bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Outcomes of Phacoemulsification Followed by iStent Implantation Versus Goniotomy With the Kahook Dual Blade in Patients With Mild Primary Open-angle Glaucoma With a Minimum of 12-Month Follow-up
Authors: Le Crystal , Kazaryan Suzie , Hubbell Margaret , Zurakowski David , Ayyala Ramesh S.
Published: November 2018

Purpose:

To study surgical outcomes after combined phacoemulsification with either iStent implantation or goniotomy using the Kahook Dual Blade (KDB) with a minimum of 12 months of follow-up.

Patients and Methods:

Patients with mild primary open-angle glaucoma who underwent phacoemulsification in combination with either iStent implantation or goniotomy using the KDB from 2011 to 2017 were included.

Results:

In total, 48 eyes in the iStent group and 29 eyes in the KDB group were included with at least 12 months of follow-up. There was no difference in patient age, sex, previous surgery, preoperative or postoperative visual acuity or intraocular pressure (IOP) between the 2 groups. Mean preoperative IOP in the iStent group decreased from 17.6±4.8 to 15.9±2.9 mm Hg (P=0.01); mean preoperative IOP in the KDB group decreased from 17.4± 4.3 to 15.0±4.0 mm Hg (P=0.01). The overall percentage of IOP reduction was 14.3% in the iStent group and 12.6% in the KDB group at 12 months of follow-up. Mean topical glaucoma medication use decreased from 2.0±0.9 to 0.7±1.1 in the iStent group and from 2.2±1.0 to 1.6±1.3 in the KDB group. Multivariable linear regression accounting for age, sex, race, baseline IOP, and number of eyes treated as covariates indicated a significant reduction in IOP from baseline with both iStent (Wald χ2=3.97, P=0.046) and KDB (Wald χ2=4.65, P=0.031). Multivariable logistic regression accounting for age, sex, race, baseline IOP, and number of eyes treated as covariates indicated no significant difference in overall success between iStent and KDB (Z-test=0.92, P=0.359).

Conclusions:

Phacoemulsification in combination with either iStent implantation or goniotomy using the KDB both achieved statistical significant reduction in IOP and number of glaucoma medications at 12 months of follow-up in patients with mild primary open-angle glaucoma with no complications.
Right Mini-Thoracotomy Subaortic Membrane Resection
Authors: Johnson Carl A. , Siordia Juan A. , Robinson Davida A. , Sagebin Fabio , Knight Peter A.
Published: November 2018

Objective

Subaortic membrane is an anatomical intracardiac anomaly that may cause discrete subaortic stenosis and aortic insufficiency. Patients requiring subaortic membrane resection may benefit from a minimally invasive approach; however, subaortic membranes are typically resected through a median sternotomy. We present our initial clinical experience of adult patients who have undergone a mini-thoracotomy subaortic membrane resection.

Methods

Eight patients who underwent an elective subaortic membrane resection performed through a mini-thoracotomy were retrospectively reviewed. A 5-cm mini-thoracotomy incision was made in the 2nd intercostal space; a videoscope was inserted through a separate incision within the same interspace. Cardiopulmonary bypass (CPB) was instituted via central arterial and peripheral venous cannulation and an aortotomy was made. The subaortic membrane was resected with shafted instruments. The left ventricular outflow tract was inspected and CPB was weaned. Thirty-day mortality, intensive care and hospital length of stay, ventilation time, operative times, postoperative morbidity, and need for additional procedures were evaluated.

Results

The median CPB and cross-clamp times were 60 and 42 minutes, respectively. The median time to extubation was 3.6 hours. The median intensive care unit and hospital stay were 22 hours and 3 days, respectively. The postoperative left ventricular outflow tract mean gradients decreased significantly (26.5 vs. 9.4 mm Hg, P = 0.001). There were no conversions to sternotomy, perioperative strokes, or 30-day mortality.

Conclusions

Subaortic membranes can be resected through a mini-thoracotomy approach with excellent clinical results.
Evaluating health warning messages specific to waterpipe smoking among university students in Jordan
Authors: Darawad Muhammad W. , Salloum Ramzi , Alhussami Mahmoud , Maharmeh Mahmoud
Published: November 2018

Background and purpose:

Health warning messages specific to waterpipe smoking (WPS) have not been tested enough in literature. This study evaluated university students' response to such messages. Specifically, this study (1) assessed the extent to which certain warning messages and pictorial signs motivate participants to quit WPS smoking; (2) identified the best location to place the warning signs of waterpipe as perceived by participants; and (3) assessed participants' intention to quit WPS.

Methods:

A descriptive, cross-sectional design was used to collect data from 397 university students in Jordan using an Internet-based survey. The following data were collected: intentions regarding WPS, response to nine warning messages, and responses to four pictorial signs.

Results:

The message that had the highest motivation to quit smoking was “ WPS during pregnancy can harm your baby” (79.3%), whereas the highest pictorial sign was regarding “Protect your children” (64.2%). Most (69.5%) participants believed that WPS products and accessories should contain warnings, and the best suggested location was the pipe handle (52.4%). Participants who reported quitting WPS and those who had an intention to quit had significantly higher responses to both types of health warning labels (HWLs).

