District division administrative disaggregation data framework for monitoring leaving no one behind in the National Health Insurance Fund of Sudan: achieving sustainable development goals in 2030.

BACKGROUND: The aim of this study is to monitor the concept of 'leaving no one behind' in the Sustainable Development Goals (SDGs) to track the implications of the mobilization of health care resources by the National Health Insurance Fund (NHIF) of Sudan. METHODS: A cross-sectional study was used to monitor 'leaving no one behind' in NHIF by analyzing the secondary data of the information system for the year 2016. The study categorized the catchment areas of health care centers (HCCS) according to district administrative divisions, which are neighborhood, subdistrict, district, and zero. The District Division Administrative Disaggregation Data (DDADD) framework was developed and investigated with the use of descriptive statistics, maps of Sudan, the Mann-Whitney test, the Kruskal-Wallis test and health equity catchment indicators. SPSS ver. 18 and EndNote X8 were also used. RESULTS: The findings show that the NHIF has mobilized HCCs according to coverage of the insured population. This mobilization protected the insured poor in high-coverage insured population districts and left those living in very low-coverage districts behind. The Mann-Whitney test presented a significant median difference in the utilization rate between catchment areas (P value < 0.001). The results showed that the utilization rate of the insured poor who accessed health care centers by neighborhood was higher than that of the insured poor who accessed by more than neighborhood in each state. The Kruskal-Wallis test of the cost of health care services per capita in each catchment area showed a difference (P value < 0.001) in the median between neighborhoods. The cost of health care services in low-coverage insured population districts was higher than that in high-coverage insured population districts. CONCLUSION: The DDADD framework identified the inequitable distribution of health care services in low-density population districts leaves insured poor behind. Policymakers should restructure the equation of health insurance schemes based on equity and probability of illness, to distribute health care services according to needs and equity, and to remobilize resources towards districts left behind.

Caffeic Acid Enhances the Anti-Leukemic Effect of Imatinib on Chronic Myeloid Leukemia Cells and Triggers Apoptosis in Cells Sensitive and Resistant to Imatinib.

Among the phenolic acids tested on the K562 cell line, a model of chronic myeloid leukemia (CML), caffeic acid (CA) was biologically active on sensitive and imatinib (IM)-resistant cells at micro-molar concentration, either in terms of reduction of cell proliferation or triggering of apoptosis. The CA treatment provoked mitochondrial membrane depolarization, genomic DNA fragmentation and phosphatidylserine exposure, hallmarks of apoptosis. Cell cycle analysis following the treatment with comparable cytotoxic concentrations of IM or CA showed marked differences in the distribution profiles. The reduction of cell proliferation by CA administration was associated with increased expression of two cell cycle repressor genes, CDKN1A and CHES1, while IM at a cytotoxic concentration increased the CHES1 but not the CDKN1A expression. In addition, CA treatment affected the proliferation and triggered the apoptosis in IM-resistant cells. Taken together, these data suggested that CA induced the anti-proliferative effect and triggered apoptosis of CML cells by a different mechanism than IM. Finally, the combined administration of IM and CA at suboptimal concentrations evidenced a synergy of action in determining the anti-proliferative effect and triggering apoptosis. The ability of CA to potentiate the anti-leukemic effect of IM highlighted the nutraceutical potential of CA in CML.

A comprehensive review on tyrosinase inhibitors.

Tyrosinase is a multi-copper enzyme which is widely distributed in different organisms and plays an important role in the melanogenesis and enzymatic browning. Therefore, its inhibitors can be attractive in cosmetics and medicinal industries as depigmentation agents and also in food and agriculture industries as antibrowning compounds. For this purpose, many natural, semi-synthetic and synthetic inhibitors have been developed by different screening methods to date. This review has focused on the tyrosinase inhibitors discovered from all sources and biochemically characterised in the last four decades.

Determinants of occupational injury for US home health aides reporting one or more work-related injuries.

