bluuebunny/crossref_metadata_2025 huggingface dataset:
Unrecognized Geriatric Depression in the Emergency Department of a Teaching Hospital in Nepal: Prevalence, Contributing Factors, and Metric Properties of 5 item Geriatric Depression Scale in this Population
Authors: Shrestha Roshana , Shrestha Anmol Purna , Shrestha Abha , Kamholz Barbara
Published: September 2020

Background: Depression is prevalent but poorly recognized in the Emergency Department (ED). We aimed to identify the frequency of unrecognized geriatric depression and its possible determinants in the ED using the 15-item geriatric depression scale (GDS). We also aimed to explore the performance of the shorter, five-item GDS as compared to the 15-item GDS.Methods: This was a cross-sectional study of the ED patients ≥ 60 years. The previously validated Nepali version of GDS-15 screened the sample into “no”, “mild-moderate” and “severe" depression using cutoff values of 4/5, and 8/9 respectively. Demographic and socioeconomic factors, comorbidities and health seeking behaviors were studied and the relation was assessed with binary (Chi-square and Kruskal-Wallis test) and multinomial regression analysis. The performance of GDS-5 was compared with the GDS-15 as standard. Cronbach’s alpha was calculated to investigate reliability. Validity was assessed by calculating sensitivity, specificity, positive predictive value, negative predictive value, Spearman’s correlation, receiver operating characteristic curve, and kappa coefficient. Results: 280 patients were enrolled with an overall prevalence of unrecognized depression of 45.7 % [104 (81.3%) mild-moderate depression, and 24 (18.8%) severe depression]. The mean age of the sample was 71.36 with female predominance (61%), and 82.5% were illiterate. In the binary analysis, those who had more pain, visited the ED more often, had musculoskeletal diseases and sleep problems, mobility problems, visited local healers previously, and who reported self-perceived “heart and mind” disease showed statistically significant differences among the three categories. In multinomial regression analysis, visits to local healers, sleep problems and frequency of pain were significantly related to depression. The sensitivity, specificity, area under curve and Spearman’s correlation of GDS-5 were 75.8%, 96%, 0.919, and 0.827 respectively. Cronbach's alpha for GDS-5 was low (0.416), therefore a new version was proposed which improved the sensitivity to 90.6% and Cronbach’s alpha to 0.623. Conclusions: Unrecognized geriatric depression was highly prevalent which urges the need for ED-based interventions for screening and referral. The proposed brief GDS-5 correlated well with the GDS-15 with better validity and internal reliability and offers a more expeditious form of screening for geriatric depression in emergency settings in Nepal.
Clinical outcomes of chemotherapy in patients with undifferentiated carcinoma of the pancreas: A retrospective multicenter cohort study
Authors: Imaoka Hiroshi , Ikeda Masafumi , Maehara Kosuke , Umemoto Kumiko , Ozaka Masato , Kobayashi Satoshi , Terashima Takeshi , Inoue Hiroto , Sakaguchi Chihiro , Tsuji Kunihiro , Shioji Kazuhiko , Okamura Keiya , Kawamoto Yasuyuki , Suzuki Rei , Shirakawa Hirofumi , Nagano Hiroaki , Ueno Makoto , Morizane Chigusa , Furuse Junji
Published: September 2020

Background: Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer. Although UC has been considered a highly aggressive malignancy, no clinical studies have addressed the efficacy of chemotherapy for unresectable UC. Therefore, we conducted multicenter retrospective study to investigate the efficacy of chemotherapy in patients with UC of the pancreas.Methods: This multicenter retrospective cohort study was conducted at 17 institutions in Japan between January 2007 and December 2017. A total of 50 patients treated with chemotherapy were analyzed.Results: The median overall survival (OS) in UC patients treated with chemotherapy was 4.08 months. The details of first-line chemotherapy were as follows: gemcitabine (n=24), S-1 (n=12), gemcitabine plus nab-paclitaxel (n=6), and other treatment (n=8). The median progression-free survival (PFS) was 1.61 months in the gemcitabine group, 2.96 months in the S-1 group, and 4.60 months in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel significantly improved PFS compared with gemcitabine (p=0.014). The objective response rate (ORR) was 4.2% in the gemcitabine group, 0.0% in the S-1 group, and 33.3% in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel also showed a significantly higher ORR compared with both gemcitabine and S-1 (gemcitabine plus nab-paclitaxel vs. gemcitabine: p=0.033; gemcitabine plus nab-paclitaxel vs. S-1: p=0.034). A paclitaxel-containing first-line regimen significantly improved OS compared with a non-paclitaxel-containing regimen (6.94 months vs. 3.75 months, respectively; p=0.041). After adjustment, use of a paclitaxel-containing regimen in any line was still an independent predictor of OS (hazard ratio for OS, 0.221; 95% confidence interval, 0.076 – 0.647; p=0.006) in multiple imputation by chained equation.Conclusions: The results of the present study indicate that a paclitaxel-containing regimen would offer relatively longer survival, and it is considered a reasonable option for treating patients with unresectable UC.
Long-Term Survival With Sebelipase Alfa Enzyme Replacement Therapy in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency Final Results From 2 Open-Label Studies
Authors: Vijay Suresh , Brassier Anais , Ghosh Arunabha , Fecarotta Simona , Abel Florian , Marulkar Sachin , Jones Simon A.
Published: September 2020

