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People living with HIV/AIDS (PLHA) are experiencing growing co-morbidities due to an increase in life expectancy and the use of long-term antiretroviral therapy (ART). The lack of integrated non-communicable diseases (NCDs) screening and management at the HIV care and treatment centres (CTCs) make it difficult to determine the trends of NCD co-morbidity among patients with HIV. This study aimed to assess the burden and determinants of common NCDs, including depression among patients with HIV.Analytical cross-sectional study of 1318 HIV patients enrolled using systematic random sampling conducted from April to November 2020. Five large CTCs in district referral hospitals were selected representing the five districts of Dar es Salaam including Mwananyamala, Temeke, and Amana regional referral hospitals and Sinza and Vijibweni hospitals. The study population consisted of adult PLHA aged 18 years and above. The primary outcome measure was the prevalence of NCDs among HIV patients. Observation of actual NCD medications or their purchase receipts or booked NCD clinic appointments that PLHA had during the study period was used to verify the reported presence of NCDs. The secondary outcome measure was the prevalence of probable depression among PLHA. The locally validated Swahili Patient Health Questionnaire (PHQ-9) was used to screen for depressive symptom severity. A logistic regression model was used to identify factors associated with common NCDs and those associated with probable depression. Potential risk factors that were statistically significant at a P-value of 0.2 or less in univariable analysis were included as potential confounders in multivariable models.The median age of participants was 42 (IQR 35-49) years, with 32.7% in the 36-45 years age group. The majority of patients were women (69%). Most (80.5%) had achieved HIV viral (VL) suppression (a serum HIV VL of1000 copies/ml). Overall, 14.3% of self-reported an NCD with evidence of their current medication for the NCD from receipts for medication purchased and appointments from NCD clinics they attended. In the multivariable analyses, higher odds of NCDs were in older patients (45 years) and those with a weight above 75 kg (P 0.05). Male patients had 51% reduced odds of NCDs (aOR 0.49; 95% CI: 0.32-0.74) than females (P 0.001). Probable depression prevalence was 11.8%, and depressed patients had more than twice the odds of having NCDs than those without depression (aOR 2.26; 95% CI: 1.45-3.51; P 0.001).This study determined co-existing previously diagnosed NCDs among PLHA accessing care and high levels of depressive symptom severity. We recommend additional research on the feasibility, acceptability, and cost implications of screening and treating NCDs on HIV care platforms to provide evidence for Tanzania's integrated HIV/NCD care model.

Magnetic resonance imaging (MRI) technology has profoundly transformed current healthcare systems globally, owing to advances in hardware and software research innovations. Despite these advances, MRI remains largely inaccessible to clinicians, patients, and researchers in low-resource areas, such as Africa. The rapidly growing burden of noncommunicable diseases in Africa underscores the importance of improving access to MRI equipment as well as training and research opportunities on the continent. The Consortium for Advancement of MRI Education and Research in Africa (CAMERA) is a network of African biomedical imaging experts and global partners, implementing novel strategies to advance MRI access and research in Africa. Upon its inception in 2019, CAMERA sets out to identify challenges to MRI usage and provide a framework for addressing MRI needs in the region. To this end, CAMERA conducted a needs assessment survey (NAS) and a series of symposia at international MRI society meetings over a 2-year period. The 68-question NAS was distributed to MRI users in Africa and was completed by 157 clinicians and scientists from across Sub-Saharan Africa (SSA). On average, the number of MRI scanners per million people remained at less than one, of which 39% were obsolete low-field systems but still in use to meet daily clinical needs. The feasibility of coupling stable energy supplies from various sources has contributed to the growing number of higher-field (1.5 T) MRI scanners in the region. However, these systems are underutilized, with only 8% of facilities reporting clinical scans of 15 or more patients per day, per scanner. The most frequently reported MRI scans were neurological and musculoskeletal. The CAMERA NAS combined with the World Health Organization and International Atomic Energy Agency data provides the most up-to-date data on MRI density in Africa and offers a unique insight into Africa's MRI needs. Reported gaps in training, maintenance, and research capacity indicate ongoing challenges in providing sustainable high-value MRI access in SSA. Findings from the NAS and focused discussions at international MRI society meetings provided the basis for the framework presented here for advancing MRI capacity in SSA. While these findings pertain to SSA, the framework provides a model for advancing imaging needs in other low-resource settings.

