Accelerated aging modulates the toxicological properties of the diazo tattoo pigment PO13.

Pigment particles used in tattooing may exert long terms effect by releasing diffusible degradation products. In the present work, aqueous suspensions of the organic orange diazo pigment PO13 were aged by exposure to simulated sunlight at 40 °C. The morphology and the surface charge of PO13 particles were barely modified upon aging, but primary particles were released by de-agglomeration.

Factors associated with Onchocerca volvulus transmission after 20 years of community treatment with ivermectin in savanah and forest areas in Central African Republic: A Cross Sectional Study.

The Central African Republic has endemic onchocerciasis in 20 health districts in savannah and forest areas. The country organised a mass distribution campaign of invermectin in 2023 through the National Onchocerciasis Control Programme. The objectives of this study were to identify factors of persistent Onchocerca volvulus transmission.

Factors Associated With Coverage in Community-directed Treatment With Ivermectin for Onchocerciasis Control in Savanah and Forest Areas in Central African Republic: A Cross-sectional Study.

Objectives: The aim of this study was to identify factors associated with coverage in community-directed treatment with ivermectin for onchocerciasis control in savannah and forest areas in the Central African Republic.

Methods: A cross-sectional study was conducted in 2 districts where onchocerciasis is endemic. We employed a pretested and validated questionnaire that included questions about the socio-demographic characteristics of the respondents and variables relevant to coverage assessment.

Influence of pneumatic transportation on the stability of monoclonal antibodies.

Pneumatic transportation systems (PTS) were recently proposed as a method to carry ready-for-injection diluted monoclonal antibodies (mAbs) from the pharmacy to the bedside of patients. This method reduces transportation time and improves the efficiency of drug distribution process. However, mAbs are highly sensitive molecules for which subtle alterations may lead to deleterious clinical effects.

Site-Selective Protein Conjugation by a Multicomponent Ugi Reaction.

The chemical bioconjugation of proteins has seen tremendous applications in the past decades, with the booming of antibody-drug conjugates and their use in oncology. While genetic engineering has permitted to produce bespoke proteins featuring key (un-)natural amino acid residues poised for site-selective modifications, the conjugation of native proteins is riddled with selectivity issues. Chemoselective strategies are plentiful and enable the precise modification of virtually any residue with a reactive side-chain; site-selective methods are less common and usually most effective on small and medium-sized proteins.

Improved characterization of trastuzumab deruxtecan with PTCR and internal fragments implemented in middle-down MS workflows.

Antibody-drug conjugates (ADCs) are highly complex proteins mainly due to the structural microvariability of the mAb, along with the additional heterogeneity afforded by the bioconjugation process. Top-down (TD) and middle-down (MD) strategies allow the straightforward fragmentation of proteins to elucidate the conjugated amino acid residues. Nevertheless, these spectra are very crowded with multiple overlapping and unassigned ion fragments.

Prospecting for yaws in the Mbaïki Health District in the Central African Republic.

Introduction: yaws is endemic in the Central African Republic. The last cases of yaws notified by CAR to WHO date back to 2012. The objective of this study was to measure the prevalence of yaws in the health district of Mbaïki and to describe its clinical and epidemiological characteristics.

Young women who sell sex in Bangui, Central African Republic: a neglected group highly vulnerable to HIV.

Background: The objectives of this study were to determine the association between the vulnerability factors linked to human immunodeficiency virus (HIV) and other sexually transmitted infection among the young women who sell sex (YWSS) group (15-24 years) and adult sex workers, engaged in consensual sex for money (AFSW).

Methods: A cross-sectional study was conducted among AFSW involved in commercial sex transactions. Prevalence ratios (PR) analysis was carried out using log-binomial regression model.

Risk factors for multidrug-resistant tuberculosis in the Central African Republic: A case-control study.

Background: The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) presents a challenge to the "End TB by 2035" strategy. This study aimed to identify the risk factors associated with MDR-TB in patients admitted to the pneumo-physiology clinic of the National University Hospital of Bangui in Central African Republic.

Methods: This was a "retrospective" chart review study.