OBJECTIVES: Home health aides (HHAs) work in a high-risk industry and experience high rates of work-related injury that have been significantly associated with reduction in workers and organisational productivity, quality and performance. The main objective of the study was to examine how worker environment and ergonomic factors affect HHA risk for reporting occupational injuries. METHOD: We used cross-sectional analysis of data from the 2007 National Home Health and Hospice Aide Survey (NHHAS). The study sample consisted of a nationally represented sample of home health aides (n=3.377) with a 76.6% response rate. We used two scales 1 : a Work Environment Scale and 2 an Ergonomic Scale. Univariate and bivariate analyses were conducted to describe HHA work-related injury across individual, job and organisational factors. To measure scale reliability, Cronbach's alphas were calculated. Multivariable logistic regression was used to determine predictors of reported occupational injury. RESULTS: In terms of Work Environment Scale, the injury risk was decreased in HHAs who did not consistently care for the same patients (OR=0.96, 95% CI: 0.53 to 1.73). In terms of Ergonomic Scale, the injury risk was decreased only in HHAs who reported not needing any other devices for job safety (OR=0.30, 95% (CI): 0.15 to 0.61). No other Work Environment or Ergonomic Scale factors were associated with HHAs' risk of injury. CONCLUSION: This study has great implications on a subcategory of the workforce that has a limited amount of published work and studies, as of today, as well as an anticipated large demand for them.

Antenatal care satisfaction in a developing country: a cross-sectional study from Nigeria.

BACKGROUND: Utilization of Antenatal Care (ANC) is very low in Nigeria. Self-reported patient satisfaction may be useful to identify provider- and facility-specific factors that can be improved to increase ANC satisfaction and utilization. METHODS: Exit interview data collected from ANC users and facility assessment survey data from 534 systematically selected facilities in four northern Nigerian states were used. Associations between patient satisfaction (satisfied, not-satisfied) and patient ratings of the provider's interactions, care processes, out-of-pocket costs, and quality of facility infrastructure were studied. RESULTS: Of 1336 mothers, 90% were satisfied with ANC. Patient satisfaction was positively associated with responsive service (prompt, unrushed service, convenient clinic hours and privacy during consultation, AOR 2.42, 95% CI 2.05-2.87), treatment-facilitation (medical care-related provider communication and ease of receiving medicines, AOR 2.03, 95% CI 1.46-2.80), equipment availability (AOR 1.10, 95% CI 1.01-1.21), staff empathy (AOR 1.82, 95% CI 1.03-3.23), non-discriminatory treatment regardless of patient's socioeconomic status (AOR: 1.87, 95% CI 1.09-3.22), provider assurance (courtesy and patient's confidence in provider's competence, AOR 1.48, 95% CI 1.26-1.75), and number of clinical examinations received (AOR 1.28, 95% CI 1.10-1.50). ANC satisfaction was negatively impacted by out-of-pocket payment for care (vs. free care, AOR 0.44, 95% CI 0.23-0.82). CONCLUSIONS: ANC satisfaction in Nigeria may be enhanced by improving responsiveness to clients, clinical care quality, ensuring equipment availability, optimizing easy access to medicines, and expanding free ANC services.

Statewide dissemination and implementation of physical activity standards in afterschool programs: two-year results.

BACKGROUND: In 2015, YMCA afterschool programs (ASPs) across South Carolina, USA pledged to achieve the YMCA physical activity standard calling for all children to accumulate 30 min of moderate-to-vigorous physical activity (MVPA) while attending their ASPs. This study presents the final two-year outcomes from the dissemination and implementation efforts associated with achieving this MVPA standard. METHODS: Twenty ASPs were sampled from all South Carolina YMCA-operated ASPs (N = 97) and visited at baseline (2015) and first (2016) and second year (2017) follow-up. All ASPs were provided training to increase MVPA during the program by extending the scheduled time for activity opportunities and modifying commonly played games to increase MVPA. The RE-AIM framework was used to evaluate the statewide intervention. Accelerometer-derived MVPA was the primary outcome. Intent-to-treat (ITT) models were conducted summer 2017. Programs were also classified, based on changes in MVPA from 2015 to 2016 and 2016-2017, into one of three categories: gain, maintain, or lost. Implementation, within the three groups, was evaluated via direct observation and document review. RESULTS: Adoption during the first year was 45% of staff attending training, with this increasing to 67% of staff during the second year. ITT models indicated no increase in the odds of accumulating 30 min of MVPA after the first year for either boys (odds ratio [OR] 1.06, 95CI 0.86-1.31) or girls (OR 1.14, 95CI 0.87-1.50), whereas an increase in the odds was observed during the second year for boys (OR 1.31, 95CI 1.04-1.64) and girls (OR 1.50 95CI 1.01-1.80). Programs that lost MVPA (avg. - 5 to - 7.5 min/d MVPA) elected to modify their program in a greater number of non-supportive ways (e.g., reduce time for activity opportunities, less time spent outdoors), whereas ASPs that gained MVPA (avg. + 5.5 to + 10.1 min MVPA) elected to modify their program in more supportive ways. CONCLUSIONS: The statewide study demonstrated minimal improvements in overall MVPA. However, child MVPA was dramatically influenced by ASPs who elected to modify their daily program in more supportive than non-supportive ways, with no one program modifying their program consistently across the multi-year initiative. These findings have important implications for organizations seeking to achieve the MVPA standard. TRIAL REGISTRATION: Clinical Trial Registration: NCT02394717 .

