bluuebunny/crossref_metadata_2025 huggingface dataset:
An update on cefepime and its future role in combination with novel β-lactamase inhibitors for MDR Enterobacterales and Pseudomonas aeruginosa
Authors: Isler Burcu , Harris Patrick , Stewart Adam G , Paterson David L
Published: December 2020

Cefepime, a wide-spectrum β-lactam antibiotic, has been in use for the treatment of serious bacterial infections for almost 25 years. Since its clinical development, there has been a dramatic shift in its dosing, with 2 g every 8 hours being preferred for serious infections to optimize pharmacokinetic/pharmacodynamic considerations. The advent of ESBLs has become a threat to its ongoing use, although future coadministration with β-lactamase inhibitors (BLIs) under development is an area of intense study. There are currently four new cefepime/BLI combinations in clinical development. Cefepime/zidebactam is generally active against MBL-producing Enterobacterales and Pseudomonas aeruginosa, in vitro and in animal studies, and cefepime/taniborbactam has activity against KPC and OXA-48 producers. Cefepime/enmetazobactam and cefepime/tazobactam are potential carbapenem-sparing agents with activity against ESBLs. Cefepime/enmetazobactam has completed Phase III and cefepime/taniborbactam is in Phase III clinical studies, where they are being tested against carbapenems or piperacillin/tazobactam for the treatment of complicated urinary tract infections. While these combinations are promising, their role in the treatment of MDR Gram-negative infections can only be determined with further clinical studies.
Role of small leucine zipper protein in hepatic gluconeogenesis and metabolic disorder
Authors: Kang Minsoo , Han Sun Kyoung , Kim Suhyun , Park Sungyeon , Jo Yerin , Kang Hyeryung , Ko Jesang
Published: December 2020

Hepatic gluconeogenesis is the central pathway for glucose generation in the body. The imbalance between glucose synthesis and uptake leads to metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Small leucine zipper protein (sLZIP) is an isoform of LZIP and it mainly functions as a transcription factor. Although sLZIP is known to regulate the transcription of genes involved in various cellular processes, the role of sLZIP in hepatic glucose metabolism is not known. In this study, we investigated the regulatory role of sLZIP in hepatic gluconeogenesis and its involvement in metabolic disorder. We found that sLZIP expression was elevated during glucose starvation, leading to the promotion of phosphoenolpyruvate carboxylase and glucose-6-phosphatase expression in hepatocytes. However, sLZIP knockdown suppressed the expression of the gluconeogenic enzymes under low glucose conditions. sLZIP also enhanced glucose production in the human liver cells and mouse primary hepatic cells. Fasting-induced cyclic adenosine monophosphate impeded sLZIP degradation. Results of glucose and pyruvate tolerance tests showed that sLZIP transgenic mice exhibited abnormal blood glucose metabolism. These findings suggest that sLZIP is a novel regulator of gluconeogenic enzyme expression and plays a role in blood glucose homeostasis during starvation.
Chronic Treatment With Hydrogen Sulfide Donor GYY4137 Mitigates Microglial and Astrocyte Activation in the Spinal Cord of Streptozotocin-Induced Diabetic Rats
Authors: Shayea Abdulaziz M F , Mousa Alyaa M A , Renno Waleed M , Nadar Mohammed Shaban , Qabazard Bedoor , Yousif Mariam H M
Published: December 2020

Long-term diabetic patients suffer immensely from diabetic neuropathy. This study was designed to investigate the effects of hydrogen sulfide (H2S) on peripheral neuropathy, activation of microglia, astrocytes, and the cascade secretion of proinflammatory cytokines in the streptozotocin (STZ)-induced peripheral diabetic neuropathy rat model. STZ-induced diabetic rats were treated with the water-soluble, slow-releasing H2S donor GYY4137 (50 mg/kg; i.p.) daily for 4 weeks. Antiallodynic/antihyperalgesic activities were evaluated using different tests and histopathological changes and the expression of proinflammatory cytokines in the spinal cord were examined. GYY4137 treatment produced neuroprotective effects in the spinal cord of diabetic animals and modulated their sensory deficits. The treatment decreased allodynia (p < 0.05) and mechanical hyperalgesia (p < 0.01) and restored thermal hyperalgesia (p < 0.001) compared with diabetic rats. The treatment decreased the microglial response and increased astrocyte counts in spinal cord gray and white matter compared with untreated diabetic rats. Proinflammatory cytokines were reduced in the treated group compared with diabetic rats. These results suggest that H2S has a potentially ameliorative effect on the neuropathic pain through the control of astrocyte activation and microglia-mediated inflammation, which may be considered as a possible treatment of peripheral nerve hypersensitivity in diabetic patients.
Detailed Clinical and Histopathological Description of 8 Cases of Molecularly Defined CNS Neuroblastomas
Authors: Holsten Till , Lubieniecki Fabiana , Spohn Michael , Mynarek Martin , Bison Brigitte , Löbel Ulrike , Rutkowski Stefan , Schüller Ulrich
Published: December 2020

