bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case Study of Engaging Hard‐to‐Reach Participants in the Research Process: Community Advisors on Research Design and Strategies (CARDS)®
Authors: Kaiser Betty L. , Thomas Gay R. , Bowers Barbara J.
Published: October 2016

Lack of diversity among study participants in clinical research limits progress in eliminating health disparities. The engagement of lay stakeholders, such as patient or community advisory boards (CABs), has the potential to increase recruitment and retention of underrepresented groups by providing a structure for gathering feedback on research plans and materials from this target population. However, many CABs intentionally recruit prominent stakeholders who are connected to or comfortable with research and academia and thus may not accurately represent the perspectives of underrepresented groups who have been labeled hard‐to‐reach, including racial minorities and low‐income or low‐literacy populations. We developed a partnership between the University of Wisconsin‐Madison School of Nursing and two community centers to deliberately engage hard‐to‐reach people in two lay advisory groups, the Community Advisors on Research Design and Strategies (CARDS)®. Community center staff recruited the CARDS from center programs, including parenting and childcare programs, women's support groups, food pantries, and senior meal programs. The CARDS model differs from other CABs in its participants, processes, and outcomes. Since 2010, the CARDS have met monthly with nurses and other researchers, helping them understand how research processes and the language, tone, appearance, and organization of research materials can discourage people from enrolling in clinical studies. We have successfully used the CARDS model to bring hard‐to‐reach populations into the research process and have sustained their participation. The model represents a promising strategy for increasing the diversity of participants in clinical research. © 2016 Wiley Periodicals, Inc.
Sit‐To‐Stand Lift: Effects of Lifted Height on Weight Borne and Upper Extremity Strength Requirements
Authors: Tang Ruoliang , Poklar Maggie , Domke Hilary , Moore Stephanie , Kapellusch Jay , Garg Arun
Published: October 2016

To prevent back and shoulder injuries to nursing personnel, sit‐to‐stand lifts are used to transfer partial‐weight‐bearing patients with upper extremity strength. However, the weight‐bearing capacity and upper extremity strength required of patients have not been defined. The objectives of this study were to determine: (a) the percentage of body weight borne by the patient when lifted to different heights in the lift and (b) whether a patient needs upper extremity strength. Nineteen healthy normal‐weight volunteers (ages 19–39) were transferred from a hospital bed to a wheelchair using (a) a gait belt and (b) a sit‐to‐stand lift. With legs secured in the lift, participants were lifted to five different heights (knee angles 120–180 degrees) while holding and not holding the lift handles. Participants supported a greater percentage of body weight as they were lifted higher, increasing from 60% to almost 100% (p < .01). Holding the handles did not have an effect on weight borne overall. At low heights, slightly less weight was borne when not using the handles than with them, and no difference in weight borne was found at heights near standing (p < .01). All participants felt more comfortable and safer transferring from bed to wheelchair with the mechanical lift than with the gait belt (p < .01). Results are limited to normal‐weight patients but suggest that sit‐stand lifts can be used in patients without upper extremity strength. Patients with limited weight‐bearing capacity can be transferred by not raising them high in the lift. © 2016 Wiley Periodicals, Inc.
Preparation of fluorescent polyaspartic acid and evaluation of its scale inhibition for CaCO3 and CaSO4
Authors: Shen Zhenling , Zhi Xin , Zhang Puyu
Published: October 2016

Polysuccinimide was synthesized from maleic anhydride and urea. A polyaspartic acid derivative (PASP‐Try‐SEA) was synthesized from the polysuccinimide with 2‐aminoethanesulfonic acid and tryptophan. The products were characterized by UV, FTIR,1H NMR, TGA and PL, respectively. The results showed that the fluorescent chromophore‐indolyl groups were successfully incorporated into PASP. The relationship between the fluorescence intensity and the concentration of fluorescent polyaspartic acid (FPASP) is linear with the excitation wavelength of 366 nm and 422 nm. FPASP also showed excellent scale inhibition properties with a scale inhibition rate of 78% achieved for CaCO3 with a dosage of 9 mg/L and a significantly enhanced scale inhibition effect for CaSO4, achieving an inhibition rate of 98%, which were determined using the static scale inhibition method. When FPASP was added to the solution, CaCO3 and CaSO4 deposits showed flower patterns with floppy accumulation by scanning electron microscopy. Copyright © 2016 John Wiley & Sons, Ltd.
Liderazgo electrónico, un reto ineludible para las organizaciones de hoy
Authors: Esguerra Gustavo A. Esguerra , Contreras Francoise
Published: October 2016

El objetivo de este estudio es describir y conceptualizar la noción de liderazgo electrónico y el reto que suponen para los líderes las nuevas formas de relación que implica este tipo de liderazgo. A partir de una revisión bibliográfica, se analiza la complejidad de liderar equipos virtuales a través de distintas formas de interacción, sugiriendo cambios en el ejercicio del liderazgo, no solo para lograr que este sea efectivo, sino también para que las organizaciones aprovechen las ventajas que ofrecen las nuevas tecnologías y eviten quedar relegadas en un mundo cada vez más virtualizado. Finalmente, se discuten las limitaciones y las posibilidades de desarrollo del liderazgo en contextos virtuales, para avanzar en este campo emergente de conocimiento.
Towards Personalized Intervention for Alzheimer’s Disease
Authors: Peng Xing , Xing Peiqi , Li Xiuhui , Qian Ying , Song Fuhai , Bai Zhouxian , Han Guangchun , Lei Hongxing
Published: October 2016

