bluuebunny/crossref_metadata_2025 huggingface dataset:
bolA gene involved in curli amyloids and fimbriae production in E. coli: exploring pathways to inhibit biofilm and amyloid formation
Authors: Azam Mohd W. , Zuberi Azna , Khan Asad U.
Published: June 2020

Background

Biofilm formation is a complex phenomenon of bacterial cells, involved in several human infections. Its formation is regulated and controlled by several protein factors. The BolA-like proteins (bolA gene) are conserved in both prokaryotes and eukaryotes. The BolA protein is a transcription factor involved in bacterial cell motility and biofilm formation. This study was initiated to elucidate the role of the bolA gene in the curli biogenesis and amyloid production as well as to observe changes in the expression of fimH, a fimbriae gene.

Methods

Knockdown mutants of Escherichia coli MG1655 bolA gene (bolA-KD) were generated using CRISPR interference. The results obtained, were validated through gene expression using RT-PCR, microscopic analysis and different biofilm and amyloid assays.

Results

The bolA knockdown mutants showed a decrement in curli amyloid fibers, in fimbriae production and biofilm formation. We have also observed a reduction in EPS formation, eDNA production and extracellular protein content. Gene expression data showed that bolA downregulation caused the suppression of csgA and csgD of curli that led to the reduction in curli fiber and the amyloid formation and also the suppression of fimH, leading to the loss of fimbriae.

Conclusions

Curli fibers and fimbriae are found to be involved in biofilm formation leading to the pathogenicity of the bacterial cell. BolA is a conserved protein and is found to play a significant role in curli and fimbriae formation in E. coli. This study further proved that CRISPRi mediated suppression of the bolA gene leads to inhibition of biofilm formation through curli and fimbriae inhibition. Hence, it may be proposed as a possible target for intervention of biofilm mediated infections.
Dyspnea due to an uncommon vascular tumor: leiomyosarcoma of the infrahepatic vena cava inferior
Authors: Gafarli Samra , Igna Dorian , Wagner Mathias , Nistor Adriana , Glanemann Matthias , Stange Barbara
Published: June 2020

Background

Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare malignancy that originated from the smooth muscle tissue of the vascular wall. Diagnoses, as well as, treatment of the disease are still challenging and to date, a radical surgical resection of the tumor is the only curative approach.

Case report

We report on the case of a 49-year old male patient who presented with suddenly experienced dyspnea. Besides bilateral pulmonary arterial embolism, a lesion close to the head of the pancreas was found using CT scan, infiltrating the infrahepatic IVC. Percutaneous ultrasound-guided biopsy revealed a low-grade LMS. Intraoperatively, a tumor of the IVC was observed without infiltration of surrounding organs or distant metastases. Consequently, the tumor was removed successfully, by en-bloc resection including prosthetic graft placement of the IVC. Histological workup revealed a completely resected (R0) moderately differentiated LMS of the IVC.

Conclusion

LMS of the infrahepatic IVC is an uncommon tumor, which may present with dyspnea as its first clinical sign. Patients benefit from radical tumor resection. However, due to the poor prognosis of vascular LMS, a careful follow-up is mandatory.
Langerhans cell histiocytosis confined to extrahepatic bile duct causing sclerosing cholangitis in child: a case report
Authors: Murakami Masakazu , Onishi Shun , Ohya Yuki , Kawabata Seiichi , Isono Kaori , Sugawara Yasuhiko , Asato Tsuguharu , Honda Yumi , Mikami Yoshiki , Inomata Yukihiro , Hibi Taizo , Ieiri Satoshi
Published: June 2020

Background

Langerhans cell histiocytosis (LCH) is an abnormal accumulation of Langerhans cells in various organs that sometimes induces organ dysfunction. LCH can affect the liver, resulting in sclerosing cholangitis and biliary cirrhosis. However, liver and bile duct involvement is usually observed in the disseminated form of LCH. We herein report a rare case of LCH localized only in the extrahepatic bile duct that resulted in severe liver cirrhosis.

Case presentation

A 3-year-old boy with elevated liver enzymes, obstructive jaundice, and dilation of the common bile duct was referred to our institution. Contrast-enhanced computed tomography showed atrophy of the right hepatic lobe, relative hypertrophy of the left hepatic lobe, choledocholiths, and biliary debris extensively with biliary duct dilation. Magnetic resonance cholangiopancreatography revealed dilation of the intrahepatic and extrahepatic bile ducts and multiple choleliths in the gallbladder and common bile duct. Laparoscopic cholecystectomy, intraoperative cholangiography, liver biopsy, and gastrointestinal fiberscopy were performed. A liver specimen showed severe biliary cirrhosis due to sclerosing cholangitis. The patient then underwent living-donor liver transplantation because of severe liver cirrhosis 3 months after the first surgery. The common bile duct was not suitable for duct-to-duct anastomosis and was resected because of severe inflammation. Histologic sections of the common bile duct showed histiocytic cell proliferation. Immunohistochemistry revealed histiocytoses that were positive for Langerin, S-100 protein, and CD1a. However, no histiocytic cell proliferation was noted in the liver tissue. The definitive diagnosis was LCH localized to the extrahepatic bile duct. LCH in the extrahepatic bile duct seemed to cause sclerosing cholangitis. The patient was discharged uneventfully 2 months after living-donor liver transplantation.

