bluuebunny/crossref_metadata_2025 huggingface dataset:
CON: COVID-19 will not result in increased antimicrobial resistance prevalence
Authors: Collignon Peter , Beggs John J
Published: July 2020

Antimicrobial resistance (AMR) is affected by many factors, but too much of our focus has been on antimicrobial usage. The major factor that drives resistance rates globally is spread. The COVID-19 pandemic should lead to improved infection prevention and control practices, both in healthcare facilities and the community. COVID-19 will also have ongoing and profound effects on local, national and international travel. All these factors should lead to a decrease in the spread of resistant bacteria. So overall, COVID-19 should lead to a fall in resistance rates seen in many countries. For this debate we show why, overall, COVID-19 will not result in increased AMR prevalence. But globally, changes in AMR rates will not be uniform. In wealthier and developed countries, resistance rates will likely decrease, but in many other countries there are already too many factors associated with poor controls on the spread of bacteria and viruses (e.g. poor water and sanitation, poor public health, corrupt government, inadequate housing, etc.). In these countries, if economies and governance deteriorate further, we might see even more transmission of resistant bacteria.
Effects of increasing Fe dosage in newborn pigs on suckling and subsequent nursery performance and hematological and immunological criteria
Authors: Williams Hayden E , DeRouchey Joel M , Woodworth Jason C , Dritz Steven S , Tokach Michael D , Goodband Robert D , Holtcamp Andrew J , Bortoluzzi Eduarda M , Gebhardt Jordan T
Published: July 2020

A total of 336 newborn pigs (DNA 241 × 600, initially 1.75 ± 0.05 kg bodyweight [BW]) from 28 litters were used in a 63-d study evaluating the effects of increasing injectable Fe dose on suckling and subsequent nursery pig performance and blood Fe status. GleptoForte (Ceva Animal Health, LLC, Lenexa, KS) contains gleptoferron which is an Fe macromolecule complex that is commercially used as an injectable Fe source for suckling piglets. On the day of processing (day 3 after birth), all piglets were weighed and 6 barrows and 6 gilts per litter were allotted within sex to 1 of 6 treatments in a completely randomized design. Treatments consisted of a negative control receiving no Fe injection and increasing injectable Fe to achieve either 50, 100, 150, 200 mg, or 200 mg plus a 100 mg injection on day 11 after birth. Pigs were weaned (~21 d of age) and allotted to nursery pens based on BW and corresponding treatment in a completely randomized design. During lactation, increasing injectable Fe up to 100 mg improved (quadratic; P < 0.05) average daily gain (ADG) and day 21 BW with no further improvement thereafter. There was no evidence of differences (P > 0.10) observed between the 200 mg and 200 mg + 100 mg treatments for growth. For the nursery period, increasing Fe dosage increased (linear; P < 0.05) ADG, average daily feed intake, and day 42 BW. There was no evidence of differences (P > 0.10) between the 200 mg and 200 mg + 100 mg treatments for nursery growth. For blood criteria, significant treatment × day interactions (P = 0.001) were observed for hemoglobin (Hb) and hematocrit (Hct). The interactions occurred because pigs that had <150 mg of injectable Fe had decreased values to day 21 and then increased to day 63 while pigs with 150 or 200 mg of injectable Fe had increased values to day 21 then stayed relatively constant to day 63. In summary, piglet performance during lactation was maximized at 100 mg while nursery growth performance and blood Fe status were maximized with a 200 mg Fe injection at processing. Providing an additional 100 mg of Fe on day 11 of age increased Hb, and Hct values at weaning and 14 d into the nursery but did not provide a growth performance benefit in lactation or nursery. These results indicate that providing 200 mg of injectable Fe provided from GleptoForte is sufficient to optimize lactation and subsequent nursery growth performance and blood Fe status.
Screening of 104 New Psychoactive Substances (NPS) and Other Drugs of Abuse in Oral Fluid by LC–MS-MS
Authors: da Cunha Kelly Francisco , Oliveira Karina Diniz , Huestis Marilyn A , Costa Jose Luiz
Published: July 2020

New psychoactive substances (NPS) are a major public health problem, primarily due to the increased number of acute poisoning cases. Detection of these substances is a challenge. The aim of this research was to develop and validate a sensitive screening method for 104 drugs of abuse, including synthetic cannabinoids, synthetic cathinones, fentanyl analogues, phenethylamines and other abused psychoactive compounds (i.e., THC, MDMA, LSD and their metabolites) in oral fluid by liquid chromatography–tandem mass spectrometry (LC–MS-MS). The Quantisal™ oral fluid device was used to collect oral fluid samples. The oral fluid–elution buffer mixture (500-μL sample) was extracted with t-butyl methyl ether, and chromatographic separation was performed on a Raptor™ biphenyl column (100 × 2.1 mm ID, 2.7 μm), with a total run time of 13.5 min. Limits of detection were established at three concentrations (0.05, 0.1 or 1 ng/mL) for most analytes, except for acetyl norfentanyl and mescaline (5 ng/mL). Matrix effects were generally <20% and overall extraction recoveries >60%. The highest matrix effect was observed within the synthetic cannabinoid group (PB22, −55.5%). Lower recoveries were observed for 2C-T (47.2%) and JWH-175 (58.7%). Recoveries from the Quantisal™ device were also evaluated for all analytes (56.7–127%), with lower recoveries noted for 25I-NBOMe, valerylfentanyl and mCPP (56.7, 63.0 and 69.9%, respectively). Drug stability in oral fluid was evaluated at 15, 60 and 90 days and at 25, 4 and −20°C. As expected, greater stability was observed when samples were stored at −20°C, but even when frozen, some NPS (e.g., synthetic cannabinoids) showed more than 20% degradation. The method was successfully applied to the analysis of seven authentic oral fluid samples positive for 17 different analytes. The method achieved good sensitivity and simultaneous detection of a wide range of NPS.
International Emigrant Selection on Occupational Skills
Authors: Patt Alexander , Ruhose Jens , Wiederhold Simon , Flores Miguel
Published: July 2020

