bluuebunny/crossref_metadata_2025 huggingface dataset:
Atypical hemolytic uremic syndrome and acute tubular necrosis induced by complement factor B gene (CFB) mutation
Authors: Wu Hao , Su Sensen , Li Lin , Zhang Li
Published: March 2021

Rationale:

Atypical hemolytic uremic syndrome (aHUS) is an uncommon and serious disease that manifests hemolytic anemia, thrombocytopenia, and acute kidney injury. Genetic complement abnormalities have been shown to be responsible. Compared with the aHUS caused by other mutated genes, aHUS secondary to CFB mutation in adults is extremely rare. We report an adult with CFB mutation developing aHUS.

Patient concerns:

A 56-year-old man was admitted for 4-day history of nausea and fatigue, anuria for 2 days, and unconsciousness for 10 hours.

Diagnoses:

The patient presented with life-threatening anemia, thrombocytopenia, acute kidney injury, and nervous system abnormalities. The patient had schistocytes on the peripheral blood smear, increased lactate dehydrogenase (LDH), and plasma-free hemoglobin levels. The patient was later found to harbor a pathogenic variant in the CFB gene (C.1598A>G), and was diagnosed with aHUS and acute kidney injury.

Intervention:

The patient was treated by plasmapheresis, continuous renal replacement therapy, blood transfusion, and anti-infective and antihypertensive treatment.

Outcomes:

After the treatment, the patient's consciousness returned to normal, and the hemoglobin, platelet, and serum creatinine recovered. The disease activity remained quiescent during the follow-up.

Lessons:

A rare heterozygous variant c.1598A>G p.Lys 533Arg in the CFB gene, which was associated with adult-onset aHUS, was described and successfully treated. This case can help in understanding the early diagnosis and effective therapies of this rare disease.
Penis as a primary site of an extraskeletal Ewing sarcoma
Authors: Krakorova Dagmar Adamkova , Halamkova Jana , Tucek Stepan , Bilek Ondrej , Kristek Jan , Kazda Tomas , Zambo Iva Staniczkova , Demlova Regina , Kiss Igor
Published: March 2021

Rationale:

The Ewing sarcoma family of malignant tumors is a group of tumors characterized by morphologically similar round-cell neoplasms and by the presence of a common chromosomal translocation; Ewing sarcoma family of tumors typically occur in children and young adults between 4 to 15 years of age. The primary tumor usually originates in the bone, extraskeletal localization is rare.

Patient concern:

We present a case report concerning a 32-year-old male patient with a primary involvement of the penis.

Diagnosis:

The histopathology from the first penile biopsy showed a small-cell neuroendocrine carcinoma; however, that result was based on a sample obtained at a different facility than the Sarcoma Center, where the investigating pathologist did not have the adequate expertise. The patient then underwent a radical penectomy and a second reading of the histology was demanded after a radical penile amputation when Ewing sarcoma with R1 resection was confirmed.

Interventions:

The patient was referred to the national Sarcoma Center, where – using a multidisciplinary approach – the treatment was started with curative intent. However, it was preceded by a non-standard initiation of the therapy due to the poor primary diagnosis.

Outcomes:

The non-standard therapy at the onset of the disease caused a poor prognosis of an otherwise curable diagnosis. Despite all that, the patient survived for a relatively long time.

Lessons:

The treatment of sarcomas with atypical localizations should be conducted by an experienced multidisciplinary team in a center with experience in sarcoma treatment.
The efficacy and safety of Kuntai capsule combined with leuprorelin acetate in the treatment of endometriosis
Authors: Zhang Shuzhen , Wang Lei , Zhang Jing , An Wei , Jia Li
Published: March 2021

Background:

Endometriosis (EMS) is one of the common diseases in women, which seriously affects the quality of life of women. Leuprorelin acetate can control the development of EMS, but long-term use can cause perimenopausal symptoms in women. Clinical studies have shown that Kuntai capsule combined with leuprorelin acetate is effective in the treatment of EMS, which can relieve perimenopausal symptoms, but it lacks of evidence-based medical evidence. Therefore, this study aims to systematically evaluate the efficacy and safety of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS.

Methods:

CNKI, VIP, Wanfang, Chinese Biomedical Literature Database, PubMed, The Cochrance Library, Embase, Web of Science, and other databases were searched by computer to collect randomized controlled trials of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS. The retrieval time was from the establishment of the database to February 2021. Two researchers screened the literatures and extracted the data and meta-analysis was performed using RevMan 5.3 software.

Results:

This study evaluated the efficacy and safety of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS by clinical effective rate, serum sex hormone levels estradiol, follicle-stimulating hormone, luteinizing hormone, visual analogue scale, Kupperman score and incidence of adverse reactions.

Conclusion:

This study will provide reliable evidence-based evidence for the clinical application of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS.

Ethics and dissemination:

Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.

