bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Hidden Population Sizes with Venue-based Sampling
Authors: Verdery Ashton M. , Weir Sharon , Reynolds Zahra , Mulholland Grace , Edwards Jessie K.
Published: July 2019

Background:

Researchers use a variety of population size estimation methods to determine the sizes of key populations at elevated risk of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), an important step in quantifying epidemic impact, advocating for high-risk groups, and planning, implementing, and monitoring prevention, care, and treatment programs. Conventional procedures often use information about sample respondents’ social network contacts to estimate the sizes of key populations of interest. A recent study proposes a generalized network scale-up method that combines two samples—a traditional sample of the general population and a link-tracing sample of the hidden population—and produces more accurate results with fewer assumptions than conventional approaches.

Methods:

We extended the generalized network scale-up method from link-tracing samples to samples collected with venue-based sampling designs popular in sampling key populations at risk of HIV. Our method obviates the need for a traditional sample of the general population, as long as the size of the venue-attending population is approximately known. We tested the venue-based generalized network scale-up method in a comprehensive simulation evaluation framework.

Results:

The venue-based generalized network scale-up method provided accurate and efficient estimates of key population sizes, even when few members of the key population were sampled, yielding average biases below ±6% except when false-positive reporting error is high. It relies on limited assumptions and, in our tests, was robust to numerous threats to inference.

Conclusions:

Key population size estimation is vital to the successful implementation of efforts to combat HIV/AIDS. Venue-based network scale-up approaches offer another tool that researchers and policymakers can apply to these problems.
Sociodemographic Profiles and Clinical Outcomes for Clients on Methadone Maintenance Treatment in a Western Canadian Clinic: Implications for Practice
Authors: Maina Geoffrey , Crizzle Alexander , Maposa Sithokozile , Fournier Bonnie
Published: July 2019

Introduction:

Clients on methadone maintenance treatment (MMT) have high attrition rates that are attributed to personal and system-related factors. To develop supportive interventions for these clients, it is imperative to understand social demographic characteristics and challenges that clients in the MMT program face.

Objectives:

This article aims to describe (a) the sociodemographic characteristics and clinical profiles of clients in a MMT program, (b) factors that impact their positive clinical outcomes, and (c) the study's implications for practice.

Methods:

A retrospective review of 101 randomly selected electronic medical records representing one third of all the records were examined for sociodemographic characteristics, clinical profiles, and outcomes. Descriptive statistics were used to analyze these variables. Interviews with 18 healthcare providers focusing on their experiences of caring for clients in the MMT program were analyzed thematically.

Results:

The average age of clients on MMT is 35.5 years. Clients had early exposure to alcohol and drugs, and at the time of enrollment to the program, they presented with complex healthcare needs, borne from chronic use, and exposure to adverse traumatic events. Personal and systemic factors impact clients' recovery. These include poverty, homelessness, and inadequate healthcare services. Understanding sociodemographic characteristics, clinical profiles, and clients' challenges is central to the development of supportive interventions that enhance retention to care and recovery.
Health Care Experiences of Black Transgender Women and Men Who Have Sex With Men: A Qualitative Study
Authors: Salerno John P. , Turpin Rodman , Howard Donna , Dyer Typhanye , Aparicio Elizabeth M. , Boekeloo Bradley O.
Published: July 2019

Black sexual and gender minorities (SGM) are at greater risk for HIV compared to their White, cisgender, heterosexual counterparts. Linkage to culturally sensitive health care is, therefore, pivotal for HIV prevention and treatment of Black SGM. Unfortunately, social and structural challenges undermine Black SGM individuals' abilities to obtain adequate health care services, indicating a need to understand Black SGM perceptions of health care. To address this gap, we interviewed Black men who have sex with men and transwomen about their experiences with health care providers. Participants discussed needs and concerns, including provider SGM identity diversity and education; assumptions, judgment, stigma, and discrimination; and ability to establish a personal bond, trust, and familiarity. Black SGM indicated that providers often did not meet their needs in different ways regarding their SGM identities. Findings suggest a need for provider cultural sensitivity education programs that address the needs of Black SGM in health care.
Cannabinoid hyperemesis syndrome: A case study and discussion
Authors: Creedon Eliza S. , Maloy Melony K. , DelloStritto Rita A.
Published: July 2019

Background and purpose:

Cannabinoid hyperemesis syndrome (CHS) was first described in the literature in 2004. The pathophysiology of CHS remains largely unknown. The syndrome is becoming more prevalent in inpatient settings and emergency departments as the legal usage of cannabis proliferates, although it is often not recognized when encountered. While symptoms of CHS are becoming better defined, early recognition and comprehensive treatment plans with reproducible outcomes remain elusive. Symptoms can be further complicated by the presence of chronic conditions or comorbidities. The purpose of this article is to consolidate findings from the literature, identify commonalities in clinical characteristics and pathogenesis, and highlight diagnostic and treatment approaches.

Methods:

Data collection methods include a review of the literature on CHS published in the past 10 years. Case study data were gathered from a patient interview and chart review.

