bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of cervical sagittal alignment with adjacent segment degeneration and heterotopic ossification following cervical disc replacement with Prestige-LP disc
Authors: Wang Xiaofei , Meng Yang , Liu Hao , Chen Hua , Wang Beiyu , Hong Ying
Published: November 2020

Purpose:

Cervical sagittal balance plays important roles in transmitting the load of the head and maintaining global spinal balance. This study aimed to identify the association of cervical sagittal alignment with adjacent segment degeneration (ASD) and heterotopic ossification (HO) after Prestige-LP cervical disc replacement (CDR).

Methods:

We enrolled 132 patients who underwent one-level Prestige-LP CDR with 2–10 years of follow-up. Cervical sagittal alignment parameters, including the degree of C2–C7 lordosis (CL), functional spinal unit angle (FSUA), sagittal vertical axis (SVA),, and T1 slope (T1s), were measured. ASD and HO were evaluated at the last follow-up. Unpaired t tests and logistic regression analysis were used to identify the associations of cervical sagittal alignment with ASD and HO.

Results:

We found that patients who developed ASD showed significantly lower FSUA (2.1° vs. −1.4°, p < 0.001) and T1s values (28.4° vs. 25.5°, p = 0.029) after surgery. Similarly, the postoperative CL was significantly better in patients without ASD or HO (18.0° vs. 14.4°, p = 0.043). The decrease in the T1s at the last follow-up was significantly larger in the patients with ASD (−11.0° vs. −3.2°, p = 0.003), HO (−6.7° vs. −2.7°, p = 0.050), and ASD or HO (−7.0° vs. −0.8°, p < 0.001) than in those without ASD or HO. Multivariate logistic regression analysis showed that both the FSUA and T1s are associated with ASD and that the degree of CL is associated with postoperative complications.

Conclusion:

The results imply that maintaining cervical sagittal alignment after Prestige-LP CDR is important.
An Acute Pulmonary Coccidioidomycosis Coinfection in a Patient Presenting With Multifocal Pneumonia With COVID-19
Authors: Chang Cameron Casey , Senining Randolph , Kim Jessica , Goyal Rajan
Published: November 2020

The ongoing coronavirus disease-2019 (COVID-19) pandemic has been the focus of health care workers as it has affected millions of people and cost hundreds of thousands of lives around the world. As hospitals struggle to identify and care for those afflicted with COVID-19, it is easy to overlook endemic diseases that potentially worsen or mimic the pulmonary manifestations or may coinfect those with COVID-19. In this case report, we present the case of a 48-year-old Hispanic female who was admitted with respiratory distress from an acute COVID-19 infection but was also found to have acute pulmonary coccidioidomycosis infection and was treated successfully.
Assessment of mental health difficulties in children and young people in care attending a specialist mental health service
Authors: Eadie Kathryn , Wegener Ashleigh , Bergh Warren
Published: November 2020

The purpose of this study is to test the validity of the Assessment Checklist measures in assessing complex mental health and behavioural difficulties of children and young people in care attending a specialist mental health service in Queensland, Australia. Fifty-eight consumers (53% male) with an average age of 8 years were assessed by carers on the Assessment Checklist for Children—Short Form and Strengths and Difficulties Questionnaire, and 44 consumers (36% male) with an average age of 13 years were assessed by carers on the Assessment Checklist for Adolescents—Short Form and Strengths and Difficulties Questionnaire. Results showed that the Assessment Checklist for Children—Short Form total score correlated with the Strengths and Difficulties Questionnaire total score. There were some correlations between subscales on both the measures. The Assessment Checklist for Adolescents—Short Form and Strengths and Difficulties Questionnaire correlated on very few domains. Domains of the Assessment Checklist measures that assess emotional dysregulation, trauma, interpersonal/attachment styles, sexual behaviour and food maintenance appear to provide additional clinical information about consumers that the standard Child and Youth Mental Health Service carer-report measure (Strengths and Difficulties Questionnaire) does not. It is recommended that the Assessment Checklist measures be used as an additional measure to assess the complexity of the children and young people in care who attend specialist mental health services.
Which patients are at high risk of recurrent venous thromboembolism (deep vein thrombosis and pulmonary embolism)?
Authors: Áinle Fionnuala Ní , Kevane Barry
Published: November 2020

Recurrent venous thromboembolism (VTE, or deep vein thrombosis and pulmonary embolism) is associated with mortality and long-term morbidity. The circumstances in which an index VTE event occurred are crucial when personalized VTE recurrence risk is assessed. Patients who experience a VTE event in the setting of a transient major risk factor (such as surgery associated with general anesthesia for >30 minutes) are predicted to have a low VTE recurrence risk following discontinuation of anticoagulation, and limited-duration anticoagulation is generally recommended. In contrast, those patients whose VTE event occurred in the absence of risk factors or who have persistent risk factors have a higher VTE recurrence risk. Here, we review the literature surrounding VTE recurrence risk in a range of clinical conditions. We describe gender-specific risks, including VTE recurrence risk following hormone- and pregnancy-associated VTE events. Finally, we discuss how the competing impacts of VTE recurrence and bleeding have shaped international guideline recommendations.
A phase 3 randomized study of 5-azacitidine maintenance vs observation after transplant in high-risk AML and MDS patients
Authors: Oran Betül , de Lima Marcos , Garcia-Manero Guillermo , Thall Peter F. , Lin Ruitao , Popat Uday , Alousi Amin M. , Hosing Chitra , Giralt Sergio , Rondon Gabriela , Woodworth Glenda , Champlin Richard E.
Published: November 2020

