bluuebunny/crossref_metadata_2025 huggingface dataset:
Jak nie postępować z dziećmi, czyli błędy w opiece i wychowaniu ukazane w literaturze poradnikowej dla rodziców z okresu Drugiej Rzeczypospolitej
Authors: Małek Agnieszka
Published: January 2019

The interwar period (1918–1939) on the Polish publishing market, was the time of mingling of the advice books presenting a conservative and progressive attitude to upbringing. Both in the publications recommending traditional educational methods, based mainly on strict discipline, and in the guide books promoting upbringing which takes into account the individuality and distinct character of child’s psyche – apart from guidelines, advice and information – one could find numerous words of criticism pointed at parents. Around a hundred of educational handbooks were published in the period of the Second Republic of Poland. A part of them were translations of books originating from foreign, mainly German pedagogical literature. Their authors were most often educationists and doctors; quite many books were written by clergymen. Advice literature for parents from the interwar period represented very different types. The majority of books were written in the form of advice or warnings directed straight to parents; large group were publications in the form of short stories, in which various problems and the means of solving them were offered; still others had a form of letters or memories, or they were collections of loose remarks concerning care and upbringing. There were also publications in which several of the mentioned forms appeared simultaneously. A frequently used technique was drawing upon personal experience or one’s own pedagogical or medical practice. That was presumably supposed to lend credibility towards the author and establish trust towards the methods of conduct he/she recommended. The scope of issues touched upon by the then advice books was incredibly broad. The advice was related to the matters connected with everyday hygiene and nourishment of children as well as moral, religious and patriotic upbringing. Some of the books were devoted completely to the selected aspects of care and upbringing, other, in turn, formed a collection of advice from many fields. A simple, understandable language of the majority of publications may attest to a broad audiences whom the authors of advice books from the interwar period tried to reach with their remarks and counsel. The far greater part of books was meant for both parents, and only few indicated mothers as their exclusive addressee. Those were primarily the publications devoted to hygiene and nourishment of children as well as formation of their religious attitudes. What is interesting, the reproaches concerning committed mistakes were always pointed at mothers as the persons who were directly involved in and responsible for the upbringing process.
Tradycje zinstytucjonalizowanego poradnictwa psychologiczno-pedagogicznego w Wielkopolsce przed rokiem 1945
Authors: Knocińska Anna
Published: January 2019

The main aim of the dissertation is to present the institutionalized traditions of psychological and pedagogical counseling in Great Poland before 1945. It brings closer the socio-political situation as well as the conditions resulting from the development of the social sciences that influenced the beginning of the first counseling institutions in Great Poland and in the whole country. It also shows the individual counseling posts that started functioning in Poznan in 1945. The outbreak of the World War II interrupted the development of psychological and pedagogical counseling in Great Poland.
Stress degradation studies of hydrochlorothiazide and development of validated method by UV spectroscopy
Authors: Velmurugan Devi
Published: January 2019

To develop a simple, precise, accurate, and stability indicating a UV-method for estimation of Hydrochlorothiazide(HCT)in bulk and formulated dosage form.The drug was alsosubjected to stress degradation at different conditions recommended by the International Conference on Harmonization (ICH).Â The samples are generated and used for the degradation studies.The Î»maxÂ of the HCTwas found to be 273nm.The linearity of calibration curve (Absorbance Vs Concentration) in pure solution was checked over the concentration ranges of about 5-30Î¼g/mLwith the correlation coefficient higher than 0.99.Â The regression equation of the curve was Y = 0.598x + 0.0042.% RSD was found to be within the limit as per ICH guidelines. The obtained percentage recovery ofÂ HCTwas found to be within the limit100% Â± SD.Â Â Stress degradation studies revealed thatitwas within the limit(5-20%).
BILATERAL ABDUCENS NERVE PALSY SECUNDARY TO INTRACRANIAL SINUSES THROMBOSIS IN A CHILD WITH NEPHROTIC SYNDROM – CASE REPORT
Authors: ALVES LARYSSA PEREIRA , SELEGATTO LETÍCIA TAVARES , BATALHA CAROLINA PERES , DE CAMARGO GUSTAVO BUENO , SOBRINHO MARCELO VICENTE DE ANDRADE
Published: January 2019

We report a case of a child with nephrotic syndrome (NS), who presented an acute convergent strabismus, double vision and papilledema one week after a history of badly treated sinusitis. The image study revealed an extensive thrombosis of the intracranial sinuses that was treated with intravenous heparin and oral corticosteroids. Four months later, the case evolved with spontaneous resolution of the ocular deviation and no diplopia.
Metformin activity in an in vitro model of posterior capsule opacification
Authors: Lasiste Jade Marie , Zoroquiain Pablo , Miyamoto Denise , Burnier Miguel
Published: January 2019

