bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of p11 expression facilitates acidity‐sensing function of TASK1 channels in mouse adrenal medullary cells
Authors: Inoue Masumi , Matsuoka Hidetada , Lesage Florian , Harada Keita
Published: July 2018

External acidity induces catecholamine secretion by inhibiting TASK1‐like channels in rat adrenal medullary (AM) cells. TASK channels can function as a heteromer or homomer in the TASK subfamily. In this study, we elucidate the molecular identity of TASK1‐like channels in mouse AM cells using gene knockout. Genetic deletion of TASK1, but not TASK3, abolished the depolarizing inward current and catecholamine secretion in response to acidity, whereas it did not affect the resting current level. Immunocytochemistry revealed that AM cells exhibited predominantly TASK1‐like and little TASK3‐like immunoreactivity. A proximity ligation assay showed that TASK1/3 heteromeric channels were not formed in AM cells or PC12 cells. However, the exogenous expression of p11 in PC12 cells resulted in the heteromeric formation of TASK isoforms, which were mainly located in the cytoplasm, and p11 was not expressed in rat adrenal medullae or PC12 cells. In AM cells, genetic deletion of TASK1 resulted in enhancement of the immunoreactivity of the TALK2 channel, but not TASK3. The results indicate that TASK1 homomeric channels function as acidity sensors in AM cells, and that function is facilitated by the lack of p11 expression.—Inoue, M., Matsuoka, H., Lesage, F., Harada, K. Lack of p11 expression facilitates acidity‐sensing function of TASK1 channels in mouse adrenal medullary cells. FASEB J. 33, 455–468 (2019). www.fasebj.org
Percutaneous needle quadriceps tenotomy for treatment of idiopathic congenital dislocation of the knee
Authors: Khaled Mohamed , Elgafary Kamal , El-adly Wael
Published: July 2018

Background:

Congenital dislocation of the knee is a rare condition with an incidence of 1:100000 and can be idiopathic or syndromic. Our study evaluated percutaneous needle tenotomy for treatment of idiopathic flexible congenital dislocation of the knee.

Methods:

A prospective case series was done on 15 infants with idiopathic congenital dislocation of the knee: nine boys and six girls. Closed reduction was first attempted, and if it failed the knee was examined. If the knee could be flexed beyond 0, serial casting was done. If the knee could not be flexed beyond 0, percutaneous needle tenotomy was done.

Results:

Fifteen infants presented with idiopathic flexible congenital dislocation of the knee. Three dislocations were reduced closed, five were reduced with serial casting with gradual flexion, and seven that could not be flexed beyond 0 underwent percutaneous needle tenotomy. All patients could walk within the normal age range with no pain. All had full range of motion and good quadriceps function. Ultrasound was done in patients who had percutaneous needle tenotomy at walking age to ensure healing of the quadriceps tendon, which was adequately healed in all patients.

Conclusions:

Percutaneous needle tenotomy is a good option for treatment of congenital dislocation of the knee. Careful selection of patients is mandatory.
Preoperative IMRT for soft-tissue sarcoma of the extremities and trunk: low rate of wound complications
Authors: Studer Gabriela , Glanzmann Christoph , Maduz Franziska , Bode Beata , Fuchs Bruno
Published: July 2018

Background:

The Canadian prospective randomized NCIC SR2 trial tested the sequence of radiation and surgery for extremity soft-tissue sarcoma. The trial was conducted in the era before intensity-modulated radiation therapy (IMRT) was clinically available. Similar disease control after preoperative and postoperative non-IMRT was found. However, the preoperative non-IMRT arm showed significantly less (persisting) late-term effects but increased (transient) wound complication rates compared to the postoperative non-IMRT arm (35% vs. 17%, P = 0.01). Consequently based on these results, preoperative radiation therapy was considered the preferred approach. Currently IMRT, with its option for highly conformal dose distribution that translates into better normal tissue sparing, is used as the general standard for sarcoma radiation therapy in most patients. Our hypothesis was that a lower wound complication rate after preoperative radiation therapy might be achievable in the IMRT era.

Methods:

We prospectively assessed our preoperative IMRT cohort (n=67 consecutive patients) treated between March 2008 and March 2016 with respect to wound complication rates.

Results:

Fourteen of 67 (21%) externally referred patients with recurrent (n=1) or incompletely resected disease (n=13), and 53 treatment-naive patients underwent planned preoperative radiation after core biopsy. After mean/median 7.3/7 wk (3-12 wk), complete tumor resection was performed. Secondary revision was required in five of 67 (i.e., wound complication rate of 7%). Two local failures were observed so far.

