bluuebunny/crossref_metadata_2025 huggingface dataset:
Satisfaction in parturients receiving epidural analgesia after prenatal shared decision-making intervention: a prospective, before-and-after cohort study
Authors: Cheng Wan-Jung , Hung Kuo-Chuan , Ho Chung-Han , Yu Chia-Hung , Chen Yi-Chen , Wu Ming-Ping , Chu Chin-Chen , Chang Ying-Jen
Published: July 2020

Background

The explanation of epidural analgesia by anesthesiologist would often begin after the parturient is admitted to the hospital. Because of labor pain, the decision of receiving epidural analgesia would often be made by the family members, instead of the parturient herself. We aimed to test whether earlier prenatal shared decision-making (SDM) interventions increase parturient’s comprehension and satisfaction of epidural labor analgesia, compared to conventional explanation after labor pain begun.

Methods

During the 28th week of gestation, we provided the SDM parturient health education as well as a leaflet with quick response codes. Scanning the code would link to education videoclips which explained what epidural analgesia is and its advantages and disadvantages. Original routine practice group parturients received explanation of analgesia after admission for delivery. To measure the satisfaction of labor pain service, the accessibility of information, and the communication with medical staff, we designed a questionnaire with reference to (1) Pregnancy and Maternity Care Patients’ Experiences Questionnaire (PreMaPEQ), (2) Preterm Birth Experience and Satisfaction Scale (P-BESS), and (3) Women’s Views of Birth Labor Satisfaction Questionnaire (WOMBLSQ). The questionnaire was amended after a pretest involving 30 parturients who had received epidural analgesia. Scree test analysis and exploratory factor analysis were performed; then, the questionnaire was revised again. A total of 200 valid questionnaires were collected—100 each from the original routine practice group and the SDM group.

Results

The SDM group reported significantly higher satisfaction with and understanding of epidural analgesia, and a significantly higher satisfaction with the information received, and the quality of pain relief. After SDM intervention, significant increasement of the average satisfaction scores in question “my epidural is effective” (9.10%; mean difference: 0.38; 95% confidence interval, 0.17 ~ 0.59;p < 0.001) and “The effect of epidural is just as what I have expected” (10.41%; mean difference: 0.41; 95% confidence interval, 0.18 ~ 0.64;p < 0.001) was demonstrated.

Conclusions

An earlier prenatal SDM intervention with sufficient information through videoclips increased parturients’ comprehensions and satisfaction of epidural analgesia service.

Trial registration

ISRCTNregistry, 14,256,563. Registered April 1st, 2020 (10.1186/ISRCTN14256563).
Vitamin D toxicity in a pediatric toxicological referral center; a cross-sectional study from Iran
Authors: Farnaghi Fariba , Hassanian-Moghaddam Hossein , Zamani Nasim , Gholami Narges , Gachkar Latif , Hosseini Yazdi Maryam
Published: July 2020

Background

Vitamin D is an essential element for body health with its supplements generally administered to prevent vitamin D deficiency. Since these supplements are available in domestic settings, vitamin D toxicity may happen in children.

Methods

All children younger than 12 years who presented to the pediatric emergency department of Loghman Hakim Hospital, Tehran, Iran with history of ingestion of more than 1500 IU/day of vitamin D supplements were enrolled. Patients’ demographic data, on-presentation signs and symptoms, laboratory findings, treatments given, and outcome were evaluated.

Result

Fifteen patients presented during the study period. Their mean age was 46.53 ± 10.14 months and 12 (80%) were girls. All of them had unintentionally ingested vitamin D. Mean ingested dose was 406700.7 ± 227400.1 IU. In eight patients (53.3%), 25 hydroxy vitamin D level was more than 100 ng/mL. One patient experienced hypercalcemia while all of them were asymptomatic and discharged without complications. There was no significant difference between patients with and without high levels of 25 OH vitamin D regarding lab tests, toxicity course, and outcome.

Conclusions

It seems that acute vitamin D toxicity is a benign condition in our pediatric population which may be due to high prevalence of vitamin D deficiency in Iran.
Housing as a social determinant of health and wellbeing: developing an empirically-informed realist theoretical framework
Authors: Rolfe Steve , Garnham Lisa , Godwin Jon , Anderson Isobel , Seaman Pete , Donaldson Cam
Published: July 2020

Background

The role of housing as a social determinant of health is well-established, but the causal pathways are poorly understood beyond the direct effects of physical housing defects. For low-income, vulnerable households there are particular challenges in creating a sense of home in a new tenancy which may have substantial effects on health and wellbeing. This study examines the role of these less tangible aspects of the housing experience for tenants in the social and private rented sectors in west central Scotland.

Methods

The paper analyses quantitative data from a mixed methods, longitudinal study of tenants from three housing organisations, collected across the first year of their tenancy. The paper postulates causal hypotheses on the basis of staff interviews and then uses a Realist Research approach to test and refine these into a theoretical framework for the connections between tenants’ broader experience of housing and their health and wellbeing.

Results

Housing service provision, tenants’ experience of property quality and aspects of neighbourhood are all demonstrated to be significantly correlated with measures of of health and wellbeing. Analysis of contextual factors provides additional detail within the theoretical framework, offering a basis for further empirical work.

