration of the plasma volume expansion lasts far beyond 5 hours.
Defective recruitment of motor proteins to autophagic compartments contributes to autophagic failure in aging
Authors: Bejarano Eloy , Murray John W. , Wang Xintao , Pampliega Olatz , Yin David , Patel Bindi , Yuste Andrea , Wolkoff Allan W. , Cuervo Ana Maria
Published: May 2018

Inability to preserve proteostasis with age contributes to the gradual loss of function that characterizes old organisms. Defective autophagy, a component of the proteostasis network for delivery and degradation of intracellular materials in lysosomes, has been described in multiple old organisms, while a robust autophagy response has been linked to longevity. The molecular mechanisms responsible for defective autophagic function with age remain, for the most part, poorly characterized. In this work, we have identified differences between young and old cells in the intracellular trafficking of the vesicular compartments that participate in autophagy. Failure to reposition autophagosomes and lysosomes toward the perinuclear region with age reduces the efficiency of their fusion and the subsequent degradation of the sequestered cargo. Hepatocytes from old mice display lower association of two microtubule‐based minus‐end‐directed motor proteins, the well‐characterized dynein, and the less‐studied KIFC3, with autophagosomes and lysosomes, respectively. Using genetic approaches to mimic the lower levels of KIFC3 observed in old cells, we confirmed that reduced content of this motor protein in fibroblasts leads to failed lysosomal repositioning and diminished autophagic flux. Our study connects defects in intracellular trafficking with insufficient autophagy in old organisms and identifies motor proteins as a novel target for future interventions aiming at correcting autophagic activity with anti‐aging purposes.
Long‐term antipsychotic polypharmacy prescribing in secondary mental health care and the risk of mortality
Authors: Kadra G. , Stewart R. , Shetty H. , MacCabe J. H. , Chang C.‐K. , Taylor D. , Hayes R. D.
Published: May 2018

Objectives

To investigate the association between long‐term antipsychotic polypharmacy use and mortality; and determine whether this risk varies by cause of death and antipsychotic dose.

Methods

Using data from a large anonymised mental healthcare database, we identified all adult patients with serious mental illness (SMI) who had been prescribed a single antipsychotic or polypharmacy, for six or more months between 2007 and 2014. Multivariable Cox regression models were constructed, adjusting for sociodemographic, socioeconomic, clinical factors and smoking, to examine the association between APP use and the risk of death.

Results

We identified 10 945 adults with SMI who had been prescribed long‐term antipsychotic monotherapy (76.9%) or APP (23.1%). Patients on long‐term APP had a small elevated risk of mortality, which was significant in some but not all models. The adjusted hazard ratios for death from natural and unnatural causes associated with APP were 1.2 (0.9–1.4, P = 0.111) and 1.1 (0.7–1.9, P = 0.619) respectively. The strengths of the associations between APP and mortality outcomes were similar after further adjusting for % BNF antipsychotic dose (P = 0.031) or olanzapine equivalence (P = 0.088).

Conclusion

The findings suggest that the effect of long‐term APP on mortality is not clear‐cut, with limited evidence to indicate an association, even after controlling for the effect of dose.
Metabolic syndrome and actigraphy measures of sleep and circadian rhythms in bipolar disorders during remission
Authors: Brochard H. , Godin O. , Geoffroy P. A. , Yeim S. , Boudebesse C. , Benizri C. , Benard V. , Maruani J. , Leboyer M. , Bellivier F. , Etain B.
Published: May 2018

Objective

This study explored the correlations between sleep and circadian rhythm measures and the metabolic syndrome (MetS) components in remitted patients with bipolar disorder (BD).

Method

Euthymic patients withBD(n= 67) were recorded by 3 weeks with actigraphy. We used nonparametric correlations to study the links between the MetS parameters, atherogenic index of plasma (AIP), sleep efficacy, sleep latency, fragmentation index, and phase and amplitude of rhythms. We performed multivariable analyses to take into account potential confounding factors such as sleep apnea risk, antipsychotics use, and smoker status.

Results

We found correlations between lower sleep efficiency and higher triglyceride levels (P= 0.002), lower M10 onset (beginning of the 10 most active hours during the 24‐h cycle) and higher systolic blood pressure (P= 0.03), higher fragmentation index and higher systolic blood pressure (P= 0.009), lower sleep efficiency, higher fragmentation index, and higherAIP(respectivelyP= 0.02 andP= 0.04). These correlations mostly remained significant when adjusting for confounders, with the exception of M10 onset and systolic blood pressure.

