bluuebunny/crossref_metadata_2025 huggingface dataset:
The heparin‐von Willebrand factor interaction and conventional tests of haemostasis – the challenges in predicting bleeding in cardiopulmonary bypass
Authors: Ranger Amita , Gaspar Mihaela , Elkhatteb Amira , Jackson Tim , Fox Steve , Aw T. C. , Vipond Lisa , Cotterill Judy , Ghori Arshad , Laffan Mike , Arachchillage Deepa R. J.
Published: December 2020

Bleeding is a significant complication of cardiopulmonary bypass (CPB), despite routine anticoagulation monitoring. This is likely to be multifactorial. In this prospective, single‐centre cohort study of 30 patients undergoing CPB surgery, our aim was to characterise the changes in von Willebrand factor (VWF) function, platelet interaction and the global coagulation changes during and after CPB surgery and to determine whether bleeding can be predicted. Samples were taken at six time points before, during and after CPB surgery. We observed a significant rise in VWF antigen (VWF:Ag) throughout surgery, which continued postoperatively. The absolute VWF collagen‐binding assays (VWF:CB) and VWF ristocetin cofactor (VWF:RCo) rose significantly but the VWF:CB/VWF:Ag and VWF:Ag/VWF:RCo fell significantly (P = 0·0015 and P = 0·0143), suggesting loss of large multimers. We detected a non‐significant trend to loss of VWF:RCo after heparinisation and a significant recovery after protamine reversal which could reflect a direct heparin effect. There was a significant increase in the R and K times with a fall in alpha angle and maximum amplitude after heparin administration, using heparinase‐thromboelastography (TEG). The parameters both significantly improved following protamine (P = 0·007 and P = 0·0054). The activated clotting time (ACT) and heparin anti‐Xa level correlated poorly; neither predicted clinically significant bleeding. None of these parameters had a relationship with intraoperative blood loss or requirement for blood product replacement.
Explaining the rise and fall of psychological distress during the COVID‐19 crisis in the United States: Longitudinal evidence from the Understanding America Study
Authors: Robinson Eric , Daly Michael
Published: December 2020

Objectives

It has been shown that psychological distress rose rapidly as the COVID‐19 pandemic emerged and then recovered to pre‐crisis levels as social lockdown restrictions were eased in the United States. The aim of the current study was to investigate psychosocial and behavioural factors that may explain the rise and fall of distress during the initial months of the COVID‐19 crisis.

Design

This study examined six waves of longitudinal nationally representative data from the Understanding America Study (UAS) collected between March and June 2020 (N = 7,138, observations = 34,125).

Methods

Mediation analysis was used to identify whether changes in distress (PHQ‐4) during the COVID‐19 pandemic were explained by the following factors: perceived infection risk and risk of death, perceived financial risks, lifestyle changes resulting from the virus, perceived discrimination related to the virus, and changes in substance use and employment status.

Results

All mediating factors played a role in explaining changes in distress and together accounted for 70% of the increase in distress between 10‐18 March and 1‐14 April and 46.4% of the decline in distress between 1‐14 April and early June 2020. Changes in perceived health risks were most important in explaining changes in distress followed by changes in lifestyle and the perceived financial risks associated with COVID‐19.

Conclusions

This study provides longitudinal population‐based evidence detailing the mediating factors explaining changes in distress during the COVID‐19 crisis. Perceived health risks associated with the virus may play a key role in explaining rising and falling levels of psychological distress during the COVID‐19 pandemic.
Review: Education and training interventions, and support tools for school staff to adequately respond to young people who disclose self‐harm – a systematic literature review of effectiveness, feasibility and acceptability
Authors: Pierret Aureliane C. S. , Anderson Joanna K. , Ford Tamsin J. , Burn Anne‐Marie
Published: December 2020

Background

Self‐harm among young people is a major public health concern, and whilst schools are well placed to identify and intervene with students who self‐harm, the literature shows that school staff lack training and confidence in this area. This systematic review investigated the effectiveness, feasibility and acceptability of training interventions and support tools intended to equip school staff with skills and knowledge to adequately respond to students’ disclosure of self‐harm.

Method

References for this review were identified through systematic searches of Medline, Embase, PsycINFO, Child Development & Adolescent Studies, ERIC, ASSIA and British Education Index on with search terms ‘self‐harm’, ‘training’, ‘school staff’ and ‘young people’. Thematic synthesis was used to analyse qualitative data.

Results

We found that all eight included studies evaluated interventions/tools that were highly effective in terms of an increase in knowledge, skills and confidence of staff in responding to self‐harming youth. Acceptability was good with high levels of satisfaction and perceived benefit by staff, though data on feasibility of the interventions were lacking. Limitations of the studies included a paucity of follow‐up data, and lack of data relating to student outcomes and actual changes in staff practice in schools.

Conclusions

The findings from this review indicate that more evidence is needed to determine the effectiveness, acceptability and feasibility of interventions/tools for school staff addressing self‐harm. Further studies should focus on maintaining knowledge, confidence and comfort levels over time, and determine the feasibility of interventions/tools with different staff cohorts and across school settings, as well as address outcomes for students.
Prospective evaluation and refinement of an S‐1 dosage formula based on renal function for clinical application
Authors: Takeuchi Masashi , Imamura Chiyo K. , Booka Eisuke , Takeuchi Hiroya , Mizukami Takuro , Kawakami Takeshi , Funakoshi Taro , Wakuda Kazushige , Aoki Yu , Hamamoto Yasuo , Kitago Minoru , Kawakubo Hirofumi , Boku Narikazu , Tanigawara Yusuke , Kitagawa Yuko
Published: December 2020