Conclusions

The findings provide an empirically-informed realist theoretical framework for causal pathways connecting less tangible aspects of the housing experience to health and wellbeing. Applying this within housing policy and practice would facilitate a focus on housing as a public health intervention, with potential for significant impacts on the lives of low-income and vulnerable tenants. The framework also offers a basis for further research to refine our understanding of housing as a social determinant of health.
Levels of self-reported and objective physical activity in individuals with age-related macular degeneration
Authors: Zult Tjerk , Smith Lee , Stringer Charlotte , Pardhan Shahina
Published: July 2020

Background

Self-report in people with age-related macular degeneration (AMD) shows that they lead less active lifestyles. Physical activity is important as it has been shown to improve quality of life, reduce co-morbidity and also slow down the progression of AMD. Self-reported measures of physical activity are prone to subjective biases and therefore less accurate in quantifying physical activity. This study compared self-reported and objective (accelerometer-based) physical activity levels and patterns in older adults with AMD.

Methods

Data were collected in 11 AMD subjects with binocular vision loss (aged 76 ± 7 years), 10 AMD subjects with good binocular vision (aged 76 ± 7 years), and 11 controls (aged 70 ± 4 years). Binocular vision was established using visual acuity score. Contrast sensitivity and visual fields were also measured. Self-reported sedentary behaviour and moderate-to-vigorous physical activity (MVPA) was assessed using the Global Physical Activity Questionnaire. Objective measurements were obtained with an Actigraph GT3X accelerometer being worn for seven consecutive days on the hip. The objective physical activity measures were sedentary behaviour, light physical activity, MVPA, and step count.

Results

Objectively measured MVPA was 33–34% higher for controls compared to both AMD groups (p < 0.05). There were no group differences for any of the other objectively measured physical activity variables and self-reported physical activity variables were also not significantly different (all p > 0.05). Comparing the objective with the self-report physical activity measure showed that all groups under-reported their sedentary behaviour and MVPA, but controls under-reported their MVPA more than both AMD groups (p < 0.05). Weak to moderate correlations were observed between the severity of vision loss and objective physical activity measures (all − 0.413 ≥ r ≤ 0.443), while correlations for self-reported physical activity measures were less strong (all − 0.303 ≥ r ≤ 0.114).

Conclusions

People with AMD, irrespective of whether they were vision impaired, were better able to estimate the time spent in MVPA compared to controls. However, objectively measured MVPA, was higher in controls than AMD subjects. Although clinicians may use self-report to monitor the compliance of AMD subjects with any prescribed exercise programs, they should be aware that a valid comparison with healthy controls can only be made when MVPA is objectively measured.
The assessment of quality of life and satisfaction with life of patients before and after surgery of an isolated apical defect using synthetic materials
Authors: Zalewski Maciej , Kołodyńska Gabriela , Mucha Anna , Bełza Łukasz , Nowak Krzysztof , Andrzejewski Waldemar
Published: July 2020

Background

Pelvic floor static disorders constitute a significant clinical and social problem. The incidence of the problem increases with the age of female patients up to 80 years of age. Due to various methods of procedural treatment, eligibility for surgery should be carefully discussed with the patient. Ideally, the surgery should be effective and with the least possible number of complications. The objective of this study was to assess the quality of life of patients before and after the surgery of an isolated apical defect with the use of BSC mesh.

Methods

The study involved 60 patients who were diagnosed with pelvic floor static disorder on the basis of physical examination. Standardised questionnaires were used to assess the quality of life and satisfaction with life: the Perceived Quality of Life (P-QOL) and the Satisfaction With Life Scale (SWLS).

Results

The P-QOL results for each domain were higher in patients before surgery compared to the results obtained after the surgery. For almost all domains, the results obtained were statistically significant. The results obtained in the SWLS questionnaire in most answers also show that after the procedure there was an improvement in satisfaction with life in the examined female patients.

Conclusion

In most patients, surgical treatment of an isolated apical defect using BSC mesh results in the subsidence of bothersome symptoms and improves the quality of life.
A case report: renal cystic tumoural calcinosis with ossification and bone marrow formation
Authors: Xia Mancheng , Liu Chun , Yang Haosen , Yin Keqiang , Wang Yusheng , Tong Xunan , Zhang Siyu , Shuang Weibing
Published: July 2020

Background

Tumoural calcinosis (TC) is a rare disorder characterized by nonneoplastic amorphous calcium deposition that tends to occur in soft tissues around the large joint. Here, we report a case of cystic TC with ossification and bone marrow formation in the kidney.

Case presentation

We report a 63-year-old woman who presented with a complaint of intermittent right lumbar pain for 2 months. Computed tomography (CT) revealed a large cystic lesion on the lateral side of the right kidney, with a circular calcified wall around the lesion, which compressed, deformed and displaced the right kidney. To relieve the symptoms of right lumbar pain, the patient underwent surgical resection of this cystic lesion without partial removal of the renal parenchyma. The pathological results further confirmed the diagnosis of cystic TC with ossification and bone marrow formation in the right kidney. No recurrence was detected 1 year after surgery.