Patient portal adoption and use by hospitalized cancer patients: a retrospective study of its impact on adverse events, utilization, and patient satisfaction.

BACKGROUND: Portal use has been studied among outpatients, but its utility and impact on inpatients is unclear. This study describes portal adoption and use among hospitalized cancer patients and investigates associations with selected safety, utilization, and satisfaction measures. METHODS: A retrospective review of 4594 adult hospitalized cancer patients was conducted between 2012 and 2014 at Mayo Clinic in Jacksonville, Florida, comparing portal adopters, who registered for a portal account prior to hospitalization, with nonadopters. Adopters were classified by their portal activity during hospitalization as active or inactive inpatient users. Univariate and several logistic and linear regression models were used for analysis. RESULTS: Of total patients, 2352 (51.2%) were portal adopters, and of them, 632 (26.8%) were active inpatient users. Portal adoption was associated with patients who were young, female, married, with higher income, and had more frequent hospitalizations (P < .05). Active inpatient use was associated with patients who were young, married, nonlocals, with higher disease severity, and were hospitalized for medical treatment (P < .05). In univariate analyses, self-management knowledge scores were higher among adopters vs nonadopters (84.3 and 80.0, respectively; P = .01) and among active vs inactive inpatient users (87.0 and 83.3, respectively; P = .04). In regression models adjusted for age and disease severity, the association between portal behaviors and majority of measures were not significant (P > .05). CONCLUSIONS: Over half of our cancer inpatients adopted a portal prior to hospitalization, with increased adoption associated with predisposing and enabling determinants (eg: age, sex, marital status, income), and increased inpatient use associated with need (eg: nonlocal residence and disease severity). Additional research and greater effort to expand the portal functionality is needed to impact inpatient outcomes.

Factors Affecting Life Satisfaction of Older Adults in Turkey.

This study aimed to examine the determinants of life satisfaction of older adults in Turkey. The sample consisted of 2,959 older adults over 65 years. The effects of psychological, daily life and instrumental activity, physical health and health status, and other important variables on life satisfaction were analyzed. The variables lessening life satisfaction for older adults included poverty, a lower self-reported health status, a decline in physical health, ability to chew, ability to do household activities, and an increase in feelings of depression and feeling social withdrawn. In contrast, being married, having a higher education level, and having an income-generating work increased life satisfaction among older adults. This study suggests the necessity of developing local and national policies that enable older adults to become more active in their communities. These policies should be coordinated under the framework of national aging policies that bridge health, social, and economic issues.

Achieving value for money in health: a comparative analysis of OECD countries and regional countries.

OBJECTIVE: To measure efficiency gains in health sector over the years 1995 to 2013 in OECD, EU, non-member European countries. METHODS: An output-oriented DEA model with variable return to scale, and residuals estimated by regression equations were used to estimate efficiencies of health systems. Slacks for health care outputs and inputs were calculated by using DEA multistage method of estimating country efficiency scores. RESULTS: Better health outcomes of countries were related with higher efficiency. Japan, France, or Sweden were found to be peer-efficient countries when compared to other developed countries like Germany and United States. Increasing life expectancy beyond a certain high level becomes very difficult to achieve. Despite declining marginal productivity of inputs on health outcomes, some developed countries and developing countries were found to have lowered their inefficiencies in the use of health inputs. Although there was no systematic relationship between political system of countries and health system efficiency, the objectives of countries on social and health policy and the way of achieving these objectives might be a factor increasing the efficiency of health systems. CONCLUSIONS: Economic and political stability might be as important as health expenditure in improving health system goals. A better understanding of the value created by health expenditures, especially in developed countries, will require analysis of specific health interventions that can increase value for money in health. Copyright © 2016 John Wiley & Sons, Ltd.

