Oral History Interview with James Kaufman (SOH-071 video recording and transcript)

In this interview, Jim Kaufman, the former managing director of the Modern Theatre and the Theatre Department at Suffolk University, discusses his educational background, early career, and his start at Suffolk University. He describes the evolution of Suffolk’s theatre program and the university’s growth from the 1990s until 2021. He also reflects on the key figures and moments that defined his experience at Suffolk University, including the value of collaboration and the importance of student-led projects.https://dc.suffolk.edu/soh/1057/thumbnail.jp

Effets de différents adjuvants de la famille de la toxine du choléra sur les lymphocytes T CD4 dans un modèle murin d'immunisation intrarectale avec des pseudoparticules virales de rotavirus

La vaccination muqueuse est un moyen efficace de lutter contre les pathogènes qui utilisent les muqueuses comme porte d entrée. Cependant, la vaccination muqueuse avec des antigènes non réplicatifs nécessite l utilisation d adjuvants. Les molécules de la famille de la toxine du choléra, l entérotoxine thermolabile d E.coli (LT), la toxine du choléra (CT) ainsi que le mutant LT-R192G et les sous-unités B non toxiques de ces toxines (LTB et CTB) ont été montrées augmenter les réponses immunitaires contre des antigènes coadministrés par voie muqueuse. Cependant leur mécanisme d action est complexe et reste encore mal connu et des différences entre molécules entières et sous-unités B ont été rapportées ainsi que, pour une même molécule, des différences selon le modèle utilisé. Dans ce travail, nous avons étudié les effets de ces cinq molécules sur les réponses anticorps ainsi que sur les lymphocytes T CD4 dans un modèle murin d immunisation intrarectale avec des pseudoparticules virales de rotavirus (VLP-2/6). Chez les souris non immunisées, nous avons montré que ces molécules, à l exception de la CTB, diminuent in vitro les lymphocytes T régulateurs naturels CD4+CD25+Foxp3+, probablement par un mécanisme d apoptose. Chez les souris immunisées, toutes les molécules étudiées induisent une même réponse anticorps sérique et fécale spécifique des VLP-2/6, qu il s agisse des molécules entières connues pour leur fort pouvoir adjuvant ou des sous-unités B qui, elles, ont été rapportées avoir un plus faible effet adjuvant voire un effet tolérogène dans certaines études. Concernant la réponse T CD4, les réponses spécifiques de l antigène et de l adjuvant ont été analysées. Des différences importantes ont été mises en évidence entre ces molécules. Notamment, seules les molécules entières (LT, LT-R192G et CT) induisent la production d IL-2 et l activation de lymphocytes T CD4+CD25+Foxp3- mémoires spécifiques de l antigène tout en permettant la mise en place d une régulation médiée par des lymphocytes T régulateurs CD4+CD25+Foxp3+ (boucle d autorégulation), qui pourraient jouer un rôle majeur lors d une réponse secondaire, afin d éviter les réactions inflammatoires délétères. Malgré ces différences, toutes les molécules étudiées induisent la production d IL-17, suggérant le rôle majeur de cette cytokine dans l effet adjuvant.L influence de la voie d administration sur ces effets est en cours d étude grâce à la comparaison avec la voie intranasaleMucosal immunization is an important goal of vaccine development to protect against pathogens that use mucosa as portals of entry. However, the use of non-replicating antigens requires the addition of adjuvants.Cholera-like enterotoxins, cholera toxin (CT) from Vibrio cholerae and the heat-labile enterotoxin (LT) from toxinogenic strains of E. coli, as well as the mutant LR-192G and their B subunits (CTB and LTB) have been shown to increase immune responses against unrelated co-administered antigens by mucosal routes. However, their mechanism of action is very complex and not completely understood and differences exist between holotoxins and B subunits and within molecules, differences exist between the models used.In this work, we have studied the effects of these five molecules on antibody responses and on CD4+ T cell responses in a murine model of intrarectal immunization using rotavirus-like particles (2/6-VLP). In non-immunized mice, we have shown that all molecules, except CTB, decreased CD4+CD25+Foxp3+ natural regulatory T cells, probably by induction of apoptosis.In immunized mice, all molecules induced similar VLP-2/6 specific systemic and fecal antibody responses, teither he holotoxins, which are well known for their strong adjuvanticity or their B subunits with a less strong adjuvanticity but with also a tolerogenic effect in some studies.Regarding the CD4+ T cell response, antigen- and adjuvant- specific responses have been analysed. Important differences have been highlighted between the molecules. Among others things, only whole toxins (LT, LT-R192G and CT) trigger IL-2 production and activation of antigen specific memory CD4+CD25+Foxp3- T cells and at the same time antigen specific CD4+CD25+Foxp3+ regulatory T cells are activated which may control the effector response (Feedback loop regulation) and avoid deleterious inflammation. In spite of these differences, all studied molecules triggered IL-17 production, suggesting the major role of this cytokine in adjuvanticity. We are currently comparing the intrarectal and intranasl routes in order to evaluate the role played by the route of immunisation in different effects of these moleculesDIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

