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[...]in the current study, the role of histone deacetylases (class I HDACs) and histones (H3 and H4) in peripheral inflammation and the epigenetic mechanisms of alcohol-induced oxidative stress were analyzed ex vivo and in vitro.

Recurrent lung infections and pneumonia are emerging as significant comorbidities in the HIV-infected population in the era of combination antiretroviral therapy (cART). HIV infection has been reported to suppress nasal mucociliary clearance (MCC). Since the primary components driving nasal MCC and bronchial MCC are identical, it is possible that bronchial MCC is affected as well. Effective MCC requires optimal ciliary beating which depends on the maintenance of the airway surface liquid (ASL), a function of cystic fibrosis transmembrane conductance regulator (CFTR) activity and the integrity of the signaling mechanism that regulates ciliary beating and fluid secretion. Impairment of either component of the MCC apparatus can compromise its efficacy and promote microbial colonization. We demonstrate that primary bronchial epithelium expresses HIV receptor CD4 and co-receptors CCR5 and CXCR4 and can be infected by both R5 and X4 tropic strains of HIV. We show that HIV Tat suppresses CFTR biogenesis and function in primary bronchial epithelial cells by a pathway involving TGF-β signaling. HIV infection also interferes with bronchial epithelial cell differentiation and suppresses ciliogenesis. These findings suggest that HIV infection suppresses tracheobronchial mucociliary clearance and this may predispose HIV-infected patients to recurrent lung infections, pneumonia and chronic bronchitis.

Human endogenous retroviruses (HERVs) are LTR retrotransposons that are present in the human genome. Among them, members of the HERV-K (HML-2) group are suspected to play a role in the development of different types of cancer, including lung, ovarian, and prostate cancer, as well as leukemia. Acute myeloid leukemia (AML) is an important disease that causes 1% of cancer deaths in the United States and has a survival rate of 28.7%. Here, we describe a method for assessing the statistical association between HERV-K (HML-2) transposable element insertion polymorphisms (or TIPs) and AML, using whole-genome sequencing and read mapping using TIP_finder software. Our results suggest that 101 polymorphisms involving HERV-K (HML-2) elements were correlated with AML, with a percentage between 44.4 to 56.6%, most of which (70) were located in the region from 8q24.13 to 8q24.21. Moreover, it was found that the TRIB1, LRATD2, POU5F1B, MYC, PCAT1, PVT1, and CCDC26 genes could be displaced or fragmented by TIPs. Furthermore, a general method was devised to facilitate analysis of the correlation between transposable element insertions and specific diseases. Finally, although the relationship between HERV-K (HML-2) TIPs and AML remains unclear, the data reported in this study indicate a statistical correlation, as supported by the χ2 test with p-values < 0.05.

The negative factor (Nef) of human immunodeficiency virus (HIV) is an accessory protein that is thought to be integral to HIV-associated immune- and neuroimmune pathogenesis. Here, we show that nef-transfected microglia-released Nef+ exosome (exNef) disrupts the apical blood–brain barrier (BBB) and that only nef-transfected microglia release Nef in exosomes. nef–gfp-transduced neurons and astrocytes release exosomes but did not release exNef in the extracellular space. Apical administration of exNef derived from nef-transfected 293T cells reduced transendothelial electrical resistance (TEER) and increased permeability of the BBB. Microglia-derived exNef applied to either the apical/basal BBB significantly reduced expression of the tight junction protein, ZO-1, suggesting a mechanism of exNef-mediated neuropathogenesis. Microglia exposed to exNef release elevated levels of Toll-like receptor-induced cytokines and chemokines IL-12, IL-8, IL-6, RANTES, and IL-17A. Magnetic nanoparticle delivery of Nef peptides containing the Nef myrisolation site across an in vitro BBB ultimately reduced nef-transfected microglia release of Nef exosomes and prevented the loss of BBB integrity and permeability as measured by TEER and dextran-FITC transport studies, respectively. Overall, we show that exNef is released from nef–gfp-transfected microglia; exNef disrupts integrity and permeability, and tight junctions of the BBB, and induces microglial cytokine/chemokine secretion. These exNef-mediated effects were significantly restricted by Nef peptides. Taken together, this study provides preliminary evidence of the role of exNef in HIV neuroimmune pathogenesis and the feasibility of a nanomedicine-based therapeutics targeting exNef to treat HIV-associated neuropathogenesis.

