Publications by authors named "Paula Paulo"

77 Publications

Rickettsia parkeri strain Atlantic rainforest infecting Amblyomma ovale (Acari: Ixodidae) in the Amazon Biome (Acre state, Brazil).

Ticks Tick Borne Dis 2021 Sep 23;13(1):101836. Epub 2021 Sep 23.

Laboratório de Entomologia, Fiocruz Rondônia, Fundação Oswaldo Cruz, Porto Velho, RO, Brazil.

There is a lack of studies regarding tick-associated Rickettsia in the Amazon biome. Aiming to contribute to this knowledge, our research group collected ticks in the Western Amazon to better understand the tick fauna and their associated Rickettsia. In this study, we detected Rickettsia parkeri strain Atlantic rainforest DNA in the tick Amblyomma ovale Koch, 1844 in Rio Branco municipality, Acre state, northern Brazil. This is the first time that the R. parkeri strain Atlantic rainforest has been reported in the Amazon biome and is the first evidence of the circulation of a pathogenic spotted fever group (SFG) Rickettsia in this biome. This finding provides substantial information to help public health authorities understand which species of Rickettsia may be related to Amazon spotted fever cases.
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http://dx.doi.org/10.1016/j.ttbdis.2021.101836DOI Listing
September 2021

Sand fly fauna and molecular detection of Leishmania species and blood meal sources in different rural environments in western Amazon.

Acta Trop 2021 Sep 22;224:106150. Epub 2021 Sep 22.

Laboratório de Entomologia, Fiocruz Rondônia, Rua da Beira, 7671, Porto Velho, RO 76812-245, Brazil; Instituto Nacional de Epidemiologia da Amazônia Ocidental (INCT-EpiAMO), Rua da Beira, 7671, Porto Velho, RO 76812-245, Brazil.

Cutaneous Leishmaniasis (CL) is a disease caused by Leishmania species and transmitted by the bites of infected female sand fly species. The diversity of these insects in Rondônia State (where CL is the predominant form) is large but unexplored, and consequently the vector species are unknown. The purpose of this study was to evaluate the sand fly fauna in two environments (forest fragment and peridomicile) in rural areas of four municipalities of the state, DNA amplification of Leishmania species and the presence of blood meal sources for these insects. After identifying the species, sample coverage was applied to estimate the fauna coverage in each environment. Females were used to amplify and detect Leishmania DNA and blood meal sources, then posteriorly identified by sequencing. A total of 1706 individuals were included in 61 species, which was a sample coverage of 97% for the forest fragments (56 species), whereas 98% was observed (32 species) in peridomiciles. Next, 41 pools were prepared from 1227 females, and none were positive for Leishmania DNA. We observed 160 engorged females (forest fragments: 21, peridomiciles: 139) belonging to females of the Antunesi complex and another eight species. Two of these females were positive for Leishmania braziliensis-DNA: one in the Antunesi complex and one in Psychodopygus hirsutus. Seven blood meal sources were identified by sequencing analysis: Bos taurus and Sus scrofa from the peridomiciles, and Dasypus novemcinctus, Pecari tajacu, Philander canus, Plecturocebus bernhardi, and Tamandua tetradactyla from the forest fragments. Our data confirmed the feeding behavior of field-caught sand flies and could contribute to our understanding about local vectors and possible reservoirs in the transmission of Leishmania spp.
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http://dx.doi.org/10.1016/j.actatropica.2021.106150DOI Listing
September 2021

Occurrence of Leishmania infection in the immediate geographic region of Ji-Paraná, Rondônia State, Brazil.

Rev Soc Bras Med Trop 2021 20;54:e02122021. Epub 2021 Aug 20.

Fundação Oswaldo Cruz, Fiocruz Rondônia, Porto Velho, RO, Brasil.

Introduction: This study evaluated the epidemiology of American cutaneous leishmaniasis in the immediate region of Ji-Paraná, Rondônia State.

Methods: Samples and epidemiological data were collected from 105 patients.

Results: Leishmania infection was observed in 58 (55.2%) patients, and Leishmania braziliensis was present in 82.9% of the 41 sequenced samples. Infected patients were predominantly male (93.1%). Leishmania infection was twice as prevalent among rural inhabitants versus urban inhabitants. Lesions were more frequent in the upper limbs (arms/hands, 41.82%).

Conclusions: The present data corroborate the zoonotic profile of cutaneous leishmaniasis; this information could help to improve surveillance and control strategies.
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http://dx.doi.org/10.1590/0037-8682-0212-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405217PMC
August 2021

Pre-exposure prophylaxis use among HIV serodiscordant couples: a qualitative study in Mozambique.

Glob Health Action 2021 01;14(1):1940764

Vanderbilt Institute for Global Health, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Pre-exposure prophylaxis (PrEP) has the potential to reduce HIV transmission and stem the HIV epidemic. Unfortunately, PrEP uptake in rural sub-Saharan Africa has been slow and medication adherence has been suboptimal.

