bluuebunny/crossref_metadata_2025 huggingface dataset:
Quitline Treatment Enrollment and Cessation Outcomes Among Smokers Linked With Treatment via Ask-Advise-Connect: Comparisons Among Smokers With and Without HIV
Authors: Bui Thanh C , Piñeiro Bárbara , Vidrine Damon J , Wetter David W , Frank-Pearce Summer G , Vidrine Jennifer I
Published: December 2019

Introduction

Given that people living with HIV (PLWH) are disproportionately burdened by tobacco-related morbidity and mortality, it is critically important to understand the degree to which evidence-based cessation interventions are utilized by and are effective among PLWH.

Aims and Methods

This secondary data analysis aimed to examine differences in Quitline treatment enrollment and 6-month cessation outcomes among smokers seeking care at 1 HIV clinic and 12 non-HIV clinics that were part of a large healthcare system in the greater Houston, Texas metropolitan area, United States. Data were from a 34-month (April 2013–February 2016) one-group implementation trial that evaluated the Ask-Advise-Connect (AAC) approach to linking smokers with Quitline treatment. Primary outcomes included (1) treatment enrollment and (2) 6-month self-reported and biochemically confirmed abstinence.

Results

The smoking status of 218 915 unique patients was recorded in the electronic health record; 5285 (2.7%) of these patients were seen at the HIV clinic where the smoking prevalence was 45.9%; smoking prevalence at the non-HIV clinics was 17.9%. The proportion of identified smokers who enrolled in treatment was 10.8% at the HIV clinic and 11.8% at the non-HIV clinics. The self-reported abstinence rate was 18.7% among HIV clinic patients and 16.5% among non-HIV clinic patients. Biochemically confirmed abstinence was lower at 4.2% and 4.5%, respectively (all ps > .05).

Conclusions

AAC resulted in rates of Quitline treatment enrollment and abstinence rates that were comparable among patients seen at an HIV clinic and non-HIV clinics. Findings suggest that AAC should be considered for widespread implementation in HIV clinics.

Implications

PLWH were as likely as other patients to enroll in evidence-based tobacco cessation treatment when it was offered in the context of a primary care visit. Cessation outcomes were also comparable. Therefore, standard care for PLWH should include routine screening for smoking status and referrals to cessation treatment.
Efficacy of fish oil and its components in the management of psoriasis: a systematic review of 18 randomized controlled trials
Authors: Chen Xi , Hong Seokgyeong , Sun Xiaoying , Xu Wenbin , Li Hongjin , Ma Tian , Zheng Qi , Zhao Huaibo , Zhou Yaqiong , Qiang Yan , Li Bin , Li Xin
Published: December 2019

Context

Fish oil and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have anti-inflammatory properties, but their effect on psoriasis and its comorbidities remains inconclusive.

Objective

The aim of this quantitative systematic review was to evaluate the efficacy and safety of fish oil and its components in the treatment of psoriasis and its comorbidities.

Data Sources

PubMed, Embase, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang databases were searched from inception to March 30, 2019.

Study Selection

Randomized controlled trials were eligible for inclusion if they measured the effect of fish oil and its components in the treatment of patients with psoriasis.

Data Extraction

Eighteen randomized controlled trials involving 927 study participants were included.

Results

Monotherapy with fish oil or ω-3 PUFAs had no effect on the Psoriasis Area and Severity Index (PASI) score (P = 0.47), lesion area (P = 0.34), or pruritus (P = 0.62). Fish oil or ω-3 PUFAs combined with conventional treatments, however, resulted in a decreased PASI score (mean difference [MD], −3.92; 95%CI, −6.15 to −1.69; P = 0.0006) and lesion area (MD, −30.00; 95%CI, −33.82 to −26.18; P < 0.0001). Safety evaluation suggested no between-group differences. Fish oil and its components reduced certain risk factors for obesity, cardiovascular disease, and metabolic disease in patients with psoriasis and also regulated several inflammatory mediators.

Conclusions

Overall, when combined with conventional treatments, fish oil and its components may have beneficial effects on psoriasis and its comorbidities, including obesity, cardiovascular disease, and metabolic disease.

Systematic Review Registration

PROSPERO registration number CRD42019128631.
How Quantitative Easing Works: Evidence on the Refinancing Channel
Authors: Di Maggio Marco , Kermani Amir , Palmer Christopher J
Published: December 2019

We document the transmission of large-scale asset purchases by the Federal Reserve to the real economy using rich borrower-linked mortgage-market data and an identification strategy based on mortgage market segmentation. We find that central bank QE1 MBS purchases substantially increased refinancing activity, reduced interest payments for refinancing households, led to a boom in equity extraction, and increased aggregate consumption. Relative to QE-ineligible jumbo mortgages, QE-eligible conforming mortgage interest rates fell by an additional 40 bp and refinancing volumes increased by an additional 56% during QE1. We estimate that households refinancing during QE1 increased their durable consumption by 12%. Our results highlight that the transmission of unconventional monetary policy to the real economy depends crucially on the composition of assets purchased and the degree of segmentation in the market.
Issueless Campus Riots: Toward a Structural Account of Disorderly Gatherings, 1997–2007
Authors: McCarthy John D , Rafail Patrick , McPhail Clark , Martin Andrew W , Walker Edward T
Published: December 2019

