bluuebunny/crossref_metadata_2025 huggingface dataset:
Dimorphic autoantigenic and protective effects of Reg2 peptide in the treatment of diabetic β‐cell loss
Authors: Yu Luting , Li Xiang , Zhang Zhiyuan , Du Pei , Liu Jun‐Li , Li Youjie , Yin Tianqi , Yu Weihong , Sun Hao , Wang Min , Luo Chen
Published: January 2019

Aims

The potential effect of regenerating (Reg) proteins in the treatment of diabetes has been indicated in the past decade, but the clinical use of Reg proteins requires more advances in translational medicine. In the present study, we produced recombinant regenerating protein 2 (rReg2), to prove its protective effect against streptozocin (STZ)‐induced diabetes in BALB/c mice.

Materials and Methods

rReg2 was administrated in STZ‐induced diabetic mice. Blood glucose, body weight, serum insulin and islet β‐cell loss were determined. However, Reg2 has also been reported to serve as an autoantigen that induces autoimmune attacks on islets and aggravates diabetic development in non‐obese diabetic mice. To address this contradiction, complete Freund's adjuvant was injected to generate a model that was hypersensitive to Reg2. In this model, islet CD8 T‐cell infiltration, serum Reg2 antibody and interleukin (IL)‐4 and IL‐10, and splenic CD4+/interferon (IFN)‐γ+ T cells were determined.

Results

Direct rReg2 pretreatment preserved islet β‐cell mass against STZ and improved glycaemia, body weight and serum insulin content. The protection against cell death was further confirmed in cultured mouse islets and MIN6 cells. On the other hand, significant elevations of serum Reg2 antibody and splenic CD4+/IFN‐γ+ T cells, and decreases in serum IL‐4 and IL‐10 were detected in rReg2‐vaccinated mice, which may contribute to the accelerated diabetes. Interestingly, these mice, upon further rReg2 treatment, exhibited alleviated diabetic conditions with less islet CD8+ T‐cell infiltration.

Conclusion

rReg2 treatment ameliorated STZ‐induced diabetes in normal BALB/c mice. By contrast, rReg2 vaccination exacerbated, but further rReg2 treatment alleviated, the severity of STZ‐induced diabetes. Thus, the protective effect of rReg2 is predominant over the autoantigenic β‐cell destruction, supporting the potential of rReg2 in the clinical treatment of diabetes.
Tricuspid atresia with restrictive foramen ovale: A rare combination with implications on fetal growth
Authors: Tseng Stephanie Y. , Alsaied Tarek , Barnard Krystle , Hahn Eunice , Divanovic Allison A. , Cnota James F.
Published: January 2019

Restrictive atrial communication is rarely reported in tricuspid atresia but when present it can lead to important morbidity. We describe two fetuses with tricuspid atresia with restrictive foramen ovale who were found to have fetal growth failure. Fetal echocardiography detected a restrictive atrial communication by flow acceleration on color Doppler and significant right atrial dilation in one patient; the atrial septum was not well interrogated in the other patient. Restrictive foramen ovale in tricuspid atresia may be associated with fetal growth failure. Color Doppler interrogation of the atrial septum on fetal echocardiogram may help identify this condition prenatally.
The left ventricle in atrial septal defect: Looking through 3D glasses
Authors: Mohanty Sweta , Solomon Angel
Published: January 2019

Objectives

To identify left ventricular (LV) dyssynchrony and associated factors in atrial septal defect (ASD) patients, using real time three‐dimensional echocardiogram (RT3DE).

Background

Left ventricular dysfunction has been observed in ASD. Few studies have utilized RT3DE to assess LV wall‐motion abnormality in ASD.

Methods

Patients aged ≥1 year with ASD, with or without partial anomalous pulmonary venous drainage (PAPVD), were included over 1 year. Additional cardiac defects or abnormalities independently affecting LV function were excluded. 2DE and RT3DE‐derived LV function data were recorded. Student's t test and Pearson's correlation were used for analysis.

Results

Of 104 patients (69 females) aged 1–57 years, ostium secundum ASD was present in 97 and sinus venosus ASD in 7. Maximum excursion increased significantly with age, weight, and body surface area (P < 0.001). Majority of children (58%) aged 3–5 years showed no delay in segmental excursion. Lateral wall excursional delay was greater beyond 5 years or with weight > 15 kg (42% as compared to 20% in <15 kg). In patients weighing < 15 kg, time to minimum systolic volume (Tmsv 16‐SD) was higher with PAPVD and with indexed defect size > 40 mm/m2, though not statistically significant. As compared to EF estimation by 2DE, EF derived using RT3DE was significantly lower (P < 0.001).

Conclusion

Left ventricular dyssynchrony is least between 3 and 5 years. Beyond 5 years, delayed lateral wall excursion is seen. With an indexed defect size exceeding 40 mm/m2, and in the presence of PAPVD, time to minimum systolic volume is higher.
Perceived stress mediates the relationship between social adaptation and quality of life in individuals at ultra high risk of psychosis
Authors: Ortega Laura , Montalvo Itziar , Monseny Rosa , Vilella Elisabet , Labad Javier
Published: January 2019

Aim

Quality of life (QoL) and social functioning have emerged as good predictors of the outcome of psychotic disorders. Poor QoL and social functioning are usually present before the onset of the first episode of psychosis. Our study aimed to explore the relationship between social adaptation and QoL in young people at risk of psychosis (ultra‐high‐risk, UHR) and healthy controls (HCs), and to investigate potential mediating effects of stress measures (perceived stress, stressful life events).

