bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic ion channel interactions in red cells of patients with Gárdos channelopathy
Authors: Jansen Julia , Qiao Min , Hertz Laura , Wang Xijia , Fermo Elisa , Zaninoni Anna , Colombatti Raffaella , Bernhardt Ingolf , Bianchi Paola , Kaestner Lars
Published: September 2021

In patients with Gárdos channelopathy (p.R352H), an increased concentration of intracellular Ca2+ was previously reported. This is a surprising finding because the Gárdos channel (KCa3.1) is a K+ channel. Here, we confirm the increased intracellular Ca2+ for patients with the KCa3.1 mutation p.S314P. Furthermore, we provide the concept of KCa3.1 activity resulting in a flickering of red blood cell (RBC) membranepotential, which activates the CaV2.1 channel allowing Ca2+ to enter the RBC. Activity of the nonselective cation channel Piezo1 modulates the aforementioned interplay in away that a closed Piezo1 is in favor of the KCa3.1-CaV2.1 interaction. In contrast, Piezo1 openings compromise the membrane potential flickering, thus limiting the activity of CaV2.1. With the compound NS309, we mimic a gain-of-function mutation of KCa3.1. Assessing the RBC Ca2+ response by Fluo-4–based flow cytometry and by measuring the membrane potential using the Macey-Bennekou-Egée method, we provide data that support the concept of the KCa3.1/CaV2.1/Piezo1 interplay as a partial explanation for an increased number of high Ca2+ RBCs. With the pharmacological inhibition of KCa3.1 (TRAM34 and Senicapoc), CaV2.1 (ω-agatoxin TK), and Piezo1 (GsMTx-4), we could project the NS309 behavior of healthy RBCs to the RBCs of Gárdos channelopathy patients.
Engraftment characterization of risk-stratified AML in NSGS mice
Authors: Díaz de la Guardia Rafael , Velasco-Hernandez Talía , Gutiérrez-Agüera Francisco , Roca-Ho Heleia , Molina Oscar , Nombela-Arrieta Cesar , Bataller Alex , Fuster Jose Luis , Anguita Eduardo , Vives Susana , Zamora Lurdes , Nomdedeu Josep , Gómez-Casares María Teresa , Ramírez-Orellana Manuel , Lapillonne Helene , Ramos-Mejia Verónica , Rodríguez-Manzaneque Juan Carlos , Bueno Clara , Lopez-Millan Belen , Menéndez Pablo
Published: September 2021

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Disease heterogeneity is well documented, and patient stratification determines treatment decisions. Patient-derived xenografts (PDXs) from risk-stratified AML are crucial for studying AML biology and testing novel therapeutics. Despite recent advances in PDX modeling of AML, reproducible engraftment of human AML is primarily limited to high-risk (HR) cases, with inconsistent or very protracted engraftment observed for favorable-risk (FR) and intermediate-risk (IR) patients. We used NSGS mice to characterize the engraftment robustness/kinetics of 28 AML patient samples grouped according to molecular/cytogenetic classification and assessed whether the orthotopic coadministration of patient-matched bone marrow mesenchymal stromal cells (BM MSCs) improves AML engraftment. PDX event-free survival correlated well with the predictable prognosis of risk-stratified AML patients. The majority (85-94%) of the mice were engrafted in bone marrow (BM) independently of the risk group, although HR AML patients showed engraftment levels that were significantly superior to those of FR or IR AML patients. Importantly, the engraftment levels observed in NSGS mice by week 6 remained stable over time. Serial transplantation and long-term culture-initiating cell (LTC-IC) assays revealed long-term engraftment limited to HR AML patients, fitter leukemia-initiating cells (LICs) in HR AML samples, and the presence of AML LICs in the CD34− leukemic fraction, regardless of the risk group. Finally, orthotopic coadministration of patient-matched BM MSCs and AML cells was dispensable for BM engraftment levels but favored peripheralization of engrafted AML cells. This comprehensive characterization of human AML engraftment in NSGS mice offers a valuable platform for in vivo testing of targeted therapies in risk-stratified AML patient samples.
Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma
Authors: Costa Luciano J. , Davies Faith E. , Monohan Gregory P. , Kovacsovics Tibor , Burwick Nicholas , Jakubowiak Andrzej , Kaufman Jonathan L. , Hong Wan-Jen , Dail Monique , Salem Ahmed Hamed , Yang Xiaoqing , Masud Abdullah A. , Munasinghe Wijith , Ross Jeremy A. , Bueno Orlando F. , Kumar Shaji K. , Stadtmauer Edward A.
Published: September 2021