Conclusion:

Both text-only and pictorial HWLs were found to encourage quitting WPS among university students. Knowing that participants are having an intention to quit mandates extra efforts to make WPS experience less appealing through reminding them regarding its harms.

Implications for practice:

Support is needed by health care providers to put those effective health warning messages in action. Furthermore, providers can use such health warnings in motivating their patients to quit WPS.
Endocrine aspects of Klinefelter syndrome
Authors: Lizarazo Adriana Herrera , McLoughlin Michelle , Vogiatzi Maria G.
Published: November 2018

Purpose of review

Klinefelter syndrome is the most common sex chromosome abnormality in men. Hypogonadism and testicular degeneration are almost universal. Truncal adiposity, metabolic syndrome and low bone mass occur frequently. This review summarizes the most recent advances in the pathogenesis and management of the endocrine abnormalities in Klinefelter syndrome. It is expected that optimal endocrine management will improve outcomes and quality of life in Klinefelter syndrome.

Recent findings

In Klinefelter syndrome, testosterone replacement is routinely prescribed despite lack of evidence on the optimal dose and time for initiation of therapy. Cross-sectional studies have linked hypogonadism to the development of metabolic abnormalities and low bone mass. Testosterone therapy, however, is not consistently associated with improved metabolic and bone outcomes. Increased truncal adiposity and high rates of metabolic syndrome are present in prepubertal children. A randomized trial of oxandrolone in prepubertal boys showed improvement in visual-motor function, socialization and cardiometabolic health. Testicular sperm extraction (TESE) has success rates similar to other causes of nonobstructive azoospermia when performed between 16 and 35 years of age.

Endocrine care in Klinefelter syndrome should start in childhood and include evaluation of metabolic risk factors and bone health. Further research to guide evidence-based endocrine care is very much needed.
Competition in Outpatient Procedure Markets
Authors: Baker Laurence C. , Bundorf M.K. , Kessler Daniel P.
Published: November 2018

Background:

More than half of all medical procedures performed in the United States occur in an outpatient setting, yet few studies have explored how competition among ambulatory surgery centers (ASCs) and hospitals affects prices for commercially insured outpatient services.

Objectives:

We examined the association between prices for commercially insured outpatient procedures and competition among ASCs and hospitals.

Research Design:

Using claims from the Health Care Cost Institute for 2008–2012, we constructed county-level price indices for outpatient procedures in hospital outpatient departments and ASCs. Using regression analysis, we estimated the association between prices and ASC availability, outpatient and inpatient hospital competition, hospital/physician integration, and several other hospital market characteristics. Our estimates were identified from changes within counties over time.

Results:

First, ASC availability was associated with decreases in overall outpatient procedure prices, mostly due to reductions in the prices paid to hospital outpatient departments. Second, competition among hospitals was also associated with decreases in outpatient procedure prices—and had an effect more than twice as large as the effect of ASC availability. Third, competition among ASCs was also associated with reductions in the prices paid to other ASCs.

Conclusions:

Our results suggest that competition from ASCs benefits consumers through lower prices for outpatient procedures. Any conclusions about the broader welfare implications of the rise in ASCs, however, must balance the price reductions that we found with the volume increases found in previous work, particularly the volume increases at physician-owned ASCs.
Open-neck organ preservation surgery for hypopharyngeal cancer: indications, techniques, limits, and outcomes
Authors: Bradley Patrick J. , Liu Liangfa
Published: November 2018

Purpose of review

To appraise the practice and role of open-neck organ preserving surgery for hypopharyngeal squamous cell carcinoma and to update the current indications, techniques, limits, and outcomes.

Recent findings

The role of primary surgery for hypopharyngeal carcinoma has shifted over the past two decades to primary nonsurgical management with the use of induction or concurrent chemoradiotherapy. The preferred and most suitable tumours for open-neck surgery are the small-volume T stage diseases, with small to medium-volume neck metastases, however such patients are exceedingly rare. Nonetheless, more advanced tumours with cartilage invasion, vocal cord paralysis, or located at piriform apex and postcricoid area, previously unsuitable for open-neck organ preserving surgery, can now be excised and repaired, minimizing morbidity and improving quality of patients’ life. Much of this surgical progress has been developed by innovative surgeons using free tissue transfer, accurate placement surgery, reconstruction of a neoglottis, and perfecting the pharyngoesophageal anastomosis. Current practice of open-neck organ preserving surgery for hypopharyngeal carcinoma has been mainly reported in Asia: Korea, Taiwan, Japan, and China.

There are some patients who are deemed unsuitable and/or unwilling for current treatment by nonsurgical approaches, and open-neck organ preserving laryngopharyngeal surgery may be a more suitable alternative than selecting a ‘lesser or modified’ chemo or bioradiotherapy regimen, resulting in a prolonged quantity and quality of life.
New age technology and social media: adolescent psychosocial implications and the need for protective measures
Authors: Shah Jay , Das Prithwijit , Muthiah Nallammai , Milanaik Ruth
Published: November 2018

Purpose of review

In recent years, breakthroughs and advancements in new age technology have revolutionized the way children communicate and interact with the world around them. As social media platforms such as Facebook, Instagram, and Snapchat continue to grow in popularity, their usage has raised concerns about their role and impact on adolescent development and behavior. This review examines the psychosocial implications of social media usage on youth outcomes related to body image, socialization, and adolescent development. It discusses ways that clinicians and parents can effectively safeguard their children from the potential threats posed by digital media while providing a fact sheet for parents that addresses these concerns and summarizes recommended strategies to combat them.