We present the first evidence on the role of occupational choices and acquired skills for migrant selection. Combining novel data from a representative Mexican task survey with rich individual-level worker data, we find that Mexican migrants to the United States have higher manual skills and lower cognitive skills than nonmigrants. Results hold within narrowly defined region–industry–occupation cells and for all education levels. Consistent with a Roy/Borjas-type selection model, differential returns to occupational skills between the United States and Mexico explain the selection pattern. Occupational skills are more important to capture the economic motives for migration than previously used worker characteristics.
Development of a Mach-Zehnder type electron interferometer on a 1.2-MV field-emission transmission electron microscope
Authors: Akashi Tetsuya , Takahashi Yoshio , Harada Ken
Published: July 2020

We have developed an amplitude-division type Mach-Zehnder electron interferometer (MZ-EI). The developed MZ-EI is composed of single crystals corresponding to amplitude-division beam splitters, lenses corresponding to mirrors and an objective aperture. The spacings and azimuth angles of interference fringes can be controlled by single crystal materials and their orientations and by diffraction spots selected by the objective aperture. We built the MZ-EI on a 1.2-MV field-emission transmission electron microscope and tested its performance. Results showed that interference fringes were created for various spacings and azimuth angles, which demonstrates the practicability of the MZ-EI as an amplitude-division type electron interferometer.
Behavioral Health Needs, Barriers, and Parent Preferences in Rural Pediatric Primary Care
Authors: Fehr Karla K , Leraas Bethany C , Littles Meghan M D
Published: July 2020

Objective

The goal of this study was to examine modifiable factors related to health disparities by exploring the role of predisposing, need, and enabling characteristics on mental/behavioral health treatment-seeking behaviors in a rural sample. Parental treatment preferences and knowledge about treatment options were also examined.

Methods

One hundred eighteen parents completed questionnaires assessing demographics, child prior psychological treatment, child psychological symptoms, barriers to care, mental health stigma, and willingness to seek services across settings. Questions also assessed preferences for treatment, awareness of behavioral/mental health services, and knowledge of community treatment options.

Results

Prior treatment use and stigma significantly predicted willingness to seek services in a doctor’s office after controlling for predisposing (demographic) and need characteristics (psychological symptoms). Symptom severity and barriers significantly differentiated between parents who previously sought treatment or reported an unmet treatment need from those who reported no prior treatment and no treatment need. Families overwhelmingly (94%) reported a preference for individual versus group treatment, and up to 10 sessions were most commonly reported (38%) as the ideal number of sessions. Forty percent of respondents reported no knowledge of treatment options in their community.

Conclusions

These results highlight the role of enabling characteristics (i.e., stigma, barriers to care, psychological symptoms) and prior service use in understanding parental treatment seeking in a rural sample. Overall, these results support integrated behavioral health in rural settings. Understanding modifiable factors and parent treatment preferences and knowledge may be important to increase access to services and reduce health disparities in rural areas. Future research directions are discussed.
Reduction in Short-term Outpatient Consultations After a Campaign With Measles Vaccine in Children Aged 9–59 Months: Substudy Within a Cluster-Randomized Trial
Authors: Varma Anshu , Aaby Peter , Thysen Sanne Marie , Jensen Aksel Karl Georg , Fisker Ane Bærent
Published: July 2020

Background

We assessed a measles vaccination campaign’s potential short-term adverse events.

Methods

In a cluster-randomized trial assessing a measles vaccination campaign’s effect on all-cause mortality and hospital admission among children aged 9–59 months in Guinea-Bissau, children received a measles vaccination (intervention) or a health check-up (control). One month to 2 months later, we visited a subgroup of children to ask mothers/guardians about outpatient consultations since enrollment. In log-binomial models, we estimated the relative risk (RR) of nonaccidental outpatient consultations.

Results

Among 8319 children (4437 intervention/3882 control), 652 nonaccidental outpatient consultations occurred (322 intervention/330 control). The measles vaccination campaign tended to reduce nonaccidental outpatient consultations by 16% (RR, 0.84 [95% confidence interval {CI}, .65–1.11]), especially if caused by respiratory symptoms (RR, 0.68 [95% CI, .42–1.11]). The reduction tended to be larger in children who prior to trial enrollment had a pentavalent vaccination (diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b) as the most recent vaccination (RR, 0.61 [95% CI, .42–.89]) than in children who prior to trial enrollment had a routine measles vaccination as the most recent vaccination (RR, 0.93 [95% CI, .68–1.26]) (P = .04 for interaction).

