bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Influencing Nurses’ Intention to Leave and Intention to Stay: An Integrative Review
Authors: Al Zamel Luma Ghazi , Lim Abdullah Khatijah , Chan Chong Mei , Piaw Chua Yan
Published: June 2020

Nursing retention is a critical issue for organization. High nurses’ turnover impact negatively on an organization requirement to meet patient needs and quality care. This integrative review aims to critically review and synthesize published studies to obtain better understanding of the determinants of nurse’s intention to leave or stay in the organization. Thirty-seven studies which met the inclusion criteria from different locations using a variety of instruments and research designs were identified using PRISMA guideline. Many factors including job satisfaction, organizational commitment, quality of work life, work environment, leadership style, bullying at work, family reason, and job security were identified to be associated negatively with nurse’s intention to leave and positively with intention to stay in organization. More qualitative studies are needed to understand in depth, the reasons and factors that underlie and influence turnover, intention to leave or remain in organization.
Targeting the user experience in the development of mobile machinery using real-time multibody simulation
Authors: Khadim Qasim , Kaikko Esa-Pekka , Puolatie Eero , Mikkola Aki
Published: June 2020

Applying a semi-recursive multibody approach enables the solution of the equations of motion of a complex system in real time. This makes it possible to conduct human-in-loop simulations and analyse the user experience. The idea of recognizing the user experience to produce more efficient, competitive, and user-friendly products has been limited thus far to the field of information technology and the development of light physical products. This study introduces a simulation modelling procedure for a complex forklift mast system that can be used to help analyse the user experience. A multibody forklift model is introduced that includes the electric motors, a pump, a freelift, a mainlift and tilt cylinders, actuators, pulley and chain mechanisms, contacts, and tyres. The viscoelastic behaviour of the chain during longitudinal and transverse movement is simulated using a discrete model approach. Triplex mast speeds and hydraulic system efficiencies across working cycles are used to verify the performance of the introduced real-time simulation model against measurements taken from an equivalent reference forklift. To better evaluate the developed model, experienced and inexperienced forklift drivers were asked to drive an updated simulator and provide feedback. User experience inputs that can be made available early on in development using this new modelling approach will permit experts to evaluate and design more efficient complex mechanical systems.
Factors Associated with High Patient Activation Level among Individuals with Metabolic Syndrome at a Primary Care Teaching Clinic
Authors: Bahrom Nur Hidayah , Ramli Anis Safura , Isa Mohamad Rodi , Abdul-Hamid Hasidah , Badlishah-Sham Siti Fatimah , Baharudin Noorhida , Mohamed-Yassin Mohamed Syarif
Published: June 2020

Background: High activation level has been associated with higher education background, better self-rated health status, and having adequate health literacy. However, there is a gap in the literature regarding the level of activation and the factors associated with it among patients with metabolic syndrome (MetS) in the Malaysian primary care setting. Objectives: This study aims to determine activation levels and the factors associated with high activation among individuals with MetS in primary care. Methods: A cross-sectional study was conducted at a university primary care clinic. Patient activation was measured using the Patient Activation Measure®–13 Malay version. Activation levels were dichotomized into “low activation” (levels 1 and 2) and “high activation” (levels 3 and 4). To determine the factors associated with high activation, simple logistic regressions (SLogR) followed by multiple logistic regressions (MLogR) were performed. Results: Of 333 participants, 280 (84.1%) were included in the final analysis. The mean activation score was 59.4 (SD ±10.20) and 61.8% had high activation level. Two variables were found to be significant on MLogR. Those who were employed have the odds of 3.135 (95% CI 1.442-6.816) of having high activation compared with those who were unemployed. Those with good self-reported health status have the odds of 6.482 (95% CI 1.243-33.792) of having high activation compared to those with poor self-reported health status. Conclusions: The majority of participants had high activation levels. Those who were employed and those who had good self-reported health status were more likely to have high activation levels. Findings of this study could be used to develop patient activation interventions to improve self-management skills among individuals with MetS in primary care. These may include problem solving support, individualized care plans, peer or family support, and skill building. Those in high activation group can be trained to become mentors to support their peers who have low activation level.
Patient Characteristics of VA Telehealth Users During Hurricane Harvey
Authors: Der-Martirosian Claudia , Heyworth Leonie , Chu Karen , Mudoh Yvonne , Dobalian Aram
Published: June 2020

Introduction: Research on patient characteristics of telehealth users is relatively new. More studies are needed to understand the characteristics of telehealth users during disasters. This study attempts to bridge this gap and examines patient characteristics of telehealth users compared with nontelehealth users at the Houston VA Medical Center (VAMC) immediately before and after Hurricane Harvey (2017). Methods: Since use of telehealth services reached its peak and gradually declined within 2 weeks after the landfall, the data analyses focused on 14 days before/14 days after Harvey. Two sets of analyses were conducted using chi-square, t test, and one-way analysis of variance: (1) Patient characteristics of telehealth users were compared with nontelehealth users. (2) Patient characteristics were compared between 3 subgroups of telehealth users. Results: Compared with nontelehealth users, telehealth users were older (mean age: 60.8 vs 58.5 years, P < .001) and had a higher mean Nosos health risk score (1.9 vs 1.4, P < .001). They also had a higher mean number of outpatient visits (28.0 vs 19.8, P < .001), higher emergency room use (37% vs 29%, P < .001), and higher rates of hospitalizations (21% vs 13%, P < .001) during the 12 months before Harvey. When compared to less frequent telehealth users, the most frequent telehealth users were the oldest and most medically complex patients. Conclusions: As the largest integrated health care system in the United States, the VA has many advantages favoring successful implementation of telehealth services during disasters. However, more research is needed to better understand how VA telehealth could meet the varying needs of veterans to lower risk of harm during differing types of disasters.
Movement of the people: Violence and internal displacement
Authors: Esparza Diego , Lucas Jessica , Martinez Enrique , Meernik James , Molinero Ignacio , Nevarez Victoria
Published: June 2020