Purpose: To determine the activity of metformin in an in vitro model of posterior capsule opacification (PCO).Design: Experimental laboratory research. Methods: The HLE-B3 lens epithelial cell line was treated with PCO induction media (PCOM) supplemented with transforming growth factor-beta (TGF-β) and fibroblast growth factor (FGF). Different metformin concentrations (0-100 mM) were used. The following cellular parameters were assessed: (1) survival, using a viability assay; (2) morphology, via microscopy and image analysis; (3) migration, using the wound assay; (4) and expression of epithelial (Pax6, E-cadherin) and mesenchymal (α-smooth muscle actin or α-SMA, fibronectin) markers via Western blot. Expression of the uptake receptor SLC22A1 was evaluated in HLE-B3 and in human donor eyes with Western blot and immunohistochemistry, respectively. Statistical analysis of variance (ANOVA) with Tukey post-hoc test was done for analysis of cytotoxicity, morphology and migration data. Results: Metformin was lethal to half (LC50) of the cells at 30 mM, and a decrease in viability (P<0.05) was noted at 5 mM. LECs in PCOM treated with 1 mM metformin showed increased Pax6 and E-cadherin and decreased α-SMA and fibronectin expression. LECs in PCOM treated with metformin also maintained epithelial morphology. Migration was inhibited with 0.5 mM metformin (P<0.05). Both HLE-B3 and the lens epithelium in donor eyes were found to express SLC22A1.Conclusion: Metformin decreased survival and migration in LECs, maintaining epithelial phenotype and reducing mesenchymal marker expression. Metformin therefore has potential as an adjunct in PCO prevention.Financial Disclosures: This work was partially funded by Mitacs Canada.
Method to quantify the decentration of the multifocal intraocular lenses in relation to the visual axis
Authors: Polit Fernando Eduardo
Published: January 2019

Since position and centration have shown to affect the effectiveness of multifocal intraocular lenses (MFIOLs), some authors have proposed using the "coaxially sighted IOL light reflex" as a landmark to allow consistent centration of MFIOLs. Postoperatively, assessing the location of the intraocular lens with respect to the visual axis is also important. Centration of the MFIOLs can be identified postoperatively by slit lamp biomicroscopy, but it is still a qualitative method. The Nidek OPD Scan III is used. The instrument obtains retro illumination images, which allows the observation of the diffractive rings of the multifocal intraocular lenses implanted following phacoemulsification. The retro illumination image describes the location of the visual axis (white cross with blue borders +), the center of the photopic (pink cross) and mesopic (turquoise cross) pupil, quantifies the distance between the center of the pupil and the visual axis, and places the visual axis in degrees. It is attempted to match the rings of the lens with that of the acetate grid. Once the best possible equidistance between the lens and grid rings has been achieved. This method can be useful to be able to have reference of a real value of decentration of the lenses and thus have a surgical plan and try to center the lenses. We are also creating a technique to properly center the lenses, in addition to performing an analysis of the results in terms of postoperative visual quality in relation to the lens's decentration and thus see how this really affects.
MESSAGE FROM THE CHAIRMAN, PAOF BOARD
Authors: Garcia Jorge Eugenio Valdez
Published: January 2019

MESSAGE FROM THE CHAIRMAN, PAOF BOARD
ALLERGAN
Authors: Dantas Paulo E.C.
Published: January 2019

ALLERGAN
ALCON
Authors: Dantas Paulo E.C.
Published: January 2019

ALCON
JOHNSON&JOHNSON
Authors: Dantas Paulo E.C.
Published: January 2019

JOHNSON&JOHNSON
VPA DIGITAL AT YOUR FINGERTIPS
Authors: Dantas Paulo E.C.
Published: January 2019

VPA DIGITAL AT YOUR FINGERTIPS
Estimating the Fitness Effect of Deleterious Mutations During the Two Phases of the Life Cycle: A New Method Applied to the Root-Rot Fungus Heterobasidion parviporum
Authors: Clergeot Pierre-Henri , Rode Nicolas O , Glémin Sylvain , Brandström Durling Mikael , Ihrmark Katarina , Olson Åke
Published: January 2019

Many eukaryote species, including taxa such as fungi or algae, have a lifecycle with substantial haploid and diploid phases. A recent theoretical model predicts that such haploid-diploid lifecycles are stable over long evolutionary time scales when segregating deleterious mutations have stronger effects in homozygous diploids than in haploids and when they are partially recessive in heterozygous diploids. The model predicts that effective dominance—a measure that accounts for these two effects—should be close to 0.5 in these species. It also predicts that diploids should have higher fitness than haploids on average. However, an appropriate statistical framework to conjointly investigate these predictions is currently lacking. In this study, we derive a new quantitative genetic model to test these predictions using fitness data of two haploid parents and their diploid offspring, and genome-wide genetic distance between haploid parents. We apply this model to the root-rot basidiomycete fungus Heterobasidion parviporum—a species where the heterokaryotic (equivalent to the diploid) phase is longer than the homokaryotic (haploid) phase. We measured two fitness-related traits (mycelium growth rate and the ability to degrade wood) in both homokaryons and heterokaryons, and we used whole-genome sequencing to estimate nuclear genetic distance between parents. Possibly due to a lack of power, we did not find that deleterious mutations were recessive or more deleterious when expressed during the heterokaryotic phase. Using this model to compare effective dominance among haploid-diploid species where the relative importance of the two phases varies should help better understand the evolution of haploid-diploid life cycles.
Variation in Antibiotic Selection and Clinical Outcomes in Infants <60 Days Hospitalized With Skin and Soft Tissue Infections
Authors: Markham Jessica L. , Hall Matthew , Queen Mary Ann , Aronson Paul L. , Wallace Sowdhamini S. , Foradori Dana M. , Hester Gabrielle , Nead Jennifer , Lopez Michelle A. , Cruz Andrea T. , McCulloh Russell J.
Published: January 2019

OBJECTIVES:

To describe variation in empirical antibiotic selection in infants <60 days old who are hospitalized with skin and soft-tissue infections (SSTIs) and to determine associations with outcomes, including length of stay (LOS), 30-day returns (emergency department revisit or readmission), and standardized cost.

