bluuebunny/crossref_metadata_2025 huggingface dataset:
Pimavanserin Treatment for Parkinson’s Disease Psychosis in Clinical Practice
Authors: Dashtipour Khashayar , Gupta Fiona , Hauser Robert A. , Karunapuzha Cherian A. , Morgan John C.
Published: January 2021

Background. Parkinson’s disease psychosis (PDP) is a common, nonmotor symptom of Parkinson’s disease (PD), which may affect up to 60% of patients and is associated with impaired quality of life, increased healthcare costs, and nursing home placement, among other adverse outcomes. Characteristic symptoms of PDP include illusions; visual, auditory, tactile, and olfactory hallucinations; and delusions. PDP symptoms typically progress over its course from being mild, infrequent, and often untroubling to complex, sometimes constant, and potentially highly disturbing. PDP has traditionally been treated with atypical antipsychotics (e.g., clozapine and quetiapine) although these are not approved for this indication and clozapine requires frequent white blood cell count monitoring due to the risk of agranulocytosis. Pimavanserin is a newer atypical antipsychotic with highly selective binding to serotonergic receptors, no evidence for worsening motor symptoms in PD, and no need for white blood cell count monitoring. It is currently the only approved medication indicated for PDP treatment. However, because it was approved relatively recently (2016), clinical experience with pimavanserin is limited. Case Presentations. A wide variety of representative clinical scenarios are presented, each with distinct variables and complications. Issues addressed include distinguishing PDP from similar symptoms caused by other disorders such as dementia, coordinating pimavanserin with other PD medications and with deep brain stimulation, adapting pimavanserin dosing for optimal benefit and tolerability, and recognizing variability of PDP symptoms due to patients’ changing life circumstances. Conclusions. These scenarios provide multiple insights regarding PDP management and the role of pimavanserin. Effective treatment of PDP may reduce disturbing symptoms of psychosis, thus improving patient function and quality of life. In addition, effective pharmacotherapy for PDP may also facilitate the use of other medications needed to treat neurological symptoms of PD (e.g., tremor, bradykinesia, and dyskinesia), although they may also have adverse effects that contribute to symptoms of PDP.
Research on a Numerical Calculation for Ball Bearings Based on a Finite Initial Value Search Method
Authors: Hu Jing , Qiao XiaoLi , Lv QiongYing , Zhang XinMing , Zhou XiaoPing
Published: January 2021

To address the disadvantages of the traditional solution method of the quasistatic ball bearing model, which requires the acquisition of the initial value with experience, this paper proposes a new method for a finite initial value optimization to solve the quasistatic ball bearing model. A bilevel solution model is established; the first layer is the initial value strategy model, and the second layer is the numerical optimization model. The Levenberg–Marquardt algorithm and the Armijo algorithm are adopted to solve the model. The correctness of the new method is proved by a case study of calculating a parameter of the bearing compared with the traditional method. The experiment results show that the proposed method can realize the fast and finite solution of the quasistatic ball bearing model. Additionally, the new method can be extended to the calculation of the double-decker ball bearings. It provides a reasonable and effective way for the exploration of the initial value problem of the solution of a quasistatic ball bearing model.
Biosynthesis of Copper Oxide Nanoparticles Using Streptomyces MHM38 and Its Biological Applications
Authors: Bukhari Sarah I. , Hamed Moaz M. , Al-Agamy Mohamed H. , Gazwi Hanaa S. S. , Radwan Hesham H. , Youssif Asmaa M.
Published: January 2021

Biosynthesis methods employing microorganisms have emerged as an eco-friendly, clean, and viable alternative to chemical and physical processes. The present study reports the synthesis of copper oxide nanoparticles (CuONPs) using cell-free culture supernatant of marine Streptomyces sp. MHM38. For the optimized production of CuONPs, the influence of some parameters, such as the concentration of copper sulfate (CuSO4), reaction time, filtrate to substrate ratio, and pH, was studied. 5 mM of CuSO4 was optimal for nanoparticle (NP) production. Well-defined CuONP formation occurred after 60 min of incubation when an equal volume of filtrate (cell-free supernatant) to substrate (CuSO4 solution) was added. UV-visible spectroscopy analysis of CuONPs exhibited a peak at 550 nm, which corresponds to the surface plasmon resonance of CuONPs. Most of the particles were spherical and were 1.72–13.49 nm when measured using a transmission electron microscope. The antimicrobial activity of CuONPs was determined using a well diffusion method against Enterococcus faecalis ATCC 29212, Salmonella typhimurium ATCC 14028, Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 8939, fungi (Rhizoctonia solani, Fusarium solani, and Aspergillus niger), and yeast (Candida albicans ATCC 10237). The highest antimicrobial activities were recorded against Candida albicans ATCC 10237, whereas Salmonella typhimurium ATCC 14028 and Escherichia coli ATCC 8939 showed the less activity. The biochemical findings of the CuONP groups were significant (

p
<
0.05

) with diminished levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total and direct bilirubin, urea, and creatinine compared with the paracetamol group. Nonenzymatic and enzymatic antioxidants of the CuONP groups were significantly elevated (

p
<
0.05

) in SOD and GSH levels, and exceptionally low nitric oxide (NO) and malondialdehyde (MAD) levels were found for the paracetamol group. The histopathological examination of the CuONP groups assured the impact of improving CuONPs against paracetamol-induced liver damage.
Associations among Dietary Omega-3 Polyunsaturated Fatty Acids, the Gut Microbiota, and Intestinal Immunity
Authors: Fu Yawei , Wang Yadong , Gao Hu , Li DongHua , Jiang RuiRui , Ge Lingrui , Tong Chao , Xu Kang
Published: January 2021