This study investigated the efficacy and safety of azacitidine maintenance in the posttransplant setting based on the encouraging phase 1/2 reports for azacitidine maintenance in patients with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). Between 2009 and 2017, a total of 187 patients aged 18 to 75 years were entered into a randomized controlled study of posttransplant azacitidine if they were in complete remission. Patients randomized to the treatment arm (n = 93) were scheduled to receive azacitidine, given as 32 mg/m2 per day subcutaneously for 5 days every 28 days for 12 cycles. The control arm (n = 94) had no intervention. Eighty-seven of the 93 patients started azacitidine maintenance. The median number of cycles received was 4; a total of 29 patients relapsed on study, and 23 patients withdrew from the study due to toxicity, patient’s preference, or logistical reasons. Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs 1.28 years in the control group (P = .43). There was also no significant difference for overall survival, with a median of 2.52 years vs 2.56 years in the azacitidine and control groups (P = .85), respectively. Multivariate Cox regression analysis revealed no improvement in RFS or overall survival with the use of azacitidine as maintenance compared with the control group (hazard ratios of 0.73 [95% confidence interval, 0.49-1.1; P = .14] and 0.84 [95% confidence interval, 0.55-1.29; P = .43]). This randomized trial with azacitidine maintenance showed that a prospective trial in the posttransplant setting was feasible and safe but challenging. Although RFS was comparable between the 2 arms, we believe the strategy of maintenance therapy merits further study with a goal to reduce the risk of relapse in patients with AML/MDS. This trial was registered at www.clinicaltrials.gov as #NCT00887068.
Constraint and Mobility Change Analysis of Rubik’s Cube-inspired Reconfigurable Joints and Corresponding Parallel Mechanisms
Authors: Li Duanling , Jia Pu , Li Jiazhou , Zhang Dan , Kong Xianwen
Published: November 2020

The current research of reconfigurable parallel mechanism mainly focuses on the construction of reconfigurable joints. Compared with the method of changing the mobility by physical locking joints, the geometric constraint has good controllability, and the constructed parallel mechanism has more configurations and wider application range. This paper presents a reconfigurable axis (rA) joint inspired and evolved from Rubik's Cubes, which have a unique feature of geometric and physical constraint of axes of joint. The effectiveness of the rA joint in the construction of the limb is analyzed, resulting in a change in mobility and topology of the parallel mechanism. The rA joint makes the angle among the three axes inside the groove changed arbitrarily. This change in mobility is completed by the case illustrated by a 3(rA)P(rA) reconfigurable parallel mechanism having variable mobility from 1 to 6 and having various special configurations including pure translations, pure rotations. The underlying principle of the metamorphosis of this rA joint is shown by investigating the dependence of the corresponding screw system comprising of line vectors, leading to evolution of the rA joint from two types of spherical joints to three types of variable Hooke joints and one revolute joint. The reconfigurable parallel mechanism alters its topology by rotating or locking the axis of rA joint to turn all limbs into different phases. The prototype of reconfigurable parallel mechanism is manufactured and all configurations are enumerated to verify the validity of the theoretical method by physical experiments.
Prediction of withdrawal resistance for a screw in hybrid cross-laminated timber
Authors: Pang Sung-Jun , Ahn Kyung-Sun , Kang Seog Goo , Oh Jung-Kwon
Published: November 2020

The aim of this study was to predict the withdrawal resistance of a screw in hybrid cross-laminated timber (CLT) composed of two types of lamina layers. A theoretical model to predict the withdrawal resistance was developed from the shear mechanism between a screw and the layers in hybrid CLT. The parameters for the developed model were the withdrawal stiffness and strength that occurs when a screw is withdrawn, and the penetration depth of a screw in layers of a wood material. The prediction model was validated with an experimental test. Screws with two different diameters and lengths (Ø6.5 × 65 mm and Ø8.0 × 100 mm) were inserted in a panel composed of solid wood and plywood layers, and the withdrawal resistances of the screws were evaluated. At least 30 specimens for each group were tested to derive the lower 5th percentile values. As a result, the developed model predictions were 86–88% of the lower 5th percentile values of hybrid CLT from the properties of the lamina layer. This shows that the withdrawal resistance of hybrid CLT can be designed from the properties of its layer.
Burden of illness of trigeminal neuralgia among patients managed in a specialist center in England
Authors: O’Callaghan Lasair , Floden Lysbeth , Vinikoor-Imler Lisa , Symonds Tara , Giblin Kathryn , Hartford Chris , Zakrzewska Joanna M.
Published: November 2020

Background

Trigeminal neuralgia (TN) causes severe episodic, unilateral facial pain and is initially treated with antiepileptic medications. For patients not responding or intolerant to medications, surgery is an option.

Methods

In order to expand understanding of the pain-related burden of illness associated with TN, a cross-sectional survey was conducted of patients at a specialist center that utilizes a multidisciplinary care pathway. Participants provided information regarding their pain experience and treatment history, and completed several patient-reported outcome (PRO) measures.