METHODS:

Using the Pediatric Health Information System, we conducted a retrospective study of infants hospitalized with SSTI from 2009 to 2014. We analyzed empirical antibiotic selection in the first 2 days of hospitalization and categorized antibiotics as those typically administered for (1) staphylococcal infection, (2) neonatal sepsis, or (3) combination therapy (staphylococcal infection and neonatal sepsis). We examined the association of antibiotic selection and outcomes using generalized linear mixed-effects models.

RESULTS:

A total of 1319 infants across 36 hospitals were included; the median age was 30 days (interquartile range [IQR]: 17–42 days). We observed substantial variation in empirical antibiotic choice, with 134 unique combinations observed before categorization. The most frequently used antibiotics included staphylococcal therapy (50.0% [IQR: 39.2–58.1]) and combination therapy (45.4% [IQR: 36.0–56.0]). Returns occurred in 9.2% of infants. Compared with administration of staphylococcal antibiotics, use of combination therapy was associated with increased LOS (adjusted rate ratio: 1.35; 95% confidence interval: 1.17–1.53) and cost (adjusted rate ratio: 1.39; 95% confidence interval: 1.21–1.58), but not with 30-day returns.

CONCLUSIONS:

Infants who are hospitalized with SSTI experience wide variation in empirical antibiotic selection. Combination therapy was associated with increased LOS and cost, with no difference in returns. Our findings reveal the need to identify treatment strategies that can be used to optimize resource use for infants with SSTI.
Smoke Exposure, Cytokine Levels, and Asthma Visits in Children Hospitalized for Bronchiolitis
Authors: Willis Amy L. , Moss Angela , Torok Michelle , Lowary Michelle , Klein Jonathan D. , Wilson Karen M.
Published: January 2019

BACKGROUND AND OBJECTIVE:

To determine if cigarette smoke exposure, marijuana smoke exposure, or cytokine levels at admission to the hospital for bronchiolitis are associated with follow-up visits for asthma.

METHODS:

We enrolled a cohort of children aged 31 days to 2 years who were hospitalized with bronchiolitis from January 2013 to April 2014. Data included the results of a baseline survey about children’s health and demographics, nasal wash samples, the results of a 6-month postdischarge follow-up survey, and a chart review. Nasal wash samples were tested for interleukin (IL)-6, IL-13, and tumor necrosis factor α (TNF-α); values were categorized for analysis. χ2, Fisher’s exact, and Wilcoxon rank tests were done to test bivariable differences; all analyses were done using SAS.

RESULTS:

We approached 180 families for enrollment; 99 consented to participate, and 74% of these completed follow-up surveys. Half of those with high levels of IL-13 had follow-up visits for asthma, whereas only 4.2% of those with low levels had follow-up visits for asthma (P = .02). Marijuana exposure was reported for 12.5% (n = 7) of study participants. There was a significant association between marijuana exposure and TNF-α levels (P = .03).

CONCLUSIONS:

Our study revealed an association between IL-13 and follow-up visits for asthma in children who were hospitalized with bronchiolitis. We found an association between family-reported marijuana smoke exposure and detectable but lower levels of TNF-α. Further research is needed to study these relationships.
Low Value of Thyroid Testing in the Pediatric Inpatient Setting
Authors: Torky Ahmed , LaRue Meredith , Kaplowitz Paul
Published: January 2019

OBJECTIVES:

Our objective was to assess the frequency of pediatric inpatient thyroid testing, frequency of detection of abnormal results, and apparent impact on patient management.

METHODS:

This is a retrospective study of admissions from July 2015 to June 2016 at a large urban children’s hospital. Chart review was conducted on all hospitalized pediatric patients who underwent thyroid testing. We used a normal range of 0.5 to 5.0 μIU/mL for thyroid-stimulating hormone (TSH) and 1.0 to 2.0 ng/dL for free thyroxine (FT4), except for neonates for whom we used the higher reference ranges specified by the hospital laboratory.

RESULTS:

Thyroid testing occurred in 1202 (5.7%) of 20 907 hospitalizations; 79.3% had combined thyroid function tests (TFTs) with TSH + FT4 being most common, and 20.6% had TSH only. Combined TFTs were ordered routinely by psychiatry and frequently by endocrine, gastrointestinal, cardiology, and neurology services, but many cases had no identified reason for testing. Of the 205 abnormal tests (17.1%), the most common abnormalities in the combined TFTs group were normal FT4 and increased TSH (35.4%) (76% of which were between 5 and 10 μIU/mL), normal FT4 and TSH 0.1 to 0.5 μIU/mL (33.1%), and high FT4 but normal TSH (14.3%). Patients with new-onset type 1 diabetes had borderline low or high TSH in about 20% of cases, but all abnormalities resolved at outpatient follow-up. Overall, 8 patients (0.66%) were started on levothyroxine.

