bluuebunny/crossref_metadata_2025 huggingface dataset:
Pain and load progression following an early maximal strength training program in total hip- and knee arthroplasty patients
Authors: Winther Siri B , Foss Olav A , Klaksvik Jomar , Husby Vigdis S
Published: April 2020

Purpose:

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients significantly increase muscle strength after maximal strength training (MST) initiated soon after surgery. Owing to severe postoperative pain, knee patients are anticipated to be more limited in performing heavy load exercises than hip patients. The aim of the present study was to describe pain and load progression during early MST in THA and TKA patients.

Methods:

Explorative study based on secondary analyses from two randomized controlled trials: 26 THA and 16 TKA patients had their training sessions logged. They trained at 85–90% of their maximal capacity in leg press, and abduction/knee-extension of the operated leg (4 × 5 repetitions) for 8–10 weeks, initiated early postoperatively.

Results:

Knee patients experienced significantly more pain than hip patients during the training sessions ( p < 0.03), however, pain before and after training was not different ( p > 0.09). All patients significantly increased leg press training load until the last intervention week ( p < 0.01).

Conclusion:

This study demonstrates that TKA patients experience more pain than THA patients during training following a MST program but not more than moderate levels during or after training. Pain before and after training is not different. Both groups significantly increased load progression during the intervention. These findings indicate that both THA and TKA patients might perform MST with extensive load progression early after surgery without compromising pain. The studies were registered at ClinicalTrials.gov .
Clinical characteristics, management, and outcome of incidental pulmonary embolism in cancer patients
Authors: Qdaisat Aiham , Kamal Mona , Al-Breiki Aisha , Goswami Biman , Wu Carol C. , Zhou Shouhao , Rice Terry W. , Alagappan Kumar , Yeung Sai-Ching Jim
Published: April 2020

Incidental pulmonary embolisms (IPEs) are common in cancer patients. Examining the characteristics and outcomes of IPEs in cancer patients can help to ensure proper management, promoting better outcomes. To determine the clinical characteristics, management, and outcomes of IPEs for cancer patients, we conducted a 1:2 ratio case-control study and identified all consecutive patients with IPE who visited the emergency department at The University of Texas MD Anderson Cancer Center between 1 January 2006 and 1 January 2016. Each IPE case was matched with 2 controls using a propensity score obtained using logistic regression for IPE status with other factors affecting overall survival. A total of 904 confirmed cases were included in the analysis. IPE frequently occurred during the first year after cancer diagnosis (odds ratio [OR], 2.79; 95% confidence interval [95% CI], 2.37-3.29; P < .001). Patients receiving cytotoxic chemotherapy had a nearly threefold greater risk of developing IPE (OR, 2.87; 95% CI, 2.42-3.40; P < .001). In-hospital mortality was 1.9%. The 7- and 30-day mortality rates among the cases were 1.8% and 9.9%, respectively, which was significantly higher than in the control groups: 0.2% and 3.1%, respectively (P < .001). IPE was associated with reduced overall survival (hazard ratio [HR], 1.93; 95% CI, 1.74-2.14; P < .001). Concurrent incidental venous thromboembolism was identified in 189 of the patients (20.9%) and was also associated with reduced overall survival (HR, 1.65; 95% CI, 1.21-2.25; P = .001). Our results show that IPE events are associated with poor outcomes in cancer patients. Proper management plans similar to those of symptomatic pulmonary embolisms are essential.
Facile Approach to Prepare rGO@Fe3O4 Microspheres for the Magnetically Targeted and NIR-responsive Chemo-photothermal Combination Therapy
Authors: Liang Chunyong , Song Jiying , Zhang Yongguang , Guo Yaping , Deng Meigui , Gao Wei , Zhang Jimin
Published: April 2020

Near-infrared (NIR)-light responsive graphene have been shown exciting effect on cancer photothermal ablation therapy. Herein, we report on the preparation of Fe3O4-decorated hollow graphene microspheres (rGO@Fe3O4) by a facile spray drying and coprecipitation method for the magnetically targeted and NIR-responsive chemo-photothermal combination therapy. The microspheres displayed very high specific surface area (~ 120.7 m2 g−1) and large pore volume (~ 1.012 cm3 g−1), demonstrating distinct advantages for a high loading capacity of DOX (~ 18.43%). NIR triggered photothermal effect of the rGO@Fe3O4microspheres responded in an on-off manner and induced a high photothermal conversion efficiency. Moreover, The Fe3O4on the microspheres exhibited an excellent tumor cells targeting ability. The chemo-photothermal treatment based on rGO@Fe3O4/DOX showed superior cytotoxicity towards Hela cells in vitro. Our studies indicated that rGO@Fe3O4/DOX microcapsules have great potential in combined chemo-photothermal cancer treatment.
Effects of resveratrol on cariogenic virulence properties of Streptococcus mutans
Authors: Li Jinheng , Wu Tiantian , Peng Weiwei , Zhu Yaqin
Published: April 2020

Background

Streptococcus mutans is the principal etiological agent of human dental caries. The major virulence factors of S. mutans are acid production, acid tolerance, extracellular polysaccharide (EPS) synthesis and biofilm formation. The aim of this study is to evaluate the effect of resveratrol, a natural compound, on virulence properties of S. mutans.

