Genetic landscape of homologous recombination repair genes in early-onset/familial prostate cancer patients.

Prostate cancer (PrCa) is one of the three most frequent and deadliest cancers worldwide. The discovery of PARP inhibitors for the treatment of tumors with deleterious variants in homologous recombination repair (HRR) genes has placed PrCa on the roadmap of precision medicine. However, the overall contribution of HRR genes to the 10%-20% of carcinomas arising in men with early-onset/familial PrCa has not been fully clarified. We used targeted next-generation sequencing (T-NGS) covering eight HRR genes (ATM, BRCA1, BRCA2, BRIP1, CHEK2, NBN, PALB2, and RAD51C) and an analysis pipeline querying both small and large genomic variations to clarify their global and relative contribution to hereditary PrCa predisposition in a series of 462 early-onset/familial PrCa cases. Deleterious variants were found in 3.9% of the patients, with CHEK2 and ATM being the most frequently mutated genes (38.9% and 22.2% of the carriers, respectively), followed by PALB2 and NBN (11.1% of the carriers, each), and finally by BRCA2, RAD51C, and BRIP1 (5.6% of the carriers, each). Using the same NGS data, exonic rearrangements were found in two patients, one pathogenic in BRCA2 and one of unknown significance in BRCA1. These results contribute to clarify the genetic heterogeneity that underlies PrCa predisposition in the early-onset and familial disease, respectively.

Exome sequencing of affected duos and trios uncovers PRUNE2 as a novel prostate cancer predisposition gene.

BACKGROUND: Prostate cancer (PrCa) is one of the most hereditable human cancers, however, only a small fraction of patients has been shown to carry deleterious variants in known cancer predisposition genes. METHODS: Whole-exome sequencing was performed in multiple affected members of 45 PrCa families to select the best candidate genes behind part of the PrCa missing hereditability. Recurrently mutated genes were prioritised, and further investigated by targeted next-generation sequencing in the whole early-onset and/or familial PrCa series of 462 patients. RESULTS: PRUNE2 stood out from our analysis when also considering the available data on its association with PrCa development. Ten germline pathogenic/likely pathogenic variants in the PRUNE2 gene were identified in 13 patients. The most frequent variant was found in three unrelated patients and identical-by-descent analysis revealed that the haplotype associated with the variant is shared by all the variant carriers, supporting the existence of a common ancestor. DISCUSSION: This is the first report of pathogenic/likely pathogenic germline variants in PRUNE2 in PrCa patients, namely in those with early-onset/familial disease. Importantly, PRUNE2 was the most frequently mutated gene in the whole series, with a deleterious germline variant identified in 2.8% of the patients, representing a novel prostate cancer predisposition gene.

Health care services for survivors of gender-based violence: a community and clinic-based intervention in Zambézia province, Mozambique.

Mozambique introduced guidelines for integrated gender-based violence (GBV) services in 2012. In 2017, we trained providers on empathetic and supportive services to GBV survivors and introduced home-based services for survivors who are loss-to-follow up. Rate ratios of clinic visits were compared before and after intervention initiation, using exact significance tests. Data of 1,806 GBV survivors were reviewed, with a total of 2005 events. The median age was 23 years (IQR 17-30) and 89% were women. Among those reporting violence, 69% reported physical violence, 18% reported sexual violence (SV), and 12% reported psychological violence. Rates of care-seeking behavior were higher in the intervention period (rate ratio 1.31 [95%CI: 1.18-1.46]); p < 0.01. Among those eligible for post-exposure prophylaxis (PEP), 94% initiated PEP. Uptake of HIV retesting improved in percentage points by 34% (14% to 48%), 34% (8% to 42%) and 26% (5% to 31%) at 1-, 3- and 6-months, respectively. The intervention led to an increase in the rate of GBV survivors seeking health care services, and improved rates of follow-up care among SV survivors initiating PEP. Strengthening of PEP adherence counseling remains crucial for improving GBV services.

Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer.

