Peroral endoscopic myotomy: a two-center retrospective study of practice and adverse events.

Background and study aims: Peroral endoscopic myotomy (POEM) is the preferred technique for the treatment of esophageal motility disorders and is less invasive than surgery. This study was performed to compare two university centers in the practice of POEM, in terms of efficacy and adverse events, for the treatment of esophageal motility disorder. Patients and methods: Retrospective comparative study of patients undergoing a POEM between September 2020 and December 2022 from the University Hospital of Liège (Belgium) and Besançon (France). The clinical success was defined by an Eckardt score ≤ 3 after the procedure. Results: Fifty-five patients were included. In both centers, 87,3% of the patients had achalasia (mostly type II), and 12,7% had another esophageal motility disorder. The use of antibiotic prophylaxis was systematic in Liège center but not in Besançon center (100% and 9.1% respectively). The mean value of the post-operative Eckardt score was 1.55± 2.48 in both center with 93.2% of patients with a score ≤ 3 (92% in Besançon and 94.74% in Liège). The rate of adverse event was generally low. There were two minor adverse events more frequent in Liège, clinical capnomediastinum and pain at day one, but they were managed with conservative treatment. Only 7.3% of the total patients had an infectious phenomenon that did not correlate with the use of antibiotic prophylaxis. Conclusion: The post-operative Eckardt score and the adverse event rate were comparable between the university centers. This study confirmed that POEM is a safe and effective technique. It also showed that using an antibiotic prophylaxis does not influence the development of infectious adverse events.

Implementation of an outbreak response vaccination campaign with typhoid conjugate vaccine - Harare, Zimbabwe, 2019.

Introduction: Typhoid fever is a public-health problem in Harare, the capital city of Zimbabwe, with seasonal outbreaks occurring annually since 2010. In 2019, the Ministry of Health and Child Care (MOHCC) organized the first typhoid conjugate vaccination campaign in Africa in response to a recurring typhoid outbreak in a large urban setting. Method: As part of a larger public health response to a typhoid fever outbreak in Harare, Gavi approved in September 2018 a MOHCC request for 340,000 doses of recently prequalified Typbar-TCV to implement a mass vaccination campaign. To select areas for the campaign, typhoid fever surveillance data from January 2016 until June 2018 was reviewed. We collected and analyzed information from the MOHCC and its partners to describe the vaccination campaign planning, implementation, feasibility, administrative coverage and financial costs. Results: The campaign was conducted in nine high-density suburbs of Harare over eight days in February-March 2019 and targeted all children aged 6 months-15 years; however, the target age range was extended up to 45 years in one suburb due to the past high attack rate among adults. A total of 318,698 people were vaccinated, resulting in overall administrative coverage of 85.4 percent. More than 750 community volunteers and personnel from the MOHCC and the Ministry of Education were trained and involved in social mobilization and vaccination activities. The MOHCC used a combination of vaccination strategies (i.e., fixed and mobile immunization sites, a creche and school-based strategy, and door-to-door activities). Financial costs were estimated at US$ 2.39 per dose, including the vaccine and vaccination supplies (US$ 0.79 operational costs per dose excluding vaccine and vaccination supplies). Conclusion: A mass targeted campaign in densely populated urban areas in Harare, using the recently prequalified typhoid conjugate vaccine, was feasible and achieved a high overall coverage in a short period of time.

Alternative observational designs to estimate the effectiveness of one dose of oral cholera vaccine in Lusaka, Zambia.

We conducted a matched case-control (MCC), test-negative case-control (TNCC) and case-cohort study in 2016 in Lusaka, Zambia, following a mass vaccination campaign. Confirmed cholera cases served as cases in all three study designs. In the TNCC, control-subjects were cases with negative cholera culture and polymerase chain reaction results. Matched controls by age and sex were selected among neighbours of the confirmed cases in the MCC study. For the case-cohort study, we recruited a cohort of randomly selected individuals living in areas considered at-risk of cholera. We recruited 211 suspected cases (66 confirmed cholera cases and 145 non-cholera diarrhoea cases), 1055 matched controls and a cohort of 921. Adjusted vaccine effectiveness of one dose of oral cholera vaccine (OCV) was 88.9% (95% confidence interval (CI) 42.7-97.8) in the MCC study, 80.2% (95% CI: 16.9-95.3) in the TNCC design and 89.4% (95% CI: 64.6-96.9) in the case-cohort study. Three study designs confirmed the short-term effectiveness of single dose OCV. Major healthcare-seeking behaviour bias did not appear to affect our estimates. Most of the protection among vaccinated individuals could be attributed to the direct effect of the vaccine.