Proteins in the antiapoptotic B-cell lymphoma 2 (BCL-2) family play a role in the pathophysiology of multiple myeloma (MM). Venetoclax is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis of MM cells, and its efficacy may be potentiated through combination with agents that increase BCL-2 dependency or have complementary mechanisms of action. The safety, tolerability, pharmacokinetics, and antitumor activity of venetoclax in combination with carfilzomib and dexamethasone (VenKd) in adults with relapsed/refractory MM (RRMM) were investigated in this phase 2 dose-escalation study. Oral venetoclax (400 or 800 mg) was administered daily in combination with intravenous carfilzomib (27, 56, or 70 mg/m2) and oral dexamethasone (20 or 40 mg) in 4 dose-finding cohorts. The expansion cohort received venetoclax 800 mg, carfilzomib 70 mg/m2, and dexamethasone 40 mg. Forty-nine patients received treatment. Median prior lines of therapy was 1 (range, 1-3), and median time in the study was 27 months. The most common treatment-emergent adverse events were diarrhea (65%), fatigue (47%), nausea (47%), and lymphopenia (35%). Serious adverse events occurred in 26 (53%) patients. Of 3 treatment-emergent deaths, 1 was considered treatment related. The overall response rate was 80% in all patients, 92% in patients with t(11;14) (n = 13), and 75% in patients without (n = 36). The rate of complete response or better was 41%. Median progression-free survival was 22.8 months. Treatment with VenKd was well tolerated and showed promising response rates in this RRMM patient population, with greater responses observed in patients with t(11;14). This trial is registered at www.clinicaltrials.gov as #NCT02899052.
Decreased parasite burden and altered host response in children with sickle cell anemia and severe anemia with malaria
Authors: Henrici Ryan C. , Sautter Casey L. , Bond Caitlin , Opoka Robert O. , Namazzi Ruth , Datta Dibyadyuti , Ware Russell E. , Conroy Andrea L. , John Chandy C.
Published: September 2021

Plasmodium falciparum malaria causes morbidity and mortality in African children with sickle cell anemia (SCA), but comparisons of host responses to P falciparum between children with SCA (homozygous sickle cell disease/hemoglobin SS [HbSS]) and normal hemoglobin genotype/hemoglobin AA (HbAA) are limited. We assessed parasite biomass and plasma markers of inflammation and endothelial activation in children with HbAA (n = 208) or HbSS (n = 22) who presented with severe anemia and P falciparum parasitemia to Mulago Hospital in Kampala, Uganda. Genotyping was performed at study completion. No child had known SCA at enrollment. Children with HbSS did not differ from children with HbAA in peripheral parasite density, but had significantly lower sequestered parasite biomass. Children with HbSS had greater leukocytosis but significantly lower concentrations of several plasma inflammatory cytokines, including tumor necrosis factor α (TNF-α). In contrast, children with HbSS had threefold greater concentrations of angiopoietin-2 (Angpt-2), a marker of endothelial dysregulation associated with mortality in severe malaria. Lower TNF-α concentrations were associated with increased risk of postdischarge mortality or readmission, whereas higher Angpt-2 concentrations were associated with increased risk of recurrent clinical malaria. Children with SCA have decreased parasite sequestration and inflammation but increased endothelial dysregulation during severe anemia with P falciparum parasitemia, which may ameliorate acute infectious complications but predispose to harmful long-term sequelae.
Towards precision in defining COPD exacerbations
Authors: Jenkins Christine R.
Published: September 2021

COPD is the most prevalent chronic respiratory disease worldwide and a major cause of disability and death. Acute exacerbations of COPD remain a key feature of the disease in many patients and research assessing interventions to prevent and treat them requires a robust definition with high sensitivity and specificity. To date, no such definition exists, and multiple different definitions are used in clinical studies depending on the research question. The strengths and weaknesses of current definitions are discussed in the context of evolving knowledge and different settings in which studies are undertaken. Whether identification and recording of exacerbations remains essentially clinical, or can be identified with a dependable biomarker, it should be sensitive and adaptable to context while retaining clarity and facilitating data collection. This is essential to progress a better understanding of the pathophysiology and phenotypic expression of exacerbations to reduce their impact and personal burden for patients.
A close association of freedom from pain, migraine-related functional disability, and other outcomes: results of a post hoc analysis of randomized lasmiditan studies SAMURAI and SPARTAN
Authors: Lipton Richard B. , Baygani Simin K. , Tepper Stewart J. , Krege John H. , Vasudeva Raghavendra , Pearlman Eric M. , Hauck Paula M. , Loo Li Shen
Published: August 2021

Background

While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing.

Methods

Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom.

Results

Patients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time.

Conclusions

This study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint.

Trial Registration

SAMURAI (NCT02439320); SPARTAN (NCT02605174).
The COVID-19 pandemic: the effect on airway Management in non-COVID emergency patients
Authors: Ruangsomboon Onlak , Boonmee Phetsinee , Nimmannit Akarin
Published: August 2021

Background

During the COVID-19 outbreak, healthcare providers might have avoided droplet/aerosol-generating procedures, such as non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) due to the concern of themselves being infected. We hypothesized that this change of practice could have also occurred to other non-COVID-infected patients in the Emergency Department (ED).

