bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of the Inflammasome Signaling Cascade Reduces Alcohol Consumption in Female But Not Male Mice
Authors: Lowe Patrick P. , Cho Yeonhee , Tornai David , Coban Sahin , Catalano Donna , Szabo Gyongyi 
Published: December 2019

BackgroundAlcohol use disorder is a significant societal and medical burden that is associated with both organ pathology and addiction. Excessive alcohol use results in neuroinflammation characterized by activation of the inflammasome, a multiprotein complex, and IL‐1β increase in the brain. Recent studies suggest that inflammation could contribute to alcohol addiction. Here, we targeted components of the NOD‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome cascade, which senses and responds to immunologic stimuli, to determine whether NLRP3 inhibition modulates alcohol consumption.MethodsC57BL/6J male and female mice were provided a 2‐bottle choice of alcohol at increasing concentrations (3, 6, 9, and 12%, 4 days each) or water, and some were treated with daily injections of an NLRP3 inhibitor (MCC950), a caspase‐1 inhibitor (VX765), IL‐1 receptor antagonist (IL‐1ra; anakinra), or vehicle injection.ResultsTreatment with VX765, MCC950, and IL‐1ra significantly reduced alcohol consumption and preference in female mice (p < 0.05). Treatment with MCC950 and IL‐1ra reduced alcohol consumption, while IL‐1ra reduced alcohol preference in male mice (p < 0.05). VX765 did not affect alcohol consumption or preference in male mice.ConclusionsThese findings highlight gender differences in alcohol preference and demonstrate that inhibition of different steps in inflammasome signaling can reduce alcohol consumption in females. Inhibition of NLRP3 inflammasome activation and the inflammasome‐IL‐1β cascade opens novel insights into the development of new therapies to address alcohol use disorder in an era of targeted and precision medicine.
A randomised controlled trial of shoulder block vs. interscalene brachial plexus block for ventilatory function after shoulder arthroscopy
Authors: Rhyner P. , Kirkham K. , Hirotsu C. , Farron A. , Albrecht E. 
Published: December 2019

SummaryThe shoulder block may impair ventilatory function and diaphragmatic movement less than the interscalene brachial plexus block. We randomly allocated 30 adults who underwent shoulder arthroscopy under general anaesthesia to ultrasound‐guided shoulder block or interscalene block with 20 ml bupivacaine 0.5%. The primary outcome, rate of ultrasound‐measured hemidiaphragmatic excursion < 25% of baseline 30 min after blockade, was reduced from 12/15 with brachial plexus block to 2/15 with shoulder block, a difference (95%CI) of 67% (40–93%), p < 0.001. The mean (SD) numeric rating scale pain scores at rest after shoulder block were higher than after interscalene block at two postoperative hours, 1.4 (1.2) vs. 0.3 (0.7), p = 0.02, but lower at 24 postoperative hours, 1.3 (1.3) vs. 3.4 (2.3), p = 0.008. Mean (SD) pain scores on movement in the shoulder and interscalene blocks were similar, with respective values of 1.9 (1.9) vs. 0.7 (1.2), p = 0.13 at two postoperative hours and 3.7 (2.3) vs. 5.3 (2.5), p = 0.41, at 24 postoperative hours.
Epistasis between phenylethanolamine N‐methyltransferase and β2‐adrenergic receptor influences extracellular epinephrine level and associates with the susceptibility to allergic asthma
Authors: Sio Yang Yie , Matta Sri Anusha , Ng Yu Ting , Chew Fook Tim 
Published: December 2019