Conclusions and implications for practice:

Through better recognition of CHS, nurse practitioners and other providers can promptly and accurately diagnosis the condition and improve treatment plans for these patients.
Differentiation Between Eosinophilic Otitis Media and Otitis Media Associated With Eosinophilic Granulomatosis With Polyangiitis
Authors: Fukuda Atsushi , Morita Shinya , Nakamaru Yuji , Hoshino Kimiko , Fujiwara Keishi , Homma Akihiro
Published: July 2019

Objective:

To perform comparisons and clarify differences in clinical manifestations between eosinophilic otitis media (EOM) and otitis media associated with eosinophilic granulomatosis with polyangiitis (EGPA).

Study Design:

Retrospective case review.

Setting:

Tertiary referral center.

Patients:

Twenty-two ears of 11 patients exhibiting EOM (EOM group) and 20 ears of 12 patients exhibiting otitis media associated with EGPA (EGPA group).

Main Outcome Measures:

Otological manifestations, nasal and paranasal manifestations, incidence of asthma, positivity for serum antineutrophil cytoplasmic antibodies (ANCA), total serum immunoglobulin (Ig) E level, peripheral blood eosinophil fraction, and hearing outcomes.

Results:

The incidence and age of onset of asthma and chronic rhinosinusitis were comparable between the EOM and EGPA groups. Moreover, otological findings and hearing outcomes at the initial visit were similar in both groups. Computed tomography images of the paranasal sinus showed predominant opacification of the ethmoid sinus in both groups. Although the total serum IgE level was not significantly different, the peripheral blood eosinophil fraction was significantly larger in the EGPA group than in the EOM group (p = 0.0035). Furthermore, the rate of myeloperoxidase–antineutrophil cytoplasmic antibodies (ANCA) positivity was significantly higher in the EGPA group than in the EOM group (p = 0.019).

Conclusions:

The findings of the present study suggest that the phenotypic characteristics of EOM closely resemble those of otitis media associated with EGPA in early stages before the appearance of vasculitis. Therefore, it is challenging to differentiate the two conditions purely on the basis of otorhinological examinations.
A Comparative Study of a Novel Adhesive Bone Conduction Device and Conventional Treatment Options for Conductive Hearing Loss
Authors: Skarzynski Piotr H. , Ratuszniak Anna , Osinska Kamila , Koziel Magdalena , Krol Bartlomiej , Cywka Katarzyna B. , Skarzynski Henryk
Published: July 2019

Objective:

To compare the audiological performance with the novel adhesive bone conduction hearing device (ADHEAR) to that with a passive bone conduction (BC) implant and to that with a bone conduction device (BCD) on a softband.

Study Design:

Prospective study in an acute setting, single-subject repeated measure in three situations: unaided, with conventional BCDs (passive implant or on softband), and with the ADHEAR.

Setting:

Tertiary referral center.

Patients:

Ten subjects with conductive hearing loss were evaluated with the ADHEAR. Five of these were users of a passive BC implant (Baha Attract with Baha4); five received a BCD (Baha4) on a softband for test purposes.

Intervention:

Use of non-invasive adhesive bone conduction system for the treatment of conductive hearing loss.

Main Outcome Measures:

Air and bone conduction thresholds, sound field thresholds, word recognition scores in quiet, and speech recognition thresholds in quiet and noise were assessed.

Results:

Users of the passive BC implant received comparable hearing benefit with the ADHEAR. The mean aided thresholds in sound field measurements and speech understanding in quiet and noise were similar, when subjects were evaluated either with the ADHEAR or the passive BC implant. The audiological outcomes for the non-implanted group were also comparable between the ADHEAR and the BCD on softband.

Conclusions:

Based on our initial data, the ADHEAR seems to be a suitable alternative for patients who need a hearing solution for conductive hearing loss but for medical reasons cannot or do not want to undergo surgery for a passive BC implant.
Evaluating the Industry Relationships of Presenting Physicians at the American Neurotological Society Spring Meetings
Authors: Desai Milap H. , Vekaria Darshak M. , McKinnon Brian J.
Published: July 2019

Objective:

1) Evaluate the accuracy of financial disclosures reporting by research presenters and moderators at the American Neurotology Society Spring meetings between 2014 and 2016. 2) Tabulate the reported monetary value of undisclosed financial relationships. 3) Determine the degree of compliance to the standards put forth by the Accreditation Council for Continuing Medical Education.

Study Design:

Cross-sectional analysis.

Setting:

N/A.

Patients:

N/A.

Interventions:

N/A.

Main Outcome Measures:

The number of undisclosed payments, the accuracy of reporting, and the value of undisclosed payments were measured to test the hypothesis.

Results:

At the 2014 American Neurotology Society Spring Meeting, the organizers maintained a median amount of $950 and $6,525.89 for the presenters. 2015 showed a median amount of undisclosed payment of $7,134.74 for organizers and $12,256.46 for presenters. Likewise, 2016 showed a median of $4,165.14 in undisclosed payment for the organizers and $12,031.70 for the presenters.

