Miracle-dz/UniFAR-FTUs huggingface dataset:
Accuracy of visual screening for cervical neoplasia: Results from an IARC multicentre study in India and Africa

Visual inspection‐based screening tests, such as visual inspection with 4% acetic acid (VIA) and with Lugol's iodine (VILI), have been proposed as alternatives to cytology in mass screening programs. To date, there is only limited information on the accuracy of these tests in detecting High‐grade Squamous Intraepithelial Lesions (HSIL). Eleven cross‐sectional studies involving 56,939 women aged 25–65 years were conducted in Burkina Faso, Congo, Guinea, India, Mali and Niger to evaluate the accuracy of VIA and VILI performed by health workers. A common protocol and questionnaire was used. For final diagnosis, all women were investigated with colposcopy and biopsies were taken when necessary. Data from the studies were pooled to calculate sensitivity, specificity and predictive values of the tests for the detection of HSIL. Of the screened women, 16.1% and 16.4% were positive on examination using, respectively, VIA and VILI; 1,063 were diagnosed with HSIL. The pooled sensitivity, specificity, positive and negative predictive values for VIA were 76.8% (95% CI: 74.2–79.4%), 85.5% (95% CI: 85.2–85.8%), 9.4% (95% CI:8.8–10.8%) and 99.5% (95% CI:99.4–99.6%), respectively. The values were 91.7% (95% CI: 89.7–93.4%), 85.4% (95% CI: 85.1–85.7%), 10.9% (95% CI: 10.2–11.6%) and 99.8% (95% CI:99.7–99.9%), respectively for VILI. The range of sensitivity and specificity for VIA was 56.1–93.9% and 74.2–93.8%, respectively, between studies and were 76.0–97.0 % and 73.0–91.3% for VILI. VILI had a significantly higher sensitivity than VIA in detecting HSIL, but specificity was similar. VILI appears to be a more accurate visual test for use in screening and treatment programs in low‐resource settings. © 2004 Wiley‐Liss, Inc.
Nasopharyngeal Carriage of Individual Streptococcus pneumoniae Serotypes During Pediatric Pneumonia as a Means to Estimate Serotype Disease Potential

Background: We aimed at estimating pneumococcal serotype-specific disease potential in pediatric community-acquired alveolar pneumonia (CAAP), by comparing nasopharyngeal pneumococcal carriage during disease to carriage in healthy children. Methods: Pneumococcal nasopharyngeal cultures were obtained from children <5 years old admitted to the emergency room or hospitalized with radiologically diagnosed CAAP and from healthy controls. Disease potential was estimated by calculating serotype-specific odds ratios (OR) of a given serotype to be carried during disease compared with healthy children (after adjustment for age, ethnicity, previous antibiotic therapy, and season). Results: A total of 603 and 1504 isolates were obtained from CAAP and healthy children, respectively. A significant OR >1.0 of a specific serotype being carried during disease (suggesting a higher disease potential) was observed with serotypes (by decreasing rank) 1, 5, 22F, 7F, 14, 9V, and 19A. A significant OR <1.0 of being carried during disease (suggesting a lower disease potential) was observed with serotypes 6A, 6B, 23A, and 35B. Carriage of PCV7 serotypes (grouped) during CAAP was highest in age group 6 to 17 months. PCV10 and PCV13 provided significantly higher coverage for both 6 to 17 and 18 to 35 month age groups. Conclusions: It is suggested that serotypes 1, 5, 7F, 9V, 14, 19A, and 22F have a higher disease potential for childhood pneumonia than do serotypes 6A, 6B, 23A, and 35B.
The major α-tubulin K40 acetyltransferase αTAT1 promotes rapid ciliogenesis and efficient mechanosensation