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs), which are essential fatty acids that humans should obtain from diet, have potential benefits for human health. In addition to altering the structure and function of cell membranes, omega-3 PUFAs (docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA), and docosapentaenoic acid (DPA)) exert different effects on intestinal immune tolerance and gut microbiota maintenance. Firstly, we review the effect of omega-3 PUFAs on gut microbiota. And the effects of omega-3 PUFAs on intestinal immunity and inflammation were described. Furthermore, the important roles of omega-3 PUFAs in maintaining the balance between gut immunity and the gut microbiota were discussed. Additional factors, such as obesity and diseases (NAFLD, gastrointestinal malignancies or cancer, bacterial and viral infections), which are associated with variability in omega-3 PUFA metabolism, can influence omega-3 PUFAs–microbiome–immune system interactions in the intestinal tract and also play roles in regulating gut immunity. This review identifies several pathways by which the microbiota modulates the gut immune system through omega-3 PUFAs. Omega-3 supplementation can be targeted to specific pathways to prevent and alleviate intestinal diseases, which may help researchers identify innovative diagnostic methods.
Prenatal High-Fat Diet Rescues Communication Deficits in Fmr1 Mutant Mice in a Sex-Specific Manner
Authors: Nolan Suzanne O. , Hodges Samantha L. , Okoh James T. , Binder Matthew S. , Lugo Joaquin N.
Published: January 2021

Using high-throughput analysis methods, the present study sought to determine the impact of prenatal high-fat dietary manipulations on isolation-induced ultrasonic vocalization production in both male and female Fmr1mutants on postnatal day 9. Prior to breeding, male FVB/129 Fmr1 wildtype and female Fmr1 heterozygous breeding pairs were assigned to 1 of 3 diet conditions: standard lab chow, omega-3 fatty acid-enriched chow, and a diet controlling for the fat increase. Prenatal exposure to omega-3 fatty acids improved reductions in the number of calls produced by Fmr1heterozygotes females. Moreover, diminished spectral purity in the female Fmr1homozygous mouse was rescued by exposure to both high-fat diets, although these effects were not seen in the male Fmr1knockout. Prenatal dietary fat manipulation also influenced several other aspects of vocalization production, such as the number of calls produced and their fundamental frequency, aside from effects due to loss of Fmr1.Specifically, in males, regardless of genotype, prenatal exposure to high omega-3s increased the average fundamental frequency of calls. These data support the need for future preclinical and clinical work elucidating the full potential of prenatal high-fat diets as a novel therapeutic alternative forFragile X syndrome.
Genetically Predicted Blood Pressure and Risk of Atrial Fibrillation
Authors: Hyman Matthew C. , Levin Michael G. , Gill Dipender , Walker Venexia M. , Georgakis Marios K. , Davies Neil M. , Marchlinski Francis E. , Damrauer Scott M.
Published: January 2021

Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. To address this question, this study explored the relationship between genetic predictors of blood pressure and risk of AF. We secondarily explored the relationship between genetically proxied use of antihypertensive drugs and risk of AF. Two-sample Mendelian randomization was performed using an inverse-variance weighted meta-analysis with weighted median Mendelian randomization and Egger intercept tests performed as sensitivity analyses. Summary statistics for systolic blood pressure, diastolic blood pressure, and pulse pressure were obtained from the International Consortium of Blood Pressure and the UK Biobank discovery analysis and AF from the 2018 Atrial Fibrillation Genetics Consortium multiethnic genome-wide association studies. Increases in genetically proxied systolic blood pressure, diastolic blood pressure, or pulse pressure by 10 mm Hg were associated with increased odds of AF (systolic blood pressure: odds ratio [OR], 1.17 [95% CI, 1.11–1.22];
P
=1×10
−11
; diastolic blood pressure: OR, 1.25 [95% CI, 1.16–1.35];
P
=3×10
−8
; pulse pressure: OR, 1.1 [95% CI, 1.0–1.2];
P
=0.05). Decreases in systolic blood pressure by 10 mm Hg estimated by genetic proxies of antihypertensive medications showed calcium channel blockers (OR, 0.66 [95% CI, 0.57–0.76];
P
=8×10
−9
) and β-blockers (OR, 0.61 [95% CI, 0.46–0.81];
P
=6×10
−4
) decreased the risk of AF. Blood pressure–increasing genetic variants were associated with increased risk of AF, consistent with a causal relationship between blood pressure and AF. These data support the concept that blood pressure reduction with calcium channel blockade or β-blockade could reduce the risk of AF.
Developing Open RDI and Education in Finnish Universities of Applied Sciences
Authors: Kärki Anne , Päällysaho Seliina , Jaalama Kaisa , Talvela Juhani , Lehto Anttoni , Hyyppä Hannu
Published: January 2021