Individuals internally displaced by conflict are a prominent feature of wars, political violence and other forms of repression. We suggest that a subnational analysis of internally displaced person (IDP) generation can help us determine the extent to which more specific flight-precipitating factors can account for individuals’ behaviors. In particular, we are interested in how different conflict actors and the interactions of these actors affect the production of internally displaced persons. We suggest that some types of conflict actors are more likely to be responsible for greater numbers of internally displaced persons because of their political strategies. We focus on one of the most complex and yet data-rich environments in which the problem of internal displacement has been profound—Colombia. Using extensive data on internally displaced persons in Colombia among its over 1100 municipalities, we examine our expectations using negative binomial analyses to better understand the dynamics of conflict actors, the violence they perpetrate and internal displacement. We find that the identity of the conflict actor does make a difference in producing more internally displaced persons and that conflict between certain conflict actors is especially likely to produce more displaced persons.
Why Don’t We Just Ask Them? A Qualitative Study Regarding College Student Perceptions on What Topics Should Be Included in an Introductory Health Course
Authors: Brewer Kristen , Diehr Aaron , Bliss Kadi
Published: June 2020

Student perceptions and opinions regarding the relevance of course content can influence their desire and motivation to learn. Instructors can benefit from including content relevant to students’ lives, possibly leading them to take a greater interest in gaining knowledge and applying the material. This study aimed to investigate the health topics included in an introductory health course offered at a medium-sized, public liberal arts university in Tennessee and to explore perceptions of current undergraduate students regarding the relevance of those topics. Over the 2018–2019 academic year, four focus groups were conducted with 14 students who discussed their perceptions, opinions, and experiences of the course and offered suggestions regarding topics they thought should be incorporated in future iterations of the course. Participants wished that topics currently covered in the course, such as nutrition and fitness, would incorporate more experiential learning to provide greater applicability to their lives as college students. Students also expressed a desire for greater coverage of topics that they considered particularly relevant to their lifestyle and health, such as mental health, sleep, time management, and decision making. Information from this study can be used to help develop course content for undergraduate personal health courses so students can feel more connected to the material.
Branched evolution and genomic intratumor heterogeneity in the pathogenesis of cutaneous T-cell lymphoma
Authors: Iyer Aishwarya , Hennessey Dylan , O’Keefe Sandra , Patterson Jordan , Wang Weiwei , Wong Gane Ka-Shu , Gniadecki Robert
Published: June 2020

Mycosis fungoides (MF) is a slowly progressive cutaneous T-cell lymphoma (CTCL) for which there is no cure. In the early plaque stage, the disease is indolent, but development of tumors heralds an increased risk of metastasis and death. Previous research into the genomic landscape of CTCL revealed a complex pattern of >50 driver mutations implicated in more than a dozen signaling pathways. However, the genomic mechanisms governing disease progression and treatment resistance remain unknown. Building on our previous discovery of the clonotypic heterogeneity of MF, we hypothesized that this lymphoma does not progress in a linear fashion as currently thought but comprises heterogeneous mutational subclones. We sequenced exomes of 49 cases of MF and identified 28 previously unreported putative driver genes. MF exhibited extensive intratumoral heterogeneity (ITH) of a median of 6 subclones showing a branched phylogenetic relationship pattern. Stage progression was correlated with an increase in ITH and redistribution of mutations from stem to clades. The pattern of clonal driver mutations was highly variable, with no consistent mutations among patients. Similar intratumoral heterogeneity was detected in leukemic CTCL (Sézary syndrome). Based on these findings, we propose a model of MF pathogenesis comprising divergent evolution of cancer subclones and discuss how ITH affects the efficacy of targeted drug therapies and immunotherapies for CTCL.
The effect of 1% glucose loading on metabolism in the elderly patients during remifentanil-induced anesthesia: a randomized controlled trial
Authors: Fukuta Kohei , Kasai Asuka , Niki Noriko , Ishikawa Yuki , Kawanishi Ryosuke , Kakuta Nami , Sakai Yoko , Tsutsumi Yasuo M. , Tanaka Katsuya
Published: June 2020

Background

Previous studies showed that remifentanil-induced anesthesia can inhibit surgical stress response in non-diabetic adult patients and that low-dose glucose loading during anesthesia may attenuate fat catabolism. However, little is known about the influence of glucose loading on metabolism in elderly patients, whose condition may be influenced by decreased basal metabolism and increased insulin resistance. We hypothesized that, in elderly patients, intraoperative low glucose infusion may attenuate the catabolism of fat without causing harmful hyperglycemia during remifentanil-induced anesthesia.