Recent findings

While social media platforms continue to experience surges in popularity, mounting evidence suggests significant correlations between their usage and adolescent mental health and behavioral issues. Increased social media usage has been linked to diminished self-esteem and body satisfaction, elevated risk of cyber-bullying, heightened exposure to pornographic material, and risky sexual behaviors.

Given how new age technology is steadily permeating everyday life, greater efforts are needed to inform adolescent users and their families about the negative consequences of social media usage. Pediatricians and parents must take cautionary measures to reduce psychosocial risks and ensure the online safety of children.
Tumor necrosis factor-driven cell death in donor organ as a barrier to immunological tolerance
Authors: Ang Rosalind L. , Ting Adrian T.
Published: November 2018

Purpose of review

Regulated cell death (RCD) is likely to play a role in organ rejection but it is unclear how it may be invoked. A well-known trigger of regulated cell death is tumor necrosis factor-alpha (TNF), which activates both caspase-dependent apoptosis and caspase-independent necroptosis. TNF is best known as a pro-inflammatory cytokine because it activates NFκB and MAPK signaling to induce expression of pro-inflammatory genes.

Recent findings

Emerging data from animal models now suggest that TNF-induced cell death can also be inflammatory. Therefore, the role of cellular demise in regulating immunity should be considered. In transplantation, TNF could have a role in cellular injury or death from ischemia reperfusion (IR) injury and this may dictate organ survival. The default response to TNF in most cells is survival, rather than death, because of the presence of cell death checkpoints. However, cells succumb to TNF-driven death when these checkpoints are disrupted, and sensitivity to death likely reflects a reduction in molecules that fortify these checkpoints. We propose that a cell's propensity to die in response to TNF may underlie allograft rejection.

Genetic, epigenetic, and posttranslational control of death checkpoint regulators in donor tissues may determine graft survival. Therapeutically, drugs that prevent donor cell demise could be useful in preventing organ rejection.
Marginal kidney transplantation: the road less traveled
Authors: Sharma Neeraj , Mahajan Arnav , Qazi Yasir A.
Published: November 2018

Purpose of review

Kidney transplantation indisputably confers a significant survival advantage and a better quality of life compared with dialysis, however, because of the increasing demand for kidney transplantation many patients continue to wait prolonged periods for kidney transplantation. The first step to alleviate the shortage is to reduce the discard rate by utilizing more marginal kidneys. This review studied the recent literature on marginal kidney transplantation.

Recent findings

More than 60% of high-KDPI kidneys are discarded. Despite the increase in posttransplant costs, use of high KDPI transplants suggests a gain in survival years, thus making marginal kidney transplant cost effective. Furthermore, recent evidence suggests that marginal kidney transplantation shows a survival benefit compared with remaining in the waitlist and minimizes the kidney discard rate.

Transplantation with marginal kidneys provides a survival benefit over dialysis or waiting for a low-KDPI kidney. As a result, clinicians should strongly consider transplantation of marginal kidneys as opposed to waiting for a better offer.
Palonosetron is a Better Choice Compared With Ondansetron for the Prevention of Chemotherapy-induced Nausea and Vomiting (CINV) in a Resource-limited Pediatric Oncology Center: Results From a Randomized Control Trial
Authors: Chaudhary Narendra K. , John Rikki R. , Boddu Deepthi , Mahasampath Gowri , Nesadeepam Nalini , Mathew Leni G.
Published: November 2018

Palonosetron (PG) is a newer, safe, and effective long-acting 5-HT3 antagonist commonly used in adults, but data in children are limited. A randomized controlled trial was carried out among children with cancer during their first cycle of moderate or highly emetogenic chemotherapy to receive either PG or ondansetron (OG) with the aim of comparing their efficacy, safety, and cost-effectiveness. In total, 200 children (mean age, 8 y, male:female=1.8:1) were recruited, 100 in each arm. Complete response, defined as no vomiting, in acute (<24 h), delayed (24 to 120 h), and overall phases (0 to 120 h) was observed in 88%, 88%, and 81% of cases, respectively, for PG versus 84%, 79%, and 72%, respectively, for OG (P=0.42, 0.09 and 0.21, respectively). Complete protection rates, defined as no nausea and vomiting in children above 6 years of age, in acute, delayed, and overall phases were 84%, 81%, and 73%, respectively, for PG versus 79%, 67%, and 60%, respectively, for OG (P=0.44, 0.06 and 0.10, respectively). Overall, the efficacy and safety of PG in the prevention of chemotherapy-induced nausea and vomiting was comparable with OG, but PG was a more cost-effective and suitable choice for busy centers in resource-limited countries.
Mortality Rates and Trends Among Bologna Community Mental Health Service Users
Authors: Berardi Domenico , Pavarin Raimondo Maria , Chierzi Federico , Terzi Laura , Manzo Valentina , Piazza Antonella , Menchetti Marco , Fioritti Angelo
Published: November 2018