Open Science (OS) and Research has reached mixed maturity levels in Finland. The meaning of the national project in the ecosystem of Finnish universities of applied sciences (UAS) is to enhance and elaborate OS and Open Education (OE) activities. Future actions were defined based on a survey and interviews carried out in the Finnish UAS sector during 2018 and 2019. The aim of both data collections was to evaluate the current status and attitudes towards open Research, Development, and Innovation (RDI) among staff members. Another purpose was to define the need for internal support services concerning open RDI and OE and to identify knowledge gaps. The results revealed several gaps in understanding OS and OE initiatives. Real-life actions were mostly vague, and the respondents experienced the need for support. On the other hand, the attitudes towards open RDI were positive, and the issue aroused questions and reflections. This study revealed gaps in knowledge and actions in Finnish UAS sectors. These results have been the basis of development actions such as joint workshops, educational webinars, and common instructions. The future plan includes the establishment of an experts' network for supporting open RDI and Education.
The Cainozoic to present-day record of Circum-Mediterranean, NE Atlantic and North Sea Cantharidinae and Trochinae (Trochoidea, Gastropoda)—a synopsis
Authors: HARZHAUSER MATHIAS
Published: January 2021

Evolutionary history, diversity and (paleo)geographic distribution of Cainozoic to present-day species of the Trochidae subfamilies Cantharidinae and Trochinae are discussed based on an extensive literature survey. In total, 393 species-level taxa, assigned to 24 genera and subgenera, are listed from the NE Atlantic, the E Atlantic, the North Sea, the (Proto)-Mediterranean Sea, the Central Paratethys Sea and the Eastern Paratethys Sea. Short diagnosis and subjective and objective junior synonyms for genus-level taxa are given. Stratigraphic ranges and geographic distribution are listed for species-level taxa.                The European fossil record suggests a first major radiation during the middle Eocene and a second diversity pulse during the Miocene, when most extant genera were already present. At the species level, however, the present-day fauna is geologically very young, originating during the Pleistocene and Holocene. Overall, no convincing correlation of evolution and diversity of European Cantharidinae and Trochinae with major geodynamic events (e.g. Tethys Closure) can be observed. An exception is the somewhat overlooked spectacular radiation of Cantharidinae following the hydrological isolation of the Paratethys Sea during the late Miocene. The critical evaluation of the fossil record provides anchor points to test molecular phylogenies. A major discrepancy between both approaches appears only for Jujubinus, which suggests that Paleocene species have to be excluded from the genus.                Gibbuliculus nov. gen. is introduced as new genus for a group of Oligocene to Pleistocene species, placed so far in “Colliculus” sensu auctores non Monterosato, 1888. Anceps siminescui nov. nom, Gibbuliculus saccoi nov. nom, Gibbula tavanii nov. nom., Gibbula s.l. lovellreevei nov. nom. and Gibbula s.l. steiningeri nov. nom. are proposed as new names for the preoccupied Trochus semistriatus Siminescu & Barbu, 1940, Gibbula protumida Sacco, 1896, Gibbula minima Tavani, 1939, Trochus (Gibbula) reevei Harmer, 1923 and Trochus amedei bicincta Schaffer, 1912.
Back to the Westminster model? The Brexit process and the UK political system
Authors: Baldini Gianfranco , Bressanelli Edoardo , Massetti Emanuele
Published: January 2021

This article investigates the impact of Brexit on the British political system. By critically engaging with the conceptualisation of the Westminster model proposed by Arend Lijphart, it analyses the strains of Brexit on three dimensions developed from from Lijphart’s framework: elections and the party system, executive– legislative dynamics and the relationship between central and devolved administrations. Supplementing quantitative indicators with an in-depth qualitative analysis, the article shows that the process of Brexit has ultimately reaffirmed, with some important caveats, key features of the Westminster model: the resilience of the two-party system, executive dominance over Parliament and the unitary character of the political system. Inheriting a context marked by the progressive weakening of key majoritarian features of the political system, the Brexit process has brought back some of the traditional executive power-hoarding dynamics. Yet, this prevailing trend has created strains and resistances that keep the political process open to different developments.
Thromboangiitis obliterans in pregnancy – Case report and literature review
Authors: Farquhar Hannah E , Lamprecht Annabelle
Published: January 2021