Methods

The study included 55 UHR subjects and 40 HC. Social functioning was assessed with the Social Adaptation Self‐evaluation Scale (SASS). Stress measures included the assessment of stressful life events and perceived stress. We compared stress and QoL measures between UHR and HC, and also compared UHR with low or normal social adaptation. A mediation analysis was performed to explore whether stress measures mediated the relationship between social adaptation and QoL.

Results

UHR were less frequently employed and reported more stress, poorer QoL and lower social adaptation than HC. QoL and social adaptation were associated with stress measures. UHR with low social adaptation reported more perceived stress and less QoL than UHR with normal social adaptation and HC. Perceived stress mediated the relationship between social adaptation and QoL.

Conclusions

Social adaptation is less developed in UHR subjects than in healthy subjects and has a negative impact on quality of life. This association is mediated by perceived stress.
Relationship between fish assemblage and angler catch in the Sulejów Reservoir, central Poland, in the context of a warming climate
Authors: Kaczkowski Zbigniew , Frankiewicz Piotr , Góralczyk Aleksander
Published: January 2019

The Pilica River has warmed at a rate of 0.06°C per year since 1969, threatening the ecological services provided by the Sulejów Reservoir. Gillnet sampling revealed that the reservoir is inhabited by a cyprinid‐dominated fish assemblage with roach, Rutilus rutilus (L.) (42% of the total biomass), the dominant species. However, the interest of the anglers was primarily focused on common bream, Abramis brama (L.) (almost 65% of the catch), as revealed by the catch statistics (2004–2014). No direct evidence was found that the temperature increase had an influence on the recreational fishery or fish assemblage structure. On the other hand, changes in the fish assemblage that were reflected in angler catch composition were observed. A decrease in the catch of common bream in gillnets was accompanied by a shift in angler choices towards roach and other fish species. The sustainability of recreational fisheries is more likely to be influenced by changes in the economic status of society, water quality (toxic cyanobacteria blooms) and water management practices in Poland. The question arises about which species will dominate in the impoundment in the future if the warming trend continues and common carp, Cyprinus carpio L., stocking is maintained.
Sports participation and physical activity in adult Dutch and Swedish patients with severe haemophilia: A comparison between intermediate‐ and high‐dose prophylaxis
Authors: Versloot Olav , Berntorp Erik , Petrini Pia , Ljung Rolf , Astermark Jan , Holmström Margareta , de Kleijn Piet , Fischer Kathelijn
Published: January 2019

Introduction

Differences in treatment and outcome have been reported for persons with haemophilia (PWH) on intermediate‐dose (Dutch) and high‐dose (Swedish) prophylaxis, but the potential influence of sports participation has not been considered.

Aim

To compare sports participation and clinical outcome between adult Dutch and Swedish PWH.

Methods

Self‐reported sports participation (type and frequency per week), physical functioning (SF‐36PF: 100‐0), joint status (HJHS: 0‐144), perceived limitations (HALsum: 100‐0) and physical activity (IPAQ) were recorded. Sports were classified according to National Haemophilia Foundation classification (5 categories, highest two were classified as high‐risk sports). Sports participation and clinical outcome were compared according to country and age (18‐22, 23‐29, 30‐40 years) using non‐parametric tests and Spearman correlations (rho).

Results

Seventy‐one adult PWH (NL: 43, SWE: 28) completed sports questionnaires (mean age: 26 years). All participants engaged in sports, including 59.2% in high‐risk sports (33.9% twice weekly). Dutch PWH showed a significant age‐related decline in (high‐risk) sports participation (7x/wk in PWH 18‐22 years to 2x/wk in PWH 30‐40 years, P < 0.05), joint health (HJHS: median 2‐15.5, P < 0.01) and physical functioning (SF‐36PF: median 100 to 77.5, P < 0.01), while Swedish did not. Sports participation was not associated with bleeding (Spearman's rho = −0.119).

Conclusion

All participants reported sports participation, including 59.2% in high‐risk sports. Dutch PWH treated with intermediate‐dose prophylaxis showed an age‐related decline in sports participation, joint status and physical functioning, whereas Swedish PWH on high‐dose prophylaxis did not. Sports participation was not associated with bleeding.
Invasive cervical cancer in HIV‐infected women: risk and survival relative to those of the general population in France. Results from the French Hospital Database on HIV (FHDH)–Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS) CO4 cohort study
Authors: Grabar S. , Hleyhel M. , Belot A. , Bouvier A.‐M. , Tattevin P. , Pacanowski J. , Genet P. , Pradier C. , Salmon D. , Simon A. , Pourcher V. , Spano J.‐P. , Poizot‐Martin I. , Costagliola D.
Published: January 2019

Objectives

We examined trends in the incidence rates of invasive cervical cancer (ICC) and in the rate of survival after ICC among women living with HIV (WLHIV) in France and compared them to those of the general population.

Methods

Histologically validated incident cases of ICC in the period 1992–2009 from the French Hospital Database on HIV (FHDH‐ANRS CO4) were included in the study. Age‐standardized incidence rates were estimated for FHDH and the general population in France for 1992–1996 [pre‐combination antiretroviral therapy (cART) period], 1997–2000 (early cART period), 2001–2004 (intermediate cART period), and 2005–2009 (late cART period). Age‐standardized incidence ratios (SIRs) were calculated. Five‐year survival was compared with that of the general population for ICC diagnosed in 2005–2009 after standardization for age.

