bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating socially engaged climate research: Scientists’ visions of a climate resilient U.S. Southwest
Authors: Owen Gigi
Published: October 2020

Socially engaged science and collaborative research practices offer promising ways to address complex environmental and societal problems like climate variability and climate change. However, it is unclear if and how these types of collaborative knowledge production result in tangible impacts. Drawing from a 6-year evaluation, this article investigates the outcomes and contributions of ten collaborative research projects supported by a federally funded climate research program in the US Southwest. Based on a series of narratives that outline researchers’ objectives, anticipated outcomes are compared to those that emerged over a 6-year period. Results indicate several contributions that the program has made toward raising awareness about climate issues in the US Southwest, increasing capacity to adapt to climate change and climate variability, and building lasting individual and institutional collaborative relationships. However, researchers sometimes envision direct applications of their work, such as informing policy, planning, and decision-making, to be different than what occurred within the 6-year timeframe. Further exploration of these results reveals implicit assumptions in understanding how scientific information translates into use. This article offers insight into how researchers envision their impact, the management and development of a mission-oriented research program, and the use of evaluation to understand how collaborative research contributes to societal and environmental change.
Spillovers in Prices: The Curious Case of Haunted Houses*
Authors: Bhattacharya Utpal , Huang Daisy , Nielsen Kasper Meisner
Published: October 2020

Exploiting the unique institutional setting of Hong Kong’s real estate market, we uncover a curious ripple effect of haunted houses on the prices of nearby houses. Prices drop on average 20% for units that become haunted, 10% for units on the same floor, 7% for units in the same block, and 1% for units in the same estate. Our study makes two contributions. First, we provide an estimate of a large negative spillover on prices caused by a quality shock. Second, we find that the demand shock rather than the fire sale supply shock explains most of the spillover.
LUNG CANCER LIFETIME RISKS IN COHORT STUDIES OF URANIUM MINERS
Authors: Tomasek Ladislav
Published: October 2020

The article summarizes the most recent results from the cohorts of uranium miners, particularly the risks at low exposures and the risk models with modifying effects of exposure rate, age and time since exposure, which are used for the calculation of lifetime risks (LRs). The excess relative risks per unit exposure (ERR/WLM) arising from low exposures were found up to 10 times higher than the crude risk coefficients. For studies that reported models with modifying effect of age, time since exposure and exposure rate, LRs were calculated using the BEIR VI projection. These LRs were also calculated for a model with effect modification on the annual exposure rate. The results were prepared for the UNSCEAR report on ‘Lung cancer from exposure to radon.’(1)
Neural reference groups: a synchrony-based classification approach for predicting attitudes using fNIRS
Authors: Dieffenbach Macrina C , Gillespie Grace S R , Burns Shannon M , McCulloh Ian A , Ames Daniel L , Dagher Munqith M , Falk Emily B , Lieberman Matthew D
Published: September 2020

Social neuroscience research has demonstrated that those who are like-minded are also ‘like-brained.’ Studies have shown that people who share similar viewpoints have greater neural synchrony with one another, and less synchrony with people who ‘see things differently.’ Although these effects have been demonstrated at the ‘group level,’ little work has been done to predict the viewpoints of specific ‘individuals’ using neural synchrony measures. Furthermore, the studies that have made predictions using synchrony-based classification at the individual level used expensive and immobile neuroimaging equipment (e.g. functional magnetic resonance imaging) in highly controlled laboratory settings, which may not generalize to real-world contexts. Thus, this study uses a simple synchrony-based classification method, which we refer to as the ‘neural reference groups’ approach, to predict individuals’ dispositional attitudes from data collected in a mobile ‘pop-up neuroscience’ lab. Using functional near-infrared spectroscopy data, we predicted individuals’ partisan stances on a sociopolitical issue by comparing their neural timecourses to data from two partisan neural reference groups. We found that partisan stance could be identified at above-chance levels using data from dorsomedial prefrontal cortex. These results indicate that the neural reference groups approach can be used to investigate naturally occurring, dispositional differences anywhere in the world.
Cognitive Subtyping in Schizophrenia: A Latent Profile Analysis
Authors: Lim Keane , Smucny Jason , Barch Deanna M , Lam Max , Keefe Richard S E , Lee Jimmy
Published: October 2020

Cognitive dysfunction is a core feature of schizophrenia. The subtyping of cognitive performance in schizophrenia may aid the refinement of disease heterogeneity. The literature on cognitive subtyping in schizophrenia, however, is limited by variable methodologies and neuropsychological tasks, lack of validation, and paucity of studies examining longitudinal stability of profiles. It is also unclear if cognitive profiles represent a single linear severity continuum or unique cognitive subtypes. Cognitive performance measured with the Brief Assessment of Cognition in Schizophrenia was analyzed in schizophrenia patients (n = 767). Healthy controls (n = 1012) were included as reference group. Latent profile analysis was performed in a schizophrenia discovery cohort (n = 659) and replicated in an independent cohort (n = 108). Longitudinal stability of cognitive profiles was evaluated with latent transition analysis in a 10-week follow-up cohort. Confirmatory factor analysis (CFA) was carried out to investigate if cognitive profiles represent a unidimensional structure. A 4-profile solution was obtained from the discovery cohort and replicated in an independent cohort. It comprised of a “less-impaired” cognitive subtype, 2 subtypes with “intermediate cognitive impairment” differentiated by executive function performance, and a “globally impaired” cognitive subtype. This solution showed relative stability across time. CFA revealed that cognitive profiles are better explained by distinct meaningful profiles than a severity linear continuum. Associations between profiles and negative symptoms were observed. The subtyping of schizophrenia patients based on cognitive performance and its associations with symptomatology may aid phenotype refinement, mapping of specific biological mechanisms, and tailored clinical treatments.
Regulated earnings security: the relationship between employment protection and unemployment scarring over the Great Recession
Authors: Gonalons-Pons Pilar , Gangl Markus
Published: October 2020