Conclusions:

The presented results support our hypothesis that preoperative IMRT may lead to a reduced wound complication rate compared to that after postoperative and mainly preoperative non-IMRT techniques.
Consumption of garlic and its interactions with tobacco smoking and alcohol drinking on esophageal cancer in a Chinese population
Authors: Jin Zi-Yi , Wallar Gina , Zhou Jin-Yi , Yang Jie , Han Ren-Qiang , Wang Pei-Hua , Liu Ai-Min , Gu Xiao-Ping , Zhang Xiao-Feng , Wang Xu-Shan , Su Ming , Hu Xu , Sun Zheng , Li Gang , Mu Li-Na , Lu Qing-Yi , Liu Xing , Li Li-Ming , He Na , Wu Ming , Zhao Jin-Kou , Zhang Zuo-Feng
Published: July 2018

Garlic consumption has been associated inversely with esophageal cancer (EC); however, its interactions with tobacco smoking and alcohol consumption have never been evaluated in an epidemiological study. We evaluated the potential interactions between garlic intake and tobacco smoking as well as alcohol consumption in a population-based case–control study with 2969 incident EC cases and 8019 healthy controls. Epidemiologic data were collected by face-to-face interviews using a questionnaire. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated and additive and multiplicative interactions were evaluated using unconditional logistic regression models, adjusting for potential confounding factors. Semi-Bayes (SB) adjustments were used to reduce potential false-positive findings. EC was associated inversely with raw garlic intake [SB-adjusted OR for more than once a week=0.68, 95% CI: 0.57–0.80], with a strong dose–response pattern in the overall analysis and in the stratified analyses by smoking and drinking. EC was associated positively with smoking and alcohol drinking, with SB-adjusted OR of 1.73 (95% CI: 1.62–1.85) and 1.37 (95% CI: 1.28–1.46) in dose–response effects of increased intensity and longer duration of smoking/drinking. Moreover, garlic intake interacts with smoking [synergy index (S)=0.83, 95% CI: 0.67–1.02; ratio of OR=0.88, 95% CI: 0.80–0.98] and alcohol drinking (S=0.73, 95% CI: 0.57–0.93; ratio of OR=0.86, 95% CI: 0.77–0.95) both multiplicatively and additively. Our findings suggested that high intake of raw garlic may reduce EC risk and may interact with tobacco smoking and alcohol consumption, which might shed a light on the development of EC as well as a potential dietary intervention among high-risk smokers and drinkers for EC prevention in the Chinese population.
Review of the Evaluation and Treatment of Vasovagal Reactions in Outpatient Procedures
Authors: Wu Wesley J. , Goldberg Leonard H. , Rubenzik Marc K. , Zelickson Blake R.
Published: July 2018

BACKGROUND

A vasovagal reaction is a commonly encountered event in outpatient procedures. There is a paucity of discussion on vasovagal reactions (VVRs) in the dermatologic surgery literature. However, recent investigations in the physiology, evaluation, and treatment of VVRs have been reported in other specialties.

OBJECTIVE

A comprehensive review of the physiology, evaluation, treatment, and prevention of VVRs.

MATERIALS AND METHODS

A search as performed using the PubMed/MEDLINE databases. Search terms included “vasovagal,” “vasovagal reaction,” “syncope,” “reflex syncope,” “neurocardiogenic syncope,” and “fainting.”

RESULTS

Studies demonstrate greater understanding in the physiology of a vasovagal reaction. Although permanent sequelae are uncommon, it is important to respond in a prompt manner. A variety of treatment and prevention options are presented.

CONCLUSION

Vasovagal reactions should be carefully evaluated. Additional studies may provide greater data in understanding and managing vasovagal reactions.
Hyaluronic Acid After Subcutaneous Injection—An Objective Assessment
Authors: Santer Verena , Molliard Samuel Gavard , Micheels Patrick , Río-Sancho Sergio del , Quinodoz Pierre , Kalia Yogeshvar N. , Salomon Denis
Published: July 2018

BACKGROUND

Hyaluronic acid (HA) fillers are the preferred injectable products for aesthetic correction of skin depressions and restoration of facial volume.

OBJECTIVE

To investigate the subcutaneous distribution of 3, biophysically distinct, CE-marked and FDA-approved HA fillers.

MATERIALS AND METHODS

BELB, JUVV, and RESL were injected ex vivo in porcine and human skin. Immediately after injection, the skin samples were snap-frozen, cross-sectioned, and visualized using stereomicroscopy and full-field optical coherence tomography. Images were compared with histological sections after hematoxylin and eosin staining.

RESULTS

Hyaluronic acid fillers were distributed as homogeneous bolus in the ex vivo skin. The injection bulks were found to preserve the fibrous trabecular network, shift the fat lobules, and displace the adjacent adipocyte layers independently of the formulation injected.

CONCLUSION

For the first time, the subcutaneous injection of 3 HA fillers with markedly different biophysical properties was systematically investigated by complementary visualization techniques. Despite their different properties, no difference in distribution was found after subcutaneous injection. The global preservation of the hypodermis structure observed was consistent with the good tolerability seen in clinical practice after implantation of the HA fillers in the subcutaneous skin layer.
Primary Modified Predescemetic Deep Anterior Lamellar Keratoplasty in Acute Corneal Hydrops
Authors: Jacob Soosan , Narasimhan Smita , Agarwal Amar , Sambath Jambulingam , Umamaheshwari Govindharaj , Saijimol Areeckal Incy
Published: July 2018

Purpose:

To report primary treatment of acute corneal hydrops (CH) with a modified technique of predescemetic deep anterior lamellar keratoplasty (pdDALK).

Methods:

This prospective interventional case series included 9 eyes with acute CH that underwent pdDALK as primary treatment. Technique modifications included a bevel-up needle, creating tissue emphysema as a guide for dissection, using small aliquots of air directed away from break, manual deeper dissection using a blunt dissector, centripetal dissection leaving the area of Descemet membrane (DM) break for last, retention of minimal stroma above DM tear, and tamponade of DM tear with air in the anterior chamber. In eyes with extensive area of edema or thin residual stroma, an inked trephine mark was manually deepened with a sharp crescent blade, followed by other modifications.