Interlaboratory Evaluation of a User-Friendly Benchtop Mass Spectrometer for Multiple-Attribute Monitoring Studies of a Monoclonal Antibody.

In the quest to market increasingly safer and more potent biotherapeutic proteins, the concept of the multi-attribute method (MAM) has emerged from biopharmaceutical companies to boost the quality-by-design process development. MAM strategies rely on state-of-the-art analytical workflows based on liquid chromatography coupled to mass spectrometry (LC-MS) to identify and quantify a selected series of critical quality attributes (CQA) in a single assay. Here, we aimed at evaluating the repeatability and robustness of a benchtop LC-MS platform along with bioinformatics data treatment pipelines for peptide mapping-based MAM studies using standardized LC-MS methods, with the objective to benchmark MAM methods across laboratories, taking nivolumab as a case study.

[Incidence of snakebites in rural communities living in the Paoua savannah and Mbaïki forest areas in Central African Republic].

Introduction: Snakebite is one of the most deadly neglected tropical diseases in Africa with more than 20,000 deaths reported each year. According to recent data from hospital in Central African Republic studies, the Paoua health district reports between 300 and 400 cases of ophidian envenomation each year. However, no epidemiological study on snakebites has been conducted at national level, nor a control strategy developed.

Incidence and risk factors for tuberculosis among people living with HIV in Bangui: A cohort study.

Objectives: The objectives of this study were to determine the incidence and risk factors of tuberculosis (TB) among people living with HIV (PLHIV).

Methods: A cohort study was carried out in an HIV infection management centre in Bangui. PLHIV aged 18 or older, with no history of TB, enrolled between January 1, 2017 and December 31, 2018 were included in the study.

A Combination of Native LC-MS Approaches for the Comprehensive Characterization of the Antibody-Drug Conjugate Trastuzumab Deruxtecan.

Background: Native mass spectrometry (nMS) approaches appear attractive to complement bottom-up strategies traditionally used in biopharmaceutical industries thanks to their quite straightforward and rapid workflows, especially through online hyphenation of non-denaturing liquid chromatography (LC) to nMS. The present work provides an overview of the state-of-the-art chromatographic tools available for the detailed characterization of monoclonal antibody (mAb) formats, exemplified on the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd).

Methods: T-DXd was first characterized by conventional reversed phase LC (rpLC) and peptide mapping.

Repeated Exposure of Macrophages to Synthetic Amorphous Silica Induces Adaptive Proteome Changes and a Moderate Cell Activation.

Synthetic amorphous silica (SAS) is a nanomaterial used in a wide variety of applications, including the use as a food additive. Two types of SAS are commonly employed as a powder additive, precipitated silica and fumed silica. Numerous studies have investigated the effects of synthetic amorphous silica on mammalian cells.

Proteomic analysis of Rhodospirillum rubrum after carbon monoxide exposure reveals an important effect on metallic cofactor biosynthesis.

Some carboxydotrophs like Rhodospirillum rubrum are able to grow with CO as their sole source of energy using a Carbone monoxide dehydrogenase (CODH) and an Energy conserving hydrogenase (ECH) to perform anaerobically the so called water-gas shift reaction (WGSR) (CO + HO → CO + H). Several studies have focused at the biochemical and biophysical level on this enzymatic system and a few OMICS studies on CO metabolism. Knowing that CO is toxic in particular due to its binding to heme iron atoms, and is even considered as a potential antibacterial agent, we decided to use a proteomic approach in order to analyze R.

High-Resolution IMS-MS to Assign Additional Disulfide Bridge Pairing in Complementarity-Determining Regions of an IgG4 Monoclonal Antibody.

Monoclonal antibodies (mAbs) have taken on an increasing importance for the treatment of various diseases, including cancers and immunological disorders. Disulfide bonds play a pivotal role in therapeutic antibody structure and activity relationships. Disulfide connectivity and cysteine-related variants are considered as critical quality attributes that must be monitored during mAb manufacturing and storage, as non-native disulfide bridges and aggregates might be responsible for loss of biological function and immunogenicity.

A proteomic-informed view of the changes induced by loss of cellular adherence: The example of mouse macrophages.