Gene expression profiling in blood from cerebral malaria patients and mild malaria patients living in Senegal

International audienceBACKGROUND:Plasmodium falciparum malaria remains a major health problem in Africa. The mechanisms of pathogenesis are not fully understood. Transcriptomic studies may provide new insights into molecular pathways involved in the severe form of the disease.METHODS:Blood transcriptional levels were assessed in patients with cerebral malaria, non-cerebral malaria, or mild malaria by using microarray technology to look for gene expression profiles associated with clinical status. Multi-way ANOVA was used to extract differentially expressed genes. Network and pathways analyses were used to detect enrichment for biological pathways.RESULTS:We identified a set of 443 genes that were differentially expressed in the three patient groups after applying a false discovery rate of 10%. Since the cerebral patients displayed a particular transcriptional pattern, we focused our analysis on the differences between cerebral malaria patients and mild malaria patients. We further found 842 differentially expressed genes after applying a false discovery rate of 10%. Unsupervised hierarchical clustering of cerebral malaria-informative genes led to clustering of the cerebral malaria patients. The support vector machine method allowed us to correctly classify five out of six cerebral malaria patients and six of six mild malaria patients. Furthermore, the products of the differentially expressed genes were mapped onto a human protein-protein network. This led to the identification of the proteins with the highest number of interactions, including GSK3B, RELA, and APP. The enrichment analysis of the gene functional annotation indicates that genes involved in immune signalling pathways play a role in the occurrence of cerebral malaria. These include BCR-, TCR-, TLR-, cytokine-, FcεRI-, and FCGR- signalling pathways and natural killer cell cytotoxicity pathways, which are involved in the activation of immune cells. In addition, our results revealed an enrichment of genes involved in Alzheimer's disease.CONCLUSIONS:In the present study, we examine a set of genes whose expression differed in cerebral malaria patients and mild malaria patients. Moreover, our results provide new insights into the potential effect of the dysregulation of gene expression in immune pathways. Host genetic variation may partly explain such alteration of gene expression. Further studies are required to investigate this in African populations

Puerperal uterine inversion managed by the uterine balloon tamponade

The uterine inversion is a rare and severe puerperal complication. Uncontrolled cord traction and uterine  expression are the common causes described.We report a case of uterine inversion stage III caused by poor management of the third stage of labor. It was about a 20 years old primigravida referred in our unit for postpartum hemorrhage due to uterine atony. After manual reduction of the uterus, the use of intra uterine balloon tamponade helped to stop the hemorrhage. The uterine inversion is a rare complication that may cause maternel death. The diagnosis is clinical and its management must be immediate to avoid maternal complications.Key words: Uterine inversion, postpartum hemorrhage, uterine balloon tamponad

Attitudes, beliefs, and practices of key opinion leaders (KOL) and providers about emergency contraception (EC) in Senegal

In 2010, the Reproductive Health Division in Senegal, with support from Population Council, performed an assessment of the emergency contraception (EC) integration process into the national health system through a national forum on EC. This forum revealed that there was a real promotional problem regarding EC in the national health system despite the efforts made. There was widespread lack of public awareness of the product, rumors concerning EC due to the sensitive nature of the product, low inclusion of EC in routine service delivery, especially during initial counseling in family planning awareness campaigns , and a better method of keeping service providers at pharmacies informed about EC provisions and protocols. This study’s overall objective is collecting information from Key Opinion Leaders (KOLs) and providers about their EC knowledge, attitudes, and practices, and understanding their options and perceptions that may influence EC policies and programs. Results from the study indicated an urgent need to improve EC accessibility and the quality of services

Evaluation de L’efficacite et de L’acceptabilite de la Prise en Charge Ambulatoire de la Malnutrition Aigue Chez les Enfants Vivants Avec le Vih (Evvih) Au Centre Hospitalier Regional De Ziguinchor (Chrz)/ Senegal