The food industry faces numerous challenges to assure provision of tasty and convenient food that possesses extended shelf life and shows long‐term high‐quality preservation. Research and development of antimicrobial materials for food applications have provided active antibacterial packaging technologies that are able to meet these challenges. Furthermore, consumers expect and demand sustainable packaging materials that would reduce environmental problems associated with plastic waste. In this review, we discuss antimicrobial composite materials for active food packaging applications that combine highly efficient antibacterial nanoparticles (i.e., metal, metal oxide, mesoporous silica and graphene‐based nanomaterials) with biodegradable and environmentally friendly green polymers (i.e., gelatin, alginate, cellulose, and chitosan) obtained from plants, bacteria, and animals. In addition, innovative syntheses and processing techniques used to obtain active and safe packaging are showcased. Implementation of such green active packaging can significantly reduce the risk of foodborne pathogen outbreaks, improve food safety and quality, and minimize product losses, while reducing waste and maintaining sustainability.

In head and neck squamous cell carcinoma, immune checkpoint inhibitors (ICI) lead to improved outcomes. There has been reports of accelerated disease progression, or hyperprogression, after ICI initiation. We present a case of hyperprogression after one dose of nivolumab in maxillary sinus squamous cell carcinoma. The patient had complete vision loss due to disease progression into the orbit, as well as intracranial invasion, lytic metastases, and new widespread distal metastases. Hyperprogression can occur after the first dose of immunotherapy. Absent biomarkers regarding individual risk of hyperprogression, caution should be exercised in using ICI in sinonasal cancers with orbital abutting disease. Laryngoscope, 130:907-910, 2020.

Introduction: Identification of low birthweight and small for gestational age is pivotal in clinical management and many research studies, but in low-income countries, birthweight is often unavailable within 24 h of birth. Newborn weights measured within days after birth and knowledge of the growth patterns in the first week of life can help estimate the weight at birth retrospectively. This study aimed to generate sex-specific prediction maps and weight reference charts for the retrospective estimation of birthweight for exclusively breastfed newborns in a low-resource setting. Material and methods: This was a prospective cohort study nested in a clinical trial of intermittent preventive treatment in pregnancy for malaria with either dihydroartemisinin–piperaquine with/without azithromycin or sulfadoxine–pyrimethamine in Korogwe District, north-eastern Tanzania (Clinicaltrials.gov: NCT03208179). Newborns were weighed at birth or in the immediate hours after birth and then daily for 1 week. Reference charts, nadir, time to regain weight, and prediction maps were generated using nonlinear mixed-effects models fitted to the longitudinal data, incorporating interindividual variation as random effects. Predictions and prediction standard deviations were computed using a linear approximation approach. Results: Between March and December 2019, 513 live newborns with birthweights measured within 24 h of delivery were weighed daily for 1 week. Complete datasets were available from 476 exclusively breastfed newborns. There was a rapid decline in weight shortly after delivery. The average weight loss, time of nadir, and time to regain weight were 4.3% (95% confidence interval [CI] 3.8–4.9) at 27 h (95% CI 24–30) and 105 h (95% CI 91–120) in boys and 4.9% (95% CI 4.2–5.6) at 28 h (95% CI 23–33) and 114 h (95% CI 93–136) in girls, respectively. The data were used to generate prediction maps with 1-h time intervals and 0.05 kg weight increments showing the predicted birthweights and weight-for-age and weight-change-for-age reference charts depicting variation in weight loss from 10%. Conclusions: The prediction maps and reference charts can be used by researchers in low-resource settings to retrospectively estimate birthweights using weights collected up to 168 h after delivery, thereby maximizing data utilization. Clinical practitioners can also use the prediction maps to retrospectively classify newborns as low birthweight or small for gestational age.