Conclusions

In the short term, a measles vaccination campaign seems not to increase nonaccidental outpatient consultations but may reduce them.

Clinical Trials Registration

NCT03460002.
Exploring the origin of ultra-diffuse galaxies in clusters from their primordial alignment
Authors: Rong Yu , Mancera Piña Pavel E , Tempel Elmo , Puzia Thomas H , De Rijcke Sven
Published: July 2020

We find that the minor axes of the ultra-diffuse galaxies (UDGs) in Abell 2634 tend to be aligned with the major axis of the central dominant galaxy, at a $\gtrsim 95{{\ \rm per\ cent}}$ confidence level. This alignment is produced by the bright UDGs with the absolute magnitudes Mr < −15.3 mag, and outer-region UDGs with R > 0.5R200. The alignment signal implies that these bright, outer-region UDGs are very likely to acquire their angular momenta from the vortices around the large-scale filament before they were accreted into A2634, and form their extended stellar bodies outside of the cluster; in this scenario, the orientations of their primordial angular momenta, which are roughly shown by their minor axes on the images, should tend to be parallel to the elongation of the large-scale filament. When these UDGs fell into the unrelaxed cluster A2634 along the filament, they could still preserve their primordial alignment signal before violent relaxation and encounters. These bright, outer-region UDGs in A2634 are very unlikely to be the descendants of the high-surface-brightness dwarf progenitors under tidal interactions with the central dominant galaxy in the cluster environment. Our results indicate that the primordial alignment could be a useful probe of the origin of UDGs in large-scale structures.
Evolutionary Genomics of Structural Variation in Asian Rice (Oryza sativa) Domestication
Authors: Kou Yixuan , Liao Yi , Toivainen Tuomas , Lv Yuanda , Tian Xinmin , Emerson J J , Gaut Brandon S , Zhou Yongfeng
Published: July 2020

Structural variants (SVs) are a largely unstudied feature of plant genome evolution, despite the fact that SVs contribute substantially to phenotypes. In this study, we discovered SVs across a population sample of 347 high-coverage, resequenced genomes of Asian rice (Oryza sativa) and its wild ancestor (O. rufipogon). In addition to this short-read data set, we also inferred SVs from whole-genome assemblies and long-read data. Comparisons among data sets revealed different features of genome variability. For example, genome alignment identified a large (∼4.3 Mb) inversion in indica rice varieties relative to japonica varieties, and long-read analyses suggest that ∼9% of genes from the outgroup (O. longistaminata) are hemizygous. We focused, however, on the resequencing sample to investigate the population genomics of SVs. Clustering analyses with SVs recapitulated the rice cultivar groups that were also inferred from SNPs. However, the site-frequency spectrum of each SV type—which included inversions, duplications, deletions, translocations, and mobile element insertions—was skewed toward lower frequency variants than synonymous SNPs, suggesting that SVs may be predominantly deleterious. Among transposable elements, SINE and mariner insertions were found at especially low frequency. We also used SVs to study domestication by contrasting between rice and O. rufipogon. Cultivated genomes contained ∼25% more derived SVs and mobile element insertions than O. rufipogon, indicating that SVs contribute to the cost of domestication in rice. Peaks of SV divergence were enriched for known domestication genes, but we also detected hundreds of genes gained and lost during domestication, some of which were enriched for traits of agronomic interest.
Kidney allograft recipients, immunosuppression, and coronavirus disease-2019: a report of consecutive cases from a New York City transplant center
Authors: Lubetzky Michelle , Aull Meredith J , Craig-Schapiro Rebecca , Lee John R , Marku-Podvorica Jehona , Salinas Thalia , Gingras Laura , Lee Jun B , Sultan Samuel , Kodiyanplakkal Rosy Priya , Hartono Choli , Saal Stuart , Muthukumar Thangamani , Kapur Sandip , Suthanthiran Manikkam , Dadhania Darshana M
Published: July 2020

Background

Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies.

Methods

We performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate.

Results

Of the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients.

Conclusions

Data from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19.
The use of future scenario thinking for child public health in a local authority
Authors: Mohiddin Abdu , Duggan Maria , Marsh Sheila , Dodhia Hiten , Oki Bimpe , Corlett Sarah
Published: July 2020

Background

Socioeconomic, cultural, technological, environment and ecological changes are rapidly transforming how children and young people (CYP) grow up, yet their impacts on CYP are difficult to predict. The traditional ways that Public Health practitioners work may not capture such complex and dynamic change. To address this, Lambeth Council used future scenario thinking.

Methods

A literature review looked at political, socioeconomic and other ‘transitions’ in the borough. Interviews, focus groups and workshops were held with CYP, parents, carers, local statutory and non-statutory stakeholders about the future for Lambeth CYP in the decade ahead. Themes were analysed to identify which had the potential for the biggest impact or the most uncertainty.