Conclusion

Sleep efficiency and fragmentation index might contribute to the cardiovascular risk of patients withBDindependently of major confounding factors. Although these associations did not imply causality, proposing interventions on sleep quality and circadian rhythm regularity might contribute to reduce cardiovascular risk in patients withBD.
Risk profiles for heavy drinking in adolescence: differential effects of gender
Authors: Seo Sambu , Beck Anne , Matthis Caroline , Genauck Alexander , Banaschewski Tobias , Bokde Arun L.W. , Bromberg Uli , Büchel Christian , Quinlan Erin Burke , Flor Herta , Frouin Vincent , Garavan Hugh , Gowland Penny , Ittermann Bernd , Martinot Jean‐Luc , Paillère Martinot Marie‐Laure , Nees Frauke , Papadopoulos Orfanos Dimitri , Poustka Luise , Hohmann Sarah , Fröhner Juliane H. , Smolka Michael N. , Walter Henrik , Whelan Robert , Desrivières Sylvane , Heinz Andreas , Schumann Gunter , Obermayer Klaus
Published: May 2018

Abnormalities across different domains of neuropsychological functioning may constitute a risk factor for heavy drinking during adolescence and for developing alcohol use disorders later in life. However, the exact nature of such multi‐domain risk profiles is unclear, and it is further unclear whether these risk profiles differ between genders. We combined longitudinal and cross‐sectional analyses on the large IMAGEN sample (N ≈ 1000) to predict heavy drinking at age 19 from gray matter volume as well as from psychosocial data at age 14 and 19—for males and females separately. Heavy drinking was associated with reduced gray matter volume in 19‐year‐olds' bilateral ACC, MPFC, thalamus, middle, medial and superior OFC as well as left amygdala and anterior insula and right inferior OFC. Notably, this lower gray matter volume associated with heavy drinking was stronger in females than in males. In both genders, we observed that impulsivity and facets of novelty seeking at the age of 14 and 19, as well as hopelessness at the age of 14, are risk factors for heavy drinking at the age of 19. Stressful life events with internal (but not external) locus of control were associated with heavy drinking only at age 19. Personality and stress assessment in adolescents may help to better target counseling and prevention programs. This might reduce heavy drinking in adolescents and hence reduce the risk of early brain atrophy, especially in females. In turn, this could additionally reduce the risk of developing alcohol use disorders later in adulthood.
AA attendance and abstinence for dually diagnosed patients: a meta‐analytic review
Authors: Tonigan J. Scott , Pearson Matthew R. , Magill Molly , Hagler Kylee J.
Published: May 2018

Background and Aims

There is consensus that best clinical practice for dual diagnosis (DD) is integrated mental health and substance use treatment augmented with Alcoholics Anonymous (AA) attendance. This is the first quantitative review of the direction and magnitude of the association between AA attendance and alcohol abstinence for DD patients.

Method

A systematic literature search (1993–2017) identified 22 studies yielding 24 effect sizes that met our inclusion criteria (8075 patients). Inverse‐variance weighting of correlation coefficients (r) was used to aggregate sample‐level findings and study aims were addressed using random‐ and mixed‐effect models. Sensitivity and publication bias analyses were conducted to assess the likelihood of bias in the overall estimate of AA‐related benefit.

Results

AA exposure and abstinence for DD patients were associated significantly and positively [rw = 0.249; 95% confidence interval (CI) = 0.203–0.293; tau = 0.097). There was also significant heterogeneity in the distribution of effect sizes and high between‐sample variance (I2 = 74.6, P < 0.001). Subgroup analyses indicated that the magnitude of AA‐related benefit did not differ between 6‐ (k = 7) and 12‐ (k = 12) month follow‐up (Q = 0.068, P = 0.794), type of treatment received (in‐patient k = 9; intensive out‐patient, out‐patient, community k = 15; Q = 2.057, P = 0.152), and whether a majority of patients in a sample had (k = 11) or did not have (k = 13) major depression (Q = 0.563, P = 0.453). Sensitivity analyses indicated that the overall meta‐analytical estimate of AA benefit was not impacted adversely or substantively by pooling randomized controlled trial (RCT) and observational samples (Q = 0.763, P = 0.382), pooling count, binary and ordinal‐based AA (Q = 0.023, P = 0.879) and outcome data (Q = 1.906, P = 0.167) and reversing direction of correlations extracted from studies (Q = 0.006, P = 0.937). No support was found for publication bias.