Conclusions

The main differential diagnoses of TC in the kidney are kidney stone, renal tuberculosis, renal cyst with a calcified wall, and tumour. Patients are treated mainly by complete surgical resection of the lesion.
Too much or too little opioids to patients receiving opioid agonist therapy in Norway (2013–2017): a prospective cohort study
Authors: Vold Jørn Henrik , Skurtveit Svetlana , Aas Christer , Johansson Kjell Arne , Fadnes Lars Thore
Published: July 2020

Background

Dispensations of opioid analgesics to patients on opioid agonist therapy (OAT) may increase the risk of overdoses. The current study’s objectives are to investigate the dispensation rates and mean daily doses of dispensed opioid analgesics among patients who received OAT opioids in Norway during 2013–2017 and evaluate whether discontinuing OAT opioids affects the dispensed dose of opioid analgesics.

Methods

Information on opioids was collected from the Norwegian Prescription Database. Dispensation rates were calculated by dividing the number of patients who were dispensed at least one opioid analgesic by the number of patients who were dispensed an OAT opioid. We calculated the mean daily dose of opioid analgesics in oral morphine equivalents. The OAT opioid dose was defined as a ratio between the dispensed doses divided by the mean recommended dose. We used logistic regression to estimate the association between the dispensation of an opioid analgesic, a dose of OAT opioids, having chronic pain, and being on palliative care.

Results

A total of 10,371 patients were dispensed at least one OAT opioid during the study period. In 2017, 18% were dispensed an opioid analgesic with a mean daily dose of 29 mg of oral morphine equivalents. Being dispensed an opioid analgesic was associated with having chronic pain (adjusted odds ratio (aOR): 3.6, 95% confidence interval: 3.2–4.2), being on palliative care (aOR: 6.1, 4.7–7.9), and receiving an OAT opioid dose below half of the recommended OAT dose (aOR: 1.7, 1.4–2.0). Similar results were seen in 2013–2016. The discontinuation of OAT opioids could increase the dose of dispensed opioid analgesics.

Conclusion

Reducing the dispensation of opioid analgesics can be achieved by increasing the OAT opioid dose for patients on a low OAT dose, and by extending the period needed to taper off the OAT opioid dose at discontinuation.
Exploring the consequences of decentralization: has privatization of health services been the perceived effect of decentralization in Khartoum locality, Sudan?
Authors: Noory Bandar , Hassanain Sara A. , Lindskog Benedikte Victoria , Elsony Asma , Bjune Gunnar Aksel
Published: July 2020

Background

The health system of Sudan has experienced several forms of decentralization, as well as, a radical reform. Authority and governance of secondary and tertiary health facilities have been shifted from federal to state levels. Moreover, the provision of health care services have been moved from large federal tertiary level hospitals such as Khartoum Teaching Hospital (KTH) and Jafaar Ibnoaf Hospital (JIH), located in the center of Khartoum, to smaller district secondary hospitals like Ibrahim Malik (IBMH), which is located in the southern part of Khartoum. Exploring stakeholders’ perceptions on this decentralisation implementation and its relevant consequences is vital in building an empirical benchmark for the improvement of health systems.

Methods

This study utilised a qualitative design which is comprised of in-depth interviews and qualitative content analysis with an inductive approach. The study was conducted between July and December 2015, and aimed at understanding the personal experiences and perceptions of stakeholders towards decentralisation enforcement and the implications on public health services, with a particular focus on the Khartoum locality. It involved community members residing in the Khartoum Locality, specifically in catchments area where hospital decentralisation was implemented, as well as, affiliated health workers and policymakers.

Results

The major finding suggested that privatisation of health services occurred after decentralisation. The study participants also highlighted that scrutiny and reduction of budgets allocated to health services led to an instantaneous enforcement of cost recovery user fee.

Devolving KTH Khartoum Teaching and Jafar Ibnoaf Hospitals into peripherals with less. Capacity, was considered to be a plan to weaken public health services and outsource services to private sector. Another theme that was highlighted in hospitals included the profit-making aspect of the governmental sector in the form of drug supplying and profit-making retail.

Conclusions

A change in health services after the enforcement of decentralisation was illustrated. Moreover, the incapacitation of public health systems and empowerment of the privatisation concept was the prevailing perception among stakeholders. Having contextualised in-depth studies and policy analysis in line with the global liberalisation and adjustment programmes is crucial for any health sector reform in Sudan.
Impact of medical professionals on Carbapenem-resistant Pseudomonas aeruginosa: moderating effect of workload based on the panel data in China
Authors: Han Meng , Zhang Xinping
Published: July 2020

Background

Antimicrobial resistance (AMR), especially carbapenem-resistant Pseudomonas aeruginosa (CRPA), causes a serious increase in morbidity, mortality and costs. Medical professionals play an important role in curbing AMR. Previous studies overlooked the impact of workload on the relationship between medical professionals and AMR. This study aimed to explore the relationship between medical professionals and the CRPA rate as well as the moderating effect of medical professionals’ workload on this relationship.

Methods

A provincial-level panel dataset from 2014 to 2017 was constructed. Medical professionals were measured by the numbers of physicians, registered nurses, pharmacists, and clinical microbiologists per 1000 population. Workload was measured by the number of daily physician visits. Fixed effect model and hierarchical regression analysis were performed to explore the moderating effect of workload on medical professionals and the CRPA rate.

