bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey about postoperative delirium in older patients among nurses and anaesthetists: implications for future practice and policy
Authors: Igwe Ezinne O , Traynor Victoria , Rodgers Sheila , Waite Alasdair , MacLullich Alasdair , Foo Irwin
Published: September 2020

Background

Postoperative delirium is a major complication associated with anaesthesia and surgery, more commonly seen in older people.

Aims

The aims of this study were to explore the knowledge and understanding of anaesthetists and nurses involved in anaesthesia through their responses to two case scenarios of postoperative delirium experienced by older people.

Methods

A 30-item online survey was sent to 500 potential respondents.

Results

Two hundred and twenty-six practitioners from Australia, New Zealand and Scotland responded. Most had no workplace protocols for anaesthesia planning in older people. There was substantial variability in practice in relation to postoperative delirium screening, detection, prevention and management.

Conclusions

Improvements in education and awareness, together with a more coherent approach, for example, as recommended in the European Society of Anaesthesiology Guidelines, could help to reduce the impact of postoperative delirium in older people. This should be combined with ongoing research into perioperative optimisation of detection, prevention and management of postoperative delirium.
Everyday Aesthetics, Locality and Racialisation
Authors: Smith Andrew , Byrne Bridget , Garratt Lindsey , Harries Bethan
Published: September 2020

In this essay we reflect on the relationship between aesthetic practices and racialised conceptions of belonging. In particular, we explore attributions of beauty and ugliness, order and disorder, as these are made in relation to local space, and we consider how these attributions can be linked to proprietorial claims about who is welcome in those spaces. Our focus is thus on the everyday aesthetics of location: the ways in which aesthetic judgements are tied to the inhabitation of space and, in this case, the exclusionary potential of ‘ways of looking’ at such spaces and at the social relations which exist within them. Drawing on data from qualitative research in two adjoining neighbourhoods in Glasgow’s Southside, we make three analytical contributions. First, we consider the racialising potential of everyday aesthetic responses to local space. Second, we explore the ways in which local social relations themselves can be aesthetically interpreted. Third, we reflect on forms of everyday aesthetic resistance.
Assessment of the additional clinical potential of X-ray dark-field imaging for breast cancer in a preclinical setup
Authors: Emons Julius , Fasching Peter A. , Wunderle Marius , Heindl Felix , Rieger Jens , Horn Florian , Pelzer Georg , Ritter Andre , Weber Thomas , Radicke Marcus , Polifka Iris , Wachter David L. , Wenkel Evelyn , Michel Thilo , Uder Michael , Hartmann Arndt , Anton Gisela , Beckmann Matthias W. , Schulz-Wendtland Rüdiger , Jud Sebastian M.
Published: September 2020

Background:

Mammography can identify calcifications up to 50–100 μm in size as a surrogate parameter for breast cancer or ductal carcinoma in situ (DCIS). Microcalcifications measuring <50 µm are also associated with breast cancer or DCIS and are frequently not detected on mammography, although they can be detected with dark-field imaging. This study examined whether additional breast examination using X-ray dark-field imaging can increase the detection rate of calcifications. Advances in knowledge:  (1) evaluation of additional modality of breast imaging;  (2) specific evaluation of breast calcifications. Implications for patient care: the addition of X-ray dark-field imaging to conventional mammography could detect additional calcifications.

Methods:

Talbot–Lau X-ray phase–contrast imaging and X-ray dark-field imaging were used to acquire images of breast specimens. The radiation dosage with the technique is comparable with conventional mammography. Three X-ray gratings with periods of 5–10 µm between the X-ray tube and the flat-panel detector provide three different images in a single sequence: the conventional attenuation image, differential phase image, and dark-field image. The images were read by radiologists. Radiological findings were marked and examined pathologically. The results were described in a descriptive manner.

Results:

A total of 81 breast specimens were investigated with the two methods; 199 significant structures were processed pathologically, consisting of 123 benign and 76 malignant lesions (DCIS or invasive breast cancer). X-ray dark-field imaging identified 15 additional histologically confirmed carcinoma lesions that were visible but not declared suspicious on digital mammography alone. Another four malignant lesions that were not visible on mammography were exclusively detected with X-ray dark-field imaging.

Conclusions:

Adding X-ray dark-field imaging to digital mammography increases the detection rate for breast cancer and DCIS associated lesions with micrometer-sized calcifications. The use of X-ray dark-field imaging may be able to provide more accurate and detailed radiological classification of suspicious breast lesions. Adding X-ray dark-field imaging to mammography may be able to increase the detection rate and improve preoperative planning in deciding between mastectomy or breast-conserving therapy, particularly in patients with invasive lobular breast cancer.
Can Scoliotic Discs Be Controls for Molecular Studies in Intervertebral Disc Research? Insights From Proteomics
Authors: Rajasekaran S. , Tangavel Chitraa , Anand K. S. Sri Vijay , Soundararajan Dilip Chand Raja , Nayagam Sharon Miracle , Sunmathi R. , Raveendran M. , Shetty Ajoy Prasad , Kanna Rishi Mugesh , Pushpa B. T.
Published: September 2020

Study Design:

Proteomic analysis of human intervertebral discs.