Conclusions

Clinical referral of dual diagnosis patients to Alcoholics Anonymous is common and, in many cases, dual diagnosis patients who attend Alcoholics Anonymous will report higher rates of alcohol abstinence relative to dual diagnosis patients who do not attend Alcoholics Anonymous.
A novel use of cardiac resynchronization therapy‐defibrillator device in hypertrophic cardiomyopathy
Authors: Cay Serkan , Ozeke Ozcan , Ozcan Firat , Aras Dursun , Topaloglu Serkan
Published: May 2018

Dual‐chamber implantable cardioverter‐defibrillator is generally used in patients with atrioventricular block and hypertrophic cardiomyopathy with preserved left ventricular ejection fraction. In the current case, a cardiac resynchronization therapy‐defibrillator device was implanted in a patient with non‐obstructive hypertrophic cardiomyopathy with preserved ejection fraction and atrioventricular block to achieve both more physiological pacing and life‐threatening ventricular arrhythmia management.
Mental health in postgraduate social work curriculum: Review of training contents in Indian schools of social work
Authors: Thomas Bino , Pradeepkumar Pattanashetty Chandrashekar
Published: May 2018

Training of social workers according to the changing needs of the society is important. To this end, we decided to review the adequacy of mental health training in postgraduate programme in social work. The Mental Health Care Act defines psychiatric social worker (PSW) in India to have additional higher qualification beyond post‐graduation in social work. The number of such qualified PSWs appears to be limited due to small number of institutes that offer advanced training in the country. Though, the number of available PSWs with such qualifications is rising, the manpower in proportion to the mental health needs in the country continues to remain low. It is therefore, relevant to review the quality of psychiatric social work education at postgraduate level if this level is to be considered as the desirable qualification for PSW. In this context, postgraduate social work syllabi from 71 universities including autonomous institutions were reviewed using semi‐structured assessment. The results show a lack of uniform teaching components, training methods and insufficient skill orientation towards mental health interventions. These observations suggest that curricula and training are modified with strengthening and enhancing the quality of training of mental health at post‐graduate level in Social Work.
Biopharmaceutical optimization in neglected diseases for paediatric patients by applying the provisional paediatric biopharmaceutical classification system
Authors: del Moral Sanchez Jose Manuel , Gonzalez‐Alvarez Isabel , Cerda‐Revert Aaron , Gonzalez‐Alvarez Marta , Navarro‐Ruiz Andres , Amidon Gordon L. , Bermejo Marival
Published: May 2018

Aims

Unavailability and lack of appropriate, effective and safe formulations are common problems in paediatric therapeutics. Key factors such as swallowing abilities, organoleptic preferences and dosage requirements determine the need for optimization of formulations. The provisional Biopharmaceutics Classification System (BCS) can be used in paediatric formulation design as a risk analysis and optimization tool. The objective of this study was to classify six neglected tropical disease drugs following a provisional paediatric BCS (pBCS) classification adapted to three paediatric subpopulations (neonates, infants and children).

Methods

Albendazole, benznidazole, ivermectin, nifurtimox, praziquantel and proguanil were selected from the 5th edition of the Model List of Essential Medicines for Children from the World Health Organization. Paediatric drug solubility classification was based on dose number calculation. Provisional permeability classification was based on log P comparison versus metoprolol log P value, assuming passive diffusion absorption mechanisms and no changes in passive membrane permeability between paediatric patients and adults. pBCS classes were estimated for each drug, according to different doses and volumes adapted for each age stage and were compared to the adult classification.

Results

All six drugs were classified into provisional pBCS in the three paediatric subpopulations. Three drugs maintained the same classification as for adults, ivermectin and benznidazole changed solubility class from low to high in neonates and proguanil changed from low to high solubility in all age stages.

Conclusion

Provisional pBCS classification of these six drugs shows potential changes in the limiting factors in oral absorption in paediatrics, depending on age stage, compared to the adult population. This valuable information will aid the optimization of paediatric dosing and formulations and can identify bioinequivalence risks when comparing different formulations and paediatric populations.
A multiple treatment comparison meta‐analysis of monoamine oxidase type B inhibitors for Parkinson's disease
Authors: Binde C. D. , Tvete I. F. , Gåsemyr J. , Natvig B. , Klemp M.
Published: May 2018

Aims

To the best of our knowledge, there are no systematic reviews or meta‐analyses that compare rasagiline, selegiline and safinamide. Therefore, we aimed to perform a drug class review comparing all available monoamine oxidase type B (MAO‐B) inhibitors in a multiple treatment comparison.

Methods

We performed a systematic literature search to identify randomized controlled trials assessing the efficacy of MAO‐B inhibitors in patients with Parkinson's disease. MAO‐B inhibitors were evaluated either as monotherapy or in combination with levodopa or dopamine agonists. Endpoints of interest were change in the Unified Parkinson's Disease Rating Scale (UPDRS) score and serious adverse events. We estimated the relative effect of each MAO‐B inhibitor versus the comparator drug by creating three networks of direct and indirect comparisons. For each of the networks, we considered a joint model.

