Selective enhancement of (6-4) photoproduct formation in dithymine dinucleotides driven by specific sugar puckering.

Four dinucleotide analogs of thymidylyl(3'-5')thymidine (TpT) have been designed and synthesized with a view to increase the selectivity, with respect to CPD, of efficient UV-induced (6-4) photoproduct formation. The deoxyribose residues of these analogs have been modified to increase north and south conformer populations at 5'- and 3'-ends, respectively. Dinucleotides whose 5'-end north population exceeds ca. 60% and whose 3'-end population is almost completely south display a three-fold selective enhancement in (6-4) adduct production when exposed to UV radiation, compared to TpT. These experimental results undoubtedly provide robust foundations for studying the singular ground-state proreactive species involved in the (6-4) photoproduct formation mechanism.

Global perspectives of determinants influencing HPV vaccine introduction and scale-up in low- and middle-income countries.

Achieving WHO cervical cancer elimination goals will necessitate efforts to increase HPV vaccine access and coverage in low-and-middle-income countries (LMICs). Although LMICs account for the majority of cervical cancer cases globally, scale-up of HPV vaccine programs and progress toward coverage targets in LMICs has been largely insufficient. Understanding the barriers and facilitators that stakeholders face in the introduction and scale-up of HPV vaccination programs will be pivotal in ensuring that LMICs are equipped to optimize the implementation of HPV vaccination programs. This qualitative study interviewed 13 global stakeholders categorized as either academic partners or global immunization partners to ascertain perspectives regarding factors affecting the introduction and scale-up of HPV vaccination programs in LMICs. Global stakeholders were selected as their perspectives have not been as readily highlighted within the literature despite their key role in HPV vaccination programming. The results of this investigation identified upstream (e.g., financial considerations, vaccine prioritization, global supply, capacity and delivery, and vaccine accessibility, equity, and ethics) and downstream (e.g., vaccine acceptability and hesitancy, communications, advocacy, and social mobilization) determinants that impact program introduction and scale-up and confirmed that strong political commitment and governance are significant in garnering support for HPV vaccines. As LMICs introduce HPV vaccines into their national immunization programs and develop plans for scaling up vaccination efforts, strategic approaches to communications and advocacy will also be needed to successfully meet coverage targets.

Sociodemographics and health-literacy as predictors of cervical cancer screening practices among Haitian women: A secondary data analysis of 2016-17 DHS surveys.

Cervical cancer screening rates in Haiti are concerningly low. Access to health-related information and health literacy may be important determinants of engagement in cervical cancer screening. This study explored the relationship between sociodemographics,literacy, and sources of information on cervical cancer screening among Haitian women. A secondary data analysis was conducted using USAID Demographics and Health Survey Haiti household data from 2016-2017. Univariate logistic regressions identified significant predictor covariates measuring sociodemographics and sources of information in cervical cancer screening uptake.Two multivariate logistic regression models with adjusted odds ratios were developed using the significant predictor variables from the univariate analysis. N = 610 women responded to questions pertaining to cervical cancer screening. The first multivariate model evaluating sociodemographics demonstrated an economic background of poorer (aOR = 4.06, 95% CI [1.16,14.27]) and richest (aOR = 19.10 , 95% CI[2.58,141.57]), higher education levels (aOR 7.58 , 95% CI [1.64,34.97]), and having insurance (aOR = 16.40, [95% CI 2.65, 101.42]) were significant predictors of cervical cancer screening. The second model evaluating literacy and sources of information indicated that access to a television (aOR = 4.28, 95% CI [1.21,9.34]), mobile phone ownership (aOR = 4.44, 95% CI [1.00,5.59]), and reading the newspaper (aOR = 3.57, [95% CI 1.10,11.59]) were significant predictors of cervical cancer screening. Diverse health communication initiatives that are adapted for literacy level and that incorporate multimedia components may effective in raising women's cervical cancer knowledge and awareness , and increasing intention and uptake of cervical cancer screening in Haiti.