Background: If symptomatic in infants, the autosomal recessive disease lysosomal acid lipase deficiency (LAL-D; sometimes called Wolman disease or LAL-D/Wolman phenotype) is characterized by complete loss of LAL enzyme activity. This very rare, rapidly progressive form of LAL-D results in severe manifestations leading to failure to thrive and death, usually by 6 months of age. We report results from 2 open-label studies of enzyme replacement therapy with sebelipase alfa, a recombinant human LAL, in infants with LAL-D: the phase 2/3 Survival of LAL-D Infants Treated With Sebelipase Alfa (VITAL) study (NCT01371825) and a phase 2 dose-escalation study (LAL-CL08 [CL08]; NCT02193867). In both, infants received once-weekly intravenous infusions of sebelipase alfa.Results: The analysis population contained 19 patients (9 in VITAL; 10 in CL08). Kaplan-Meier estimates of survival to 12 months and 5 years of age were 79% and 68%, respectively, in the combined population, and the median age of surviving patients was 5.2 years in VITAL and 3.2 years in CL08. In both studies, median weight-for-age, length-for-age, and mid-upper arm circumference-for-age z scores increased from baseline to end of study. Decreases in median liver and spleen volume over time were noted in both studies. Short-term transfusion-free hemoglobin normalization was achieved by 100% of patients eligible for assessment in VITAL, in an estimated median (95% confidence interval [CI]) time of 4.6 (0.3–16.6) months. In CL08, short-term transfusion-free hemoglobin normalization was achieved by 70% of patients eligible for assessment, in an estimated median (95% CI) time of 5.5 (3.7–19.6) months. No patient discontinued treatment because of treatment-emergent adverse events. Most infusion-associated reactions (94% in VITAL and 88% in CL08) were mild or moderate in severity.Conclusions: The findings of these 2 studies of infants with rapidly progressive LAL-D demonstrated that enzyme replacement therapy with sebelipase alfa prolonged survival with normal psychomotor development, improved growth, hematologic, and liver parameters, and was generally well tolerated, with an acceptable safety profile.
Understanding the causes of errors in eukaryotic protein-coding gene prediction: a case study of primate proteomes
Authors: Meyer Corentin , Scalzitti Nicolas , Jeannin-Girardon Anne , Collet Pierre , Poch Olivier , Thompson Julie
Published: September 2020

Background. Recent advances in sequencing technologies have led to an explosion in the number of genomes available, but accurate genome annotation remains a major challenge. The prediction of protein-coding genes in eukaryotic genomes is especially problematic, due to their complex exon-intron structures. Even the best eukaryotic gene prediction algorithms can make serious errors that will significantly affect subsequent analyses. Results. We first investigated the prevalence of gene prediction errors in a large set of 176,478 proteins from ten primate proteomes available in public databases. Using the well-studied human proteins as a reference, a total of 82,305 potential errors were detected, including 44,001 deletions, 27,289 insertions and 11,015 mismatched segments where part of the correct protein sequence is replaced with an alternative erroneous sequence. We then focused on the mismatched sequence errors that cause particular problems for downstream applications. A detailed characterization allowed us to identify the potential causes for the gene misprediction in approximately half (5446) of these cases. As a proof-of-concept, we also developed a simple method which allowed us to propose improved sequences for 603 primate proteins. Conclusions. Gene prediction errors in primate proteomes affect up to 50% of the sequences. Major causes of errors include undetermined genome regions, genome sequencing or assembly issues, and limitations in the models used to represent gene exon-intron structures. Nevertheless, existing genome sequences can still be exploited to improve protein sequence quality. Perspectives of the work include the characterization of other types of gene prediction errors, as well as the development of a more comprehensive algorithm for protein sequence error correction.
Veno-venous-ECMO as a platform to evaluate lung lavage and surfactant replacement therapy in an animal model of severe ARDS
Authors: Qaqish Robert , Watanabe Yui , Galasso Marcos , Summers Cara , Ali Aadil , Takahashi Mamoru , Gazzalle Anajara , Liu Mingyao , Keshavjee Shaf , Cypel Marcelo , Sorbo Lorenzo Del
Published: September 2020