Results

Among 28 977 WLHIV, 60 incident ICCs were histologically validated. There was a nonsignificant decreasing trend for the incidence across the cART periods (P = 0.07), from 60 to 36/100 000 person‐years. The risk of ICC was consistently significantly higher in WLHIV than in the general population; the SIR was 5.4 [95% confidence interval (CI) 3.0–8.9] during the pre‐cART period and 3.3 (95% CI 2.2–4.7) in 2005–2009. Survival after ICC did not improve across periods (log‐rank P = 0.14), with overall estimated 5‐year survival of 78% (95% CI 0.67–0.89%). Five‐year survival was similar for WLHIV and the general population for women diagnosed with ICC in 2005–2009, after standardization (P = 0.45).

Conclusions

ICC risk is still more than three times higher in WLHIV than in the general population. Survival after ICC did not improve over time and was similar to that of the general population during the most recent period. Such results call for promotion of the uptake of screening in WLHIV.
HIV coinfection among persons diagnosed with hepatitis B in England in 2008–2014
Authors: Ireland G , Simmons R , Balogun K , Kirwan P , Sabin CA , Ramsay M , Delpech V , Mandal S
Published: January 2019

Objectives

The aim of the study was to estimate HIV prevalence among persons with hepatitis B virus (HBV) infection in England and to examine associated risk factors.

Methods

Persons aged ≥ 15 years with an HBV surface antigen (HBsAg) test reported to Public Health England (PHE) sentinel surveillance during 2008–2014 were linked to the PHE national HIV/AIDS database. Coinfection was defined as an HIV diagnosis prior to, or within 6 months following, a positive HBsAg test.

Results

During 2008–2014, 2 149 933 persons were tested for HBsAg and 3.9% (1129 of 28 789) of HBsAg‐positive persons were HIV positive. The probable route of HIV infection was heterosexual exposure for 95.3% of female patients and 32.3% of male patients, with 61.5% of male patients reporting sex between men. Among African‐born coinfected persons, 84% probably acquired HIV there. Predictors of HIV positivity included older age [adjusted odds ratio (aOR) 1.1] and being of black ethnicity (aOR 15.5 for males; aOR 16.4 for females) or being male and of white ethnicity (aOR 8.2) compared with being female and of white ethnicity. HIV coinfection was more likely when HBV was diagnosed in sexual health (aOR 55.0), specialist liver (aOR 6.7), emergency department (aOR 5.3) and renal services (aOR 2.8) compared with general practice. Most (60.4%; 682 of 1129) coinfected persons were diagnosed with HIV infection > 6 months before HBV diagnosis.

Conclusions

Persons testing positive for HBsAg had a low HIV infection rate and fell largely into two groups: those of black ethnicity with probable Africa‐acquired infections and white men who have sex with men (MSM) with probable UK‐acquired infections. Findings reinforce existing recommendations to sustain and improve both HBV testing of migrants from HBV‐prevalent countries and vaccination among HIV‐positive MSM. Findings also support blood‐borne virus testing in sexual health services and emergency departments.
MARKETS, EXTERNALITIES, AND THE DYNAMIC GAINS OF OPENNESS
Authors: Monge‐Naranjo Alexander
Published: January 2019

Inflows of foreign knowledge are key for developing countries to catch up with the world technology frontier. I construct a model to analyze the entry decisions of foreign firms and the incentives of domestic firms to invest in their own know‐how, given the exposure to foreign ideas and competition. The model embeds two diffusion mechanisms typically considered separately in the literature: externalities and markets. I find that openness allows developing countries to fully catch up only when market transactions dominate the diffusion of ideas. Externalities are never enough to catch up and may lead to losses in income and welfare.
MISMATCH IN HUMAN CAPITAL ACCUMULATION
Authors: Cooper Russell , Liu Huacong
Published: January 2019

This article studies the allocation of heterogeneous agents to levels of educational attainment. The goal is to understand the magnitudes and sources of mismatch in this assignment, both in theory and in the data. The article presents evidence of substantial mismatch between ability and educational attainment across 21 OECD countries, with a main focus on Germany, Italy, Japan, and the United States. Model parameters are estimated using a simulated method of moments approach. The main empirical finding is that measured mismatch arises largely from noise in test scores and does not reflect borrowing constraints. Taste shocks play a minor role in explaining mismatch.
Biggest decision of them all – death and assisted dying: capacity assessments and undue influence screening
Authors: Peisah Carmelle , Sheahan Linda , White Ben P.
Published: January 2019

Arguably, deciding the timing and manner of one’s death is the biggest decision of all. With the Victorian Voluntary Assisted Dying Act 2017 commencing in 2019, assessing capacity to choose Voluntary Assisted Dying (VAD) becomes a critical issue for clinicians in Victoria, and elsewhere with on‐going efforts to change the law across Australia and in New Zealand. We consider how capacity assessment and undue influence screening can be approached for VAD, the role and risks of supported decision‐making, and argue for the importance of training to ensure health care professionals are educated about their role.
Exploring family activities and child engagement: A study on children with a significant cognitive and motor developmental delay
Authors: Van keer Ines , Van Leeuwen Karla , Maes Bea
Published: January 2019

Background

Everyday activities are an important setting for stimulating child functioning, but are understudied in young children with a significant cognitive and motor developmental delay. Therefore, we aim to characterize their family activities in terms of diversity, frequency, child engagement and family member's presence, compared to typically developing children.

Methods

By asking a parent to fill out an adapted version of the Child Participation in Family Activities questionnaire, the activity pattern of 49 children within the study group and 45 children within the control group were assessed and compared.