Results

The systematic literature search and study selection process identified 27 publications eligible for our three network analyses. We found the relative effects of rasagiline, safinamide and selegiline treatment given alone and compared to placebo in a model without explanatory variables to be 1.560 (1.409, 1.734), 1.449 (0.873, 2.413) and 1.532 (1.337, 1.757) respectively. We also found all MAO‐B inhibitors to be efficient when given together with levodopa. When ranking the MAO‐B inhibitors given in combination with levodopa, selegiline was the most effective and rasagiline was the second best.

Conclusions

All of the included MAO‐B inhibitors were effective compared to placebo when given as monotherapy. Combination therapy with MAO‐B inhibitors and levodopa showed that all three MAO‐B inhibitors were effective compared to placebo, but selegiline was the most effective drug.
Transdifferentiation of human somatic cells by ribosome
Authors: Ito Naofumi , Anam Mohammad Badrul , Ahmad Shah Adil Ishtiyaq , Ohta Kunimasa
Published: May 2018

Ribosomes are intracellular organelles ubiquitous in all organisms, which translate information from mRNAs to synthesize proteins. They are complex macromolecules composed of dozens of proteins and ribosomal RNAs. Other than translation, some ribosomal proteins also have side‐jobs called “Moonlighting” function. The majority of these moonlighting functions influence cancer progression, early development and differentiation. Recently, we discovered that ribosome is involved in the regulation of cellular transdifferentiation of human dermal fibroblasts (HDFs). In vitro incorporation of ribosomes into HDFs arrests cell proliferation and induces the formation of cell clusters, that differentiate into three germ layer derived cells upon induction by differentiation mediums. The discovery of ribosome induced transdifferentiation, that is not based on genetic modification, find new possibilities for the treatment of cancer and congenital diseases, as well as to understand early development and cellular lineage differentiation.
Downregulation of NHP2 promotes proper cyst formation in Drosophila ovary
Authors: Morita Shumpei , Ota Ryoma , Kobayashi Satoru
Published: May 2018

In Drosophila ovary, germline stem cells (GSCs) divide to produce two daughter cells. One daughter is maintained as a GSC, whereas the other initiates cyst formation, a process involving four synchronous mitotic divisions that form 2‐, 4‐, 8‐, and 16‐cell cysts. In this study, we found that reduction in the level of NHP2, a component of the H/ACA small nucleolar ribonucleoprotein complex that catalyzes rRNA pseudouridylation, promotes progression to 8‐cell cysts. NHP2 protein was concentrated in the nucleoli of germline cells during cyst formation. NHP2 expression, as well as the nucleolar size, abruptly decreased during progression from 2‐cell to 4‐cell cysts. Reduction in NHP2 activity in the germline caused accumulation of 4‐ and 8‐cell cysts and decreased the number of single cells. In addition, NHP2 knockdown impaired the transition to 16‐cell cysts. Furthermore, a tumorous phenotype caused by Sex‐lethal (Sxl) knockdown, which is characterized by accumulation of single and two‐cell cysts, was partially rescued by NHP2 knockdown. When Sxl and NHP2 activities were concomitantly repressed, the numbers of four‐ and eight‐cell cysts were increased. In addition, Sxl protein physically interacted with NHP2 mRNA in ovaries. Thus, it is reasonable to conclude that Sxl represses NHP2 activity at the post‐transcriptional level to promote proper cyst formation. Because NHP2 knockdown did not affect global protein synthesis in the germarium, we speculate that changes in NHP2‐dependent pseudouridylation, which is involved in translation of specific mRNAs, must be intact in order to promote proper cyst formation.
Intergenerational Earnings Persistence and Economic Inequality in the Long Run: Evidence from French Cohorts, 1931–75
Authors: Lefranc Arnaud
Published: May 2018

This paper analyses long‐term trends in intergenerational earnings persistence in France for male cohorts born between 1931 and 1975. This time period has witnessed important changes in the French labour market and educational system, in particular an important compression of earnings differentials as well as a large expansion in access to secondary and higher education. Using a two‐sample instrumental variables approach, I estimate two measures of intergenerational economic persistence: the intergenerational earnings elasticity (IGE) and the intergenerational correlation (IGC). Over the period, the IGE exhibits a V‐shaped pattern. It falls from a high of value of 0.6 for cohorts born in the 1930s to around 0.4 for those born in the 1950s, but subsequently rises to a level close to that at the beginning of the period. In contrast, the IGC remains relatively stable over the period. This suggests that changes in the IGE are partly driven by transitory responses to changes in cross‐sectional inequality rather than long‐term changes in the degree of intergenerational persistence.
The value of prolactin in predicting prolactinοma in hyperprolactinaemic polycystic ovarian syndrome
Authors: Kyritsi Eleni Magdalini , Dimitriadis Georgios K. , Angelousi Anna , Mehta Hiten , Shad Amjad , Mytilinaiou Maria , Kaltsas Gregory , Randeva Harpal S.
Published: May 2018

Background

To identify a serum prolactin (PRL) cut‐off value indicative of a PRL‐producing adenoma in women with polycystic ovarian syndrome (PCOS) and hyperprolactinaemia and characterize such patients.