Methods

A retrospective analytic study was conducted in the ED of Siriraj Hospital, Bangkok, Thailand, including adult patients presenting with signs and symptoms of respiratory distress between 1 March and 30 April 2020 (the COVID period). A comparison group using the same inclusion criteria was retrieved from 1 March to 30 April 2019 (the pre-COVID period). The primary outcome was rate of NIV and HFNC use. The secondary outcomes were rate of intubation, failure of NIV and HFNC, complications, and mortality.

Results

A total of 360 and 333 patients were included during the pre-COVID and COVID periods, respectively. After adjusting for baseline differences, patients in the COVID period were less likely to receive either NIV or HFNC than the pre-COVID period (adjusted OR 0.52 [95%CI 0.29–0.92]). Overall, intubation rate was similar between the two study periods. However, patients in respiratory distress with pulmonary edema had a relatively higher intubation rate in the COVID period. There were higher failure rates of NIV and HFNC, more infectious complications, and a higher rate of mortality in the pre-COVID period.

Conclusion

During the COVID-19 pandemic, the overall usage of NIV and HFNC in emergency non-COVID patients decreased. Although not affecting the overall intubation rate, this change of practice could have affected some groups of patients. Therefore, treatment decisions based on a balance between the benefits to the patients and the safety of healthcare providers should be made.
Assessment of COVID-19 progression on day 5 from symptoms onset
Authors: Gentilotti Elisa , Savoldi Alessia , Compri Monica , Górska Anna , De Nardo Pasquale , Visentin Alessandro , Be Giorgia , Razzaboni Elisa , Soriolo Nicola , Meneghin Dario , Girelli Domenico , Micheletto Claudio , Mehrabi Sara , Righi Elda , Tacconelli Evelina
Published: August 2021

Background

A major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19.

Methods

Prospective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or transfer to ICU and/or respiratory failure (PaO2/FiO2 ratio < 200) within day-11 of symptoms onset. Multivariate regression was performed to identify predictors of COVID-19 progression. A model assessed at day-5 of symptoms onset including male sex, age > 65 years, dyspnoea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) was proposed. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values.

Results

A total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. The proposed model showed an AUC of 0.73 (95% CI 0.66–0.81) for predicting disease progression by day-11.

Conclusion

An easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate clinicians’ decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients.
Overexpression of UTX promotes tumor progression in Oral tongue squamous cell carcinoma patients receiving surgical resection: a case control study
Authors: Chen Yen-Hao , Chen Chang-Han , Chien Chih-Yen , Su Yan-Ye , Luo Sheng-Dean , Li Shau-Hsuan
Published: September 2021

Background

Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) has been identified as a histone 3 lysine 27 (H3K27) demethylase and acted as a tumor suppressor gene or oncogenic function. The current study was to explore the significance of UTX in oral tongue squamous cell carcinoma (OTSCC) patients who received surgical resection.

Methods

A total of 148 OTSCC patients who underwent surgical resection were identified, including 64 patients (43%) with overexpression of UTX and 84 patients (57%) harboring low expression of UTX. We also used two OTSCC cell lines, SAS and Cal 27, to determine the modulation of cancer. Chi-square test was used to investigate the difference of categorical variables between the groups; survival outcome was analyzed using the Kaplan–Meier method in univariate analysis, and a Cox regression model was performed for multivariate analyses.

Results

Univariate and multivariate analyses showed overexpression of UTX were significantly related to worse disease-free survival (P = 0.028) and overall survival (P = 0.029). The two OTSCC cell lines were treated with GSK-J4, a potent inhibitor of UTX, and transwell migration and invasion assays showed an inhibitory effect with a dose-dependent manner. In addition, western blot analyses also revealed the inhibition of cell cycle and epithelial-mesenchymal transition.

Conclusion

Our study suggests that UTX plays an important role in the process of OTSCC and overexpression of UTX may predict poor prognosis in OTSCC patients who received surgical resection.
Simulated weightbearing computed tomography for verification of radiographic staging of varus ankle osteoarthritis: a cross-sectional study
Authors: Tomiwa Kiyonori , Tanaka Yasuhito , Kurokawa Hiroaki , Kadono Kunihiko , Taniguchi Akira , Maliwankul Korakot
Published: August 2021

Background

Varus ankle osteoarthritis is classified using only weightbearing anteroposterior ankle radiographs; however, sagittal ankle alignment may also affect the position and extent of joint space obliteration. We hypothesized that the sagittal alignment of the ankle may also affect the position and extent of joint space obliteration visible on the coronal section; therefore, we identified the sites of joint space obliteration in patients with stage 3 varus ankle osteoarthritis for comparison with the sites observed on simulated weightbearing computed tomography and investigated the effects of anterior and posterior ankle subluxation.