Results

Children in the study group generally experience less diverse activities (with an additional lower frequency of out‐of‐home activities) and show lower engagement levels compared to typically developing children.

Conclusions

Incorporating high levels of personal interaction, highly stimulating activities and adapted leisure activities into the daily activity pattern of children with multiple disabilities might be a pathway to increased engagement levels.
Effects of sodium intake on postural lightheadedness: Results from the DASH‐sodium trial
Authors: Peng Allison W. , Appel Lawrence J. , Mueller Noel T. , Tang Olive , Miller Edgar R. , Juraschek Stephen P.
Published: January 2019

Lightheadedness after standing contributes to adverse clinical events, including falls. Recommendations for higher sodium intake to treat postural lightheadedness have not been evaluated in a trial setting. The Dietary Approaches to Stop Hypertension (DASH)‐Sodium trial (1998‐1999) tested the effects of the DASH diet and sodium reduction on blood pressure (BP). Participants were randomly assigned to DASH or a typical Western diet (control). During either diet, participants ate three sodium levels (50, 100, 150 meq/d at 2100 kcal) in random order for 30‐days, separated by 5‐day breaks. Participants reported the presence and severity of postural lightheadedness at baseline and after each feeding period. There were 412 participants (mean age 48 years; 57% women; 57% black). Mean baseline SBP/DBP was 135/86 mm Hg; 9.5% reported baseline lightheadedness. Among those consuming the DASH diet, high vs low sodium increased lightheadedness (OR 1.71; 95% CI: 1.01, 2.90; P = 0.047) and severity of lightheadedness (P = 0.02), but did not affect lightheadedness in those consuming the control diet (OR 0.77; 95% CI: 0.46, 1.29; P = 0.32). Among those consuming high vs low sodium in the context of the DASH diet, adults <60 vs ≥60 years old experienced more lightheadedness (P‐interaction = 0.04), along with obese vs non‐obese adults (P‐interaction = 0.01). In the context of the DASH diet, higher sodium intake was associated with more frequent and severe lightheadedness. These findings challenge traditional recommendations to increase sodium intake to prevent lightheadedness.
Evolution and assessment of colour patterns in stream‐resident and anadromous male threespine sticklebackGasterosteus aculeatusfrom three regions
Authors: Stuckert Adam M. M. , Drury Sara , Anderson Christopher M. , Bowling Tyler B. T. , Mckinnon Jeffrey S.
Published: January 2019

We compared the colour patterns of free swimming, reproductively active male threespine sticklebackGasterosteus aculeatusof the anadromous and stream ecotypes from three geographically distinct regions. Consistent with the hypothesis of environmentally mediated selection, our results indicate ecologically replicated differences inG. aculeatuscoloration between anadromous and stream‐resident populations, and thatG. aculeatusprobably have the visual acuity to discriminate colour pattern differences between anadromous and stream‐resident fish.
Technological properties of durum wheat semolina treated by heating and UV irradiation for reduction of mycotoxin content
Authors: Shanakhat Hina , Sorrentino Angela , Raiola Assunta , Reverberi Massimo , Salustri Manuel , Masi Paolo , Cavella Silvana
Published: January 2019

Physical methods, such as heating and irradiation with ultraviolet light (UVC), are among the strategies that may be used to reduce mycotoxin content in foodstuffs. This research studied the technological effects of heating at 100, 150, and 200 °C and UVC irradiation at 254 nm for 15, 30, 60, and 120 min applied on semolina to decrease the amount of mycotoxins. The impact of the most efficient treatments (150 °C for 30 min and UVC irradiation for 120 min) was evaluated both on semolina and dough technological properties, such as color, hydration, and gluten indices, farinograph and calorimetric parameters, and microstructure. Thermal treatment significantly increased hydration of semolina and swelling power; farinograph analyses revealed a marked increase in water absorption and dough development time and a reduction of dough stability and degree of softening and elasticity compared to the control. Calorimetric analyses showed a significant reduction in both temperature peaks and enthalpy of starch gelatinization and a decrease in enthalpy for melting of lipids with starch. Scanning electron micrograph images representing the dough microstructure confirmed the occurrence of these changes; UVC‐treated samples showed less pronounced changes compared to the control.

Practical applications

This work reports some strategies that could be integrated in semolina‐based products chains, with the aim of reducing mycotoxin contamination. Thermal treatment and UVC irradiation are known to be cost‐effective techniques, combining a high thermal efficiency with the simplicity of application. Understanding the technological changes resulting from these treatments could be useful to food companies for the realization of safer semolina‐based products with different structural properties. This is the first study aiming to investigate the technological impacts of physical processing methods for reducing mycotoxin contamination.
A scale‐up process for the manufacture of reduced‐cholesterol butter using beta‐cyclodextrin
Authors: Alonso Leocadio , Calvo María V. , Fontecha Javier
Published: January 2019

This article describes a scale‐up process for manufacturing butter with reduced free cholesterol via the treatment of raw milk with beta‐cyclodextrin (β‐CD) at 4°C. The β‐CD–cholesterol complexes formed were eliminated using a centrifugal separator. Once pasteurized, the cream obtained was used to manufacture butter with >90% less cholesterol than present in the initial milk fat. No significant differences were seen between this reduced‐cholesterol butter and control butter in terms of their fat, protein, lactose, or total solid contents. Neither was any differences recorded in their sensorial or organoleptic qualities.