Serious public disorders on or near US college and university campuses became common in the mid-1990s and have remained widespread. This research examines the structural conditions of campus communities where disorders are more likely to occur, drawing on findings from earlier work on racial disorders occurring in American cities during the 1960s. We propose several predictors of disorderly events, including concentrated student populations, alcohol availability, campus drinking behavior, and police behavior. We use a sample of 226 disorders occurring on the largest 274 campus communities between 1997 and 2007. Our results show that institutions with a combination of high student density and extensive alcohol availability experience the most disturbances. Aggressive policing of alcohol-related infractions is also associated with the likelihood of disturbances.
Urinary TCP1-eta: A Cortical Damage Marker for the Pathophysiological Diagnosis and Prognosis of Acute Kidney Injury
Authors: Sancho-Martínez Sandra M , Sánchez-Juanes Fernando , Blanco-Gozalo Víctor , Fontecha-Barriuso Miguel , Prieto-García Laura , Fuentes-Calvo Isabel , González-Buitrago José M , Morales Ana I , Martínez-Salgado Carlos , Ramos-Barron María A , Gómez-Alamillo Carlos , Arias Manuel , López-Novoa José M , López-Hernández Francisco J
Published: December 2019

Acute kidney injury (AKI) is a serious syndrome with increasing incidence and health consequences, and high mortality rate among critically ill patients. Acute kidney injury lacks a unified definition, has ambiguous semantic boundaries, and relies on defective diagnosis. This, in part, is due to the absence of biomarkers substratifying AKI patients into pathophysiological categories based on which prognosis can be assigned and clinical treatment differentiated. For instance, AKI involving acute tubular necrosis (ATN) is expected to have a worse prognosis than prerenal, purely hemodynamic AKI. However, no biomarker has been unambiguously associated with tubular cell death or is able to provide etiological distinction. We used a cell-based system to identify TCP1-eta in the culture medium as a noninvasive marker of damaged renal tubular cells. In rat models of AKI, TCP1-eta was increased in the urine co-relating with renal cortical tubule damage. When kidneys from ATN rats were perfused in situ with Krebs-dextran solution, a portion of the urinary TCP1-eta protein content excreted into urine disappeared, and another portion remained within the urine. These results indicated that TCP1-eta was secreted by tubule cells and was not fully reabsorbed by the damaged tubules, both effects contributing to the increased urinary excretion. Urinary TCP1-eta is found in many etiologically heterogeneous AKI patients, and is statistically higher in patients partially recovered from severe AKI. In conclusion, urinary TCP1-eta poses a potential, substratifying biomarker of renal cortical damage associated with bad prognosis.
Frequent cross-species transmissions of foamy virus between domestic and wild felids
Authors: Kraberger Simona , Fountain-Jones Nicholas M , Gagne Roderick B , Malmberg Jennifer , Dannemiller Nicholas G , Logan Ken , Alldredge Mat , Varsani Arvind , Crooks Kevin R , Craft Meggan , Carver Scott , VandeWoude Sue
Published: December 2019

Emerging viral outbreaks resulting from host switching is an area of continued scientific interest. Such events can result in disease epidemics or in some cases, clinically silent outcomes. These occurrences are likely relatively common and can serve as tools to better understand disease dynamics, and may result in changes in behavior, fecundity, and, ultimately survival of the host. Feline foamy virus (FFV) is a common retrovirus infecting domestic cats globally, which has also been documented in the North American puma (Puma concolor). The prevalent nature of FFV in domestic cats and its ability to infect wild felids, including puma, provides an ideal system to study cross-species transmission across trophic levels (positions in the food chain), and evolution of pathogens transmitted between individuals following direct contact. Here we present findings from an extensive molecular analysis of FFV in pumas, focused on two locations in Colorado, and in relation to FFV recovered from domestic cats in this and previous studies. Prevalence of FFV in puma was high across the two regions, ∼77 per cent (urban interface site) and ∼48 per cent (rural site). Comparison of FFV from pumas living across three states; Colorado, Florida, and California, indicates FFV is widely distributed across North America. FFV isolated from domestic cats and pumas was not distinguishable at the host level, with FFV sequences sharing >93 per cent nucleotide similarity. Phylogenetic, Bayesian, and recombination analyses of FFV across the two species supports frequent cross-species spillover from domestic cat to puma during the last century, as well as frequent puma-to-puma intraspecific transmission in Colorado, USA. Two FFV variants, distinguished by significant difference in the surface unit of the envelope protein, were commonly found in both hosts. This trait is also shared by simian foamy virus and may represent variation in cell tropism or a unique immune evasion mechanism. This study elucidates evolutionary and cross-species transmission dynamics of a highly prevalent multi-host adapted virus, a system which can further be applied to model spillover and transmission of pathogenic viruses resulting in widespread infection in the new host.
Clindamycin, Gentamicin, and Risk of Clostridium difficile Infection and Acute Kidney Injury During Delivery Hospitalizations
Authors: Duffy Cassandra R. , Huang Yongmei , Andrikopoulou Maria , Stern-Ascher Conrad N. , Wright Jason D. , Goffman Dena , D'Alton Mary E. , Friedman Alexander M.
Published: December 2019

OBJECTIVE:

To describe risk of Clostridium difficile infection associated with clindamycin and acute kidney injury associated with gentamicin during delivery hospitalizations.

METHODS:

Women admitted for delivery from January 2006 to March 2015 were analyzed using an inpatient administrative database. Primary outcomes were C difficile infection and acute kidney injury. C difficile infection was compared between women receiving clindamycin (with or without other antibiotics) and women receiving antibiotics other than clindamycin. Acute kidney injury was compared between women receiving gentamicin (with or without other antibiotics), women receiving antibiotics other than gentamicin, and women receiving no antibiotics. Unadjusted and adjusted log linear models analyzing the role of patient demographics, mode of delivery, and hospital-level characteristics were created evaluating risk of C difficile infection and acute kidney injury with risk ratios (RRs) and adjusted risk ratios with 99% CIs as measures of association. A sensitivity analysis for gentamicin and acute kidney injury was performed restricted to women with preeclampsia.