Results

Of 129 respondents, 69/128 (54%; 1 missing) reported no pain in the past 4 weeks. However, 84 (65%) respondents were on medications, including 49 (38%) on monotherapy and 35 (27%) on polytherapy. A proportion of patients had discontinued at least one medication in the past, mostly due to lack of efficacy (n = 62, 48%) and side effects (n = 51, 40%). A total of 52 (40%) patients had undergone surgery, of whom 30 had microvascular decompression (MVD). Although surgery, especially MVD, provided satisfactory pain control in many patients, 29% of post-surgical patients reported complications, 19% had pain worsen or stay the same, 48% were still taking pain medications for TN, and 33% reported new and different facial pain.

Conclusions

In most PRO measures, respondents with current pain interference had poorer scores than those without pain interference. In the Patient Global Impression of Change, 79% expressed improvement since beginning of treatment at this clinic. These results indicate that while the multidisciplinary approach can substantially alleviate the impact of TN, there remains an unmet medical need for additional treatment options.
The necessity of routine postoperative laboratory tests after total hip arthroplasty for hip fracture in a semi-urgent clinical setting
Authors: Wu Xiang-Dong , Liu Jia-Cheng , Li Yu-Jian , Wang Jia-Wei , Qiu Gui-Xing , Huang Wei
Published: November 2020

Background

Recent studies suggest that routine postoperative laboratory tests are not necessary after primary elective total hip arthroplasty (THA). This study aims to evaluate the utility of routine postoperative laboratory tests in patients undergoing THA for hip fracture in a semi-urgent clinical setting.

Materials and methods

This retrospective study included 213 consecutive patients who underwent primary unilateral THA for hip fractures. Patient demographics, clinical information, and laboratory tests were obtained from the electronic medical record system. Multivariate logistic regression analysis was performed to identify risk factors associated with abnormal laboratory test-related interventions.

Results

A total of 207 patients (97.18%) had abnormal postoperative laboratory results, which were mainly due to anemia (190/213, 89.20%) and hypoalbuminemia (154/213, 72.30%). Overall, 54 patients (25.35%) underwent a clinical intervention, 18 patients received blood transfusion, and 42 patients received albumin supplementation. Factors associated with blood transfusion were long operative time and low preoperative hemoglobin levels. Factors associated with albumin supplementation were long operative time and low preoperative albumin levels. Of the 33 patients with abnormal postoperative creatinine levels, 7 patients underwent a clinical intervention. For electrolyte abnormalities, sodium supplementation was not given for hyponatremia, three patients received potassium supplementation, and one patient received calcium supplementation.

Conclusions

This study demonstrated a high incidence of abnormal postoperative laboratory tests and a significant clinical intervention rate in patients who underwent THA for hip fracture in a semi-urgent clinical setting, which indicates that routine laboratory tests after THA for hip fracture are still necessary for patients with certain risk factors.

Level of Evidence

Level III.

Trial registration Clinical trial registry number ChiCTR1900020690.
A small-molecule screen reveals novel modulators of MeCP2 and X-chromosome inactivation maintenance
Authors: Lee Hyeong-Min , Kuijer M. Bram , Ruiz Blanes Nerea , Clark Ellen P. , Aita Megumi , Galiano Arjona Lorena , Kokot Agnieszka , Sciaky Noah , Simon Jeremy M. , Bhatnagar Sanchita , Philpot Benjamin D. , Cerase Andrea
Published: November 2020

Background

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. While MeCP2 mutations are lethal in most males, females survive birth but show severe neurological defects. Because X-chromosome inactivation (XCI) is a random process, approximately 50% of the cells silence the wild-type (WT) copy of the MeCP2 gene. Thus, reactivating the silent WT copy of MeCP2 could provide therapeutic intervention for RTT.

Methods

Toward this goal, we screened ~ 28,000 small-molecule compounds from several libraries using a MeCP2-luciferase reporter cell line and cortical neurons from a MeCP2-EGFP mouse model. We used gain/increase of luminescence or fluorescence as a readout of MeCP2 reactivation and tested the efficacy of these drugs under different drug regimens, conditions, and cellular contexts.

Results

We identified inhibitors of the JAK/STAT pathway as XCI-reactivating agents, both by in vitro and ex vivo assays. In particular, we show that AG-490, a Janus Kinase 2 (JAK2) kinase inhibitor, and Jaki, a pan JAK/STAT inhibitor, are capable of reactivating MeCP2 from the inactive X chromosome, in different cellular contexts.

Conclusions

Our results suggest that inhibition of the JAK/STAT pathway is a new potential pathway to reinstate MeCP2 gene expression as an efficient RTT treatment.
Comparative analysis of differentially abundant proteins quantified by LC–MS/MS between flash frozen and laser microdissected OCT-embedded breast tumor samples
Authors: Sturtz Lori A. , Wang Guisong , Shah Punit , Searfoss Richard , Raj-Kumar Praveen-Kumar , Hooke Jeffrey A. , Fantacone-Campbell J. Leigh , Deyarmin Brenda , Cutler Mary Lou , Sarangarajan Rangaprasad , Narain Niven R. , Hu Hai , Kiebish Michael A. , Kovatich Albert J. , Shriver Craig D.
Published: November 2020

Background

Proteomic studies are typically conducted using flash-frozen (FF) samples utilizing tandem mass spectrometry (MS). However, FF specimens are comprised of multiple cell types, making it difficult to ascertain the proteomic profiles of specific cells. Conversely, OCT-embedded (Optimal Cutting Temperature compound) specimens can undergo laser microdissection (LMD) to capture and study specific cell types separately from the cell mixture. In the current study, we compared proteomic data obtained from FF and OCT samples to determine if samples that are stored and processed differently produce comparable results.