Methods

Elderly, non-diabetic patients scheduled to undergo elective surgery were enrolled and randomized to receive no glucose (0G group) or low-dose glucose infusion (0.1 g/kg/hr. for 1 h followed by 0.05 g/kg/hr. for 1 h; LG group) during surgery. Glucose, adrenocorticotropic hormone (ACTH), 3-methylhistidine (3-MH), insulin, cortisol, free fatty acid (FFA), creatinine (Cr), and ketone body levels were measured pre-anesthesia, 1 h post-glucose infusion, at the end of surgery, and on the following morning.

Results

A total of 31 patients (aged 75–85) were included (0G, n = 16; LG, n = 15). ACTH levels during anesthesia decreased significantly in both groups. In the LG group, glucose levels increased significantly after glucose loading but hyperglycemia was not observed. During surgery, ketone bodies and FFA were significantly lower in the LG group than the 0G group. There were no significant differences in insulin, Cr, 3-MH, and 3-MH/Cr between the two groups.

Conclusion

Remifentanil-induced anesthesia inhibited surgical stress response in elderly patients. Intraoperative low-dose glucose infusion attenuated catabolism of fat without inducing hyperglycemia.

Trial registration

This study has been registered with the University hospital Medical Information Network Center (http://www.umin.ac.jp/english/). Trial registration number: UMIN000016189. The initial registration date: January 12th 2015.
Towards reduction in bias in epidemic curves due to outcome misclassification through Bayesian analysis of time-series of laboratory test results: case study of COVID-19 in Alberta, Canada and Philadelphia, USA
Authors: Burstyn Igor , Goldstein Neal D. , Gustafson Paul
Published: June 2020

Background

Despite widespread use, the accuracy of the diagnostic test for SARS-CoV-2 infection is poorly understood. The aim of our work was to better quantify misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves using publicly available surveillance data from Alberta, Canada and Philadelphia, USA.

Methods

We examined time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, the sensitivity and specificity of the diagnostic test.

Results

Our analysis revealed that the data were compatible with near-perfect specificity, but it was challenging to gain information about sensitivity. We applied these insights to uncertainty/bias analysis of epidemic curves under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the adjusted epidemic curves likely falls within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60–70% range. In the extreme scenario, hundreds of undiagnosed cases, even among the tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate.

Conclusion

The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves.
Subclinical hypothyroidism in childhood, treatment or only follow-up?
Authors: Murillo-Vallés Marta , Martinez Santiago , Aguilar-Riera Cristina , Garcia-Martin Miguel Angel , Bel-Comós Joan , Ybern Maria Luisa Granada
Published: June 2020

Background

Subclinical hypothyroidism (SH) is defined as serum levels of thyroid-stimulating hormone (TSH) above the upper limit with normal concentrations of free T4 (fT4). Its management remains challenging. The aim of the study was to evaluate clinical and laboratory findings as well as the clinical course of children with SH followed in a third level hospital. Sixty-five patients aged between 2 and 18 years old were retrospectively studied.

Methods

The patients were followed for a median period of 9 months (range 6 months to 24 months). Those who normalized TSH levels were discharged (Group 1). If TSH persisted mildly elevated (5-10μUI/mL) with normal fT4 and negative TPOAb/TgAb, they were classified as Group 2 and followed semi-annually without treatment. Those patients whose TSH raised ≥10μUI/mL or who maintained TSH 5-10μUI/mL and positive TPOAb/TgAb were considered suitable for thyroxin therapy (Group 3, G3).

Results

In 89% of our patients, TSH concentrations spontaneously reverted to normality or remained stable without treatment (Groups 1 and 2), whereas less than 11% progressed to clinical hypothyroidism (Group 3). Baseline TSH was significantly lower in group 1 than in group 3. In group 3 the prevalence of female sex (71%) was higher and TPO antibodies were present in 85% of patients. The risk of developing overt hypothyroidism in patients with positive anti-thyroid antibodies respect to those who normalized TSH was 45 (95%CI 6.5–312.5).

Conclusion

Baseline TSH, female sex and the presence of thyroid autoimmunity were the best predictors of the evolution to SH over time.
The relationship between depression risk perception and self-help behaviours in high risk Canadians: a cross-sectional study
Authors: Warner Emily , Nannarone Molly , Smail-Crevier Rachel , Manuel Douglas , Lashewicz Bonnie , Patten Scott , Schmitz Norbert , MacQueen Glenda , Wang Jian Li
Published: June 2020

Background

Self-help may reduce the risk of depression, and risk perception of depression may influence initiating self-help. It is unknown how risk perception is associated with self-help behaviours. The objectives of this study are to (1) describe the self-help strategies used by high-risk Canadians in relation to the accuracy of perceived depression risk, by sex, and (2) identify demographic and clinical factors associated with self-help behaviours.

