381 research outputs found

    Cellular and molecular mechanisms of pancreatitis in atrophy and regeneration

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    Investigating the long-term effects of air pollution on soil properties in the vicinity of the Arnot power station

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    A study was conducted in 2006 to investigate the long-term effects of air pollution on soil properties in the vicinity of the Arnot power station, Mpumalanga, South Africa. Fifteen sites were re-sampled and the soil chemical properties compared to baseline data gathered in 1996, resulting in a ten year period after which changes in soil properties were investigated. A spatial gradient was incorporated into the study in order to better understand the deposition of pollutants with increasing distance from the power station. The study indicates that long-term acidic deposition has led to detectable changes in soil chemical properties. Three chemical properties, namely the concentrations of calcium and magnesium in both the topsoils and the subsoils, as well as the effective cation exchange capacity in the subsoils showed a significant increase since 1996. However, five soil chemical properties, namely soil pH (K2SO4), the concentration of hydrogen and aluminium and total sulphur in both the topsoils and the subsoils, as well as extractable sulphate in the topsoils and soluble sulphate in the subsoils, all show that the soils have become more acidic over the ten years. The acidic components in the soil override the basic components, as shown by the ratio of basic cations to acidic cations in the soils. The spatial gradient generally indicates that at approximately 8 km from the power station, there is a decrease in the concentration of acidic soil properties and one explanation for this may be a reduction in the acidic components of atmospheric deposition at this site. However, this needs further investigation. Two significant relationships with distance were found, namely a significant negative relationship with soluble sulphate and a significant positive relationship with acid neutralising capacity. This research will form part of a database for other long-term monitoring programmes and will allow data to be compared to other data from this area of research. It will also provide information to important industry leaders such as Eskom

    Cognitive Behavioural Therapy with Exposure and Response Prevention in the treatment of Obsessive-Compulsive Disorder: A systematic review and meta-analysis of randomised controlled trials

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    © 2021 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Background: Cognitive behavioural therapy (CBT), incorporating exposure and response prevention (ERP) is widely recognised as the psychological treatment of choice for obsessive-compulsive disorder (OCD). Uncertainty remains however about the magnitude of the effect of CBT with ERP and the impact of moderating factors in patients with OCD. Method: This systematic review and meta-analysis assessed randomised-controlled trials of CBT with ERP in patients of all ages with OCD. The study was preregistered in PROSPERO (CRD42019122311). The primary outcome was end-of-trial OCD symptom scores. The moderating effects of patient-related and study-related factors including type of control intervention and risk of bias were examined. Additional exploratory analyses assessed the effects of treatment fidelity and impact of researcher allegiance. Results: Thirty-six studies were included, involving 2020 patients (537 children/adolescents and 1483 adults) with 1005 assigned to CBT with ERP and 1015 to control conditions. When compared against all control conditions, a large pooled effect size (ES) emerged in favour of CBT with ERP (g = 0.74: 95% CI = 0.51 to 0.97 k = 36), which appeared to diminish with increasing age. While CBT with ERP was more effective than psychological placebo (g = 1.13 95% CI 0.71 to 1.55, k = 10), it was no more effective than other active forms of psychological therapy (g = −0.05: 95% CI -0.27 to 0.16, k = 8). Similarly, whereas CBT with ERP was significantly superior when compared to all forms of pharmacological treatment (g = 0.36: 95% CI 0.7 to 0.64, k = 7), the effect became marginal when compared with adequate dosages of pharmacotherapy for OCD (g = 0.32: 95% CI -0.00 to 0.64, k = 6).A minority of studies (k = 8) were deemed to be at low risk of bias. Moreover, three quarters of studies (k = 28) demonstrated suspected researcher allegiance and these studies reported a large ES (g = 0.95: 95% CI 0.69 to 1.2), while those without suspected researcher allegiance (k = 8) indicated that CBT with ERP was not efficacious (g = 0.02: 95% CI -0.29 to 0.33). Conclusions: A large effect size was found for CBT with ERP in reducing the symptoms of OCD, but depends upon the choice of comparator control. This meta-analysis also highlights concerns about the methodological rigor and reporting of published studies of CBT with ERP in OCD. In particular, efficacy was strongly linked to researcher allegiance and this requires further future investigation.Peer reviewe