Planning, implementation, and sustaining high coverage of human papillomavirus (HPV) vaccination programs: What works in the context of low-resource countries?

Cervical cancer due to human papillomavirus (HPV) infection is a leading cause of mortality among women in low-resource settings. Many Sub-Saharan African countries have introduced HPV vaccination programs at the national level in the last few years. However, countries are struggling to maintain sustainable coverage. This study focuses on the introduction and sustainability challenges, context-specific key lessons learned, and mechanisms of action to achieve high sustainable coverage from low and lower-middle-income countries (LLMICs) that have introduced HPV vaccination programs by collating evidence from a literature review and key informant interviews. Local data availability was a challenge across countries, with the lack or absence of registries, data collection and reporting mechanisms. Multi-sectoral coordination and early involvement of key stakeholders were cited as an integral part of HPV programs and facilitators for sustainable coverage. Key informants identified periodic sensitization and training as critical due to high staff turnover. Health workforce mobilization was fundamental to ensure that the health workforce is aware of the disease etiology, eligibility requirements, and can dispel misinformation. Schools were reported to be an ideal sustainable platform for vaccination. However, this required teachers to be trained, which was often not considered in the programs. District-level staff were often poorly informed and lacked the technical and logistic capacity to support vaccination rounds and data collection. To improve the sustainability of HPV vaccination programs, there is a need for timely microplanning, efficient preparedness assessment, assessing training approaches, periodic training, finding innovative ways to achieve equity and adoption of a bottom-up approach to ensure that processes between districts and central level are well-connected and resources are distributed efficiently.

Acceptability of an integrated school-based HPV vaccination program within two districts of Tanzania: A qualitative descriptive study.

Tanzania has one of the highest cervical cancer incidence and mortality rates in sub-Saharan Africa. The Tanzanian Ministry of Health developed an integrated adolescent health program, HPV-Plus, that combines HPV vaccination with additional health services: nutritional assessments, vision screening, and vaccination for adolescent girls, and education for all genders. This qualitative descriptive study evaluated the acceptability of the HPV-Plus program in two districts in Tanzania. Key informants comprising of adolescent girls, parents, program planners, and program implementers in Njombe and Dar es Salaam Tanzania were interviewed to assess the program acceptability. Transcripts were analyzed using a team-based iterative thematic analysis approach, consisting of both inductive and deductive coding. The Theoretical Framework of Acceptability was used to guide analysis, with themes categorized according to theoretical constructs of intervention coherence, affective attitudes and perceptions, and perceived effectiveness. Overall acceptability of the HPV-Plus program was high among stakeholders. The most salient finding regarding factors that influenced HPV vaccine acceptability was largely related to education and knowledge levels surrounding the HPV, cervical cancer, and HPV vaccines. The educational component of the HPV-Plus program was key in increasing acceptability. Parents reported the lowest acceptability towards the program. This was found to be primarily due to perceptions of not being sufficiently engaged throughout program implementation. Increasing acceptability of HPV vaccination programs among key stakeholders is critical to facilitating vaccine uptake and meeting vaccination coverage targets. Our results demonstrate that the inclusion of a comprehensive education component within the HPV-Plus program was key in facilitating HPV vaccine acceptability amongst stakeholders.

Feasibility and sustainability of a school-based platform for integrated delivery of HPV vaccination with adolescent health services in Tanzania: qualitative insights from stakeholders.

