Increased Cardiovascular Risk Associated with Chemical Sensitivity to Perfluoro-Octanoic Acid: Role of Impaired Platelet Aggregation

Perfluoro\u2013alkyl substances (PFAS), particularly perfluoro\u2013octanoic acid (PFOA), are persisting environmental chemicals showing bioaccumulation in human tissues. Recently, exposure to PFAS has been associated with increased prevalence of cardiovascular diseases (CVDs). However, a causal role of PFAS in atherosclerosis pathogenesis is under-investigated. Here, we investigated the effect of PFOA exposure on platelets\u2019 function, a key player in atherosclerosis process. PFOA accumulation in platelets was evaluated by liquid chromatography-mass spectrometry. Changes in platelets\u2019 membrane fluidity and activation after dose-dependent exposure to PFOA were evaluated by merocyanine 540 (MC540) and anti P-Selectin immune staining at flow cytometry, respectively. Intracellular calcium trafficking was analyzed with Fluo4M probe, time-lapse live imaging. Platelets\u2019 aggregation state was also evaluated with Multiplate\uae aggregometry analyzer in 48 male subjects living in a specific area of the Veneto region with high PFAS environmental pollution, and compared with 30 low-exposure control subjects. Platelets\u2019 membrane was the major target of PFOA, whose dose-dependent accumulation was associated in turn with increased membrane fluidity, as expected by a computational model; increased activation at resting condition; and both calcium uptake and aggregation upon activation. Finally, exposed subjects had higher serum and platelets levels of PFOA, together with increased aggregation parameters at Multiplate\uae, compared with controls. These data help to explain the emerging association between PFAS exposure and CVD

ACTA OTORHINOLARYNGOLOGICA ITALICA

Le asimmetrie maxillo-mandibolari riconoscono numerose eziologie: congenita, traumatica, iatrogena e post resezione oncologica. I pazienti affetti da malformazioni congenite vengono generalmente sottoposti a chirurgia ortognatica con o senza procedure aggiuntive (genioplastica, impianti alloplastici) con risultati soddisfacenti. Tuttavia, nonostante il raggiungimento della simmetria scheletrica può esitare una asimmetria residua più o meno evidente. Lo studio presentato è stato effettuato su 45 pazienti (29 femmine e 16 maschi), trattati chirurgicamente tra Dicembre 2012 e Giugno 2014. Tutti i pazienti erano affetti da asimmetria maxillo-mandibolare e sono stati sottoposti a chirurgia ortognatica per la correzione ossea della deformità. Le alterazioni residue sono state trattate con lipofilling. In tutti i casi si è osservato un buon attecchimento del grasso a livello del sito ricevente. Lanalisi retrospettiva della documentazione fotografica ha dimostrato un progressivo decremento dei volumi raggiunti in seguito al trattamento con lipofilling fino a sei mesi dalla procedura, dopodiché i volumi sono rimasti invariati. Non sono state riportate complicanze significative sia a livello del sito donatore sia del ricevente. Un lieve edema ecchimotico è stato osservato frequentemente nella prima settimana post-operatoria, non sono stati riportati casi di ematoma, infezioni, danni nervosi o vascolari. 24 pazienti hanno avuto necessità di ulteriori applicazioni, una seconda applicazione si è resa necessaria in 22 pazienti ed una terza in 2 pazienti. (totale di 69 procedure). Sulla base dei risultati di questo studio la metodica del lipofilling si è dimostrata semplice, efficace e facilmente riproducibile, mostrando un alto indice di soddisfazione da parte dei pazienti e una scarsa incidenza di svantaggi e complicanze. Abbiamo inoltre dimostrato come il successo del riempimento con grasso autologo sia dipendente dalla subunità del viso che viene trattata. Le regioni malare e della guancia hanno mostrato i migliori risultati mentre le subunità corrispondenti al labbro inferiore e superiore hanno mostrato uno scarso attecchimento del grasso innestato, con una conseguente maggiore perdita di volume. In conclusione si può dire che le procedure composite, che prevedono lutilizzo congiunto della correzione chirurgica delle basi scheletriche e un successivo ritocco per mezzo di innesto di grasso autologo, costituiscono una opzione addizionale e personalizzabile per i pazienti affetti da malformazioni maxillo-mandibolari

Welcoming low testosterone as a cardiovascular risk factor

Male hypogonadism now has a new spectrum of complications. They are mainly cardiometabolic in nature. Low serum testosterone levels are a risk factor for diabetes, metabolic syndrome, inflammation and dyslipidemia. These metabolic and inflammatory complications are not without consequences. Recent studies have shown low serum testosterone levels to be an independent risk factor of cardiovascular and all-cause mortality. It is time to welcome low serum testosterone levels as a cardiovascular risk factor

A One-Step Real-Time Multiplex PCR for Screening Y-Chromosomal Microdeletions without Downstream Amplicon Size Analysis