Methods

Baseline data from a randomized controlled trial including 358 men and 356 women at high-risk of developing depression were used. Following methods used in cancer research, risk perception accuracy was determined by comparing the participant’s self-perceived and objective risk of developing depression and classifying as accurate, over-estimation and under-estimation based on a ± 10% threshold. The participant’s objective depression risk was assessed using sex-specific multivariable risk predictive algorithms. Frequency of using 14 self-help strategies was assessed. One-way ANOVA testing was used to detect if differences in risk perception accuracy groups existed, stratified by sex. Linear regression was used to investigate the clinical and demographic factors associated with self-help behaviours, also stratified.

Results

Compared to accurate-estimators, male over-estimators were less likely to “leave the house daily,” and “participate in activities they enjoy.” Male under-estimators were also less likely to “participate in activities they enjoy.” Both male ‘inaccurate’ perception groups were more likely to ‘create lists of strategies which have worked for feelings of depression in the past and use them’. There were no significant differences between self-help behaviours and risk perception accuracy in women. Regression modeling showed negative relationships between self-rated health and self-help scores, irrespective of sex. In women, self-help score was positively associated with age and educational attainment, and negatively associated with perceived risk. In men, a positive relationship with unemployment was also seen.

Conclusions

Sex differences exist in the factors associated with self-help. Risk perception accuracy, work status, and self-rated health is associated with self-help behaviours in high-risk men. In women, factors related to self-help included age, education, self-rated health status, and perceived risk. More research is needed to replicate findings.

Trial registration

Prospectively registered at ClinicalTrials.gov (NCT02943876) as of 10/21/16.
Correction to: Screw fixation in stemless shoulder arthroplasty for the treatment of primary osteoarthritis leads to less osteolysis when compared to impaction fixation
Authors: Alikhah Arad , Imiolczyk Jan-Phillipp , Krukenberg Anna , Scheibel Markus
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Cancer rates not explained by smoking: a county-level analysis
Authors: Myers Douglas J. , Hoppin Polly , Jacobs Molly , Clapp Richard , Kriebel David
Published: June 2020

Background

Debates over the importance of “lifestyle” versus “environment” contributions to cancer have been going on for over 40 years. While it is clear that cigarette smoking is the most significant cancer risk factor, the contributions of occupational and environmental carcinogens in air, water and food remain controversial. In practice, most cancer prevention messaging focuses on reducing cigarette smoking and changing other personal behaviors with little mention of environmental chemicals, despite widespread exposure to many known carcinogens. To inform decision-making on cancer prevention priorities, we evaluated the potential impact of smoking cessation on cancer rates.

Methods

Using cancer incidence data from 612 counties in the SEER database, and county-level smoking prevalences, we investigated the impact of smoking cessation on incidence for 12 smoking-related cancer types, 2006—2016. A multilevel mixed-effects regression model quantified the association between county-level smoking prevalence and cancer incidence, adjusting for age, gender and variability over time and among counties. We simulated complete smoking cessation and estimated the effects on county-level cancer rates.

Results

Regression models showed the expected strong association between smoking prevalence and cancer incidence. Simulating complete smoking cessation, the incidence of the 12 smoking-related cancer types fell by 39.8% (54.9% for airways cancers; 28.9% for non-airways cancers). And, while the actual rates of smoking-related cancers from 2006 to 2016 declined (annual percent change (APC) = − 0.8, 95% CI = − 1.0 to − 0.5%), under the scenario of smoking elimination, the trend in cancer incidence at these sites was not declining (APC = − 0.1, 95% CI = − 0.4 to + 0.1%). Not all counties were predicted to benefit equally from smoking elimination, and cancer rates would fall less than 10% in some counties.

Conclusions

Smoking prevention has produced dramatic reductions in cancer in the US for 12 major types. However, we estimate that eliminating smoking completely would not affect about 60% of cancer cases of the 12 smoking-related types, leaving no improvement in the incidence trend from 2006 to 2016. We conclude that cancer prevention strategies should focus not only on lifestyle changes but also the likely contributions of the full range of risk factors, including environmental/occupational carcinogens.
Non-esterified fatty acids in the ovary: friends or foes?
Authors: Baddela Vijay Simha , Sharma Arpna , Vanselow Jens
Published: June 2020

A majority of common metabolic diseases can result in excessive lipolysis, leading to elevated levels of non-esterified fatty acids (NEFAs) in the body fluids. In females, increased NEFA levels in the follicular fluid markedly alter the functions of intrafollicular cells such as granulosa cells (GCs) and oocytes. Therefore, elevated levels of NEFAs have been suggested to be a significant player of subfertility in females of both human and economically important animal species such as cattle, buffalo, sheep, pig, chicken, and dog. However, the effects imposed by saturated and unsaturated fatty acids (SFAs and UFAs) on ovarian follicles are controversial. The present review emphasizes that SFAs induce apoptosis in granulosa and cumulus cells of ovarian follicles in different species. They further could adversely affect oocyte maturation and developmental competence. Many types of UFAs affect steroidogenesis and proliferation processes and could be detrimental for follicular cells, especially when at elevated concentrations. Interestingly, monounsaturated fatty acids (MUFAs) appear to contribute to the etiology of the polycystic ovarian syndrome (PCOS) as they were found to induce the transcription and translation of the androgenic transcription factor SOX9 while downregulating its estrogenic counterpart FOXL2 in GCs. Overall, this review presents our revised understanding of the effects of different fatty acids on the female reproductive success, which may allow other researchers and clinicians to investigate the mechanisms for treating metabolic stress-induced female infertility.
MicroRNA-33a-5p sponges to inhibit pancreatic β-cell function in gestational diabetes mellitus LncRNA DANCR
Authors: Feng Yan , Qu Xin , Chen Yu , Feng Qi , Zhang Yinghong , Hu Jianwei , Li Xiaoyan
Published: June 2020