Results

The main transitions were described, 100 stakeholders interviewed, and five ‘drivers’ of the future were identified: protracted austerity, technological explosion, demographic shift, ‘democratic shake-up‘ and planetary health. From all these data, four future scenarios were developed: ‘communities care for themselves’, ‘collaborating to care for all’, ‘nobody cares’ and ‘who cares?’

Conclusions

New insights were gained about promoting more responsibility for, and active participation of CYP. This led to Lambeth’s CYP Plan and the ‘Made in Lambeth’ campaign aiming to enlist the community and business in creating a child-friendly borough.
High-frequency follow-up studies in musculoskeletal disorders: a scoping review
Authors: Tung Hsiu Yen , Galloway James , Matcham Faith , Hotopf Matthew , Norton Sam
Published: July 2020

Objectives

This scoping review identifies research in musculoskeletal disorders that uses high frequency follow-up of symptoms. The aim was to investigate whether symptom variability is investigated as a predictor of disease outcome and how intensive follow-up methods are used in musculoskeletal research.

Methods

Embase, MEDLINE and PsycInfo were searched using OVID, and the Institute of Electrical and Electronic Engineers was also searched using the Institute of Electrical and Electronic Engineers Xplore search engine. Studies were systematically reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, but no meta-analysis was done because the priority in this study is to identify gaps in available literature.

Results

Twenty-one papers were included. There was a mean of 54 patients per study (s.d. of 27.7). Two-thirds of the papers looked at how a symptom influences another in the short-term (subsequent assessment in the same day or next day), but none looked at the long-term. Only one study considered symptom variability investigating how higher variability in pain (defined by the s.d.) is associated with higher average pain severity and lower average sleep quality.

Conclusion

The methodology of musculoskeletal disorder research has changed from completing paper booklets to using electronic data capture (smartphones). There has also been a trend of collecting more intensive longitudinal data, but very little research utilizes these data to look at how symptom variability affects symptom outcomes. This demonstrates a gap in research where furthering understanding of this will help clinicians decide on the most important symptom to address in future patients.
How Intimate Partner Violence and Intersectional Identities Converge to Influence Women’s Sexual Health across Environmental Contexts
Authors: Bagwell-Gray Meredith E , Jen Sarah , Schuetz Nikolaus
Published: July 2020

In this qualitative study, authors examine women’s sexual risk and protective factors based on their experiences of intimate partner violence (IPV) and positioning within society relative to power. This analysis examines sexual risk and protective factors across intersectional identities—including gender, race, socioeconomic conditions, and age—among women survivors of IPV. The sample (N = 28) included women of diverse ages (range = 22–60 years) and races (57 percent White, 14 percent African American, 11 percent Hispanic, 7 percent Native American, 7 percent multiracial, and 4 percent South Asian). Findings demonstrated that IPV experiences differentially affect women’s sexual health according to intersectional identities and across various levels of environmental context by influencing the (in)stability of their lives and their experiences of (dis)empowerment. This analysis offers a nuanced understanding of how social workers can support women in planning for their own sexual health and safety and shows how an intersectional feminist framework enriches our understanding of the grand challenge to “build healthy relationships to end violence.”
The Role of Gender in Adolescent Dating Abuse: An Interpretive Meta-Synthesis of the Qualitative Literature
Authors: Storer Heather L , Schultz Katie , Hamby Sherry L
Published: July 2020

The role of gender has received considerable attention in the academic literature on intimate partner violence (IPV). The Grand Challenges for Social Work take a gender-neutral approach, without regard to the influence of gender on adolescent development and dating relationships. This positioning is inconsistent with gender mainstreaming approaches that have been integrated into international framings of IPV. The purpose of this article is to conduct a qualitative interpretive meta-synthesis to investigate how gender is represented in research on adolescent dating abuse across qualitative literature (N = 17 articles). Results underscore that gender influences the impact of abuse, with female adolescents more likely to be fearful in relationships, at higher risk for damage to their social standing, and more likely to be blamed for the abuse. Gender-specific attitudes affect perceptions of the seriousness of abuse, antecedents of abuse, and rationales for perpetrating violence. Findings across the studies indicate that adolescents have internalized gender scripts. Therefore, strategies to prevent dating abuse need to be cognizant of the socializing role of gender and the myriad ways it influences adolescents’ lived experiences. Therefore, the American Academy of Social Work and Social Welfare should consider revising the language of the existing challenges to mainstream gender.
Indigenous Women, Water Protectors, and Reciprocal Responsibilities
Authors: Dennis Mary Kate , Bell Finn McLafferty
Published: July 2020

Indigenous women in North America have traditionally had reciprocal relationships with and responsibilities to the Earth. The process of colonization violently transformed both the treatment of the Earth and of Indigenous women. Current environmental crises highlight not only the vulnerability of Indigenous women, but also their long-standing leadership in resisting environmental injustices affecting their families, relationships, and nations. In this article, authors focus on the resistance of Dakota water protectors with the #NoDAPL movement in the United States and Anishinaabe water protectors in Mother Earth Water Walks in Canada. Recommendations for social workers in supporting Indigenous women in a thoughtful and effective way include incorporating a definition of a “social” response to more-than-human world relationships and responsibilities, supporting direct action as a necessary social response to environmental issues, and acting in solidarity with Indigenous women in these movements.
Collaborative Responses to Commercial Sexual Exploitation as a Model of Smart Decarceration
Authors: Abrams Laura S , Godoy Sarah M , Bath Eraka P , Barnert Elizabeth S
Published: July 2020