Conclusions:

It is promising to see improvement in disclosure rates as organizers and presenters are effectively complying with the requirements set by Accreditation Council for Continuing Medical Education. However, there is a substantial difference in disclosures by the presenters group compared with the organizers. The presenters had more undisclosed financial relationships than the organizers and although, not all undisclosed financial relationships are actual conflict of interest, it is safer and better practice to avoid the potential for undisclosed conflict of interest altogether. Presenters should be encouraged to fully disclose all relationships in the manner that organizers are required to do so.
Expansion of phenotype of DDX3X syndrome: six new cases
Authors: Beal Bryony , Hayes Ian , McGaughran Julie , Amor David J. , Miteff Christina , Jackson Victoria , van Reyk Olivia , Subramanian Gopinath , Hildebrand Michael S. , Morgan Angela T. , Goel Himanshu
Published: July 2019

Pathogenic variants in DDX3X have recently been identified to be a relatively common cause of intellectual disability in females. In this study, we describe six female probands, from five unrelated families, with five novel heterozygous variants in DDX3X, and the identification of potential germline mosaicism. Consistent features between this cohort and previously described cases include developmental delay or intellectual disability, growth disturbance and movement disorder. Common facial dysmorphism within the cohort include short palpebral fissures, micrognathia, bulbous nasal tip, protruding ears, high arched palate, thin upper vermillion and smooth philtrum. Novel clinical features identified from this cohort include facial dysmorphisms, perinatal complications, valgus feet deformity, lipoatrophy, dystonic episodes, and cutaneous mastocytosis. This case series attempts to expand the phenotype of the DDX3X syndrome; however, it remains heterogeneous. Description of further cases is required to more accurately identify the significance of novel phenotypes within this cohort.
Effect and safety of LCZ696 in the treatment of hypertension
Authors: Li Qiongqiong , Li Lina , Wang Fanghao , Zhang Wei , Guo Yipeng , Wang Fuzhen , Liu Youxia , Jia Junya , Lin Shan
Published: July 2019

Background:

LCZ696 has been introduced in patients with hypertension in several trials. Here, we performed a meta-analysis to evaluate the effect and safety of LCZ696 in hypertensive patients.

Methods:

PubMed, Embase, the Cochrane Library and ClinicalTrials.gov databases were searched to identify the available randomized controlled trials (RCTs) investigating the effect and safety of LCZ696 in hypertension patients. The last search date was October 31, 2018.

Results:

Nine RCTs with 6765 subjects were finally included, in which 8 trials compared the effect and safety between LCZ696 and angiotensin receptor antagonists (ARBs). Evidences showed LCZ696, compared with ARBs, achieved a better blood pressure control rate (OR 1.24, 95% CI: 1.14–1.35), specifically, LCZ696 were better at reducing systolic blood pressure [WMD −4.11 mmHg, 95% CI: (−5.13, −3.08) mmHg], diastolic blood pressure [WMD −1.79 mmHg, 95% CI: (−2.22, −1.37) mmHg], mean 24-hour ambulatory systolic blood pressure [WMD −3.24 mmHg, 95% CI: (−4.48, −1.99) mmHg] and mean 24-hour ambulatory diastolic blood pressure [WMD −1.25 mmHg, 95% CI: (−1.81, −0.69) mmHg]. There was no difference in the events of adverse events (risk ratio [RR] 1.01, 95% CI: 0.39–1.09), serious adverse events (RR 0.80, 95% CI: 0.52–1.22) and discontinuation of treatment for any adverse events (RR 0.79, 95% CI: 0.56–1.11) between LCZ696 group and ARB/placebo group, except LCZ696 reduced the rate of headaches (RR 0.69, 95% CI: 0.48-0.99) while increased cough (RR 2.12, 95% CI: 1.11–4.04; P = .02; I

2
= 25%).

Conclusion:

Our finding provides evidence that LCZ 696 was more effective than ARB on blood pressure control and was safe enough in patients with hypertension.
Fabry disease and immunoglobulin A nephropathy presenting with Alport syndrome-like findings
Authors: Ren Hang , Li Lin , Yu Jiyun , Wu Shan , Zhou Shanshan , Zheng Yang , Sun Weixia
Published: July 2019

Rationale:

Fabry's disease is an X-linked inherited syndrome. Herein, we presented an unusual case of Fabry disease coexisting with immunoglobulin A nephropathy (IgAN) presenting with Alport syndrome-like pathological findings.

Patient concerns:

We report a 30-year-old male who presented with proteinuria and elevated serum creatinine and for whom the initial pathologic diagnosis supported Alport syndrome.

Diagnoses:

A diagnosis of Fabry disease with immunoglobulin A nephropathy (IgAN) was finally made after further examination.

Interventions:

After the initial diagnosis the patient was treated with herbal medications and mecobalamin.

Outcomes:

The patient was discharged 1 week later. He was maintained on these treatments and received regular follow-up in our hospital.

Lessons subsections as per style:

FD coexisting with IgAN is rare and may have nonspecific clinical presentations. Laboratory examination and genetic diagnosis is needed for confirmation. Timely diagnosis and reproductive intervention is needed for therapy.
Risk factors for velopharyngeal dysfunction following orthognathic surgery in the cleft population
Authors: Vella Joseph B. , Tatum Sherard A.
Published: July 2019

Purpose of review

This article highlights important trends in speech outcomes following orthognathic surgery in the cleft lip and palate populations. The geometric changes in the velopharyngeal port caused by maxillary advancement by standard means and distraction are only one consideration in predicting speech outcomes. Myriad and variable preoperative risk factors, both anatomic and functional, have been identified in the literature because of weaknesses in experimental design and small patient populations. Therefore, elucidating risk factors for postoperative velopharyngeal dysfunction remains a challenge in our field.