A Low-Cost Partner Notification Strategy for the Control of Sexually Transmitted Diseases: A Case Study From Louisiana.

OBJECTIVES: We estimated the costs and effectiveness of implementing a partner notification (PN) strategy for highly prevalent sexually transmitted diseases (STDs) within the Louisiana STD/HIV Program. METHODS: We carried out a telephone-based PN approach on an experimental basis in 2 public STD clinics in Louisiana from June 2010 to May 2012. We monitored data on the resources used for identifying, tracing, treating, and managing the infected cases and their partners to estimate the intervention costs. RESULTS: Our results indicated that implementation of telephone-based PN should not increase the STD control program's expenses by more than 4.5%. This low-cost PN approach could successfully identify and treat 1 additional infected case at a cost of only $171. We found that the cost per disability-adjusted life year averted (a health outcome measure), because of the adoption of selective screening with partner tracing, was $4499. This was significantly lower than the gross domestic product per capita of the United States, a threshold used for defining highly cost-effective health interventions. CONCLUSIONS: Adoption of PN for gonorrhea and chlamydia should be considered a national strategy for prevention and control of these diseases.

Genome analysis of the new human polyomaviruses.

Polyomaviridae is a growing family of naked, double-stranded DNA viruses that infect birds and mammals. The last few years, several new members infecting birds or primates have been discovered, including seven human polyomaviruses: KI, WU, Merkel cell polyomavirus, HPyV6, HPyV7, trichodysplasia spinulosa-associated polyomavirus, and HPyV9. In addition, DNA and antibodies against the monkey lymphotropic polyomavirus have been detected in humans, indicating that this virus can also infect man. However, little is known about the route of infection, transmission, cell tropism, and, with the exception of Merkel cell polyomavirus and trichodysplasia spinulosa-associated polyomavirus, the pathogenicity of these viruses. This review compares the genomes of these emerging human polyomaviruses with previously known polyomaviruses detected in man, reports mutations in different isolates, and predicts structural and functional properties of their viral proteins.

Utilization of telehealth services in low- and middle-income countries amid the COVID-19 pandemic: a narrative summary.

BACKGROUND: During the current period of the pandemic, telehealth has been a boon to the healthcare system by providing quality healthcare services at a safe social distance. However, there has been slow progress in telehealth services in low- and middle-income countries with little to no evidence of the cost and effectiveness of such programmes. OBJECTIVE: To provide an overview of the expansion of telehealth in low- and middle-income countries amid the COVID-19 pandemic and identify the challenges, benefits, and costs associated with implementing telehealth services in these countries. METHODS: We performed a literature review using the search term: '*country name* AND ((telemedicine[Title][Abstract]) OR (telehealth[Title][Abstract] OR eHealth[Title][Abstract] OR mHealth[Title][Abstract]))'. Initially, we started with 467 articles, which were reduced to 140 after filtering out duplicates and including only primary research studies. Next, these articles were screened based on established inclusion criteria and 44 articles were finalised to be used in the review. RESULTS: We found telehealth-specific software being used as the most common tool to provide such services. Nine articles reported patient satisfaction of greater than 90% with telehealth services. Moreover, the articles identified the ability to make a correct diagnosis to resolve the condition, efficient mobilisation of healthcare resources, increased accessibility for patients, increased service utilisation, and increased satisfaction as benefits of telehealth services, whereas inaccessibility, low technological literacy, and lack of support, poor security standards and technological concerns, loss of interest by the patients, and income impacts on physicians as challenges. The review could not find articles that explored the financial information on telehealth programme implementation. CONCLUSION: Although telehealth services are growing in popularity, the research gap on the efficacy of telehealth is high in low- and middle-income countries. To better guide the future development of telehealth services, rigorous economic evaluation of telehealth is needed.

BK virus-associated infection in cerebrospinal fluid of neurological patients and mutation analysis of the complete VP1 gene in different patient groups.