Long-lived microtubules found in ciliary axonemes, neuronal processes, and migrating cells are marked by α-tubulin acetylation on lysine 40, a modification that takes place inside the microtubule lumen. The physiological importance of microtubule acetylation remains elusive. Here, we identify a BBSome-associated protein that we name αTAT1, with a highly specific α-tubulin K40 acetyltransferase activity and a catalytic preference for microtubules over free tubulin. In mammalian cells, the catalytic activity of αTAT1 is necessary and sufficient for α-tubulin K40 acetylation. Remarkably, αTAT1 is universally and exclusively conserved in ciliated organisms, and is required for the acetylation of axonemal microtubules and for the normal kinetics of primary cilium assembly. In Caenorhabditis elegans, microtubule acetylation is most prominent in touch receptor neurons (TRNs) and MEC-17, a homolog of αTAT1, and its paralog αTAT-2 are required for α-tubulin acetylation and for two distinct types of touch sensation. Furthermore, in animals lacking MEC-17, αTAT-2, and the sole C. elegans K40α-tubulin MEC-12, touch sensation can be restored by expression of an acetyl-mimic MEC-12[K40Q]. We conclude that αTAT1 is the major and possibly the sole α-tubulin K40 acetyltransferase in mammals and nematodes, and that tubulin acetylation plays a conserved role in several microtubule-based processes.
Room for improvement? Leadership, innovation culture and uptake of quality improvement methods in general practice.

BACKGROUND Leadership and innovation are currently seen as essential elements for the development and maintenance of high-quality care. Little is known about the relationship between leadership and culture of innovation and the extent to which quality improvement methods are used in general practice. This study aimed to assess the relationship between leadership behaviour, culture of innovation and adoption of quality improvement methods in general practice. METHOD Self-administered postal questionnaires were sent to general practitioner quality improvement leads in one county in the UK between June and December 2007. The questionnaire consisted of background information, a 12-item scale to assess leadership behaviour, a seven-dimension self-rating scale for culture of innovation and questions on current use of quality improvement tools and techniques. RESULTS Sixty-three completed questionnaires (62%) were returned. Leadership behaviours were not commonly reported. Most practices reported a positive culture of innovation, featuring relationship most strongly, followed by targets and information but rated lower on other dimensions of rewards, risk and resources. There was a significant positive correlation between leadership behaviour and the culture of innovation (r = 0.57; P < 0.001). Apart from clinical audit and significant event analysis, quality improvement methods were not adopted by most participating practices. CONCLUSIONS Leadership behaviours were infrequently reported and this was associated with a limited culture of innovation in participating general practices. There was little use of quality improvement methods beyond clinical and significant event audit. Practices need support to enhance leadership skills, encourage innovation and develop quality improvement skills if improvements in health care are to accelerate.
Risk of age-related macular degeneration in eyes with macular drusen or hyperpigmentation: the Blue Mountains Eye Study cohort.

OBJECTIVE To quantify the 5-year risk of age-related macular degeneration (AMD) in eyes with different macular drusen characteristics (ie, size, type, location, and total area) or hyperpigmentation in a population-based cohort. METHODS The Blue Mountains Eye Study examined 3654 residents during 1992-1994; 2335 (75.1% of survivors) were reexamined during 1997-1999. Retinal photographs were graded using the Wisconsin Age-Related Maculopathy Grading System. Incident AMD lesions were defined by development of neovascular AMD or geographic atrophy in eyes without these lesions at baseline (eyes at risk). Age-adjusted relative risks (RRs) were determined. Generalized estimating equation models were used to estimate odds ratios, adjusting for the correlation between eyes and other AMD risk factors. Main Outcome Measure Incidence of AMD. RESULTS Of the 4634 eyes at risk, 52 (1.1%) developed neovascular or atrophic AMD lesions over 5 years. In right eyes, presence vs absence of the following macular signs predicted AMD: drusen that were 125 micro m or larger (13.9 vs 0.6%; age-adjusted RR, 5.7; 95% confidence interval [CI], 3.6-9.0), indistinct soft or reticular drusen (23.2% vs 0.4%; RR, 9.9; 95% CI, 6.4-15.4), total drusen area of half the disc area or more (31.4% vs 0.6%; RR, 13.5; 95% CI, 8.0-22.8), and hyperpigmentation (14.4% vs 0.5%; RR, 8.0; 95% CI, 5.4-11.9). After adjusting for age, sex, and smoking status, eyes with these signs at baseline had a high likelihood of developing AMD. Eyes with Age-Related Eye Disease Study categories 3 and 4 were 5 times more likely to develop AMD compared with eyes in categories 1 and 2. CONCLUSION This study quantifies the 5-year risk of AMD in eyes with macular drusen and hyperpigmentation.
Effects of Chronic Sumatriptan and Zolmitriptan Treatment on 5-HT1 Receptor Expression and Function in Rats