[Osteoarticular tuberculosis nosology and diagnostic pitfalls]. / Tuberculose ostéoarticulaire : nosologie et pièges diagnostiques.

Osteoarticular or skeletal tuberculosis is a clinical manifestation of extrapulmonary tuberculosis, occurring during the lympho-hematogenous spread of Mycobacterium tuberculosis from a pulmonary primary infection or reactivation of latent infection, years or even decades after the initial infection. Bone and joint tuberculosis is a rare disease with non-specific symptoms and radiological characteristics, often delaying diagnosis for more than a year after clinical onset. First-line hospital departments should develop a clinical suspicion when confronted with a subacute inflammatory bone or joint pathology in patients with underlying comorbidities, especially when coming from tuberculosis-endemic countries. We report a clinical case characterized by lumbar and pelvic abscesses, before addressing in detail the different types of skeletal involvement related to tuberculosis, through a review of the literature.

La tuberculose ostéoarticulaire ou osseuse est une manifestation clinique de la tuberculose extra-pulmonaire, apparaissant lors de la dissémination lympho-hématogène de Mycobacterium tuberculosis à la suite d'une infection pulmonaire primaire ou la réactivation d'une infection latente, des années, voire des décennies après une primo-infection. Il s'agit d'une maladie rare dont les symptômes ainsi que les signes radiologiques sont non spécifiques, ce qui retarde souvent le diagnostic de plus d'un an après les premiers signes cliniques. Les services hospitaliers de première ligne doivent suspecter le diagnostic en cas de pathologie inflammatoire subaiguë des os ou des articulations chez des patients avec comorbidités, surtout s'ils sont originaires de régions endémiques pour la tuberculose. Nous rapporterons un cas clinique caractérisé par des abcès lombaires et pelviens avant d'aborder en détail les différents types d'atteintes squelettiques de la tuberculose au travers d'une revue de la littérature.

Ebola outbreak in Conakry, Guinea: epidemiological, clinical, and outcome features.

OBJECTIVES: The authors studied the epidemiological, clinical, and outcome features of the Ebola virus disease in patients hospitalized at the Ebola treatment center (ETC) in Conakry to identify clinical factors associated with death. MATERIALS AND METHODS: A prospective study was conducted from March 25 to August 20, 2014. The diagnosis of Ebola virus infection was made on real-time PCR. RESULTS: Ninety patients, with a positive test result, were hospitalized. Their mean age was 34.12±14.29 years and 63% were male patients. Most worked in the informal sector (38%) and in the medical and paramedical staff (physicians 12%, nurses 6%, and laboratory technicians 1%). Most patients lived in the Conakry suburbs (74%) and in Boffa (11%). The main clinical signs were physical asthenia (80%) and fever (72%). Hemorrhagic signs were observed in 26% of patients. The comparison of clinical manifestations showed that hiccups (P=0.04), respiratory distress (P=0.04), and hemorrhagic symptoms (P=0.01) were more frequent among patients who died. Malaria (72%) and diabetes (2%) were the most frequent co-morbidities. The crude case fatality rate was 44% [95% confidence interval (33-54%)]. The average hospital stay was 7.96±5.81 days. CONCLUSION: The first Ebola outbreak in Conakry was characterized by the young age of patients, discrete hemorrhagic signs related to lethality. Its control relies on a strict use of preventive measures.

Depth of remission in Crohn's disease patients seen in a referral centre : associated factors and impact on disease outcome.