Practical applications

This article describes an industrial scale‐up process for the manufacture of reduced‐cholesterol butter (reduction >90%) from raw cow's milk. The results have application in the food industry, especially in the production of dairy products. The butter produced could be of benefit to persons who need to control their intake of cholesterol, particularly those with hypercholesterolemia.
Sofosbuvir‐based direct acting antiviral therapies for patients with hepatitis C virus genotype 2 infection
Authors: Liu Chen‐Hua , Su Tung‐Hung , Liu Chun‐Jen , Hong Chun‐Ming , Yang Hung‐Chih , Tseng Tai‐Chung , Chen Pei‐Jer , Chen Ding‐Shinn , Kao Jia‐Horng
Published: January 2019

Background and Aim

Data regarding the comparative effectiveness and safety of sofosbuvir (SOF) in combination with ribavirin (RBV), daclatasvir (DCV), or ledipasvir (LDV) for hepatitis C virus genotype 2 (HCV‐2) patients were limited. We aimed to evaluate the performance of these regimens in Taiwan.

Methods

One hundred eighty‐seven HCV‐2 patients with compensated liver diseases receiving SOF in combination with RBV (n = 82), DCV (n = 66), or LDV (n = 39) for 12 weeks were retrospectively enrolled. The effectiveness was determined by sustained virologic response 12 weeks off therapy (SVR12). The patient characteristics potentially related to SVR12 were compared. The safety profiles and laboratory abnormalities were assessed.

Results

The SVR12 rates were 93.9% (95% confidence interval [CI]: 86.5–97.4%), 98.5% (95% CI: 91.9–99.7%), and 100% (95% CI: 91.0–100%) in patients receiving SOF combined with RBV, DCV, and LDV, respectively. All patients tolerated treatment well. The stratified SVR12 rates were comparable regardless of baseline characteristics or week 4 viral decline among these regimens. Six (3.2%) patients had serious adverse events which were not related to treatment. The rates of fatigue, pruritus, and anemia tended to be higher in patients receiving RBV (22.0%, 19.5%, and 8.5%) combination than those receiving DCV (10.6%, 6.1%, and 1.5%) or LDV (10.3%, 5.1%, and 0%) combination.

Conclusions

Sofosbuvir in combination with RBV, DCV, or LDV for 12 weeks is effective and well‐tolerated for HCV‐2 patients. Compared with DCV or LDV combination, the risks of fatigue, pruritus, and anemia are higher in patients receiving RBV combination.
An Assessment of Oral Health Training Among Geriatric Fellowship Programs: A National Survey
Authors: Thompson Lisa , Jiang Tien , Savageau Judith A. , Silk Hugh , Riedy Christine A.
Published: January 2019

Oral health (OH) has profound effects on the overall health of elderly people. While oral disease is prevalent in the geriatric population and access to care is a major issue, it is unclear the extent of OH training among US geriatric fellowship programs. A 19‐item electronic survey was sent to all 148 accredited geriatric fellowship training programs via the Association of Directors of Geriatric Medicine. Directors were asked about hours of trainings, barriers, and evaluation of trainees among other topics. Univariate and bivariate analyses were performed. Seventy‐five directors completed the survey (51% response rate). Sixty‐three percent (46/73) report their fellows receive 1 to 2 hours of OH instruction (ie, lectures, workshops) during their training. Almost a quarter (23%; 17/73) reported 0 hours of OH content. Only 17% (13/75) have clinical experiences in a dental setting. Barriers to more OH education include competing priorities or lack of time (57%; 43/75), lack of faculty expertise (55%; 41/75), and no clear geriatric national educational competencies (44%; 33/75). Programs with an OH champion or dental school/residency affiliation had more hours of OH instruction. Geriatric fellowships appear to need more OH training, which could be achieved by creating OH champions and connecting fellowships with dental schools/residencies. Barriers could be overcome by exposing fellowships to existing resources and creating national competencies. J Am Geriatr Soc 67:1079–1084, 2019.
Tricyclic Antidepressant and/or γ‐Aminobutyric Acid–Analog Use Is Associated With Fall Risk in Diabetic Peripheral Neuropathy
Authors: Randolph Amanda C. , Lin Yu‐Li , Volpi Elena , Kuo Yong‐Fang
Published: January 2019

BACKGROUND/OBJECTIVES

Peripheral neuropathy is a common diabetes complication that can increase fall risk. Regarding fall risk, the impact of pain management using tricyclic antidepressants (TCAs) or γ‐aminobutyric acid (GABA) analogs is unclear because these medications can also cause falls. This study investigates the impact of these drugs on fall and fracture risk in older diabetic peripheral neuropathy (DPN) patients.

DESIGN

Historical cohort study with 1‐to‐1 propensity matching of TCA/GABA‐analog users and nonusers.

SETTING

Nationally representative 5% Medicare sample between the years 2008 and 2010.

PARTICIPANTS

After applying all selection criteria, 5,550 patients with prescription and 22,200 patients without prescription of TCAs/GABA‐analogs were identified. Both patient groups were then stratified for fall history and matched based on propensity of receiving TCAs/GABA‐analogs within each group.

MEASUREMENTS

Patients were followed until the first incidence of fall or the first incidence of fracture during the follow‐up period (for up to 5 years).

RESULTS

After matching, users and nonusers were largely similar. After covariate adjustment, TCA/GABA‐analog use was associated with a statistically significant increase in fall risk (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 1.03‐1.20), but was not associated with fracture risk (adjusted HR = 1.09; 95% CI = 0.99‐1.19) in the conventional analysis. Treating TCA/GABA‐analog use as a time‐dependent covariate resulted in statistically significant associations of TCA/GABA‐analog use with both fall and fracture risk (HR = 1.26 [95% CI = 1.17‐1.36]; and HR = 1.12 [95% CI = 1.02‐1.24], respectively).

