Search

Bovine spongiform encephalopathy (BSE) is a neurodegenerative disease of cattle caused by abnormally folded prion proteins. Two regulatory region polymorphisms in the bovine prion gene are associated with resistance to classical BSE disease: a 23-bp region in the promoter that contains a binding site for the repressor protein RP58, and a 12-bp region in intron 1 that has a binding site for the transcription factor SP1. The presence of these binding sites enhances BSE resistance in cattle, whereas cattle that lack these regions are more susceptible to the disease. The present study examined the allele, genotype, and haplotype frequencies for the 23-bp and 12-bp polymorphisms in Holstein cattle from 9 different US states, and these frequencies were compared with data previously established for Holstein cattle from the United Kingdom, Germany, and Japan. Additionally, the coding region of the prion gene was sequenced from the US samples. Finally, archival samples from US Holstein sires born between 1953 and 1957 were analyzed. We found that the resistant allele and genotype frequencies for the US Holstein cattle were as high, or higher, relative to that observed in other countries. Furthermore, the current US frequencies were comparable to those determined in the archival samples from the 1950s. Based on the frequencies of these regulatory region polymorphisms, the US Holstein population is not at a greater risk for BSE than Holsteins worldwide. [ABSTRACT FROM AUTHOR]

The international community has spent considerable time, money, and effort attempting to establish a series of national and regional Centres of Excellence (COEs), also known as Nuclear Security Training and Support Centres (NSSCs). These Centres tend to have a wide variety of objectives, structures, and methods of delivery. Unsurprisingly, no internationally accepted standard exists on how they should operate. The IAEA has produced some excellent guidance (TECDOC 1734), but by virtue of its role cannot provide standards for benchmarking success. Against this backdrop, the World Institute for Nuclear Security (WINS) launched the WINS Academy, an initiative to provide practitioners with opportunities to earn certification in Nuclear Security Management. Underpinning the programme is certification against the ISO 9001 and ISO 29990 quality management standards, which provide an internationally recognised external benchmark of quality; demonstrate credibility, competence and professionalism; and give potential employers and others in the industry an objective measurement of participants’ knowledge. WINS recommends that NSSCs follow a similar model, in which their participants receive an evaluation leading to qualification or certification, and utilizing professional standards developed by a recognised, respected certifying body rather than developing their own ad hoc arrangements, which are ultimately unsustainable. With the end of the Nuclear Security Summit (NSS) process, sustainability is the key consideration for many nuclear security training centres; WINS has sought political and industry commitments to sustain security training programmes, and these efforts were recognised in a Joint Statement on Certified Training for Nuclear Security Management at the 2016 NSS.

The objective of this paper is to report a case of extramammary Paget disease of the vulva, to describe its diagnosis, surgical treatment, and outcome, and to discuss the general characteristics of this pathology. This is a rare neoplasm, found principally in areas in which apocrine and eccrine glands are numerous. This case report is relevant to the literature since the differential diagnosis of extramammary Paget disease is difficult to be done only with the macroscopic appearance of the lesion and even with the microscopic characteristics, requiring further studies, immunohistochemistry, as to differentiate pathologies. The present report describes the case of a 63-year-old patient at the Santa Casa de Misericórdia Hospital in Vitória, Espírito Santo, Brazil, who presented with a hardened, ulcerated, and purplish lesion with hyperchromic and hypochromic spots, measuring 4 cm in diameter, located on the lower third of right labium majus, close to the vaginal fourchette. A right hemivulvectomy was performed, leaving wide margins all around. The patient progressed satisfactorily following surgery. Although extramammary Paget disease is rare, its incidence increases as a function of the patient’s age. Patients should be followed up closely because of the risk of persistence and/or recurrence of the disease.