Considering that mutations in known prostate cancer (PrCa) predisposition genes, including those responsible for hereditary breast/ovarian cancer and Lynch syndromes, explain less than 5% of early-onset/familial PrCa, we have sequenced 94 genes associated with cancer predisposition using next generation sequencing (NGS) in a series of 121 PrCa patients. We found monoallelic truncating/functionally deleterious mutations in seven genes, including ATM and CHEK2, which have previously been associated with PrCa predisposition, and five new candidate PrCa associated genes involved in cancer predisposing recessive disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4. Furthermore, using in silico pathogenicity prediction of missense variants among 18 genes associated with breast/ovarian cancer and/or Lynch syndrome, followed by KASP genotyping in 710 healthy controls, we identified "likely pathogenic" missense variants in ATM, BRIP1, CHEK2 and TP53. In conclusion, this study has identified putative PrCa predisposing germline mutations in 14.9% of early-onset/familial PrCa patients. Further data will be necessary to confirm the genetic heterogeneity of inherited PrCa predisposition hinted in this study.

Chlorella vulgaris growth on anaerobically digested sugarcane vinasse: influence of turbidity.

This paper shows the influence of turbidity (in Nephelometric Turbidity Units - NTU), chemical oxygen demand (COD) and aeration (CO2 supply) on the productivity and growth rate and lipid content of microalgae (a mixed culture predominantly composed of Chlorella vulgaris), using anaerobically digested vinasse as a culture medium. The microalgae can be cultivated in anaerobically digested vinasse, at turbidity and chemical oxygen demand of 690 NTU and 2.5 gCOD L -1, respectively, according to the modified Gompertz model, and removal of turbidity by filtration did not influence the microalgae productivity (≈ 77 mg L1 d1). Furthermore, aeration increased the productivity up to 139 mg L1 d1, with a biomass dry weight of 2.7 g L-1. Finally, a maximum lipid content of 265 mg L -1 was obtained, while a nitrogen removal of 98% was recorded for all conditions. Thus, the combination of anaerobic digestion followed by the use of the digestate for the cultivation of microalgae may be an efficient way to treat large quantities of this residue, in turn yielding large amounts of microalgae biomass, which can be transformed into fertilizer and biofuel.

Diversity of free-living ticks and serological evidence of spotted fever group Rickettsia and ticks associated to dogs, Porto Velho, Western Amazon, Brazil.

Rondônia is the only state in the North Region of Brazil to have registered confirmed cases of Brazilian Spotted Fever (BSF). The present study investigated the epidemiological cycle of Rickettsia spp. by surveying free-living ixodofauna and tick parasitism of dogs in the municipality of Porto Velho, Rondônia State. Ticks and dogs were tested for the presence of Rickettsia spp. DNA and dog serum was tested for reactivity to anti-Rickettsia spp. antibodies. Tick collection and dog blood sampling were performed in peri-urban and rural environments at 11 locations. Eight free-living Amblyomma species and one Haemaphysalis species were collected: A. scalpturatum, A. naponense, A. oblongoguttatum, A. coelebs, A. latepunctatum, A. pacae, A. ovale, Amblyomma sp., and H. juxtakochi. Three tick species were found parasitizing dogs: Rhipicephalus sanguineus sensu lato, A. oblongoguttatum and A. ovale. Molecular analysis did not identify the presence of the gltA gene fragment in any tick specimen. Results from an indirect immunofluorescent assay (IFA) showed that 20.8% of peri-urban and 15.4% of rural dog sera exhibited reactivity to Rickettsia rhipicephali, Rickettsia amblyommatis, Rickettsia bellii and Rickettsia parkeri antigens. Antibody prevalence in dogs was 16.4%. This study is the first to describe the prevalence of Rickettsia spp. infection in dogs from Porto Velho municipality. Our findings enhance current knowledge of Rickettsia spp. circulation in the Western Amazon.

Hereditary Predisposition to Prostate Cancer: From Genetics to Clinical Implications.