Results

The numbers of physicians, registered nurses, pharmacists and clinical technicians were significantly negative associated with the CRPA rate (coef. = − 0.889, − 0.775, − 1.176, and − 0.822; P = 0.003, 0.003, 0.011, and 0.007, respectively). Workload had a significant and positive moderating effect on physicians, registered nurses, pharmacists, clinical technicians and the CRPA rate (coef. = 1.270, 1.400, 2.210, and 1.634; P = 0.004, 0.001, 0.035, and 0.003, respectively).

Conclusions

Increasing the number of medical professionals may help curb the CRPA rate. Measures aimed at reducing medical professionals’ workload should be implemented to further improve CRPA performance.
Timing-dependent effects of transcranial direct current stimulation with mirror therapy on daily function and motor control in chronic stroke: a randomized controlled pilot study
Authors: Liao Wan-wen , Chiang Wei-chi , Lin Keh-chung , Wu Ching-yi , Liu Chien-ting , Hsieh Yu-wei , Lin Yun-chung , Chen Chia-ling
Published: July 2020

Background

The timing of transcranial direct current stimulation (tDCS) with neurorehabilitation interventions may affect its modulatory effects. Motor function has been reported to be modulated by the timing of tDCS; however, whether the timing of tDCS would also affect restoration of daily function and upper extremity motor control with neurorehabilitation in stroke patients remains largely unexplored. Mirror therapy (MT) is a potentially effective neurorehabilitation approach for improving paretic arm function in stroke patients. This study aimed to determine whether the timing of tDCS with MT would influence treatment effects on daily function, motor function and motor control in individuals with chronic stroke.

Methods

This study was a double-blinded randomized controlled trial. Twenty-eight individuals with chronic stroke received one of the following three interventions: (1) sequentially combined tDCS with MT (SEQ), (2) concurrently combined tDCS with MT (CON), and (3) sham tDCS with MT (SHAM). Participants received interventions for 90 min/day, 5 days/week for 4 weeks. Daily function was assessed using the Nottingham Extended Activities of Daily Living Scale. Upper extremity motor function was assessed using the Fugl-Meyer Assessment Scale. Upper extremity motor control was evaluated using movement kinematic assessments.

Results

There were significant differences in daily function between the three groups. The SEQ group had greater improvement in daily function than the CON and SHAM groups. Kinematic analyses showed that movement time of the paretic hand significantly reduced in the SEQ group after interventions. All three groups had significant improvement in motor function from pre-intervention to post-intervention.

Conclusion

The timing of tDCS with MT may influence restoration of daily function and movement efficiency of the paretic hand in chronic stroke patients. Sequentially applying tDCS prior to MT seems to be advantageous for enhancing daily function and hand movement control, and may be considered as a potentially useful strategy in future clinical application.

Trial registration

ClinicalTrials.gov Identifier:NCT02827864. Registered on 29th June, 2016.
Comparative effects of Novirhabdovirus genes on modulating constitutive transcription and innate antiviral responses, in different teleost host cell types
Authors: Gorgoglione Bartolomeo , Ringiesn Jeffery L. , Pham Loc H. , Shepherd Brian S. , Leaman Douglas W.
Published: July 2020

Background

Infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) are highly contagious, pathogenic Novirhabdoviruses affecting fish and are thusly notifiable diseases with the World Organization for Animal Health. This study assessed the relative capacities of IHNV and VHSV genes to modulate host general transcription and explores the abilities of specific IHNV genes to interfere with the interferon pathway in heterogenous teleost cell-lines.

Methods

Optimized protocols allowed for efficient transient transfections in EPC, BF-2, RTG-2 and RTgill-W1 cell lines of plasmids encoding IHNV (M genogroup) and VHSV (-IVb genotype) genes, including N, P, M, G and NV. Their impact on general cellular transcription was measured 48 hours post transfection (hpt) with luciferase constructs driven by a modified β-Actin promoter (pCAG). Their modulation of the innate antiviral immune response was characterized 72 hpt, using luciferase constructs measuring rainbow trout Type I IFN or MX-1 promoter augmentation, upon MAVS co-transfection.

Results

M was generally confirmed as the strongest constitutive transcriptional suppressor while IHNV P, but not VHSV P, augmented constitutive transcription in fibroblastic cell types. Cell-specific effects were observed for viral G gene, with VHSV G exhibiting suppression of basal transcription in EPC and BF-2 but not in trout cells; while IHNV G was stimulatory in RTG-2, but inhibitory in RTgill-W1. NV consistently stimulated constitutive transcription, with higher augmentation patterns seen in fibroblastic compared to epithelial cells, and for IHNV NV compared to VHSV NV. The innate antiviral immune response, focusing on the IFN pathway, was silenced by IHNV M in all cell lines tested. IHNV N showed a dose-dependent suppression of type I IFN, but with minor effects on MX-1. IHNV P and G played minor IFN-inhibitory roles, consistent and dose-dependent only for G in rainbow trout cells. IHNV NV mediated a consistent stimulatory effect on either Type I IFN or MX-1, but much less pronounced in RTgill-W1.

Conclusions

This study extends our understanding of Novirhabdoviruses-host interaction, showing differential innate immune responses in heterogenous cell types. Viral regulators of innate immune signaling are identified, either as dose-dependent suppressors (such as M and N) or stimulators (mainly NV), indicating novel targets for the design of more efficient vaccination strategies.
Interactions between cortisol and lipids in human milk
Authors: Linderborg Kaisa M. , Kortesniemi Maaria , Aatsinki Anna-Katariina , Karlsson Linnea , Karlsson Hasse , Yang Baoru , Uusitupa Henna-Maria
Published: July 2020

Background

Human breast milk is one of the key early postnatal biological exposures for the developing child. It includes bioactive compounds, such as cortisol and fatty acids, which may be linked via the mother’s lipid metabolism.