Methods

Proteins were extracted from FF and OCT-embedded invasive breast tumors from 5 female patients. FF specimens were lysed via homogenization (FF/HOM) while OCT-embedded specimens underwent LMD to collect only tumor cells (OCT/LMD-T) or both tumor and stromal cells (OCT/LMD-TS) followed by incubation at 37 °C. Proteins were extracted using the illustra triplePrep kit and then trypsin-digested, TMT-labeled, and processed by two-dimensional liquid chromatography-tandem mass spectrometry (2D LC–MS/MS). Proteins were identified and quantified with Proteome Discoverer v1.4 and comparative analyses performed to identify proteins that were significantly differentially expressed amongst the different processing methods.

Results

Among the 4,950 proteins consistently quantified across all samples, 216 and 171 proteins were significantly differentially expressed (adjusted p-value < 0.05; |log2 FC|> 1) between FF/HOM vs. OCT/LMD-T and FF/HOM vs. OCT/LMD-TS, respectively, with most proteins being more highly abundant in the FF/HOM samples. PCA and unsupervised hierarchical clustering analysis with these 216 and 171 proteins were able to distinguish FF/HOM from OCT/LMD-T and OCT/LMD-TS samples, respectively. Similar analyses using significantly differentially enriched GO terms also discriminated FF/HOM from OCT/LMD samples. No significantly differentially expressed proteins were detected between the OCT/LMD-T and OCT/LMD-TS samples but trended differences were detected.

Conclusions

The proteomic profiles of the OCT/LMD-TS samples were more similar to those from OCT/LMD-T samples than FF/HOM samples, suggesting a strong influence from the sample processing methods. These results indicate that in LC–MS/MS proteomic studies, FF/HOM samples exhibit different protein expression profiles from OCT/LMD samples and thus, results from these two different methods cannot be directly compared.
Development of an aquatic exposure assessment model for Imidacloprid in sewage treatment plant discharges arising from use of veterinary medicinal products
Authors: Anthe Mechthild , Valles-Ebeling Beatrice , Achtenhagen Jan , Arenz-Leufen Martina , Atkinson Jackie , Starp Michael , Corsing Christian
Published: November 2020

Background

Imidacloprid is an active ingredient included in plant protection, biocidal and veterinary medicinal products (VMPs). VMPs containing Imidacloprid are formulated as spot-on products or collars and designed to protect pets, predominantly dogs and cats, from parasite infestation. Monitoring data collected under the Water Framework Directive between 2016 and 2018 showed detectable and varying levels of Imidacloprid in the UK surface water bodies. The aim of the work was to investigate the potential contribution of VMPs by developing a model for predicting the emissions from sewage treatment plants from the use of dog and cat spot-on and collar VMPs. Due to the absence of appropriate exposure models for VMPs, the model was built based on the principles of environmental exposure assessment for biocidal products.

Results

Three emission paths were considered to be the most likely routes for repeated emissions to waterways from the use of spot-on and collar VMPs, i.e., transfer to pet bedding followed by washing, washing/bathing of dogs, and walking dogs in the rain. The developed model was used to calculate the Imidacloprid concentrations in surface water after discharge from wastewater treatment plants. Realistic worst-case input parameters were deduced from sales and survey data and experimental studies. Modelled total concentrations in surface water for each pathway ranged from 0.84 to 4.8 ng/L. The calculated concentrations did not exceed the ecological thresholds for the most sensitive aquatic invertebrate organisms and were found to be much lower than the UK monitoring data for river water. For example, the calculated concentration from the bathing/washing of dogs was < 3% of the highest levels of Imidacloprid measured in surface waters.

Conclusion

In conclusion, a model has been successfully built and applied. The modelled data indicate that these VMPs make only a very small contribution to the levels of Imidacloprid observed in the UK water monitoring programme. Further, calculated concentrations do not exceed ecotoxicological threshold values indicating acceptable chronic safety to aquatic organisms.
Can a chemical be both readily biodegradable AND very persistent (vP)? Weight-of-evidence determination demonstrates that phenanthrene is not persistent in the environment
Authors: Hughes Christopher B. , Brown David M. , Camenzuli Louise , Redman Aaron D. , Arey J. Samuel , Vione Davide , Wang Neil , Vaiopoulou Eleni
Published: November 2020