Objective: To explore the perspectives, attitudes, and experiences of HIV serodiscordant partners taking PrEP and develop a messaging campaign to improve PrEP uptake in rural Mozambique to reduce HIV transmission among serodiscordant partners.

Methods: In this qualitative study, we interviewed 20 people in serodiscordant relationships using PrEP at a rural health center in Zambézia province, Mozambique and employed inductive and deductive coding to elicit their perspectives, attitudes, and experiences related to learning their partner's HIV status, barriers to PrEP uptake, obstacles to PrEP adherence, and decisions to disclose their PrEP use with family and friends using thematic analysis.

Results: Our analysis generated nine themes across various levels of the socioecological model. Participants reported a strong desire to stay in the discordant relationship and highlighted the importance of working together to ensure PrEP and antiretroviral therapy adherence, with the majority skeptical that adherence could be achieved without both partners' support (individual and interpersonal). Although most participants were reticent about sharing their serodiscordant status with family and friends (individual and interpersonal), those who did found their family and friends supportive (interpersonal). Participants suggested increasing community health agent availability to help people navigate HIV prevention and treatment (organizational). We then created three oral stories, using themes from the interviews, with examples from various levels of the socioecological model that will be used to generate support for PrEP use among community members.

Conclusions: Our findings informed oral template stories that will be used to emphasize how couples can work together to improve PrEP uptake and reduce incident HIV infections in serodiscordant couples elsewhere in rural Mozambique.
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http://dx.doi.org/10.1080/16549716.2021.1940764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266225PMC
January 2021

DNA-based blood meal analysis of Culicoides (Diptera: Ceratopogonidae) species from Jamari National Forest, Southwestern Amazon, Brazil.

Acta Trop 2021 Sep 25;221:106025. Epub 2021 Jun 25.

Laboratório de Entomologia, Fiocruz Rondônia, Rua da Beira, 7671, Lagoa, Porto Velho, RO, Brazil; Instituto Nacional de Ciência e Tecnologia de Epidemiologia da Amazônia Ocidental - INCT-EpiAmO, Rua da Beira, 7671, Lagoa, Porto Velho, RO, Brazil.

Culicoides biting midges are insects involved in the transmission of filarial nematodes, protozoans, and viruses. Greater knowledge of Culicoides blood meal sources could improve our understanding of parasite transmission cycles. Our study used molecular tools to evaluate the blood meal sources of Culicoides biting midges from sylvatic environments. This study was conducted in Jamari National Forest, Rondônia, Brazil. Culicoides were captured using HP light traps positioned at ground level (1.5 m above ground) and in canopy (15 m above ground). To identify blood meal sources, females were subjected to DNA extraction and PCR targeting the cytb gene fragment, and the obtained sequences were analyzed and compared with sequences from GenBank. DNA extraction and PCR were performed on 455 Culicoides females, and blood meal sources were identified in 186 females. Thirty Culicoides specimens were collected from the Potosi trail and 156 were collected from the Santa Maria trail. A total of 22 species were captured; all 22 species were collected in canopy (100%) but only three species were collected at ground level (13.6%). The cytb fragment was amplified in 162 of 186 samples. Sample sequencing identified cytb DNA from nine blood-meal sources: Pauxi sp., Psophia viridis, Ramphastos tucanus tucanus, Choloepus didactylus, Choloepus hoffmanni, Tamandua tetradactyla, Ateles chamek, Homo sapiens and Pithecia irrorata. We observed that several different blood meal sources were utilized by a high diversity of Culicoides species. The abundance of Culicoides in the canopy may be related to the fact that the majority of blood meal hosts feed in treetops. We observed that C. (Hoffmania) sp. and C. coutinhoi tend to be more generalist, feeding on a range of mammals and piciform, gruiform and galliform birds. This data improves our knowledge of the feeding profile of biting midges from forest environments and should serve as a future basis for defining zoonotic transmission cycles.
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http://dx.doi.org/10.1016/j.actatropica.2021.106025DOI Listing
September 2021

Glycoproteomics identifies HOMER3 as a potentially targetable biomarker triggered by hypoxia and glucose deprivation in bladder cancer.

J Exp Clin Cancer Res 2021 Jun 9;40(1):191. Epub 2021 Jun 9.

Experimental Pathology and Therapeutics Group, Research Center (CI-IPOP), Portuguese Institute of Oncology, 4200-072, Porto, Portugal.

Background: Muscle invasive bladder cancer (MIBC) remains amongst the deadliest genitourinary malignancies due to treatment failure and extensive molecular heterogeneity, delaying effective targeted therapeutics. Hypoxia and nutrient deprivation, oversialylation and O-glycans shortening are salient features of aggressive tumours, creating cell surface glycoproteome fingerprints with theranostics potential.