Methods

This study investigated the associations between cortisol and lipids in human milk at the infant age of 2.5 months. Human milk cortisol concentrations were measured using luminescence immunoassay, and two groups of milks (n = 50 each) were formed based on either high (> 10 nmol/L) or low (< 3 nmol/L) cortisol levels. Lipids, as fatty acid content and composition of neutral (triacylglycerol-rich) and polar (phospholipid-rich) lipids, were measured with gas chromatography. The samples originated from the FinnBrain Birth Cohort Study.

Results

The percentage of phospholipid-rich lipids of total lipids was 33.08% ± 1.33%. In triacylglycerol-rich lipids, high cortisol level in milk was associated with higher lauric (12:0, mass % and mg/mL), myristic (14:0, mass % and mg/mL), eicosenoic (20:1n − 9, mass %), docosenoic (22:1n − 9, mass %, and mg/mL) acids, and to lower palmitic acid (16:0, mass %) compared with low cortisol levels in milk. In phospholipid-rich lipids, high cortisol level was associated with higher myristic (14:0, mass %) and docosenoic (22:1n − 9, mass %) acids. After adjusting for pre-pregnancy BMI and sampling time by linear regression, the milk cortisol remained a significant predictor for lauric and myristic acids in triacylglycerol-rich lipids, and myristic and docosenoic acid in phospholipid-rich lipids (β = 0.23 to 0.38 andp < 0.05 for each).

Conclusions

This study revealed certain significant associations between milk cortisol and the fatty acid composition of human milk, indicating that cortisol might be one of the factors affecting the origin of the lipids in human milk.
Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge
Authors: Yang Ting , Chen Wei-Cong , Shi Pei-Cong , Liu Man-Ru , Jiang Tao , Song Hu , Wang Jia-Qi , Fan Rui-Zhi , Pei Dong-Sheng , Song Jun
Published: July 2020

Background

Long noncoding RNAs (lncRNAs) are considered critical regulators in cancers; however, the clinical significance and mechanisms of MAPKAPK5-AS1 (hereinafter referred to as MK5-AS1) in colorectal cancer (CRC) remain mostly unknown.

Methods

In this study, quantitative real-time PCR (qPCR) and western blotting were utilized to detect the levels of MK5-AS1, let-7f-1-3p and MK5 (MAPK activated protein kinase 5) in CRC tissues and cell lines. The biological functions of MK5-AS1, let-7f-1-3p and MK5 in CRC cells were explored using Cell Counting Kit-8 (CCK8), colony formation and transwell assays. The potential mechanisms of MK5-AS1 were evaluated by RNA pull-down, RNA immunoprecipitation (RIP), dual luciferase reporter assay, chromatin immunoprecipitation (ChIP) and bioinformatics analysis. The effects of MK5-AS1 and MK5 on CRC were investigated by a xenotransplantation model.

Results

We confirmed that MK5-AS1 was significantly increased in CRC tissues. Knockdown of MK5-AS1 suppressed cell migration and invasion in vitro and inhibited lung metastasis in mice. Mechanistically, MK5-AS1 regulated SNAI1 expression by sponging let-7f-1-3p and cis-regulated the adjacent gene MK5. Moreover, MK5-AS1 recruited RBM4 and eIF4A1 to promote the translation of MK5. Our study verified that MK5 promoted the phosphorylation of c-Jun, which activated the transcription of SNAI1 by directly binding to its promoter.

Conclusions

MK5-AS1 cis-regulated the nearby gene MK5 and acted as a let-7f-1-3p sponge, playing a vital role in CRC tumorigenesis. This study could provide novel insights into molecular therapeutic targets of CRC.
Neoadjuvant endocrine therapy in locally advanced estrogen or progesterone receptor-positive breast cancer: determining the optimal endocrine agent and treatment duration in postmenopausal women—a literature review and proposed guidelines
Authors: Madigan Lauren I. , Dinh Phuong , Graham J. Dinny
Published: July 2020

Introduction

For patients with locally advanced estrogen receptor or progesterone receptor-positive breast cancer, neoadjuvant endocrine therapy (NET) facilitates down-staging of the tumor and increased rates of breast-conserving surgery. However, NET remains under-utilized, and there are very limited clinical guidelines governing which therapeutic agent to use, or the optimal duration of treatment in postmenopausal women. This literature review aims to discuss the evidence surrounding (1) biomarkers for patient selection for NET, (2) the optimal neoadjuvant endocrine agent for postmenopausal women with locally advanced breast cancer, and (3) the optimal duration of NET. In addition, we make initial recommendations towards developing a clinical guideline for the prescribing of NET.

Method

A wide-ranging search of online electronic databases was conducted using a truncated PIC search strategy to identify articles that were relevant to these aims and revealed a number of key findings.