The Great Recession raised the concern that employment protective institutions that are effective during macroeconomic stability might become counterproductive under growing macroeconomic volatility. We study this question by examining the relationship between employment protection legislation (EPL) and unemployment scars on earnings in 21 countries during the period surrounding the Great Recession. We use harmonized work history data for 21 countries from 2004 to 2014 and combine propensity score matching and multilevel-regression to estimate how earnings losses due to unemployment vary with the strength of labor market regulation and over changing macroeconomic conditions. We find that unemployment scarring is lower in contexts with robust employment protection, both under positive and negative macroeconomic environments. We also show that economic downturns intensify unemployment scarring significantly more in countries with weak EPL, largely because long-term unemployment is more strongly penalized. Taken together, our study finds that the positive effects of employment protection for workers remain robust during economic downturns.
A 3-ketoacyl-CoA synthase 11 (KCS11) homolog from Malania oleifera synthesizes nervonic acid in plants rich in 11Z-eicosenoic acid
Authors: Li Zhuowei , Ma Shijie , Song Huan , Yang Zheng , Zhao Cuizhu , Taylor David , Zhang Meng
Published: October 2020

Nervonic acid (24:1) is a major component in nerve and brain tissues and it has important applications in food and pharmaceutical industries. Malania oleifera seeds contain about 40% nervonic acid. However, the mechanism of nervonic acid biosynthesis and accumulation in seeds of this endangered tree species remains unknown. In this study, developmental changes in fatty acid composition within embryos and their pericarps were investigated. Nervonic acid proportions steadily increased in developing embryos but 24:1 was not detected in pericarps at any stage. Two 3-ketoacyl-CoA synthase (KCS) homologs have been isolated from M. oleifera developing seeds by homologous cloning methods. Both KCSs are expressed in developing embryos but not detected in pericarps. Based on a phylogenetic analysis, these two KCSs were named as MoKCS4 and MoKCS11. Seed-specific expression of the MoKCS11 in Arabidopsis thaliana led to about 5% nervonic acid accumulation, while expression of the MoKCS4 did not show an obvious change in fatty acid composition. It is noteworthy that the transformation of the same MoKCS11 construct into two Brassica napus cultivars with high erucic acid did not produce the expected accumulation of nervonic acid, although expression of MoKCS11 was detected in the developing embryos of transgenic lines. In contrast, overexpression of MoKCS11 results in similar level of nervonic acid accumulation in camelina, a species which contains a similar level of 11Z-eicosenoic acid as does Arabidopsis thaliana. Taken together, the MoKCS11 may have a substrate preference for 11Z-eicosenoic acid, but not for erucic acid, in planta.
Molecular phylogeny of the limacoid snail family Dyakiidae in Southeast Asia, with the description of a new genus and species
Authors: Jirapatrasilp Parin , Tongkerd Piyoros , Jeratthitikul Ekgachai , Liew Thor-Seng , Pholyotha Arthit , Sutcharit Chirasak , Panha Somsak
Published: September 2020

Members of the terrestrial snail family Dyakiidae from Southeast Asia show a distinct geographical distribution pattern and possess different degrees of complexity in their amatorial organ gland. This study is the first molecular phylogeny of ten of the 12 genera in this family, performed to provide insights into the origin of Dyakiidae and the evolution of their shells and amatorial organ gland structure. A new genus and new species, Pseudoquantula lenticularis Jirapatrasilp & Panha gen. & sp. nov., was uncovered based on its distinct morphological characters and molecular divergence. All other genera were retrieved as monophyletic except for Dyakia. Mainland Southeast Asia was inferred to be the ancestral range of the Dyakiidae, and the lineages then dispersed to and diversified in Borneo. Cladistic analysis showed that all 14 morphological characters used in this study were homoplastic. These results disagree with the previous amatorial organ transformation series, in which neither Pseudoplecta nor Quantula was ancestral to the other genera. The enigmatic genus Pseudoplecta, which lacks an amatorial organ gland, exhibited secondary loss.
Complete Genome Sequence Data of Tumorigenic Rhizobium vitis Strain VAT03-9, a Causal Agent of Grapevine Crown Gall Disease
Authors: Noutoshi Yoshiteru , Toyoda Atsushi , Ishii Tomoya , Saito Kirara , Watanabe Megumi , Kawaguchi Akira
Published: October 2020