To meet lofty human papillomavirus (HPV) immunization goals in Tanzania, the Ministry of Health integrated HPV vaccination with adolescent health services using a school-based approach. A qualitative study was conducted in June-July 2021, examining the feasibility and sustainability of an integrated service package, HPV Plus. In-depth interviews with 46 programme implementers (i.e. health-care workers and teachers) and planning stakeholders (i.e. government officials and school administrators) in Dar es Salaam and Njombe Regions explored enablers and constraints to HPV Plus programme implementation, including resource and staffing requirements. Two facilitators and three barriers to HPV Plus feasibility and sustainability were identified from thematic analysis of interviews. Interviewed stakeholders emphasized the programme's feasibility, especially if the efficiencies offered by a school-based platform were optimized. Implementation facilitators included (1) optimized service delivery efficiency through a school-based platform and (2) resources saved by combining adolescent health services and HPV immunization into a single programme package. Key barriers to HPV Plus feasibility and sustainability were (1) time, space and resource constraints (e.g. commodity stockouts and challenges delivering the complete service package to large cohorts of students within allotted times); (2) human resource gaps and increased workloads within the health workforce and (3) insufficient referral mechanisms linking schools to health facilities. Scaling up HPV Plus will require proactive commodity procurement and security; resource mobilization to reach ambitious service delivery targets and close co-ordination of programme implementation with school administrators.

Exploring engagement in cervical cancer prevention services among Haitian women in Haiti and in the United States: a scoping review.

PROBLEM IDENTIFICATION: Haitian women in Haiti and in the United States experience a disproportionate burden of cervical cancer, however their uptake of cervical cancer prevention services remains concerningly low. LITERATURE SEARCH: A comprehensive search on bibliographic databases coupled with a grey literature search was conducted. A total of 401 studies were identified, with 28 studies retained after following Arksey and O'Malley's Scoping Review Guidelines. DATA EVALUATION/SYNTHESIS: Knowledge levels of HPV and cervical cancer, along with preventative measures was alarmingly low. Traditional health practices, cultural worldviews, and social networks had an influence on the uptake of cervical cancer prevention. Health systems barriers were found to be a prevalent barrier among Haitian women in the U.S. CONCLUSIONS: Future health promotion interventions developed for Haitian women must address personal, cultural, social, and structural factors with an emphasis on modifying knowledge and beliefs to improve engagement in cervical cancer prevention behaviors.

Key decision-making factors for human papillomavirus (HPV) vaccine program introduction in low-and-middle-income-countries: Global and national stakeholder perspectives.

Low-and-middle-income countries (LMICs) experience a high burden of cervical cancer. The human papillomavirus (HPV) vaccine prevents high-risk strains of HPV that cause cervical cancer; however, the integration of HPV vaccines into national immunization programs within many LMICs has been suboptimal. Our study evaluated key factors that drive the decision-making process for the implementation of HPV vaccine programs in LMICs. Stakeholder analysis and semi-structured in-depth interviews were conducted with national and global stakeholders. Interview data were analyzed through qualitative descriptive methods. Findings from our study revealed the decision-making process for HPV vaccines requires the involvement of multiple institutions and stakeholders from national and global levels, with decision-making being a country-specific process. Partner considerations, locally driven processes, availability of data, and infrastructure and resource considerations were found to be critical factors in the decision-making process. Future programs should evaluate the best approaches for investing in initiatives to enhance coordination, ensure vaccine introduction is locally driven, increase the availability of data needed for decision-making, and equip countries with the necessary resources to guide country decision-making in the face of increasingly complex decision-making environments.

Barriers to Cervical Cancer Screening Among Women Living With HIV in Low- and Middle-Income Countries: A Systematic Review.

Women living with HIV in low-and-middle-income countries (LMICs) are at high risk of developing cervical cancer due to their immunocompromised status. Screening is an imperative prevention measure for early detection and for ultimately reducing high rates of cervical cancer; however, cervical cancer screening uptake among this group remains low. This systematic review aimed to identify barriers to cervical cancer screening among women living with HIV in LMIC. A comprehensive literature search was undertaken, and an analysis of included studies was completed to abstract major themes related to cervical cancer screening barriers for women living with HIV in LMIC. Lack of cervical cancer and cervical cancer screening knowledge among patients was found to be the most prevalent barrier to cervical cancer screening. Our findings highlight a dire need for interventions to increase knowledge and awareness of cervical cancer screening among women living with HIV in LMIC, along with addressing barriers within health care systems.