In patients with impaired renal function, S‐1–related toxicities increase due to higher exposure of 5‐fluorouracil (5‐FU). Our previous pharmacokinetic study in 16 cancer patients with various renal functions developed an S‐1 dosage formula based on individual creatinine clearance (CLcr) and body surface area (BSA). To evaluate and refine the formula, this prospective study was conducted. Thirty‐three patients with various renal functions received S‐1 for 4 weeks at doses determined by the nomogram derived from the previously developed formula. A series of blood samples were collected after the first dose to calculate the area under the concentration‐time curve (AUC) of 5‐FU. Thirty patients with BSA of 1.14‐1.84 m2 and CLcr of 23.8‐96.4 mL/min were assessable for pharmacokinetics. The observed daily AUC ranged from 712.6 to 2868.7 ng·h/mL, and 18 patients achieved the target AUC (1447.8 ± 545.4 ng·h/mL). Three patients experienced S‐1–related grade 3 adverse events during the first course. In the population pharmacokinetic analysis from the combined data of 46 patients in this study and the previous study, sex was identified as a statistically significant covariate for 5‐FU clearance. Hence, the refined formula includes sex as an additional factor: Recommended daily dose = target AUC × (14.5 + 8.23 × SEX [0 for female and 1 for male] + 0.301 × CLcr) × BSA. Revised nomograms for recommended daily doses derived from the refined formula can be used in clinical practice to achieve the target AUC ensuring efficacy and safety of S‐1.
Will implants with a fixed dental prosthesis in the molar region enhance the longevity of teeth adjacent to distal free‐end edentulous spaces?
Authors: Hatta Kodai , Takahashi Toshihito , Sato Hitomi , Murakami Shinya , Maeda Yoshinobu , Ikebe Kazunori
Published: December 2020

Objectives

Clinical evidence demonstrating the effectiveness of implants in preventing tooth loss is limited because of the many risk factors involved in tooth loss. This retrospective cohort study investigated whether an implant in the molar region of a distal free‐end edentulous space affects the loss of the most distal tooth after 6 years, adjusting for other risk factors associated with tooth loss using propensity score matching analysis.

Material and Methods

A total of 571 subjects and 1,085 teeth adjacent to a distal free‐end edentulous space were evaluated. At baseline, the 1,085 teeth were divided into two groups according to the presence or absence of a molar implant with a fixed dental prosthesis in the distal free‐end edentulous space. Propensity score matching analysis was used to reduce the effects of bias by matching teeth with and without implants according to similar background factors at baseline. The adjusted variables were age group, occlusal support status, Kennedy classification, tooth position, tooth type, restoration status, dental caries, periodontal pocket depth, and condition of the opposing tooth.

Results

A total of 56 teeth (28 associated with a molar implant; 28 with no implant) were enrolled according to propensity score matching. Fisher's exact test showed that a molar implant significantly protected the tooth adjacent to the distal free‐end edentulous space (p = .01).

Conclusions

Within the limitations of this retrospective cohort study, it was found that implants in free‐end edentulous spaces may be beneficial in extending the longevity of adjacent teeth. Further research will be necessary to confirm this finding.
Effect of Crohn’s Disease on Villous Length and CYP3A4 Expression in the Pediatric Small Intestine
Authors: Vyhlidal Carrie A , Chapron Brian D. , Ahmed Atif , Singh Vivekanand , Casini Rebecca , Shakhnovich Valentina
Published: December 2020

Changes in absorptive capacity and first‐pass metabolism in the small intestine affect oral drug bioavailability. Characterization of such changes as a consequence of inflammation is important for developing physiologically‐based pharmacokinetic (PBPK) models for inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn’s disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal and terminal ileum (TI) biopsies from 107 children (1–19 years) with and without CD were evaluated for active inflammation. Villous length and CYP3A4 mRNA/protein expression were compared among regions of active and inactive inflammation in CD and controls. A twofold reduction in villous length was observed in inflamed duodena and ilia of children with CD, but in the absence of regional inflammation, villi in CD were comparable in length to controls. Expression of CYP3A4 mRNA correlated significantly with villous length in the TI (P = 0.0003), with a trend observed in the duodenum that did not reach statistical significance. In the presence of active inflammation, a significant decrease in CYP3A protein expression was confirmed in the duodenum, where protein expression also correlated significantly with villous length across diagnoses (P < 0.0001). Our findings suggest that previous observations of decreased CYP3A4 expression and function in inflamed intestine may not be due solely to downregulation by inflammatory cytokines, but also to villous blunting and subsequent loss of surface area for protein expression. This information is relevant for PBPK model development and could aid with dose adjustment decisions for oral CYP3A4 substrates administered during CD flare (e.g., budesonide).
Sarcopenia in Patients With Normal Body Mass Index Is an Independent Predictor for Postoperative Complication and Long‐Term Survival in Gastric Cancer
Authors: Sun Xiangwei , Xu Jianfeng , Chen Xiaodong , Zhang Weiteng , Chen Wenjing , Zhu Ce , Sun Jing , Yang Xinxin , Wang Xiang , Hu Yingying , Cai Yiqi , Shen Xian
Published: December 2020