Materials and methods

In the present retrospective case–control study, the medical records of 528 PCOS women were reviewed. Pituitary magnetic resonance imaging (MRI) was performed in PCOS patients with PRL levels ≥94.0 ng/mL and/or symptoms suspicious of a pituitary adenoma (PA). Prolactinoma diagnosis was made in the presence of an MRI‐identifiable PA with biochemical and radiological response to dopamine agonists. Receiver operating characteristic (ROC) curve analysis was performed to determine a serum PRL threshold that could identify hyperprolactinaemic PCOS subjects with prolactinomas. Clinical, metabolic and endocrine parameters were also analysed.

Results

Among 528 patients with PCOS, 60 (11.4%) had elevated PRL levels. Of 44 (73.3%) patients who had pituitary imaging, 19 had PAs, 18 normal MRI and 7 other abnormalities. Patients harbouring prolactinomas had significantly higher PRL levels compared to patients without adenomas (median PRL 95.4 vs 49.2 ng/mL, P < .0001). A PRL threshold of 85.2 ng/mL could distinguish patients with prolactinomas with 77% sensitivity and 100% specificity [Area Under the curve (AUC) (95%) 0.91(0.8‐1.018), P = .0001]. PCOS women with prolactinomas were younger and had lower LH levels compared to women without prolactinomas.

Conclusions

In women with PCOS, PRL levels exceeding 85.2 ng/mL are highly suggestive of a prolactinoma warranting pituitary imaging. Pituitary MRI could also be considered in young PCOS patients with milder PRL elevation and low LH levels.
Busulfan‐based myeloablative conditioning regimens for haploidentical transplantation in high‐risk acute leukemias and myelodysplastic syndromes
Authors: Gayoso Jorge , Balsalobre Pascual , Kwon Mi , Herrera Pilar , Bermúdez Arancha , Sampol Antonia , Jiménez Santiago , López‐Corral Lucía , Serrano David , Piñana Jose Luis , Pascual María J. , Heras Inmaculada , Bento Leyre , Varela Rosario , Humala Karem , Zabalza Amaya , Laiglesia Almudena , Bastos‐Oreiro Mariana , Pérez‐Corral Ana , Martínez‐Laperche Carolina , Buño Ismael , Díez‐Martín José L. ,   GETH (Grupo Español de Trasplante Hematopoyético), Spain
Published: May 2018

Background

High‐risk acute leukemia (AL) and myelodysplastic syndrome (MDS) remain a therapeutic challenge. Unmanipulated haploidentical‐related donor transplantation based on a myeloablative conditioning regimen (HAPLO‐MAC) and post‐transplant cyclophosphamide (PT‐Cy) as prophylaxis against graft vs host disease (GvHD) is now a promising rescue strategy that could become universally available.

Objective

To evaluate the results of HAPLO‐MAC with PT‐Cy in patients with AL and MDS reported to the Haploidentical Transplantation Subcommittee of the Spanish Group for Hematopoietic Transplantation (GETH).

Patients and methods

We report our multicenter experience using an IV busulfan‐based HAPLO‐MAC regimen and PT‐Cy for treatment of 65 adults with high‐risk AL and MDS.

Results

Engraftment was recorded in 64 patients (98.5%), with a median time to neutrophil and platelet recovery of 16 and 27 days, respectively. The cumulative incidence of grade II‐IV acute GvHD and chronic GvHD was 28.6% and 27.5%, respectively. After a median follow‐up of 31 months for survivors, the cumulative incidence of non‐relapse mortality and relapse at 2 years was 18.8% and 25%, respectively. Estimated 30‐month event‐free survival and overall survival were 56% and 54.5%, respectively.

Conclusion

HAPLO‐MAC comprising an IV busulfan‐based conditioning regimen enabled long‐term disease control with acceptable toxicity in high‐risk AL and MDS.
Early versus later treatment start in multiple sclerosis: a register‐based cohort study
Authors: Chalmer T. A. , Baggesen L. M. , Nørgaard M. , Koch‐Henriksen N. , Magyari M. , Sorensen P. S. ,   the Danish Multiple Sclerosis Group
Published: May 2018

Background and purpose

To assess long‐term treatment effectiveness of disease‐modifying therapy (DMT) initiated early in disease course versus later treatment start.

