bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploratory study on the safety and effectiveness of Yizhi Qingxin Decoction (capsules) in the treatment of hypertension in the elderly with mild cognitive impairment (deficiency of kidney essence syndrome)
Authors: Wang Bi-Qing , Mei Jun , Liu Lu , Ju Chun-Xiao , Zhao Jun-Nan , Zhang Ping , Xu Feng-Qin , Chen Ke-Ji
Published: June 2020

Background:

Hypertension in the elderly with cognitive impairment has been one of the global health issues. Mild cognitive impairment (MCI) is the state of transition between the normal aging process and cognitive changes of unformed dementia. Diagnosis and treatment of MCI are the keys to prevent dementia, and hypertension is one of the important influencing factors of MCI. Our preclinical experiment found that Yizhi Qingxin Decoction (YQD) could effectively reduce the blood pressure of spontaneously hypertensive rats (SHR), improve their spatial learning and memory abilities in Morris water maze, and play a neuroprotective role. The objective is to estimate the safety and efficacy of YQD (capsules) in the treatment of hypertension in the elderly with MCI (deficiency of kidney essence syndrome) through this study.

Methods:

According to the random number generated by the block random method, 100 participants will be randomly and equally divided into the treatment group (YQD) or the control group (Ginkgo biloba extract tablets). The conversion rate of dementia will be used as the main evaluating indicator by the CDR scale. The MoCA scale, MMSE scale, ADCS-MCI-ADL-24 scale, CGIC-KDS scale, and 24-h ambulatory blood pressure will be used as the secondary evaluating indicator. Safety will be evaluated based on specific manifestations of adverse reactions and the incidence of adverse events.

Objective:

The objective is to estimate the curative effect of YQD (capsules) on hypertension in the elderly with MCI (deficiency of kidney essence syndrome), and to evaluate the safety of its clinical application.

Trial registration:

Chinese Clinical Trial Registry (ICTRP member): ChiCTR2000030292.
Big data-based identification of methylated genes associated with drug resistance and prognosis in ovarian cancer
Authors: Yan Bingbing , Xiong Chunqiu , Huang Feifeng , Zhang Mingming , Mo Yan , Bai Hua
Published: June 2020

It is imperative to further the understanding of the drug resistance mechanisms of ovarian cancer (OC) and to identify useful biological markers for prognosis prediction.

Cormine, cBioportal, and The Cancer Genome Atlas databases were used to search microarray data of gene methylation related to OC, drug resistance in OC, and prognosis, and to analyze methylated genes potentially inducing the drug resistance in OC. Fifty-five DNA-methylated genes significantly associated with drug resistance in OC were screened, and the regulatory mechanisms underlying changes in methylation levels of these genes were systematically integrated.

Enrichment and annotation of biological processes indicated that most of the above DNA-methylated genes were significantly associated with cell proliferation and cell cycle. In addition, pathway enrichment demonstrated that the above DNA-methylated genes were significantly associated with PI3K-AKT and P53 signaling pathways. Among the 55 genes, 4 were significantly associated with OC prognostic disease-free survival, namely bromodomain containing 4, PDZ domain containing 1 (PDZK1), phosphatase and tensin homolog, and TNF receptor superfamily member 10c; 5 were significantly related to overall survival, namely bromodomain containing 4, PDZK1, PIK3C2B, Rh associated glycoprotein, and DYRK; among them, the degree of methylation of TNF receptor superfamily member 10c, PDZK1, and Rh associated glycoprotein genes was significantly correlated with mRNA expression. Furthermore, PDZK1, Rh associated glycoprotein, and TNF receptor superfamily member 10c genes showed significant hypomethylation in drug-resistance tissues of OC, and their mRNAs had significantly high expression.

The association between the methylation of these 55 genes and OC and drug resistance in OC, in addition to bioinformatics analyses clarify the important mechanisms of gene methylation in the development, progression, and drug resistance of OC.
Serum minerals (Ca, P, Co, Mn, Ni, Cd) and growth hormone (IGF-1 and IGF-2) levels in postmenopausal Saudi women with osteoporosis
Authors: Yakout Sobhy M. , Alharbi Fatimah , Abdi Saba , Al-Daghri Nasser M. , Al-Amro Abir , Khattak Malak Nawaz Khan
Published: June 2020

Osteoporosis is reported to be common among Saudi women. Several minerals appear to be important determinants of insulin-like growth factor (IGF), the bioactivity of which regulates bone and mineral metabolism. Here we proposed that mineral status may alter the IGF system among individuals with osteoporosis. This study aims to evaluate the relationships between essential elements and IGF levels among postmenopausal Saudi women with osteoporosis. A total of 128 postmenopausal Saudi women aged ≥50 years old were recruited in this study. Diagnosis of osteoporosis was done by using dual-energy x-ray absorptiometry to determine the bone minerals density (BMD). Serum calcium and phosphate were determined using routine chemical analyzer. Serum Co, Mn, Ni, Cd were measured using inductively coupled plasma mass spectrometry. Serum IGF-1 and IGF-2 were determined using Luminex xMAP. Using stepwise linear regression analysis, only Cd was identified to be significantly associated with IGF1 in osteoporosis, explaining 3% (confidence interval 0.01–0.05; P = 0001) of the variance perceived. Our results suggest that Cd exposure indirectly affects BMD which may increase the risk of osteoporosis in postmenopausal women. Further longitudinal study using a larger sample size is recommended to determine causality of Cd levels and IGF-1.
A case report of a patient with bulky uterine cervical neoplasm who achieved complete response with “intentional internal high-dose policy” high-dose-rate interstitial brachytherapy
Authors: Kashihara Tairo , Kobayashi Kazuma , Iijima Kotaro , Murakami Naoya , Yoshida Ken , Okuma Kae , Nakamura Satoshi , Takahashi Kana , Inaba Koji , Igaki Hiroshi , Nakayama Yuko , Kato Tomoyasu , Uno Takashi , Itami Jun
Published: June 2020