Malnutrition in patients with gastric cancer (GC) with normal body mass index (BMI) is often ignored. This study aimed to explore the role of sarcopenia in predicting postoperative complication and long‐term survival in patients with GC with normal BMI. We included patients with normal BMI (18.5 kg/m2 ≤ BMI < 23 kg/m2) who underwent radical gastrectomy between July 2014 and December 2016. Sarcopenia was assessed by muscle mass, handgrip strength, and gait speed. Kaplan–Meier survival analysis was used to analyze the association between sarcopenia and the prognosis of patients with GC. Univariate and multivariate analyses were used to identify risk factors contributing to postoperative complications and long‐term survival. Overall, 267 patients with GC with normal BMI were included in this study; of which 49 (18.35%) patients were diagnosed with sarcopenia. Patients with sarcopenia had higher incidence of a major postoperative complication, longer postoperative hospital stays, and greater hospital costs. The Kaplan–Meier survival analysis showed that patients with sarcopenia had poorer overall survival than non‐sarcopenia patients. Univariate and multivariate analyses showed that sarcopenia was an independent predictor for postoperative complication and long‐term survival in such patients. Sarcopenia is an independent predictor for postoperative complications and long‐term survival in patients with normal BMI after radical gastrectomy for GC. We recommend that patients with normal BMI should perform nutritional risk screening by sarcopenia.
Clinical Evaluation of an Investigational 5 mL Wearable Injector in Healthy Human Subjects
Authors: Woodley Wendy D. , Yue Wen , Morel Didier R. , Lainesse Audrey , Pettis Ronald J. , Bolick Natasha G.
Published: December 2020

An investigational wearable injector (WI), the BD Libertas Wearable Injector (BD Libertas is a trademark of Becton, Dickinson and Company), was evaluated in an early feasibility clinical study for functional performance, tissue effects, subject tolerability, and acceptability of 5 mL, non‐Newtonian ~ 8 cP subcutaneous placebo injections in 52 healthy adult subjects of 2 age groups (18–64 years and ≥ 65 years). Randomized WI subcutaneous injections (n = 208, 4/subject) were delivered to the right and left abdomen and thigh of each subject, 50% (1 thigh and 1 abdomen) with a defined movement sequence during injection. Injector functional performance was documented. Deposition was qualified and quantified with ultrasound. Tissue effects and tolerability (pain) were monitored through 24 hours with corresponding acceptability questionnaires administered through 72 hours. WI (n = 205) automatically inserted the needle, delivered 5 mL ± 5% in 5.42 minutes (SD 0.74) and retracted. Depots were entirely (93.2%) or predominantly (5.4%) localized within the target subcutaneous tissue. Slight to moderate wheals (63.9%) and erythema (75.1%) were observed with ≥ 50% resolution within 30–60 minutes. Subject pain (100 mm Visual Analog Scale) peaked mid‐injection (mean 9.1 mm, SD 13.4) and rapidly resolved within 30 minutes (mean 0.4 mm, SD 2.6). Subjects’ peak pain (≥ 90.2%), injection site appearance (≥ 92.2%) and injector wear, size, and removal (≥ 92.1%) were acceptable (Likert responses) with 100% likely to use the injector if prescribed. Injection site preference was divided between none (46%), abdomen (25%), or thigh (26.9%). The investigational WI successfully delivered 5 mL viscous subcutaneous injections. Tissue effects and pain were transient, well‐tolerated and acceptable. Neither injection site, movement or subject age affected injector functional performance or subject pain and acceptability.
Long‐term endoscopic surveillance for Barrett's esophagus in Japan: Multicenter prospective cohort study
Authors: Norita Kazuaki , Koike Tomoyuki , Saito Masahiro , Shinkai Hirohiko , Ami Reiko , Abe Yasuhiko , Dairaku Naohiro , Inomata Yoshifumi , Kayaba Shoichi , Ishiyama Fumitake , Oikawa Tomoyuki , Ohyauchi Motoki , Ito Hirotaka , Asonuma Sho , Hoshi Tatsuya , Kato Katsuaki , Ohara Shuichi , Shimodaira Yosuke , Watanabe Kenta , Shimosegawa Tooru , Masamune Atsushi , Iijima Katsunori
Published: December 2020

Objects

Although a recent study showed the cancer incidence of Barrett's esophagus (BE) to be 1.2%/year in 251 patient‐years in Japan, the long‐term outcomes remain unclear. The present study estimated the cancer risk of BE in Japan using our original prospective multicenter cohort.

Methods

A total of 98 patients with BE of maximum length of ≥2 cm were enrolled during the period of 2010–2012 and received at least one follow‐up endoscopy over 5 years thereafter. Cancer incidence rates with 95% confidence interval for occurrence of esophageal adenocarcinoma (EAC) were calculated as the number of events divided by patient‐years of follow‐up and were expressed as %/year.

Results

Overall, the median endoscopic follow‐up period was 59.9 (first and third quartiles, 48.5–60.8) months, constituting a total of 427 patient‐years of observation. Since two EAC cases developed, the cancer incidence was 0.47% (0.01%–1.81%)/year. The cancer incidence was 0.39% (−0.16% to 2.44%) in 232 patient‐years and 0.31% (−0.13% to 1.95%)/year in 318 patient‐years for 55 cases with specialized intestinal metaplasia and 70 with BE ≥3 cm (maximum), respectively. At the end of follow‐up, 12 of 92 patients (13.0%) died, but none died from EAC.

Conclusion

This is the largest prospective follow‐up study with endoscopy to investigate the incidence of EAC in unequivocal BE with the maximum length of ≥2 cm in Japan. Although a further large‐scale study will be required to validate our results, the cancer risk of BE in Japan would be lower than previously reported (0.47% vs 1.2%/year).
Trends in prevalence and incidence of type 2 diabetes among adults in Beijing, China, from 2008 to 2017
Authors: Wang Zijing , Wu Yao , Wu Junhui , Wang Mengying , Wang Xiaowen , Wang Jiating , Wu Tao , Wu Yiqun , Hu Yonghua
Published: December 2020

Aims

To describe secular trends in diagnosed type 2 diabetes prevalence and incidence in Beijing, China.