Results

Resveratrol at sub-MIC levels significantly decreased acid production and acid tolerance, inhibited synthesis of water-soluble polysaccharide and water-insoluble polysaccharide, compromised biofilm formation. Related virulence gene expression (ldh, relA, gtfC, comDE) was down-regulated with increasing concentrations of resveratrol.

Conclusions

Resveratrol has an inhibitory effect on S. mutans cariogenic virulence properties and it represents a promising anticariogenic agent.
Ventriculoperitoneal shunt insertion in human immunodeficiency virus infected adults: a systematic review and meta-analysis
Authors: Loan James J. M. , Poon Michael T. C. , Tominey Steven , Mankahla Ncedile , Meintjes Graeme , Fieggen A. Graham
Published: April 2020

Background

Hydrocephalus is a common, life threatening complication of human immunodeficiency virus (HIV)-related central nervous system opportunistic infection which can be treated by insertion of a ventriculoperitoneal shunt (VPS). In HIV-infected patients there is concern that VPS might be associated with unacceptably high mortality. To identify prognostic indicators, we aimed to compare survival and clinical outcome following VPS placement between all studied causes of hydrocephalus in HIV infected patients.

Methods

The following electronic databases were searched: The Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), EMBASE, CINAHL Plus, LILACS, Research Registry, the metaRegister of Controlled Trials, ClinicalTrials.gov, African Journals Online, and the OpenGrey database. We included observational studies of HIV-infected patients treated with VPS which reported of survival or clinical outcome. Data was extracted using standardised proformas. Risk of bias was assessed using validated domain-based tools.

Results

Seven Hunderd twenty-three unique study records were screened. Nine observational studies were included. Three included a total of 75 patients with tuberculous meningitis (TBM) and six included a total of 49 patients with cryptococcal meningitis (CM). All of the CM and two of the TBM studies were of weak quality. One of the TBM studies was of moderate quality. One-month mortality ranged from 62.5–100% for CM and 33.3–61.9% for TBM. These pooled data were of low to very-low quality and was inadequate to support meta-analysis between aetiologies. Pooling of results from two studies with a total of 77 participants indicated that HIV-infected patients with TBM had higher risk of one-month mortality compared with HIV non-infected controls (odds ratio 3.03; 95% confidence-interval 1.13–8.12; p = 0.03).

Conclusions

The evidence base is currently inadequate to inform prognostication in VPS insertion in HIV-infected patients. A population-based prospective cohort study is required to address this, in the first instance.
Household food insecurity associated with gestacional and neonatal outcomes: a systematic review
Authors: Augusto Ana Lucia Pires , de Abreu Rodrigues Aléxia Vieira , Domingos Talita Barbosa , Salles-Costa Rosana
Published: April 2020

Background

Food insecurity (FI) occurs when people lack secure access to sufficient amounts of safe and nutritious food. FI has been associated with negative effects on human health, including during the prenatal and neonatal periods. The objective of this study is to evaluate the consequences of FI for pregnant women’s and newborns’ health.

Methods

A literature search was performed with three independent researchers based on the PRISMA guidelines; the search covered the period of November 2008 to July 2019 and was conducted in the following databases: the US National Library of Medicine at the National Institutes of Health (PubMed), Latin American and Caribbean Health Sciences (LILACS), Cochrane Library, Web of Science, Embase, Scopus and OpenGrey. The terms and descriptors were defined by consulting the Medical Subject Headings (MeSH) and Health Sciences Descriptors (DeCS) platforms and mainly included “food security”, “food insecurity”, “pregnancy” and “newborn”. The studies were selected through a title and abstract review and then a reading of the full text. The quality of the studies and the risk of bias were analysed based on the criteria defined in the “Joanna Briggs Institute Reviewers’ Manual” and by Guyatt and colleagues for interventional studies. The population, study design, FI measurement instruments, FI proportions, outcomes, confounders and results were extracted from the 37 studies that were selected according to the eligibility and quality criteria.

Results

FI ​​proportions ranged from 5.2 to 87%. Most studies were conducted with African populations (42.2%) and applied globally used scales to assess FI (56.7%); 27% of the studies adapted scales. There were wide variations in the instruments used to estimate FI. The main outcomes related to FI included stress, anxiety and depression during pregnancy, followed by dietary quality and dietary diversity. Associations of FI with birth defects, neonatal mortality and the early introduction of animal milk to the infant’s diet were also observed.

Conclusions

It is necessary to pay attention to the diversity of FI measurement instruments before FI results are compared. FI can be a risk factor for depression and stress during pregnancy, as well as for neonatal mortality, newborn health problems and breastfeeding interruption.

Trial registration

This systematic review was registered on PROSPERO (CRD42018109478).
Fertility intentions and the way they change following birth- a prospective longitudinal study
Authors: Preis Heidi , Tovim Selen , Mor Pnina , Grisaru-Granovsky Sorina , Samueloff Arnon , Benyamini Yael
Published: April 2020

Background

Women’s fertility intentions, their desired number of children and desired inter-pregnancy interval (IPI) are related to micro (personal) and macro (socio-cultural) level factors. We investigated factors that contribute to changes in women’s fertility intentions in Israel, a developed country with high birth rates.