Conclusions

LCH localized to the extrahepatic bile duct is extremely rare; however, LCH can still affect the extrahepatic bile ducts on occasion. LCH should be considered as a differential diagnosis if pediatric patients show the presence of sclerosing cholangitis.
Successful two-stage operation for esophageal necrosis due to proton beam therapy followed by sorafenib in a case of large hepatocellular carcinoma
Authors: Higaki Eiji , Fukaya Masahide , Miyata Kazushi , Kawai Ryosuke , Abe Tetsuya
Published: June 2020

Background

Locally advanced hepatocellular carcinoma (HCC), which is unsuitable for standard locoregional therapies, remains a challenge to manage. Among the recently developed treatments, proton beam therapy (PBT) has been reported to achieve good local control. However, in patients with large HCC adjacent to the esophagus, high-dose PBT may rarely lead to radiation-induced esophageal necrosis or perforation. Furthermore, the optimal strategy to safely treat these fatal complications remains unclear.

Case presentation

A 49-year-old man who was diagnosed with a large (16 cm) HCC in the right lobe with tumor thrombosis in the main trunk of the portal vein (PVTT) received high-dose hypofractionated PBT in another hospital. A total dose of 66 GyE in 10 fractions was administered to the primary tumor and the PVTT. After 5 months, a 1-cm solitary nodule was noted in the upper lobe of the right lung. Therefore, sorafenib was started. About 6 months after the PBT, lower esophageal mucosal inflammation that progressed to an ulcer was noted. About 7 months after the PBT, the lower esophagus developed full-thickness necrosis. Therefore, emergency thoracoscopic esophagectomy was performed, followed by two-stage reconstruction 2 months later. The operation and postoperative clinical course were mostly uneventful, except for a minor anastomotic leakage. The outcome of the primary HCC, including the PVTT, was graded as a complete response, which has been maintained for 51 months after the PBT.

Conclusion

PBT is a promising option for patients with locally advanced HCC; however, for large tumors adjacent to the esophagus, ischemic esophageal necrosis due to antiangiogenic effects may occur, particularly with the combined use of PBT and sorafenib. In such a life-threatening condition, the thoracoscopic esophagectomy and the two-stage reconstruction are a safe option that can prevent critical postoperative complications due to the poor general condition, effects of PBT on the remnant gastric conduit, and use of sorafenib.
A randomized pilot study to evaluate graft versus fistula vascular access strategy in older patients with advanced kidney disease: results of a feasibility study
Authors: Murea Mariana , Geary Randolph L. , Houston Denise K. , Edwards Matthew S. , Robinson Todd W. , Davis Ross P. , Hurie Justin B. , Williams Timothy K. , Velazquez-Ramirez Gabriela , Bagwell Benjamin , Tuttle Audrey B. , Moossavi Shahriar , Rocco Michael V. , Freedman Barry I. , Williamson Jeff D. , Chen Haiying , Divers Jasmin
Published: June 2020

Background

Although older adults encompass almost half of patients with advanced chronic kidney disease, it remains unclear which long-term hemodialysis vascular access type, arteriovenous fistula or arteriovenous graft, is optimal with respect to effectiveness and patient satisfaction. Clinical outcomes based on the initial AV access type have not been evaluated in randomized controlled trials. This pilot study tested the feasibility of randomizing older adults with advanced kidney disease to initial arteriovenous fistula versus graft vascular access surgery.

Methods

Patients 65 years or older with pre-dialysis chronic kidney disease or incident end-stage kidney disease and no prior arteriovenous vascular access intervention were randomized in a 1:1 ratio to undergo surgical placement of a fistula or a graft after providing informed consent. Trial feasibility was evaluated as (i) recruitment of ≥ 70% of eligible participants, (ii) ≥ 50 to 70% of participants undergo placement of index arteriovenous access within 90 to 180 days of enrollment, respectively, (iii) ≥ 80% adherence to study-related assessments, and (iv) ≥ 70% of participants who underwent index arteriovenous access placement will have a follow-up duration of ≥ 12 months after index surgery date.

Results

Between September 2018 and October 2019, 81% (44/54) of eligible participants consented and were enrolled in the study; 11 had pre-dialysis chronic kidney disease, and 33 had incident or prevalent end-stage kidney disease. After randomization, 100% (21/21) assigned to arteriovenous fistula surgery and 78% (18/23) assigned to arteriovenous graft surgery underwent index arteriovenous access placement within a median (1st, 3rd quartile) of 5.0 (1.0, 14.0) days and 13.0 (5.0, 44.3) days, respectively, after referral to vascular surgery. The completion rates for study-specific assessments ranged between 40.0 and 88.6%. At median follow-up of 215.0 days, 5 participants expired, 7 completed 12 months of follow-up, and 29 are actively being followed. Assessments of grip strength, functional independence, and vascular access satisfaction were completed by > 85% of patients who reached pre-specified post-operative assessment time point.