CONCLUSIONS:

Pediatric inpatient thyroid testing is relatively common at our institution, and although results are often abnormal, they do not point to thyroid disease that has contributed to the reason for hospitalization and do not identify patients in urgent need of starting therapy.
Encounters From Device Complications Among Children With Medical Complexity
Authors: Nackers Allison , Ehlenbach Mary , Kelly Michelle M. , Werner Nicole , Warner Gemma , Coller Ryan J.
Published: January 2019

OBJECTIVES:

Children with medical complexity (CMC) are commonly assisted by medical devices to support essential body functions, although complications may lead to preventable emergency department (ED) and hospital use. Our objective was to identify predictors of device-complicated ED visits and hospitalizations.

METHODS:

This single-center retrospective cohort study included patients referred to a Pediatric Complex Care Program between April 1, 2014, and April 30, 2016, assisted by at least 1 medical device. Hospitalizations and ED visits in the year before enrollment were rated for likelihood for being due to device complications. Interrater reliability among 3 independent reviewers was assessed. Bivariate followed by multivariate logistic regression clustered by patient helped us identify associations between demographic, clinical, and device characteristics associated with device-complicated ED or hospital encounters.

RESULTS:

Interrater reliability was high (κ = 0.92). Among 98 CMC, device-complicated encounters represented 17% of 258 hospitalizations and 31% of 228 ED visits. Complications of 3 devices (central venous catheters, enteral tubes, and tracheostomy tubes) accounted for 13% of overall hospitalizations and 28% of overall ED visits. Central venous catheter presence (adjusted odds ratio [aOR] 3.2 [95% confidence interval (CI) 1.1–9.5]) was associated with device-complicated ED visits. Gastrojejunostomy/jejunostomy tube presence (aOR 3.3 [95% CI 1.5–7.5]) or tracheostomies with (aOR 8.1 [95% CI 2.3–28.5]) or without (aOR 4.5 [95% CI 1.7–7.5]) ventilator use was associated with device-complicated hospitalizations. Clinical variables were poor predictors of device-complicated encounters.

CONCLUSIONS:

Device-complicated ED visits and hospitalizations comprised a substantial proportion of total hospital and ED use. Developing interventions to prevent device complications may be a promising strategy to reduce overall CMC use.
Newborn Vitamin K Prophylaxis: A Historical Perspective to Understand Modern Barriers to Uptake
Authors: Majid Atif , Blackwell Miranda , Broadbent Roland S. , Barker David P. , Al-Sallami Hesham S. , Edmonds Liza , Kerruish Nikki , Wheeler Benjamin J.
Published: January 2019

Since its initial discovery almost a century ago, vitamin K has been labeled as both lifesaving and malignancy causing. This has led to debate of not only its use in general but also regarding its appropriate dose and route. In this article, we review through a historical lens the past 90 years of newborn vitamin K from its discovery through to its modern use of preventing vitamin K deficiency bleeding (VKDB). Although researchers in surveillance studies have shown considerable reductions in VKDB following intramuscular vitamin K prophylaxis, ongoing barriers to the universal uptake of vitamin K prophylaxis remain. Reviewing the history of newborn vitamin K provides an opportunity for a greater understanding of the current barriers to uptake that we face. Although at times difficult, improving this understanding may allow us to address contentious issues related to parental and health professional beliefs and values as well as improve overall communication. The ultimate goal is to improve and maintain the uptake of vitamin K to prevent VKDB in newborns.
Racial, Ethnic, and Socioeconomic Disparities in Patient Safety Events for Hospitalized Children
Authors: Stockwell David C. , Landrigan Christopher P. , Toomey Sara L. , Westfall Matthew Y. , Liu Shanshan , Parry Gareth , Coopersmith Ari S. , Schuster Mark A. ,   for the GAPPS Study Group
Published: January 2019

OBJECTIVES:

Previous studies have revealed racial/ethnic and socioeconomic disparities in quality of care and patient safety. However, these disparities have not been examined in a pediatric inpatient environment by using a measure of clinically confirmed adverse events (AEs). In this study, we do so using the Global Assessment of Pediatric Patient Safety (GAPPS) Trigger Tool.

METHODS:

GAPPS was applied to medical records of randomly selected pediatric patients discharged from 16 hospitals in the Pediatric Research in Inpatient Settings Network across 4 US regions from January 2007 to December 2012. Disparities in AEs for hospitalized children were identified on the basis of patient race/ethnicity (black, Latino, white, or other; N = 17 336 patient days) and insurance status (public, private, or self-pay/no insurance; N = 19 030 patient days).

RESULTS:

Compared with hospitalized non-Latino white children, hospitalized Latino children experienced higher rates of all AEs (Latino: 30.1 AEs per 1000 patient days versus white: 16.9 AEs per 1000 patient days; P ≤ .001), preventable AEs (Latino: 15.9 AEs per 1000 patient days versus white: 8.9 AEs per 1000 patient days; P = .002), and high-severity AEs (Latino: 12.6 AEs per 1000 patient days versus white: 7.7 AEs per 1000 patient days; P = .02). Compared with privately insured children, publicly insured children experienced higher rates of preventable AEs (public: 12.1 AEs per 1000 patient days versus private: 8.5 AEs per 1000 patient days; P = .02). No significant differences were observed among other groups.

