[The Causes of Harm: Ethnography of Representations of the Emergence during the 9th Ebola Outbreak in DRC (Equateur Province, 8 May-24 July 2018)]. / Les causes du mal : ethnographie des représentations de l'émergence de la 9e épidémie d'Ebola en RDC (province de l'Équateur, 8 mai-24 juillet 2018).

The article focuses on describing the different causal models of misfortune and their social constructions in the context of the Ebola virus disease which emerged in Equateur Province, Democratic Republic of Congo, in May 2018. Based on a corpus of qualitative data collected during three weeks of fieldwork, this article details the explanatory models relating to the chains of contamination and their hybridization between biomedical models and sorcery and/or political logic. By also addressing the impacts of discourse on the animal origin of the virus, this article contributes to an analysis of the gap between the different understandings and responses to the epidemic phenomenon and the scale of the response.

Cet article s'attache à décrire les différents modèles de causalité du malheur et leurs constructions sociales suite à l'émergence de la neuvième épidémie de la maladie à virus Ebola dans la province de l'Équateur, en République démocratique du Congo en mai 2018. Fondé sur un corpus de données qualitatives collecté lors de trois semaines de terrain, l'article détaille les modèles explicatifs ayant trait aux chaînes de contaminations et leur hybridation entre modèle biomédical et logique mystique et/ou politique. En traitant également de la réception du discours scientifique sur l'origine animale du virus, cet article contribue à une analyse du fossé existant entre les différentes compréhensions et réactions locales et biomédicales face au phénomène épidémique et à l'ampleur de la riposte.

Are HMGB1 protein expression and secretion markers of upper airways inflammatory diseases?

Taking into account the mechanisms at the origin of the airways inflammatory pathologies, our attention has been recently addressed to the study of HMGB1, a protein belonging to the group of alarmins. Alarmins are those molecules which in homeostatic conditions carry out specific metabolic and/or structural functions; furthermore, after a direct trauma or an infection, these molecules are released in the extracellular milieu becoming there activators of the innate immunity and powerful inflammatory factors. In a previous research we found in patients affected with chronic rhinosinusitis with/without nasal polyposis (CRSwNP) an increased expression of this protein in the nucleus of nasal mucosa epithelial cells. HMGB1 was overexpressed also as focal subepithelial infiltration and in the inflammatory cells of patients in comparison with controls. These results suggested a possible pathogenetic role of HMGB1 in CRSwNP. The aim of the present study was to investigate if the expression and localization (nuclear, cytoplasmic and extracellular) of the HMGB1 protein-cytokine is somehow related to the severity and complexity of the histological and clinical picture. We noticed values which have around statistical significance between nuclear HMGB1 and eosinophils infiltrate (p=0.0607) and between nuclear HMGB1 and inflammatory infiltrate (P=0.0524). Even more significant was the correlation between extra-cellular HMGB1 expression and the presence of allergic-hyper reactive conditions such as asthma, allergic rhinitis, NSADs intolerance, antibiotic allergy. HMGB1 was significantly more expressed in the nucleus (p=0.0499) and in the intercellular space (p=0.0380) in allergic patients than in non-allergic subjects and as extra-cellular infiltrate in patients with NSADs intolerance (p=0.0022). These results confirm the role of HMGB1 in the pathogenesis of chronic rhinosinusitis with/without nasal polyposis; besides the higher extra-cellular expression in patients with a more severe clinical and inflammatory picture and the presence of associated co-morbidities suggests to seek for new compounds: these compounds, decreasing the extra-cellular release of this alarmin through a scavenger mechanism, could keep under control the inflammatory process without interfering with the nuclear transcriptional messengers.

The health of adult women in Accra, Ghana: self-reporting and objective assessments 2008-2009.