Conclusions

Results from this study reveal it is feasible to enroll and randomize older adults with advanced kidney disease to one of two different arteriovenous vascular access placement surgeries. The study can progress with minor protocol adjustments to a multisite clinical trial.

Trial registration

Clinical Trials ID, NCT03545113.
Effects of fire on native columnar and globular cacti of Puerto Rico: a case study of El Faro, Cabo Rojo
Authors: Carrera-Martínez Roberto , Ruiz-Arocho Jorge , Aponte-Díaz Laura , Jenkins David A. , O’Brien Joseph J.
Published: June 2020

Background

Many Puerto Rican ecosystems evolved without a regular fire regime. As such, many native plants lack adaptations necessary to survive even low-intensity fires. Human-caused fires are increasing in frequency, in part promoted by the presence of invasive grasses. During the afternoon of 19 February 2014, a wildfire burned a large portion of the dry forest in El Faro Natural Reserve, Cabo Rojo, Puerto Rico. Using a previously monitored population, we documented the mortality and morphological damage on three columnar and semi-epiphytic cactus species (Pilosocereus royenii [L.] Byles & Rowley, Harrisia portoricensis Britton, and Leptocereus quadricostatus Britton) and one globular species (Melocactus intortus [Mill.] Urb.) in relation to canopy cover and cactus growth strategy.

Results

Our results suggest that M. intortus and H. portoricensis were more susceptible to fire damage. Cacti growing in areas dominated by grasses and shrubs were significantly more likely to burn than those growing under a closed tree canopy. Apart from L. quadricostatus, cacti that survived at least one year after the fire had lost spines, developed scarring tissue in some or all ribs, and few were able to regrow.

Conclusions

Because extensive tissue damage and environmental alterations were observed during the post-fire survey, which occurred between 14 to 19 months after the fire, we argue there will be significant delayed mortality and that the mortality estimates presented here are conservative.
P300 cognitive assessment in patients with first-episode psychosis: a prospective case-control study
Authors: Hassan Wageeh A. , Darweesh Alaa Eldin M. , Abdel-Rahman Ahmed A. , Ahmad Hossam Eddin Khalifa , Hassaan Shehab H. , Noaman Mostafa M. , Fahmy Iman F. G.
Published: June 2020

Background

Several studies using event-related potential (ERP) methods have reported a relationship between the cognitive dysfunction of patients with psychosis and P300 latency and amplitude. P300 follow-up studies in patients with schizophrenia receiving antipsychotic treatment revealed that the P300 amplitudes were increased while other studies showed limited changes in the P300 amplitude even after antipsychotics use.

Results

We found that at the first presentation, all patients’ groups have significantly lower amplitude and more prolonged latency of P300 than controls. All the first-episode psychosis patients showed a significant improvement of P300 amplitude mean scores after 1 year, but with no significant change in the P300 latency. There was an inverse correlation between the patients’ PANSS scores and their P300 latency and amplitude values.

Conclusion

P300 amplitude and latency might be of clinical value in the evaluation of cognitive functions in the first-episode psychosis patients. The abnormalities in P300 may be improved with continuous control of psychotic symptoms with psychotropic medications.
Role of abbreviated MRI protocol for screening of HCC in HCV related cirrhotic patients prior to direct-acting antiviral treatment
Authors: Ahmed Nora Nabil Abdou , El Gaafary Sahar Mohamed , Elia Remon Zaher , Abdulhafiz Essam Mohamed
Published: June 2020

Background

Chronic HCV infection is a global health problem causing progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). Recent advantage of direct-acting antiviral drugs (DAA) with a high sustained virologic response (SVR) reduces overall HCV-related morbidity and mortality, yet recent studies report a high recurrence rate of HCC after DAA; this calls availability of a reliable screening method to properly exclude HCC before DAA treatment.

The primary objective of our cohort study was to assess the feasibility of an abbreviated MRI protocol as a screening tool for the detection of hepatic focal lesions/early HCC in patients with HCV-related liver cirrhosis.

The study included 41 patients with HCV-related cirrhosis candidates to DAA therapy. All patients underwent routine screening for HCC by combined abdominal ultrasound and serum alfa-fetoprotein. An abbreviated MRI protocol (Abr-MR) including combined T2-weighted image and diffusion-weighted imaging (DWI) followed by dynamic contrast-enhanced MRI (CE-MRI) was performed for all subjects, assessing for presence and characterization of focal lesions.

Results

For all included 41patients, no elevation of the alpha-fetoprotein was shown. Ultrasound detected a single focal lesion in one patient. Abbreviated MR demonstrated 15 focal lesions; for detected lesions, 1 lesion shows “shine though” and the rest showing moderate and high degrees of restriction. CE-MRI characterized lesions as 1 lesion = LIRADS-1, 3 lesions = LR-M, and 11 lesions = LR-5.The standard screening using combined ultrasound and alpha-fetoprotein had sensitivity, specificity, PPV, and NPV of 6.6 % (95% CI = 0.0034–0.29), 100% (95% CI = 0.89–1.000), 100% (95% CI = 0.051–1.000), and 68.8% (95% CI = 0.54–0.80). Abr-MR protocol showed sensitivity, specificity, PPV, and NPV of 100% for all parameters (95% CI = 0.79–1.000, 0.89–1.000, 0.79–1.000, and 0.89–1.000 respectively).