OSF Registration number:

DOI 10.17605/OSF.IO/AZU47
The effect of dance-based mind-motor activities on the quality of life in the patients recovering from COVID-19
Authors: Ding Yi , Guo Chenchen , Yu Shaohong , Zhang Peng , Feng Ziyun , Sun Jinglong , Meng Xiangxia , Li Li , Zhuang He
Published: March 2021

Background:

Since the outbreak of coronavirus disease 2019 (COVID-19), with the improvement of diagnosis and treatment level in various countries, more and more patients have been discharged after systematic treatment. In order to effectively promote the overall recovery of patients’ physical and mental function and quality of life (QOL), the focus of clinical work should be gradually shifted to rehabilitation treatment. Dance-based mind-motor activities were defined as coordinated upright mind-motor movements that emphasize dynamic balance, structured through music or an inner rhythm (e.g., breathing) and distinctive instructions or choreography, and that involve social interaction. It has positive effects on motor function, lung function, psychological mood and other aspects, so it can be used as a safe alternative therapy for patients recovering from COVID-19. At present, there are no relevant articles for systematic review.

Methods:

From its inception until March 2021, we will conduct a comprehensive electronic search, including Cochrane Library, MEDLINE, PubMed, Springer, EMBASE, Chinese Science Citation Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Wan-fang database. Two independent researchers will conduct article retrieval, screening, quality assessment, and data analysis through the Review Manager (V. 5.3.5).

Results:

The results of this study will evaluate the effectiveness and safety of dance-based mind-motor activities for the improvement of QOL in COVID-19 patients during the recovery period.

Conclusion:

The conclusion of the study will provide an evidence to judge whether dance-based mind-motor activities is effective and safe for COVID-19 in recovery period.

Ethics and dissemination:

This protocol will not evaluate individual patient information or infringe patient rights and therefore does not require ethical approval.

PROSPERO registration number:

CRD42021232995.
Evaluation of ustekinumab trough levels during induction and maintenance therapy with regard to disease activity status in difficult to treat Crohn disease patients
Authors: Mechie Nicolae-Catalin , Burmester Merle , Mavropoulou Eirini , Pilavakis Yiannis , Kunsch Steffen , Ellenrieder Volker , Amanzada Ahmad
Published: March 2021

Ustekinumab (UST) is approved for the treatment of moderate and severe Crohn disease (CD). Therapeutic drug monitoring (TDM) can help monitor the therapeutic effects of biologics. Therefore, the aim of this study was to evaluate the clinical outcomes of UST-treated CD patients and to determine the UST trough level in clinical and corticosteroid-free remission.

This retrospective study included patients with moderate and severe active disease (AD) treated intravenously with a weight-adapted induction dose of UST. The maintenance therapy consisted of 90 mg UST subcutaneously at week 8 and thereafter every 8 or 12 weeks, depending on the clinical response. Clinical and corticosteroid-free remission, Harvey-Bradshaw-Index (HBI), UST trough level, and further laboratory parameters were measured just before the injection of UST at each follow-up evaluation until week 40.

37 CD patients with a median HBI of 9 at week 0 were included in the study. Starting from 24% at the beginning of the monitoring period, and 38% of patients at the end of the monitoring period were treated with an 8-week interval (P = .18). There was a significant improvement in clinical (P = .0004), corticosteroid-free remission (P = .03), and HBI (P < .0001) from week 0 until the end of the observation period. The serum UST trough level decreased significantly from 2.0 at week 8 to 0.3, in the maintenance therapy and 0.4 μg/ml at the end of the therapy (P < .0001). Neither UST trough level nor levels of C-reactive protein (CRP) or fecal calprotectin (FC) were associated with disease outcome. Concomitant immunomodulator therapy did not appear to affect the UST trough level or clinical course.

UST is an effective treatment option for difficult-to-treat patients with CD. UST trough levels may not be associated with treatment efficacy or the prediction of treatment outcomes in patients with CD. Further prospective randomized trials should be conducted to evaluate whether UST trough levels are associated with treatment outcomes in patients with CD.
Association between lncRNA ANRIL genetic variants with the susceptibility to ischemic stroke
Authors: Wang Qianwen , Zhao Jingjing , Chang Hongtao , Liu Xu , Zhu Ruixia
Published: March 2021

Background:

Recent studies have reported that lncRNA (long noncoding RNAs) antisense non-coding RNA in the INK4 locus (ANRIL) plays important roles in the development of atherosclerosis through regulating cell apoptosis, proliferation, and adhesion. GWAS (genome-wide association studies) identified common genetic variants within ANRIL could confer risk of ischemic stroke (IS) in southern Sweden.

Methods:

We performed a case-control study, including 567 IS patients and 552 healthy controls from unrelated northern Chinese Han population, aiming to explore the association between lncRNA ANRIL rs2383207, rs4977574 polymorphisms and the risk of IS. Subsequently we implemented a meta-analysis to further assess the relationship of these variants and the disease.

Results:

In our case-control study, no significant associations were observed in all models between above 2 polymorphisms and IS. Next in our subgroup analysis, we detected significant association between GA genotype of rs4977574 and the increased risk of LAA-IS (large-artery atherosclerotic ischemic stroke), similar elevated risk also appeared in the GG + GA genotype under the dominant model (P = .048, OR = 1.385, 95% CIs 1.002–1.914; P = .040, OR = 1.378, 95% CIs 1.015–1.872, respectively). As for rs2383207, negative results were obtained under all models and subgroups. Our meta-analysis showed a significant association between rs4977574 polymorphism and IS risk in allele model (G vs A P = .002, OR = 1.137, 95% CIs 1.048–1.234); with respect to rs2383207 polymorphism, no significant association between that and the risk of IS was detected under the dominant model (GA + AA vs GG, P = .061, OR = 0.923, 95% CIs 0.849–1.004), or recessive model (AA vs GA + GG, P = .656, OR = 0.972, 95% CIs 0.858–1.101), or allele model (A vs G, P = .326, OR = 0.952, 95% CIs 0.863–1.050). Likewise, no significant association between rs2383207 and IS was found in different stoke subtypes (P > .05).

