The First Case of Huntington's Disease like 2 in Mali, West Africa.

Background: Huntington's disease like 2 (HDL2) has been reported exclusively in patients with African ancestry, mostly originating from South Africa. Case report: We report three patients in Mali including a proband and his two children who have been examined by neurologists and psychiatrists after giving consent. They were aged between 28 and 56 years old. Psychiatric symptoms were predominant in the two younger patients while the father presented mainly with motor symptoms. Genetic testing identified a heterozygous 40 CTG repeat expansion in the Junctophilin-3 (JPH3) gene in all three patients. Discussion: This study supports the hypothesis that HDL2 may be widely spread across Africa. Highlights: We report here the first case of HDL2 in West Africa, suggesting that HDL2 is widely spread across African continent, and increasing access to genetic testing could uncover other cases.

Factors influencing pregnancy care and institutional delivery in rural Mali: a secondary baseline analysis of a cluster-randomised trial.

OBJECTIVE: The vast majority of the 300 000 pregnancy-related deaths every year occur in South Asia and sub-Saharan Africa. Increased access to quality antepartum and intrapartum care can reduce pregnancy-related morbidity and mortality worldwide. We used a population-based cross-sectional cohort design to: (1) examine the sociodemographic risk factors and structural barriers associated with pregnancy care-seeking and institutional delivery, and (2) investigate the influence of residential distance to the nearest primary health facility in a rural population in Mali. METHODS: A baseline household survey of Malian women aged 15-49 years was conducted between December 2016 and January 2017, and those who delivereda baby in the 5 years preceding the survey were included. This study leverages the baseline survey data from a cluster-randomised controlled trial to conduct a secondary analysis. The outcomes were percentage of women who received any antenatal care (ANC) and institutional delivery; total number of ANC visits; four or more ANC visits; first ANC visit in the first trimester. RESULTS: Of the 8575 women in the study, two-thirds received any ANC in their last pregnancy, one in 10 had four or more ANC visits and among those that received any ANC, about one-quarter received it in the first trimester. For every kilometre increase in distance to the nearest facility, the likelihood of the outcomes reduced by 5 percentage points (0.95; 95% CI 0.91 to 0.98) for any ANC; 4 percentage points (0.96; 95% CI 0.94 to 0.98) for an additional ANC visit; 10 percentage points (0.90; 95% CI 0.86 to 0.95) for four or more ANC visits; 6 percentage points (0.94; 95% CI 0.94 to 0.98) for first ANC in the first trimester. In addition, there was a 35 percentage points (0.65; 95% CI 0.56 to 0.76) decrease in likelihood of institutional delivery if the residence was within 6.5 km to the nearest facility, beyond which there was no association with the place of delivery. We also found evidence of increase in likelihood of receiving any ANC care and its intensity increased with having some education or owning a business. CONCLUSION: The findings suggest that education, occupation and distance are important determinants of pregnancy and delivery care in a rural Malian context. TRIAL REGISTRATION NUMBER: NCT02694055.

Spatial distribution and associated factors of co-occurrence of overweight/obesity and Anemia among women in the reproductive age in sub-Saharan Africa: A multilevel analysis, DHS 2016-2021.