RESULTS:

Of 5,657,523 women admitted for delivery hospitalization, 266,402 (4.7%) received clindamycin and 165,726 (2.9%) received gentamicin. C difficile infection was diagnosed in 0.04% of women receiving clindamycin. Compared with women receiving other antibiotics, clindamycin was associated with a nearly threefold increased risk of C difficile infection (RR 2.93, 99% CI 2.21–3.90). Acute kidney injury was diagnosed in 0.24% of women receiving gentamicin. Gentamicin was associated with a threefold increased risk of acute kidney injury (RR 3.01, 99% CI 2.62–3.45) compared with women receiving other antibiotics, whereas receipt of no antibiotics was associated with significantly lower risk (RR 0.18, 99% CI 0.15–0.20). In adjusted analyses, these associations retained significance. Significantly increased risk of acute kidney injury was noted for women with preeclampsia receiving gentamicin (RR 2.04, 99% CI 1.64–2.53).

CONCLUSION:

Receipt of clindamycin was associated with significantly increased likelihood for C difficile infection and receipt of gentamicin with significantly increased likelihood of acute kidney injury, although the absolute risk of these complications was low.
17β-Estradiol Prevents Extracellular Matrix Degradation by Downregulating MMP3 Expression via PI3K/Akt/FOXO3 Pathway
Authors: Gao Xiao-Wen , Su Xiao-Tao , Lu Zheng-Hao , Ou Jun
Published: December 2019

Study Design.

In vitro studies of the role of 17β-estradiol (E2) and its possible targets in intervertebral disc degeneration (IDD).

Objective.

To define the regulatory role of E2 in IDD and the potential mechanisms.

Summary of Background Data.

IDD has intricate etiology that is influenced by multiple risk factors. However, the underlying molecular mechanisms of occurrence and progression of IDD are not well elucidated. The degradation of extracellular matrix (ECM) has been extensively observed in IDD. E2 was found to inhibit ECM degradation in human nuleus pulposus cells (HNPCs), but the molecular mechanism remained to be determined.

Methods.

Western blot and qPCR was performed to quantify the expression of target proteins in HNPCs. Luciferase reporter gene assay was applied to detect the effects of E2 and forkhead box O-3 (FOXO3) on matrix metalloproteinases (MMP)-3 promoter activity. Chromatin immunoprecipitation assay analyzed the binding of FOXO3 to MMP-3 and the effect of E2 on this process.

Results.

We identified the upregulation of collagen II and aggrecan by E2 independent of time and concentration. And E2 downregulated MMP-3 expression in human nucleus pulposus cells. The phosphorylation of FOXO3 led to the reduction of MMP-3 promoter activity. Furthermore, 17β-estradiol-induced the activation of PI3K/Akt pathway is required for FOXO3 phosphorylated.

Conclusion.

E2 prevents the degradation of ECM by upregulating collagen II and aggrecan expression via reducing MMP-3 expression in HNPCs, and PI3K/Akt/FOXO3 pathway is dispensable for MMP-3 downregulated. Therefore, E2 protects against IDD by preventing ECM degradation.

Level of Evidence: 3
A Deep Convolutional Neural Network With Performance Comparable to Radiologists for Differentiating Between Spinal Schwannoma and Meningioma
Authors: Maki Satoshi , Furuya Takeo , Horikoshi Takuro , Yokota Hajime , Mori Yasukuni , Ota Joji , Kawasaki Yohei , Miyamoto Takuya , Norimoto Masaki , Okimatsu Sho , Shiga Yasuhiro , Inage Kazuhide , Orita Sumihisa , Takahashi Hiroshi , Suyari Hiroki , Uno Takashi , Ohtori Seiji
Published: December 2019

Study Design.

Retrospective analysis of magnetic resonance imaging (MRI).

Objective.

The aim of this study was to evaluate the performance of our convolutional neural network (CNN) in differentiating between spinal schwannoma and meningioma on MRI. We compared the performance of the CNN and that of two expert radiologists.

Summary of Background Data.

Preoperative discrimination between spinal schwannomas and meningiomas is crucial because different surgical procedures are required for their treatment. A deep-learning approach based on CNNs is gaining interest in the medical imaging field.

Methods.

We retrospectively reviewed data from patients with spinal schwannoma and meningioma who had undergone MRI and tumor resection. There were 50 patients with schwannoma and 34 patients with meningioma. Sagittal T2-weighted magnetic resonance imaging (T2WI) and sagittal contrast-enhanced T1-weighted magnetic resonance imaging (T1WI) were used for the CNN training and validation. The deep learning framework Tensorflow was used to construct the CNN architecture. To evaluate the performance of the CNN, we plotted the receiver-operating characteristic (ROC) curve and calculated the area under the curve (AUC). We calculated and compared the sensitivity, specificity, and accuracy of the diagnosis by the CNN and two board-certified radiologists.

Results.