Rationale

Gynecological high-dose-rate (HDR) brachytherapy has progressed for years, but it remains difficult for bulky tumors to be controlled locally. Dose limitations to organs at risk (OARs) are invariably obstacles in increasing the prescription dose. Additionally, it is controversial that the excessive hyperdose sleeve, the volume receiving a dose equal to or greater than twice the reference dose, should be eliminated in gynecological HDR brachytherapy. On the other hand, the technique of simultaneous integrated protection was reported for large hepatocellular carcinoma treatment, and similarly, internal high-dose brachytherapy could be used for treating bulky cervical carcinoma.

Patient Concerns

A 54-year-old female had irregular genital bleeding and lost 13 kg in one year.

Diagnosis

She was diagnosed with T3bN1M0 cervical cancer in another hospital. The transverse diameter of the primary tumor was 10.5 cm.

Interventions

The whole pelvis and para-aortic lymph node were irradiated with a total of 50 Gy in 25 fractions, but the size of the tumor showed only a slight decrease to 8.9 cm. After external beam radiotherapy, first-time high-dose-rate interstitial brachytherapy (HDR-ISBT) was administered without “intentional internal high-dose (IIHD) policy,” the technique of high-dose administration to only the inside of the tumor. Considering the rectum dose limitation, in the additional 2 times of brachytherapy, “IIHD policy” HDR-ISBT was applied. In the second and third HDR-ISBT, the percentage of the volume exposed to 200% of the prescribed dose for high-risk clinical target volume increased by 241% and 204% compared with the first HDR-ISBT, while the doses to OARs were not significantly higher than those of the first-time HDR-ISBT.

Outcomes

Complete response was obtained, and no recurrence findings and side effects caused by HDR-ISBT have been detected for 2 years and 9 months.

Lessons

To our knowledge, this is the first report of IIHD HDR-ISBT for bulky cervical cancer. This technique can be the solution for treating bulky cervical cancer.
Tumor grade in soft-tissue sarcoma
Authors: Hong Ji Hyun , Jee Won-Hee , Jung Chan-Kwon , Chung Yang-Guk
Published: June 2020

To determine the value of 3T magnetic resonance imaging (MRI) texture analysis in differentiating high- from low-grade soft-tissue sarcoma.

Forty-two patients with soft-tissue sarcomas who underwent 3T MRI were analyzed. Qualitative and texture analysis were performed on T1-, T2- and fat-suppressed contrast-enhanced (CE) T1-weighted images. Various features of qualitative and texture analysis were compared between high- and low-grade sarcoma. Areas under the receiver operating characteristic curves (AUC) were calculated for texture features. Multivariate logistic regression analysis was used to analyze the value of qualitative and texture analysis.

There were 11 low- and 31 high-grade sarcomas. Among qualitative features, signal intensity on T1-weighted images, tumor margin on T2-weighted images, tumor margin on fat-suppressed CE T1-weighted images and peritumoral enhancement were significantly different between high- and low-grade sarcomas. Among texture features, T2 mean, T1 SD, CE T1 skewness, CE T1 mean, CE T1 difference variance and CE T1 contrast were significantly different between high- and low-grade sarcomas. The AUCs of the above texture features were > 0.7: T2 mean, .710 (95% confidence interval [CI] .543–.876); CE T1 mean, .768 (.590–.947); T1 SD, .730 (.554–.906); CE T1 skewness, .751 (.586–.916); CE T1 difference variance, .721 (.536–.907); and CE T1 contrast, .727 (.530–.924). The multivariate logistic regression model of both qualitative and texture features had numerically higher AUC than those of only qualitative or texture features.

Texture analysis at 3T MRI may provide additional diagnostic value to the qualitative MRI imaging features for the differentiation of high- and low-grade sarcomas.
High rate of burnout among residents under standardized residency training in a tertiary teaching hospital of middle China
Authors: Geng Hongfang , Tan Fang , Deng Yingqing , Lai Lifei , Zhang Jiaqiang , Wu Zhenlong , Liu Peibin , Zhu Qianqian
Published: June 2020

Burnout has been commonly observed in health care workers. Though research has been conducted involving burnout among doctors in China, few studies have focused on residents during standardized residency training (SRT). The professional status of the residents during SRT remains largely unclear. The present study was conducted in order to clarify the prevalence and potential risk factors of burnout in residents during SRT.

An electronic questionnaire comprised 2 parts. The first part was designed to collect some basic characteristic information. Maslach Burnout Inventory-Human Services Survey was included in the second part.

As many as 71.05% residents had at least 1 scale of burnout. Emotional exhaustion (EE) was found in 55.6% residents, depersonalization (DP) in 29.7% and reduced personal accomplishment (RPA) in 41.6%. Being older than 27, senior SRT year, working time more than 60 hours per week and poor sleeping quality was independently associated with at least on scale of burnout. Being unable to receive timely supervisor support significantly increased the probability of DP and EE. Not having friends at work or feeling cared for by the hospital were independently related to all 3 symptoms of burnout as well as overall burnout.

