bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Indicator Derived From Reticulocyte Hemoglobin Content for Screening Iron Deficiency in an Area Prevalent for Thalassemia
Authors: Jamnok Jutatip , Sanchaisuriya Kanokwan , Chaitriphop Chaninthorn , Sanchaisuriya Pattara , Fucharoen Goonnapa , Fucharoen Supan
Published: December 2019

Objective

To establish a new indicator derived from reticulocyte hemoglobin (Ret-He) content and red blood cell (RBC) indices for screening for iron deficiency anemia (IDA) in an area in whch thalassemia is prevalent.

Methods

Blood specimens from 304 women aged between 18 and 30 years residing in northeast Thailand were collected and measured for RBC and reticulocyte parameters. Iron deficiency was diagnosed when a participant had a serum ferritin level of less than 15 ng per mL. Thalassemia genotypes were defined by hemoglobin (Hb) and DNA analyses.

Results

Of the total participants, 25% had iron deficiency (ID) and 50% carried the thalassemia gene. Various mathematical formulas were established and analyzed using the receiver operating characteristic (ROC) curve. The formula derived from Ret-He: (Ret-He/RDW-SD) × 10, was the best predictor for identifying ID among participants (area under the curve [AUC] = 0.812). Further testing of this indicator among individuals with positive thalassemia-screening results revealed stronger performance with an AUC of 0.874.

Conclusions

The findings indicate that the formula derived from Ret-He might be applicable for screening ID in areas in which thalassemia is prevalent.
Identification and characterization of occult human-specific LINE-1 insertions using long-read sequencing technology
Authors: Zhou Weichen , Emery Sarah B , Flasch Diane A , Wang Yifan , Kwan Kenneth Y , Kidd Jeffrey M , Moran John V , Mills Ryan E
Published: December 2019

Long Interspersed Element-1 (LINE-1) retrotransposition contributes to inter- and intra-individual genetic variation and occasionally can lead to human genetic disorders. Various strategies have been developed to identify human-specific LINE-1 (L1Hs) insertions from short-read whole genome sequencing (WGS) data; however, they have limitations in detecting insertions in complex repetitive genomic regions. Here, we developed a computational tool (PALMER) and used it to identify 203 non-reference L1Hs insertions in the NA12878 benchmark genome. Using PacBio long-read sequencing data, we identified L1Hs insertions that were absent in previous short-read studies (90/203). Approximately 81% (73/90) of the L1Hs insertions reside within endogenous LINE-1 sequences in the reference assembly and the analysis of unique breakpoint junction sequences revealed 63% (57/90) of these L1Hs insertions could be genotyped in 1000 Genomes Project sequences. Moreover, we observed that amplification biases encountered in single-cell WGS experiments led to a wide variation in L1Hs insertion detection rates between four individual NA12878 cells; under-amplification limited detection to 32% (65/203) of insertions, whereas over-amplification increased false positive calls. In sum, these data indicate that L1Hs insertions are often missed using standard short-read sequencing approaches and long-read sequencing approaches can significantly improve the detection of L1Hs insertions present in individual genomes.
Assessing interobserver variability and accuracy in the histological diagnosis and classification of cutaneous neurofibromass
Authors: Ortonne Nicolas , Carroll Steven L , Rodriguez Fausto J , Miller Douglas C , Nazarian Rosalynn M , Blakeley Jaishri O , Madaj Zachary B , Verma Sharad K , Stemmer-Rachamimov Anat
Published: December 2019

Background

Cutaneous neurofibromas (cNFs) are the most common tumors in people with neurofibromatosis type 1 (NF1) and are associated with reduced quality of life. There is currently no widely accepted standardized language for describing cNFs clinically or histopathologically. The objective of this study was to evaluate interobserver agreement across pathologists in describing and reporting of neurofibromas involving the skin.

Methods

Twenty-eight (H&E)-stained slides of cNF were scanned using an Aperio XT scanner. The digital images were reviewed by 6 pathologists, who entered free text of up to a 200 word description for each case into a REDcap database. Responses were analyzed for the most commonly used terms based on frequency, as well as agreement (reported as concordance) between reviewers.

Results

A set of the terms most commonly used by pathologists for the histological classification of cNF along with areas of agreement and disagreement have been identified. The study shows that there was strong agreement across reviewers that not all neurofibromas involving the skin are cutaneous neurofibromas and regarding the presence or absence of atypical features and heterologous elements. Areas of less concordance were identified and include cNF subtypes, definition of extension and pattern of growth, as well as the distinction of a cNF from a plexiform without an intraneural component involving skin.