Historically, youths who are affected by commercial sexual exploitation (CSE) in the United States have been implicated as perpetrators of crime and overrepresented in the juvenile justice system. As an intriguing example of the “smart decarceration” social work grand challenge, policy and practice initiatives have converged to decriminalize cisgender girls and young women experiencing CSE by reframing them as victims of exploitation rather than as criminals. To date, these efforts have largely focused on gender-specific programming for cisgender girls and young women. In this article, the authors describe how federal, state, and local policy and practice innovations have supported reframing CSE as a form of child maltreatment and rerouted girls and young women from the juvenile justice system to specialized services. Using Los Angeles County as a case example, the authors detail how innovative prevention, intervention, and aftercare programs can serve as models of smart decarceration for CSE-affected cisgender girls and young women with the potential to address the needs of youths with diverse gender and sexual identities.
A Defect in the Twin-Arginine Translocation Pathway Decreases the Tolerance of Xanthomonas campestris pv. campestris to Phenazines
Authors: Wu Jian , Pan Xiayan , Xu Shu , Duan Yabing , Wang Jueyu , Wang Jianxin , Gao Tongchun , Zhang Yong , Zhou Mingguo
Published: July 2020

Phenazine-1-carboxylic acid (PCA), a member of phenazines secreted by microorganisms, inhibits the growth of many bacteria and fungi. Xanthomonas campestris pv. campestris is the causal agent of black rot, the most important disease of cruciferous crops worldwide, and is more tolerant to PCA than other Xanthomonas species. Previous studies reported that reactive oxygen species (ROS) scavenging ability is involved in regulating the PCA tolerance of Xanthomonas species. Additionally, the cytochrome c maturation (CCM) system has been found to play a more important role in tolerance to phenazines than the ROS scavenging system. In this study, a highly PCA-sensitive insertion mutant of X. campestris pv. campestris, X-5, was identified and studied. The insertion site of X-5 was found to be in tatB gene (XC_4183), which encodes a subunit of the twin-arginine translocation (TAT) complex. Disruption of the three genes of TAT pathway resulted in decreased biological fitness and reduced tolerance to phenazines in comparison with the wild-type strain 8004. These results imply that the tolerance mechanism of the TAT pathway to phenazines is related to the CCM system, but not due to the ROS scavenging system. Furthermore, respiration-related characteristic tests and peptide analysis suggested that disruption of the TAT complex causes a defect in the cytochrome bc1 complex, which may be involved in the tolerance to phenazines. In summary, this study sheds new light on the critical role of the TAT pathway in influencing the fitness and phenazines tolerance of Xanthomonas species.
Transient Receptor Potential Cation Channels and Calcium Dyshomeostasis in a Mouse Model Relevant to Malignant Hyperthermia
Authors: Rafael Lopez Jose , Kaura Vikas , Hopkins Phillip , Liu Xiaochen , Uryach Arkady , Adams Jose , Allen Paul D.
Published: July 2020

Background

Until recently, the mechanism for the malignant hyperthermia crisis has been attributed solely to sustained massive Ca2+ release from the sarcoplasmic reticulum on exposure to triggering agents. This study tested the hypothesis that transient receptor potential cation (TRPC) channels are important contributors to the Ca2+ dyshomeostasis in a mouse model relevant to malignant hyperthermia.

Methods

This study examined the mechanisms responsible for Ca2+ dyshomeostasis in RYR1-p.G2435R mouse muscles and muscle cells using calcium and sodium ion selective microelectrodes, manganese quench of Fura2 fluorescence, and Western blots.

Results

RYR1-p.G2435R mouse muscle cells have chronically elevated intracellular resting calcium and sodium and rate of manganese quench (homozygous greater than heterozygous) compared with wild-type muscles. After exposure to 1-oleoyl-2-acetyl-sn-glycerol, a TRPC3/6 activator, increases in intracellular resting calcium/sodium were significantly greater in RYR1-p.G2435R muscles (from 153 ± 11 nM/10 ± 0.5 mM to 304 ± 45 nM/14.2 ± 0.7 mM in heterozygotes P < 0.001] and from 251 ± 25 nM/13.9 ± 0.5 mM to 534 ± 64 nM/20.9 ± 1.5 mM in homozygotes [P < 0.001] compared with 123 ± 3 nM/8 ± 0.1 mM to 196 ± 27 nM/9.4 ± 0.7 mM in wild type). These increases were inhibited both by simply removing extracellular Ca2+ and by exposure to either a nonspecific (gadolinium) or a newly available, more specific pharmacologic agent (SAR7334) to block TRPC6- and TRPC3-mediated cation influx into cells. Furthermore, local pretreatment with SAR7334 partially decreased the elevation of intracellular resting calcium that is seen in RYR1-p.G2435R muscles during exposure to halothane. Western blot analysis showed that expression of TRPC3 and TRPC6 were significantly increased in RYR1-p.G2435R muscles in a gene–dose–dependent manner, supporting their being a primary molecular basis for increased sarcolemmal cation influx.