Burnout rate is high in residents under SRT from middle part of China. Organizational, professional, and social support was demonstrated critical by the potential roles in protecting against burnout. Residents with burnout were prone to considering turnover. Strategies for managing burnout related factors among residents should be focused in future studies.
Methylphenidate has mild hyperglycemic and hypokalemia effects and increases leukocyte and neutrophil counts
Authors: Charach Gideon , Karniel Eli , Grosskopf Itamar , Rabinovich Alexander , Charach Lior
Published: June 2020

Various psychotropic drugs may affect the hematological and biochemical profiles of plasma and its metabolism. Carbamazepine, the most well-known psychotropic drug, can cause substantial hyponatremia. Methylphenidate, a piperidine derivative structurally related to amphetamines, acts as a central nervous system stimulant. The current study evaluated whether methylphenidate affects hematological and biochemical parameters of patients diagnosed with attention deficit hyperactivity disorder.

Patients undergoing treatment for attention deficit hyperactivity disorder at our Adolescent Psychiatric Clinic were enrolled in the study. Blood samples for complete blood count and common biochemical analyses were collected before patients started methylphenidate and after 3 months of continuous treatment.

Participants included 64 patients comprised the study cohort. There were 48 (75%) males and 16 (25%) females, with a median age of 16 years (range 11–31). The total median potassium level decreased by 0.6 mg/dL (P < .0001), while glucose rose by 15 mg/dL (P < .0001), sodium decreased in 0.7meq/L, (P = .006). The white blood count rose by 1350 cells/μL (P < .033) due to neutrophilia, lymphocytosis and eosinophilia. Hemoglobin rose slightly by 0.1 (P = .041). Changes in calcium, phosphorus, protein, albumin, and liver enzyme levels were not significant.

The results indicate that methylphenidate may cause hypokalemia and elevated glucose, leukocyte, neutrophil, lymphocyte and eosinophil counts.
Role of psychotherapy on antenatal depression, anxiety, and maternal quality of life
Authors: Li Caixia , Sun Xiaohua , Li Qing , Sun Qian , Wu Beibei , Duan Dongyun
Published: June 2020

Background:

Depression and anxiety are common psychological manifestations encountered during the antenatal stage of pregnancy. Treatments by pharmacological interventions have been reported to impart negative implications on maternal and fetal health outcomes. Therefore, the use of psychotherapeutic interventions to bypass these side-effects and manage depression, anxiety has received a lot of attention. A meta-statistical consensus regarding the intervention is available, but with several limitations. In this study, we attempt to address these limitations and provide the current state of evidence evaluating the influence of psychotherapy on antenatal depression, anxiety, and maternal quality of life.

Objective:

To demonstrate the effects of psychotherapy on depression, anxiety, and maternal quality of life during the antenatal stage of pregnancy.

Methods:

A systematic identification of literature was performed according to PRISMA guidelines on four academic databases: MEDLINE, Scopus, EMBASE, and CENTRAL. A meta-analysis evaluated the influence of psychotherapy on depression, anxiety, and maternal quality of life as compared to conventional obstetric care.

Results:

Out of 1146 records, 22 articles including 2146 pregnant women (mean age: 28.6 ± 2.8 years) were included in this review. This systematic review presents a 1b level of evidence supporting the use of psychotherapy for reducing depression, anxiety and enhancing maternal quality of life. The meta-analysis reveals the beneficial effects of psychotherapy for reducing depression (Hedge g: −0.48), anxiety (−0.47) and enhancing maternal quality of life (0.19) as compared to conventional obstetric care.

Conclusions:

The current systematic review and meta-analysis recommend the use of psychotherapy as for reducing depression, anxiety and enhancing maternal quality of life during the antenatal stage of pregnancy.
Predictors of urinary tract infection in acute stroke patients
Authors: Li Ya-ming , Xu Jian-hua , Zhao Yan-xin
Published: June 2020

Patients with stroke have a high risk of infection which may be predicted by age, procalcitonin, interleukin-6, C-reactive protein, National Institute of Health stroke scale (NHSS) score, diabetes, etc. These prediction methods can reduce unfavourable outcome by preventing the occurrence of infection.

We aim to identify early predictors for urinary tract infection in patients after stroke.

In 186 collected acute stroke patients, we divided them into urinary tract infection group, other infection type groups, and non-infected group. Data were recorded at admission. Independent risk factors and infection prediction model were determined using Logistic regression analyses. Likelihood ratio test was used to detect the prediction effect of the model. Receiver operating characteristic curve and the corresponding area under the curve were used to measure the predictive accuracy of indicators for urinary tract infection.

Of the 186 subjects, there were 35 cases of urinary tract infection. Elevated interleukin-6, higher NIHSS, and decreased hemoglobin may be used to predict urinary tract infection. And the predictive model for urinary tract infection (including sex, NIHSS, interleukin-6, and hemoglobin) have the best predictive effect.

This study is the first to discover that decreased hemoglobin at admission may predict urinary tract infection. The prediction model shows the best accuracy.
Prophylactic antibiotics for miscarriage surgery
Authors: Fu Yu , Jin Ruirui , Wang Xiaoxia , Sun Qingmei , Lin Xiaojuan , Wang Xiaozhuan , Tang Zhongfeng , Song Xiaoyu , Zhao Youhong
Published: June 2020

Background:

Infection is a serious potential consequence of surgery to complete a spontaneous abortion. Antibiotic prophylaxis before some operations has been shown to reduce the risk of postoperative infections. However, for miscarriage surgery, evidence is lacking to show effectiveness.