Results:

All patients underwent uneventful surgery without enlargement of DM tear. The average follow-up period was 18 ± 13 months. All showed a clear, nonedematous graft with an area of DM defect seen and overlying cornea continuing to remain clear at final postoperative follow-up. ASOCT showed 90.8 ± 32 μm residual predescemetic host stroma on either side of the defect. CDVA improved from 0.002 ± 0.005 preoperatively to 0.35 ± 0.1 by an average of 2.3 ± 0.8 weeks and to 0.52 ± 0.13 at final postoperative follow-up.

Conclusions:

Primary pdDALK was possible as single-stage definitive treatment with early visual rehabilitation and avoidance of scarring in our case series. Simultaneous correction of pathology by closure of DM break, anatomical correction of ectasia and thinning, optical correction by improved corneal topography and by regaining corneal structure and transparency, and retention of host DM and endothelium are advantages. Advanced DALK surgeons may use this technique.
Butyrate, a Gut Bacterial Metabolite, Lowers Intraocular Pressure in Normotensive But Not in Hypertensive Rats
Authors: Skrzypecki Janusz , Żera Tymoteusz , Ufnal Marcin
Published: July 2018

Background:

Accumulating evidence supports a role of gut bacterial metabolites in arterial blood pressure (BP) regulation. Since the mechanisms controlling intraocular pressure (IOP) and BP overlap, we hypothesized that butyrate, a bacterial metabolite, might affect both IOP and BP.

Methods:

IOP, BP, and heart rate (HR) were measured at baseline and after the intraperitoneal administration of either butyrate or a vehicle (0.9% NaCl) in anaesthetized normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR).

Results:

At baseline, there was no significant difference between WKY and SHR in IOP and HR, whereas BP was significantly higher in SHR. In WKY administration of butyrate produced a significant decrease in IOP and BP, which lasted throughout the experiment. IOP response to butyrate was similar between sham WKY and WKY, which had undergone unilateral superior cervical ganglion excision. In contrast, in SHR butyrate treatment did not affect IOP and produced only a transient decrease in BP. WKY showed no significant changes in HR whereas SHR exhibited an increase in HR.

Conclusions:

Butyrate, a gut bacterial metabolite, lowers IOP in normotensive but not in hypertensive rats. The effect is independent of ocular sympathetic innervation. Given that changes in BP followed a different pattern than changes in IOP it seems that butyrate lowers IOP independently of BP changes.
Comparing the Clinical Severity of Disease Caused by Enteroviruses and Human Parechoviruses in Neonates and Infants
Authors: Black Sally , Bradley Carina , Lai Florence Y. , Shenoy Savitha , Bandi Srini , Allen David J. , Tang Julian W.
Published: July 2018

Comparison of children hospitalized with enterovirus or human parechovirus (HPeV) detected in their cerebrospinal fluid revealed that HPeV infections presented with more persistent fever, irritability and feeding problems, more frequent leukopenia and lymphopenia and higher admission rates to high dependency or intensive care units. Few HPeV cases were followed up, further studies on long-term outcomes are needed.
Prioritization of Reimplantation in Previously Successful Cochlear Implantation Following Natural Device Failure
Authors: Hochman Jordan B. , Pisa Justyn , Cham Bonnie
Published: July 2018

Introduction:

Cochlear reimplantation procedures account for approximately 5% of all implant cases and may be caused by internal device failure, skin flap complications, or an unexpected decline in auditory performance. This issue, in concert with changing demographics, expanded audiometric candidacy criteria, adult bilateral implantation, and implantation for unilateral hearing loss, all place escalating pressure on device availability and resource allocation in a publically funded health care system.

Objective:

The predictable and problematic access to a scare medical resource requires rigor in establishing program priority and formal policy. We present a single cochlear implant center's working reflections and an attempt at a principled approach to rationing health care decisions.

Methods:

Different approaches to health care rationing are examined and discussed. We describe a method of allocation that is currently employed by a large Canadian quaternary care center and ground this method in important principles of distributive justice as they apply to health care systems.

Results:

We elect to recognize device failure as analogous to sudden sensorineural hearing loss, with the associated need to expedite reimplantation. We consider this an ethical approach grounded in the egalitarian principle of equality of opportunity within cohorts of patients.

Conclusion:

Porting the practice from sudden sensorineural hearing loss, the time-sensitive need for hearing restoration, and maximized communication outcomes, dictates prioritization for this patient population. The predicted evolution of health systems globally and the shape of future medical practice will be heavily influenced by both the macro and micro level resource-dependent decisions implant centers currently face.
Patients With Normal Hearing Thresholds but Difficulty Hearing in Noisy Environments: A Study on the Willingness to Try Auditory Training
Authors: Spehar Brent P. , Lichtenhan Jeffery T.
Published: July 2018

Hypothesis:

Persons with normal audiometric thresholds but excessive difficulty hearing in background noise will choose auditory training as a treatment option.

Background:

Auditory training has traditionally been reserved for those with marked hearing loss. We investigated auditory training as a treatment option for those who have normal auditory thresholds but complain about hearing in noise—a population of patients for which no therapy or intervention currently exists. We also determined the willingness of this patient population to volunteer for a free auditory training program.

Methods:

We administered a 14-item, telephone-based questionnaire to assess perceived difficulty hearing in noise and willingness to volunteer for auditory training. We developed questions to identify those who consistently reported difficulty hearing in noise, but not quiet.