Prostate cancer (PrCa) ranks among the top five cancers for both incidence and mortality worldwide. A significant proportion of PrCa susceptibility has been attributed to inherited predisposition, with 10-20% of cases expected to occur in a hereditary/familial context. Advances in DNA sequencing technologies have uncovered several moderate- to high-penetrance PrCa susceptibility genes, most of which have previously been related to known hereditary cancer syndromes, namely the hereditary breast and ovarian cancer (BRCA1, BRCA2, ATM, CHEK2, and PALB2) and Lynch syndrome (MLH1, MSH2, MSH6, and PMS2) genes. Additional candidate genes have also been suggested, but further evidence is needed to include them in routine genetic testing. Recommendations based on clinical features, family history, and ethnicity have been established for more cost-efficient genetic testing of patients and families who may be at an increased risk of developing PrCa. The identification of alterations in PrCa predisposing genes may help to inform screening strategies, as well as treatment options, in the metastatic setting. This review provides an overview of the genetic basis underlying hereditary predisposition to PrCa, the current genetic screening recommendations, and the implications for clinical management of the disease.

Surfactant removal and biomass production in a microalgal-bacterial process: effect of feeding regime.

The influence of the feeding regime on surfactant and nutrient removal and biomass production was evaluated in three high rate algal ponds for primary domestic wastewater treatment. Feeding times of 24, 12 and 0.1 h d-1 were studied in each reactor at a similar hydraulic retention time of 7.0 days and organic load of 2.3 mg m-2 d-1. Semi-continuous feeding at 12 and 0.1 h d-1 showed better microalgal biomass production (0.21-0.23 g L-1) and nutrient removal, including nitrogen (74-76%) and phosphorus (80-86%), when compared to biomass production (0.13 g L-1) and nitrogen (69%) and phosphorus (46%) removals obtained at continuous feeding (24 h d-1). Additionally, the removal efficiency of surfactant in the three reactors ranged between 90 and 97%, where the best result was obtained at 0.1 h d-1, resulting in surfactant concentrations in the treated effluent (0.3 mg L-1) below the maximum freshwater discharge limits.

Diversity, natural infection and blood meal sources of phlebotomine sandflies (Diptera, Psychodidae) in the western Brazilian Amazon.

BACKGROUND: The state of Rondônia (RO) is a hot spot for human cases of cutaneous leishmaniasis. Many sandfly species in RO are putative vectors of leishmaniasis. OBJECTIVES: This study examines the diversity patterns and the presence of Leishmania DNA and blood meal sources of sandflies in RO. METHODS: A sandfly survey was performed between 2016 and 2018 in 10 municipalities categorised into three different environment types: (i) Conservation Unit (CUN) - comprised of preserved ombrophilous forests; (ii) Forest Edge (FE) - small forest fragments; and (iii) Peridomicile (PE) - areas around dwellings. FINDINGS: A total of 73 species were identified from 9,535 sandflies. The most abundant species were Psychodopygus davisi (1,741 individuals), Nyssomyia antunesi (1,397), Trichophoromyia auraensis (1,295) and Trichophoromyia ubiquitalis (1,043). Diversity was the highest in CUN, followed by the FE and PE environments. One pool of Ps. davisi tested positive for Leishmania braziliensis, reinforcing the possibility that Ps. davisi acts as a vector. The cytochrome b (cytb) sequences were used to identify three blood meal sources: Bos taurus, Homo sapiens and Tamandua tetradactyla. MAIN CONCLUSIONS: Our results demonstrated that sandflies can switch between blood meal sources in differing environments. This study enhances the knowledge of the vector life cycle in RO and provides information relevant to leishmaniasis surveillance.

Effects of graywater on the growth and survival of ornamental plants in nature-based systems.