Central nervous system neuroblastoma with FOXR2 activation (CNS NB FOXR2) has recently been described as a class of brain tumors sharing common genetic events and a highly similar DNA methylation profile. Most of these tumors have previously been diagnosed as primitive neuroectodermal tumor (PNET). Whereas the entity of PNET has been removed from the WHO classification of brain tumors in its current edition, CNS neuroblastoma was kept as an entity, but still lacks any molecular detail. Here, we describe 8 cases of CNS NB FOXR2 focusing on histomorphological and immunohistochemical features and include magnetic resonance imaging (MRI) for 2 of these cases. MRI revealed large supratentorial masses in superficial location with prominent cysts and necrosis, but little edema. Diffusion and enhancement characteristics were variable. Histological analyses showed that most of the cases displayed neuronal differentiation with necrosis, endothelial proliferation, and high vascularity. Immunohistochemistry revealed strong expression of synaptophysin, MAP2, and OLIG2 as well as moderate proliferation. These findings suggest that tumors with the molecular diagnosis of CNS NB FOXR2 may fit well into the WHO entity of CNS neuroblastoma. Our findings may be helpful when establishing an integrated diagnosis and may be indispensable if molecular data are unavailable.
Clinicopathological Staging of Dynamics of Neurodegeneration and Neuronal Loss in Alzheimer Disease
Authors: Wegiel Jerzy , Flory Michael , Kuchna Izabela , Nowicki Krzysztof , Ma Shuang Yong , Wegiel Jarek , Badmaev Eulalia , Leon Mony de , Wisniewski Thomas , Reisberg Barry
Published: December 2020

Clinical and neuropathological staging of Alzheimer disease (AD) neurodegeneration and neuronal loss dynamics is the baseline for identification of treatment targets and timing. The aim of this study of 14 brain regions in 25 subjects diagnosed with AD and 13 age-matched control subjects was to establish the pattern of neurodegeneration, and the severity and rate of neuronal loss in mild cognitive impairment/mild AD (Functional Assessment Staging [FAST] test 3–4), moderate to moderately severe AD (FAST 5–6), and severe AD (FAST 7). The study revealed (1) the most severe neuronal loss in FAST 3–4; (2) the highest rate of neuronal loss in FAST 5–6, to the “critical” point limiting further increase in neuronal loss; (3) progression of neurofibrillary degeneration, but decline of neuronal loss to a floor level in FAST 7; and (4) structure-specific rate of neuronal loss caused by neurofibrillary degeneration and a large pool of neuronal loss caused by other mechanisms. This study defines a range and speed of progression of AD pathology and functional decline that might potentially be prevented by the arrest of neuronal loss, both related and unrelated to neurofibrillary degeneration, during the 9-year duration of mild cognitive impairment/mild AD.
Study of UV-bright stellar populations in the globular cluster NGC 1261 using Astrosat
Authors: Rani Sharmila , Pandey Gajendra , Subramaniam Annapurni , Sahu Snehalata , Rao N Kameswara
Published: December 2020

We present UV photometry of the globular cluster NGC 1261 using images acquired with the Ultraviolet Imaging Telescope (UVIT) on board Astrosat. We performed point-spread function (PSF) photometry on four near-UV (NUV) and two far-UV (FUV) images and constructed UV colour–magnitude diagrams (CMDs), in combination with the Hubble Space Telescope (HST), Gaia, and ground-based optical photometry for member stars. We detected the full horizontal branch (HB) in the NUV and blue HB in the FUV and identified two extreme HB (EHB) stars. HB stars have a tight sequence in UV–optical CMDs, well fitted with isochrones generated (age 12.6 Gyr, [Fe/H] = −1.27 metallicity) using updated BaSTI-IAC models. Effective temperatures (Teff), luminosities, and radii of bright HB stars were estimated using the spectral energy distribution. As we detect the complete sample of UV-bright HB stars, the hot end of the HB distribution is found to terminate at the G-jump ($T_{\rm eff}\, \sim$ 11500 K). The two EHB stars, fitted well with single spectra, have Teff = 31000 K and a mass = 0.495 M⊙, and follow the same Teff–radius relation as the blue HB stars. We constrain the formation pathways of these EHB stars to extreme mass loss in the RGB phase (due either to rotation or enhanced helium) or a early hot-flash scenario.
The clustering of DESI-like luminous red galaxies using photometric redshifts
Authors: Zhou Rongpu , Newman Jeffrey A , Mao Yao-Yuan , Meisner Aaron , Moustakas John , Myers Adam D , Prakash Abhishek , Zentner Andrew R , Brooks David , Duan Yutong , Landriau Martin , Levi Michael E , Prada Francisco , Tarle Gregory
Published: December 2020

We present measurements of the redshift-dependent clustering of a DESI-like luminous red galaxy (LRG) sample selected from the Legacy Survey imaging data set, and use the halo occupation distribution (HOD) framework to fit the clustering signal. The photometric LRG sample in this study contains 2.7 million objects over the redshift range of 0.4 < z < 0.9 over 5655 deg2. We have developed new photometric redshift (photo-z) estimates using the Legacy Survey DECam and WISE photometry, with σNMAD = 0.02 precision for LRGs. We compute the projected correlation function using new methods that maximize signal-to-noise ratio while incorporating redshift uncertainties. We present a novel algorithm for dividing irregular survey geometries into equal-area patches for jackknife resampling. For a five-parameter HOD model fit using the MultiDark halo catalogue, we find that there is little evolution in HOD parameters except at the highest redshifts. The inferred large-scale structure bias is largely consistent with constant clustering amplitude over time. In an appendix, we explore limitations of Markov chain Monte Carlo fitting using stochastic likelihood estimates resulting from applying HOD methods to N-body catalogues, and present a new technique for finding best-fitting parameters in this situation. Accompanying this paper, we have released the Photometric Redshifts for the Legacy Surveys catalogue of photo-z’s obtained by applying the methods used in this work to the full Legacy Survey Data Release 8 data set. This catalogue provides accurate photometric redshifts for objects with z < 21 over more than 16 000 deg2 of sky.
A brain-penetrant microtubule-targeting agent that disrupts hallmarks of glioma tumorigenesis
Authors: Horne Eric A , Diaz Philippe , Cimino Patrick J , Jung Erik , Xu Cong , Hamel Ernest , Wagenbach Michael , Kumasaka Debra , Wageling Nicholas B , Azorín Daniel D , Winkler Frank , Wordeman Linda G , Holland Eric C , Stella Nephi
Published: December 2020

Background

Glioma is sensitive to microtubule-targeting agents (MTAs), but most MTAs do not cross the blood brain barrier (BBB). To address this limitation, we developed the new chemical entity, ST-401, a brain-penetrant MTA.