Triptans are commonly used anti-migraine drugs and show agonist action mainly at serotonin 5-HT1B/1D/1F receptors. It is not known whether frequent or long-term treatment with these drugs would alter 5-HT receptor function. We investigated the effects of protracted (14-18 days) sumatriptan and zolmitriptan treatment in rats on 5-HT1 receptor mRNA expression and function in tissues related to migraine pathophysiology. RT-PCR analysis revealed that 5-HT1B/1D/1F receptor mRNA was reduced in the trigeminal ganglion after treatment with either triptan (reduction by: sumatriptan 39% and zolmitriptan 61% for 5-HT1B; 60% vs 41% for 5-HT1D; 32% vs 68% for 5-HT1F). Sumatriptan attenuated 5-HT1D receptor mRNA by 49% in the basilar artery, whereas zolmitriptan reduced 5-HT1B mRNA in this tissue by 70%. No change in 5-HT1 receptor mRNA expression was observed in coronary artery and dura mater. Chronic triptan treatment had no effect in two functional assays [sumatriptan mediated inhibition (50 mg/kg, i.p.) of electrically induced plasma protein extravasation in dura mater and 5-nonyloxytryptaminestimulated [35S]guanosine-5′-O-(3-thio)triphosphate binding in substantia nigra]. Furthermore, vasoconstriction to 5-HT in isolated basilar artery was not affected by chronic triptan treatment, while it was slightly reduced in coronary artery. We conclude that, although our treatment protocol altered mRNA receptor expression in several tissues relevant to migraine pathophysiology, it did not attenuate 5-HT1 receptor-dependent functions in rats.
Suggestive evidence for functionally distinct, tumor-suppressor genes on chromosomes 1 and 11 for a human fibrosarcoma cell line, HT1080.

One approach for identifying chromosomes which carry putative tumor-suppressor genes is the introduction of specific chromosomes into the tumor cells of interest. We examined the ability of human chromosomes derived from normal fibroblasts to suppress or modulate tumorigenicity in nude mice and the in vitro properties of HT1080, a human fibrosarcoma cell line. We first isolated mouse A9 cells containing a single human chromosome (1, 2, 7, 11, or 12) integrated with pSV2neo plasmid DNA. Following fusion of microcells from these A9 cells with the HT1080 cells, clones that were resistant to G418 were isolated and karyotypically analysed. Three of 4 microcell-hybrids with an introduced chromosome 1 were non-tumorigenic (#1-7, -8 and -13), whereas the parental HT1080 cells were highly tumorigenic. The other microcell-hybrid clone (#1-1) formed tumors, the cells of which had lost one copy of chromosome 1. Two clones from the #1-1 cells were isolated; one contained an extra copy of chromosome 1, and the other one did not. The former was non-tumorigenic and the latter was tumorigenic. The introduction of chromosome 11 also suppressed the tumorigenicity of HT1080 cells, while the introduction of other chromosomes, i.e., 2, 7, or 12, had minimal or no effect on the tumorigenicity of these cells. Cells from tumors formed by microcell-hybrids with the introduction of chromosome 2, 7, or 12 still contained the introduced chromosome. Interestingly, only the microcell-hybrids with an introduced chromosome 1 had an alteration in cellular morphology and modulation of in vitro transformed properties, i.e., cell-growth and saturation density in a medium containing 10% calf serum and cell-growth in soft-agar. Thus, the results indicate the presence of putative tumor-suppressor genes for HT1080 cells on chromosomes 1 and 11, and further suggest that the genes on these chromosomes control different neoplastic phenotypes.
Haematopoietic stem cell transplantation in inborn errors of metabolism

Purpose of reviewThis review summarizes the main results of haematopoietic stem cell transplantation (HSCT) in selected inborn errors of metabolism (IEMs). Recent findingsEarly diagnosis and immediate referral to an IEM specialist is of paramount importance to improve clinical outcome: patients who are transplanted early or in their presymptomatic phase generally achieve better correction of their somatic symptoms and neurocognitive development. Long-term outcome in children with Hurler syndrome is influenced by age at HSCT, baseline clinical status and post-HSCT enzyme levels. Myeloablative Busulfan-based conditioning regimens with therapeutic drug monitoring are recommended to achieve full donor engraftment and more robust enzyme delivery after HSCT. Gene therapy can lead to production of supranormal enzyme levels, and preliminary clinical results are also promising in IEMs historically not responsive to allogeneic HSCT. SummaryAllogeneic HSCT has largely contributed to the improved survival and quality of life of many children affected by IEMs. Neonatal screening could enable earlier HSCT, and this might significantly reduce residual disease burden and improve clinical outcome. Novel strategies, such as gene therapy, have shown encouraging clinical results in selected IEMs and might become more widely available in the future, with potentially better enzyme delivery and reduced transplant-related toxicity.
Fiscal Devaluation and Real Exchange Rates in the Euro Area: Some Econometric Insights