Abstract Background Serovars of the human pathogen Chlamydia trachomatis occupy one of three specific tissue niches. Genomic analyses indicate that the serovars have a phylogeny congruent with their pathobiology and have an average substitution rate of less than one nucleotide per kilobase. In contrast, the gene that determines serovar specificity, ompA, has a phylogenetic association that is not congruent with tissue tropism and has a degree of nucleotide variability much higher than other genomic loci. The ompA gene encodes the major surface-exposed antigenic determinant, and the observed nucleotide diversity at the ompA locus is thought to be due to recombination and host immune selection pressure. The possible contribution of a localized increase in mutation rate, however, has not been investigated. Results Nucleotide diversity and phylogenetic relationships of the five constant and four variable domains of the ompA gene, as well as several loci surrounding ompA, were examined for each serovar. The loci flanking the ompA gene demonstrated that nucleotide diversity increased monotonically as ompA is approached and that their gene trees are not congruent with either ompA or tissue tropism. The variable domains of the ompA gene had a very high level of non-synonymous change, which is expected as these regions encode the surface-exposed epitopes and are under positive selection. However, the synonymous changes are clustered in the variable regions compared to the constant domains; if hitchhiking were to account for the increase in synonymous changes, these substitutions should be more evenly distributed across the gene. Recombination also cannot entirely account for this increase as the phylogenetic relationships of the constant and variable domains are congruent with each other. Conclusions The high number of synonymous substitutions observed within the variable domains of ompA appears to be due to an increased mutation rate within this region of the genome, whereas the increase in nucleotide substitution rate and the lack of phylogenetic congruence in the regions flanking ompA are characteristic motifs of gene conversion. Together, the increased mutation rate in the ompA gene, in conjunction with gene conversion and positive selection, results in a high degree of variability that promotes host immune evasion.

Abstract Background Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect several mammalian species. At least three factors related to the host prion protein are known to modulate susceptibility or resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats, and expression level. These factors have been extensively studied in breeds of Bos taurus cattle in relation to classical bovine spongiform encephalopathy (BSE). However, little is currently known about these factors in Bos indicus purebred or B. indicus × B. taurus composite cattle. The goal of our study was to establish the frequency of markers associated with enhanced susceptibility or resistance to classical BSE in B. indicus purebred and composite cattle. Results No novel or TSE-associated PRNP-encoded amino acid polymorphisms were observed for B. indicus purebred and composite cattle, and all had the typical number of octapeptide repeats. However, differences were observed in the frequencies of the 23-bp and 12-bp insertion/deletion (indel) polymorphisms associated with two bovine PRNP transcription regulatory sites. Compared to B. taurus, B. indicus purebred and composite cattle had a significantly lower frequency of 23-bp insertion alleles and homozygous genotypes. Conversely, B. indicus purebred cattle had a significantly higher frequency of 12-bp insertion alleles and homozygous genotypes in relation to both B. taurus and composite cattle. The origin of these disparities can be attributed to a significantly different haplotype structure within each species. Conclusion The frequencies of the 23-bp and 12-bp indels were significantly different between B. indicus and B. taurus cattle. No other known or potential risk factors were detected for the B. indicus purebred and composite cattle. To date, no consensus exists regarding which bovine PRNP indel region is more influential with respect to classical BSE. Should one particular indel region and associated genotypes prove more influential with respect to the incidence of classical BSE, differences regarding overall susceptibility and resistance for B. indicus and B. taurus cattle may be elucidated.

Salmonella is estimated to cause 1.2 million cases of human foodborne illness each year in the United States, and pigs can often be asymptomatically colonized with Salmonella (>50% of farms). Recent reports state that 18.3% of Salmonella enterica serovar Typhimurium (S. Typhimurium) isolates are resistant to ≥3 antimicrobial classes, and multidrug resistant (MDR) strains are associated with an increased hospitalization rate and other complications. Chlortetracycline is commonly used in swine production to prevent/treat various diseases; therefore, chlortetracycline treatment of pigs unknowingly colonized with MDR Salmonella may have collateral effects on Salmonella (and other gut bacteria). In this study, we determined the effect of in-feed chlortetracycline (400 g/ton) on shedding and colonization of pigs challenged with an MDR S. Typhimurium DT104 strain (n = 11/group). We also assessed the impact on the fecal microbiota over the 12-day experimental period and on the ileum, cecum, and tonsil microbiota at 7 days post-inoculation (dpi). In MDR S. Typhimurium-inoculated pigs, chlortetracycline administration significantly increased fecal shedding at 2 dpi (+1.4 log10 CFU/g; P < 0.001) and enhanced tonsil colonization (+3.1 log10 CFU/g; P < 0.001). There were few major alterations detected in the gut or tonsillar microbiota of pigs treated with MDR S. Typhimurium and/or chlortetracycline. The tonsillar transcriptome was largely unaffected despite increased colonization by MDR S. Typhimurium following inoculation of the chlortetracycline-treated pigs. These results highlight that chlortetracycline administration can enhance shedding and colonization of MDR S. Typhimurium in pigs, which could increase the risk of environmental dissemination of MDR Salmonella strains. Importance Salmonella is an important cause of foodborne illness in North America, and pork products are associated with sporadic cases and outbreaks of human salmonellosis. Isolates of Salmonella may be resistant to multiple antibiotics, and infections with multidrug-resistant (MDR) Salmonella are more difficult to treat, leading to increased hospitalization rates. Swine operations commonly use antimicrobials such as chlortetracycline to prevent/treat infections, which may have collateral effects on pig microbial populations. Recently, we demonstrated that chlortetracycline induces the expression of genes associated with pathogenesis and invasion in MDR Salmonella enterica serovar Typhimurium in vitro. In our current study, we show increased tonsillar colonization and fecal shedding of a MDR S. Typhimurium DT104 strain from pigs administered chlortetracycline. Therefore, pigs unknowingly colonized with multidrug-resistant Salmonella and receiving chlortetracycline for an unrelated infection may be at a greater risk for disseminating MDR Salmonella to other pigs and to humans through environmental or pork product contamination. [ABSTRACT FROM AUTHOR]