Methods

We included all Danish patients with multiple sclerosis (MS) treated with DMT through two nationwide population‐based MS registries. Patients were categorized as early treated if treatment started within 2 years after the first MS symptom (n = 2316) and later treated if treatment started between 2 and 8 years after clinical onset (n = 1479). We compared time from treatment start to progression to an Expanded Disability Status Scale (EDSS) score of 6 and mortality between cohorts as hazard ratio (HR) using a Cox proportional hazards model with adjustment for stabilized inverse probability of treatment weights. Several sensitivity analyses were conducted.

Results

The median follow‐up time of 3795 patients was 7.0 (range 0.6–19.5) years for the EDSS score of 6 outcome and 10.4 (range 1.2–20.1) years for the mortality outcome. Patients with later treatment start showed a 42% increased hazard rate of reaching an EDSS score of 6 compared with the early‐treated patients [HR, 1.42; 95% confidence interval (CI), 1.18–1.70; P < 0.001]. When stratified by sex, the increased hazard among later‐treated women persisted (HR, 1.53; 95% CI, 1.22–1.93; P < 0.001), whereas the HR was lower in men (1.25; 95% CI, 0.93–1.69; P = 0.15). Mortality was increased by 38% in later starters (HR, 1.38; 95% CI, 0.96–1.99; P = 0.08).

Conclusions

Patients who started treatment with DMT later reached an EDSS score of 6 more quickly compared with patients who started early and the delay showed a tendency to shorten time to death. Our results support the use of early treatment.
Outsourcing justice?
Authors: Stafford Anne , Stapleton Pamela
Published: May 2018

The paper takes an institutional logics theoretical approach to examine how an outsourcing scandal of overcharging for electronic monitoring of offenders was managed so that, despite public outrage, government was able to maintain its outsourcing policies. Using secondary data archival sources in the public domain, it examines the actions of the contractors and state agencies. The paper shows how organisations with different logics became co‐dependent and worked together to resolve the scandal. Market logics were temporarily reined back and state logics emphasised as the contractual environment was stabilised. But ultimately their purpose was protection of the markets logics‐driven policy.
Certified Reference Materials of Molybdenum Ore and Molybdenum Concentrate (GBW07141, GBW07142, GBW07143 and GBW07144)
Authors: Liu Mei , Cheng Zhizhong , Huang Hongku , Gu Tiexin , Yan Weidong , Wang Lijun , Bai Jinfeng
Published: May 2018

This study describes the preparation and characterisation of certified reference materials of three molybdenum ores (GBW07141 to GBW07143, abbreviated to GMo‐1 to GMo‐3) and one molybdenum concentrate (GBW07144, abbreviated to GMo‐4). The source of these materials was molybdenum deposits in Luanchuan in Henan Province, China. Sample homogeneity was tested by WD‐XRF. All the relative standard deviations were < 3.0%, and F‐tests showed that all four materials were homogeneous. Thirteen laboratories participated in this interlaboratory programme, and to set the values, various reliable analytical methods based on different principles were adopted. Up to twenty‐six elements and compounds in the three molybdenum ores and eighteen components in the molybdenum concentrate were characterised as certified values. Owing to the wide spread of the data, only indicative values could be obtained for Ag and Re in GMo‐1 and for nine components in GMo‐4. The certified values and uncertainties for Mo of the three molybdenum ores and the molybdenum concentrate were, respectively, 0.066 ± 0.003, 0.15 ± 0.01, 0.54 ± 0.02 and 50.08 ± 0.14% m/m.
Effects of the differential expression of ZO‐1 and ZO‐2 on podocyte structure and function
Authors: Itoh Masahiko , Nakadate Kazuhiko , Matsusaka Taiji , Hunziker Walter , Sugimoto Hiroyuki
Published: May 2018