Conclusion

In our study, we demonstrate the superiority of a proposed cost-effective Abr-MR protocol in the detection of hepatic focal lesions and small-sized HCC compared to routine screening using alpha-fetoprotein and ultrasound in HCV-related liver cirrhosis.
Implementation opportunities and challenges identified by key stakeholders in scaling up HIV Treatment as Prevention in British Columbia, Canada: a qualitative study
Authors: Chayama Koharu Loulou , McNeil Ryan , Shoveller Jean , Small Will , Knight Rod
Published: June 2020

Background

The province of British Columbia (BC), Canada, was among the first jurisdictions to scale up HIV Treatment as Prevention (TasP) to the population level, including funding and policy commitments that enhanced HIV testing efforts (e.g., expansion of routine, opt-out testing), while also making antiretroviral therapy universally available to all people living with HIV. As such, BC represents a critical context within which to identify factors that influenced the scalability of TasP (e.g., acceptability, adoption, fidelity, equitable reach, sustainability), including key opportunities and challenges.

Methods

We draw on in-depth, semi-structured interviews with 10 key stakeholders, comprised policymakers at the local and provincial levels and representatives from community-based organizations. Using the Consolidated Framework for Implementation Research (CFIR) to guide data collection, coding, and analysis, we identified key factors that influenced practice transformation and scale up.

Results

Key factors that contributed to the successful scale up of TasP included: (i) opportunities that enhanced stakeholder buy-in based on features of the intervention characteristics, including with regard to assessments about the quality and strength of evidence supporting TasP; (ii) an inner setting implementation climate that was, in part, shaped by the large and highly symbolic government investments into TasP; (iii) features of the outer setting such as external policies (e.g., harm reduction) that cultivated opportunities to implement new “systems-level” approaches to HIV intervention; (iv) the personal attributes of some “middle-level” influencers, including a team that was comprised of some highly motivated and social justice-oriented individuals (e.g., folks who were deeply committed to serving marginalized populations); and (v) the capacity to develop various implementation processes that could maintain “nimble and evidence-informed” adaptations across a highly decentralized service delivery system, while also creating opportunities to adapt features of TasP programming based on “real time” program data.

Conclusion

Constructs across all five domains of CFIR (intervention characteristics, outer setting, inner setting, characteristics of individuals, and process) were identified to influence the success of TasP in BC. Our findings provide important insights into how BC can successfully implement and scale up other systems-level interventions that have demonstrated efficacy, while also offering insights for other jurisdictions that are currently or planning to scale up TasP.
Clinical diagnosis of Lewy body dementia
Authors: Surendranathan Ajenthan , Kane Joseph P. M. , Bentley Allison , Barker Sally A. H. , Taylor John-Paul , Thomas Alan J. , Allan Louise M. , McNally Richard J. , James Peter W. , McKeith Ian G. , Burn David J. , O'Brien John T.
Published: June 2020

Background

Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.

Aims

This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.

Method

We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.

Results

The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.

Conclusions

Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
The Effect of Cross-linking Efficiency of Drug-Loaded Novel Freeze Gelated Chitosan Templates for Periodontal Tissue Regeneration
Authors: Qasim Syed Saad B. , Nogueria Liebert Parreiras , Fawzy Amr S. , Daood Umer
Published: June 2020

Innovative strategies for periodontal regeneration have been the focus of research clusters across the globe for decades. In order to overcome the drawbacks of currently available options, investigators have suggested a novel concept of functionally graded membrane (FGM) templates with different structural and morphological gradients. Chitosan (CH) has been used in the past for similar purpose. However, the composite formulation of composite and tetracycline when cross-linked with glutaraldehyde have received little attention. Therefore, the purpose of the study was to investigate the drug loading and release characteristics of novel freeze gelated chitosan templates at different percentages of glutaraldehyde. These were cross-linked with 0.1 and 1% glutaraldehyde and loaded with doxycycline hyclate. The electron micrographs depicted porous morphology of neat templates. After cross-linking, these templates showed compressed ultrastructures. Computerized tomography analysis showed that the templates had 88 to 92% porosity with average pore diameter decreased from 78 to 44.9 μm with increasing concentration. Fourier transform infrared spectroscopy showed alterations in the glycosidic segment of chitosan fingerprint region which after drug loading showed a dominant doxycycline spectral composite profile. Interestingly, swelling profile was not affected by cross-linking either at 0.1 and 1% glutaraldehyde and template showed a swelling ratio of 80%, which gained equilibrium after 15 min. The drug release pattern also showed a 40 μg/mL of release after 24 h. These doxycycline-loaded templates show their tendency to be used in a functionally graded membrane facing the defect site.
Overexpression of Wnt7a enhances radiosensitivity of non-small-cell lung cancer via the Wnt/JNK pathway
Authors: Ai Pingping , Xu Xianhua , Xu Shijie , Wei Zhixia , Tan Shun , Li Junzhe
Published: June 2020

