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Abstract Novel approaches for malaria prophylaxis remain important. Synthetic DNA-encoded monoclonal antibodies (DMAbs) are a promising approach to generate rapid, direct in vivo host-generated mAbs with potential benefits in production simplicity and distribution coupled with genetic engineering. Here, we explore this approach in a malaria challenge model. We engineered germline-reverted DMAbs based on human mAb clones CIS43, 317, and L9 which target a junctional epitope, major repeat, and minor repeat of the Plasmodium falciparum circumsporozoite protein (CSP) respectively. DMAb variants were encoded into a plasmid vector backbone and their expression and binding profiles were characterized. We demonstrate long-term serological expression of DMAb constructs resulting in in vivo efficacy of CIS43 GL and 317 GL in a rigorous mosquito bite mouse challenge model. Additionally, we engineered an Fc modified variant of CIS43 and L9-based DMAbs to ablate binding to C1q to test the impact of complement-dependent Fc function on challenge outcomes. Complement knockout variant DMAbs demonstrated similar protection to that of WT Fc DMAbs supporting the notion that direct binding to the parasite is sufficient for the protection observed. Further investigation of DMAbs for malaria prophylaxis appears of importance.

Latent Epstein-Barr virus (EBV) infection is associated with several types of cancer. Several clinical studies have targeted EBV antigens as immune therapeutic targets with limited efficacy of EBV malignancies, suggesting that additional targets might be important. BamHI-A rightward frame 1 (BARF1) is an EBV antigen that is highly expressed in EBV+ nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC). BARF1 antigen can transform human epithelial cells in vivo. BARF1-specific antibodies and cytotoxic T cells were detected in some EBV+ NPC patients. However, BARF1 has not been evaluated as an antigen in the context of therapeutic immunization. Its possible importance in this context is unclear. Here, we developed a synthetic-DNA-based expression cassette as immunotherapy targeting BARF1 (pBARF1). Immunization with pBARF1 induced potent antigen-specific humoral and T cell responses in vivo. Immunization with pBARF1 plasmid impacted tumor progression through the induction of CD8+ T cells in novel BARF1+ carcinoma models. Using an in vivo imaging system, we observed that pBARF1-immunized animals rapidly cleared cancer cells. We demonstrated that pBARF1 can induce antigen-specific immune responses that can impact cancer progression. Further study of this immune target is likely important as part of therapeutic approaches for EBV+ malignancies.

There is currently no licensed SARS-CoV-2 vaccine. Here, the authors generate an optimized DNA vaccine candidate encoding the SARS-CoV-2 spike antigen, demonstrating induction of specific T cells and neutralizing antibody responses in mice and guinea pigs. These initial results support further development of this vaccine candidate.

Neisseria gonorrhoeae

The need for a malaria vaccine is indisputable. A single vaccine for Plasmodium pre-erythrocytic stages targeting the major sporozoite antigen circumsporozoite protein (CSP) has had partial success. Additionally, CD8+ T cells targeting liver-stage (LS) antigens induced by live attenuated sporozoite vaccines were associated with protection in human challenge experiments. To further evaluate protection mediated by LS antigens, we focused on exported pre-erythrocytic proteins (exported protein 1 (EXP1), profilin (PFN), exported protein 2 (EXP2), inhibitor of cysteine proteases (ICP), transmembrane protein 21 (TMP21), and upregulated in infective sporozoites-3 (UIS3)) expressed in all Plasmodium species and designed optimized, synthetic DNA (synDNA) immunogens. SynDNA antigen cocktails were tested with and without the molecular adjuvant plasmid IL-33. Immunized animals developed robust T cell responses including induction of antigen-specific liver-localized CD8+ T cells, which were enhanced by the co-delivery of plasmid IL-33. In total, 100% of mice in adjuvanted groups and 71%−88% in non-adjuvanted groups were protected from blood-stage disease following Plasmodium yoelii sporozoite challenge. This study supports the potential of synDNA LS antigens as vaccine components for malaria parasite infection.

Solid pseudopapillary epithelial neoplasms of the pancreas are rare entities, first described in 1959 by Frantz. These tumors represent less than 2% of pancreatic cancers and mainly affect young women. They can reach a significant size and its radiological features can lead to diagnostic pitfalls, such as gastrointestinal stromal tumors, which are rare soft-tissue sarcomas that can appear anywhere along the gastrointestinal tract. Clinicians and radiologists need to be aware of the existing diagnostic pitfalls between these two entities, because of their possible similarities. We report here the case of a 33-year-old woman with a solid pseudopapillary epithelial neoplasms of the pancreas initially misdiagnosed as an exophytic gastric stromal tumor.