Methods: A glycomics guided glycoproteomics workflow was employed to identify potentially targetable biomarkers using invasive bladder cancer cell models. The 5637 and T24 cells O-glycome was characterized by mass spectrometry (MS), and the obtained information was used to guide glycoproteomics experiments, combining sialidase, lectin affinity and bottom-up protein identification by nanoLC-ESI-MS/MS. Data was curated by a bioinformatics approach developed in-house, sorting clinically relevant molecular signatures based on Human Protein Atlas insights. Top-ranked targets and glycoforms were validated in cell models, bladder tumours and metastases by MS and immunoassays. Cells grown under hypoxia and glucose deprivation disclosed the contribution of tumour microenvironment to the expression of relevant biomarkers. Cancer-specificity was validated in healthy tissues by immunohistochemistry and MS in 20 types of tissues/cells of different individuals.

Results: Sialylated T (ST) antigens were found to be the most abundant glycans in cell lines and over 900 glycoproteins were identified potentially carrying these glycans. HOMER3, typically a cytosolic protein, emerged as a top-ranked targetable glycoprotein at the cell surface carrying short-chain O-glycans. Plasma membrane HOMER3 was observed in more aggressive primary tumours and distant metastases, being an independent predictor of worst prognosis. This phenotype was triggered by nutrient deprivation and concomitant to increased cellular invasion. T24 HOMER3 knockdown significantly decreased proliferation and, to some extent, invasion in normoxia and hypoxia; whereas HOMER3 knock-in increased its membrane expression, which was more pronounced under glucose deprivation. HOMER3 overexpression was associated with increased cell proliferation in normoxia and potentiated invasion under hypoxia. Finally, the mapping of HOMER3-glycosites by EThcD-MS/MS in bladder tumours revealed potentially targetable domains not detected in healthy tissues.

Conclusion: HOMER3-glycoforms allow the identification of patients' subsets facing worst prognosis, holding potential to address more aggressive hypoxic cells with limited off-target effects. The molecular rationale for identifying novel bladder cancer molecular targets has been established.
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http://dx.doi.org/10.1186/s13046-021-01988-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188679PMC
June 2021

Effect of a storytelling intervention on the retention of serodiscordant couples in ART/PrEP services at antenatal clinic in Namacurra province in Zambézia, Mozambique.

Contemp Clin Trials Commun 2021 Jun 6;22:100782. Epub 2021 May 6.

Friends in Global Health, Avenida da Maguiguana, 32 R/C, Maputo, Mozambique.

Background: Sub-Saharan Africa reported 550,000 new HIV infections among women in 2018. Pregnancy and the postpartum period are associated with an increased risk of HIV acquisition (adjusted risk ratio [RR]: 2.8 during pregnancy and 4.0 in postpartum period vs. non-pregnant or postpartum women, respectively). Acquisition of HIV during pregnancy and breastfeeding increases risk of mother to child transmission. We propose to test the impact of a peer-delivered oral storytelling intervention to increase retention in, and adherence to, pre-exposure prophylaxis (PrEP)/combination antiretroviral treatment (ART) among expectant couples.

Design: We propose a randomized controlled trial (RCT) (35 intervention and 35 control couples) at a health facility where 11% of expectant couples were in serodiscordant relationships in 2018. Couples randomized to the storytelling arm will be visited by a two community volunteers and who successfully adhered to PrEP/ART during a recent pregnancy. This expert couple will orate to participating couples three stories (at 1, 3 and 5 weeks after study enrollment) designed to empower, educate, and establish "ideal" interpersonal communication strategies within couples/families, and support adherence practices among participants. The primary outcome among HIV-uninfected women will be adherence to PrEP at 3 months.

Conclusions: PrEP among at-risk pregnant women must be implemented so that high levels of adherence and retention are achievable for them and their partners. We will test our storytelling intervention to identify an optimal strategy for PrEP education and family engagement in a region with high HIV prevalence. Our results will have an impact by effectively engaging serodiscordant couples in prevention/treatment during pregnancy and beyond.
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http://dx.doi.org/10.1016/j.conctc.2021.100782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167234PMC
June 2021

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

An Acad Bras Cienc 2021 23;93(1):e20190084. Epub 2021 Apr 23.

Programa de Pós-Graduação em Tecnologias Ambientais(PGTA), Universidade Federal de Mato Grosso do Sul (UFMS), Faculdade de Engenharias, Arquitetura e Urbanismo e Geografia(FAENG), Av. Costa e Silva, s/n, Pioneiros, 79070-900 Campo Grande, MS, Brazil.

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.
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http://dx.doi.org/10.1590/0001-3765202120190084DOI Listing
April 2021

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

Exp Appl Acarol 2021 Apr 29;83(4):555-573. Epub 2021 Mar 29.