Methods

Simulated weightbearing computed tomography scans of 83 ft with varus ankle osteoarthritis (26 stage 3a, 57 stage 3b) were performed to check for joint space obliteration in the ankle. Further classification as exhibiting either anterior, posterior, or no subluxation on weightbearing lateral radiographs was performed.

Results

Anterior, posterior, and no subluxation was seen in 5, 9, and 12 ankles among the 26 classified as stage 3a, respectively, and in 22, 12, and 23 ankles among the 57 classified as stage 3b, respectively. The mean tibial lateral surface angle on weightbearing lateral radiographs in stage 3a ankles was 75.6, 83.3, and 80.3 degrees in the anterior, posterior, and no subluxation groups, respectively; and 75.5, 86.6, and 82.7 degrees in stage 3b ankles (p < .05). In stage 3b ankles, widespread joint space obliteration was observed at the anterior distal articular surface of the tibia in all 22 ankles with anterior subluxation and at the posterior distal articular surface of the tibia in all 12 ankles with posterior subluxation.

Conclusions

Simulated weightbearing computed tomography revealed joint space obliteration at the anterior distal articular surface of the tibia in stage 3b ankles with anterior subluxation and at the posterior side in stage 3a and 3b ankles with posterior subluxation. In some patients with stage 3 varus ankle osteoarthritis, the obliteration of the joint space is difficult to evaluate accurately using only weightbearing anteroposterior radiographs; weightbearing lateral radiographs should also be performed.
Effects of mobile learning on writing panoramic radiograph reports: a quasi-experimental trial in dental education
Authors: Bock Anna , Elvers Dirk , Peters Florian , Kramer Chris , Kniha Kristian , Hölzle Frank , Spreckelsen Cord , Modabber Ali
Published: September 2021

Background

In dentistry, the reporting of panoramic radiographs is particularly challenging, as many structures are depicted in one image and pathologies need to be identified completely. To enhance the learning process for these interpretations, the advantages of the increasingly popular education method of mobile learning could be used. Therefore, this study aimed to determine the effectiveness of learning to report panoramic radiographs using an application (app) on a mobile device.

Methods

The existing e-learning programme ‘PantoDict’ was further developed into a mobile app with a new training section. Participants of a dental radiology course were divided into two groups, one of which additionally had the chance to practise reporting panoramic radiographs using the app. A test to assess the knowledge gained was conducted at the end of the semester; the course and the app were also evaluated.

Results

The group that used the app showed significantly better results in the test than the control group (p < 0.05). Although the app group approved a high satisfaction using the app as an additional supplement to the course, this did not result in a higher overall satisfaction with the course. Further, these students observed that the traditional face-to-face seminar could not be replaced by the app.

Conclusion

By using the PantoDict app, students were offered better training options for writing reports on panoramic radiographs, which resulted in significantly better test results than the results of the control group. Therefore, the mobile app is a useful supplement to classical education formats within the context of a blended learning approach.
Efficacy of Normalisation of Advance Care Planning (NACP) for people with chronic diseases in hospital and community settings: a quasi-experimental study
Authors: Jeong Sarah , Cleasby Peter , Ohr Se Ok , Barrett Tomiko , Davey Ryan , Oldmeadow Christopher
Published: September 2021

Background

Advance Care Planning (ACP) has emerged to improve end-of-life processes and experiences. However, the available evidence presents the gloomy picture of increasing number of older people living with chronic diseases and the mismatch between their preferences for and the actual place of death. The study aimed to investigate the efficacy of normalisation of an Advance Care Planning (NACP) service delivered by specially trained Registered Nurses (RNs) in hospital and community settings.

Methods

A quasi-experimental study was conducted involving 16 sites (eight hospital and eight community sites) in Australia. Patients who were aged ≥18 years, who had at least one of nine chronic conditions, and who did not have an Advance Care Directive (ACD) were offered the NACP service. ACP was normalised as part of routine service on admission. The intervention, NACP, was a series of facilitated conversations about the components of ACP. The primary outcomes which included the completion of ACDs, and/or appointment of an Enduring Guardian (EG), were assessed in both intervention and control sites at pre and post intervention stages. Numbers of patients who completed an ACD or appointed an EG were described by count (percentage). ACD completion was compared between intervention and control sites using a logistic mixed effects regression model. The model includes fixed effects for treatment group, period, and their interaction, as well as random site level intercepts. Secondary model included potentially confounding variables as covariates, including age, sex and chronic diseases.