Abstract Introduction Abdominal surgical emergencies remain prevalent in various healthcare settings, particularly in regions with limited access to basic surgical care, such as Africa. The aim of this literature review is to systematically assess publications on abdominal surgical emergencies in adults in sub-Saharan Africa to estimate their prevalence and mortality rate. Methodology A systematic review was conducted. The latest search was performed on October 31, 2022. We estimated the pooled prevalence with a 95% confidence interval (CI) for each abdominal surgical emergency, as well as overall postoperative mortality and morbidity rates. Results A total of 78 studies were included, and 55.1% were single-center retrospective and monocentric studies. The mean age of the patients was 32.5 years, with a sex ratio of 1.94. The prevalence of each abdominal surgical emergency among all of them was as follows: appendicitis: 30.0% (95% CI: 26.1–33.9); bowel obstruction: 28.6% (95% CI: 25.3–31.8); peritonitis: 26.6% (95% CI: 22.2–30.9); strangulated hernias: 13,4% (95% CI: 10,3–16,5) and abdominal trauma: 9.4% (95% CI: 7.5–11.3). The prevalence of complications was as follows: mortality rate: 7.4% (95% CI: 6.0-8.8); overall postoperative morbidity: 24.2% (95% CI: 19.4–29.0); and surgical site infection 14.4% (95% CI: 10.86–18.06). Conclusion Our study revealed a high prevalence of postoperative complications associated with abdominal surgical emergencies in sub-Saharan Africa. More research and efforts should be made to improve access and quality of patient care.

Introduction. Ixodes ticks are vectors for pathogens of many infectious diseases. Recently, during the study of Rhipicephalus geigyi ticks collected from livestock in the Republic of Guinea, a new multicomponent flavi-like RNA virus, called Kindia tick virus (KITV), was discovered with an unusual mechanism for the implementation of genetic information. The aim of the work is to detect and study the genetic diversity of KITV in ixodes ticks collected in the territory of the Kindia province of the Republic of Guinea. Material and methods. In 2021, 324 specimens of ticks of the species Amblyomma variegatum, Rh. geigyi, Rh. annulatus, Rh. decoloratus, Rh. senegalensis were collected from cattle. The detection of viral RNA was carried out in individual samples of ticks by RT-PCR, followed by the determination of the nucleotide sequence and phylogenetic analysis. Results and discussion. KITV detection rates in ticks of the species Rh. geigyi was 12.2%, Rh. annulatus 4.4%, Rh. decoloratus 3.3%. However, the KITV genetic material has not been identified in Am. variegatum ticks, which are one of the dominant species in West Africa. For all virus isolates, a partial nucleotide sequences of each of the four viral segments (GenBank, OK345271OK345306) were determined. The phylogenetic analysis showed a high level of identity (98.599.8%) for each of the four segments of the viral genome with those previously found in the Republic of Guinea. The obtained KITV isolates are most genetically close to Mogiana tick virus, which was previously detected in South America in Rh. microplus ticks and significantly differed from other multicomponent viruses circulating in Europe and Asia, including the Russian Federation. Conclusion. KITV genetic material was found in three species of ixodid ticks collected from livestock in a number of prefectures of the Republic of Guinea. The infection rate in ticks was 3.312.2%. The continuation of research in this direction remains relevant.

Ultra-fine-grained (UFG) Al-1050 processed by equal channel angular pressing and UFG Al-Mg-Cu-Mn processed by high-pressure torsion (HPT) were embossed at both room temperature and 300 degC, with the aim of producing micro-channels. The behaviour of Al alloys during the embossing process was analysed using finite element modelling. The cold embossing of both Al alloys is characterized by a partial pattern transfer, a large embossing force, channels with oblique sidewalls and a large failure rate of the mould. The hot embossing is characterized by straight channel sidewalls, fully transferred patterns and reduced loads which decrease the failure rate of the mould. Hot embossing of UFG Al-Mg-Cu-Mn produced by HPT shows a potential of fabrication of microelectromechanical system components with micro channels. [ABSTRACT FROM AUTHOR]