BACKGROUND: Overweight/obesity is one of the major public health problems that affect both developed and developing nations. The co-occurrence of overweight/obesity and anemia is thought to be largely preventable if detected early. To date, no spatial analyses have been performed to identify areas of hotspots for the co-occurrence of overweight/obesity and anemia among reproductive women in sub-Saharan Africa. Therefore, this study aimed to assess the spatial distribution and associated factors of the co-occurrence of overweight/obesity and anemia among women of reproductive age. METHODS: Data for the study were drawn from the Demographic and Health Survey, a nationally representative cross-sectional survey conducted in the era of Sustainable Development Goals, in which the World Health Assembly decided and planned to cease all forms of malnutrition by 2030. Seventeen sub-Saharan African countries and a total weighted sample of 108,161 reproductive women (15-49 years) were included in our study. The data extraction, recoding and analysis were done using STATA V.17. For the spatial analysis (autocorrelation, hot-spot and interpolation), ArcGIS version 10.7 software, and for the SaTScan analysis, SaTScan version 10.1 software was used. Descriptive statistics were presented using frequency tables and percentages. We employed multilevel logistic regression to investigate associated factors. In the multivariable analysis, variables with a p-value of ≤0.05 are considered as a significant factor associated with co-occurrence of overweight/obesity and anemia among women aged 15-49 years. RESULTS: The overall co-occurrence of overweight/obesity and anemia among women in sub-Saharan Africa was 12% (95%CI: 9-14%). The spatial analysis revealed that the co-occurrence of overweight/obesity and anemia among women significantly varied across sub-Saharan Africa. (Global Moran's I = 0.583163, p<0.001). In the spatial window, the primary-cluster was located in Liberia, Guinea, Gambia, Sira Leon, Mauritania, Mali, Cameron and Nigeria with a Log-Likelihood Ratio (LRR) of 1687.30, and Relative Risk (RR) of 2.58 at a p-value < 0.001. In multilevel analysis, women aged 25-34 years (AOR = 1.91, 95%CI: 1.78, 2.04), women aged 35-49 years (AOR = 2.96, 95% CI: 2.76, 3.17), married (AOR = 1.36, 95% CI: 1.27, 1.46), widowed (AOR = 1.22, 95%CI: 1.06, 1.40), divorced (AOR = 1.36, 95% CI: 1.23, 1.50), media exposure (AOR = 1.31, 95%CI: 1.23, 1.39), middle income (AOR = 1.19, 95%CI: 1.11, 1.28), high income/rich (AOR = 1.36, 95%CI: 1.26, 1.46), not working (AOR = 1.13, 95% CI:1.07, 1.19), traditional contraceptive utilization (AOR = 1.39, 95%CI: 1.23, 1.58) and no contraceptive use (AOR = 1.27, 95%CI: 1.20, 1.56), and no health insurance coverage (AOR = 1.36, 95%CI: 1.25, 1.49), were individual level significant variables. From community-level variables urban residence (AOR = 1.61, 95%CI: 1.50, 1.73), lower middle-income country (AOR = 2.50, 95%CI: 2.34, 2.66) and upper middle-income country (AOR = 2.87, 95%CI: 2.47, 3.34), were significantly associated with higher odds of co-occurrence of overweight/ obesity and anemia. CONCLUSION AND RECOMMENDATIONS: The spatial distribution of the co-occurrence of overweight/obesity and anemia was significantly varied across the sub-Saharan African country. Both individual and community-level factors were significantly associated with the co-occurrence of overweight/obesity and anemia. Therefore, public health programmers and other stalk holders who are involved in maternal healthcare should work together and give priority to hotspot areas of co-occurrence in sub-Saharan Africa.

Scientific writing quality of theses in Medicine and Pharmacy at the University of Bamako (Mali).

AIM: To describe the scientific editorial quality of practice theses defended at the Faculties of Medicine and Pharmacy of Bamako (Mali), during the period 2016-2018. METHODS: This was a cross-sectional study conducted on practice theses in health science, defended between 2016 and 2018, and the electronic version of which was available at the libraries of the Faculties of Medicine and Pharmacy in Bamako. An adjusted STROBE grid was used to measure a scientific editorial conformity score for 18 iso-weighted items of the IMRaD structure (i.e. a total of 18 points). In this way, the scientific editorial quality of practice theses in health sciences was judged to be highly conform (14-18 points), fairly conform (9-13 points), poorly conform (5-8 points), or not conform (<5 points). An ordinal logistic regression model was used to identify determining factors independently associated with the scientific editorial quality of the health sciences practice thesis, with a significance level of 5%. RESULTS: A total of 534 practice theses in health sciences were included in this study, whose scientific editorial quality was judged to be highly or fairly conform (12.2%), poorly conform (43.1%) or not conform (44.8%). These standards scientific editorial conformity, which was higher in a "Medicine" thesis than in a "Pharmacy" thesis (ORa=2.45; IC95% [1.62-3.27], p<=0.05), was attributed to the supervisor's membership of a research structure (ORa=2.88; IC95% [1.6-3.2]; p<0.05). CONCLUSION: The research methodology profile of the practice health sciences thesis supervisor and the thesis section are associated with scientific editorial standard with the IMRaD.

Female genital mutilation/cutting among girls aged 0-14: evidence from the 2018 Mali Demographic and Health Survey data.