Objectives:

To compare the characters of scoliotic discs and discs from magnetic resonance imaging (MRI)–normal voluntary organ donors controls used in disc research employing proteomics and establish “true controls” that can be utilized for future intervertebral disc (IVD) research.

Methods:

Eight MRI-normal discs from 8 brain-dead voluntary organ donors (ND) and 8 scoliotic discs (SD) from 3 patients who underwent anterior surgery for adolescent idiopathic scoliosis were subjected to tandem mass spectrometry, and further analysis was performed.

Results:

Mass spectrometry identified a total of 235 proteins in ND and 438 proteins in the SD group. Proteins involved in extracellular matrix integrity (Versican, keratins KRT6A, KRT14, KRT5, and KRT 13A1, A-kinase anchor protein 13, coagulation factor XIII A chain, proteoglycan 4) and proteins involved in transcription and DNA repair (Von Willebrand factor A domain-containing 3B, eukaryotic initiation factor 2B, histone H4, leukocyte cell–derived chemotaxin 2) were found to be downregulated in SD. Inflammatory proteins (C3, C1S), and oxidative stress response proteins (peroxiredoxin-2,6, catalase, myeloperoxidase, apolipoprotein E) were found to be upregulated in SD. These changes were reflected at the pathway level also.

Conclusion:

Findings of our study confirm that scoliotic discs have an abundance of inflammatory, oxidative stress response proteins, which are either absent or downregulated in the ND group indicating that scoliotic discs are not pathologically inert. Furthermore, this study has established MRI-normal discs from voluntary organ donors as the “true” control for molecular studies in IVD research.
Vogesella perlucida-induced bacteremia in an advanced-age patient: first case report
Authors: Yu Zengxian , Zhu Fang , Tao Xinghe , Zhang Lu , Wu Suliu , Dong Chunfu , Dong Yeqing , chen Ge , Zhou Xinyang , Fang Yinfei , Xu Kechen
Published: September 2020

Background

Vogesella species are common aquatic, Gram-negative rod-shaped bacteria, originally described in 1997. Vogesella perlucida was first isolated from spring water in 2008. Furthermore, bacterial pathogenicity of Vogesella perlucida has never been reported. Here, we report the first case of rare Vogesella perlucida-induced bacteremia in an advanced-age patient with many basic diseases and history of dexamethasone abuse.

Case presentation

A 71-year-old female was admitted with inflamed upper and lower limbs, rubefaction, pain and fever (about 40 °C). She had been injured in a fall at a vegetable market and then touched river snails with her injury hands. A few days later, soft tissue infection of the patient developed and worsened. Non-pigmented colonies were isolated from blood cultures of the patient. Initially, Vogesella perlucida was wrongly identified as Sphingomonas paucimobilis by Vitek-2 system with GN card. Besides, we failed to obtain an acceptable identification by the MALDI-TOF analysis. Finally, the isolated strain was identified as Vogesella perlucida by 16S rRNA gene sequences. In addition, the patient recovered well after a continuous treatment of levofloxacin for 12 days.

Conclusion

Traditional microbiological testing system may be inadequate in the diagnosis of rare pathogenic bacteria. Applications of molecular diagnostics techniques have great advantages in clinical microbiology laboratory. By using 16S rRNA gene sequence analysis, we report the the first case of rare Vogesella perlucida-induced bacteremia.
Membranous nephropathy in patients with HIV: a report of 11 cases
Authors: Charu Vivek , Andeen Nicole , Walavalkar Vighnesh , Lapasia Jessica , Kim Jin-Yon , Lin Andrew , Sibley Richard , Higgins John , Troxell Megan , Kambham Neeraja
Published: September 2020

Background

Membranous nephropathy (MN) has been recognized to occur in patients with human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. The prevalence of phospholipase A2 receptor (PLA2R)-associated MN in this group has not been well studied.

Methods

We conducted a retrospective review of electronic pathology databases at three institutions to identify patients with MN and known HIV at the time of renal biopsy. Patients with comorbidities and coinfections known to be independently associated with MN were excluded.

Results

We identified 11 HIV-positive patients with biopsy-confirmed MN meeting inclusion and exclusion criteria. Patient ages ranged from 39 to 66 years old, and 10 of 11 patients (91%) were male. The majority of patients presented with nephrotic-range proteinuria, were on anti-retroviral therapy at the time of biopsy and had low or undetectable HIV viral loads. Biopsies from 5 of 10 (50%) patients demonstrated capillary wall staining for PLA2R. Measurement of serum anti-PLA2R antibodies was performed in three patients, one of whom had positive anti-PLA2R antibody titers. Follow-up data was available on 10 of 11 patients (median length of follow-up: 44 months; range: 4–145 months). All patients were maintained on anti-retroviral therapy (ARV) and 5 patients (52%) received concomitant immunosuppressive regimens. Three patients developed end-stage renal disease (ESRD) during the follow-up period.