Methods

Synthesis of ST-401. Measures of MT assembly and dynamics. Cell proliferation and viability of patient-derived (PD) glioma in culture. Measure of tumor microtube (TM) parameters using immunofluorescence analysis and machine learning-based workflow. Pharmacokinetics (PK) and experimental toxicity in mice. In vivo antitumor activity in the RCAS/tv-a PDGFB-driven glioma (PDGFB-glioma) mouse model.

Results

We discovered that ST-401 disrupts microtubule (MT) function through gentle and reverisible reduction in MT assembly that triggers mitotic delay and cell death in interphase. ST-401 inhibits the formation of TMs, MT-rich structures that connect glioma to a network that promotes resistance to DNA damage. PK analysis of ST-401 in mice shows brain penetration reaching antitumor concentrations, and in vivo testing of ST-401 in a xenograft flank tumor mouse model demonstrates significant antitumor activity and no over toxicity in mice. In the PDGFB-glioma mouse model, ST-401 enhances the therapeutic efficacies of temozolomide (TMZ) and radiation therapy (RT).

Conclusion

Our study identifies hallmarks of glioma tumorigenesis that are sensitive to MTAs and reports ST-401 as a promising chemical scaffold to develop brain-penetrant MTAs.
Testing the Feasibility and Acceptability of a Religiously-Tailored Text Messaging Intervention to Reduce Smoking Among Somali Muslim Men During Ramadan
Authors: Pratt Rebekah , Ojo-Fati Olamide , DuBois Diana , Okuyemi Kolawole , Graham Amanda L , Mohamed Sharif , Janowiec Mark , Kahin Abdillahi , Mahamud Abdirahman , Tessier Katelyn M , Busch Andrew M , Joseph Anne M
Published: December 2020

Introduction

The prevalence of smoking among Somali Muslim male immigrants residing in Minnesota is estimated at 44%, however smoking reduction is common during the month of Ramadan. This study evaluated the feasibility and impact of a religiously tailored text message intervention delivered during Ramadan to encourage smoking reduction among Somali Muslim men who smoke.

Methods

Fifty Somali men were recruited. Participants received two text messages per day starting 1 week prior to and throughout the month of Ramadan. Approximately half were religiously tailored and half were about the risks of smoking and benefits of quitting. Smoking behavior was assessed at baseline, and at weeks 4 (end of Ramadan), 8, and 16. Outcomes included feasibility, acceptability, and preliminary impact of the text message intervention on smoking reduction and bioverified abstinence.

Results

The average age was 41 years. Average time to first cigarette was 1.8 hours at baseline, and 46% of participants smoked menthol cigarettes. Eighteen of 50 participants selected English and 32 selected Somali text messages. Subjects significantly reduced self-reported cigarettes per day (CPD) from 12.4 CPD at baseline to 5.8 CPD at week 16 (p < 0.001). Seven subjects reported quitting at week 16, five completed CO testing, confirming self-reported abstinence. The majority of participants found the cultural and religious references encouraging at the end of the week 16 survey.

Conclusions

Religiously tailored text messages to decrease smoking are feasible and acceptable to Somali Muslim men who smoke during Ramadan. This intervention for addressing smoking disparities is worthy of further study.

Implications

Recruitment of Somali Muslim men who smoke is feasible and supports the idea that further studies targeting smoking during Ramadan are practical. Ramadan presents a window of opportunity upon which to build smoking cessation interventions for smokers who identify as Muslim. These preliminary findings suggest that text messaging is a feasible and acceptable intervention strategy, and that religious tailoring was well received. Such an approach may offer potential for addressing smoking disparities among Somali Muslim male smokers.

Trial Registration

ClinicalTrial.gov: NCT03379142
Sexual Difficulties in the Population with Musculoskeletal Chronic Pain: A Systematic Review
Authors: Katz Haydee , Newton-John Toby R O , Shires Alice
Published: December 2020

Objective

To review the current literature on the nature and prevalence of sexual difficulties in the population with chronic musculoskeletal pain, as well as to identify the biopsychosocial factors that maintain these difficulties.

Design

Systematic review.

Methods

Studies were found by using multiple electronic databases and examining reference lists. After application of inclusion and exclusion criteria, 10 studies were eligible for review. Data were extracted and characteristics were described for outcomes of interest (i.e., sexual dysfunction, pain condition, pain intensity, psychosocial factors, gender differences). Cochrane Risk of Bias was assessed for all included studies.

Results

Ten studies (2,941 participants) were included in the review. Musculoskeletal conditions included low back pain and fibromyalgia. All studies examining sexual functioning found evidence of sexual difficulty among patients with chronic pain. Three studies demonstrated that sexual dysfunction was significantly greater in patients than in healthy matched controls. Nine studies found that greater pain levels significantly correlated with greater sexual dysfunction. Eight studies noted an increased prevalence of sexual difficulties in those with comorbid psychological problems. Heterogeneity between studies was identified, particularly with regard to gender outcomes. The risk-of-bias assessment also highlighted limitations in approximately half of studies.

