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Raoul Emeric Guetiya Wadoum,1,&ast; Stephen Sevalie,2,&ast; Maurice Baimba Kargbo,3 Andrew Clarke,4,5 Sherry Bangura,6 Mariatu Kargbo,6 Hawa Mariama Sesay,7 Abdul H Kamara,6 Jamil Bangura,6 Alie F Kamara,6 Sophie Allieu,1 Hassan Rogers,1 Maurizio Mattei,8 Vittorio Colizzi,9 Carla Montesano,8 Edwin JJ Momoh1,3 1Department of Public Health, Microbiology and Immunology, Ernest Bai Koroma University of Science and Technology, Makeni, Sierra Leone; 2 34th Military Hospital, The Republic of Sierra Leone Armed Forces, Freetown, Sierra Leone; 3Department of Agriculture and Food Security; Ernest Bai Koroma University of Science and Technology, Makeni, Sierra Leone; 4Global Programs Division, Save the Children UK, London, UK; 5Department/Division of Health Research, Lancaster University, Lancaster, UK; 6Sierra Leone Association of Ebola Survivors, Freetown, Sierra Leone; 7Department of Public Health, University of Makeni, Makeni, Sierra Leone; 8Department of Biology, University of Rome Tor Vergata, Rome, Italy; 9Department of Sciences and Technology, Evangelical University of Cameroon, Bandjoun, Cameroon&ast;These authors contributed equally to this workCorrespondence: Raoul Emeric Guetiya Wadoum; Edwin JJ Momoh, Email ergwadoum@ebkustsl.edu.sl; raoulemeric@gmail.com; emomoh@ebkust.edu.slBackground: The clinical management of persistent medical conditions affecting Ebola survivors, generally described as a post-Ebola syndrome, remains a public health concern. We aimed to analyze Ebola survivors’ laboratory biomarkers as compared to their non-infected household relatives to identify biomarkers that could guide the identification of survivors at increased risk of developing severe at odds with the non-severe post-Ebola syndrome.Materials and Methods: Data were extracted from medical records of the Ebola survivors clinic, and we included only Ebola survivor’s parameters recorded during the first baseline follow-up visit 2 weeks interval after their second negative PCR result. Moreover, household non-infected family contacts of survivors visiting the clinic during the same period were recruited as community control.Results: The mean age of survivors was 32.65 (IQR: 15.5, 38.25) years, and Ebola IgG immunoglobulin was detected in all, thus confirming their status. The statistical significance (all p < 0.05) observed in monocyte percentage (MONO%), cluster of differentiation 4 percentage (CD4%), alanine aminotransferase (ALT), creatinine (CREA), and creatinine kinase (C-kinase) proved to be clinically significant as compared to the household relatives’ group. Interestingly, the linear regression analysis indicated that the duration at ETU was negatively associated with lymphocyte percentage with a 5% lymphocyte decrease per day spent at ETU. Finally, there was a significant (p < 0.05) association between hematological (Hb, PCV, MCV, MCH), biochemical (ALT, CREA, C-kinase, T-cholesterol, triglycerides) parameters and the risk of developing severe complications.Conclusion: We recommend clinicians closely monitor Hb, PCV, MCV, MCH, ALT, CREA, C-kinase, T-cholesterol, triglycerides and lymphocytes as clinically relevant laboratory biomarkers to identify survivors at higher risk of developing severe post-acute syndrome upon discharge from Ebola treatment unit including headache, abdominal pain, chest pain, ocular complication, arthralgia, hearing difficulty and erectile dysfunction which can impact health-related quality of life among Ebola survivors.Keywords: Ebola virus disease, hematological, immunological, biochemical, biomarkers, post-acute syndrome