Alzheimer’s disease (AD) remains to be a grand challenge for the international community despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripotent cells (iPSCs). Comprehensive information collection, better understanding of the disease mechanisms, and diversified strategies of drug development would help with more effective intervention in the foreseeable future.
Which types of mental work demands may be associated with reduced risk of dementia?
Authors: Then Francisca S. , Luck Tobias , Heser Kathrin , Ernst Annette , Posselt Tina , Wiese Birgitt , Mamone Silke , Brettschneider Christian , König Hans‐Helmut , Weyerer Siegfried , Werle Jochen , Mösch Edelgard , Bickel Horst , Fuchs Angela , Pentzek Michael , Maier Wolfgang , Scherer Martin , Wagner Michael , Riedel‐Heller Steffi G. , Abholz Heinz‐Harald , Brettschneider Christian , Bachmann Cadja , Bickel Horst , Blank Wolfgang , van den Bussche Hendrik , Eifflaender‐Gorfer Sandra , Eisele Marion , Ernst Annette , Fuchs Angela , Heser Kathrin , Jessen Frank , Kaduszkiewicz Hanna , Kaufeler Teresa , Köhler Mirjam , König Hans‐Helmut , Koppara Alexander , Lange Carolin , Lubisch Diana , Luck Tobias , Luppa Melanie , Maier Wolfgang , Mayer Manfred , Mösch Edelgard , Pentzek Michael , Posselt Tina , Prokein Jana , Riedel‐Heller Steffi , Röhr Susanne , Scherer Martin , Schumacher Anna , Stein Janine , Steinmann Susanne , Tebarth Franziska , Wagner Michael , Weckbecker Klaus , Weeg Dagmar , Werle Jochen , Weyerer Siegfried , Wiese Birgitt , Wolfsgruber Steffen , Zimmermann Thomas , van den Bussche Hendrik , Maier Wolfgang , Scherer Martin
Published: October 2016

Introduction

Previous studies have demonstrated that an overall high level of mental work demands decreased dementia risk. In our study, we investigated whether this effect is driven by specific mental work demands and whether it is exposure dependent.

Methods

Patients aged 75+ years were recruited from general practitioners and participated in up to seven assessment waves (every 1.5 years) of the longitudinal AgeCoDe study. Analyses of the impact of specific mental work demands on dementia risk were carried out via multivariate regression modeling (n = 2315).

Results

We observed a significantly lower dementia risk in individuals with a higher level of “information processing” (HR, 0.888), “pattern detection” (HR, 0.878), “mathematics” (HR, 0.878), and “creativity” (HR, 0.878). Yet, exposure‐dependent effects were only significant for “information processing” and “pattern detection.”

Discussion

Our longitudinal observations suggest that dementia risk may be reduced by some but not all types of mental work demands.
The financial burden and health care utilization patterns associated with amnestic mild cognitive impairment
Authors: Ton Thanh G.N. , DeLeire Thomas , May Suepattra G. , Hou Ningqi , Tebeka Mahlet G. , Chen Er , Chodosh Joshua
Published: October 2016

Introduction

Individuals with amnestic mild cognitive impairment (aMCI) are at elevated risk of developing Alzheimer's disease (AD) dementia.

Methods

With data from the Aging, Demographics, and Memory Study, we used the Clinical Dementia Rating Sum of Boxes classifications to conduct a cross‐sectional analysis assessing the relationship between cognitive state and various direct and indirect costs and health care utilization patterns.

Results

Patients with aMCI had less medical expenditures than patients with moderate and severe AD dementia (P < .001) and were also significantly less likely to have been hospitalized (P = .04) and admitted to nursing home (P < .001). Compared to individuals with normal cognition, patients with aMCI had significantly less household income (P = .018).

Discussion

Patients with aMCI had lower medical expenditures than patients with AD dementia. Poor cognitive status was linearly associated with lower household income, higher medical expenditures, higher likelihood of nursing and home care services, and lower likelihood of outpatient visits.
Longitudinal brain structural changes in preclinical Alzheimer's disease
Authors: Pegueroles Jordi , Vilaplana Eduard , Montal Victor , Sampedro Frederic , Alcolea Daniel , Carmona‐Iragui Maria , Clarimon Jordi , Blesa Rafael , Lleó Alberto , Fortea Juan ,   Alzheimer's Disease Neuroimaging Initiative
Published: October 2016

Introduction

Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood.

Methods

We compared the changes in cortical thickness in the ADNI cohort during a 2‐year follow‐up between the NIA‐AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates.

Results

At follow‐up, stage 1 subjects showed reduced atrophy rates in medial frontal areas and precuneus compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures. Low CSF Aβ1–42 levels were associated with reduced atrophy rates in subjects with normal tau levels and high CSF tau levels with accelerated atrophy only in subjects with low Aβ1–42 levels.