Results

Randomized trials have consistently demonstrated that aromatase inhibitors are more effective than tamoxifen, in terms of objective response rate and rate of BCS, and should be used as first-line NET. The three available aromatase inhibitors have so far been demonstrated to be biologically equivalent, with the choice of aromatase inhibitor not having been shown to affect clinical outcomes. There is increasing evidence for extending the duration of NET beyond 3 to 4 months, to at least 6 months or until maximal clinical response is achieved. While on-treatment levels of the proliferation marker Ki67 are predictive of long-term outcome, the choice of adjuvant therapy in patients who have received NET and then surgery is best guided by the preoperative endocrine prognostic index, or PEPI, which incorporates Ki67 with other clinical parameters.

Conclusion

This study reveals that in appropriately selected patients, NET can provide equivalent clinical benefit to neoadjuvant chemotherapy in the same cohort, if suitable treatments and durations are chosen. Our findings highlight the need for better defined biomarkers both for guiding patient selection and for measuring outcomes. Development of standard guidelines for the prescribing of NET has the potential to improve both clinical outcomes and quality of life in this patient cohort.
Use of olanzapine to treat agitation in traumatic brain injury: study protocol for a randomised controlled trial
Authors: Phyland Ruby K , McKay Adam , Olver John , Walterfang Mark , Hopwood Malcolm , Hicks Amelia J , Mortimer Duncan , Ponsford Jennie L
Published: July 2020

Background

Agitation is common in the early stages of recovery from traumatic brain injury (TBI), when patients are in post-traumatic amnesia (PTA). Agitation is associated with risk of harm to patients and caregivers. Recent guidelines recommend that agitation during PTA is managed using environmental modifications. Agitation is also frequently treated pharmacologically, with the use of atypical antipsychotics such as olanzapine among the most common. This is despite a lack of well-designed studies to support the use of antipsychotics within this context. This study will be a double-blind, placebo-controlled randomised controlled trial. We will examine the efficacy, safety, cost-effectiveness and outcomes associated with the use of olanzapine for reducing agitation in patients in PTA following TBI over and above recommended environmental management.

Methods

Fifty-eight TBI rehabilitation inpatients who are in PTA and are agitated will receive olanzapine or placebo for the duration of PTA. All participants will additionally receive optimal environmental management for agitation. Measures of agitation, PTA and health will be undertaken at baseline. Treatment administration will begin at a dose of 5 mg daily and may be escalated to a maximum dose of 20 mg per day. Throughout the treatment period, agitation and PTA will be measured daily, and adverse events monitored weekly. Efficacy will be assessed by treatment group comparison of average Agitated Behaviour Scale scores during PTA. Participants will cease treatment upon emergence from PTA. Agitation levels will continue to be monitored for a further 2 weeks, post-treatment measures of health will be undertaken and cognitive and functional status will be assessed. Level of agitation and functional health will be assessed at hospital discharge. At 3 months post-discharge, functional outcomes and health service utilisation will be measured.

Discussion

This trial will provide crucial evidence to inform the management of agitation in patients in PTA following TBI. It will provide guidance as to whether olanzapine reduces agitation over and above recommended environmental management or conversely whether it increases or prolongs agitation and PTA, increases length of inpatient hospitalisation and impacts longer term cognitive and functional outcomes. It will also speak to the safety and cost-effectiveness of olanzapine use in this population.

Trial registration

ANZCTRACTRN12619000284167. Registered on 25 February 2019
Infection patterns of dengue, Zika and endosymbiont Wolbachia in the mosquito Aedes albopictus in Hong Kong
Authors: Huang Elaine Y. Y. , Wong Annette Y. P. , Lee Ivy H. T. , Qu Zhe , Yip Ho Yin , Leung Chi-wah , Yin Shuk-may , Hui Jerome H. L.
Published: July 2020

Background

The mosquitoAedes albopictusis a vector of dengue and Zika viruses. Insecticide-resistant mosquito populations have evolved in recent decades, suggesting that new control strategies are needed. Hong Kong has a monsoon-influenced humid subtropical climate, which favours the spread of mosquitoes. However, baseline information on the composition and dynamics of the occurrence of endosymbiontWolbachiain localAe. albopictusis lacking, hindering the development of scientifically-informed control measures. This study identifies the presence and absence of dengue and Zika viruses, andWolbachiainfection inAedes albopictusin Hong Kong.

Methods

Oviposition traps were set at 57 areas in Hong Kong, and both immature and adult mosquitoes were collected on a monthly basis between April 2018 and April 2019 as the study sample. Each individual mosquito in this sample was processed and screened for the presence of the dengue and Zika viruses and the endosymbiontsWolbachia wAlbA andwAlbB with PCR.

Results

Totals of 967 and 984 mosquitoes were tested respectively for the presence of dengue and Zika viruses, and no trace of either infection was found in these samples. The presence ofwAlbA andwAlbB was also tested in 1582 individuals. Over 80% of these individuals were found to be stably infected withWolbachiathroughout the thirteen-month collection period (~ 47% singly-infected; ~ 36.8% doubly infected with bothwAlbA andwAlbB).

Conclusions

The high degree ofWolbachia wAlbA andwAlbB infection inAe. albopictusmosquitoes in Hong Kong, coupled with the absence of any signs of infection by dengue and Zika viruses, contrasts significantly with the pattern of mosquito infection in other parts of Asia. Further studies of the infection pattern in local mosquitoes are warranted before mosquito control strategies used in other regions are implemented in Hong Kong.
Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo
Authors: Carvalho Leonardo J. M. , Tuvshintulga Bunduurem , Nugraha Arifin B. , Sivakumar Thillaiampalam , Yokoyama Naoaki
Published: July 2020

Background

Babesiosis represents a veterinary and medical threat, with a need for novel drugs. Artemisinin-based combination therapies (ACT) have been successfully implemented for malaria, a human disease caused by related parasites, Plasmodium spp. The aim of this study was to investigate whether ACT is active against Babesia in vitro and in vivo.