. The AUC of ROC curves of the CNN based on T2WI and contrast-enhanced T1WI were 0.876 and 0.870, respectively. The sensitivity of the CNN based on T2WI was 78%; 100% for radiologist 1; and 95% for radiologist 2. The specificity was 82%, 26%, and 42%, respectively. The accuracy was 80%, 69%, and 73%, respectively. By contrast, the sensitivity of the CNN based on contrast-enhanced T1WI was 85%; 100% for radiologist 1; and 96% for radiologist 2. The specificity was 75%, 56, and 58%, respectively. The accuracy was 81%, 82%, and 81%, respectively.

Conclusion.

We have successfully differentiated spinal schwannomas and meningiomas using the CNN with high diagnostic accuracy comparable to that of experienced radiologists.

Level of Evidence: 4
Effectiveness of Surgical Treatment for Degenerative Cervical Myelopathy in Preventing Falls and Fall-related Neurological Deterioration
Authors: Kimura Atsushi , Takeshita Katsushi , Shiraishi Yasuyuki , Inose Hiroyuki , Yoshii Toshitaka , Maekawa Asato , Endo Kenji , Miyamoto Takuya , Furuya Takeo , Nakamura Akira , Mori Kanji , Seki Shoji , Kanbara Shunsuke , Imagama Shiro , Matsunaga Shunji , Okawa Atsushi
Published: December 2019

Study Design.

Prospective multi-center study.

Objective.

The aim of this study was to evaluate the effectiveness of surgical treatment in reducing falls and fall-related neurological deterioration in a prospective cohort of patients undergoing surgery for degenerative cervical myelopathy (DCM).

Summary of Background Data.

Current evidence is limited for the effectiveness of surgical interventions for DCM in reducing the risk of fall-related neurological deterioration.

Methods.

Patients with DCM scheduled for surgical treatment were enrolled prospectively at eight participating institutes. At the time of enrollment, participants were given diaries to record details of their falls, to be returned at the 1-year postoperative follow-up. In the fall diary, patients were asked whether they had experienced any deterioration in neurological symptoms at each fall episode. Deterioration of neurological symptoms was categorized as follows: only deterioration of sensory function in the limbs; or deterioration of motor deficits. The incidence rate of falls was calculated separately for the preoperative and postoperative periods, as the total number of falls divided by the time over which falls were monitored (100 person-years). Functional outcome was assessed with the Japanese Orthopaedic Association (JOA) score and Neck Disability Index.

Results.

Of the initial 168 participants, 159 completed the 1-year follow-up, and 132 fall diaries were retrieved and analyzed. Of these 132 patients, 65 (49%) reported at least one fall during the survey period. The incidence rate of falls decreased significantly from 497.4 to 90.3 falls per 100 person-years after surgery. The incidence of motor deterioration per fall decreased significantly from 34% to 8% after surgery. Patients who experienced preoperative fall-related motor deterioration had a significantly lower JOA score compared with patients without fall-related motor deterioration at 1-year follow-up.

Conclusion.

Surgical intervention for DCM is effective not only in reducing the frequency of falls, but also in reducing the risk of fall-related deterioration of motor deficits.

Level of Evidence: 2
The Practice of Continuation of Anti-platelet Therapy During the Perioperative Period in Lumbar Minimally Invasive Spine Surgery (MISS)
Authors: Kulkarni Arvind G. , Patel Jwalant , Khandge Ashwin , Mewara Navin
Published: December 2019

Study Design.

Cohort.

Objective.

To evaluate perioperative morbidity in patients undergoing minimally invasive spine surgery of the lumbar spine while continuing the antiplatelet drug (APD) perioperatively as compared with those not continuing these drugs and those not on these drugs.

Summary of Background Data.

While discontinuation of antiplatelet drugs carries with it the risk of thrombosis of the cardiac stents, myocardial infarction, peripheral vascular occlusion, cerebro-vascular events and other thrombotic complications, continuation of these drugs has the risk of intra spinal bleeding and the serious consequences of subsequent epidural hematoma with associated spinal cord compression.

Methods.

This institutional review board approved study included 1587 patients from 2011 to 2018. Perioperative parameters were analyzed for 216 patients who underwent spinal surgery after the discontinuation of anticoagulation therapy, 240 patients who continued to take APD daily through the perioperative period and 1131 patients who were never exposed to APD therapy. The operative time, intraoperative estimated blood loss, length of hospital stay, incidence of clinically evident hematoma, and transfusion of blood products were also recorded and compared in three cohorts.

Results.

The patients who continued taking APD in the perioperative period had a longer length of hospital stay on average (2.5 ± 0.67 vs. 1.59 ± 0.76 and 1.67 ± 0.83, P < 0.05), whereas there was no significant difference in the operative time, estimated blood loss, the amount of blood products transfused, and overall intra and postoperative complication rate. There were no instances of postoperative wound soakage or neurological deficit suggestive of possible spinal epidural hematomas in either of the study groups.

Conclusion.

The current study has observed no appreciable increase in perioperative morbidities including bleeding related complication rates in patients undergoing lumbar minimally invasive spine surgery while continuing to take APD compared with patients who either discontinued APD prior to surgery or those not taking APD.

Level of Evidence: 4
Black Patients Experience Highest Rates of Cancer-associated Venous Thromboembolism
Authors: Addo-Tabiri Nana Oduraa , Chudasama Rani , Vasudeva Rhythm , Leiva Orly , Garcia Brenda , Ravid Jonathan D. , Bunze Tamala , Rosen Linda , Belghasem Mostafa , Francis Jean , Brophy Mary , Johnson Brett , Ferguson Ryan , Weinberg Janice , Chitalia Vipul C.
Published: December 2019

Purpose:

Cancer patients are at a higher risk of venous thromboembolism (VTE) than the general population. In the general population, blacks are at a higher risk of VTE compared with whites. The influence of race on cancer-associated VTE remains unexplored. We examined whether black cancer patients are at a higher risk of VTE and whether these differences are present in specific cancer types.