CONCLUSION

Among older patients with DPN, GABA‐analogs or TCAs increase fall risk and possibly fracture risk. Use of these medications is therefore a potentially modifiable risk factor for falls and fractures in this population.
AGS Report on Engagement Related to the NIH Inclusion Across the Lifespan Policy
Authors: Vaughan Camille P. , Dale William , Allore Heather G. , Binder Ellen F. , Boyd Cynthia M. , Bynum Julie P.W. , Gurwitz Jerry H. , Lundebjerg Nancy E. , Trucil Daniel E. , Supiano Mark A. , Colón‐Emeric Cathleen
Published: January 2019

After passage of the 21st Century Cures Act, the National Institutes of Health held a workshop in 2017 to consider expanding its inclusion policy to encompass individuals of all ages. American Geriatrics Society (AGS) leaders and members participated in the workshop and formal feedback period. AGS advocacy clearly impacted the resulting workshop report and Inclusion Across the Lifespan policy that eliminates upper‐age limits for research participation unless risk justified and changes the language used to describe older adults and other vulnerable groups. AGS recommendations that were not specifically stated in the updated policy were to encourage active recruitment of older adults, add standard measures of function and/or frailty, and change review criteria to ensure the health status of a study population mirrors typical clinical populations. The updated inclusion policy ultimately offers academic geriatrics programs the opportunities to expand knowledge about health in aging and to continue to provide leadership for research and advocacy efforts on behalf of older adults. J Am Geriatr Soc 67:211–217, 2019.
Safety concerns with human papilloma virus immunization in Japan: Analysis and evaluation of Nagoya City's surveillance data for adverse events
Authors: Yaju Yukari , Tsubaki Hiroe
Published: January 2019

Aim

To assess the safety of human papilloma virus (HPV) vaccines by using data from the “Nagoya City Cervical Cancer Immunization Program Survey”.

Methods

Unadjusted odds ratios (OR) were calculated between HPV‐vaccinated cases and un‐vaccinated controls. Age‐stratified analyses were performed to evaluate the interaction between age and events. Adjusted ORs were also estimated with multiple logistic regression models.

Results

In the 15–16‐year‐old group, the unadjusted ORs were significantly higher for symptoms of memory impairment, dyscalculia, and involuntary movement. The age‐adjusted multivariate analyses demonstrated that the vaccinated cases were less likely than the unvaccinated controls to have experienced symptoms in almost all symptoms, except for two symptoms such as involuntary movement and weakness. However, study period‐adjusted multivariate analyses demonstrated that the vaccinated cases were significantly more likely than un‐vaccinated controls to have experienced symptoms of memory impairment and involuntary movement.

Conclusions

Based on our analysis using data from the Nagoya City surveillance survey, a possible association between HPV vaccination and distinct symptoms such as cognitive impairment or movement disorders exists. A consistent causal relationship between HPV vaccination and these symptoms remains uncertain. However, given the seriousness of symptoms, we believe that a more comprehensive and large‐scale study is essential to confirm the safety of HPV vaccination.
Effects of an Online Mindfulness Intervention Focusing on Attention Monitoring and Acceptance in Pregnant Women: A Randomized Controlled Trial
Authors: Yang Mengye , Jia Ge , Sun Shiwen , Ye Cuiwei , Zhang Rong , Yu Xiaoyan
Published: January 2019

Introduction

Attention monitoring and acceptance underlie the effects of mindfulness meditation. This study tested the feasibility and acceptability of an online mindfulness intervention for pregnant women as an approach to reduce depressive and anxious symptoms.

Method

We developed an 8‐week mindfulness intervention program that trained participants to monitor their internal and external experiences in an accepting way. The mindfulness course was based on the Wechat platform. This study was conducted in a women's hospital in China. A total of 123 women with scores on the Generalized Anxiety Disorder Scale and Patient Health Questionnaire suggesting mild or moderate symptoms of depression and anxiety were recruited from the outpatient department between April and June 2018. The participants were randomized to receive the mindfulness intervention or routine prenatal care. The Generalized Anxiety Disorder Scale, the Patient Health Questionnaire, and the Five Facets of Mindfulness Questionnaire were used to evaluate the levels of anxiety, depression, and mindfulness, respectively, before and after the intervention.

Results

Of the 123 women enrolled in this study, 10 in the intervention group and 11 in the control group did not complete the intervention. The retention rate and feedback suggested that the mindfulness intervention was feasible and acceptable among pregnant women. Participants in the intervention group showed greater declines in depressive and anxious symptoms compared with those in the control group, as well a significant improvement in mindfulness skills (eg, attention monitoring and acceptance).

