bluuebunny/crossref_metadata_2025 huggingface dataset:
Germline RAD54L with somatic POLE defect implicated in Hypermutation phenotype: case report
Authors: Zohud Bisan Abdalfatah , Wang Meiling , Cai Xin
Published: August 2020

Background

Colorectal cancer is one of the most frequent causes of death among cancer patients. Hypermutated CRC is an extraordinary case of cancer, but curable if detected at early stages. However, the mechanism for developing a hypermutated CRC remains unclear. An association between RAD54L germline mutation and POLE exonuclease domain hypermutated cancer has not been reported before.

Case presentation

We present a rare case of a 41-year-old Chinese female with a right-sided colon adenocarcinoma who harboured a (p.P286R) POLE somatic mutation. Genomic analysis was performed using the Illumina HiSeq Sequencing platform, which, identified MSS tumour with a (c.1093_1169 + 15dup) germline mutation in RAD54L gene and tumour mutation burden of 377.0 Muts/Mb. Based on our report a new mechanism for developing hypermutated colon cancer has been conjectured through a novel RAD54L_POLE DSBR pathway.

Conclusion

This report highlights the clinical importance of next-generation sequencing technology in diagnosing rare tumours and investigating novel mechanisms for developing exceptional genetic diseases.
Medication omission rates in New Zealand residential aged care homes: a national description
Authors: Garratt Stephanie. M. , Kerse Ngaire. M. , Peri Kathryn , Jonas Monique. F.
Published: August 2020

Background

A medication omission is an event where a prescribed medication is not taken before the next scheduled dose. Medication omissions are typically classed as errors within Residential Aged Care (RAC) homes, as they have the potential to lead to harm if poorly managed, but may also stem from good clinical decision-making. This study aimed to quantify the incidence, prevalence, and types of medication omissions in RAC homes on a national scale, using a New Zealand-based sample.

Methods

We conducted retrospective pharmacoepidemiology of de-identified medication administration e-records from December 1st 2016 to December 31st 2017. Four tiers of de-identified data were collected: RAC home level data (ownership, levels of care), care staff level data (competency level/role), resident data (gender, age, level of care), and medication related data (omissions, categories of omissions, recorded reasons for omission). Data were analysed using SPSS version 24 and Microsoft Excel.

Results

A total of 11, 015 residents from 374 RAC homes had active medication charts; 8020 resided in care over the entire sample timeframe. A mean rate of 3.59 medication doses were omitted per 100 (±7.43) dispensed doses/resident. Seventy-three percent of residents had at least one dose omission. The most common omission category used was ‘not-administered’ (49.9%), followed by ‘refused’ (34.6%). The relationship between ownership type and mean rate of omission was significant (p = 0.002), corporate operated RAC homes had a slightly higher mean (3.73 versus 3.33), with greater variation. The most commonly omitted medications were Analgesics and Laxatives. Forty-eight percent of all dose omissions were recorded without a comment justifying the omission.

Conclusions

This unique study is the first to report rate of medication omissions per RAC resident over a one-year timeframe. Although the proportion of medications omitted reported in this study is less than previously reported by hospital-based studies, there is a significant relationship between a resident’s level of care, RAC home ownership types, and the rate of omission.
Prevalence and associated factors of malaria among pregnant women in Sherkole district, Benishangul Gumuz regional state, West Ethiopia
Authors: Gontie Girma Bekele , Wolde Haileab Fekadu , Baraki Adhanom Gebreegziabher
Published: August 2020

Background

Malaria during pregnancy leads to serious adverse effects on mothers and the fetus. Approximately 25 million pregnant women in sub-Saharan Africa live at risk of malaria. This study would help to achieve Sustainable Development Goals (SDGs) by improving programs that deal with the prevention of malaria. Therefore, this study aimed to assess the prevalence and associated factors of malaria among pregnant women.

Methods

A community-based cross-sectional study was conducted from July to August 2018 in Sherkole district, West Ethiopia. A multi-stage sampling technique was used to select 504 pregnant women. The interviewer-administered semi-structured questionnaire was used for data collection. Malaria was also diagnosed using a rapid diagnostic test. The data was entered using EPI info version 7.2.2.2 and transferred to SPSS version 20 for analysis. Descriptive statistics were done using frequency and percentages. Both bivariable and multivariable logistic regression models were employed. Variables having p-value < 0.2 were included in the final multivariable model. Variables having p-values < 0.05 from the multivariable model were considered to be significantly associated with the dependent variable. The adjusted odds ratio with its 95% confidence interval (CI) was used as a measure of association.

Results

Of the total 498 pregnant women who participated in this study, 51(10.2, 95% CI: 7.72–13.24) were found to have malaria. Of these, 46 (90.2%) and 5 (9.8%) were caused by Plasmodium falciparum and Plasmodium vivax, respectively. Decreasing Age (Adjusted Odds Ratio (AOR) 0.78; 95% CI 0.67–0.911), not using insecticide-treated bed net (ITN) (AOR 12.5; 95% CI 4.86–32.21), lack of consultation and health education about malaria prevention (AOR 7.18; 95% CI 2.74–18.81), being on second-trimester pregnancy (AOR 7.58; 95% CI 2.84–20.2), gravidae II (AOR 5.99; 95% CI 1.68–21.44) were found to be significantly associated with malaria during pregnancy.