Conclusions

This work is the first step towards development of a robust classification system and devising “gold standard” histopathologic diagnostic criteria for cutaneous neurofibromas.
Organic photovoltaic cell with 17% efficiency and superior processability
Authors: Cui Yong , Yao Huifeng , Hong Ling , Zhang Tao , Tang Yabing , Lin Baojun , Xian Kaihu , Gao Bowei , An Cunbin , Bi Pengqing , Ma Wei , Hou Jianhui
Published: December 2019

The development of organic photoactive materials, especially the newly emerging non-fullerene electron acceptors (NFAs), has enabled rapid progress in organic photovoltaic (OPV) cells in recent years. Although the power conversion efficiencies (PCEs) of the top-performance OPV cells have surpassed 16%, the devices are usually fabricated via a spin-coating method and are not suitable for large-area production. Here, we demonstrate that the fine-modification of the flexible side chains of NFAs can yield 17% PCE for OPV cells. More crucially, as the optimal NFA has a suitable solubility and thus a desirable morphology, the high efficiencies of spin-coated devices can be maintained when using scalable blade-coating processing technology. Our results suggest that optimization of the chemical structures of the OPV materials can improve device performance. This has great significance in larger-area production technologies that provide important scientific insights for the commercialization of OPV cells.
Real-World Effectiveness of Smoking Cessation Strategies for Young and Older Adults: Findings From a Nationally Representative Cohort
Authors: Watkins Shannon Lea , Thrul Johannes , Max Wendy , Ling Pamela M
Published: December 2019

Introduction

Young adults have high combustible cigarette and e-cigarette use rates, and low utilization of evidence-based smoking cessation strategies compared to older adults. It is unknown whether young adults who try to quit smoking without assistance, with evidence-based strategies, or with e-cigarettes, are equally successful compared to older adults.

Aims and Methods

This analysis used a population-based sample from the Population Assessment of Tobacco and Health study of young adult (aged 18–24, n = 745) and older adult (aged 25–64, n = 2057) established cigarette smokers at Wave 1 (2013–2014) who reported having made a quit attempt at Wave 2 (2014–2015). Cessation strategies were: behavioral therapy, pharmacotherapy, product substitution, 2+ strategies, and unassisted. Logistic regression estimated associations between cessation strategy and short-term cessation status at Wave 2 (quit, no quit); multinomial logistic regression predicted long-term cessation patterns at Waves 2 and 3 (sustained quit, temporary quit, delayed quit, no quit).

Results

No cessation strategy (ref: unassisted) significantly predicted short-term cessation. No cessation strategy (ref: unassisted) significantly predicted long-term cessation patterns for young adults. Substitution with e-cigarettes predicted short-term cessation for older daily smokers of ≥5 cigarettes/day (adjusted odds ratio [AOR]: 1.70; 95% confidence interval: 1.08, 2.67) but did not predict long-term cessation patterns.

Conclusions

Despite differences in cessation strategy use between young and older adult smokers, strategy effectiveness largely did not differ by age group. No strategy examined, including e-cigarettes, was significantly associated with successful cessation for young adults. More work is needed to identify effective interventions that help young adult smokers quit.

Implications

(1) Neither behavioral support, pharmacotherapy, nor product substitution was associated with short-term cessation for young or older adults compared to quitting unassisted. (2) Neither behavioral support, pharmacotherapy, nor product substitution was associated with longer-term cessation for young or older adults compared to quitting unassisted. (3) Substitution with e-cigarettes predicted short-term cessation for older daily smokers of ≥5 cigarettes/day but was not associated with longer-term cessation.
A Phase-3 Study to Compare Delafloxacin to Moxifloxacin for the Treatment of Adults with Community-acquired Bacterial Pneumonia (DEFINE-CABP)
Authors: Horcajada Juan P , Salata Robert A , Álvarez-Sala Rodolfo , Nitu Floarea Mimi , Lawrence Laura , Quintas Megan , Cheng Chun-Yen , Cammarata Sue ,   DEFINE-CABP Study Group
Published: December 2019

Background

The clinical and economic burden of community-acquired bacterial pneumonia (CABP) is significant and is anticipated to increase as the population ages and pathogens become more resistant. Delafloxacin is a fluoroquinolone antibiotic approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections. Delafloxacin’s shape and charge profile uniquely impacts its spectrum of activity and side effect profile. This phase 3 study compared the efficacy and safety of delafloxacin to moxifloxacin for the treatment of CABP.

Methods

A randomized, double-blind, comparator-controlled, multicenter, global Phase 3 study compared the efficacy and safety of delafloxacin 300 mg BID or moxifloxacin 400 mg QD in adults with CABP. The primary endpoint was early clinical response (ECR) defined as improvement at 96 (± 24) hours after first dose of study drug. Clinical response at test of cure (TOC) and microbiologic response were also assessed.

Results

In the intent-to-treat analysis population (ITT), ECR rates were 88.9% in the delafloxacin group and 89.0% in the moxifloxacin group. Noninferiority of delafloxacin compared with moxifloxacin was demonstrated. At TOC in the ITT population, the success rates were similar between groups. Treatment-emergent adverse events considered at least possibly related to the study drug occurred in 65 subjects (15.2%) in the delafloxacin group and 54 (12.6%) in the moxifloxacin group.

Conclusions

IV/oral delafloxacin monotherapy is effective and well tolerated in the treatment of adults with CABP, providing coverage for grampositive, gramnegative, and atypical pathogens.
Telemedicine Infectious Diseases Consultations and Clinical Outcomes: A Systematic Review
Authors: Burnham Jason P , Fritz Stephanie A , Yaeger Lauren H , Colditz Graham A
Published: December 2019

Background

Telemedicine use is increasing in many specialties, but its impact on clinical outcomes in infectious diseases has not been systematically reviewed. We reviewed the current evidence for clinical effectiveness of telemedicine infectious diseases consultations, including outcomes of mortality, hospital readmission, antimicrobial use, cost, length of stay, adherence, and patient satisfaction.