BACKGROUND: Y-chromosomal microdeletions (YCMD) are one of the major genetic causes for non-obstructive azoospermia. Genetic testing for YCMD by multiplex polymerase chain reaction (PCR) is an established method for quick and robust screening of deletions in the AZF regions of the Y-chromosome. Multiplex PCRs have the advantage of including a control gene in every reaction and significantly reducing the number of reactions needed to screen the relevant genomic markers. PRINCIPAL FINDINGS: The widely established "EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions (2004)" were used as a basis for designing a real-time multiplex PCR system, in which the YCMD can simply be identified by their melting points. For this reason, some AZF primers were substituted by primers for regions in their genomic proximity, and the ZFX/ZFY control primer was exchanged by the AMELX/AMELY control primer. Furthermore, we substituted the classical SybrGreen I dye by the novel and high-performing DNA-binding dye EvaGreen™ and put substantial effort in titrating the primer combinations in respect to optimal melting peak separation and peak size. SIGNIFICANCE: With these changes, we were able to develop a platform-independent and robust real-time based multiplex PCR, which makes the need for amplicon identification by electrophoretic sizing expendable. By using an open-source system for real-time PCR analysis, we further demonstrate the applicability of automated melting point and YCMD detection

Genetic instability and anti-HPV immune response as drivers of infertility associated with HPV infection

Funding Information: RFBR grant 17–54-30002, Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075–15–2019-1660) to Olga Smirnova. Publisher Copyright: © 2021, The Author(s).Human papillomavirus (HPV) is a sexually transmitted infection common among men and women of reproductive age worldwide. HPV viruses are associated with epithelial lesions and cancers. HPV infections have been shown to be significantly associated with many adverse effects in reproductive function. Infection with HPVs, specifically of high-oncogenic risk types (HR HPVs), affects different stages of human reproduction, resulting in a series of adverse outcomes: 1) reduction of male fertility (male infertility), characterized by qualitative and quantitative semen alterations; 2) impairment of couple fertility with increase of blastocyst apoptosis and reduction of endometrial implantation of trophoblastic cells; 3) defects of embryos and fetal development, with increase of spontaneous abortion and spontaneous preterm birth. The actual molecular mechanism(s) by which HPV infection is involved remain unclear. HPV-associated infertility as Janus, has two faces: one reflecting anti-HPV immunity, and the other, direct pathogenic effects of HPVs, specifically, of HR HPVs on the infected/HPV-replicating cells. Adverse effects observed for HR HPVs differ depending on the genotype of infecting virus, reflecting differential response of the host immune system as well as functional differences between HPVs and their individual proteins/antigens, including their ability to induce genetic instability/DNA damage. Review summarizes HPV involvement in all reproductive stages, evaluate the adverse role(s) played by HPVs, and identifies mechanisms of viral pathogenicity, common as well as specific for each stage of the reproduction process.publishersversionPeer reviewe

Climatic and cultural changes in the west Congo Basin forests over the past 5000 years

Central Africa includes the world's second largest rainforest block. The ecology of the region remains poorly understood, as does its vegetation and archaeological history. However, over the past 20 years, multidisciplinary scientific programmes have enhanced knowledge of old human presence and palaeoenvironments in the forestry block of Central Africa. This first regional synthesis documents significant cultural changes over the past five millennia and describes how they are linked to climate. It is now well documented that climatic conditions in the African tropics underwent significant changes throughout this period and here we demonstrate that corresponding shifts in human demography have had a strong influence on the forests. The most influential event was the decline of the strong African monsoon in the Late Holocene, resulting in serious disturbance of the forest block around 3500 BP. During the same period, populations from the north settled in the forest zone; they mastered new technologies such as pottery and fabrication of polished stone tools, and seem to have practised agriculture. The opening up of forests from 2500 BP favoured the arrival of metallurgist populations that impacted the forest. During this long period (2500–1400 BP), a remarkable increase of archaeological sites is an indication of a demographic explosion of metallurgist populations. Paradoxically, we have found evidence of pearl millet (Pennisetum glaucum) cultivation in the forest around 2200 BP, implying a more arid context. While Early Iron Age sites (prior to 1400 BP) and recent pre-colonial sites (two to eight centuries BP) are abundant, the period between 1600 and 1000 BP is characterized by a sharp decrease in human settlements, with a population crash between 1300 and 1000 BP over a large part of Central Africa. It is only in the eleventh century that new populations of metallurgists settled into the forest block. In this paper, we analyse the spatial and temporal distribution of 328 archaeological sites that have been reliably radiocarbon dated. The results allow us to piece together changes in the relationships between human populations and the environments in which they lived. On this basis, we discuss interactions between humans, climate and vegetation during the past five millennia and the implications of the absence of people from the landscape over three centuries. We go on to discuss modern vegetation patterns and African forest conservation in the light of these events.Peer reviewe

Choline Dehydrogenase Polymorphism rs12676 Is a Functional Variation and Is Associated with Changes in Human Sperm Cell Function

Approximately 15% of couples are affected by infertility and up to half of these cases arise from male factor infertility. Unidentified genetic aberrations such as chromosomal deletions, translocations and single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic male infertility. Deletion of the choline dehydrogenase (Chdh) gene in mice results in decreased male fertility due to diminished sperm motility; sperm from Chdh−/− males have decreased ATP concentrations likely stemming from abnormal sperm mitochondrial morphology and function in these cells. Several SNPs have been identified in the human CHDH gene that may result in altered CHDH enzymatic activity. rs12676 (G233T), a non-synonymous SNP located in the CHDH coding region, is associated with increased susceptibility to dietary choline deficiency and risk of breast cancer. We now report evidence that this SNP is also associated with altered sperm motility patterns and dysmorphic mitochondrial structure in sperm. Sperm produced by men who are GT or TT for rs12676 have 40% and 73% lower ATP concentrations, respectively, in their sperm. rs12676 is associated with decreased CHDH protein in sperm and hepatocytes. A second SNP located in the coding region of IL17BR, rs1025689, is linked to altered sperm motility characteristics and changes in choline metabolite concentrations in sperm