Despite the availability of vaccines and antibiotics, pneumonia remains the leading cause of mortality among children under 5 years of age. The objective of this study was to identify modifiable risk factors for community-acquired pneumonia (CAP) in children under 5 years of age in a vaccinated population.A case-control study was conducted between January and December 2017. The cases included children aged 2-59 months with X-ray-confirmed pneumonia, whereas the controls were children from the community with no history of respiratory infection. A multivariable logistic regression model was used to determine the modifiable risk factors for CAP.A total of 113 children with X-ray-confirmed pneumonia and 350 healthy children were enrolled in this study. The median ages for the cases and controls were 13.7 (IQR = 7.2-25.3) and 13.4 (IQR = 6.0-24.8) months respectively. One (0.9%) child died after the enrolment. The independent predictors of CAP included a lack of exclusive breastfeeding for 6 months (aOR = 1.7, 95% CI = 1.0-2.9), underweight (aOR = 2.1, 95% CI = 1.0-4.5), unclean cooking fuel (aOR = 1.8, 95% CI = 1.0-3.3) and low income (aOR = 2.9, 95% CI = 1.6-5.4). No association was found between vaccination status and CAP.In addition to a lack of exclusive breastfeeding, children from families of low-economic status were at risk of contracting CAP. Since the risk factors are complex, the study results call for more concerted efforts by and collaboration among the health, agriculture and development sectors to address mortality caused by CAP.Malgré la disponibilité des vaccins et des antibiotiques, la pneumonie reste la principale cause de mortalité chez les enfants de moins de cinq ans. L'objectif de cette étude était d'identifier les facteurs de risque modifiables pour la pneumonie acquise en communauté (PAC) chez les enfants de moins de cinq ans dans une population vaccinée. MÉTHODES: Une étude cas-témoins a été menée entre janvier et décembre 2017. Les cas concernaient des enfants âgés de 2 à 59 mois atteints de pneumonie confirmée par la radiographie, alors que les témoins étaient des enfants de la communauté sans antécédents d'infection respiratoire. Un modèle de régression logistique multivariée a été utilisé pour déterminer les facteurs de risque modifiables pour la PAC. RÉSULTATS: Au total, 113 enfants atteints de pneumonie confirmée par la radiographie et 350 enfants en bonne santé ont été inclus dans cette étude. Les âges médians pour les cas et les témoins étaient respectivement de 13,7 (IQR = 7,2 - 25,3) et de 13,4 (IQR = 6,0 - 24,8) mois. Un enfant (0,9%) est décédé après l'inscription. Les prédicteurs indépendants de la PAC comprenaient une absence d'allaitement exclusif pendant six mois (aOR = 1,7; IC95%: 1,0 - 2,9), un poids insuffisant (aOR = 2,1; IC95%: 1,0 - 4,5), un combustible de cuisson non propre (aOR = 1,8; IC95%: 1,0 - 3,3) et un faible revenu (aOR = 2,9; IC95%: 1,6 - 5,4). Aucune association n'a été trouvée entre le statut de vaccination et la PAC.Outre l'absence d'allaitement maternel exclusif, les enfants issus de familles à faible statut économique étaient à risque de contracter la PAC. Les facteurs de risque étant complexes, les résultats de l’étude appellent à des efforts plus concertés et une collaboration accrue entre les secteurs de la santé, de l'agriculture et du développement afin de lutter contre la mortalité causée par la PAC.

Objectives Sinigrin is a major glucosinolate present in plants of the Brassicaceae family. Recently, sinigrin and its phytosome formulations have been investigated for its wound-healing actions, by our research group. The aim of this study was to demonstrate sinigrin drug release from its phytosome complex and also to determine whether the phytosome complex enhances the delivery of sinigrin into the skin when compared to free sinigrin. Methods In vitro Franz cell diffusion studies were performed on human abdominal skin. The morphology of the phytosome complex was examined by transmission electron microscopy. The in vitro drug release was determined using dialysis sacks. Key findings The in vitro drug release indicated a controlled and sustained release of sinigrin from the phytosome complex. Tape stripping results showed that the sinigrin–phytosome complex (0.5155 μg/ml) statistically significantly enhanced the delivery of sinigrin into the stratum corneum–epidermis when compared to the free sinigrin (0.0730 μg/ml). Conclusions These results suggested the possibility of utilizing sinigrin–phytosome complex, to optimally deliver sinigrin to the skin which can be further used for various skin-related diseases including wound healing.