BACKGROUND: Female genital mutilation/cutting (FGM/C) is considered a social norm in many African societies, with varying prevalence among countries. Mali is one of the eight countries with very high prevalence of FGM/C in Africa. This study assessed the individual and contextual factors associated with female FGM/C among girls aged 0-14 years in Mali. METHODS: We obtained data from the 2018 Mali Demographic and Health Survey. The prevalence of FGM/C in girls was presented using percentages while a multilevel binary logistic regression analysis was conducted to assess the predictors of FGM/C and the results were presented using adjusted odds ratios with associated 95% confidence intervals (CIs). RESULTS: The results indicate that more than half (72.7%, 95% CI = 70.4-74.8) of women in Mali with daughters had at least one daughter who has gone through circumcision. The likelihood of circumcision of girls increased with age, with women aged 45-49 having the highest odds compared to those aged 15-19 (aOR = 17.68, CI = 7.91-31.79). A higher likelihood of FGM/C in daughters was observed among women who never read newspaper/magazine (aOR = 2.22, 95% CI = 1.27-3.89), compared to those who read newspaper/magazine at least once a week. Compared to women who are not circumcised, those who had been circumcised were more likely to have their daughters circumcised (aOR = 53.98, 95% CI = 24.91-117.00). CONCLUSION: The study revealed the age of mothers, frequency of reading newspaper/magazine, and circumcision status of mothers, as factors associated with circumcision of girls aged 0-14 in Mali. It is, therefore, imperative for existing interventions and new ones to focus on these factors in order to reduce FGM/C in Mali. This will help Mali to contribute to the global efforts of eliminating all harmful practices, such as child, early and forced marriage and female genital mutilation by 2030.

Effectiveness of decentralizing outpatient acute malnutrition treatment with community health workers and a simplified combined protocol: a cluster randomized controlled trial in emergency settings of Mali.

Background: Outpatient treatment of acute malnutrition is usually centralized in health centers and separated into different programs according to case severity. This complicates case detection, care delivery, and supply chain management, making it difficult for families to access treatment. This study assessed the impact of treating severe and moderate cases in the same program using a simplified protocol and decentralizing treatment outside health centers through community health workers (CHWs). Methods: A three-armed cluster randomized controlled trial under a non-inferiority hypothesis was conducted in the Gao region of Mali involving 2,038 children between 6 and 59 months of age with non-complicated acute malnutrition. The control arm consisted of 549 children receiving standard treatment in health centers from nursing staff. The first intervention arm consisted of 800 children treated using the standard protocol with CHWs added as treatment providers. The second intervention arm consisted of 689 children treated by nurses and CHWs under the ComPAS simplified protocol, considering mid-upper arm circumference as the sole anthropometric criterion for admission and discharge and providing a fixed dose of therapeutic food for severe and moderate cases. Coverage was assessed through cross-sectional surveys using the sampling evaluation of access and coverage (SLEAC) methodology for a wide area involving several service delivery units. Results: The recovery rates were 76.3% in the control group, 81.8% in the group that included CHWs with the standard protocol, and 92.9% in the group that applied the simplified protocol, confirming non-inferiority and revealing a significant risk difference among the groups. No significant differences were found in the time to recovery (6 weeks) or in anthropometric gain, whereas the therapeutic food expenditure was significantly lower with the simplified combined program in severe cases (43 sachets fewer than the control). In moderate cases, an average of 35 sachets of therapeutic food were used. With the simplified protocol, the CHWs had 6% discharge errors compared with 19% with the standard protocol. The treatment coverage increased significantly with the simplified combined program (SAM +42.5%, MAM +13.8%). Implications: Implementing a simplified combined treatment program and adding CHWs as treatment providers can improve coverage while maintaining non-inferior effectiveness, reducing the expenditure on nutritional intrants, and ensuring the continuum of care for the most vulnerable children.

Influence of type of violence on women's help-seeking behaviour: Evidence from 10 countries in sub-Saharan Africa.