Conclusions

This review reiterates the importance of investigating sexual functioning in the chronic musculoskeletal pain population, given the high prevalence of chronic musculoskeletal pain across all age bands. Given methodological limitations, future research should develop measures that sensitively cater to the various needs of patients with chronic pain. By modifying assessment to include biopsychosocial concerns, practitioners can tailor treatment to address transdiagnostic factors that maintain sexual dysfunction.
All-Pay Oligopolies: Price Competition with Unobservable Inventory Choices
Authors: Montez Joao , Schutz Nicolas
Published: December 2020

We study production in advance in a setting where firms first source inventories that remain unobservable to rivals, and then simultaneously set prices. In the unique equilibrium, each firm occasionally holds a sale relative to its reference price, resulting in firms sometimes being left with unsold inventory. In the limit as inventory costs become fully recoverable, the equilibrium converges to an equilibrium of the game where firms only choose prices and produce to order—the associated Bertrand game (examples of which include fully asymmetric clearinghouse models). Thus, away from that limit, our work generalizes Bertrand-type equilibria to production in advance, and challenges the commonly held view associating production in advance with Cournot outcomes. The analysis involves, as an intermediate step, mapping the price-inventory game into an asymmetric all-pay contest with outside options and non-monotonic winning and losing functions. We apply our framework to public policy towards information sharing, mergers, cartels, and taxation.
Activity of a subset of vesicular GABA-transporter neurons in the ventral zona incerta anticipates sleep onset
Authors: Blanco-Centurion Carlos , Luo SiWei , Vidal-Ortiz Aurelio , Swank Colby , Shiromani Priyattam J
Published: December 2020

Study Objectives

Sleep and wake are opposing behavioral states controlled by the activity of specific neurons that need to be located and mapped. To better understand how a waking brain falls asleep it is necessary to identify activity of individual phenotype-specific neurons, especially neurons that anticipate sleep onset. In freely behaving mice, we used microendoscopy to monitor calcium (Ca2+) fluorescence in individual hypothalamic neurons expressing the vesicular GABA transporter (vGAT), a validated marker of GABA neurons.

Methods

vGAT-Cre mice (male = 3; female = 2) transfected with rAAV-FLEX-GCaMP6M in the lateral hypothalamus were imaged 30 days later during multiple episodes of waking (W), non-rapid-eye movement sleep (NREMS) or REMS (REMS).

Results

372 vGAT neurons were recorded in the zona incerta. 23.9% of the vGAT neurons showed maximal fluorescence during wake (classified as wake-max), 4% were NREM-max, 56.2% REM-max, 5.9% wake/REM max, while 9.9% were state-indifferent. In the NREM-max group, Ca2+ fluorescence began to increase before onset of NREM sleep, remained high throughout NREM sleep, and declined in REM sleep.

Conclusions

We found that 60.2% of the vGAT GABA neurons in the zona incerta had activity that was biased towards sleep (NREM and REMS). A subset of vGAT neurons (NREM-max) became active in advance of sleep onset and may induce sleep by inhibiting the activity of the arousal neurons. Abnormal activation of the NREM-max neurons may drive sleep attacks and hypersomnia.
Rapid and Visual Detection of Meloidogyne hapla Using Recombinase Polymerase Amplification Combined with a Lateral Flow Dipstick Assay
Authors: Song Zhiqiang , Yang Xiai , Zhang Xiaowei , Luan Mingbao , Guo Bing , Liu Chunjie , Pan Jiangpeng , Mei Shiyong
Published: December 2020

The northern root-knot nematode, Meloidogyne hapla, is a biotrophic parasite that infects many crops and causes severe economic losses worldwide. Rapid and accurate detection of M. hapla is crucial for disease forecasting and control. We developed a recombinase polymerase amplification combined with a lateral flow dipstick (RPA-LFD) assay for rapid detection of M. hapla. The primers and probe were designed based on the effector gene 16D10 sequence and were highly specific to M. hapla. The RPA reaction was performed at a wide range of temperatures from 25 to 45°C within 5 to 25 min, and the amplicon was visualized directly on the LFD within 5 min. The detection limits of the RPA-LFD assay were 10−3 females and 10−2 second-stage juveniles/0.5 g of soil, which was 10 times more sensitive than the conventional PCR assay. In addition, the RPA-LFD assay can detect M. hapla from infested plant roots and soil samples, and the entire detection process can be completed within 1.5 h. These results indicate that the RPA-LFD assay is a simple, rapid, specific, sensitive, and visual method that can be used for rapid detection of M. hapla in the field and in resource-limited conditions.
Molecular and Biological Characterization of Recombinant Isolates of Potato virus Y Circulating in Potato Fields in Mexico
Authors: Rodriguez-Rodriguez Mariana , Quintero-Ferrer Arturo , Green Kelsie J. , Robles-Hernández Loreto , Gonzalez-Franco Ana C. , Karasev Alexander V.
Published: December 2020