Conclusions

Muscle cells in knock-in mice expressing the RYR1-p.G2435R mutation are hypersensitive to TRPC3/6 activators. This hypersensitivity can be negated with pharmacologic agents that block TRPC3/6 activity. This reinforces the working hypothesis that transient receptor potential cation channels play a critical role in causing intracellular calcium and sodium overload in malignant hyperthermia–susceptible muscle, both at rest and during the malignant hyperthermia crisis.

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Elevated d-Dimer Levels Are Associated With Increased Risk of Mortality in Coronavirus Disease 2019
Authors: Shah Siddharth , Shah Kuldeep , Patel Siddharth B. , Patel Foram S. , Osman Mohammed , Velagapudi Poonam , Turagam Mohit K. , Lakkireddy Dhanunjaya , Garg Jalaj
Published: July 2020

The 2019 novel coronavirus, declared a pandemic, has infected 2.6 million people as of April 27, 2020, and has resulted in the death of 181,938 people. d-dimer is an important prognostic tool, is often elevated in patients with severe coronavirus disease-19 (COVID-19) infection and in those who suffered death. In this systematic review, we aimed to investigate the prognostic role of d-dimer in COVID-19-infected patients. We searched PubMed, Medline, Embase, Ovid, and Cochrane for studies reporting admission d-dimer levels in COVID-19 patients and its effect on mortality. Eighteen studies (16 retrospective and 2 prospective) with a total of 3682 patients met the inclusion criteria. The pooled weighted mean difference (WMD) demonstrated significantly elevated d-dimer levels in patients who died versus those who survived (WMD, 6.13 mg/L; 95% confidence interval [CI] 4.16–8.11; P < 0.001). Similarly, the pooled mean d-dimer levels were significantly elevated in patients with severe COVID-19 infection (WMD, 0.54 mg/L; 95% CI 0.28–0.80; P < 0.001). The risk of mortality was fourfold higher in patients with positive d-dimer versus negative d-dimer (risk ratio, 4.11; 95% CI, 2.48–6.84; P < 0.001) and the risk of developing severe disease was twofold higher in patients with positive d-dimer levels versus negative d-dimer (risk ratio, 2.04; 95% CI, 1.34–3.11; P < 0.001). Our meta-analysis demonstrates that patients with COVID-19 infection presenting with elevated d-dimer levels have an increased risk of severe disease and mortality.
Repeated administration of inorganic nitrate on blood pressure and arterial stiffness: a systematic review and meta-analysis of randomized controlled trials
Authors: Li Dandan , Nishi Stephanie K. , Jovanovski Elena , Zurbau Andreea , Komishon Allison , Mejia Sonia Blanco , Khan Tauseef A. , Sievenpiper John L. , Milicic Davor , Jenkins Alexandra , Vuksan Vladimir
Published: July 2020

Objective:

We aim to synthesize effects of repeated administration (≥3 days) of inorganic nitrate on blood pressure and arterial stiffness measures.

Methods:

We conducted a systematic review and meta-analysis of randomized controlled trials with at least 3 days treatment of inorganic nitrate on blood pressure and arterial stiffness in individuals with or without elevated cardiovascular disease risk. MEDLINE, EMBASE and the Cochrane Library were searched through 2 July 2019. Two independent reviewers extracted relevant study data. Data were pooled using the generic inverse variance method with random-effects model, and expressed as mean differences with 95% confidence intervals. Certainty in the evidence was assessed using GRADE.

Results:

Forty-seven trials were included (n = 1101). Administration of inorganic nitrate significantly lowered SBP [mean difference: −2.91 mmHg, 95% confidence interval (95% CI): −3.92 to −1.89, I
2 = 76%], DBP (mean difference: −1.45 mmHg, 95% CI: −2.22 to −0.68, I
2 = 78%], central SBP (mean difference: −1.56 mmHg, 95% CI: −2.62 to −0.50, I
2 = 30%) and central DBP (mean difference: −1.99 mmHg, 95% CI: −2.37 to −1.60, I
2 = 0%). There was no effect on 24-h blood pressure, augmentation index or pulse wave velocity. Certainty in the evidence was graded moderate for central blood pressure, pulse wave velocity and low for peripheral blood pressure, 24-h blood pressure and augmentation index.

Conclusion:

Repeated administration (≥3 days) of inorganic nitrate lower peripheral and central blood pressure. Results appear to be driven by beneficial effects in healthy and hypertensive individuals. More studies are required to increase certainty in the evidence.
A novel angiotensin II peptide vaccine without an adjuvant in mice
Authors: Nakamaru Ryo , Nakagami Hironori , Hayashi Hiroki , Sun Jiao , Tenma Akiko , Yamamoto Koichi , Shimamura Munehisa , Morishita Ryuichi , Rakugi Hiromi
Published: July 2020

Objectives:

We recently developed a novel peptide, AJP001, that possesses both a mouse T-cell epitope and adjuvant action. Direct conjugation to the antigen is useful for peptide vaccines without the addition of adjuvants. In this study, the efficacy of an angiotensin (Ang) II and AJP001-conjugated peptide vaccine (AJ-Ang II) was evaluated in mice.

