Public health approach to prevent cervical cancer in HIV-infected women in Kenya : issues to consider in the design of prevention programs

Women living with HIV in Africa are at increased risk to be co-infected with Human Papilloma Virus (HPV), persistent high risk (HR) HPV infection and bacterial vaginosis (BV), which compounds HPV persistence, thereby increasing the risk for cervical dysplasia. New guidance from WHO in 2014 advocating for a "screen and treat" approach in resource poor settings is becoming a more widely recommended screening tool for cervical cancer prevention programs in such contexts. This review article summarizes the risk factors to be considered when designing a primary and secondary cervical prevention program in a post-vaccination era for HIV-infected women in Kenya. This review article is based on our prior research on the epidemiology of pHR/HR-HPV genotypes in HIV-infected women and CIN 2+ in Kenya and other sub-Saharan contexts. In order to contextualize the findings, a literature search was carried out in March 2017 by means of four electronic databases: PUBMED, EMBASE, SCOPUS, and PROQUEST. Risk factors for potential (pHR)/HR HPV acquisition, including CD4 count, HAART initiation, Female Sex Worker status (FSW) and BV need to be considered. Furthermore, there may be risk factors for abnormal cytology, including FSW status, multiple potential (p) HR/HR HPV genotypes, which may require that HIV-infected women be subjected to screening at more frequent intervals than the three year recommended by the WHO. The quadruple synergistic interaction between HIV, HPV and BV and its related cervicitis may need to be reflected within a larger prevention framework at the community level. The opportunities brought forth by the roll out of HAART could lead to task shifting of HIV-HPV-BV care to nurses, which may increase access in poorly-served areas

Which role do excited states play in radiation damage to organic solid-state compounds?

Ionizing radiation induces radicals in organic materials. When such species are created in biological macromolecules like DNA, they harm living organisms. This detrimental effect is explicitly exploited for the sterilisation of e.g. foodstuffs, and radiation-induced radicals are quantitatively used for radiation dosimetry purposes. For understanding radiation actions at different levels of molecular and cellular organisation, knowledge of the radical structures and their formation mechanisms is of fundamental importance. In this context, radiation-induced processes in solid sugars are studied, among others, to gain insight into the role of the deoxyribose unit in the radiation chemistry of DNA. X-irradiation typically gives rise to a variety of primary radicals in these systems, which transform into stable radicals or diamagnetic species via one or more radical reactions. By combining electron magnetic resonance experiments and density functional theory (DFT) calculations, we recently identified the major stable [1,2], as well as the major primary [3] radiation-induced radicals in solid sucrose (see figure). We are currently investigating how the primary radicals transform into the stable ones. A general but important observation is that in sucrose and similar carbohydrates, e.g. rhamnose, the primary radical formation (typically by way of net H-abstraction) is selective: it preferentially takes place at particular carbons and oxygens. This selectivity apparently cannot be explained simply on thermodynamical grounds. It may be hypothesised that, after the initial oxidation event (leaving the radical cation in an excited state), the hole ‘migrates’ to a particular carbon or oxygen, after which de-excitation and deprotonation processes yield a neutral radical. It is our goal to examine factors possibly explaining the experimentally observed selectivity. So far we have made some preliminary ground-state calculations on energy profiles of deprotonation reactions in rhamnose single crystals, as well as time-dependent DFT calculations of excited states in this system

Hydrodynamic lift of vesicles under shear flow in microgravity

The dynamics of a vesicle suspension in a shear flow between parallel plates has been investigated under microgravity conditions, where vesicles are only submitted to hydrodynamic effects such as lift forces due to the presence of walls and drag forces. The temporal evolution of the spatial distribution of the vesicles has been recorded thanks to digital holographic microscopy, during parabolic flights and under normal gravity conditions. The collected data demonstrates that vesicles are pushed away from the walls with a lift velocity proportional to $\dot{\gamma} R^3/z^2$ where $\dot{\gamma}$ is the shear rate, $R$ the vesicle radius and $z$ its distance from the wall. This scaling as well as the dependence of the lift velocity upon vesicle aspect ratio are consistent with theoretical predictions by Olla [J. Phys. II France {\bf 7}, 1533--1540 (1997)].Comment: 6 pages, 8 figure

Do Surgical Interventions Influence Psychosexual and Cosmetic Outcomes in Women with Disorders of Sex Development?

Clinical practice developed to promote psychosexual well-being in DSD is under scrutiny. Although techniques for genital surgery have much improved lately, long-term studies on psychosexual functioning and cosmetic outcome on which to base treatment and counseling are scarce. We studied 91 women with a DSD. Feminizing surgery was performed in 64% of the women; in 60% of them, resurgery in puberty was needed after a single-stage procedure. Both patients and gynecologists were satisfied with the cosmetic appearance of the genitalia. However, forty percent of these females experienced sexuality-related distress and 66% was at risk for developing a sexual dysfunction, whether they had surgery or not. Recognizing the difficulty of accurate assessment, our data indicate that feminizing surgery does not seem to improve nor hamper psychosexual outcome, especially in patients with severe virilization

High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation

Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple cafe-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P \u3c 0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients

Electron Magnetic Resonance study of the Structure and Thermal Stability of Radiation-Induced Free Radicals in Trehalose Single Crystals