Under the European REACH regulation, chemicals are assessed for persistence as part of weight-of-evidence determinations of persistence, bioaccumulation and toxicity (PBT), as required under Annex XIII and supported by an Integrated Assessment and Testing Strategy (ITS). This study describes the persistence assessment of phenanthrene, a data-rich polycyclic aromatic hydrocarbon (PAH), in accordance with this framework. All available data from screening and simulation tests, for water, soil and sediment compartments, plus other relevant information, have been compiled. These have been evaluated for reliability and relevance, and a weight-of-evidence determination of persistence has been carried out. Aspects relevant to the assessment, such as degradation metabolites, non-extractable residues (NER), test temperature and bioavailability, have also been considered. The resulting assessment considered a wide range of evidence, including 101 experimental data points. Phenanthrene was demonstrated to be readily biodegradable, a first-tier screen for non-persistence in the ITS. Furthermore, weight-of-evidence assessment of data for water, soil and sediment compartments supported a conclusion of “not persistent” (not P). In non-standard soil studies with sludge-amended soils, longer half-lives were observed. This was attributable to pyrogenic sources of and significantly reduced bioavailability of phenanthrene, highlighting the importance of bioavailability as a major source of variability in persistence data. Available simulation test data for the sediment compartment were found to be unreliable due to the anoxic impact of the use of a biodegradable solvent in a closed system, and were inconsistent with the broader weight of evidence. Estimation of photodegradation using AOPWIN and the APEX model demonstrated this to be an important fate process not currently considered in persistence assessments under REACH. The assessment is not in agreement with a recent regulatory decision in which phenanthrene was determined to be very persistent (vP). This assessment provides a case study for persistence assessment using the REACH ITS and highlights the need for improved guidance to improve consistency and predictability of assessments. This is particularly important for complex cases with data-rich chemicals, such as phenanthrene.
Long term outcomes of colon polyps with high grade dysplasia following endoscopic resection
Authors: Chang Jia-Jang , Chien Cheng-Hung , Chen Shuo-Wei , Chen Li-Wei , Liu Ching-Jung , Yen Cho-Li
Published: November 2020

Background

The risk of recurrent colonic adenoma associated with high-grade dysplasia (HGD) colon polyps at baseline colonoscopy remains unclear. We conducted a clinical cohort study with patients who underwent polypectomy during screen colonoscopy to assess recurrent colonic adenoma risk factors.

Methods

11,565 patients at our facility underwent screen colonoscopy between September 1998 and August 2007. Data from patients with HGD colon polyps who had undergone follow-up colonoscopy were included for analysis.

Results

Data from 211 patients was included. Rates of metachronous adenoma and advanced adenoma at follow-up were 58% and 20%, respectively. Mean follow-up period was 5.5 ± 1.8 (3–12) years. Univariate logistic regression analysis revealed that an adenoma count of ≥ 3 at baseline colonoscopy was strongly associated with overall recurrence, multiple recurrence, advanced recurrence, proximal recurrence, and distal adenoma recurrence with odds ratios of 4.32 (2.06–9.04 95% CI), 3.47 (1.67–7.22 95% CI), 2.55 (1.11–5.89 95% CI), 2.46 (1.16–5.22 95% CI), 2.89 (1.44–5.78 95% CI), respectively. Multivariate analysis revealed gender (male) [P = 0.010; OR 3.09(1.32–7.25 95% CI)] and adenoma count ≥ 3 [P = 0.002; OR 3.08(1.52–6.24 95% CI)] at index colonoscopy to be significantly associated with recurrence of advanced adenoma.

Conclusion

Recurrence of colonic adenoma at time of follow-up colonoscopy is common in patients who undergo polypectomy for HGD colon adenomas during baseline colonoscopy. Risk of further developing advanced adenomas is associated with gender and the number of colon adenomas present.
Evaluation of TaqMan Array card (TAC) for the detection of 28 respiratory pathogens
Authors: Liu Keke , Jing Hongbo , Chen Ying , Zheng Xin , Jiang Hua , Kong Decong , Zheng Yvling , Chen Shuiping , Liu Peng , Jiang Yongqiang
Published: November 2020

Background

Respiratory infections are a serious threat to human health. So, rapid detection of all respiratory pathogens can facilitate prompt treatment and prevent the deterioration of respiratory disease. Previously published primers and probes of the TaqMan array card (TAC) for respiratory pathogens are not sensitive to Chinese clinical specimens. This study aimed to develop and improve the TAC assay to detect 28 respiratory viral and bacterial pathogens in a Chinese population.

Methods

To improve the sensitivity, we redesigned the primers and probes, and labeled the probes with minor groove binders. The amplification efficiency, sensitivity, and specificity of the primers and probes were determined using target-gene containing standard plasmids. The detection performance of the TAC was evaluated on 754 clinical specimens and the results were compared with those from conventional methods.

Results

The performance of the TAC assay was evaluated using 754 clinical throat swab samples and the results were compared with those from gold-standard methods. The sensitivity and specificity were 95.4 and 96.6%, respectively. The lowest detection limit of the TAC was 10 to 100 copies/μL.

Conclusions

TAC is an efficient, accurate, and high-throughput approach to detecting multiple respiratory pathogens simultaneously and is a promising tool for the identification of pathogen outbreaks.
A novel genetic variant in DNAI2 detected by custom gene panel in a newborn with Primary Ciliary Dyskinesia: case report
Authors: Rocca Maria Santa , Piatti Gioia , Michelucci Angela , Guazzo Raffaella , Bertini Veronica , Vinanzi Cinzia , Caligo Maria Adelaide , Valetto Angelo , Foresta Carlo
Published: November 2020

Background

Primary ciliary dyskinesia (PCD) is a highly heterogeneous genetic disorder caused by defects in motile cilia. The hallmark features of PCD are the chronic infections of the respiratory tract, moreover, clinical manifestations include also laterality defects and risk of male infertility.

Clinical phenotypes of PCD are the result of mutations in genes encoding components of axonema or factors involved in axonemal assembly. Recent studies have identified over 45 PCD-associated genes, therefore, molecular analysis represents a powerful diagnostic tool to confirm and uncover new genetic causes of this rare disease.

Case presentation

Here, we describe a female infant of Moroccan origin with normal pressure hydrocephalus (NPH) in addition to most common PCD symptoms. Transmission Electron Microscopy (TEM) and molecular tests, such as a Next generation Sequencing panel and a custom array CGH, were performed for diagnosis of PCD. TEM revealed outer dynein arm (ODA) defects, whilst molecular analyses detected a novel 6,9 kb microdeletion in DNAI2 gene.