Results

The prevalence of legally binding ACDs in intervention sites has increased from five to 85 (from 0.85% in pre to 17.6% in post), whereas it has slightly decreased from five to 2 (from 1.2% in pre and to 0.49% in post) in control sites (the difference in these changes being statistically significantp < 0.001). ACD completion rate was 3.6% (n = 4) in LHD1 and 1.2% (n = 3) in LHD2 in hospital whereas it was 53% (n = 26) in LHD1 and 80% (n = 52) in LHD2 in community.

Conclusions

The study demonstrated that NACP service delivered by ACP RNs was effective in increasing completion of ACDs (interaction odds ratio = 50) and was more effective in community than hospital settings. Involvement of various healthcare professionals are warranted to ensure concordance of care.

Trial registration

The study was retrospectively registered with the Australian New Zealand Clinical Trials Registry (Trial ID:ACTRN12618001627246) on 03/10/2018. The URL of the trial registry recordhttp://www.anzctr.org.au/trial/MyTrial.aspx
Isolated growth hormone deficiency type IA due to a novel GH1 variant: a case report
Authors: Yang Xi , Yuan Mingming , Li Zhuoguang , Ying Yanqin , Hou Ling , Luo Xiaoping
Published: September 2021

Background

A case of isolated growth hormone deficiency type IA (IGHD IA) caused by novel compound heterozygous mutation in the GH1 gene was reported in this study, which aimed to provide insights that will benefit future diagnosis and treatment.

Case presentation

We analyzed and summarized the clinical data and genetic test results from a patient with IGHD admitted in March 2019 to the Department of Pediatrics Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. We described the results from a 1-year-9-months old female, whose chief complaint was “growth retardation for more than one year”. Her birth length was 49.0 cm, and her birth weight was 3.05 kg. Suboptimal intake (breastfeeding) jaundice lasted for approximately two months following birth. When evaluated at the age of 1-year-9-months old, the patient’s height was 61.0 cm (− 7.24 SD), and her weight was 6.4 kg (− 1.50 SD). The patient’s physical characteristics included yellowish hair, large and unclosed anterior fontanelles, raised forehead, and a low and flat nose. The major abnormalities observed from the auxiliary examinations included low GH (< 0.05 μg/l), low IGF-1 (16.99 μg/l), and elevated TSH (6.97 mIU/l). Genetic testing revealed two heterozygous variants: a splicing mutation (NG_011676.1(NM_022560.4): c.10 + 1G>T, inherited from her mother) in intron 1 of the GH1 gene and a deletion that encompassed the same gene (chr17: 61973811–61996255, inherited from her father). After hormone replacement therapy with L-thyroxine and recombinant human GH (rhGH), the patient’s thyroid function returned to normal, and her serum IGF-1 level significantly improved, which resulted in an accelerated increase in height.

Conclusion

This study described a case of IGHD caused by novel compound heterozygous mutations in the GH1 gene. This study suggested that closer attention should be directed to genetic testing and diagnosis based on clinical characteristics to avoid misdiagnosis.
Copy number variations of chromosome 17p11.2 region in children with development delay and in fetuses with abnormal imaging findings
Authors: Zhang Yuanyuan , Liu Xiaoliang , Gao Haiming , He Rong , Chu Guoming , Zhao Yanyan
Published: September 2021

Background

Deletion and duplication of the 3.7 Mb region in 17p11.2 result in two syndromes, Smith-Magenis syndrome and Potocki-Lupski syndrome, which are well-known development disorders. The purpose of this study was to determine the prevalence, genetic characteristics and clinical phenotypes of 17p11.2 deletion/duplication in Chinese children with development delay and in fetuses with potential congenital defects.

Methods

7077 children with development delay and/or intellectual disability were screened by multiplex ligation-dependent probe amplification P245 assay. 7319 fetuses with potential congenital defects were tested using next generation sequencing technique.

Results

417 of 7077 pediatric patients were determined to carry chromosome imbalance. 28 (28/7077, 0.4%) cases had imbalance at chromosome 17p11.2. Among them, 12 cases (42.9%) had heterozygous deletions and 16 cases (57.1%) had heterozygous duplications. The clinical phenotypes were variable, including neurobehavioral disorders, craniofacial/skeletal anomalies, immunologic defects, ocular problems and organ malformations. 263 of 7319 fetuses were recognized to have genomic copy number variations. Only 2 of them were found to harbor 17p11.2 imbalance. The fetus with deletion presented with ventricular septal defect and the fetus with duplication had cerebral ventricle dilation.

Conclusion

Our study highlights the phenotypic variability associated with 17p11.2 variations in China. The results further expand the phenotypic spectrum of SMS/PTLS and increase awareness of these disruptive mutations among clinicians.
Early implanon discontinuation and associated factors among women ever used implanon in Mettu district, Oromia regional state, southwest Ethiopia, 2021
Authors: Tesfaye Hana , Negara Ebissa , Bayisa Kenbon
Published: August 2021

Background

Implanon is an effective form of long-acting reversible contraceptive used to prevent conception with a clinical failure rate of less than one per 100 users. However, in sub-Saharan countries the utilization of implanon was very low. Regardless of low utilization; its early discontinuation is very common in most developing countries including Ethiopia.