The Wingless-type protein 7a (Wnt7a) plays an antiproliferative role in non-small-cell lung cancer (NSCLC). Previous studies have indicated that Wnt7a expression was downregulated in radiation-resistant NSCLC cells. However, little is known about its biological functions and molecular mechanisms in radiosensitivity of NSCLC. Thus, NSCLC cell proliferation and apoptosis in response to Wnt7a overexpression and/or radiation were determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl-tertazolium bromide (MTT) assay and flow cytometry, respectively. The activation of the Wnt/cJun N-terminal kinase (JNK) and Wnt/β-catenin signaling pathways were further examined by western blot in NSCLC cell lines H1650 and A549. Wnt7a overexpression combined with radiation-inhibited cell proliferation and induced apoptosis in NSCLC cell lines compared to Wnt7a overexpression or radiotherapy alone. In addition, the phosphorylation of JNK, but not β-catenin, was congruent with the changes in Wnt7a overexpression and/or radiation. Moreover, the Wnt/JNK pathway could induce the apoptosis of NSCLC cells through the mitochondrial pathway. Inhibition of the Wnt/JNK signaling pathway by SP600125, a JNK inhibitor, contributed to proliferation induction in NSCLC cells. Taken together, these results showed that Wnt7a overexpression sensitized NSCLC cell lines to radiotherapy through the Wnt/JNK signaling pathway.
Gain-of-function genetic screen of the kinome reveals BRSK2 as an inhibitor of the NRF2 transcription factor
Authors: Tamir Tigist Y. , Bowman Brittany M. , Agajanian Megan J. , Goldfarb Dennis , Schrank Travis P. , Stohrer Trent , Hale Andrew E. , Siesser Priscila F. , Weir Seth J. , Murphy Ryan M. , LaPak Kyle M. , Weissman Bernard E. , Moorman Nathaniel J. , Major M. Ben
Published: June 2020

Nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as NRF2) is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, but conversely NRF2 activity diminishes with age and in neurodegenerative and metabolic disorders. Although NRF2-activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here, we describe use of a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the under-studied protein kinase brain-specific kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives 5′-AMP-activated protein kinase α2 (AMPK) signaling and suppresses the mTOR pathway. As a result, BRSK2 kinase activation suppresses ribosome-RNA complexes, global protein synthesis and NRF2 protein levels. Collectively, our data illuminate the BRSK2 and BRSK1 kinases, in part by functionally connecting them to NRF2 signaling and mTOR. This signaling axis might prove useful for therapeutically targeting NRF2 in human disease.

This article has an associated First Person interview with the first author of the paper.
Primary operator radiation dose in the cardiac catheter laboratory
Authors: Crowhurst James A , Whitby Mark , Aroney Nicholas , Dautov Rustem , Walters Darren , Raffel Owen
Published: June 2020

Objectives:

Radiation from cardiac angiography procedures is harmful to patients and the staff performing them. This study sought to investigate operator radiation dose for a range of procedures and different operators in order to investigate trends and optimise dose.

Methods:

Real-time dosemeters (RTDs) were worn by operators for angiography procedures for 3 years. Dose–area product (DAP) and RTD were collected. RTD was normalised to DAP (RTD/DAP) to compare radiation dose and radiation protection measures. Comparisons were made across procedure categories and individual operators.

Results:

In 7626 procedures, median and 75th percentile levels were established for operator dose for 8 procedure categories. There was a significant difference in all operator dose measures and DAP across procedure categories (p<0.001). DAP, RTD, and RTD/DAP were significantly different across 22 individual operators (p<0.001).

Conclusion:

DAP was significantly different across procedure categories and a higher RTD was seen with higher DAP. RTD/DAP can demonstrate radiation protection effectiveness and identified differences between procedures and individual operators with this measure. Procedures and individuals were identified where further optimisation of radiation protection measures may be beneficial. A reference level for operator dose can be created and audited against on a regular basis.

Advances in knowledge:

This study demonstrates that operator dose can be easily and routinely measured on a case by case basis to investigate dose trends for different procedures. Normalising the operator dose to DAP demonstrates radiation protection effectiveness for the individual operator which can then be optimised as part of an ongoing audit program.
Comparison of radiographer interobserver image registration variability using cone beam CT and MR for cervix radiotherapy
Authors: Rodgers John , Hales Rosie , Whiteside Lee , Parker Jacqui , McHugh Louise , Cree Anthea , van Herk Marcel , Choudhury Ananya , Hoskin Peter , McWilliam Alan , Eccles Cynthia L
Published: June 2020

Objectives:

The aim of this study was to assess the consistency of therapy radiographers performing image registration using cone beam computed tomography (CBCT)-CT, magnetic resonance (MR)-CT, and MR-MR image guidance for cervix cancer radiotherapy and to assess that MR-based image guidance is not inferior to CBCT standard practice.

