Epidemiology of Porcine Circovirus Type 2 Circulating in Wild Boars of Portugal during the 2018–2020 Hunting Seasons Suggests the Emergence of Genotype 2d

Porcine circovirus type 2 (PCV-2) is associated with several syndromes affecting swine, also known as porcine-circovirus-associated diseases, of which post-weaning multi-systemic wasting syndrome stands out due to its high economic impact on swine production. Recent data suggest the increasing circulation of the PCV-2d genotype in several countries worldwide. To provide updated data on PCV-2 genotypes currently circulating in swine in Portugal, we screened wild boar stools collected from several districts across Portugal, during the 2018–2020 hunting seasons, for PCV-2 and genetically characterized detected strains. From a total of 76 stool samples of wild boar tested by PCR for the partial PCV-2 ORF2 gene, two sequences were obtained (2/76; 2.6%, 95% confidence interval: 0.032–9.18). Bidirectional sequencing showed that the sequences were 100% identical and both of the PCV-2d genotype, showing for the first time the presence of this genotype in Portugal. Monitoring wild PCV-2 reservoirs is important for both veterinary public health and economic reasons, since PCV-2 infection has a strong economic impact on the swine industry. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding text 1: Funding: Sérgio Santos-Silva thanks Fundação para a Ciência e a Tecnologia (FCT) for the financial support of his PhD work under the 2021 scholarship. 09461.BD contract through the Maria de Sousa-2021 program. Part of this research was funded by the project EcoARUn: POCI-01-0145-FEDER-030310 funded by FEDER, through COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI), and by national funds (OE), through Fundação para a Ciência e a Tecnologia/Ministério da Ciência e Tecnologia e Ensino Superior. R. T. Torres is funded by national funds (OE) and through FCT, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. Thanks are due to FCT/MCTES for the financial support to CESAM (UIDP/50017/2020 + UIDB/50017/2020), through national funds (FCT). This work is financed by national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the projects UIDB/04750/2020 and LA/P/0064/2020.; Funding text 2: S?rgio Santos-Silva thanks Funda??o para a Ci?ncia e a Tecnologia (FCT) for the financial support of his PhD work under the 2021 scholarship. 09461.BD contract through the Maria de Sousa-2021 program. Part of this research was funded by the project EcoARUn: POCI-01-0145-FEDER-030310 funded by FEDER, through COMPETE2020-Programa Operacional Competitividade e Internacionaliza??o (POCI), and by national funds (OE), through Funda??o para a Ci?ncia e a Tecnologia/Minist?rio da Ci?ncia e Tecnologia e Ensino Superior. R. T. Torres is funded by national funds (OE) and through FCT, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. Thanks are due to FCT/MCTES for the financial support to CESAM (UIDP/50017/2020 + UIDB/50017/2020), through national funds (FCT). This work is financed by national funds through FCT?Funda??o para a Ci?ncia e a Tecnologia, I.P., under the projects UIDB/04750/2020 and LA/P/0064/2020

Dirofilaria immitis antigenemia and microfilaremia in Iberian wolves and red foxes from Portugal

Background: Dirofilaria immitis is a parasitic nematode endemic in the Mediterranean countries, which causes cardiopulmonary dirofilariosis in wild and domestic animals. Despite being recognized hosts of D. immitis, wild carnivores such as wolves and foxes are frequently disregarded when considering a potential role in the transmission of these zoonotic nematodes. In Portugal, studies available regarding D. immitis circulation are scarce, likely underestimating its relevance. To add knowledge on this, we sought to assess Iberian wolves (Canis lupus signatus) and red foxes (Vulpes vulpes) from northern Portugal for D. immitis antigenemia and microfilaremia. Methods: Blood samples from 42 Iberian wolves and 19 red foxes were collected, during 2010–2012, in Peneda-Gerês National Park. Antigenemia was searched for by rapid antigen detection test kits (Uranotest Dirofilaria ®). Microfilaremia was assessed by polymerase chain reaction (PCR). Nucleic acids were extracted from blood using QIAamp® DNA Mini Kit (Qiagen), and DNA was screened for the presence of microfilaria using a conventional PCR targeting the 5.8S-internal transcribed spacer 2–28S regions, followed by bidirectional sequencing, Basic Local Alignment Search Tool analysis and phylogenetic analysis. Results: Three red foxes had antigenemia, with an occurrence of 15.8% (95% confidence interval [CI] 3.4–39.6), while showing no evidence for the presence of microfilaremia. No wolf samples presented evidence for D. immitis antigenemia. Nevertheless, two wolves were positive for D. immitis microfilaremia (4.8%; 95% CI 0.6–16.2%) as revealed by PCR and confirmed by bidirectional sequencing. Conclusions: Although Dirofilaria microfilaremia in wolves does not necessarily correlate to an endangerment of the infected animal's health, positive individuals can act as a reservoir for further infection if the intermediate mosquito hosts are present. To the best of our knowledge, one single study had reported that wolves were suitable Dirofilaria hosts, but microfilaremia have never been reported. Graphical Abstract: [Figure not available: see fulltext.] © 2022, The Author(s).Funding text 1: Publication of this paper has been sponsored by Elanco Animal Health in the framework of the 17th CVBD®World Forum Symposium.; Funding text 2: This work was supported by national funds, through Fundação para a Ciência e a Tecnologia (FCT, Portuguese Foundation for Science and Technology), under projects UIDB/04750/2020 and LA/P/0064/2020; and projects UIDB/CVT/00772/2020 and LA/P/0059/2020, also funded by FCT