Except cells circulating in the bloodstream, most cells in vertebrates are adherent. Studying the repercussions of adherence per se in cell physiology is thus very difficult to carry out, although it plays an important role in cancer biology, e.g.

A proteomic view of cellular responses of macrophages to copper when added as ion or as copper-polyacrylate complex.

Copper is an essential metal for life, but is toxic at high concentrations. In mammalian cells, two copper transporters are known, CTR1 and CTR2. In order to gain insights on the possible influence of the import pathway on cellular responses to copper, two copper challenges were compared: one with copper ion, which is likely to use preferentially CTR1, and one with a copper-polyacrylate complex, which will be internalized via the endosomal pathway and is likely to use preferentially CTR2.

How Reversible Are the Effects of Fumed Silica on Macrophages? A Proteomics-Informed View.

Synthetic amorphous silica is one of the most used nanomaterials, and numerous toxicological studies have studied its effects. Most of these studies have used an acute exposure mode to investigate the effects immediately after exposure. However, this exposure modality does not allow the investigation of the persistence of the effects, which is a crucial aspect of silica toxicology, as exemplified by crystalline silica.

A Proteomic View of Cellular Responses to Anticancer Quinoline-Copper Complexes.

Metal-containing drugs have long been used in anticancer therapies. The mechansims of action of platinum-based drugs are now well-understood, which cannot be said of drugs containing other metals, such as gold or copper. To gain further insights into such mechanisms, we used a classical proteomic approach based on two-dimensional elelctrophoresis to investigate the mechanisms of action of a hydroxyquinoline-copper complex, which shows promising anticancer activities, using the leukemic cell line RAW264.

A quantitative proteomic analysis of cofilin phosphorylation in myeloid cells and its modulation using the LIM kinase inhibitor Pyr1.

LIM kinases are located at a strategic crossroad, downstream of several signaling pathways and upstream of effectors such as microtubules and the actin cytoskeleton. Cofilin is the only LIM kinases substrate that is well described to date, and its phosphorylation on serine 3 by LIM kinases controls cofilin actin-severing activity. Consequently, LIM kinases inhibition leads to actin cytoskeleton disorganization and blockade of cell motility, which makes this strategy attractive in anticancer treatments.

A Novel Online Four-Dimensional SEC×SEC-IM×MS Methodology for Characterization of Monoclonal Antibody Size Variants.

The determination of size variants is a major critical quality attribute of a therapeutic monoclonal antibody (mAb that may affect the drug product safety, potency, and efficacy. Size variant characterization often relies on size-exclusion chromatography (SEC), which could be hampered by difficult identification of peaks. On the other hand, mass spectrometry (MS)-based techniques performed in nondenaturing conditions have proven to be valuable for mAb-related compound characterization.

The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.

Background & Aims: Embedded into a complex signaling network that coordinates glucose uptake, usage and production, the nuclear bile acid receptor FXR is expressed in several glucose-processing organs including the liver. Hepatic gluconeogenesis is controlled through allosteric regulation of gluconeogenic enzymes and by glucagon/cAMP-dependent transcriptional regulatory pathways. We aimed to elucidate the role of FXR in the regulation of fasting hepatic gluconeogenesis.

Mortality during road traffic accidents in Bangui, Central African Republic.

The authors examined mortality during road traffic accidents (RTAs) to propose solutions for their prevention. This descriptive prospective study took place over a 12-month period (June 1, 2011, to May 30, 2012) and included all fatalities from RTAs brought to selected hospitals. These RTA fatalities were studied in the morgues and selected sites.

Risk factors for HIV infection among female sex workers in Bangui, Central African Republic.

Objective: The aims of the study were i) to categorize female sex workers (FSW) according to socio-anthropologic criteria in Bangui; ii) to examine the association between a selection of demographic and risk variables with the different categories of female sex work as outcome, and iii) to investigate factors associated with HIV status.

Methods: A cross-sectional questionnaire survey was conducted to describe the spectrum of commercial sex work in Bangui among 345 sexually active women. After collection of social and behavioral characteristics, each woman received a physical examination and a blood sample was taken for biological analyses, including HIV testing.