Potato virus Y (PVY) is a significant threat to potato (Solanum tuberosum) production in Mexico. The presence of recombinant strains of PVY circulating in potato has been reported in the country, but no systematic study on the genetic diversity of PVY in potato and prevalence of PVY strains has been conducted yet. We report on a series of surveys in seed potato production areas in two states in Mexico, namely, Chihuahua and Jalisco, between 2011 and 2019. PVY was detected through the period of nine years in multiple potato cultivars in both states, often remaining asymptomatic in the most popular cultivars, such as ‘Fianna’ and ‘Agata’. When typed to strain, all PVY samples studied were found to have N-serotype, and were all identified molecularly as isolates of the same recombinant strain, PVYNTN. Five of these PVY isolates were tested on tobacco (Nicotiana tabacum), where they induced vein necrosis supporting the molecular typing. This identification was also confirmed biologically on differential potato cultivars, where one PVYNTN isolate from the 2013 survey triggered the hypersensitive resistance conferred by the Nztbr gene in the cv. Maris Bard. Seven of these Mexican PVYNTN isolates, collected between 2013 and 2019, including two PVY isolates from potato tubers exhibiting potato tuber necrotic ringspot disease, were subjected to whole genome sequencing and found to show a typical PVYNTNa recombinant structure. When subjected to phylogenetic analysis, Mexican PVYNTN sequences clustered in more than three separate clades, suggesting multiple introductions of PVYNTN in the country. The wide circulation of the PVYNTN strain in Mexican potato should be considered by potato producers, to develop mitigation strategies for this PVY strain associated with tuber necrotic symptoms.
Residue Dynamics of Streptomycin in Citrus Delivered by Foliar Spray and Trunk Injection and Effect on ‘Candidatus Liberibacter asiaticus’ Titer
Authors: Li Jinyun , Kolbasov Vladimir G. , Lee Donghwan , Pang Zhiqian , Huang Yixiao , Collins Nicole , Wang Nian
Published: December 2020

Streptomycin (STR) has been used to control citrus huanglongbing (HLB) caused by ‘Candidatus Liberibacter asiaticus’ (CLas) via foliar spray. Here, we studied the residue dynamics of STR and its effect on CLas titers in planta applied by foliar spray and trunk injection of 3-year-old citrus trees that were naturally infected by CLas in the field. After foliar spray, STR levels in leaves peaked at 2 to 7 days postapplication (dpa) and gradually declined thereafter. The STR spray did not significantly affect CLas titers in leaves of treated plants as determined by quantitative PCR. After trunk injection, peak levels of STR were observed 7 to 14 dpa in the leaf and root tissues, and near-peak levels were sustained for another 14 days before significantly declining. At 12 months after injection, moderate to low or undetectable levels of STR were observed in the leaf, root, and fruit, depending on the doses of STR injected, with a residue level of 0.28 µg/g in harvested fruit at the highest injection concentration of 2.0 µg/tree. CLas titers in leaves were significantly reduced by trunk injection of STR at 1.0 or 2.0 g/tree, starting from 7 dpa and throughout the experimental period. The reduction of CLas titers was positively correlated with STR residue levels in leaves. The in planta minimum effective concentration of STR needed to suppress the CLas titer to an undetectable level (cycle threshold ≥36.0) was 1.92 µg/g fresh weight. Determination of the in planta minimum effective concentration of STR against CLas and its spatiotemporal residue levels in planta provides the guidance to use STR for HLB management.
The Need for Biochemical Testing for Alcohol in Integrated Addiction Treatment Settings During the Opioid Epidemic
Authors: Marcovitz David , Sullivan William , Cobb Cheryl
Published: December 2020

As the opioid crisis drives expansion of integrated opioid use disorder (OUD) treatment programs in generalist settings, these programs will contend with significant rates of co-occurring alcohol use. The authors present a brief literature review and commentary regarding nondisordered and disordered alcohol use in OUD treatment settings and biochemical detection techniques. Biochemical testing for alcohol in integrated OUD treatment settings is both important for detecting alcohol use disorder and feasible. Breathalyzer testing may assist with management of acutely intoxicated patients. Biochemical testing for alcohol is an important part of integrated OUD treatment. More research is needed on the impact of alcohol use on OUD treatment outcomes and the role of breathalyzer testing in management of intoxicated patients in the outpatient setting.
Addressing Physician Burnout and Ensuring High-Quality Care of the Physician Workforce
Authors: Bradford Leslie , Glaser Gretchen
Published: December 2020

Burnout in health care is a public health crisis. Burnout is a triad of emotional exhaustion, depersonalization, and feelings of reduced personal accomplishment. More than half of practicing physicians and trainees experience burnout, and the rates are increasing. This review highlights the current prevalence of burnout among U.S. physicians, especially obstetrician–gynecologists. We review personal and systemic risk factors for burnout, consequences of burnout, and proven interventions, especially at the systems level, to treat and prevent burnout.
Consensus Bundle on Postpartum Care Basics
Authors: Stuebe Alison M. , Kendig Susan , Suplee Patricia D. , D'Oria Robyn
Published: December 2020

In the weeks after childbirth, a woman navigates multiple challenges. She must recover from birth, learn to care for herself and her newborn, and cope with fatigue and postpartum mood changes as well as chronic health conditions. Alongside these common morbidities, the number of maternal deaths in the United States continues to increase, and unacceptable racial inequities persist. One third of pregnancy-related deaths occur between 1 week and 1 year after delivery, with a growing proportion of these deaths due to cardiovascular disease; one fifth occur between 7 and 42 days postpartum. In addition, pregnancy-associated deaths due to self-harm or substance misuse are increasing at an alarming rate. Rising maternal mortality and morbidity rates, coupled with significant disparities in outcomes, highlight the need for tailored interventions to improve safety and well-being of families during the fourth trimester of pregnancy, which includes the period from birth to the comprehensive postpartum visit. Targeted support for growing families during this transition can improve health and well-being across generations.
Outpatient Penicillin Allergy Testing in Pregnant Women Who Report an Allergy
Authors: Desravines Nerlyne , Waldron Jamie , Venkatesh Kartik K. , Kwan Mildred , Boggess Kim A.
Published: December 2020

OBJECTIVE:

To estimate the feasibility, acceptability, and safety of outpatient penicillin allergy testing among pregnant women.