Conclusions

MN in the setting of HIV is often identified in the setting of an undetectable viral loads, and similar to other chronic viral infection-associated MNs, ~ 50% of cases demonstrate tissue reactivity with PLA2R antigen, which may be seen without corresponding anti-PLA2R serum antibodies.
Pain management in patients with end-stage renal disease and calciphylaxis- a survey of clinical practices among physicians
Authors: Chinnadurai Rajkumar , Sinha Smeeta , Lowney Aoife C , Miller Mary
Published: September 2020

Background

Calciphylaxis is a rare condition usually seen in patients with end-stage renal disease. Pain is a hallmark of this condition and can be extremely difficult to control. Anecdotal data suggests that pain management in calciphylaxis is challenging with variable approaches across the United Kingdom (UK) and internationally. A knowledge and practice survey was conducted to establish current practice in the management of pain in patients with calciphylaxis, in the UK. Based on the results and clinical experience the authors suggest a clinical practice guideline.

Methods

An online questionnaire was circulated among physicians (renal and palliative care) involved in the management of pain in calciphylaxis. The questionnaire included a mix of open-ended questions and questions with drop down options.

Results

One hundred and six clinicians responded to the survey of which 60 (57%) respondents were from palliative medicine; the remaining 46 (43%) were from renal medicine. 31 (30%) respondents across both specialties had not encountered any patients with a diagnosis of calciphylaxis (renal-2, palliative care-29). A referral to the palliative care team was undertaken by 18% of renal physicians, 32% referred to the pain team and 50% referred to both. Only 3% of the palliative medicine respondents indicated that they had received a referral from the renal team at the time of diagnosis. Opioids were the preferred initial drug of choice for the management of all types of pain. Paracetamol was universally selected as the preferred first-choice adjuvant agent for management of all types of pain. The importance of advance care planning was highlighted with 72% undertaking advanced care planning discussions often or most of the time.

Conclusion

There was wide variation in the current practice of pain management in patients with calciphylaxis, with variation between renal specialists and palliative care specialists. Referral to specialists in pain management is not universal despite the severe nature of the pain experienced by patients with calciphylaxis. The data generated has facilitated the development of a clinical practice guideline to support complex pain management in a group of patients with multiple comorbidities.
Survival outcomes in men with a positive family history of prostate cancer: a registry based study
Authors: Ang Mann , Borg Martin , O’Callaghan Michael E. ,   for the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC)
Published: September 2020

Background

To investigate the correlation between family history of prostate cancer (PCa) and survival (overall and cancer specific) in patients undergoing treatment for PCa.

Methods

ine thousand four hundred fifty-nine patients with PCa were extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Diagnosis occurred after 1998 and treatment before 2014. Cox proportional-hazards modeling was used to assess the effect of family history on overall survival after adjustment for confounders (age at diagnosis, NCCN risk category and year of treatment), and with stratification by primary treatment group. Competing risks regression modelling was used to assess PCa specific mortality.

Results

Men with a positive family history of PCa appear to have a lower Gleason score at the time of diagnosis (50% with Gleason < 7, compared to 39% in those without family history) and be diagnosed at a lower age (64 vs 69). Men with a positive family history of PCa appear to have better overall survival outcomes (p < 0.001, log rank test). In analysis adjusting for age at diagnosis, NCCN risk category and year of treatment, family history remained a significant factor when modelling overall survival (HR 0.72 95% CI 0.55–0.95, p = 0.021).

There were no significant differences in treatment subgroups of radical prostatectomy (p = 0.7) and radiotherapy (0.054).

Conclusion

Men with a positive family history of PCa appear to have better overall survival outcomes. This better survival may represent lead time bias and early initiation of PSA screening. Family history of PCa was not associated with different survival outcomes in men who were treated with either radical prostatectomy or radiotherapy.
Pulse oximetry curves in healthy children living at moderate altitude: a cross-sectional study from the Ecuadorian Andes
Authors: Andrade Vinicio , Andrade Felipe , Riofrio Pablo , Nedel Fúlvio B. , Martin Miguel , Romero-Sandoval Natalia
Published: September 2020

Background

In populations above 3,000 meters above sea level (m.a.s.l.) normal values of oxygen saturation (SpO2) above 90% have been reported. Few studies have been conducted in cities of moderate altitude (between 2,500 and 3,000 m a.s.l). We set out to describe the range of SpO2 values measured with a pulse oximeter in healthy children between 1 month and 12 years of age living in an Ecuadorian Andean city.

Methods

A cross-sectional study was carried out in Quito, Ecuador, located at 2,810 m a.s.l. SpO2 measurement in healthy children of ages ranging from 1 month to 12 years of age residents in the city were recorded by pulse oximetry. Age and gender were recorded, and median and 2.5th and 5th percentile were drawn. Non parametric tests were used to compare differences in SpO2 values by age and gender.

Results

1,378 healthy children were included for the study, 719 (52.2%) males. The median SpO2 for the entire population was 94.5%. No differences were observed between SpO2 median values by age and gender. The 2.5th percentile for global SpO2 measurements was 90%, in children under 5 years of age was 91% and it was 90% in children older than 7.