Discussion

These results suggest that an online mindfulness intervention may be a promising technique to help women use mindfulness skills to reduce depressive and anxious symptoms. The mindfulness intervention could constitute part of the psychological care provided to pregnant women.
SURVEY OF ECONOMIC IMPLICATIONS OF MARITIME AND TERRITORIAL DISPUTES
Authors: Mendoza Ronald Umali , Siriban Charles , Ty Tea Jalin
Published: January 2019

Drawing on studies on the economics of conflict, this paper reviews the literature on maritime and territorial disputes; and it examines an array of economic implications associated with territorial and maritime disputes. These include adverse effects on certain economic and development outcomes arising from possible armed confrontation, with some of these possibly lingering in the aftermath of conflict. There are also various economic disruptions and costs associated with these disputes, emphasizing how they also affect the livelihoods of resource users in the disputed areas. A clearer understanding of these economic links could help inform and motivate policymakers on mitigating the risks of conflict. Based on the review of evidence herein, the economic implications of conflict in terms of foregone average trade among the country pairs considered in the West Philippine Sea/South China Sea (in 1985 dollars) – which differ in important ways but hint at some common channels of impact – could range from US$ 909.3 million to US$ 98.8 billion. More broadly, the impacts on a disrupted global production chain can easily amplify these results even further, affecting global growth prospects for many decades, according to experience.
Can levamisole upregulate the equine cell‐mediated macrophage (M1) dendritic cell (DC1) T‐helper 1 (CD4 Th1) T‐cytotoxic (CD8) immune response in vitro?
Authors: Witonsky Sharon , Buechner‐Maxwell Virginia , Santonastasto Amy , Pleasant Robert , Werre Stephen , Wagner Bettina , Ellison Siobhan , Lindsay David
Published: January 2019

Background

Equine protozoal myeloencephalitis (EPM) is a common and devastating neurologic disease of horses in the United States. Because some EPM‐affected horses have decreased immune responses, immunomodulators such as levamisole have been proposed as supplemental treatments. However, little is known about levamisole's effects or its mechanism of action in horses.

Objective

Levamisole in combination with another mitogen will stimulate a macrophage 1 (M1), dendritic cell 1 (DC1), T‐helper 1 (CD4 Th1), and T‐cytotoxic (CD8) immune response in equine peripheral blood mononuclear cells (PBMCs) in vitro as compared to mitogen alone.

Animals

Ten neurologically normal adult horses serologically negative for Sarcocystis neurona.

Methods

Prospective study. Optimal conditions for levamisole were determined based on cellular proliferation. Peripheral blood mononuclear cells were then cultured using optimal conditions of mitogen and levamisole to identify the immune phenotype, based on subset‐specific activation markers, intracellular cytokine production, and cytokine concentrations in cell supernatants. Subset‐specific proliferation was determined using a vital stain.

Results

Concanavalin A (conA) with levamisole, but not levamisole alone, resulted in a significant decrease (P < .05) in PBMC proliferation compared to conA alone. Levamisole alone did not elicit a specific immune phenotype different than that induced by conA.

Conclusion and Clinical Importance

Levamisole co‐cultured with conA significantly attenuated the PBMC proliferative response as compared with conA. If the mechanisms by which levamisole modulates the immune phenotype can be further defined, levamisole may have potential use in the treatment of inflammatory diseases.
Classifications and misclassification in cholangiocarcinoma
Authors: Cardinale Vincenzo
Published: January 2019

See Article on Page 316
Herbal‐induced liver injury: The price to pay for a healthier life?
Authors: Andrade Raúl J.
Published: January 2019

See Article on Page 389
Effects of combined aerobic and resistance training in patients with heart failure: A meta‐analysis of randomized, controlled trials
Authors: Wang ZeQuan , Peng Xin , Li Kun , Wu Chiung‐Jung Jo
Published: January 2019

Cardiac rehabilitation programs consisting of core features of exercise training for patients with heart failure have demonstrated a wide range of physical and psychological benefits. In study, a meta‐analysis of combined aerobic and resistance training was conducted on various outcomes in patients with heart failure. Database searches included EMBASE, PubMed, Medline, Cochrane Library, Web of Science, OVID, and CINAHL. Only randomized, controlled trials were included. Review Manager 5.3 software was used to perform the meta‐analysis. In total, 12 studies and 516 patients were included. The results demonstrated that combined aerobic and resistance training is effective in promoting exercise capacity, muscle strength, and 6 min walk distance. Furthermore, combined training significantly improves the quality of life of patients with heart failure. However, there was no significant difference found for outcomes of depression and sleep. Future studies with rigorous methodological designs and long‐term follow ups are recommended to evaluate the sustainable benefits of combined aerobic and resistance intervention programs.
Long‐term efficacy of photodynamic therapy with methyl aminolevulinate in treating Bowen's disease in clinical practice: A retrospective cohort study (2006‐2017)
Authors: Aguilar‐Bernier Miguel , Rodríguez‐Barón Diego , Rivas‐Ruiz Francisco , Segura‐Palacios Juan Manuel , de Troya Martín Magdalena
Published: January 2019

Background

Photodynamic treatment with methyl aminolevulinate (MAL‐PDT) is considered an effective and highly recommended treatment for Bowen's disease. However, its long‐term efficacy remains to be established, as significant differences have been reported in this respect.

Objective

The aim of the present study was to describe the results of a retrospective analysis of patients with Bowen's disease treated with MAL‐PDT during the period 2006‐17 at the Costa del Sol Hospital (Marbella, Spain).

Material and Methods

This study is based on a retrospective descriptive analysis of the clinical records of patients treated with MAL‐PDT from June 2006 to September 2017. The analysis was based on calculating the mean and standard deviation values for the quantitative variables, and frequency distributions for the qualitative ones. The survival curves were plotted by the Kaplan‐Meier method, and the log‐rank test was used to assess differences in survival between groups. A cox regression analysis was performed to clarify the significant prognostic factors.

Results

A total of 537 tumours with histologically confirmed Bowen's disease were treated with MAL‐PDT. Recurrence‐free survival at one year was 88%, and at 5 years, 71%. Tumour size >300 mm2 (≥21 mm in diameter P = 0.019), its location in the upper extremities (P = 0.029) and patient's age <70 years (P = 0.028) were all associated with an increased risk of recurrence.