Background

Gestational diabetes mellitus (GDM) is the most common medical complication associated with pregnancy, which may impose risks on both mother and fetus. Micro RNAs (miRNAs) and long noncoding RNAs (lncRNAs) are implied as vital regulators in GDM. A recent paper revealed dysregulation of miR-33a-5p in placental tissues of GDM patients. However, the biological function of miR-33a-5p in GDM remains elusive. This study focused on exploring the function and underlying mechanisms of miR-33a-5p in GDM.

Methods

12 GDM pregnancies and 12 healthy pregnancies were enrolled in the study. INS-1 cell line was applied in in vitro experiments. The expression levels of miR-33a-5p, lnc-DANCR (Differentiation Antagonizing Non-Protein Coding RNA), and ABCA1 (ATP-binding cassette transporter 1) mRNA were determined by RT-qPCR assay. Glucose and insulin levels were measured by ELISA assay. Luciferase reporter assay and western blot assay were applied to validate the target of miR-33a-5p.

Results

miR-33a-5p was upregulated in the blood samples from GDM, and was positively correlated with blood glucose (p < 0.0001). Overexpression or inhibition of miR-33a-5p significantly inhibited or promoted cell growth and insulin production of INS-1 cells (p < 0.01). Furthermore, ABCA1 is a direct target of miR-33a-5p, and lnc-DANCR functions as a sponge for miR-33a-5p to antagonize the function of miR-33a-5p in INS-1 cells.

Conclusion

Our study demonstrated that lnc-DANCR-miR-33a-5p-ABCA1 signaling cascade plays a crucial role in the regulation of the cellular function of INS-1 cells.
IL-33 and its decoy sST2 in patients with Alzheimer’s disease and mild cognitive impairment
Authors: Saresella Marina , Marventano Ivana , Piancone Federica , La Rosa Francesca , Galimberti Daniela , Fenoglio Chiara , Scarpini Elio , Clerici Mario
Published: June 2020

Background

Interleukin-33 is a cytokine endowed with pro- and anti-inflammatory properties that plays a still poorly defined role in the pathogenesis of a number of central nervous system (CNS) conditions including Alzheimer’s disease (AD). We analyzed this cytokine and its decoy receptor sST2 in Alzheimer’s disease (AD) and mild cognitive impairment (MCI).

Method

IL-33 and sST2 were analyzed in serum and CSF of AD and MCI patients, comparing the results to those obtained in age-matched healthy controls (HC). Because of the ambiguous role of IL-33 in inflammation, the concentration of both inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokines was analyzed as well in serum and cerebrospinal fluid (CSF) of the same individuals. Finally, the effect of IL-33 on in vitro Aβ42-stimulated monocytes of AD, MCI, and HC individuals was examined.

Results

As compared to HC, (1) IL-33 was significantly decreased in serum and CSF of AD and MCI, (2) sST2 was increased in serum of AD and MCI but was undetectable in CSF, (3) serum and CSF IL-1β concentration was significantly increased and that of IL-10 was reduced in AD and MCI, whereas no differences were observed in IL-6. In vitro addition of IL-33 to LPS+Aβ 42-stimulated monocytes downregulated IL-1β generation in MCI and HC, but not in AD, and stimulated IL-10 production in HC alone. IL-33 addition also resulted in a significant reduction of NF-kB nuclear translocation in LPS+Aβ42-stimulated monocytes of HC alone.

Conclusions

These data support the hypothesis that IL-33 plays a complex anti-inflammatory role that is lost in AD- and MCI-associated neuroinflammation; results herein also suggest a possible use of IL-33 as a novel therapeutic approach in AD and MCI.
A first case report of clinical response to targeted therapy in a patient with primary myoepithelial carcinoma of the lung harboring EGFR exon 19 deletion
Authors: Xie Xiaohong , Lin Xinqing , Liu Ming , Qin Yinyin , Ouyang Ming , Li Shiyue , Gu Yingying , Chen Shuyin , Xiang Jianxing , Zhou Chengzhi
Published: June 2020

Background

Primary myoepithelial carcinoma of the lung is a rare subtype in lung cancer. Comprehensive molecular profiling of myoepithelial carcinoma of the lung is absent, neither was clinical evidence of targeted therapy available for this disease. Therefore, the optimal treatment regimen of this tumor needs to be established.

Case presentation

Here we present a case of a 68-year-old patient with stage IVB primary myoepithelial carcinoma of the lung who harbored EGFR exon 19 deletion and KRAS mutation and underwent icotinib targeted therapy, achieving partial response (PR) with progression free survival (PFS) of 3 months.