METHODS:

We conducted a prospective cohort study at a large academic hospital from March 2019 to March 2020. We recruited pregnant women with a self-reported penicillin allergy who underwent allergy testing between 14 0/7 and 36 6/7 weeks of gestation.

RESULTS:

Of 127 eligible women pregnant women, 74 (58%, 95% CI 4–67%) accepted allergy testing. Fifty completed or intended to complete allergy testing, yielding a feasibility rate of 68% (95% CI 56–78%). Among the 46 women actually tested (who ranged in age from 18 to 42), 93% (95% CI 68–100%) had a negative test result. A systemic reaction (symptoms consistent with anaphylaxis) occurred in only 2 women (4%, 95% CI 0.5–15%) despite 20 (43%) reporting a severe allergy. No woman suffered an adverse event as a result of allergy testing. In multivariate analysis adjusting for age and parity, women with public insurance had decreased odds of undergoing penicillin allergy testing (adjusted odds ratio 0.24, 95% CI 0.08–0.69).

CONCLUSION:

Outpatient penicillin allergy testing is acceptable and feasible in pregnancy.
Coronavirus Disease 2019 (COVID-19)–Related Multisystem Inflammatory Syndrome in a Pregnant Woman
Authors: Gulersen Moti , Staszewski Cara , Grayver Evelina , Tam Tam Hima , Gottesman Eric , Isseroff Donnie , Rochelson Burton , Bonanno Clarissa
Published: December 2020

BACKGROUND:

Recent reports have described a rare but severe complication of coronavirus disease 2019 (COVID-19) in nonpregnant adults that is associated with extrapulmonary organ dysfunction and appears to be secondary to a hyperinflammatory state.

CASE:

A multiparous woman at 28 weeks of gestation, diagnosed with COVID-19 4 weeks prior, was admitted with chest pain. Evaluation indicated myocarditis and marked elevations of inflammatory markers consistent with multisystem inflammatory syndrome in adults. The patient developed cardiogenic shock and required mechanical ventilation. Treatment with intravenous immunoglobulin and high-dose corticosteroids was associated with a favorable maternal and fetal outcome.

CONCLUSION:

Multisystem inflammatory syndrome in adults associated with COVID-19 in pregnancy is a critical illness, presenting several weeks after initial infection. Treatment with intravenous immunoglobin and corticosteroids was associated with a favorable outcome.
Association Between Social Determinants of Health and Postoperative Outcomes in Patients Undergoing Single-Level Lumbar Fusions
Authors: Khalid Syed I. , Maasarani Samantha , Nunna Ravi S. , Shanker Rachyl M. , Cherney Alecia A. , Smith Jennifer S. , Reme Anne-Isabelle , Adogwa Owoicho
Published: December 2020

Study Design.

Retrospective cohort.

Objective.

The aim of this study was to analyze association between social determinants of health (SDH) disparity on postoperative complication rates, and 30-day and 90-day all-cause readmission in patients undergoing single-level lumbar fusions.

Summary of Background Data.

Decreasing postoperative complication rates is of great interest to surgeons and healthcare systems. Postoperative complications are associated with poor convalescence, inferior patient reported outcomes measures, and increased health care resource utilization. Better understanding of the association between Social Determinants of Health (SDH) on postoperative outcomes maybe helpful to decrease postoperative complication rates.

Methods.

MARINER 2020, an all-payer claims database, was utilized to identify patients undergoing single-level lumbar fusions between 2010 and 2018. The primary outcomes were the rates of any postoperative complication, symptomatic pseudarthrosis, need for revision surgery, or 30-day and 90-day all-cause readmission.

Results.

The exact matched population analyzed in this study contained 16,560 patients (8280 [50.0%] patients undergoing single-level lumbar fusion with an SDH disparity; 8280 [50.0%] patients undergoing single-level lumbar fusion without a disparity). Both patient groups were balanced at baseline. The rate of symptomatic pseudarthrosis (1.0% vs. 0.6%, P < 0.05) or any postoperative complication (16.3% vs. 10.4%, P < 0.05) in the matched analysis was higher in the disparity group. The presence of a disparity was associated with 70% increased odds of developing any complication (OR 1.7, 95% CI 1.53–1.84) or symptomatic pseudarthrosis (OR 1.7, 95% CI 1.17–2.37). Unadjusted and adjusted sensitivity analyses yielded similar results as the primary analysis.

Conclusion.

Social Determinants of Health affect outcomes in spine surgery patients and are associated with an increased risk of developing postoperative complications following lumbar spine fusion.

Level of Evidence: 3
Long-term, Time-course Evaluation of Ligamentum Flavum Hypertrophy Induced by Mechanical Stress
Authors: Hori Yusuke , Suzuki Akinobu , Hayashi Kazunori , Ohyama Shoichiro , Yabu Akito , Maruf Mohammad Hasib , Habibi Hasibullah , Salimi Hamidullah , Nakamura Hiroaki
Published: December 2020

Study Design.

Experimental animal study.

Objective.

The aim of this study was to clarify chronological effects of mechanical stress on ligamentum flavum (LF) using a long-term fusion rabbit model.

Summary of Background Data.

LF hypertrophy is a major pathology of lumbar spinal stenosis (LSS), but its mechanism remains unclear. We previously demonstrated mechanical-stress-induced LF hypertrophy with a rabbit model. However, we only investigated LFs at a single time point in the short-term; the effects of long-term mechanical stress have not been elucidated.

