National Non-Communicable Diseases Conferences- A Platform to Inform Policies and Practices in Tanzania.

Background: Non-communicable diseases (NCDs) arise from diverse risk factors with differences in the contexts and variabilities in regions and countries. Addressing such a complex challenge requires local evidence. Tanzania has been convening stakeholders every year to disseminate and discuss scientific evidence, policies, and implementation gaps, to inform policy makers in NCDs responses. This paper documents these dissemination efforts and how they have influenced NCDs response and landscape in Tanzania and the region. Methods: Desk review was conducted through available MOH and conference organizers' documents. It had both quantitative and qualitative data. The review included reports of the four NCDs conferences, conference organization, and conduct processes. In addition, themes of the conferences, submitted abstracts, and presentations were reviewed. Narrative synthesis was conducted to address the objectives. Recommendations emanated from the conference and policy uptake were reviewed and discussed to determine the impact of the dissemination. Findings: Since 2019, four theme-specific conferences were organized. This report includes evidence from four conferences. The conferences convened researchers and scientists from research and training institutions, implementers, government agencies, and legislators in Tanzania and other countries within and outside Africa. Four hundred and thirty-five abstracts were presented covering 14 sub-themes on health system improvements, financing, governance, prevention intervention, and the role of innovation and technology. The conferences have had a positive effect on governments' response to NCDs, including health care financing, NCDs research agenda, and universal health coverage. Conclusion: The National NCDs conferences have provided suitable platforms where stakeholders can share, discuss, and recommend vital strategies for addressing the burden of NCDs through informing policies and practices. Ensuring the engagement of the right stakeholders, as well as the uptake and utilization of the recommendations from these platforms, remains crucial for addressing the observed epidemiological transition in Tanzania and other countries with similar contexts.

Non-communicable Diseases Week: Best Practices in Addressing the NCDs Burden from Tanzania.

Background: Five million people die every year from non-communicable diseases (NCDs) globally. In Tanzania, more than two-thirds of deaths are NCD-related. The country is investing in preventive and advocacy activities as well as interventions to reduce the burden. Of particular interest, the Ministry of Health (MoH) commemorates NCDs' week using a multisectoral and multi-stakeholders' approach. This paper highlights activities conducted during NCDs week with the aim of sharing lessons for other countries with similar context and burdens. Methods: A thorough review of official reports and the national strategic plans for NCDs was done including the 2020 and 2021 National NCDs' week reports, the National Strategic Plan for NCDs 2015-2020, and the National NCDs agenda. Findings: NCDs week is commemorated annually throughout the country involving the five key activities. First, community awareness and participation are encouraged through media engagement and community-based preventive and advocacy activities. Second, physical activities and sports festivals are implemented with a focus on developing and renovating infrastructures for sports and recreation. Third, health education is provided in schools to promote healthy behaviors for secondary school adolescents in transition to adulthood. Fourth, health service provision and exhibitions are conducted involving screening for hypertension, diabetes, obesity, alcohol use, and physical activities. The targeted screening of NCDs identified 10% of individuals with at least one NCD in 2020. In 2021, a third of all screened individuals were newly diagnosed with hypertension, and 3% were found to have raised blood glucose levels. Fifth, the national NCDs scientific conferences conducted within the NCDs week provide an avenue for stakeholders to discuss scientific evidence related to NCDs and recommend strategies to mitigate NCDs burden. Conclusion: The initiation of NCDs week has been a cornerstone in advocating for NCDs control and prevention in the country. It has created awareness on NCDs, encourage healthy lifestyles and regular screening for NCDs. The multi-stakeholder and multi-sectoral approaches have made the implementation of the mentioned activities feasible and impactful. This has set an example for the united efforts toward NCD control and prevention at national, regional, and global platforms while considering contextual factors during adoption and implementation.

Mitigating the Rising Burden of Non-Communicable Diseases through Locally Generated Evidence-Lessons from Tanzania.