Conclusion

Malaria is still a public health problem among pregnant women in the Sherkole district. Age, ITN use, gravidity, gestational age, and health education had a significant association with malaria. Screening pregnant women for asymptomatic malaria infection and educating and consulting on the appropriate malaria preventive methods shall be provided.
Identification of compound mutations of SLC12A3 gene in a Chinese pedigree with Gitelman syndrome exhibiting Bartter syndrome-liked phenotypes
Authors: Dong Bingzi , Chen Ying , Liu Xinying , Wang Yangang , Wang Fang , Zhao Yuhang , Sun Xiaofang , Zhao Wenjuan
Published: August 2020

Background

Gitelman syndrome is a rare salt-losing renal tubular disorder associated with mutation of SLC12A3 gene, which encodes the Na-Cl co-transporter (NCCT). Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation. Different SLC12A3 variants may lead to phenotypic variability and severity.

Methods

In this study, we reported the clinical features and genetic analysis of a Chinese pedigree diagnosed with Gitelman syndrome.

Results

The proband exhibited hypokalaemia, hypomagnesemia, metabolic alkalosis, but hypercalciuria and kidney stone formation. The increased urinary calcium excretion made it confused to Bartter syndrome. The persistent renal potassium wasting resulted in renal tubular lesions, and might affect urinary calcium reabsorption and excretion. Genetic analysis revealed mutations of SLC12A3 gene with c.433C > T (p.Arg145Cys), c.1077C > G (p.Asn359Lys), and c.1666C > T (p.Pro556Ser). Potential alterations of structure and function of NCCT protein due to those genetic variations of SLC12A3 are predicted. Interestingly, one sibling of the proband carried the same mutant sites and exhibited similar clinical features with milder phenotypes of hypokalemia and hypomagnesemia, but hypocalciuria rather than hypercalciuria. Family members with at least one wild type copy of SLC12A3 had normal biochemistry. With administration of spironolactone, potassium chloride and magnesium supplement, the serum potassium and magnesium were maintained within normal ranges.

Conclusions

In this study, we identified compound mutations of SLC12A3 associated with varieties of clinical features. Further efforts are needed to investigate the diversity in clinical manifestations of Gitelman syndrome and its correlation with specific SLC12A3 mutations.
The TRACK-PD study: protocol of a longitudinal ultra-high field imaging study in Parkinson’s disease
Authors: Wolters A. F. , Heijmans M. , Michielse S. , Leentjens A. F. G. , Postma A. A. , Jansen J. F. A. , Ivanov D. , Duits A. A. , Temel Y. , Kuijf M. L.
Published: August 2020

Background

The diagnosis of Parkinson’s Disease (PD) remains a challenge and is currently based on the assessment of clinical symptoms. PD is also a heterogeneous disease with great variability in symptoms, disease course, and response to therapy. There is a general need for a better understanding of this heterogeneity and the interlinked long-term changes in brain function and structure in PD. Over the past years there is increasing interest in the value of new paradigms in Magnetic Resonance Imaging (MRI) and the potential of ultra-high field strength imaging in the diagnostic work-up of PD. With this multimodal 7 T MRI study, our objectives are: 1) To identify distinctive MRI characteristics in PD patients and to create a diagnostic tool based on these differences. 2) To correlate MRI characteristics to clinical phenotype, genetics and progression of symptoms. 3) To detect future imaging biomarkers for disease progression that could be valuable for the evaluation of new therapies.

Methods

The TRACK-PD study is a longitudinal observational study in a cohort of 130 recently diagnosed (≤ 3 years after diagnosis) PD patients and 60 age-matched healthy controls (HC). A 7 T MRI of the brain will be performed at baseline and repeated after 2 and 4 years. Complete assessment of motor, cognitive, neuropsychiatric and autonomic symptoms will be performed at baseline and follow-up visits with wearable sensors, validated questionnaires and rating scales. At baseline a blood DNA sample will also be collected.

Discussion

This is the first longitudinal, observational, 7 T MRI study in PD patients. With this study, an important contribution can be made to the improvement of the current diagnostic process in PD. Moreover, this study will be able to provide valuable information related to the different clinical phenotypes of PD and their correlating MRI characteristics. The long-term aim of this study is to better understand PD and develop new biomarkers for disease progression which may help new therapy development. Eventually, this may lead to predictive models for individual PD patients and towards personalized medicine in the future.

Trial registration

Dutch Trial Register, NL7558. Registered March 11, 2019.
Factors influencing institutional delivery and the role of accredited social health activist (ASHA): a secondary analysis of India human development survey 2012
Authors: Paul Pooja L. , Pandey Shanta
Published: August 2020

Background

India has focused on incentivizing institutional delivery and introducing the ASHA worker as a key strategy to improve maternal health outcomes. We examined the determinants of institutional delivery and the role of the ASHA worker in shaping choice regarding place of delivery.

Methods

We used data from the India Human Development Survey-II conducted in 2011–12, and extracted an analytic sample of women (N = 8711) who reported having at least one child since 2005. Logistic regression was used to examine influence of socio-demographic factors, frequency of antenatal care (ANC) contacts and exposure to ASHA worker on institutional delivery.