Conclusions

Our results provide SpO2 values for healthy children from 1 to 12 years old residents in Quito, a city of moderate altitude. The SpO2 percentile curve could contribute as a healthy range for the clinical evaluation of children residing at this altitude.
Disparities in physical fitness of 6–11-year-old children: the 2012 NHANES National Youth Fitness Survey
Authors: Guseman E. H. , Tanda R. , Haile Z. T.
Published: September 2020

Background

Children’s physical fitness is an important predictor of metabolic health, physical function, and academic achievement. Although fitness is determined partially by heritable factors, it can be maintained and improved through regular physical activity. Because physical activity is known to vary by socioeconomic status, physical fitness may be expected to vary similarly. With this in mind, the purpose of this study was to examine disparities in physical fitness performance among a nationally-representative sample of 6–11 year-old children living in the United States.

Methods

We conducted secondary analysis of physical fitness data of children ages 6–11 years (n = 686) from the nationally representative National Health and Nutrition Survey (NHANES) Youth Fitness Survey (NNYFS) 2012. We estimated sex-stratified weighted means of four fitness performance tests: cardiorespiratory endurance, upper-, lower-, and core-muscular strength. The weighted mean for each fitness assessment was compared by income groups (federal income to poverty ratio – FIPR) accounting for complex sampling design and adjusting for age.

Results

Income disparities in physical fitness performance were evident among girls but not among boys. Girls from lower income groups (< 130% FIPR and 130–349% FIPR groups) showed significantly lower cardiorespiratory endurance and core muscle strength compared to those from the highest income group (≥ 350% FIPR).

Conclusion

These findings highlight the need to support health-promoting physical activity among girls from disadvantaged backgrounds prior to the adolescent period.
Geostatistical analysis and mapping: social and environmental determinants of under-five child mortality, evidence from the 2014 Ghana demographic and health survey
Authors: Aheto Justice Moses K. , Yankson Robert , Chipeta Michael Give
Published: September 2020

Background

Under-five mortality (U5M) rates are among the health indicators of utmost importance globally. It is the goal 3 target 2.1 of the Sustainable Development Goals that is expected to be reduced to at least 25 per 1000 livebirths by 2030. Despite a considerable reduction in U5M observed globally, several countries especially those in sub-Saharan Africa (SSA) like Ghana are struggling to meet this target. Evidence-based targeting and utilization of the available limited public health resources are critical for effective design of intervention strategies that will enhance under-five child survival. We aimed to estimate and map U5M risk, with the ultimate goal of identifying communities at high risk where interventions and further research can be targeted.

Methods

The 2014 Ghana Demographic and Health Survey data was used in this study. Geostatistical analyses were conducted on 5884 children residing in 423 geographical clusters. The outcome variable is child survival status (alive or dead). We employed a geostatistical generalised linear mixed model to investigate both measured and unmeasured child specific and spatial risk factors for child survival. We then visualise child mortality by mapping the predictive probability of survival.

Results

Of the total sampled under 5 children, 289 (4.91%) experienced the outcome of interest. Children born as multiple births were at increased risk of mortality with an adjusted odds ratio (aOR) (aOR: 8.2532, 95% CI: [5.2608–12.9477]) compared to singletons. Maternal age increased risk of mortality (aOR: 1.0325, 95% CI: [1.0128–1.0527]). Child’s age (aOR: 0.2277, 95% CI: [0.1870–0.2771]) and number of children under 5 within each household (aOR: 0.3166, 95% CI: [0.2614–0.3835]) were shown to have a protective effect. Additionally, mothers with secondary education level (aOR: 0.6258, 95% CI: [0.4298–0.9114]) decreased the risk of U5M. The predicted U5M risk in 2014 was at 5.98%. Substantial residual spatial variations were observed in U5M.

Conclusion

The analysis found that multiple births is highly associated with increased U5M in Ghana. The high-resolution maps show areas and communities where interventions and further research for U5M can be prioritised to have health impact.
Use of complementary and alternative therapies for the treatment of dysmenorrhea among undergraduate pharmacy students in Malaysia: a cross sectional study
Authors: Abubakar Usman , Zulkarnain Amni Izzati , Samri Fatihah , Hisham Sabrina Ros , Alias Anis , Ishak Muhammad , Sugiman Hajarah , Ghozali Taufik
Published: September 2020

Background

Dysmenorrhea is a common problem that affects female students’ quality of life and academic activities. Complementary and alternative therapies (CATs) are used for the treatment of dysmenorrhea. This study investigated the practices and perceptions of female undergraduate students with dysmenorrhea towards CATs.

Methods

This was a cross-sectional study conducted among undergraduate pharmacy students in a public university in Malaysia using a validated and pre-tested self-administered questionnaire. The study was conducted in November and December 2019. The data was analysed using descriptive and inferential statistical tests.

Results

Of the 318 female undergraduate students invited, 219 completed the questionnaire (response rate: 68.9%) with 52% aged between 21 and 23 years. The prevalence of dysmenorrhea was 72.1%, and the prevalence of ever-use and current use of CATs was 70.3 and 54.4%, respectively. Bed rest (71.5%), hot compress/heating pad (47.5%) and massage (43.0%) were the most common CATs used by the respondents. The most common reasons for using CAT were to reduce the need for analgesics (61.4%), efficacy (37.3%) and recommendation by others (32.9%). About 23 and 9% of the respondents believed that CATs were equally “effective” and “more effective” than analgesics, respectively. Reducing the need for analgesics (AOR: 4.066, 95% CI: 2.136–7.739) and those who agreed that CATs are effective (AOR: 2.701, 95% CI: 1.337–5.457) were independently associated with the current use CATs for the treatment of menstrual pain.