Discussion

Our longitudinal data confirm a biphasic trajectory of changes in brain structure in preclinical AD. These have implications in AD trials, both in patient selection and the use of MRI as a surrogate marker of efficacy.
mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease
Authors: Norambuena Andrés , Wallrabe Horst , McMahon Lloyd , Silva Antonia , Swanson Eric , Khan Shahzad S. , Baerthlein Daniel , Kodis Erin , Oddo Salvatore , Mandell James W. , Bloom George S.
Published: October 2016

A major obstacle to presymptomatic diagnosis and disease‐modifying therapy for Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle reentry (CCR) mediated by amyloid‐β oligomers (AβOs) and tau, the precursors of plaques and tangles. We now report that CCR results from AβO‐induced activation of the protein kinase complex, mTORC1, at the plasma membrane and mTORC1‐dependent tau phosphorylation, and that CCR can be prevented by insulin‐stimulated activation of lysosomal mTORC1. AβOs were also shown previously to reduce neuronal insulin signaling. Our data therefore indicate that the decreased insulin signaling provoked by AβOs unleashes their toxic potential to cause neuronal CCR, and by extension, neuron death.
Usefulness of early colonoscopy in the diagnosis and treatment of moderate or severe lower gastrointestinal bleeding
Authors: Correa Paulo , Teixeira Carolina , Zago Rodrigo R. , Rossini Giulio , Paccos Jose Luiz , Popoutchi Pedro , Loureiro Jarbas F. , Borges Jose Luiz , Averbach Marcelo
Published: October 2016

A total of 38,686 colonoscopies were performed between January 1985 and December 2012 at Hospital Sírio-Libanês, in São Paulo, Brazil. Two hundred thirty-four patients (0.6%) had acute lower gastrointestinal bleeding of moderate or severe intensity. A definitive diagnosis was possible in 151 cases, 64.5% of these patients.

This study was approved by the Institutional Review Board. Medical charts were reviewed.

All examinations were done under sedation by the same medical team.

The predominant sources of bleeding were colonic diverticula (73 patients; 31%), ischemic or infectious colitis (18 patients; 7.7%) and radiation proctitis (18 patients; 7.7%).

A specific therapeutic intervention was performed on 61 of the 151 patients who had the diagnosis confirmed (40.4%), according to the source of bleeding. Most patients with postpolypectomy bleeding were treated with injection of epinephrine (40%) and clipping (40%). Patients with angiodysplasia were treated predominantly with argon plasma coagulation (42%).

Injection of epinephrine was the most frequent treatment, regardless of the source of bleeding (34.4%), followed by argon plasma coagulation (31.1%).

Control of active hemorrhage was achieved endoscopically in 98.8% of the patients.

Our data shows that early colonoscopy in the management of patients with suspected acute lower gastrointestinal bleeding is a useful tool for diagnosis and treatment.
TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women with Vulvar and Vaginal Atrophy: The REJOICE Trial
Authors: Kingsberg Sheryl A. , Derogatis Leonard , Simon James A. , Constantine Ginger D. , Graham Shelli , Bernick Brian , Gasper Gina , Mirkin Sebastian
Published: October 2016

Introduction

TX-004HR is an investigational, applicator-free, vaginal soft gel capsule containing low-dose solubilized 17β-estradiol. The phase 3, randomized, double-blinded, placebo-controlled, multicenter REJOICE trial has shown TX-004HR to be safe and effective for the treatment of moderate to severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy (VVA).

Aim

To evaluate the effect of TX-004HR on female sexual dysfunction in postmenopausal women with VVA.

Methods

The REJOICE study compared the effects of 12-week treatment with TX-004HR (4, 10, or 25 μg) with placebo in postmenopausal women (40–75 years old) with VVA and a most bothersome symptom of moderate to severe dyspareunia. Changes in the percentage of superficial and parabasal cells, vaginal pH, and dyspareunia were measured as co-primary end points. Female sexual dysfunction was evaluated as a secondary end point using the Female Sexual Function Index (FSFI) patient self-report inventory.

Main Outcome Measures

Changes from baseline to week 12 in total and individual domain FSFI scores for each TX-004HR dose were compared with those for placebo.

Results

All three TX-004HR doses increased the baseline total FSFI score after 12 weeks, with 10 μg (P < .05) and 25 μg (P = .0019) having a significantly greater effect than placebo. A similar trend was observed for the individual FSFI domains, with 10 and 25 μg significantly improving baselines scores for pain and lubrication at 12 weeks (P ≤ .015 for all vs placebo). Changes from baseline to week 12 in arousal (P = .0085) and satisfaction (P = .0073) were significantly greater for TX-004HR 25 μg vs placebo. All three TX-004HR doses were comparable to placebo in their effect on desire and orgasm.

Conclusion

TX-004HR improved FSFI scores in a dose-dependent manner. The observed improvements in sexual function suggest that TX-004HR is a promising treatment option for postmenopausal VVA with a potential added beneficial effect on female sexual dysfunction.
Role of Body Esteem in the Sexual Excitation and Inhibition Responses of Women with and Without a History of Childhood Sexual Abuse
Authors: Kilimnik Chelsea D. , Meston Cindy M.
Published: October 2016

Introduction

Women's sexuality is influenced by their perceptions of their bodies. Negative body appraisals have been implicated in the development and maintenance of sexual concerns in women with a history of childhood sexual abuse (CSA). The sexuality of these women is often expressed in extremes of approach and avoidant sexual tendencies, which have been related to the sexual inhibition and sexual excitation pathways of the dual control model.

Aim

To test the influence of body esteem on the sexual excitation and inhibition responses of women with and without a history of CSA.