Methods.

Eighteen-week-old male New Zealand White rabbits were randomly divided into two groups: the mechanical stress group underwent L2–3 and L4–5 posterolateral fusion and resection of the L3–4 supraspinal muscle, whereas the control group underwent only surgical exposure. Rabbits were sacrificed 16 and 52 weeks after the procedure. Axial specimens of LFs at L3–4 were evaluated histologically. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) was performed to assess the numbers of vessels and myofibroblasts.

Results.

In the mechanical stress group, LFs at the L3–4 level exhibited hypertrophy with elastic fiber disruption and cartilage matrix production at 16 and 52 weeks. A trend test indicated that mechanical stress induced LF hypertrophy, elastic fiber disruption, and cartilage matrix production in a time-dependent manner, with the lowest levels before treatment and the highest at 52 weeks. Immunostaining for α-SMA showed similar numbers of vessels in both groups, whereas the percentage of myofibroblasts was significantly larger at 16 and 52 weeks in the mechanical stress group than in the control group.

Conclusion.

We demonstrated that long-term mechanical stress caused LF hypertrophy with progressive elastic fiber disruption and cartilage matrix production accompanied by enhanced myofibroblasts. In addition, the reported rabbit model could be extended to elucidate the mechanism of LF hypertrophy and to develop new therapeutic strategies for LSS by preventing LF hypertrophy.

Level of Evidence: SSSSS
Optical Coherence Tomography Angiography and Visual Field Progression in Primary Angle Closure Glaucoma
Authors: Rao Harsha L. , Srinivasan Thanemozhi , Pradhan Zia S. , Sreenivasaiah Shruthi , Rao Dhanaraj A.S. , Puttaiah Narendra K. , Devi Sathi , Moghimi Sasan , Mansouri Kaweh , Webers Carroll A.B. , Weinreb Robert N.
Published: December 2020

Precis:

Lower whole enface disc (coefficient: 0.02, P=0.03) and macular vessel densities (coefficient: 0.04, P=0.02) on optical coherence tomography angiography (OCTA) were significantly associated with faster rate of mean deviation (MD) decline.

Purpose:

To evaluate the association between OCTA features and prior visual field (VF) progression in primary angle closure glaucoma (PACG).

Methods:

In a cross-sectional study, 46 eyes of 31 PACG patients with 5 reliable VF examinations performed over ≥3 years of follow-up underwent OCTA imaging. Effect of clinical (age, sex, number of antiglaucoma medications, mean, and SD of intraocular pressure during follow-up), optical coherence tomography (average retinal nerve fiber layer and ganglion cell complex thickness) and OCTA (whole enface vessel density of disc and macular scan, deep-layer microvascular dropout) parameters on the rate of MD change was evaluated using linear mixed models.

Results:

Average (±SD) MD of the baseline VF was −7.4±7.3 dB, and rate of MD change was −0.32±0.29 dB/y. Whole enface vessel density of disc and macular scans was 39.5%±8.1% and 38.7%±4.4%, respectively. Microvascular dropout was noted in 33.3% of the eyes. Multivariate mixed models showed that lower whole enface disc (coefficient: 0.02, P=0.03) and macular vessel densities (coefficient: 0.04, P=0.02) were significantly associated with faster rate of MD decline. Other factors significantly associated with faster progression in multivariate models were older age (coefficient: −0.02, P<0.05) and the presence of systemic hypertension (coefficient: −0.37, P=0.01) and diabetes (coefficient: −0.28, P=0.05).

Conclusions:

Lower superficial vessel density measured using OCTA was significantly associated with faster VF progression in PACG. In these eyes, OCTA parameters can serve as biomarker suggestive of past VF progression.
Cyclodiode Laser as the First Surgical Approach in Childhood Glaucoma Under the Age of 8 Years
Authors: Sakaorat Petchyim , Mohamed-Noriega Jibran , Sharara Ahmad , Daniel Moritz C. , Brookes John
Published: December 2020

Précis:

Cyclodiode as a primary treatment for childhood glaucoma patients younger than 8 years has a 12-month success rate of 55.24%. It can delay the need for penetrating glaucoma surgery.

Purpose:

The purpose of this study was to evaluate the treatment outcome of cyclodiode laser in childhood glaucoma for patients under the age of 8 years.

Design:

This was a retrospective, consecutive, noncomparative case series

Participants:

All childhood glaucoma patients who underwent cyclodiode from March 2005 to January 2017 as a primary surgical treatment under the age of 8 years.

Methods:

A retrospective review of the medical records of consecutive patients who underwent cyclodiode by a single surgeon.

Main Outcome Measures:

Success for single-diode intervention was defined as intraocular pressure (IOP) (>6 wk postoperative) ≤21 mm Hg with antiglaucoma medications and ≥20% IOP reduction, no further glaucoma surgery including cyclodiode, no loss of perception of light, and no major complications. Success for multiple-diode interventions was defined similar to the single diode, except that repeated cyclodiode is not considered a failure.

Results:

In all, 59 eyes of 43 patients were studied. The most common diagnosis was aphakic glaucoma. The mean age at cyclodiode treatment was 2.7 years (SD=2.2). Fifty-six percent of the patients were under 3 years. Success rates at 12 months after the procedure were 46.67% and 55.24% for single-diode and multiple-diode interventions, respectively. An IOP of >20 mm Hg 6 weeks after a cyclodiode session is a significant risk factor for failure with an hazard ratio of 2.41 (95% confidence interval: 1.00-5.81; P=0.05). Among the operated eyes, the surgeon could avoid further glaucoma surgery in 67.8% of the eyes during the first year after single or multiple cyclodiode sessions. None of the eyes experienced phthisis bulbi, hypotony, and severe uveitis.