Methods:

The anti-Ang II antibody titer was measured in Balb/C mice following three injections of AJ-Ang II at 2-week intervals. SBP was measured during vaccination of Balb/C mice treated with Ang II infusion (1 μg/kg per min).

Results:

AJ-Ang II treatment resulted in an increase in the anti-Ang II antibody titer in a dose-dependent manner without the addition of adjuvants. In the analysis of the humoral immune response, AJ-Ang II mainly elicited IgG1 antibodies and IL-4 and IL-10 production, as measured by an enzyme-linked immune absorbent spot assay, which suggests the induction of a Th2 response. Importantly, cotreatment with purified antibodies attenuated Ang II-induced extracellular signal-regulated kinase phosphorylation and nuclear factor (NF)-κB activation in cultured vascular smooth muscle cells. The SBP in immunized mice was significantly lower than that in nonimmunized mice (135.9 ± 8.5 vs. 154.9 ± 16.8 mmHg, P = 0.02). Furthermore, Ang II-induced perivascular fibrosis in the heart was significantly attenuated in immunized mice, which also exhibited decreased mRNA expression of collagen I/III and transforming growth factor-β.

Conclusion:

AJ-Ang II may be a simple and useful therapeutic peptide vaccine without the addition of any adjuvants.
Prediagnostic Image Data, Artificial Intelligence, and Pancreatic Cancer
Authors: Young Matthew R. , Abrams Natalie , Ghosh Sharmistha , Rinaudo Jo Ann S. , Marquez Guillermo , Srivastava Sudhir
Published: July 2020

Pancreatic cancer continues to be one of the deadliest malignancies and is the third leading cause of cancer-related mortality in the United States. Based on several models, it is projected to become the second leading cause of cancer-related deaths by 2030. Although the overall survival rate for patients diagnosed with pancreatic cancer is less than 10%, survival rates are increasing in those whose cancers are detected at an early stage, when intervention is possible. There are, however, no reliable biomarkers or imaging technology that can detect early-stage pancreatic cancer or accurately identify precursors that are likely to progress to malignancy. The Alliance of Pancreatic Cancer Consortia, a virtual consortium of researchers, clinicians, and advocacies focused on early diagnosis of pancreatic cancer, was formed in 2016 to provide a platform and resources to discover and validate biomarkers and imaging methods for early detection. The focus of discussion at the most recent alliance meeting was on imaging methods and the use of artificial intelligence for early detection of pancreatic cancer.
Redeployment of Orthopaedic Advanced Practice Providers at Academic Medical Centers During the COVID-19 Pandemic
Authors: Kidd Vasco Deon
Published: July 2020

The novel coronavirus (SARS-CoV-2) represents a rapidly evolving pandemic. Health systems are scrambling to mobilize and redeploy their medical staff in the fight against COVID-19. Orthopaedic nurse practitioners/physician assistants should be part of any redeployment strategy to address unmet needs during these unprecedented times. This article discusses redeployment considerations and strategies that utilize these providers appropriately while mitigating risks.
A Quality Initiative for Reducing Postoperative Hypothermia for Neonatal Intensive Care Unit Surgical Patients
Authors: Cronin Jessica A. , Soghier Lamia , Ryan Kara , Shen Christine , Bhattarai Sopnil , Rana Sohel , Shah Rahul , Heitmiller Eugenie
Published: July 2020

Introduction:

The association between hypothermia in the neonatal intensive care unit (NICU) patients and morbidity and mortality is well described. Neonates are at higher risk of perioperative hypothermia when compared to older children. Previous studies showed that quality improvement tools reduced postoperative hypothermia in NICU patients, but none showed sustained improvement at incidence rates of <10%. As a single institution, we aimed to reduce the percentage of postoperative temperatures < 36°C in NICU patients from 10% to 6% over 6 months and sustain for 6 months.

Methods:

An interdisciplinary team created a key driver diagram and implemented interventions, including monthly reporting of postoperative hypothermia incidence to the anesthesiologists, individual feedback sessions with the anesthesiologists, use of a perioperative checklist, and continuous axillary temperature monitoring of the infant throughout the perioperative period. Data were collected retrospectively using a chart review of electronic medical records. The primary outcome was the percentage of hypothermic patients (T < 36°C) based on the first postoperative temperature taken in the NICU. We tracked this measure using a statistical control chart and evaluated it using Plan-Do-Study-Act cycles.

Results:

From February 1, 2016 to May 30, 2018, data were collected for 554 patients (pre-intervention: 242 and post-intervention: 312). The percentage of surgical patients who returned to the NICU hypothermic decreased from 9.7% to 2.5% (P < 0.002)—a change sustained for greater than 12 months.

Conclusions:

Quality improvement tools are useful in reducing postoperative hypothermia in NICU surgical patients and in maintaining these results.
A Positive Psychology–Motivational Interviewing Intervention to Promote Positive Affect and Physical Activity in Type 2 Diabetes: The BEHOLD-8 Controlled Clinical Trial
Authors: Huffman Jeff C. , Golden Julia , Massey Christina N. , Feig Emily H. , Chung Wei-Jean , Millstein Rachel A. , Brown Lydia , Gianangelo Taylor , Healy Brian C. , Wexler Deborah J. , Park Elyse R. , Celano Christopher M.
Published: July 2020

Objective

Physical activity is associated with superior health outcomes in patients with type 2 diabetes (T2D), but most T2D patients do not follow physical activity recommendations. The objective of this study was to assess the feasibility and impact of a novel combined positive psychology–motivational interviewing (PP-MI) intervention to promote physical activity in T2D.