Recent findings

Recent pharyngeal morphologic studies using computed tomography demonstrate volumetric discrepancies in the unilateral and bilateral cleft lip and palate populations before and after orthognathic surgery, suggesting differing requirements of velar adaptation among these two populations. Perceptual and instrumental speech evaluation studies and cephalometric correlates revisit ‘borderline’ velopharyngeal insufficiency and isolate preoperative velar length as a risk factor for velopharyngeal dysfunction following orthognathic surgery.

Research design heterogeneity, small patient populations, and inherent risk of bias of retrospective reviews obscure velopharyngeal dysfunction risk factor identification prior to orthognathic surgery. However, recent reports on the volumetric changes in the pharyngeal airway and preoperative ‘borderline’ velopharyngeal insufficiency and velar length offer improved predictive value in anticipating postoperative velopharyngeal dysfunction.
Challenges in the Diagnosis of Medulloblastoma Recurrence at an Unusual Site in a Patient With Prader-Willi Syndrome
Authors: Panagopoulou Paraskevi , Sattar Shaista , Aquilina Kristian , Jan Wajanat , Jacques Thomas , Slater Olga
Published: July 2019

Medulloblastoma is the most common malignant pediatric brain tumor. Survival rates range between 50% and 80% depending on histology and other biologic features, metastases, and treatment approach. Prader-Willi syndrome (PWS) is a genetically inherited disorder characterized by dysmorphic features, mental retardation, obesity, and hypogonadism among other features. We describe a 10.5-year-old girl with PWS and previous standard-risk medulloblastoma that relapsed in the pons 3 years after the end of treatment. Diagnosis of relapse was delayed by a preceding varicella infection, an initial clinical/radiologic response to steroids and the unusual location, and was confirmed with a stereotactic biopsy. Second-line therapy was commenced, however, the patient rapidly deteriorated and died. This is the first report of medulloblastoma in a patient with PWS.
Using Deliberate Practice and Simulation for Psychomotor Skill Competency Acquisition and Retention
Authors: Johnson Cynthia E. , Kimble Laura P. , Gunby Susan Sweat , Davis Alison H.
Published: July 2019

Background

Quality, safe patient care is dependent on graduates who are proficient in the psychomotor skills of nursing. Competent skill acquisition and retention are key to reducing skill-based errors and reducing the risk of adverse patient events.

Purpose

The purpose of this study was to explore the effect of deliberate practice combined with skill practice during high-fidelity simulation (HFS) scenarios on urinary catheter insertion skill competency and retention in prelicensure nursing students.

Methods

A convergent, parallel mixed-methods design was used.

Results

The group participating in skill practice before and during HFS scenarios demonstrated a reduction in errors when performing the skill and an improvement in retention of skill competency.

Conclusions

This article describes how the combination of deliberate skill practice prior to and during HFS scenarios may improve student skill acquisition and retention.
Hypercapnia Impairs Vasoreactivity to Changes in Blood Pressure and Intraocular Pressure in Rat Retina
Authors: Liu Guodong , Cull Grant , Wang Lin , Bui Bang V.
Published: July 2019

SIGNIFICANCE

The balance between oxygen and carbon dioxide sets the resting tone (or diameter) of retinal blood vessels. Eyes that are hypercapnic use up their “vasodilatory reserve” and therefore fail to respond adequately to changes in intraocular or blood pressure.

PURPOSE

Retinal vessels are regulated by both myogenic and metabolic mechanisms. We considered whether alteration of metabolic status would modify the vascular response to ocular perfusion pressure (OPP) lowering in rat retina.

METHODS

In pentobarbital anesthetized adult Brown-Norway rats, normocapnia or hypercapnia was achieved by artificially ventilating animals with air or 5% carbon dioxide in ~30% oxygen, respectively. Ocular perfusion pressure was gradually reduced to ~20 mmHg by either lowering blood pressure (slowly drawing blood from a femoral artery/vein) or manometrically increasing intraocular pressure under normocapnic or hypercapnic conditions. In all four groups (n = 7 eyes for each), a confocal scanning laser ophthalmoscope was used to acquire image sequences centered on the optic nerve throughout pressure modification. The diameter of arterioles and venules at various OPP levels was measured and expressed as percentage relative to their own baseline. The response of arterioles and venules to OPP lowering was compared between normocapnic and hypercapnic groups.

RESULTS

Average arterial carbon dioxide partial pressures were 36.9 ± 2.6 mmHg in normocapnic and 64.1 ± 5.9 mmHg in hypercapnic (P < .001) animals. In the normocapnic groups, blood pressure lowering and intraocular pressure elevation resulted in significant vasodilation of both arterioles and venules (P < .0001). In the hypercapnic groups, OPP lowering–induced vasodilation was significantly attenuated compared with the corresponding normocapnic groups (P < .0001 for both, two-way analysis of variance).