Design:

A retrospective study was performed in the largest safety net hospital of New England using a cohort of cancer patients characterized by a substantial number of nonwhites.

Results:

We identified 16,498 subjects with solid organ and hematologic malignancies from 2004 to 2018. Among them, we found 186 unique incident VTE events, of which the majority of the events accrued within the first 2 years of cancer diagnosis. Overall, blacks showed a 3-fold higher incidence of VTE (1.8%) compared with whites (0.6%; P<0.001). This difference was observed in certain cancer types such as lung, gastric and colorectal. In lung cancer, the odds of developing VTE in blacks was 2.77-times greater than those in white patients (confidence interval, 1.33-5.91; P=0.007). Despite the greater incidence of cancer-associated VTE in blacks, their Khorana risk score of VTE was not higher.

Conclusions:

In a diverse cancer cohort, we observed a higher incidence of cancer-associated VTE in blacks compared with patients from other races. This study indicates the consideration of race in the risk assessment of cancer-associated VTE. It could also lead to future mechanistic studies aiming at identifying reasons for differential VTE risk depending on cancer type.
Retiform Purpura as a Complication of Microsphere Emboli Following Transarterial Chemoembolization for Primary Hepatocellular Carcinoma: A Case Report and Literature Review
Authors: Kuan Amanda , Khoo Lawrence , Yang Sam S. , Chia Hui Yi , Lee Joyce S. S.
Published: December 2019

We report an elderly man with hepatocellular carcinoma who developed a rash after undergoing transarterial chemoembolization (TACE). On examination, there was a reticulated macular pigmentation over the chest and upper abdomen. Skin biopsy revealed foreign material that occluded the small dermal cutaneous vessels. These structures were perfectly spherical, homogeneously eosinophilic, and were also nonrefractile. They had a maximum diameter of 40 μm, consistent with the size of the microspheres used in TACE. TACE is a palliative measure used to treat hepatocellular carcinoma in patients who are not surgical candidates. Vaso-occlusive manifestations of the skin are rare occurrences, with only 8 reported cases. Seven cases attributed this to nontarget embolization of the hepatic falciform artery and 1 case postulated that collateral supply of the targeted area allowed for hematogenous migration of the occluding beads via the microcirculation. Pertaining to treatment, all patients were treated with oral nonsteroidal anti-inflammatory agents to good effect, with 1 patient receiving additional laser treatment and another having local steroid injections. Prognosis is excellent, because the skin lesions tend to resolve within a year. Several methods have been suggested to prevent these vaso-occlusive skin complications, including prophylactic application of ice or placing the tip of the microcatheter distal to the origin of the hepatic falciform artery and falciform artery.
Expression of Connexin 43 in 32 Cases of Merkel Cell Carcinoma
Authors: Fernandez-Flores Angel , Varela-Vazquez Adrian , Suárez Peñaranda Jose Manuel , Mayan Maria D. , Fonseca Eduardo
Published: December 2019

Introduction:

Connexins (Cxs) are channel proteins that allow direct connection among cells and between cells and the extracellular space. There is very little information in the literature on the expression of Cxs by Merkel cell carcinoma (MCC).

Materials and Methods:

Thirty-two cases of MCC were recovered from our archives and studied immunohistochemically for Cx43.

Results:

All our cases expressed several neuroendocrine markers. Most cases showed nonimmunohistochemically perceptible staining for Cx43. There was no difference between Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative cases. One case could not be evaluated. Only 2 cases showed a focal (10% of the tumor) membranous staining of Cx43. One of these cases was MCPyV-negative and, in the other, CM2B4 could not be evaluated. CM2B4 was positive in 18 cases and negative in 13 cases, and it could not be evaluated in 1 case.

Conclusions:

MCC shows a low Cx43 level, with no differences between MCPyV-positive and MCPyV-negative cases. Therefore, this opens the door for Cx43 targeting in therapeutic approaches to MCC.
Child-Adult Relationship Enhancement in Primary Care: A Randomized Trial of a Skill-Based Parent Training with Parent Mentor Adaptation
Authors: Schilling Samantha , Ritter Victor , Wood Joanne N. , Fine Jason , Zolotor Adam J.
Published: December 2019

Introduction:

Child-Adult Relationship Enhancement in Primary Care (PriCARE) is a 6-session group training designed to teach positive parenting skills. Parent engagement in such programs is a common implementation barrier. Our objectives were to (1) examine the impact of a peer mentor on attendance and stigma and (2) replicate a previous study by measuring PriCARE's impact on child behavior and parenting practices.

Method:

Parents of 2- to -6-year-old children without specific behavior problems were randomized to mentored PriCARE (n = 50), PriCARE (n = 50), or control (n = 50). Stigma was measured at 10 weeks. Child behavior and parenting practices were measured at baseline and 10 weeks using the Eyberg Child Behavior Inventory (ECBI) and Parenting Scale (PS). Analysis of variance models were used to examine differences across groups.

Results:

There was no significant difference in attendance between mentored PriCARE and PriCARE arms (mean 3.80 vs 3.36 sessions, p = 0.35). Parents randomized to the mentor reported lower stigma (3.75 vs 5.04, p = 0.02). Decreases in the mean ECBI scores between 0 and 10 weeks were greater in the PriCARE arms (n = 100) compared with the control arm (n = 50), reflecting larger improvements in behavior [intensity: −7 (−2 to −13) vs 4 (−3 to 12) to p = 0.014; problem: −3 (−1 to −4) vs 1 (−1 to 3) to p = 0.007]. Scores on all PS subscales reflected greater improvements in parenting behaviors in PriCARE arms compared with control (all p < 0.04).

