bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of Initial Pancreatic Enzyme Replacement Therapy Dose With Weight Gain in Infants With Cystic Fibrosis
Authors: Schechter Michael S. , Michel Suzanne , Liu Shufang , Seo B. Woun , Kapoor Mudra , Khurmi Rupal , Haupt Mark
Published: July 2018

Objective:

The aim of the study is to test the hypothesis of a positive relationship between initial dose of pancreatic enzyme replacement therapy (PERT) in infants with cystic fibrosis (CF) and optimal weight gain over the first 2 years of life.

Methods:

Using the CF Foundation Patient Registry, we identified 502 children born in 2010 and used multivariable models to compare as our primary analysis their 2‐year changes in weight‐for‐age z score (WAZ) and as our secondary analysis weight‐for‐length percentile (W/L%) by initial PERT dose. We focused on initial dose without reference to subsequent changes in treatment to avoid confounding by indication (severity).

Results:

Initial PERT dose demonstrated a linear relationship to change in WAZ and W/L% at age 2 years. An initial dose of >1500 lipase units/kg/largest meal resulted in a higher likelihood of attaining WAZ at 2 years at or above the birth WAZ (adjusted odds ratio [aOR] 1.87, 95% confidence interval [CI] 1.22–2.86) and at the top quartile for improvement over 2 years in WAZ (aOR 1.90, 95% CI 1.19–3.05). There was no correlation between initial PERT dose and weight at initial PERT encounter (P = 0.35). Findings were similar for W/L% and when the cohort was restricted to infants who began PERT in the first 3 months of life.

Conclusions:

Infants receiving higher initial PERT dose demonstrate better weight‐related outcomes, as reflected by attainment of favorable changes in WAZ and W/L%, at age 2 years.
In Screening for Celiac Disease, Deamidated Gliadin Rarely Predicts Disease When Tissue Transglutaminase Is Normal
Authors: Gould Michelle J. , Brill Herbert , Marcon Margaret A. , Munn Natalie J. , Walsh Catharine M.
Published: July 2018

Objective:

While tissue transglutaminase (tTG) antibodies are the most established serological test for celiac disease, newer deamidated gliadin peptide (DGP) screening tests are increasingly being completed. No pediatric study has systematically assessed the incidence of celiac disease in patients with an isolated positive DGP result. We sought to determine the positive predictive value of DGP serology for biopsy‐confirmed celiac disease in pediatric patients with elevated DGP and normal tTG, to help guide clinicians’ decision making when screening for this common condition and avoid unnecessary invasive follow‐up diagnostic testing.

Methods:

A multicenter retrospective review of children, from birth to age 18, with isolated DGP immunoglobulin G (IgG) positive serology referred to 3 Canadian centers was completed. The positive predictive value of an isolated elevated DGP result was calculated.

Results:

Forty patients with DGP positive, tTG negative serology underwent endoscopy with duodenal biopsy. Of these, only 1 patient had biopsy‐confirmed celiac disease. This patient was IgA deficient. This yields a positive predictive value of 2.5% (95% confidence interval 0.1%–14.7%) for isolated DGP IgG positive serology.

Conclusions:

In isolation, DGP positive serology has a poor positive predictive value for celiac disease in children, especially in IgA sufficient individuals. Our findings suggest that DGP IgG testing should not be completed as part of the initial screening for celiac disease in the pediatric population as it does not effectively differentiate between individuals with and without the disease. Further research is needed to clarify to role of DGP IgG in children under the age of 2 and those with IgA deficiency.
Assessing the Role of Cattle in Sustainable Food Systems
Authors: Layman Donald K.
Published: July 2018

Food production has a global link to the environment. As the world population increases, there are ever expanding demands on agriculture, but there are also increasing concerns about the impact of agriculture on the environment. Initial attempts to measure the impact of agriculture on the environment used a metric of greenhouse gas emissions/kcal of food produced to assess the relative impact of different foods and agriculture practices. This metric highlights the differential costs for production of grains versus livestock and led to conclusions that livestock have disproportionate negative impacts on the environment, leading many researchers and policy makers to call for a shift toward more plant-based diets. However, this metric implies that production of calories is the most important diet criterion and has been criticized for ignoring diet quality. One of the nutrients that must be considered in formulation of a sustainable diet is protein. Currently, livestock produces more than one-third of the world’s protein, and ruminant animals (ie, cattle, sheep and goats) have the unique capacity to convert nondigestible biomass (ie, grasses and forages) into high-quality protein. These factors highlight the need for prudent use of ruminants to optimize land use for production of adequate quantity and quality of protein. Any recommendations for changes in agriculture should consider impact on climate but must also focus on making optimal use of natural resources for creating healthy diets.
Malignant Melanoma: Diagnostic and Management Update
Authors: Knackstedt Thomas , Knackstedt Rebecca W. , Couto Rafael , Gastman Brian
Published: July 2018

Learning Objectives:

After studying this article, the participant should be able to: 1. Summarize the changes to the American Joint Committee on Cancer Eighth Edition Melanoma Staging System. 2. List advances in genetic, molecular, and histopathologic melanoma diagnosis and prognostication. 3. Recommend sentinel lymph node biopsy and appropriate surgical margins based on individualized patient needs. 4. Recognize the currently available treatments for in-transit metastasis and advanced melanoma. 5. Describe current and future therapies for melanoma with distant visceral or brain metastases.