Conclusions:

Our findings indicated G allele of lncRNA ANRIL rs4977574 could increase the risk of IS, and the variant may be associated with susceptibility to LAA-IS in Chinese Han population.
The mediating role of patient satisfaction and perceived quality of healthcare in the emergency department
Authors: Abidova Alina , Silva Pedro Alcântara da , Moreira Sérgio
Published: March 2021

The purpose of this research was to identify whether a certain set of drivers of satisfaction/perceived quality of healthcare (PQHC) could indirectly affect patients’ confidence/trust in the emergency department (ED).

Patients were seen at an ED in the public hospital in Lisbon, Portugal between January and December 2016. Data were collected between May and November 2017, using a questionnaire, by mail or e-mail. The total sample size comprised 382 patients. The data analysis included structural equation modeling to test the conceptual model with specific drivers of satisfaction/PQHC (privacy; accessibility and availability; doctors; meeting expectations; waiting time for triage [perception]; waiting time to be called back by the doctor following examinations and/or tests [perception]; information about possible delays in receiving treatment/waiting times) and with the main outcome (confidence/trust in the ED) using path analysis.

The analysis of the coefficients revealed that all the mediated paths are statistically significant (P ≤ .05). Although, altogether, the direct paths did not prove statistically significant (P > .05), the overall satisfaction with doctors (P ≤ .01) and meeting expectations (P = .01) can still directly explain the confidence/trust in the ED without the mediating role of satisfaction and PQHC. Hence, overall satisfaction with doctors and meeting expectations can influence, both directly and indirectly, confidence/trust in the ED. All other variables can only indirectly affect confidence/trust in the ED, either through PQHC or through satisfaction.

Even though there are more variables that influence confidence/trust in the ED through PQHC (1)waiting time to be called back by the doctor following examinations and/or tests [perception]; 2) privacy; 3) accessibility and availability; 4) doctors; 5) meeting expectations than through satisfaction (1)waiting time for triage [perception]; 2) information about possible delays in receiving treatment/waiting times; 3) doctors; 4) meeting expectations), we observe the strongest contribution in the mediation model through satisfaction, which reveals its dominant role over PQHC.
Effects of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer
Authors: Liu Chao , Yang Jing , Dong Weiwei , Yuan Jinyan
Published: March 2021

Background:

Gastrointestinal complications and malnutrition are common problems that affect postoperative rehabilitation and survival of patients with esophageal cancer. Evidence has shown that probiotics have a positive effect on improving gastrointestinal complications and nutritional status of patients with esophageal cancer after surgery, but there is a lack of prospective studies on this topic. We designed this prospective randomized controlled trial to evaluate the effects of probiotics on gastrointestinal complications and nutritional status in patients with postoperative esophageal cancer.

Methods:

This is a prospective, randomized, double-blind, placebo-controlled trial. It was approved by the Clinical Research Ethics Committee of our hospital. 192 patients will be randomly divided into probiotics group and the placebo group in a 1:1 ratio. After operation, probiotics and placebo will be given orally for 8 weeks. The indexes of nutritional status and incidence of digestive tract complications will be recorded and the data will be analyzed by SPSS 18.0 software.

Discussion:

This study will evaluate the effect of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer. The results of this study will provide clinical basis for the use of probiotics in postoperative treatment of esophageal cancer.

Trial registration:

OSF Registration number: D DOI 10.17605/OSF.IO/QHW86
Institutional experience of in-stent stenosis after pipeline flow diverter implantation
Authors: Wang Ting , Richard Seidu A. , Jiao He , Li Junrao , Lin Sen , Zhang Changwei , Wang Chaohua , Xie Xiaodong , You Chao
Published: March 2021

Pipeline embolization devices (PLEDs) are flow diverting stents that have exhibited be safe and efficient in the treatment of complex aneurysms. Nevertheless, in-stent stenosis (ISS) has been reported as one of the cardinal complications associated with PLED. The association of wall malapposition and ISS in patient treated with PLED has not been reported.

A retrospective study was conducted to identify patients with ISS after implantation of PLED as treatment for intracranial aneurysms from April 25, 2018 to April 24, 2019. Incidence of ISS and its associated causes such as sharp change of the PLED, distal wall malapposition, inconsistent compliance between parent artery as well as the PLED occlusion due to intimal hyperplasia and vessel tortuosity. Assessment of conservative treatment and retreatment outcomes of ISS were documented.