The use of glucose sensors to triage post-discharge follow-up was investigated among hospital inpatients with type 2 diabetes. Feasibility, utility and patient satisfaction with this model of care were studied. Feasibility was 36.5%, with 90/198 (45.5%) inpatients discharged with glucose sensors but 9.0% unable to use glucose sensors effectively. Follow-up plans were altered in 76.3% of the patients able to use the sensor technology. Patient satisfaction was high and was improved on follow-up after 6 months., (© 2024 The Author(s). Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Cryptosporidium spp. are protozoan parasites that cause severe illness in vulnerable human populations. Obtaining pure Cryptosporidium DNA from clinical and environmental samples is challenging because the oocysts shed in contaminated feces are limited in quantity, difficult to purify efficiently, may derive from multiple species, and yield limited DNA (<40 fg/oocyst). Here, we develop and validate a set of 100,000 RNA baits (CryptoCap&#95;100k) based on six human-infecting Cryptosporidium spp. ( C. cuniculus , C. hominis , C. meleagridis , C. parvum , C. tyzzeri , and C. viatorum ) to enrich Cryptosporidium spp. DNA from a wide array of samples. We demonstrate that CryptoCap&#95;100k increases the percentage of reads mapping to target Cryptosporidium references in a wide variety of scenarios, increasing the depth and breadth of genome coverage, facilitating increased accuracy of detecting and analyzing species within a given sample, while simultaneously decreasing costs, thereby opening new opportunities to understand the complex biology of these important pathogens., Competing Interests: Competing Interests B.B. and M.B. are employed by Diacel Arbor Biosciences, which manufactures and sells the baits described herein.

Background: Diabetes management often requires close cooperation between primary and specialist services, but a range of challenges in Australia and elsewhere make seamless care difficult., Aims: To evaluate the effectiveness of a new locality-based integrated diabetes care service for people with Type 2 diabetes in an inner regional area., Methods: A quasi-experimental evaluation comparing baseline and follow-up clinical data collected from general practices and specialist services participating in an integrated diabetes care programme in an inner-regional area. Patients had at least one specialist service consultation. The primary outcome was glycated haemoglobin (HbA1c)., Results: Clinical data were collected for 178 (74.5%) of 239 patients (age ± standard deviation, 65 ± 11 years; 46% female; median (interquartile range) diabetes duration, 19 (11.0-24.0) years) from seven general practices over 33 months (median 18.5 months). There were reductions in HbA1c (0.7 ± 1.6% (8 ± 18 mmol/mol); P < 0.001), systolic blood pressure (5.8 ± 19.5 mmHg; P < 0.001), diastolic blood pressure (2.4 ± 14.3 mmHg; P = 0.04), total cholesterol (0.5 ± 1.3 mmoL/L; P < 0.001), low-density lipoprotein (0.4 ± 0.9 mmoL/L; P < 0.001), body mass index (0.5 ± 1.6 kg/m 2 ; P < 0.001) and weight (1.8 ± 4.7 kg; P < 0.001). The proportion without microalbuminuria increased from 48.4% to 59.3% (P = 0.03)., Conclusions: Glycaemia and cardiovascular risk factors can be reduced in patients with long-standing Type 2 diabetes by moving to a locality-based integrated primary-secondary care diabetes care service., (© 2021 Royal Australasian College of Physicians.)