Conclusion

To our knowledge, this study describes the first documented case of primary myoepithelial carcinoma lung cancer patient harboring EGFR exon 19 deletion and KRAS mutation, and showed clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) treatment in this patient.
Emergency management in epidermolysis bullosa: consensus clinical recommendations from the European reference network for rare skin diseases
Authors: Mellerio Jemima E. , El Hachem Maya , Bellon Nathalia , Zambruno Giovanna , Buckova Hana , Autrata Rudolf , Salavastru Carmen , Caldaro Tamara , Greco Celine , Has Cristina , Bodemer Christine
Published: June 2020

Epidermolysis bullosa (EB) comprises a group of genetic disorders with the hallmark of fragility of the skin and mucosal surfaces. The severity of different types of EB varies markedly as does the occurrence of extra-cutaneous involvement and complications. A number of emergency situations may occur in the context of EB including obstruction to oral intake from oral or esophageal blisters or scarring, acute airway obstruction, acute urinary retention, sepsis and corneal erosions. Whilst general management principles apply in each of these settings, specific considerations are essential in managing EB to avoid undue trauma or damage to delicate tissues. These recommendations have been developed from a literature review and consensus from experts of the European Network for Rare Skin Disorders (ERN-Skin) to aid decision-making and optimize clinical care by non-EB expert health professionals encountering emergency situations in babies, children and adults with EB.
Morbidity and mortality in critically ill patients with invasive group A streptococcus infection: an observational study
Authors: Björck Viveka , Påhlman Lisa I. , Bodelsson Mikael , Petersson Ann-Cathrine , Kander Thomas
Published: June 2020

Background

Group A streptococci (GAS) are known to cause serious invasive infections, but little is known about outcomes when patients with these infections are admitted to intensive care. We wanted to describe critically ill patients with severe sepsis or septic shock due to invasive GAS (iGAS) and compare them with other patients with severe sepsis or septic shock.

Methods

Adult patients admitted to a general intensive care unit (ICU) in Sweden (2007–2019) were screened for severe sepsis or septic shock according to Sepsis 2 definition. Individuals with iGAS infection were identified. The outcome variables were mortality, days alive and free of vasopressors and invasive mechanical ventilation, maximum acute kidney injury score for creatinine, use of continuous renal replacement therapy and maximum Sequential Organ Failure Assessment score during the ICU stay. Age, Simplified Acute Physiology Score (SAPS 3) and iGAS were used as independent, explanatory variables in regression analysis. Cox regression was used for survival analyses.

Results

iGAS was identified in 53 of 1021 (5.2%) patients. Patients with iGAS presented a lower median SAPS 3 score (62 [56–72]) vs 71 [61–81]), p <  0.001), had a higher frequency of cardiovascular cause of admission to the ICU (38 [72%] vs 145 [15%], p <  0.001) and had a higher median creatinine score (173 [100–311] vs 133 [86–208] μmol/L, p <  0.019). Of the GAS isolates, 50% were serotyped emm1/T1 and this group showed signs of more pronounced circulatory and renal failure than patients with non-emm1/T1 (p = 0.036 and p = 0.007, respectively). After correction for severity of illness (SAPS 3) and age, iGAS infection was associated with lower mortality risk (95% confidence interval (CI) of hazard ratio (HR) 0.204–0.746, p <  0.001). Morbidity analyses demonstrated that iGAS patients were more likely to develop renal failure.

Conclusion

Critically ill patients with iGAS infection had a lower mortality risk but a higher degree of renal failure compared to similarly ill sepsis patients. emm1/T1 was found to be the most dominant serotype, and patients with emm1/T1 demonstrated more circulatory and renal failure than patients with other serotypes of iGAS.
Maternal factors associated with hyperglycemia in pregnancy and perinatal outcomes: a Brazilian reference center cohort study
Authors: Nicolosi Bianca F. , Vernini Joice M. , Costa Roberto A. , Magalhães Claudia G. , Rudge Marilza V. C. , Corrente José E. , Cecatti Jose G. , Calderon Iracema M. P.
Published: June 2020

Background

While sufficient evidence supporting universal screening is not available, it is justifiable to look for specific risk factors for gestational diabetes mellitus (GDM) or hyperglycemia in pregnancy (HIP). The objective of this study is to identify independent risk factors for HIP and its adverse perinatal outcomes in a Brazilian public referral center.

Methods

We included 569 singleton pregnant women who were split into three groups by glucose status: GDM (n = 207), mild gestational hyperglycemia (MGH; n = 133), and control (n = 229). Women who used corticosteroids or had a history of DM were excluded. HIP comprised both GDM and MGH, diagnosed by a 100 g- or 75 g-oral glucose tolerance test (OGTT) and a glucose profile at 24–28 weeks. Maternal characteristics were tested for their ability to predict HIP and its outcomes. Bivariate analysis (RR; 95% CI) was used to identify potential associations. Logistic regression (RRadj; 95% CI) was used to confirm the independent risk factors for HIP and its perinatal outcomes (p < 0.05).