Background: There are limited therapeutic options directed at the underlying pathological processes in acute respiratory distress syndrome (ARDS). Experimental therapeutic strategies have targeted the protective systems that become deranged in ARDS such as surfactant. Although results of surfactant replacement therapy (SRT) in ARDS have been mixed, questions remain incompletely answered regarding timing and dosing strategies of surfactant. Furthermore, there are only few truly clinically relevant ARDS models in the literature. The primary aim of our study was to create a clinically relevant, reproducible model of severe ARDS requiring extracorporeal membrane oxygenation (ECMO). Secondly, we sought to use this model as a platform to evaluate a bronchoscopic intervention that involved saline lavage and SRT. Methods: Yorkshire pigs were tracheostomized and cannulated for veno-venous ECMO support, then subsequently given lung injury using gastric juice via bronchoscopy. Animals were randomized postinjury to either receive bronchoscopic saline lavage combined with SRT and recruitment maneuvers (treatment, n=5) or recruitment maneuvers alone (control, n=5) during ECMO.Results: PaO2/FiO2 after aspiration injury was 62.6 ±8 mmHg and 60.9 ±9.6 mmHg in the control and treatment group, respectively (p=0.95) satisfying criteria for severe ARDS. ECMO reversed the severe hypoxemia. After treatment with saline lavage and SRT during ECMO, lung physiologic and hemodynamic parameters were not significantly different between treatment and controls. Conclusions: A clinically relevant severe ARDS pig model requiring ECMO was established. Bronchoscopic saline lavage and SRT during ECMO did not provide a significant physiologic benefit compared to controls.
In vivo optical cellular diagnosis for uterine cervical or vaginal intraepithelial neoplasia using flexible gastrointestinal endocytoscopy -a prospective pilot study-
Authors: Ono Shoko , Nozaki Ayako , Matsuda Kana , Takakuwa Emi , Sakamoto Naoya , Watari Hidemichi
Published: September 2020

Background For patients with any kind of atypical squamous intraepithelial lesion of the uterine cervix or vagina, colposcopy and punch biopsy are common procedures for histological determination following cytology. However, colposcopy-guided biopsy does not provide a high level of diagnostic accuracy. The aim of this study was to determine the usefulness of optical biopsy in vivo using endocytoscopy compared with conventional procedures using colposcopy.Methods Between May 2018 and March 2019, patients who were scheduled for cervical conization or mapping biopsies of the vagina were prospectively enrolled. Endocytoscopy was performed by senior endoscopists prior to scheduled procedures, and endocytoscopic images and biopsy samples were taken from the most prominent site and surrounding area of the cervical or vaginal lesions. The collection process of images was randomized and anonymous, and three doctors separately evaluated the images according to the ECA classification. ECA 4 and 5 are indicative of endoscopic malignancy. The primary endpoint was diagnostic accuracy (benign or malignant: cervical intraepithelial neoplasia (CIN) 3 or vaginal intraepithelial neoplasia (VAIN) 3 or worse) of cell images at the most prominent site in each patient.Results A total of 28 consecutive patients were enrolled. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of endocytoscopic images were 95.0% (84.8-98.6%), 87.5% (61.9-96.5%), 95.0% (84.8-98.6%), 87.5% (61.9-96.5%) and 92.9% (78.2-98.0%), respectively. Inter-observer agreement among three reviewers was 0.78 (0.08-9.88, P < 0.01). On the other hand, the accuracy of colposcopy-guided biopsy was 74.1% (64.0-84.0%).Conclusions Optical cell diagnosis of cervical or vaginal intraepithelial neoplasia using endocytoscopy provides a high level of diagnostic accuracy. Trial registration The study was registered with the UMIN database (ID: 000031712).UMIN000031712. Registered 16 March 2017, https://rctportal.niph.go.jp/detail/um?trial_id=UMIN000031712
Analysis of Exosome-derived MicroRNAs as Early Biomarkers of Lipopolysaccharide-induced Acute Kidney Injury in Rats
Authors: Da-Silva Carolina Carvalho Serres , Anauate Ana Carolina , Maquigussa Edgar , Guirão Tatiana Pinotti , Novaes Antônio da Silva , Boim Mirian A
Published: September 2020

Background: Sepsis contributes to the high prevalence of acute kidney injury (AKI), which mainly occurs in hospitalized patients. The delay in AKI detection is a risk factor for death and chronicity; thus, early diagnosis is essential for initiating proper treatment strategies. Although serum creatinine is used as biomarker, it is increased in plasma serum creatinine only at late stages of AKI. MicroRNAs (miRNAs), a class of noncoding RNAs responsible for gene regulation, can be found in biological fluids within vesicles such as exosomes and may be promising tools for the early detection of AKI. We aimed to identify potential blood miRNAs that can be used as early biomarkers of sepsis-induced AKI in rats. Methods: Adult male Wistar rats received a single dose of lipopolysaccharide (LPS). The earliest significant increase in serum creatinine was detected 4 h after LPS administration. To evaluate whether miRNAs could act as early biomarkers, blood samples were collected before and 2 h after LPS infusion. Serum NGAL levels were used as a comparative marker. Results: Serum miRNAs were derived from exosomes, and their expression were evaluated by the PCR array. miR-181a-5p and miR-23b-3p showed higher expression in LPS-treated rats than in the control animals (p<0.05). Bioinformatics analysis showed that both miRNAs target molecules associated with transcription factors that regulate genes related to proinflammatory cytokines. Conclusion: Considering that LPS activates transcription factors that lead to the production of proinflammatory cytokines, possible premature changes in the serum levels of miR-181a-5p and miR-23b-3p may be used to identify sepsis-induced AKI earlier.
Exploring Views of Orthopaedic Surgeons, Rheumatologists, and General Practitioners About Osteoarthritis Management
Authors: Wallis Jason Andrew , Barton Christian J , Brusco Natasha K , Kemp Joanne L , Sherwood James , Young Kirby , Jennings Sophie , Trivett Adrian , Ackerman Ilana N
Published: September 2020