Methods:

10 patients receiving cervix radiation therapy underwent daily CBCT guidance and magnetic resonance (MR) imaging weekly during treatment. Offline registration of each MR image, and corresponding CBCT, to planning CT was performed by five radiographers. MR images were also registered to the earliest MR interobserver variation was assessed using modified Bland–Altman analysis with clinically acceptable 95% limits of agreement (LoA) defined as ±5.0 mm.

Results:

30 CBCT-CT, 30 MR-CT and 20 MR–MR registrations were performed by each observer. Registration variations between CBCT-CT and MR-CT were minor and both strategies resulted in 95% LoA over the clinical threshold in the anteroposterior direction (CBCT-CT ±5.8 mm, MR-CT ±5.4 mm). MR–MR registrations achieved a significantly improved 95% LoA in the anteroposterior direction (±4.3 mm). All strategies demonstrated similar results in lateral and longitudinal directions.

Conclusion:

The magnitude of interobserver variations between CBCT-CT and MR-CT were similar, confirming that MR-CT radiotherapy workflows are comparable to CBCT-CT image-guided radiotherapy. Our results suggest MR–MR radiotherapy workflows may be a superior registration strategy.

Advances in knowledge:

This is the first publication quantifying interobserver registration of multimodality image registration strategies for cervix radical radiotherapy patients.
Oral manifestation of Waardenburg syndrome: a case report and review of the literature
Authors: Jagtap Rohan , Srivastava Ambika , Jadhav Aniket , Gupta Swati
Published: June 2020

Waardenburg syndrome is a rare autosomal dominant genetic disorder of neural crest cell migration. It is characterized by congenital sensorineural hearing loss, heterochromia iridis, depigmentation of hair and skin, and increased intercanthal distance. It is subdivided into four subtypes with I and II being most common. These subtypes are categorized based on genetic mutations. Although medical literature has well documented this syndrome, dental and radiographical findings have been rarely presented. In this case report and literature review, we have presented and discussed oral as well as head and neck radiology findings of a 20-year-old girl with Waardenburg syndrome.
Influence of windowing and metal artefact reduction algorithms on the volumetric dimensions of five different high-density materials: a cone-beam CT study
Authors: Coelho-Silva Fernanda , Martins Luciano Augusto Cano , Braga Daniela Azeredo , Zandonade Eliana , Haiter-Neto Francisco , de-Azevedo-Vaz Sergio Lins
Published: June 2020

Objective:

To assess the influence of windowing and metal artefact reduction (MAR) algorithms on the volumetric dimensions of high-density materials using two CBCT systems.

Methods:

Four cylinders of amalgam, cobalt-chromium, gutta-percha, titanium and zirconium, were manufactured and their physical volumes (PV) were measured. A polymethyl methacrylate phantom containing the cylinders was submitted to CBCT acquisitions with Picasso Trio and OP300 units with their MAR enabled and disabled. The tomographic volume (TV) of all the cylinders was obtained by semi-automatic segmentation using two windowing adjustments: W1—large window width and upper window level; W2—narrow window width and low window level. Volumetric distortion was expressed as the difference between TV and PV. Statistics comprised intraclass correlation coefficient (ICC) and analysis of variance (ANOVA) for repeated measures with Tukey post hoc test (α = 5%).

Results:

The ICC values ​​indicated excellent reproducibility of TV. Gutta-percha and titanium resulted in the smallest volumetric distortion. Using W1 provided less volumetric distortion for almost all experimental conditions (p < 0.05). Activating MAR algorithm of Picasso Trio underestimated gutta-percha and titanium TV (p < 0.05) and was inefficient in significantly reducing the volumetric distortion of the other materials (p > 0.05). Disabling MAR algorithm of OP300 resulted in smaller volumetric distortion for almost all experimental conditions (p < 0.05).

Conclusions:

The TV of gutta-percha and titanium were closer to the PV. In general, the MAR algorithms of both systems were inefficient in significantly reducing the volumetric distortion of high-density materials. We encourage the use of large window width and upper window level to evaluate high-density materials.
Neuronal regulation of bone marrow stem cell niches
Authors: Fielding Claire , Méndez-Ferrer Simón
Published: June 2020

The bone marrow (BM) is the primary site of postnatal hematopoiesis and hematopoietic stem cell (HSC) maintenance. The BM HSC niche is an essential microenvironment which evolves and responds to the physiological demands of HSCs. It is responsible for orchestrating the fate of HSCs and tightly regulates the processes that occur in the BM, including self-renewal, quiescence, engraftment, and lineage differentiation. However, the BM HSC niche is disturbed following hematological stress such as hematological malignancies, ionizing radiation, and chemotherapy, causing the cellular composition to alter and remodeling to occur. Consequently, hematopoietic recovery has been the focus of many recent studies and elucidating these mechanisms has great biological and clinical relevance, namely to exploit these mechanisms as a therapeutic treatment for hematopoietic malignancies and improve regeneration following BM injury. The sympathetic nervous system innervates the BM niche and regulates the migration of HSCs in and out of the BM under steady state. However, recent studies have investigated how sympathetic innervation and signaling are dysregulated under stress and the subsequent effect they have on hematopoiesis. Here, we provide an overview of distinct BM niches and how they contribute to HSC regulatory processes with a particular focus on neuronal regulation of HSCs under steady state and stress hematopoiesis.
Comparison of WHO growth standard and national Indonesian growth reference in determining prevalence and determinants of stunting and underweight in children under five: a cross-sectional study from Musi sub-district
Authors: Flynn Jeannie , Alkaff Firas Farisi , Sukmajaya William Putera , Salamah Sovia
Published: June 2020

Background:Determination of stunting and wasting always uses the WHO growth standard in Indonesia. However, it is believed that Indonesian children are “below” the global standard, thus the WHO standard is not reliable to present the actual prevalence. This study aims to compare the prevalence and determinants of stunting and underweight using WHO growth standard and national Indonesian growth reference.