Conclusions

Since DNAI2 mutations are very rare, this case report contributes to better delineate the important role of DNAI2 as causative of PCD phenotype, suggesting, furthermore, that the variations in DNAI2 may be as a new genetic risk factor for NPH. Indeed, although the association of hydrocephalus with PCD has been well documented, however, only a small number of human patients show this defect.

Furthermore, this study highlights the importance of high-throughput technologies in advancing our understanding of heterogeneous genetic disorders.
Effect of hydroxychloroquine in patients with IgA nephropathy with insufficient responses to immunosuppressive therapy: a retrospective case-control study
Authors: Tang Chen , Lv Ji-Cheng , Shi Su-Fang , Chen Yu-Qing , Liu Li-Jun , Zhang Hong
Published: November 2020

Background

Hydroxychloroquine (HCQ) is a well-known immunomodulator that was recently used in immunoglobulin A (IgA) nephropathy (IgAN) due to its antiproteinuric effects. We investigated the effects of HCQ in patients with IgAN whose proteinuria remained above 1 g/d after conventional immunosuppressive (IS) therapy.

Methods

This study was a retrospective case-control study. Twenty-six patients with IgAN who received HCQ and had insufficient responses to IS therapy (corticosteroid (CS) therapy with/without IS agents) were included. Twenty-six matched historical controls who received conventional IS therapy were selected using propensity score matching. The clinical data from 6 months were compared.

Results

Proteinuria at baseline was comparable between the “IS therapy plus HCQ” and “conventional IS therapy” groups (2.35 [interquartile range (IQR), 1.47, 2.98] vs. 2.35 [IQR, 1.54, 2.98] g/d, p = 0.920). A significant reduction in proteinuria was noted in IgAN patients with HCQ treatment (2.35 [IQR, 1.47, 2.98] vs. 1.10 [IQR, 0.85, 1.61] g/d, p = 0.002). The percent reduction in proteinuria at 6 months was similar between the two groups (− 39.81% [− 66.26, − 12.37] vs. -31.99% [− 67.08, − 9.14], p = 0.968). The cumulative frequency of patients with a 50% reduction in proteinuria during the study was also comparable between the two groups (53.8% vs. 57.7%, p = 0.780). No serious adverse events (SAEs) were observed during the study.

Conclusions

Use of HCQ achieved has similar reduction in proteinuria compared to conventional IS therapy in patients with IgAN who had insufficient responses to IS therapy.
Elevated blood urea nitrogen is associated with recurrence of post-operative chronic subdural hematoma
Authors: Wang Ning , Hu Jiangnan , Oppong-Gyebi Anthony , Zhu Xuanhao , Li Yihao , Yang Jianjing , Ruan Linhui , Zhuge Qichuan , Ye Sheng
Published: November 2020

Background

Chronic subdural hematoma (CSDH) is fundamentally treatable with about a 2–31% recurrence rate. Recently, there has been renewed interest in the association between Blood Urea Nitrogen (BUN) and intracranial lesion. Therefore, this paper attempts to show the relationship between BUN and CSDH recurrence.

Methods

A total of 653 CSDH cases with Burr-hole Irrigation (BHI) were enrolled from December 2014 to April 2019. The analyzed parameters included age, gender, comorbidities, laboratory investigations, medication use and hematoma location. The cases were divided into recurrence and non-recurrence groups while postoperative BUN concentration was further separated into quartiles (Q1 ≤ 4.0 mmol/L, 4.0 < Q2 ≤ 4.9 mmol/L, 4.9 < Q3 ≤ 6.4 mmol/L, Q4 > 6.4 mmol/L). Restricted cubic spline regressions and logistic regression models were performed to estimate the effect of BUN on CSDH recurrence.

Results

CSDH recurrence was observed in 96 (14.7%) cases. Significant distinctions were found between recurrence and non-recurrence groups in postoperative BUN quartiles of cases (P = 0.003). After adjusting for the potential confounders, the odds ratio of recurrence was 3.069 (95%CI =1.488–6.330, p = 0.002) for the highest quartile of BUN compared with the lowest quartile. In multiple-adjusted spline regression, a high BUN level visually showed a significantly high OR value of recurrence risk.

Conclusions

Elevated BUN at post-operation is significantly associated with the recurrence of CSDH, and it is indicated that high levels of serum BUN after evacuation may serve as a risk factor for CSDH recurrence.
Improving outcomes after autologous transplantation in relapsed/refractory Hodgkin lymphoma: a European expert perspective
Authors: Sureda Anna , André Marc , Borchmann Peter , da Silva Maria G. , Gisselbrecht Christian , Vassilakopoulos Theodoros P. , Zinzani Pier Luigi , Walewski Jan
Published: November 2020

Autologous stem cell transplantation (ASCT) is a well-established approach to treatment of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) recommended by both the European Society for Medical Oncology and the National Comprehensive Cancer Network based on the results from randomized controlled studies. However, a considerable number of patients who receive ASCT will progress/relapse and display suboptimal post-transplant outcomes. Over recent years, a number of different strategies have been assessed to improve post-ASCT outcomes and augment HL cure rates. These include use of pre- and post-ASCT salvage therapies and post-ASCT consolidative therapy, with the greatest benefits demonstrated by targeted therapies, such as brentuximab vedotin. However, adoption of these new approaches has been inconsistent across different centers and regions.