Bolsista Fundapam/Laboratório de Biologia do Carrapato, Embrapa Gado de Corte, Campo Grande, MS, 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.
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http://dx.doi.org/10.1007/s10493-021-00604-8DOI Listing
April 2021

Change in microbial profile and environmental conditions in a constructed wetland system treating greywater.

Environ Sci Pollut Res Int 2021 Jul 2;28(26):34539-34552. Epub 2021 Mar 2.

Faculty of Engineering, Architecture and Urbanism and Geography (FAENG), Federal University of Mato Grosso do Sul (UFMS), Campo Grande, MS, 79070-900, Brazil.

The objective of this work was to verify the relationships between environmental conditions and microbial processes along a raw-light greywater flow in an improved constructed wetland (CW) system. Physicochemical analysis and high-throughput DNA sequencing were performed in the different zones to investigate the environmental conditions and microbial communities. The results showed that the system operated predominantly under anaerobic conditions, with redox potential (Eh) increasing from the inlet (-342.9 mV) to the outlet (-316.4 mV). Conversely, the chemical oxygen demand (COD) decreased along the greywater flow, suggesting negative correlation between these characteristics. The zones of the evapotranspiration and treatment tank (CEvaT) were characterized by lower community diversity and richness and by the presence of specific groups: Proteobacteria and Synergistetes related to the first steps of the conversion of organic carbon, in the bottom layer inside the anaerobic chamber (AnC); methanogens (Methanosaeta and Methanobacterium) and sulphate-reducing bacteria (Desulfovibrio, Desulforhabdus and Desulfomonile) in the middle layer; and microorganisms associated with the nitrogen cycle and oxygen release (Acinetobacter, Novosphingobium, Candidatus Nitrososphaera) in the top layer. On the other hand, the increase of the ORP and decrease of organic matter concentrations were associated with higher community diversity and richness in the middle layer of the CW, which showed higher abundance of microorganisms involved in methane (Methylobacterium and Candidatus Koribacter) and sulphur (Rhodoblastus and Thiobacillus) oxidation.
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http://dx.doi.org/10.1007/s11356-021-12822-zDOI Listing
July 2021

Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study.

Eur Urol Oncol 2021 Aug 9;4(4):570-579. Epub 2021 Jan 9.

Institute of Biomedicine, University of Turku, Turku, Finland.

Background: Germline ATM mutations are suggested to contribute to predisposition to prostate cancer (PrCa). Previous studies have had inadequate power to estimate variant effect sizes.

Objective: To precisely estimate the contribution of germline ATM mutations to PrCa risk.

Design, Setting, And Participants: We analysed next-generation sequencing data from 13 PRACTICAL study groups comprising 5560 cases and 3353 controls of European ancestry.

Outcome Measurements And Statistical Analysis: Variant Call Format files were harmonised, annotated for rare ATM variants, and classified as tier 1 (likely pathogenic) or tier 2 (potentially deleterious). Associations with overall PrCa risk and clinical subtypes were estimated.

Results And Limitations: PrCa risk was higher in carriers of a tier 1 germline ATM variant, with an overall odds ratio (OR) of 4.4 (95% confidence interval [CI]: 2.0-9.5). There was also evidence that PrCa cases with younger age at diagnosis (<65 yr) had elevated tier 1 variant frequencies (p = 0.04). Tier 2 variants were also associated with PrCa risk, with an OR of 1.4 (95% CI: 1.1-1.7).

Conclusions: Carriers of pathogenic ATM variants have an elevated risk of developing PrCa and are at an increased risk for earlier-onset disease presentation. These results provide information for counselling of men and their families.

Patient Summary: In this study, we estimated that men who inherit a likely pathogenic mutation in the ATM gene had an approximately a fourfold risk of developing prostate cancer. In addition, they are likely to develop the disease earlier.
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http://dx.doi.org/10.1016/j.euo.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381233PMC
August 2021

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Nat Genet 2021 01 4;53(1):65-75. Epub 2021 Jan 4.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
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http://dx.doi.org/10.1038/s41588-020-00748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148035PMC
January 2021

Detection of Leishmania species (Kinetoplastida, Trypanosomatidae) in phlebotomine sand flies (Diptera, Psychodidae) from Porto Velho, Northern Brazil.

Acta Trop 2021 Jan 12;213:105757. Epub 2020 Nov 12.