Background: Delivery of recommended treatments for hip and knee osteoarthritis (OA) is known to be discordant with guideline recommendations. However, professional opinions related to OA management across medical and surgical disciplines are not well understood. The aim of this study was to explore the views of medical professionals about management of hip and knee OA.Methods: Qualitative study. Semi-structured individual interviews were conducted with orthopaedic surgeons, rheumatologists and general practitioners routinely involved in the management of OA. Interviews were audiotaped, transcribed, member-checked, coded and thematically analysed. Results: Fifteen medical professionals were interviewed. Three main themes were: (i) recognition of the importance of non-surgical management of hip and knee OA, focussed on exercise-therapy, weight management and analgesia, (ii) joint replacement being considered the ‘last resort’ for end stage disease not responding to non-surgical management, and (iii) determination of management ‘success’ through patient perceptions was more common than the use of validated instruments. Views on management broadly converged across disciplines, except for the role of joint replacement, considered an adjunct in the overall management of OA by rheumatologists, and as a definitive cure by orthopaedic surgeons.Conclusions: Aligning with current guidelines, medical professionals recognised the importance of non-surgical management focussed on exercise-therapy for hip and knee OA, and concurred that joint replacement surgery should be a last resort. A focus on patient education was less prominent, which along with implementation of validated outcome measures in routine medical practice, may require greater health system support.
Measles-based Zika vaccine induces long-term immunity and requires NS1 antibodies to protect the female reproductive tract.
Authors: Schnell Matthias , Kurup Drishya , Wirblich Christoph
Published: September 2020

Zika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV-E vaccine, MV-E2, protected mice from the non-lethal Zika Asian strain (PRVABC59) and the lethal African strain (MR766) challenge. Despite 100% survival of the MV-E2 mice, however, complete viral clearance was not achieved in the brain and reproductive tract of the lethally challenged mice. We then tested a combination of two MV-based vaccines, the MV-E2 and a vaccine expressing NS1 (MV-NS1[2]), and we observed durable plasma cell responses, complete clearance of ZIKV from the female reproductive tract, and complete fetal protection in the lethal African challenge model. Our findings suggest that NS1 antibodies are required to enhance the protection achieved by ZIKV-E antibodies in the female reproductive tract.
Effect of ultrasound-guided transversus abdominis plane block with rectus sheath block on patients undergoing laparoscopy-assisted radical resection of rectal cancer: a randomized, double-blind, placebo-controlled trial
Authors: Liang Min , Xv Xia , Ren Chunguang , Yao Yongxing , Gao Xiujuan
Published: September 2020

BackgroundMany patients complain of pain following laparoscopic surgery. Clinicians have used ultrasound-guided posterior transversus abdominis plane block (TAPB) and rectus sheath block (RSB) for multimodal analgesia after surgery. We investigated the analgesic effects of US-guided posterior TAPB with RSB on postoperative pain following laparoscopy-assisted radical resection of early-stage rectal cancer.MethodsSeventy-eight adults scheduled for laparoscopy-assisted radical resection of rectal cancer were enrolled in this double-blind placebo-controlled trial. Patients were randomized into 3 groups: the TR Group underwent US-guided bilateral posterior TAPB (40 mL 0.33% ropivacaine) with RSB (20 mL 0.33% ropivacaine); the T Group underwent US-guided bilateral posterior TAPB alone; and the Control Group received saline alone. All patients also had access to patient-controlled intravenous analgesia (PCIA) with sufentanil. The primary outcome was postoperative sufentanil consumption at 0–24, 24–48, and 48–72 h. The secondary outcomes were postoperative pain intensity and functional activity score at rest and while coughing for the same three time periods, intraoperative medication dosage, use of rescue analgesia, recovery parameters, and adverse effects.ResultsThe three groups had no significant differences in baseline demographic and perioperative data, use of intraoperative medications, recovery parameters, and adverse effects. The TR group had significantly lower postoperative use of PCIA and rescue analgesic than in the other two groups (P < 0.05), but the Control Group and T Group had no significant differences in these outcomes.ConclusionsPostoperative US-guided posterior TAPB with RSB reduced postoperative opioid use in patients following laparoscopy-assisted radical resection of rectal cancer.Trial registrationThe trial was registered with chictr.org (ChiCTR2000029326) on January 25, 2020.
Fungus (Alternaria sp.) Mediated Silver Nanoparticles Synthesis, Characterization and Application as Phyto-Pathogens Growth Inhibitor
Authors: Win Theint Theint , Khan Sikandar , Fu Pengcheng
Published: September 2020