Pro-apoptotic activity of new triterpenoid saponins from the roots of Albizia adianthifolia (Schumach.) W.Wight.

As part of our study of the proapoptotic function of saponins from Cameroonian's Albizia genus, phytochemical investigation of the roots of Albizia adianthifolia led to the isolation of three new triterpenoid saponins, named adianthifoliosides GI (13). Their structures were established on the basis of extensive analysis of 1D and 2D NMR (1H-, 13C NMR, DEPT, COSY, TOCSY, NOESY, HSQC, HSQC-TOCSY and HMBC) and HRESIMS experiments, and by chemical evidence as 3-O-[ß-d-glucopyranosyl-(1 → 2)-ß-D-fucopyranosyl-(1 → 6)-ß-d-glucopyranosyl]-21-O-{(2E,6S)-2-(hydroxymethyl)-6-methyl-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]}acacic acid-28-O-ß-d-xylopyranosyl-(1 → 3)-[5-O-acetyl-α-L-arabinofuranosyl-(1 → 4)]-α-L-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl ester (1), 3-O-[ß-d-glucopyranosyl-(1 → 2)-ß-D-fucopyranosyl-(1 → 6)-ß-d-glucopyranosyl]-21-O-{(2E,6S)-2-(hydroxymethyl)-6-methyl-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]}acacic acid 28-O-ß-d-xylopyranosyl-(1 → 3)-[α-L-arabinofuranosyl-1 → 4)]-α-L-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl ester (2), and 3-O-[ß-d-glucopyranosyl-(1 → 2)-ß-D-fucopyranosyl-(1 → 6)-ß-d-glucopyranosyl]-21-O-{(2E,6S)-2-(hydroxymethyl)-6-methyl-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-ß-D-quinovopyranosyl}-2,6-dimethylocta-2,7-dienoyl}acacic acid 28-O-ß-d-xylopyranosyl-(1 → 3)-[α-L-arabinofuranosyl-1 → 4)]-α-L-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl ester (3). The apoptotic effect of saponins 1-3 was evaluated on the A431 human epidermoid cancer cell. Flow cytometric analyses showed that saponins 1-3 induced apoptosis of human epidermoid cancer cell (A431) in a dose-dependent manner.

New Cytotoxic Triterpenoid Saponins from the Roots of Albizia gummifera (J.F.Gmel.) C.A.Sm.

As part of our search for new bioactive saponins from Cameroonian medicinal plants, two new oleanane-type saponins, named gummiferaosides D and E (1 and 2), along with one known saponin, julibroside J8 (3), were isolated from the roots of Albizia gummifera. Their structures were established on the basis of extensive 1D- and 2D-NMR (1 H- and 13 C-NMR, DEPT, COSY, TOCSY, NOESY, HSQC, HSQC-TOCSY, and HMBC) and HR-ESI-MS studies, and by chemical evidence. The apoptotic effect of saponins 1 - 3 was evaluated on the A431 human epidermoid cancer cell. Flow cytometric analyses showed that saponins 1 - 3 induced apoptosis of human epidermoid cancer cell (A431) in a dose-dependent manner.

Phenotype-specific apoptosis induced by three new triterpenoid saponins from Albizia glaberrima (Schumach. & Thonn.) Benth.