Methods

This controlled clinical trial compared an 8-week, phone-delivered PP-MI intervention to an attention-matched MI-enhanced behavioral counseling condition among 60 participants with T2D and suboptimal moderate to vigorous physical activity (MVPA; <150 min/wk). The primary study outcome was feasibility (proportion of sessions completed) and acceptability (0–10 ease and utility ratings of each session). Secondary outcomes were between-group differences in changes in positive affect (main psychological outcome) and accelerometer-measured physical activity (MVPA and steps per day), using mixed-effects regression models, at 8 and 16 weeks.

Results

Ninety-two percent of PP-MI sessions were completed, and mean participant ratings of ease/utility were 8.5 to 8.8/10, surpassing a priori benchmarks for feasibility and acceptability. PP-MI participants had small-medium effect size (ES) difference improvements in positive affect compared with MI (8 weeks: estimated mean difference [EMD] = 3.07 [SE = 1.41], p = .029, ES = 0.44; 16 weeks: EMD = 2.92 [SE = 1.73], p = .092, ES = 0.42). PP-MI participants also had greater improvements in MVPA (8 weeks: EMD = 13.05 min/d [SE = 5.00], p = .009, ES = 1.24; 16 weeks: EMD = 7.96 [SE = 4.53], p = .079, ES = 0.75), with similar improvements in steps per day.

Conclusions

The PP-MI intervention was feasible and well accepted. Next-step efficacy studies can more rigorously explore the intervention’s effects on physical activity and clinical outcomes.

Trial Registration: ClinicalTrials.gov Registration No. NCT03150199.
The relative contributions of HIV drug resistance, nonadherence and low-level viremia to viremic episodes on antiretroviral therapy in sub-Saharan Africa
Authors: Inzaule Seth C. , Bertagnolio Silvia , Kityo Cissy M. , Siwale Margaret , Akanmu Sulaimon , Wellington Maureen , de Jager Marleen , Ive Prudence , Mandaliya Kishor , Stevens Wendy , Boender Tamara S. , Ondoa Pascale , Sigaloff Kim C.E. , Rinke de Wit Tobias F. , Hamers Raph L.
Published: July 2020

Introduction:

To achieve viral suppression among more than 90% of people on antiretroviral therapy (ART), improved understanding is warranted of the modifiable causes of HIV viremic episodes. We assessed the relative contributions of drug-resistance, nonadherence and low-level viremia (LLV) (viral load 50–999 cps/ml) on viremic episodes in sub-Saharan Africa.

Methods:

In a multicountry adult cohort initiating nonnucleoside reverse transcriptase inhibitor-based first-line ART, viremic episodes (viral load ≥1000 cps/ml) were classified as first, viral nonsuppression at 12 months; second, virological rebound at 24 months (after initial viral suppression at 12 months); third, failure to achieve viral resuppression at 24 months (after viremic episode at 12 months). We used adjusted odds ratios from multivariable logistic regression to estimate attributable fractions for each risk factor.

Results:

Of 2737 cohort participants, 1935 had data on pretreatment drug resistance (PDR) and at least 1 viral load outcome. Viral nonsuppression episodes [173/1935 (8.9%)] were attributable to nonadherence in 30% (35% in men vs. 24% in women) and to PDR to nonnucleoside reverse transcriptase inhibitors in 10% (15% in women vs. 6% in men). Notably, at contemporary PDR prevalences of 10–25%, PDR would explain 13–30% of viral nonsuppression. Virological rebound episodes [96/1515 (6.3%)] were mostly attributable to LLV (29%) and nonadherence (14%), and only rarely to PDR (1.1%). Failures to achieve viral resuppression [66/81 (81.5%)] were mostly attributable to the presence of acquired drug resistance (34%) and only rarely to nonadherence (2.4%).

Conclusion:

Effective adherence interventions could substantially reduce viral nonsuppression (especially in men) and virological rebound (especially during LLV), but would have limited effect on improving viral resuppression. Alternative ART regimens could circumvent PDR and acquired resistance.
Nonmelanoma skin cancer and melanoma in HIV-1-infected patients
Authors: Latini Alessandra , Alei Lavinia , Magri Francesca , Eibenschutz Laura , Cota Carlo , Dona’ Maria Gabriella , Cameli Norma , Cristaudo Antonio , Zaccarelli Mauro
Published: July 2020

In the cART era, the incidence of AIDS-defining cancers decreased, whereas a persistence of non-AIDS-defining cancers has been observed. In particular, concerning the risk of melanoma and nonmelanoma skin cancers in HIV patients, conflicting data are available. In this study, our aim was to assess the occurrence of cutaneous malignancies in 97 HIV-positive individuals visited in our Institute, and to evaluate the association with immunological parameters, as well as combination antiretroviral therapy (cART) duration.