Background: Biogenic nanoparticles have proved to be effective biocontrol agents for certain plant diseases. It possesses the potential for extensive use for sustainable agriculture. Many attempts have been made to synthesize nano-based antifungal compounds for the management of soil borne pathogenic fungi for crops.Results: In our work, silver nanoparticles (AgNPs) was constructed with phytopathogenic fungi (Alternaria sp.) which was isolated from banana cultivated soil. Alternaria sp. was able to grow rapidly and produce highly bioactive compounds as safe antifungal agent against plant pathogenic fungi (Fusarium spp. and Alternaria sp.). The size of synthesized silver nanoparticles ranged between 5-10 nm. Analytic tools, such as UV-visible spectroscopy, Fourier transformed infra-red (FTIR) spectroscopy, scanning transmission electron microscopy (STEM), EDS and elemental mapping were used to visualize the formation of AgNPs. The UV-visible spectra showed the peak at 435 nm. The maximum inhibition zone was observed at 100 µl concentration of AgNPs for Fusarium oxysporum (21 ± 2 mm) following Alternaria sp. (20± 2 mm), suggested that the efficacy of the biosynthesized NPs against the phytopathogenic fungi.Conclusions: The resulting AgNPs showed distinct antifungal activity against selected pathogenic plant fungi. The work indicates that green reduction and biogenic synthesis of nanoparticles with benign fungi is an effective, low cost, sustainable and environmentally friendly approach for prevention of soil borne plant diseases.
Assessing the Quality of Deliberative Stakeholder Consultations with Pediatric Palliative Care Clinicians and Oncologists in Canada
Authors: Rahimzadeh Vasiliki , Longo Cristina , Gagnon Justin , Fernandez Conrad , Bartlett Gillian
Published: September 2020

Objective—This paper presents findings from a quality assessment of deliberative stakeholder consultations with healthcare professionals in Canada on the implementation of a precision diagnostic for life-threatening pediatric brain tumors. Background—Advanced understanding of the basic biology and pharmacogenomics of pediatric brain tumors portend a clinical future in which oncologists base their clinical decisions in large part on results from laboratory derived tests (LDT) using next generation sequencing. Less is known, however, about how interprofessional healthcare teams perceive the opportunities and challenges of adopting LDTs in clinical practice, or how to best communicate LDT results to pediatric patients and their families. Deliberative stakeholder consultations present a promising alternative to traditional deliberative democratic methods. They allow researchers to unveil normative ethical and social values underpinning a forthcoming policy or new standard of care from the perspectives of key stakeholder groups, as well as make practical recommendations relevant for implementation.Methods—Using the DeVries framework for assessing the quality of deliberative process and information, we analyzed data from 44 post-consultation evaluation surveys from pediatric oncology and palliative care teams at two tertiary pediatric healthcare centers in Canada. Medians/means based on a 10-point Likert scale are reported. We also conducted turn-taking analysis and word-contribution analysis from the text transcriptions of each deliberation to assess equality of participation.Results—Deliberants agreed the quality of the deliberative process was fair (averages ranging from 9-10/10) and the opportunities to both receive expert information and discuss with others about the implementation of a new LDT were helpful (9.5/10). While the session improved understanding of the implementation barriers and opportunities, the session had marginal effects on deliberants’ perceived impact on their own clinical practice where median ratings ranged from 3-10/10. Participation was proportionate in at least four of the six deliberations, where no deliberant took more than 20% of total turns and contributed equal to, or less than 20% of total words.Conclusion—The quality assessments performed lend evidence to the informational value and overall fairness of the deliberative process achieved in this study to identify implementation and communication needs of healthcare professionals at the point when LDTs become standard for diagnosing life-threatening brain tumors in children.
The I, the T or the Q? Which fishing opportunity attributes are associated with sustainable fishing?
Authors: Oostdijk Maartje , Carpenter Griffin
Published: September 2020

While several prominent studies link the use of individual transferable quotas (ITQs) to sustainable fishing, it remains unclear which attributes of this system (i.e., individual, transferable, or quota), or any other system, lead to sustainable outcomes. To test for a linkage between management systems and sustainable fishing, we systematically classified how fishing opportunities are allocated for 443 fish stocks from 1990 to 2018 to produce the largest database of its kind. Using mixed-effects models and a difference-in-differences approach, we tested the occurrence of system attributes against two metrics of sustainable fishing: mortality (i.e., overfishing) and biomass (i.e., overfished). Our results reveal that quota limits and individual allocation reduce the probability of overfishing, but offer no evidence supporting the transferability of fishing opportunities or the length of time they are held for. These results highlight the importance of considering specific attributes in the design of fisheries management systems.
Circulating MicroRNA-486 and MicroRNA-146a Serve as Potential Biomarkers of Sarcopenia in the Elderly
Authors: Liu Huang-Chun , Han Der‐Sheng , Hsu Chih-Chin , Wang Jong-Shyan
Published: September 2020