The present study aimed to determine mortality rates and trends among community mental health service users in Bologna (Italy) between 2001 and 2013. Standardized mortality ratios (SMRs) were calculated, and Poisson multiple regression analysis was performed. The cohort comprised 42,357 patients, of which 3556 died. The overall SMR was 1.62 (95% confidence interval = 1.57–1.67). SMRs for natural causes of death ranged from 1.25 to 2.30, whereas the SMR for violent deaths was 3.45. Both serious and common mental disorders showed a significant excess of mortality, although higher rates were found in severe mental disorders, especially in personality disorders. Different from most published studies, the overall SMR slightly decreased during the study period. The present study, though confirming that people with mental disorders present a higher risk of mortality, calls for prevention strategies oriented to all psychiatric diagnoses.
The Face as Diversity: What Was the Medical-Scientific Value of Lombrosian Morphoanthropology?
Authors: Chirchiglia Domenico , Chirchiglia Pasquale , Marotta Rosa
Published: November 2018

The face seen as an element of diversity. The ugliness of a face or a body and deformities were considered in 1800 as symbols of atavism, regression to being primates, or expression of inferior beings. The Italian physician Cesare Lombroso was the author of the concept of morphoanthropology, according to which the human being is judged on the basis of his or her physical connotations. An individual with ugly features of the face and body would be brought in as a criminal. Time has dissolved the value of Lombrosian theories, and scientific research has highlighted the influence of various factors in the genesis of crime. Genetic, biological, socioenvironmental factors, regulated by neurophysiology, which adds the effect of antagonism between the prefrontal cortex and the limbic cortex, explain the tendency to commit crime.
Supervised Classification of CYP2D6 Genotype and Metabolizer Phenotype With Postmortem Tramadol-Exposed Finns
Authors: Wendt Frank R. , Novroski Nicole M.M. , Rahikainen Anna-Liina , Sajantila Antti , Budowle Bruce
Published: November 2018

Cytochrome p450 family 2, subfamily D, polypeptide 6 (CYP2D6) may be used to infer the metabolizer phenotype (MP) of an individual as poor, intermediate, extensive/normal, or ultrarapid. Metabolizer phenotypes may suggest idiosyncratic drug responses as contributing factors to cause and/or manner of death in postmortem investigations. Application of CYP2D6 has used long-range amplification of the locus and restriction enzyme digestion to detect single-nucleotide variants (SNVs) associated with MPs. This process can be cumbersome and requires knowledge of genotype phase. Phase may be achieved using long-read DNA sequencing and/or computational methods; however, both can be error prone, which may make it difficult or impractical for implementation into medicolegal practice. CYP2D6 was interrogated in postmortem autopsied Finns using supervised machine learning and feature selection to identify SNVs indicative of MP and/or rate of tramadol O-demethylation (T:M1). A subset of 18 CYP2D6 SNVs could predict MP/T:M1 with up to 96.3% accuracy given phased data. These data indicate that phase contributes to classification accuracy when using CYP2D6 data. Of these 18 SNVs, 3 are novel loci putatively associated with T:M1. These findings may enable design of small multiplexes for easy forensic application of MP prediction when cause and/or manner of death is unknown.
Response to the US FDA LeadCare Testing Systems Recall and CDC Health Alert
Authors: Mason Jacquelyn , Ortiz Denise , Pappas Siobhan , Quigley Susan , Yendell Stephanie , Ettinger Adrienne S.
Published: November 2018

On May 17, 2017, the Food and Drug Administration issued a safety recall for the Magellan Diagnostics' LeadCare Testing Systems due to the potential for inaccurately low blood lead test results when used with venous blood samples. Concurrently, the Centers for Disease Control and Prevention (CDC) issued a health alert with retesting recommendations for specific high-risk populations. The purpose of the CDC retesting recommendations was to help identify high-risk individuals so that those potentially impacted by falsely low test results could be retested and receive appropriate follow-up care. The CDC's Lead Poisoning Prevention Program sought to understand how the recall and recommendations impacted state and local public health agencies. Childhood lead poisoning prevention programs (CLPPPs) in state and local public health agencies collect blood lead test results for children and had a lead role in identifying children for retesting. Case studies are presented that highlight the experiences of 4 state CLPPPs in responding to the recall and recommendations. Collectively, the case studies point to several lessons learned, including the importance of (1) having a well-functioning surveillance system in place prior to a serious incident; (2) having a clear understanding of the roles partners play in the continuum of care for children potentially exposed to lead; and (3) ensuring effective communications with all staff, both internal and external, to public health agencies that have a role in responding to a serious incident. The ability to respond to public health emergencies or other serious incidents takes the combined effort of federal, state, and local public health agencies as well as others in the health care delivery system. The CDC will continue to support state and local lead poisoning prevention programs so that they have the information and tools they need to address and prevent the health effects of lead exposures in communities.
Blood Lead Surveillance and Exposure Sources Among Alaska Children
Authors: Bressler Jonathan M. , Yoder Sarah , Cooper Stacey , McLaughlin Joe
Published: November 2018

Context:

Nationally, the child lead poisoning prevention strategy focuses on children in low-income communities living in old housing with lead paint. In Alaska, however, only about 3% of existing homes were built before 1950 and 38% were built during 1950-1979. As such, lead paint in old housing is a less frequent source of exposure for Alaska children with elevated blood lead levels (EBLLs).