While BK virus (BKV) is frequently associated with pathological conditions in bone marrow and renal transplant recipients, BKV infection in neurological individuals has been rarely reported. As a result of a BKV, JCV, and SV40 large T antigen-specific multiplex PCR on 2,062 cerebrospinal fluid (CSF) samples from neurological patients suspicious of JCV infection, we identified 20 subjects with at least 1 CSF specimen positive for BKV large T antigen DNA. Because VP1 protein has been suggested to influence the biological/pathological properties of BKV, we tried to sequence the entire VP1 gene in the BKV-positive neurological patients and succeeded in 14 of the 20 neurological patients. To compare the VP1 sequence of the BKV neurological strains with that of non-neurotropic strains in other clinical situations, full-length VP1 DNA was sequenced in 15 renal and 6 bone marrow transplant recipients positive to BKV-viremia, and in 8 pregnant women as non-pathological controls. An increased (respectively, decreased) tendency for mutations in the BC loop (respectively, EF loop) was observed, and no mutations were detected in the CD, GH, and HI loops. Subtype I was predominant (93%) and compared to archetypal BKV (WW), amino acid substitutions were detected in 4/14 neurological patients, 10/15 renal transplant recipients, 3/6 bone marrow transplant patients, and in all the pregnant women. Each patient group had distinctive VP1 mutations, but these unique substitutions were not present in all patients of this group. However, molecular modeling simulations of the VP1 mutants predicted changes in protein surface properties which might affect the VP1-receptor interaction.

The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitor.

The mitogen-activated protein kinase-activated protein kinase MK5 is ubiquitously expressed in vertebrates and is implicated in cell proliferation, cytoskeletal remodeling, and anxiety behavior. This makes MK5 an attractive drug target. We tested several diterpenoid alkaloids for their ability to suppress MK5 kinase activity. We identified noroxoaconitine as an ATP competitor that inhibited the catalytic activity of MK5 in vitro (IC50 = 37.5 µM; K(i) = 0.675 µM) and prevented PKA-induced nuclear export of MK5, a process that depends on kinase active MK5. MK5 is closely related to MK2 and MK3, and noroxoaconitine inhibited MK3- and MK5- but not MK2-mediated phosphorylation of the common substrate Hsp27. Molecular docking of noroxoaconitine into the ATP binding sites indicated that noroxoaconitine binds more strongly to MK5 than to MK3. Noroxoaconitine and derivatives may help in elucidating the precise biological functions of MK5 and may prove to have therapeutic values.

Specific interactions and binding free energies between thermolysin and dipeptides: molecular simulations combined with ab initio molecular orbital and classical vibrational analysis.

Thermolysin (TLN) is a metalloprotease widely used as a nonspecific protease for sequencing peptide and synthesizing many useful chemical compounds by the chemical industry. It was experimentally shown that the activity and functions of TLN are inhibited by the binding of many types of amino acid dipeptides. However, the binding mechanisms between TLN and dipeptides have not been clarified at the atomic and electronic levels. In this study, we investigated the binding mechanisms between TLN and four dipeptides. Specific interactions and binding free energies (BFEs) between TLN and the dipeptides were calculated using molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital (FMO) methods. The molecular systems were embedded in solvating water molecules during calculations. The calculated BFEs were qualitatively consistent with the trend of the experimentally observed inhibition of TLN activity by binding of the dipeptides. In addition, the specific interactions between the dipeptides and each amino acid residue of TLN or solvating water molecules were elucidated by the FMO calculations.

Cluster spin-glass-like dynamics in Mn-rich La2Ni0.5Mn1.5O6ferromagnetic insulator.

We report on the physical properties of Mn-rich, nonstoichiometric La2Ni0.5Mn1.5O6ferromagnetic insulator, prepared by sol-gel method. The single-phase orthorhombicPbnmstructure for the compound was confirmed by x-ray diffraction measurements. Dc magnetization measurements revealed a high saturation magnetization of ∼5.95 µB/f.u. at 5 K, and a ferromagnetic to paramagnetic transition at ∼162 K. Ac magnetic susceptibility measurements confirmed a broad frequency-dependent anomaly at lower temperatures indicating the presence of spin-glass type magnetic interactions. The ac susceptibility data have been discussed within the framework of the critical slowing down model and Vogel-Fulcher law, and confirmed the cluster spin-glass dynamics with a relaxation time of the order of 10-5 s. The valence of Ni and Mn ions was verified from the x-ray absorption near edge structure spectroscopy. The origin of cluster spin-glass state was discussed in terms of several possible magnetic exchange interaction pathways among Ni and Mn ions.