Results:

The 11,938-person database included 2,299 patients with pure-tone averages less than 25. A total of 474 of these patients completed our questionnaire, 135 of who had normal audiometric thresholds at all octave frequencies 0.25 to 8 kHz. We found that difficulty hearing in noise was a graded problem. Our approach to find consistent reports about hearing in noise showed that the majority of people who consistently had difficulty hearing in noise, but not quiet, were the most likely to try auditory training.

Conclusions:

While relatively few patients with both normal hearing thresholds and complaints of severe difficulty hearing in noise were in the database, these patients were generally willing to volunteer for auditory training. Our results provide evidence that many in this underserved population would volunteer for auditory training.
Tolerance induction in hemophilia: innovation and accomplishments
Authors: Sherman Alexandra , Biswas Moanaro , Herzog Roland W.
Published: July 2018

Purpose of review

Hemophilia is an X-linked blood coagulation genetic disorder, which can cause significant disability. Replacement therapy for coagulation factor VIII (hemophilia A) or factor IX (hemophilia B) may result in the development of high-affinity alloantibodies (’inhibitors’) to the replacement therapy, thus making it ineffective. Therefore, there is interest in directing immunological responses towards tolerance to infused factors.

Recent findings

In this review, we will discuss latest advancements in the development of potentially less immunogenic replacement clotting factors, optimization of current tolerance induction protocols (ITI), preclinical and clinical data of pharmacological immune modulation, hepatic gene therapy, and the rapidly advancing field of cell therapies. We will also evaluate publications reporting data from preclinical studies on oral tolerance induction using chloroplast-transgenic (transplastomic) plants.

Until now, no clinical prophylactic immune modulatory protocol exists to prevent inhibitor formation to infused clotting factors. Recent innovative technologies provide hope for improved eradication and perhaps even prevention of inhibitors.
Factor XII in inflammation and wound healing
Authors: Stavrou Evi X.
Published: July 2018

Purpose of review

This review describes the contribution of coagulation factor XII (FXII) in sterile inflammation and wound healing, focusing on recently identified roles for zymogen FXII in neutrophil functions.

Recent findings

Recent studies have identified an important role for FXII in neutrophil trafficking. In particular, following neutrophil activation, autocrine FXII signals through the urokinase plasminogen activator receptor (uPAR) on the neutrophil surface to upregulate neutrophil functions. The sum of these activities leads to neutrophil adhesion, chemotaxis, and neutrophil extracellular (NET) formation. Downregulating FXII-mediated signaling in neutrophils is associated with improved wound healing.

These recent findings show the sophisticated role of FXII in vivo and create new opportunities for research on the treatment of chronic inflammatory diseases.
Influencing the Binge-Drinking Culture on a College Campus
Authors: Kessler Theresa A. , Kurtz Christine P.
Published: July 2018

Background

The college years are a time of transition in which students experiment with behaviors including use of alcohol. Nursing students can be instrumental in supporting positive health behaviors and influencing the drinking culture.

Purpose

This article describes the findings of a collaborative nursing student-faculty research project about alcohol use with a focus on binge drinking.

Methods

Using a nursing student-faculty collaborative model, a longitudinal design was used to evaluate a mass media campaign with social norming messages and education to influence the drinking culture on a college campus.

Results

Students in Greek life and athletics engaged in binge drinking significantly more than other students. Students observed the mass media messages, with 81.9% viewing posters. A significant decrease in binge drinking was reported.

Conclusions

The nursing student-faculty team implemented a mass media campaign, which was effective at influencing the drinking culture on a college campus.
Intrahepatic Cholangiocarcinomas Have Histologically and Immunophenotypically Distinct Small and Large Duct Patterns
Authors: Sigel Carlie S. , Drill Esther , Zhou Yi , Basturk Olca , Askan Gokce , Pak Linda M. , Vakiani Efsevia , Wang Tao , Boerner Thomas , Do Richard K.G. , Simpson Amber L. , Jarnagin William , Klimstra David S.
Published: July 2018

Intrahepatic cholangiocarcinomas are histologically heterogenous. Using a cohort of 184 clinically defined, resected intrahepatic cholangiocarcinomas, we retrospectively classified the histology into 4 subtypes: large duct (LD), small duct (SD) (predominantly tubular [SD1] or predominantly anastomosing/cholangiolar, [SD2]), or indeterminate. Then, we tested the 4 subtypes for associations with risk factors, patient outcomes, histology, and immunophenotypic characteristics. SD was the most common (84%; 24% SD1 and 60% SD2) with lower proportions of LD (8%), and indeterminate (8%). Primary sclerosing cholangitis was rare (2%), but correlated with LD (P=0.005). Chronic hepatitis, frequent alcohol use, smoking, and steatosis had no histologic association. LD was associated with mucin production (P<0.001), perineural invasion (P=0.002), CA19-9 staining (P<0.001), CK7+, CK19+, CD56− immunophenotype (P=0.005), and negative albumin RNA in situ hybridization (P<0.001). SD was histologically nodular (P=0.019), sclerotic (P<0.001), hepatoid (P=0.042), and infiltrative at the interface with hepatocytes (P<0.001). Albumin was positive in 71% of SD and 18% of LD (P=0.0021). Most albumin positive tumors (85%) lacked extracellular mucin (P<0.001). S100P expression did not associate with subtype (P>0.05). There was no difference in disease-specific or recurrence-free survival among the subtypes. Periductal infiltration and American Joint Committee on Cancer eighth edition pT stage predicted survival by multivariable analysis accounting for gross configuration, pT stage, and histologic type. pT2 had worse outcome relative to other pT stages. Significant differences in histology and albumin expression distinguish LD from SD, but there is insufficient evidence to support further subclassification of SD.
Pulmonary Carcinomas With Mucinous and Neuroendocrine Differentiation
Authors: Weissferdt Annikka
Published: July 2018