Conclusion

The prevalence of ever-use and current use of CATs is high among female undergraduate pharmacy students. Bed rest and heat applications are the most common CATs used. Reducing the need for analgesics and efficacy are the factors associated with the current use of CATs. Students should be educated about the safe and effective use of CATs to reduce adverse effects and improve their quality of life.
A fuzzy TOPSIS based analysis toward selection of effective security requirements engineering approach for trustworthy healthcare software development
Authors: Ansari Md Tarique Jamal , Al-Zahrani Fahad Ahmed , Pandey Dhirendra , Agrawal Alka
Published: September 2020

Background

Today’s healthcare organizations want to implement secure and quality healthcare software as cyber-security is a significant risk factor for healthcare data. Considering security requirements during trustworthy healthcare software development process is an essential part of the quality software development. There are several Security Requirements Engineering (SRE) methodologies, framework, process, standards available today. Unfortunately, there is still a necessity to improve these security requirements engineering approaches. Determining the most suitable security requirements engineering method for trustworthy healthcare software development is a challenging process. This study is aimed to present security experts’ perspective on the relative importance of the criteria for selecting effective SRE method by utilizing the multi-criteria decision making methods.

Methods

The study was planned and conducted to identify the most appropriate SRE approach for quality and trustworthy software development based on the security expert’s knowledge and experience. The hierarchical model was evaluated by using fuzzy TOPSIS model. Effective SRE selection criteria were compared in pairs. 25 security experts were asked to response the pairwise criteria comparison form.

Results

The impact of the recognized selection criteria for effective security requirements engineering approaches has been evaluated quantitatively. For each of the 25 participants, comparison matrixes were formed based on the scores of their responses in the form. The consistency ratios (CR) were found to be smaller than 10% (CR = 9.1% < 10%). According to pairwise comparisons result; with a 0.842 closeness coefficient (Ci), STORE methodology is the most effective security requirements engineering approach for trustworthy healthcare software development.

Conclusions

The findings of this research study demonstrate various factors in the decision-making process for the selection of a reliable method for security requirements engineering. This is a significant study that uses multi-criteria decision-making tools, specifically fuzzy TOPSIS, which used to evaluate different SRE methods for secure and trustworthy healthcare application development.
Community health worker motivation to perform systematic household contact tuberculosis investigation in a high burden metropolitan district in South Africa
Authors: Kigozi Gladys , Heunis Christo , Engelbrecht Michelle
Published: September 2020

Background

South Africa faces a chronic shortage of professional health workers. Accordingly, community health workers (CHWs) are being employed to mitigate the ongoing health workforce deficiencies. As increased access to quality service delivery hinges upon their motivation, this study explored CHWs’ motivation to deliver systematic household contact tuberculosis (TB) investigation (SHCI).

Methods

In 2017, a cross-sectional survey was conducted among CHWs in the Mangaung Metropolitan District, Free State Province. Exploratory factor analysis was performed on a 30-item scale to determine the dimensions underlying CHW motivation. Items with factor loadings of 0.4 and above were retained. Descriptive and inferential analyses were used to determine CHW motivation levels. Multiple linear regression analysis was used to investigate the determinants of CHW motivation.

Results

Out of 235 participants, 89.2% were female. Participants’ median age was 39 (inter-quartile range: 33–45) years. CHW motivation was defined by 16 items across three dimensions — intrinsic job satisfaction, burnout and team commitment, together explaining 56.04% of the total variance. The derived scale showed satisfactory internal consistency (Cronbach’s alpha: 0.81), with a mean motivation score of 52.26 (standard deviation [sd]: 5.86) out of 64. Statistically significant differences were observed between formal CHWs — those with at least phase 1 standardised accredited training, and informal CHWs — those without such accredited training regarding team commitment scores (17.82 [sd: 2.48] vs. 17.07 [sd: 2.82]; t(233) = 2.157; p = 0.013). CHW age (β = 0.118, p = 0.029), location (β = 1.737, p = 0.041), length of service (β = − 0.495, p < 0.001), attendance of TB SHCI training (β = 1.809, p = 0.036), and TB SHCI competence (β = 0.706, p < 0.001), contributed statistically significantly to CHW motivation.