Thromboangiitis obliterans, also known as Buerger’s disease, is rarely reported in young women in pregnancy. It is an occlusive vascular disorder, characterised by episodic non-atherosclerotic thrombosis of small- and medium-sized blood vessels. Thromboangiitis obliterans predominantly occurs in males aged less than 50 years and is almost exclusively diagnosed in smokers. The small number of published cases have frequently reported worsening of thrombotic symptoms, due to the hypercoagulable state of pregnancy, and potential pregnancy complications of intra-uterine growth restriction and pre-term labour. This report provides a summary of the literature and outlines the case of a pregnant 23-year-old female with thromboangiitis obliterans, who was managed with low-dose enoxaparin and aspirin. Her thrombotic symptoms were stable during pregnancy; however, her pregnancy was complicated by placental malperfusion and intra-uterine growth restriction.
Absolute reliability and agreement between Stryd and RunScribe systems for the assessment of running power
Authors: Cartón-Llorente Antonio , Roche-Seruendo Luis E , Jaén-Carrillo Diego , Marcen-Cinca Noel , García-Pinillos Felipe
Published: January 2021

The advent of portable power meters has revolutionized training in cycling, allowing an accurate field-based assessment of athletes. In a similar way, researchers have recently developed low-cost gait analysis equipment to assess running power in a more natural environment. The purpose of this study was to evaluate the absolute reliability of two different power meters and the agreement between these two wearable devices (i.e., Stryd™ and RunScribe™) for measuring power during treadmill running. About 49 endurance runners performed a running protocol on a treadmill at self-selected comfortable velocities. Power output (W) was measured using the Stryd™ and RunScribe™ systems, which were attached to the same shoe. The absolute reliability, based on coefficient of variation, was 0.32 ± 0.29% for Stryd™ and 1.68 ± 1.49% for RunScribe™, while the standard error of the mean were 0.3 ± 0.2 W and 2.6 ± 2.5 W for Stryd™ and RunScribe™, respectively. Data from both devices showed significant correlations ( r = 0.783, p < 0.001) and the ICC ( r = 0.855) reported an almost perfect reliability. Bland–Altman plots revealed no heteroscedasticity of error ( r2 = 0.030), although a moderate systematic bias (−12.3 ± 26.6 W), and wide limits of agreement (39.8–64.3 W) were found. Considering the increased popularity of using power meter devices in running, scientists, coaches, athletes, and general users should be aware that data from these devices are reliable, but not interchangeable, due to the variation shown for running power output data.
A novel high-content screening approach for the elucidation of C. jejuni biofilm composition and integrity
Authors: Whelan Matthew V. X. , Simpson Jeremy C. , Ó Cróinín Tadhg
Published: January 2021

Background

Campylobacter jejuni is the leading cause of bacterial gastroenteritis worldwide and the main source of infection is contaminated chicken meat. Although this important human pathogen is an obligate microaerophile, it must survive atmospheric oxygen conditions to allow transmission from contaminated chicken meat to humans. It is becoming increasingly evident that formation of biofilm plays a key role in the survival of this organism for extended periods on poultry products. We have recently demonstrated a novel inducible model for the study of adherent C. jejuni biofilm formation under aerobic conditions. By taking advantage of supercoiling mediated gene regulation, incubation of C. jejuni with subinhibitory concentrations of the Gyrase B inhibitor novobiocin was shown to promote the consistent formation of metabolically active adherent biofilm.

Results

In this study, we implement this model in conjunction with the fluorescent markers: TAMRA (live cells) and SytoX (dead cells, eDNA) to develop a novel systematic high-content imaging approach and describe how it can be implemented to gain quantifiable information about the integrity and extracellular polymeric substance (EPS) composition of adherent C. jejuni biofilm in aerobic conditions. We show that this produces a model with a consistent, homogenous biofilm that can be induced and used to screen a range of inhibitors of biofilm adherence and matrix formation.

Conclusions

This model allows for the first time a high throughput analysis of C. jejuni biofilms which will be invaluable in enabling researchers to develop mechanisms to disrupt these biofilms and reduce the viability of these bacteria under aerobic conditions.
A dimension reduction technique applied to regression on high dimension, low sample size neurophysiological data sets
Authors: Santana Adrielle C. , Barbosa Adriano V. , Yehia Hani C. , Laboissière Rafael
Published: January 2021

Background

A common problem in neurophysiological signal processing is the extraction of meaningful information from high dimension, low sample size data (HDLSS). We present RoLDSIS (regression on low-dimension spanned input space), a regression technique based on dimensionality reduction that constrains the solution to the subspace spanned by the available observations. This avoids regularization parameters in the regression procedure, as needed in shrinkage regression methods.

Results

We applied RoLDSIS to the EEG data collected in a phonemic identification experiment. In the experiment, morphed syllables in the continuum /da/–/ta/ were presented as acoustic stimuli to the participants and the event-related potentials (ERP) were recorded and then represented as a set of features in the time-frequency domain via the discrete wavelet transform. Each set of stimuli was chosen from a preliminary identification task executed by the participant. Physical and psychophysical attributes were associated to each stimulus. RoLDSIS was then used to infer the neurophysiological axes, in the feature space, associated with each attribute. We show that these axes can be reliably estimated and that their separation is correlated with the individual strength of phonemic categorization. The results provided by RoLDSIS are interpretable in the time-frequency domain and may be used to infer the neurophysiological correlates of phonemic categorization. A comparison with commonly used regularized regression techniques was carried out by cross-validation.