Background: Age-related sarcopenia meaningfully increases the risks of functional limitations and mortality in the elderly. Although circulating microRNAs (c-miRNAs) are associated with aging-related cellular senescence and inflammation, the relationships between c-miRNAs and sarcopenia in the elderly remain unclear. This study investigates whether circulating myo-miRNAs and inflammation-related miRNAs are associated with sarcopenia in the elderly. Methods: This investigation recruited 77 eligible subjects (41 males and 36 females) from 597 community-dwelling older adults, and then divided into normal (n=24), dynapenic (loss of muscular function without mass, n=35), and sarcopenic groups (loss of muscular function with mass, n=18). Moreover, myo- (c-miRNA-133a and c-miRNA-486) and inflammation- (c-miRNA-21 and c-miRNA-146a) related miRNAs, as well as, inflammatory-related cytokine and peroxide levels in plasma were determined using quantitative polymerase chain reaction and ELISA, respectively. Results: Sarcopenic group exhibited lesser skeletal muscle mass index (SMI), handgrip strength, and gait speed, as well as, lower c-miR-486 and c-miR-146a levels, compared to those of normal and dynapenic groups. Moreover, c-miR-486 level was positively related to SMI (r=0.334, P=0.003), whereas c-miR-146a level was positively associated with SMI (r=0.240, P=0.035) and handgrip strength (r=0.253, P=0.027). In the receiver operating characteristic analysis for predicting sarcopenia, the area under the curve in c-miR-486 was 0.708 (95% confidence interval: 0.561-0.855, P=0.008) and c-miR-146a was 0.676 (95% CI: 0.551-0.801, P=0.024). However, no significant relationships were observed between SMI/handgrip strength/gait speed and plasma myeloperoxidase/interleukin-1𝛽/interleukin-6 levels. Conclusions: Myo-miRNA (c-miR-486) and inflammation-related miRNA (c-miR-146a) are superior to inflammatory peroxide/cytokines in plasma for serving as critical biomarkers of age-related sarcopenia.
Expression and Functional Identification of INPP4B in Gallbladder Cancer Patients and Gallbladder Cancer Cells
Authors: Wu Youliang , Meng Delong , Xu Xin , Bao Junjun , You Yexiang , Sun Yanjun , Li Yongxiang , Sun Dengqun
Published: September 2020

Purpose: Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of PI3K-Akt signaling pathway and plays a contradictory role in different types of cancers. However, its biological role in human gallbladder cancer (GBC) remain unclear. Here we aimed to investigate the expression, clinical significance and biological function of INPP4B in GBC clinical dates and GBC cell lines. Methods: The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analyzed. Knockdown and overexpression of INPP4B on GBC-SD and SGC-996 cells were used to identify INPP4B function in vitro, using cell proliferation assay, clonogenic assay, apoptosis detection, cratch wound-healing assay and transwell assay.Results: INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues, and was related to histopathological differentiation. Here, we observed that INPP4B was highly expressed in high-moderate differentiated compared to low-undifferentiated. Additionally, we found that INPP4B expression was not associated with overall survival in GBC patients and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and prognosis of GBC from histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression at different degrees of differentiation. In addition, INPP4B knockdown inhibited tumorigenicity in vitro, and INPP4B overexpression induced tumorigenicity in vitro, which may play a role as an oncoprotein.Conclusions: These findings implicated that INPP4B may play a dual role in the prognosis of GBC with different degrees of differentiation, and might act as an oncogene in gallbladder cancer cells.
Sexual and Reproductive Health knowledge of Postgraduate Students at the University of Cape Town, in South Africa
Authors: Mwamba Bupe , Mayers Pat , Shea Jawaya
Published: September 2020

BackgroundGlobally and in South Africa, university students’ knowledge of sexual and reproductive health (SRH) is low. This study was conducted in response to the dearth of information about the sexual and reproductive health knowledge of postgraduate students. Research conducted to explore the SRH knowledge of undergraduate students suggests that the level of SRH knowledge among undergraduate students is low. The aim of this study was to determine the SRH knowledge of postgraduate students with regards to contraceptives, sexually transmitted illnesses (STI), human immunodeficiency virus (HIV), Pap smear and clinical breast examination at University of Cape Town (UCT), in South Africa. MethodA cross sectional survey design was utilized, using an adapted and pretested online questionnaire. All postgraduate students enrolled in the first semester of 2017 (9444) were invited to anonymously complete the online survey.ResultsFour hundred and six (406) students completed the online survey, of whom 293 were female and 107 males. The age range of respondents was between 18 years and 57 years, with the median age for both male and female respondents being 24 years. Six survey responses were excluded from the statistical analysis because of incomplete data. Post graduate students from the African continent comprised 90.75% of the respondents. Most respondents were white (51.50%) from both Africa and abroad. The results indicated that respondents knew about sexually transmitted infections, and human immunodeficiency virus (HIV) & acquired immune deficiency syndrome (AIDS). Female respondents were more aware of breast examination, and the role of Papanicolaou smear (Pap smear) in SRH. Almost half of the respondents in this study (49%) stated that they had no need for more information about contraceptives. Lecturers were identified as one of the top five sources of information, which suggests that the university environment provides students with important SRH-related information.ConclusionMost postgraduate students had knowledge of sexual and reproductive health with regards to contraception, Pap smear, clinical breast examination, STIs, HIV and AIDS. Further research should focus on the relationship between SRH knowledge and usage among this population. As university lecturers were identified as an important source of information across faculties, the University should consider the incorporation of SRH education in the broader curriculum and as an integral component of student health services.
Users’ Experiences With an Interactive Evidence to Decision (iEtD) Framework: A Qualitative Analysis
Authors: Meneses-Echavez Jose Francisco , Rosenbaum Sarah , Rada Gabriel , Flottorp Signe , Moberg Jenny , Alonso-Coello Pablo
Published: September 2020