    Landscape of Epidermal Growth Factor Receptor Heterodimers in Brain Metastases

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    HER2+ breast cancer patients have an elevated risk of developing brain metastases (BM), despite adjuvant HER2-targeted therapy. The mechanisms underpinning this reduced intracranial efficacy are unclear. We optimised the in situ proximity ligation assay (PLA) for detection of the high-affinity neuregulin-1 receptor, HER2-HER3 (a key target of pertuzumab), in archival tissue samples and developed a pipeline for high throughput extraction of PLA data from fluorescent microscope image files. Applying this to a large BM sample cohort (n = 159) showed that BM from breast, ovarian, lung and kidney cancers have higher HER2-HER3 levels than other primary tumour types (melanoma, colorectal and prostate cancers). HER2 status, and tumour cell membrane expression of pHER2(Y1221/1222) and pHER3(Y1222) were positively, but not exclusively, associated with HER2-HER3 frequency. In an independent cohort (n = 78), BM had significantly higher HER2-HER3 levels than matching primary tumours (p = 0.0002). For patients who had two craniotomy procedures, HER2-HER3 dimer levels were lower in the consecutive lesion (n = 7; p = 0.006). We also investigated the effects of trastuzumab and pertuzumab on five different heterodimers in vitro: HER2-EGFR, HER2-HER4, HER2-HER3, HER3-HER4, HER3-EGFR. Treatment significantly altered the absolute frequencies of individual complexes in SKBr3 and/or MDA-MB-361 cells, but in the presence of neuregulin-1, the overall distribution was not markedly altered, with HER2-HER3 and HER2-HER4 remaining predominant. Together, these findings suggest that markers of HER2 and HER3 expression are not always indicative of dimerization, and that pertuzumab may be less effective at reducing HER2-HER3 dimerization in the context of excess neuregulin

    Association of Sperm-Associated Antigen 5 and Treatment Response in Patients With Estrogen Receptor-Positive Breast Cancer

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    There is no proven test that can guide the optimal treatment, either endocrine therapy or chemotherapy, for estrogen receptor-positive breast cancer. Objective: To investigate the associations of sperm-associated antigen 5 (SPAG5) transcript and SPAG5 protein expressions with treatment response in systemic therapy for estrogen receptor-positive breast cancer. Design, Settings, and Participants: This retrospective cohort study included patients with estrogen receptor-positive breast cancer who received 5 years of adjuvant endocrine therapy with or without neoadjuvant anthracycline-based combination chemotherapy (NACT) derived from 11 cohorts from December 1, 1986, to November 28, 2019. The associations of SPAG5 transcript and SPAG5 protein expression with pathological complete response to NACT were evaluated, as was the association of SPAG5 mRNA expression with response to neoadjuvant endocrine therapy. The associations of distal relapse-free survival with SPAG5 transcript or SPAG5 protein expressions were analyzed. Data were analyzed from September 9, 2015, to November 28, 2019. Main Outcomes and Measures: The primary outcomes were breast cancer-specific survival, distal relapse-free survival, pathological complete response, and clinical response. Outcomes were examined using Kaplan-Meier, multivariable logistic, and Cox regression models. Results: This study included 12 720 women aged 24 to 78 years (mean [SD] age, 58.46 [12.45] years) with estrogen receptor-positive breast cancer, including 1073 women with SPAG5 transcript expression and 361 women with SPAG5 protein expression of locally advanced disease stage IIA through IIIC. Women with SPAG5 transcript and SPAG5 protein expressions achieved higher pathological complete response compared with those without SPAG5 transcript or SPAG5 protein expressions (transcript: odds ratio, 2.45 [95% CI, 1.71-3.51]; P < .001; protein: odds ratio, 7.32 [95% CI, 3.33-16.22]; P < .001). Adding adjuvant anthracycline chemotherapy to adjuvant endocrine therapy for SPAG5 mRNA expression in estrogen receptor-positive breast cancer was associated with prolonged 5-year distal relapse-free survival in patients without lymph node involvement (hazard ratio, 0.34 [95% CI, 0.14-0.87]; P = .03) and patients with lymph node involvement (hazard ratio, 0.35 [95% CI, 0.18-0.68]; P = .002) compared with receiving 5-year endocrine therapy alone. Mean (SD) SPAG5 transcript was found to be downregulated after 2 weeks of neoadjuvant endocrine therapy compared with pretreatment levels in 68 of 92 patients (74%) (0.23 [0.18] vs 0.34 [0.24]; P < .001). Conclusions and Relevance: These findings suggest that SPAG5 transcript and SPAG5 protein expressions could be used to guide the optimal therapies for estrogen receptor-positive breast cancer. Retrospective and prospective clinical trials are warranted

    Association between guidelines and medical practitioners' perception of best management for patients attending with an apparently uncomplicated acute sire throat: a cross-sectional survey in five countries