INTRODUCTION: Our goals were to assess the prevalence of biological and tissue remission in routine practice in Crohn's disease, and to evaluate the correlation between biological or tissue remission and clinical or demographic characteristics as well as their impact on disease outcome. METHODS: We performed a retrospective monocenter study. Biological remission was defined by a CRP < 5 mg/I. Tissue remission was defined by the absence of ulcer at endoscopy and/or absence of signs of acute inflammation at MRI. Association with demographic, clinical and laboratory markers was studied by logistic regression models and rates of relapses, hospitalizations and surgeries were compared using the logrank test. RESULTS: Among the 263 patients included, 147 were in clinical remission; 102/147 (69%) were in biological remission. Fifty-six patients also had morphological evaluation: 37 (66%) were in tissue remission. Biological remission was associated with older age, higher hemoglobin and lower BMI. Tissue remission was associated with older age, lower platelets count, absence of previous surgery, and the use of immunosuppressant. Time-to-relapse was significantly longer in patients with biological remission and in patients with tissue remission as compared to patients without biological or tissue remission. CONCLUSIONS: Among the patients in clinical remission seen as outpatients, two thirds were either in biological and/or tissue remission. Biological and/or tissue remission was associated with a better outcome than clinical remission alone.

B. anthracis in a wool-processing factory: seroprevalence and occupational risk.

In a Belgian wool-processing factory, living anthrax spores were found in raw goat hair and air dust, but confirmed anthrax cases had never been reported. Anthrax vaccines are not licensed nor recommended in Belgium. We conducted a B. anthracis seroprevalence study to investigate risk factors associated with positive serology and advise on protective measures. Overall 12·1% (8/66) employees were seropositive; 30% of persons processing raw goat hair and 20% of persons sorting raw goat hair were seropositive compared to 3% in less exposed jobs [adjusted prevalence ratio (aPR) 44·4, P=0·001; aPR 14·5, P=0·016, respectively). The number of masks used per day was protective (aPR 0·3, P=0·015). Results suggest a dose-response association for those processing raw goat hair. Host-related factors probably played a role as antibody response varied from person to person within an exposure group. Workers exposed to raw goat hair should be offered higher protection against anthrax and have access to anthrax vaccines.

Tinea capitis in two black african adults with HIV infection.

Tinea capitis is rare in adults, although a few cases have been described in HIV-infected patients. We present two cases in black African adults who were HIV positive. In one, the condition led to the diagnosis of HIV infection. It is possible that the rarity of tinea capitis in HIV-positive adults could be related to increased colonization of their scalp by Pityrosporum (Malassezia) spp. In patients well controlled with an antiviral therapy, the treatment of tinea capitis seems no more difficult than in non-immunosuppressed patients. There is possibly a relation between clinical presentation and degree of immunodeficiency.

Structure and dynamics of ferrocytochrome c553 from Desulfovibrio vulgaris studied by NMR spectroscopy and restrained molecular dynamics.

The solution structure of Desulfovibrio vulgaris Hildenborough (DvH) ferrocytochrome c553 has been determined by nuclear magnetic resonance spectroscopy and combined simulated annealing/high temperature restrained molecular dynamics calculations. This three-stage protocol consists of an initial determination of overall fold from randomised co-ordinates, followed by a 20 picosecond exploratory stage, during which the non-bonded terms are simplified to facilitate as broad a sampling of conformational space as possible, and a 26 picosecond refinement stage, using the full AMBER force field. This latter stage systematically improved the energetic and convergence characteristics of the ensemble, while still satisfying the experimental restraints. Forty structures have been obtained from a total of 875 distance constraints for this protein of 79 amino acid residues. The root-mean-square deviation over all residues with respect to the mean is 0.70(+/- 0.12)A for the backbone (N, C alpha and C') atoms. Two conformations of the turn motif at the solvent/heme cleft interface have been identified, both fulfilling the experimental data and having equally viable energetic characteristics. The stability of the ensemble and the dynamic characteristics have been further investigated by subjecting ten of the structures to constraint-free molecular dynamics calculations (130 picoseconds) in vacuo. The structures were found to be stable to within 1.5 A of the initial backbone conformation. Comparison with the dynamic behaviour of the restrained molecular dynamics calculations has been used to identify regions of inherent flexibility in the molecule.

Radiation-induced cognitive dysfunction: an experimental model in the old rat.

PURPOSE: To develop a model of radiation-induced behavioral dysfunction. METHODS AND MATERIALS: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. RESULTS: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p < or = 0.001) and two-way avoidance (18% vs. 40%, p < or = 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p < or = 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. CONCLUSION: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes.

Proteinase inhibitor homologues as potassium channel blockers.