Background: The burden of Non-Communicable Diseases (NCDs) is rapidly increasing globally, and low- and middle-income countries (LMICs) bear the brunt of it. Tanzania is no exception. Addressing the rising burden of NCDs in this context calls for renewed efforts and commitment by various stakeholders. This paper highlights local initiatives and strategies to combat NCDs in Tanzania and provides lessons for countries with similar contexts. Methods: We reviewed published and grey literature and conducted policy analysis on NCDs in Tanzania to examine the burden of NCDs and the national response addressing it. The documents included National NCD strategic plans, NCD research agenda, and reports from the World Diabetes Foundation and the World Health Organization. Moreover, a scoping review of ongoing NCD activities and programs in other countries was also conducted to supplement the evidence gathered. Results: The rising burden of NCDs as a result of the epidemiological transition in Tanzania called for the launching of a dedicated National NCD Control and Prevention Program. The Ministry of Health collaborates with local, national, and international partners on NCD prevention and curative strategies. This led to the development of important guidelines and policies on NCDs, including strengthening the capacity of health facilities and healthcare workers, increased community engagement and awareness of NCDs, and increased advocacy for more resources in NCD initiatives. Strong governmental commitment has been vital; this is demonstrated by a renewed commitment to the fight through national NCD week and related advocacy activities conducted annually. To ensure multi-stakeholders' engagement and political commitment, all these activities are coordinated at the Prime Minister's office and provide strong lessons for countries with contexts similar to Tanzania. Conclusion: Multi-stakeholders' engagement, innovative approaches, and coordinated governmental efforts to address NCDs have shone a light on addressing the burden of NCDs and may be sustainable if aligned with locally available resources. Such initiatives are recommended for adoption by other nations to address the burdens of NCDs.

Reduction of aerosols and splatter generated during ultrasonic scaling by adding food-grade thickeners to coolants: an in-vitro study.

OBJECTIVE: The effectiveness of using food-grade coolant thickener solutions on the amount of aerosols generated and splatter contamination spread distance during simulated ultrasonic scaling was examined. MATERIALS AND METHODS: The study was performed using a phantom lower jaw placed on a black box. Simulated ultrasonic scaling was performed for 2 min using four coolant solutions: distilled water (control), 2% wt. polyacrylic acid (PAA), 0.4% wt. xanthan gum (XA), and 0.4% wt. carboxymethyl cellulose (CMC). The simulation was repeated 10 times for each coolant group. The generated aerosols and droplets were quantified using a handheld particle counter, and the splatter contamination spread distance was evaluated by adding tracing fluorescent dye to the coolant reservoir supplying the scaler unit. One-way multivariate analysis of variance was performed to determine the difference among coolant groups (a = .05). RESULTS: The amount of aerosols and droplets and splatter contamination distance (p < .001) pertaining to the three food-grade coolant thickener solutions were considerably lower than those for the distilled water (control). The PAA group exhibited a significantly lower splatter contamination distance (p < .001) and a number of generated droplets (p = .031) than those of the XA group. The CMC group exhibited a significantly lower splatter contamination distance (p < .001) than that of the XA group. No statistically significant difference was observed between the PAA and CMC in terms of the three dependent variables (p > .05). CONCLUSION: The food-grade coolant thickeners could reduce the amount of generated aerosols and splatter contamination distance but not completely eliminate them. PAA and CMC solutions were more effective in reducing the aerosol/splatter during scaling compared to XA. CLINICAL RELEVANCE: Many dental procedures generate aerosols and splatter, which pose a potential risk to the patients and dental personnel, especially during the current COVID-19 pandemic.

Novel glycolipid agents for killing cisplatin-resistant human epithelial ovarian cancer cells.

BACKGROUND: Chemotherapy resistance is one of the major factors contributing to mortality from human epithelial ovarian cancer (EOC). Identifying drugs that can effectively kill chemotherapy-resistant EOC cells would be a major advance in reducing mortality. Glycosylated antitumour ether lipids (GAELs) are synthetic glycolipids that are cytotoxic to a wide range of cancer cells. They appear to induce cancer cell death in an apoptosis-independent manner. METHODS: Herein, the effectiveness of two GAELs, GLN and MO-101, in killing chemotherapy-sensitive and -resistant EOC cells lines and primary cell samples was tested using monolayer, non-adherent aggregate, and non-adherent spheroid cultures. RESULTS: Our results show that EOC cells exhibit a differential sensitivity to the GAELs. Strikingly, both GAELs are capable of inducing EOC cell death in chemotherapy-sensitive and -resistant cells grown as monolayer or non-adherent cultures. Mechanistic studies provide evidence that apoptotic-cell death (caspase activation) contributes to, but is not completely responsible for, GAEL-induced cell killing in the A2780-cp EOC cell line, but not primary EOC cell samples. CONCLUSIONS: Studies using primary EOC cell samples supports previously published work showing a GAEL-induced caspase-independent mechanism of death. GAELs hold promise for development as novel compounds to combat EOC mortality due to chemotherapy resistance.

Anti-IgE and Biologic Approaches for the Treatment of Asthma.