OBJECTIVES: The study provides a full description of the state of women's health in Accra, Ghana using self-reported as well as objective health measures. Using data from the Women's Health Survey of Accra, Wave 2 (WHSA-2), the authors a) examine the consistency of the objective measures of health status (anthropometry and blood pressures) with self-report measures, including the Short Form 36 indices for 8 separate domains of health; and b) describe the main socio-economic differentials in morbidity. METHODS: Cross-sectional household survey with field measurements. 2814 women aged 18 and over were interviewed and measured in their homes in late 2008 and early 2009. The physical measurements included height, weight, waist and hip measurement and 3 or more measures of resting blood pressure. RESULTS: Using the 8 domains of self-reported health captured by the Short Form 36 instrument, we find that physical health worsens more sharply with age than mental health. Social class differentials are narrow in the younger cohorts but widen amongst the elderly. The physical measurements reveal unhealthy levels of obesity and hypertension, worsening steadily with rising age. Age and the wealth of the household influence women's health more than their individual characteristics such as education. CONCLUSIONS: Younger women appear to be in good health with steady declines in physical and mental health with age. The major threat to women's health appears to be the rising levels of obesity and hypertension with mean BMIs for all women over age 45 in excess of 30, producing elevated blood pressures and associated high risks of heart attacks and stroke rising sharply amongst the elderly.

Clinic visits and cervical cancer screening in accra.

OBJECTIVE: To determine the factors that increase the chances of a woman in Accra having a Pap smear and whether women who have recently visited clinics have higher chances of having had Pap smears. DESIGN: A cross-sectional study METHODS: A representative sample of women in Accra, Ghana was interviewed and the clinical and demographic factors influencing cervical cancer screening was assessed. RESULTS: Out of 1193 women with complete data, only 25 (2.1%) had ever had a Pap smear performed though 171 (14.3%) had their last outpatient clinic visit for either a gynaecological consultation or a regular check up. Simple logistic regression showed that a high educational level, high socioeconomic status and a history over the past month of postmenopausal or intermenstrual bleeding significantly increased the odds of ever having a pap smear. Neither monthly income nor last clinic visit for a gynaecological consultation or regular check up increased the odds of having a pap smear. Multiple logistic regression showed that a high educational level and experiencing postmenopausal or intermenstrual bleeding were the most important determinants of ever having a Pap smear. CONCLUSION: While we wait for a national program for cervical cancer screening, there is a need for clinicians to put more individual effort into ensuring that asymptomatic women are screened for cervical cancer.

Health of urban Ghanaian women as identified by the Women's Health Study of Accra.

OBJECTIVE: The purpose of the Women's Health Study of Accra was to provide an assessment of the prevalence of communicable and non-communicable illnesses. METHOD: This was a prospective, community-based study that included an interview for medical illnesses, a comprehensive physical examination, and laboratory testing. A total of 1328 women were examined at Korle Bu Teaching Hospital, University of Ghana. RESULTS: Prevalent conditions included poor vision (66.8%), malaria (48.7%), pain (42.8%), poor dentition (41.6%), hypertension (40.2%), obesity (34.7%), arthritis (27.1%), chronic back pain (19.4%), abnormal rectal (16.0%) and pelvic examinations (12.7%), HIV in women age 24-29 (8.3%), and hypercholesterolemia (22.7%). Increasing age, lack of formal education, and low-income adversely affected health conditions. CONCLUSION: The high prevalence of preventable illnesses in this expanding urban population indicates that the health care services are obligated to develop and provide screening, preventive strategies and treatment for both general health and gynecologic health conditions.

Prevalence of obesity in women of Accra: Ghana

The Women/'s Health Study of Accra, Ghana measured the burden of obesity and obesitylinked illnesses in urban women. This is a Cross-sectional community based study. 1328 adult women, age 18 years and older, were selected as a representative sampling of the women of Accra. A comprehensive medical history, physical examination and laboratory tests were performed. Overweight and obesity status was determined by calculating the body mass index (BMI) (kg/m2). BMI measurements are available for 1237 non-pregnant women. A total of 430 women (34.8%) were obese; 340 (27.4%) were overweight; 369 (29.8%) were normal weight; and 98 (8.0%) were underweight. Risk factors for obesity include age 50 to 70 years, OR 2.12 [1.72 -2.62], p<0.001; total pregnancies > 5 (p<0.001); mean age of last delivery > 34 years (p<0.001); ownership of a television OR 1.57 [1.20-2.07], p=0.001; telephone OR 1.55 [1.22-1.98], p=0.001; or a refrigerator OR 1.55 [1.20-2.00], p=0.001. There was no significant association with socioeconomic status. Significant medical conditions associated with obesity include hypertension OR 2.97 CI [2.17-4.05], p<0.001; elevated fasting blood glucose OR 1.94 [CI 1.04 ­ 3.62], p=0.037. This study identifies an unexpected high prevalence of obesity and obesity-linked illnesses in this population. Public and professional awareness of the prevalence of obesity and the associated health risks are critical for programs designed to improve women/'s health