Strides in melanoma surveillance, detection, and treatment continue to be made. The American Joint Committee on Cancer Eighth Edition Cancer Staging System has improved risk stratification of patients, introduced new staging categories, and resulted in stage migration of patients with improved outcomes. This review summarizes melanoma advances of the recent years with an emphasis on the surgical advances, including techniques and utility of sentinel node biopsy, controversies in melanoma margin selection, and the survival impact of time-to-treatment metrics. Once a disease manageable only with surgery, a therapeutic paradigm shift has given a more promising outlook to melanoma patients at any stage. Indeed, a myriad of novel, survival-improving immunotherapies have been introduced for metastatic melanoma and more recently in the high-risk adjuvant setting.
Improving Safety after Abdominoplasty: A Retrospective Review of 1128 Cases
Authors: Dutot Marie-Charlotte , Serror Kevin , Al Ameri Omar , Chaouat Marc , Mimoun Maurice , Boccara David
Published: July 2018

Background:

Over the course of several decades, abdominoplasty has undergone numerous improvements, thereby improving patient safety. The choice of the site of the incision and the extent of the detachment directly influence the occurrence of the main complications.

Methods:

A retrospective study was carried out involving 1128 patients who underwent abdominoplasty between January of 1990 and June of 2014. The main postoperative complications were analyzed.

Results:

The hematoma rate was 5.7 percent; in addition, infections (4.5 percent), cutaneous necrosis (2.7 percent), seromas (2.7 percent), disunions (1.3 percent), and deep venous thrombosis (0.2 percent) were observed. Three main risk factors for complications were highlighted: age older than 40 years, obesity, and smoking. The authors noted a significant variation in the rate of complications depending on the technique used, with a substantial rate of necrosis in case of inverted-T abdominoplasty. Liposuction was not a source of complications, regardless of the patient’s background or the type of intervention.

Conclusions:

Abdominoplasty is currently a reliable technique that allows the abdomen to be repaired and quality of life to be restored. Other means remain to be explored to improve the overall treatment and to move toward a maximal reduction of the risks.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Medicare for the Plastic and Reconstructive Surgeon
Authors: Firouzbakht Peter K. , Israel Jacqueline S. , Chen Jenny T. , Rao Venkat K.
Published: July 2018

Medicare, a federally funded insurance program in the United States, is a complex program about which many physicians may not receive formal training or education. Plastic surgeons, residents, and advanced practitioners may benefit from at least a basic understanding of Medicare, its components, reimbursement methods, and upcoming health care trends. Medicare consists of Parts A through D, each responsible for a different form of insurance coverage. Medicare pays hospitals, physicians, and graduate medical education. Since the introduction of Medicare, several reforms and programs have been introduced, particularly in recent years with the implementation of the Affordable Care Act. Many of these changes are moving reimbursement systems away from the traditional fee-for-service model toward quality-of-care programs. The aim of this review is to provide a brief history of Medicare, explain the basics of coverage and relevant reforms, and describe how federal insurance programs relate to plastic surgery both at academic institutions and in a community practice environment.
Gluteal Ligamentous Anatomy and Its Implication in Safe Buttock Augmentation
Authors: Ghavami Ashkan , Villanueva Nathaniel L. , Amirlak Bardia
Published: July 2018

Background:

The number of buttock augmentations with fat transfer is steadily increasing, but a number of fatalities caused as a direct result of gluteal fat grafting have been reported. The technical details relating to cannula size, injection angle or trajectory, and plane of injection are critical for avoiding morbidity and mortality. However, the ligamentous anatomy has not been thoroughly explored, particularly how the ligaments are encountered in the clinical setting of fat transfer by means of cannulas.

Methods:

The gluteal regions of five fresh cadavers were dissected, for a total of 10 hemidissections. All pertinent cutaneous ligaments in the region were identified. In addition, cannulas were used to simulate typical variations in injection planes.

Results:

The osseocutaneous and fasciocutaneous ligaments of the buttocks were identified.

Conclusions:

The authors describe important ligamentous structures consistently found in the region in cadaveric dissections and discuss the implications while safely performing gluteal augmentation. The anatomical features, boundaries, and soft-tissue attachment points may play a role in cannula-directed fat injection misguidance. The ligaments, when not released, can lead to undesired deep injection and therefore fat lobule migration into the venous system. The density, danger zones, and soft-tissue attachments must be clarified further as we continue to offer our patients improved buttock contour with a higher safety profile.
Food Insecurity and Odds of High Allostatic Load in Puerto Rican Adults: The Role of Participation in the Supplemental Nutrition Assistance Program During 5 Years of Follow-Up
Authors: McClain Amanda C. , Xiao Rui S. , Gao Xiang , Tucker Katherine L. , Falcon Luis M. , Mattei Josiemer
Published: July 2018

Objective

Limited evidence demonstrates pathways linking food insecurity (FI) to chronic disease. Allostatic load (AL) may elucidate potential pathways, capturing both primary (neuroendocrine, inflammation) and secondary (metabolic, cardiovascular) physiological disturbances. We examined the longitudinal association of FI with 5-year AL and primary and secondary subsystem dysregulation and tested moderation by Supplemental Nutrition Assistance Program (SNAP) participation.