Results

About 15% of the respondents had eight or more ANC contacts. The odds of having an institutional delivery were higher among those respondents who had 8 or more ANC contacts (OR = 3.39, p < 0.001, 95% CI: 2.26, 5.08), and those who had 4–7 ANC contacts (OR = 1.72, p < 0.001, 95% CI: 1.48, 1.99) as compared to those with less than 4 ANC contacts. About 26% of the respondents had any exposure to an ASHA worker. After controlling for ANC contacts, these respondents had three times the odds of institutional delivery (OR = 3.04, p < 0.001, 95% CI: 2.37, 3.89) compared to those who had no exposure to ASHA workers. Further, several sociodemographic variables were associated with institutional delivery. While age of spouse, age at marriage, level of education and urban residence were positively associated with institutional delivery; age of respondent and number of children were inversely associated with institutional delivery.

Conclusions

Both frequency of ANC contacts and exposure to ASHA worker independently emerge as important determinants of institutional delivery. Furthermore, ASHA workers may have a crucial role in promoting antenatal care, thereby strengthening the association between ANC contacts and institutional delivery.
UGT1A1 polymorphism has a prognostic effect in patients with stage IB or II uterine cervical cancer and one or no metastatic pelvic nodes receiving irinotecan chemotherapy: a retrospective study
Authors: Matsuoka Hideki , Murakami Ryusuke , Abiko Kaoru , Yamaguchi Ken , Horie Akihito , Hamanishi Junzo , Baba Tsukasa , Mandai Masaki
Published: August 2020

Background

Uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) is a predictive biomarker for the side-effects of irinotecan chemotherapy, which reduces the volume of tumors harboring UGT1A1 polymorphisms. We aimed to determine whether UGT1A1 polymorphisms can predict progression-free survival in patients with local cervical cancer treated with irinotecan chemotherapy.

Methods

We retrospectively analyzed the data of 51 patients with cervical cancer treated at a single institution between 2010 and 2015. All patients were diagnosed with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IB1, IB2, IIA, or IIB squamous cell carcinoma, underwent radical hysterectomy, and received irinotecan chemotherapy as neoadjuvant and/or adjuvant treatment. All patients were examined for irinotecan side effects using UGT1A1 tests. Conditional inference tree and survival analyses were performed considering the FIGO stage, age, the UGT1A1 status, and the number of metastatic lymph nodes to determine primary factors associated with progression-free survival.

Results

The tree-structured survival model determined high recurrence-risk factors related to progression-free survival. The most relevant factor was ≥2 metastatic lymph nodes (p = 0.004). The second most relevant factor was UGT1A1 genotype (p = 0.024). Among patients with ≤1 metastatic lymph node, those with UGT1A1 polymorphisms benefited from irinotecan chemotherapy and demonstrated significantly longer progression-free survival (p = 0.020) than those with wild-type UGT1A1.

Conclusions

Irinotecan chemotherapy might be beneficial in patients with cervical cancer, UGT1A1 polymorphisms, and ≤ 1 metastatic lymph nodes.
Association of number of siblings, birth order, and thinness in 3- to 12-year-old children: a population-based cross-sectional study in Shanghai, China
Authors: Yu Tingting , Chen Chang , Jin Zhijuan , Yang You , Jiang Yanrui , Hong Li , Yu Xiaodan , Mei Hao , Jiang Fan , Huang Hong , Liu Shijian , Jin Xingming
Published: August 2020

Background

Sibship size and structure have a significant association with overweight and obesity in children, but the relationship with thinness has not been fully studied and understood, especially in Asia. This study evaluated the associations among number of siblings, birth order, and childhood thinness and investigated the association of number of younger or older siblings with childhood thinness.

Methods

In this study, we performed a population-based cross-sectional study among 84,075 3- to 12-year-old children in Shanghai using multistage stratified cluster random sampling. We defined grades 1, 2, and 3 thinness according to the body mass index cutoff points set by the International Obesity Task Force and used multinomial logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (95% CI).

Results

Compared with only children, for boys, children with two or more siblings were more likely to suffer from grade 2 (OR = 1.29, 95% CI 1.02, 1.64) and grade 3 thinness (OR = 1.60, 95% CI 1.07, 2.40); and the youngest child faced a higher risk of grade 2 (OR = 1.44, 95% CI 1.09, 1.90) and grade 3 thinness (OR = 1.53, 95% CI 1.01, 2.33). For girls, children with one sibling were more likely to suffer from grade 1 thinness (OR = 1.22, 95% CI 1.05, 1.42); the oldest child, middle child, and youngest child faced a higher risk of grade 1 (OR = 1.42, 95% CI 1.09, 1.84), grade 2 (OR = 1.26, 95% CI 1.03, 1.54), and grade 1 thinness (OR = 1.87, 95% CI 1.21, 2.88) respectively. There was no statistically significant relationship, however, between a larger number of younger or older siblings and childhood thinness.