Formation of Lipofuscin-Like Autofluorescent Granules in the Retinal Pigment Epithelium Requires Lysosome Dysfunction

PURPOSE: We aim to characterize the pathways required for autofluorescent granule (AFG) formation by RPE cells using cultured monolayers. METHODS: We fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24 hours the cells started accumulating AFGs that were comparable to lipofuscin in vivo. Using this model, we used a variety of light and electron microscopical techniques, flow cytometry and Western blot to analyze the formation of AFGs. We also generated a mutant RPE line lacking cathepsin D by gene editing. RESULTS: AFGs seem to derive from incompletely digested POS-containing phagosomes and after 3 days are surrounded by a single membrane positive for lysosome markers. We show by various methods that lysosome-phagosome fusion is required for AFG formation, and that impairment of lysosomal pH or catalytic activity, particularly cathepsin D activity, enhances AF accumulation. CONCLUSIONS: We conclude that lysosomal dysfunction results in incomplete POS degradation and enhanced AFG accumulation

Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Leukocyte telomere length (LTL) and mitochondrial genome (mtDNA) copy number and deletions have been proposed as risk markers for various cancer types, including breast cancer (BC)

Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe

Background: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to- hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence. Methods: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models. Results: After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02–1.21) for BMI, 1.13 (95% CI 1.04–1.23) for WC, 1.09 (95% CI 0.98–1.21) for HC, and 1.15 (95% CI 1.00–1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer ( P interaction o 0.001), where never HT users showed an B 20% increased risk per s.d. of BMI, WC, and HC compared to ever users. Conclusions: BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modification by HT use

Captive-born collared peccary (Pecari tajacu, Tayassuidae) fails to discriminate between predator and non-predator models

Captive animals may lose the ability to recognize their natural predators, making conservation programs more susceptible to failure if such animals are released into the wild. Collared peccaries are American tayassuids that are vulnerable to local extinction in certain areas, and conservation programs are being conducted. Captive-born peccaries are intended for release into the wild in Minas Gerais state, southeastern Brazil. In this study, we tested the ability of two groups of captive-born collared peccaries to recognize their predators and if they were habituated to humans. Recognition tests were performed using models of predators (canids and felids) and non-predators animals, as well as control objects, such as a plastic chair; a human was also presented to the peccaries, and tested as a separate stimulus. Anti-predator defensive responses such as fleeing and threatening displayswere not observed in response to predator models. Predator detection behaviors both from visual and olfactory cues were displayed, although they were not specifically targeted at predator models. These results indicate that collared peccaries were unable to recognize model predators. Habituation effects, particularly on anti-predator behaviors, were observed both with a 1-h model presentation and across testing days. Behavioral responses to humans did not differ from those to other models. Thus, if these animals were to be released into the wild, they should undergo anti-predator training sessions to enhance their chances of survival

Topical microbicides to prevent the transmission of HIV: formulation gaps and challenges

The efforts of the topical microbicide field to identify a safe and effective topical microbicide were realized in July of 2010 with the reporting of the results of the Centre for the AIDS Programme of Research in South Africa 004 trial. In this trial, a 1% tenofovir gel was found to reduce women’s risk for HIV acquisition by 39% compared to placebo. To understand the impact of this trial on future microbicide development, we must view it from the historical perspective of previous phases 2 and 3 clinical trials with detergents and sulfated polyanions. This knowledge and emerging information must then be parlayed into the next steps needed to create a safe, effective, and acceptable topical microbicide. This review will look at the lessons learned from preclinical and clinical development of topical microbicides, focusing on two significant future challenges: (1) topical microbicide formulation safety and (2) the critical role that adherence to product use has in determining safety and efficacy in clinical trials and ultimately commercial viability of the licensed product. In addition to framing these issues within our current understanding of formulation and prevention of HIV acquisition, recent advances in our understanding of the mechanism of HIV transmission and how it informs on future formulation strategies will be briefly discussed