Glomerular podocytes in the kidney originate from columnar epithelial cells possessing tight junctions. During podocyte differentiation, tight junctions are replaced by slit diaphragms, which are formed between foot processes and function as a blood filtration barrier. Although the expression of most tight junction components is suppressed during podocyte differentiation, several components, including ZO‐1 and ZO‐2, are consistently expressed. We recently showed that podocyte‐specific deletion of ZO‐1 gene impaired slit diaphragm formation, leading to proteinuria and glomerular sclerosis. Here, we address the relevance of ZO‐2, whose sequence is highly similar to ZO‐1, in the maintenance of the structure and function of podocytes. In glomerular development, the spatiotemporal expression of ZO‐2 was similar to that of ZO‐1 until the capillary loop stage. Subsequently, the distribution patterns of ZO‐1 and ZO‐2 diverged at the maturation stage, when slit diaphragms are formed. This divergence could partly rely on the ability of ZO‐2 to interact with the slit diaphragm membrane proteins. Podocyte‐specific deletion of the ZO‐2 gene did not cause overt defects; however, double knockout of ZO‐1 and ZO‐2 genes accelerated the defects observed in ZO‐1 knockout mice. These results suggest that ZO‐2 plays supportive roles in the ZO‐1‐dependent regulation of podocyte filtration barrier.
First‐line antiretroviral therapy with efavirenz plus tenofovir disiproxil fumarate/emtricitabine or rilpivirine plus tenofovir disiproxil fumarate/emtricitabine: a durability comparison
Authors: Taramasso L , Di Biagio A , Maggiolo F , Tavelli A , Lo Caputo S , Bonora S , Zaccarelli M , Caramello P , Costantini A , Viscoli C , d'Arminio Monforte A , Cozzi‐Lepri A ,   the Italian Cohort Naive Antiretrovirals (ICONA) Foundation Study Group
Published: May 2018

Objectives

The aim of this study was to compare the durabilities of efavirenz (EFV) and rilpivirine (RPV) in combination with tenofovir/emtricitabine (TDF/FTC) in first‐line regimens.

Methods

A multicentre prospective and observational study was carried out. We included all patients participating in the Italian Cohort Naive Antiretrovirals (ICONA) Foundation Study who started first‐line combination antiretroviral therapy (cART) with TDF/FTC in combination with RPV or EFV, with a baseline viral load < 100 000 HIV‐1 RNA copies/mL. Survival analyses using Kaplan–Meier (KM) curves and Cox regression with time‐fixed covariates at baseline were employed.

Results

Overall, 1490 ART‐naïve patients were included in the study, of whom 704 were initiating their first cART with EFV and 786 with RPV. Patients treated with EFV, compared with those on RPV, were older [median 36 (interquartile range (IQR) 30–43) years vs. 33 (IQR 27–39) years, respectively; P < 0.001], were more frequently at Centers for Disease Control and Prevention (CDC) stage C (3.1% vs. 1.4%, respectively; P = 0.024), and had a lower median baseline CD4 count [340 (IQR 257–421) cells/μL vs. 447 (IQR 347–580) cells/μL, respectively; P < 0.001] and a higher median viral load [4.38 (IQR 3.92–4.74) log10 copies/mL vs. 4.23 (IQR 3.81–4.59) log10 copies/mL, respectively], (P = 0.004). A total of 343 patients discontinued at least one drug of those included in the first cART regimen, more often EFV (26%) than RPV (13%), by 2 years (P < 0.0001). After adjustment, patients treated with EFV were more likely to discontinue at least one drug for any cause [relative hazard (RH) 4.09; 95% confidence interval (CI) 2.89–5.80], for toxicity (RH 2.23; 95% CI 1.05–4.73) for intolerance (RH 5.17; 95% CI 2.66–10.07) and for proactive switch (RH 10.96; 95% CI 3.17–37.87) than those starting RPV.

Conclusions

In our nonrandomized comparison, RPV was better tolerated, less toxic and showed longer durability than EFV, without a significant difference in rates of discontinuation because of failures.
Caring for the suicidal person: A Delphi study of what characterizes a recovery‐oriented caring approach
Authors: Sellin Linda , Kumlin Tomas , Wallsten Tuula , Wiklund Gustin Lena
Published: May 2018

More research is needed for supporting mental health nurses in their caring for suicidal individuals. This study aimed to describe what characterizes a recovery‐oriented caring approach, and how this can be expressed through caring acts involving suicidal patients and their relatives. Delphi methodology was used, and research participants were recruited as experts by experience to explore a recovery‐oriented caring approach in a dialogical process between the experts and the researchers. The results highlight that it is important to acknowledge the view of the uniqueness of each person and reflected understanding of each individual person and experience. The results also reveal that a recovery‐oriented caring approach is characterized by a ‘communicative togetherness’. This communicative togetherness is associated with enabling a nurturing and caring space for suicidal patients to really express themselves and to reach for their own resources. The recovery‐oriented caring approach has thereby potential to facilitate a mutual understanding of the complexities of the patient's situation, and supports patients in influencing their care and regaining authority over their own lives. Accordingly, mental health nurses need to listen sensitively to what suicidal patients really say by acknowledging their lifeworlds and being open to individual variations of their recovery processes. This includes recognizing available and supportive relatives as capable of contributing to the patient's life project to continue living.
A constructivist grounded theory of generalist health professionals and their mental health work
Authors: Brunero Scott , Ramjan Lucie M. , Salamonson Yenna , Nicholls Daniel
Published: May 2018