In all, 6 ISS cases were identified by 2 independent neurointerventionalists out of 118 aneurysm patients treated with PLED. Thus, the incidence rate of ISS in patients treated with PLED was as low as 5% at our institution compared to other studies. The follow-up time for detection of ISS ranged from 6 to 12 months after implantation. Several combinations of reasons such as sharp change of the PLED, distal wall malapposition, inconsistent compliance between parent arteries as well as PLED occlusion due to intimal hyperplasia and vessel tortuosity accounted for the causes of ISS during our analysis. Conservative treatment with a combination of antiplatelet during follow-ups did not resolve the ISS in our study probably due to associated underlying factors above.
Does CYP2C19 polymorphisms affect neurological deterioration in stroke/TIA patients?
Authors: Wang Jiajing , Kuang Jie , Yi Yingping , Peng Chen , Ge Yanqiu , Yin Shujuan , Zhang Xiaolin , Chen Jibiao
Published: March 2021

Background:

The association between cytochrome P450 2C19 (CYP2C19) polymorphisms and neurological deterioration in stroke or transient ischemic attack (TIA) patients is not completely understood. Hence, we performed a systematic review and meta-analysis of prospective cohort studies to quantify this association.

Methods:

PubMed, Cochrane Library, Excerpta Medica Database, China National Knowledge Infrastructure and WanFang databases were searched for studies published up to April 2019. Prospective cohort studies that reported an association between CYP2C19 polymorphisms and neurological deterioration in stroke/TIA patients were included. Data on risk ratio (RR) and 95% confidence intervals (CI) were extracted and pooled by the authors. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed.

Results:

Twelve eligible studies were included. Twelve studies reported CYP2C19∗2, ∗3 loss-of-function alleles and 5 studies reported CYP2C19∗17 gain-of-function allele. Compared to non-carriers, carriers of CYP2C19∗2, ∗3 loss-of-function alleles had a significantly higher risk of neurological deterioration (RR, 1.63; 95%CI, 1.32–2.02). Conversely, carriers of CYP2C19∗17 gain-of-function allele had a significantly lower risk of neurological deterioration (RR, 0.520; 95%CI, 0.393–0.689) compared to non-carriers.

Conclusions:

This meta-analysis demonstrated that the carriers of CYP2C19∗2, ∗3 loss-of-function alleles have an increased risk of neurological deterioration compared to non-carriers in stroke or TIA patients. Additionally, CYP2C19∗17 gain-of-function allele can reduce the risk of neurological deterioration.
Difference in the efficacy of intravitreal dexamethasone implant before and after silicone oil removal
Authors: An Jae Hong , Kim Yu Cheol
Published: March 2021

Rationale:

An intravitreal dexamethasone (IV-DEX) implant is safe and effective for the treatment of macular edemas; however, the efficacy of IV-DEX implants in silicone oil (SO)-filled eyes remains controversial. There is no previous study comparing an IV-DEX implant in the same eye with and without intravitreal SO.

Patient concerns:

A 72-year-old man with proliferative diabetic retinopathy, macular edema, and rhegmatogenous retinal detachment, treated with pars plana vitrectomy with SO tamponade had refractory macular edema.

Diagnosis:

Refractory macular edema.

Intervention:

Subtenon triamcinolone injection, intravitreal anti-vascular endothelial growth factor injection, and IV-DEX implantation were performed; this was followed by intravitreal SO removal combined with IV-DEX implantation.

Outcomes:

The macular edema did not decrease significantly with posterior subtenon triamcinolone injection, intravitreal anti-vascular endothelial growth factor injection, and IV-DEX implantation; however, the edema was relieved after SO removal and a new IV-DEX implantation.

Lessons:

IV-DEX implant may be less efficacious in the treatment of macular edema in an SO-filled eye than that in a normal vitreous cavity.
Ruxolitinib in conjunction with the HLH-94 protocol for Epstein-Barr virus-related hemophagocytic lymphohistiocytosis in the intensive care unit
Authors: Huang Zoufang , Xie Jiangbo
Published: March 2021

Rationale:

The HLH-94 protocol is a standard induction treatment for hemophagocytic lymphohistiocytosis. However, about 30% of patients may not respond. Ruxolitinib has been clinically proven to be an effective treatment for hemophagocytic lymphohistiocytosis (HLH).

Patient concerns:

A previously healthy 14-year-old girl presented to the local hospital with a 4-day history of persistent fever and sore throat.

Diagnosis:

Clinical and laboratory tests revealed fever >38.5°C, hepatosplenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia, and an elevated interleukin-2 receptor level.

Intervention:

This patient was treated with ruxolitinib and the HLH-94 protocol.

Outcomes:

The patient's clinical and some laboratory indices improved. Unfortunately, vital signs such as respiratory function and consciousness did not improve.

Lessons:

This case report highlights the effect of using ruxolitinib in conjunction with the HLH-94 protocol. However, safety evaluation of this regimen was not performed because critically ill patient died too fast.
Recurrent monocular exudative retinal detachment as the first manifestation of squamous cell lung cancer
Authors: Zarzecki Mateusz , Saeed Emil , Mariak Zofia , Konopińska Joanna
Published: March 2021

Rationale:

In this report, we present an extremely rare case of recurrent monocular exudative retinal detachment without concomitant ocular metastases. This turned out to be the first symptom of squamous cell lung cancer.

Patient concerns:

A 63-year-old woman was referred to our ophthalmology clinic by her primary care physician with a complaint of deteriorating vision in her right eye that had started four months prior, without concomitant pain.

Diagnoses:

We observed a detachment in the lower part of the retina during her ophthalmoscopy. We did not find any tears, holes, or degenerative changes in the periphery of the retina of the right eye during the surgery. In addition, plaques, tumor masses, and metastases were absent. Therefore, we diagnosed her with unilateral paraneoplastic exudative retinal detachment. Imaging tests performed before surgery revealed perihilar density with a visible air bronchogram in the middle field of the left lung. This turned out to be squamous cell carcinoma.