Conclusions

Regardless of sex, having either siblings or a higher birth order was positively associated with childhood thinness. The present study has suggested that future interventions to prevent childhood thinness should consider family background as an important factor, especially in multi-child-families.
Cortisol and DHEA-S levels in pregnant women with severe anxiety
Authors: Leff-Gelman Philippe , Flores-Ramos Mónica , Carrasco Ariela Edith Ávila , Martínez Margarita López , Takashima María Fernanda Sarabia , Coronel Fausto Manuel Cruz , Labonne Blanca Farfán , Dosal José Antonio Zorrilla , Chávez-Peón Paola Barriguete , Morales Saul Garza , Camacho-Arroyo Ignacio
Published: August 2020

Background

A complex interaction between cortisol and dehydroepiandrosterone-sulphate (DHEA-S) is crucial in the stress system balance; several studies have reported increased cortisol levels during chronic stress and a weak counter-regulation by DHEA-S. During pregnancy, scarce information about this system is available, although cortisol and DHEA-S play an important role in the initiation and acceleration of labor. We conducted the present study in order to determine both cortisol and DHEA-S levels during the last trimester of pregnancy in patients exhibiting severe anxiety.

Methods

Pregnant women during the 3rd trimester of pregnancy were evaluated by using the self-reported version of the Hamilton Anxiety Rating Scale (HARS). According to the scores obtained from the psychometric scale, participants were divided into two groups: 1) patients exhibiting a cutoff score > 15 were considered with severe anxiety (ANX) (n = 101), and control pregnant subjects (CTRL) (n = 44) with a cutoff score < 5. Morning cortisol, DHEA-S and Cortisol/DHEA-S index were measured in all participants. Comparisons between groups were performed; additionally, correlations between clinical variables, biochemical data and HARS were calculated.

Results

Cortisol levels were significantly higher in the ANX group (p < 0.001), whereas those of DHEA-S were significantly lower in the same group (p < 0.01) when compared to healthy pregnant subjects. An increased cortisol/DHEA-S index was observed in the ANX group (p < 0.05). A significant association between cortisol and HARS scores (p = 0.03), was observed even after adjusting by gestational weeks (p = 0.004).

Conclusions

Our data support that the cortisol/DHEA-S index is higher in pregnant women with high anxiety levels as compared with healthy pregnant women.
OCD symptoms in succinic semialdehyde dehydrogenase (SSADH) deficiency: a case report
Authors: Phakey Sachin , Rego Thomas , Gaillard Frank , Panetta Julie , Evans Andrew , De Jong Gerard , Walterfang Mark
Published: August 2020

Background

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare neurometabolic disorder resulting in a heterogeneous clinical phenotype. Adolescent and adult patients with SSADH deficiency may present with OCD symptoms. There is minimal literature regarding the pathological basis of OCD symptoms and their management amongst SSADH deficiency patients.

Case presentation

A 26-year-old woman with SSADH deficiency experienced obsessional slowness and hesitancy in her activities of daily living, with motor rituals and stereotypies of her hands and face. Neuroimaging revealed T2 hyperintensities of the globi pallidi bilaterally. Commencement of the serotonergic escitalopram moderately improved her OCD symptoms. The addition of the dopaminergic pramipexole hydrochloride yielded further improvement, following unsuccessful trial of other adjuncts: risperidone, methylphenidate and mirtazapine.

Conclusions

Pallidal pathology may explain the manifestation of OCD symptoms amongst individuals with SSADH deficiency. Serotonergic and concomitant dopaminergic therapy may be a viable treatment regimen for SSADH deficiency patients presenting with OCD symptoms.
Management of dual traumatic arterial-venous fistula from a single shotgun injury: a case report and literature review
Authors: Nasser Eldine Rakan , Dehaini Hassan , Hoballah Jamal J , Haddad Fady Fayez
Published: August 2020

Background

Traumatic arteriovenous fistula (TAVF) is an uncommon vascular entity that arises in various locations, often from penetrating injuries, with a wide spectrum of signs and symptoms. This case report highlights the importance of suspecting multiple TAVFs after a single gunshot wound, especially if it involves pellets. It also sheds light on adapting treatment, whether endovascular or open repair, to the location and characteristics of each fistula.

Case presentation

A 35-year-old male, with history of shotgun wound 5 months earlier, presented to our clinic with right lower extremity (RLE) edema and pain. Arterial duplex scan and subsequent angiogram showed two TAVFs at the popliteal and posterior tibial (PT) arteries, both of which could not be exactly localized with a computed tomography angiography (CTA) due to artifacts. The fistula connecting the posterior tibial artery (PTA) and vein was repaired endovascularly using a covered-stent, while the fistula between the popliteal artery and vein was repaired surgically. Postoperative follow-up at 3 months showed no arteriovenous fistula (AVF), patent vessels and distal stent stenosis at the PTA.

Conclusions

Patients who sustain gunshot injuries with shrapnel or pellets and develop TAVF consequentially need to be followed up with the possibility of multiple AVFs in mind. Arterial duplex scan is highly sensitive to detect those AVFs, yet angiography remains gold standard, particularly with extensive metal artefacts. Endovascular repair, when feasible, should be considered first, unless the patient is unstable or has anatomical constraints that increase the risk of complications. Lastly, surgeons should be weary of deep venous thrombosis (DVT), the Branham effect and arterial aneurysmal dilation postoperatively.
An exploration of factors affecting the quality of life of women with primary ovarian insufficiency: a qualitative study
Authors: Golezar Samira , Keshavarz Zohreh , Ramezani Tehrani Fahime , Ebadi Abbas
Published: August 2020

Background

Menopause before the age of 40 years is known as primary ovarian insufficiency (POI). Besides physical effects, being diagnosed with this disorder adversely affects the psychological health and quality of life (QOL). The present study aimed at shedding light on the factors affecting the QOL of women with POI.