BACKGROUND: Intimate partner violence (IPV) is a major public health concern that mostly impacts women's health and social well-being. This study explored how the various types of IPV (physical, sexual, and emotional) including women's experience of childhood violence influence their help-seeking behavior in sub-Saharan Africa (SSA). METHODS: We analyzed data from the most recent Demographic and Health Surveys (DHS), carried out between 2018 and 2021. The outcome variable was help-seeking behavior. Descriptive and inferential analyses were carried out. The descriptive analysis looked at the bivariate analysis between the country and outcome variables. Using a binary logistic regression model, a multivariate analysis was utilized to determine the association between the outcome variable and the explanatory variables. Binary logistic regression modelling was used based on the dichotomous nature of the outcome variable. The results were sample-weighted to account for any under- or over-sampling in the sample. RESULTS: The proportion of women who sought help for intimate partner violence was 36.1 percent. This ranged from 19.2 percent in Mali to 49.6 percent in Rwanda. Women who experienced violence in childhood (OR = 0.75, CI = 0.69, 0.82) have a lower likelihood of seeking help compared to those who did not experience violence in their childhood. Women who had experienced emotional violence (OR = 1.94, CI = 1.80, 2.08), and physical violence (OR = 1.37, CI = 1.26, 1.48) have a higher likelihood of seeking help compared to those who have not. Women with secondary educational levels (aOR = 1.13, CI = = 1.02, 1.24) have a higher likelihood of seeking help compared to those with no education. Cohabiting women have a higher likelihood (aOR = 1.22, CI = 1.10, 1.35) of seeking help compared to married women. CONCLUSION: The study highlights the importance of early identification of IPV and fit-for-purpose interventions to demystify IPV normalization to enhance women's willingness to seek help. The study's findings suggest that education is crucial for increasing women's awareness of the legalities surrounding IPV and available structures and institutions for seeking help.

Assessing the accuracy of health facility typology in representing the availability of health services: a case study in Mali.

INTRODUCTION: Using health facility types as a measure of service availability is a common approach in international standards for health system policy and planning. However, this proxy may not accurately reflect the actual availability of specific health services. OBJECTIVE: This study aims to evaluate the reliability of health facility typology as an indicator of specific health service availability and explore whether certain facility types consistently provide particular services. DESIGN: We analysed a comprehensive dataset containing information from 1725 health facilities in Mali. To uncover and visualise patterns within the dataset, we used two analytical techniques: Multiple Correspondence Analysis and Between-Class Analysis. These analyses allowed us to quantitatively measure the influence of health facility types on the variation in health service provisioning. Additionally, we developed and calculated a Consistency Index, which assesses the consistency of a health facility type in providing specific health services. By examining various health facilities and services, we sought to determine the accuracy of facility types as indicators of service availability. SETTING: The study focused on the health system in Mali as a case study. RESULTS: Our findings indicate that using health facility types as a proxy for service availability in Mali is not an accurate representation. We observed that most of the variation in service provision does not stem from differences between facility types but rather within facility types. This suggests that relying solely on health facility typology may lead to an incomplete understanding of health service availability. CONCLUSIONS: These results have significant implications for health policy and planning. The reliance on health facility types as indicators for health system policy and planning should be reconsidered. A more nuanced and evidence-based understanding of health service availability is crucial for effective health policy and planning, as well as for the assessment and monitoring of health systems.

SARS-CoV-2 seroprevalence in vaccine-naïve participants from the Democratic Republic of Congo, Guinea, Liberia, and Mali.

OBJECTIVES: The InVITE study, starting in August 2021, was designed to examine the immunogenicity of different vaccine regimens in several countries including the Democratic Republic of Congo, Guinea, Liberia, and Mali. Prevaccination baseline samples were used to obtain estimates of previous SARS-CoV-2 infection in the study population. METHODS: Adult participants were enrolled upon receipt of their initial COVID-19 vaccine from August 2021 to June 2022. Demographic and comorbidity data were collected at the time of baseline sample collection. SARS-CoV-2 serum anti-Spike and anti-Nucleocapsid antibody levels were measured. RESULTS: Samples tested included 1016, 375, 663, and 776, from DRC, Guinea, Liberia, and Mali, respectively. Only 0.8% of participants reported a prior positive SARS-CoV-2 test, while 83% and 68% had anti-Spike and anti-Nucleocapsid antibodies, respectively. CONCLUSIONS: Overall SARS-CoV-2 seroprevalence was 86% over the accrual period, suggesting a high prevalence of SARS-CoV-2 infection. Low rates of prior positive test results may be explained by asymptomatic infections, limited access to SARS-CoV-2 test kits and health care, and inadequate surveillance. These seroprevalence rates are from a convenience sample and may not be representative of the population in general, underscoring the need for timely, well-conducted surveillance as part of global pandemic preparedness.