Background: In the Republic of the Congo, malaria represents a major public health problem affecting all age groups. A regular surveillance of the current efficacy of first-line anti-malarial drugs is required in the face of possible emergence and spread of artemisinin-resistant Plasmodium falciparum strains in Africa. The purpose of this study was to determine the prevalence of malaria among febrile patients of all ages and assess the efficacy of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) in Congolese children., Methods: Febrile patients of all ages were initially screened for malaria by both rapid diagnostic test (RDT) and microscopy. Patients less than 12 years of age, with parasitaemia ≥ 1000 asexual parasites of P. falciparum/µL of blood, without any signs of severity, were enrolled in a therapeutic efficacy study and treated after obtaining their parents' (or legal guardian's) informed consent in two health centres in Dolisie. The patients were followed for 28 days in accordance with the 2009 World Health Organization standard protocol. If parasitaemia reappeared on or after day 7, the genetic profiles (genes expressing merozoite surface protein-1 [msp1], merozoite surface protein-2 [msp2], and glutamine-rich protein [glurp]) of pre-treatment and post-treatment isolates were compared by nested polymerase chain reaction (PCR) followed by capillary electrophoresis to make a distinction between recrudescence and re-infection. The clinical and parasitological outcome was analysed by the per-protocol method and Kaplan-Meier survival curves., Results: A total of 994 febrile patients of all ages were screened by RDT and microscopy. Of 994 patients, 323 (32.5%) presented a positive RDT, and 266 (26.8%) were microscopy-positive. Based on microscopy as the reference diagnostic method, the sensitivity and the specificity of the RDT were 98.9 and 91.8%, respectively. The Cohen's kappa coefficient was 0.86. A total of 121 children aged less than 12 years (61 in AL treatment group and 60 in ASAQ treatment group) were included in therapeutic efficacy study. Before PCR correction, the proportions of adequate clinical and parasitological response were 96.6% for AL and 86.0% for ASAQ in the per-protocol population (P < 0.05). The PCR-corrected efficacy rates were 98.2% and 94.2% for AL and ASAQ, respectively (P > 0.05). Both treatments were well tolerated., Conclusions: AL and ASAQ remain highly effective for the first-line treatment of uncomplicated P. falciparum malaria in Dolisie. Despite high efficacy of first- and second-line treatment, there is a continuing need to scale up effective malaria preventive interventions and vector control strategies in the country., Trial Registration Number: ACTRN12616001422415., (© 2022. The Author(s).)

Genomic data contribute invaluable information to the epidemiological investigation of pathogens of public health importance. However, whole-genome sequencing (WGS) of bacteria typically relies on culture, which represents a major hurdle for generating such data for a wide range of species for which culture is challenging. In this study, we assessed the use of culture-free target-enrichment sequencing as a method for generating genomic data for two bacterial species: (1) Bacillus anthracis, which causes anthrax in both people and animals and whose culture requires high-level containment facilities; and (2) Mycoplasma amphoriforme , a fastidious emerging human respiratory pathogen. We obtained high-quality genomic data for both species directly from clinical samples, with sufficient coverage (>15×) for confident variant calling over at least 80% of the baited genomes for over two thirds of the samples tested. Higher qPCR cycle threshold ( Ct ) values (indicative of lower pathogen concentrations in the samples), pooling libraries prior to capture, and lower captured library concentration were all statistically associated with lower capture efficiency. The Ct value had the highest predictive value, explaining 52 % of the variation in capture efficiency. Samples with Ct values ≤30 were over six times more likely to achieve the threshold coverage than those with a Ct > 30. We conclude that target-enrichment sequencing provides a valuable alternative to standard WGS following bacterial culture and creates opportunities for an improved understanding of the epidemiology and evolution of many clinically important pathogens for which culture is challenging.