Rhizobium vitis strain VAT03-9 (MAFF 211676) is a causal agent of crown gall disease in grapevine. It is one of the pathogenic strains of R. vitis isolated from graft unions of grapevine in Okayama Prefecture, Japan. Inoculation tests verified its virulence for gall formation on grapevine, tomato, and sunflower. It harbors tumor-inducing plasmid. Here, we present the complete genome sequence with annotation of R. vitis VAR03-9 obtained by assembling reads from PacBio and Illumina-sequencers. This genome sequence should be useful for the analyses of pathogenicity and evolutionary lineage of the pathogens of crown gall disease.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Physiological and Biochemical Effects on Napier Grass Plants Following Napier Grass Stunt Phytoplasma Infection
Authors: Asudi George O. , Omenge Keziah M. , Paulmann Maria K. , Reichelt Michael , Grabe Veit , Mithöfer Axel , Oelmüller Ralf , Furch Alexandra C. U.
Published: September 2020

Napier grass stunt (NGS) phytoplasma, a phloem-limited bacterium, infects Napier grass leading to severe yield losses in East Africa. The infected plants are strongly inhibited in growth and biomass production. In this study, phytoplasma-induced morphological changes of the vascular system and physiological changes were analyzed and compared with uninfected plants. The study showed that the phytoplasmas are more abundant in source leaves and range from 103 bacteria/μg total DNA in infected roots to 106 in mature Napier grass leaves. Using microscopical, biochemical, and physiological tools, we demonstrated that the ultrastructure of the phloem and sieve elements is severely altered in the infected plants, which results in the reduction of both the mass flow and the translocation of photoassimilates in the infected leaves. The reduced transport rate inhibits the photochemistry of photosystem II in the infected plants, which is accompanied by loss of chloroplastic pigments in response to the phytoplasma infection stress eventually resulting in yellowing of diseased plants. The phytoplasma infection stress also causes imbalances in the levels of defense-related antioxidants, glutathione, ascorbic acid, reactive oxygen species (ROS), and—in particular—hydrogen peroxide. This study shows that the infection of NGS phytoplasma in the phloem of Napier grass has an impact on the primary metabolism and activates a ROS-dependent defense response.
Lessons From the First Decade of the Native American Summer Research Internship at the University of Utah
Authors: Holsti Maija , Clark Edward B. , Fisher Simon , Hawkins Sam , Keenan Heather , Just Steven , Lee Jaymus , Napia Ed , Rodriguez Jose E. , Taylor Franci , White Richard , Willie Scott , Byington Carrie L.
Published: October 2020

Problem

American Indian/Alaska Native (AI/AN) populations are facing multiple health crises, including limited access to care, high rates of chronic disease, and early mortality that is far worse than other underrepresented minorities in the United States. According to the Association of American Indian Physicians, AI/AN people represent 2.0% of the U.S. population but only 0.2% of medical students and 0.1% of full-time faculty at MD-granting institutions. Increasing the number of AI/AN clinicians and scientists is one strategy to improve health outcomes in the AI/AN population and address these crises.

Approach

In 2010, the University of Utah partnered with research, cultural, and professional mentors to create a 10-week summer Native American Research Internship (NARI) program for AI/AN college students across the United States who are interested in pursuing biomedical careers. NARI attracts and supports AI/AN students by offering mentored summer research internships in an innovative, culturally aware framework that adapts to observed challenges to optimize educational experiences and support biomedical career aspirations.

Outcomes

During the first decade of the NARI program, 128 students from 22 U.S. states, representing 46 tribal nations and 57 colleges and universities, participated. Of those 128 students, 113 (88%) have completed a bachelor’s degree and the remaining 15 (12%) are currently working toward a bachelor’s degree. No NARI student has dropped out of college. Twenty-six (20%) NARI alumni have matriculated to medical school and 30 (23%) to graduate school. Eight (6%) participants have completed medical school, and 3 (2%) are pursuing a PhD in science. An additional 36 (28%) have gained employment in biomedical research fields.

Next Steps

The NARI program has increased the participation of AI/AN students in medicine and the biomedical sciences. The innovative, culturally aware, and adaptive framework is a model for other programs for AI/AN students and students in other underrepresented communities.
The COVID-19 Pandemic as an Imperative to Advance Medical Student Assessment: Three Areas for Change
Authors: Hauer Karen E. , Lockspeiser Tai M. , Chen H. Carrie
Published: October 2020