Current asthma treatments are effective for the majority of patients with mild-to-moderate disease. However, in those with more severe refractory asthma, agents other than inhaled corticosteroids and beta-agonists are needed both to better manage this group of patients and to avoid the side effects of high-dose corticosteroids and the social and personal hardship endured. Several biological pathways have been targeted over the last 20 years, and this research has resulted in pharmacological approaches to attempt to better treat patients with severe refractory asthma. The flagship of the biologics, the anti-IgE monoclonal antibody, omalizumab, has proven efficacious in selected subgroups of asthma patients. Tailoring asthma treatments to suit specific subtypes of asthma patients is in keeping with ideals of personalized medicine. Research in the complex interplay of allergens, epithelial host defenses, cytokines, and innate and adaptive immunity interactions has allowed better understanding of the mechanics of allergy and inflammation in asthma. As a result, new biologic treatments have been developed that target several different phenotypes and endotypes in asthma. As knowledge of the efficacy of these biological agents in asthma emerges, as well as the type of patients in whom they are most beneficial, the movement toward personalized asthma treatment will follow.

Allergen-induced airway responses.

Environmental allergens are an important cause of asthma and can contribute to loss of asthma control and exacerbations. Allergen inhalation challenge has been a useful clinical model to examine the mechanisms of allergen-induced airway responses and inflammation. Allergen bronchoconstrictor responses are the early response, which reaches a maximum within 30 min and resolves by 1-3 h, and late responses, when bronchoconstriction recurs after 3-4 h and reaches a maximum over 6-12 h. Late responses are followed by an increase in airway hyperresponsiveness. These responses occur when IgE on mast cells is cross-linked by an allergen, causing degranulation and the release of histamine, neutral proteases and chemotactic factors, and the production of newly formed mediators, such as cysteinyl leukotrienes and prostaglandin D2. Allergen-induced airway inflammation consists of an increase in airway eosinophils, basophils and, less consistently, neutrophils. These responses are mediated by the trafficking and activation of myeloid dendritic cells into the airways, probably as a result of the release of epithelial cell-derived thymic stromal lymphopoietin, and the release of pro-inflammatory cytokines from type 2 helper T-cells. Allergen inhalation challenge has also been a widely used model to study potential new therapies for asthma and has an excellent negative predictive value for this purpose.

Comparison of the provocative concentration of methacholine causing a 20% fall in FEV1 between the AeroEclipse II breath-actuated nebulizer and the wright nebulizer in adult subjects with asthma.

RATIONALE: The American Thoracic Society guidelines for methacholine testing for the diagnosis of asthma recommends the 2-minute tidal breathing protocol with the Wright nebulizer, which produces more aerosol than required, generates a small particle size, and requires cleaning between tests. OBJECTIVES: To evaluate methacholine testing using a disposable, breath-actuated AeroEclipse II, which produces aerosol during inspiration and was developed for single-patient use. METHODS: Forty-six adult subjects with asthma (19 men), aged 27.3 (SD, 9.5) years, with FEV1 98.5 (SD, 18.1) % predicted participated in a randomized, crossover, observational study. Subjects were first screened using the Wright nebulizer, then assigned to 2 minutes of tidal breathing from the Wright or 20 seconds of tidal breathing from the AeroEclipse nebulizer on 2 separate days, in random order. Provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) values were calculated by linear interpolation of log dose-versus-response curves, log-transformed, and compared using paired Student t test and Pearson correlation. MEASUREMENTS AND MAIN RESULTS: The 38 subjects demonstrating reproducible PC20 measurements of within 1.5 doubling concentrations were included in the comparison. The geometric mean methacholine PC20 measured with the AeroEclipse nebulizer was approximately 1 doubling concentration lower than the geometric mean methacholine PC20 of the Wright nebulizer (P < 0.05). The Pearson correlation coefficient between the two nebulizers was 0.86 (P < 0.05). CONCLUSIONS: The PC20 measurements using the two nebulizers were highly correlated; however, the PC20 determined with the AeroEclipse nebulizer was significantly lower than those determined using the Wright nebulizer. Clinical trial registered with www.clinicaltrials.gov (NCT 01919424).

Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells.