Methods

Pregnant women (N = 1163), recruited from prenatal clinics and hospitals in two major metropolitan areas, completed self-report questionnaires prenatally (≥24 weeks gestation) and postpartum (2 months after childbirth). Women reported their socio-demographic background and obstetric history prenatally, their desired number of children and IPI at both time-points, and their objective and subjective birth experiences postpartum.

Results

The findings indicated that background characteristics were related to prenatal fertility intentions. The strongest contributor to prenatal fertility intentions was women’s degree of religiosity- the more religious they were, the more children they desired and the shorter their intended IPI. Women’s postpartum fertility intentions were mostly consistent with their prenatal reports. In regression models, women who were very-religious, more educated and had previously given birth were less likely to report a lower number of desired of children at postpartum, compared to their prenatal report. Women who reported greater birth satisfaction and gave birth for the first time were less likely to change desired IPI.

Conclusion

Having a negative birth experience could adversely affect women’s fertility intentions. Yet, in a pronatalist and medicalized birth culture, social pressures may decrease the effects of birth experiences on fertility intentions.
Busulfan systemic exposure and its relationship with efficacy and safety in hematopoietic stem cell transplantation in children: a meta-analysis
Authors: Feng Xinying , Wu Yunjiao , Zhang Jingru , Li Jiapeng , Zhu Guanghua , Fan Duanfang , Yang Changqing , Zhao Libo
Published: April 2020

Background

Busulfan (Bu) is a key component of several conditioning regimens used before hematopoietic stem cell transplantation (HSCT). However, the optimum systemic exposure (expressed as the area under the concentration-time curve [AUC]) of Bu for clinical outcome in children is controversial.

Methods

Research on pertinent literature was carried out at PubMed, EMBASE, Web of science, the Cochrane Library andClinicalTrials.gov. Observational studies were included, which compared clinical outcomes above and below the area under the concentration-time curve (AUC) cut-off value, which we set as 800, 900, 1000, 1125, 1350, and 1500 μM × min. The primary efficacy outcome was notable in the rate of graft failure. In the safety outcomes, incidents of veno-occlusive disease (VOD) were recorded, as well as other adverse events.

Results

Thirteen studies involving 548 pediatric patients (aged 0.3–18 years) were included. Pooled results showed that, compared with the mean Bu AUC (i.e., the average value of AUC measured multiple times for each patient) of > 900 μM × min, the mean AUC value of < 900 μM × min significantly increased the incidence of graft failure (RR = 3.666, 95% CI: 1.419, 9.467). The incidence of VOD was significantly decreased with the mean AUC < 1350 μM × min (RR = 0.370, 95% CI: 0.205–0.666) and < 1500 μM × min (RR = 0.409, 95% CI: 0182–0.920).

Conclusions

In children, Bu mean AUC above the cut-off value of 900 μM × min (after every 6-h dosing) was associated with decreased rates of graft failure, while the cut-off value of 1350 μM × min were associated with increased risk of VOD, particularly for the patients without VOD prophylaxis therapy. Further well-designed prospective and multi centric randomized controlled trials with larger sample size are necessary before putting our result into clinical practices.
Atypical hemolytic uremic syndrome precipitated by thyrotoxicosis: a case report
Authors: Hou Ling , Du Yue
Published: April 2020

Background

Autoimmune thyroid disease (AITD) has a complex pathogenesis and is associated with the development of autoimmunity against the thyroid. Graves’ disease and Hashimoto’s thyroiditis are the two main types of AITD, and they are characterized by thyrotoxicosis and hypothyroidism, respectively. Atypical hemolytic uremic syndrome (aHUS) is a rare disease, presenting with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. aHUS is caused by dysregulation of the alternative complement pathway, and its co-existence with AITD is rare.

Case presentation

We report the case of a 12-year-old girl with recent onset thyrotoxicosis. She was first treated with propylthiouracil for 2 months and then developed AITD presenting as abrupt-onset thrombocytopenia, acute kidney injury, and microangiopathic hemolytic anemia. Thyroid function tests favored hyperthyroidism, with increased free T4 and free T3 levels and a very low level of thyroid-stimulating hormone (TSH). We suspected aHUS, and the patient’s condition responded dramatically to therapeutic plasma exchange (TPE) with disease remission. She experienced recurrent aHUS after subsequently receiving methimazole for 1 month, and in the recurrent episode, her condition responded again to TPE and concomitant glucocorticoids. She achieved euthyroidism with thiamazole ointment treatment, without aHUS recurrence during the 6-month follow-up. Mycophenolate mofetil was administered to manage proteinuria after 3 months of treatment with the steroid and angiotensin-converting enzyme inhibitor.

Conclusions

The coexistence of aHUS and AITD in this case is likely more than coincidence, because both are autoimmune in origin. aHUS is associated with a high mortality without appropriate therapy, and treatment with TPE and adjunct immunosuppressants can be helpful.
Autosomal dominant transmission of transient neonatal lactic acidosis: a case report
Authors:   Care4Rare Consortium, Mardian Emily B. , Lines Matthew A. , Moore Gregory P.
Published: April 2020

Background

Lactic acidosis is a common finding in neonates, in whom mitochondrial dysfunction is often secondary to tissue hypoperfusion, respiratory failure, and/or sepsis. Primary (non-physiological) lactic acidosis is comparatively rare, and suggests the presence of an inborn error of mitochondrial energy metabolism. Optimal medical management and accurate prognostication requires the correct determination of the etiology of lactic acidosis in a given patient. Unfortunately, genetic diagnoses are rare and highly variable for neonates presenting with primary lactic acidosis; individual case reports may offer the most promise for treatment considerations.