Methods

The present study is a qualitative one. The data were collected using semi-structured in-depth interviews with 16 women having POI, selected purposively. Data rigor was ensured using Lincoln and Guba’s criteria. The recorded data were transcribed verbatim and then analyzed constantly at the same time as gathering the data using conventional content analysis.

Results

Three themes emerged regarding the QOL of women with POI, i.e. disease effect (physical and psychological effects), distorted self-concept (threatened identity and disease stigma), and hormone replacement therapy effect (positive and negative physical/psychological effects).

Conclusions

Due to the profound effects of the disease on different aspects of the biopsychosocial health of women with POI, a multifaceted health care approach is recommended to improve their QOL.
Walking together: women with the severe symptoms of menopause propose a platform for a walking program; outcome from focus groups
Authors: Sydora Beate C. , Alvadj Tatjana , Malley Alexandra , Mayan Maria , Shandro Tami , Ross Sue
Published: August 2020

Background

Menopause and midlife are stages in a woman’s life that can be marked by debilitating symptoms and increasing risks for cancer, cardiovascular, metabolic, and bone health issues. Walking represents a simple, low cost, and widely accessible activity with proven health benefits, though its therapeutic effect on alleviating menopause symptoms is not well characterized. Women are generally not opposed to exercise programs; however, increasing or maintaining exercise levels remains a challenge. We undertook a qualitative descriptive study to explore features of a walking program that would be conductive to menopausal women’s participation, as well as to inform the development of such a program.

Methods

We conducted focus groups with women recruited from two menopause clinics and who suffered from moderate to severe menopause symptoms. The focus groups were audio recorded and transcribed. Women were prompted to talk about their menopause experience and exercise practice and how they would envision a walking exercise program that would keep them engaged. Qualitative content analysis was used to analyze the data and to identify characteristics of a walking exercise program.

Results

Twenty women participated in 5 focus groups. Women were very interested in trying walking as a means of staying healthy and possibly reducing menopause symptoms. Four major characteristics emerged as important for a walking program: (a) sensitivity to health realities of menopausal women, (b) inclusivity of various needs/levels of physical ability, (c) attentiveness to the need for mutual social support, (d) flexibility in planning of locations and scheduling.

A restricted social network platform with features catering to women in menopause was suggested as suitable to initiate and sustain an adequate walking program.

Conclusions

The findings of this study will be essential in designing a program that would be attractive for women to start and maintain a walking habit. The program would assist in elucidating whether walking is a useful and valuable alternative therapy for menopausal symptoms and, ultimately, might help women staying fit in midlife and postmenopausal.
Psychological predictors of medical residents’ perspectives on shared decision-making with patients: a cross-sectional study
Authors: Kheirkhah Farzan , Larijani Reza Mousavi , Faramarzi Mahbobeh , Yadollahpour Mohamahd Hadi , Khafri Soraya
Published: August 2020

Background

Shared Decision Making (SDM) is as ideal model for resident-patient relationship which may improve medical outcomes. Nevertheless, predictive psychological factors influencing residents’ perspective regarding SDM are unclear. The current study investigated the relationship between two psychological factors, mental health and personality traits, and residents’ views toward SDM.

Method

In a cross-sectional study, 168 medical residents of the Babol University of Medical Sciences studying in 13 field specialties were recruited. The residents completed three questionnaires including Shared Decision-Making Questionnaire (SDM-Q-Doc, physician version), General Health Questionnaire (GHQ-12), and Big Five Personality (NEO-FFI).

Results

Residents had an overall agreement of about 88% regarding SDM with patients. There was no significant difference between male and female residents in terms of the degree of agreement for SDM. Concerning SDM, there was no significant relationship either between residents’ views and neuroticism, extraversion, agreeableness, and conscientiousness. In multivariate regression, mental health did not predict the SDM, but openness to experience negatively predicted residents’ views concerning SDM (β = − 0.388,p < 0.001).

Conclusion

The residents’ personality trait of openness to experience was a significant negative predictor of SDM with patients. A better understanding of how psychological factors relate to residents’ perspectives may help clinicians properly discuss the treatment options with the patient thereby encouraging them for SDM or to consider their own preferences.
Using creative co-design to develop a decision support tool for people with malignant pleural effusion
Authors: Grindell Cheryl , Tod Angela , Bec Remi , Wolstenholme Daniel , Bhatnagar Rahul , Sivakumar Parthipan , Morley Anna , Holme Jayne , Lyons Judith , Ahmed Maryam , Jackson Susan , Wallace Deirdre , Noorzad Farinaz , Kamalanathan Meera , Ahmed Liju , Evison Mathew
Published: August 2020

Background

Malignant pleural effusion (MPE) is a common, serious problem predominantly seen in metastatic lung and breast cancer and malignant pleural mesothelioma. Recurrence of malignant pleural effusion is common, and symptoms significantly impair people’s daily lives. Numerous treatment options exist, yet choosing the most suitable depends on many factors and making decisions can be challenging in pressured, time-sensitive clinical environments. Clinicians identified a need to develop a decision support tool. This paper reports the process of co-producing an initial prototype tool.