Methods

One hundred thirty-nine women with CSA and 83 non-abused women reported on their abuse history, depressive symptomology, sexual response, and affective appraisals of their body.

Main Outcome Measures

Validated self-report measurements of sexual excitation and inhibition responses (Sexual Excitation/Sexual Inhibition Inventory for Women) and body esteem (Body Esteem Scale) were administered.

Results

Body esteem was significantly associated with sexual inhibition responses of women regardless of CSA history status but was significantly related only to the sexual excitation responses of women with a CSA history. Perceived sexual attractiveness was a unique predictor of sexual excitation in women with a history of CSA.

Conclusion

Women with a history of CSA have lower body esteem than non-abused women, particularly in self-perceived sexual attractiveness, and these perceptions appear to influence their sexual responses by acting on the sexual excitation and inhibition response pathways.
Psychosexual Outcome Among Iranian Individuals with 5α-Reductase Deficiency Type 2 and Its Relationship with Parental Sexism
Authors: Khorashad Behzad S. , Aghili Zahra , Kreukels Baudewijntje P.C. , Hiradfar Mehran , Roshan Ghasem M. , Afkhamizadeh Mozhgan , Abbaszadegan Mohammad Reza , Ghaemi Nosrat , Khazai Behnaz , Cohen-Kettenis P.T.
Published: October 2016

Introduction

Few studies exist on the psychosexual outcome of homogeneous groups of individuals with 5α-reductase deficiency type 2 (5α-RD-2) and the relation between gender changes and parental hostile and benevolent sexism, which are two components of ambivalent sexism that assume a stereotypical approach toward women in an overtly negative way or a chivalrous, seemingly positive way.

Aim

To report on the psychosexual outcome of individuals with 5α-RD-2 and to investigate its relation to the level of parental sexism in a relatively large sample of Iranians with 5α-RD-2.

Methods

Twenty participants (mean age = 19.5 years, SD = 6.345) with a molecularly confirmed diagnosis of 5α-RD-2 who were assigned the female gender at birth and raised as female were included in the study. Participants and their parents were interviewed and their medical records were assessed. Parents also completed the Ambivalent Sexism Inventory (ASI), which includes hostile and benevolent sexism subscales.

Main Outcome Measures

Psychosexual outcome and parental hostile and benevolent sexism measurements.

Results

Twelve of 20 participants (60%) were diagnosed with gender identity disorder not otherwise specified (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision). Ten of these transitioned to the male gender. The other 10 participants (50%), including the two diagnosed with gender identity disorder not otherwise specified, continued living in a female gender role. When comparing the ASI subscale scores between families of participants who changed their gender and those who did not, no significant difference was found for ASI total and hostile sexism scores, but there was a difference for benevolent sexism (P = .049): those whose daughters had changed their gender had higher benevolent sexism scores.

Conclusion

The high prevalence of gender change and gender dysphoria reported in the literature was confirmed in this relatively large and homogeneous sample of Iranians with 5-α-RD-2 raised as female. Prenatal exposure to testosterone is hypothesized to play a role in the development of gender identity and sexual orientation, but parental attitudes also might be important. Although gender change in individuals with 5-α-RD-2 is often attributed to high levels of hostile sexism in some cultures, our findings show this to be associated with benevolent sexism.
Differential Effects of Cyproterone Acetate vs Spironolactone on Serum High-Density Lipoprotein and Prolactin Concentrations in the Hormonal Treatment of Transgender Women
Authors: Fung Raymond , Hellstern-Layefsky Miriam , Tastenhoye Camille , Lega Iliana , Steele Leah
Published: October 2016

Introduction

Spironolactone and cyproterone acetate (CPA) are the two main antiandrogen medications used in feminizing hormone therapy in transgender women. Previous studies have suggested that these two agents might have opposite effects on high-density lipoprotein (HDL) level when used in this context, and limited data have suggested CPA increases prolactin more than spironolactone.

Aim

To compare the effects of spironolactone and CPA on HDL and prolactin serum concentrations in transgender women.

Methods

A retrospective chart review was conducted at three clinical sites in Toronto, Ontario, Canada. Patients were selected if they (i) identified as a transgender woman, (ii) had newly started spironolactone or CPA with estrogen or restarted spironolactone or CPA after a washout period of at least 6 months, and (iii) had not used other antiandrogens within the previous 6 months.

Main Outcome Measures

HDL and prolactin concentrations between the two treatment groups at baseline and at 12 months.

Results

Eighty-two patients were included in the spironolactone group and 31 patients were included in the CPA group. Baseline HDL and prolactin levels were not significantly different between the two groups. At 12 months, HDL increased by 0.10 mmol/L (SD = 0.24) in the spironolactone group but decreased by 0.07 mmol/L (SD = 0.21) in the CPA group (P = .002). The difference remained significant after adjusting for baseline HDL, use of lipid-lowering drugs, and age. The change in prolactin was +3.10 μg/L (SD = 5.70) in the spironolactone group and +11.8 μg/L (SD = 8.63) in the CPA group (P < 0.001). This difference also remained significant after adjusting for baseline prolactin level.