Inherent or acquired drug resistance is a major contributor to epithelial ovarian cancer (EOC) mortality. Novel drugs or drug combinations that produce EOC cell death or resensitize drug resistant cells to standard chemotherapy may improve patient treatment. After conducting drug tolerability studies for the multikinase inhibitors dorsomorphin (DM) and it is structural analogue LDN-193189 (LDN), these drugs were tested in a mouse intraperitoneal xenograft model of EOC. DM significantly increased survival, whereas LDN showed a trend toward increased survival. In vitro experiments using cisplatin (CP)-resistant EOC cell lines, A2780-cp or SKOV3, we determined that pretreatment or cotreatment with DM or LDN resensitized cells to the killing effect of CP or carboplatin (CB). DM was capable of blocking EOC cell cycle and migration, whereas LDN produced a less pronounced effect on cell cycle and no effect on migration. Subsequent analyses using primary human EOC cell samples or additional established EOC cells lines showed that DM or LDN induced a dose-dependent autophagic or cell death response, respectively. DM induced a characteristic morphological change with the appearance of numerous LC3B-containing acidic vacuoles and an increase in LC3BII levels. This was coincident with a decrease in cell growth and the altered cell cycle consistent with DM-induced cytostasis. By contrast, LDN produced a caspase 3-independent, reactive oxygen species-dependent cell death. Overall, DM and LDN possess drug characteristics suitable for adjuvant agents used to treat chemotherapy-sensitive and -resistant EOC.

[Illicit drug trade on the markets of Yaounde (Cameroon) and Niamey (Niger): characteristics of salesmen and quality of drugs]. / Le circuit informel des médicaments à Yaoundé et à Niamey: étude de la population des vendeurs et de la qualité des médicaments distribués.

This study characterizes salesmen and evaluates the drugs offer and quality of the drugs in the illicit selling network in Yaoundé (Cameroon) and Niamey (Niger). A sample of 75 and 124 drug salesmen working in these cities was questioned using a standardized questionnaire. The prescription of drugs and the advices provided by these poorly trained salesmen could have an important impact in term of public health: 32% and 67% of the salesmen in Yaoundé give systematically or occasionally advices regarding the prescription. The active substances are always present in the 153 drugs of our analysed sample, except for chloroquine-based drugs, among which 5/30 samples did not contain active substance. However, the rate of nonconformity is approximately 50% in the two cities. Complementary studies are needed to explore the origin of these nonconformities, between counterfeiting, low quality of the products provided by the factories, defects of conservation or instability of the formulations.

Ethnic differences in propofol and fentanyl response: a comparison among Caucasians, Kenyan Africans and Brazilians.

BACKGROUND AND OBJECTIVE: Differences in sensitivity to anaesthetic drugs may exist among human races. Allelic variants for drug metabolizing isoenzymes and other pharmacokinetic/pharmacodynamic differences may account for a variable response to anaesthetic drugs. This study was designed to investigate comparatively the anaesthetic requirements and the recovery trends of three different ethnic groups: Caucasians, African blacks and Brazilians. METHODS: The anaesthetic depth and recovery of groups of 45 patients undergoing total intravenous anaesthesia with propofol and fentanyl were compared. The bispectral index and clinical parameters were used to assess the depth of anaesthesia. The bispectral index, the response to verbal stimuli and the eye opening time were used to assess recovery. RESULTS: After stopping propofol, the bispectral index values of Caucasians returned to the baseline in about 10.8 +/- 4 min, that of Kenyan African blacks in 18 +/- 7 min and that of Brazilians in a highly variable time ranging from 5 to 25 min, (14.9 +/- 9.9). The time from discontinuation of propofol and fentanyl infusion to eye opening was 18.8 +/- 7.1 min in African blacks (P < 0.01) and 13.5 +/- 8.8 min in Brazilians (P > 0.05) vs. 11.6 +/- 4.5 min in Caucasians. Time to respond to verbal commands was 16.8 +/- 8 min in African blacks (P < 0.01) and 12.8 +/- 8.1 min in Brazilians (P > 0.05) vs. 9.9 +/- 4.5 min in Caucasians. CONCLUSIONS: The recovery of Kenyan African blacks from anaesthesia with propofol and fentanyl is much slower, in comparison with Caucasians. The recovery time of Brazilians is much more variable, in comparison with Caucasians.

Study of cell mediated and humoral immunity in acute bacterial meningitis.

Twenty (20) patients suffering from acute bacterial meningitis and ten (10) normal individuals were included in this study. Patient's age ranged from 3-50 years; they were chosen from Abassia Fever Hospital. Serum as well as CSF immunoglobulin G and M were measured at admittance and 2 days later, E rosette test was done and compared with the control group. Significant increase in IgM in CSF was recorded in early acute cases. IgG was significantly increased in CSF in both early and late cases. The increase in serum immunoglobulins was insignificant in all cases. Using E rosette test no significant difference was detected in T-lymphocytes in patient groups as compared with normal controls. From this work we can conclude that the increase in the type of CSF immunoglobulin could differentiate acute (increase in IgM) from late cases (increase in IgG). Also we can conclude that cell mediated immunity has no role in bacterial meningitis as the increase in T lymphocytes was insignificant.