CONCLUSION

Hypercapnia significantly modified myogenic vascular autoregulation in response to OPP reduction.
Fatality Due to Button Battery Lodgment in the Upper Digestive Tract of a Neonate
Authors: Janarthanan Venkatesh , Moorthi Kumaran , Shaha Kusa Kumar
Published: July 2019

Foreign body ingestion is not uncommonly seen in children, with most such ingestions occurring between 6 months to 3 years of age. Button battery ingestion constitutes approximately 2% of all ingested foreign bodies in children. Button batteries are disc-shaped power units used for various electronic appliance, gadgets, and toys and often contain various toxic chemical substances such as heavy metal salts and alkali. Button batteries may become lodged in the upper digestive tract, producing severe damage to the adjacent tissues by various mechanisms. A death of a neonate due to a button battery lodging in the upper digestive tract leading to tracheoesophageal fistula and esophageal perforation is presented. To the best of authors' knowledge, the present case is the youngest death reported due to button battery lodgment, and the challenges of investigation in such a case are discussed.
Pilot Trial of the Performance of Electrocardiogram in the Evaluation of Childhood Syncope in the Emergency Department
Authors: Gonzalez-Garcia Javier , Fernandez-Alvarez Ramon , Angelats Carlos M. , Ballestero Yolanda , Martinez Jaime , Mintegi Santiago
Published: July 2019

Introduction

The electrocardiogram (ECG) is widely considered a standard part of the syncope workup, and it is recommended to be obtained in all children with syncope. Nevertheless, a newly recognized cardiac cause is rare and largely incidental findings are commonly seen, leading to unneeded worry, additional testing, and added health care costs.

Objective

The aim of this study was to analyze the performance of ECG in the evaluation of childhood syncope in the emergency department (ED).

Methods

This was a descriptive, retrospective, multicenter pilot study of patients younger than 14 years diagnosed with syncope in which an ECG was obtained in the ED in 2015 and 2016.

Results

During the study period, 440 patients were diagnosed with syncope, of which an ECG was performed in 197 (44.7%). Of these, 64 (32.5%) were related to any concerning features associated with the event, including 33 occurring during or after physical exertion. No major alteration of the ECG was noted, and the ECG revealed multiple minor findings in 38 (19.2%; 95% confidence interval, 14.4–25.4). Twenty-five (12.7%) children were referred to a pediatric cardiologist. No patient was noted to have a previously undiagnosed cardiac cause of syncope.

Conclusions

A newly recognized cardiac cause is extremely rare among children evaluated for syncope in the ED, and ECG is not systematically obtained in this population. Larger studies are needed to clarify if it is possible to identify a group of children that can be safely managed without a systematic ECG. Best practices need to be better implemented for an adequate management of pediatric syncope in the ED.
A Community Capitals Framework for Identifying Rural Adaptation in Maternal-Child Home Visiting
Authors: Whittaker Jennifer , Kellom Katherine , Matone Meredith , Cronholm Peter
Published: July 2019

Objective:

To understand how maternal and child home-visiting programs are adapted, enhanced, and expanded to meet the unique needs of rural communities.

Design:

We explored factors shaping the role of home visiting with data from a 2013-2015 statewide evaluation of Maternal, Infant, and Early Childhood Home Visiting–funded programs. Features unique to a rural experiences were mapped onto the Community Capitals Framework.

Setting:

Individual, semistructured interviews were conducted at 11 of 38 home-visiting sites across Pennsylvania.

Participants:

Program administrators, home visitors, and clients.

Main Outcome Measure:

Program adaptation.

Results:

Our analysis represents 150 interviews with 11 program sites serving 14 counties. We document how rural home-visiting programs address community-wide limitations to maternal and child health by adapting program content to better meet the needs of families in rural areas. Data demonstrate how rural home-visiting program's provision of economic and social services reach beyond maternal child health care, building the capacity of individual families and the broader community.

Conclusions:

Home-visiting programs should be viewed as a vehicle for improving community well-being beyond health outcomes. These programs have become an integral part of our public health framework and should be leveraged as such.
Functional and histological improvements of small nerve neuropathy after high-concentration capsaicin patch application: A case study
Authors: Trouvin Anne-Priscille , Perrot Serge
Published: July 2019

Introduction:

Small fiber neuropathy has been found to occur in a large variety of pathological onditions, and the gold standard for diagnosis of small fiber neuropathy is skin biopsy. Sudorimetry is now considered an accurate technique to evaluate small fiber function with a good sensitivity and specificity for the diagnosis of small fiber neuropathy. Capsaicin high-concentration patch is approved for the treatment of peripheral neuropathic pain in adults either alone or in combination with other medicinal products for pain.

Methods:

We describe the case of a 50-year-old woman diagnosed with small fiber neuropathy. After 2 previous treatment failures, she was proposed a treatment with high-dose capsaicin patches on the sole of her foot. The patient experienced an important diminution of her neuropathic pain. There was a 50% decrease in the pain numeric scale. Electrochemical skin conductance and skin biopsy were repeated 3 months after patch application.

Results:

At 3 months, the patient then experienced an important diminution of her neuropathic pain, electrochemical skin conductance had normalized both in the hands and feet and intraepidermal nerve fiber density at distal leg increased almost reaching normal range.