Conclusion

These data suggest that spironolactone use in transgender women increases HDL levels and that CPA has the opposite effect. CPA also is associated with a larger increase in prolactin. These factors should be considered when choosing between these two antiandrogen agents.
Surgical Outcomes of Erectile Implants After Phalloplasty: Retrospective Analysis of 95 Procedures
Authors: Neuville Paul , Morel-Journel Nicolas , Maucourt-Boulch Delphine , Ruffion Alain , Paparel Philippe , Terrier Jean-Etienne
Published: October 2016

Introduction

The creation of a neophallus is a complex surgery that must meet functional and esthetic requirements. It is a long and demanding surgical process whose final stage consists of the implantation of a rigid or inflatable material that can be used to reproduce an erection. Data in the literature are scarce, with only the pioneering series present, which includes the use of the first devices and techniques.

Aim

To report the outcome of patients with phalloplasty after implantation of erectile implants using standardized surgical techniques and the use of recent prosthesis types with or without a vascular graft.

Methods

This is a retrospective hospital-based analysis of all patients with phalloplasty who underwent implantation of an erectile prosthesis from March 2007 to May 2015. Factors associated with complications were investigated by multivariate logistic regression analysis.

Main Outcome Measures

Early-onset (during the first month after surgery) and late-onset complications, including erosion, infections, malpositioning, and dysfunction.

Results

Sixty-nine patients were included in the study and 95 procedures were analyzed. After a median follow-up of 4 years (minimum = 169 days, maximum = 6.1 years), the original prosthesis was still in place in 43 patients (62.3%). Patients underwent phalloplasty after female-to-male transsexualism (n = 62, 89.9%), malformation (n = 4, 5.8%), or trauma (n = 3, 4.3%). The proportions for the different types of phalloplasty were 58% for forearm free flap phalloplasty (n = 40), 33.3% for suprapubic phalloplasty (n = 23), and 7% for other (n = 6). The erectile prostheses used were the two-piece AMS Ambicor (n = 71, 74.7%), the Ambicor with a vascular graft (n = 19, 20.0%), and the AMS 700CXR, AMS 700CX, or AMS600-650 (n = 5, 5.2%). There were no early-onset complications in 89 procedures (93.7%) and, when present, they were always related to infection (n = 4, 4.2%). Late-onset complications were erosion (n = 4, 4.2%), infection (n = 4, 4.2%), dysfunction (n = 10, 10.5%), and malpositioning (n = 12, 12.6%). No significant difference was observed for malpositioning (12.7% vs 10.5%, P = .87) and dysfunction (7.0% vs 10.5%, P = .78) between the AMS Ambicor prosthesis and the Ambicor prosthesis with a vascular graft.

Conclusion

This study provides updated data on complications after the implantation of erectile implants. Multicenter studies, including the evaluation of patient satisfaction, are needed to increase our understanding of factors associated with the outcomes.
VCP inhibitors induce endoplasmic reticulum stress, cause cell cycle arrest, trigger caspase‐mediated cell death and synergistically kill ovarian cancer cells in combination with Salubrinal
Authors: Bastola Prabhakar , Neums Lisa , Schoenen Frank J. , Chien Jeremy
Published: October 2016

Valosin‐containing protein (VCP) or p97, a member of AAA‐ATPase protein family, has been associated with various cellular functions including endoplasmic reticulum‐associated degradation (ERAD), Golgi membrane reassembly, autophagy, DNA repair, and cell division. Recent studies identified VCP and ubiquitin proteasome system (UPS) as synthetic lethal targets in ovarian cancer. Here, we describe the preclinical activity of VCP inhibitors in ovarian cancer. Results from our studies suggest that quinazoline‐based VCP inhibitors initiate G1 cell cycle arrest, attenuate cap‐dependent translation and induce programmed cell death via the intrinsic and the extrinsic modes of apoptosis. Mechanistic studies point to the unresolved unfolded protein response (UPR) as a mechanism by which VCP inhibitors contribute to cytotoxicity. These results support an emerging concept that UPR and endoplasmic reticulum (ER) stress pathways may be targeted in ovarian cancer as a source of vulnerability. Since prolonged ER stress may result in CHOP‐mediated cell death, we tested the hypothesis that VCP inhibitors act synergistically with compounds that enhance CHOP expression. Here, we show that VCP inhibitors act synergistically with Salubrinal, an inhibitor of eIF2α dephosphorylation, by enhancing CHOP expression in ovarian cancer cell lines. Our results provide a proof‐of‐concept that VCP inhibitors can be used as a single agent and can be synergized with compounds that enhance CHOP expression to induce cell death in ovarian cancer cells.
La simulación clínica como estrategia para el desarrollo del pensamiento crítico en estudiantes de medicina
Authors: Valencia Castro Johanna Lizbeth , Tapia Vallejo Sara , Olivares Olivares Silvia Lizett
Published: October 2016

Introducción: Las instituciones que ofrecen carreras de medicina han centrado su atención en formar estudiantes para el desarrollo de competencias genéricas, entre ellas el pensamiento crítico. Una estrategia que se ha utilizado para su desarrollo es la simulación clínica mediante sus etapas. Sin embargo, es relevante identificar cómo la simulación clínica da al estudiante la oportunidad de pensar en diversos momentos de su aprendizaje (por adelantado, durante la acción y en retrospectiva) con la finalidad de razonar, deliberar y emitir juicios con objetivos y fines establecidos para autorregular su aprendizaje.