Methods

Mefloquine, tafenoquine, primaquine, methylene blue and lumefantrine, alone or in combination with artesunate, were tested in vitro against Babesia bovis. Parasite growth was verified using a SYBR green I-based fluorescence assay. Mice infected with Babesia microti were treated with mefloquine or tafenoquine, alone or in combination with artesunate, and parasitemia was verified by microscopy and PCR.

Results

All drugs, except lumefantrine, showed in vitro activity against B. bovis, with methylene blue showing the most potent activity (concentration 0.2 μM). Combination with artesunate led to improved activity, with mefloquine showing a striking 20-fold increase in activity. Tafenoquine (10 mg/kg, base), combined or not with artesunate, but not mefloquine, induced rapid clearance of B. microti in vivo by microscopy, but mice remained PCR-positive. Blood from mice treated with tafenoquine alone, but not with tafenoquine-artesunate, was infective for naive mice upon sub-inoculation.

Conclusions

Tafenoquine, and most likely other 8-aminoquinoline compounds, are promising compounds for the development of ACT for babesiosis.
Evaluation and utility of mitochondrial ribosomal genes for molecular systematics of parasitic nematodes
Authors: Chan Abigail Hui En , Chaisiri Kittipong , Morand Serge , Saralamba Naowarat , Thaenkham Urusa
Published: July 2020

Background

Molecular advances have accelerated our understanding of nematode systematics and taxonomy. However, comparative analyzes between various genetic markers have led to discrepancies in nematode phylogenies. This study aimed to evaluate the suitability of using mitochondrial12Sand16Sribosomal RNA genes for nematode molecular systematics.

Methods

To study the suitability of mitochondrial12Sand16Sribosomal RNA genes as genetic markers for nematode molecular systematics, we compared them with the other commonly used genetic markers, nuclear internal transcribed spacer 1 and 2 regions, nuclear18Sand28Sribosomal RNA genes, and mitochondrial cytochromecoxidase subunit 1 gene. After that, phylum-wide primers for mitochondrial12Sand16Sribosomal RNA genes were designed, and parasitic nematodes of humans and animals from 75 taxa with 21 representative species were inferred through phylogenetic analyzes. Phylogenetic analyzes were carried out using maximum likelihood and Bayesian inference algorithms.

Results

The phylogenetic relationships of nematodes based on the mitochondrial12SrRNA gene supported the monophyly of nematodes in clades I, IV, and V, reinforcing the potential of this gene as a genetic marker for nematode systematics. In contrast, the mitochondrial16SrRNA gene only supported the monophyly of clades I and V, providing evidence that the12SrRNA gene is more suitable for nematode molecular systematics. In this study, subclades of clade III containing various nematode families were not monophyletic when the16Sor12SrRNA gene was used as the genetic marker. This is similar to the phylogenetic relationship revealed by previous studies using whole mitochondrial genomes as genetic markers.

Conclusions

This study supports the use of the12SrRNA gene as a genetic marker for studying the molecular systematics of nematodes to understand intra-phyla relationships. Phylum-wide primers for nematodes using mitochondrial ribosomal genes were prepared, which may enhance future studies. Furthermore, sufficient genetic variation in the mitochondrial12Sand16SrRNA genes between species also allowed for accurate taxonomy to species level, revealing the potential of these two genes as genetic markers for DNA barcoding.
Cytokine-induced molecular responses in airway smooth muscle cells inform genome-wide association studies of asthma
Authors: Thompson Emma E. , Dang Quynh , Mitchell-Handley Blair , Rajendran Kavitha , Ram-Mohan Sumati , Solway Julian , Ober Carole , Krishnan Ramaswamy
Published: July 2020

Background

A challenge in the post-GWAS era is to assign function to disease-associated variants. However, available resources do not include all tissues or environmental exposures that are relevant to all diseases. For example, exaggerated bronchoconstriction of airway smooth muscle cells (ASMCs) defines airway hyperresponsiveness (AHR), a cardinal feature of asthma. However, the contribution of ASMC to genetic and genomic studies has largely been overlooked. Our study aimed to address the gap in data availability from a critical tissue in genomic studies of asthma.

Methods

We developed a cell model of AHR to discover variants associated with transcriptional, epigenetic, and cellular responses to two AHR promoting cytokines, IL-13 and IL-17A, and performed a GWAS of bronchial responsiveness (BRI) in humans.

Results

Our study revealed significant response differences between ASMCs from asthma cases and controls, including genes implicated in asthma susceptibility. We defined molecular quantitative trait loci (QTLs) for expression (eQTLs) and methylation (meQTLs), and cellular QTLs for contractility (coQTLs) and performed a GWAS of BRI in human subjects. Variants in asthma GWAS were significantly enriched for ASM QTLs and BRI-associated SNPs, and near genes enriched for ASM function, many with smallPvalues that did not reach stringent thresholds of significance in GWAS.