Amphicrine carcinoma is a distinct type of carcinoma characterized by synchronous exocrine and endocrine differentiation within the same tumor cell. Such tumors are exceedingly rare and most commonly recognized in the gastrointestinal tract. In the lung, sporadic descriptions of such lesions exist. This report presents 3 more such tumors, expanding the spectrum of amphicrine carcinomas in this organ. The patients were 3 men, 53 to 78 years of age (mean: 63 y) and all were current or former smokers. In one patient the tumor was an incidental finding, the others presented with lower respiratory symptoms. Microscopically, the lesions had an organoid pattern, consisting of nests of large tumor cells with peripheral palisading, vesicular nuclei and prominent nucleoli reminiscent of large cell neuroendocrine carcinoma. In addition, the tumor nests also showed glandular features, characterized by gland-like lumina filled with mucin and intracytoplasmic mucin droplets. Immunohistochemical studies showed diffuse reactivity of the tumor cells with synaptophysin and chromogranin and variable reactivity with TTF-1. Mucin stains highlighted extracellular and intracellular mucin deposition. Clinical follow-up demonstrated that one patient had died of his disease 12 months after surgery while another was alive and free of disease 21 months after surgery. The third patient was alive with widespread metastatic disease 8 months after diagnosis. This series highlights a rare variant of pulmonary carcinoma showing synchronous exocrine and endocrine differentiation. Recognition of this type of tumor is important in terms of tumor classification and to identify an entity with potential aggressive behavior.
Simulation Modeling and Metamodeling to Inform National and International HIV Policies for Children and Adolescents
Authors: Ciaranello Andrea , Sohn Annette H. , Collins Intira Jeannie , Rothery Claire , Abrams Elaine J. , Woods Beth , Pei Pamela , Penazzato Martina , Mahy Mary
Published: July 2018

Objective and Approach:

Computer-based simulation models serve an important purpose in informing HIV care for children and adolescents. We review current model-based approaches to informing pediatric and adolescent HIV estimates and guidelines.

Findings:

Clinical disease simulation models and epidemiologic models are used to inform global and regional estimates of numbers of children and adolescents living with HIV and in need of antiretroviral therapy, to develop normative guidelines addressing strategies for diagnosis and treatment of HIV in children, and to forecast future need for pediatric and adolescent antiretroviral therapy formulations and commodities. To improve current model-generated estimates and policy recommendations, better country-level and regional-level data are needed about children living with HIV, as are improved data about survival and treatment outcomes for children with perinatal HIV infection as they age into adolescence and adulthood. In addition, novel metamodeling and value of information methods are being developed to improve the transparency of model methods and results, as well as to allow users to more easily tailor model-based analyses to their own settings.

Conclusions:

Substantial progress has been made in using models to estimate the size of the pediatric and adolescent HIV epidemic, to inform the development of guidelines for children and adolescents affected by HIV, and to support targeted implementation of policy recommendations to maximize impact. Ongoing work will address key limitations and further improve these model-based projections.
Making Implementation Science Work for Children and Adolescents Living With HIV
Authors: Mark Daniella , Geng Elvin , Vorkoper Susan , Essajee Shaffiq , Bloch Kim , Willis Nicola , Stewart Bethany , Bakeera-Kitaka Sabrina , Sugandhi Nandita , Sturke Rachel , Achebe Kechi , Ferguson B. Jane , Vicari Marissa , Luo Chewe , Putta Nande , John-Stewart Grace , Guay Laura , Mushavi Angela , Muhammad Imran , Ross David A.
Published: July 2018

The global HIV response is leaving children and adolescents behind. Because of a paucity of studies on treatment and care models for these age groups, there are gaps in our understanding of how best to implement services to improve their health outcomes. Without this evidence, policymakers are left to extrapolate from adult studies, which may not be appropriate, and can lead to inefficiencies in service delivery, hampered uptake, and ineffective mechanisms to support optimal outcomes. Implementation science research seeks to investigate how interventions known to be efficacious in study settings are, or are not, routinely implemented within real-world programmes. Effective implementation science research must be a collaborative effort between government, funding agencies, investigators, and implementers, each playing a key role. Successful implementation science research in children and adolescents requires clearer policies about age of consent for services and research that conform to ethical standards but allow for rational modifications. Implementation research in these age groups also necessitates age-appropriate consultation and engagement of children, adolescents, and their caregivers. Finally, resource, systems, technology, and training must be prioritized to improve the availability and quality of age-/sex-disaggregated data. Implementation science has a clear role to play in facilitating understanding of how the multiple complex barriers to HIV services for children and adolescents prevent effective interventions from reaching more children and adolescents living with HIV, and is well positioned to redress gaps in the HIV response for these age groups. This is truer now more than ever, with urgent and ambitious 2020 global targets on the horizon and insufficient progress in these age groups to date.
A Pilot Randomized Controlled Double-Blind Trial of High- Versus Low-Dose Weekly Folic Acid in People With Rheumatoid Arthritis Receiving Methotrexate
Authors: Stamp Lisa K. , O'Donnell John L. , Frampton Christopher , Drake Jill , Zhang Mei , Barclay Murray , Chapman Peter T.
Published: July 2018

Background/Objective

The aim of this study was to determine whether reducing the dose of supplemental folic acid used in conjunction with methotrexate (MTX) therapy in people with active rheumatoid arthritis (RA) improved disease control and/or increased MTX-related adverse effects.