Environmental microbial diversity is often investigated from a molecular perspective using 16S ribosomal RNA (rRNA) gene amplicons and shotgun metagenomics. While amplicon methods are fast, low-cost, and have curated reference databases, they can suffer from amplification bias and are limited in genomic scope. In contrast, shotgun metagenomic methods sample more genomic regions with fewer sequence acquisition biases, but are much more expensive (even with moderate sequencing depth) and computationally challenging. Here, we develop a set of 16S rRNA sequence capture baits that offer a potential middle ground with the advantages from both approaches for investigating microbial communities. These baits cover the diversity of all 16S rRNA sequences available in the Greengenes (v. 13.5) database, with no sequence having <78% sequence identity to at least one bait for all segments of 16S. The use of our baits provide comparable results to 16S amplicon libraries and shotgun metagenomic libraries when assigning taxonomic units from 16S sequences within the metagenomic reads. We demonstrate that 16S rRNA capture baits can be used on a range of microbial samples (i.e., mock communities and rodent fecal samples) to increase the proportion of 16S rRNA sequences (average > 400-fold) and decrease analysis time to obtain consistent community assessments. Furthermore, our study reveals that bioinformatic methods used to analyze sequencing data may have a greater influence on estimates of community composition than library preparation method used, likely due in part to the extent and curation of the reference databases considered. Thus, enriching existing aliquots of shotgun metagenomic libraries and obtaining modest numbers of reads from them offers an efficient orthogonal method for assessment of bacterial community composition., Competing Interests: The EHS DNA lab provides oligonucleotide aliquots and library preparation services at cost, including some oligonucleotides and services used in this manuscript (baddna.uga.edu). BB and AD were employed by, and thereby have financial interest in, Daicel Arbor Biosciences, who provided the in-solution capture reagents used in this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Beaudry, Wang, Kieran, Thomas, Bayona-Vásquez, Gao, Devault, Brunelle, Lu, Wang, Rhodes and Glenn.)

Background: Leptospirosis is a zoonotic, bacterial disease, posing significant health risks to humans, livestock, and companion animals around the world. Symptoms range from asymptomatic to multi-organ failure in severe cases. Complex species-specific interactions exist between animal hosts and the infecting species, serovar, and strain of pathogen. Leptospira borgpetersenii serovar Hardjo strains HB203 and JB197 have a high level of genetic homology but cause different clinical presentation in the hamster model of infection; HB203 colonizes the kidney and presents with chronic shedding while JB197 causes severe organ failure and mortality. This study examines the transcriptome of L. borgpetersenii and characterizes differential gene expression profiles of strains HB203 and JB197 cultured at temperatures during routine laboratory conditions (29°C) and encountered during host infection (37°C)., Methodology/principal Findings: L. borgpetersenii serovar Hardjo strains JB197 and HB203 were isolated from the kidneys of experimentally infected hamsters and maintained at 29°C and 37°C. RNAseq revealed distinct gene expression profiles; 440 genes were differentially expressed (DE) between JB197 and HB203 at 29°C, and 179 genes were DE between strains at 37°C. Comparison of JB197 cultured at 29°C and 37°C identified 135 DE genes while 41 genes were DE in HB203 with those same culture conditions. The consistent differential expression of ligB, which encodes the outer membrane virulence factor LigB, was validated by immunoblotting and 2D-DIGE. Differential expression of lipopolysaccharide was also observed between JB197 and HB203., Conclusions/significance: Investigation of the L. borgpetersenii JB197 and HB203 transcriptome provides unique insight into the mechanistic differences between acute and chronic disease. Characterizing the nuances of strain to strain differences and investigating the environmental sensitivity of Leptospira to temperature is critical to the development and progress of leptospirosis prevention and treatment technologies, and is an important consideration when serovars are selected and propagated for use as bacterin vaccines as well as for the identification of novel therapeutic targets., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Digestive metastases (DMs) from renal cell cancer (RCC) are rare. Over the past decade, the overall survival of metastatic RCC (mRCC) has been improved by tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors. The main objective of this study was to assess the incidence of metastases of the digestive tract in this new field of treatment. The secondary objectives were to evaluate the clinical characteristics, prognosis, treatments used for DMs, and median time between the diagnosis of RCC or mRCC and DMs. Materials and Methods: A retrospective analysis of data collected from all patients with mRCC between 2007 (the time of TKI was a standard of care) and 2019 was carried out at the Paoli-Calmettes Institute (Marseille, France). Computer research software using artificial intelligence (ConSoRe®) was used to identify patients and assess their characteristics. Results: Between January 2007 and December 2019, 11 out of 660 (1.6%) mRCC patients had metastases of the gastrointestinal tract. The median age was 62 years. Of the 11 patients, 81.8% experienced digestive bleeding or anemia. Only 2 patients were asymptomatic. The metastases were mainly duodenal (50%) and gastric (41.6%). The median time from cancer diagnosis and from metastatic disease to gastrointestinal metastasis was 4.3 years (3 months-19.2 years) and 2.25 years (0 days-10.2 years), respectively. Local treatment was performed in 38.5% of cases by endoscopy (60%), surgery (20%) and radiotherapy (40%) with success rates of 33, 100, and 50%, respectively. Etiological treatment was modified following the discovery of DM in 84.6% of the cases. The median survival was 1 year from the diagnosis of DM (13 days-9.4 years). Two patients were still alive 2.9 and 9.4 years after the diagnosis of DM. Conclusion: This is the largest monocentric retrospective analysis of DM in patients with RCC. It seems to be a rare and late event in the course of the disease. Local treatment combined with systemic treatment could improve survival. In the context of prolonged survival with the new based immunotherapy treatments in mRCC, we suggest that unexplained anemia or persistent digestive symptoms could be explored by endoscopy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Maelle, Jean-Philippe, Jochen, Geraldine, Fabrice, Christian, Mathilde, Slimane, Serge, Naji, Cecile, Stanislas, Thomas, Sami, Manuel, Marc and Gwenaelle.)