Interventions:

Patient underwent pars plana vitrectomy and routine laboratory and imaging tests before the procedure that utilized 20-gauge instrumentation. The subretinal fluid and was drained and a tamponade using Densiron (Fluoron Co, Neu-Ulm, Germany) was applied. After ophthalmic treatment, patient underwent complex oncological treatment based on chemotherapy and radiotherapy.

Outcomes:

Despite the application of heavy silicone oil (Densiron) into the vitreous chamber, we observed a recurrence of retinal detachment in the right eye during the follow-up visit, 13 months after the first ophthalmic surgery. Following subsequent pars plana vitrectomy, the Densiron and subretinal membranes were removed. Despite oncological treatment, the patient died, twenty months after the appearance of the first ocular symptoms.

Lessons:

Exudative retinal detachment without tumor metastasis to the eyeball can be one of the first signs of lung cancer in rare cases. Multidisciplinary care and imaging methods with greater accuracy will provide comprehensive care to the patients. It will not only facilitate timely detection and treatment of lung tumors but also for a plethora of oncological diseases.
Using the health belief model to explore nursing students’ relationships between COVID-19 knowledge, health beliefs, cues to action, self-efficacy, and behavioral intention
Authors: Tsai Fu-Ju , Hu Yih-Jin , Chen Cheng-Yu , Tseng Chie-Chien , Yeh Gwo-Liang , Cheng Jin-Fong
Published: March 2021

Nursing educators should equip nursing students with sufficient knowledge about coronavirus disease 2019 (COVID-19), perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, self-efficacy, and behavioral intention in order to prevent the spread of COVID-19.

The purpose of this study was to use the health belief model to elucidate nursing students’ relationships between knowledge about COVID-19, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, self-efficacy, and behavioral intention.

A cross-sectional survey design was adopted and purposive sampling was utilized. A total of 361 nursing students participated in the study. Quantitative analysis was employed for all data analysis.

The findings showed that the nursing students had the following mean scores on knowledge of COVID-19 9.43 [standard deviation (SD)1.19], perceived susceptibility 19.41 (SD2.68), perceived severity 20.31 (SD 4.09), perceived benefits 26.52 (SD 4.08), perceived barriers 15.17 (SD5.88), cues to action 3.30 (SD1.70), self-efficacy 17.68 (SD2.83), and behavioral intention 18.46 (SD2.33). Nursing students’ demographic background, knowledge of COVID-19, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, and self-efficacy explained 58.1% of the variance in behavioral intention (R

2
 = 0.581, F = 29.775, P < .001).

Nursing educators can increase nursing students’ knowledge of COVID-19, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, and self-efficacy as effective means of health promotion to improve their behavioral intention to prevent the spread of COVID-19.
Immediate effects of stance and swing phase training on gait in patients with stroke
Authors: Sakuma Kaoru , Tateuchi Hiroshige , Nishishita Satoru , Okita Yusuke , Kitatani Ryosuke , Koyama Yumiko , Ibuki Satoko , Ichihashi Noriaki
Published: March 2021

To compare the effects of gait trainings targeting the stance (stance training) and the swing phases (swing training) among the subjects with stroke, and quantify the characteristics in the subjects who benefitted from either the stance training or the swing training. Sixteen subjects with stroke performed the stance training, which focused on the center of pressure to move from the heel to the forefoot, and the swing training, which focused on the improvement of hip flexion in the swing phase. To investigate the immediate effects of the stance training and the swing training, the instrumented gait analysis was performed before and after training. To quantify the characteristics, subjects were divided into two groups based on the gait speed change. These two groups were compared using clinical examinations. After the stance training, the center of pressure displacement of the paretic limb was increased compared with the swing training. Subjects who benefitted from the stance training had slower Timed Up and Go and weaker paretic hip muscle strength than those who benefitted from the swing training. Stance training may be more effective in subjects with slower Timed Up and Go outcomes and weaker hip muscles.
Correlation between Oswestry disability index and 12-item self-administered version of World Health Organization Disability Assessment Schedule (WHODAS 2.0) in patients with chronic low back pain
Authors: Bärlund Esa T. , Katajapuu Niina K. , Paltamaa Jaana P. , Saltychev Mikhail M.
Published: March 2021

The objective of the study was to investigate the correlation between the 12-item WHO Disability Assessment Schedule (WHODAS 2.0) and the Oswestry disability index (ODI). Prospective cross-sectional study of 1379 patients (age 48 years) with chronic low back pain. The Spearman’s rank correlation test was employed. Of all the possible 143 correlations, 46 (32%) were strong and nine (6%) were very strong. The strongest correlations ≥0.6 were seen for ‘personal care’ (ODI) vs. ‘washing whole body’ (WHODAS 2.0), ‘personal care’ (ODI) vs. ‘getting dressed’ (WHODAS 2.0), ‘walking’ (ODI) vs. ‘walking long distances’ (WHODAS 2.0) and ‘social life’ (ODI) vs. the WHODAS 2.0 total score. In conclusion, while items defining physical functioning were mostly strongly correlated, items defining social or psychological functioning were less associated. Both scales could be used together providing valuable information regarding the functioning of people with chronic low back pain.
Physical Activity Measurement in Children Who Use Mobility Assistive Devices: Accelerometry and Global Positioning System
Authors: Kerfeld Cheryl I. , Hurvitz Philip M. , Bjornson Kristie F.
Published: March 2021

Purpose:

To explore the usefulness of combining accelerometry, global positioning systems, and geographic information systems, to describe the time spent in different locations and physical activity (PA) duration/count levels by location for 4 children with cerebral palsy (CP) who use assistive devices (AD).