Conclusion

The prediction errors obtained by RoLDSIS are comparable to those obtained with Ridge Regression and smaller than those obtained with LASSO and SPLS. However, RoLDSIS achieves this without the need for cross-validation, a procedure that requires the extraction of a large amount of observations from the data and, consequently, a decreased signal-to-noise ratio when averaging trials. We show that, even though RoLDSIS is a simple technique, it is suitable for the processing and interpretation of neurophysiological signals.
Correction to: Selenium supplementation in patients with peripartum cardiomyopathy: a proof‑of‑concept trial
Authors: Karaye Kamilu M. , Sa’idu Hadiza , Balarabe Suleiman A. , Ishaq Naser A. , Sanni Bushra , Abubakar Haruna , Mohammed Baba Lawan , Abdulsalam Tijjani , Tukur Jamilu , Mohammed Idris Y.
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
End-stage knee osteoarthritis with and without sarcopenia and the effect of knee arthroplasty – a prospective cohort study
Authors: Ho Kevin Ki-Wai , Lau Lawrence Chun-Man , Chau Wai-Wang , Poon Queena , Chung Kwong-Yin , Wong Ronald Man-Yeung
Published: January 2021

Background

Sarcopenia often accompanies osteoarthritis (OA), which is managed by total knee arthroplasty (TKA) in the late stage. Recent studies have suggested a higher risk of post-operative complications after TKA in sarcopenic OA subjects, but whether TKA can benefit them similar to non-sarcopenic subjects remains unexplored. This study aimed to examine the dynamic, mutual impact of sarcopenia and TKA in a one-year post-operative period.

Methods

This prospective cohort study was conducted between 2015 to 2018 at our hospital. Patients with end-stage OA of the knee waiting for TKA were recruited into the study. Primary outcome measures were change in muscle strength, mass and function. Secondary outcome measures were quality of life (QOL) measurements for pain, psychological and physical health.

Results

Fifty-eight patients were recruited, of which 79.3% were female and 32.8% already had sarcopenia at baseline. The average age of sarcopenic subjects and non-sarcopenic subjects was comparable (67.89 ± 7.07 vs. 67.92 ± 6.85; p = 0.99), but sarcopenic subjects had a lower body mass index (BMI) (25.64 ± 2.64 vs. 28.57 ± 4.04; p = 0.01). There was a statistically significant improvement in walking speed (10.24 ± 5.35 vs. 7.69 ± 2.68, p < 0.01) and muscle strength in both sarcopenic and non-sarcopenic patients after TKA. This was accompanied by an improvement trend in muscle mass in all subjects. There was no change in handgrip power before and after TKA and subsequent follow-up (19.31 ± 5.92 vs. 18.98 ± 6.37 vs. 19.36 ± 7.66; p = 0.97). QOL measured before, after and at follow-up with WOMAC (total: 42.27 ± 15.98 vs. 20.65 ± 15.24 vs. 16.65 ± 18.13) and SF12v2 (PCS: 33.06 ± 8.55 vs. 38.96 ± 8.01 vs. 40.67 ± 7.93) revealed progressive significant improvement (both comparisons p ≤ 0.01). Further analysis with the IPAQ also found increased engagement of high-intensity activities.

Conclusions

This study showed that sarcopenia among patients with end-stage OA of the knee is not uncommon, but both sarcopenic and non-sarcopenic OA patients achieved significant clinical and functional improvement after TKA. Further studies with a larger sample size and different ethnicities could help ascertain a beneficial role of TKA in sarcopenic OA subjects.

Trial registration

Registry: ClinicalTrials.gov, Registration number: NCT03579329. Date of registration: 6 July 2018. Retrospectively registered.
Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific?
Authors: Onoe Tamehito , Hara Satoshi , Yamada Kazunori , Zoshima Takeshi , Mizushima Ichiro , Ito Kiyoaki , Mori Takayasu , Daimon Shoichiro , Muramoto Hiroaki , Shimizu Maki , Iguchi Akira , Kuma Akihiro , Ubara Yoshifumi , Mitobe Michihiro , Tsuruta Hiroaki , Kishimoto Nao , Imura Junko , Konoshita Tadashi , Kawano Mitsuhiro
Published: January 2021

Background

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients.

Methods

Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed.

Results

Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6–53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected.

Conclusions

Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously.
Identification of a novel GRIN2D variant in a neonate with intractable epileptic encephalopathy-a case report
Authors: Jiao Jiancheng , Li Li , Sun Min , Fang Junchen , Meng Lingzhi , Zhang Yudong , Jia Chao , Ma Li
Published: January 2021

Background

N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. The functional NMDA receptors are heterotetramers consisting mainly of two GluN1 and two GluN2 subunits. GluN2 is encoded by the GRIN2D gene. A few case series have shown that GRIN2D variants are linked to developmental and epileptic encephalopathy. In this article, we report a novel GRIN2D variant, namely c.2021C > A (p.T674K) in a neonate with intractable epileptic encephalopathy.