The mitochondrion is a complex molecular machine incorporating the products of > 1000 distinct nuclear genes. Primary lactic acidoses are therefore characterized by high genetic heterogeneity and a specific genetic diagnosis currently remains out of reach in most cases. Most mitochondriopathies with neonatal onset follow autosomal recessive inheritance and carry a poor prognosis. Here we detail the case of a father and daughter with dominantly-inherited, resolving (i.e. transient) neonatal hyperlactatemia due to complex IV deficiency. We found no other published descriptions of benign transient complex IV deficiency with autosomal dominant inheritance.

Case presentation

Both individuals presented as neonates with unexplained, marked lactic acidosis suggesting a primary mitochondrial disorder. Within the first weeks of life, elevated blood lactate levels normalized. Their clinical and developmental outcomes were normal. Biochemical studies in the proband showed multiple abnormalities consistent with a complex IV respiratory chain defect. Cultured skin fibroblasts showed an elevated lactate-to-pyruvate ratio, deficient complex IV activity, and normal pyruvate dehydrogenase and pyruvate carboxylase activities. Whole-exome sequencing of the proband and both parents did not identify a causative mutation.

Conclusion

We conclude that the proband and her father appear to have a dominant form of transient neonatal hyperlactatemia due to heterozygous changes in an as-yet unidentified gene. This transient neonatal complex IV deficiency should be considered in the differential diagnosis of primary neonatal hyperlactatemia; notable clinical features include autosomal-dominant inheritance and an apparently benign postnatal course. This report exemplifies the growing differential diagnosis for neonatal lactic acidosis and highlights the importance of both physician counselling and the use of family history in communicating with parents.
Towards improving the identification of anterior cruciate ligament tears in primary point-of-care settings
Authors: Whittaker Jackie L. , Chan Michelle , Pan Bo , Hassan Imran , Defreitas Terry , Hui Catherine , Macedo Luciana , Otto David
Published: April 2020

Background

Only a small proportion of anterior cruciate ligament (ACL) tears are diagnosed on initial healthcare consultation. Current clinical guidelines do not acknowledge that primary point-of-care practitioners rely more heavily on a clinical history than special clinical tests for diagnosis of an ACL tear. This research will assess the accuracy of combinations of patient-reported variables alone, and in combination with clinician-generated variables to identify an ACL tear as a preliminary step to designing a primary point-of-care clinical decision support tool.

Methods

Electronic medical records (EMRs) of individuals aged 15–45 years, with ICD-9 codes corresponding to a knee condition, and confirmed (ACL+) or denied (ACL−) first-time ACL tear seen at a University-based Clinic between 2014 and 2016 were eligible for inclusion. Demographics, relevant diagnostic indicators and ACL status based on orthopaedic surgeon assessment and/or MRI reports were manually extracted. Descriptive statistics calculated for all variables by ACL status. Univariate between group comparisons, clinician surveys (n = 17), availability of data and univariable logistic regression (95%CI) were used to select variables for inclusion into multivariable logistic regression models that assessed the odds (95%CI) of an ACL-tear based on patient-reported variables alone (consistent with primary point-of-care practice), or in combination with clinician-generated variables. Model performance was assessed by accuracy, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (95%CI).

Results

Of 1512 potentially relevant EMRs, 725 were included. Participant median age was 26 years (range 15–45), 48% were female and 60% had an ACL tear. A combination of patient-reported (age, sport-related injury, immediate swelling, family history of ACL tear) and clinician-generated (Lachman test result) variables were superior for ACL tear diagnosis [accuracy; 0.95 (90,98), sensitivity; 0.97 (0.88,0.98), specificity; 0.95 (0.82,0.99)] compared to the patient-reported variables alone [accuracy; 84% (77,89), sensitivity; 0.60 (0.44,0.74), specificity; 0.95 (0.89,0.98)].

Conclusions

A high proportion of individuals without an ACL tear can be accurately identified by considering patient-reported age, injury setting, immediate swelling and family history of ACL tear. These findings directly inform the development of a clinical decision support tool to facilitate timely and accurate ACL tear diagnosis in primary care settings.
Associations between learning environment variables and students’ approaches to studying: a cross-sectional study
Authors: Mørk Gry , Magne Trine A. , Carstensen Tove , Stigen Linda , Åsli Lene A. , Gramstad Astrid , Johnson Susanne G. , Bonsaksen Tore
Published: April 2020

Background

Aspects of the learning environment may be related to students` approaches to studying, but few studies have investigated these relationships in the context of occupational therapy education.

Objective

To examine associations between occupational therapy students’ perceptions of the learning environment and their approaches to studying.

Method

One hundred eighty-seven first-year occupational therapy students in Norway (response rate 61.3%) participated in this study. Aside from sociodemographic information, the students completed the Course Experience Questionnaire and the Approaches and Study Skills Inventory for Students. Associations between learning environment variables and study approaches were investigated with hierarchical linear regression analyses.