Abnormal skin findings are identified in over 90% of human immunodeficiency virus (HIV)-infected persons globally. A prospective cohort study of HIV-infected patients with skin complaints commencing antiretroviral therapy (ART) in northern Tanzania was undertaken. Consecutive HIV-infected subjects presenting with skin complaints who met criteria for ART initiation were recruited at a Tanzanian Regional Dermatology Training Center. A single dermatologist evaluated all subjects; baseline skin biopsies were performed and CD4(+) cell counts and plasma HIV RNA levels were measured. All subjects received a fixed-dose combination of stavudine lamivudine and nevirapine. A total of 100 subjects were enrolled; 86 subjects completed six months of follow-up. Median baseline CD4(+) cell counts and plasma HIV RNA levels were 120 cells/mul and 5.2 log10 copies/ml. The most common dermatologic condition was papular pruritic eruption (47%). The median baseline score on the Burn Scale was 38%. After six months 10 subjects had achieved the complete resolution of skin abnormalities. In those without complete resolution the median Burn Scale score improved to 7%. Five patients developed new eruptions by month 3 which in two cases were attributed to drug reactions. In the 86 subjects remaining on ART after six months the median CD4(+) cell count had increased to 474 cells/mul and plasma HIV RNA levels were

Objectives: The aim of this study was to investigate the in vitro permeation enhancement effects of the gel and whole leaf materials of Aloe vera, Aloe marlothii and Aloe ferox using ketoprofen as a marker compound. Methods: The permeation studies were conducted across excised female abdominal skin in Franz diffusion cells and the delivery of ketoprofen into the stratum corneum-epidermis and epidermis-dermis layers of the skin was investigated using a tape stripping technique. Key findings: Aloe vera gel showed the highest permeation enhancing effect on ketoprofen (enhancement ratio or ER = 2.551) when compared to the control group, followed by Aloe marlothii gel (ER = 1.590) and Aloe ferox whole leaf material (ER = 1.520). Non-linear curve fitting calculations indicated that the drug permeation enhancing effect of Aloe vera gel can be attributed to an increased partitioning of the drug into the skin,while Aloe ferox whole leaf modified the diffusion characteristics of the skin for ketoprofen. The tape stripping results indicated that Aloe marlothii whole leaf delivered the highest concentration of the ketoprofen into the different skin layers. Conclusions: Of the selected aloe species investigated, Aloe vera gel material showed the highest potential as transdermal drug penetration enhancer across human skin. http://www.pharmpress.com/product/00223573/jpp/

The development of insecticide resistance is a threat to the control of malaria in Africa. We report the findings of a national survey carried out in Tanzania in 2011 to monitor the susceptibility of malaria vectors to pyrethroid, organophosphate, carbamate and DDT insecticides, and compare these findings with those identified in 2004 and 2010. Standard World Health Organization (WHO) methods were used to detect knock-down and mortality rates in wild female Anopheles gambiae s.l. (Diptera: Culicidae) collected from 14 sentinel districts. Diagnostic doses of the pyrethroids deltamethrin, lambdacyhalothrin and permethrin, the carbamate propoxur, the organophosphate fenitrothion and the organochlorine DDT were used. Anopheles gambiae s.l. was resistant to permethrin in Muleba, where a mortality rate of 11% [95% confidence interval (CI) 6-19%] was recorded, Muheza (mortality rate of 75%, 95% CI 66-83%), Moshi and Arumeru (mortality rates of 74% in both). Similarly, resistance was reported to lambdacyhalothrin in Muleba, Muheza, Moshi and Arumeru (mortality rates of 31-82%), and to deltamethrin in Muleba, Moshi and Muheza (mortality rates of 28-75%). Resistance to DDT was reported in Muleba. No resistance to the carbamate propoxur or the organophosphate fenitrothion was observed. Anopheles gambiae s.l. is becoming resistant to pyrethoids and DDT in several parts of Tanzania. This has coincided with the scaling up of vector control measures. Resistance may impair the effectiveness of these interventions and therefore demands close monitoring and the adoption of a resistance management strategy.