Raoul Emeric Guetiya Wadoum,1 Stephen Sevalie,2 Antonella Minutolo,3 Andrew Clarke,4,5 Gianluca Russo,6 Vittorio Colizzi,7 Maurizio Mattei,8 Carla Montesano8 1Department of Public Health, Microbiology and Immunology, Ernest Bai Koroma University of Science and Technology, Makeni, Sierra Leone; 2 34th Regimental Military Hospital, The Republic of Sierra Leone Armed Forces, Freetown, Sierra Leone; 3Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy; 4Global Programs Division, Save the Children United Kingdom, London, UK; 5Division of Health Research, Lancaster University, Lancaster, UK; 6Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy; 7Department of Biomedical Sciences, Faculty of Science and Technology, Evangelical University of Cameroon, Bandjoun, Cameroon; 8Department of Biology, School of Mathematics, Physics and Natural Sciences, University of Rome Tor Vergata, Rome, ItalyCorrespondence: Raoul Emeric Guetiya Wadoum Tel +232 78425924Email ergwadoum@ebkustsl.edu.sl; raoulemeric@gmail.comAbstract: The Ebola virus disease, formerly known as Ebola hemorrhagic fever, is a severe and often fatal zoonosis in humans. The 2013– 2016 West African Ebola outbreak had distinctive characteristics, and it was the largest and most complex epidemic since the virus discovery in 1976. Although the 2018– 2020 Ebola outbreak in the Democratic Republic of the Congo had many similarities, there were additional challenges due to the presence of armed rebel groups at the epicenters of the epidemic. Despite these challenges, the extraordinary commitment of the World Health Organization (WHO) regional office for Africa, in collaboration with Africa Union (AU) member states through the Africa Centres for Disease Control and Prevention (Africa CDC), and WHO’s prompt declaration of a Public Health Emergency of International Concern (PHEIC) shepherded an effective coordinated response to contain the epidemic. Learning from previous Ebola virus epidemics and the current Coronavirus disease 2019 (COVID-19) pandemic, the AU member states should strengthen inter-state coordination towards the development and implementation of a preparedness and readiness plan which will enable the continent to build and sustain resilient capacities to prevent, detect, and respond to future outbreaks following the International Health Regulations (IHR).Keywords: United Nations, Africa Union, WHO, Africa CDC, Ebola virus disease, COVID-19

Perceived stress in Italian coaches and sport mental health were investigated during the rebooting of sport activities following the first COVID-19 lockdown period. A sample of 237 coaches from various sports were asked to answer the Italian version of the Perceived Stress Scale and the Sport Mental Health Continuum, together with reporting of demographic information. Coaches’ perceived stress levels were compared with data collected during the lockdown period. Women showed a significant decrease in their perceived stress levels compared to the lockdown period, whereas this was not true for men. Hierarchical regression indicated that, during the rebooting phase, increased age of coaches and their psychological well-being experienced in sporting contexts (a sport mental health dimension) were predictive of decreased perceived stress levels. Practical implications for practitioners working in this field are discussed in the conclusions.

Novel psychoactive substances (NPS) represent a broad class of drugs new to the illicit market that often allow passing drug-screening tests. They are characterized by a variety of structures, rapid transience on the drug scene and mostly unknown metabolic profiles, thus creating an ever-changing scenario with evolving analytical targets. The present study aims at developing an indirect screening strategy for NPS monitoring, and specifically for new synthetic opioids (NSOs), based on assessing changes in endogenous urinary metabolite levels as a consequence of the systemic response following their intake. The experimental design involved in-vivo mice models: 16 animals of both sex received a single administration of morphine or fentanyl. Urine was collected before and after administration at different time points; the samples were then analysed with an untargeted metabolomics LC-HRMS workflow. According to our results, the intake of opioids resulted in an elevated energy demand, that was more pronounced on male animals, as evidenced by the increase in medium and long chain acylcarnitines levels. It was also shown that opioid administration disrupted the pathways related to catecholamines biosynthesis. The observed alterations were common to both morphine and fentanyl: this evidence indicate that they are not related to the chemical structure of the drug, but rather on the drug class. The proposed strategy may reinforce existing NPS screening approaches, by identifying indirect markers of drug assumption., (© 2024. The Author(s).)