The current paper investigates the development of two ornamental plants, canna lily (Canna x generalis) and giant horsetail (Equisetum giganteum), at both bench and pilot scale. Combinations of gravel-filled mesocosm, planted and unplanted (control), irrigated with light greywater (GWL) or tap water (WT), were used. Both species were able to grow under the tested conditions with no indication of toxicity that could affect the development. Irrigation with GWL, resulted in higher evapotranspiration (2.2 mm-2.8 mm) in canna lily than giant horsetail (1.7 mm-2.3 mm) in mesocosm system. When the plants were mature and the season was more humid and warmer, canna lily and giant horsetail irrigated with GWL evapotranspirated 69.23% and 30.77%, respectively as compared to the unplanted GWL-irrigated-mesocosm. Principal components and cluster analysis identified similarity between evapotranspiration (ET) and the characteristics of the plants. Both species can thus be used in constructed wetlands taking into consideration elements such as the space available, level of water and solar incidence so as to allow the full development of the plants. The roots of giant horsetail require high water availability. Low solar incidence is indicated for giant horsetail, and the opposite for canna lily, if flowering is desired.

Prostate cancer risk regions at 8q24 and 17q24 are differentially associated with somatic TMPRSS2:ERG fusion status.

Molecular and epidemiological differences have been described between TMPRSS2:ERG fusion-positive and fusion-negative prostate cancer (PrCa). Assuming two molecularly distinct subtypes, we have examined 27 common PrCa risk variants, previously identified in genome-wide association studies, for subtype specific associations in a total of 1221 TMPRSS2:ERG phenotyped PrCa cases. In meta-analyses of a discovery set of 552 cases with TMPRSS2:ERG data and 7650 unaffected men from five centers we have found support for the hypothesis that several common risk variants are associated with one particular subtype rather than with PrCa in general. Risk variants were analyzed in case-case comparisons (296 TMPRSS2:ERG fusion-positive versus 256 fusion-negative cases) and an independent set of 669 cases with TMPRSS2:ERG data was established to replicate the top five candidates. Significant differences (P < 0.00185) between the two subtypes were observed for rs16901979 (8q24) and rs1859962 (17q24), which were enriched in TMPRSS2:ERG fusion-negative (OR = 0.53, P = 0.0007) and TMPRSS2:ERG fusion-positive PrCa (OR = 1.30, P = 0.0016), respectively. Expression quantitative trait locus analysis was performed to investigate mechanistic links between risk variants, fusion status and target gene mRNA levels. For rs1859962 at 17q24, genotype dependent expression was observed for the candidate target gene SOX9 in TMPRSS2:ERG fusion-positive PrCa, which was not evident in TMPRSS2:ERG negative tumors. The present study established evidence for the first two common PrCa risk variants differentially associated with TMPRSS2:ERG fusion status. TMPRSS2:ERG phenotyping of larger studies is required to determine comprehensive sets of variants with subtype-specific roles in PrCa.

Alternative use of Pseudomonas aeruginosa as indicator for greywater disinfection.

Greywater presents great potential for reuse; if treated correctly and efficiently, it can be used for several residential uses. The objective of this work was to test advanced oxidation for greywater disinfection through UV/TiO2, UV/TiO2/H2O2, photo-Fenton, UV/H2O2 and photolysis (UV) processes, using Pseudomonas aeruginosa as an alternative indicator. In general, the processes with hydrogen peroxide (150 mg.L-1) mixed in the pretreated greywater and exposed to solar radiation or artificial radiation from UV lamps were the most efficient in the disinfection experiments, with total inactivation of P. aeruginosa. These processes (UV/H2O2 and photo-Fenton) were better fitted to the log-linear/caudal decay model with remaining microorganism for the hydrogen peroxide concentration of 25 mg.L-1. The use of P. aeruginosa as an alternative indicator for the greywater disinfection was very promising due to its high resistance and high natural concentration in the effluent used in the experiments. The treatment applied with the UV/H2O2 process with the hydrogen peroxide concentration at 150 mg.L-1 was the only one that showed acute toxicity, even though it removed a good part of the surfactant concentration from the pre-treated greywater.

Hydraulic and hydrological aspects of an evapotranspiration-constructed wetland combined system for household greywater treatment.