Methods:This was a cross-sectional study carried out in Musi sub-district, East Nusa Tenggara province in July 2019. East Nusa Tenggara province had the highest prevalence of stunting and underweight in Indonesia. The study population were children under five, and total sampling method was used for this study. Length/height-for-age and weight-for-age were plotted using WHO standard and national Indonesian reference. Univariate and multivariate binomial logistic regression were used for statistical analysis.

Results:The prevalence of stunting and underweight were higher for the WHO standard than the national reference (53.9% vs 10.7% and 29.17% vs 17.7%; all p < 0.001). After adjusted for confounding factors, when the WHO standard was used, determinants of stunting were maternal mid-upper arm circumference below 23.5cm and maternal height below 150cm; determinants of underweight were intrauterine growth restriction, young maternal age during pregnancy, and multiple parities. When the national reference was used, no determinants was found for stunting; the determinants of underweight were intrauterine growth restriction and maternal education.

Conclusions:The WHO standard is not suitable for representing child growth in Musi sub-district. Future studies should be done to re-evaluate the prevalence and determinants of stunting and underweight nationwide using the national Indonesian reference.
Including a pen and/or cover letter, containing social incentive text, had no effect on questionnaire response rate: a factorial randomised controlled Study within a Trial
Authors: James Sophie , Parker Adwoa , Cockayne Sarah , Rodgers Sara , Fairhurst Caroline , Torgerson David J. , Rhodes Sarah , Cotterill Sarah
Published: June 2020

Background: Postal questionnaires are frequently used in randomised controlled trials to collect outcome data on participants; however, poor response can introduce bias, affect generalisability and validity, and reduce statistical power. The objective of this study was to assess whether a pen and/or social incentive text cover letter sent with a postal follow-up questionnaire increased response rates in a trial.

Method: A two-by-two factorial randomised controlled trial was embedded within the OTIS host trial. Participants due their 12-month (final) follow-up questionnaire were randomised to be sent: a pen; a social incentive text cover letter; both; or neither. The primary outcome measure was the proportion of participants in each group who returned the questionnaire. Secondary outcomes were: time to return, completeness of the questionnaire, necessity of a reminder letter, and the cost effectiveness.

Results: The overall 12-month questionnaire response rate was 721 out of 755 (95.5%). Neither the pen nor social incentive cover letter had a statistically significant effect on response rate: pen 95.2% vs. no pen 95.8%, adjusted OR 0.90 (95% CI 0.45 to 1.80; p=0.77); social incentive cover letter 95.2% vs. no social incentive cover letter 95.8%, adjusted OR 0.84 (95% CI 0.42 to 1.69, p=0.63). No statistically significant differences were observed between either of the intervention groups on time to response, need for a reminder or completeness. Therefore, neither intervention was cost-effective.

Conclusions: We found no evidence of a difference in response rates associated with the inclusion of a pen and/or social incentive cover letter with the final follow-up postal questionnaire of the host trial. However, when these results are combined with previous SWATs, the meta-analysis evidence remains that including a pen increases response rates. The social incentive cover letter warrants further investigation to determine effectiveness.

Trial registration: ISRCTN22202133 (21st June 2020).
Frequency and clinical significance of prostatic involvement in men with febrile urinary tract infection: a prospective observational study
Authors: Arjunlal Thayyil Shahilal , Deepanjali Surendran , Manikandan Ramanitharan , Medha Rajappa
Published: June 2020

Background: Frequent asymptomatic involvement of the prostate has been demonstrated in men with febrile urinary tract infection (fUTI). In view of this, men with fUTI are often given a longer duration of antibiotic treatment; however, evidence to support this is limited.

Methods: We prospectively studied adult men with fUTI admitted under the Department of Medicine in a tertiary care hospital in southern India.  fUTI was defined as fever of ≥38°C with at least one symptom/sign of UTI and pyuria, requiring hospitalization. We estimated serum total prostate-specific antigen (PSA) levels at enrollment, one month and three months after treatment completion. We assessed prostatic volume by transrectal ultrasonography (TRUS) and estimated the serum high sensitivity C-reactive protein (hs-CRP) levels at baseline and after three months.