Program:

The Alaska Department of Health and Social Services collects and maintains data for all blood lead level (BLL) tests in the state and is responsible for following up on EBLLs.

Implementation:

The Alaska Department of Health and Social Services conducts telephone interviews with parents of children with an EBLL to identify and remove possible sources of lead from the child's environment and prevent subsequent exposure.

Evaluation:

This review summarizes the surveillance data on BLLs in Alaska children for 2011-2015 and describes the most commonly identified possible sources of childhood lead exposure statewide since 2011.

Discussion:

While the proportion of children in Alaska who received a BLL test during these years is low compared with other states and EBLL prevalence is low among children tested, several possible sources of exposure were identified among children with EBLLs, including nonpaint sources. This report summarizes the challenges of combatting childhood lead exposure in a rural state where housing is a less common exposure source and describes ongoing work to prevent childhood lead exposure in Alaska.
LAMP: A CDC Program to Ensure the Quality of Blood-Lead Laboratory Measurements
Authors: Caldwell Kathleen L. , Cheng Po-Yung , Vance Kathryn A. , Makhmudov Amir , Jarrett Jeffery M. , Caudill Samuel P. , Ho De-Pei , Jones Robert L.
Published: November 2018

Context:

The Lead and Multielement Proficiency (LAMP) program is an external quality assurance program promoting high-quality blood-lead measurements.

Objectives:

To investigate the ability of US laboratories, participating in the Centers for Disease Control and Prevention (CDC) LAMP program to accurately measure blood-lead levels (BLL) 0.70 to 47.5 μg/dL using evaluation criteria of ±2 μg/dL or 10%, whichever is greater.

Methods:

The CDC distributes bovine blood specimens to participating laboratories 4 times per year. We evaluated participant performance over 5 challenges on samples with BLL between 0.70 and 47.5 μg/dL. The CDC sent 15 pooled samples (3 samples shipped in 5 rounds) to US laboratories. The LAMP laboratories used 3 primary technologies to analyze lead in blood: inductively coupled plasma mass spectrometry, graphite furnace atomic absorption spectroscopy, and LeadCare technologies based on anodic stripping voltammetry. Laboratories reported their BLL analytical results to the CDC. The LAMP uses these results to provide performance feedback to the laboratories.

Setting:

The CDC sent blood samples to approximately 50 US laboratories for lead analysis.

Participants:

Of the approximately 200 laboratories enrolled in LAMP, 38 to 46 US laboratories provided data used in this report (January 2017 to March 2018).

Results:

Laboratory precision ranged from 0.26 μg/dL for inductively coupled plasma mass spectrometry to 1.50 μg/dL for LeadCare instruments. All participating US LAMP laboratories reported accurate BLL for 89% of challenge samples, using the ±2 μg/dL or 10% evaluation criteria.

Conclusions:

Laboratories participating in the CDC's LAMP program can accurately measure blood lead using the current Clinical Laboratory Improvement Amendments of 1988 guidance of ±4 μg/dL or ±10%, with a success rate of 96%. However, when we apply limits of ±2 μg/dL or ±10%, the success rate drops to 89%. When challenged with samples that have target values between 3 and 5 μg/dL, nearly 100% of reported results fall within ±4 μg/dL, while 5% of the results fall outside of the acceptability criteria used by the CDC's LAMP program. As public health focuses on lower blood lead levels, laboratories must evaluate their ability to successfully meet these analytical challenges surrounding successfully measuring blood lead. In addition proposed CLIA guidelines (±2 μg/dL or 10%) would be achievable performance by a majority of US laboratories participating in the LAMP program.
Successfully Changing a State's Climate to Increase Blood Lead Level Testing
Authors: Gettens Gail Coppins , Drouin Beverly Baer
Published: November 2018

Childhood lead poisoning continues to be a persistent environmental pediatric health problem in New Hampshire (NH). In 2015, 660 (4.9%) children younger than 6 years had blood lead levels of 5 µg/dL or more, the Centers for Disease Control and Prevention's recommended level for public health action. Yet, only 16.8% of NH children younger than 6 years were tested. NH's Healthy Homes and Lead Poisoning Prevention Program (HHLPPP) identified 2 barriers to blood lead testing and the opportunities to resolve them: (1) venous testing had lower compliance and resulted in costly follow-up time for providers and (2) lack of understanding in the medical community about the importance of blood lead testing. Strategies to engage pediatric providers needed to recognize the realities of this rural state. In 2016, a strategy with goals of increasing blood lead screening and testing rates statewide with focus on high-risk communities was developed and implemented. The 5-part integrated strategy included the following: (1) implement a medical education program for pediatric providers; (2) increase provider awareness of point-of-care testing equipment; (3) create and distribute medical reference materials; (4) develop parent reminders for blood lead tests; and (5) increase the availability of point-of-care testing equipment. During 2016, NH's HHLPPP presented 25 medical education sessions. Blood lead testing rates improved dramatically, especially at medical sites where both face-to-face education and point-of-care testing were implemented. NH's success serves as a model for other rural areas seeking to improve lead screening rates.
Childhood Lead Poisoning: A Perpetual Environmental Justice Issue?
Authors: Whitehead LaToria S. , Buchanan Sharunda D.
Published: November 2018