Results

Higher scores on Generic skills were associated with higher scores on the deep and strategic approach scales (β ranging 0.18–0.51), while lower scores were associated with higher surface approach scale scores (β = − 0.24). Lower scores on Clear goals and standards and Appropriate workload were associated with higher surface approach scores (β ranging − 0.16 - -0.42).

Conclusion

By improving aspects of the learning environment, there may be a potential for influencing occupational therapy students’ approaches to studying. Based on this study, emphasizing how generic skills developed in the study program may become useful in practising a profession, ensuring clarity of goals and standards, and maintaining an appropriate workload on students appear to be important.
Resilient Health Care: a systematic review of conceptualisations, study methods and factors that develop resilience
Authors: Iflaifel Mais , Lim Rosemary H. , Ryan Kath , Crowley Clare
Published: April 2020

Background

Traditional approaches to safety management in health care have focused primarily on counting errors and understanding how things go wrong. Resilient Health Care (RHC) provides an alternative complementary perspective of learning from incidents and understanding how, most of the time, work is safe. The aim of this review was to identify how RHC is conceptualised, described and interpreted in the published literature, to describe the methods used to study RHC, and to identify factors that develop RHC.

Methods

Electronic searches of PubMed, Scopus and Cochrane databases were performed to identify relevant peer-reviewed studies, and a hand search undertaken for studies published in books that explained how RHC as a concept has been interpreted, what methods have been used to study it, and what factors have been important to its development. Studies were evaluated independently by two researchers. Data was synthesised using a thematic approach.

Results

Thirty-six studies were included; they shared similar descriptions of RHC which was the ability to adjust its functioning prior to, during, or following events and thereby sustain required operations under both expected and unexpected conditions. Qualitative methods were mainly used to study RHC. Two types of data sources have been used: direct (e.g. focus groups and surveys) and indirect (e.g. observations and simulations) data sources. Most of the tools for studying RHC were developed based on predefined resilient constructs and have been categorised into three categories: performance variability and Work As Done, cornerstone capabilities for resilience, and integration with other safety management paradigms. Tools for studying RHC currently exist but have yet to be fully implemented. Effective team relationships, trade-offs and health care ‘resilience’ training of health care professionals were factors used to develop RHC.

Conclusions

Although there was consistency in the conceptualisation of RHC, methods used to study and the factors used to develop it, several questions remain to be answered before a gold standard strategy for studying RHC can confidently be identified. These include operationalising RHC assessment methods in multi-level and diverse settings and developing, testing and evaluating interventions to address the wider safety implications of RHC amidst organisational and institutional change.
Comparison of ELISA with electro-chemiluminescence technology for the qualitative and quantitative assessment of serological responses to vaccination
Authors: Bolton Jessica S. , Chaudhury Sidhartha , Dutta Sheetij , Gregory Scott , Locke Emily , Pierson Tony , Bergmann-Leitner Elke S.
Published: April 2020

Background

Profiling immune responses induced by either infection or vaccination can provide insight into identification of correlates of protection. Furthermore, profiling of serological responses can be used to identify biomarkers indicative of exposure to pathogens. Conducting such immune surveillance requires readout methods that are high-throughput, robust, and require small sample volumes. While the enzyme-linked immunosorbent assay (ELISA) is the classical readout method for assessing serological responses, the advent of multiplex assays has significantly increased the throughput and capacity for immunoprofiling. This report describes the development and assay performance (sensitivity, linearity of detection, requirement for multiple dilutions for each sample, intra- and inter-assay variability) of an electro-chemiluminescence (ECLIA)-based multiplex assay.

Methods

The current study describes the development of a multiplex ECLIA-based assay and characterizes the sensitivity, linear range, and inter- and intra-assay variability of the ECLIA platform and its agreement with the traditional ELISA. Special emphasis was placed on potential antigenic competition when testing closely related antigens in the multiplex format.

Results

Multiplexing of antigens in ECLIA provides significant practical benefits in terms of reducing sample volume requirements and experimental time. Beyond the practical advantages of multiplexing, the ECLIA provides superior assay performance when compared to the ELISA. Not only does ECLIA show good agreement with the ELISA assay, but the linear range of ECLIA is also sufficiently wide to permit single-dilution measurements of concentration without the need to do serial dilutions. The lack of antigenic competition allows the simultaneous testing of closely related antigens, such as plate antigens representing different alleles of the same protein, which can inform about cross-reactivities—or lack thereof—of serological responses.

Conclusion

The advantages of the newly developed tool for assessing the antigen profiles of serological responses may ultimately lead to the identification of biomarkers associated with various disease stages and or protection against disease.
Health-related quality of life and scar satisfaction in a cohort of children operated on for sacrococcygeal teratoma
Authors: Hambraeus Mette , Hagander Lars , Arnbjörnsson Einar , Börjesson Anna , Stenström Pernilla
Published: April 2020

Aim

The aims of this study were to evaluate health-related quality of life (HRQoL) in children with sacrococcygeal teratoma and to explore the effect of the scar on physical, emotional and behavioral aspects.

Methods

A cohort of children operated on for sacrococcygeal teratoma between 2000 and 2013 at Lund University Hospital, Sweden, and their parents were interviewed. HRQoL was evaluated with PedsQL, and scar satisfaction was estimated through Patient Observer Scar Assessment Score (POSA).