Methods

Using health insurance claims for 17.7 million adults ≥20 years in 2008–2017, we identified people with diabetes using hospital diagnoses and drug prescriptions. Results were age‐standardised using data for Beijing from China's 2010 census. Trends in prevalence and incidence were analysed using Joinpoint regression analysis.

Results

From 2008 to 2017, we identified 2,104,159 people diagnosed with type 2 diabetes. Type 2 diabetes prevalence increased from 3.7% [95% CI: (3.6, 3.8)] to 6.6% (6.4, 6.7), but the annual rate of increase slowed from 18.1% (14.4, 22.0) to 1.5% (0.8, 2.2) before and after 2011 respectively. Women had a higher diabetes prevalence than men, for all years. The yearly increase in prevalence was greater in people younger than 40 years, with an average annual percentage change of 13.6% (10.7, 16.5) compared to 6.5% (5.6, 7.4) in those over 40 years. Over the 10 years, the overall incidence decreased from 24.3 (24.2, 24.4) to 11.5 (11.5, 11.6) per 1000 person‐years, but it increased in people younger than 40 years. The average age at diabetes diagnosis dropped from 62 to 56 years (p < 0.001). Among incident cases of diabetes, the percentage of people under 40 years increased from 3.0% to 10.9% (p < 0.001).

Conclusions

The prevalence of diagnosed type 2 diabetes in Beijing increased continuously over the 10 years, the incidence decreased, except in people under 40 years. Continuous efforts are needed to prevent diabetes in China.
Evaluation of pregnancy outcomes in women with GCK‐MODY
Authors: López Tinoco Cristina , Sánchez Lechuga Begoña , Bacon Siobhan , Colclough Kevin , Ng Nicholas , Wong Eleanor , Goulden Eirena L. , Edwards Jackie , Fleming Aileen , Byrne Bridgette , Byrne Maria M.
Published: December 2020

Aims

To determine the fetal and maternal outcomes in pregnant women with Glucokinase‐Maturity onset diabetes of the young (GCK‐MODY).

Methods

We studied the obstetric and perinatal outcomes in 99 pregnancies of 34 women with GCK‐MODY. The mutation status of the offspring was known in 29 and presumed in 33. Clinical outcomes were determined and compared between affected (n = 39) and unaffected (n = 23) offspring.

Results

59% of pregnancies were treated with diet alone and 41% received insulin. Birthweight, percentage of large for gestational age (LGA) and caesarean section (CS) in GCK‐unaffected offspring was significantly higher than in GCK‐affected offspring (4.0 ± 0.7 vs. 3.4 ± 0.4 kg, p = 0.001), 15 (65%) vs. 5(13%) (p = 0.00006) and 17 (74%) vs. 11 (28%) (p = 0.001), respectively. We observed an earlier gestational age at delivery on insulin in unaffected offspring (38.3 ± 1.0 vs. 39.5 ± 1.5 weeks, p = 0.03) with no significant change in LGA (9 (82%) vs. 6 (50%); p = 0.12), and a higher rate of CS (8 [73%] vs. 3 [11%]; p < 0.001), and no change in small for gestational age (0 [0%] vs. 4 [14%]; p = 0.30) in affected offspring.

Conclusion

Insulin therapy in unaffected offspring did not reduce LGA and was associated with earlier gestational age at delivery. Insulin treatment in GCK‐affected offspring was associated with an increased incidence of CS, but did not adversely affect fetal outcome. Fetal genotype determines birthweight rather than treatment. Pre‐pregnancy diagnosis of GCK‐MODY, use of continuous glucose monitoring and non‐invasive fetal genotyping may enable further investigation of targeted therapy in this condition.
Topsy‐turvy heart: A first recorded case report with intracardiac anomaly
Authors: Alkhateeb Areej , Mansour Amr , Tanidir Ibrahim Cansaran
Published: December 2020

Topsy‐turvy heart is a rare congenital anomaly; it has a specific characteristic of cardiac malrotation and superior–inferior arrangement of right/left ventricles. A five‐day‐old patient was diagnosed antenatally with hypoplastic left heart and right hydronephrosis and had been admitted to the hospital with symptoms of respiratory distress. The postnatal imaging studies revealed an abnormal ventricular arrangement with a large aortopulmonary window, ventricular septal defect (VSD), and the upside‐down orientation resulting in the posterior–inferior displacement of the common arterial confluence and, in turn, the left main bronchial stenosis. For the first time, the diagnosis of a topsy‐turvy heart with the intracardiac anomaly (VSD) was confirmed.
Odd one in: Oddity within mixed‐species shoals does not affect shoal preference by vagrant tropical damselfish in the presence or absence of a predator
Authors: Paijmans Kai C. , Booth David J. , Wong Marian Y. L.
Published: December 2020

Grouping behaviour displayed by animals is usually attributed to predation and foraging‐related benefits. The mechanisms of predator protection and foraging efficiency are diverse and often produce conflicting drivers of grouping behaviour. One key conflict is that between group size and phenotypic oddity. Theoretically, individuals should choose the largest available group due to multiple mechanisms associated with “safety in numbers”. However, individuals should also choose the most phenotypically similar group members due to the “predator confusion effect”. This conflict is particularly important within the context of mixed‐species groups because, while their formation may facilitate large group size, phenotypic differences between species may be costly due to oddity. To investigate the interacting effects of shoal size, composition and predator presence on grouping decisions, choice experiments were conducted using displaced tropical damselfish,Abudefduf vaigiensis, settling in temperate south‐eastern Australia (termed vagrants) as a model species. Contrary to predictions,A. vaigiensisdisplayed no preference for single‐ over mixed‐species shoals, with or without a predator present. These results suggest that shoal composition may not be an important driver of shoal choice in this system. Further,A. vaigiensisshowed no preference for larger mixed‐species shoals over smaller single‐species shoals. These outcomes are discussed within the context of climate change‐driven redistribution ofA. vaigiensisin temperate south‐eastern Australia.
Influenza A virus infection‐induced macroautophagy facilitates MHC class II‐restricted endogenous presentation of an immunodominant viral epitope
Authors: Deng Jieru , Lu Chunni , Liu Chuanxin , Oveissi Sara , Fairlie W. Douglas , Lee Erinna F. , Bilsel Pamuk , Puthalakath Hamsa , Chen Weisan
Published: December 2020