As the amount of lead in the environment has significantly decreased with the removal of lead in gasoline and paint, the United States has made great strides in preventing lead poisoning or reducing levels of lead in young children's blood. Even so, lead exposure is not equal for all children—low-income and minority children continue to bear a disproportionate burden of exposure primarily through contact with deteriorating lead-based paint from older housing and potentially through drinking contaminated water resulting from failing leaded pipes, as evidenced by the recent events in Flint, Michigan. These facts suggest that childhood lead poisoning is an environmental justice issue worthy of public health consideration and action; “environmental justice” is focused on identifying and addressing disproportionately high and adverse effects of environmental hazards on low-income and minority communities. The question remains, however, as to whether addressing the quality-of-life “risk” factors associated with lead poisoning might eventually lead to reduction in exposure, as well as potentially resulting in adverse health effects. Utilizing an environmental justice framework and examining this issue through a multidimensional environmental justice lens, we contemplated the quality-of-life factors that may essentially predispose minority children and their families to lead poisoning. Specifically, we examined American Community Survey data (2012-2016) focused on comparing race/ethnicity with other sociodemographic variables known to be associated with risks for childhood lead poisoning. The results provide thought-provoking context for making progress toward eliminating lead poisoning as a major environmental justice concern.
TaTME: 2 Years of Experience of a Single Center
Authors: Piatkowski Jacek , Jackowski Marek , Nowak Mariusz , Szeliga Jacek
Published: November 2018

Introduction:

Concomitant transanal and transabdominal access has shown potential benefits for patients with lower and medial rectal cancers and led to better short-term and medium-term outcomes, a better quality of surgical specimen and a lower number of positive radial margins.

Materials and Methods:

Between 2015 and 2017, 36 patients with rectal cancer underwent transanal total mesorectal excision (TaTME) surgery. The group included 21 males and 16 females. The mean age of the patients was 68.7 years and ranged from 41 to 83 years. In all cases, concomitant transanal and laparoscopic access via abdomen were used. Transanal access was achieved with the use of GelPoint Path Transanal Access Platform (Applied Medical). The lower rectum was visualized with the use of Lone Star retractor (Lone Star Medical Products Inc.).

Results:

In 35 cases R0 resection was reported and R1 in 1 case (2.7%). Mean number of lymph nodes in the specimen was 13.7 (8 to 20 nodes). The mesorectal quality was graded as complete in 34 cases (94.4%) and nearly complete in 2 cases (5.6%). Symptoms of anastomotic leak were observed in 6 cases with 3 patients (8.3%) requiring reoperation.

Conclusions:

TaTME seems to be a promising method of treatment for patients with lower and middle rectal cancer. Short-term outcomes show an advantage of TaTME over laparoscopic total mesorectal excision.
Single-Anastomosis Plication Ileal Bypass (SAPI) in Treatment of Morbid Obesity
Authors: Elbanna Hosam , Emile Sameh , Abdel-Razik Mohamed A.
Published: November 2018

Background:

This report aimed to demonstrate the technical steps and preliminary outcome of a novel bariatric procedure, the single-anastomosis plication ileal bypass (SAPI), for the treatment of morbid obesity.

Materials and Methods:

Totally, 5 female patients with morbid obesity underwent SAPI procedure. The procedure consisted of 2 steps; the first step involved greater curvature plication done in a standardized manner, and the second step involved performing a stapled side-to-side anastomosis between an ileal loop 300 cm distal to the duodenojejunal junction and the gastric antrum. Body mass index (BMI) and percentage excess weight loss (%EWL) at 4 months postoperatively were measured.

Results:

The median age of patients was 38 years. The mean preoperative BMI decreased from 47.3±7.1 kg/m2 to 36.3±6.1 at 4 months, postoperatively. The mean %EWL at 4 months after SAPI was 51.5±10.8. The mean operation time was 66±5.47 minutes. The median hospital stay was one day. No postoperative complications were recorded.

Conclusions:

Despite the small numbers included, the preliminary results of this report show that SAPI is a promising bariatric procedure that achieved significant decrease in BMI and satisfactory excess weight loss. Long-term follow-up of larger number of patients is necessary to reach more firm conclusions on the efficacy and safety of this novel technique.
Cannabinoid drugs: will they relieve or exacerbate tinnitus?
Authors: Zheng Yiwen , Smith Paul F.
Published: November 2018

Purpose of review

Recent enthusiasm for cannabinoid drugs for the treatment of chronic pain and some forms of epilepsy, raises the question of whether they could be useful for other disorders associated with abnormal neuronal activity in the brain, such as subjective tinnitus. Indeed, there is evidence to indicate that some tinnitus sufferers self-medicate usingCannabis.The aim of this review is to critically evaluate the available evidence relating to the effects of cannabinoids on tinnitus.