CONCLUSIONS:

The GAPPS analysis revealed racial and/or ethnic and socioeconomic disparities in rates of AEs experienced by hospitalized children across a broad range of geographic and hospital settings. Further investigation may reveal underlying mechanisms of these disparities and could help hospitals reduce harm.
Safety of Peripherally Inserted Central Catheter Use in Children From Rural Versus Urban Settings Receiving Long-term Parenteral Antimicrobial Therapy
Authors: Beachum Natasha , Dehority Walter
Published: January 2019

OBJECTIVES:

To determine the safety of peripherally inserted central catheter (PICC) use for delivery of outpatient parenteral antimicrobial therapy (PAT) in children discharged to rural or urban locales. We hypothesized that children from rural settings would experience higher complication rates.

PATIENTS AND METHODS:

We conducted a retrospective cohort study of children admitted to an academic medical center in the Southwestern United States over 9 years who were discharged with a PICC to complete a course of PAT with follow-up at our institution. To classify rural versus urban residence, we used rural-urban continuum codes from the US Department of Agriculture, the driving time in hours to the nearest trauma center, and the discharging center using Google Maps.

RESULTS:

In total, 221 children met inclusion criteria (mean age 9.8 years). Osteoarticular infections and cystic fibrosis exacerbations were the most common indications for PICC use (68.8%). The mean driving time to the discharging hospital was significantly longer for those children residing in the most rural regions of the state (3.6 vs 0.8 hours; P < .001) as well as to the nearest level 1, 2, or 3 trauma center (2.2 vs 0.4 hours; P < .001). PICC complications occurred in 47 children (21.3%). No association was found between rural-urban continuum codes, driving times to the discharging hospital, or nearest trauma center with any complication nor with complications overall.

CONCLUSIONS:

In our study, we demonstrate an equivalent safety profile for children in rural and urban settings with PICCs for receipt of outpatient PAT.
Probiotics and Human Milk Oligosaccharides in Premature Infants
Authors: Underwood Mark A.
Published: January 2019

Intestinal dysbiosis precedes and is a likely causative factor in necrotizing enterocolitis (NEC) and many cases of late-onset sepsis. Randomized controlled trials and observational cohort studies demonstrate decreased risk of NEC, sepsis, and death with the administration of probiotic microbes and decreased risk of NEC and sepsis with feeding of human milk. Animal studies suggest promising mechanisms by which probiotic microbes and human milk oligosaccharides alter the composition of the intestinal microbiota and may prevent disease in premature infants. Inclusion of parents in discussions of the risks and benefits of human milk and probiotics for premature infants is essential.
Gastrointestinal, Pancreatic, and Hepatic Manifestations of Cystic Fibrosis in the Newborn
Authors: Galante Gary , Freeman A. Jay
Published: January 2019

Gastrointestinal, pancreatic, and hepatic signs and symptoms represent the most common presentation of early disease among patients with cystic fibrosis and may be the initial indication of disease. Regardless of whether cystic fibrosis is diagnosed early by newborn screening or later by clinical course, the impact of gastrointestinal, pancreatic, and hepatic manifestations on early life is nearly ubiquitous. Conditions strongly linked with cystic fibrosis, such as meconium ileus and pancreatic insufficiency, must be recognized and treated early to optimize both short- and long-term care. Similarly, less specific conditions such as reflux, poor weight gain, and cholestasis are frequently encountered in infants with cystic fibrosis. In this population, these conditions may present unique challenges in which early interventions may have significant influence on both short- and long-term morbidity and mortality outcomes.
Macronutrient Digestion and Absorption in the Preterm Infant
Authors: Rogido Marta , Griffin Ian
Published: January 2019

The human fetus receives oral nutrition through swallowed amniotic fluid and this makes a significant nutritional contribution to the fetus. Postnatally, macronutrient absorption and digestion appear to function well in the preterm infant. Although pancreatic function is relatively poor, the newborn infant has several mechanisms to overcome this. These include a range of digestive enzymes in human milk, novel digestive enzymes involved in fat and protein digestion that do not appear to be present in the older child or adult, and the presence of a Bifidobacterium-rich colonic microbiome that may “scavenge” unabsorbed macronutrients and make them available to the infant.
Ethical and Psychosocial Issues in Whole Genome Sequencing (WGS) for Newborns
Authors: Lantos John D.
Published: January 2019

In this article, I review some of the ethical issues that have arisen in the past when genetic testing has been done in newborns. I then suggest how whole genome sequencing may raise a new set of issues. Finally, I introduce a series of other articles in which the authors address different controversies that arise when whole genome sequencing is used in the newborn period.
Perceived Benefits, Risks, and Utility of Newborn Genomic Sequencing in the BabySeq Project
Authors: Pereira Stacey , Robinson Jill Oliver , Gutierrez Amanda M. , Petersen Devan K. , Hsu Rebecca L. , Lee Caroline H. , Schwartz Talia S. , Holm Ingrid A. , Beggs Alan H. , Green Robert C. , McGuire Amy L. ,   on behalf of The BabySeq Project Group
Published: January 2019

BACKGROUND AND OBJECTIVES:

There is interest in applying genomic sequencing (GS) to newborns’ clinical care. Here we explore parents’ and clinicians’ attitudes toward and perceptions of the risks, benefits, and utility of newborn GS compared with newborn screening (NBS) prior to receiving study results.

METHODS:

The BabySeq Project is a randomized controlled trial used to explore the impact of integrating GS into the clinical care of newborns. Parents (n = 493) of enrolled infants (n = 309) and clinicians (n = 144) completed a baseline survey at enrollment. We examined between-group differences in perceived utility and attitudes toward NBS and GS. Open-ended responses about risks and benefits of each technology were categorized by theme.