Objectif : La malnutrition aigüe est fréquente chez les enfants infectés par le VIH. L’objectif de notre travail était d’évaluer l’efficacité et l’acceptabilité des protocoles de récupération nutritionnelle ambulatoire basés sur les aliments prêts à l’emploi (ATPE) chez les EVVIH. Matériel et méthodes : Il s’agissait d’une étude prospective, réalisée à la pédiatrie du CHRZ du 7 janvier au 31 Septembre 2018. Ont été inclus les EVVIH, âgés de 6 mois à 19 ans présentant une malnutrition aigüe modérée ou sévère sans complication. Le suivi était bimensuel jusqu’à l’atteinte du poids cible. Un bilan clinico-biologique et anthropométrique, la délivrance des ATPE et la mesure de l’observance aux prescriptions étaient réalisés. Résultats : Douze enfants vivants avec le VIH ont été inclus dont 3 MAS et 9 MAM sur un total de 25 enfants suivis soit une prévalence de 48%. Le sexe ratio (1,4) en faveur des garçons. L’âge médian (9,5 ans). Ils étaient sous ARV dans 92% des cas. La moitié des patients avait un âge > à 10 ans. La toux était le symptôme le plus retrouvé (67%) suivie de la diarrhée (58,3%), des vomissements (8,3%), une otite moyenne chronique (8,3%). La charge virale au début de l'étude a montré (5cas < 50 copies, 3cas < 5000 copies, 4cas > 15 000 copies). Le taux d'hémoglobine était < 10g/dl dans 92% des cas. Un problème d'observance de la prise d'ATPE a été noté dans 58,3%. Onze enfants ont atteint leur poids cible. Nous n’avons pas noté de perdu de vu ni d’hospitalisé. Conclusion : Les ATPE bien que efficaces, pausent souvent un problème d’acceptabilité. On gagnerait à améliorer le gout et la présentation pour permettre une meilleure observance. Objective: Acute malnutrition is common in children with HIV infection. The objective of our work was to evaluate the efficiency and acceptability of ambulatory nutritional recovery protocols (ATPE) based on ready-to-use food) in HIV-positive children (EVVIH). Methods: This was a prospective study, conducted at the pediatrics of the regional hospital center of Ziguinchor (CHRZ) from January 7th to September 31st, 2018. We included all HIV-positive children (EVVIH), aged between 6 months and 19 years with relatively acute or severe malnutrition without complication. The follow-up was done every two months until target weight was reached. A clinic-biological and anthropometric report, the issuing of ATPE and the measurement of compliance with prescriptions were carried out. Results: We chose 12 children living with HIV, including 3 MAS and 9 MAM out of a total of 25 children followed, with a prevalence of 48%. The sex ratio (1.4) was in favor of boys. The medium age was (9.5 years). They were under ARV in 92% of cases. Half of the patients were > 10 years old. Coughing was the most common symptom (67%) followed by diarrhea (58.3%), vomiting (8.3%), medium chronic otitis (8.3%). The viral affection at the beginning of the study showed (5cases <50 copies, 3cases <5000 copies, 4cases> 15,000 copies). The hemoglobin level was <10g / dl in 92% of cases. A problem of respect of ATPE taking was noted in 58.3%. Eleven children reached their target weight. We did not notice any loss ofsight and no child was hospitalized. Conclusion: Although the ATPE are efficient, they often cause a problem of acceptability. It would be better to improve the taste and the presentation to allow a better observance

NCR3 polymorphism, haematological parameters, and severe malaria in Senegalese patients

Background Host factors, including host genetic variation, have been shown to influence the outcome of Plasmodium falciparum infection. Genome-wide linkage studies have mapped mild malaria resistance genes on chromosome 6p21, whereas NCR3-412 polymorphism (rs2736191) lying within this region was found to be associated with mild malaria. Methods Blood samples were taken from 188 Plasmodium falciparum malaria patients (76 mild malaria patients, 85 cerebral malaria patients, and 27 severe non-cerebral malaria patients). NCR3-412 (rs2736191) was analysed by sequencing, and haematological parameters were measured. Finally, their association with clinical phenotypes was assessed. Results We evidenced an association of thrombocytopenia with both cerebral malaria and severe non-cerebral malaria, and of an association of high leukocyte count with cerebral malaria. Additionally, we found no association of NCR3-412 with either cerebral malaria, severe non-cerebral malaria, or severe malaria after grouping cerebral malaria and severe non-cerebral malaria patients. Conclusions Our results suggest that NCR3 genetic variation has no effect, or only a small effect on the occurrence of severe malaria, although it has been strongly associated with mild malaria. We discuss the biological meaning of these results. Besides, we confirmed the association of thrombocytopenia and high leukocyte count with severe malaria phenotypes

Estimating the contribution of key populations towards the spread of <scp>HIV</scp> in Dakar, Senegal