Fundação Oswaldo Cruz - Fiocruz Rondônia, Porto Velho, RO, Brazil; Instituto Nacional de Ciência e Tecnologia de Epidemiologia da Amazônia Ocidental - INCT-EpiAmO, Porto Velho, RO, Brazil. Electronic address:

Cutaneous Leishmaniasis (CL) is a vector-borne disease caused by Leishmania species and transmitted by infected female sand flies. CL is widely distributed in Brazil, but knowledge about vectors and transmission cycles could be complex according to localities. The sand fly fauna in Rondônia State is extensive, diverse, and largely unexplored. Although the state records a mean of 1,000 CL cases per year, the vectors of CL are unknown. The aim of this study was to assess phlebotomine sand fly fauna composition using diversity indexes (Shannon [H'] and Simpson [1/D]) and to detect the prevalence of Leishmania infection to verify potential vectors in three ecotopes: (i) forest fragment (FF), (ii) forest edge (FE), and (iii) peridomicile (PE). Captures were performed in four rural districts in the municipality of Porto Velho. A total of 7,026 specimens were captured comprising 72 species, and individuals classified in subgenus level. Overall, the most abundant species were Lutzomyia davisi (n: 1,105), Lutzomyia melloi (n: 760), Lutzomyia auraensis (n: 738) and Lutzomyia antunesi (n: 479). Fauna was most diverse in the FF ecotope (H' = 20.2, 1/D = 11.2), followed by the FE (H' = 18.0, 1/D = 10.1) and PE (H' = 16.6, 1/D = 10.1) ecotopes. Leishmania DNA was detected in 24 of 232 pools. In every ecotope, Leishmania naiffi DNA was identified in the following sand fly species: Lu. antunesi, Lu. davisi, Lu. hirsuta hirsuta, Lu. shawi, Lu. sordellii and Lu. (Trichophoromyia) spp. This observation may indicate that a Le. naiffi transmission focus is present in the study localities. In addition, Leishmania lainsoni was detected in Lutzomyia (Trichophoromyia) spp. Our findings show that sand fly fauna in the study localities is diverse, that Leishmania parasites are circulating in all three ecotopes, and that some sand fly species may be implicated in the transmission of Leishmania to humans in localities evaluated.
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http://dx.doi.org/10.1016/j.actatropica.2020.105757DOI Listing
January 2021

The Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor.

Cancers (Basel) 2020 Nov 4;12(11). Epub 2020 Nov 4.

Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
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http://dx.doi.org/10.3390/cancers12113254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694218PMC
November 2020

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

Water Sci Technol 2020 Sep;82(6):1176-1183

Post-graduate Programme of Environmental Technology (PGTA), Federal University of Mato Grosso do Sul (UFMS), Campo Grande-MS, Brazil.

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 were studied in each reactor at a similar hydraulic retention time of 7.0 days and organic load of 2.3 mg m d. Semi-continuous feeding at 12 and 0.1 h d showed better microalgal biomass production (0.21-0.23 g L) and nutrient removal, including nitrogen (74-76%) and phosphorus (80-86%), when compared to biomass production (0.13 g L) and nitrogen (69%) and phosphorus (46%) removals obtained at continuous feeding (24 h d). 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, resulting in surfactant concentrations in the treated effluent (0.3 mg L) below the maximum freshwater discharge limits.
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http://dx.doi.org/10.2166/wst.2020.276DOI Listing
September 2020

Adolescents in situations of poverty: resilience and vulnerabilities to sexually transmitted infections.

Rev Bras Enferm 2020 21;73(suppl 4):e20190242. Epub 2020 Sep 21.

Universidade Federal do Ceará. Fortaleza, Ceará, Brazil.

Objective: To analyze the association between vulnerabilities to Sexually Transmitted Infections (STIs/HIV/AIDS) of adolescents in poverty and their level of resilience.

Method: Cross-sectional study with 287 students between 11 and 17 years old in a school in the outskirts of Fortaleza-Ce. The study was conducted from August to October 2016. Three instruments related to characterization, vulnerability to STIs/HIV/AIDS and resilience were used. The association between the instruments was calculated using the Mann-Whitney and Kruskal-Wallis tests. Association between vulnerability to STIs/HIV/AIDS and resilience was assessed through the Spearman's correlation coefficient. Statistical significance was set at p<0.05.

Results: There was a significant association between the factors "housing" (p=0.022), "family income" (p=0.037) and vulnerability to STIs/HIV/AIDS. Adolescents whose father has completed high school (p=0.043) have moderately high resilience.

Conclusion: Adolescents with low socioeconomic status and who live on less than a minimum wage tends to be more susceptible to vulnerabilities to STIs/HIV/AIDS and to have low resilience.
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http://dx.doi.org/10.1590/0034-7167-2019-0242DOI Listing
June 2021

Vertical stratification of sand fly diversity in relation to natural infections of Leishmania sp. and blood-meal sources in Jamari National Forest, Rondônia State, Brazil.

Parasit Vectors 2020 Aug 17;13(1):422. Epub 2020 Aug 17.

Fundação Oswaldo Cruz - Fiocruz Rondônia, Porto Velho, RO, 76812-245, Brazil.