CD4+T cells recognize peptides presented by major histocompatibility complex class II molecules (MHC‐II). These peptides are generally derived from exogenous antigens. Macroautophagy has been reported to promote endogenous antigen presentation in viral infections. However, whether influenza A virus (IAV) infection‐induced macroautophagy also leads to endogenous antigen presentation through MHC‐II is still debated. In this study, we show that IAV infection leads to endogenous presentation of an immunodominant viral epitope NP311–325by MHC‐II to CD4+T cells. Mechanistically, such MHC‐II‐restricted endogenous IAV antigen presentation requiresde novoprotein synthesis as it is inhibited by the protein synthesis inhibitor cycloheximide, and a functional ER‐Golgi network as it is totally blocked by Brefeldin A. These results indicate that MHC‐II‐restricted endogenous IAV antigen presentation is dependent onde novoantigen and/or MHC‐II synthesis, and transportation through the ER‐Golgi network. Furthermore, such endogenous IAV antigen presentation by MHC‐II is enhanced by TAP deficiency, indicating some antigenic peptides are of cytosolic origin. Most importantly, the bulk of such MHC‐II‐restricted endogenous IAV antigen presentation is blocked by autophagy inhibitors (3‐MA and E64d) and deletion of autophagy‐related genes, such asBeclin1andAtg7. We have further demonstrated that in dendritic cells, IAV infection prevents autophagosome–lysosome fusion and promotes autophagosome fusion with MHC class II compartment (MIIC), which likely promotes endogenous IAV antigen presentation by MHC‐II. Our results provide strong evidence that IAV infection‐induced autophagosome formation facilitates endogenous IAV antigen presentation by MHC‐II to CD4+T cells. The implication for influenza vaccine design is discussed.
Anthropogenic litter is a novel habitat for aquatic macroinvertebrates in urban rivers
Authors: Wilson Hazel L. , Johnson Matthew F. , Wood Paul J. , Thorne Colin R. , Eichhorn Markus P.
Published: December 2020

Anthropogenic litter (solid manufactured waste) is an understudied but pervasive element of river systems worldwide. Its physical structure generally differs from natural substrates, such as gravel and cobbles (hereafter rocks). Consequently, anthropogenic litter could influence ecological communities in urban rivers by providing novel habitats.

This study compares the macroinvertebrates recorded on anthropogenic litter with those on rocks to test whether the different substrates support distinct communities. Macroinvertebrates were collected from individual rocks and anthropogenic litter, predominantly plastic, metal, and glass, in three U.K. rivers.

Macroinvertebrate communities on anthropogenic litter were consistently more diverse than those found on rocks, reflecting its greater surface complexity, but the density of macroinvertebrates was similar among substrates. The community composition also varied between substrates, with five taxa only recorded on anthropogenic litter. Community differences largely reflected greater abundances of common taxa on anthropogenic litter, which were relatively insensitive to environmental quality. Plastic and fabric anthropogenic litter communities were the most dissimilar to those on rocks, probably due to their flexibility, which could replicate the physical structure of aquatic macrophytes.

Our findings indicate that anthropogenic litter supports a distinct and diverse community of macroinvertebrates in urban rivers, which are otherwise relatively homogenous in habitat structure.

Removal of anthropogenic litter from urban rivers may not be beneficial for local biodiversity. Understanding the functional habitats provided by anthropogenic litter could help better manage urban rivers to replace habitat lost through urbanisation.
Caspofungin combined with TMP/SMZ as a first‐line therapy for moderate‐to‐severe PCP in patients with human immunodeficiency virus infection
Authors: Tian Q , Si J , Jiang F , Xu R , Wei B , Huang B , Li Q , Jiang Z , Zhao T
Published: December 2020

Objectives

The effectiveness of trimethoprim/sulfamethoxazole (TMP/SMZ) for pneumocystis pneumonia (PCP) is limited with adverse events. Caspofungin, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, the availability of clinical data about caspofungin combined with TMP/SMZ in the treatment of PCP in HIV‐infected patients is limited. Thus, we aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first‐line therapy for moderate‐to‐severe PCP in HIV‐infected patients.

Methods

From January 2017 to December 2019, data of HIV‐infected patients with moderate‐to‐severe PCP who received either TMP/SMZ alone or caspofungin combined with TMP/SMZ as first‐line therapy were retrospectively reviewed to assess the effectiveness and safety of each regimen. The Kaplan–Meier curve and log‐rank test were used for survival analysis.