AbstractBackgroundReduced extracellular epinephrine level often associates with asthma‐related symptoms; however, the correlation between asthma and genetic variants in genes participating in the epinephrine signalling pathway remains unclear.ObjectiveTo characterize the functions of single nucleotide polymorphisms (SNPs) in phenylethanolamine N‐methyltransferase (PNMT) and β2‐adrenergic receptor (ADRB2), and to study the effects, including both direct and epistatic, of these SNPs on serum epinephrine level and asthma susceptibility.MethodsSingle nucleotide polymorphisms functions were characterized through in vitro luciferase assay. ADRB2 gene expression level in peripheral blood mononuclear cell (PBMC) was measured by transcriptome sequencing and expression microarray on two separate Asian cohorts (NUS‐UTAR, n = 278 and NUS‐TA, n = 58). Serum epinephrine level was assessed on a Singapore Chinese cohort (NUS‐SH, n = 314) with 155 asthmatic and 159 non‐asthmatic subjects. A separate Singapore Chinese cohort (NUS‐G, n = 3009) was genotyped to show disease association (direct and epistatic effect) of functional SNPs in PNMT and ADRB2.ResultsReduced serum epinephrine level was associated with increased asthma risk in Singapore Chinese. The minor allele of rs876493 was shown to increase PNMT promoter activity and reduce asthma risk. Multiple SNPs in ADRB2 forms a haplotype that was associated with the differential promoter activity of this gene. In this haplotype, rs11168070 was associated directly with ADRB2 expression in PBMCs. Both minor alleles from rs876493 and rs11168070 contribute synergistically to reduce asthma risk and increase serum epinephrine level.Conclusion and Clinical RelevanceEpistatic interaction between genetic variants from PNMT (rs876493) and ADRB2 (rs11168070) is associated with serum epinephrine level and the susceptibility of asthma. Our findings improved the current understanding of the genetic basis of this disease, while genotypic states of these SNPs may serve as potential biomarkers to predict susceptibility to the disease.
Bridging antifungal prophylaxis with 50 mg or 100 mg micafungin in allogeneic stem cell transplantation: A retrospective analysis
Authors: Rothe Achim , Claßen Annika , Carney Jonathan , Hallek Michael , Mellinghoff Sibylle C. , Scheid Christoph , Holtick Udo , von Bergwelt‐Baildon Michael 
Published: December 2019

AbstractObjectiveFluconazole or posaconazole is a standard of care in antifungal prophylaxis for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). However, many patients need to interrupt standard prophylaxis due to intolerability, drug‐drug interactions, or toxicity. Micafungin has come to prominence for these patients. However, the optimal biological dose of micafungin stays unclear.MethodsWe retrospectively evaluated the efficacy of micafungin as antifungal prophylaxis in HSCT patients. Micafungin was applied as bridging in patients who were not eligible to receive oral posaconazole. Micafungin was either given at a dose of 100 mg or 50 mg SID.ResultsA total of 173 patients received micafungin prophylaxis, 62 in the 100 mg and 111 in the 50 mg dose group. The incidence of probable or proven breakthrough IFDs during the observation period was one in the 100 mg and one in the 50 mg group. Fungal‐free survival after 100 days was 98% and 99% (P = .842), and overall survival after 365 days was 60% and 63% (P = .8) respectively. In both groups, micafungin was well tolerated with no grade 3 or 4 toxicities.ConclusionIn this retrospective analysis, which was not powered to detect non‐inferiority, micafungin is effective and complements posaconazole as fungal prophylaxis in HSCT.
Contralateral delay activity is not a robust marker of cognitive function in older adults at risk of mild cognitive impairment
Authors: Farina Francesca R. , Pragulbickaitė Gabija , Bennett Marc , Judd Cian , Walsh Kevin , Mitchell Samantha , O'Connell Redmond G. , Whelan Robert 
Published: December 2019

AbstractContralateral delay activity (CDA) has been proposed as a pre‐clinical neural marker for mild cognitive impairment (MCI). However, existing evidence is limited to one study with a small sample size (n = 24). Our aim was to extend previous work by investigating the relationship between the CDA and MCI risk in a large sample of older adults (n = 76). We used a regression approach to determine whether (and when) CDA amplitude predicted MCI risk, as indexed by the Montreal Cognitive Assessment (MoCA). CDA amplitude from ~300‐500 and ~800‐900 ms predicted MoCA performance. However, significant effects were only observed for specific electrodes (P5/P6 and CP3/CP4, but not PO7/PO8) and the nature of the relationship between the CDA and MoCA scores differed across time and according to set size. Bayesian regression analysis indicated partial evidence in favour of the null hypothesis (BF10 values = 4–1.18). Contrary to previous results, our findings suggest that the CDA may not a robust marker of MCI risk. More broadly, our results highlight the difficulty in identifying at‐risk individuals, particularly as MCI is a heterogeneous, unstable condition. Future research should prioritise longitudinal approaches in order to track the progression of the CDA and its association with cognitive decline in later life.
Ultrasonographic features associated with the lumbosacral or lumbar 5–6 symphyses in 64 horses with lumbosacral‐sacroiliac joint region pain (2012–2018)
Authors: Boado A. , Nagy A. , Dyson S. 
Published: December 2019