Results

All eligible children (n = 17) were included (100% response rate). Median age was 7.3 years (range 3.5–16.0). Mean total PedsQL score was 92.3 (range 72.0 to 99.0). Patients with comorbidity scored lower (87.5) than those without (95.0) (p < 0.05). Pain during sitting down was reported by two (20%) patients, and itching was reported by another two patients (20%) aged > 8 years. No children reported that they avoided situations due to the scar, and most (80% of children and 90% of parents) reported absent or only mild negative emotions when considering the scar.

Conclusion

Children with sacrococcygeal teratoma had a good overall HRQoL, but comorbidity reduced the outcome. A few children reported scar-related impact on physical, behavioral and emotional aspects.
Low DLG2 gene expression, a link between 11q-deleted and MYCN-amplified neuroblastoma, causes forced cell cycle progression, and predicts poor patient survival
Authors: Keane Simon , Améen Sophie , Lindlöf Angelica , Ejeskär Katarina
Published: April 2020

Background

Neuroblastoma (NB) is a childhood neural crest tumor. There are two groups of aggressive NBs, one with MYCN amplification, and another with 11q chromosomal deletion; these chromosomal aberrations are generally mutually exclusive. The DLG2 gene resides in the 11q-deleted region, thus makes it an interesting NB candidate tumor suppressor gene.

Methods

We evaluated the association of DLG2 gene expression in NB with patient outcomes, stage and MYCN status, using online microarray data combining independent NB patient data sets. Functional studies were also conducted using NB cell models and the fruit fly.

Results

Using the array data we concluded that higher DLG2 expression was positively correlated to patient survival. We could also see that expression of DLG2 was inversely correlated with MYCN status and tumor stage. Cell proliferation was lowered in both 11q-normal and 11q-deleted NB cells after DLG2 over expression, and increased in 11q-normal NB cells after DLG2 silencing. Higher level of DLG2 increased the percentage of cells in the G2/M phase and decreased the percentage of cells in the G1 phase. We detected increased protein levels of Cyclin A and Cyclin B in fruit fly models either over expressing dMyc or with RNAi-silenced dmDLG, indicating that both events resulted in enhanced cell cycling. Induced MYCN expression in NB cells lowered DLG2 gene expression, which was confirmed in the fly; when dMyc was over expressed, the dmDLG protein level was lowered, indicating a link between Myc over expression and low dmDLG level.

Conclusion

We conclude that low DLG2 expression level forces cell cycle progression, and that it predicts poor NB patient survival. The low DLG2 expression level could be caused by either MYCN-amplification or 11q-deletion.

Graphical abstract
Salvage use of tissue plasminogen activator (tPA) in the setting of acute respiratory distress syndrome (ARDS) due to COVID-19 in the USA: a Markov decision analysis
Authors: Choudhury Rashikh , Barrett Christopher D. , Moore Hunter B. , Moore Ernest E. , McIntyre Robert C. , Moore Peter K. , Talmor Daniel S. , Nydam Trevor L. , Yaffe Michael B.
Published: April 2020

Background

COVID-19 threatens to quickly overwhelm our existing critical care infrastructure in the USA. Systemic tissue plasminogen activator (tPA) has been previously demonstrated to improve PaO2/FiO2(mmHg) when given to critically ill patients with acute respiratory distress syndrome (ARDS). It is unclear to what extent tPA may impact population-based survival during the current US COVID-19 pandemic.

Methods

A decision analytic Markov state transition model was created to simulate the life critically ill COVID-19 patients as they transitioned to either recovery or death. Two patient groups were simulated (50,000 patients in each group); (1) Patients received tPA immediately upon diagnosis of ARDS and (2) patients received standard therapy for ARDS. Base case critically ill COVID-19 patients were defined as having a refractory PaO2/FiO2of < 60 mmHg (salvage use criteria). Transition from severe to moderate to mild ARDS, recovery, and death were estimated. Markov model parameters were extracted from existing ARDS/COVID-19 literature.

Results

The use of tPA was associated with reduced mortality (47.6% [tTPA] vs. 71.0% [no tPA]) for base case patients. When extrapolated to the projected COVID-19 eligible for salvage use tPA in the USA, peak mortality (deaths/100,000 patients) was reduced for both optimal social distancing (70.5 [tPA] vs. 75.0 [no tPA]) and no social distancing (158.7 [tPA] vs. 168.8 [no tPA]) scenarios.

Conclusions

Salvage use of tPA may improve recovery of ARDS patients, thereby reducing COVID-19-related mortality and ensuring sufficient resources to manage this pandemic.
The French paediatric cohort of Castleman disease: a retrospective report of 23 patients
Authors: Borocco Charlotte , Ballot-Schmit Claire , Ackermann Oanez , Aladjidi Nathalie , Delaleu Jeremie , Giacobbi-Milet Vannina , Jannier Sarah , Jeziorski Eric , Maurier François , Perel Yves , Piguet Christophe , Oksenhendler Eric , Koné-Paut Isabelle , Galeotti Caroline
Published: April 2020

Background

Castleman disease (CD) is a rare non-malignant lymphoproliferation of undetermined origin. Two major disease phenotypes can be distinguished: unicentric CD (UCD) and multicentric CD (MCD). Diagnosis confirmation is based on histopathological findings in a lymph node. We attempted to survey all cases of paediatric CD identified to date in France to set up a national registry aiming to improve CD early recognition, treatment and follow-up, within the context of a new national reference center (http://www.castleman.fr).