Case presentation

A 12-day-old boy who had stiffness of the lower and upper extremities since birth was transferred from a local hospital to our department. On admission, the patient presented with head tilting backwards, staring, apnea and hypertonia of limbs. Video electroencephalogram showed continuous, generalized or multi-focal spike-wave and spike-and-slow wave discharges and hypsarrhythmia. A treatment regimen composed of phenobarbital, midazolam, levetiracetam and clonazepam was administered, which however led to only partial control of the seizure. Whole-exome sequencing identified c.2021C > A (p.T674K) in GRIN2D in the patient while such a mutation was not detected in the parents. The patient was hospitalized for 1 month and died of sudden cardio-respiratory arrest 2 weeks after discharge.

Conclusions

A novel variant of GRIN2D was identified in a neonate with epileptic encephalopathy. Epilepsy associated with this GRIN2D mutation is refractory to conventional anti-epileptic medications.
Correction to: Gender differences and determinants of prevalence, awareness, treatment and control of hypertension among adults in China and Sweden
Authors: Santosa Ailiana , Zhang Yue , Weinehall Lars , Zhao Genming , Wang Na , Zhao Qi , Wang Weibing , Ng Nawi
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
Correction to: Improving lifestyles sustainability through community gardening: results and lessons learnt from the JArDinS quasi-experimental study
Authors: Tharrey Marion , Sachs Ashby , Perignon Marlène , Simon Chantal , Mejean Caroline , Litt Jill , Darmon Nicole
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
Thickness of subcutaneous fat is a risk factor for incisional surgical site infection in acute appendicitis surgery: a prospective study
Authors: Thapa Bikas , Sutanto Edward , Bhandari Raju
Published: January 2021

Background

Incisional surgical site infection (SSI) is a significant source of postoperative morbidity resulting in increased length of stay and cost. In this study, our aim was to evaluate the association between thickness of subcutaneous fat (TSF) and incisional SSI among patients undergoing open appendectomy in low-resource settings.

Methods

90 patients with acute uncomplicated appendicitis who underwent emergency open appendectomy from December 2017 to August 2018 were included in this prospective study. TSF was measured preoperatively using ultrasound. TSF and other possible predictors of incisional SSI, including body mass index and other clinical characteristics, were assessed by univariate and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analysis evaluated the predictive value of TSF and the optimum cut-off value for TSF was determined using the Youden index.

Results

The prevalence of incisional SSI was 13.3% (12/90). TSF was independently associated with incisional SSI (P < 0.001). Additionally, history of smoking (P = 0.048) was also associated with incisional SSI. A model of incisional SSI using a cut-off of 23.0 mm for TSF was moderately accurate (area under curve 0.83, confidence interval 0.70–0.97; sensitivity 83.3%; specificity 76.9%).

Conclusions

The study demonstrated that TSF, as evaluated by ultrasound, is a predictor in the development of incisional SSI in patients with acute appendicitis undergoing open appendectomy. These findings suggest that ultrasound is useful both for the evaluation of TSF and the prediction of incisional SSI risk factor in low-resource settings.
Short and long-term impact of four sets of actions on acute ischemic stroke management in Rhône County, a population based before-and-after prospective study
Authors: Schott A. M. , Termoz A. , Viprey M. , Tazarourte K. , Vecchia C. Della , Bravant E. , Perreton N. , Nighoghossian N. , Cakmak S. , Meyran S. , Ducreux B. , Pidoux C. , Bony T. , Douplat M. , Potinet V. , Sigal A. , Xue Y. , Derex L. , Haesebaert J.
Published: January 2021

Background

Optimizing access to recanalization therapies in acute ischemic stroke patients is crucial. Our aim was to measure the short and long term effectiveness, at the acute phase and 1 year after stroke, of four sets of actions implemented in the Rhône County.

Methods

The four multilevel actions were 1) increase in stroke units bed capacity and development of endovascular therapy; 2) improvement in knowledge and skills of healthcare providers involved in acute stroke management using a bottom-up approach; 3) development and implementation of new organizations (transportation routes, pre-notification, coordination by the emergency call center physician dispatcher); and 4) launch of regional public awareness campaigns in addition to national campaigns. A before-and-after study was conducted with two identical population-based cohort studies in 2006–7 and 2015–16 in all adult ischemic stroke patients admitted to any emergency department or stroke unit of the Rhône County. The primary outcome criterion was in-hospital management times, and the main secondary outcome criteria were access to reperfusion therapy (either intravenous thrombolysis or endovascular treatment) and pre-hospital management times in the short term, and 12-month prognosis measured by the modified Rankin Scale (mRS) in the long term.