Methods:

A descriptive multiple-case study.

Results:

Combining the 3 instruments was useful in describing and differentiating duration by location, and amount and location of PA across differing functional levels and AD. For example, the child classified with a Gross Motor Function Classification System (GMFCS) level II exhibited large amounts of PA in community settings. In contrast, the child classified with a GMFCS level V had small amounts of PA and spent most measured time at home.

Conclusions:

Combined accelerometry, global positioning system, and geographic information system have potential to capture time spent and amount/intensity of PA relative to locations within daily environments for children with CP who use AD.
Evidence of SARS-CoV-2 Infection in Cells, Tissues, and Organs and the Risk of Transmission Through Transplantation
Authors: Gaussen Amaury , Hornby Laura , Rockl Gary , O’Brien Sheila , Delage Gilles , Sapir-Pichhadze Ruth , Drews Steven J. , Weiss Matthew J. , Lewin Antoine
Published: March 2021

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has raised concerns for programs overseeing donation and transplantation of cells, tissues, and organs (CTO) that this virus might be transmissible by transfusion or transplantation. Transplant recipients are considered particularly vulnerable to pathogens because of immunosuppression, and SARS-CoV-2 is likely to generate complications if contracted. Several signs and symptoms observed in COVID-19 positive patients reflect damage to multiple organs and tissues, raising the possibility of extrapulmonary SARS-CoV-2 infections and risk of transmission. At the beginning of the pandemic, a consensus has emerged not to consider COVID-19 positive patients as potential living or deceased donors, resulting in a global decrease in transplantation procedures. Medical decision-making at the time of organ allocation must consider safely alongside the survival advantages offered by transplantation. To address the risk of transmission by transplantation, this review summarizes the published cases of transplantation of cells or organs from donors infected with SARS-CoV-2 until January 2021 and assesses the current state of knowledge for the detection of this virus in different biologic specimens, cells, tissues, and organs. Evidence collected to date raises the possibility of SARS-CoV-2 infection and replication in some CTO, which makes it impossible to exclude transmission through transplantation. However, most studies focused on evaluating transmission under laboratory conditions with inconsistent findings, rendering the comparison of results difficult. Improved standardization of donors and CTO screening practices, along with a systematic follow-up of transplant recipients could facilitate the assessment of SARS-CoV-2 transmission risk by transplantation.
Assessment of Carfilzomib Treatment Response in Lung Transplant Recipients With Antibody-mediated Rejection
Authors: Pham Christine , Pierce Brett J. , Nguyen Duc T. , Graviss Edward A. , Huang Howard J.
Published: March 2021

Background.

Data supporting the use of carfilzomib (CFZ) for treatment of antibody-mediated rejection (AMR) in lung transplantation in combination with plasmapheresis and intravenous immunoglobulin suggest positive outcomes through donor-specific antibody (DSA) depletion or conversion to noncomplement-activating antibodies. Herein, we describe our center’s experience treating AMR with CFZ.

Methods.

All patients treated with CFZ for AMR from 2014 to 2019 were included. The primary outcome was a positive response to CFZ was defined as: (1) loss of DSA C1q-fixing ability after last CFZ dose; (2) clearance of de novo DSA; or (3) decrease in de novo DSA mean fluorescence intensity of >3000.

Results.

Twenty-eight patients with 31 AMR episodes were treated with CFZ. A positive response was observed in 74.4% of AMR episodes and 82.1% of patients. This response was driven by loss of complement 1q fixation (70.6%), elimination of class I DSAs (78.6%), and reduction in both classes I (median 2815, 79.5% reduction from baseline) and II DSA mean fluorescence intensity (3171, 37.1%).

Conclusions.

CFZ shows potential for ameliorating AMR; however, additional studies are needed to define optimal time of administration.
Efficacy and safety of pentoxifylline combination therapy in major depressive disorder: a randomized, double-blind, placebo-controlled clinical trial
Authors: Farajollahi-Moghadam Mostafa , Sanjari-Moghaddam Hossein , Ghazizadeh Hasemi Maryam , Sanatian Zahra , Talaei Ali , Akhondzadeh Shahin
Published: March 2021

In this randomized, double-blind, placebo-controlled clinical trial, we assessed the efficacy and safety of pentoxifylline combination therapy with sertraline in treatment of major depressive disorder (MDD). A total of 56 patients with MDD were assigned into two parallel groups to receive sertraline (100 mg/day) plus placebo or sertraline (100 mg/day) plus pentoxifylline (400 mg three times daily) for six weeks. Patients were evaluated with the Hamilton rating scale for depression (HAM-D) at baseline and weeks 2, 4 and 6. The sertraline plus pentoxifylline group demonstrated greater improvement in HAM-D scores from baseline to all three study time points (P = 0.013, 0.007 and 0.016 for week 2, 4 and 6, respectively). Response to treatment rate was also significantly higher in the sertraline plus pentoxifylline group compared to the sertraline plus placebo group at week 4 [57.1 vs. 21.4%, P = 0.013] and the study endpoint [96.4 vs. 57.1%, P = 0.001]. However, the remission rate, time to remission and time to treatment response did not show any significant difference between trial groups. Our findings support the efficacy and safety of pentoxifylline combination therapy in patients with MDD.
Prevalence and predictors of laxatives use in clozapine-related constipation: an observational study
Authors: Nakamura Masaru , Nagamine Takahiko
Published: March 2021