Abstract Malaria is the leading cause of morbidity and mortality in Mali. Between 2017 and 2020, the number of cases increased in the country, with 2,884,827 confirmed cases and 1454 reported deaths in 2020. We performed a malaria risk stratification at the health district level in Mali with a view to proposing targeted control interventions. Data on confirmed malaria cases were obtained from the District Health Information Software 2, data on malaria prevalence and mortality in children aged 6–59 months from the 2018 Demographic and Health Survey, entomological data from Malian research institutions working on malaria in the sentinel sites of the National Malaria Control Program (NMCP), and environmental data from the National Aeronautics and Space Administration. A stratification of malaria risk was performed. Targeted malaria control interventions were selected based on spatial heterogeneity of malaria incidence, malaria prevalence in children, vector resistance distribution, health facility usage, child mortality, and seasonality of transmission. These interventions were discussed with the NMCP and the different funding partners. In 2017–2019, median incidence across the 75 health districts was 129.34 cases per 1000 person-years (standard deviation = 86.48). Risk stratification identified 12 health districts in very low transmission areas, 19 in low transmission areas, 20 in moderate transmission areas, and 24 in high transmission areas. Low health facility usage and increased vector resistance were observed in high transmission areas. Eight intervention combinations were selected for implementation. Our work provides an updated risk stratification using advanced statistical methods to inform the targeting of malaria control interventions in Mali. This stratification can serve as a template for continuous malaria risk stratifications in Mali and other countries.

A robust epidemic-prone disease surveillance system is a critical component of public health infrastructure and supports compliance with the International Health Regulations (IHR). One digital health platform that has been implemented in numerous low- and middle-income countries is the District Health Information System Version 2 (DHIS2). In 2015, in the wake of the Ebola epidemic, the Ministry of Health in Guinea established a strategic plan to strengthen its surveillance system, including adoption of DHIS2 as a health information system that could also capture surveillance data. In 2017, the DHIS2 platform for disease surveillance was piloted in two regions, with the aim of ensuring the timely availability of quality surveillance data for better prevention, detection, and response to epidemic-prone diseases. The success of the pilot prompted the national roll-out of DHIS2 for weekly aggregate disease surveillance starting in January 2018. In 2019, the country started to also use the DHIS2 Tracker to capture individual cases of epidemic-prone diseases. As of February 2020, for aggregate data, the national average timeliness of reporting was 72.2%, and average completeness 98.5%; however, the proportion of individual case reports filed was overall low and varied widely between diseases. While substantial progress has been made in implementation of DHIS2 in Guinea for use in surveillance of epidemic-prone diseases, much remains to be done to ensure long-term sustainability of the system. This paper describes the implementation and outcomes of DHIS2 as a digital health platform for disease surveillance in Guinea between 2015 and early 2020, highlighting lessons learned and recommendations related to the processes of planning and adoption, pilot testing in two regions, and scale up to national level.

Les cardiopathies congénitales surviennent dans 0.5-1% des naissances. La prise en charge d’enfants souffrant de malformation cardiaque nécessite un centre adapté, un matériel médical adéquat et des connaissances particulières tant sur le plan anesthésique que chirurgical. L’objectif de ce travail était d’évaluer la prise en charge anesthésique de ces cardiopathies dans notre centre après une première année d’activité et de comparer les résultats obtenus aux données de la littérature. Nous avons mené une étude rétrospective, descriptive sur une année allant de janvier à décembre 2017. Ont été inclus tous les patients opérés au cours de cette période pour une cure de cardiopathie congénitale sous circulation extracorporelle. Nous avons colligé 80 dossiers de patients opérés pour une cardiopathie congénitale. Parmi ces 80 patients, 60 ont été opéré sous CEC soit un taux de 75%. L’âge moyen de nos patients était de 7,41 ans avec un sex- ratio de 1,22. La durée de la CEC était en moyenne de 82,82 mn et la durée moyenne du clampage aortique était de 58,31 mn. 70% des patients ont eu des catécholamines en fin d’intervention. La complication la plus fréquente en post opératoire était la défaillance cardiaque droite (69%). La durée moyenne de séjour en réanimation était de 4,33 jours. Nous avons noté le décès d’un patient portant la mortalité à 1,6%. Les cardiopathies congénitales sont complexes et très variables. Avec l’amélioration des techniques de prise en charge, leur morbi-mortalité a fortement diminué.