Conclusions

Our study identified significant differences between ASMCs from asthma cases and controls, potentially reflecting trained tolerance in these cells, as well as a set of variants, overlooked in previous GWAS, which reflect the AHR component of asthma.
Multiple brain abscesses with good prognosis in an infant with cyanotic congenital heart disease: a case report
Authors: Kudo-Kubo Atsuko , Shimakawa Shuichi , Odanaka Yutaka , Ikeda Naokado , Kitahara Hikaru , Toshikawa Hiromitsu , Ashida Atsuko , Fukui Miho , Ozaki Noriyasu , Kishi Kanta , Wanibuchi Masahiko , Ashida Akira
Published: July 2020

Background

Brain abscesses are relatively rare, but they are a potentially life-threatening condition. Predictive factors for poor outcome are a young age and the presence of multiple abscesses. We report a case of a 15-month-old girl with cyanotic congenital heart disease who developed multiple brain abscesses caused by Streptococcus intermedius. The patient was treated with a combination of surgical aspiration and antimicrobial therapy without apparent neurological sequelae. To the best of our knowledge, this is the youngest such patient to have been reported in the literature. We explore the possible causes of her good outcome.

Case presentation

At the age of 15 months, the Japanese patient initially was presented to our hospital with transient eye deviation to the left and vomiting. In a blood examination, her white blood cell count (12,720 per mm3 with a left shift) and C-reactive protein level (1.23 mg/ml) were slightly elevated. Magnetic resonance imaging of the brain showed three mass lesions. These were 1.5-cm, 1.9-cm, and 1.2-cm rim-enhancing lesions with extensive surrounding edema. Brain abscesses were diagnosed, and vancomycin (50 mg every 12 hours) and meropenem (40 mg every 8 hours) were started empirically. However, because each brain abscess was enlarged at 8 days after admission, surgical aspiration was performed at 10 days after admission, and cultures of the aspirated pus grew S. intermedius. Penicillin G (0.7 million units every 4 hours) and ceftriaxone (280 mg every 12 hours), to which this isolate is susceptible, were then administered, and the brain abscesses reduced in size. After 1 month of ceftriaxone and 3 months of penicillin G treatment, all of the brain abscesses disappeared. Apparent neurological sequelae were not observed at 6 months after onset.

Conclusions

A good outcome can be obtained if multiple brain abscesses develop in infancy or early childhood in cases without unconsciousness at admission, meningitis, or sepsis. Appropriate antimicrobial therapy should be started immediately after diagnosis, with surgical aspiration performed to identify the causative pathogen and avoid intraventricular rupture of the brain abscesses.
An interaction between fetal sex and placental weight and efficiency predicts intrauterine growth in response to maternal protein insufficiency and gestational exposure window in a mouse model of FASD
Authors: Kwan Sze Ting Cecilia , Presswood Brandon H. , Helfrich Kaylee K. , Baulch Joshua W. , Mooney Sandra M. , Smith Susan M.
Published: July 2020

Background

Individuals exposed to gestational stressors such as alcohol exhibit a spectrum of growth patterns, suggesting individualized responses to the stressors. We hypothesized that intrauterine growth responses to gestational alcohol are modified not only by the stressor’s severity but by fetal sex and the placenta’s adaptive capacity.

Methods

Pregnant C57BL/6J mice were assigned to one of three groups. Group 1 consumed a normal protein diet (18% protein by weight) and received 4.5 g alcohol/kg body weight (NP-Alc-8) or isocaloric maltodextrin (NP-MD-8) daily from embryonic day (E) 8.5–E17.5. Group 2 consumed the same diet but received alcohol (NP-Alc-13) or maltodextrin (NP-MD-13) daily from E13.5–E17.5. Group 3 consumed the same diet but containing a lower protein content (12% protein by weight) from E0.5 and also received alcohol (LP-Alc-8) or maltodextrin (LP-MD-8) daily from E8.5–E17.5. Maternal, placental, and fetal outcomes were assessed on E17.5 using 2-way ANOVA or mixed linear model.

Results

We found that intrauterine growth differed in the alcohol-exposed fetuses depending on sex and insult severity. Both NP-Alc-8 (vs. NP-MD-8) males and females had lower body weight and asymmetrical growth, but only NP-Alc-8 females had lower placental weight (P< 0.05). NP-Alc-13 (vs. NP-MD-13) females, but not their male littermates, had lower body weight (P= 0.019). Alcohol exposure beginning from E8.5 (vs. E13.5) decreased the ratio of fetal liver-to-body weight and increased the ratio of fetal brain-to-liver weight in both sexes (P< 0.05). LP-Alc-8 (vs. NP-MD-8) group had smaller litter size (P= 0.048), but the survivors had normal placental and body weight at E17.5. Nevertheless, LP-Alc-8 fetuses still showed asymmetrical growth. Correlation analyses reveal a relationship between litter size and placental outcomes, which were related to fetal outcomes in a sex-dependent manner, suggesting that the placenta may mediate the consequence of LP-Alc-altered litter size on fetal development.

Conclusions

Our data indicate that the placenta is strongly involved in the fetal stress response and adapts in a sex-dependent fashion to support fetal development under the alcohol stressor. These variables may further influence the spectrum of intrauterine growth outcomes observed in those diagnosed with fetal alcohol spectrum disorder.