Results

Between 2015–16 and 2006–7 periods ischemic stroke patients increased from 696 to 717, access to reperfusion therapy increased from 9 to 23% (p < 0.0001), calls to emergency call-center from 40 to 68% (p < 0.0001), first admission in stroke unit from 8 to 30% (p < 0.0001), and MRI within 24 h from 18 to 42% (p < 0.0001). Onset-to-reperfusion time significantly decreased from 3h16mn [2 h54-4 h05] to 2h35mn [2 h05-3 h19] (p < 0.0001), mainly related to a decrease in delay from admission to imaging. A significant decrease of disability was observed, as patients with mild disability (mRS [0–2]) at 12 months increased from 48 to 61% (p < 0.0001). Pre-hospital times, however, did not change significantly.

Conclusions

We observed significant improvement in access to reperfusion therapy, mainly through a strong decrease of in-hospital management times, and in 12-month disability after the implementation of four sets of actions between 2006 and 2016 in the Rhône County. Reducing pre-hospital times remains a challenge.
Outreach-based clinical pharmacist prescribing input into the healthcare of people experiencing homelessness: a qualitative investigation
Authors: Johnsen Sarah , Cuthill Fiona , Blenkinsopp Janice
Published: January 2021

Background

Severely and multiply disadvantaged members of the homeless population are disproportionately vulnerable to exceptionally high levels of multi-morbidity and premature death. Given widespread calls for the development of interventions that might improve the uptake and effectiveness of healthcare for this population, this study investigated patient and other stakeholder perspectives regarding an outreach service, delivered by prescribing pharmacists in collaboration with a local voluntary sector provider, within homelessness services and on the street in Glasgow (UK).

Methods

The qualitative study involved semi-structured face-to-face interviews with 40 purposively sampled individuals with current or recent experience of homelessness (32 of whom had direct experience of the service and 8 of whom did not), all (n = 4) staff involved in frontline delivery of the service, and 10 representatives of stakeholder agencies working in partnership with the service and/or with the same client group. Pseudonymised verbatim interview transcriptions were analysed systematically via thematic and framework analysis.

Results

The service was effective at case finding and engaging with patients who were reluctant to utilise or physically unable to access existing (mainstream or specialist ‘homeless’) healthcare provision. It helped patients overcome many of the barriers that homeless people commonly face when attempting to access healthcare, enabled immediate diagnosis and prescription of medication, and catalysed and capitalised on windows of opportunity when patients were motivated to address healthcare needs. A number of improvements in health outcomes, including but not limited to medication adherence, were also reported.

Conclusions

A proactive, informal, flexible, holistic and person-centred outreach service delivered within homelessness service settings and on the street can act as a valuable bridge to both primary and secondary healthcare for people experiencing homelessness who would otherwise ‘fall through the gaps’ of provision. Prescribing pharmacist input coupled with third sector involvement into healthcare for this vulnerable population allows for the prompt treatment of and/or prescription for a range of conditions, and offers substantial potential for improving health-related outcomes.
Impact of peroxisome proliferator-activated receptor-α on diabetic cardiomyopathy
Authors: Wang Lin , Cai Yin , Jian Liguo , Cheung Chi Wai , Zhang Liangqing , Xia Zhengyuan
Published: January 2021

The prevalence of cardiomyopathy is higher in diabetic patients than those without diabetes. Diabetic cardiomyopathy (DCM) is defined as a clinical condition of abnormal myocardial structure and performance in diabetic patients without other cardiac risk factors, such as coronary artery disease, hypertension, and significant valvular disease. Multiple molecular events contribute to the development of DCM, which include the alterations in energy metabolism (fatty acid, glucose, ketone and branched chain amino acids) and the abnormalities of subcellular components in the heart, such as impaired insulin signaling, increased oxidative stress, calcium mishandling and inflammation. There are no specific drugs in treating DCM despite of decades of basic and clinical investigations. This is, in part, due to the lack of our understanding as to how heart failure initiates and develops, especially in diabetic patients without an underlying ischemic cause. Some of the traditional anti-diabetic or lipid-lowering agents aimed at shifting the balance of cardiac metabolism from utilizing fat to glucose have been shown inadequately targeting multiple aspects of the conditions. Peroxisome proliferator-activated receptor α (PPARα), a transcription factor, plays an important role in mediating DCM-related molecular events. Pharmacological targeting of PPARα activation has been demonstrated to be one of the important strategies for patients with diabetes, metabolic syndrome, and atherosclerotic cardiovascular diseases. The aim of this review is to provide a contemporary view of PPARα in association with the underlying pathophysiological changes in DCM. We discuss the PPARα-related drugs in clinical applications and facts related to the drugs that may be considered as risky (such as fenofibrate, bezafibrate, clofibrate) or safe (pemafibrate, metformin and glucagon-like peptide 1-receptor agonists) or having the potential (sodium–glucose co-transporter 2 inhibitor) in treating DCM.
History of lower-limb complications and risk of cancer death in people with type 2 diabetes
Authors: Mohammedi Kamel , Harrap Stephen , Mancia Giuseppe , Marre Michel , Poulter Neil , Chalmers John , Woodward Mark
Published: January 2021

Background

Individuals with diabetes and lower-limb complications are at high risk for cardiovascular and all-cause mortality, but uncertainties remain in terms of cancer-related death in this population. We investigated this relationship in a large cohort of people with type 2 diabetes.