Results: We enrolled 64 men (median [IQR] age 53 [45-60] years); 50 patients completed follow-up. At baseline, the median (IQR) serum PSA level was 2.15 (1.18-3.02) ng/mL and median (IQR) serum hs-CRP level was 2.43 (2.28-2.58) mg/L. At three months, serum PSA levels decreased by ≥25% in 47 (94%) of 50 patients. The median (IQR) of prostatic volume was 25.4 (18.9-34) mL at baseline, and ≥10% decrease in prostatic volume was observed in 24 (48%) of 50 patients at three months. The change in the serum PSA levels did not correlate with clinical findings like prostatic tenderness or with prostatic volume changes. Further, serum PSA levels did not correlate with hs-CRP levels. On follow-up, seven patients had lower urinary tract symptoms; only one of them had recurrent fUTI.  

Conclusions: Asymptomatic prostatic involvement, although common in men with fUTI, does not seem to influence the treatment outcomes.
Mid-level health providers for primary healthcare: a rapid evidence synthesis
Authors: Moola Sandeep , Bhaumik Soumyadeep , Nambiar Devaki
Published: June 2020

Background: Health care services, in many countries, are increasingly being provided by cadres not trained as physicians, but capable of performing several diagnostic and clinical functions. These substitute health workers are referred to as mid-level health providers (MLHPs). The health and wellness centres under India’s Comprehensive Primary Health Care programme have teams led by MLHPs who can aid doctors. The objective of this study was to rapidly synthesise evidence on the effectiveness of MLHPs for primary health care.

Methods: The review team undertook a rapid overview of systematic reviews that compared MLHPs with doctors and different types of MLHPs involved in the delivery of health care were included, with a perspective on low- and middle-income countries, including India.

Results: Seven systematic reviews were included in the final report. Mortality outcomes in relation to pregnancy and childbirth care services showed no significant differences in care provided by MLHPs when compared with doctors. Pregnancy care provided by midwives was found to slightly improve quality of care when compared to care delivered by doctors. The risk of failure or incomplete abortion for surgical abortion procedures provided by MLHPs was twice when compared to the procedures provided by doctors. Moderate to high certainty evidence showed that initiation and maintenance of antiretroviral therapy for HIV-infected patients by a nurse or clinical officer slightly reduced mortality. High certainty evidence showed that chronic disease management by non-medical prescribers reduced some important physiological measures when compared to medical prescribing by doctors.

Conclusions: To date, this is the first rapid overview of evidence on MLHPs. Evidence suggests that MLHPs might be suitable to deliver quality care in certain areas of health and they may be relevant and feasible in countries like India. However, the roles and subsequent training and regulation of MLHPs might be different for different care domains.
Hepatocellular carcinoma: recent advances and emerging medical therapies
Authors: Ko Kwan-Lung , Mak Lung-Yi , Cheung Ka-Shing , Yuen Man-Fung
Published: June 2020

Hepatocellular carcinoma remains a deadly disease with poor prognosis in patients with unresectable cancer. Trans-arterial chemoembolization is the primary locoregional therapy for intermediate-stage hepatocellular carcinoma, with an estimated median overall survival of less than two years. For almost a decade, sorafenib has been the only standard systemic treatment for metastatic disease or tumors which progress or are considered unsuitable for locoregional therapy. Major breakthroughs have been made over the past few years in the management of hepatocellular carcinoma, especially in medical therapies for advanced disease. In this article, recent advances in intra-arterial therapy, multi-kinase inhibitors, and immunotherapy will be reviewed.
The NEUBIAS Gateway: a hub for bioimage analysis methods and materials
Authors: Cimini Beth A. , Nørrelykke Simon F , Louveaux Marion , Sladoje Nataša , Paul-Gilloteaux Perrine , Colombelli Julien , Miura Kota
Published: June 2020

We introduce the NEUBIAS Gateway, a new platform for publishing materials related to bioimage analysis, an interdisciplinary field bridging computer science and life sciences. This emerging field has been lacking a central place to share the efforts of the growing group of scientists addressing biological questions using image data. The Gateway welcomes a wide range of publication formats including articles, reviews, reports and training materials. We hope the Gateway further supports this important field to grow and helps more biologists and computational scientists learn about and contribute to these efforts.
How are countries planning for costs of nutrition data and information systems?
Authors: Manorat Renee , Rana Yashodhara , Borces Kyle , Becker Laura , Flory Augustin
Published: June 2020

Background: The first Global Nutrition Report in 2014 called for a “data revolution” in nutrition, so that countries have the latest data to set priorities and monitor progress. Integral to this revolution is understanding how countries are investing in the data, systems and capacity required to support decision-making around nutrition, i.e. their nutrition data and information system (NDIS).

Methods: For this reason, our team conducted a desk review of national nutrition plans for 58 Scaling Up Nutrition (SUN) countries to better understand how countries are planning for and estimating the costs of their NDIS.

Results: We found that of the SUN national nutrition plans that are publicly accessible, not all are costed and less than half of these have explicit data and monitoring and evaluation (M&E) sections. Of the 19 national plans that had costed data and M&E sections, our initial estimates show costs for data systems ranged from 0.1%-12.8% of total plan costs with limited information on data system components.

Conclusions: There is an imminent need for more comprehensive and strategic approaches – including the planning for and financing of – NDIS in countries.