Identification of novel quinazolin-4(3H)-ones as inhibitors of thermolysin, the prototype of the M4 family of proteinases.

A combinatorial series of novel quinazolin-4(3H)-ones were synthesised and their structures were established based on spectroscopic data (IR, NMR, EI-MS, and FAB-MS). The compounds were tested for inhibition of the zinc metalloproteinase thermolysin (TLN) utilizing a chemical array-based approach. Some of the compounds were found to inhibit TLN, with IC(50) values ranging from 0.0115 microM (compound 3) to 122,637 microM (compound 29). Compound 3 [3-phenyl-2-(trifluoromethyl) quinazolin-4(3H)-one] (IC(50)=0.0115 microM) and compound 35 [3-(isopropylideneamino)-2,2-dimethyl-2,3-dihydroquinazolin-4 (1H)-one] (IC(50)=0.2477 microM) were found to be the most potent inhibitors.

Tyrosinase inhibitory effect of benzoic acid derivatives and their structure-activity relationships.

A series of benzoic acid derivatives 1-10 have been synthesised by two different methods. Compounds 1-6 were synthesised by a facile procedure for esterification using N,N'-dicyclohexylcarbodiimide (DCC) as a coupling agent, methylene chloride as a solvent system and dimethylaminopyridine (DMAP). While 7-10 were synthesised by converting benzoic acid into benzoyl chloride by treating with thionyl chloride in the presence of benzene and performing a further reaction with amine in dried benzene. The structures of all the synthesised derivatives of benzoic acid (1-10) were assigned on the basis of extensive NMR studies. All of them showed inhibitory potential against tyrosinase. Among them, compound 7 was found to be the most potent (1.09 µM) when compared with the standard tyrosinase inhibitors of kojic acid (16.67 µM) and L-mimosine (3.68 µM). Finally in this paper, we have discussed the structure-activity relationships of the synthesised molecules.

Health-related quality of life after total hip replacement: a Taiwan study.

This study applied the generalised estimating equations (GEE) in a large-scale prospective cohort study of predictors of health-related quality of life (HRQoL) in a Taiwan population. The study population included all patients who had undergone primary total hip replacement (THR) performed between March 1998 and December 2002 by either of two orthopaedic surgeons in two hospitals. The SF-36 was used in pre- and postoperative assessments of 335 patients. Young age, male gender, minimal comorbidity, use of epidural anaesthesia, lack of readmission within the previous 30 days, and higher preoperative functional status were positively associated with HRQoL (P < 0.05). Patients should be advised that their postoperative HRQoL may depend not only on their postoperative health care but also on their preoperative functional status. These analytical results should be applicable to other Taiwan hospitals and to other countries with similar social and cultural practices.

Atom- and bond-based 2D TOMOCOMD-CARDD approach and ligand-based virtual screening for the drug discovery of new tyrosinase inhibitors.

Two-dimensional atom- and bond-based TOMOCOMD-CARDD descriptors and linear discriminant analysis (LDA) are used in this report to perform a quantitative structure-activity relationship (QSAR) study of tyrosinase-inhibitory activity. A database of inhibitors of the enzyme is collected for this study, within 246 highly dissimilar molecules presenting antityrosinase activity. In total, 7 discriminant functions are obtained by using the whole set of atom- and bond-based 2D indices. All the LDA-based QSAR models show accuracies above 90% in the training set and values of the Matthews correlation coefficient (C) varying from 0.85 to 0.90. The external validation set shows globally good classifications between 89% and 91% and C values ranging from 0.75 to 0.81. Finally, QSAR models are used in the selection/identification of the 20 new dicoumarins subset to search for tyrosinase inhibitory activity. Theoretical and experimental results show good correspondence between one another. It is important to remark that most compounds in this series exhibit a more potent inhibitory activity against the mushroom tyrosinase enzyme than the reference compound, Kojic acid (IC(50) = 16.67 muM), resulting in a novel nucleus base (lead) with antityrosinase activity, and this could serve as a starting point for the drug discovery of novel tyrosinase inhibitor lead compounds. ( Journal of Biomolecular Screening 2008:1014-1024).