BackgroundEvidence to Decision (EtD) frameworks bring clarity, structure and transparency to health care decision making. The interactive Evidence to Decision (iEtD) tool, developed in the context of the DECIDE project and published by Epistemonikos, is a stand-alone online solution for producing and using EtD frameworks. Since its development, little is known about how organizations have been using the iEtD tool and what characterizes users’ experiences with it.MethodsThis study aimed to describe users’ experiences with the iEtD and identify main barriers and facilitators related to use. We contacted all users registered in the iEtD via email and invited people who identified themselves as having used the solution to a semi-structured interview. Audio recordings were transcribed, and one researcher conducted a content analysis of the interviews guided by a user experience framework. Two researchers checked the content independently for accuracy. ResultsOut of 860 people contacted, 81 people replied to our introductory email (response rate 9.4%). Twenty of these had used the tool in a real scenario and were invited to an interview. We interviewed all eight users that accepted this invitation (from six countries, four continents). ‘Guideline development’ was the iEtD use scenario they most commonly identified. Most participants reported an overall positive experience, without major difficulties navigating or using the different sections. They reported having used most of the EtD framework criteria. Participants reported tailoring their frameworks, for instance by adding or deleting criteria, translating to another language, or rewording headings. Several people preferred to produce a Word version rather than working online, due to the burden of completing the framework, or lack of experience with the tool. Some reported difficulties working with the exportable formats, as they needed considerable editing.ConclusionA very limited number of guideline developers have used the iEtD tool published by Epistemonikos since its development. Although users’ general experiences are positive, our work has identified some aspects of the tool that need improvement. Our findings could be also applied to development or improvement of other solutions for producing or using EtD frameworks.
Plasma Levels and Tissue Expression of Soluble TGFbrIII Receptor in Women With Early-stage Breast Cancer and in Healthy Women: a Prospective Observational Study
Authors: Grgurevic Lovorka , Novak Ruder , Trkulja Vladimir , Hrkac Stela , Salai Grgur , Bilandzic Josko , Hamzic Lejla Ferhatovic , Milas Ivan , Vucemilo Tiha , Balja Melita Peric , Bilic Karmen
Published: September 2020

BackgroundMammary carcinogenesis is partly regulated by the transforming growth factor beta (TGFβ) signaling pathway. Its function in cancer progression and metastasis is highly dependent on disease stage, and it is likely modulated by the ratio of membrane-bound vs. soluble TGFβrIII (sTGFβrIII). In this prospective observational study, we assessed tissue expression and plasma levels of sTGFβrIII in healthy women, women with benign breast lesions and in early-stage breast cancer patients. MethodsIn a preliminary study, plasma sTGFβrIII levels were determined in 13 healthy women (age 19-40 years) at different phases of the ovarian cycle, and in 15 patients (age 35-75 years) at different times of the day. The main study assessed plasma concentrations of sTGFβrIII in : (i) 158 healthy women in whom breast lesions were excluded; (ii) 65 women with benign breast lesions; (iii) 147 women with newly diagnosed breast cancer classified as American Joint Committee on Cancer (AJCC) stages 0 to IIB. Completers provided blood samples before surgery and at 10-30 and 160-180 days after surgery. Plasma sTGFβrIII concentrations were determined using an indirect ELISA kit. Part of the removed tissues underwent immunohistochemical (IHC) staining and analysis of tissue TGFβrIII expression. ResultsThere appeared no relevant variations in plasma sTGFßrIII levels at different times of the day or different ovarian cycle phases. Before surgery, breast cancer patients had somewhat higher sTGFβrIII then healthy women, or those with benign breast lesions (by 14.5 and 26 ng/mL, respectively), with a tendency of larger differences at higher age. This correlated with lower expression of TGFβrIII in breast cancer vs. healthy tissue samples. At 160-180 days after surgery, plasma sTGFβrIII levels in breast cancer patients declined by 23-26 ng/mL. ConclusionsPlasma sTGFβrIII levels do not seem to relevantly vary during the day or the ovarian cycle. The coinciding higher plasma levels in newly diagnosed cancer patients then in healthy subjects and lower TGFβrIII expression in the malignant than in healthy breast tissue suggest ectodomain shedding as a source of circulating sTGFβrIII. Decline in plasma levels after tumor removal supports such a view.
Factors Influencing Post-icu Psychological Distress in Family Members of Critically Ill Patients: A Linear Mixed-effects Model
Authors: Naef Rahel , Felten Stefanie van , Ernst Jutta
Published: September 2020