SummaryThe ultrasonographic appearance of the lumbosacral symphysis of horses with no history of hindlimb lameness or thoracolumbosacral pain has previously been documented. The aims of the study were to describe the signalment and clinical findings in horses with ultrasonographic lesions of the fifth and sixth lumbar (L) vertebrae and lumbosacral symphyses and to determine whether lesions of the L5‐6 symphysis are only seen in horses with congenital sacralisation or other abnormalities of the lumbosacral symphysis. Horses in Group 1 (n = 25) underwent poor performance investigation and improved in ridden performance after infiltration of mepivacaine around the sacroiliac joints. Horses in Group 2 (n = 39) presented for investigation of changes in thoracolumbosacral shape or poor performance but did not undergo anaesthesia of the sacroiliac joint regions. The median ages were 10 and 19 years respectively for Groups 1 and 2. Mares (53.1%) were over‐represented relative to the normal populations of the clinics. All horses had poor development of the thoracolumbar epaxial and pelvic muscles and prominence of the lumbar spinous processes and the tubera sacrale. Most horses (70%) had reduced range of movement of the thoracolumbosacral region. Ultrasonographic features included irregular vertebral end plates; heterogeneous echogenicity of the intervertebral disc ± ventral protrusion; and displacement of the ventral longitudinal ligament ± alteration in its echogenicity. In Group 1, abnormalities of the L5‐6 symphysis were seen in 13 horses, of which 84.6% had congenital sacralisation or narrowing of the lumbosacral symphysis. In Group 2, the majority of horses had lesions of both the L5‐6 and lumbosacral symphyses; only 9/39 horses (23.1%) had congenital fusion of either joint. Limitations include the lack of age‐matched control horses. However, the purpose of the study was to raise awareness of lesions of the L5‐6 and lumbosacral symphyses, which may contribute to pain and poor performance.
Cardioprotective effect of hemin in isoprenaline‐induced myocardial infarction: role of ATP‐sensitive potassium channel and endothelial nitric oxide synthase
Authors: Refaie Marwa M.M. , Rifaai Rehab A. , Bayoumi Asmaa M.A. , Shehata Sayed 
Published: December 2019

AbstractIschemic heart disease is a common cardiac health problem. Despite the significant advances in prevention and treatment of this disorder, its incidences and complications are very serious. So, the search for more antioxidants and anti‐inflammatory agents with cardioprotective effects is an urgent task. We aimed to evaluate the effects of a heme oxygenase 1 (HO1) inducer, hemin (HEM), on isoprenaline (ISO)‐induced myocardial damage. Forty‐five Wistar albino rats were used. Animals were treated with HEM (25 mg/kg/day) i.p. for 5 days and injected with ISO (150 mg/kg/day) i.p. on 4th and 5th day of the experiment. Detection of the role of ATP‐sensitive potassium channel (KATP) was performed by administration of glibenclamide (GP) (5 mg/kg/day) orally 2 h before HEM. Moreover, the role of endothelial nitric oxide synthase (eNOS) was detected by coadministration of Nitro‐ ω‐L‐arginine (L‐NNA) (25 mg/kg/day) for 5 days. The ISO group showed increase in heart weight, cardiac enzymes, tumor necrosis factor alpha (TNFα), and malondialdehyde (MDA) with decrease in reduced glutathione (GSH), HO1, and total antioxidant capacity (TAC). In addition, there were increases in Bcl‐2 associated X protein (Bax) and cleaved caspase‐3, but decreases in B‐cell lymphoma‐2 (Bcl‐2) and eNOS. Moreover, the histopathological examination of the ISO group showed degeneration of the cardiac muscle fibers and marked infiltration of the inflammatory cells. The biochemical and histopathological changes induced by ISO were markedly ameliorated in the HEM plus ISO group. This protective effect was diminished with coadministration of GP or L‐NNA; thus, KATP and eNOS might mediate HEM cardioprotection.
Association between mastication‐related factors and the prevalence of dementia in Korean elderly women visiting senior centres
Authors: Shin Hae‐Eun , Cho Min‐Jeong , Amano Atsuo , Song Keun‐Bae , Choi Youn‐Hee 
Published: December 2019