Methods

We queried Ovid MEDLINE 1946-, Embase.com 1947-, Scopus 1823-, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov 1997- through August 5, 2019, for studies looking at clinical outcomes of infectious diseases in the setting of telemedicine use. We did not restrict by language or year of publication. Clinical outcomes searched included 30-day all-cause mortality, 30-day readmissions, patient compliance/adherence, patient satisfaction, cost or cost-effectiveness, length of hospital stay, antimicrobial use, and antimicrobial stewardship. Bias was assessed using standard methodologies. PROSPERO CRD42018105225.

Results

From a search pool of 1154 studies, only 18 involved telemedicine infectious diseases consultation and our selected clinical outcomes. The outcomes tracked were heterogeneous, precluding meta-analysis, and the majority of studies were of poor quality. Overall, clinical outcomes with telemedicine infectious diseases consultation seem comparable to in-person infectious diseases consultation.

Conclusions

Although in widespread use, the clinical effectiveness of telemedicine infectious diseases consultations has yet to be sufficiently studied. Further studies, or publication of previously collected and available data, are warranted to verify the cost-effectiveness of this widespread practice.

Systematic review registration

PROSPERO CRD42018105225.
Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections
Authors: Jorgensen Sarah C J , Trinh Trang D , Zasowski Evan J , Lagnf Abdalhamid M , Bhatia Sahil , Melvin Sarah M , Steed Molly E , Simon Samuel P , Estrada Sandra J , Morrisette Taylor , Claeys Kimberly C , Rosenberg Joshua R , Davis Susan L , Rybak Michael J
Published: December 2019

Background

We conducted this study to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam (CZA) for a range of multidrug-resistant Gram-negative (MDR-GN) infections.

Methods

This is a multicenter, retrospective cohort study conducted at 6 medical centers in the United States between 2015 and 2019. Adult patients who received CZA (≥72 hours) were eligible. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of infection on CZA.

Results

In total, data from 203 patients were evaluated. Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas spp were isolated from 117 (57.6%) and 63 (31.0%) culture specimens, respectively. The most common infection sources were respiratory (37.4%), urinary (19.7%), and intra-abdominal (18.7%). Blood cultures were positive in 22 (10.8%) patients. Clinical failure, 30-day mortality, and 30-day recurrence occurred in 59 (29.1%), 35 (17.2%), and 12 (5.9%) patients, respectively. On therapy, CZA resistance developed in 1 of 62 patients with repeat testing. Primary bacteremia or respiratory tract infection and higher SOFA score were positively associated with clinical failure (adjusted odds ratio [aOR] = 2.270, 95% confidence interval [CI] = 1.115–4.620 and aOR = 1.234, 95% CI = 1.118–1.362, respectively). Receipt of CZA within 48 hours of infection onset was protective (aOR, 0.409; 95% CI, 0.180–0.930). Seventeen (8.4%) patients experienced a potential drug-related adverse effect (10 acute kidney injury, 3 Clostridioides difficile infection, 2 rash, and 1 each gastrointestinal intolerance and neutropenia)

Conclusions

Ceftazidime-avibactam is being used to treat a range of MDR-GN infections including Pseudomonas spp as well as CRE.
Designing an improved T-cell mobilising CXCL10 mutant through enhanced GAG binding affinity
Authors: Gerlza Tanja , Nagele Michael , Gschwandtner Martha , Winkler Sophie , Kungl Andreas
Published: December 2019

The chemokine CXCL10 is released by a plethora of cells, including immune and metastatic cancer cells, following stimulation with interferon-gamma. It acts via its GPC receptor on T-cells attracting them to various target tissues. Glycosaminoglycans (GAGs) are regarded as co-receptors of chemokines, which enable the establishment of a chemotactic gradient for target cell migration. We have engineered human CXCL10 towards improved T-cell mobilisation by implementing a single site-directed mutation N20K into the protein, which leads to a higher GAG binding affinity compared to the wild type. Interestingly, this mutation not only increased T-cell migration in a transendothelial migration assay, the mutant intensified T-cell chemotaxis also in a Boyden chamber set-up thereby indicating a strong role of T-cell-localised GAGs on leukocyte migration. A CXCL10 mutant with increased GAG-binding affinity could therefore potentially serve as a T-cell mobiliser in pathological conditions where the immune surveillance of the target tissue is impaired, as is the case for most solid tumors.
Using hierarchical clustering to explore patterns of deprivation among English local authorities
Authors: Senior Steven L
Published: December 2019

Background

The English Indices of Multiple Deprivation (IMD) is widely used as a measure of deprivation. However, similarly ranked areas can differ substantially in the underlying domains of deprivation. These domains contain a richer set of data that might be useful for classifying local authorities. Clustering methods offer a set of techniques to identify groups of areas with similar patterns of deprivation.

Methods

Hierarchical agglomerative (i.e. bottom-up) clustering methods were applied to domain scores for 152 upper tier local authorities. Advances in statistical testing allow clusters to be identified that are unlikely to have arisen from random partitioning of a homogeneous group. The resulting clusters are described in terms of their subdomain scores and basic geographic and demographic characteristics.