We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae snake Dendroaspis polylepis polylepis (black mamba), calculated from an experimentally-derived set of 719 geometric restraints. The backbone of the toxin superimposes on bovine pancreatic trypsin inhibitor (BPTI) with a root-mean-square deviation of < 1.7 A. The surface electrostatic potential calculated for dendrotoxin I and BPTI, reveal an important difference which might account for the differences in function of the two proteins. These proteins may provide examples of adaptation for specific and diverse biological functions while at the same time maintaining the overall three-dimensional structure of a common ancestor.

Postischemic breakdown in hippocampal protein synthesis and mnesic deficits in rats: pharmacological improvement by curative naftidrofuryl treatment.

This work was designed to investigate the effects of brain ischemia on mnesic retention in the model of unilateral microsphere embolization in rats. Using various radioactive tracers as well as a learning/memory test, we could correlate following parameters: regional blood flow, protein synthesis and memory retention. All were severely impaired by the hemispheric multi-infarction. A curative treatment with naftidrofuryl (15 mg/kg i.p.) for 3 consecutive days strongly improved the mnesic capacities of the animals, and this effect was corroborated by a marked protective drug action on protein synthesis in the hippocampus. Indeed, studies on valine incorporation into proteins revealed that, despite having no quantitative effect on regional blood flow, naftidrofuryl allowed an almost normal functioning of protein synthesis. As naftidrofuryl had also no direct effect on protein synthesis in the intact contralateral hemisphere, this effect was consequently attributed to the metabolic and/or antiserotoninergic effects of the drug.

DNA flexibility as a function of allomorphic conformation and of base sequence.

Systematic theoretical modeling of symmetric DNA oligomers, carried out earlier for the B conformation, is now extended to A-DNA. In contrast to the previous results, it is found that A-DNA shows no multiplicity of low-energy substate conformations. The possibilities of the Jumna algorithm are subsequently applied to studying deformations of the oligomers. Controlled winding and stretching deformations are used to study how the two allomorphs and different base sequences absorb such external stress. The results help explain the internal mechanics of the DNA double helix and the extent to which fine structure influences this behavior. The results point to some differences between the A and B double helices, but also to many similarities. Sequence effects on flexibility are relatively limited compared to their impact on optimal energy conformations. It is also shown that the conformational substates detected for B-DNA oligomers are preserved under deformation, but have little influence on its energetics.

Conformational sub-states in B-DNA.

Theoretical studies of the sequence-dependent conformation of B-DNA have been carried out using Jumna, a helicoidal co-ordinate minimization algorithm. The results obtained for a series of six oligomers with repetitive sequences show that, with the exception of the homopolymers (dA)n.(dT)n and (dG)n.(dC)n, all sequences can adopt a variety of conformations characterized by considerable changes in helicoidal parameters and also in sugar puckers which adopt C(2')-endo (falling into 2 classes) or, in the case of pyrimidine nucleotides, O(1')-endo forms. These studies lead to an improved understanding of the role of base sequence on DNA conformation and point to a number of interesting correlations between the various structural parameters describing the double helix.

Calicheamicin gamma 1I and DNA: molecular recognition process responsible for site-specificity.

Calicheamicin gamma 1I is a recently discovered diyne-ene-containing antitumor antibiotic that cleaves DNA in a double-stranded fashion, a rarity among drugs, at specific sequences. It is proposed that the cutting specificity is due to a combination of the complementarity of the diyne-ene portion of the aglycone with DNA secondary structures and stabilization by association of the thiobenzoate-carbohydrate tail with the minor groove.

Memory complaints in the elderly: a study of 367 community-dwelling individuals from 50 to 80 years old.

State of memory was evaluated by a Memory Clinic in 367 community-dwelling patients aged from 50 to 80. They performed an exhaustive subjective evaluation including: severity of memory complaint, social status, activity scale, subjective Memory score, Zung's anxiety and depression scales and Well Being Questionnaire. Objective memory performance was evaluated by a complete memory scanning leading to a Global Objective Memory Score. No relationship was found between severity of memory complaints and age, sex, educational level, marital status, living alone or in family, and memory tests performance. More severe complaints were reported in people with poor social network, negative stereotypes on aging, and poor affective status. A strong correlation was found between severity of memory complaints and scores in self-reporting depression questionnaire, even in people with low depression scores.