Methods:

In this systematic review, the electronic databases of Cochrane Central Register of Controlled Trials, EMBASE, and PUBMED will be searched from inception to May 1, 2020. Randomized controlled trials that assessed the effectiveness and safety of antibiotic prophylaxis for preventing infection for patients undergoing miscarriage surgery will be included. All process of the study selection, data extraction, and methodology evaluation will be carried out by two authors independently. RevMan 5.3 software will be utilized for statistical analysis.

Results:

This study will provide a detailed summary of latest evidence related to the effectiveness and safety of antibiotic prophylaxis for preventing infection for patients undergoing miscarriage surgery.

Conclusion:

The findings of this study may provide possible guidance for the use of antibiotic prophylaxis for preventing infection for patients undergoing miscarriage surgery.

Dissemination and ethics:

Ethical approval is not required in this study, because it will not collect the original data from individual patient. The results are expected to publish through a peer-reviewed journal.

Systematic review registration:

PROSPERO CRD CRD42020155643
Different acupuncture therapies for spastic paralysis after stroke
Authors: Wang Ruiqi , Xie Rongfang , Hu Jinwen , Wu Qingzhong , Rao Wangfu , Huang Chunhua
Published: June 2020

Background:

Stroke is emerging as a significant health issue that threatens human health worldwide and as a common sequela of stroke spastic paralysis after stroke (SPAS) has received wide attention. Currently, several systematic reviews have suggested that the commonly used acupuncture therapy (electroacupuncture, fire acupuncture, warm acupuncture, and filiform needle acupuncture) has achieved significant efficacy in the treatment of SPAS. In this study, network meta-analysis will be used to analyze the results of different clinical trials and evaluate the differences in the efficacy of different acupuncture treatments for SPAS.

Methods:

Only randomized controlled trials will be included and all patients were diagnosed as spastic paralysis after stroke. A computer-based retrieval will be conducted at CNKI, WanFang databases, VIP, Sinoed, Pubmed, Embase, Web of Science, and the Cochrane library. The search period limit is from the time the date of database establishment to April 17, 2020. To avoid omissions, we will manually retrieve relevant references and conference papers. The risk of bias in the final included studies will be evaluated based on the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by Revman5.3, WinBUGS 1.4.3, and Stata14.2.

Results:

This study quantified the effectiveness of each intervention for different outcome indicators. The primary outcomes include the Fugl-Meyer Assessment score, the modified Ashworth scale for the assessment of spasticity, and Barthel Index. The secondary outcomes include clinical effectiveness and adverse reactions.

Conclusion:

It will provide evidence-based medical evidence for clinicians to choose more effective acupuncture therapy for SPAS
Treatment of high risk human papillomavirus infection in low grade cervical squamous intraepithelial lesion with mild local thermotherapy
Authors: Yang Yang , Zhang Lan , Qi Ruiqun , Huo Wei , Li Xiaodong , Wu Xin , Chen Hongduo , Gao Xing-Hua
Published: June 2020

Introduction:

Mild local hyperthermia at 44°C has been proven efficacious in the treatment of cutaneous warts induced by human papillomavirus (HPV), while its effect on cervical intraepithelial neoplasia (CIN) caused by high risk type of HPVs has not been reported.

Patient concerns:

Three patients with low grade CIN and positive high risk HPV types (HPV 16, 31, 52, 56, 58) are reported in this study.

Diagnosis:

The diagnosis was based on identification of HPV types and abnormal cytological findings.

Interventions:

The 3 patients were treated with local hyperthermia from ceramic heating (surface temperature, 44°C) to cervix. The treatment was delivered once a day for 3 consecutive days, plus two similar treatments 10 ± 3 days later, with each session lasting 30 minutes. HPV and cytology test were performed 3 months thereafter.

Outcomes:

All the 3 patients recovered to normal cytological findings. Two of the patients were negative for HPV, the remaining patient with pre-treatment HPV 56 and 58 positivity changed to HPV58 positive alone.

Conclusion:

This pilot observation inspires that mild local hyperthermia be recommended as a new method in the treatment of CIN patients with persistent HPV infection, once validated by qualified RCT.
Evaluation of cell-mediated immune response by QuantiFERON Monitor Assay in kidney transplant recipients presenting with infective complications
Authors: Margeta Ivan , Mareković Ivana , Pešut Ana , Zelenika Marina , Dorotić Marija , Mrnjec Ivana , Knotek Mladen
Published: June 2020

The net level of immunosuppression in kidney transplant recipients is difficult to assess. QuantiFERON Monitor (QFM) is an in vitro diagnostic test that detects interferon-γ (IFN-γ) release in peripheral blood. The aim of our study was to compare QFM testing results in stable kidney transplant recipients and kidney transplant recipients with infection, in a single-centre cohort.

We enrolled 71 kidney transplant recipients from our transplantation centre. They were divided into 2 groups according to clinical presentation (Stable kidney transplant recipients or Infection).

There were no significant differences in interferon-γ release between the 2 groups (Stable kidney transplant recipients 140.59 ± 215.28 IU/ml, Infection group 78.37 ± 197.03 IU/ml, P = .24). A further analysis revealed that kidney transplant recipients presenting with bacterial infection had significantly lower IFN-γ release when compared to stable kidney transplant recipients (26.52 ± 42.46 IU/ml vs 140.59 ± 215.28 IU/ml, P = .04).