Conclusion:

Adapting PriCARE with a peer mentor may decrease stigma but does not improve program attendance. PriCARE shows promise in improving behavior in preschool-aged children and increasing positive parenting practices.
Testing Unconventional Matrices to Monitor for Prenatal Exposure to Heroin, Cocaine, Amphetamines, Synthetic Cathinones, and Synthetic Opioids
Authors: Carlier Jeremy , La Maida Nunzia , Di Trana Annagiulia , Huestis Marilyn A. , Pichini Simona , Busardò Francesco P.
Published: December 2019

Background:

The prevalence of drug use during pregnancy continues to increase despite the associated serious adverse obstetrical outcomes, including increased risk of miscarriage, fetal growth restriction, brain development impairment, neonatal abstinence syndrome, preterm delivery, and stillbirths. Monitoring drug use during pregnancy is crucial to limit prenatal exposure and provide suitable obstetrical health care. The authors reviewed published literature reporting the concentrations of common drugs of abuse and new psychoactive substances (NPS), such as synthetic cathinones and synthetic opioids, NPS, and their metabolites using unconventional matrices to identify drug use during pregnancy and improve data interpretation.

Methods:

A literature search was performed from 2010 to July 2019 using PubMed, Scopus, Web of Science scientific databases, and reports from international institutions to review recently published articles on heroin, cocaine, amphetamine, methamphetamine, synthetic cathinone, and synthetic opioid monitoring during pregnancy.

Results:

Meconium has been tested for decades to document prenatal exposure to drugs, but data regarding drug concentrations in amniotic fluid, the placenta, the umbilical cord, and neonatal hair are still lacking. Data on prenatal exposure to NPS are limited.

Conclusions:

Maternal hair testing is the most sensitive alternative matrix for identifying drug use during pregnancy, while drug concentrations in the meconium, placenta, and umbilical cord offer the identification of prenatal drug exposure at birth. Adverse developmental outcomes for the infant make it critical to promptly identify maternal drug use to limit fetal exposure or, if determined at birth, to provide resources to the exposed child and family. Alternative matrices offer choices for monitoring and challenge laboratories to deliver highly sensitive and specific analytical methods for detection.
A Rare Case Report of Frank Ter Haar Syndrome in a Sibling Pair Presenting With Congenital Glaucoma
Authors: Ratukondla Banushree , Prakash Sarvesswaran , Reddy Sindhura , Puthuran George V. , Kannan Naresh B. , Pillai Manju R.
Published: December 2019

Frank Ter Haar syndrome (FTHS) is a rare autosomal recessive disorder with characteristic skeletal, cardiac, ocular, and craniofacial abnormalities. We report a sibling pair presenting with clinical features typical of FTHS, born to consanguineous parents, with a novel mutation in the SH3PXD2B gene on chromosome 5q35.1 that results in premature truncation of the protein encoded. The children presented with brachycephaly, multiple joint contractures, cardiac valvular defects, bilateral megalocornea, and congenital glaucoma. Trabeculotomy combined with trabeculectomy was performed in both siblings to control intraocular pressure. The characteristic clinical features with the underlying genetic defects confirmed the diagnosis of FTHS. Early diagnosis and treatment of congenital glaucoma preserved vision in the children.
Next-Generation Staffing Models
Authors: Boston-Fleischhauer Carol
Published: December 2019

Despite Health Resources and Services Administration projecting a national excess of approximately 300 000 RNs as compared with demand by 2030, continued regional and local shortages have been confirmed. Pockets of chronic nurse shortages for various reasons, continued margin pressures, increased inpatient care complexity, continued RN turnover, and overall RN resilience are prompting chief nurse executives to investigate staffing model innovations. Next-generation staffing models include those that significantly embrace new teams and technology, as well as the philosophy of primary nursing care. Chief nurse executives must carefully analyze all models from the standpoint of organizational, cultural, and professional norms, as well their role in spearheading such efforts.
Evolution of a Newly Licensed RN Transition-to-Practice Program
Authors: Halfer Diana , Benedetto Casey
Published: December 2019

Nursing leaders have embraced newly licensed registered nurse (NLRN) transition-to-practice programs, which contribute to nursing confidence, competence, work satisfaction, and retention in a complex healthcare environment. We report on the evolution of a Midwest urban pediatric medical center's transition-to-practice program, guided for 2 decades by foundational and emerging theory, research, and evidence that has supported accreditation with distinction as a Practice Transition Accreditation Program (PTAP) by the American Nurses Credentialing Center's Commission in Accreditation. Nursing leaders should use emerging evidence to inform curricular revisions that accelerate NLRN role transition and practice integration, increase organizational commitment, improve patient safety and satisfaction, and achieve PTAP accreditation.
KPNA2/ERG Coexpression is Associated With Early Recurrence in Advanced Prostate Cancers
Authors: D’Antonio Antonio , Caputo Alessandro , Fraggetta Filippo , Pepe Pietro , Insabato Luigi , Barra Enrica , Barresi Valeria , Altieri Vincenzo , Greco Umberto , Savastano Riccardo , Zeppa Pio
Published: December 2019