Conclusion

CHW motivation to perform TB SHCI was both intrinsic and extrinsic. The high overall mean score implies that the CHWs were well-motivated to perform TB SHCI. To ensure sustained improved access to quality TB SHCI service provision, programme managers in the Free State and similar settings could potentially use the tool derived from this study to monitor and inform CHW motivation interventions. Interventions should pay close attention to the CHWs’ formalisation, competence and training.
Type of Track and Trigger system and incidence of in-hospital cardiac arrest: an observational registry-based study
Authors: Hogan Helen , Hutchings Andrew , Wulff Jerome , Carver Catherine , Holdsworth Elizabeth , Nolan Jerry , Welch John , Harrison David , Black Nick
Published: September 2020

Background

Failure to recognise and respond to patient deterioration on hospital wards is a common cause of healthcare-related harm. If patients are not rescued and suffer a cardiac arrest as a result then only around 15% will survive. Track and Trigger systems have been introduced into the NHS to improve both identification and response to such patients. This study examines the association between the type of Track & Trigger System (TTS) (National Early Warning Score (NEWS) versus non-NEWS) and the mode of TTS (paper TTS versus electronic TTS) and incidence of in-hospital ward-based cardiac arrests (IHCA) attended by a resuscitation team.

Methods

TTS type and mode was retrospectively collected at hospital level from 106 NHS acute hospitals in England between 2009 to 2015 via an organisational survey. Poisson regression and logistic regression models, adjusted for case-mix, temporal trends and seasonality were used to determine the association between TTS and hospital-level ward-based IHCA and survival rates.

Results

The NEWS was introduced in England in 2012 and by 2015, three-fifths of hospitals had adopted it. One fifth of hospitals had instituted an electronic TTS by 2015. Between 2009 and 2015 the incidence of IHCA fell. Introduction or use of NEWS in a hospital was associated with a reduction of 9.4% in the rate of ward-based IHCA compared to non-NEWS systems (incidence rate ratio 0.906, p < 0.001). The use of an electronic TTS was also associated with a reduction of 9.8% in the rate of IHCA compared with paper-based TTS (incidence rate ratio 0.902, p = 0.009). There was no change in hospital survival.

Conclusions

The introduction of standardised TTS and electronic TTS have the potential to reduce ward-based IHCA. This is likely to be via a range of mechanisms from early intervention to institution of treatment limits. The lack of association with survival may reflect the complexity of response to triggering of the afferent arm of the rapid response system.
Functionalized nanoparticles with targeted antibody to enhance imaging of breast cancer in vivo
Authors: Chen Jesse S. , Chen Jingwen , Bhattacharjee Somnath , Cao Zhengyi , Wang Han , Swanson Scott D. , Zong Hong , Baker James R. , Wang Su He
Published: September 2020

Background

Targeted contrast nanoparticles for breast tumor imaging facilitates early detection and improves treatment efficacy of breast cancer. This manuscript reports the development of an epidermal growth factor receptor-2 (HER-2) specific, bi-modal, dendrimer conjugate to enhance computed tomography (CT) and magnetic resonance imaging (MRI) of HER-2-positive breast cancer. This material employs generation 5 poly(amidoamine) dendrimers, encapsulated gold nanoparticles, chelated gadolinium, and anti-human HER-2 antibody to produce the nanoparticle contrast agent.

Results

Testing in two mouse tumor models confirms this contrast agent’s ability to image HER-2 positive tumors. Intravenous injection of this nanoparticle in mice bearing HER-2 positive mammary tumors significantly enhances MRI signal intensity by ~ 20% and improves CT resolution and contrast by two-fold. Results by flow cytometry and confocal microscopy validate the specific targeting of the conjugate and its internalization in human HER-2 positive cells.

Conclusion

These results demonstrate that this nanoparticle conjugate can efficiently target and image HER-2 positive tumors in vivo and provide a basis for the development of this diagnostic tool for early detection, metastatic assessment and therapeutic monitoring of HER-2 positive cancers.
Constitutively active androgen receptor supports the metastatic phenotype of endocrine-resistant hormone receptor-positive breast cancer
Authors: Bahnassy Shaymaa , Thangavel Hariprasad , Quttina Maram , Khan Ashfia Fatima , Dhanyalayam Dhanya , Ritho Joan , Karami Samaneh , Ren Jing , Bawa-Khalfe Tasneem
Published: September 2020

Background

Hormone receptor positive (HR+) breast cancer (BCa) is the most frequently diagnosed subtype. Acquired and intrinsic resistance to conventional endocrine therapy (ET) commonly occurs and prompts incurable metastatic disease. Hence, ET-resistant (ET-R) HR+ BCa presents a therapeutic challenge. Previous studies show elevated androgen receptor (AR) that supports resistance to ET tamoxifen and correlates with HR+ BCa metastasis. Yet surprisingly, studies with AR-blocker enzalutamide (Enz) in ET-R HR+ BCa present conflicting results. We now report that a constitutively active, unique from canonical Enz-targeted, AR accumulates in endocrine resistant HR+ BCa cells.

Methods

AR protein profiles in acquired and intrinsic ET-R HR + -BCa were defined with cell-free modification tests, in-house in-vivo SUMOylation assays, and PLA imaging. Genomic activity of native AR and modified-AR mimetic was tested with reporter assays and limited transcriptome analysis. Spheroid growth and migration studies were used to evaluate inhibitory actions of Enz and combinatorial therapy.