Methods

Creative co-design methods were used. Three pleural teams from three disparate clinical sites in the UK were involved. To overcome the geographical distance between sites and the ill-health of service users, novel distributed methods of creative co-design were used. Local workshops were designed and structured, including video clips of activities. These were run on each site with clinicians, patients and carers. A joint national workshop was then conducted with representatives from all stakeholder groups to consider the findings and outputs from local meetings.

The design team worked with participants to develop outputs, including patient timelines and personas. These were used as the basis to develop and test prototype ideas.

Results

Key messages from the workshops informed prototype development. These messages were as follows. Understanding and managing the pleural effusion was the priority for patients, not their overall cancer journey. Preferred methods for receiving information were varied but visual and graphic approaches were favoured. The main influences on people’s decisions about their MPE treatment were personal aspects of their lives, for example, how active they are, what support they have at home.

The findings informed the development of a first prototype/service visualisation (a video representing a web-based support tool) to help people identify personal priorities and to guide shared treatment decisions.

Conclusion

The creative design methods and distributed model used in this project overcame many of the barriers to traditional co-production methods such as power, language and time. They allowed specialist pleural teams and service users to work together to create a patient-facing decision support tool owned by those who will use it and ready for implementation and evaluation.
Care priorities for stroke patients developing cognitive difficulties: a Delphi survey of UK professional views
Authors: Tang Eugene Y. H. , Robinson Louise , Exley Catherine , Flynn Darren , Stephan Blossom C. M. , Price Christopher
Published: August 2020

Background

Post stroke cognitive difficulties are common but generally prioritised below other impairments. In the UK, clinical guidelines recommend a holistic review at six-months post-stroke including an assessment of cognitive function. In order to assist clinicians to provide better care for patients with post-stroke cognitive deficits and assist with service planning, our aim was to establish professional consensus on key actions at the six-month review.

Methods

An electronic Delphi survey was developed with ten potential actions for clinicians to prioritise across five different clinical scenarios describing patients with cognitive difficulties. Scenarios varied in terms of age of the stroke-survivor, stroke severity and use of dementia risk assessment. A panel of professional volunteers was obtained through the British Association of Stroke Physicians and the UK National Stroke Nursing Forum.

Results

Forty-five stroke clinicians completed round one, with 21 participants completing round two. Priorities consistently supported by professionals included access to psychological services, screening for a mood disorder and ensuring multi-professional input. Direct access to specialist memory services was not generally supported unless a dementia risk assessment tool indicated that the individual was at high risk of dementia.

Conclusions

Assessment of post-stroke cognitive deficits needs to be routinely considered during the six-month review. A formal risk assessment tool could be a way to streamline direct access to memory clinic services to ensure that individuals at-risk of dementia receive ongoing care.
Changes in health inequalities for patients with diabetes among middle-aged and elderly in China from 2011 to 2015
Authors: Cao Guizhen , Cui Zhizhen , Ma Qinghua , Wang Congju , Xu Yong , Sun Hongpeng , Ma Yana
Published: August 2020

Background

The purpose of this paper is to measure income-related health inequality among middle-aged and elderly patients with diabetes in China from 2011 to 2015 and to investigate factors that might be related to this inequality.

Methods

The data for this study were obtained from the China Health and Retirement Longitudinal Study that was carried out in 2011, 2013 and 2015. In total, 48,519 Chinese middle-aged and elderly population were included (15,457 in 2011, 16,576 in 2013 and 16,486 in 2015). A principal component analysis was performed to measure asset-based economic status. The concentration index was used to measure income-related inequality in patients with diabetes. Additionally, by used generalized linear model, we decomposed the concentration index to identify factors that explained wealth-related inequality in patients with diabetes.

Results

The prevalence of self-reported diabetes among middle-aged and elderly Chinese was 5.61, 7.49 and 8.99% in 2011, 2013 and 2015, respectively. The concentration indices and 95% confidence intervals for diabetes were 0.1359 (0.0525–0.0597), 0.1207 (0.0709–0.0789), 0.1021 (0.0855–0.0942) in 2011, 2013, and 2015, respectively, which are indicative of inequality that favors the rich. The decomposition of the concentration index showed that residence (39.38%), BMI (31.16%), education (7.28%), and region (6.09%) had positive contributions to the measured inequality in diabetes in China in 2015. Age (− 29.93%) had a negative contribution to inequality.

Conclusion

The findings confirm a health inequality in diabetes that favor the rich. Furthermore, the inequality declined from 2011 to 2015. We suggest that policy and intervention strategies should be developed to alleviate this health inequality, such as narrow the gap between urban and rural areas by improving the urban-rural medical insurance scheme, implementing strategies to enhance hygiene health education, control obesity rate.
LncRNA DLX6-AS1 aggravates the development of ovarian cancer via modulating FHL2 by sponging miR-195-5p
Authors: Kong Lijun , Zhang Chengyan
Published: August 2020

Background

Ovarian cancer (OC) is a huge burden on women’s lives. Recently, the implication of long non-coding RNAs (lncRNAs) in cancers, including OC, has aroused much attention. The objective of this study was to explore the role and functional mechanism of lncRNA distal-less homeobox 6 antisense 1 (DLX6-AS1) in OC.