Most prostate cancers (PC) overexpress the ERG oncogene and karyopherin α 2 (KPNA2). These genes play a role in prostatic carcinogenesis, but their prognostic significance is still debated. The aim of this study was to determine the prognostic significance of ERG and KPNA2 expression, and their association to early prostate-specific antigen (PSA) biochemical recurrence in advanced PC with lymph node metastases. A series of 65 consecutive pN1 M0 R0 PC samples obtained by radical prostatectomy with lymphadenectomy has been analyzed for ERG and KPNA2 expression by immunohistochemistry. For each case, the following clinical data were collected: age, preoperative serum PSA levels, Gleason grade group, TNM stage, and follow-up. PC recurrence was investigated by serum PSA assay and defined by a PSA concentration >0.2 ng/mL after a nadir of <0.1 ng/mL following radical prostatectomy. ERG-positive staining was found in 25/65 cases (38%), and KPNA2 in 56/65 cases (86%); neither was detected in normal prostatic tissue. Immunohistochemical concordance was found between primary tumor and lymph node metastases in 24/25 (96%) of ERG and 53/56 (95%) of KPNA2-positive cases. The follow-up was known in all cases, and early PSA recurrence occurred in 25/65 cases (38%). ERG positivity, both alone and in conjunction with KPNA2 positivity, was strongly associated with early PSA recurrence [both ERG+ and KPNA+, odds ratio: 22.2 (95% confidence interval, 6.0-82.3); ERG+ alone odds ratio: 17.9 (95% confidence interval, 5.1-63.5); P<0.0001 for both]. KPNA2 expression was significantly associated with the tumor stage (P<0.00001). The results suggest that the ERG+ phenotype might be selected in metastasis-initiating clones. ERG and KPNA2 may have a prognostic value, and their positivity in PC might warrant more aggressive treatments.
The Clinical Application of Medial Sural Vessels as Recipient Vessels in Repairing Traumatic Tissue Defects in the Lower Limbs
Authors: Fu Jile , Gao Junqing , Yi Yanhua , Jia James , Miao Yong , Chen Yuxin , Hu Zhiqi , Gao Jianhua
Published: December 2019

Background

The use of medial sural vessels (MSVs) as recipient vessels to repair wounds in the lower limbs has been previously reported. However, there is controversy regarding the methods used to expose MSVs and the repairable area of the wound.

Methods

Eight fresh cadavers were used to determine the shape, outer diameter, and length of the MSVs arising from the popliteal vessels. Lower extremity wounds were repaired in 7 patients using free latissimus dorsi flaps with the MSVs as recipient vessels. The flap area ranged from 18 × 11 cm to 24 × 17 cm, and the postoperative follow-up time ranged from 7 to 60 months.

Results

The outer diameter of the medial sural artery from the starting point of the popliteal artery was 2.48 ± 0.24 mm. After descending 29.98 ± 4.62 mm, the vessels entered the muscle; the outer diameter of the blood vessel upon entry was 2.24 ± 0.17 mm. Notably, the outer diameter of the vessel was 1.88 ± 0.09 mm only 2 cm after entering the muscle. Seven cases were treated clinically. In 6 cases, we used an approach between the medial head of the gastrocnemius muscle and the tibia to expose and anastomose the MSVs. In 1 case, the vascular diameter was mismatched. After surgery, the flap survived completely in 6 cases. The remaining case experienced epidermal necrosis in the distal part of the flap, which resolved spontaneously. There were no obvious complications.

Conclusions

An approach between the medial head of the gastrocnemius muscle and the tibia can easily expose and anastomose the MSVs in a lateral position. Latissimus dorsi flaps were useful in repairing limb wounds as far as the talocrural region with the MSVs as the recipient vessels.
Update on the classification of higher ranks in the phylum Actinobacteria
Authors: Salam Nimaichand , Jiao Jian-Yu , Zhang Xiao-Tong , Li Wen-Jun
Published: December 2019

Genome analysis is one of the main criteria for description of new taxa. Availability of genome sequences for all the actinobacteria with a valid nomenclature will, however, require another decade’s works of sequencing. This paper describes the rearrangement of the higher taxonomic ranks of the members of the phylum ‘

Actinobacteria

’, using the phylogeny of 16S rRNA gene sequences and supported by the phylogeny of the available genome sequences. Based on the refined phylogeny of the 16S rRNA gene sequences, we could arrange all the members of the 425 genera of the phylum ‘

Actinobacteria

’ with validly published names currently in use into six classes, 46 orders and 79 families, including 16 new orders and 10 new families. The order

Micrococcales

Prévot 1940 (Approved Lists 1980) emend. Nouioui et al. 2018 is now split into 11 monophyletic orders: the emended order

Micrococcales

and ten proposed new orders

Aquipuribacterales

,

Beutenbergiales

,

Bogoriellales

,

Brevibacteriales

,

Cellulomonadales

,

Demequinales

,

Dermabacterales

,

Dermatophilales

,

Microbacteriales

and

Ruaniales

. Further, the class ‘

Actinobacteria

’ Stackebrandt et al. 1997 emend. Nouioui et al. 2018 was described without any nomenclature type, and therefore the name ‘

Actinobacteria

’ is deemed illegitimate. In accordance to Rule 8 of the International Code of Nomenclature of Prokaryotes, Parker et al. 2019, we proposed the name

Actinomycetia

which is formed by using the stem of the name

Actinomycetales

Buchanan 1917 (Approved Lists 1980) emend. Zhi et al. 2009, to replace the name ‘