Objetivo: Valorar el desarrollo del pensamiento crítico a partir de la simulación clínica en cada una de sus etapas (diagnóstico, intervención y reflexión) en estudiantes de la carrera de medicina en una institución privada.

Método: Cualitativo descriptivo. Se diseñó y aplicó una rúbrica a 4 equipos de 5 estudiantes con el objetivo de valorar el desarrollo del pensamiento crítico en las etapas de la simulación clínica, utilizando simulación de alta fidelidad. A partir de la observación se identificaron los niveles bajo, medio y alto de la competencia para cada equipo.

Resultados: En cuanto al nivel de pensamiento crítico, 2 de 4 equipos fueron capaces de diagnosticar y analizar el balance entre los beneficios y los riesgos de las pruebas y de los tratamientos; 1 de 4 equipos fue capaz de reconocer opciones de tratamiento a partir de datos relevantes; y 3 de 4 equipos fueron capaces de describir objetiva y subjetivamente la experiencia de simulación. La etapa de reflexión fue en la que los estudiantes se posicionaron en un nivel alto de pensamiento crítico medido durante la simulación clínica.

Conclusiones: Las actividades simuladas brindan a los estudiantes la oportunidad de analizar, reflexionar, evaluar contenidos y enfrentar situaciones asociadas con su quehacer profesional mediante la aproximación a la realidad clínica que enfrentarán en el futuro, logrando aprendizaje interactivo y retroalimentación inmediata.
Switching to Drought-Tolerant Plants Could Alter Urban Climates
Authors: Stanley Sarah
Published: October 2016

In Los Angeles, replacing lawns with native plants that need less water could lead to hotter days and cooler nights.
Rosetta Spacecraft Death-Dives into Comet Companion—On Purpose
Authors: Cowen Ron
Published: October 2016

On the way to its demise, the probe intimately viewed a dust-spewing pit and measured close up the gravity field, temperature, and other features of the comet.
Membrane protein extraction and purification using styrene–maleic acid (SMA) copolymer: effect of variations in polymer structure
Authors: Morrison Kerrie A. , Akram Aneel , Mathews Ashlyn , Khan Zoeya A. , Patel Jaimin H. , Zhou Chumin , Hardy David J. , Moore-Kelly Charles , Patel Roshani , Odiba Victor , Knowles Tim J. , Javed Masood-ul-Hassan , Chmel Nikola P. , Dafforn Timothy R. , Rothnie Alice J.
Published: October 2016

The use of styrene–maleic acid (SMA) copolymers to extract and purify transmembrane proteins, while retaining their native bilayer environment, overcomes many of the disadvantages associated with conventional detergent-based procedures. This approach has huge potential for the future of membrane protein structural and functional studies. In this investigation, we have systematically tested a range of commercially available SMA polymers, varying in both the ratio of styrene and maleic acid and in total size, for the ability to extract, purify and stabilise transmembrane proteins. Three different membrane proteins (BmrA, LeuT and ZipA), which vary in size and shape, were used. Our results show that several polymers, can be used to extract membrane proteins, comparably to conventional detergents. A styrene:maleic acid ratio of either 2:1 or 3:1, combined with a relatively small average molecular mass (7.5–10 kDa), is optimal for membrane extraction, and this appears to be independent of the protein size, shape or expression system. A subset of polymers were taken forward for purification, functional and stability tests. Following a one-step affinity purification, SMA 2000 was found to be the best choice for yield, purity and function. However, the other polymers offer subtle differences in size and sensitivity to divalent cations that may be useful for a variety of downstream applications.
Sterile neutrinos give IceCube and other experiments the cold shoulder
Authors: Chang Sung
Published: October 2016

Recent null results heighten the tension between the bulk of neutrino experiments and the few that hint at the putative particle’s existence.
A droplet that won’t freeze harbors a crystal that won’t melt
Authors: Smart Ashley G.
Published: October 2016

The gallium nanodroplet’s anomalous phase behavior is a new twist on the maxim “small is different.”
Clinton and Trump: Where do they stand on science?
Authors: Kramer David
Published: October 2016

The candidates’ positions on climate change and energy policy differ starkly. Comparing their views on other issues is harder.
Between research and development: IBM and Josephson computing
Authors: Mody Cyrus C. M.
Published: October 2016

For years the dream of turning the semiconductor industry into a superconductor industry has been only that. In the 1970s IBM—with help from the National Security Agency—made a run at turning that dream into reality.
A bridge too far: The demise of the Superconducting Super Collider
Authors: Riordan Michael
Published: October 2016

The largest basic scientific project ever attempted, the supercollider proved to be beyond the management capacity of the US high-energy physics community. A smaller proton collider would have been substantially more achievable.
Turbulence in breaking waves
Authors: Deane Grant B. , Stokes Dale , Callaghan Adrian H.
Published: October 2016

Laboratory experiments suggest that, on average, turbulent energy dissipation in whitecaps is the same for waves lapping on the beach and waves storming in the seas.
Redox-assisted regulation of Ca
2+
homeostasis in the endoplasmic reticulum by disulfide reductase ERdj5
Authors: Ushioda Ryo , Miyamoto Akitoshi , Inoue Michio , Watanabe Satoshi , Okumura Masaki , Maegawa Ken-ichi , Uegaki Kaiku , Fujii Shohei , Fukuda Yasuko , Umitsu Masataka , Takagi Junichi , Inaba Kenji , Mikoshiba Katsuhiko , Nagata Kazuhiro
Published: October 2016