Clozapine-induced constipation is a frequently overlooked side effect that can prove fatal. This study aimed to investigate the prevalence of constipation and the breakdown of laxatives, and to identify whether use of laxative may be predicted by demographics or baseline metabolic markers in 53 Japanese treatment-resistant schizophrenia inpatients switched to clozapine. Differences of present age, onset age and duration of illness, previous antipsychotic dose using the chlorpromazine equivalent, and 10-items of metabolic markers, including fasting plasma glucose and ratio of triglyceride to high-density lipoprotein cholesterol levels were compared between the laxative and nonlaxative user groups. Sequential changes of defecation scores using Bristol stool form scale, and clozapine dosage at 1, 2 and 3 months were evaluated within each group. Multiple linear stepwise regression analysis was performed to assess the predicting use of laxatives. Half of subjects required treatment with laxative, were significantly older and had longer durations of illness than nonlaxative users. Magnesium oxide and lubiprostone were mainly used singly or in combination. Longer disease duration, and lower levels of fasting blood glucose and insulin resistance were predicting the use of laxatives. Screening and preventive strategies for minimizing clozapine-related constipation should be established in future study.
Effects of celecoxib augmentation of antidepressant or anxiolytic treatment on affective symptoms and inflammatory markers in patients with anxiety disorders: exploratory study
Authors: Elnazer Hesham Y. , Sampson Anthony P. , Baldwin David S.
Published: March 2021

Prolonged stress has been associated with elevated levels of circulating proinflammatory cytokines. Cyclo-oxygenase-2 inhibitors such as celecoxib exert anti-inflammatory effects and may enhance the response to antidepressant drug treatment in patients with depressive disorders, but their effect on anxiety symptoms in patients with anxiety disorders is uncertain. Patients with a primary diagnosis of an anxiety disorder, with stabilised symptoms, underwent either 6 weeks of celecoxib augmentation of continued treatment (n = 18) or continued ‘treatment as usual’ (n = 9). Assessments included the Warwick–Edinburgh mental well-being Scale (WEMWEBS), Hospital Anxiety and Depression Scale (HADS), Oxford questionnaire of emotional side effects of antidepressants (OQUESA) and Clinical Global Impression of Illness Severity (CGI-S). Venous blood samples were collected for assays of inflammatory cytokines. Patients who underwent celecoxib augmentation showed significant reductions in anxiety (HADS-A −3.17) and depressive (HADS-D −2.11) symptoms and in overall illness severity (CGI-S −1.11), and improvements in mental well-being (WEMWBS 7.5) and positive changes in emotional responsiveness (OQUESA-RP −3.56; OQUESA-AC −4.22): these were not seen with ‘treatment as usual’. There were no significant changes in blood levels of inflammatory cytokines in either group. Celecoxib augmentation appeared associated with beneficial effects on anxiety and depressive symptoms and mental well-being. The findings from this pilot study merit further exploration within a double-blind, randomised placebo-controlled study.
Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2
Authors: Dejnirattisai Wanwisa , Zhou Daming , Supasa Piyada , Liu Chang , Mentzer Alexander J. , Ginn Helen M. , Zhao Yuguang , Duyvesteyn Helen M.E. , Tuekprakhon Aekkachai , Nutalai Rungtiwa , Wang Beibei , Paesen Guido C. , López-Camacho César , Slon-Campos Jose , Walter Thomas S. , Skelly Donal , Clemens Sue Ann Costa , Naveca Felipe Gomes , Nascimento Valdinete , Nascimento Fernanda , da Costa Cristiano Fernandes , Resende Paola C. , Pauvolid-Correa Alex , Siqueira Marilda M. , Dold Christina , Levin Robert , Dong Tao , Pollard Andrew J. , Knight Julian C. , Crook Derrick , Lambe Teresa , Clutterbuck Elizabeth , Bibi Sagida , Flaxman Amy , Bittaye Mustapha , Belij-Rammerstorfer Sandra , Gilbert Sarah , Carroll Miles W. , Klenerman Paul , Barnes Eleanor , Dunachie Susanna J. , Paterson Neil G. , Williams Mark A. , Hall David R. , Hulswit Ruben J. G. , Bowden Thomas A. , Fry Elizabeth E. , Mongkolsapaya Juthathip , Ren Jingshan , Stuart David I. , Screaton Gavin R.
Published: March 2021

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.
Phylogeography and Proline amino acid usage of Asian tiger mosquitoAedes albopictus(Skuse 1894) populations along landscape gradients in Indonesia
Authors: Wibowo Andri
Published: March 2021