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    Objective To investigate the relationship between guidelines and the medical practitioners' perception of optimal care for patients attending with an apparently uncomplicated acute sore throat in five countries (Australia, Germany, Sweden, UK and USA). Design International cross-sectional survey. Setting Primary healthcare (PHC). Participants Medical practitioners working in PHC. Main outcome measures ORs for: (A) perception of throat swabs as important, (B) perception of blood tests (C reactive protein, B-ESR and B-leucocytes) as important and (C) antibiotic prescriptions if no pathogenic bacteria isolated on throat swab. Results Guidelines differed significantly; those recommending throat swabs (Sweden and USA) were associated with practitioners perceiving them as important. The UK guideline was the only one actively discouraging the use of throat swabs. Hence, compared with the USA (reference), a throat swab showing no pathogenic bacteria increased the probability of antibiotic prescribing in the UK with OR 3.2 (95% CI 1.7 to 6.1) for adults, whereas it reduced the probability in Sweden for adults OR 0.35 (95% CI 0.13 to 0.96) and children 0.19 (95% CI 0.069 to 0.50). Conclusions The differences between practitioners' perceptions of best management were associated with their guidelines. It remains unclear if guidelines influenced medical practitioners' perception or if guidelines merely reflect the consensus of current practice. A larger effort should be made to reach an international consensus in high-income countries about the best management of patients attending for an uncomplicated acute sore throat

    Commentary on the article: “Maintenance of Wellness in Patients With Obsessive-Compulsive Disorder Who Discontinue Medication After Exposure/Response Prevention Augmentation A Randomized Clinical Trial”

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    © 2022 The Authors. Published by Elsevier Inc. This is an open access article distributed under the Creative Commons Non Commercial-No Derivatives Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by-nc-nd/4.0/Peer reviewe

    Data resource profile: : the Hospital Electronic Prescribing and Medicines Administration (HEPMA) national data collection in Scotland

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    Introduction To support both electronic prescribing and documentation of medicines administration in secondary care, hospitals in Scotland are currently implementing the Hospital Electronic Prescribing and Medicines Administration (HEPMA) software. Driven by the COVID-19 pandemic, agreements have been put in place to centrally collate data stemming from the operational HEPMA system. The aim was to develop a national data resource based on records created in secondary care, in line with pre-existing collections of data from primary care. Methods HEPMA is a live clinical system and updated on a continuous basis. Data is automatically extracted from local systems at least weekly and, in most cases, on a nightly basis, and integrated into the national HEPMA dataset. Subsequently, the data are subject to quality checks including data consistency and completeness. Records contain a unique patient identified (Community Health Index number), enabling linkage to other routinely collected data including primary care prescriptions, hospital admission episodes, and death records. Results The HEPMA data resource captures and compiles information on all medicines prescribed within the ward/hospital covered by the system; this includes medicine name, formulation, strength, dose, route, and frequency of administration, and dates and times of prescribing. In addition, the HEPMA dataset also captures information on medicines administration, including dates and time of administration. Data is available from January 2019 onwards and held by Public Health Scotland. Conclusion The national HEPMA data resource supports cross-sectional/point-prevalence studies including drug utilisation studies, and also offers scope to conduct longitudinal studies, e.g., cohort and case-control studies. With the possibility to link to other relevant datasets, additional areas of interest may include health policy evaluations and health economics studies. Access to data is subject to approval; researchers need to contact the electronic Data Research and Innovation Service (eDRIS) in the first instance

    Differential effects of sertraline and cognitive behavioural therapy on behavioural inhibition in patients with obsessive compulsive disorder

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    © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Patients with obsessive compulsive disorder (OCD) randomised to sertraline, manualised cognitive behavioural therapy (CBT), or combination (sertraline + CBT), underwent cognitive assessment. Cognitive testing was conducted at baseline and at week 16. The stop signal reaction time task (SSRT) was used to evaluate motor impulsivity and attentional flexibility was evaluated using the intra/extra-dimensional set shifting task. Paired-samples t-tests or nonparametric variants were used to compare baseline and posttreatment scores within each treatment group. Forty-five patients were tested at baseline (sertraline n = 14; CBT n = 14; sertraline + CBT n = 17) and 23 patients at week 16 (sertraline n = 6; CBT n = 7; sertraline + CBT n = 10). The mean dosage of sertraline was numerically higher in those taking sertraline as a monotherapy (166.67 mg) compared with those taking sertraline in combination with CBT (100 mg). Analysis of pre-post treatment scores using an intent-to-treat-analysis found a significant reduction in the SSRT in those treated with sertraline, whilst there was no significant change on this task for those treated with CBT or the combination. This study found that motor inhibition improved significantly following sertraline monotherapy. Suboptimal sertraline dosing might explain the failure to detect an effect on motor inhibition in the group receiving combination of sertraline + CBT. Higher dose sertraline may have broader cognitive effects than CBT for OCD, motor impulsivity may have value as a measure of treatment outcome and, by extension, the SSRT could serve as a biomarker for personalising care.Peer reviewe
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