We explore whether a fiscal devaluation, that is, a reduction in employers’ social security contributions and an increase in value added tax, affects two indicators of bilateral real exchange rates in the euro area: one based on unit labor costs, and another based on consumer prices. We find that, in the short term, cuts in employers’ contributions depreciate real exchange rates based on unit labor costs, while value added tax hikes appreciate real exchange rates based on consumer prices. In the long run, a value added tax increase also appreciates the real exchange rates based on unit labor costs.
Glucocorticoids and cardiovascular and cerebrovascular events in polymyalgia rheumatica.

OBJECTIVE To examine the effect of glucocorticoid use on the risk of various cardiovascular diseases in patients with polymyalgia rheumatica (PMR). METHODS We assembled a population-based incidence cohort of 364 patients with PMR first diagnosed between January 1, 1970 and December 31, 1999. Inclusion criteria were age > or = 50 years, bilateral aching and morning stiffness involving at least 2 areas (neck, shoulders, hips, or proximal aspects of the thighs), and erythrocyte sedimentation rate (ESR) > or = 40 mm/hour. In patients who fulfilled the first 2 criteria but had a normal ESR, a rapid response to low-dose glucocorticoids served as the third criterion. Patients were followed up until death or December 31, 2004. Cox models with time-dependent covariates were used to examine the association between glucocorticoid exposure and risk of myocardial infarction, heart failure, peripheral vascular disease, and cerebrovascular disease. RESULTS A total of 364 PMR patients (mean age 73 years, 67% women) were followed for a median of 7.6 years. During the disease course, 310 (85%) patients received glucocorticoids. After adjusting for age, calendar year, and ESR, patients who received glucocorticoids did not have a significantly higher risk for myocardial infarction, heart failure, peripheral vascular disease, or cerebrovascular disease (hazard ratio [95% confidence interval] 0.58 [0.29-1.18], 0.85 [0.45-1.54], 0.58 [0.24-1.40], and 0.65 [0.33-1.26], respectively) compared with those who did not receive glucocorticoids. In fact, a trend for a protective effect was seen. No significant association was observed between cumulative glucocorticoid dose and any of the outcomes (P = 0.39). CONCLUSION In patients with PMR, treatment with glucocorticoids is not associated with an increased risk of cardiovascular diseases.
Topiramate-induced weight loss in schizophrenia: a retrospective case series study.

OBJECTIVE Atypical antipsychotics have been associated with weight gain. This study examines the efficacy of adjunctive topiramate in patients with schizophrenia and schizoaffective disorder with antipsychotic-induced weight gain. METHODS A 2-year retrospective case analysis was performed in all 300 patients of the outpatient Special Follow-up Clinic for chronic schizophrenia and related psychoses at the Allan Memorial Institute, McGill University Health Centre (Montreal, Canada), a tertiary care University teaching hospital. RESULTS 10 patients met study inclusion criteria. Mean daily topiramate dose was 197.5 mg (A+/-77) (range, 125-400 mg). Topiramate produced continued weight loss throughout the study duration without tolerance. Patients treated for 6 months and more had significantly higher Body Mass Index (BMI) differences than those treated for shorter durations (BMI-d6 months=-4.7A+/-2.4; BMI-d2 months=-3.2A+/-2.3; P=0.015). BMI changes were similar across genders. CONCLUSION This study supports topiramate use to target weight loss in stable overweight schizophrenic patients as a potential therapy that requires further investigation.
Mortality in people with Type 2 diabetes in the UK