Castor bean (Ricinus communis) seeds contain ricinine, an alkaloid with insecticidal and insectistatic activities. Elicitation with salicylic acid (SA) has proven to stress R. communis and might modify the ricinine concentration. The aim of this study was to evaluate the concentration of ricinine in the bagasse of seeds from R. communis elicited with exogenous SA under greenhouse conditions. Plants were grown and divided into five groups, which were sprayed with SA and drench with 50 mL 60 days after sowing with concentrations of SA (0, 100, 300, 600 and 900 µM). Clusters were mixed and separated according to the treatment, and dried. The seeds were ground, the oil was extracted by Soxhlet with hexane, and then the bagasse was extracted with methanol. Ricinine was determined by HPLC. Elicitation did not change the plant height or diameter; the control group had 9.17 µg mL−1 of ricinine; and the concentrations followed a hormesis curve with the peak at 300 µM of SA that had a ricinine concentration of 18.25 µg mL−1. Elicitation with SA might be a cost-effective technique to increase ricinine from R. communis bagasse.

In the wake of the 2014–2016, West Africa Ebola virus disease (EVD) outbreak, the Government of Guinea recognized an opportunity to strengthen its national laboratory system, incorporating capacity and investments developed during the response. The Ministry of Health (MOH) identified creation of a holistic, safe, secure, and timely national specimen referral system as a priority for improved detection and confirmation of priority diseases, in line with national Integrated Disease Surveillance and Response guidelines. The project consisted of two parts, each led by different implementing partners working collaboratively together and with the Ministry of Health: the development and approval of a national specimen referral policy, and pilot implementation of a specimen referral system, modeled on the policy, in three prefectures. This paper describes the successful execution of the project, highlighting the opportunities and challenges of building sustainable health systems capacity during and after public health emergencies, and provides lessons learned for strengthening national capabilities for surveillance and disease diagnosis.

L'anesthésie des personnes âgées de 65 ans et plus en urgence reste complexe. La survenue d'incidents peropératoires et en l'occurrence l'hypotension artérielle est conditionnée par leur état de santé initial et par la qualité de la prise en charge péri-opératoire. L'étude a pour but de déterminer l'incidence de l'hypotension artérielle per-anesthésique du sujet âgé pour une chirurgie urgente et évaluer l'implication de certains facteurs dans sa survenue: âge, sexe, terrain, classe ASA, technique anesthésique. Une étude rétrospective descriptive et analytique a été réalisée aux blocs des urgences chirurgicales du CHU Aristide LE DANTEC allant du 1er mars 2014 au 28 février 2015. Nous avons colligé 210 patients sur 224 anesthésies en urgence du sujet âgé de 65 ans et plus, soit 10,93%. On notait 101 hommes et 109 femmes dont les 64,3% présentaient au moins une tare. L'évaluation de l'état préopératoire des patients a été faite avec la classification de l'American Society of Anesthesiology (ASA), avec 71% pour les classes ASA 1 et 2 et 29% pour les classes ASA 3 et 4. L'anesthésie locorégionale était la technique anesthésique la plus pratiquée (56,7%). L'hypotension artérielle peropératoire a été objectivée chez 28 patients soit 13,33%, dont 16 cas sous anesthésie générale et 12 cas sous anesthésie locorégionale. Elle était plus fréquente chez les patients de classe ASA élevée et un peu moins sur terrain d'HTA et de cardiopathie sous-jacente. L'anesthésie du sujet âgé en urgence expose à un risque d'hypotension artérielle peropératoire non négligeable notamment chez les patients de classes ASA élevée. Sa prévention repose sur une bonne évaluation préopératoire et une prise en charge anesthésique adéquate.