Conditions caused by the COVID-19 pandemic have disrupted clinical practice and all aspects of medical education. Yet the need to continue to train physicians to care for patients and communities is greater than ever. Medical educators are responding by adapting curricula in response to requirements for social distancing, changing availability of clinical learning opportunities, and limitations on testing center availability for examinations. These disruptions require a systems approach to ensure that learners achieve competence in preparation for advancement in training toward unsupervised practice. In this article, the authors assert that medical educators, obligated by current conditions to adapt educational experiences, should seize the opportunity presented by the pandemic to make needed changes in 3 areas aligned with competency-based medical education: focusing on outcomes, broadening the assessment toolbox, and improving the undergraduate medical education-to-graduate medical education (UME-to-GME) transition. Defined outcomes, as exemplified by entrustable professional activities, will enable curricular designers to shorten and adapt learning experiences by focusing on students’ achievement of prespecified learning outcomes. Broadening the assessment toolbox entails capturing more and different assessment information about learners to provide a well-rounded view of their strengths and areas for growth in both traditional and novel settings, such as telehealth. Limitations on available data, such as licensing examination scores and clerkship grades, heighten the urgency to revise the system for the UME-to-GME transition by enhancing the quality and usability of information available to residency program directors. Educators should capitalize on the opportunity presented by altered conditions due to the COVID-19 pandemic to make these needed changes to the educational system, to prepare physicians to provide health care and lead the health care system into the future.
Spinal anesthesia for ambulatory surgery: current controversies and concerns
Authors: Stewart Jesse , Gasanova Irina , Joshi Girish P.
Published: September 2020

Purpose of review

General anesthesia is a popular choice for ambulatory surgery. Spinal anesthesia is often avoided because of perceived delays due to time required to administer it and prolonged onset, as well as concerns of delayed offset, which may delay recovery and discharge home. However, the reports of improved outcomes in hospitalized patients undergoing total joint arthroplasty have renewed the interest in spinal anesthesia. This review article critically assesses the role of spinal anesthesia in comparison with fast-track general anesthesia for the outpatient setting.

Recent findings

The purported benefits of spinal anesthesia include avoidance of airway manipulation and the adverse effects of drugs used to provide general anesthesia, improved postoperative pain, and reduced postoperative opioid requirements. Improved postoperative outcomes after spinal anesthesia in hospitalized patients may not apply to the outpatient population that tends to be relatively healthier. Also, it is unclear if spinal anesthesia is superior to fast-track general anesthesia techniques, which includes avoidance of benzodiazepine premedication, avoidance of deep anesthesia, use of an opioid-sparing approach, and minimization of neuromuscular blocking agents with appropriate reversal of residual paralysis.

The benefits of spinal anesthesia in the outpatient setting remain questionable at best. Further studies should seek clarification of these goals and outcomes.
Barriers and Facilitators to Early Rehabilitation in the ICU: A Theory Driven Delphi Study
Authors: Cuthbertson Brian H. , Goddard Shannon L. , Lorencatto Fabiana , Koo Ellen , Rose Louise , Fan Eddy , Kho Michelle E. , Needham Dale M. , Rubenfeld Gordon D. , Francis Jill J.
Published: October 2020

Objectives:

There is conflicting evidence for the effectiveness of early rehabilitation in the intensive care and marked variation in rates of implementation in practice. We aimed to identify barriers and facilitators to early rehabilitation in mechanically ventilated patients and their relevance to practice, as perceived by key ICU clinicians across North America.

Design:

A Delphi study using the Theoretical Domains Framework, consisting of an initial qualitative round and subsequent quantitative rounds, was conducted to gather clinician agreement and perceived importance of barriers and facilitators to early rehabilitation. The survey included questions on the range of individual, sociocultural, and broader organizational influence on behaviors.

Setting:

Clinical practice in North America.

Subjects:

Four clinician groups (intensive care physicians, nurses, therapists, and respiratory therapists).

Interventions:

A three-round Delphi study.

Measurements and Main Results:

Fifty of 74 (67%) of invited clinicians completed the study. Agreement and consensus with Delphi survey items were high in both rounds within and between professional groups. Agreement was highest for items related to the domain “Beliefs about Consequences” (e.g., mortality reduction) and lowest for items related to the domain “Behavioral Regulation” (e.g., team discussion of barriers). Beliefs expressed about improved mortality and improvements in a variety of other long-term outcomes were not consistent with the current evidence base. Individual agreement scores changed very little from Round 2 to Round 3 of the Delphi, suggesting stability of beliefs and existing consensus.

Conclusions:

This study identified a wide range of beliefs about early rehabilitation that may influence provider behavior and the success and appropriateness of further implementation. The apparent inconsistency between the optimism of stakeholders regarding mortality reductions and a low level of implementation reported elsewhere represent the most major challenge to future implementation success. Other foci for future implementation work include planning, barriers, feedback, and education of staff.
Improved Oxygenation After Prone Positioning May Be a Predictor of Survival in Patients With Acute Respiratory Distress Syndrome*
Authors: Lee Hong Yeul , Cho Jaeyoung , Kwak Nakwon , Choi Sun Mi , Lee Jinwoo , Park Young Sik , Lee Chang-Hoon , Yoo Chul-Gyu , Kim Young Whan , Lee Sang-Min
Published: October 2020

Objectives:

Prone position ventilation improves oxygenation and reduces the mortality of patients with severe acute respiratory distress syndrome. However, there is limited evidence about which patients would gain most survival benefit from prone positioning. Herein, we investigated whether the improvement in oxygenation after prone positioning is associated with survival and aimed to identify patients who will gain most survival benefit from prone positioning in patients with acute respiratory distress syndrome.

Design:

A retrospective cohort study.

Setting:

Medical ICU at a tertiary academic hospital between 2014 and 2020.