AbstractObjectiveThe purpose of this study was to evaluate the mastication ability of elderly women by assessing the number of their remaining teeth, subjective mastication comfort, subjective chewing ability of five food items, relative occlusion balance and mastication performance involving in chewing gum.BackgroundKorea has already entered an aged society, issues related to the elderly are also growing; for example, dementia is emerging as a social problem. In addition, oral health of the elderly is very important because it is directly related to nutrient intake. A total of 101 subjects aged ≥65 who attended senior citizen centres in Daegu city provided consent and were included in this study.Materials and methodsThe Korean version of the Mini‐Mental State Examination (MMSE‐DS) was used to evaluate cognitive function. To assess the degree of objective mastication, we measured colour changes using a chewing gum and posterior occlusion force using a T‐scan Ⅲ® system.ResultsThere was an association between mastication ability and cognitive function, indicated by the colour changes in the chewing gum (P < .05). The participants with greater relative posterior occlusion forces had higher MMSE‐DS scores than those with stronger relative anterior occlusion forces. There was a positive correlation between cognitive function and posterior occlusion force.ConclusionThe elderly having more occlusion force of posterior teeth rather than anterior teeth were associated with better cognitive ability. Therefore, it may be important for the elderly to restore the masticatory function for the posterior part to prevent against deterioration of cognitive function.
Effects of rikkunshito supplementation on resistance to oxidative stress and lifespan in mice
Authors: Wang Zi , Komatsu Toshimitsu , Ohata Yoshihisa , Watanabe Yukari , Yuan Yiwen , Yoshii Yuki , Park Seongjoon , Mori Ryoichi , Satou Motoyasu , Kondo Yoshitaka , Shimokawa Isao , Chiba Takuya 
Published: December 2019

AimCaloric restriction (CR), which limits the caloric intake to 60–70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite‐stimulating peptide, is essential for the anti‐oxidative and life‐extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR‐like life‐extending effects.MethodsFirst, we evaluated the life‐extending activity of RKT by examining the effect of long‐term RKT administration on wild‐type and NPY knockout mice. Furthermore, we tested whether RKT enhances CR‐mediated beneficial effects under AL conditions with a normal diet and under mild CR conditions with a high‐fat diet. We then used 3‐nitropropionic acid or doxorubicin to induce oxidative stress, and analyzed the differences in survival rate, weight loss, gene expression and cellular oxidative damage among groups.ResultsRKT administration did not extend the lifespan of wild‐type or NPY knockout mice. In the oxidative stress models, RKT treatment upregulated anti‐oxidative gene expression in the liver. Furthermore, RKT administration reduced the oxidative damage in the liver compared to the CR conditions alone. However, on induction of oxidative stress by 3‐nitropropionic acid or doxorubicin, RKT administration did not affect the survival rate.ConclusionsThese results show that RKT administration only partially mimics the effects of CR at the cellular level, but not at the organismal level to increase the lifespan of mice. Geriatr Gerontol Int 2019; ••: ••–••.
Association between redox state of human serum albumin and exercise capacity in older women: A cross‐sectional study
Authors: Ashikawa Hironobu , Adachi Takuji , Ueyama Jun , Yamada Sumio 
Published: December 2019

AimOxidative stress plays a key role in declining exercise capacity, which is one of the major health problems in old age. The redox state of human serum albumin (HSA) has been considered a biomarker reflecting oxidative stress; however, its relationship to exercise capacity in older people remains to be examined. We aimed to examine the redox state of HSA as a potential biomarker of exercise capacity in community‐dwelling older women.MethodsWe analyzed 125 women aged ≥75 years. Exercise capacity was evaluated using 6‐min walk distance (6MWD). The redox state of HSA was analyzed using the high‐performance liquid chromatography post‐column bromocresol green reaction method. The fraction of human mercaptalbumin in HSA (f[HMA]) was considered the redox state of HSA. Pearson's correlation coefficient (r) or Spearman's correlation coefficient (ρ) was used to assess correlations between 6MWD, f(HMA) and HSA. The association between 6MWD and f(HMA) was further examined using multivariate linear regression analysis adjusted for age, diabetes mellitus, renal function, number of medications, HSA and knee extensor isometric strength.ResultsThe 6MWD was significantly correlated with f(HMA; ρ = 0.44, P < 0.001), but not with HSA (r = 0.05, P = 0.562). The f(HMA) was not significantly correlated with HSA (ρ = 0.03, P = 0.769). Multivariate linear regression analysis showed that f(HMA) was independently associated with 6MWD (standardized β = 0.27, P = 0.004).ConclusionsThe findings of this study suggest that f(HMA) might serve as a novel biomarker for exercise capacity in community‐dwelling older women. Geriatr Gerontol Int 2019; ••: ••–••.
Individualized nutritional treatment for acute stroke patients with malnutrition risk improves functional independence measurement: A randomized controlled trial
Authors: Otsuki Ikuto , Himuro Nobuaki , Tatsumi Hiroomi , Mori Mitsuru , Niiya Yoshimasa , Kumeta Yukihiro , Yamakage Michiaki 
Published: December 2019