Kidney transplant recipients presenting with bacterial infection had lower IFN-γ release when compared to stable kidney transplant recipients. The QFM test may be useful as a tool to help guide immunosuppression dosing in kidney transplant recipients, but further studies are required to confirm its diagnostic value.
The association of obesity with health insurance coverage and demographic characteristics: a statewide cross-sectional study
Authors: Mylona Evangelia K. , Benitez Gregorio , Shehadeh Fadi , Fleury Elvira , Mylonakis Sophia C. , Kalligeros Markos , Mylonakis Eleftherios
Published: June 2020

We evaluated the statewide burden of obesity and its complications among government and state funded programs (Medicare and Medicaid) and commercial insurance.

We calculated the prevalence of obesity and the prevalence of relevant comorbidities among different demographic groups and based on health insurance, among adults (18–65 years old) who visited a statewide health network in the state of Rhode Island, in 2017.

The overall prevalence of obesity among 74,089 individuals was 38.88% [Asians 16.77%, Whites 37.49%, Hispanics 44.23%, and Blacks 48.44%]. Medicare or Medicaid beneficiaries were 26% and 27%, respectively, more likely to have obesity than those who had commercial insurance (Odds Ratio:1.26, 95% confidence interval [CI]:1.20–1.32; Odds Ratio:1.27, 95%CI:1.22–1.32). Moreover, Medicaid and Medicare beneficiaries with obesity had a higher prevalence of diabetes compared with privately insured with obesity (10.58% and 10.44% vs 4.45%). Medicare beneficiaries with obesity had a statistically higher prevalence of ischemic heart disease (4.34%, 95%CI: 3.77–4.91) than privately insured (3.21%, 95%CI: 2.94–3.47).

Based on statewide data among 18 to 65 years old adults, Medicare and Medicaid provide health coverage to 40% of individuals with obesity and 46% of those with the obesity-related comorbidities and complications. State and federal health care programs need to support and expand obesity-related services and coverage.
Serum bilirubin level correlates with mortality in patients with traumatic brain injury
Authors: Wang Ruoran , He Min , Xu Jianguo
Published: June 2020

As a catabolic product of hemoglobin, bilirubin has been confirmed playing an important role in the development of various central nervous system disease. The aim of this study is to explore the correlation between serum bilirubin level and mortality in patients with traumatic brain injury (TBI).

Patients admitted with traumatic brain injury (TBI) in our hospital between January 2015 and January 2018 were enrolled in this study. Clinical and laboratory data of 361 patients were retrospectively collected to explore the independent risk factors of mortality.

The comparison of baseline characteristics showed that non-survivors had lower Glasgow Coma Scale (GCS) (P < .001) and higher level of serum total bilirubin (TBIL) (P < .001) and direct bilirubin (DBIL) (P < .001). We found that only GCS (P < .001), glucose (P < .001), lactate dehydrogenase (LDH) (P = .042) and DBIL (P = .005) were significant risk factors in multivariate logistic regression analysis. GCS and DBIL had comparable AUC value (0.778 vs 0.750, P > .05) on predicting mortality in TBI patients. The AUC value of the combination of GCS and DBIL is higher than the single value of these two factors (P < .05). Moreover, predictive model 1 consisted of GCS, glucose, LDH and DBIL had the highest AUC value of 0.894.

DBIL is a significant risk factor of mortality in TBI patients. Assessing the level of DBIL is beneficial for physicians to evaluate severity and predict outcome for TBI patients.
Use sonoelastography to predict the reparability of large-to-massive rotator cuff tears
Authors: Tseng Yu-Hsuan , Chou Wen-Yi , Wu Kuan-Ting , Chang Ching-Di , Chen Yi-Cun , Huang Yu-Chi , Lin Wei-Che , Chen Po-Cheng
Published: June 2020

Introduction:

Most symptomatic large-to-massive rotator cuff tears (RCTs) should be operated, but the surgical reparability depended on the degree of rotator cuff muscle atrophy or fatty infiltration. The orthopedic surgeons will decide whether the teared stump is reparable during the surgery, but preoperative evaluation can be done by some assessment tools. Magnetic resonance imaging (MRI) was used in recent studies to predict the reparability of large-to-massive RCTs, but the clinical availability was not as good as ultrasound. We hypothesize that the ultrasound elastography can predict the reparability of large-to-massive RCTs.

Methods:

This is a prospective observational study and participants with large-to-massive RCTs who are going to have surgeries will be included. Out investigators will evaluate the shoulder passive range of motion (ROM) and strength of all participants. Participants’ degree of shoulder pain and activities of daily living (ADLs) will be assessed by American Shoulder and Elbow Surgeons (ASES) score. The ultrasound elastography will be used to evaluate the tissue quality of supraspinatus muscle and infraspinatus muscle. To test the reliability of the ultrasound elastography, two physicians will perform the ultrasound elastography independently and twenty participants will be selected for the reliability test. Besides, MRI will be used to evaluate the size of tear, the degree of tendon retraction, fatty infiltration of rotator cuff muscles, and muscle atrophy. Finally, the orthopedic surgeons will perform surgeries and decide whether the teared stump can be completely repaired intraoperatively. The primary analysis is the predictive validity of ultrasound elastography for the reparability of large-to-massive RCTs. Before the predictive validity of ultrasound elastography is measured, our investigators will assess the reliability of ultrasound elastography when administered to cases with large-to-massive RCTs, and we will check the correlations between the findings of ultrasound elastography and MRI.

Discussion:

The outcome will provide the evidence of ultrasound elastography for preoperative evaluation of large-to-massive RCTs. The relationships between the findings of ultrasound elastography and MRI will also be examined for further analysis.