Patients:

Adult patients receiving prone positioning for moderate-to-severe acute respiratory distress syndrome.

Interventions:

None.

Measurements and Main Results:

The main outcomes were ICU and 28-day mortality. A total of 116 patients receiving prone positioning were included, of whom 45 (38.8%) were ICU survivors. Although there was no difference in Pao
2:Fio
2 ratio before the first prone session between ICU survivors and nonsurvivors, ICU survivors had a higher Pao
2:Fio
2 ratio after prone positioning than nonsurvivors, with significant between-group difference (p < 0.001). The area under the receiver operating characteristic curve of the percentage change in the Pao
2:Fio
2 ratio between the baseline and 8–12 hours after the first prone positioning to predict ICU mortality was 0.87 (95% CI, 0.80–0.94), with an optimal cutoff value of 53.5% (sensitivity, 91.5%; specificity, 73.3%). Prone responders were defined as an increase in Pao
2:Fio
2 ratio of greater than or equal to 53.5%. In the multivariate Cox regression analysis, prone responders (hazard ratio, 0.11; 95% CI, 0.05–0.25), immunocompromised condition (hazard ratio, 2.15; 95% CI, 1.15–4.03), and Sequential Organ Failure Assessment score (hazard ratio, 1.16; 95% CI, 1.06–1.27) were significantly associated with 28-day mortality.

Conclusions:

The Pao
2:Fio
2 ratio after the first prone positioning differed significantly between ICU survivors and nonsurvivors. The improvement in oxygenation after the first prone positioning was a significant predictor of survival in patients with moderate-to-severe acute respiratory distress syndrome.
Fluid Overload and Mortality in Adult Critical Care Patients—A Systematic Review and Meta-Analysis of Observational Studies*
Authors: Messmer Anna S. , Zingg Carina , Müller Martin , Gerber Joel Loic , Schefold Joerg Christian , Pfortmueller Carmen Andrea
Published: October 2020

Objective:

Fluid administration in combination with the increase in vasopermeability induced by critical illness often results in significant fluid overload in critically ill patients. Recent research indicates that mortality is increased in patients who have received large volumes of fluids. We have systematically reviewed and synthesized the evidence on fluid overload and mortality in critically ill patients and have performed a meta-analysis of available data from observational studies.

Data Sources:

A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases.

Study Selection and Data Extraction:

All studies were eligible that investigated the impact of fluid overload (defined by weight gain > 5%) or positive cumulative fluid balance on mortality in adult critical care patients. We excluded animal studies and trials in pediatric populations (age < 16 years old), pregnant women, noncritically ill patients, very specific subpopulations of critically ill patients, and on early goal-directed therapy. Randomized controlled trials were only evaluated in the section on systematic review. Assessment followed the Cochrane/meta-analysis of observational trials in epidemiology guidelines for systematic reviews.

Data Synthesis:

A total of 31 observational and three randomized controlled trials including 31,076 ICU patients met the inclusion criteria. Only observational studies were included in the meta-analysis. Fluid overload and cumulative fluid balance were both associated with pooled mortality: after 3 days of ICU stay, adjusted relative risk for fluid overload was 8.83 (95% CI, 4.03–19.33), and for cumulative fluid balance 2.15 (95% CI, 1.51–3.07), at any time point, adjusted relative risk for fluid overload was 2.79 (95% CI, 1.55–5.00) and 1.39 (95% CI, 1.15–1.69) for cumulative fluid balance. Fluid overload was associated with mortality in patients with both acute kidney injury (adjusted relative risk, 2.38; 95% CI, 1.75–2.98) and surgery (adjusted relative risk, 6.17; 95% CI, 4.81–7.97). Cumulative fluid balance was linked to mortality in patients with sepsis (adjusted relative risk, 1.66; 95% CI, 1.39–1.98), acute kidney injury (adjusted relative risk, 2.63; 95% CI, 1.30–5.30), and respiratory failure (adjusted relative risk, 1.19; 95% CI, 1.03–1.43). The risk of mortality increased by a factor of 1.19 (95% CI, 1.11–1.28) per liter increase in positive fluid balance.

Conclusions:

This systematic review and meta-analysis of observational studies reporting adjusted risk estimates suggests that fluid overload and positive cumulative fluid balance are associated with increased mortality in a general population and defined subgroups of critically ill patients.
Adverse drug reactions: five historical scandals
Authors: Horwitz Henrik , Gotfredsen Ditte Resendal , Christoffersen Thea
Published: September 2020

It is estimated that eight percentage of all acute medical admissions are due to adverse drug reactions, and three percentage of all approved new medical entities are later withdrawn from the market due to safety issues. Adverse drug reactions are of public health concern and this paper reviews five selected adverse drug reaction scandals that all caused significant stir and had a huge impact on our way of thinking, drug development and legislation.
Combination of the Phosphodiesterase Inhibitors Sildenafil and Milrinone Induces Cardioprotection With Various Conditioning Strategies
Authors: Torregroza Carolin , Maas Kitti , Feige Katharina , Raupach Annika , Stroethoff Martin , Heinen André , Hollmann Markus W. , Huhn Ragnar
Published: October 2020