AimThe aim of the present study was to investigate the effects of individualized nutritional treatment on the activities of daily living of acute stroke patients.MethodsThis was a randomized controlled study. The eligibility criteria were acute stroke, age >65 years and the presence of malnutrition risk. Between September 2016 and December 2017, 128 patients were assigned to either the standard or intensive group (individualized nutritional treatment). The intensive group received energy that was calculated using the Harris–Benedict equation. The main outcome measures were the total functional independence measurement gain from the time of assignment to the time of discharge from the recovery hospital or at 3 months after the stroke onset, and motor and cognitive functional independence measurement gains.ResultsCompared with the standard group, the intensive group had significantly higher median energy intake (P < 0.001); significantly greater functional independence measurement gains in the total score (42 vs. 22; P = 0.02) and motor subscore (P = 0.01), but similar cognitive subscore.ConclusionIndividualized nutritional treatment improved the activities of daily living of older acute stroke patients with malnutrition risk. Geriatr Gerontol Int 2019; ••: ••–••.
Measuring the impact of participatory research in psychiatry: How the search for epistemic justifications obscures ethical considerations
Authors: Friesen Phoebe , Lignou Sapfo , Sheehan Mark , Singh Ilina 
Published: December 2019

AbstractContextBoth within politics and practice, the field of psychiatry is undergoing a significant transformation, as increasing emphasis is placed on the importance of involving those with lived experience in research. In response to this participatory turn, a push towards measuring the impact of patient involvement is also growing, seeking to identify how participation can improve research.ObjectiveThis paper examines the recent push towards measuring impact in relation to justifications underlying the democratization of research in psychiatry, revealing a disconnect between the two, and harms that could result from a singular focus on measuring impact.DiscussionWhile those promoting and regulating participatory research tend to focus on the epistemic benefits of such research, many have pointed to both epistemic and ethical justifications underlying participatory research. The ethical reasons for involving service users loom especially large in psychiatry, given its unique history of abuse, the ways diagnoses can be utilized as tools for oppression, and the prevalence of coercion. The current focus on measuring the impact of involvement can be harmful, in that it obscures ethical reasons in favour of epistemic ones, potentially exacerbating issues common to participatory research, such as role confusion and ineffective, tokenistic participatory efforts.ConclusionsWe argue that to take the ethical reasons behind involvement in mental health research seriously will involve looking beyond impact and towards sharing power. We suggest three ways this can be done: measuring more than impact, building service user capacities and sharing power in realms outside of research.
Updated direct costs of medical care for HIV‐infected patients within a regional population from 2006 to 2017
Authors: Krentz HB , Vu Q , Gill MJ 
Published: December 2019

ObjectivesThe aim of the study was to reappraise the precise costs of HIV care and cost drivers, to determine the optimal tools for modelling costs for HIV care, and to understand the implications of changing medical management of HIV‐infected patients for both subsequent outcomes and health care budgets.MethodsWe obtained all drug, laboratory, out‐patient and in‐patient care costs for all HIV‐infected patients followed between 1 January 2006 and 31 December 2017 (2017 Cdn$). Mean cost per patient per month (PPPM) was used as the standard comparator value. Patients were stratified based on CD4 count: (1) ≤ 75, (2) 76–200, (3) 201–500 and (4) > 500 cells/μL. We determined the cost for only HIV‐related expenses. We compared current costs with costs previously reported for the same population.ResultsThe number of HIV‐infected patients in care doubled from 2006 to 2017; total costs increased from $12.4 to $30.1 million, with antiretroviral (ARV) drugs accounting for 78.8% of costs by 2017. Out‐patient/laboratory costs declined from 12% to 8.5%, while in‐patient costs exhibited more annual variation. Mean PPPM costs increased from $1316 in 2006 to $1712 in 2014, declining to $1446 in 2017. Higher PPPM costs were associated with CD4 counts < 200 cells/μL. Costs have shifted. While the cost of ARV drugs increased by 32%, the costs of out‐patient and in‐patient services decreased by 80% and 71%, respectively. Most of the decrease for in‐patient costs was attributable to a substantial decrease in HIV‐related hospitalizations.ConclusionsAlthough antiretroviral therapy (ART) provides immense benefits, it is not inexpensive. ARV drugs remain the largest cost driver. Hospital costs have remained low. Substantial costs of lifelong ART necessitate innovative, locally applicable strategies for ARV selection and use.