RESULTS:

The majority of parents (71%) and clinicians (51%) agreed that there are health benefits of GS, although parents and clinicians agreed more that there are risks associated with GS (35%, 70%) than with NBS (19%, 39%; all P < .05). Parents perceived more benefit and less risk of GS than did clinicians. Clinicians endorsed concerns about privacy and discrimination related to genomic information more strongly than did parents, and parents anticipated benefits of GS that clinicians did not.

CONCLUSIONS:

Parents and clinicians are less confident in GS than NBS, but parents perceive a more favorable risk/benefit ratio of GS than do clinicians. Clinicians should be aware that parents’ optimism may stem from their perceived benefits beyond clinical utility.
Rapid Challenges: Ethics and Genomic Neonatal Intensive Care
Authors: Gyngell Christopher , Newson Ainsley J. , Wilkinson Dominic , Stark Zornitza , Savulescu Julian
Published: January 2019

NICUs are a priority implementation area for genomic medicine. Rapid genomic testing in the NICU is expected to be genomic medicine’s “critical application,” providing such clear benefits that it drives the adoption of genomics more broadly. Studies from multiple centers worldwide have now demonstrated the clinical utility and cost-effectiveness of rapid genomic sequencing in this setting, paving the way for widespread implementation. However, the introduction of this potentially powerful tool for predicting future impairment in the NICU also raises profound ethical challenges. Developing models of good practice that incorporate the identification, exploration, and analysis of ethical issues will be critical for successful implementation. In this article, we analyze 3 such issues: (1) the value and meaning of gaining consent to a complex test in a stressful, emotionally charged environment; (2) the effect of rapid diagnosis on parent-child bonding and its implications for medical and family decisions, particularly in relation to treatment limitation; and (3) distributive justice (ie, whether the substantial cost and diversion of resources to deliver rapid genomic testing in the NICU can be justified).
Challenging the Current Recommendations for Carrier Testing in Children
Authors: VanNoy Grace E. , Genetti Casie A. , McGuire Amy L. , Green Robert C. , Beggs Alan H. , Holm Ingrid A. ,   The BabySeq Project Group
Published: January 2019

The authors of current professional guidelines generally do not support the return of information about genetic carrier status for infants and children because of a perceived lack of immediate benefit and an abundance of caution regarding potential harm and desire to protect the children’s future autonomy. The advent of genomic sequencing, used either as a diagnostic or a screening tool, and the increasing use of this technology in childhood creates the potential for the identification of carrier status in the pediatric period. As part of the BabySeq Project, researchers are exploring the implications of genomic sequencing in both newborns who are healthy and newborns who are sick and developing policies and procedures for the return of carrier status information to the parents and physicians of newborns. In this commentary, we review the history of carrier testing in children and explore the potential benefits, risks, and challenges of returning such results both for the children, their parents, and potential future siblings.
The False-negative Phenotype
Authors: Lantos John D.
Published: January 2019

Ethical controversies may arise when genome sequencing reveals a genetic variant that is thought to be pathogenic, but the patient has no symptoms. This could be due to variable penetrance or expressivity. It could also result from a misclassification of the gene as pathogenic. In this article, I analyze 2 possibilities when such a situation occurs. The first is straightforward. We could conclude that the sequencing results should be considered a “false-positive” test result. The second is a bit more counterintuitive. In some cases, we could consider the test result to be a true-positive but in way that has not yet led to phenotypic findings. Somewhat playfully, we imagine that, in such cases, we could consider the patient’s phenotype to be falsely negative. Sometimes, as odd as it seems, we act is if that is what we believe.
Returning a Genomic Result for an Adult-Onset Condition to the Parents of a Newborn: Insights From the BabySeq Project
Authors: Holm Ingrid A. , McGuire Amy , Pereira Stacey , Rehm Heidi , Green Robert C. , Beggs Alan H. ,   and the BabySeq Project Team
Published: January 2019

The return of information from genomic sequencing in children, especially in early life, brings up complex issues around parental autonomy, the child’s future autonomy, the best interest standard, and the best interests of the family. These issues are particularly important in considering the return of genomic results for adult-onset–only conditions in children. The BabySeq Project is a randomized trial used to explore the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of newborns who are healthy or sick. We discuss a case in which a variant in a gene for an actionable, adult-onset–only condition was detected, highlighting the ethical issues surrounding the return of such finding in a newborn to the newborn’s parents.
Physician Communication of Genomic Results in a Diagnostic Odyssey Case Series
Authors: Rubanovich Caryn Kseniya , Cheung Cynthia , Torkamani Ali , Bloss Cinnamon S.
Published: January 2019

BACKGROUND AND OBJECTIVES:

The availability of whole genome sequencing (WGS) is increasing in clinical care, and WGS is a promising tool in diagnostic odyssey cases. Physicians’ ability to effectively communicate genomic information with patients, however, is unclear. In this multiperspective study, we assessed physicians’ communication of patient genome sequencing information in a diagnostic odyssey case series.

METHODS:

We evaluated physician communication of genome sequencing results in the context of an ongoing study of the utility of WGS for the diagnosis of rare and idiopathic diseases. A modified version of the Medical Communication Competence Scale was used to compare patients’ ratings of their physicians’ communication of general medical information to communication of genome sequencing information. Physician self-ratings were also compared with patient ratings.