Secular trends in menarcheal age among Ghanaian women in Accra.

The Women's Health Study of Accra is a population-based cross-sectional survey that was conducted between March and September 2003 to assess the burden of disease in women in Accra. In addition to data relating to general health and living conditions, data on age at first menstruation was collected during the survey. A retrospective cohort analysis of the reported age at menarche was conducted using data from 2,644 women aged between 18 and 100 years. The median age of first menstruation of the entire cohort was 15.5 years and the median age of first menstruation among those aged <20 was 14.5 years. There was a statistically significant difference in median age at menstruation among the different age and socioeconomic groups. Multiple linear regression showed a significant decline of 0.2 years per decade in the mean age at menarche among Ghanaian women.

American ginseng transcriptionally activates p21 mRNA in breast cancer cell lines.

American ginseng (AG) has been demonstrated to inhibit breast cancer cell growth in vitro. p21 protein, a universal cell cycle inhibitor, binds cyclin-CDK complexes, an important mechanism in cell cycle regulation. The purpose of this investigation was to determine if AG induces p21 gene expression in hormone sensitive (MCF-7) and insensitive (MDA-MB-231) breast cancer cell lines. Cells grown in steroid stripped medium (SSM) were treated with AG, 17-beta-estradiol (E2), genistein or cycloheximide (CHX). Northern blot analyses were performed using human p21Cip1 and 36B4 cDNA probes. Cell lines were transiently transfected with select mouse p21 CAT reporter constructs, including those lacking a p53 binding site. Cell cycle analyses was performed by FACScan. The results revealed that AG induced p21 mRNA expression in MCF-7 and MDA-MB-231 cells (p=0.0004; p < or =0.0001, respectively). Neither E2 nor genistein alter p21 mRNA expression. CHX, a protein synthesis inhibitor, did not block p21 mRNA expression induced by AG, indicating that p21 is induced as an immediate early gene. AG activated p21 reporter constructs in transfected cells, independent of p53 binding sites. The cell cycle proliferative phase was significantly decreased by AG and increased by E2 (p < or =0.0001). AG may inhibit breast cancer cell growth by transcriptional activation of the p21 gene, independent of p53.

Virus maturation involving large subunit rotations and local refolding.

Large-scale conformational changes transform viral precursors into infectious virions. The structure of bacteriophage HK97 capsid, Head-II, was recently solved by crystallography, revealing a catenated cross-linked topology. We have visualized its precursor, Prohead-II, by cryoelectron microscopy and modeled the conformational change by appropriately adapting Head-II. Rigid-body rotations ( approximately 40 degrees) cause switching to an entirely different set of interactions; in addition, two motifs undergo refolding. These changes stabilize the capsid by increasing the surface area buried at interfaces and bringing the cross-link-forming residues, initially approximately 40 angstroms apart, close together. The inner surface of Prohead-II is negatively charged, suggesting that the transition is triggered electrostatically by DNA packaging.

Elevation localization and head-related transfer function analysis at low frequencies.