Methods

We used data from the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. The primary outcome was adjudicated cancer death; secondary outcomes were overall and site-specific incident cancers, determined according to the International Classification of Diseases Code (ICD-10). We compared outcomes in individuals with (versus without) a baseline history of lower-limb complications (peripheral artery disease (PAD) or sensory peripheral neuropathy) using Cox regression models.

Results

Among 11,140 participants (women 42%, mean age 66 years), lower-limb complications were reported at baseline in 4293 (38%) individuals: 2439 (22%) with PAD and 2973 (27%) with peripheral neuropathy. Cancer death occurred in 316 (2.8%) participants during a median of 5.0 (25th–75th percentile, 4.7–5.1) years of follow-up corresponding to 53,550 person-years and an incidence rate of 5.9 (95% CI 5.3–6.6) per 1000 person-years. The risk of cancer death was higher in individuals with (versus without) lower-limb complication [hazard ratio 1.53 (95% CI, 1.21–1.94), p = 0.0004], PAD [1.32 (1.02–1.70), p = 0.03] or neuropathy (1.41 (1.11–1.79), p = 0.004], adjusting for potential confounders and study allocations. PAD, but not neuropathy, was associated with excess risk of incident cancers.

Conclusions

PAD and peripheral neuropathy were independently associated with increased 5-year risk of cancer death in individuals with type 2 diabetes. PAD was also associated with increased risk of incident cancers. Our findings provide new evidence on the non-cardiovascular prognostic burden of lower-limb complications in people with type 2 diabetes.
RETRACTED ARTICLE: Histone methyltransferase SUV39H2 regulates LSD1-dependent CDH1 expression and promotes epithelial mesenchymal transition of osteosarcoma
Authors: Miao Yingying , Liu Guifeng , Liu Lin
Published: January 2021

Objective

Osteosarcoma (OS) is a malignant tumor characterized by the direct production of bone or osteoid tissues by proliferating tumor cells. Suppressor of variegation 3–9 homolog 2 (SUV39H2) is implicated in the occurrence of OS. Therefore, we designed this study to investigate effects of SUV39H2 in OS meditated by the lysine specific demethylase-1/E-cadherin (LSD1/CDH1) axis.

Methods

Clinical OS tissues and paracancerous tissues were collected for analysis of SUV39H2, LSD1 and CDH1 expression, and Kaplan–Meier survival analysis was applied to test the relationship between SUV39H2 expression and overall survival. Loss- and gain-of-function assays were conducted to determine the roles of SUV39H2, LSD1 and CDH1 in OS epithelial mesenchymal transition (EMT) and migration in OS cells, with quantitation of relevant proteins by immunofluorescence. We confirmed the effects of modulating the SUV39H2/CDH1 axis in a mouse OS tumor model.

Results

SUV39H2 and LSD1 were highly expressed, while CDH1 was downregulated in OS tissues and cells. SUV39H2 expression correlated inversely with overall survival of patients with OS. SUV39H2 positively regulated LSD1 expression, while LSD1 negatively regulated CDH1 expression. SUV39H2 or LSD1 overexpression, or CDH1 silencing promoted migration and EMT, as indicated by reduced E-cadherin and dramatically upregulated Vimentin and N-cadherin of OS cells. SUV39H2 expedited the progression of OS, which was reversed by CDH1 repression in the setting of OS in vitro and in vivo.

Conclusions

Collectively, our results demonstrate highly expressed SUV39H2 in OS elevates the expression of LSD1 to downregulate CDH1 expression, thereby aggravating OS, providing a potential therapeutic target for treatment of OS.
Caloric restriction in female reproduction: is it beneficial or detrimental?
Authors: Sun Jiayi , Shen Xin , Liu Hui , Lu Siying , Peng Jing , Kuang Haibin
Published: January 2021

Caloric restriction (CR), an energy-restricted intervention with undernutrition instead of malnutrition, is widely known to prolong lifespan and protect against the age-related deteriorations. Recently it is found that CR significantly affects female reproduction via hypothalamic (corticotropin releasing hormone, neuropeptide Y, agouti-related peptide) and peripheral (leptin, ghrelin, insulin, insulin-like growth factor) mediators, which can regulate the energy homeostasis. Although CR reduces the fertility in female mammals, it exerts positive effects like preserving reproductive capacity. In this review, we aim to discuss the comprehensive effects of CR on the central hypothalamus-pituitary-gonad axis and peripheral ovary and uterus. In addition, we emphasize the influence of CR during pregnancy and highlight the relationship between CR and reproductive-associated diseases. Fully understanding and analyzing the effects of CR on the female reproduction could provide better strategies for the management and prevention of female reproductive dysfunctions.