Results

Sustained higher molecular weight SUMO-modified AR (SUMO-AR) persists in acquired and intrinsic ET-R BCa cell lines. Concurrently, SUMO isoforms and global SUMO-modified proteome also accumulates in the same cell lines. We identified AR as a novel substrate for the SUMO-E3 ligase HSPB1/Hsp27. Independent of ligand, SUMO-AR is resilient to ubiquitin-mediated proteasomal degradation, enriched in the nucleus, readily chromatin-bound, and transcriptionally active. Constitutive SUMO-AR initiates a gene-expression profile that favors epithelial-mesenchymal transition. Enz combined with a SUMO inhibitor attenuates migration and metastatic phenotype of ET-R HR+ BCa.

Conclusion

Targeting both unmodified and SUMO-modified AR prevents the metastatic progression of HR+ BCa with ET-R.
Resveratrol alleviates the interleukin-1β-induced chondrocytes injury through the NF-κB signaling pathway
Authors: Yi Hong , Zhang Wei , Cui Zhi-Ming , Cui Sheng-Yu , Fan Jian-Bo , Zhu Xin-Hui , Liu Wei
Published: September 2020

Background

Osteoarthritis (OA) is a regular age-related disease that affects millions of people. Resveratrol (RSV) is a flavonoid with a stilbene structure with different pharmacological effects. The purpose of the experiment was to evaluate the protective role of RSV against the human OA chondrocyte injury induced by interleukin-1β (IL-1β).

Methods

Chondrocytes were isolated from OA patients and identified by type II collagen, safranin O staining, and toluidine blue staining. Differentially expressed genes in chondrocytes treated RSV were identified by RNA sequencing. Kyoto encyclopedia of genes and genomes (KEGG) pathway as well as gene ontology (GO) were further conducted through Metascape online tool. A cell counting kit-8 (CCK-8) assay was applied to discover the viability of chondrocytes (6, 12, 24, and 48 μM). Many genes associated with inflammation and matrix degradation are evaluated by real-time PCR (RT-PCR) as well as western blot (WB). The mechanism of RSV for protecting IL-1β induced chondrocytes injury was further measured through immunofluorescence and WB assays.

Results

A total of 845 differentially expressed genes (upregulated = 499, downregulated = 346) were found. These differentially expressed genes mainly enriched into negative regulation of catabolic process, autophagy, and cellular catabolic process, intrinsic apoptotic, apoptotic, and regulation of apoptotic signaling pathway, cellular response to abiotic stimulus, external stimuli, stress, and radiation. These differentially expressed genes were obviously enriched in NF-kB signaling pathway. RSV at the concentration of 48 μM markedly weakened the viability of the cells after 24 h of treatment (87% vs 100%, P < 0.05). No obvious difference was observed between the 6, 12, and 24 μM groups (106% vs 100%, 104% vs 100%, 103% vs 100%, P > 0.05). RSV (24 μM) also markedly depressed the levels of PGE2 and NO induced by IL-1β by 25% and 29% respectively (P < 0.05). Our experiment pointed out that RSV could dramatically inhibit the inflammatory response induced by IL-1β, including the MMP-13, MMP-3, and MMP-1 in human OA chondrocytes by 50%, 35%, and 33% respectively. On the other hand, RSV inhibited cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, and inducible nitric oxide synthase (iNOs) expression (P < 0.05), while increased collagen-II and aggrecan levels (P < 0.05). From a mechanistic perspective, RSV inhibited the degradation of IκB-α as well as the activation of nuclear factor-kappa B (NF-κB) induced by IL-1β.

Conclusion

In summary, RSV regulates the signaling pathway of NF-κB, thus inhibiting inflammation and matrix degradation in chondrocytes. More studies should be focused on the treatment efficacy of RSV for OA in vivo.
Neonatal hyperinsulinemic hypoglycemia: case report of kabuki syndrome due to a novel KMT2D splicing-site mutation
Authors: Piro Ettore , Schierz Ingrid Anne Mandy , Antona Vincenzo , Pappalardo Maria Pia , Giuffrè Mario , Serra Gregorio , Corsello Giovanni
Published: September 2020

Background

Persistent neonatal hypoglycemia, owing to the possibility of severe neurodevelopmental consequences, is a leading cause of neonatal care admission. Hyperinsulinemic hypoglycemia is often resistant to dextrose infusion and needs rapid diagnosis and treatment. Several congenital conditions, from single gene defects to genetic syndromes should be considered in the diagnostic approach. Kabuki syndrome type 1 (MIM# 147920) and Kabuki syndrome type 2 (MIM# 300867), can be associated with neonatal hyperinsulinemic hypoglycemia.

Patient presentation

We report a female Italian (Sicilian) child, born preterm at 35 weeks gestation, with persistent hypoglycemia. Peculiar facial dysmorphisms, neonatal hypotonia, and cerebellar vermis hypoplasia raised suspicion of Kabuki syndrome. Hyperinsulinemic hypoglycemia was confirmed with glucagon test and whole-exome sequencing (WES) found a novel heterozygous splicing-site mutation (c.674-1G > A) in KMT2D gene. Hyperinsulinemic hypoglycemia was successfully treated with diazoxide. At 3 months corrected age for prematurity, a mild global neurodevelopmental delay, postnatal weight and occipitofrontal circumference growth failure were reported.