Conclusion:

This case report shows the correlation between clinical improvement, electrochemical skin conductance normalization, and intraepidermal nerve fiber density improvement after a high-dose capsaicin patch in a patient with small fiber neuropathy.
Tissue-Engineered Soft-Tissue Reconstruction Using Noninvasive Mechanical Preconditioning and a Shelf-Ready Allograft Adipose Matrix
Authors: Giatsidis Giorgio , Succar Julien , Waters Trevon D. , Liu Wenyue , Rhodius Patrick , Wang Chenglong , Nilsen Todd J. , Chnari Evangelia , Orgill Dennis P.
Published: July 2019

Background:

Adipose tissue defects leading to severe functional (disability) and morphologic (disfigurement) morbidity are often treated in plastic surgery with fat grafting, which can be limited by resorption, necrosis, and cyst formation. This study aimed to assess whether adipose scaffolds could provide an environment for in situ autologous fat grafting, and to study whether adipose cell migration and proliferation (adipogenesis) within scaffolds could be enhanced by preliminarily increasing the vascularity (preconditioning) of the surrounding tissue receiving the scaffolds.

Methods:

Using an established rodent model of subcutaneous tissue/scaffold grafting, the authors tested the potential of a human-derived, shelf-ready, injectable, decellularized allograft adipose matrix to reconstruct soft-tissue defects when used in combination with noninvasive mechanical (suction-induced) skin preconditioning.

Results:

Combined use of the allograft adipose matrix and noninvasive skin preconditioning significantly improved long-term volume retention (50 to 80 percent higher at a 12-week follow-up) and histologic quality of reconstructed tissues compared with standard of care (autologous adipose grafts). The components of the allograft adipose matrix supported adipogenesis and angiogenesis. Combining the allograft adipose matrix with living adipose grafts mitigated negative outcomes (lower long-term volume retention, higher presence of cystic-like areas).

Conclusions:

This study suggests that the synergistic use of the allograft adipose matrix and noninvasive tissue preconditioning provides an effective solution for improving fat grafting. These strategies can easily be tested in clinical trials and could establish the basis for a novel therapeutic paradigm in reconstructive surgery.
Adult Living Donor Versus Deceased Donor Liver Transplant (LDLT Versus DDLT) at a Single Center
Authors: Humar Abhinav , Ganesh Swaytha , Jorgensen Dana , Tevar Amit , Ganoza Armando , Molinari Michele , Hughes Christopher
Published: July 2019

Objective:

The aim of this study was to compare outcomes between living donor liver transplant (LDLT) and deceased donor liver transplant (DDLT) at a single center to demonstrate the advantages of LDLT and provide justification for the increased utilization and application of this procedure.

Summary of Background Data:

LDLT comprises a very small percentage of all liver transplants performed in the United States, this despite its advantages and a shortage of the availability of deceased donor organs.

Methods:

A retrospective review of all adult LDLT (n = 245) and DDLT (n = 592) performed at a single center over 10 years (2009–2019), comparing survival outcomes by Kaplan-Meier analysis and comparing other measures of outcome such as recovery times, complications, costs, and resource utilization.

Results:

Patient survival outcomes were superior in LDLT recipients (3-year 86% vs 80%, P = 0.03). Other outcomes demonstrated shorter length of hospital stay (11 vs 13 days, P = 0.03), less likelihood of intraoperative blood transfusion (52% vs 78%, P < 0.01), and less likelihood of need for posttransplant dialysis (1.6% vs 7.4%, P < 0.01). Early reoperation and biliary/vascular complication rates were similar. Hospital costs related to the transplant were 29.5% lower for LDLT. Complications in living donors were acceptable with no early or late deaths, 3-month reoperation rate of 3.1%, and overall complication rate of 19.5%. Given its advantages, we have expanded LDLT—in 2018, LDLT comprised 53.6% of our transplants (national average 4.8%), and our transplant rate increased from 44.8 (rate per 100-person years) in 2015 to 87.5 in 2018.

Conclusions:

LDLT offers advantages over DDLT including superior outcomes and less resource utilization. The time has come to change the paradigm of how LDLT is utilized in this country.
Multilocus Mitochondrial Mutations Do Not Directly Affect the Efficacy of Gene Therapy for Leber Hereditary Optic Neuropathy
Authors: Yang Shuo , Chen Chen , Yuan Jia-Jia , Wang Shuai-Shuai , Wan Xing , He Heng , Ma Si-Qi , Li Bin
Published: July 2019

Purpose:

Clinical trials of gene therapy for Leber hereditary optic neuropathy (LHON) were conducted in 9 volunteers with the mitochondrial mutation, G11778A in ND4. The purpose of this study was to investigate whether multilocus mitochondrial mutations directly influence the efficacy of gene therapy for LHON.

Methods:

Nine volunteers with LHON participated in a clinical trial with intravitreal injection of an adenoviral vector expressing wild-type ND4. Patients were subsequently divided into 2 groups: according to the differences in therapy efficacy and based on improvements in visual acuity. Full mitochondrial DNA sequences of the 2 groups of patients were generated and compared using PubMed, PolyPhen, and PROVEAN. Furthermore, the association between the detected mutations and clinical effects of gene therapy was analyzed.

Results:

Best-corrected visual acuity (BCVA) significantly improved (≥0.3 log of minimum angle of resolution [logMAR]) in 7 patients 6 months after gene therapy, whereas there was no significant change in BCVA (<0.3 logMAR) of the remaining 2 patients. All 9 patients carried the G1178A mutation in addition to other nonsynonymous mutations. Among these mutations, some were predicted to be neutral and deleterious. Meanwhile, different mitochondrial mutations in the group in which treatment was ineffective, compared with those in responders, were at nucleotide positions 6569 (CO1; Patient 3), 9641 (CO3; Patient 3), and 4491 (ND2; Patient 5).