Objectives

To assess the prevalence of early implanon discontinuation and associated factors among women ever used implanon in Mettu district.

Methods

A community based cross-sectional study design was conducted from October 11 to December 4, 2020 G C. A total of 430 women were included in the study by systematic random sampling technique. Data were entered into epi data version 3.1 and analyzed by SPSS version 25.0. Descriptive analysis was computed to describe descriptive results. Logistics regression was computed to see the relative effect of factors on the outcome variable. Adjusted odds ratio was calculated with 95% confidence intervals to show strength of association and p-value < 0.05 was used to declare statistical significance. The finding of the study was presented using narrations, tables and chart.

Result

The total proportion of early implanon discontinuation among 430 mothers was 19.3%. Women who did not counseled about the presence of alternatives methods [AOR = 2.28: 95% CI (1.22–4.26)], women who experienced dizziness after insertion of implanon [AOR = 1.90: 95% CI (1.06–3.43)] and being having menstrual disturbance after insertion of implanon [AOR = 2.17: 95% CI (1.16–4.08)] were significantly associated with early implanon discontinuation. Women who were counseled about the advantage of implanon [AOR: 0.49: 95% CI (0.28–0.87)] were protective from early implanon discontinuation.

Conclusion and recommendation

Early implanon discontinuation among mothers was found to be high. Hence, effective counseling on advantages and side effects of implanon and proper management of the side effects should be made to increase implanon retention.
Good practices in perinatal care and breastfeeding protection during the first wave of the COVID-19 pandemic: a national situation analysis among BFHI maternity hospitals in Spain
Authors: Muñoz-Amat Barbara , Pallás-Alonso Carmen Rosa , Hernández-Aguilar María-Teresa
Published: August 2021

Background

Although the positive effects of good clinical quality standards in perinatal care and breastfeeding support for women, newborns and families have been already demonstrated, many of these practices were disrupted during the COVID-19 pandemic. The objective of this study was to analyse the impact of the COVID-19 pandemic on perinatal care and breastfeeding support practices offered by the Spanish maternity hospitals committed to the UNICEF Baby-friendly Hospital Initiative (BFHI), to women with and without COVID-19.

Methods

Implementation of perinatal practices was assessed by a cross-sectional survey conducted in May 2020 using an online questionnaire. Comparison with pre-pandemic situation and level of commitment to BFHI practices was performed.

Results

Response rate was 50% (58/116). Mothers with COVID-19 suffered greater restrictions in the practices compared to women without COVID-19, with lower rates of companion of choice during labour (84% vs 100%; p = 0.003), skin-to-skin contact (32% vs 52%; p = 0.04), rooming-in (74% vs 98%; p <  0.001), companion of choice during hospital stay (68% vs 90%; p = 0.006), and breastfeeding support (78% vs 94%; p = 0.02). Practices were significantly less prevalent in COVID-19 mothers compared to pre-pandemic situation. A lower accompaniment rate was observed in non-COVID-19 group during delivery (24% vs 47.9%; p <  0.01). Hospitals with higher commitment to BFHI practices reported higher rates of skin-to-skin contact (45.2% vs 10.5%; p = 0.01) and rooming-in (83.9% vs 57.9%; p <  0.05) in COVID mothers. Fewer restrictions were observed in hospitals located in the regions where the pandemic hit harder. In these regions there was a significantly higher level of BFHI commitment of the hospitals, but no significant differences were observed in the average size of the hospital. All the practices suffered even more restrictions during the first weeks of the pandemic.

Conclusion

All mothers suffered restrictions in perinatal care during the COVID-19 pandemic. Women with COVID-19 infection suffered more restrictions in perinatal practices than women without infection. The degree of commitment to WHO-UNICEF perinatal quality standards, integrated into the BFHI, was associated with maintenance of good clinical practices.
Psychometric properties of leadership scales for health professionals: a systematic review
Authors: Carlson Melissa A. , Morris Sarah , Day Fiona , Dadich Ann , Ryan Annika , Fradgley Elizabeth A. , Paul Christine
Published: August 2021

Background

The important role of leaders in the translation of health research is acknowledged in the implementation science literature. However, the accurate measurement of leadership traits and behaviours in health professionals has not been directly addressed. This review aimed to identify whether scales which measure leadership traits and behaviours have been found to be reliable and valid for use with health professionals.

Methods

A systematic review was conducted. MEDLINE, EMBASE, PsycINFO, Cochrane, CINAHL, Scopus, ABI/INFORMIT and Business Source Ultimate were searched to identify publications which reported original research testing the reliability, validity or acceptability of a leadership-related scale with health professionals.