Background: Adverse responses to critical illness, such as symptoms of depression, anxiety or posttraumatic stress, are relatively common among family members. The role of risk factors, however, remains insufficiently understood, but may be important to target those family members most in need for support. We therefore examined the association of patient-, family member- and care-related factors with post-ICU psychological distress in family members in a general population of critical ill patients.Methods: We conducted a prospective, single-centre observational study in a twelve-bed surgical ICU in a 900-bed University Hospital in Switzerland. Participants were family members of patients treated in ICU who completed the Family Satisfaction in ICU-24 Survey, the Hospital Anxiety Depression Scale, Impact of Event Scale-Revised-6, and a demographic form within the first three months of their close other’s ICU stay. Data were analysed using linear mixed-effects models, with depression, anxiety, and posttraumatic stress as outcome measures. Results: A total of 214 family members (53% return rate) returned a completed questionnaire. We found that higher levels of satisfaction were significantly associated with lower levels of depression, anxiety and posttraumatic stress. There was no statistically significant association between family member characteristics and any measure of psychological distress. Among the included patient characteristics, younger patient age was associated with higher levels of depression and anxiety, and patient death was associated with higher levels of depression and posttraumatic stress.Conclusions: Our results suggest that satisfaction with ICU care is strongly associated with family well-being post-ICU. Family members of younger patients and of those who die seem to be most at risk for psychological distress, requiring specific support, whereas family member characteristics may have less relevance.
Bimetallic Fe-Ag arrays with extraordinary nonlinear refraction and nonlinear Faraday rotation at telecommunication wavelength (1550 nm)
Authors: Koirala Krishna Prasad , Garcia Hernando , Sandireddy Venkatanarayana Prasad , Kalyanaraman Ramki , Duscher Gerd
Published: September 2020

There is a pressing need to discover magneto-optical materials and devices with better performance and lower cost that operate at telecommunication wavelengths. Here we report the discovery of giant negative nonlinear refraction and nonlinear Faraday rotation at 1550 nm using an array of bimetallic Fe-Ag nanopyramids. This system exhibited a very large third order nonlinear refractive index (n2 = -2.32 cm2/GW) and nonlinear figure of merit (F = 2.3). The same system also exhibited an extraordinarily large magneto-optical susceptibility (χi4 = 6.5 × 10-12 esu) and photoinduced nonlinear Faraday rotation up to 2.5 radian/μm at a magnetic field of 0.5 T. The nonlinear response was dependent on the degree of overlap of the Fe nanopyramid on the Ag nanopyramid which influences the strength of plasmon induced dipoles on the Ag nanopyramid. This nanoscale system opens up a rich new set of possibilities in utilizing magneto-plasmonic materials to miniaturize future multifunctional devices at telecommunication wavelengths.
Economic Burden of Public Health Care Was Higher Than That of Hospitalization and Treatment Associated With COVID-19 in China
Authors: Liang Xiaohua , Xiao Lun , Yang Xue-Li , Zhong Xue-Fei , Zhang Peng , Tang Xian , Luo Ye-Tao , Gu Dong-Feng , Bi Yang
Published: September 2020

Background: During the coronavirus disease 2019 (COVID-19) pandemic, it is essential to evaluate the socioeconomic burden imposed on the Chinese health care system.Methods: We prospectively collected information from the Center for Disease Control and Prevention and the designated hospitals to determine the cost of public health care and hospitalization due to COVID-19. We estimated the resource use and direct medical costs per confirmed case and the costs associated with public health care per thousand people at the national level.Results: The average costs per case for specimen collection and nucleic acid testing (NAT) were $29.49 and $53.44, respectively, while the average cost of NAT for high-risk populations was $297.94 per capita. The average costs per thousand people for epidemiological surveys, disinfectant, health education and centralized isolation were $49.54, $247.01, $90.22 and $543.72, respectively. A single hospitalization for COVID-19 in China cost an average of $3,792.69 ($2,754.82-$5,393.76) in direct medical costs incurred only during hospitalization, while the total costs associated with hospitalization were estimated to have reached nearly $31,229.39 million in China as of 20 May 2020. The cost of public health care ($6.81 billion) was 20 times that of hospitalization.Conclusions: This study highlights the magnitude of resources needed to control the COVID-19 pandemic and treat COVID-19 cases. Public health measures implemented by the Chinese government have been valuable with regard to reducing the infection rate and may be cost-effective ways to control emerging infectious diseases.
Antithyroid Peroxidase Antibodies and Histopathological Outcomes in Egyptian Patients Subjected to Total Thyroidectomy for Nonmalignant Nodular Goiter
Authors: Salman Mohamed AbdAlla , Rabiee Ahmed , Salman Ahmed , Ftohy Tarek Elsayed
Published: September 2020

Objective: The study aimed to assess antithyroid antibodies in patients with benign thyroid masses and the effect of total thyroidectomy on the antibodies titers.Patients and Methods: This is a retrospective work of 112 cases managed with total thyroidectomy who have positive antithyroid peroxidase antibodies (TPO-Ab), antithyroglobulin antibodies (Tg-Ab), or both. All patients were euthyroid before surgery. Thyroid function tests and thyroid antibodies levels were measured before and 6 and 12 months after surgery.Results: Histopathological evaluation revealed Hashimoto thyroiditis (47.3%), colloid nodules (22.3%), and lymphocytic thyroiditis (30.4%). All patients were TPO-Ab positive, while 96 patients (85.7%) were Tg-Ab positive before surgery. There was no considerable change in TPO-Ab and Tg-Ab after surgery (p = 0.817, and p=0.560, respectively). Also, there was no significant difference between the three histopathological diagnoses in the levels of TPO-Ab (p = 0.086) or Tg-Ab (p = 0.673). Conclusion: Antithyroid antibodies are not valuable markers for diagnosis or prognosis of benign thyroid diseases subjected to total thyroidectomy. We do not recommend their use beyond being a supportive evidence of the possibility of autoimmune nature of the disease if other criteria are confirmed.