Methods

We analyzed data from the longitudinal Boston Puerto Rican Health Study among 733 adults aged 45 to 75 years. Participants categorized as food insecure (assessed by US survey module) experienced FI at baseline and/or year 5. AL score comprised 11 biological components (5 primary, 6 secondary). We classified participants as having high scores for AL (≥6 dysregulated components), primary system (≥3), and secondary system (≥4). Multivariate models estimated odds ratios (OR), adjusting for baseline AL, sociodemographic, cultural, and behavioral characteristics.

Results

By study end, 33.8% had experienced FI, 65.5% had participated in SNAP, and 37.5% had high AL. In adjusted models, FI was not associated with AL (OR [95% confidence intervals] = 1.07 [0.70–1.64]) or secondary system (0.82 [0.48–1.40]) scores, but was associated with high primary system scores (1.71 [1.25–2.36]). SNAP participation seemed to moderate the FI-primary system relationship (p = .06); food-insecure participants never receiving SNAP (mean (SE) = 2.06 (0.14)) had higher scores than food-secure participants receiving (1.72 (0.06], p = .02) or never receiving SNAP (1.64 (0.10), p = .01) and food-insecure participants receiving SNAP (1.80 (0.07), p = .08).

Conclusions

FI is associated with dysregulated components of the primary AL system, and this relationship may be stronger for those not receiving SNAP. Research is needed in additional populations to test AL as a plausible pathway connecting FI to chronic disease and SNAP as a moderator.
Recent insights into Shigella: a major contributor to the global diarrhoeal disease burden
Authors: Baker Stephen , The Hao Chung
Published: July 2018

Purpose of review

Diarrhoea is a major global health problem, and recent studies have confirmed Shigella as a major contributor to this burden. Here, we review recent advances in Shigella research; focusing on their epidemiology, pathogenesis, antimicrobial resistance, and the role of the gut microbiome during infection.

Recent findings

Enhanced epidemiological data, combined with new generation diagnostics, has highlighted a greater burden of Shigella disease than was previously estimated, which is not restricted to vulnerable populations in low-middle income countries. As we gain an ever more detailed insight into the orchestrated mechanisms that Shigella exploit to trigger infection, we can also begin to appreciate the complex role of the gut microbiome in preventing and inducing such infections. The use of genomics, in combination with epidemiological data and laboratory investigations, has unravelled the evolution and spread of various species. Such measures have identified resistance to antimicrobials as a key contributor to the success of specific clones.

We need to apply novel findings towards sustainable approaches for treating and preventing Shigella infections. Vaccines and alternative treatments are under development and may offer an opportunity to reduce the burden of Shigella disease and restrict the mobility of antimicrobial resistant clones.
Increase of Perfusion Index During Vascular Occlusion Test is Paradoxically Associated With Higher Mortality in Septic Shock After Fluid Resuscitation: A Prospective Study
Authors: Menezes Igor Alexandre Côrtes de , Cunha Cláudio Leinig da , Junior Hipolito Carraro , Luy Alain Márcio
Published: July 2018

Microcirculation disturbances imply poor prognosis in septic shock. Microvascular reserve can be assessed by oximetry-derived Perfusion Index (PI) after vascular occlusion test (VOT). We investigated the relationship between PI during VOT, hyperlactatemia and mortality in septic shock and the role of adrenergic stimulus in these findings. The tests were performed in 106 patients within 24 h after admission. PI was evaluated before/after 03-min flow occlusion. Peaks of PI (ΔPI peak) and time-to-peak were evaluated. PI was also evaluated in hyperemic phases derived by mechanosensitive (ΔPI0–60) and metabolic mechanisms (ΔPI60–120). We compared nonsurvivors with survivors and patients with lowest and highest ΔPI peaks, divided by 50th percentile. ΔPI peak was evaluated in presence/absence of hyperlactatemia. A correlation test between ΔPI peaks and noradrenaline doses and an assessment after doses increasing were also performed. The ΔPI peak values were higher in nonsurvivors [79% (47%–169%) vs. 48% (25%–85%); P=0.003] although peaks were reached slower in nonsurvivors. ΔPI0–60 was similar between groups [−12% (−42% to 28%) vs. 01% (−16%–23%); P = 0.211]. However, ΔPI60–120 was higher in nonsurvivors [49% (29%–84%) vs. 31% (12%–65%); P = 0.035]. Additionally, the group with higher ΔPI peaks had higher mortality than those with lower peaks [HR 2.25 (95% CI = 1.32–4.14); P = 0.003]. Mortality was extremely high in the presence of hyperlactatemia. ΔPI peaks were positively correlated with noradrenaline doses and increased after increasing doses.

In conclusion, high values of PI during VOT indicate higher mortality in septic shock and are associated with adrenergic stimulus. Additionally, the assessment of PI-VOT appears to improve the predictive value of arterial lactate.
Epidemiology of Emergency Department Sepsis: A National Cohort Study Between 2001 and 2012
Authors: Yu Chin-Wei , Chang Shy-Shin , Lai Chih-Cheng , Wu Jiunn-Yih , Yen Debra W. , Lee Meng-tse Gabriel , Yeh Chien-Chun , Chung Jui-Yuan , Lin Yu-Jiun , Lee Chien-Chang
Published: July 2018

The aim of this study is to examine the incidence trend of sepsis over 11 years and compared mortality outcomes among Taiwanese patients with sepsis admitted from emergency department (ED) and non-ED routes. We used a nationwide health insurance database from Taiwan, which comprise of 23 million beneficiaries. Patients with sepsis were identified by ICD-9 CM codes for infection and organ dysfunction from 2001 to 2012. We performed propensity score matching and compared mortality rates between ED-admitted and non ED-admitted patients.