Significance

Ca
2+
is one of the most important second messengers regulating numerous cellular functions; therefore, the regulation of Ca
2+
release from and its uptake into the endoplasmic reticulum (ER) are both critical for calcium signaling. The activity of sarco/endoplasmic reticulum Ca
2+
-ATPase isoform 2b (SERCA2b), a calcium pump on the ER membrane, was reported to be negatively regulated by the oxidation of two cysteines in its ER-luminal portion, and it is expected to be activated by its reduction. However, no molecules responsible for this reduction have been identified. Here, we showed for the first time that ERdj5, the reductase in the ER of mammalian cells, activates SERCA2b by reducing its disulfide bonds in a [Ca
2+
]
ER
-dependent manner.
Combining natural language processing and network analysis to examine how advocacy organizations stimulate conversation on social media
Authors: Bail Christopher Andrew
Published: October 2016

Significance

Social media provide potent opportunities for advocacy organizations to shape public debates because of the rapidly increasing number of people who frequent such forums each day. However, social scientists have not yet explained why some advocacy organizations create large-scale public debate whereas most others do not. Using automated text analysis and a Facebook application, I found that advocacy organizations are more likely to stimulate conversation if they produce messages that link discursive themes that are usually discussed in isolation from each other. Such messages not only resonate with multiple audiences, but also put such audiences in conversation with each other. This manuscript thereby contributes a theory of public deliberation on social media for the emerging field of computational social science.
Activation of Notch1 synergizes with multiple pathways in promoting castration-resistant prostate cancer
Authors: Stoyanova Tanya , Riedinger Mireille , Lin Shu , Faltermeier Claire M. , Smith Bryan A. , Zhang Kelvin X. , Going Catherine C. , Goldstein Andrew S. , Lee John K. , Drake Justin M. , Rice Meghan A. , Hsu En-Chi , Nowroozizadeh Behdokht , Castor Brandon , Orellana Sandra Y. , Blum Steven M. , Cheng Donghui , Pienta Kenneth J. , Reiter Robert E. , Pitteri Sharon J. , Huang Jiaoti , Witte Owen N.
Published: October 2016

Significance

A high nuclear Notch homolog 1, translocation-associated (Notch1) intracellular domain level distinguishes high-risk prostate cancer and castration-resistant prostate cancer from benign and low/intermediate-risk prostate cancer. Chronic activation of Notch1 cooperates with multiple oncogenic pathways altered in early prostate cancer, including AKT, Myc, and Ras/Raf/MAPK, to promote progression to androgen ablation-resistant prostate adenocarcinoma.
Force– and power–time curve comparison during jumping between strength‐matched male and female basketball players
Authors: Rice Paige E. , Goodman Courtney L. , Capps Christopher R. , Triplett N. Travis , Erickson Travis M. , McBride Jeffrey M.
Published: October 2016

The purpose of this study was to compare force– and power–time curve variables during jumping between Division I strength‐matched male and female basketball athletes. Males (n = 8) and females (n = 8) were strength matched by testing a one‐repetition maximum (1RM) back squat. 1RM back squat values were normalised to body mass in order to demonstrate that strength differences were a function of body mass alone. Subjects performed three countermovement jumps (CMJ) at maximal effort. Absolute and relative force– and power–time curve variables from the CMJs were analysed between males and females. Average force– and power–time curves were generated for all subjects. Jump height was significantly greater (p ≤ .05) in males than females. Absolute force was higher in males during the concentric phase, but not significantly different (p ≥ .05) when normalised to body mass. Significance was found in absolute concentric impulse between sexes, but not when analysed relative to body mass. Rate of force development, rate of power development, relative peak force, and work were not significantly different between sexes. Males had significantly greater impulse during the eccentric phase as well as peak power (PP) during the concentric phase of the CMJ than did females in both absolute and relative terms. It is concluded that sex differences are not a determining factor in measured force during a CMJ when normalised to body mass between strength‐matched subjects. However, eccentric phase impulse and concentric phase PP appear to be influenced by sex differences independent of matching strength levels.
Overlap syndrome
Authors: Borukhov Ilana , Rizzolo Denise
Published: October 2016

Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) both cause an inflammatory response and hypoxia. Patients who have both conditions (overlap syndrome) have increased morbidity and mortality. This article aims to increase awareness of the potential effects that untreated OSA can have on COPD and the importance of treating patients with overlap syndrome.
Benign anal disease
Authors: Clark Susannah J.
Published: October 2016

Benign anal disease encompasses common problems including hemorrhoids, anal fissures, pruritus ani, perianal abscesses, and fistulae. Although many people will suffer from at least one of these conditions in their lives, healthcare practitioners diagnose and treat them accurately about 50% to 83% of the time. This article reviews common anal problems and the importance of a thorough history and physical examination to proper patient management.
Extubation Failure in Brain-injured Patients
Authors: Godet Thomas , Chabanne Russell , Marin Julien , Kauffmann Sophie , Futier Emmanuel , Pereira Bruno , Constantin Jean-Michel
Published: October 2016

Background

The decision to extubate brain-injured patients with residual impaired consciousness holds a high degree of uncertainty of success. The authors developed a pragmatic clinical score predictive of extubation failure in brain-injured patients.