Results

Age ≥ 25 years [1.83, 1.12–2.99], prepregnancy BMI ≥ 25 kg/m2 [2.88, 1.89–4.39], family history of DM [2.12, 1.42–3.17] and multiparity [2.07, 1.27–3.37] were independent risk factors for HIP. Family history of DM [169, 1.16–2.16] and hypertension [2.00, 1.36–2.98] were independent risk factors for C-section. HbA1c ≥ 6.0% at birth was an independent risk factor for LGA [1.99, 1.05–3.80], macrosomia [2.43, 1.27–4.63], and birthweight Z-score > 2.0 [4.17, 1.57–11.10].

Conclusions

MGH presents adverse pregnancy outcomes similar to those observed in the GDM group but distinct from those observed in the control (no diabetes) group. In our cohort, age ≥ 25 years, prepregnancy BMI ≥ 25 kg/m2, family history of DM, and multiparity were independent risk factors for HIP, supporting the use of selective screening for this condition. These results should be validated in populations with similar characteristics in Brazil or other low- and middle-income countries.
Management of critically ill patients with COVID-19 in ICU: statement from front-line intensive care experts in Wuhan, China
Authors: Shang You , Pan Chun , Yang Xianghong , Zhong Ming , Shang Xiuling , Wu Zhixiong , Yu Zhui , Zhang Wei , Zhong Qiang , Zheng Xia , Sang Ling , Jiang Li , Zhang Jiancheng , Xiong Wei , Liu Jiao , Chen Dechang
Published: June 2020

Background

The ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept all over the world, posing a great pressure on critical care resources due to large number of patients needing critical care. Statements from front-line experts in the field of intensive care are urgently needed.

Methods

Sixteen front-line experts in China fighting against the COVID-19 epidemic in Wuhan were organized to develop an expert statement after 5 rounds of expert seminars and discussions to provide trustworthy recommendation on the management of critically ill COVID-19 patients. Each expert was assigned tasks within their field of expertise to provide draft statements and rationale. Parts of the expert statement are based on epidemiological and clinical evidence, without available scientific evidences.

Results

A comprehensive document with 46 statements are presented, including protection of medical personnel, etiological treatment, diagnosis and treatment of tissue and organ functional impairment, psychological interventions, immunity therapy, nutritional support, and transportation of critically ill COVID-19 patients. Among them, 5 recommendations were strong (Grade 1), 21 were weak (Grade 2), and 20 were experts’ opinions. A strong agreement from voting participants was obtained for all recommendations.

Conclusion

There are still no targeted therapies for COVID-19 patients. Dynamic monitoring and supportive treatment for the restoration of tissue vascularization and organ function are particularly important.
Asthma management with breath-triggered inhalers: innovation through design
Authors: Morais-Almeida Mário , Pité Helena , Cardoso João , Costa Rui , Cordeiro Carlos Robalo , Silva Eurico , Todo-Bom Ana , Vicente Cláudia , Marques José Agostinho
Published: June 2020

Background

Asthma affects the lives of hundred million people around the World. Despite notable progresses in disease management, asthma control remains largely insufficient worldwide, influencing patients’ wellbeing and quality of life. Poor patient handling of inhaling devices has been identified as a major persistent problem that significantly reduces inhaled drugs’ efficacy and is associated with poor adherence to treatment, impairing clinical results such as asthma control and increasing disease-related costs. We herein review key research and development (R&D) innovation in inhaler devices, highlighting major real-world critical errors in the handling and inhalation technique with current devices and considering potential solutions. Furthermore, we discuss current evidence regarding breath-triggered inhalers (BTI).

Main body

The two most common significant problems with inhalers are coordinating actuation and inhalation with pressurized metered-dose inhalers (pMDIs), and the need to inhale forcibly with a dry powder inhaler. BTI R&D plans were designed to overcome these problems. Its newest device k-haler® has several other important features, generating a less forceful aerosol plume than previous pMDIs, with efficient drug delivery and lung deposition, even in patients with low inspiratory flow. The local and systemic bioavailability of fluticasone propionate and formoterol (FP/FORM) administered via k-haler® has been shown to be therapeutically equivalent when administered via the previous FP/FORM pMDI. This device requires very few steps and has been considered easy to use (even at first attempt) and preferred by the patients in a randomized crossover study. In our country, FP/FORM k-haler is available without additional costs compared to FP/FORM pMDI. All devices continue to require education and regular checking of the correct inhalation technique.

Conclusion

BTI R&D can bring advantage over current available inhalers, avoiding the two most common identified critical errors in inhalation technique. K-haler® BTI is currently available, without an increased cost, and approved for adolescents and adults with asthma in whom treatment with inhaled combined therapy with long-acting beta2-agonists and corticosteroids is indicated. Its attractive and practical design to facilitate its use has been awarded. K-haler® represents added value through innovation to fulfill actual asthma patient needs, thus with potential relevant impact in asthma management and effective control.
Mitochondrial Nutrient Utilization Underlying the Association Between Metabolites and Insulin Resistance in Adolescents
Authors: LaBarre Jennifer L , Peterson Karen E , Kachman Maureen T , Perng Wei , Tang Lu , Hao Wei , Zhou Ling , Karnovsky Alla , Cantoral Alejandra , Téllez-Rojo Martha María , Song Peter X K , Burant Charles F
Published: June 2020

Context

A person’s intrinsic metabolism, reflected in the metabolome, may describe the relationship between nutrient intake and metabolic health.