In this article, we provide a European perspective on the available treatment options and likely future developments in the salvage and consolidation settings, with the aim to improve management of patients with HL who have a high risk of post-ASCT failure.

Conclusions

We conclude that early intervention with post-ASCT consolidation improves outcomes in patients with R/R HL who require ASCT. Future approvals of targeted agents are expected to further improve outcomes and provide additional treatment options in the coming age of personalized medicine.
A large decrease in the magnitude of seasonal fluctuations in mortality among elderly explains part of the increase in longevity in Sweden during 20th century
Authors: Ledberg Anders
Published: November 2020

Background

Mortality rates are known to depend on the seasons and, in temperate climates, rates are highest during winter. The magnitude of these seasonal fluctuations in mortality has decreased substantially in many countries during the 20th century, but the extent to which this decrease has contributed to the concurrent increase in life expectancy is not known. Here, I describe how the seasonality of all-cause mortality among people ages 60 years or more has changed in Sweden between 1860 and 1995, and investigate how this change has contributed to the increase in life expectancy observed during the same time period.

Methods

Yearly sex-specific birth cohorts consisting of all people born in Sweden between 1800 and 1901 who reached at least 59 years of age were obtained from a genealogical database. The mortality rates for each cohort were modeled by an exponential function of age modulated by a sinusoidal function of time of year. The potential impact of seasonal fluctuations on life expectancy was investigated by a novel decomposition of the total mortality rate into a seasonal part and a part independent of the seasons. Cohort life expectancy at age 60 was used to quantify changes in lifespan during the time period.

Results

The magnitude of seasonal fluctuations in mortality rates decreased substantially between 1860 and 1995. For cohorts born in 1800, the risk of dying during the winter season was almost twice that of dying during summer. For cohorts born in 1900, the relative increase in winter mortality was 10%. Cohort life expectancy at age 60 increased by 4.3 years for men and 6.8 years for women, and the decrease in seasonal mortality fluctuations accounted for approximately 40% of this increase in average lifespan.

Conclusion

By following a large number of extinct cohorts, it was possible to show how the decrease in seasonal fluctuations in mortality has contributed to an increase in life expectancy. The decomposition of total mortality introduced here might be useful to better understand the processes and mechanisms underlying the marked improvements in life expectancy seen over the last 150 years.
Disability-adjusted life years for respiratory syncytial virus in children under 2 years
Authors: Villamil Juana Patricia Sánchez , Polack Fernando P. , Buendía Jefferson Antonio
Published: November 2020

Background

Respiratory syncytial virus infection is the leading cause of bronchiolitis in Colombia. There is growing evidence about the impact of Respiratory syncytial virus on society in terms of years of life lost due to this condition. The objective of the present study is to determine the Disability-Adjusted Life Years for respiratory syncytial virus in children under 2 years in Colombia.

Methods

Data from the national epidemiological surveillance system were used to estimate DALYs, calculated from the sum of years of life lost and years lived with disability due to RSV infection in Colombia. A bootstrapped method with 10,000 iterations was used to estimate each statistical parameter using the package DALY calculator in R.

Results

In 2019, 260,873 years of life (CI95% 208,180–347,023) were lost due to RSV bronchiolitis in Colombian children under 2 years. The estimated rate was 20 DALYs / 1000 person-year (95% CI 16–27).

Conclusion

This is the first report estimating the impact of RSV bronchiolitis morbidity and mortality in Colombia. The findings of the present study suggest that the actual burden and cost of bronchiolitis due to RSV is high. Prevention strategies, such as RSV vaccination, to reduce morbidity associated with RSV infection should be encouraged in our country.
Serum and salivary levels of lactate dehydrogenase in oral squamous cell carcinoma, oral lichen planus and oral lichenoid reaction
Authors: Gholizadeh Narges , Alipanahi Ramandi Maryam , Motiee-Langroudi Maziar , Jafari Mehrdad , Sharouny Hadi , Sheykhbahaei Nafiseh
Published: November 2020

Background

Increased levels of lactate dehydrogenase (LDH) as a tumor marker have been reported in malignant and some premalignant oral lesions such as oral lichen planus (OLP) and oral lichenoid reactions (OLRs). This study aimed to assess the level of total LDH in the saliva and serum of patients with oral squamous cell carcinoma (OSCC), OLP and OLRs.

Methods

In this case–control study, the participants were divided into four groups (n = 25) of healthy controls, OLP, OLRs, and OSCC. The serum and stimulated/unstimulated salivary levels of LDH were spectrophotometrically measured using standard LDH kits (Pars Azmoun). One-way ANOVA, Chi-square test, Pearson’s correlation test, and receiver operating characteristic (ROC) analysis were applied to analyze the data.

Results

The serum and salivary levels of LDH in OSCC patients were significantly higher than that the corresponding values in other groups (P = 0.0001). The serum level of LDH in OLR group was significantly higher than that in the control and OLP groups (P = 0.0001), but the difference in salivary level of LDH was not significant. The ROC analysis showed that both the serum and salivary levels of LDH had significant diagnostic ability for detection of OSCC and OLRs. Significant associations were noted between the serum and salivary levels of LDH.