Results

Five statistically significant clusters of local authorities were identified. These clusters only partially reflect different levels of overall deprivation. In particular, two clusters share similar overall IMD scores but have contrasting patterns of deprivation.

Conclusion

Hierarchical clustering methods identify five distinct clusters that do not correspond closely to quintiles of deprivation. This approach may help to distinguish between places that face similar underlying challenges, and places that appear similar in terms of overall deprivation scores, but that face different challenges.
Opioid prescriptions in patients with osteoarthritis: a population-based cohort study
Authors: van den Driest Jacoline J , Schiphof Dieuwke , de Wilde Marcel , Bindels Patrick J E , van der Lei Johan , Bierma-Zeinstra Sita M A
Published: December 2019

Objectives

To examine the incidence, prevalence and trends for opioid prescriptions in patients with OA. Furthermore, types of opioids prescribed and long-term prescription rates were examined. Finally, the patient characteristics associated with the prescription of opioids were assessed.

Methods

A population-based cohort study was conducted using the Integrated Primary Care Information database. Incidence and prevalence of opioid prescriptions were calculated for the period 2008–2017. Logistic regression was used to assess which patient characteristics were associated with opioid prescriptions.

Results

In total, 157 904 OA patients were included. The overall prescription rate remained fairly stable, at around 100 incident and 170 prevalent prescriptions per 1000 person years. However, the incident prescription rate for oxycodone increased from 7.1 to 40.7 per 1000 person years and for fentanyl from 4.2 to 7.4 per 1000 person years. The incident prescription rate for paracetamol/codeine decreased from 63.0 to 13.3 per 1000 person years. Per follow-up year, long-term use was found in 3% of the patients with incident OA. Finally, factors associated with more prescriptions were increasing age, OA in ≥2 joint groups [odds ratio (OR) 1.56; 95% CI: 1.51, 1.65] and the presence of other musculoskeletal disorders (OR 4.91; 95% CI: 4.76, 5.05). Men were less likely to be prescribed opioids (OR 0.78; 95% CI: 0.76, 0.80).

Conclusion

Prescription rates for opioids remained stable, but types of opioids prescribed changed. Oxycodone and fentanyl were increasingly prescribed, while prescriptions of paracetamol/codeine decreased. Since the benefit of opioids for OA pain is questionable and side effects are common, opioids should be prescribed with caution.
Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli
Authors: Moon Anna L , Brydges Nichola M , Wilkinson Lawrence S , Hall Jeremy , Thomas Kerrie L
Published: December 2019

CACNA1C, a gene that encodes an alpha-1 subunit of L-type voltage-gated calcium channels, has been strongly associated with psychiatric disorders including schizophrenia and bipolar disorder. An important objective is to understand how variation in this gene can lead to an increased risk of psychopathology. Altered associative learning has also been implicated in the pathology of psychiatric disorders, particularly in the manifestation of psychotic symptoms. In this study, we utilize auditory-cued fear memory paradigms in order to investigate whether associative learning is altered in rats hemizygous for the Cacna1c gene. Cacna1c hemizygous (Cacna1c+/−) rats and their wild-type littermates were exposed to either delay, trace, or unpaired auditory fear conditioning. All rats received a Context Recall (24 h post-conditioning) and a Cue Recall (48 h post-conditioning) to test their fear responses. In the delay condition, which results in strong conditioning to the cue in wild-type animals, Cacna1c+/− rats showed increased fear responses to the context. In the trace condition, which results in strong conditioning to the context in wild-type animals, Cacna1c+/− rats showed increased fear responses to the cue. Finally, in the unpaired condition, Cacna1c+/− rats showed increased fear responses to both context and cue. These results indicate that Cacna1c heterozygous rats show aberrantly enhanced fear responses to inappropriate cues, consistent with key models of psychosis.
Metabolic Basis for Nonlinearity in 1,3-Dichloropropene Toxicokinetics and Use in Setting a Kinetically-derived Maximum Inhalation Exposure Concentration in Mice
Authors: Bartels Michael J , Hackett Michael J , Himmelstein Matthew W , Green John W , Walker Carl , Terry Claire , Rasoulpour Reza , Challender Mary , Yan Zhongyu (June)
Published: December 2019

1,3-Dichloropropene (1,3-D) showed a statistically increased incidence of bronchioloalveolar adenomas in male B6C3F1 mice at 60 ppm air concentration during previous chronic inhalation testing. No tumors were observed in female mice, nor in either sex of F344 rats up to 60 ppm, the highest dose tested. Therefore, to understand if lung tumors observed in high dose male mice are due to saturation of metabolic clearance, the linearity of 1,3-D concentrations in mouse blood was investigated on day 15 of repeated nose-only inhalation exposure to 0, 10, 20, 40, 60, 90, and 120 ppm (6 h/d, 7 d/week). Additional groups were included at 20, 60, and 120 ppm for blood collection at 1.5 and 3 h of exposure and up to 25 or 40 min post-exposure to determine area-under-the-curve. The data provide multiple lines of evidence that systemic exposures to 1,3-D in the mouse become nonlinear at inhalation exposure levels of 30 ppm or above. A reduction in minute volume occurred at the highest exposure concentration. The glutathione (GSH)-dependent metabolism of 1,3-D results in significant depletion of GSH at repeated exposure levels of 30 ppm and above. This loss of GSH results in decreased metabolic clearance of this test material, with a concomitant increase of the 1,3-D isomers in circulating blood at exposure concentrations ≥30 ppm. Shifts in the ratio of cis- and trans-1,3-D also support nonlinear toxicokinetics well below 60 ppm. Based on this data, a kinetically derived maximum dose for 1,3-D in mice for repeated exposures should be at or below 30 ppm. These results support non-relevance of 1,3-D-induced benign pulmonary tumorigenicity in mice for human health risk assessment.
Stigma, participation restriction and mental distress in patients affected by leprosy, cutaneous leishmaniasis and Chagas disease: a pilot study in two co-endemic regions of eastern Colombia
Authors: Gómez Libardo J , van Wijk Robin , van Selm Lena , Rivera Alberto , Barbosa Martha C , Parisi Sandra , van Brakel Wim H , Arevalo Jofren , Quintero William , Waltz Mitzi , Puchner Karl Philipp
Published: December 2019