During the 11-year study period, we identified 1,256,684 patients with sepsis. 493,397 (29.3%) were admitted through the ED, and 763,287 (70.7%) were admitted directly to the floor. For patients with sepsis, mortality in ED-admitted patients decreased from 27.2% in 2002 to 21.1% in 2012 while that in non-ED admitted patients decreased from 35.3% in 2002 to 30.7% in 2012. Although patients with sepsis admitted through the ED had a higher incidence of organ dysfunction than patients who were directly admitted, they had more favorable outcomes in mortality, length of intensive care unit stay, and hospital stay. After propensity score matching, ED-admitted patients had a 7% lower risk of 90-day mortality (HR, 0.93, 95% CI, 0.89–0.97) compared with directly admitted patients. During the study period, mortality declined faster among ED admitted sepsis patients than directly admitted sepsis patients. Results of this study should be interpreted in light of limitations. Like other administrative database studies, treatment details are not available. Further clinical studies evaluating the treatment and outcome difference between ED and non-ED admitted sepsis patients are warranted.
Delay in Seeking Care for Pelvic Floor Disorders Among Caregivers
Authors: Mishra Kavita , Locci-Molina Natalie C. , Chauhan Bhavya , Raker Christina A. , Sung Vivian W.
Published: July 2018

Objective

In 2015, 44 million adults were informal, unpaid caregivers to an adult or child. Caregiving (CG) is associated with poor self-care, higher depression rates, and decreased quality of life. Our primary objective was to determine if CG is associated with a delay in seeking care for pelvic floor disorders (PFDs).

Methods

We performed a cross-sectional survey of new urogynecology patients from September 2015 to January 2016. Subjects completed the Pelvic Floor Distress Inventory, Pelvic Floor Impact Questionnaire, Patient Reported Outcomes Measurement Information System–Depression surveys, and a survey of care-seeking practices. Caregiving was defined as considering one’s self a primary caregiver and assisting with 2 or more activities and instrumental activities of daily living. Multiple logistic regression identified variables associated with delayed care-seeking for 1 or more year.

Results

Two hundred fifty-six patients completed the survey, 82 caregivers (32%) and 174 noncaregivers (NCGs). Sixty-seven percent of caregivers cared for a child and 33% for an adult. There was no difference between caregivers and NCGs in PFD symptom duration, Pelvic Floor Distress Inventory, or Patient Reported Outcomes Measurement Information System depression scores. Caregiving had higher mean Pelvic Floor Impact Questionnaire scores (69.6 vs 51.0, P = 0.02). There was no difference in proportion of patients who delayed care for 1 year or more (42% vs 54%, P = 0.08). A higher proportion of caregivers for an adult waited for 1 year or more (75% vs 42% NCG, P = 0.001). On multiple logistic regression, CG for adults only was associated with delaying care for 1 year or more (adjusted odds ratio, 3.73; confidence interval, 1.33–10.44; P = 0.01).

Conclusions

One third of patients presenting to a urogynecology practice are caregivers. Caregiving for an adult was associated with a delay in seeking care for PFDs.
Evaluation of Interprofessional Education Implementation Among Nutrition Program Directors in the United States
Authors: Patton Zena , Vernon Marlo , Haymond Kelsey , Anglin Judith , Heboyan Vahé , De Leo Gianluca
Published: July 2018

Interprofessional education (IPE) promotes multidisciplinary learning to encourage team collaboration and improved patient outcomes. This study investigates the beliefs, application, and structure of IPE within programs accredited by the Accreditation Council for Education in Nutrition and Dietetics. An online survey was sent to nutrition program directors. Respondents agreed with the core values of IPE and the benefits they present. Communication ranked significantly different as an IPE competency by not-for-profit versus for-profit and among differing program types (didactic, coordinated, internship). Nutrition program directors support the idea of IPE but have not yet translated this into effective implementation.
Low Protein Intake Among College Males Is Associated With Increased BMI
Authors: Colby Sarah , Sparks Amy , Thompson Dixie , Overstreet Brittney , Monroe Courtney , Appelo Shanthi , Hansen-Petrik Melissa , Kavanagh Katie
Published: July 2018

A convenience sample of male nonathlete college students (n = 47) was assessed (diet intake, physical activity, and anthropometrics) and interviewed on protein knowledge/behavior. Most participants were unaware or misinformed about protein and were using supplements. Fifteen percent of participants consumed less than 0.8 g/kg per day, 70% consumed 0.8 to 1.99 g/kg per day, and 15% consumed 2 g/kg per day or more of protein. Differences between protein intake groups were assessed using a multivariate analysis of variance. The low protein intake group had higher body fat percentages, body mass indexes, and waist circumferences (P < .05). Future experimental research is needed to examine the impact of differing protein intakes on body composition in college male populations.
Literacy's Role in Health Disparities
Authors: Shupe Emily S. , Pohlig Ryan T. , Fanelli Kuczmarski Marie , Zonderman Alan B. , Evans Michele K.
Published: July 2018