Introduction: Key populations including female sex workers (FSW) and men who have sex with men (MSM) bear a disproportionate burden of HIV. However, the role of focusing prevention efforts on these groups for reducing a country’s HIV epidemic is debated. We estimate the extent to which HIV transmission among FSW and MSM contributes to overall HIV transmission in Dakar, Senegal, using a dynamic assessment of the population attributable fraction (PAF). Methods: A dynamic transmission model of HIV among FSW, their clients, MSM and the lower-risk adult population was parameterized and calibrated within a Bayesian framework using setting-specific demographic, behavioural, HIV epidemiological and antiretroviral treatment (ART) coverage data for 1985 to 2015. We used the model to estimate the 10-year PAF of commercial sex between FSW and their clients, and sex between men, to overall HIV transmission (defined as the percentage of new infections prevented when these modes of transmission are removed). In addition, we estimated the prevention benefits associated with historical increases in condom use and ART uptake, and impact of further increases in prevention and treatment. Results: The model projections suggest that unprotected sex between men contributed to 42% (2.5 to 97.5th percentile range 24 to 59%) of transmissions between 1995 and 2005, increasing to 64% (37 to 79%) from 2015 to 2025. The 10-year PAF of commercial sex is smaller, diminishing from 21% (7 to 39%) in 1995 to 14% (5 to 35%) in 2015. Without ART, 49% (32 to 71%) more HIV infections would have occurred since 2000, when ART was initiated, whereas without condom use since 1985, 67% (27 to 179%) more HIV infections would have occurred, and the overall HIV prevalence would have been 60% (29 to 211%) greater than what it is now. Further large decreases in HIV incidence (68%) can be achieved by scaling up ART in MSM to 74% coverage and reducing their susceptibility to HIV by two-thirds through any prevention modality. Conclusions: Unprotected sex between men may be an important contributor to HIV transmission in Dakar, due to suboptimal coverage of evidence-informed interventions. Although existing interventions have effectively reduced HIV transmission among adults, it is crucial that further strategies address the unmet need among MSM

Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G

LT-R192G, a mutant of the thermolabile enterotoxin of E. coli, is a potent adjuvant of immunization. Immune responses are generally analyzed at the end of protocols including at least 2 administrations, but rarely after a prime. To investigate this point, we compared B and T cell responses in mice after one and two intrarectal immunizations with 2/6 rotavirus-like particles (2/6-VLP) and LT-R192G. After a boost, we found, an unexpected lower B cell expansion measured by flow cytometry, despite a secondary antibody response. We then analyzed CD4+CD25+Foxp3+ regulatory T cells (Tregs) and CD4+CD25+Foxp3− helper T cells after in vitro (re)stimulation of mesenteric lymph node cells with the antigen (2/6-VLP), the adjuvant (LT-R192G) or both. 2/6-VLP did not activate CD4+CD25+Foxp3− nor Foxp3+ T cells from non-immunized and 2/6-VLP immunized mice, whereas they did activate both subsets from mice immunized with 2/6-VLP in the presence of adjuvant. LT-R192G dramatically decreased CD4+CD25+Foxp3+ T cells from non-immunized and 2/6-VLP immunized mice but not from mice immunized with 2/6-VLP and adjuvant. Moreover, in this case, LT-R192G increased Foxp3 expression on CD4+CD25+Foxp3+ cells, suggesting specific Treg activation during the recall. Finally, when both 2/6-VLP and LT-R192G were used for restimulation, LT-R192G clearly suppressed both 2/6-VLP-specific CD4+CD25+Foxp3− and Foxp3+ T cells. All together, these results suggest that LT-R192G exerts different effects on CD4+CD25+Foxp3+ T cells, depending on a first or a second contact. The unexpected immunomodulation observed during the recall should be considered in designing vaccination protocols

Cholera-Like Enterotoxins and Regulatory T cells

Cholera toxin (CT) and the heat-labile enterotoxin of E. coli (LT), as well as their non toxic mutants, are potent mucosal adjuvants of immunization eliciting mucosal and systemic responses against unrelated co-administered antigens in experimental models and in humans (non toxic mutants). These enterotoxins are composed of two subunits, the A subunit, responsible for an ADP-ribosyl transferase activity and the B subunit, responsible for cell binding. Paradoxically, whereas the whole toxins have adjuvant properties, the B subunits of CT (CTB) and of LT (LTB) have been shown to induce antigen specific tolerance when administered mucosally with antigens in experimental models as well as, recently, in humans, making them an attractive strategy to prevent or treat autoimmune or allergic disorders. Immunomodulation is a complex process involving many cell types notably antigen presenting cells and regulatory T cells (Tregs). In this review, we focus on Treg cells and cholera-like enterotoxins and their non toxic derivates, with regard to subtype, in vivo/in vitro effects and possible role in the modulation of immune responses to coadministered antigens