Recent findings

Despite the fact that cannabinoids have been shown to decrease neuronal hyperactivity in many parts of the brain, the current evidence suggests that in auditory brain regions such as the dorsal cochlear nucleus, they have the potential to facilitate neuronal hyperactivity and exacerbate tinnitus. All of the available experimental evidence from animal studies suggests that cannabinoid CB1receptor agonists will either have no effect on tinnitus or will worsen it.

In our opinion, the use of the available cannabinoid drugs to alleviate tinnitus, based on their alleged efficacy for neuropathic pain conditions and some forms of epilepsy, is premature and not supported by the available evidence.
Divergent mesolimbic dopamine circuits support alcohol-seeking triggered by discrete cues and contexts
Authors: Valyear M.D. , Glovaci I. , Zaari A. , Lahlou S. , Trujillo-Pisanty I. , Chapman C.A. , Chaudhri N.
Published: November 2018

Discrete and contextual cues that predict alcohol trigger alcohol-seeking. However, the extent to which context influences alcohol-seeking triggered by discrete cues, and the neural mechanisms underlying these responses, are not well known. We show that, relative to a neutral context, a context associated with alcohol persistently elevated alcohol-seeking triggered by a discrete cue, and supported higher levels of priming-induced reinstatement. Alcohol-seeking triggered by a discrete cue in a neutral context was reduced by designer receptor-mediated inhibition of ventral tegmental area (VTA) dopamine neurons in TH::Cre rats. Inhibiting terminals of VTA dopamine neurons in the nucleus accumbens (NAc) core reduced alcohol-seeking triggered by a discrete cue, irrespective of context, whereas inhibiting VTA dopamine terminals in the NAc shell selectively reduced the elevation of alcohol-seeking triggered by a discrete cue in an alcohol context. This dissociation highlights unique roles for divergent mesolimbic dopamine circuits in alcohol-seeking driven by discrete and contextual environmental cues.
A Novel Method for Quantifying Traction Forces from Hexagonal Micropatterned Features on Deformable Poly-Dimethyl Siloxane Sheets
Authors: Griffin Brian P. , Largaespada Christopher J. , Rinaldi Nicole A. , Lemmon Christopher A.
Published: November 2018

Many methods exist for quantifying cellular traction forces, including traction force microscopy and microfabricated post arrays. However, these methodologies have limitations, including a requirement to remove cells to determine undeflected particle locations and the inability to quantify forces of cells with low cytoskeletal stiffness, respectively. Here we present a novel method of traction force quantification that eliminates both of these limitations. Through the use of a hexagonal pattern of microcontact-printed protein spots, a novel computational algorithm, and thin surfaces of polydimethyl siloxane (PDMS) blends, we demonstrate a system that quantifies cellular forces on a homogeneous surface that is stable, easily manufactured, and can quantify forces without need for cellular removal.
The genetic robustness of RNA and protein from evolutionary, structural and functional perspectives
Authors: Coray Dorien S. , Sibaeva Nellie , McGimpsey Stephanie , Gardner Paul P.
Published: November 2018

The reactions of functional molecules like proteins and RNAs to mutation affect both host cell viability and biomolecular evolution. These molecules are considered robust if function is maintained despite mutations. Proteins and RNAs have different structural and functional characteristics that affect their robustness, and to date, comparisons between them have been theoretical. In this work, we test the relative mutational robustness of RNA and protein pairs using three approaches: evolutionary, structural, and functional. We compare the nucleotide diversities of functional RNAs with those of matched proteins. Across different levels of conservation, we found the nucleotide-level variations between the biomolecules largely overlapped, with proteins generally supporting more variation than matched RNAs. We then directly tested the robustness of the protein and RNA pairs with in vitro and in silico mutagenesis of their respective genes. The in silico experiments showed that proteins and RNAs reacted similarly to point mutations and insertions or deletions, yet proteins are slightly more robust on average than RNAs. In vitro, mutated fluorescent RNAs retained greater levels of function than the proteins. Overall this suggests that proteins and RNAs have remarkably similar degrees of robustness, with the average protein having moderately higher robustness than RNA as a group.