Monaural spectral features due to pinna diffraction are the primary cues for elevation. Because these features appear above 3 kHz where the wavelength becomes comparable to pinna size, it is generally believed that accurate elevation estimation requires wideband sources. However, psychoacoustic tests show that subjects can estimate elevation for low-frequency sources. In the experiments reported, random noise bursts low-pass filtered to 3 kHz were processed with individualized head-related transfer functions (HRTFs), and six subjects were asked to report the elevation angle around four cones of confusion. The accuracy in estimating elevation was degraded when compared to a baseline test with wideband stimuli. The reduction in performance was a function of azimuth and was highest in the median plane. However, when the source was located away from the median plane, subjects were able to estimate elevation, often with surprisingly good accuracy. Analysis of the HRTFs reveals the existence of elevation-dependent features at low frequencies. The physical origin of the low-frequency features is attributed primarily to head diffraction and torso reflections. It is shown that simple geometrical approximations and models of the head and torso explain these low-frequency features and the corresponding elevations cues.

Genome organization and characterization of mycobacteriophage Bxb1.

Mycobacteriophage Bxb1 is a temperate phage of Mycobacterium smegmatis. The morphology of Bxb1 particles is similar to that of mycobacteriophages L5 and D29, although Bxb1 differs from these phages in other respects. First, it is heteroimmune with L5 and efficiently forms plaques on an L5 lysogen. Secondly, it has a different host range and fails to infect slow-growing mycobacteria, using a receptor system that is apparently different from that of L5 and D29. Thirdly, it is the first mycobacteriophage to be described that forms a large prominent halo around plaques on a lawn of M. smegmatis. The sequence of the Bxb1 genome shows that it possesses a similar overall organization to the genomes of L5 and D29 and shares weak but detectable DNA sequence similarity to these phages within the structural genes. However, Bxb1 uses a different system of integration and excision, a repressor with different specificity to that of L5 and encodes a large number of novel gene products including several with enzymatic functions that could degrade or modify the mycobacterial cell wall.

Topologically linked protein rings in the bacteriophage HK97 capsid.

The crystal structure of the double-stranded DNA bacteriophage HK97 mature empty capsid was determined at 3.6 angstrom resolution. The 660 angstrom diameter icosahedral particle contains 420 subunits with a new fold. The final capsid maturation step is an autocatalytic reaction that creates 420 isopeptide bonds between proteins. Each subunit is joined to two of its neighbors by ligation of the side-chain lysine 169 to asparagine 356. This generates 12 pentameric and 60 hexameric rings of covalently joined subunits that loop through each other, creating protein chainmail: topologically linked protein catenanes arranged with icosahedral symmetry. Catenanes have not been previously observed in proteins and provide a stabilization mechanism for the very thin HK97 capsid.

Genomic sequences of bacteriophages HK97 and HK022: pervasive genetic mosaicism in the lambdoid bacteriophages.

We report the complete genome DNA sequences of HK97 (39,732 bp) and HK022 (40,751 bp), double-stranded DNA bacteriophages of Escherichia coli and members of the lambdoid or lambda-like group of phages. We provide a comparative analysis of these sequences with each other and with two previously determined lambdoid family genome sequences, those of E. coli phage lambda and Salmonella typhimurium phage P22. The comparisons confirm that these phages are genetic mosaics, with mosaic segments separated by sharp transitions in the sequence. The mosaicism provides clear evidence that horizontal exchange of genetic material is a major component of evolution for these viruses. The data suggest a model for evolution in which diversity is generated by a combination of illegitimate and homologous recombination and mutational drift, and selection for function produces a population in which most of the surviving mosaic boundaries are located at gene boundaries or, in some cases, at protein domain boundaries within genes. Comparisons of these genomes highlight a number of differences that allow plausible inferences of specific evolutionary scenarios for some parts of the genome. The comparative analysis also allows some inferences about function of genes or other genetic elements. We give examples for the generalized recombination genes of HK97, HK022 and P22, and for a putative headtail adaptor protein of HK97 and HK022. We also use the comparative approach to identify a new class of genetic elements, the morons, which consist of a protein-coding region flanked by a putative delta 70 promoter and a putative factor-independent transcription terminator, all located between two genes that may be adjacent in a different phage. We argue that morons are autonomous genetic modules that are expressed from the repressed prophage. Sequence composition of the morons implies that they have entered the phages' genomes by horizontal transfer in relatively recent evolutionary time.