Conclusions:

Detection of the 3 primary mitochondrial mutations causing LHON is sufficient for screening before gene therapy; sequencing of the entire mitochondrial genome is unnecessary before treatment. Patients with LHON can respond to targeted gene therapy irrespective of additional multilocus mitochondrial mutations.
A phylogenetic model for the recruitment of species into microbial communities and application to studies of the human microbiome
Authors: Darcy John L. , Washburne Alex D. , Robeson Michael S. , Prest Tiffany , Schmidt Steven K. , Lozupone Catherine A.
Published: July 2019

Understanding when and why new species are recruited into microbial communities is a formidable problem with implications for managing microbial systems, for instance by helping us better understand whether a probiotic or pathogen would be expected to colonize a human microbiome. Much theory in microbial temporal dynamics is focused on how phylogenetic relationships between microbes impact the order in which those microbes are recruited; for example species that are closely related may competitively exclude each other. However, several recent human microbiome studies have observed closely-related bacteria being recruited into microbial communities in short succession, suggesting that microbial community assembly is historically contingent, but competitive exclusion of close relatives may not be important. To address this, we developed a mathematical model that describes the order in which new species are detected in microbial communities over time within a phylogenetic framework. We use our model to test three hypothetical assembly modes: underdispersion (species recruitment is more likely if a close relative was previously detected), overdispersion (recruitment is more likely if a close relative has not been previously detected), and the neutral model (recruitment likelihood is not related to phylogenetic relationships among species). We applied our model to longitudinal human microbiome data, and found that for the individuals we analyzed, the human microbiome generally follows the underdispersion (i.e. nepotism) hypothesis. Exceptions were oral communities and the fecal communities of two infants that had undergone heavy antibiotic treatment. None of the data sets we analyzed showed statistically significant phylogenetic overdispersion.
Structure of D. melanogaster ARC1 reveals a repurposed molecule with characteristics of retroviral Gag
Authors: Cottee Matthew A. , Letham Suzanne C. , Young George R. , Stoye Jonathan P. , Taylor Ian A.
Published: July 2019

The tetrapod neuronal protein ARC and its D. melanogaster homologue, dARC1, have important but differing roles in neuronal development. Both are thought to originate through exaptation of ancient Ty3/Gypsy retrotransposon Gag genes, with their novel function relying on an original capacity for self-assembly and encapsidation of nucleic acids. Here, we present the crystal structure of dARC1 CA and examine the relationship between dARC1, mammalian ARC and the CA protein of circulating retroviruses. We show that whilst the overall architecture is highly related to that of orthoretroviral and spumaretroviral CA, there are significant deviations in both N- and C-terminal domains, potentially affecting recruitment of partner proteins and particle assembly. The degree of sequence and structural divergence suggests that Ty3/Gypsy Gag has been exapted on two separate occasions and that, although mammalian ARC and dARC1 share functional similarity, the structures have undergone different adaptations after appropriation into the tetrapod and insect genomes.
Resting-state network topology and planning ability in healthy adults
Authors: Vriend Chris , Wagenmakers Margot J. , van den Heuvel Odile A. , van der Werf Ysbrand D.
Published: July 2019

Functional magnetic resonance imaging (fMRI) studies have been used extensively to investigate the brain areas that are recruited during the Tower of London (ToL) task. Nevertheless, little research has been devoted to study the neural correlates of the ToL task using a network approach. Here we investigated the association between functional connectivity and network topology during resting-state fMRI and ToL task performance, that was performed outside the scanner. Sixty-two (62) healthy subjects (21-74 years) underwent eyes-closed rsfMRI and performed the task on a laptop. We studied global (whole-brain) and within subnetwork resting-state topology as well as functional connectivity between subnetworks, with a focus on the default-mode, fronto-parietal and dorsal and ventral attention networks. Efficiency and clustering coefficient were calculated to measure network integration and segregation, respectively, at both the global and subnetwork level. Our main finding was that higher global efficiency was associated with slower performance (β = .22, Pbca = .04) and this association seemed mainly driven by inter-individual differences in default-mode network connectivity. The reported results were independent from age, sex, education-level and motion. Although this finding is contrary to earlier findings on general cognition, we tentatively hypothesize that the reported association may indicate that individuals with a more integrated brain during the resting-state are less able to further increase network efficiency when transitioning from a rest to task state, leading to slower responses. This study also adds to a growing body of literature supporting a central role for the default-mode network in individual differences in cognitive performance.
A CRISPR/Cas9 mediated 53 kb deletion of the NRC4 gene cluster of tomato does not affect bacterial flagellin-triggered immunity
Authors: Wu Chih-Hang , Adachi Hiroaki , De la Concepcion Juan Carlos , Castells-Graells Roger , Nekrasov Vladimir , Kamoun Sophien
Published: July 2019