Trial registration:

Clinicaltrials.gov NCT03682679. Date of Registration: 25 September 2018, https://clinicaltrials.gov/ct2/show/NCT03682679?cond=rotator+cuff&cntry=TW&draw=2&rank=1.
Does Tc-99m ECD ictal brain SPECT have incremental value in localization of epileptogenic zone and predicting postoperative seizure freedom in cases with discordant video electroencephalogram and MRI findings?
Authors: Pawar Shwetal Uday , Ravat Sangeeta Hasmukh , Muzumdar Dattatraya Prakash , Sankhe Shilpa Sushilkumar , Chheda Akash Harakchand , Manglunia Ashmi Shyam , Maldar Arnaaz Noormohamed
Published: June 2020

Objective

Localization of epileptogenic focus in drug-refractory epilepsy using Tc-99m ethylene cystine dimer (ECD) brain single photon emission computed tomography (SPECT) is less studied in patients with discordant findings on video electroencephalogram (VEEG) and MRI. The study was done to evaluate brain SPECT for epileptogenic focus localization and postoperative seizure freedom.

Methods

Epilepsy patients with discordant VEEG and MRI findings underwent brain SPECT at ictal and interictal phases. Various groups unilateral/bilateral mesial temporal sclerosis (MTS), solitary and multifocal lesional, nonlesional epilepsy were studied for localization of epileptogenic focus and postoperative seizure freedom (>2 years) using Engels classification. Reasons for nonoperability was evaluated in nonoperated group.

Results

SPECT could localize epileptogenic focus in 49/67 (73.13%) and guided surgery in 19/33 (57.57%) patients in operated group. SPECT was useful in 12 (46.12%) of unilateral (2)/bilateral (10) MTS. Postoperative seizure freedom of Engels Class I and II in 22 (66.67%), III in six (18.2%) and IV in one patient based on SPECT findings (P = 0.0086). Overall sensitivity and specificity were 79.3% and 85.7%, respectively. SPECT could localize epileptogenic focus in 23/34 (67.64%) patients in nonoperated group; 10 (29.41%) patients refused for surgery and no epileptogenic focus was localized in the rest of 14 (41.2%).

Conclusion

Ictal SPECT showed incremental value and was found necessary for epileptogenic focus localization and subsequent surgery in unilateral/bilateral MTS in this study. Seizure freedom in patients undergoing epilepsy surgery based on ictal SPECT assistance was comparable to the surgical group not requiring ictal SPECT.
STEMI, Cardiogenic Shock, and Mortality in Patients Admitted for Acute Angiography: Associations and Predictions from Plasma Proteome Data
Authors: Debrabant Birgit , Halekoh Ulrich , Soerensen Mette , Møller Jacob Eifer , Hassager Christian , Frydland Martin , Palstrøm Nicolai , Hjelmborg Jacob , Beck Hans Christian , Rasmussen Lars Melholt
Published: June 2020

Aim:

Acute myocardial infarction (AMI) remains a major cause of mortality and morbidity, and cardiogenic shock (CS) a major cause of hospital mortality after AMI. Especially for ST elevation myocardial infarction (STEMI) patients, fast intervention is essential.

Few proteins have proven clinically applicable for AMI. Most proposed biomarkers are based on a priori hypothesis-driven studies of single proteins, not enabling identification of novel candidates. For clinical use, the ability to predict AMI is important; however, studies of proteins in prediction models are surprisingly scarce.

Consequently, we applied proteome data for identifying proteins associated with definitive STEMI, CS, and all-cause mortality after admission, and examined the ability of the proteins to predict these outcomes.

Methods and Results:

Proteome-wide data of 497 patients with suspected STEMI were investigated; 381 patients were diagnosed with STEMI, 35 with CS, and 51 died during the first year. Data analysis was conducted by logistic and Cox regression modeling for association analysis, and by multivariable LASSO regression models for prediction modeling.

Association studies identified 4 and 29 proteins associated with definitive STEMI or mortality, respectively. Prediction models for CS and mortality (holding two and five proteins, respectively) improved the prediction ability as compared with protein-free prediction models; AUC of 0.92 and 0.89, respectively.

Conclusion:

The association analyses propose individual proteins as putative protein biomarkers for definitive STEMI and survival after suspected STEMI, while the prediction models put forward sets of proteins with putative predicting ability of CS and survival. These proteins may be verified as biomarkers of potential clinical relevance.
SWELL1-LRRC8 complex regulates skeletal muscle cell size, intracellular signalling, adiposity and glucose metabolism
Authors: Kumar Ashutosh , Xie Litao , Ta Chau My , Hinton Antentor J. , Gunasekar Susheel K. , Minerath Rachel A. , Shen Karen , Maurer Joshua M. , Grueter Chad E. , Abel E. Dale , Meyer Gretchen , Sah Rajan
Published: June 2020

Maintenance of skeletal muscle is beneficial in obesity and Type 2 diabetes. Mechanical stimulation can regulate skeletal muscle differentiation, growth and metabolism, however the molecular mechanosensor remains unknown. Here, we show that SWELL1 (LRRC8a) functionally encodes a swell-activated anion channel that regulates PI3K-AKT, ERK1/2, mTOR signaling, muscle differentiation, myoblast fusion, cellular oxygen consumption, and glycolysis in skeletal muscle cells. SWELL1 over-expression in SWELL1 KO myotubes boosts PI3K-AKT-mTOR signaling to supra-normal levels and fully rescues myotube formation. Skeletal muscle targeted SWELL1 KO mice have smaller myofibers, generate less forceex vivo, and exhibit reduced exercise endurance, associated with increased adiposity under basal conditions, and glucose intolerance and insulin resistance when raised on a high-fat diet, compared to WT mice. These results reveal that the SWELL1-LRRC8 complex regulates insulin-PI3K-AKT-mTOR signalling in skeletal muscle to influence skeletal muscle differentiationin vitroand skeletal myofiber size, muscle function, adiposity and systemic metabolismin vivo.
Persistence of viral RNA, widespread thrombosis and abnormal cellular syncytia are hallmarks of COVID-19 lung pathology
Authors: Bussani Rossana , Schneider Edoardo , Zentilin Lorena , Collesi Chiara , Ali Hashim , Braga Luca , Secco Ilaria , Volpe Maria Concetta , Colliva Andrea , Zanconati Fabrizio , Berlot Giorgio , Silvestri Furio , Zacchigna Serena , Giacca Mauro
Published: June 2020