RESULTS:

A total of 47 patients, parents, and physicians across 11 diagnostic odyssey cases participated. In 6 of 11 cases (54%), the patient respondent rated the physician’s communication of genome sequencing information as worse than that of general medical information. In 9 of 11 cases (82%), physician self-ratings of communication of genome sequencing information were worse than the patient respondent’s rating. Identification of a diagnosis via WGS was positively associated with physician self-ratings (P = .021) but was not associated with patient respondent ratings (P = .959).

CONCLUSIONS:

These findings reveal that even in diagnostic odyssey cases, in which genome sequencing may be clinically beneficial, physicians may not be well-equipped to communicate genomic information to patients. Future studies may benefit from multiperspective approaches to assessing and understanding physician-patient communication of genome-sequencing information.
Neonatologists’ Attitudes About Diagnostic Whole-Genome Sequencing in the NICU
Authors: Knapp Brett , Decker Carole , Lantos John D.
Published: January 2019

Using focus group methodology, we studied the attitudes of neonatologists regarding diagnostic rapid genome sequencing for newborns who were critically ill in a NICU. One focus group took place within the first year after whole-genome sequencing testing became available, and another focus group took place 3 years later. Focus groups were audiotaped, transcribed, and analyzed by using standard techniques of grounded theory. Different analysts coded them for themes. The analysts then discussed differences and agreed on major themes. Twelve doctors participated in the first focus group, and 9 doctors participated in the second; 62% were attending physicians, and the rest were fellows. There were 14 women and 7 men. We did not collect any other demographic information on participants. Surprisingly, we found few differences between the earlier focus group and the later one. Comments were categorized as falling into 4 domains: (1) uncertainty about the interpretation of results, (2) issues about parental consent and limits on their right to know genomic information, (3) different opinions about whether and how genomic results could be clinically useful, and (4) potential harms of genomic testing.
The relationship between bacterial types and antibiotic resistance with the clinical outcomes of sepsis patients in Pediatric Intensive Care Unit at Sanglah Hospital Denpasar, Bali-Indonesia
Authors: Agustini Ni Made Ayu , Wati Dyah Kanya , Suparyatha IBG , Hartawan I Nyoman Budi , Utama I Made Gede Dwi Lingga , Budayanti Ni Nyoman Sri , Tunas I Ketut
Published: January 2019

Background: Sepsis in children could significantly increase the morbidity and mortality rates particularly in the Pediatric Intensive Care Unit (PICU). Moreover, the prevalence of antibiotic resistance is continuously increasing around the world mainly caused by uncontrolled used of antibiotic. Henceforth, this study aimed to determine the relationship between bacterial type and the resistance with clinical outcome of sepsis patients in PICU.Methods: An observational analytic retrospective cohort study using medical record data from January 2015-April 2017 was conducted. All subjects were sepsis patients with positive blood cultures treated at PICU Sanglah Hospital. Factors related to mortality and relative risk (RR) were analyzed using Chi-Square Test with a significance value of p <0.05 with 95% confidence interval (CI).Results: 75 subjects met the inclusion criteria, but only 63 subjects with complete data were enrolled. The gram-negative and MDR bacteria types were detected in 31 (49%) subjects and 33 (52.4%) subjects respectively. The number of deaths was 29 (46%). The most common types of gram-negative bacteria were Pseudomonas aeruginosa (16%) followed by gram-positive Staphylococcus hominis (25%). The most common multi-drug resistant (MDR) bacteria were Staphylococcus hominis. The presence of MDR bacteria significantly increase the mortality (p = 0.015, RR 2.02, 95% CI: 1.096-3.725), whereas gram-negative had no significant mortality impact (p = 0.891: RR 0.96; 95% CI: 0.564- 1.645). Compared to non-MDR bacteria, most MDR related mortality occurred during the first 10 days.Conclusion: MDR bacteria significantly increased the mortality rates in pediatric patient treated in PICU compared to non-MDR ones.Â
The early onset of Chronic Kidney Disease stage five in 11 years old boy with Autosomal Dominant Polycystic Kidney Disease due to PKD-1 mutation
Authors: Agustini Ni Made Ayu , Suarta I Ketut , Nilawati Gusti Ayu Putu , Arijana I Gusti Kamasan Nyoman
Published: January 2019

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Only a few renal cysts are detected in most affected individuals before 30 years of ages and only 2% of patients with ADPKD present with early clinical manifestations before 15 years old. The average age at onset of chronic kidney disease (CKD) was 50 years. ADPKD is caused by mutations in one of two genes, PKD 1 and PKD 2. PKD1 was associated with more severe disease than PKD2, with earlier age at diagnosis, higher number of kidney cysts, the earlier onset of hypertension and faster progression to CKD stage five. Â Objective: To describe of the factors that caused early onset of CKD stage five in ADPKD.Case: An 11 years old boy diagnosed with CKD stage 5 caused by ADPKD with urinary tract infection. The patient complaint with fatigue, pale, fever, flank pain and cloudy urine. The grandfather got the renal failure history and aunty got hypertension since she was young. The parents of patient have consanguinous mating. In the physical examination has been found hypertension grade 1. The laboratory test has been shown decrease of glomerular filtration rate, anemia, imbalance electrolite and metabolic acidosis. Urine investigationÂ  with leucosituria and positive E. Colli. UltrasonographyÂ  and CT stonography showed bilateral multiple cysts in the kidneys with left kidney enlargement. His parents also got multiple cysts in both of kidneys with the normal size of kidneys. Gene analysis showed homozygous for missense mutations 11734insC, in exon 43 of the PKD 1 gene. The patient got regular hemodialysis and other supportive therapy.Conclusion: The early onset of CKD stage five in ADPKD is related to PKD 1 homozygous gene mutation, male gender and enlargement of kidney.
Sweet pranajiwa (Sterculia javanica R. Br) seed extract increases spermatogenesis and sexual behavior in mice (Mus musculus)
Authors: Widianti I Gusti Ayu , Wardana I Nyoman Gede , Wirata Gede
Published: January 2019