Results

A total of 278 patients met the criteria. The overall positive response rate of PCP treatment was 48.92%, and the overall all‐cause in‐hospital mortality rate was 33.09%. Patients who received combination therapy consisting of caspofungin and TMP/SMZ had a better positive response rate (59.44% vs. 37.78%, P < 0.001) and lower all‐cause in‐hospital mortality rate (24.48% vs. 42.22%, P = 0.003). Also, patients who received combination therapy had higher survival rate during a hospital stay (75.52% vs. 57.78%, P = 0.004), and those who received longer combination therapy were more likely to have higher survival rate (P = 0.042). We found that age (P = 0.019), CD4 cell count (P = 0.001) and therapeutic regimen (P = 0.002) were significant risk factors for all‐cause in‐hospital mortality rate in univariate analysis. In multivariate analysis, only CD4 cell count and therapeutic regimen were statistically significant factors associated with all‐cause in‐hospital mortality rate. Patients with a CD4 count of > 30 cells/µL and patients who received combination therapy consisting of caspofungin and TMP/SMZ were more likely to survive from PCP (P = 0.011 and P = 0.002, respectively). There were no additional severe adverse events caused by adding caspofungin.

Conclusions

For HIV‐infected patients with moderate‐to‐severe PCP, combination therapy with caspofungin and TMP/SMZ is an effective and promising first‐line therapy with no greater number of adverse events compared with TMP/SMZ monotherapy. Patients who received caspofungin had better positive response rates and lower all‐cause in‐hospital mortality rates. Also, we recommend early initiation of caspofungin.
Targeted dry skin treatment using a multifunctional topical moisturizer
Authors: Stettler Hans , Crowther Jonathan M. , Brandt Marianne , Lu Bailu , Boxshall Alison , de Salvo Raffaella , Laing Sabrina , Hennighausen Natascha , Bielfeldt Stephan , Blenkiron Peter
Published: December 2020

Objective

The development of dry skin is a complex process, with a wide variety of factors each playing different roles in its evolution. Given this, it is important when designing a formulation to tackle dry skin that these varied aspects of skin behaviour are addressed. Presented here are the results of a 3‐week moisturization study carried out on dry legs. A wide range of traditional and more recently developed biophysical measurement methods have been combined with visual assessment of skin condition to enable multiple aspects of skin function to be determined. The observed changes in the skin are discussed in terms of the ingredients used in the moisturizing formulation.

Methods

A range of novel and traditional skin assessment methods and techniques were used to assess the effects of an oil in water‐based moisturizing product compared to an untreated site during a 3‐week in vivo study on dry lower leg skin.

Results

Statistically significant improvements were observed in a range of skin parameters as a result of product usage. Skin hydration assessed using Corneometer®, Epsilon® and visual dry skin grading all increased after 3 weeks of use. Skin barrier function measured using transepidermal water loss also improved. Levels of cholesterol, free fatty acids and Ceramide NH increased, as well as the average length of the stratum corneum (SC) lipid lamella bilayers, and the ratio of lipid to protein increased (measured using Lipbarvis® and in vivo Confocal Raman Spectroscopy). Increases in the levels of Ceramide EOS and NP were also observed, along with an improvement in corneocyte maturity, although these were not statistically significant.

Conclusions

Using a variety of traditional and novel skin assessment techniques, a wide range of factors associated with the evolution of dry skin have been assessed upon treatment with a new topical moisturizer. Product usage resulted in significant improvements to skin hydration and barrier function, the levels and morphology of SC barrier lipids, and overall epidermal differentiation. As a result there was a significant reduction in the characteristics associated with the development of dry skin after use of the test product.
Morpho‐physiological, biochemical and isotopic response of tall wheatgrass populations to salt stress
Authors: Borrajo Celina I. , Sánchez‐Moreiras Adela M. , Reigosa Manuel J.
Published: December 2020

Tall wheatgrass [Elymus elongatus subsp. ponticus (Podp.) Melderis] is a C3 grass native from dry or saline habitats in SE Europe. The aim of this study was to better understand response mechanisms of populations from different origins to salinity and to provide new tools to select germoplasm with high salinity tolerance. Four populations (P3‐P4‐P5‐P9) were irrigated with five solutions of increasing salinity (Salt: 0–0.1–0.2–0.3–0.4 M NaCl) and evaluated in pots in a greenhouse. Two experiments were carried out, a short 40‐day long experiment with vegetative plants, and a longer 85‐day long one with plants that underwent vegetative‐reproductive stage. No evidence was found of an interaction between population and salt. Morpho‐physiological, biochemicals, isotopic and productive variables were differently affected by increasing salinity and were also different among populations. Proline, Na+ and Cl− consistently appeared to function as osmotic agents. P5 showed the highest biomass in the 85‐day experiment and had the highest leaf length, tiller density, water use efficiency and δ13C isotope; and the lowest Cl− concentration and evapotranspiration rate. However, P5 showed the lowest biomass in the 40‐day experiment, suggesting that duration of the stress is an important aspect to consider when selecting germoplasm for tolerance to salinity. Differences among populations in growth strategies and physiological mechanisms could be related to their origin environment.
A bundled phosphate control intervention (4Ds) for adults with end‐stage kidney disease receiving haemodialysis: A cluster randomized controlled trial
Authors: Milazi Molly , Douglas Clint , Bonner Ann
Published: December 2020

Aim

To evaluate the effectiveness of a bundled self‐management intervention (taking control of your phosphate with the 4Ds) to improve phosphate control among adults receiving haemodialysis.

Background

Hyperphosphataemia occurs in end‐stage kidney disease and is managed by diet, drinks, drugs (phosphate binder medication), and dialysis (the 4Ds). Adherence to the 4Ds is challenging for patients.

Design

A pragmatic cluster randomized controlled trial with repeated measures.