Results

Of 2814 records, a total of 39 studies met the inclusion criteria, from which 33 scales were identified as having undergone some form of psychometric testing with health professionals. The most commonly used was the Implementation Leadership Scale (n = 5) and the Multifactor Leadership Questionnaire (n = 3). Of the 33 scales, the majority of scales were validated in English speaking countries including the USA (n = 15) and Canada (n = 4), but also with some translations and use in Europe and Asia, predominantly with samples of nurses (n = 27) or allied health professionals (n = 10). Only two validation studies included physicians. Content validity and internal consistency were evident for most scales (n = 30 and 29, respectively). Only 20 of the 33 scales were found to satisfy the acceptable thresholds for good construct validity. Very limited testing occurred in relation to test-re-test reliability, responsiveness, acceptability, cross-cultural revalidation, convergent validity, discriminant validity and criterion validity.

Conclusions

Seven scales may be sufficiently sound to be used with professionals, primarily with nurses. There is an absence of validation of leadership scales with regard to physicians. Given that physicians, along with nurses and allied health professionals have a leadership role in driving the implementation of evidence-based healthcare, this constitutes a clear gap in the psychometric testing of leadership scales for use in healthcare implementation research and practice.

Trial registration

This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (see Additional File 1) (PLoS Medicine. 6:e1000097, 2009) and the associated protocol has been registered with the PROSPERO International Prospective Register of Systematic Reviews (Registration Number CRD42019121544).
Relationship between pain intensity, pain catastrophizing, and self-efficacy in patients with frozen shoulder: a cross-sectional study
Authors: Hirata Junya , Tomiyama Minori , Koike Yasuhiro , Yoshimura Manabu , Inoue Keiko
Published: September 2021

Background

Pain catastrophizing and self-efficacy are useful for predicting pain; these are associated with pain intensity and facilitate evaluation of psychological factors. However, it remains unclear whether the effects are direct or indirect in patients with frozen shoulder; the impact on each variable has also not been clarified. Thus, this study aimed to examine the structural relationship between pain catastrophizing, self-efficacy, and pain intensity in patients with frozen shoulder.

Methods

Participants who were diagnosed with frozen shoulder between January 2016 and March 2017 were recruited from a single orthopedic clinic. Patients aged 18 years or older, who had been symptomatic for < 1 year and reported localized pain in one shoulder, experienced night pain, and had restricted active and passive shoulder motions were included. Pain intensity (Numerical Rating Scale (NRS)), pain catastrophizing (Pain Catastrophizing Scale (PCS)), and self-efficacy (Pain Self-Efficacy Questionnaire (PSEQ)) were measured at the first examination, and the relationship was examined using the Bayesian estimation method. The model was modified repeatedly based on the posterior prediction p value, deviance information criterion (DIC), and Bayesian information criterion (BIC); the model with the highest explanatory power was adopted as the final model.

Results

Ninety-three patients diagnosed with frozen shoulder were included in this study. On path analysis, the model in which pain intensity affected psychological factors had the most explanation. The convergence index potential scale reduction was below 1.1, and the convergence of the estimate was confirmed. The posterior prediction p value was 0.25, DIC = 1328.705, and BIC = 1356.872; the validity of the fit of the model was confirmed. The path coefficients from the NRS to the PSEQ, from the NRS to the PCS, and from the PSEQ to the PCS scores were − 0.232 (95% confidence interval (CI), − 0.406 to − 0.033), 0.259 (95% CI, 0.083–0.419), and − 0.504 (95% CI, − 0.646 to − 0.334), respectively; these values were statistically significant (p < 0.05).

Conclusion

Our results show that pain intensity increases the risk of chronic pain including pain catastrophizing and self-efficacy and that pain catastrophizing increases by decreasing self-efficacy in patients with frozen shoulder.
Carbon emissions from a temperate coastal peatland wildfire: contributions from natural plant communities and organic soils
Authors: Mickler Robert A.
Published: September 2021

Background

One of the scientific challenges of understanding climate change has been determining the important drivers and metrics of global carbon (C) emissions and C cycling in tropical, subtropical, boreal, subarctic, and temperate peatlands. Peatlands account for 3% of global land cover, yet contain a major reservoir of 550 gigatons (Gt) of soil C, and serve as C sinks for 0.37 Gt of carbon dioxide (CO2) a year. In the United States, temperate peatlands are estimated to store 455 petagrams of C (PgC). There has been increasing interest in the role of wildfires in C cycling and altering peatlands from C sinks to major C sources. We estimated above- and below-ground C emissions from the Pains Bay Fire, a long-duration wildfire (112 days; 18,329 ha) that burned a coastal peatland in eastern North Carolina, USA.