Literacy impacts diet quality and may play a role in preventing anemia. This study investigated whether literacy mediates the relationships between race or poverty status and diet quality and anemia. Diet quality was evaluated using mean adequacy ratios for 1895 white and African American adults from Healthy Aging in Neighborhoods of Diversity across the Life Span study. Anemia was diagnosed by World Health Organization standards. Path analysis explored the influence of race and poverty on anemia. Anemia was diagnosed in 223 participants. The synergistic effects of poverty, race, and diet quality influence anemia. Literacy mediated the effects of race and poverty on mean adequacy ratios and anemia, highlighting the role of literacy in physical well-being.
Elevated Risk of Cancer After Solid Organ Transplant in Childhood: A Population-based Cohort Study
Authors: Kitchlu Abhijat , Dixon Stephanie , Dirk Jade S. , Chanchlani Rahul , Vasilevska-Ristovska Jovanka , Borges Karlota , Dipchand Anne I. , Ng Vicky L. , Hebert Diane , Solomon Melinda , Michael Paterson J. , Gupta Sumit , Joseph Kim S. , Nathan Paul C. , Parekh Rulan S.
Published: July 2018

Background.

Cancer risk is elevated among adult transplant recipients, but there is limited data regarding long-term cancer risk and mortality in pediatric recipients.

Methods.

We conducted a population-based retrospective cohort study in Ontario, Canada. We included pediatric recipients of solid organ transplants at the Hospital for Sick Children, Toronto, from 1991 to 2014, and compared rates of new cancers and cancer-specific mortality to nontransplanted Ontario children born in the same year. We constructed standard and time-dependent Cox proportional hazards models accounting for competing risk of death.

Results.

A total of 951 recipients (kidney, n = 400; liver, n = 283; heart, n = 218; lung, n = 36; multiorgan/small bowel, n = 14) were compared with 5.3 million general population children. Mean (SD) age was 8.2 (6.4) years; 50% were male. Over a mean (SD) follow-up of 10.8 (7.1) years, cumulative incidence of cancer was 20% in recipients and 1.2% in the general population (incidence rate ratio, 32.9; 95% confidence interval [CI], 26.6–40.8). Risk was highest in the first year posttransplant (adjusted hazard ratio [aHR],176; 95% CI, 117–264), but remained elevated beyond 10 years (aHR, 10.8; 95% CI, 6.3–18.6). Lymphoproliferative disorders were predominant (77%); however, solid cancers (renal, sarcomas, genital, thyroid) were seen. Recipients of lung or multiorgan transplants were at highest risk. Cancer-specific mortality was also higher among recipients (HR, 93.1; 95% CI, 59.6–145.2).

Conclusions.

Childhood transplant recipients have a 30 times greater cancer incidence versus the general population. Further investigation is needed to guide screening strategies in this at-risk population.
Regional Variation in Utilization and Outcomes of Liver Allografts From Donors With High Body Mass Index and Graft Macrosteatosis: A Role for Liver Biopsy
Authors: Steggerda Justin A. , Kim Irene K. , Malinoski Darren , Klein Andrew S. , Bloom Matthew B.
Published: July 2018

Background

Obesity, defined as a high body mass index (hBMI) of 30 kg/m2 or greater, is a growing epidemic worldwide and is associated with multiple comorbidities. High BMI individuals account for an increasing portion of potential liver donors. Here we evaluate trends in the utilization and outcomes of hBMI donors on a national and regional level and the potential role of liver biopsy in donor evaluation.

Methods

United Network for Organ Sharing Standard Transplant Analysis and Research database was evaluated for deceased donor liver transplants between 2006 and 2016 across 11 Organ Procurement and Transplantation Network regions. High BMI donors were compared with lower BMI counterparts and evaluated for biopsy rates, utilization rates and allograft outcomes. Univariate and multivariable analyses were performed.

Results

Seventy-seven thousand fifty potential donors were identified and 60 200 transplants were evaluated. Utilization rates for hBMI donors were 66.1% versus 78.1% for lower BMI donors (P < 0.001). Pretransplant biopsy was performed more frequently in hBMI donors (52.1% vs 33.1%, P < 0.001) and macrosteatosis of 30% or greater was identified more often (21.1% vs 12.2%, P < 0.001). Biopsy performance increased utilization rate of hBMI donors in 7 of 11 Organ Procurement and Transplantation Network regions. region 6 showed the highest rate of biopsy performance, high rate of hBMI donor utilization, and highest 5-year estimated graft survival rates of all regions.

Conclusions

High BMI donors have not previously been associated with worse graft survival in multivariable analyses; however, they are used much less frequently. Liver biopsy may increase the utilization rate of hBMI donors and improve donor selection. Further evaluation of regions with high rates of utilization and good outcomes is warranted.
Cell Spray Transplantation of Adipose-derived Mesenchymal Stem Cell Recovers Ischemic Cardiomyopathy in a Porcine Model
Authors: Mori Daisuke , Miyagawa Shigeru , Yajima Shin , Saito Shunsuke , Fukushima Satsuki , Ueno Takayoshi , Toda Koichi , Kawai Kotoe , Kurata Hayato , Nishida Hiroyuki , Isohashi Kayako , Hatazawa Jun , Sawa Yoshiki
Published: July 2018

Background

Allogeneic adipose-derived mesenchymal stem cells (ADSC) are promising cell sources for cell therapy to treat ischemic cardiomyopathy (ICM). We hypothesized that ADSC transplantation via the new cell spray method may be a feasible, safe, and effective treatment for ICM.