Background

Leprosy, cutaneous leishmaniasis (CL) and Chagas disease (CD) are neglected tropical diseases with a high psychosocial burden (PSB). These conditions are endemic in Norte de Santander and Arauca in Colombia, but data on the related PSB are scarce. Therefore, we assessed mental distress, participation restriction and stigma among CD, CL and leprosy patients.

Methods

In 2018, 305 leprosy, CD or CL patients were interviewed using a self-report questionnaire to assess mental distress, participation scale for participation restriction and explanatory model interview catalogue (EMIC) for stigma. Descriptive statistics and the significance of median score differences were compared.

Results

Fifty percent of CD patients and 49% of leprosy patients exhibited mental distress, percentages which were significantly higher than that of CL (26%). Twenty-seven percent of leprosy patients experienced participation restriction, which was lower for CL (6%) and CD (12%). Median EMIC scores were significantly higher for leprosy patients than for CD (27%) and CL (17%) patients.

Conclusions

We found high levels of PSB among leprosy, CD and CL patients. Mental distress was highest among CD patients. Participation restriction and stigma were more prevalent in leprosy patients. Rural residence or lower educational status may impact PSB. Further investigation is needed to formulate evidence-based, holistic interventions.
Exercise improves metabolic function and alters the microbiome in rats with gestational diabetes
Authors: Mahizir Dayana , Briffa Jessica F. , Wood Jennifer L. , Anevska Kristina , Hill‐Yardin Elisa L. , Jefferies Andrew J. , Gravina Sogand , Mazzarino Gisella , Franks Ashley E. , Moritz Karen M. , Wadley Glenn D. , Wlodek Mary E.
Published: December 2019

Gestational diabetes mellitus (GDM) is a common pregnancy complication, particularly prevalent in obese women. Importantly, exercise has beneficial impacts on maternal glucose control and may prevent GDM in “at‐risk” women. We aimed to determine whether a high‐fat diet (HFD) exacerbates metabolic dysfunction and alters gut microbiome in GDM and whether endurance exercise prevents these changes. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham (Control) surgery on E18 in Wistar‐Kyoto rats. Female offspring were fed a Chow or HFD (23% fat) from weaning (5 weeks) and at 16 weeks randomly allocated to remain Sedentary or to an exercise protocol of either Exercise prior to and during pregnancy (Exercise); or Exercise during pregnancy only (PregEx). Females were mated (20 weeks) and underwent indirect calorimetry (embryonic day 16; E16), glucose tolerance testing (E18), followed by 24‐hr feces collection at E19 (n = 8‐10/group). HFD consumption in female rats with GDM exacerbated the adverse metabolic adaptations to pregnancy and altered gut microbial populations. Specifically, the Firmicutes‐to‐Bacteroidetes ratio was increased, due to an underlying change in abundance of the orders Clostridiales and Bacteroidales. Maternal Exercise, but not PregEx, prevented the development of metabolic dysfunction, increased pancreatic β‐cell mass, and prevented the alteration of the gut microbiome in GDM females. Our findings suggest that maternal exercise and diet influence metabolic and microbiome dysfunction in females with GDM, which may impact long‐term maternal and offspring health.
A human co‐culture cell model incorporating microglia supports glioblastoma growth and migration, and confers resistance to cytotoxics
Authors: Leite Diana M. , Zvar Baskovic Barbara , Civita Prospero , Neto Catia , Gumbleton Mark , Pilkington Geoffrey J.
Published: December 2019

Despite the importance of the tumor microenvironment in regulating tumor progression, few in vitro models have been developed to understand the effects of non‐neoplastic cells and extracellular matrix (ECM) on drug resistance in glioblastoma (GBM) cells. Using CellTrace‐labeled human GBM and microglial (MG) cells, we established a 2D co‐culture including various ratios of the two cell types. Viability, proliferation, migration, and drug response assays were carried out to assess the role of MG. A 3D model was then established using a hyaluronic acid‐gelatin hydrogel to culture a mixture of GBM and MG and evaluate drug resistance. A contact co‐culture of fluorescently labeled GBM and MG demonstrated that MG cells modestly promoted tumor cell proliferation (17%‐30% increase) and greater migration of GBM cells (>1.5‐fold increase). Notably, the presence of MG elicited drug resistance even when in a low ratio (10%‐20%) relative to co‐cultured tumor cells. The protective effect of MG on GBM was greater in the 3D model (>100% survival of GBM when challenged with cytotoxics). This new 3D human model demonstrated the influence of non‐neoplastic cells and matrix on chemoresistance of GBM cells to three agents with different mechanisms of action suggesting that such sophisticated in vitro approaches may facilitate improved preclinical testing.
A Randomized Trial of Multiple-Patient Simulation Preparation to Improve Novice Nurses’ Competence and Self-Efficacy
Authors: Franklin Ashley E. , Sideras Stephanie , Dodd Caitlin , Hutson Jeremy
Published: December 2019