Background: The Republic of Congo adopted a new anti-malarial treatment policy in 2006, with artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) as the first- and second-line anti-malarial drugs, respectively. Only three clinical studies had been conducted before the policy change. A randomized study on these two artemisinin-based combinations was conducted, and the effect that sickle cell trait may have on treatment outcomes was evaluated in children under 10 years old followed during 12 months in Brazzaville in 2010-2011., Methods: A cohort of 330 children under 10 years of age living in a suburban area in the south of Brazzaville were passively followed for registration of malaria episodes. Uncomplicated Plasmodium falciparum episodes were randomly treated with co-formulated ASAQ (Coarsucam(®)) or AL (Coartem(®)). Patients were followed according to the 2009 World Health Organization protocol for the evaluation of anti-malarial drug efficacy. Plasmodium falciparum recrudescent isolates were compared to pre-treatment isolates by polymerase chain reaction (PCR) to distinguish between re-infection and recrudescence. PCR-uncorrected and PCR-corrected responses to treatment were determined using per protocol analysis. Haemoglobin type (AA, AS, SS) was determined by PCR., Results: Of 282 clinical malaria episodes registered during 1-year follow-up period, 262 children with uncomplicated malaria were treated with ASAQ (129 patients) or AL (133 patients). The PCR-corrected efficacy, expressed as the percentage of adequate clinical and parasitological response, was 97.0 % for ASAQ and 96.4 % for AL. Among ASAQ-treated patients, 112 (86.8 %) carried AA genotype and 17 (13.2 %) were AS carriers. The PCR-corrected efficacy was 96.4 % for AA-carriers and 100 % for AS-carriers treated with ASAQ [relative risk (RR) = 0.96; 95 % confidence interval, 0.93-1.00, p = 0.5]. Among 133 AL-treated children, 109 (82 %) carried AA, and 24 (18 %) AS genotypes. The PCR-corrected efficacy was 96.7 % among AA-carriers and 95.2 % among AS-carriers [RR = 1.01 (0.92-1.12), p = 0.6]. Nausea, jaundice, headache, dizziness, vomiting, pruritus, abdominal pain, and diarrhoea were registered as adverse events in both groups. ASAQ was associated with significantly more frequent adverse events (P < 0.05)., Conclusion: This first randomized study in Brazzaville confirmed the excellent efficacy of these co-formulated anti-malarial drugs in children. Sickle cell genotype did not influence the treatment efficacy of artemisinin-based combination therapy.

The objective of this paper is to report a case of extramammary Paget disease of the vulva, to describe its diagnosis, surgical treatment, and outcome, and to discuss the general characteristics of this pathology. This is a rare neoplasm, found principally in areas in which apocrine and eccrine glands are numerous. This case report is relevant to the literature since the differential diagnosis of extramammary Paget disease is difficult to be done only with the macroscopic appearance of the lesion and even with the microscopic characteristics, requiring further studies, immunohistochemistry, as to differentiate pathologies. The present report describes the case of a 63-year-old patient at the Santa Casa de Misericórdia Hospital in Vitória, Espírito Santo, Brazil, who presented with a hardened, ulcerated, and purplish lesion with hyperchromic and hypochromic spots, measuring 4 cm in diameter, located on the lower third of right labium majus, close to the vaginal fourchette. A right hemivulvectomy was performed, leaving wide margins all around. The patient progressed satisfactorily following surgery. Although extramammary Paget disease is rare, its incidence increases as a function of the patient's age. Patients should be followed up closely because of the risk of persistence and/or recurrence of the disease.