MicroRNAs are a class of non-coding RNAs that post-transcriptionally regulate target gene expression. Previous studies have shown that microRNA gene variability can interfere with its function, resulting in phenotypic variation. Polymorphisms within microRNA genes present a source of novel biomarkers for phenotypic traits in animal breeding. However, little is known about microRNA genetic variability in livestock species, which is also due to incomplete data in genomic resource databases. Therefore, the aim of this study was to perform a genome-wide in silico screening of genomic sources and determine the genetic variability of microRNA genes in livestock species using mirna sniper 3.0 (http://www.integratomics-time.com/miRNA-SNiPer/), a new version of our previously developed tool. By examining Ensembl and miRBase genome builds, it was possible to design a tool-based generated search of 16 genomes including four livestock species: pig, horse, cattle and chicken. The analysis revealed 65 polymorphisms located within mature microRNA regions in these four species, including 28% within the seed region in cattle and chicken. Polymorphic microRNA genes in cattle and chicken were further examined for mapping to quantitative trait loci regions associated with production and health traits. The developed bioinformatics tool enables the analysis of polymorphic microRNA genes and prioritization of potential regulatory polymorphisms and therefore contributes to the development of microRNA-based biomarkers in livestock species. The assembled catalog and the developed tool can serve the animal science community to efficiently select microRNA SNPs for further quantitative and molecular genetic evaluations of their phenotypic effects and causal associations with livestock production traits.

Objective. To identify factors associated with perinatal mortality in northeastern Tanzania. Design. Prospective cohort study. Setting. Northeastern Tanzania. Population. 872 mothers and their newb ...

Background: Drug addiction and alcoholism involve a complex etiopathogenesis with a variable degree of risk contributions from the host (person), environment, and addictive substances. In this work, temperament and character features of individuals addicted to opiates or alcohol are compared with normal controls to study personality factors in the overall risk for drug addiction. Methods: The study was done in a permissive environment, with easy access to alcohol and heroin, which facilitated analyses of personality factors in drug choice. Participants included 412 consecutive patients (312 opiate addicts, 100 alcohol addicts) treated at the Specialized Hospital for Chemical Dependency in Belgrade, Serbia, and a community sample of 346 controls. Results: Opiate addicts manifested antisocial temperament configuration (high Novelty Seeking, low Reward Dependence) coupled with high Self-transcendence (ie, susceptibility to fantasy and imagination). Alcohol addicts manifested sensitive temperament configuration (high Novelty Seeking coexisting with high Harm Avoidance). Immature personality was observed far more frequently in opiate addicts than in alcoholics or normals. Conclusions: Novelty Seeking appears to be a general risk factor for drug addiction. High Harm Avoidance appears to channel individuals with high Novelty Seeking towards alcoholism. Immature character traits and probable Personality Disorder increase the risk of illegal drugs. Based on equivalent research in nonpermissive environments, at least a portion of our opiate addicts could have developed alcoholism instead in environments with more limited access to opiates. Personality factors provide useful guidelines for preventive work with young individuals with personality risk factors for drug addiction. (Am J Addict 2012;21:462–467)