Background: Surveillance of SARS-CoV-2 variants of concern (VOCs) and lineages is crucial for decision-making. Our objective was to study the SARS-CoV-2 clade dynamics across epidemiological waves and evaluate the reliability of SNPsig® SARS-CoV-2 EscapePLEX CE in detecting VOCs in Cameroon., Material and Methods: A laboratory-based study was conducted on SARS-CoV-2 positive nasopharyngeal specimens cycle threshold (Ct)≤30 at the Chantal BIYA International Reference Centre in Yaoundé-Cameroon, between April-2020 to August-2022. Samples were analyzed in parallel with Sanger sequencing and (SNPsig® SARS-CoV-2 EscapePLEX CE ) , and performance characteristics were evaluated by Cohen's coefficient and McNemar test., Results: Of the 130 sequences generated, SARS-CoV-2 clades during wave-1 (April-November 2020) showed 97 % (30/31) wild-type lineages and 3 % (1/31) Gamma-variant; wave-2 (December-2020 to May-2021), 25 % (4/16) Alpha-variant, 25 % (4/16) Beta-variant, 44 % (7/16) wild-type and 6 % (1/16) mu; wave-3 (June-October 2021), 94 % (27/29) Delta-variant, 3 % (1/29) Alpha-variant, 3 % (1/29) wild-type; wave-4 (November-2021 to August-2022), 98 % (53/54) Omicron-variant and 2 % (1/54) Delta-variant. Omicron sub-variants were BA.1 (47 %), BA.5 (34 %), BA.2 (13 %) and BA.4 (6 %). Globally, the two genotyping methods accurately identified the SARS-CoV-2 VOCs (P = 0.17, McNemar test; Ka = 0.67)., Conclusion: Genomic surveillance reveals a rapid dynamic in SARS-CoV-2 strains between epidemiological waves in Cameroon. For wide-spread variant surveillance in resource-limited settings, SNPsig® SARS-CoV-2 EscapePLEX CEkit represents a suitable tool, pending upgrading for distinguishing Omicron sub-lineages., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Huntington's disease (HD) is caused by the expansion of a polyglutamine (polyQ)-encoding tract in exon 1 of the huntingtin gene to greater than 35 CAG repeats. It typically has a disease course lasting 15-20 years, and there are currently no disease-modifying therapies available. Thus, there is a need for faithful mouse models of HD to use in preclinical studies of disease mechanisms, target validation, and therapeutic compound testing. A large variety of mouse models of HD were generated, none of which fully recapitulate human disease, complicating the selection of appropriate models for preclinical studies. Here, we present the urinary liquid chromatography-high-resolution mass spectrometry analysis employed to identify metabolic alterations in transgenic R6/2 and zQ175DN knock-in mice. In R6/2 mice, the perturbation of the corticosterone metabolism and the accumulation of pyrraline, indicative of the development of insulin resistance and the impairment of pheromone excretion, were observed. Differently from R6/2, zQ175DN mice showed the accumulation of oxidative stress metabolites. Both genotypes showed alterations in the tryptophan metabolism. This approach aims to improve our understanding of the molecular mechanisms involved in HD neuropathology, facilitating the selection of appropriate mouse models for preclinical studies. It also aims to identify potential biomarkers specific to HD.