Background: As regards the increasing number of infertility cases in male, it induces them to use various kinds of medicine include alternative medicine. Some drugs that improve the sexual behavior previously have been approved for several years. Especially for pranajiwa seed extract, its sexual effect had not been tested previously. Aim: This study was designed to show a botanical product named: pranajiwa seed widely used as an aphrodisiac, could increases spermatogenesis and sexual behavior Methods: The design of this experimental research is a randomized pre-posttest control group design. Data were collected from 44 mice divided into 4 groups: the first is the control group, the second group is 2.5% Pranajiwa seed extract, the third group contains 5% sweet Pranajiwa seed extract and the last is treated with 10% Pranajiwa seed extract. Results: Sweet Pranajiwa seed extract, in different concentration 2.5%, 5% and 10% respectively, which is given every day for 35 days could increase the spermatogenesis, frequency of mounting and intromission, and there was a decrease of time for mounting and intromission. Conclusion: All of pranajiwa seed extract concentration were significantly increase spermatogenesis and sexual behavior instead of control group (p<0.05).Â
Oncogenic role of miRNA-221/222 in breast cancer
Authors: Ardyan Sudharta Putra I Wayan , Supadmanaba I Gede Putu , Sudarsa I Wayan
Published: January 2019

Breast cancer stills remains as one of the major health problems in the world which ranks as the top cause of death of women with a percentage of 21.4%. There is connection of microRNAs (miRNA) with carcinogenesis process. miRNAs are small non coding RNAs (18 to 24 nucleotides) and formed as single-stranded RNAs (ssRNAs). The action of miRNAs is depended from their expression levels and function which can either promote oncogenesis (oncomiRs) or act as tumor suppressor pathways. One of the oncomiRs is miR-221 and miR-222, both are expressed by single transcription that are found on the X chromosome. The regulation transcription of miR-221/222 gene is control by positive and negative feedback. miR-221/222 directly targets PTEN, pro-apoptotic protein and tumor suppression gene, SOCS1 and CDKN1B in order to promote the proliferation of the cells. Â miR-221/222 enhances the aggressiveness of tumor through regulates the epithelial to mesenchymal transition (EMT) by targeting Tricho-rhino phalangeal syndrome type 1 (TRPS1) gene. miR-221/222 induces resistance of endocrine therapy in breast cancer especially tamoxifen and fulvestrant. The role of miR-221/222 in carcinogenesis is very complex that can upregulate or downregulate a protein. In addition, overexpression of miR-221/222 also enhances aggressiveness characteristics of breast cancer.Â
Vascular Endothelial Growth Factor (VEGF) on rabbit meniscus injury in the white-white zone expressed higher blood vessels distribution and type 1 collagen bridging post meniscal suturing
Authors: Meregawa Putu Feryawan , Suyasa I Ketut , Kawiyana I Ketut Siki , KG Mulyadi Ridia
Published: January 2019

Background: Meniscus injury can occur in red - red zone with good prognostic as well as in white - white zone with bad one. General treatment of meniscus injury in white â€“ white is menisectomy. It will destroy the articular surface of the knee joint cartilage. Administration the Vascular Endothelial Growth Factor (VEGF) will increase the proliferation of endothelial cells, fibroblast cells, collagen fibers type 1, and good prognostic for the healing of meniscus injury in white â€“ white zone. Aim: The study aims to explore the effect of VEGF on rabbit meniscus injury. Methods: This research implemented an experimental study with randomized post-test control group design which used 38 male New Zealand Rabbits. There were two groups (18 rabbits as a control group and 18 rabbits as treatment one). They were adapted for one week, then control group had a sharp incision and sutured in white â€“ white zone meniscus only, and treatment group had administration VEGF after done a sharp incision and sutured in white â€“ white zone meniscus. In the next three weeks, all rabbits have been euthanized and then examined the meniscus for the expression of blood vessels distribution and the bridging of collagen type 1 by histopathology and immunohistochemistry examination. Results: The average median number for blood vessels distribution after administration VEGF in the sutured white-white zone was about 11.00 (interquartile range 2.00) and without VEGF was about 5.00 (interquartile range 1.00). In the treatment group with VEGF, 18 rabbits (100%) showed bridging collagen type 1, and the control one showed in 6 rabbits (33.33%). An inferential test for blood vessels distribution in white â€“ white zone meniscus between treatment group with VEGF and control group without VEGF was significantly different (p=0.000). Analysis for bridging collagen type 1 between treatment group with VEGF and control group without VEGF showed significant differences (p=0.000). Conclusion: Administration VEGF on rabbit meniscus injury in the post suturing white-white zone expressed higher blood vessels distribution and bridging collagen type 1 compared with suturing only without VEGF.