Expérience d'un processus participatif autour d'un programme de recherche-action au Mali.

INTRODUCTION: Mali has implemented social protection initiatives in the context of universal health coverage, including the RAMED (medical assistance plan). PURPOSE OF THE RESEARCH: This article describes the participatory process involving researchers and national technical staff as part of an action-research program linked to this policy. RESULTS: The process allowed the interests of the target public, those living in poverty, to take priority over individual and institutional interests, without, however, allowing for their active participation. Despite this positive outcome, the recommendations were not taken on board. CONCLUSION: The main failure of this process was its political component, but there is still time to address this.

User requirements for non-invasive and minimally invasive glucose self-monitoring devices in low-income and middle-income countries: a qualitative study in Kyrgyzstan, Mali, Peru and Tanzania.

AIMS: Development of non-invasive and minimally invasive glucose monitoring devices (NI-MI-GMDs) generally takes place in high-income countries (HICs), with HIC's attributes guiding product characteristics. However, people living with diabetes (PLWD) in low-income and middle-income countries (LMICs) encounter different challenges to those in HICs. This study aimed to define requirements for NI-MI-GMDs in LMICs to inform a target product profile to guide development and selection of suitable devices. METHODS: This was a multiple-methods, exploratory, qualitative study conducted in Kyrgyzstan, Mali, Peru and Tanzania. Interviews and group discussions/activities were conducted with healthcare workers (HCWs), adults living with type 1 (PLWD1) or type 2 diabetes (PLWD2), adolescents living with diabetes and caregivers. RESULTS: Among 383 informants (90 HCW, 100 PLWD1, 92 PLWD2, 24 adolescents, 77 caregivers), a range of differing user requirements were reported, including preferences for area of glucose measurement, device attachment, data display, alert type and temperature sensitivity. Willingness to pay varied across countries; common requirements included ease of use, a range of guiding functions, the possibility to attach to a body part of choice and a cost lower than or equal to current glucose self-monitoring. CONCLUSIONS: Ease-of-use and affordability were consistently prioritised, with broad functionality required for alarms, measurements and attachment possibilities. Perspectives of PLWD are crucial in developing a target product profile to inform characteristics of NI-MI-GMDs in LMICs. Stakeholders must consider these requirements to guide development and selection of NI-MI-GMDs at country level, so that devices are fit for purpose and encourage frequent glucose monitoring among PLWD in these settings.

Evaluation of the Performance of Rapid Diagnostic Tests for Malaria Diagnosis and Mapping of Different Plasmodium Species in Mali.

BACKGROUND: The first-line diagnosis of malaria in Mali is based on the use of rapid diagnostic tests (RDT) that detect the Histidin Rich Protein 2 (HRP2) antigen specific to Plasmodium falciparum. Our study, based on a real-time polymerase chain reaction (qPCR) gold standard, aimed to describe the distribution of the Plasmodium species in each administrative region of Mali and to assess the performance of RDTs. METHODS: We randomly selected 150 malaria-negative and up to 30 malaria-positive RDTs in 41 sites distributed in 9 regions of Mali. DNA extracted from the RDT nitrocellulose strip was assayed with a pan-Plasmodium qPCR. Positive samples were then analyzed with P. falciparum-, P. malariae-, P. vivax-, or P. ovale-specific qPCRs. RESULTS: Of the 1496 RDTs, 258 (18.6%) were positive for Plasmodium spp., of which 96.9% were P. falciparum. The P. vivax prevalence reached 21.1% in the north. RDT displayed acceptable diagnostic indices; the lower CI95% bounds of Youden indices were all ≥0.50, except in the north (Youden index 0.66 (95% CI [0.44-0.82]) and 0.63 (95% CI [0.33-0.83]. CONCLUSIONS: Overall, RDT diagnostic indices are adequate for the biological diagnosis of malaria in Mali. We recommend the use of RDTs detecting P. vivax-specific antigens in the north.

Determinants of household-, maternal- and child-related factors associated with nutritional status among children under five in Mali: evidence from a Demographic and Health Survey, 2018.