Antiretroviral therapy (ART) has improved the lifespan of people living with HIV. However, their immune system remains in a state of sustained activation/inflammation, which favors viral replication and depletion of helper T-cells with varying profiles according to ART-response. We herein sought to ascertain the inflammatory profile of adolescents living with perinatal HIV-1 infection (ALPHI) receiving ART in an African context. In this cross-sectional and comparative study among ART-experienced ALPHI in Yaoundé-Cameroon, HIV-1 RNA was measured by Abbott Real-time PCR; CD4 cells were enumerated using flow cytometry; serum cytokines were measured by ELISA; HIV-1 proviral DNA was genotyped by Sanger-sequencing; and archived drug resistance mutations (ADRMs) were interpreted using Stanford HIVdb.v9.0.1. Overall, 73 adolescents were enrolled (60 ALPHI and 13 HIV-1 negative peers) aged 15 (13-18) years; 60.00% were female. ART median duration was 92 (46-123) months; median viral load was 3.99 (3.17-4.66) RNA Log 10 (copies)/mL and median CD4 count was 326 (201-654) cells/mm 3 . As compared to HIV-negative adolescents, TNFα was highly expressed among ALPHI (p<0.01). Following a virological response, inflammatory cytokines (IFNγ and IL-12), anti-inflammatory cytokines (IL-4 and IL-10) and inflammation-related cytokines (IL-6 and IL-1β) were highly expressed with viral suppression (VS) vs. virological failure (VF), while the chemokine CCL3 was highly expressed with VF (p<0.01). Regarding the immune response, the inflammatory cytokine TNFα was highly expressed in those that are immunocompetent (CD4≥500 cell/mm 3 ) vs. immunocompromised (CD4<500 cell/mm 3 ), p ≤ 0.01; while chemokine CCL2 was highly expressed in the immunocompromised (p<0.05). In the presence of ADRMs, IL-4 and CCL3 were highly expressed (p=0.027 and p=0.043 respectively). Among ART-experienced ALPHI in Cameroon, the TNFα cytokine was found to be an inflammatory marker of HIV infection; IFNγ, IL-1β, IL-6, and IL-12 are potential immunological markers of VS and targeting these cytokines in addition to antiretroviral drugs may improve management. Moreover, CCL3 and CCL2 are possible predictors of VF and/or being immunocompromised and could serve as surrogates of poor ART response., 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 © 2023 Ka’e, Nanfack, Ambada, Santoro, Takou, Semengue, Nka, Bala, Endougou, Elong, Beloumou, Djupsa, Gouissi, Fainguem, Tchouaket, Sosso, Kesseng, Ndongo, Sonela, Kamta, Tchidjou, Ndomgue, Ndiang, Nlend, Nkenfou, Montesano, Halle-Ekane, Cappelli, Tiemessen, Colizzi, Ceccherini-Silberstein, Perno and Fokam.)

Introduction: The analysis of organic residue in ancient vessels to investigate early-age civilization habits is an important archeological application that needs advanced analytical methods. However, these procedures should meet inherent requisites such as low sampling invasiveness and high sensitivity for trace analysis. This study deals with the development of advanced analytical methods for the detection of opium alkaloids in ceramic vessels and its first application to the study of Daunian pots dating back to the VIII-IV sec BC. Methods: All the stages of the analytical procedure, from sampling to analysis, were carefully optimized. Concerning sampling, the traditional scraping approach was compared with a swabbing strategy which permitted minimizing sample encroachment. Extraction was based on pressurized liquid extraction or ultrasound-assisted liquid extraction, followed by dispersive liquid-liquid microextraction, which allowed concentration enrichment. On the other hand, a UHPLC-MS/MS method was specifically developed and validated to obtain reliable data. Some Daunian pots, belonging to the Ceci-Macrini private archeological collection, were selected for sample withdrawal as their iconography could suggest opium usage. Results: Several of the analyzed samples resulted positive to thebaine and less frequently to morphine and codeine; furthermore, 70% of the analyzed items tested positive for at least one opium alkaloid. Positive findings were common to all the samples collected in the pots, suggesting that scraping and swabbing provided comparable results and validating this unusual sampling strategy. All samples were additionally analyzed by UHPLC-HRMS to further improve the confidence level of the identified compounds. The obtained results shed new light on the hypothesis of opium usage by the ancient Daunian civilization. Furthermore, this study provided suitable analytical tools for further investigations on the same topic, with a good level of confidence in the quality of the results., 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 © 2023 Vincenti, Montesano, Ciccola, Serafini, Favero, Pallotta, Pagano, Di Francesco, Croce, Leone, Muntoni and Sergi.)