Methods

Human ADSCs were acquired from white adipose tissue. Porcine ICM models were established by constriction of the left anterior descending coronary artery. Adipose-derived mesenchymal stem cells were spread over the surface of the heart via cell spray in fibrinogen and thrombin solutions. The cardiac function was compared with that of the control group.

Results

Adipose-derived mesenchymal stem cells were successfully transplanted forming a graft-like gel film covering the infarct myocardium. Premature ventricular contractions were rarely detected in the first 3 days after transplantation. Echocardiography and magnetic resonance imaging revealed improved cardiac performance of the ADSC group at 4 and 8 weeks after transplantation. Systolic and diastolic parameters were significantly greater in the ADSC group at 8 weeks after transplantation. Histological examination showed significantly attenuated left ventricular remodeling and a greater vascular density in the infarct border area in the ADSC group. Moreover, the coronary flow reserve was maintained, and expression levels of angiogenesis-related factors in the infarct border and remote areas were significantly increased.

Conclusions

Spray method implantation of allogenic ADSCs can improve recovery of cardiac function in a porcine infarction model. This new allogenic cell delivery system may help to resolve current limitations of invasiveness and cost in stem cell therapy.
Vascularized Brachial Plexus Allotransplantation—An Experimental Study in Brown Norway and Lewis Rats
Authors: Chang Tommy Nai-Jen , Chen Kuang-Te , Gorden Tessa , Daniel Bassem W. , Hernon Catherine , Shafarenko Mark , Huang Yen-Lin , Lu Johhny Chuieng-Yi , Chuang David Chwei-Chin
Published: July 2018

Background

Brachial plexus injuries are devastating. Current reconstructive treatments achieve limited partial functionality. Vascularized brachial plexus allotransplantation could offer the best nerve graft fulfilling the like-with-like principle. In this experimental study, we assessed the feasibility of rat brachial plexus allotransplantation and analyzed its functional outcomes.

Methods

A free vascularized brachial plexus with a chimeric compound skin paddle flap based on the subclavian vessels was transplanted from a Brown Norway rat to a Lewis rat. This study has 2 parts. Protocol I aimed to develop the vascularized brachial plexus allotransplantation (VBP-allo) model. Four groups are compared: no reconstruction, VBP-allo with and without cyclosporine A immunosuppression, VBP autotransplantation (VBP-auto). Protocol II compared the recovery of the biceps muscle and forearm flexors when using all 5, 2 (C5 + C6) or 1 (isolated C6) spinal nerve as the donor nerves. The assessment was performed on week 16 and included muscle weight, functionality (grooming tests, muscle strength), electrophysiology and histomorphology of the targeted muscles.

Results

Protocol I showed, the VBP-allo with cyclosporine A immunosuppression was electrophysiologically and functionally comparable to VBP-auto and significantly superior to negative controls and absent immunosuppression. In protocol II, all groups had a comparable functional recovery in the biceps muscle. Only with 5 donor nerves did the forearm show good results compared with only 1 or 2 donor nerves.

Conclusions

This study demonstrated a useful vascularized complete brachial plexus allotransplantation rodent model with successful forelimb function restoration under immunosuppression. Only the allotransplantation including all 5 roots as donor nerves achieved a forearm recovery.
Ocular ptosis: differential diagnosis and treatment
Authors: Díaz-Manera Jordi , Luna Sabina , Roig Carles
Published: July 2018

Purpose of review

The current article provides a brief summary of the clinical approach to congenital and acquired ptosis. An increasing number of publications analyze causes of ptosis or describe diagnostic tests or advances in ptosis genetics. The aim of our work is to summarize these findings and provide an updated algorithm for the diagnosis and treatment of patients with ptosis. This review covers important clinical research and studies relevant for neurologists recently published.

Recent findings

Ptosis is a common cause of referral to neuromuscular units. Knowledge of the different causes of this symptom has grown substantially in recent years, from diagnostic tests and genetics studies to potential new therapeutic agents, making it essential to keep up to date on the diagnostic and therapeutic relevance of these contributions.

We emphasize that ptosis should be studied as a complex symptom. Efforts should be made to identify accompanying neurologic or ophthalmologic signs in clinical examination that could lead to a diagnosis. A growing number of diagnostics tests are available in the field, especially in genetics. Meanwhile, surgery continues being the most used therapeutic approach for these patients.
DeepSeqPan, a novel deep convolutional neural network model for pan-specific class I HLA-peptide binding affinity prediction
Authors: Liu Zhonghao , Cui Yuxin , Xiong Zheng , Nasiri Alierza , Zhang Ansi , Hu Jianjun
Published: July 2018