Conclusions

Patients with OSCC and OLRs had higher serum levels of LDH than OLP and control groups. Further prospective longitudinal studies are required to assess the tissue level of LDH and monitor the transformation of OLRs because they have low rate of malignant transformation compared with other oral premalignant lesions.
Jianpi Yangwei decoction promotes apoptosis and suppresses proliferation of 5-fluorouracil resistant gastric cancer cells in vitro and in vivo
Authors: Tang Huijuan , Huang Wenjie , Yang Qiang , Lin Ying , Chen Yihui , Shu Peng
Published: November 2020

Background

The exploration of new therapeutic agents targeting 5-Fu resistance may open a new opportunity to gastric cancer treatment. The objective is to establish a 5-Fu resistant gastric cancer cell line and observe the effect of Jianpi Yangwei decoction (JPYW) on its apoptosis and drug-resistance related proteins.

Methods

MTT assay was used to measure the effect of JPYW on the BGC823 cells proliferation, and the apoptosis was observed by flow cytometry and Hoechst fluorescence staining. The BGC823 xenograft tumor nude mice models were established, the apoptosis was detected by Tunel method. BGC-823/5-Fu was established by repeated low-dose 5-Fu shocks, the drug resistance index and proliferation were detected by the MTT assay; MDR1 mRNA was detected by real-time RT-PCR; Western blot was used to detect the ratio of p-AKT to AKT; The BGC823/5-Fu xenograft tumor nude mice models were established and apoptosis was measured. The expressions of MRP1, MDR1, ABCG2, AKT, p-AKT, caspase-3 and bcl-2 were detected by immunohistochemistry and the AKT mRNA expression was detected by real-time RT-PCR.

Results

JPYW induced apoptosis in BGC823 cells; Drug-resistant cell line BGC-823/5-Fu was sucessfully established; JPYW induced apoptosis of BGC823/5-Fu cells, down-regulated the expression of MRP1, MDR1 and ABCG2 in vitro and in vivo, and further decreased MDR1 expression when combined with pathway inhibitor LY294002 (P < 0.05); JPYW down-regulated the ratio of p-AKT to AKT in vitro in a dose-dependent manner, the same as after the combination with LY294002 (P < 0.05).

Conclusion

JPYW can induce apoptosis of BGC823 and BGC823/5-Fu cells, and down-regulate the expression of MDR1, MRP1, ABCG2 in vitro and in vivo. Its in vitro effect is related to the PI3K/AKT signaling pathway.
Disclosure of herbal medicine use to health care providers among pregnant women in Nepal: a cross-sectional study
Authors: Ahmed Mansoor , Im Hyea Bin , Hwang Jung Hye , Han Dongwoon
Published: November 2020

Background

Pregnant women’s disclosure of herbal medicine (HM) use to their health care providers during pregnancy is crucial, as misuse of HM can have a detrimental effect on both pregnant woman and the fetus. However, the lack of disclosure of HM use to physicians remains a public health concern in developing countries such as Nepal.

Methods

A cross-sectional study was conducted among 400 postpartum women admitted at Maternity and Women’s Hospital located in Kathmandu, Nepal. The survey instrument included 30 questions on the use of HM during pregnancy, sociodemographic and health characteristics, and pregnancy outcomes. Chi-square test and logistic regression were conducted for data analysis using SPSS ver. 21.0., and a p-value of less than 0.05 was considered statistically significant for all analyses.

Results

60.3% of respondents used at least one herbal remedy during their previous pregnancy, and the overall disclosure rate of HM use to healthcare providers was 54.6%. Women with secondary education level and four or more antenatal care visits were more likely to disclose their HM use to healthcare providers.

Conclusions

This study highlights that despite the popular use of HM among pregnant women in Nepal, most women obtained HM-related information from informal sources and did not disclose their HM use to physicians. To ensure the safe use of HM, physicians should integrate questions regarding patients’ HM use into their routine patient assessments to facilitate active communication and improve the quality of care.
Gender differences in the effect of medical humanities program on medical students’ empathy: a prospective longitudinal study
Authors: Lwow Michal , Canetti Laura , Muszkat Mordechai
Published: November 2020

Background

Previous studies have suggested that Medical students’ empathy declines during medical school, especially during the clinical studies. The aim of this study was to examine. Changes in medical students’ empathy during their first clinical experience, and to determine the impact of gender and humanities curriculum on empathy changes.

Methods

In this prospective longitudinal study, 262 4th year students from three consecutive classes were assessed. Empathy was assessed before and at 4th-year-end, using the Jefferson Scale of Physician Empathy-Student Version (JSPE-S). The three classes differed in humanities curriculum [limited Medical Humanities (MH(lim)) vs. extended Medical Humanities (MH(ext))], and in admission system [Personal Interview (PI) vs. multiple mini interviews (MMI)].

Results

Overall, there was a small but significant decrease in JSPE-S during the fourth year (114.40 ± 11.32 vs. 112.75 ± 14.19, p = 0.034). Among men there was a statistically significant decline in JSPE-S during the fourth year, and the MH(ext) (but not the MH(lim)) was associated with the decline (t(35) = 2.38, p = 0.023). Women students showed no decline in empathy during the fourth-year of studies, regardless of type of humanities program. In addition, women who participated in MH(ext) had a higher JSPE-S scores during the 4th -year as compared to women who participated in MH(lim).

Conclusion

Pre-clinical humanities program was associated with a decline in empathy among men medical students during the fourth-year of medical studies. Gender differences in response to medical humanities programs require further study.