Frequent plateletpheresis is associated with severe lymphopenia of uncertain clinical significance. We assessed the functional impact of frequent platelet donations and associated lymphopenia on the response to neoantigens. We conducted a prospective study of 102 platelet donors (HIV uninfected) who were naive to meningococcal vaccination recruited at Brigham and Women's Hospital. One dose of quadrivalent meningococcal conjugate vaccine was administered. Seroresponse was defined as a fourfold increase of serum bactericidal antibody titers and seroprotection was defined as postvaccination titers of ≥1:8, for each of the 4 vaccine antigens (A, C, W, and Y). Mean age of participants was 61 years, 69% were male, and medial number of platelet donations in prior year was 14 (interquartile range, 4-20). Frequent platelet donors had a low CD4 count (14% with ≤200/μL and 34% with ≤350/μL). Seroresponse rates varied from 68% for serogroup Y to 86% for serogroup A and were higher for participants with baseline titers of <1:8. Postvaccination seroprotection rates varied from 76% for serogroup Y to 96% for serogroup A. After adjustments for age, sex, and frequent donations, lower total lymphocyte or lower CD4 counts were not associated with lower responses. These data suggest no impairment by plateletpheresis-associated lymphopenia on response to these neoantigens. This trial was registered at www.clinicaltrials.gov as #NCT04224311., (© 2023 by The American Society of Hematology.)

The introduction of synthetic dyes completely changed the industrial production and use of colorants for art materials. From the synthesis of the first synthetic dye, mauveine, in 1856 until today, artists have enjoyed a wider range of colors and selection of chemical properties than was ever available before. However, the introduction of synthetic dyes introduced a wider variety and increased the complexity of the chemical structures of marketed dyes. This work looks towards the analysis of synthetically dyed objects in heritage collections, applying an extraction protocol based on the use of ammonia, which is considered favorable for natural anthraquinone dyes but has never before been applied to acid synthetic dyes. This work also presents an innovative cleanup step based on the use of an ion pair dispersive liquid-liquid microextraction for the purification and preconcentration of historical synthetic dyes before analysis. This approach was adapted from food science analysis and is applied to synthetic dyes in heritage science for the first time in this paper. The results showed adequate recovery of analytes and allowed for the ammonia-based extraction method to be applied successfully to 15 samples of suspected azo dyes from the Azienda Coloranti Nazionali e Affini (ACNA) synthetic dye collection, identified through untargeted HPLC-HRMS analyses.

To date, it is still not possible to obtain exhaustive information about organic materials in cultural heritage without sampling. Nonetheless, when studying unique objects with invaluable artistic or historical significance, preserving their integrity is a priority. In particular, organic dye identification is of significant interest for history and conservation research, but it is still hindered by analytes' low concentration and poor fastness. In this work, a minimally invasive approach for dye identification is presented. The procedure is designed to accompany noninvasive analyses of inorganic substances for comprehensive studies of complex cultural heritage matrices, in compliance with their soundness. Liquid extraction of madder, turmeric, and indigo dyes was performed directly from paint layers and textiles. The extraction was supported by hydrogels, which themselves can undergo multitechnique analyses in the place of samples. After extraction, Ag colloid pastes were applied on the gels for SERS analyses, allowing for the identification of the three dyes. For the HPLC-MS/MS analyses, re-extraction of the dyes was followed by a clean-up step that was successfully applied on madder and turmeric. The colour change perceptivity after extraction was measured with colorimetry. The results showed ΔE values mostly below the upper limit of rigorous colour change, confirming the gentleness of the procedure.

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir-an orally available inhibitor of the 3-chymotrypsin-like cysteine protease-has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using mouse models of SARS-CoV-2 infection, we show that nirmatrelvir administration blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)