AIM

The purpose of the study was to determine best practices for multiple-patient simulation (MPS) preparation and frequency to improve behavioral performance in nursing students.

BACKGROUND

MPS provides a safe environment for novice nurses to practice priority setting, delegation, and multitasking, but evidence for best practices is needed.

METHOD

A multisite, blinded, randomized trial was conducted to evaluate the effect of three simulation preparation methods (expert modeling, voice-over PowerPoint, and reading assignments) on students’ competence and self-efficacy for providing care to multiple patients in the simulation lab. Participants (n = 73) were enrolled in capstone clinical courses at two schools of nursing.

RESULTS

Though there was no difference in raw change in competence score among the study groups, there was a statistically significant difference in pretest and posttest scores. The change in self-efficacy did not correlate with the change in competence.

CONCLUSION

These findings will help educators understand how novice nurses benefit from repeated MPS activities.
Thoughtful Ileostomy Creation in Patients Undergoing Redo IPAA
Authors: Schwartzberg David M. , Esen Eren , Remzi Feza H.
Published: December 2019

INTRODUCTION:

Redo IPAA is a viable option to maintain intestinal continuity in patients with ileal pouch failure. Most patients with ileal pouch failure are physiologically and psychologically too deconditioned to undergo a 1- or 2-stage redo ileal pouch surgery, so a 3-staged redo ileal pouch surgery is needed. This consists of an initial proximal diverting loop ileostomy for 6 months, followed by redo ileal pouch construction with temporary stoma, and, lastly, stoma closure. The location of the initial diverting ileostomy is paramount, because 40% of cases will require pouch excision and construction of a de novo pouch, and a thoughtfully placed ileostomy will allow construction of a redo pouch without sacrificing any bowel length. In our report, we described our technique to create thoughtful ileostomy in patients who undergo redo IPAA.

TECHNIQUE:

We create a loop ileostomy ≈20 cm proximal to the existing ileal pouch, from the level of the tip of the J or the proximal inlet of an S-pouch. We call this a thoughtful ileostomy. By doing that, the thoughtful ileostomy site can be used as the apex of the new ileal pouch and become the ileal-anal anastomosis when a de novo ileal pouch needs to be constructed.

RESULTS:

We created a thoughtful ileostomy in 50 patients in the Inflammatory Bowel Disease Center at New York University Langone Health who either subsequently underwent or will undergo a redo IPAA between September 2016 and March 2019 (laparoscopic, n = 37; open, n = 13). Ten of the laparoscopic cases were preemptively converted to open because of dense adhesions.

CONCLUSION:

A thoughtful ileostomy is important so as to not sacrifice bowel in patients being prepared for redo ileal pouch surgery. Initial diversion with thoughtful ileostomy 6 months before redo ileal pouch construction also allows patients to be prepared for a major operation both physiologically and psychologically.
Expert Commentary on Complicated Diverticulitis
Authors: Shah Nishit
Published: December 2019

Complicated diverticulitis encompasses a variety of clinical scenariors as outlined in the well-written and succinct review by Drs Mendez and Garcia-Henriquez. These range from acute presentations, such as abscesses and free perforations with peritonitis, to more chronic, insidious sequelae such as fistulas and strictures.

The contemporary surgical management of diverticular disease has evolved considerably with better appreciation of the pathophysiology and natural history. Just as in uncomplicated diverticulitis, there has been a significant shift toward a less aggressive surgical strategy in complicated diverticulitis, aided further with improved diagnostic and interventional radiology.

I would like to add a few salient points for each listed complication.
Biomarkers that may predict response to immunotherapy in ovarian malignancies
Authors: Chin Curtis D. , Fares Charlene M. , Konecny Gottfried E. , Rao Jianyu
Published: December 2019

Purpose of review

Immune checkpoint blockade (ICB) is a promising area of cancer therapeutic research. Therapies targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) mechanism of tumor immune evasion have resulted in durable responses in many difficult-to-treat tumor types. While these inhibitors are being actively investigated in clinical trials for ovarian cancer, most patients fail to respond to initial treatment with immune therapy. This review focuses on biomarkers for predicting response to treatment, and discusses clinical trials using ICB for recurrent ovarian cancer.

Recent findings

While PD-L1 detection by immunohistochemistry (IHC) is approved as a companion or complementary diagnostic in some cancers, there are many limitations with its use as a predictive marker. Recent research has explored biomarkers beyond PD-L1 that assess for somatic mutations, immune cell infiltrate, and gene signatures.