Actinobacteria

’. The nomenclature type of the proposed new class

Actinomycetia

is the order

Actinomycetales

Buchanan 1917 (Approved Lists 1980) emend. Zhi et al. 2009.
Interactive Psychometrics for Autism with the Human Dynamic Clamp: Interpersonal Synchrony from Sensory-motor to Socio-cognitive Domains
Authors: Baillin Florence , Lefebvre Aline , Pedoux Amandine , Beauxis Yann , Engemann Denis , Maruani Anna , Amsellem Frédérique , Bourgeron Thomas , Delorme Richard , Dumas Guillaume
Published: December 2019

Background: The Human Dynamic Clamp (HDC) is a human-machine interface for studying realistic social interaction under controlled and reproducible conditions. Here, we propose to probe the validity of the HDC as psychometric instrument for quantifying social abilities in children with Autism Spectrum Disorder (ASDs) and neurotypical development. Methods: To study behavioral synchrony, we derived from interaction with the HDC avatar, five standardized scores following a gradient from sensory-motor and motor to higher socio-cognitive skills, in a sample of 155 individuals (113 with ASDs, 42 typically developing participants; aged 5 to 25 years; IQ>70). Results: We conducted regression analyses with normative modeling on global scores according to four sub-conditions (avatar behavior "cooperative/competitive", human task "in-phase/anti-phase", diagnosis and age at inclusion). Children with ASDs tend to have significant lower scores than controls for motor skills. Independently of the phenotype, socio-cognitive skills increase with developmental age, while being affected by the ongoing task and the behavior of the avatar. Discussion: The weaker performance in participants with ASDs for motor skills suggests convergent validity for this score of the HDC during social interaction. Results provide additional evidence of a relationship between sensory-motor and socio-cognitive skills. As we found a significant main effect of age at inclusion, HDC may be used as a marker of aging of socio-cognitive skills during real-time social interaction. Conclusion: Through its standardized and objective evaluation, the HDC not only represents a valid paradigm for the study of interpersonal synchrony but also a clinically relevant psychometric instrument for the evaluation and stratification of socio-motor dysfunctions.
The Trk fused gene-product (Tfg) is part of a 600-700kDa CARMA1 complex
Authors: Grohmann Markus , Steinmetz Tobit , Jäck Hans-Martin , Mielenz Dirk
Published: December 2019

B cell receptor (BCR) mediated activation of nuclear factor κB (NF-κB) is key to humoral immunity. CARMA1 (CARD11) is essential for BCR mediated NF-κB activation by interacting with Bcl10 and MALT1. Besides these two main players, few interaction partners of the CARMA1 complex are known. Here we identified new interaction partners of CARMA1. We generated two rabbit antisera against mouse CARMA1 to immunopurify endogenous CARMA1 from lysates of mouse B cells. Nik-binding protein (NIBP), Ras-GAP SH3 binding protein 2 (G3BP1) and Trk-fused gene (Tfg) were identified by peptide mass fingerprinting in immunopurified CARMA1 complexes. The interaction of Tfg and CARMA1 was confirmed by co-immunoprecipitation and Blue native polyacrylamide gel electrophoresis using the anti CARMA1 and newly generated anti Tfg antibodies. This analysis revealed that CARMA1 formed complexes of 600-1000 kDa. Additionally, Tfg was found in complexes of 500-600 kDa which increased in size to ∼740 kDa upon overexpresssion.
ADP is the dominant controller of AMP-activated protein kinase activity dynamics in skeletal muscle during exercise
Authors: Coccimiglio Ian F. , Clarke David C.
Published: December 2019

Exercise training elicits profound metabolic adaptations in skeletal muscle cells. A key molecule in coordinating these adaptations is AMP-activated protein kinase (AMPK), whose activity increases in response to cellular energy demand. AMPK activity dynamics are primarily controlled by the adenine nucleotides ADP and AMP, but how each contributes to its control in skeletal muscle during exercise is unclear. We developed and validated a mathematical model of AMPK signaling dynamics, and then applied global parameter sensitivity analyses with data-informed constraints to predict that AMPK activity dynamics are determined principally by ADP and not AMP. We then used the model to predict the effects of two additional direct-binding activators of AMPK, ZMP and Compound 991, further validating the model and demonstrating its applicability to understanding AMPK pharmacology. The relative effects of direct-binding activators can be understood in terms of four properties, namely their concentrations, binding affinities for AMPK, abilities to enhance AMPK phosphorylation, and the magnitudes of their allosteric activation of AMPK. Despite AMP’s favorable values in three of these four properties, ADP is the dominant controller of AMPK activity dynamics in skeletal muscle during exercise by virtue of its higher concentration.

Author Summary

During exercise, the enzyme “AMP-activated protein kinase” (AMPK) detects the disrupted cellular energy state by binding to the adenine nucleotides ATP, ADP, and AMP, which are the major chemical energy carriers of the cell. How the adenine nucleotides interact to control AMPK activity is poorly understood. In this study, we used mathematical modeling to investigate the control of AMPK activity by the adenine nucleotides in skeletal muscle during exercise. We simulated the model many times with randomly generated parameter sets. Ultimately the parameters affect four key properties of an AMPK activator, namely its concentration, the tightness with which it binds to AMPK, its ability to activate AMPK by promoting its phosphorylation, and its ability to activate AMPK through allostery. We found that ADP is the dominant controller of AMPK activity, instead of AMP, due to its high concentration relative to that of AMP. We also modeled AMPK activity in response to drugs that activate it, which further demonstrated the validity and applicability of the model. Overall, our research enhances understanding of AMPK action during exercise and could inform the development of drugs that target AMPK.