Ischemic preconditioning and postconditioning are strong measures preserving the heart against ischemia–reperfusion injury in experimental setting but are too invasive and impractical for clinical routine. The cardioprotective effects of ischemic preconditioning and postconditioning can be imitated pharmacologically, for example, with the phosphodiesterase inhibitors sildenafil and milrinone. We hypothesize that sildenafil-induced preconditioning is concentration dependent and further that a combined treatment of “nonprotective” versus “protective” concentrations of sildenafil and milrinone leads to a significant infarct size reduction. Experiments were performed on isolated hearts of male Wistar rats, randomized into 12 groups, mounted onto a Langendorff system, and perfused with Krebs–Henseleit buffer. All hearts underwent 33 minutes ischemia and 60 minutes of reperfusion. For determination of a concentration-dependent effect of sildenafil, hearts were perfused with increasing concentrations of sildenafil (0.1–1 µM) over 10 minutes before ischemia. In a second series of experiments, hearts were treated with 0.3 µM sildenafil or 1 µM milrinone as the “protective” concentrations. A higher concentration of respective drugs did not further reduce infarct size. In addition, a combination of “protective” and “nonprotective” concentrations of sildenafil and milrinone was applied. Sildenafil and milrinone in lower concentrations led to significant infarct size reduction, whereas combining both substances in cardioprotective concentrations did not enhance this effect. Sildenafil in a concentration of 0.3 µM induces myocardial protection. Furthermore, treatment with sildenafil and milrinone in lower concentrations had an equally strong cardioprotective effect regarding infarct size reduction compared with the administration of “protective” concentrations.
Hospitalization in South African Adolescents With Perinatally Acquired HIV on Antiretroviral Therapy
Authors: Frigati Lisa J. , Brown Karryn , Cotton Mark F. , Myer Landon , Zar Heather J.
Published: October 2020

Background:

Little is known about hospitalization in African adolescents with perinatally acquired HIV (PHIV+ adolescents). We described the incidence and causes of hospitalization in participants enrolled in the Cape Town Adolescent Antiretroviral Cohort in South Africa.

Methods:

Data collected from July 2013 to October 2018 from PHIV+ and HIV− adolescents were analyzed. Participants were assessed every 6 months and data on intercurrent hospitalization were abstracted. Causes of hospitalizations were classified according to ICD-10 codes. Descriptive statistics, time-to-event analysis and Poisson regression were used to describe causes and incidence and to determine incidence rate ratios for factors associated with hospitalization.

Results:

Five hundred fifteen PHIV+ and 109 HIV− participants had a median follow-up of 4.1 years [interquartile range (IQR): 3.7–4.6]. At enrollment HIV+ participants had a median duration of ART of 7.6 years (IQR: 4.6–9.2), median CD4 count of 713 cells/mm3 (IQR: 561.0–957.5) and 387 (75%) had a viral load <50 copies/mL. There were 149 hospital admissions over 64 months. Crude incidence rates for hospitalization were 6.6 [95% confidence interval (CI): 5.7–7.8] and 2.2 (95% CI: 1.2–4.3) per 100-person-years (P = <0.01) in HIV + and HIV−, respectively. Ninety of 149 (60%) admissions in HIV+ participants were classified as non-infectious, 36/149 (24%) were infectious and 23/149 (16%) were “other HIV-related” or “unknown.” Older age (15–19 years) and maintaining a CD4 >500 cells/cm3 were associated with decreased risk of hospitalization: adjusted incidence rate ratios of 0.61 (CI: 0.44–0.86, P = <0.01) and 0.68 (CI: 0.49–0.94, P = 0.02), respectively.

Conclusions:

PHIV+ adolescents had a high incidence of hospitalization despite ART. Strategies addressing infectious and non-infectious morbidity must be strengthened.
A Case of Lemierre Syndrome in the Era of COVID-19: All That Glitters Is Not Gold
Authors: Repper Danielle C. , Arrieta Antonio C. , Cook Jason E. , Renella Pierangelo
Published: October 2020

We report a case of a 15-year-old female presenting with a serious multisystemic inflammatory illness during a surge of SARS-CoV-2 (COVID-19) cases in our county. The initial clinical findings of sore throat and neck stiffness, followed by signs of sepsis, raised suspicion of Lemierre syndrome early in her hospital course. However, the presence of severe respiratory distress, multifocal pneumonia with pleural effusion on chest radiograph, acute kidney injury, and the discovery of coronary artery ectasia, pointed to the new entity “multisystem inflammatory syndrome in children (MIS-C).” Immune modulatory treatment was thus considered. However, progressive neck pain and swelling, coupled with the eventual growth of Fusobacterium necrophorum on blood culture, eventually led to the correct diagnosis of Lemierre syndrome.
When pain becomes uncontrollable: an experimental analysis of the impact of instructions on pain-control attempts
Authors: Kissi Ama , Hughes Sean , Van Ryckeghem Dimitri , De Houwer Jan , Crombez Geert
Published: October 2020