Background: Almost 1000 cases of American cutaneous leishmaniasis have been registered yearly in Rondônia State, Brazil. Little is known about the Leishmania transmission cycle (vectors and reservoirs) in the state. This study aimed to evaluate sand fly fauna from two vertical stratification layers in order to identify potential vectors and their blood-meal sources.

Methods: The study was conducted in Jamari National Forest. Sand flies were collected in the canopy (15 m) and at ground level (1 m) using HP light traps during four months, February, April, August and October, 2018. Insects were identified to the species level, and females were subjected to DNA extraction and PCR targeting minicircle kDNA and hsp70 (for Leishmania detection and species identification), and cytb (to identify blood-meal sources). Exploratory data analysis was used to determine mean of abundance and species richness between stratifications. The hsp70 and cytb sequences were analyzed and compared with sequences from GenBank.

Results: Overall, 68 species were identified from 15,457 individuals. On the Potosi trail, 7531 individuals of 49 species were collected; canopy captures totaled 6463 individuals of 46 species, while ground captures totaled 1068 individuals of 38 species. On the Santa Maria trail, 7926 individuals of 61 species were collected; canopy captures totaled 6136 individuals of 51 species, while ground captures totaled 1790 individuals of 53 species. A total of 23 pools were positive for kDNA (canopy n = 21, ground n = 2). Only two samples were sequenced for hsp70 (both in canopy); one sequence exhibited similarity with Leishmania braziliensis (Lutzomyia davisi pool) and another with L. naiffi (Lu. antunesi pool). The cytb fragment was amplified in 11 of 86 samples. Sample sequencing identified cytb DNA from 5 blood-meal sources: Micrastur gilvicollis, Psophia viridis, Tamandua tetradactyla, Homo sapiens and Choloepus didactylus.

Conclusions: Sand fly fauna is more diverse in the canopy than at ground level. Factors such as blood-meal sources, resting sites, and abiotic components probably contribute to high abundance in the canopy. Our results reinforce the possibility that Lu. antunesi and Lu. davisi participate in Leishmania transmission in forest environments and may play an important role in transmission from sylvatic to human hosts.
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http://dx.doi.org/10.1186/s13071-020-04295-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433131PMC
August 2020

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

Int J Mol Sci 2020 Jul 16;21(14). Epub 2020 Jul 16.

Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal.

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 (, , , and ) and Lynch syndrome (, , , and ) 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.
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http://dx.doi.org/10.3390/ijms21145036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404100PMC
July 2020

A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data.

Cancer Epidemiol Biomarkers Prev 2020 09 24;29(9):1731-1738. Epub 2020 Jun 24.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening.

Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups.

Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age.

Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS.

Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483627PMC
September 2020

The effect of sample size on polygenic hazard models for prostate cancer.

Eur J Hum Genet 2020 10 8;28(10):1467-1475. Epub 2020 Jun 8.

Humangenetik Tuebingen, Paul-Ehrlich-Str 23, D-72076, Tuebingen, Germany.

We determined the effect of sample size on performance of polygenic hazard score (PHS) models in prostate cancer. Age and genotypes were obtained for 40,861 men from the PRACTICAL consortium. The dataset included 201,590 SNPs per subject, and was split into training and testing sets. Established-SNP models considered 65 SNPs that had been previously associated with prostate cancer. Discovery-SNP models used stepwise selection to identify new SNPs. The performance of each PHS model was calculated for random sizes of the training set. The performance of a representative Established-SNP model was estimated for random sizes of the testing set. Mean HR (hazard ratio of top 2% to average in test set) of the Established-SNP model increased from 1.73 [95% CI: 1.69-1.77] to 2.41 [2.40-2.43] when the number of training samples was increased from 1 thousand to 30 thousand. Corresponding HR of the Discovery-SNP model increased from 1.05 [0.93-1.18] to 2.19 [2.16-2.23]. HR of a representative Established-SNP model using testing set sample sizes of 0.6 thousand and 6 thousand observations were 1.78 [1.70-1.85] and 1.73 [1.71-1.76], respectively. We estimate that a study population of 20 thousand men is required to develop Discovery-SNP PHS models while 10 thousand men should be sufficient for Established-SNP models.
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http://dx.doi.org/10.1038/s41431-020-0664-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608255PMC
October 2020

Mo-CBP, a purified chitin-binding protein from Moringa oleifera seeds, is a potent antidermatophytic protein: In vitro mechanisms of action, in vivo effect against infection, and clinical application as a hydrogel for skin infection.

Int J Biol Macromol 2020 Apr 28;149:432-442. Epub 2020 Jan 28.

Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address:

Dermatophytes belonging to Trichophyton ssp. are important anthropophilic and zoophilic pathogens, which developed resistance to griseofulvin, the common antifungal drug used to treat dermatophytosis. In this context, Moringa oleifera seed proteins have been described as antifungal agents with potential applications. Thus, this work aimed to evaluate the antidermatophytic in vitro, focusing on mechanisms, and in vivo potential of Mo-CBP, purified from M. oleifera seeds. Mo-CBPwas purified after protein extraction with 50 mM Tris-HCl buffer, pH 8.0, and chromatography on chitin and CM Sepharose™ columns and antidermatophytic potential of Mo-CBP evaluated in vitro and in vivo. In vitro, Mo-CBP reduced in 50% the germination of microconidia of Trichophyton mentagrophytes at 45 μM; but did not show inhibition of mycelial growth. Mo-CBP (45 μM) presents the inhibitory activity even when incubated with N-acetyl-d-glucosamine (NAG). Analysis of the mechanisms of Mo-CBP revealed an increase in membrane permeability, ROS overproduction and damage to cell wall leading to microconidia death. Furthermore, using in vivo models, Mo-CBP (5, 10 and 20 mg g) reduced the severity and time of dermatophytosis. Altogether, these findings indicate that Mo-CBP has great potential for the development of novel antifungal drugs for the clinical treatment of dermatophytosis.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.257DOI Listing
April 2020

Evaluation of biomethanization during co-digestion of thermally pretreated microalgae and waste activated sludge, and estimation of its kinetic parameters.

Sci Total Environ 2020 Mar 27;706:135745. Epub 2019 Nov 27.

Faculty of Engineering, Architecture and Urbanism and Geography, Federal University of Mato Grosso do Sul, Avenida Costa e Silva s/n, Campo Grande, MS, Brazil.

The maximum methane yield that can be obtained from anaerobic co-digestion of microalgae and waste activated sludge (WAS) mixtures, after thermal pretreatment at 65 °C during 4 h, was investigated. Furthermore, the fitting of the experimental data by five kinetic models (first-order, second-order, modified Gompertz, Logistic, and two-substrate) was evaluated. Thermal pretreatment increased the methane yield of single microalgae and WAS digestion by ≈ 44 and by ≈ 52%, respectively. The results also showed that up to 60% of WAS can be co-digested with microalgae without impairing the methane yield, producing up to 338 mL g. Data from digestion of non-pretreated microalgae and WAS were well described by all kinetic models, but digestion of thermally pretreated microalgae, WAS, and their co-digestion mixtures, was best fitted by means of a two-substrate model, indicating that after pretreatment it is necessary to take into account the contribution of both rapidly and slowly biodegradable fractions.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135745DOI Listing
March 2020

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

Mem Inst Oswaldo Cruz 2019 29;114:e190170. Epub 2019 Jul 29.

Fundação Oswaldo Cruz, Laboratório de Entomologia, Porto Velho, RO, Brasil.

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.
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http://dx.doi.org/10.1590/0074-02760190170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663149PMC
August 2019

Brazil's first free-mating laboratory colony of Nyssorhynchus darlingi.

Rev Soc Bras Med Trop 2019 Jul 18;52:e20190159. Epub 2019 Jul 18.

Laboratório de Entomologia, Fiocruz Rondônia, Porto Velho, RO, Brasil.

Introduction: The lack of highly-productive Nyssorhynchus darlingi laboratory colonies limits some studies. We report the first well-established laboratory colony of Ny. darlingi in Brazil.

Methods: Mosquitoes were collected from Porto Velho and were reared at the Laboratory of Fiocruz/RO. After induced mating by light stimulation in the F1 to F6, the subsequent generations were free mating. Larvae were reared in distilled water and fed daily until pupation.

Results: In 11 generations, the colony produced a high number of pupae after the F5 generation.

Conclusions: These results demonstrate the potential for permanently establishing Ny. darlingi colonies for research purposes in Brazil.
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http://dx.doi.org/10.1590/0037-8682-0159-2019DOI Listing
July 2019

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

J Environ Sci Health A Tox Hazard Subst Environ Eng 2019 28;54(10):1023-1034. Epub 2019 May 28.

Faculty of Engineering, Architecture and Urbanism, and Geography, Federal University of Mato Grosso do Sul , Campo Grande , MS , Brazil.

The current paper investigates the development of two ornamental plants, canna lily ( x ) and giant horsetail (), at both bench and pilot scale. Combinations of gravel-filled mesocosm, planted and unplanted (control), irrigated with light greywater (GW) or tap water (W), were used. Both species were able to grow under the tested conditions with no indication of toxicity that could affect the development. Irrigation with GW, 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 GW evapotranspirated 69.23% and 30.77%, respectively as compared to the unplanted GW-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.
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http://dx.doi.org/10.1080/10934529.2019.1620028DOI Listing
November 2019

Life Cycle Assessment of prospective MSW management based on integrated management planning in Campo Grande, Brazil.

Waste Manag 2019 May 24;90:59-71. Epub 2019 Apr 24.