COVID-19 is a deadly pulmonary disease with unique clinical features. A thorough understanding of the molecular and histological correlates of the disease is still missing, especially because post-mortem analysis of COVID-19-affected organs has been so far scant and often anecdotical. Here we report the results of the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. We found that the disease is characterized by extensive alveolar damage and thrombosis of the lung micro- and macro-vasculature. Thrombi were in different stages of organization, consistent with an ongoing, endogenous thrombotic process. In all the analyzed samples, in situ RNA hybridization showed that pneumocytes and vascular endothelial cells had massive presence of viral RNA even at the later stages of the disease. An additional feature of the disease was the presence, in the vast majority of patients, of a large number of dysmorphic pneumocytes, often forming large syncytial elements, a consequence of the fusogenic activity of the viral Spike protein, detected with specific antibodies. Despite occasional presence of virus-positive cells in the heart, no overt signs of viral infection were detected in other organs, which showed common alterations compatible with prolonged hypoxia, multifocal organ disease or previous comorbidities. In summary, COVID-19 is a unique interstitial pneumonia with extensive lung thrombosis, long-term persistence of viral replication in pneumocytes and endothelial cells, along with the presence of infected cellular syncytia in the lung. We propose that several of the COVID-19 disease features are due to the persistence of virus-infected cells in the lungs of the infected individuals for the duration of the disease.
Phylogenomics and phylodynamics of SARS-CoV-2 retrieved genomes from India
Authors: Farah Sameera , Atkulwar Ashwin , Praharaj Manas Ranjan , Khan Raja , Gandham Ravikumar , Baig Mumtaz
Published: June 2020

The ongoing SARS-CoV-2 pandemic is one of the biggest outbreaks after the Spanish flu of 1918. Understanding the epidemiology of viral outbreaks is the first step towards vaccine development programs. This is the first phylodynamics study attempted on of SARS-CoV-2 genomes from India to infer its current evolution in the context of an ongoing pandemic. Out of 286 retrieved SARS-CoV-2 whole genomes from India, 138 haplotypes were generated and analyzed. Median-joining network was built to investigate the relatedness of SARS-CoV-2 haplotypes in India. The BDSIR package of BEAST2 was used to calculate the reproduction number (R0) and the infectious rate of the virus. Past and current population trend was investigated using the stamp date method in coalescent Bayesian skyline plot, implemented in BEAST2 and by exponential growth prior in BEAST 1.10.4. Median-joining network reveals two distinct ancestral clusters A and B showing genetic affinities with Wuhan outbreak sample. The network also illustrates the autochthonous development of isolates in a few instances. High basic reproduction number of SARS-nCoV-2 in India points towards the phase of active community transmission. The Bayesian skyline plot revel exponential rise in the effective population size (Ne) of Indian isolates from the first week of January to the first week of April 2020. More genome sequencing and analyses of the virus will be required in coming days to monitor COVID19 after the upliftment of lock down in India.
Novel coronavirus (COVID-19) Outbreak in Iraq: The First Wave and Future Scenario
Authors: Sarhan Adil R. , Flaih Mohammed H. , Hussein Thaer A. , Hussein Khwam R.
Published: June 2020

The first patient with COVID-19 was reported in Iraq on 24 February 2020 for the Iranian student came from Iran. As of 24 May 2020, the confirmed cases of COVID-19 infections reached 4469, with 160 deaths and 2738 patients were recovered from the infection. Significant public health strategies have been implemented by the authorities to contain the outbreak nationwide. Nevertheless however, the number of cases is still rising dramatically. Here, we aim to describe a comprehensive and epidemiological study of all cases diagnosed in Iraq by 24 May 2020. Most of the cases were recorded in Baghdad followed by Basra and Najaf. About 45% of the patients were female (with 31% deaths of the total cases) and 55% were male (with 68% deaths of the total cases). Most cases are between the ages of (20-59) years old, and (30-39) years are the most affected range (19%) Approximately (8%) of cases are children under 10 years old. Iraq has shown a cure rate lower than those reported by Iran, Turkey and Jordan; and higher than Saudi Arabia and Kuwait. Healthcare workers represented about (5%) of the total confirmed cases. These findings enable us to understand COVID-19 epidemiology and prevalence in Iraq that can alert the our community to the risk of this novel coronavirus and serve as a baseline for future studies.
Household finished flooring and soil-transmitted helminth and Giardia infections among children in rural Bangladesh and Kenya: a prospective cohort study
Authors: Benjamin-Chung Jade , Crider Yoshika S. , Mertens Andrew , Ercumen Ayse , Pickering Amy J. , Lin Audrie , Steinbaum Lauren , Swarthout Jenna , Rahman Mahbubur , Parvez Sarker M. , Haque Rashidul , Njenga Sammy M. , Kihara Jimmy , Null Clair , Luby Stephen P. , Colford John M. , Arnold Benjamin F.
Published: June 2020

Background

Soil-transmitted helminths (STH) and Giardia duodenalis are responsible for a large burden of disease globally. In low-resource settings, household finished floors (e.g., concrete floors) may reduce transmission of STH and G. duodenalis.