Methods

The expression of DLX6-AS1, miR-195-5p, and four and a half LIM domains protein 2 (FHL2) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation, apoptosis, migration, and invasion were assessed by cell count kit 8 (CCK-8), flow cytometry and transwell assays, respectively. The protein levels of proliferating cell nuclear antigen (PCNA), cleaved-caspase-3 (C-caspase 3), N-cadherin, Vimentin, E-cadherin and FHL2 were quantified by western blot. The relationship between miR-195-5p and DLX6-AS1 or FHL2 was predicted by bioinformatics tool starBase and verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft tumor model was established to observe the role of DLX6-AS1 in vivo.

Results

DLX6-AS1 and FHL2 were up-regulated in OC tissues and cells, while miR-195-5p was down-regulated. DLX6-AS1 knockdown inhibited proliferation, migration, and invasion but induced apoptosis of OC cells. However, miR-195-5p inhibition reversed these effects. Overexpression of miR-195-5p also depleted proliferation, migration, and invasion but promoted apoptosis of OC cells, while FHL2 overexpression overturned these influences. DLX6-AS1 knockdown blocked tumor growth in vivo.

Conclusion

DLX6-AS1, as an oncogene in OC, accelerated tumor progression by up-regulating FHL2 via mediating miR-195-5p, suggesting that DLX6-AS1 was a hopeful target for the lncRNA-targeted therapy in OC.
The combination of Biochanin A and SB590885 potentiates the inhibition of tumour progression in hepatocellular carcinoma
Authors: Xiao Yi , Gong Qiang , Wang Wenhong , Liu Fang , Kong Qinghong , Pan Feng , Zhang Xiaoke , Yu Changyan , Hu Shanshan , Fan Fang , Li Sanhua , Liu Yun
Published: August 2020

Background

Hepatocellular carcinoma (HCC) is the most aggressive and frequently diagnosed malignancy of the liver. Despite aggressive therapy, life expectancy of many patients in these cases is extended by only a few months. Hepatocellular carcinoma (HCC) has a particularly poor prognosis and would greatly benefit from more effective therapies.

Methods

The CCK-8 assay and colony formation assays were used to test the cell proliferation and viability. The effects of combination Biochanin A and SB590885 on apoptosis and cell cycle arrest of HCC cells were analysed by flow cytometry. The expression of ERK MAPK and PI3K/AKT/mTOR signalling as well as apoptosis and cell cycle-related proteins in HCC cells were tested by western blotting. The HCC cell xenograft model was established to test the tumor proliferation. Serum and plasma were tested for liver and kidney safety markers (ALP, ALT, AST, total bilirubin, creatinine, urea nitrogen) by using SpectraMax i3X.

Results

The combination of natural product Biochanin A with the BRAF inhibitor SB590885 synergistically suppressed proliferation, and promoted cell cycle arrest and apoptosis in vitro. Furthermore, we demonstrated that the combination of Biochanin A and SB590885 led to increased impairment of proliferation and HCC tumour inhibition through disrupting of the ERK MAPK and the PI3K/AKT pathways in vitro. The volumes tumors and the weights of tumours were significantly reduced by the combination treatment compared to the control or single treatments in vivo. In addition, we found that there was no significant hepatorenal toxicity with the drug combination, as indicated by the hepatorenal toxicity test.

Conclusion

The results identify an effective combination therapy for the most aggressive form of HCC and provide the possibility of therapeutic improvement for patients with advanced HCC.
A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression
Authors: Luo Lingli , Wang Min , Li Xianping , Luo Can , Tan Shan , Yin Sheng , Liu Lei , Zhu Xiaolin
Published: August 2020

Background

Long non-coding RNAs (LncRNAs) have been increasingly confirmed to be abnormally expressed in human cancer and closely related to tumorigenesis. LncRNA ACTA2-AS1 is abnormally expressed in multiple tumors and participates in their development. However, whether ACTA2-AS1 plays a role in the development of cervical cancer (CC) and the exact mechanism of its role has not been elucidated.

Methods

Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of messenger RNA of ACTA2-AS1, miR-143-3p and SMAD3 in tumor tissues and cells. Additionally, SMAD3 protein expression by western blots in cells. Small interference RNA against ACTA2‐AS1 or SMAD3 and miR‐143‐3p mimic/inhibitor was designed and transfected into CC cell lines to investigate their correlations and potential impacts on cell function. Cell Counting Kit-8 (CCK-8) assay, colony formation, cell cycle assay, transwell assay and flow cytometry analysis were performed to detect the specific effects on cell line proliferation, metastasis and apoptosis.