Under some conditions, people persist in their attempts to control their pain even when no such control is possible. Theory suggests that such pain-control attempts arise from actual pain experiences. Across 3 experiments we examined how (1) losing control over pain and (2) instructions concerning pain, moderated pain-control attempts. In each experiment, participants completed a learning task. Before the task, one group of participants received instructions outlining a strategy through which they could control pain, whereas another group had to develop such a strategy through trial-and-error learning. During the first half of the task, the pain-control instructions allowed participants to successfully control pain, whereas during the second half of the task, this was no longer the case. Instead, participants lost control over pain because of an unannounced change in the learning task. Results indicated that when participants lost control over pain, they generally stuck to the previously effective pain-control strategy, and that this tendency was larger if they received instructions from others than when they developed a strategy by themselves. These findings suggest that when pain is no longer controllable, very persistent pain-control attempts might be the result of adherence to previously effective pain-control instructions.
An unusual complication of quadriparesis after trigger point injection: a case report
Authors: Sangondimath Gururaj , Varma Kalidindi Kalyan Kumar , Pandrakula Phani , Kumar Vivek , Hari Krishan Mahajan
Published: October 2020

Quadriparesis after intramuscular trigger point injections for myofascial pain syndrome has been rarely reported in the literature. A 37-year-old male patient presented with myofascial pain syndrome and was given trigger point injections in trapezius muscles under ultrasound guidance. The patient noticed weakness in all the 4 limbs at approximately 12 hours after the procedure, which gradually progressed to functional quadriplegia at the time of presentation to the emergency department. On examination, he had quadriparesis with no sensory involvement and superficial reflexes were normal. MRI screening of the whole spine was unremarkable, and MRI brain suggested an incidental granuloma, which could not explain his symptoms. Blood tests revealed severe hypokalemia (2.2 mEq/L) and deranged thyroid function tests. Immediate potassium correction with intravenous and oral potassium chloride was initiated, and the patient showed improvement within 6 hours of initiating correction. Stress of the procedure, use of steroids with mineralocorticoid effects such as methylprednisolone, or deranged thyroid function tests may have acted as triggers to precipitate hypokalemic paralysis in the patient. Knowledge of this complication is essential as prompt diagnosis and timely management of hypokalemia can result in complete resolution of the symptoms.
Effect of a brief scenario-tailored educational program on parents' risk knowledge, perceptions, and decisions to administer prescribed opioids: a randomized controlled trial
Authors: Voepel-Lewis Terri , Malviya Shobha , Grant John A. , Dwyer Sarah , Becher Asif , Schwartz Jacob H. , Tait Alan R.
Published: October 2020

This randomized, controlled trial evaluated whether a brief educational program (ie, Scenario-Tailored Opioid Messaging Program [STOMP]) would improve parental opioid risk knowledge, perceptions, and analgesic efficacy; ensure safe opioid use decisions; and impact prescription opioid use after surgery. Parent–child dyads (n = 604) who were prescribed an opioid for short-term use were randomized to routine instruction (Control) or routine plus STOMP administered preoperatively. Baseline and follow-up surveys assessed parents' awareness and perceived seriousness of adverse opioid effects, and their analgesic efficacy. Parents' decisions to give an opioid in hypothetical scenarios and total opioid doses they gave to children at home were assessed at follow-up. Scenario-Tailored Opioid Messaging Program parents gained enhanced perceptions of opioid-related risks over time, whereas Controls did not; however, risk perceptions did not differ between groups except for addiction risk. Scenario-Tailored Opioid Messaging Program parents exhibited marginally greater self-efficacy compared to Controls (mean difference vs controls = 0.58 [95% confidence interval 0.08-1.09], P = 0.023). Scenario-Tailored Opioid Messaging Program parents had a 53% lower odds of giving an opioid in an excessive sedation scenario (odds ratio 0.47 [95% confidence interval 0.28-0.78], P = 0.003), but otherwise made similar scenario-based opioid decisions. Scenario-Tailored Opioid Messaging Program was not associated with total opioid doses administered at home. Instead, parents' analgesic efficacy and pain-relief preferences explained 7%, whereas child and surgical factors explained 22% of the variance in opioid doses. Scenario-tailored education enhanced parents' opioid risk knowledge, perceptions, and scenario-based decision-making. Although this may inform later situation-specific decision-making, our research did not demonstrate an impact on total opioid dosing, which was primarily driven by surgical and child-related factors.
SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia
Authors: Moutal Aubin , Martin Laurent F. , Boinon Lisa , Gomez Kimberly , Ran Dongzhi , Zhou Yuan , Stratton Harrison J. , Cai Song , Luo Shizhen , Gonzalez Kerry Beth , Perez-Miller Samantha , Patwardhan Amol , Ibrahim Mohab M. , Khanna Rajesh
Published: October 2020

Global spread of severe acute respiratory syndrome coronavirus 2 continues unabated. Binding of severe acute respiratory syndrome coronavirus 2's spike protein to host angiotensin-converting enzyme 2 triggers viral entry, but other proteins may participate, including the neuropilin-1 receptor (NRP-1). Because both spike protein and vascular endothelial growth factor-A (VEGF-A)—a pronociceptive and angiogenic factor, bind NRP-1, we tested whether spike could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuron firing was blocked by spike protein and NRP-1 inhibitor EG00229. Pronociceptive behaviors of VEGF-A were similarly blocked through suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A “silencing” of pain through subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.
Leydig stem cells and future therapies for hypogonadism
Authors: Achua Justin K. , Frech Fabio S. , Ramasamy Ranjith
Published: October 2020

Purpose of review

In this review, we outline the most recent advances in the development of Leydig stem cells (LSCs) and summarize the current and upcoming treatments for hypogonadism.