As part of our search of new bioactive saponins from Cameroonian medicinal plants, phytochemical investigation of the roots of Albizia glaberrima led to the isolation of three new oleanane-type saponins, named glaberrimosides A-C (1-3). Their structures were established by direct interpretation of their spectral data, mainly HRESIMS, 1D NMR (1H, 13C NMR, and DEPT) and 2D NMR (COSY, ROESY, HSQC and HMBC) as 3-O-[α-L-arabinopyranosyl-(1 → 6)-[ß-D-glucopyranosyl-(1 → 2)]-ß-D-glucopyranosyl]-28-O-[ß-D-glucopyranosyl-(1 → 6)-[ß-d-glucopyranosyl-(1 → 2)]-ß-D-glucopyranosyl]-oleanolic acid (1), 3-O-[α-L-arabinopyranosyl-(1 → 6)-[ß-D-glucopyranosyl-(1 → 2)]-ß-D-glucopyranosyl]-28-O-[ß-D-glucopyranosyl-(1 → 6)-ß-D-glucopyranosyl]-oleanolic acid (2), and 3-O-[ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl]-28-O-[ß-D-glucopyranosyl-(1 → 6)-[ß-D-fucopyranosyl-(1 → 2)]-ß-D-glucopyranosyl]-oleanolic acid (3). The pro-apoptotic effect of the three saponins was evaluated on three human cell lines (pancreatic carcinoma AsPC-1, hematopoietic monocytic THP-1, and human fibroblast cell line BJ). Saponins 1-3 specifically induced apoptosis of pancreatic carcinoma cell (AsPC-1) in a dose-dependent manner. More interestingly, there were inactive on monocytic (THP-1) and normal human fibroblast (BJ) cell lines.

Triterpenoid saponins from Albizia lebbeck (L.) Benth and their inhibitory effect on the survival of high grade human brain tumor cells.

As part of our search of new bioactive triterpenoid saponins from Cameroonian Mimosaceae plants, phytochemical investigation of the roots of Albizia lebbeck led to the isolation of two new oleanane-type saponins, named lebbeckosides A-B (1-2). Their structures were established on the basis of extensive 1D and 2D NMR ((1)H, (13)C NMR, DEPT, COSY, TOCSY, ROESY, HSQC, and HMBC) and HRESIMS studies, and by chemical evidence. Compounds 1-2 were evaluated for their inhibitory effect on the metabolism of high grade human brain tumor cells, the human glioblastoma U-87 MG cell lines and the glioblastoma stem-like TG1 cells isolated from a patient tumor, and known to be particularly resistant to standard therapies. The isolated saponins showed significant cytotoxic activity against U-87 MG and TG1 cancer cells with IC50 values of 3.46 µM and 1.36 µM for 1, and 2.10 µM and 2.24 µM for 2, respectively.

A minute amount of s-puckered sugars is sufficient for (6-4) photoproduct formation at the dinucleotide level.

The di-2'-α-fluoro analogue of thymidylyl(3',5')thymidine, synthesized to probe the effect of a minimum amount of S conformer on the photoreactivity of dinucleotides, is endowed with only 3% and 8% of S sugar conformation at its 5'- and 3'-end, respectively. This analogue gives rise to the (6-4) photoproduct as efficiently as the dithymine dinucleotide (74% and 66% at the 5'- and 3'-end, respectively) under 254 nm. Our results suggest that the 5'-N, 3'-S conformer gives rise to the (6-4) photoproduct.

Oxidative stability of cosmetic argan oil: a one-year study.

The objective of this work is to determine the chemical stability of cosmetic argan oil (INCI: Argania spinosa kernel oil). The methodology involves the repeated measurement over a 1-year period of the quality metrics used in the cosmetic industry: acid and peroxide value and specific absorbance. During this year, storage is performed at 40° or 25°C to assess the importance of temperature. In this latter case, oil samples have been either protected or exposed to sunlight. In addition, sterol and fatty acid composition is determined to attest argan oil chemical integrity over 1 year. Storage of argan oil at 40°C results in a rapid loss of quality. Stored at 25°C and protected from sunlight, argan oil quality is still satisfactory after 12 months according to the official Moroccan norm, but storage should not be longer than 6 months to fulfill industrial standards.

New rotenoids and coumaronochromonoids from the aerial part of Boerhaavia erecta.