Methods

One hundred and forty brain-injured patients were prospectively included after the first spontaneous breathing trial success. Assessment of multiparametric hemodynamic, respiratory, and neurologic functions was performed just before extubation. Extubation failure was defined as the need for ventilatory support during intensive care unit stay. Extubation failure within 48 h was also analyzed. Neurologic outcomes were recorded at 6 months.

Results

Extubation failure occurred in 43 (31%) patients with 31 (24%) within 48 h. Predictors of extubation failure consisted of upper-airway functions (cough, gag reflex, and deglutition) and neurologic status (Coma Recovery Scale-Revised visual subscale). From the odds ratios, a four-item predictive score was developed (area under the curve, 0.85; 95% CI, 0.77 to 0.92) and internally validated by bootstrap. Cutoff was determined with sensitivity of 92%, specificity of 50%, positive predictive value of 82%, and negative predictive value of 70% for extubation failure. Failure before and beyond 48 h shared similar risk factors. Low consciousness level patients were extubated with 85% probability of success providing the presence of at least two operating airway functions.

Conclusions

A simplified clinical pragmatic score assessing cough, deglutition, gag reflex, and neurologic status was developed in a preliminary prospective cohort of brain-injured patients and was internally validated (bootstrapping). Extubation appears possible, providing functioning upper airways and irrespective of neurologic status. Clinical practice generalizability urgently needs external validation.
Cephalomedullary nail versus sliding hip screw for fixation of AO 31 A1/2 intertrochanteric femoral fracture: a 12-year comparison of failure, complications, and mortality
Authors: Whale Casey S. , Hulet D. Andrew , Beebe Michael J. , Rothberg David L. , Zhang Chong , Presson Angela P. , Stuart Ami R. , Kubiak Erik N.
Published: October 2016

Background:

In the United States intertrochanteric and pertrochanteric fractures occur at a rate of more than 150,000 cases annually. Current standard of care for these fractures includes fixation with either a cephalomedullary nail (CMN) or a sliding hip screw (SHS). The purpose of this study was to compare failure and medical complications of intertrochanteric femoral fractures repaired by CMN or SHS.

Methods:

This study is a retrospective cohort study that included 249 patients with AO/OTA 31 A1.1-3, 31 A2.1-3 nonpathological fractures of the femur, of which 137 received CMN and 112 received SHS. Analysis was stratified by fracture type as stable (AO 31A1.1-2.1) or unstable (AO 31A2.2-3).

Results:

The tip-apex distance in stable fractures fixed with CMN was 17.3±5.9 compared to 26.2±7.9 in the stable SHS group (P<0.001) while it was 19.0±5.3 in the unstable CMN group compared to 24.0±6.7 in the unstable SHS patients (P=0.004). Among patients with stable fracture patterns there was no difference in collapse, complications, failure, or mortality (all P>0.05). Among patients with unstable fractures CMN had significantly less collapse (P<0.001) and failure (P=0.046) but no difference in complications (P=0.126) or mortality (P=0.586).

Conclusions:

There were no significant differences in failure or complication rates when comparing the CMN to the SHS in stable intertrochanteric fractures. CMN demonstrated significantly reduced failure and collapse rates in unstable intertrochanteric fractures when compared to SHS; however, this study had a relatively small sample size of unstable fractures and all results must be interpreted within this context.
Articular cartilage: injury, healing, and regeneration
Authors: Sharifi Ali Mohammad , Moshiri Ali , Oryan Ahmad
Published: October 2016

Treatment of large articular cartilage defects is technically demanding, and healing is a complicated process often associated with failure. The aim of treatment of articular cartilage injuries is to induce an acceptable healing process. Invasive and noninvasive treatments usually have good short- to mid-term outcomes; however, long-term results have been disappointing probably due to scar formation. Thus, current options are more palliative than curative. Tissue engineering and regenerative medicine (TERM) that includes scaffolds, healing factors, stem cells, and genetic engineering was introduced to orthopaedic research in the last 2 decades. Although TERM has demonstrated utility, the expected goals are not necessarily realistic. Despite advancements, several problems still exist and must be solved. This review discusses articular cartilage structure and function, injury types, the healing process, and factors that influence the healing response. Current treatment modalities, including TERM-based strategies, and their limitations are reviewed to provide future directions for treatment.
Early clinical and functional results of short modular femoral metaphyseal stem hip arthroplasty: a pilot study
Authors: Karampinas Panagiotis , Vlamis John , Papadelis Eustratios , Pneumatikos Spiros
Published: October 2016

Background:

The purpose of this study was to evaluate the short-term results, complications, and functional outcomes associated with short femoral metaphyseal hip arthroplasty.

Methods:

Twenty-nine hips with coxarthrosis were included in the study. Each patient had outpatient clinical examination and follow-up (mean 20 mo) with evaluation using the Harris Hip Score (HHS), Western Ontario and McMaster University (WOMAC) score, Short-Form 36 (SF-36), and anteroposterior and lateral radiographs of the hip.

Results:

Statistical analysis revealed a significant difference between the preoperative and the postoperative outcome scores. The radiographic evaluation revealed no differences. No one had cup or femoral implant loosening and no heterotopic ossification.

Conclusions:

This study showed that a short femoral metaphyseal stem can obtain early satisfactory clinical and functional outcomes without compromising implant stability. Future investigations should evaluate whether such results may be maintained after a longer time.