Methods

A randomized double-blind randomized controlled trial comparing 5 mg/wk and 0.8 mg/wk folic acid was undertaken. Rheumatoid arthritis patients on MTX for 3 months or more at a stable dose for 1 month or more were recruited. All participants had DAS28 of 3.2 or greater or required a change in therapy determined by the treating clinician. Disease activity, full blood count, liver function tests, red blood cell (RBC) folate, and RBC MTX polyglutamates were assessed at weeks 0, 4, 8, 16, and 24 along with reports of adverse events.

Results

Forty participants were recruited. The mean (SD) change in RBC folate between week 0 and 24 was +87.9 (57.4) nmol/L in the high-dose group and −113.3 (65.7) nmol/L in the low-dose group (p < 0.05). There was no significant difference in the change in DAS28 between the high- and low-dose groups at 24 weeks (−0.13 [95% confidence interval, −0.69 to 0.43] vs −0.25 [−0.87 to 0.37], respectively [p = 0.78]). There was no significant difference in MTX-related adverse effects between the 2 groups.

Conclusions

A reduction in RBC folate secondary to reduction in folic acid dose was not associated with a change in RA disease activity or MTX-related adverse effects. The prevention of MTX-related adverse effects remains the primary reason for coprescribing folic acid with MTX.

Trial Registration

Australian New Zealand Clinical Trials Registry (ANZCTR12610000739011).
Efficacy of Repeat Midurethral Sling for Persistent or Recurrent Stress Urinary Incontinence: A Fellows Pelvic Research Network Study
Authors: Smithling Katelyn R. , Adams-Piper Emily E. , Tran Alexis M. , Davé Bhumy A. , Chu Christine M. , Chan Robert C. , Antosh Danielle D. , Gutman Robert E.
Published: July 2018

Objective

The objective of this study is to compare quality of life and success rates of repeat midurethral slings (RMUS) using retropubic (RP) and transobturator (TO) routes.

Materials and Methods

Multicenter retrospective cohort with prospective follow-up of patients undergoing RMUS from 2003 to 2016. Prospective Urinary Distress Inventory (UDI-6) and Patient Global Impression of Improvement (PGI-I) were collected by phone. Primary outcome was success of repeat sling by approach (RP vs TO), defined as responses of no to UDI-6 number 3 and very much better or much better on PGI-I.

Results

A total of 122 patients prospectively completed UDI-6. Average ± SD time to failure after initial sling was 51.6 ± 56.1 months; mean follow-up after repeat sling was 30.7 months. Route of initial sling was RP 30.3%, TO 49.2%, and minisling 16.4%. Of the patients, 55.8% met our success definition following RMUS. About 71.3% were very much better or much better on PGI-I, and 30.3% reported stress urinary incontinence (SUI) on UDI-6. Of the RMUS, 73.8% were RP versus 26.2% TO.

There was no difference in success between repeat RP and TO routes (53.3% versus 63.3%, P = 0.34), nor for individual components: PGI-I response of very much better or much better (68.9% vs 78.1%), UDI-6 total score (25.9 vs 22.7, P = 0.29), or SUI on UDI-6 number 3 (32.2% vs 25.0%, P = 0.45), although the predetermined sample size was not met. No predictors of success or failure of RMUS were identified.

Conclusions

Majority of patients are very much better or much better after RMUS, although 30% still report bothersome SUI. No difference in success was observed between RP and TO RMUS.
Cold Storage Injury to Rat Small-bowel Transplants—Beneficial Effect of a Modified HTK Solution
Authors: Lautenschläger Ingmar , Pless-Petig Gesine , Middel Peter , de Groot Herbert , Rauen Ursula , Stojanovic Tomislav
Published: July 2018

Background

The small bowel is prone to ischemic injury during transport before transplantation, an injury that endangers the recipient patient. The small-bowel mucosal microcirculation in particular appears to be highly sensitive to injury. Current preservation solutions such as histidine-tryptophan-ketoglutarate (HTK) solution provide some protection to the graft. However, these were developed decades ago and do not address several critical processes, such as hypoxia-induced membrane pores and free radical-mediated hypothermic injury.

Methods

To protect the graft from cold ischemic injury, we implemented a modified HTK solution here, including glycine, alanine, and iron chelators in a heterotopic, syngeneic small-bowel transplantation model of the rat. The effects of the modified solution and its major components were compared against the conventional HTK solution using intravital microscopy in the early reperfusion period.

Results

The amino acid glycine, added to HTK solution, slightly improved mucosal perfusion. Both, the modified base solution (without iron chelators) and iron chelators increased functional capillary density of the mucosa during the early reperfusion period. The complete modified solution (with glycine, alanine, and iron chelators) significantly increased the perfusion index, functional capillary density of the mucosa, and red blood cell velocity in the grafts after reperfusion in comparison with the grafts preserved with HTK.