Constructed wetlands systems demand preliminary and primary treatment to remove solids present in greywater (GW) to avoid or reduce clogging processes. The current paper aims to assess hydraulic and hydrological behavior in an improved constructed wetland system, which has a built-in anaerobic digestion chamber (AnC), GW is distributed to the evapotranspiration and treatment tank (CEvaT), combined with a subsurface horizontal flow constructed wetland (SSHF-CW). The results show that both the plants present in the units and the AnC improve hydraulic and volumetric efficiency, decrease short-circuiting and improve mixing conditions in the system. Moreover, the hydraulic conductivity measured on-site indicates that the presence of plants in the system and the flow distribution pattern provided by the AnC might reduce clogging in the SSHF-CW. It is observed that rainfall enables salt elimination, thus increasing evapotranspiration (ET), which promotes effluent reduction and enables the system to have zero discharge when reuse is unfeasible.

Truncating and missense PPM1D mutations in early-onset and/or familial/hereditary prostate cancer patients.

Truncating activating mutations in the last exon of PPM1D have been described in patients with breast, ovarian, colorectal and non-small cell lung cancer, but recent data indicate that they may be associated with previous chemotherapy. In this study we evaluated the prevalence of PPM1D mutations in white blood cells (WBC) of 462 patients with early-onset and/or familial/hereditary prostate cancer (PrCa) by sequencing the coding region of exon 6. Two truncating mutations were found in two patients (0.4%), both treated with androgen-ablation therapy but no chemotherapy prior to blood collection. Next generation sequencing analysis showed that the truncating variants were present in 21.4% and 32.4% of the reads, indicating that they were in mosaic in WBC, something that was confirmed by its absence in a different tissue from one of these patients. Additionally, nine patients (1.95%) were found to harbor non-synonymous germline mutations, with three patients sharing the same missense variant, c.1607G > A, p.Arg536Lys. This variant was predicted to be deleterious by different in silico tools and was not found in the 293 male control subjects tested. Large cohorts and/or functional evaluation are needed to clarify the nature of the truncating mosaic mutations in PrCa patients treated with and without androgen-ablation therapy and to evaluate the contribution of the recurrent missense variant to the risk of developing PrCa. © 2016 Wiley Periodicals, Inc.

NCOA2 is a candidate target gene of 8q gain associated with clinically aggressive prostate cancer.

Prostate carcinomas harboring 8q gains are associated with poor clinical outcome, but the target genes of this genomic alteration remain to be unveiled. In this study, we aimed to identify potential 8q target genes associated with clinically aggressive prostate cancer (PCa) using fluorescence in situ hybridization (FISH), genome-wide mRNA expression, and protein expression analyses. Using FISH, we first characterized the relative copy number of 8q (assessed with MYC flanking probes) of a series of 50 radical prostatectomy specimens, with available global gene expression data and typed for E26 transformation specific (ETS) rearrangements, and then compared the gene expression profile of PCa subsets with and without 8q24 gain using Significance Analysis of Microarrays. In the subset of tumors with ERG fusion genes (ERG+), five genes were identified as significantly overexpressed (false discovery rate [FDR], ≤ 5%) in tumors with relative 8q24 gain, namely VN1R1, ZNF417, CDON, IKZF2, and NCOA2. Of these, only NCOA2 is located in 8q (8q13.3), showing a statistically higher mRNA expression in the subgroup with relative 8q gain, both in the ERG+ subgroup and in the whole series (P = 0.000152 and P = 0.008, respectively). Combining all the cases with NCOA2 overexpression, either at the mRNA or at the protein level, we identified a group of tumors with NCOA2 copy-number increase, independently of ETS status and relative 8q24 gain. Furthermore, for the first time, we detected a structural rearrangement involving NCOA2 in PCa. These findings warrant further studies with larger series to evaluate if NCOA2 relative copy-number gain presents prognostic value independently of the well-established poor prognosis associated with MYC relative copy-number gain.

Herbicide toxicity, selectivity and hormesis of nicosulfuron on 10 Trichogrammatidae (Hymenoptera) species parasitizing Anagasta ( = Ephestia) kuehniella (Lepidoptera: Pyralidae) eggs.