Methods

Participants were adults receiving haemodialysis with high serum phosphate (>1.6 mmol/L for at least 3 months) recruited between August 2017 ‐May 2018. Cluster randomization was according to haemodialysis treatment shifts. The ‘teach‐back’ intervention was designed to improve phosphate control. Expected outcomes were reduced serum phosphate and increased knowledge of phosphate in end‐stage kidney disease, self‐efficacy and adherence to diet, drugs, and dialysis.

Results

There were no differences between groups at baseline. Both groups had similar mean serum phosphate over time; at three months, 46% of the intervention group achieved reductions that met the target serum phosphate level compared with 33% of the control group. There were significant improvements in knowledge of phosphate in end‐stage kidney disease, self‐efficacy and adherence to diet, drugs, and dialysis (missing) in the intervention group compared with control group.

Conclusion

The 4Ds, a bundled self‐management intervention, was effective in improving patient confidence and adherence to phosphate control methods.

Impact

The 4Ds intervention bundles together four essential strategies for preventing and controlling hyperphosphataemia in end‐stage kidney disease.

Trial registration

ACTRN12617000703303 Registered 16/05/2017.
Clinical and histological comparison of the soft tissue morphology between zirconia and titanium dental implants under healthy and experimental mucositis conditions—A randomized controlled clinical trial
Authors: Bienz Stefan P. , Hilbe Monika , Hüsler Jürg , Thoma Daniel S. , Hämmerle Christoph H. F. , Jung Ronald E.
Published: December 2020

Objectives

To analyse the soft tissue morphology under healthy and experimental mucositis conditions comparing zirconia and titanium implants.

Methods

Forty‐two patients with two adjacent missing teeth received one zirconia (Zr) and one titanium (Ti) implant, with the mesial and distal position randomized. At 3 months, half of the patients were instructed to continue (healthy; h) and the other half to omit (experimental mucositis; m) oral hygiene around the implants for 3 weeks. Clinical parameters were evaluated before and after the experimental phase, and a soft tissue biopsy was harvested. Mixed model analyses were performed to analyse the data.

Results

The plaque control record increased significantly for the two mucositis groups, reaching 68.3 ± 31.9% (mean ±SD) for Zr‐m and 75.0 ± 29.4% for Ti‐m (p < .0001), being also significantly lower for Zr‐m than for Ti‐m. Bleeding on probing remained stable in group Zr‐m and amounted to 21.7 ± 23.6%, but increased significantly in group Ti‐m (p = .040), measuring 32.5 ± 27.8%. The number of inflammatory cells and the length of the junctional epithelium did not significantly differ between the groups.

Conclusion

Both implants rendered similar outcomes under healthy conditions. Lower plaque and bleeding scores were detected for zirconia implants under experimental mucositis conditions. Histologically, only minimal differences were observed.
Insectivory leads to functional convergence in a group of Neotropical rodents
Authors: Missagia Rafaela V. , Patterson Bruce D. , Krentzel Dallas , Perini Fernando A.
Published: December 2020

The mandible of vertebrates serves as insertion area for masticatory muscles that originate on the skull, and its functional properties are subject to selective forces related to trophic ecology. The efficiency of masticatory muscles can be measured as mechanical advantage on the mandible, which, in turn, has the property of correlating with bite force and shape. In the present work, we quantify the mechanical advantage of the mandible of akodontine rodents, which present a diverse radiation of insectivorous specialists, to assess their relationship to the estimated bite force and diet. We also tested the degree of morphofunctional convergence in response to insectivory on the group. We found the mechanical advantages to be convergent on insectivorous species, and associated with the estimated bite force, with higher mechanical advantages in species with a stronger bite and short, robust mandibles and lower mechanical advantages in insectivorous species with weaker bites and more elongated, dorso‐ventrally compressed mandibles. Insectivorous species of Akodontini are functional specialists for the consumption of live prey and may exploit the resources that shrews, moles and hedgehogs consume elsewhere.
Tray bleaching status and insights
Authors: Haywood Van B. , Sword Rhoda J.
Published: December 2020

Objective

To provide an update on tray bleaching for various tooth discoloration conditions, including a complete examination form as well as an information and consent form.

Clinical considerations

Since the bleaching process was first documented in 1989, it has become a safe, successful, and conservative treatment for consistently whitening the color of patients' natural teeth. Though initially used on a limited basis, the process has expanded to include bleaching nicotine and tetracycline stains, single dark teeth, brown spots, reducing white spots, caries control as well as color change from aging. Ten percent carbamide peroxide is the material most used in research and has shown to be the most effective with the least amount of adverse side effects, including sensitivity or gingival irritation. Bleaching overnight using a smooth nonscalloped, nonreservoir vacuum‐formed tray has been shown to be the method of choice for most clinicians, leading to greater patient compliance and an overall successful treatment. When possible, conservative bleaching treatment should be considered prior to more invasive, irreversible procedures such as veneers, or crowns to meet patients' esthetic requirements. Because of its basic pH, and potential for caries inhibition, complete restorative treatment does not have to be performed prior to initiating bleaching, making it an extremely flexible treatment.

Conclusion

With a thorough bleaching analysis, proper treatment of appropriate discolorations over an ideal timeframe, tray bleaching is a powerfully predictable tool in restorative dentistry.