Methods

In 2016, we e-mailed a questionnaire to members of the French paediatric immunohaematology society, the paediatric rheumatology society and the Reference Centre for Castleman Disease to retrospectively collect cases of paediatric CD (first symptoms before age 18 years). Anatomopathological confirmation was mandatory.

Results

We identified 23 patients (12 girls) with a diagnosis of UCD (n = 17) and MCD (n = 6) between 1994 and 2018. The mean age at first symptoms was 11.47 ± 4.23 years for UCD and 8.3 ± 3.4 years for MCD. The mean diagnosis delay was 8.16 ± 10.32 months for UCD and 5.16 ± 5.81 years for MCD. In UCD, the initial symptoms were isolated lymph nodes (n = 10) or lymph node associated with other symptoms (n = 7); fever was present in 3 patients. Five patients with MCD presented fever. No patients had HIV or human herpesvirus 8 infection. Autoinflammatory gene mutations were investigated in five patients. One patient with MCD carried a K695R heterozygous mutation in MEFV, another patient with MCD and Duchenne myopathy carried two variants in TNFRSF1A and one patient with UCD and fever episodes carried two heterozygous mutations, in IL10RA and IL36RN, respectively. Treatment of UCD was mainly surgical resection, steroids, and radiotherapy. Treatment of MCD included tocilizumab, rituximab, anakinra, steroids, chemotherapy, and splenectomy. Overall survival after a mean of 6.1 ± 6.4 years of follow-up, was 100% for both forms.

Conclusion

Paediatric CD still seems underdiagnosed, with a significant diagnosis delay, especially for MCD, but new international criteria will help in the future. Unlike adult CD, which is strongly associated with HIV and human herpesvirus 8 infection, paediatric CD could be favored by primary activation of innate immunity and may affect life expectancy less.
HVEM/HIF-1α promoted proliferation and inhibited apoptosis of ovarian cancer cells under hypoxic microenvironment conditions
Authors: Duan Liyan , Tao Jie , Yang Xiaoqian , Ye Lei , Wu Yueqian , He Qizhi , Duan Yingchun , Chen Li , Zhu Jianlong
Published: April 2020

Background

Our previous studies showed the expression of herpes virus entry mediator (HVEM) is high in ovarian cancer samples and correlated to the patient clinic pathological features. As we all know, the hypoxic environment is the main feature of tumor. In this work, we explored the role of HVEM in hypoxic ovarian cancer cells and its effects on HIF-1α, a transcription factor responding to hypoxia.

Methods

The expression of HVEM, HIF-1α and apoptosis-related genes was detected by qRT-PCR and western blot. The proliferation and apoptosis of the ovarian cancer cells were determined with the Cell Counting Kit-8 assay and AnnexinV-FITC/PI-stained flow cytometry assay, respectively.

Results

The expression of HVEM was positively correlated to that of HIF-1α. The expression of HVEM and HIF-1α under hypoxic conditions was higher than that under normoxic conditions, which suggested that the level of HVEM and HIF-1α correlates with prolonged periods of hypoxia in ovarian cancer. The overexpression of HVEM promoted cell proliferation and inhibited cell apoptosis under hypoxic condition. HVEM overexpression elevated the expression of HIF-1α and Bcl-2 (anti-apoptotic protein), and reduced the expression of Bax (pro-apoptotic protein). In addition, overexpression of HVEM activated the AKT/mTOR signaling. Moreover, knockdown of HVEM had the completely opposite effects.

Conclusion

These data indicated that HVEM signaling might promote HIF-1α activity via AKT/mTOR signaling pathway and thus to regulate tumor growth in ovarian cancer under the hypoxic conditions. Furthermore, these findings indicate that this molecular mechanism could represent a therapeutic target for ovarian cancer.
Lifestyle changes and glycemic control in type 1 diabetes mellitus: a trial protocol with factorial design approach
Authors: Sawani Sobiya , Siddiqui Amna Rehana , Azam Syed Iqbal , Humayun Khadija , Ahmed Asma , Habib Aysha , Naz Sabahat , Tufail Mayera , Iqbal Romaina
Published: April 2020

Background

Type 1 diabetes (T1D) has been increasing globally over the past three decades. Self-monitoring of blood glucose is a challenge in both developed as well as developing countries. Self-management guidelines include maintaining logbooks for blood glucose, physical activity, and dietary intake that affect glycated hemoglobin (HbA1c) and a multitude of life-threatening acute complications. Innovative, cost-effective interventions along with beneficial lifestyle modifications can improve home-based self-monitoring of blood glucose in T1D patients. The overall objective of this study is to evaluate the relationship between maintaining log books for blood glucose levels, reinforcement by e-messages, and/or daily step count and changes in HbA1c.