'Superior mesenteric artery syndrome is a rare complication occurring after surgical treatment for scoliosis. Surgical correction of the scoliotic spine produces vertical traction on the mesenteric artery and the narrowing of the aortomesenteric angle, hence the compression of the third part of the duodenum causing the syndrome. We here report the case of a young girl with an early form of superior mesenteric artery syndrome secondary to surgical correction of idiopathic scoliosis. The patient underwent posterior spinal fusion for idiopathic scoliosis. On the third postoperative day she experienced uncontrollable vomiting associated with no evacuation of faeces and no passing of flatus. Urgent abdominal CT scan was performed which allowed the diagnosis of superior mesenteric artery syndrome. Treatment consisted in the rest of the digestive tract associated with early parenteral nutrition and correction of fluid and electrolyte imbalances. Lacking evidence of clinical improvement, surgical indication was posed. The evolution was favourable with an uneventful postoperative recovery and the resumption of adequate food intake on the fourth postoperative day. The patient was discharged on the seventh postoperative day. Contributing factors are young age, long-limbed morphotype with BMI below 18. CT scan shows an important gastric dilatation associated with complete halt of the third part of the duodenum. The treatment is multidisciplinary, medical (first-line treatment) and surgical (if medical treatment do not help). A better knowledge of the predictors of medical treatment failure would reduce the length of hospital stay.

La prise en charge périopératoire des urgences chirurgicales abdominales reste une préoccupation majeure des anesthésistes du fait des désordres hémodynamiques et/ou métaboliques souvent présentes en préopératoire ; mais également des complications postopératoires auxquelles elles sont exposées. Les objectifs de ce travail étaient d'étudier les aspects épidémiologiques, diagnostiques, thérapeutiques et pronostiques des urgences abdominales. Etude rétrospective descriptive sur une période de 6 mois portant sur les patients âgés de plus de 16 ans opérés d'une urgence abdominale à l'hôpital Aristide Le Dantec. Les paramètres étudiés portaient sur les aspects épidémiologiques, diagnostiques, thérapeutiques et pronostiques des urgences chirurgicales abdominales. Nous avions colligé 161 cas, près de 20% de l'activité du service. L'âge moyen était de 41 ans [16, 80 ans]. Le sex ratio était de 2, 9. Le délai moyen de consultation était de 4,6 jours. Les péritonites étaient les pathologies les plus fréquentes (25,5%). La fréquence cardiaque moyenne des patients était de 92 bpm (battements/min)et 97 bpm pour ceux ayant eu une préparation hémodynamique préopératoire. La moyenne PAM était de 9,66 cmhg et 8,61 cmhg chez les patients préparés. 49,1% des patients étaient de la classe ASA1, 39,9% ASA2, 8,7% ASA3, 2,5% ASA4 et 0,6% ASA5. Une antibioprophylaxie était faite chez 46,30% des patients et 53,41% d'entre eux avaient eu une antibiothérapie.95,6% des patients avaient eu une anesthésie générale et 4,4% une rachianesthésie. La fréquence des incidents peropératoires était de 11,08%. La morbidité était de 4,3% et la mortalité 4,96%. La prise en charge des urgences chirurgicales abdominales doit être multidisciplinaire impliquant anesthésistes, chirurgiens et biologistes afin de réduire davantage le taux de morbimortalité qui reste de nos jours non négligeable.

En el presente trabajo se diseñó y aplicó un procedimiento para la planificación energética teniendo en cuenta los requerimientos de la NC-ISO 50001: 2011 ¨Gestión de la energía¨. El diseño tuvo como premisas requisitos de las normas internacionales relacionadas con la gestión de la energía ISO 50001: 2011, UNE 216301: 2007, DIN EN 16001, ANSI/MSE 2000: 2008 y de gestión de la calidad ISO 9001: 2008. Para la aplicación se seleccionó como caso de estudio la Empresa Oleohidráulica Cienfuegos, utilizándose herramientas y técnicas, tales como: trabajo con expertos, revisión de documentos, las herramientas de la Tecnología de Gestión Total Eficiente de la Energía y de calidad, obteniéndose como resultados la planificación energética, a través de la determinación de la estructura de consumo energético, las áreas de consumo significativo , lo que conllevó a establecer la línea base y meta energética de la organización. In this paper we designed and implemented a process for considering energy planning requirements of the NC-ISO 50001: 2011 ¨Energy Management¨. The premise was to design requirements of international standards related to energy management ISO 50001: 2011, UNE 216301: 2007, DIN EN 16001, ANSI / MSE 2000: 2008 and quality management ISO 9001: 2008. For application was selected as a case study Hydraulics Company Cienfuegos, using tools and techniques such as: working with experts, review of documents, tools Total Technology Management Energy Efficient and quality, obtaining as results the energy planning, through the determination of the structure of energy consumption, significant consumption areas, which led to establish base line and energy goal of the organization.