Conclusions

Kabuki syndrome should be considered when facing neonatal persistent hypoglycemia. Diazoxide may help to improve hyperinsulinemic hypoglycemia. A multidisciplinary and individualized follow-up should be carried out for early diagnosis and treatment of severe pathological associated conditions.
Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study
Authors: Shah Akshay , Donovan Killian , McHugh Anna , Pandey Manish , Aaron Louise , Bradbury Charlotte A. , Stanworth Simon J. , Alikhan Raza , Von Kier Stephen , Maher Keith , Curry Nicola , Shapiro Susan , Rowland Matthew J. , Thomas Matt , Mason Richard , Holland Matthew , Holmes Tom , Ware Michael , Gurney Stefan , McKechnie Stuart R.
Published: September 2020

Background

Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications.

Methods

We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications.

Results

A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49–64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not.

Conclusion

Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.

Graphical abstract
A cohort study among 402 patients with penile cancer in Maranhão, Northeast Brazil with the highest worldwide incidence
Authors: Vieira Ciro Bezerra , Teixeira-Júnior Antonio , Feitoza Laisson , Pinho Jaqueline , Calixto José , do Nascimento Francisco Sérgio Moura Silva , Campos Marcos Adriano Garcia , Lages Joyce , Junior Antonio Machado Alencar , Soares Fernando , Cunha Isabela , Silva Gyl Eanes Barros
Published: September 2020

Objective

Maranhão State—Northeast Brazil–has the world’s highest incidence of penile cancer. This study describes the epidemiological, histopathological and clinical profile of patients stricken across that Brazilian state. The study is aimed at providing new data on neoplasia.

Data description

402 men stricken with penile cancer were studied from January 2004 to December 2018. A retrospective stage was developed with collection of physical and electronic records. A prospective stage was performed with collection of clinical and epidemiological information through a questionnaire. The surgical material was looked into by a uropathologist, and the lesions were evaluated for macroscopic characteristics and various microscopic parameters. Three articles using this data have already been published.
Rapid and economical drug resistance profiling with Nanopore MinION for clinical specimens with low bacillary burden of Mycobacterium tuberculosis
Authors: Chan Wai Sing , Au Chun Hang , Chung Yvonne , Leung Henry Chi Ming , Ho Dona N. , Wong Elaine Yue Ling , Lam Tak Wah , Chan Tsun Leung , Ma Edmond Shiu Kwan , Tang Bone Siu Fai
Published: September 2020

Objective

We designed and tested a Nanopore sequencing panel for direct tuberculosis drug resistance profiling. The panel targeted 10 resistance-associated loci. We assessed the feasibility of amplifying and sequencing these loci from 23 clinical specimens with low bacillary burden.

Results

At least 8 loci were successfully amplified from the majority for predicting first- and second-line drug resistance (14/23, 60.87%), and the 12 specimens yielding all 10 targets were sequenced with Nanopore MinION and Illumina MiSeq. MinION sequencing data was corrected by Nanopolish and recurrent variants were filtered. A total of 67,082 bases across all consensus sequences were analyzed, with 67,019 bases called by both MinION and MiSeq as wildtype. For the 41 single nucleotide variants (SNVs) called by MiSeq with 100% variant allelic frequency (VAF), 39 (95.1%) were called by MinION. For the 22 mixed bases called by MiSeq, a SNV with the highest VAF (70%) was called by MinION. With short assay time, reasonable reagent cost as well as continuously improving sequencing chemistry and signal correction pipelines, this Nanopore method can be a viable option for direct tuberculosis drug resistance profiling in the near future.
A novel target enrichment strategy in next-generation sequencing through 7-deaza-dGTP-resistant enzymatic digestion
Authors: Peng Peng , Xu Yanjuan , Di Bisceglie Adrian M. , Fan Xiaofeng
Published: September 2020

Objective

Owing to the overwhelming dominance of human and commensal microbe sequences, low efficiency is a major concern in clinical viral sequencing using next-generation sequencing. DNA composed of 7-deaza-2′-deoxyguanosine 5′-triphosphate (c7dGTP), an analog of deoxyguanosine triphosphate (dGTP), is resistant to selective restriction enzymes. This characteristic has been utilized to develop a novel strategy for target enrichment in next-generation sequencing.

Results

The new enrichment strategy is named target enrichment via enzymatic digestion in next-generation sequencing (TEEDseq). It combined 7-deaza-2′-deoxyguanosine 5′-triphosphate (c7dGTP)-involved primer extension, splinter-assisted intracellular cyclization, c7dGTP)-resistant enzymatic digestion, and two-phase rolling cycle amplification. We first estimated c7dGTP for its efficiency in PCR amplification and its resistance to three restriction enzymes, AluI, HaeIII, and HpyCH4V. We then evaluated TEEDseq using a serum sample spiked with a 1311-bp hepatitis B virus (HBV) fragment. TEEDseq achieved an HBV on-target rate of 3.31 ± 0.39%, which was equivalent to 454× the enrichment of direct Illumina sequencing. Therefore, the current study has provided a concept proof for TEEDseq as an alternative option for clinical viral sequencing that requires an enrichment in next-generation sequencing.