Maturation dynamics of a viral capsid: visualization of transitional intermediate states.

Typical of DNA bacteriophages and herpesviruses, HK97 assembles in two stages: polymerization and maturation. First, capsid protein polymerizes into closed shells; then, these precursors mature into larger, stabler particles. Maturation is initiated by proteolysis, producing a metastable particle primed for expansion-the major structural transition. We induced expansion in vitro by acidic pH and monitored the resulting changes by time-resolved X-ray diffraction and cryo-electron microscopy. The transition, which is not synchronized over the population, proceeds in a series of stochastically triggered subtransitions. Three distinct intermediates were identified, which are comparable to transitional states in protein folding. The intermediates' structures reveal the molecular events occurring during expansion. Integrated into a movie (see Dynamic Visualization below), they show capsid maturation as a dynamic process.

Bacteriophage T4 self-assembly: localization of gp3 and its role in determining tail length.

Gene 3 of bacteriophage T4 participates at a late stage in the T4 tail assembly pathway, but the hypothetical protein product, gp3, has never been identified in extracts of infected cells or in any tail assembly intermediate. In order to overcome this difficulty, we expressed gp3 in a high-efficiency plasmid expression vector and subsequently purified it for further analysis. The N-terminal sequence of the purified protein showed that the initial methionine had been removed. Variant C-terminal amino acid sequences were resolved by determining the cysteine content of the protein. The molecular mass of 20.6 kDa for the pure protein was confirmed by Western blotting, using a specific anti-gp3 serum for which the purified protein was the immunogen. We also demonstrated, for the first time, the physical presence of gp3 in the mature T4 phage particle and localized it to the tail tube. By finding a nonleaky, nonpermissive host for a gene 3 mutant, we could clearly demonstrate a new phenotype: the slow, aberrant elongation of the tail tube in the absence of gp3.

American ginseng and breast cancer therapeutic agents synergistically inhibit MCF-7 breast cancer cell growth.

BACKGROUND AND OBJECTIVES: American ginseng (Panax quinquefolius L.) purportedly alleviates menopause symptoms because of putative estrogenicity. METHODS: Using a standardized American ginseng (AG) extract in MCF-7 breast cancer cells, the objectives were to evaluate the ability of AG to induce the estrogen- regulated gene pS2 by Northern blot analysis, determine the effect on cell growth using the MTT assay, and evaluate the cell cycle effects by flow cytometry. RESULTS: AG and estradiol equivalently induced RNA expression of pS2. AG, in contrast to estradiol, caused a dose-dependent decrease in cell proliferation (P < 0.005). AG had no adverse effect on the cell cycle while estradiol significantly increased the proliferative phase (percent S-phase) and decreased the resting phase (G(0)-G(1) phase) (P < 0.005). Concurrent use of AG and breast cancer therapeutic agents resulted in a significant (P < 0.005) suppression of cell growth for most drugs evaluated. CONCLUSIONS: In vitro use of AG and breast cancer therapeutics synergistically inhibited cancer cell growth.

Crystallographic analysis of the dsDNA bacteriophage HK97 mature empty capsid.