Methods/design

A randomized controlled trial will enroll participants aged 15 years and above in four groups. Each group of 30 participants will be working with a newly designed standard log book for documenting their blood glucose. The first group will be entirely on routine clinical care, the second group will be on routine care and will receive an additional e-device for recording step count (fit bit), the third group will receive routine care and daily motivational e-messages to maintain the log book, and the fourth group along with routine care will receive an e-device for measuring step count (fit bit) and e-messages about maintaining the log book. Patients will be enrolled from pediatric and endocrine clinics of a tertiary care hospital in Karachi. All groups will be followed up for a period of 6 months to evaluate outcomes. Log book data will be obtained every 3 months electronically or during a patient’s clinic visit. HbA1c as a main outcome will be measured at baseline and will be evaluated twice every 3 months. A baseline questionnaire will determine the socio-demographic, nutritional, and physical activity profile of patients. Clinical information for T1D and other co-morbidities for age of onset, duration, complications, hospitalizations, habits for managing T1D, and other lifestyle characteristics will be ascertained. Behavioral modifications for maintaining daily log books as a routine, following e-messages alone, fit bit alone, or e-messages plus using fit bit will be assessed for changes in HbA1c using a generalized estimated equation.

Discussion

The proposed interventions will help identify whether maintaining log books for blood glucose, motivational e-messages, and/or daily step count will reduce HbA1c levels.

Trial registration

ClinicalTrials.gov,NCT03864991. March 6, 2019.
Synthesis of new 2-amino-1,3,4-oxadiazole derivatives with anti-salmonella typhi activity evaluation
Authors: Salama Eid E.
Published: April 2020

Reaction of phenyl acetic acid derivatives with thiosemicarbazide in the presence of POCl3 afforded 5-(4-bromobenzyl)-1,3,4-oxadiazole-2-amine 1 and 5-(3-nitrophenyl)-1,3,4-oxadiazole -2-amine 2. Acylation of the amino group of oxadiazoles 1 and 2 with some acid chlorides such as methyl 4-(chlorocarbonyl) benzoate, 3-nitrobenzoyl chloride, 4-methoxy-benzoyl chloride, 4-isobutylbenzoyl chloride and chloroacetyl chloride yielded the acylated compounds 3–8. Cyclization of acetamides 7 and 8 by reaction with ammonium thiocyanate gave the thiazolidinones 9 and 10. Coupling of chloroacetamide 7 with two mercaptothiazoles gave coupled heterocyclic derivatives 11 and 12. Coupling of amino-oxadiazole 1 with N-Boc-glycine and N-Boc-phenylalanine lead to the formation of 16 and 17 respectively. All compounds were screened for their antibacterial activity against Salmonella typhi where compounds 3, 4, 10, 11 and 15 showed significant activity. Structures of the new synthesized compounds were confirmed using the spectral analysis such as IR, 1H NMR and 13C NMR and mass spectrometry.
Phlebotomine sand flies in Southwest Germany: an update with records in new locations
Authors: Oerther Sandra , Jöst Hanna , Heitmann Anna , Lühken Renke , Krüger Andreas , Steinhausen Irmgard , Brinker Christine , Lorentz Susanne , Marx Michael , Schmidt-Chanasit Jonas , Naucke Torsten , Becker Norbert
Published: April 2020

Background

Vector-borne diseases (VBD) are of growing global importance. Sand flies are potential vectors for phleboviruses (family Phenuiviridae) including Toscana virus (TOSV), Sicilian virus, Sandfly fever, Naples virus, and Leishmania parasites in Europe. To date, only two phlebotomine species have been recorded for Germany: Phlebotomus perniciosus and Phlebotomus mascittii. This study updates the distribution and abundance of the two occurring species.

Methods

An entomological field study was carried out during 2015–2018 to assess the abundance of sand flies in Southwest Germany within the federal states Baden-Wuerttemberg (BW) and Rhineland-Palatinate (RLP). A total of 176 collection sites were examined using CDC light traps.

Results

A total of 149 individuals of P. mascittii were collected. During 2015–2018, P. mascittii was found at all sites known positive from previous studies and was detected at 15 additional sites previously unknown for the presence of sand flies. Although the environment has changed considerably in 30 years, no significant difference in sand fly dynamics and distribution was found. Phlebotomus perniciosus has only been trapped once since 2001.

Conclusions

This study showed that sand flies occur in different areas in Southern Germany where they had not been recorded previously. Therefore, it can be assumed that they are more widespread than expected. In addition, sand flies could be found over several years at the same trapping sites, indicating population stability. This supports the need for continued surveillance of possible vector populations and urgent clarification of the vector competence of P. mascittii.
Don’t let sleeping dogs lie: unravelling the identity and taxonomy of Babesia canis, Babesia rossi and Babesia vogeli
Authors: Penzhorn Barend L.
Published: April 2020

For most of the 20th century the causative agent of canine babesiosis, wherever it occurred in the world, was commonly referred to as Babesia canis. Early research, from the 1890s to the 1930s, had shown that there were three distinctly different vector-specific parasite entities occurring in specific geographical regions, that host response to infection ranged from subclinical to acute, and that immunity to one stock of the parasite did not necessarily protect against infection with other stocks. This substantial body of knowledge was overlooked or ignored for 50 years. In this review the first records and descriptions of the disease in four geographical regions were traced: sub-Saharan Africa, Europe, North Africa and Asia. Research leading to identification of the specific tick vector species involved is documented. Evidence is given of the growing realisation that there were substantial biological differences between stocks originating from different geographical regions. Etymological provenance for Babesia vogeli is proposed.