Selective agrochemicals including herbicides that do not affect non-target organisms such as natural enemies are important in the integrated pest management (IPM) programs. The aim of this study was to evaluate the herbicide toxicity, selectivity and hormesis of nicosulfuron, recommended for the corn Zea mays L. (Poaceae) crop, on 10 Trichogrammatidae (Hymenoptera) species. A female of each Trichogramma spp. or Trichogrammatoidea annulata De Santis, 1972 was individually placed in plastic test tubes (no choice) with a cardboard containing 45 flour moth Anagasta ( = Ephestia) kuehniella Zeller, 1879 (Lepidoptera: Pyralidae) eggs. Parasitism by these natural enemies was allowed for 48 h and the cardboards were sprayed with the herbicide nicosulfuron at 1.50 L.ha-1, along with the control (only distilled water). Nicosulfuron reduced the emergence rate of Trichogramma bruni Nagaraja, 1983 females, but increased that of Trichogramma pretiosum Riley, 1879, Trichogramma acacioi Brun, Moraes and Smith, 1984 and T. annulata females. Conversely, this herbicide increased the emergence rate of Trichogramma brasiliensis Ashmead, 1904, T. bruni, Trichogramma galloi Zucchi, 1988 and Trichogramma soaresi Nagaraja, 1983 males and decreased those of T. acacioi, Trichogramma atopovilia Oatman and Platner, 1983 and T. pretiosum males. In addition, nicosulfuron reduced the sex ratio of T. galloi, Trichogramma bennetti Nagaraja and Nagarkatti, 1973 and T. pretiosum and increased that of T. acacioi, T. bruni, T. annulata, Trichogramma demoraesi Nagaraja, 1983, T. soaresi and T. brasiliensis. The herbicide nicosulfuron was "harmless" (class 1, <30% reduction) for females and the sex ratio of all Trichogrammatidae species based on the International Organization for Biological Control (IOBC) classification. The possible hormesis effect of nicosulfuron on Trichogrammatidae species and on the bacterium Wolbachia sp. (Rickettsiales: Rickettsiaceae) was also discussed.

Nicosulfuron Plus Atrazine Herbicides and Trichogrammatidae (Hymenoptera) in No-Choice Test: Selectivity and Hormesis.

The aim of this study was to evaluate the effect of the herbicide mixture nicosulfuron + atrazine on 10 trichogrammatid species. A female of each trichogrammatid was placed in a test tube (no-choice) with a card with 45 Anagasta kuehniella eggs. Parasitism was allowed over a 48 h period, then the cards were sprayed with a solution containing nicosulfuron (30 g ha-1) + atrazine (1500 g ha-1), besides the control (distilled water). The nicosulfuron + atrazine mixture increased the Trichogramma atopovirilia and T. pretiosum female emergence. The percentage of T. acacioi, T. atopovilia and T. pretiosum male parasitoids emerged was higher in the control, and for T. demoraesi and Trichogrammatoidea annulata with nicosulfuron + atrazine. Sex ratio of the trichogrammatids was similar with nicosulfuron + atrazine.

Implementation of next-generation sequencing for molecular diagnosis of hereditary breast and ovarian cancer highlights its genetic heterogeneity.

Molecular diagnosis of hereditary breast and ovarian cancer (HBOC) by standard methodologies has been limited to the BRCA1 and BRCA2 genes. With the recent development of new sequencing methodologies, the speed and efficiency of DNA testing have dramatically improved. The aim of this work was to validate the use of next-generation sequencing (NGS) for the detection of BRCA1/BRCA2 point mutations in a diagnostic setting and to study the role of other genes associated with HBOC in Portuguese families. A cohort of 94 high-risk families was included in the study, and they were initially screened for the two common founder mutations with variant-specific methods. Fourteen index patients were shown to carry the Portuguese founder mutation BRCA2 c.156_157insAlu, and the remaining 80 were analyzed in parallel by Sanger sequencing for the BRCA1/BRCA2 genes and by NGS for a panel of 17 genes that have been described as involved in predisposition to breast and/or ovarian cancer. A total of 506 variants in the BRCA1/BRCA2 genes were detected by both methodologies, with a 100 % concordance between them. This strategy allowed the detection of a total of 39 deleterious mutations in the 94 index patients, namely 10 in BRCA1 (25.6 %), 21 in BRCA2 (53.8 %), four in PALB2 (10.3 %), two in ATM (5.1 %), one in CHEK2 (2.6 %), and one in TP53 (2.6 %), with 20.5 % of the deleterious mutations being found in genes other than BRCA1/BRCA2. These results demonstrate the efficiency of NGS for the detection of BRCA1/BRCA2 point mutations and highlight the genetic heterogeneity of HBOC.