Objective The aim of the study was to monitor the insecticide susceptibility status of malaria vectors in 12 sentinel districts of Tanzania. Methods WHO standard methods were used to detect knock-down and mortality in the wild female Anopheles mosquitoes collected in sentinel districts. The WHO diagnostic doses of 0.05% deltamethrin, 0.05% lambdacyhalothrin, 0.75% permethrin and 4% DDT were used. Results The major malaria vectors in Tanzania, Anopheles gambiae s.l., were susceptible (mortality rate of 98–100%) to permethrin, deltamethrin, lambdacyhalothrin and DDT in most of the surveyed sites. However, some sites recorded marginal susceptibility (mortality rate of 80–97%); Ilala showed resistance to DDT (mortality rate of 65% [95% CI, 54–74]), and Moshi showed resistance to lambdacyhalothrin (mortality rate of 73% [95% CI, 69–76]) and permethrin (mortality rate of 77% [95% CI, 73–80]). Conclusions The sustained susceptibility of malaria vectors to pyrethroid in Tanzania is encouraging for successful malaria control with Insecticide-treated nets and IRS. However, the emergency of focal points with insecticide resistance is alarming. Continued monitoring is essential to ensure early containment of resistance, particularly in areas that recorded resistance or marginal susceptibility and those with heavy agricultural and public health use of insecticides. Objectif: Surveiller l’etat de la sensibilite aux insecticides des vecteurs du paludisme dans 12 districts sentinelles de la Tanzanie. Methodes: Les methodes standard de l’OMS ont ete utilisees pour mesurer l’inhibition et la mortalite des moustiques anopheles femelles sauvages recueillis dans les districts sentinelles. Les doses diagnostiques OMS de 0,05% pour le deltamethrine, 0,05% pour le lambdacyhalothrine, 0,75% pour la permethrine et 4% pour le DDT ont ete utilisees. Resultats: Les vecteurs majeurs du paludisme en Tanzanie, Anopheles gambiae sl, etaient sensibles (taux de mortalite de 98–100%) a la permethrine, au deltamethrine, au lambdacyhalothrine et au DDT dans la plupart des sites etudies. Cependant, certains sites ont enregistre une sensibilite marginale (taux de mortalite de 80 a 97%). Une resistance au DDT (taux de mortalite de 65% [IC 95%: 54–74]) a ete observee a Ilala et une resistance au lambdacyhalothrine (taux de mortalite de 73% [IC 95%: 69–76]) et a la permethrine (taux de mortalite de 77% [IC 95%: 73–80]) a ete observee a Moshi. Conclusions: La sensibilite maintenue des vecteurs du paludisme aux pyrethrinoides en Tanzanie est encourageante pour la lutte efficace contre le paludisme avec les moustiquaires impregnees et les pulverisations de residus d’interieur. Cependant, l’emergence de foyers avec une resistance aux insecticides est alarmante. La surveillance continue est essentielle pour permettre le confinement precoce de la resistance, en particulier dans les zones qui ont enregistre une resistance ou une sensibilite marginale et celles avec un usage intensif d’insecticides dans la sante publique et agricole. Objetivo: Monitorizar el nivel de susceptibilidad frente a insecticidas de los vectores de malaria en 12 distritos centinela de Tanzania. Metodos: Se utilizaron metodos estandar de la OMS para detectar mosquitos abatidos y mortalidad en hembras anofeles recogidas en los distritos centinela. Se utilizaron las dosis diagnosticas de la OMS de Deltametrina0.05%, Lambdacialotrina 0.05%, Permetrina0.75%, y DDT 4%. Resultados: Los principales vectores de malaria en Tanzania, Anopheles gambiae s.l., eran susceptibles (tasa de mortalidad de 98–100%) a la permetrina, deltametrina, Lambdacialotrina y al DDT en la mayoria de los lugares estudiados. Sin embargo, en algunos de los emplazamientos se registro una susceptibilidad marginal (tasa de mortalidad de 80–97%); en Ilala se observo resistencia al DDT (tasa de mortalidad del 65% [95% IC: 54–74]); y en Moshi se observo resistencia a la Lambdacialotrina (tasa de mortalidad de 73% [95% IC: 69–76]) y permetrina (tasa de mortalidad del 77% [95% IC: 73–80]) Conclusiones: La susceptibilidad sostenida a piretroides de los vectores de malaria en Tanzania es esperanzadora para un control de malaria exitoso con mosquiteras impregnadas y rociamiento intradomiciliario. Sin embargo, la aparicion de puntos focales con resistencia a insecticidas es alarmante. Una monitorizacion continuada es esencial para asegurar el control temprano de la resistencia, particularmente en areas en las que se haya detectado resistencia o susceptibilidad marginal y aquellas con un uso intensivo de insecticidas en agricultura y salud publica.

BACKGROUND: Even though patients with prostate cancer commonly respond to endocrine treatment, in most cases the disease progresses to castration resistant prostate cancer (CRPC). Our objective was to generate a novel cell line model representing the endocrine treatment naive prostate cancer for testing treatments that target the androgen receptor (AR) and androgen metabolism. METHODS: After culturing DuCaP cells 20 passages with additional 1 nM R1881, DuCaP-N(aive) cell line was developed and validated for testing endocrine therapy combinations. Cell viability, apoptosis and cell cycle distribution were assessed in DuCaP and DuCaP-N when interfering with the hormonal content. RESULTS: Addition of 1 nM R1881 to DuCaP reduces cell viability and induces cell cycle inhibition and apoptosis. Eventually, an androgen accustomed DuCaP-N cell line developed. An antiandrogen (bicalutamide), a histone deacetylase (HDAC) inhibitor (trichostatin A) and a 5alpha-reductase (SRD5A) inhibitor (finasteride) reduce cell viability, and their combinations give a synergistic response in inducing apoptosis. CONCLUSIONS: The TMPRSS2-ERG expressing DuCaP-N cell line represents human prostate cancer prior to endocrine treatment, and its parental DuCaP cell line is a model for CRPC. These cell lines can be used for preclinical evaluation of compounds that target the androgenic pathway.