Plants utilise cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding domain leucine-rich repeat containing receptors (NLRs) to fend off invading pathogens. Although PRR- and NLR-triggered immunity are generally thought to activate distinct pathways, they can induce similar outputs. However, whether these two pathways converge at some point to potentiate and strengthen the immune response remains unclear. For instance, the extent to which the tomato NLR helper NRC4 is implicated in response to the bacterial flagellin peptide flg22 needs to be elucidated. One challenge is that the tomato NRC4 gene cluster consists of three paralogues and the related NRC5 gene. Here, we took advantage of the CRISPR/Cas9 system to generate a tomato mutant with a 53 kb deletion that encompasses the four NRC genes. Although this mutant failed to respond to the NRC4-dependent NLR Rpi-blb2, it remained unaltered in flg22-induced responses. We conclude that the NRC4 genes are not essential for flg22-induced responses in tomato.
Proteins required for vacuolar function are targets of lysine polyphosphorylation in yeast
Authors: McCarthy Liam , Bentley-DeSousa Amanda , Denoncourt Alix , Tseng Yi-Chieh , Gabriel Matthew , Downey Michael
Published: July 2019

Polyphosphates (polyP) are long chains of inorganic phosphates that can be attached to lysine residues of target proteins as a non-enzymatic post-translational modification. This modification, termed polyphosphorylation, may be particularly prevalent in bacterial and fungal species that synthesize and store large quantities of polyP. In this study, we applied a proven screening strategy to evaluate the polyphosphorylation status of over 200 candidate targets in the budding yeastS. cerevisiae.We report 8 new polyphosphorylated proteins that interact genetically and physically with a previously identified network of targets implicated in ribosome biogenesis. The expanded target network includes vacuolar proteins Prb1 and Apl5, whose modification with polyP suggests a model for feedback regulation of polyP synthesis, while raising additional questions regarding the location of polyphosphorylationin vivo.
Emergence of consciousness and complexity amidst diffuse delta rhythms: the paradox of Angelman syndrome
Authors: Frohlich Joel , Bird Lynne M. , Dell’Italia John , Johnson Micah A. , Hipp Joerg F. , Monti Martin M.
Published: July 2019

Numerous theories link consciousness to informationally rich, complex neural dynamics. This idea is challenged by the observation that children with Angelman syndrome (AS), while fully conscious, display a hypersynchronous electroencephalogram (EEG) phenotype typical of information-poor dynamics associated with unconsciousness. If informational complexity theories are correct, then sufficiently complex dynamics must still exist during wakefulness and exceed that observed in sleep despite pathological delta (1 – 4 Hz) rhythms in children with AS. As characterized by multiscale metrics, EEGs from 35 children with AS feature significantly greater complexity during wakefulness compared with sleep, even when comparing the most pathological segments of wakeful EEG to the segments of sleep EEG least likely to contain conscious experiences, and when factoring out delta power differences across states. These findings support theories linking consciousness with complexity and warn against reverse inferring an absence of consciousness solely on the basis of clinical readings of EEG.
A Survey and Systematic Assessment of Computational Methods for Drug Response Prediction
Authors: Chen Jinyu , Zhang Louxin
Published: July 2019

Drug response prediction arises from both basic and clinical research of personalized therapy, as well as drug discovery for cancer and other diseases. With gene expression profiles and other omics data being available for over 1000 cancer cell lines and tissues, different machine learning approaches have been applied to solve drug response prediction problems. These methods appear in a body of literature and have been evaluated on different datasets with only one or two accuracy metrics. We systematically assessed 17 representative methods for drug response prediction, which have been developed in the past five years, on four large public datasets in nine metrics. This study provides insights and lessons for future research into drug response prediction.
Timescales of motor memory formation in dual-adaptation
Authors: Forano Marion , Franklin David W.
Published: July 2019

The timescales of adaptation to novel dynamics are well explained by a dual-rate model with slow and fast states. This model can predict interference, savings and spontaneous recovery, but cannot account for adaptation to multiple tasks, as each new task drives unlearning of the previously learned task. Nevertheless, in the presence of appropriate contextual cues, humans are able to adapt simultaneously to opposing dynamics. Consequently this model was expanded, suggesting that dual-adaptation occurs through a single fast process and multiple slow processes. However, such a model does not predict spontaneous recovery within dual-adaptation. Here we assess the existence of multiple fast processes by examining the presence of spontaneous recovery in two experimental variations of an adaptation-de-adaptation-error-clamp paradigm within dual-task adaptation in humans. In both experiments, evidence for spontaneous recovery towards the initially learned dynamics (A) was found in the error-clamp phase, invalidating the one-fast-two-slow dual-rate model. However, as adaptation is not only constrained to two timescales, we fit twelve multi-rate models to the experimental data. BIC model comparison again supported the existence of two fast processes, but extended the timescales to include a third rate: the ultraslow process. Even within our single day experiment, we found little evidence for decay of the learned memory over several hundred error-clamp trials. Overall, we show that dual-adaptation can be best explained by a two-fast-triple-rate model over the timescales of adaptation studied here. Longer term learning may require even slower timescales, explaining why we never forget how to ride a bicycle.

Author Summary

Retaining motor skills is crucial to perform basic daily life tasks. However we still have limited understanding of the computational structure of these motor memories, an understanding that is critical for designing rehabilitation. Here we demonstrate that learning any task involves adaptation of independent fast, slow and ultraslow processes to build a motor memory. The selection of the appropriate motor memory is gated through a contextual cue. Together this work extends our understanding of the architecture of motor memories, by merging disparate computational theories to propose a new model.