Epigenetic regulation of EFEMP1 in prostate cancer: biological relevance and clinical potential.

Epigenetic alterations are common in prostate cancer (PCa) and seem to contribute decisively to its initiation and progression. Moreover, aberrant promoter methylation is a promising biomarker for non-invasive screening. Herein, we sought to characterize EFEMP1 as biomarker for PCa, unveiling its biological relevance in prostate carcinogenesis. Microarray analyses of treated PCa cell lines and primary tissues enabled the selection of differentially methylated genes, among which EFEMP1 was further validated by MSP and bisulfite sequencing. Assessment of biomarker performance was accomplished by qMSP. Expression analysis of EFEMP1 and characterization of histone marks were performed in tissue samples and cancer cell lines to determine the impact of epigenetic mechanisms on EFEMP1 transcriptional regulation. Phenotypic assays, using transfected cell lines, permitted the evaluation of EFEMP1's role in PCa development. EFEMP1 methylation assay discriminated PCa from normal prostate tissue (NPT; P < 0.001, Kruskall-Wallis test) and renal and bladder cancers (96% sensitivity and 98% specificity). EFEMP1 transcription levels inversely correlated with promoter methylation and histone deacetylation, suggesting that both epigenetic mechanisms are involved in gene regulation. Phenotypic assays showed that EFEMP1 de novo expression reduces malignant phenotype of PCa cells. EFEMP1 promoter methylation is prevalent in PCa and accurately discriminates PCa from non-cancerous prostate tissues and other urological neoplasms. This epigenetic alteration occurs early in prostate carcinogenesis and, in association with histone deacetylation, progressively leads to gene down-regulation, fostering cell proliferation, invasion and evasion of apoptosis.

HIV self-test performance evaluation among priority populations in rural Mozambique: Results from a community-based observational study.

BACKGROUND: In 2021, Mozambique initiated community-based oral HIV self-testing (HIVST) to increase testing access and uptake among priority groups, including adult males, adolescents, and young adults. Within an HIVST pilot project, we conducted a performance evaluation assessing participants' ability to successfully conduct HIVST procedures and interpret results. METHODS: A cross-sectional study was performed between February-March 2021 among employees, students (18-24 years of age), and community members, using convenience sampling, in two rural districts of Zambézia Province, Mozambique. We quantified how well untrained users performed procedures for the oral HIVST (Oraquick®) through direct observation using a structured checklist, from which we calculated an HIVST usability index (scores ranging 0-100%). Additionally, participants interpreted three previously processed anonymous HIVST results. False reactive and false non-reactive interpretation results were presented as proportions. Bivariate analysis was conducted using Chi-square and Fisher exact tests. RESULTS: A total of 312 persons participated (131[42%] community members, 71[23%] students, 110[35%] employees); 239 (77%) were male; the mean age was 28 years (standard deviation 10). Average usability index scores were 80% among employees, 86% among students, and 77% among community members. Main procedural errors observed included "incorrect tube positioning" (49%), "incorrect specimen collection" (43%), and "improper waiting time for result interpretation" (42%). From the presented anonymous HIVST results, 75% (n = 234) correctly interpreted all three results, while 9 (3%) of study participants failed to correctly interpret any results. Overall, 36 (12%) gave a false non-reactive result interpretation, 21 (7%) a false reactive result interpretation, and 14 (4%) gave both false non-reactive and false reactive result interpretations. Community members generally had lower performance. CONCLUSIONS: Despite some observed testing procedural errors, most users could successfully perform an HIVST. Educational sessions at strategic places (e.g., schools, workplaces), and support via social media and hotlines, may improve HIVST performance quality, reducing the risk of incorrect interpretation.