Aims Under‐reporting of diabetes on death certificates contributes to the unreliable estimates of mortality as a result of diabetes. The influence of obesity on mortality in Type 2 diabetes is not well documented. We aimed to study mortality from diabetes and the influence of obesity on mortality in Type 2 diabetes in a large cohort selected from the General Practice Research Database (GPRD).
Functional TFIIH Is Required for UV-Induced Translocation of CSA to the Nuclear Matrix

ABSTRACT Transcription-coupled repair (TCR) efficiently removes a variety of lesions from the transcribed strand of active genes. Mutations in Cockayne syndrome group A and B genes (CSA and CSB) result in defective TCR, but the molecular mechanism of TCR in mammalian cells is not clear. We have found that CSA protein is translocated to the nuclear matrix after UV irradiation and colocalized with the hyperphosphorylated form of RNA polymerase II and that the translocation is dependent on CSB. We developed a cell-free system for the UV-induced translocation of CSA. A cytoskeleton (CSK) buffer-soluble fraction containing CSA and a CSK buffer-insoluble fraction prepared from UV-irradiated CS-A cells were mixed. After incubation, the insoluble fraction was treated with DNase I. CSA protein was detected in the DNase I-insoluble fraction, indicating that it was translocated to the nuclear matrix. In this cell-free system, the translocation was dependent on UV irradiation, CSB function, and TCR-competent CSA. Moreover, the translocation was dependent on functional TFIIH, as well as chromatin structure and transcription elongation. These results suggest that alterations of chromatin at the RNA polymerase II stall site, which depend on CSB and TFIIH at least, are necessary for the UV-induced translocation of CSA to the nuclear matrix.
Investigation of the Photodynamic Effects of Curcumin Against Candida albicans

This study describes the association of curcumin with light emitting diode (LED) for the inactivation of Candida albicans. Suspensions of Candida were treated with nine curcumin concentrations and exposed to LED at different fluences. The protocol that showed the best outcomes for Candida inactivation was selected to evaluate the effect of the preirradiation time (PIT) on photodynamic therapy (PDT) effectiveness, the uptake of curcumin by C. albicans cells and the possible involvement of singlet oxygen in the photodynamic action. Curcumin‐mediated PDT was also assessed against biofilms. In addition to the microbiological experiments, similar protocols were tested on a macrophage cell line and the effect was evaluated by Methyltetrazolium assay (MTT) and SEM analysis. The optical properties of curcumin were investigated as a function of illumination fluence. When compared with the control group, a statistically significant reduction in C. albicans viability was observed after PDT (P < 0.05), for both planktonic and biofilm cultures. Photodynamic effect was greatly increased with the presence of curcumin in the surrounding media and the PIT of 20 min improved PDT effectiveness against biofilms. Although PDT was phototoxic to macrophages, the therapy was more effective in inactivating the yeast cell than the defense cell. The spectral changes showed a high photobleaching rate of curcumin.
Effectiveness of Agricultural Extension Wildlife Mitigation Strategies on Human-Wildlife Conflict Among Small-Scale Maize Farmers in Laikipia County, Kenya

Agriculture is critical in the achievement of food security, employment of creation opportunities, steering economic growth, and also a source of raw materials for agricultural industries in many Sub-Saharan countries. However, farmers face various challenges which negatively affect farm productivity and production. Human-wildlife conflict is one of the most pressing challenges that smallholder maize farmers experience in some parts of Kenya. It arises from either people’s encroachment on wildlife habitats or the movement of wildlife from their natural habitat into neighboring farmland. Small-scale farmers use various agricultural extension strategies to mitigate the conflict. However, the effectiveness of the agricultural extension mitigation strategies adopted by smallholder maize farmers in Laikipia County had not been investigated and information on the same was inadequate and poorly documented. This study sought to determine the effectiveness of the agricultural extension wildlife conflict mitigation strategies adopted by smallholder maize farmers in Laikipia County. Whereas a document review guide was used to collect secondary data, semi-structured questionnaires were used to collect primary data from maize farmers and extension agents. Descriptive statistics were used to analyze primary data. It was established that crop damage was very severe, even up to 70% per cropping season although farmers used mitigation strategies such growing of unpalatable plants, live fences, hairy crops, and digging trenches. This study concluded that the Agricultural Extension Mitigation Strategies used were not effective. It was recommended concerted efforts between stakeholders in the conflict to realize the benefits of synergies so as to stem crop damage and give small-scale farmers a chance to be food secure.