Conclusions

The modified preservation solution improved the microcirculation of the transplants and needs detailed evaluation in further models of small-bowel transplantation.
Incontinence, Incontinence-Associated Dermatitis, and Pressure Injuries in a Health District in Australia
Authors: Barakat-Johnson Michelle , Barnett Catherine , Lai Michelle , Wand Timothy , White Kathryn
Published: July 2018

PURPOSE:

This purpose of this study was to measure the prevalence of incontinence, incontinence-associated dermatitis (IAD), and pressure injuries (PIs) in a local health district in Australia. We also aimed to determine associated evidence-into-practice gaps.

DESIGN:

Multisite mixed-methods study.

SUBJECTS AND SETTINGS:

The sample comprised 250 adult patients in 12 units across 4 hospitals; their mean age was 73 years. Nurses caring for the patient at the time of the audit were questioned on nursing practice for patients with incontinence.

METHODS:

A 2-page audit tool was developed and used to capture demographic data, continence and mobility status, IAD and PI, incontinence products, nursing practice observations, and nurses' comments. Each patient was assessed by 2 senior nurses. Quantitative analysis included descriptive statistics and bivariate analysis using a χ2 test to examine the association between mobility and incontinence and a Fisher exact test to examine the association between IAD and PI. Content analysis was used to analyze qualitative data and develop themes.

RESULTS:

Almost half of patients had incontinence (n = 111/250), 20.7% of patients with incontinence (n = 23/111) had IAD, and 6.3% (n = 7/111) had hospital-acquired PI. There was a significant association between incontinence and mobility, and between IAD and PIs. In addition, 22.3% of patients who were continent (31/139) were wearing an incontinence product. Analysis of qualitative data found that both incontinence management and language used to refer to incontinence pads were incompatible with current best practices.

CONCLUSION:

The prevalence of incontinence among patients observed in this study was similar to rates reported internationally, but the prevalence of IAD was slightly lower. The association between IAD and PIs, as well as incontinence and mobility, was statistically and clinically significant. Nurses commonly used interventions with little or no evidence. Hospitals should put measures in place to improve nurses' knowledge of incontinence, IAD, and PI practices.
Microglia Regulate Neuroglia Remodeling in Various Ocular and Retinal Injuries
Authors: Paschalis Eleftherios I. , Lei Dylan , Zhou Chengxin , Chen Xiaohong Nancy , Kapoulea Vassiliki , Hui Pui-Chuen , Dana Reza , Chodosh James , Vavvas Demetrios , Dohlman Claes H.
Published: July 2018

Reactive microglia and infiltrating peripheral monocytes have been implicated in many neurodegenerative diseases of the retina and central nervous system (CNS). However, their specific contribution in retinal degeneration remains unclear. We recently showed that peripheral monocytes that infiltrate the retina after ocular injury in mice become permanently engrafted into the tissue, establishing a pro-inflammatory phenotype that promotes neurodegeneration. Here, we show in mice that microglia regulate the process of neuroglia remodeling during ocular injury, and their depletion results in marked upregulation of inflammatory markers, such as Il17f, Tnfsf11, Ccl4, Il1a, Ccr2, Il4, Il5, and Csf2 in the retina, abnormal engraftment of peripheral CCR2+ CX3CR1+ monocytes into the retina and is associated with increased retinal ganglion cell (RGC) loss, retinal nerve fiber layer thinning, and RPE65+ cell migration onto the retinal surface. Furthermore, we show that other types of ocular injuries, such as penetrating corneal trauma and ocular hypertension, also cause similar changes. However, optic nerve crush injury mediated RGC loss evokes neither peripheral monocyte response in the retina, nor RPE65+ cell migration, although peripheral CX3CR1+ and CCR2+ monocytes infiltrate the optic nerve injury site and remain present for months. Our study suggests that microglia are key regulators of peripheral monocyte infiltration and RPE migration and their depletion results in abnormal neuroglia remodeling that exacerbates neuroretinal tissue damage. This mechanism of retinal damage through neuroglia remodeling may be clinically important for the treatment of patients with ocular injuries, including surgical traumas.
Listeria monocytogenescell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria
Authors: Ortega Fabian E. , Koslover Elena F. , Theriot Julie A.
Published: July 2018

L. monocytogeneshijacks host actin to promote its intracellular motility and intercellular spread. WhileL. monocytogenesvirulence hinges on cell-to-cell spread, little is known about the dynamics of bacterial spread in epithelia at a population level. Here, we use live microscopy and statistical modeling to demonstrate thatL. monocytogenescell-to-cell spread proceeds anisotropically in an epithelial monolayer in culture. We show that boundaries of infection foci are irregular and dominated by rare pioneer bacteria that spread farther than the rest. We extend our quantitative model for bacterial spread to show that heterogeneous spreading behavior can improve the chances of creating a persistentL. monocytogenesinfection in an actively extruding epithelium. Thus, our results indicate thatL. monocytogenescell-to-cell spread is heterogeneous, and that rare pioneer bacteria determine the frontier of infection foci and may promote bacterial infection persistence in dynamic epithelia.
OLGA: fast computation of generation probabilities of B- and T-cell receptor amino acid sequences and motifs
Authors: Sethna Zachary , Elhanati Yuval , Callan Curtis G. , Walczak Aleksandra M. , Mora Thierry
Published: July 2018

Motivation

High-throughput sequencing of large immune repertoires has enabled the development of methods to predict the probability of generation by V(D)J recombination of T- and B-cell receptors of any specific nucleotide sequence. These generation probabilities are very non-homogeneous, ranging over 20 orders of magnitude in real repertoires. Since the function of a receptor really depends on its protein sequence, it is important to be able to predict this probability of generation at the amino acid level. However, brute-force summation over all the nucleotide sequences with the correct amino acid translation is computationally intractable. The purpose of this paper is to present a solution to this problem.