Radiation-induced radicals in sugars have recently gained considerable interest with respect to both fundamental and applied research. A number of studies are available that focus on the dosimetric characteristics of sugar systems. Other studies, like ours, aim to understand the identity and the structural properties of the involved radicals, and the radical reactions in which the primary or secondary products can be linked to the stable radicals. We present here experimental results obtained on radiation-induced radicals in trehalose single crystals. A major purpose of this study is to check if the cleavage of the glycosidic bond and carbonyl formation are common radiation-induced processes produced by irradiation in disaccharides. Recently, the chemical structures of three dominant radicals obtained after room temperature (RT) irradiation in sucrose single crystals, were identified by De Cooman et al.1-3 All three radicals have a broken glycosidic bond and a carbonyl group. Trehalose was selected as the object of this study because of its close structural similarity with sucrose : it is a disaccharide composed of two [...]-D-glucosyl units linked by a glycosidic oxygen bridge between their two anomeric carbon atoms, C1 and C1’. After RT irradiation of trehalose single crystals three dominant radicals are present. One radical species is characterized by a rather isotropic triplet due to the interaction of the unpaired electron with two almost equivalent protons in [...] positions. The other two radical species exhibit only proton hyperfine couplings smaller than 20 MHz and therefore are characterized by a broad EPR singlet. In addition to these radicals, two other less dominant species characterized by a doublet structure are present. Storing the irradiated trehalose crystal at RT for three months or heating it to 40° for three days, changes the EPR spectrum completely, the dominant species now being characterized by a doublet of doublets

Quantum Fluctuation Relations for the Lindblad Master Equation

An open quantum system interacting with its environment can be modeled under suitable assumptions as a Markov process, described by a Lindblad master equation. In this work, we derive a general set of fluctuation relations for systems governed by a Lindblad equation. These identities provide quantum versions of Jarzynski-Hatano-Sasa and Crooks relations. In the linear response regime, these fluctuation relations yield a fluctuation-dissipation theorem (FDT) valid for a stationary state arbitrarily far from equilibrium. For a closed system, this FDT reduces to the celebrated Callen-Welton-Kubo formula

Challenge of teaching complex, end-to-end space system design and development process: Earth Observation Satellite System Design training course

The Earth Observation Satellite System Design training course was first offered in 2018 at ESA Academy’s Training and Learning Facility at ESA’s ESEC Galaxia site in Belgium, and again in 2021 in an online format under the Covid-19 pandemic situation. The course covers the end-to-end design and development process of satellite Earth observation systems. Two major challenges were faced by the teaching experts, consisting of the active and retired ESA staff, as well as ESA Academy’s instructional designers for its development: (1) Condensing such a vast subject domain, associated with a complex, multi-disciplinary engineering undertaking, into a compact format (e.g. 4.5 days in 2018) without sacrificing the quality of the essential technical knowledge, engineering practices and logic as taught; (2) Presenting the course materials in a comprehensive form to a group of 30 M.S. and Ph.D. students with their backgrounds generally not covering all of the technical disciplines associated with the course subject domain. The 2021 online edition of the training course, which drew on lessons learnt from 2018, consisted of 18 lectures, plus 5 group project sessions where the students put their acquired knowledge into practice and learned to work in a project team environment. This paper concentrates on the approach and logic adopted by the instructional team to address the above 2 challenges. Difficulties encountered in some of the areas, e.g. remote sensing instrumentation designs, are discusse

Characterization of antibody-mediated neutralization directed against the hypervariable region 1 of hepatitis C virus E2 glycoprotein

The hypervariable region 1 (HVR1) comprising the first 27 aa of E2 glycoprotein is a target for neutralizing antibodies against hepatitis C virus (HCV), but the mechanisms of this neutralization in the cell-culture-infectious genotype 2a strain JFH1 HCV virus (HCVcc) system are unknown. Two rabbit polyclonal sera, R1020 and R140, recognizing the HVR1 of the genotype 1a isolates H77c and Glasgow (Gla), respectively, and a Gla HVR1-specific mouse mAb AP213 have been described previously. However, attempts to generate of antibodies to the JFH1 HVR1 were unsuccessful. Therefore, this study produced chimeric JFH1 HCVcc viruses harbouring the H77c or Gla HVR1 to assess the reactivity of antibodies to this region and their effects on virus infectivity. The inter-genotypic HVR1 swap did not significantly affect virus infectivity. The genotype 1a HVR1-specific antibodies neutralized chimeric viruses in an isolate-dependent manner, underlining the role of HVR1 in HCV infection. The neutralizing antibodies reacted mainly with the C-terminal portion of HVR1, and detailed mapping identified A17, F20 and Q21 in the Gla HVR1 sequence and T21 (and possibly L20) in the corresponding H77c sequence as key epitope residues for AP213 and R140, and R1020, respectively. Importantly, none of the antibodies inhibited in vitro binding of viral envelope glycoproteins to the best-characterized HCV receptor, CD81, or to the glycosaminoglycan attachment factors. However, the HVR1 antibodies were capable of post-attachment neutralization. Overall, this study emphasizes the role of HVR1 in HCVcc entry and provides new tools to study this region further in the context of complete virions

Synchrotron Mössbauer spectroscopy using high-speed shutters

A new method of performing Mössbauer spectroscopy using a fast shutter in combination with microfocused synchrotron radiation is demonstrated