OBJECTIVE: The current study aims to determine household-, maternal- and child-related factors influencing nutritional status among children under five in Mali. DESIGN: Quantitative cross-sectional study using secondary data extracted from Mali DHS-VI 2018. SETTING: Urban and rural areas of Mali. PARTICIPANTS: A total of 8908 children participated, with 3999 in the younger age group (0-24 months) and 4909 in the older age group (25-59 months). RESULTS: In the younger age group, the prevalence of stunting, wasting and underweight was 18·8 % (95 % CI%: 17·5, 20·0), 24·6 % (95 % CI: 23·2, 26·0) and 13·2 % (95 % CI: 12·1, 14·3), respectively, while in the older age group, it was 24·9 % (95 % CI: 23·7, 26·2), 22·7 % (95 % CI: 21·5, 24·0) and 5·7 % (95 % CI: 5·0, 6·5), respectively. Being average or large size at birth, having piped source of water, receiving Zn, deworming, high maternal BMI, receiving Fe during pregnancy, higher maternal education and being rich were associated with lower odds of one or more form of undernutrition in both groups. On the other hand, children who were anaemic, drank from a bottle, maternal anaemia, current pregnancy of mothers and living in rural areas were associated with higher odds of stunting, wasting or underweight. Interestingly, children who received Fe supplementation had a higher odds of wasting in the younger group but lower odds of all forms of undernutrition in the older group. CONCLUSIONS: This study emphasised the potential risk factors associated with undernutrition in children. Children who consume non-potable water, have mothers with lower levels of education and BMI and reside in rural areas are more likely to experience undernutrition.

Advancing Health Security and Disease Eradication Through Peace and Health: A Mali Case Study.

Conflict and violence constitute threats to public health. As levels of conflict increase within and between countries, it is important to explore how conflict resolution initiatives can be adapted to meet the health needs of communities, and how addressing the health needs of communities can assist in conflict resolution and contribute to health security. In conflict-affected central Mali, a Peace through Health Initiative, piloted between 2018 and 2022, used conflict resolution trainings, facilitated community meetings, and human and animal health interventions to negotiate "periods of tranquility" to achieve public health goals. Project activities resulted in improved health, improved livelihoods, reduced violence, improved trust among stakeholders, and greater inclusion of community members in peace and health decisionmaking. The Peace-Health Initiative generated several lessons learned related to 3 phases of peace-health programming: preintervention, program development, and implementation. These lessons can be applied to support expanded Peace through Health Initiatives within Mali, may be adaptable to other conflict-afflicted contexts, and should be considered in relation to the implementation of global health security.

Leuconostoc mesenteroides and Liquorilactobacillus mali strains, isolated from Algerian food products, are producers of the postbiotic compounds dextran, oligosaccharides and mannitol.

Six lactic acid bacteria (LAB) isolated from Algerian sheep's milk, traditional butter, date palm sap and barley, which produce dextran, mannitol, oligosaccharides and vitamin B2 have been characterized. They were identified as Leuconostoc mesenteroides (A4X, Z36P, B12 and O9) and Liquorilactobacillus mali (BR201 and FR123). Their exopolysaccharides synthesized from sucrose by dextransucrase (Dsr) were characterized as dextrans with (1,6)-D-glucopyranose units in the main backbone and branched at positions O-4, O-2 and/or O-3, with D-glucopyranose units in the side chain. A4X was the best dextran producer (4.5 g/L), while the other strains synthesized 2.1-2.7 g/L. Zymograms revealed that L. mali strains have a single Dsr with a molecular weight (Mw) of ~ 145 kDa, while the Lc. mesenteroides possess one or two enzymes with 170-211 kDa Mw. As far as we know, this is the first detection of L. mali Dsr. Analysis of metabolic fluxes from sucrose revealed that the six LAB produced mannitol (~ 12 g/L). The co-addition of maltose-sucrose resulted in the production of panose (up to 37.53 mM), an oligosaccharide known for its prebiotic effect. A4X, Z36P and B12 showed dextranase hydrolytic enzymatic activity and were able to produce another trisaccharide, maltotriose, which is the first instance of a dextranase activity encoded by Lc. mesenteroides strains. Furthermore, B12 and O9 grew in the absence of riboflavin (vitamin B2) and synthesized this vitamin, in a defined medium at the level of ~ 220 µg/L. Therefore, these LAB, especially Lc. mesenteroides B12, are good candidates for the development of new fermented food biofortified with functional compounds.