Objectives

Untargeted metabolomics was used to identify metabolites associated with metabolic health. Path analysis classified how habitual dietary intake influences body mass index z-score (BMIz) and insulin resistance (IR) through changes in the metabolome.

Design

Data on anthropometry, fasting metabolites, C-peptide, and dietary intake were collected from 108 girls and 98 boys aged 8 to 14 years. Sex-stratified linear regression identified metabolites associated with BMIz and homeostatic model assessment of IR using C-peptide (HOMA-CP), accounting for puberty, age, and muscle and fat area. Path analysis identified clusters of metabolites that underlie the relationship between energy-adjusted macronutrient intake with BMIz and HOMA-CP.

Results

Metabolites associated with BMIz include positive associations with diglycerides among girls and positive associations with branched chain and aromatic amino acids in boys. Intermediates in fatty acid metabolism, including medium-chain acylcarnitines (AC), were inversely associated with HOMA-CP. Carbohydrate intake is positively associated with HOMA-CP through decreases in levels of AC, products of β-oxidation. Approaching significance, fat intake is positively associated with HOMA-CP through increases in levels of dicarboxylic fatty acids, products of omega-oxidation.

Conclusions

This cross-sectional analysis suggests that IR in children is associated with reduced fatty acid oxidation capacity. When consuming more grams of fat, there is evidence for increased extramitochondrial fatty acid metabolism, while higher carbohydrate intake appears to lead to decreases in intermediates of β-oxidation. Thus, biomarkers of IR and mitochondrial oxidative capacity may depend on macronutrient intake.
An Intronic HCP5 Variant Is Associated With Age of Onset and Susceptibility to Graves Disease in UK and Polish Cohorts
Authors: Lane Laura Claire , Kuś Aleksander , Bednarczuk Tomasz , Bossowski Artur , Daroszewski Jacek , Jurecka-Lubieniecka Beata , Cordell Heather Jane , Pearce Simon Henry Schofield , Cheetham Timothy , Mitchell Anna Louise
Published: June 2020

Context

The genetic background of young-onset Graves disease (GD) remains largely unknown. An intronic variant in human leukocyte antigen (HLA) complex P5 (HCP5) has previously been associated with GD susceptibility and age of onset in a cohort of Polish patients.

Objective

We aimed to investigate the association of the HCP5 variant rs3094228 with GD susceptibility and age of onset in a UK cohort and conduct a meta-analysis of UK and Polish data.

Design and Participants

rs3094228 was genotyped in 469 UK patients with GD using Taqman chemistry. Genotype frequencies were compared with genotypic data available from the Wellcome Trust case-control consortium using logistic regression analysis. To determine whether rs3094228 is independently associated with age of GD onset, the HLA DRB1*0301 tagging variant, rs535777, was also genotyped.

Results

The C allele of rs3094228 was overrepresented in the UK GD cohort compared with controls (P allele=5.08 × 10–9, odds ratio 1.76; [95% confidence interval, 1.46-2.13]). This association was more marked in young-onset GD (<30 years) (P allele=1.70 × 10–10 vs P allele=0.0008). The meta-analysis of UK and Polish data supported the association of the C allele with GD susceptibility (P allele=1.79 × 10–5) and age of onset (P allele=5.63 × 10–8). Haplotype analysis demonstrated that rs3094228 is associated with age of GD onset (P = 2.39 × 10-6) independent of linkage disequilibrium with HLA DRB1*0301.

Conclusion

The rs3094228 HCP5 polymorphism is independently associated with GD susceptibility and age of onset in a UK GD cohort. Our findings indicate a potential role of long noncoding ribonucleic acids, including HCP5, in GD pathogenesis, particularly in the younger population.
Anti-racist Feminism or Barbarism
Authors: Filigrana Pastora
Published: June 2020

In September 2017, feminist assemblies began meeting on the eighth day of each month in multiple cities and towns across Spain to prepare for the feminist strike in the country. That same fall, the trial is held for the “wolf pack,” the gang rape that occurred during the festival of San Fermín in 2016: once again, the woman who was raped is put on trial, and not the rapists. With the slogans, “I believe you” and “Listen, sister, here is your pack,” the call goes viral, filling streets, plazas, and social media. This viral call is repeated in April when the sentence in announced that only condemns the members of the group for “abuse” and not for rape, and with even one vote from a judge who dared to say that there was enjoyment on all sides. The streets are dyed a feminist purple: a capillary feminism that reacts as a single body against each piece of news of sexist violence. In that atmosphere, and following a massive feminist strike on March 8, the denunciation of sexual abuse presented by several seasonal strawberry pickers in Huelva leaps into the media. Some collectives call for a march, expecting it to go viral again. However, the response it not at all the same either in number or in intensity. What happened? Debates catch fire. There are accusations: the feminism organized around March 8 and that was expressed in the protests against the wolf pack is racist. The answer is more complex, but there is no doubt that the feminist defiance of the seasonal strawberry workers challenges organized feminism and the unions in an unprecedented way. It speaks of the capillary quality of feminist sensibility, but also of its limits and paradoxes.