Significance Statement

The ability of proteins and non-coding RNAs to maintain function despite mutations in their respective genes is known as mutational robustness. Robustness impacts how molecules maintain and change phenotypes, which has a bearing on the evolution and the origin of life as well as influencing modern biotechnology. Both protein and RNA have mechanisms that allow them to absorb DNA-level changes. Proteins have a redundant genetic code and non-coding RNAs can maintain structure and function through flexible base-pairing possibilities. The few theoretical treatments comparing protein and RNA robustness differ in their conclusions. In this experimental comparison of protein and RNA, we find that they have remarkably similar degrees of overall genetic robustness.
Neuropathy and neural plasticity in the subcutaneous white adipose depot
Authors: Blaszkiewicz Magdalena , Willows Jake W. , Dubois Amanda L. , Waible Stephen , Johnson Cory P. , DiBello Kristen , Lyons Lila L. , Breeding William P. , Tilbury Karissa B. , Michael Merilla , Harrison Benjamin , Townsend Kristy L.
Published: November 2018

The difficulty in obtaining as well as maintaining weight loss, together with the loss of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ and metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and less neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature. These findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with exercise, cold exposure or neurotrophic factor treatment, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health.
Metabolism-Induced Oxidative Stress and DNA Damage Selectively Trigger Genome Instability in Polyploid Cells
Authors: Thomson Gregory J. , Hernon Claire , Nicanor Austriaco O.P. , Shapiro Rebecca S. , Belenky Peter , Bennett Richard J.
Published: November 2018

Understanding the forces impacting genome stability is important for diverse processes such as tumorigenesis and reproductive biology. The pathogenic yeastCandida albicansdisplays unusual genome dynamics in which tetraploid cells, but not diploid cells, become unstable when grown on a glucose-rich ‘pre-sporulation’ medium. Here, we reveal thatC. albicanspolyploid cells are metabolically hyperactive on this medium as evidenced by increased expression of metabolic genes as well as higher rates of fermentation and oxidative respiration. These cells also show elevated levels of reactive oxygen species (ROS), activate the ROS-responsive transcription factor Cap1, and accrue DNA double-strand breaks. Suppression of ROS levels reduced oxidative stress, DNA damage and chromosome instability. These studies reveal how metabolic flux can generate endogenous ROS, triggering DNA damage and genome instability in polyploid, but not diploid, cells. We discuss parallels with metabolism-induced instability in cancer cells and propose that ROS-induced DNA damage could have facilitated ploidy cycling in eukaryotes prior to the evolution of meiosis.
Determining targeting specificity of nuclear-encoded organelle proteins with the self-assembling split-fluorescent protein toolkit
Authors: Sharma Mayank , Kretschmer Carola , Lampe Christina , Stuttmann Johannes , Klösgen Ralf Bernd
Published: November 2018

A large number of nuclear-encoded proteins are targeted to the organelles of endosymbiotic origin, namely mitochondria and plastids. To determine the targeting specificity of these proteins, fluorescent protein tagging is a popular approach. However, ectopic expression of fluorescent protein fusions commonly results in considerable background signals and often suffers from the large size and robust folding of the reporter protein, which may perturb membrane transport. Among the alternative approaches that have been developed in recent years, the self-assembling split-fluorescent protein (sasplit-FP) technology appears particularly promising to analyze protein targeting specificityin vivo. Here, we have improved this technology with respect to sensitivity and systematically evaluated its utilization to determine protein targeting to plastids and mitochondria. Furthermore, to facilitate high throughput screening of candidate proteins we have developed aGolden Gate-based vector toolkit, named PlaMiNGo (Plastid and/orMitochondria targeted proteinsN-terminally fused toGFP11 tags viaGolden Gatecloning). As a result of these improvements, dual targeting could be detected for a number of proteins, which had earlier been characterized as being targeted to a single organelle only. These results were independently confirmed with a plant phenotype complementation approach thus demonstrating the sensitivity and robustness of thesasplit-FP-based method to analyze the targeting specificity of nuclear-encoded proteins.

Highlight

Several mono-specific proteins showed dual targeting to plastids and mitochondria with the self-assembling split-GFP system. AGolden Gate-based vector toolkit was constructed to facilitate easy cloning and subsequent determination of protein targeting specificity.
Dynamic properties of internal noise probed by modulating binocular rivalry
Authors: Baker Daniel H. , Richard Bruno
Published: November 2018

Neural systems are inherently noisy, and this noise can affect our perception from moment to moment. This is particularly apparent in binocular rivalry, where our perception of competing stimuli shown to the left and right eyes alternates over time in a seemingly random fashion. We investigated internal noise using binocular rivalry by modulating rivalling stimuli using dynamic sequences of external noise of various rates and amplitudes. As well as measuring the effect on dominance durations, we repeated each external noise sequence twice, and assessed the consistency of percepts across repetitions. External noise modulations with standard deviations above 4% contrast increased consistency scores above baseline, and were most effective at 1/8Hz. A computational model of rivalry in which internal noise has a 1/f (pink) temporal amplitude spectrum, and a standard deviation of 16%, provided the best account of our data, and was able to correctly predict perception in additional conditions. Our novel technique provides detailed estimates of the dynamic properties of internal noise during binocular rivalry, and by extension the stochastic processes that drive our perception and other types of spontaneous brain activity.

Significance statement

Although our perception of the world appears constant, sensory representations are variable because of the ‘noisy’ nature of biological neurons. Here we used a binocular rivalry paradigm, in which conflicting images are shown to the two eyes, to probe the properties of this internal variability. Using a novel paradigm in which the contrasts of rivalling stimuli are modulated by two independent external noise streams, we infer the amplitude and character of this internal noise. The temporal amplitude spectrum of the noise has a 1/f spectrum, similar to that of natural visual input, and consistent with the idea that the visual system evolved to match its environment.