Background: Incidence of acute rheumatic fever (ARF) and prevalence of rheumatic heart disease (RHD) in the Pacific region, including New Caledonia, are amongst the highest in the world. The main priority of long-term management of ARF or RHD is to ensure secondary prophylaxis is adhered to. The objectives of this study were to evaluate rates of adherence in people receiving antibiotic prophylaxis by intramuscular injections of penicillin in Lifou and to determine the factors associated with a poor adherence in this population., Methods: We conducted a retrospective cohort study and we included 70 patients receiving injections of antibiotic prophylaxis to prevent ARF recurrence on the island of Lifou. Patients were classified as "good-adherent" when the rate of adherence was ≥80% of the expected injections and as "poor-adherent" when it was <80%. Statistical analysis to identify factors associated with adherence was performed using a multivariate logistic regression model., Results: Our study showed that 46% of patients from Lifou receiving antibiotic prophylaxis for ARF or RHD had a rate of adherence <80% and were therefore at high risk of recurrence of ARF. Three independent factors were protective against poor adherence: a household with more than five people (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.75), a previous medical history of symptomatic ARF (odds ratio, 0.20; 95% CI, 0.04 to 0.98) and an adequate healthcare coverage (odds ratio, 0.21; 95% CI 0.06 to 0.72)., Conclusions: To improve adherence to secondary prophylaxis in Lifou, we therefore propose the following recommendations arising from the results of this study: i) identifying patients receiving antibiotic prophylaxis without medical history of ARF to strengthen their therapeutic education and ii) improving the medical coverage in patients with ARF or RHD. We also recommend that the nurse designated for the ARF prevention program in Lifou coordinate an active recall system based on an updated local register. But the key point to improve adherence among Melanesian patients is probably to give appropriate information regarding the disease and the treatment, taking into account the Melanesian perceptions of the disease.

To determine the transmissibility of chronic wasting disease (CWD) to fallow deer (Dama dama) and to provide information about clinical course, lesions and suitability of currently used diagnostic procedures for detection of CWD in this species, 13 fawns were inoculated intracerebrally with CWD brain suspension from elk (n=6) or white-tailed deer (n=7). Three other fawns were kept as uninfected controls. Three CWD-inoculated deer were killed 7.6 months post-inoculation (mpi). None had abnormal prion protein (PrPd) in their tissues. One sick deer died at 24 mpi and one deer without clinical signs was killed at 26 mpi. Both animals had a small focal accumulation of PrPd in the midbrain. Between 29 and 37 mpi, three other deer became sick and were killed. All had shown gradual decrease in appetite and some loss of body weight. Microscopical lesions of spongiform encephalopathy were not observed, but PrPd was detected in tissues of the central nervous system (CNS) by immunohistochemistry, western blot and by two commercially available rapid diagnostic tests. This study demonstrates that intracerebrally inoculated fallow deer amplified CWD PrPd from white-tailed deer and elk in the absence of lesions of spongiform encephalopathy. Four years after CWD inoculation, the remaining five inoculated and two control deer are alive and apparently healthy.

The binding of tritiated S21403, a novel insulin-releasing agent of the meglitinide family, to multilamellar liposomes formed of egg yolk phosphatidylcholine was compared to that of tritiated glibenclamide. The binding of [3H]S21403 reached equilibrium within 5 min of incubation at 37 degrees C, was virtually proportional to its concentration (2.8 to 56.0 nM) and failed to be inhibited by a much higher concentration (0.1 mM) of unlabelled S21403. It was much lower than that of [3H]glibenclamide tested at a comparable concentration (14.8 nM) and only slightly decreased by 0.1 mM unlabelled glibenclamide. The latter sulfonylurea inhibited more severely the binding of [3H]glibenclamide, which was unaffected, however, by 0.1 mM unlabelled S21403. These findings suggest a much higher affinity of glibenclamide than S21403 for the artificial phospholipid bilayer, this coinciding with a higher biological potency, as insulin secretagogue, of the hypoglycemic sulfonylurea as compared to meglitinide analog. It is proposed, therefore, that the insertion of these antidiabetic agents in the phospholipid domain of the B-cell membrane may condition their access to the ATP-responsive K+ channels known to represent the main target for their insulinotropic action.