Methods

In a prospective cohort of children nested within two randomised trials in rural Bangladesh and Kenya, we estimated associations between household finished flooring and STH and G. duodenalis prevalence. In 2015-2016, we collected stool samples from children aged 2-16 years in rural Bangladesh and Kenya. We detected STH infection using qPCR (Bangladesh N=2,800; Kenya N=3,094) and detected G. duodenalis using qPCR in Bangladesh (N=6,894) and ELISA in Kenya (N=8,899). We estimated adjusted prevalence ratios (aPRs) using log-linear models adjusted for potential confounders.

Findings

At enrolment, 10% of households in Bangladesh and 5% in Kenya had finished floors. In both countries, household finished flooring was associated with lower Ascaris lumbricoides prevalence (Bangladesh aPR: 0.33, 95% CI 0.14, 0.78; Kenya aPR: 0.62, 95% CI 0.39, 0.98) and any STH (Bangladesh aPR: 0.73, 95% CI 0.52, 1.01; Kenya aPR: 0.57, 95% CI 0.37, 0.88). Household finished floors were also associated with lower Necator americanus prevalence in Bangladesh (aPR: 0.52, 95% CI 0.29, 0.94) and G. duodenalis prevalence in both countries (Bangladesh aPR: 0.78, 95% CI 0.64, 0.95; Kenya: aPR: 0.82, 95% CI 0.70, 0.97).

Interpretation

In low-resource settings, living in households with finished floors over a two-year period was associated with lower prevalence of G. duodenalis and certain STH in children.

Funding

Bill & Melinda Gates Foundation grant OPPGD759
Antiviral Drug Screen of Kinase inhibitors Identifies Cellular Signaling Pathways Critical for SARS-CoV-2 Replication
Authors: Garcia Gustavo , Sharma Arun , Ramaiah Arunachalam , Sen Chandani , Kohn Donald , Gomperts Brigitte , Svendsen Clive N. , Damoiseaux Robert D , Arumugaswami Vaithilingaraja
Published: June 2020

Emergence of a highly contagious novel coronavirus, SARS-CoV-2 that causes COVID-19, has precipitated the current global health crisis with over 479,000 deaths and more than 9.3 million confirmed cases. Currently, our knowledge of the mechanisms of COVID-19 disease pathogenesis is very limited which has hampered attempts to develop targeted antiviral strategies. Therefore, we urgently need an effective therapy for this unmet medical need. Viruses hijack and dysregulate cellular machineries in order for them to replicate and infect more cells. Thus, identifying and targeting dysregulated signaling pathways that have been taken over by viruses is one strategy for developing an effective antiviral therapy. We have developed a high-throughput drug screening system to identify potential antiviral drugs targeting SARS-CoV-2. We utilized a small molecule library of 430 protein kinase inhibitors, which are in various stages of clinical trials. Most of the tested kinase antagonists are ATP competitive inhibitors, a class of nucleoside analogs, which have been shown to have potent antiviral activity. From the primary screen, we have identified 34 compounds capable of inhibiting viral cytopathic effect in epithelial cells. Network of drug and protein relations showed that these compounds specifically targeted a limited number of cellular kinases. More importantly, we have identified mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-Damage Response (DDR) pathways as key cellular signaling pathways critical for SARS-CoV-2 infection. Subsequently, a secondary screen confirmed compounds such as Berzosertib (VE-822), Vistusertib (AZD2014), and Nilotinib with anti SARS-CoV-2 activity. Finally, we found that Berzosertib, an ATR kinase inhibitor in the DDR pathway, demonstrated potent antiviral activity in a human epithelial cell line and human induced pluripotent stem cell (hIPSC)-derived cardiomyocytes. These inhibitors are already in clinical trials of phase 2 or 3 for cancer treatment, and can be repurposed as promising drug candidates for a host-directed therapy of SARS-CoV-2 infection. In conclusion, we have identified small molecule inhibitors exhibiting anti SARS-CoV-2 activity by blocking key cellular kinases, which gives insight on important mechanism of host-pathogen interaction. These compounds can be further evaluated for the treatment of COVID-19 patients following additional in vivo safety and efficacy studies.

Disclosures

None declared.
Global and local tension measurements in biomimetic skeletal muscle tissues reveals early mechanical homeostasis
Authors: Hofemeier Arne D. , Limon Tamara , Muenker Till M. , Wallmeyer Bernhard , Jurado Alejandro , Afshar Mohammad E. , Ebrahimi Majid , Gilbert Penney M. , Betz Timo
Published: June 2020

The mechanical properties and tension of muscle tissue are tightly related to proper skeletal muscle function, which makes experimental access to the biomechanics of muscle tissue development a key requirement to advance our understanding of muscle function and development. Recently developed elasticin vitroculture chambers allow for raising 3D muscle tissue under controlled conditions and measurements of tissue force generation. However, these chambers are inherently incompatible with high resolution microscopy limiting their usability to global force measurements, and preventing the exploitation of modern fluorescence based investigation methods for live and dynamic measurements. Here we present a new chamber design pairing global force measurements, quantified from post deflection, with local tension measurements obtained from elastic hydrogel beads embedded in the muscle tissue. High resolution 3D video microscopy of engineered muscle development, enabled by the new chamber, shows an early mechanical tissue homeostasis that remains stable in spite of continued myotube maturation.