Recent findings

In-vitro and in-vivo studies show that inducing stem cells to differentiate into testosterone-producing adult Leydig cells is possible. In addition, LSCs can be grafted with Sertoli cells to increase testosterone levels in vivo. This therapy causes minimal effects on luteinizing hormone and follicle stimulating hormone levels. Novel therapies for hypogonadism include varying methods of testosterone delivery such as intranasal and oral agents, as well as novel selective estrogen and androgen receptor modulators.

LSC therapies provide an effective way of increasing testosterone levels without detrimentally affecting gonadotropin levels. Next steps in developing viable Leydig cell grafting options for the treatment of hypogonadism should include the assessment of efficacy and potency of current animal models in human trials. Recently, both intranasal and oral testosterone have been made available and shown promising results in treating hypogonadism while maintaining fertility. Enclomiphene citrate and selective androgen receptor modulators have been suggested as future therapies for hypogonadism; however, further studies assessing efficacy and adverse effects are needed.
Establishing Reference Values for Lean Muscle Mass in the Pediatric Patient
Authors: Metzger Gregory A. , Sebastião Yuri V. , Carsel Alex C. , Nishimura Leah , Fisher Jeremy G. , Deans Katherine J. , Minneci Peter C.
Published: October 2020

Objectives:

Adults with decreased muscle mass experience worse outcomes and more frequent complications. The effects of sarcopenia on pediatric outcomes are unknown. Our objective was to define reference values for lean muscle mass in a healthy pediatric population to facilitate future studies on the impact of lean muscle mass on pediatric outcomes.

Patients and Methods:

Bilateral psoas muscle surface area was measured by computed tomography in a healthy pediatric population undergoing evaluation after trauma. Pearson correlation coefficients (PCCs) were calculated for age, weight, height, body mass index (BMI), total psoas muscle area, and psoas muscle index (PMI; defined as psoas muscle area divided by height squared). Quantile regression was used to determine age‐ and sex‐specific percentiles of psoas muscle area and PMI.

Results:

Analysis of 494 male and 288 female patients with available imaging (median age: 9.3 years, interquartile range: 5.4–13.4; 63.1% male) was performed. For males, age correlated strongly with total psoas volume (PCC = 0.87), height (0.95), and weight (0.88) and poorly with BMI (0.45). In females, age correlated strongly with total psoas volume (0.88), height (0.92), weight (0.88) and poorly with BMI (0.19). Gender‐specific curves and charts were created using output from the quantile regression from reference values of the total psoas muscle area corresponding to the 25th, 50th, and 75th percentiles across all ages.

Conclusions:

We created gender‐specific reference charts for total and height‐normalized psoas muscle area in healthy children based on age. These results can be used in future studies to establish the effects of sarcopenia in pediatric patients.
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the Society for Pediatric Radiology Joint Position Paper on Noninvasive Imaging of Pediatric Pancreatitis
Authors: Trout Andrew T. , Anupindi Sudha A. , Freeman A. Jay , Macias‐Flores Jorge Alberto , Martinez J. Andres , Parashette Kalyan R. , Shah Uzma , Squires Judy H. , Morinville Veronique D. , Husain Sohail Z. , Abu‐El‐Haija Maisam
Published: October 2020

The reported incidence of pediatric pancreatitis is increasing. Noninvasive imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), play important roles in the diagnosis, staging, follow‐up, and management of pancreatitis in children. In this position paper, generated by members of the Pancreas Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the Abdominal Imaging Committee of The Society for Pediatric Radiology (SPR), we review the roles of noninvasive imaging in pediatric acute, acute recurrent, and chronic pancreatitis. We discuss available evidence related to noninvasive imaging, highlighting evidence specific to pediatric populations, and we make joint recommendations for use of noninvasive imaging. Further, we highlight the need for research to define the performance and role of noninvasive imaging in pediatric pancreatitis.
A Novel Use of Romiplostim for SARS-CoV-2–induced Thrombocytopenia
Authors: Schneider Coursen W. , Penney Scott W. , Helfrich Alison M. , Hartman Kip R. , Lieuw Kenneth
Published: October 2020

The literature regarding coronavirus disease of 2019 (COVID-19) infection in pediatrics indicates that children have less severe clinical presentations and lower mortality rates. There remains limited data regarding hematologic sequelae in pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Romiplostim has shown a platelet response in pediatric patients with chronic immune thrombocytopenic purpura, and eltrombopag is proven to increase platelet counts in patients with inherited thrombocytopenia. We review SARS-CoV-2–associated thrombocytopenia and present a pediatric patient with acute on chronic thrombocytopenia in the setting of COVID-19 with subsequent platelet recovery using romiplostim.