SDU Life Cycle Engineering, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Electronic address:

A crucial first step in transforming problematic waste management into sustainable integrated systems is comprehensive planning and analysis of environmental and socio-economic effects. The work presented here is a Life Cycle Assessment (LCA) that addressed the environmental performance of prospective development pathways for the municipal solid waste (MSW) management system in a large urban area, i.e. Campo Grande, Brazil. The research built on data and expanded the main development pathway proposed in the municipalities integrated waste management plan, which covers a period of 20 years (2017-2037). The system progression was assessed for milestone years (5-year intervals) considering projections of future population and waste generation growth, as well as addressing the development of surrounding systems, such as energy production. Results reveal that the rather conservative planned development pathway, which is largely based on gradual increase in selective collection, could successfully counter negative environmental externalities that would otherwise materialize due to increasing waste generation. A second, more ambitious, pathway with additionally scheduled actions to treat mixed MSW and upgrade certain treatment technologies (e.g. from composting to anaerobic digestion of collected organics), was used to illustrate a potential range for significantly higher impact reduction and even positive externalities, given a zero burden approach before waste generation.
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http://dx.doi.org/10.1016/j.wasman.2019.04.035DOI Listing
May 2019

Sustainable Sanitation Management Tool for Decision Making in Isolated Areas in Brazil.

Int J Environ Res Public Health 2019 03 28;16(7). Epub 2019 Mar 28.

Faculty of Engineering, Architecture, Urbanism and Geography, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil.

There is a worldwide range of technical sanitation guidelines focusing on small or traditional and isolated communities for ecological alternatives at the household level. However, a computational tool (software) that has a database and connects these guidelines in a single reference for resource-oriented sanitation concept decision making is still lacking. In this regard, an easy-to-use tool was developed using a participatory approach for the decision-making process from a choice of technical solutions to a type of system management. The results obtained from a pilot study indicate that the proposed tool in this paper will help with the decision-making process to aid in not only choosing sustainable sanitation solutions, but also sustainable operation and maintenance options for the systems. When presenting and discussing the tool with research groups and technicians, the potential for participatory application was noticed. The proposed tool can be used in the elaboration of municipal sanitation plans, assisting local technicians and environmental licensing agencies, designers and engineering students, among others. The software can be applied with other management tools, such as 5W2H and Canvas business model.
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http://dx.doi.org/10.3390/ijerph16071118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479376PMC
March 2019

Author Correction: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.

Nat Genet 2019 02;51(2):363

Dame Roma Mitchell Cancer Research Centre, University of Adelaide, Adelaide, South Australia, Australia.

In the version of this article initially published, the name of author Manuela Gago-Dominguez was misspelled as Manuela Gago Dominguez. The error has been corrected in the HTML and PDF version of the article.
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http://dx.doi.org/10.1038/s41588-018-0330-6DOI Listing
February 2019

Prevalence of Depressive Symptoms in Patients Requesting Cosmetic Breast Surgery in Midwestern Brazil.

Plast Reconstr Surg Glob Open 2018 Oct 2;6(10):e1899. Epub 2018 Oct 2.

Hospital das Clínicas Teaching Hospital, Federal University of Goiás, Goiânia, Goiás, Brazil.

Background: The prevalence of depressive symptoms (DS) before cosmetic breast surgery was analyzed in the public (PbI) and private (PrI) institutions, comparing types of surgery and patients' sociodemographic characteristics.

Methods: A cross-sectional, observational, analytical study to evaluate the prevalence of DS in 185 patients of 18-71 years of age requesting 4 different cosmetic breast surgeries (with and without implants) at public and private institutions. Patients were assessed using the Beck Depression Inventory and analyzed for statistical comparison.

Results: The most common surgical procedures were reduction mammoplasty in the PbI and augmentation mammoplasty in the PrI. The prevalence of the positive risk for depressive disorder (≥15 points in Beck Depression Inventory) in the PbI was 25.8%, whereas in the PrI: 11.4% ( = 0.012). Moderate and severe DS were, respectively, 120% and 242% higher in the PbI than in the PrI. No patients requesting mastopexy without implants had DS. The highest prevalence (51.4%) of DS occurred in patients with breast implants indications (augmentation mammoplasty and mastopexy with implants). The presence ( = 0.12) or absence ( = 0.33) of implant did not demonstrate a higher risk of DS. Among all patients, 7% answered positively to the statements on suicide ideation, with predominance within the group of implants (54.5%). There were significant differences between the PbI and PrI.

Conclusions: The prevalence of DS was high (18.9%), with the risk being 2.3 times greater in the PbI. Patients from PbI and PrI showed significant different profiles. Patients for breast implants showed a higher score for suicide ideation.
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http://dx.doi.org/10.1097/GOX.0000000000001899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250461PMC
October 2018
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