With improved understanding of the tumor microenvironment and genomic classifications of ovarian tumors, new diagnostics and biomarkers that supplement conventional IHC may help predict response to therapy.
Multimodality screening and prevention of cervical cancer in sub-Saharan Africa: a collaborative model
Authors: Chinn Justine , Tewari Krishnansu S.
Published: December 2019

Purpose of review

Although cervical cancer continues to decrease in incidence throughout the developed world because of rigorous screening and vaccination campaigns, the disease remains a major cause of cancer-related morbidity and mortality in resource-limited regions including sub-Saharan Africa. This review summarizes current efforts to implement cost-effective and widespread cervical cancer education, screening, and community-based interventions in Africa and the challenges faced by local healthcare workers.

Recent findings

Effective screening with cytology (with or without high-risk human papillomavirus [HPV] DNA testing) as well as HPV self-sampling remains problematic in African countries because of a paucity of cytopathologists and resources. Accordingly, visual inspection of the cervix with acetic acid (VIA) with cryotherapy triage has gained traction in mass-screening campaigns because of low-cost supplies.

Public education to facilitate screening is essential. VIA remains a strong community-based approach. The involvement of technology in teaching local providers, advertising screenings to the community, and helping improve follow-up may also improve screening efforts. Ultimately, the best form of prevention is through HPV vaccination, which also requires implementation of ongoing public education programs.
Effectiveness of acupuncture for the treatment of postoperative pain
Authors: Zhang Qinhong , Yue Jin-Huan , Sun Zhong-Ren , Golianu Brenda
Published: December 2019

Background:

This aim of this study is to assess the effectiveness and safety of acupuncture for the treatment of patients with postoperative pain (PPP).

Methods:

We will carry out a systematic review of the published literature and will comprehensively search Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception to the present with no language restrictions. Randomized controlled trials comparing acupuncture with other interventions or sham acupuncture will be included. Two reviewers will independently conduct study selection, data collection, and study quality. A third reviewer will resolve any discrepancies. We will apply RevMan 5.3 software for statistical analysis.

Results:

The protocol of this study will systematically assess the effectiveness and safety of acupuncture for patients with PPP. The primary outcome is postoperative pain intensity. The secondary outcomes comprise of: analgesic consumption, postoperative recovery parameters, vital signs, quality of life, and treatment related adverse events.

Conclusion:

This study will summarize the current evidence base for the effectiveness and safety of acupuncture for patients with PPP.
Lab monitoring and acute care utilization during initiation of renin angiotensin aldosterone inhibitors or diuretics in chronic kidney disease
Authors: Garlo Katherine G. , Bates David W. , Seger Diane L. , Fiskio Julie M. , Charytan David M.
Published: December 2019

Renin angiotensin aldosterone system inhibitors (RAASi) and diuretics are among the most frequently prescribed anti-hypertensives. Individuals with chronic kidney disease (CKD) are particularly at risk for electrolyte disturbances and kidney injury but the appropriate use of lab monitoring following RAASi or diuretic initiation is uncertain in CKD.

We describe the frequency and time interval of lab monitoring during initiation of RAASi and diuretics in CKD and assess whether close lab monitoring associates with one-year risk of emergency department (ED) visit or hospitalization.

We evaluated an observational cohort of 8,217 individuals with stage 3–5 non-dialysis CKD newly prescribed a RAASi (52.3%) or diuretic (47.7%) from thirty-six primary care offices affiliated with Brigham and Women's Hospital and Massachusetts General Hospital between 2009 and 2011.

Overall, 3306 (40.2%) individuals did not have pre-prescription labs done within 2 weeks, and 5957 (72.5%) did not have post-prescription labs done within 2 weeks which includes 524 (6.4%) individuals without post-prescription within 1 year. Close monitoring occurred in only 1547 (20.1%) and was more likely in individuals prescribed diuretics compared to RAASi (adjusted OR 1.39; 95%CI 1.20–1.62), with CKD stage 4,5 compared with stage 3 (adjusted OR 1.47; 95%CI 1.16–1.86) and with cardiovascular disease (adjusted OR 1.42; 95%CI 1.21–1.66). Close monitoring was not associated with decreased risk of ED visit or hospitalization.

Close lab monitoring during initiation of RAASi or diuretics was more common in participants with cardiovascular disease and advanced CKD suggesting physicians selected high-risk individuals for close monitoring. As nearly 80% of individuals did not receive close lab monitoring there may be value in future research on electronic physician decision tools targeted at lab monitoring.
Effect of placement of acetabular prosthesis on hip joint function after THA
Authors: Fan Guang , Xiang Chuan , Li Shuaijie , Gao Zhenzhong , Liu Xiaohu , He Dongdong , Sun Jian
Published: December 2019