From the aerial part of Boerhaavia erecta L., three new rotenoids (3, 8, 10) and two new coumaronochromonoids (6, 11) were isolated, together with ten known compounds. The structure of the new compounds was established by one dimensional (1D)- and 2D-NMR spectroscopy, as well as high resolution-electrospray ionization (HR-ESI)-MS analysis. The absolute configuration of compound 11 was determined by UV circular dichroism spectroscopy. Compounds were evaluated for their cytotoxic activity against HeLa (human epithelial carcinoma), NCI-H460 (human lung cancer) and MCF-7 (human breast cancer) cell lines at the concentration of 100 µg/mL. Rotenoids 3, 4 and 5 showed a strong cytotoxic activity against HeLa cell line and rotenoids 5 and 8 showed good activity against MCF-7 cell line.

The origin of virgin argan oil's high oxidative stability unraveled.

To prepare either virgin edible or beauty argan oil, roasted or unroasted argan kernels are cold-pressed, respectively. Comparing the physicochemical parameters of edible and beauty argan oil immediately after preparation and after a two-year delay has led to the suggestion that phospholipids are a new and essential type of oil component participating in the excellent oxidative stability of edible argan oil, in addition to the already suggested Maillard-reaction products, phenols, and tocopherols.

Antimycobacterial activity of the fractions and compounds from Scutia buxifolia

The antimycobacterial activity of Scutia buxifolia Reissek, Rhamnaceae, leaves extracts and fractions were evaluated for the first time. Four compounds were identified, flavonoids (quercetin and quercitrin) and phenolic acids (gallic and caffeic acids) and quantified by HPLC-DAD. Promising anti-Mycobacterium smegmatis activity was observed with ethyl acetate extract (MIC 312.50 µg/mL) and their fractions (MIC values ranging from 78.12 to above 312.50 µg/mL). The fractions III and VI of S. buxifolia leaves showed a high level of activity against M. smegmatis (MIC 78.12 and 156.25 µg/mL, respectively), M. tuberculosis (MIC 156.25 µg/mL) and M. avium (MIC 312.50 µg/mL), whereas to the other fractions the values varied from 312.50 to 1250.00 µg/mL against these strains. The better MIC result was associated with two fractions that contain bigger amounts of quercetin, quercitrin, gallic and caffeic acids. The results provided evidence that the studied plants fractions might be potential sources of new antimicrobial drug.

Composition of the essential oil of Argania spinosa (Sapotaceae) fruit pulp.

The composition of the essential oil from the fresh and dried pulp of the fruit of Argania spinosa (Skeels) L. has been studied. Camphor was the major component in both oil types, but in addition, the fresh fruit oil had significant amounts of 1,8-cineole, endo-borneol, and 2-(4-methylcyclohex-3-enyl)-propan-2-ol., and the dried pulp oil 3,5-dimethyl-4-ethylidene-cyclohex-2-ene-1-one, 1,8-cineole, and 2-methylbutanoic acid. The presence of camphor and 1,8-cineole in argan fruit essential oil suggests that it could be used locally as an insect repellent, offering an output for argan fruit pulp that is at present a waste product.

Should the amazigh diet (regular and moderate argan-oil consumption) have a beneficial impact on human health?

Virgin argan oil, cosmetic or dietary grade, is prepared by cold-pressing the kernels of argan fruits. Both types of oil, traditionally used by the amazighs (the argan grove traditional dwellers), are now available on the shelves of the most-developed country stores. Argan oil contains a high level of oleic and linoleic acid and is also particularly rich in phenols. Since these metabolites are currently considered as essential to explain some of the protective effects against cancer and coronary heart disease attributed to other oils, similar effects can be expected from argan oil consumption as suggested by the amazigh medicine claims. Interestingly, argan oil content in gamma -tocopherol is much higher than that of any other oils. gamma -Tocopherol has recently been shown to possess strong chemopreventive and anti-inflammatory properties. This indicates that argan oil should readily find a place of choice amid the most profitable oils for human health. Because of its reduced geographical origin, the chemical composition (major as well as minor components) of argan oil is also highly reproducible. Therefore argan oil consumption should confer health benefits in a reliable and efficient manner.