Asian tiger mosquitoAedes albopictus(Skuse 1894) is one of mosquito-borne vector that globally distributed including Southeast Asia. Despite its wide distributions, information on phylogeography and its determinant factors influencingA. albopictusgenetic diversity and speciation is still lacking, mainly in SE Asia country. Considering this, the phylogeography ofA. albopictusalong with its genetic attributes in Indonesia has been assessed. The results identify that there are 2 distinct clades ofA. albopictusphylogeography. First clade was related to the human-mediated dissemination. Relative Synonymous Codon Usage (RSCU) shows the TTG, CTG, GTG, ACG, GCG, and GGG codons were seldom represented. While GGA, CGA, and followed by TAT, CAT, CCT, TCT, AAC, and TTC codons were common. From a total of 60 codons, 40% codon has RSCU > 1and 21.6 % has RSCU < 1. The differences between west and east part populations can be observed in proline amino acid signaled by CCT and CCC codons. In this amino acid, eastA. albopictushas higher CCC than CCT codons. Since proline is functioned to provide energy for flight, then the differences of this proline related codon amongA. albopictuspopulations were related to the landscape variations in west and east parts of Indonesia with east parts have more rugged landscape and this condition is quite demanding for aerial animal distribution since it requires more flight energy.
Effects of Mutations in the Receptor-Binding Domain of SARS-CoV-2 Spike on its Binding Affinity to ACE2 and Neutralizing Antibodies Revealed by Computational Analysis
Authors: Bozdaganyan Marine E. , Sokolova Olga S. , Shaitan Konstantin V. , Kirpichnikov Mikhail P. , Orekhov Philipp S.
Published: March 2021

SARS-CoV-2 causing coronavirus disease 2019 (COVID-19) is responsible for one of the most deleterious pandemics of our time. The interaction between the ACE2 receptors at the surface of human cells and the viral Spike (S) protein triggers the infection making the receptor-binding domain (RBD) of the SARS-CoV-2 S-protein a focal target for the neutralizing antibodies (Abs). Despite the recent progress in the development and deployment of vaccines, the emergence of novel variants of SARS-CoV-2 insensitive to Abs produced in response to the vaccine administration and/or monoclonal ones represents upcoming jeopardy. Here, we assessed the possible effects of single and multiple mutations in the RBD of SARS-CoV-2 S-protein on its binding energy to various antibodies and the human ACE2 receptor. The performed computational analysis indicates that while single amino acid replacements in RBD may only cause partial impairment of the Abs binding, moreover, limited to specific epitopes, some variants of SARS-CoV-2 (with as few as 8 mutations), which are already present in the population, may potentially result in a much broader antigenic escape. We also identified a number of point mutations, which, in contrast to the majority of replacements, reduce RBD affinity to various antibodies without affecting its binding to ACE2. Overall, the results provide guidelines for further experimental studies aiming at the identification of the high-risk RBD mutations allowing for an antigenic escape.
Trans-cinnamaldehyde attenuatesEnterococcus faecalisvirulence and inhibits biofilm formation
Authors: Ali Islam A. A. , Matinlinna Jukka P. , Lévesque Celine M. , Neelakantan Prasanna
Published: March 2021

Enterococcus faecalisas an important nosocomial pathogen is critically implicated in the pathogenesis of endocarditis, urinary tract and surgical wound infections. Its major virulence attributes (biofilm formation, production of proteases and hemolytic toxins) enable it to cause extensive host tissue damage. With the alarming increase in enterococcal resistance to antibiotics, novel therapeutics are required to inhibitE. faecalisbiofilm formation and virulence.Trans-cinnamaldehyde (TC), the main phytochemical in cinnamon essential oils has demonstrated promising activity against a wide range of pathogens. Here, we comprehensively investigated the effect of TC on planktonic growth, biofilm formation, proteolytic and hemolytic activities, as well as gene regulation inE. faecalis. Our findings revealed that sub-inhibitory concentrations of TC reduced biofilm formation, biofilm exopolysaccharides as well as its proteolytic and hemolytic activities. Mechanistic studies revealed significant down regulation of the quorum sensingfsrlocus and downstreamgelE, which are major virulence regulators inE. faecalis. Taken together, our study highlights the potential of TC to inhibitE. faecalisbiofilm formation and its virulence.
Gα13 loss promotes tumor progression in the KPC transgenic mouse model of advanced pancreatic cancer
Authors: Shields Mario A. , Spaulding Christina , Khalafalla Mahmoud G. , Pham Thao N.D. , Munshi Hidayatullah G.
Published: March 2021

Gα13 transduces signals from G protein-coupled receptors. Gα13 is pro-tumorigenic in epithelial cancer cell lines, which contrasts with its tumor-suppressive function in transgenic mouse models of lymphomas. Here we show that while loss of Gα13 in pancreatic cell lines decreases tumor growthin vivo, Gα13 loss in the Kras-driven (KC) mouse model of pancreatic tumor initiation does not affect tumor development or survival. Instead, Gα13 loss in the Kras/Tp53 (KPC) transgenic mouse model of advanced pancreatic cancer promotes well-differentiated tumors with increased tumor burden and reduced survival. Mechanistically, Gα13 loss in the KPC mouse model enhances E-cadherin-mediated cell-cell junctions and mTOR signaling. Importantly, human pancreatic cancers with low Gα13 expression exhibit increased E-cadherin protein expression and mTOR signaling. This work establishes a context-dependent role of Gα13 in pancreatic tumorigenesis, demonstrating a tumor-suppressive role in transgenic mouse models of advanced pancreatic cancer.