The good recovery of hip function after THA depends on reconstruction of acetabular prosthesis accurately. So we investigated the effect of acetabular prosthesis placement on hip joint function after THA and analyzed the clinical data of 432 patients with unilateral THA retrospectively . The patients were followed-up to evaluate the Harris score and hip range of motion (ROM). The hip ROM, the Harris score and the good rate of Harris score were compared between different groups. Comparison of the good rate of Harris score showed that 85%∼100% group of the rotation center horizontal position ratio was higher than >100% group; 80%∼120% group of the rotation center vertical position ratio was higher than >160% group; and the 90%∼110% group and 110%∼130% group of femoral offset ratio were higher than 90% and >130% groups. Comparison of Harris score showed that 85%∼100% and 70%∼85% groups of rotation center horizontal position ratio were higher than 70% and >100% groups; 80%∼120% group of rotation center vertical position ratio was the highest; and 90%∼110% group and 110%∼130% group of femoral offset ratio were higher than >130% and 90% groups. Comparison of hip ROM showed that 85%∼100% and 70%∼85% groups of the rotation center horizontal position ratio were higher than 70% and >100% groups; 80%∼120% group of the rotation center vertical position ratio was the highest; and hip ROM from high to low are 90%∼110%, 110%∼130%, >130% and 90% groups of femoral offset ratio. These findings indicated that during the early follow-up period of THA, if the horizontal position of femoral head rotation center was reconstructed in 0.85 to 1 times of healthy side when compared with reconstruction >1 times of the healthy side and if the vertical position of femoral head rotation center was reconstructed in 0.8 to 1.2 times of the healthy side when compared with reconstruction in >1.6 times of the healthy side, better hip function recovery and optimal hip ROM were obtained. The optimal reconstruction range of femoral offset is 0.9 to 1.3 times of the healthy side.
Risk factors of chronic urticaria among nurses with insomnia
Authors: Liao Kuang-Ming , Ho Chung-Han , Lee Huan-Fang , Yu Chia-Hung , Wang Jhi-Joung , Liang Fu-wen
Published: December 2019

Chronic urticaria has a high economic burden and reduces patient's quality of life. Nurses experience insomnia because of their shifting work, especially if they work night shifts and 3-shift rotational schedules. This study aimed to examine whether insomnia is a risk factor of chronic urticaria in nurses.

Data were obtained from the Registry for Medical Personnel, which contains all registered medical staff between 2007 and 2008. All study subjects were divided into those with insomnia and without insomnia. The primary exposure of interest was chronic urticaria. In addition, potential comorbidities including diabetes mellitus, hypertension, hyperlipidemia, anxiety, and depression were estimated.

A total of 103,242 registered nurses between 2007 and 2008 were enrolled. Around 97,899 (94.8%) nurses did not have insomnia, and 5343 (5.2%) had insomnia. The proportion of chronic urticaria in nurses with insomnia was significantly higher than those without (0.92% vs 0.50%, P < .0001). The odds ratio of chronic urticaria in nurses with insomnia was 1.67 (95% confidence interval: 1.22–2.29, P = 0.0014) compared to those without insomnia after adjusting for age, sex, hospital level, and comorbidities.

The risk of chronic urticaria was higher in nurses with insomnia than in those without insomnia. The relationship between insomnia and chronic urticaria might not be a direct causal association. Other contributing factors of insomnia include different perceptions of stress from night shift work, stress coping and adaptation, positive self-image, and emotional equilibrium related to person's capacity to adapt to change. The same situation may have different effects on different individuals.
Percutaneous endoscopic lumbar discectomy for lumbar disc herniation as day surgery – short-term clinical results of 235 consecutive cases
Authors: Cao Jian , Huang Wenzhou , Wu Tianlong , Jia JingYu , Cheng Xigao
Published: December 2019

Many studies have reported the good outcomes of percutaneous endoscopic lumbar discectomy (PELD) for the treatment of lumbar disc herniation (LDH). However, the majority of published studies on PELD showed an average hospital stay of 2 to 5 days. Thus, the purpose of this retrospective study was to evaluate and compare the clinical outcomes of patients undergoing PELD for LDH as day surgery with the outcomes of patients managed as inpatients.

A total of 402 patients who underwent PELD for single-level LDH were included. The visual analog scale score (VAS) for leg and back pain, Oswestry Disability Index (ODI) score, and Macnab criteria were evaluated preoperatively and at 2 years postoperatively (final follow-up). Operation time, duration of hospital stay, cost, postoperative complications, and the rates of and reasons for delayed discharge and readmission were recorded and analyzed.

The mean operative time was 45.8 ± 8.4 minutes in the PELD-A (nonday surgery mode) group and 41.3 ± 8.7 minutes in the PELD-D (day surgery mode) group (P = .63). The average duration of hospital stay was 2.8 ± 1.1 days in the PELD-A group and 3.2 ± 0.9 hours in the PELD-D group (P < .001). The average hospitalization expenses of the PELD-A and PELD-D groups were 28,090 ± 286 RMB and 24,356 ± 126 RMB (P = .03), respectively. In both groups, the mean VAS and ODI scores improved significantly postoperatively compared with the preoperative scores. The satisfactory result rate was 89.8% in the PELD-D group and 91.0% in the PELD-A group, without a significant difference (P = .68). The delayed discharge rate in the PELD-A and PELD-D groups was 8.20% and 8.43%, respectively (P = .93). The main reasons for delayed discharge were dysesthesia, neurologic deficit, nausea, headache and residential distance from the hospital. The overall readmission rates were 5.99% and 5.53% in the PELD-A and PELD-D groups, respectively (P = .85). The most common reasons for readmission were reherniation, sequestered herniation and pain.

In conclusion, PELD is safe and effective for the treatment of LDH and can reduce medical costs as day surgery, and it thus warrants increased attention.