Generalist health professionals, often without formal mental health training, provide treatment and care to people with serious mental illness who present with physical health problems in general hospital settings. This article will present findings from a constructivist grounded theory study of the work delivered by generalist health staff to consumers with mental illness on the general medical/surgical wards of two metropolitan hospitals in Sydney, Australia. The results analysed included three participant observations, two focus groups, and 21 interviews and hospital policy and protocol documents. A substantive theory of mental health work in general hospital settings is illustrated which conceptualizes the following categories: (i) the experience: conflicting realities and ideals; (ii) The Context: facilitating social distancing; and (iii) the social processes: invisibility affecting confidence. The categories are understood through the theoretical lens of symbolic interactionism with the theory providing insights into how the generalist health professionals understand their sense of self or identity.
Cross‐Country Variability in Cost of Raising Equity: Evidence from Seasoned Equity Offerings
Authors: Gupta Manu , Prakash Puneet , Rangan Nanda K.
Published: May 2018

We examine how county‐level governance affects the cost of raising equity. Using data on seasoned equity offerings, we find that the underwriting spread is determined by the litigation risk of issue certifiers, and offer underpricing is largely determined by the investment risk of the equity issue. Underwriting spread increases with enhanced legal enforcement, offsetting the reduction in underpricing associated with strong legal enforcement. Our study offers insight into the effect of legal enforcement and regulatory policy on the cost of raising equity.
Longitudinal psychosocial adjustment of women to human papillomavirus infection
Authors: Hsu Yu‐Yun , Wang Wei‐Ming , Fetzer Susan Jane , Cheng Ya‐Min , Hsu Keng‐Fu
Published: May 2018

Aim

The aim of this study was to examine the psychosocial adjustment trajectory, focusing on psychological distress, sexual relationships and healthcare information, and factors which have an impact on adjustment on receiving a positive diagnosis of human papillomavirus infection.

Background

Human papillomavirus is a common sexually transmitted infection in females. To date, knowledge of the longitudinal psychosocial response to the diagnosis of human papillomavirus is limited.

Design

A prospective longitudinal design was conducted with a convenience sample.

Methods

Women aged 20–65 years old were followed at one, 6 and 12 months after a diagnosis of HPV. Participants completed measures of initial emotional distress and followed up psychosocial adjustment. A mixed‐effects model was applied to analyse the longitudinal changes in psychosocial adjustment.

Results

Seventy human papillomavirus positive women participated in the study with nearly 20% of the women reporting emotional distress during their first visit. Mixed‐effects model analyses showed that a trajectory of psychosocial adjustment in healthcare orientation, sexual relationship and psychosocial distress occur from one to 6 months after HPV diagnosis. However, a declining trend from 6 to 12 months was significant in healthcare orientation. Initial emotional distress was associated with changes in psychological adjustment.

Conclusions

Psychosocial adjustment to human papillomavirus was worse at 1 month compared with 6 and 12 months after diagnosis. Healthcare providers should offer health information and psychosocial support to women according to their disease progression.
Burden changes in caregivers of patients with type 2 diabetes: A longitudinal study
Authors: Costa M. Suely Alves , Machado José C. , Pereira M. Graça
Published: May 2018

Aims

The aim of this study was to explore changes in the burden of caregivers of patients with type 2 diabetes experiencing lower limb amputation after surgery.

Background

Literature suggests the burden overload experienced by the caregivers of new amputees is related to an imbalance between the demands and the resources available to these caregivers.

Design

The study followed a longitudinal design assessing caregiver burden at 1 (T1), 7 (T2) and 10 (T3) months after the patient's surgery.

Methods

We used a convenience sample of caregivers of patients with type 2 diabetes amputated with recent lower limb amputation. Data were collected in several hospital units over 18 months in 2014‐2015. Sample size included at T1, T2 and T3 110, 101 and 84. Participants completed the socio‐demographic questionnaire, the Burden Assessment Scale and the Self‐Assessment Caregiver Questionnaire scale.

Results

Caregivers who received help reported lower levels of burden from at baseline with no variation over time. Those caregivers with high levels of stress showed an increase in burden over time, although these results were not significant. Also, caregivers who did not receive help showed higher levels of burden and stress over time compared with the initial baseline that decreased over time.

Conclusion

These results highlight the importance of receiving help, in care, especially among caregivers who care for patients who have undergone major amputation.