Interactions between human leukocyte antigens (HLAs) and peptides play a critical role in the human immune system. Accurate computational prediction of HLA-binding peptides can be used for peptide drug discovery. Currently, the best prediction algorithms are neural network based pan-specific models, which take advantage of the large amount of data across HLA alleles. However, current pan-specific models are all based on the pseudo sequence encoding for modeling the binding context and depend on the available HLA protein-peptide bound structures. In this work, we proposed a novel deep convolutional neural network model (DCNN) for HLA-peptide binding prediction, in which the encoding of the HLA sequence and the binding context are both learned by the network itself without requiring the HLA-peptide bound structure information. Our DCNN model is also characterized by its binding context extraction layer and dual outputs with both binding affinity output and binding probability outputs. Evaluation on public benchmark datasets shows that our DeepSeqPan model without HLA structural information in training achieves state-of-the-art performance on a large number of HLA alleles with good generalization capability. Since our model only needs raw sequences from the HLA-peptide binding pairs, it can be applied to binding predictions of HLAs without structure information and can also be applied to other protein binding problems such as protein-DNA and protein-RNA bindings. The implementation code and trained models are freely available at https://github.com/pcpLiu/DeepSeqPan.
A single-cell atlas of human glioblastoma reveals a single axis of phenotype in tumor-propagating cells
Authors: Müller Sören , Di Lullo Elizabeth , Bhaduri Aparna , Alvarado Beatriz , Yagnik Garima , Kohanbash Gary , Aghi Manish , Diaz Aaron
Published: July 2018

Tumor-propagating glioblastoma (GBM) stem-like cells (GSCs) of the proneural and mesenchymal molecular subtypes have been described. However, it is unknown if these two GSC populations are sufficient to generate the spectrum of cellular heterogeneity observed in GBM. The lineage relationships and niche interactions of GSCs have not been fully elucidated. We perform single-cell RNA-sequencing (scRNA-seq) and matched exome sequencing of human GBMs (12 patients; >37,000 cells) to identify recurrent hierarchies of GSCs and their progeny. We map sequenced cells to tumor-anatomical structures and identify microenvironment interactions using reference atlases and quantitative immunohistochemistry. We find that all GSCs can be described by a single axis of variation, ranging from proneural to mesenchymal. Increasing mesenchymal GSC (mGSC) content, but not proneural GSC (pGSC) content, correlates with significantly inferior survival. All clonal expressed mutations are found in the GSC populations, with a greater representation of mutations found in mGSCs. While pGSCs upregulate markers of cell-cycle progression, mGSCs are largely quiescent and overexpress cytokines mediating the chemotaxis of myeloid-derived suppressor cells. We find mGSCs enriched in hypoxic regions while pGSCs are enriched in the tumor’s invasive edge. We show that varying proportions of mGSCs, pGSCs, their progeny and stromal/immune cells are sufficient to explain the genetic and phenotypic heterogeneity observed in GBM. This study sheds light on a long-standing debate regarding the lineage relationships between GSCs and other glioma cell types.
In Vitro Assay for the Detection of Network Connectivity in Embryonic Stem Cell-Derived Cultures
Authors: Gamble Jeffrey R , Zhang Eric T , Iyer Nisha , Sakiyama-Elbert Shelly , Barbour Dennis L
Published: July 2018

Stem cell transplantation holds great promise as a repair strategy following spinal cord injury. Embryonic stem cell (ESC) transplantation therapies have elicited encouraging though limited improvement in motor and sensory function with the use of heterogeneous mixtures of spinal cord neural progenitors and ESCs. Recently, transgenic lines of ESCs have been developed to allow for purification of specific candidate populations prior to transplantation, but the functional network connectivity of these populations and its relationship to recovery is difficult to examine with current technological limitations. In this study, we combine an ESC differentiation protocol, multi-electrode arrays (MEAs), and previously developed neuronal connectivity detection algorithms to develop an in vitro high-throughput assay of network connectivity in ESC-derived populations of neurons. Neuronal aggregation results in more consistent detection of individual neuronal activity than dissociated cultures. Both aggregated and dissociated culture types exhibited synchronized bursting behaviors at days 17 and 18 on MEAs, and thousands of statistically significance functional connections were detected in both culture types. Aggregate cultures, however, demonstrate a tight linear relationship between the inter-neuron distance of neuronal pairs and the time delay of the neuronal pair functional connections, whereas dissociated cultures do not. These results suggest that ESC-derived aggregated cultures may reflect some of the spatiotemporal connectivity characteristics of in vivo tissue and prove to be useful models of investigating potentially therapeutic populations of ESC-derived neurons in vitro.

NOVELTY AND SIGNIFICANCE

Previous investigations of stem cell-derived network connectivity on multi-electrode arrays (MEAs) have been limited to characterizations of bursting activity or broad averages of overall temporal network correlations, both of which overlook neuronal level interactions. The use of spike-sorting and short-time cross-correlation histograms along with statistical techniques developed specifically for MEAs allows for the characterization of functional connections between individual stem cell-derived neurons. This high-throughput connectivity assay will open doors for future examinations of the differences in functional network formation between various candidate stem cell-derived populations for spinal cord injury transplantation therapies—a critical inquiry into their therapeutic viability.
Water quality and microbial load: a double-threshold identification procedure intended for space applications
Authors: Amalfitano Stefano , Levantesi Caterina , Garrelly Laurent , Giacosa Donatella , Bersani Francesca , Rossetti Simona
Published: July 2018