Clinical significance

Tray bleaching with 10% carbamide peroxide should be the first consideration for treatment of discolorations of any type, with varying times of treatment, even in the presence of mild decay.
Novel atypical Aeromonas salmonicida bath challenge model for juvenile ballan wrasse (Labrus bergylta, Ascanius)
Authors: Papadopoulou Athina , Garvey Kathryn , Hill Tom , Ramirez‐Paredes Jose G. , Monaghan Sean J. , Baily Johanna L. , Davie Andrew , Katsiadaki Ioanna , Verner‐Jeffreys David , Wallis Timothy , Migaud Herve , Adams Alexandra
Published: December 2020

Atypical Aeromonas salmonicida (aAs) is currently one of the most routinely recovered bacterial pathogens isolated during disease outbreaks in farmed cleaner fish, ballan wrasse (Labrus bergylta, Ascanius). Vibrionaceae family bacteria have also been isolated from ballan wrasse in Scotland. This study determined the infectivity, pathogenicity and virulence of aAs and Vibrionaceae isolates in juvenile farmed ballan wrasse (n = 50; approx. 2 g) using a bath challenge, and fish were monitored for a period of 16 days. Atypical As caused significant mortalities in contrast to Vibrionaceae isolates. Notably, differential virulence was observed between two aAs vapA type V strains at similar challenge doses. Diseased fish exhibited a systemic infection where aAs was detected in all analysed tissues (liver, spleen and kidney) by PCR and qPCR. Macroscopically, moribund and survivor fish exhibited hepatomegaly and splenomegaly. In moribund and surviving fish, histopathology showed granulomatous hepatitis with eosinophilic granular cells surrounding bacterial colonies and endocarditis along with splenic histiocytosis. This is the first report of a successful aAs bath challenge model for juvenile ballan wrasse which provides an important tool for future studies on vaccine efficacy and immunocompetence.
Evaluation of quality changes in big‐eye tuna (Thunnus obesus) based on near‐infrared reflectance spectroscopy (NIRS) and low field nuclear magnetic resonance (LF‐NMR)
Authors: Lan Weiqing , Liu Jiali , Hu Xiaoyu , Xiao Lei , Sun Xiaohong , Xie Jing
Published: December 2020

The purpose of this study was to investigate the effect of temperature fluctuations on quality of big‐eye tuna (Thunnus obesus). In this work, different logistical processes, including cold chain (CK) and cold chain breaks (L1, L2), were simulated. Near‐infrared spectroscopy (NIRS) and low‐field nuclear magnetic resonance (LF‐NMR) were used for determination the quality changes. Meanwhile, water holding capacity (WHC), water activity (aw), sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), and scanning electron microscope (SEM) were measured. The results indicated that WHC dropped more than 20% in L2 group and the degradation rate of protein was accelerated with the increase of temperature for 216 hr. The curve of NIRS was showed the certain changing trends and its absorbance value showed a downward tendency, which had a decrease from 0.7 at 192 hr to CK > 0.4, L1 ≈ 0.4, L2 < 0.4 at 216 hr. The NIRS further exhibited the changing trend of freshness, which consistent with the results of WHC, SDS‐PAGE and SEM. LF‐NMR showed that immobilized water (T22) decreased while free water (T23) increased during processes. The results were coincidence with other indexes. Therefore, NIRS combined with LF‐NMR could effectively reflect the quality changes of big‐eye tuna during circulation.

Practical applications

Near‐infrared spectroscopy (NIRS) and Low‐field nuclear magnetic resonance (LF‐NMR) can be used to estimate the protein change and water migration of fish. This study indicated that NIRS and LF‐NMR could better characterize the quality change of big‐eye tuna during logistical processes. Moreover, this study provided a theory foundation for the application of NIRS and LF‐NMR on aquatic products.
Fetal teratogenicity in a rhesus macaque (Macaca mulatta): Association with the chronic maternal treatment of amitriptyline
Authors: Hunter Carissa E. , Stammen Rachelle L. , Hamlet Terell , Bonenberger Denise , Li Chunxia , Zhang Xiaodong , Stroud Fawn C. , Chan Anthony W. S.
Published: December 2020

Amitriptyline is a tricyclic antidepressant commonly prescribed in humans for pain and sleep disorders and in non‐human primates for self‐injurious behaviors. Here, we report a clinical case on the teratogenic effect of maternal‐fetal amitriptyline exposure.
Pimavanserin, a 5HT2A receptor inverse agonist, rapidly suppresses Aβ production and related pathology in a mouse model of Alzheimer’s disease
Authors: Yuede Carla M. , Wallace Clare E. , Davis Todd A. , Gardiner Woodrow D. , Hettinger Jane C. , Edwards Hannah M. , Hendrix Rachel D. , Doherty Brookelyn M. , Yuede Kayla M. , Burstein Ethan S. , Cirrito John R.
Published: December 2020

Amyloid‐β (Aβ) peptide aggregation into soluble oligomers and insoluble plaques is a precipitating event in the pathogenesis of Alzheimer's disease (AD). Given that synaptic activity can regulate Aβ generation, we postulated that 5HT2A‐Rs may regulate Aβ as well. We treated APP/PS1 transgenic mice with the selective 5HT2A inverse agonists M100907 or Pimavanserin systemically and measured brain interstitial fluid (ISF) Aβ levels in real‐time using in vivo microdialysis. Both compounds reduced ISF Aβ levels by almost 50% within hours, but had no effect on Aβ levels in 5HT2A‐R knock‐out mice. The Aβ‐lowering effects of Pimavanserin were blocked by extracellular‐regulated kinase (ERK) and NMDA receptor inhibitors. Chronic administration of Pimavanserin by subcutaneous osmotic pump to aged APP/PS1 mice significantly reduced CSF Aβ levels and Aβ pathology and improved cognitive function in these mice. Pimavanserin is FDA‐approved to treat Parkinson's disease psychosis, and also has been shown to reduce psychosis in a variety of other dementia subtypes including Alzheimer's disease. These data demonstrate that Pimavanserin may have disease‐modifying benefits in addition to its efficacy against neuropsychiatric symptoms of Alzheimer's disease.

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Read the Editorial Highlight for this article on page 560.