Limitations

Given the retrospective design of our study, the possible existence of information bias cannot be ruled out.

Conclusions

Although it is an appropriate treatment option for patients with Bowen's disease, MAL‐PDT presents a risk of recurrence of almost 30% at 5 years. Larger lesions (>300 mm2; ≥21 mm in diameter) are more likely to recur than smaller ones. Therefore, appropriate selection is needed of the tumour to be treated, and prolonged follow‐up should be provided.
Phytotoxic potential of Senna occidentalis (L.) Link extracts on seed germination and oxidative stress of Ipê seedlings
Authors: da Silva Í. F. , Vieira E. A.
Published: January 2019

Senna occidentalis is an invasive plant producing a series of allelochemicals that might inhibit the development of other plants. The objective of this study was to assess the phytotoxic effect of S. occidentalis extracts on the germination, development and antioxidant defence of the native species Tabebuia chrysotricha, T. pentaphylla, T. roseoalba and Handroanthus impetiginosus (Ipê species).

We evaluated the effects of chemicals extracted from S. occidentalis on the germination rate, germination speed index (GSI) and biometric parameters of the test species under controlled conditions. The effect of the extracts on the pigment content, amount of H2O2 and malondialdehyde (MDA), and the activity of the antioxidant enzymes in roots and leaves were also tested.

Alkaloids, coumarins, phenols, saponins, free steroids and condensed tannins were present in all extracts of S. occidentalis, while catechins were present only in leaf and stem extracts. Stem and root extracts caused a growth reduction in all Ipê species and total inhibition of seed germination in T. chrysotricha and T. roseoalba. All target species showed an increase in H2O2 and MDA in radicles and leaves. Oxidative stress contributed strongly to the morphological changes, such as seed blackening, thinning and darkening of radicle tips and reduction of biomass allocation in all Ipê species.

Although there was activation of antioxidant defence mechanisms, such as an increase in activity of ascorbate peroxidase (APX) and peroxidase (POD) enzymes, the joint action of the allelochemicals caused phytotoxicity, leading to cell dysfunction in all Ipê species.
Severe asthma treated by bronchial thermoplasty: A success not due to the small airways?
Authors: Chanez Pascal , Pahus Laurie , Charriot Jeremy , Bourdin Arnaud
Published: January 2019

See related Article
When to stop renal replacement therapy in anticipation of renal recovery in AKI: The need for consensus guidelines
Authors: Kelly Yvelynne P. , Waikar Sushrut S. , Mendu Mallika L.
Published: January 2019

There is wide variation in clinical practice regarding timing of discontinuation of renal replacement therapy (RRT) in patients with acute kidney injury (AKI). Prolonged, unnecessary RRT treatment can contribute to length of stay, overall hospital costs, and risk of complications associated with RRT. In addition, prolonged RRT can paradoxically lengthen the time for which the patient remains dialysis‐dependent. Well‐designed, randomized clinical trials have utilized varied discontinuation criteria specifically related to urine output and creatinine clearance, which impedes the comparison of outcomes from such studies. Other observational studies have attempted to assess the sensitivity and specificity of various criteria for discontinuation of RRT. Whether diuretics influence renal recovery has not been fully elucidated as well. In this article, we propose a starting framework for RRT discontinuation criteria to guide clinicians and clinical researchers. We emphasize the importance of frequent clinical assessment while considering discontinuation of RRT for AKI patients with a creatinine clearance >15 mL/min on a timed urine collection and/or a urine output >400 mL/24 h without diuretics, or >2000 mL/24 h with diuretics. We also discuss newer biomarkers, methods of GFR estimation, and imaging techniques that may play a greater role in the future. Clinical trials objectively comparing the success of RRT discontinuation criteria will be required to provide high‐quality evidence for our proposed guidelines.
Shoe‐mounted accelerometers should be used with caution in gait retraining
Authors: Cheung Roy T. H. , Zhang Janet H. , Chan Zoe Y. S. , An Winko W. , Au Ivan P. H. , MacPhail Aislinn , Davis Irene S.
Published: January 2019

Real‐time biofeedback gait retraining has been reported to be an effective intervention to lower the impact loading during gait. While many of the previous gait retraining studies have utilized a laboratory‐based setup, some studies used accelerometers affixed at the distal tibia to allow training outside the laboratory environment. However, many commercial sensors for gait modification are shoe‐mounted. Hence, this study sought to compare impact loading parameters measured by shoe‐mounted and tibia sensors in participants before and after a course of walking or running retraining using signal source from the shoe‐mounted sensors. We also compared the correlations between peak positive acceleration measured at shoe (PPAS) and tibia (PPAT) and vertical loading rates, as these loading rates have been related to injury. Twenty‐four and 14 participants underwent a 2‐week visual biofeedback walking and running retraining, respectively. Participants in the walking retraining group experienced lower PPAS following the intervention (P < 0.005). However, they demonstrated no change in PPAT (P = 0.409) nor vertical loading rates (P > 0.098) following the walking retraining. In contrast, participants in the running retraining group experienced a reduction in the PPAT (P = 0.001) and vertical loading rates (P < 0.013) after running retraining. PPAS values were four times that of PPAT for both walking and running suggesting an uncoupling of the shoe with tibia. As such, PPAS was not correlated with vertical loading rates for either walking or running, while significant correlations between PPAT and vertical loading rates were noted. The present study suggests potential limitations of the existing commercial shoe‐mounted sensors.