During longer-lasting future space missions, water renewal by ground-loaded supplies will become increasingly expensive and unmanageable for months. Space exploration by self-sufficient space-crafts is thus demanding the development of culture-independent microbiological methods for in-flight water monitoring to counteract possible contamination risks. In this study, we aimed at evaluating microbial load data assessed by selected techniques with current or promising perspectives in space applications (i.e., HPC, ATP-metry, qPCR, flow cytometry), through the analysis of water sources with constitutively different contamination levels (i.e., chlorinated and unchlorinated tap waters, groundwaters, river waters, wastewaters). Using a data-driven double-threshold identification procedure, we identified and presented new alternative standards of water quality based on the assessment of the total microbial load. Our approach is suitable to provide an immediate alert of microbial load peaks, thus enhancing the crew responsiveness in case of unexpected events due to water contamination and treatment failure. Finally, the backbone dataset could help in managing water quality and monitoring issues for both space and Earth-based applications.
Unraveling the genetic architecture of grain size in einkorn wheat through linkage and homology mapping, and transcriptomic profiling
Authors: Yu Kang , Liu Dongcheng , Chen Yong , Wang Dongzhi , Yang Wenlong , Yang Wei , Yin Lixin , Zhang Chi , Zhao Shancen , Sun Jiazhu , Liu Chunming , Zhang Aimin
Published: July 2018

Highlight

Genome-wide linkage and homology mapping revealed 17 genomic regions through a high-density einkorn wheat genetic map constructed using RAD-seq, and transcription levels of 20 candidate genes were explored using RNA-seq.

Understanding the genetic architecture of grain size is a prerequisite to manipulate the grain development and improve the yield potential in crops. In this study, we conducted a whole genome-wide QTL mapping of grain size related traits in einkorn wheat by constructing a high-density genetic map, and explored the candidate genes underlying QTL through homologous analysis and RNA sequencing. The high-density genetic map spanned 1873 cM and contained 9937 SNP markers assigned to 1551 bins in seven chromosomes. Strong collinearity and high genome coverage of this map were revealed with the physical maps of wheat and barley. Six grain size related traits were surveyed in five agro-climatic environments with 80% or more broad-sense heritability. In total, 42 QTL were identified and assigned to 17 genomic regions on six chromosomes and accounted for 52.3-66.7% of the phenotypic variations. Thirty homologous genes involved in grain development were located in 12 regions. RNA sequencing provided 4959 genes differentially expressed between the two parents. Twenty differentially expressed genes involved in grain size development and starch biosynthesis were mapped to nine regions that contained 26 QTL, indicating that the starch biosynthesis pathway played a vital role on grain development in einkorn wheat. This study provides new insights into the genetic architecture of grain size in einkorn wheat, the underlying genes enables the understanding of grain development and wheat genetic improvement, and the map facilitates the mapping of quantitative traits, map-based cloning, genome assembling and comparative genomics in wheat taxa.
Filopodome mapping identifies p130Cas as a mechanosensitive regulator of filopodia stability
Authors: Jacquemet Guillaume , Saup Rafael , Hamidi Hellyeh , Miihkinen Mitro , Ivaska Johanna
Published: July 2018

Filopodia are adhesive cellular protrusions specialised in the detection of extracellular matrix (ECM)-derived cues. While ECM engagement at focal adhesions is known to trigger the recruitment of hundreds of proteins (“adhesome”) to fine-tune cellular behaviour, the components of the filopodia adhesions remain undefined. Here, we performed a structured illumination microscopy-based screen to map the localisation of 80 target proteins, linked to cell adhesion and migration, within filopodia. We demonstrate preferential enrichment of several adhesion proteins to either filopodia tips, filopodia shafts, or shaft subdomains suggesting divergent, spatially restricted functions for these proteins. Moreover, proteins with phospho-inositide (PI) binding sites are particularly enriched in filopodia. This, together with the strong localisation of PI(3,4)P2 in filopodia tips, predicts critical roles for PIs in regulating filopodia ultra-structure and function. Our mapping further reveals that filopodia adhesions consist of a unique set of proteins, the filopodome, that are distinct from classical nascent adhesions, focal adhesions and fibrillar adhesions. Using live imaging, we observe that filopodia adhesions can give rise to nascent adhesions, which, in turn, form focal adhesions. Finally, we demonstrate that p130Cas (BCAR1) is recruited to filopodia tips via its CCHD domain and acts as a mechanosensitive regulator of filopodia stability.
Sexual behavior of the desert locust during intra-and inter-phase interactions
Authors: Golov Y. , Rillich J. , Douek M. , Harari A.R. , Ayali A
Published: July 2018

Mating and reproduction behaviors and strategies are fundamental aspects of an organism’s evolutionary and ecological success. In locusts, intra- as well as inter-phase reproductive interactions among gregarious and solitarious locust populations have a major impact on the locust population dynamics. However, practically all previous work on locust sexual behavior has been limited to the gregarious phase. Here we provide a first detailed description of pre-copulatory behavior of solitarious desert locusts. We compare our findings with those of previous reports of pre-copulatory behavior of gregarious locusts, focusing on the behavioral elements that serve in inter-sex signaling and communication. We also studied inter-phase (mixed pairs) reproductive interactions. Solitarious males were found to invest more in pre-copulatory courtship and signaling compared to their gregarious counterparts; and the solitarious females played a comparatively more dominant role in the inter-sex communication. The solitarious females were also less prone to demonstrate the typical rejection-related behavioral patterns displayed by the gregarious females. As a consequence of the particular characteristic behavior of each phase, the most successful among intra- and inter-phase pairs were gregarious males with solitary females. Least successful were solitary males encountered with gregarious females, indicating a strong asymmetry in inter-phase reproductive interactions. We discuss these results in the context of non-random or assortative mating in locust mixed or sympatric solitarious-gregarious populations.