Results

Soil C emissions were estimated from pre- and post-burn Light Detection and Ranging (LIDAR) soil elevation data, soils series and C content mapping, remotely sensed soil burn severity, and post-burn field surveys of soil elevation. Total above-ground C emissions from the fire were 2,89,579 t C and 214 t C ha−1 for the 10 vegetation associations within the burn area perimeter. Above-ground sources of C emissions were comprised of litter (69,656 t C), shrub (1,68,983 t C), and foliage (50,940 t C). Total mean below-ground C emissions were 5,237,521 t C, and ranged from 2,630,529 to 8,287,900 t C, depending on organic matter content of different soil horizons within each of the 7 soil series. The mean below-ground C emissions within the burn area were 1,595.6 t C ha−1 and ranged from 629.3 to 2511.3 t C ha−1.

Conclusions

In contrast to undisturbed temperate peatlands, human induced disturbances of the natural elevation gradient of the peatland has resulted in increased heterogeneity of floristic variation and assemblages that are a product of the spatial and temporal patterns of the water table level and the surface wetness across peatlands. Human induced changes in surface hydrology and land use influenced the fuel characteristics of natural vegetation and associated soils, thus influencing wildfire risk, behavior, and the resulting C emissions.
The adaptation of Turkish health literacy scale for literate Syrian adult refugees living in Turkey: a reliability–validity study
Authors: Bahar Özvarış Şevkat , Güçiz Doğan Bahar , Konşuk Ünlü Hande , Aktuna Gamze , İnandı Tacettin , Kurt A. Öner , Aydın Neriman , Kutluk M. Tezer
Published: August 2021

Background

Turkey hosts the world’s largest refugee population of whom 3.5 million are Syrians and this population has been continuously growing since the year 2011. This situation causes various problems, mainly while receiving health-care services. In planning the migrant health-care services, for the policy makers of host countries, health literacy level of migrants is an important measure. Determination of health literacy level of Syrian refugees in Turkey would be supportive for planning some interventions to increase health-care service utilization, as well as health education and health communication programs. An “original health literacy scale” for 18–60 years of age Turkish literate adults (Hacettepe University Health Literacy Scale-HLS) was developed to be used as a reference scale in 2018. Since it would be useful to compare the health literacy levels of Turkish adults with Syrian adult refugees living in Turkey with an originally developed scale, in this study, it was aimed to adapt the HLS-Short Form for Syrian refugees.

Methods

This methodological study was carried out between the years 2019–2020 in three provinces of Turkey where the majority of Syrians reside. The data was collected by pre-trained, Arabic speaking 12 interviewers and three supervisors via a questionnaire on household basis. At first, the original Scale and questionnaire were translated into Arabic and back translated into the original language. The questionnaire and the Scale were pre-tested among 30 Syrian refugees in Ankara province. A total of 1254 refugees were participated into the main part of the study; 47 health-worker participants were excluded from the validity-reliability analysis. Confirmatory factor analysis (CFA) was performed. Cronbach’s alpha and Spearman–Brown coefficients were calculated.

Results

Of the participants, 52.9% was male; 26.1% had secondary education level or less; almost half of them had moderate economic level; 27.5% could not speak Turkish. The Cronbach’s Alpha was 0.75, Spearman–Brown Coefficient was 0.76; RMSEA = 0.073, CFI = 0.93, TLI = 0.92 and GFI = 0.95 for the Scale. The Cronbach’s Alpha was 0.76, Spearman–Brown Coefficient was 0.77; RMSEA = 0.085, CFI = 0.93, TLI = 0.91 and GFI = 0.95 for self-efficacy part.

Conclusion

In conclusion, the adapted HLS would be a reliable instrument to evaluate the health-literacy level of Syrian refugees living in Turkey and could allow for a comparison of the host country’s health literacy level to that of the refugees using the same scale.
Revisiting caregiver satisfaction with children’s mental health services in the United States
Authors: Seibel Lauren F. , Peth-Pierce Robin , Hoagwood Kimberly E.
Published: August 2021

Nearly four decades ago, Unclaimed Children documented the gaps in the United States between mental health programs and caregivers’ perspectives about those services for their children. This absence of attention to parent or caregiver perspectives, including their satisfaction with these services, was a key finding of the report, which detailed system failure in caring for youth with mental health needs. Since then, the focus on caregiver satisfaction with children’s mental health services has been largely overlooked in research, and when examined has been mostly included as an indicator of the feasibility of program implementation. In striking contrast, overall healthcare system reforms have highlighted the importance of improving consumer’s direct experience of care. However, caregiver satisfaction remains largely disconnected to these overall health system reforms, even as reforms focus increasingly on value-based, coordinated and integrated care. In this paper, we review literature from 2010 to 2020, revisit the measurement of caregiver satisfaction, identify how and when it is being measured, and delineate a research agenda to both realign it with health system improvements, refine its focus on expectancies and appropriateness, and root it more firmly in the principles of user experience (UX) and human-centered design (HCD).