Results

We use dynamic programming to construct an efficient and flexible algorithm, called OLGA (Optimized Likelihood estimate of immunoGlobulin Amino-acid sequences), for calculating the probability of generating a given CDR3 amino acid sequence or motif, with or without V/J restriction, as a result of V(D)J recombination in B or T cells. We apply it to databases of epitope-specific T-cell receptors to evaluate the probability that a typical human subject will possess T cells responsive to specific disease-associated epitopes. The model prediction shows an excellent agreement with published data. We suggest that OLGA may be a useful tool to guide vaccine design.

Availability

Source code is available at https://github.com/zsethna/OLGA
miR-263b
controls circadian rhythms and structural plasticity of small ventral lateral neurons by inhibition of Beadex
Authors: Nian Xiaoge , Chen Wenfeng , Bai Weiwei , Zhao Zhangwu , Zhang Yong
Published: July 2018

Circadian clocks drive rhythmic physiology and behavior to allow adaption to daily environmental changes. In
Drosophila
, the small ventral lateral neurons (sLNvs) are the master pacemakers that control circadian rhythms. Circadian changes are observed in the dorsal axonal projections of the sLNvs, but their physiological importance and the underlying mechanism are unclear. Here we identified
miR-263b
as an important regulator of circadian rhythms in
Drosophila
. Flies depleted of
miR-263b
(

miR-263b
KO

) exhibited dramatically impaired rhythms under constant darkness. Indeed,
miR-263b
is rhythmically expressed and controls circadian output by affecting the structural plasticity of sLNvs through inhibition of expression of the LIM-only protein
Beadex
(
Bx
). The misexpression of
Bx
in flies phenocopied

miR-263b
KO

in behavior and molecular characteristics. In addition, the circadian phenotypes of

miR-263b
KO

were recapitulated by mutating the
miR-263b
binding sites in the
Bx
3′UTR. Together, these results establish
miR-263b
as an important regulator of circadian locomotor behavior.
Leveraging customer knowledge to enhance process innovation
Authors: Nguyen Hung , Harrison Norma
Published: July 2018

Purpose

Nowadays, companies compete and win based on the capabilities they can leverage across their supply chains. With unpredictable and turbulent business environment, supply chains are seeking to customer knowledge as sources of competitive advantage. The purpose of this paper is to empirically test a conceptual framework to investigate the roles of customer leverage (CL) on process innovation and the relationships to performance.

Design/methodology/approach

Drawing upon the knowledge-based view, this study argues that CL is the sources of firms’ process innovation. This study also posits that process innovation mediates the relationship between CL and performance based on transaction cost economics. This empirical study employed 650 manufacturers across different regions.

Findings

This study showed that strong association exists between a manufacturing firm’s CL capability and its process innovation and performances. Process innovation play critical mediating roles in absorbing and transforming customer knowledge in supply chains. In a more dynamic market, CL strengthens the positive impacts on process innovation.

Research limitations/implications

This study further highlights the need to emphasize both strategic and CL capability in dynamic environments as these may be needed to enable the firm to seize market niches that may open up in such environments. Similarly, managers should emphasize CL capability and process changes in competitive environments as they are more difficult to imitate from competitors in regards of new product or services.

Practical implications

These results extend the limited existing research on global manufacturing context that the customer knowledge are effective sources for increasing innovative processes. The higher the market turbulence, the stronger the pressures for CL demanded by process innovation. The findings also confirm that process innovation plays a mediating role in absorbing and transforming customer knowledge in improving costs and financial measures. This is an important result that highlights the mechanism by which customer knowledge can influence a firm’s bottom line.

Originality/value

This study examined the linkages between a marketing concept and operations and supply chain management.
The effect of digital technologies adoption in healthcare industry: a case based analysis
Authors: Laurenza Elena , Quintano Michele , Schiavone Francesco , Vrontis Demetris
Published: July 2018

Purpose

The purpose of this paper is to contribute to the extant literature regarding the exploitation of digital technologies by illustrating how this type of IT can influence business process improvements in the healthcare industry.

Design/methodology/approach

The paper reports an illustrative case study for MSD Italy, the Italian subsidiary of the USA-based company Merck & Co., Inc. The group sells drugs for human use in Italy but is also active in the veterinary (MSD Animal Health) industry, with Vree Health, and in solutions and software-based services for the healthcare industry.

Findings

The results show that the adoption of digital technologies could improve the performance of main healthcare business processes, particularly those processes that can be simplified with the adoption of information technology. More specifically, digital technologies could increase efficiency and, at the same time, allow for the delivery of better quality and reduced response times, with many benefits for several stakeholders, such as national health systems, clinicians and patients.

Originality/value

Although some studies report the need for effective business processes for sustainable healthcare systems, there is a lack of literature regarding the specific implications of the adoption of such digital technologies for the business process management of healthcare firms. This paper attempts to fill in this gap.