Conclusions:

Cyclodiode laser in childhood glaucoma patients under the age of 8 years can be considered a safe alternative for glaucoma patients who can have a high risk of surgical complications. Performing cyclodiode laser can delay the need for penetrating glaucoma surgery. The IOP at 6 weeks may be a good predictor for the treatment outcome.
Review of the current information on erectile dysfunction in hypertensive males with 40 years of age or older
Authors: Teixeira Elisabete , Soares Paula
Published: December 2020

Hypertension (HT) is a prevalent disease, which origin frequently remains undetermined. Antihypertensive treatment (AHT) has been linked with erectile dysfunction (ED), mainly in middle-aged and older males. On the other side, some drugs used in AHT seem to be themselves associated with ED as a secondary effect. This led to the search of coadjuvant therapies for hypertensive patients with ED, considering that both illnesses cause high physical, psychological and economic burden. While the association between AHT and ED has been approached several times, the direct association between blood pressure and ED remains unclear. This review aims to summarize the current knowledge on the relationship between HT, AHT and ED specifically in males with age ≥40 years.
Risk Factors of SARS-CoV-2 Antibodies in Arapahoe County First Responders—The COVID-19 Arapahoe SErosurveillance Study (CASES) Project
Authors: Sabourin Katherine R. , Schultz Jonathan , Romero Joshua , Lamb Molly M. , Larremore Daniel , Morrison Thomas E. , Frazer-Abel Ashley , Zimmer Shanta , Kedl Ross M. , Jaenisch Thomas , Rochford Rosemary
Published: December 2020

Objectives:

Define the seroprevalence and risk factors for SARS-CoV-2 antibodies in Arapahoe County, Colorado first responders (eg, law enforcement, human services, fire departments).

Methods:

Two hundred sixty four first responders were enrolled June to July 2020. SARS-CoV-2 seropositivity was defined as detection of immunoglobulin G (IgG) antibodies to both spike receptor binding domain and nucleocapsid in venous blood by validated enzyme-linked immunosorbent assay. We compared risk factors for being seropositive versus seronegative.

Results:

4% (11/264) were SARS-CoV-2 seropositive. Seropositive participants were significantly more likely to have lung disease (% seropositive, % seronegative; P-value) (36%, 8%; P = 0.01), prior SARS-CoV-2/COVID-19 testing (36%, 8%; P ≤ 0.01), a prior positive result (18%, less than 1%), and to believe they previously had COVID-19 (64%, 15%; P < 0.01). Only 15% of those believing they had COVID-19 had anti-SARS-CoV-2 antibodies.

Conclusions:

Human services employees and individuals with lung disease are at SARS-CoV-2 exposure risk. Few individuals believed they had COVID-19 had prior exposure.
Leadership Style, Headache, and Neck Pain
Authors: Christensen Jan Olav , Nielsen Morten Birkeland , Sannes Ann Christin , Gjerstad Johannes
Published: December 2020

Objective:

Leadership styles can influence subordinates’ health. We investigated how the gene encoding the Catechol-O-Methyltransferase (COMT) enzyme (ie, COMT rs4680 Val158Met) influenced effects of abusive supervision and transformational leadership on subordinates’ headache and neck pain.

Methods:

Multiple group structural equation modeling (SEM) was employed to test associations of leadership with subordinates’ pain 6 months after in a representative sample of the Norwegian working population (n = 996). Genotyping was performed by TaqMan technology.

Results:

Abusive supervision was associated with increased risk, and transformational leadership with decreased risk, of headache and neck pain. Both leadership styles exhibited more pronounced effects in individuals with the Met/Met genotype.

Conclusion:

Met/Met employees were relatively vulnerable to adversity, but also relatively responsive to constructive leadership. Many workers may benefit more from constructive leadership than population-averaged associations might suggest.
Dabigatran in ibrutinib-treated patients with atrial fibrillation and chronic lymphocytic leukemia: experience of three cases
Authors: Santoro Rita Carlotta , Falbo Mariapia , Levato Luciano , Iannaccaro Piergiorgio , Prejanò Simona
Published: December 2020

Ibrutinib is the first clinically approved inhibitor of Bruton's tyrosine kinase, an essential enzyme for survival and proliferation of B cells by activating the B-cell receptor-signalling pathway. Ibrutinib has been shown to be highly effective in B-cell malignancies and is recommended in current international guidelines as a first-line and/or second-line treatment of chronic lymphocytic leukemia. The drug has a favorable tolerability and safety profile but the occurrence of specific side effects (e.g. atrial fibrillation, bleeding and hypertension). If atrial fibrillation is diagnosed, anticoagulant therapy may be required. Such patients receiving concomitant anticoagulation should be followed closely. DOAC is preferred over a VKA because of the lower risk of major bleeding events and because of the favorable stroke risk--benefit profile. Of all, Dabigatran offers the availability of an antidote and shows reduced potential for CYP3A4 interactions. We report the cases relating to three patients in concomitant therapy with Ibrutinib and Dabigatran.
A Place for the Professional Introduction in Practice
Authors: Henneman Elizabeth A. , Burke Mary Ellen A. , LeBlanc Raeann , Smithline Ellen
Published: December 2020

This article describes a survey exploring the use of professional introductions by nurses.

For this project, a survey inquiring about introduction practices was administered to nurses attending a regional research conference.