HK97 is a member of the Siphovirus family of dsDNA bacteriophages. It is similar in architecture to bacteriophage lambda, the type member of this family, with an icosahedral capsid of triangulation number T = 7. No high-resolution structural information is available for the dsDNA phages, and HK97 is the only dsDNA bacteriophage capsid to produce crystals which diffract X-rays. At 650 A in diameter, the large size of the particle and resultant large unit cell create crystallographic challenges. The empty Head II (mature) particles were expressed in Escherichia coli and assembled in vitro, but they have the same morphology as the mature HK97 capsid. Previously reported Head II crystals diffracting to 3.5 A resolution are examined here in detail. Although the cell dimensions suggest an orthorhombic lattice, further analysis demonstrated that the space group was monoclinic. This has been confirmed by the present study. Images were recorded on the F1 beamline at CHESS and they were processed and scaled, resulting in a data set with a cumulative completeness of 65% and a scaling R factor of 7.7% to 7 A. The cell dimensions after post-refinement were a = 580, b = 626, c = 788 A, beta = 90.0 degrees. From the particle dimensions determined by cryo-electron microscopy (cryo-EM), there were determined to be two particles per unit cell. Systematic absences of even reflections along the 0k0 lattice line indicate that the space group is P21. The rotation function was used to determine the orientation of the particles in the unit cell and to confirm the space group. An icosahedral twofold axis is approximately, but not exactly, aligned with the crystallographic screw (b) axis. An icosahedral twofold axis orthogonal to the one approximately parallel to the b axis, is rotated 18 degrees away from the a axis. The centers of the two particles must be positioned close to the minimum-energy packing arrangement for spheres, which places one particle at ((1/4), 0, (1/4)) and the other particle at ((3/4), (1/2), (3/4)). The particle position and orientation were confirmed by calculating a Patterson function. The particles interact closely along icosahedral threefold axes, which occurs both along the crystallographic a axis and along the b axis. The particle dimensions derived from this packing arrangement agree well with those determined by cryo-EM and image reconstruction. The cryo-EM reconstruction will be used as a model to initiate phase determination; structure determination at 7 A is under way.

[Epidemiological observations on the physical activities of patients with arterial hypertension]. / Unele observatii epidemiologice privind activitatea fizica a bolnavilor cu hipertensiune arteriala.

The authors point out the results of some multidisciplinary epidemiological researches concerning the relation between the multifactorial etiology of arterial hypertension (AHT) in employers working in two factories and the nature of physical activity. The results show that the highest percentage of AHT cases is in the persons which do not have physical activity (occupational, housing or leisure). The women with AHT, which are frequently supra-ponderously, make a low level of physical activity. They have effort respiratory modifications in 40% of cases. The decreasing interest for control and prevention of health risks of the level of occupational health services has medical and social negative effects on long term.

Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma.

We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.

Skin-sparing mastectomy and immediate reconstruction: oncologic risks and aesthetic results in patients with early-stage breast cancer.

Skin-sparing mastectomy has been advocated as an oncologically safe approach for the management of patients with early-stage breast cancer that minimizes deformity and improves cosmesis through preservation of the skin envelope of the breast. Because chest wall skin is the most frequent site of local failure after mastectomy, concerns have been raised that inadequate skin excision could result in an increased risk of local recurrence. Precise borders of the skin resection have not been well established, and long-term local recurrence rates after skin-sparing mastectomy are not known. The purpose of this study was to evaluate the oncologic safety and aesthetic results for skin-sparing mastectomy and immediate breast reconstruction with a latissimus dorsi myocutaneous flap and saline breast prosthesis. Fifty-one patients with early-stage breast cancer (26 with ductal carcinoma in situ and 25 with invasive carcinoma) undergoing primary mastectomy and immediate reconstruction with a latissimus flap were studied from 1991 through 1994. For 32 consecutive patients, skin-sparing mastectomy was defined as a 5-mm margin of skin designed around the border of the nipple-areolar complex. After the mastectomy, biopsies were obtained from the remaining native skin flap edges. Patients were followed for 44.8 months. Histologic examination of 114 native skin flap biopsy specimens failed to demonstrate breast ducts in the dermis of any of the 32 consecutive patients studied. One of 26 patients with ductal carcinoma in situ had metastases to the skin of the lateral chest wall and back. Four other patients, one with stage I disease and three with stage II-B disease, had recurrent breast carcinoma. The stage I patient had a local recurrence in the subcutaneous tissues near the mastectomy specimen. Two patients suffered axillary relapse, and one had distant metastases to the spine. The findings of this study support the technique of skin-sparing mastectomy as an oncologically safe one, based on an absence of breast ductal epithelium at the margins of the native skin flaps and a local recurrence rate of 2 percent after 45 months of follow-up. Although these results need to be confirmed with greater numbers of patients and longer follow-up, skin-sparing mastectomy and immediate breast reconstruction may be considered an excellent alternative treatment to breast conservation for patients with ductal carcinoma in situ and early-stage invasive breast cancer.