Results

ACTA2-AS1 was significantly increased in CC tissues and cells and miR‐143‐3p was down-regulated. Clinically, the higher expression of ACTA2-AS1 was significantly correlated with higher FIGO stage. Loss-of-function assay revealed that silencing of ACTA2-AS1 inhibited cell proliferation, colony formation, migration and promoted apoptosis in CC. Additionally, Pearson correlation analysis showed that the expression of ACTA2-AS1 and miR-143-3p were negatively correlated. Dual-luciferase reporter assay and further mechanistic experiments confirmed that ACTA2-AS1 could sponge and regulate the expression of miR-143-3p. Furthermore, SMAD3 was the target gene of miR-143-3p and ACTA2-AS1 could upregulate SMAD3 through acting as a competitive endogenous RNA (ceRNA) of miR-143-3p. Finally, rescue assay demonstrated that the ACTA2-AS1/miR-143-3p/SMAD3 axis played an important role in the proliferation, migration and apoptosis of CC cells.

Conclusions

In summary, our study revealed that ACTA2-AS1 upregulates SMAD3 by competitively binding miR-143-3p, thereby accelerating CC progression. The ACTA2-AS1/miR-143-3p/SMAD3 axis can play a crucial role in cervical carcinogenesis, providing new clues for the early diagnosis and treatment of CC.
Gravidity-dependent associations between interferon response and birth weight in placental malaria
Authors: Quanquin Natalie M. , Barres Lauren G. , Aliyari Saba R. , Day Nathan T. , Gerami Hoda , Fisher Susan J. , Kakuru Abel , Kamya Moses R. , Havlir Diane V. , Feeney Margaret , Dorsey Grant , Cheng Genhong , Gaw Stephanie L.
Published: August 2020

Background

Maternal malarial infection leads to poor perinatal outcomes, including low birth weight from preterm delivery and/or fetal growth restriction, particularly in primigravidas. In placental malaria, Plasmodium falciparum-infected red blood cells cause an inflammatory response that can interfere with maternal–fetal exchange, leading to poor growth. The type I interferon (IFN-I) pathway plays an immunomodulatory role in viral and bacterial infections, usually by suppressing inflammatory responses. However, its role in placental malaria is unknown. This study examines the cytokine responses in placental tissue from subsets of malaria-infected and uninfected women, and attempts to correlate them with particular birth outcomes.

Methods

40 whole placental biopsy samples were obtained from pregnant women at least 16 years of age recruited to a larger prospective chemoprevention trial against malaria. These were patients at Tororo District Hospital in Uganda, an area of high malaria endemicity where approximately 40% of women have evidence of malaria infection at delivery. They were regularly followed at a local clinic and monitored for fever, with blood smears performed then and at time of delivery to diagnose malaria infection. Placenta biopsies were taken for histological diagnosis of placental malaria, as well as quantitative PCR analysis of genes in the IFN-I pathway (IFN-β, IL-10 and MX-1). Parameters such as infant birth weight and gestational age were also recorded.

Results

Histological analysis revealed placental malaria in 18 samples, while 22 were found to be uninfected. RT-PCR analysis showed a four-fold increase in IFN-β and IL-10 expression in multigravidas with placental malaria when compared to gravidity-matched, uninfected controls. This effect was not observed in primigravidas. Interestingly, linear regression analysis showed a positive association between IFN-β levels and higher birth weights (β = 101.2 g per log2-fold increase in IFN-β expression, p = 0.042). This association was strongest in primigravidas with placental malaria (β = 339.0, p = 0.006).

Conclusions

These results demonstrate differential regulation of the IFN-I pathway in placental malaria according to gravidity, with the greatest anti-inflammatory response seen in multigravidas. The association between IFN-β levels and higher birth weight also suggests a protective role for IFN-I against fetal growth restriction in placental malaria.
Disability inclusiveness of government responses to COVID-19 in South America: a framework analysis study
Authors: Sakellariou Dikaios , Malfitano Ana Paula Serrata , Rotarou Elena S.
Published: August 2020

Background

Disabled people are particularly exposed to the risks of COVID-19, as well as to the measures taken to address it, and their impact. The aim of the study was to examine the disability-inclusiveness of government responses to COVID-19 in four South American Countries: Argentina, Brazil, Chile, and Peru.

Methods

We conducted documentary research, using framework analysis to analyse reports, legislation, decrees, and other official documents that communicated measures taken in response to the pandemic, published from February 1st until May 22nd, 2020. We included documents reporting measures that affected disabled people either directly (measures specifically designed for disabled people) or indirectly (measures for the general population). We developed an analytical framework based on recommendations for disability-inclusive response to COVID-19 published by the Economic Commission for Latin America and the Carribean, the World Health Organisation, and other international organisations.

Results

We analysed 72 documents. The findings highlight that while some positive measures were taken, the needs of disabled people were not fully considered. Several countries published recommendations for a disability-inclusive response to COVID-19, without ensuring their translation to practice. All countries took at least some steps to ensure access to financial support, health, and education for disabled people, but at the same time they also implemented policies that had a detrimental impact on disabled people. The populations that are most exposed to the impacts of COVID-19, including disabled people living in institutional care, were protected in several cases only by recommendations rather by legislation.

Conclusions

This study illustrates how the official government responses taken by four countries in the region – while positive, in several aspects – do not fully address the needs of disabled people, thus further disadvantaging them. In order to ensure response to COVID − 19 is disability inclusive, it is necessary to translate recommendations to practice, consider disabled people both in mainstream policy and in disability-specific measures, and focus on the long-term reconstruction phase.