IntroductionHuntington’s disease (HD) is a rare (1-9/100 000), inherited disease characterized by an elongated CAG repeat on chromosome 4p, leading to a degeneration of neurons. Also, psychiatric symptoms are very common in the early stage and may appear before motor symptoms.ObjectivesTo characterize neuropsychiatric symptoms in a group of individuals with manifest or pre-motor Huntington’s disease in Medellín, Colombia.MethodsData obtained from clinical records of individuals with HD (motor-manifest or pre-motor with triplets count) evaluated for ENROLL-HD project in the Group of Neuroscience of Antioquia. We explored variables related to substances abuse, neuropsychiatric symptoms, the respective age of onset, sex, and triplet count when available.ResultsTwenty-six (53%) were women, 8% had a familiar history of psychotic illness in a first-degree relative and 88% presented motor symptoms. Also, 59% had a history of depression, 53% irritability, 57% aggressiveness, 34% apathy, 29% perseverative/obsessive behavior, 14% psychosis, and 30% mild cognitive impairment. Ten individuals (20%) had motor without neuropsychiatric symptoms. Also, thirty-seven individuals (76%) presented motor and neuropsychiatric symptoms; of these, 41% had neuropsychiatric symptoms before motor symptoms. No psychiatric symptoms were associated with the use of alcohol, cigarettes, or drugs of abuse.ConclusionsNeuropsychiatric symptoms are highly prevalent among individuals with HD and studies oriented to create relevant knowledge for the development of advice oriented to people with this disease are necessary.DisclosureNo significant relationships.

IntroductionThere is limited evidence favoring the use of the sentinel lymph node technique in ovarian cancer, and no standardized approach has been studied. The objective of the present pilot study is to determine the feasibility of the sentinel lymph node technique by applying a clinical algorithm.MethodsPatients with confirmed ovarian cancer were included. 99mTc and indocyanine green were injected into the ovarian and infundubulo-pelvic ligament stump. A gamma probe and near-infrared fluorescence imaging were used for sentinel lymph node detection.ResultsThe sentinel lymph node technique was performed in nine patients with a detection rate in the pelvic and/or para-aortic region of 100%. The tracer distribution rates of sentinel lymph nodes in the pelvic and para-aortic regions were 87.5% and 70%, respectively.ConclusionThe detection of sentinel lymph nodes in early-stage ovarian cancer appears to be achievable. Based on these results, a clinical trial entitled SENTOV (SENtinel lymph node Technique in OVarian cancer) will be performed.

Waste milk (WM), a byproduct of dairy production, is often used as a cost-effective feed for calves, but it can contain pathogens and antimicrobial residues, which pose health risks. This study examined the microbiological quality and the presence of antimicrobial residues in WM from 36 dairy farms in southern Chile. In a cross-sectional study, WM samples were collected, and farm management data were gathered through a questionnaire. The samples were analyzed for total bacterial load, coliforms, staphylococci, streptococci/streptococci-like organisms (SSLOs), Salmonella spp., Mycobacterium avium subsp. paratuberculosis (MAP), Mycobacterium bovis , Mycoplasma spp., Prototheca spp., methicillin-resistant Staphylococcus aureus (MRSA), and extended-spectrum beta-lactamase (ESBL)-producing E. coli . Antimicrobial residues were detected using a commercial test. A high average bacterial load (7.63 × 10 6  CFU/mL) and significant levels of staphylococci, SSLOs, and coliform were found. In addition, S. aureus (33.3%), MAP (11.1%), and Salmonella spp. (2.8%) were detected. ESBL- E. coli was found on five farms, with bla CTX-M being the predominant gene. Antimicrobial residues, mainly beta-lactams, were present in 55.6% of samples. These results show that WM in this region frequently contains pathogens, antimicrobial residues, and resistant bacteria. Current farm practices, such as feeding untreated WM to calves, may contribute to the spread of antimicrobial resistance and compromise calf health.

Recurrent lung infections are a common cause of morbidity and mortality in people living with HIV and this is exacerbated in smokers even when administered combination antiretroviral therapy (cART). The incidence of pneumonia is increased with smoking and treatment interruption and is directly dependent on viral load in patients when adjusted for CD4 counts. CFTR dysfunction plays an important role in aberrant airway innate immunity as it is pivotal in regulating mucociliary clearance (MCC) rates and other antibacterial mechanisms of the airway. In our earlier work, we have demonstrated that bronchial epithelium expresses canonical HIV receptors CD4, CCR5 and CXCR4 and can be infected with HIV. HIV Tat suppresses CFTR mRNA and function via TGF-β signaling. In the present study, we demonstrate that cigarette smoke (CS) potentiates HIV infection of bronchial epithelial cells by upregulating CD4 and CCR5 expression. HIV and CS individually and additively suppress CFTR biogenesis and function, possibly explaining the increased incidence of lung infections in HIV patients and its exacerbation in HIV smokers.

Background Rhipicephalus ( Boophilus ) annulatus and Rhipicephalus ( Boophilus ) microplus (southern cattle fever tick; SCFT), collectively known as cattle-fever ticks (CFTs), are vectors of protozoal parasites ( Babesia bigemina and Babesia bovis ) that cause bovine babesiosis (also known as cattle fever). One traditional strategy for CFT eradication involves the implementation of a “pasture vacation,” which involves removing cattle ( Bos taurus ) from an infested pasture for an extended period of time. However, vacated pastures are often inhabited by wildlife hosts, such as white-tailed deer (WTD; Odocoileus virginianus ), which can serve as alternate hosts for questing CFTs. We hypothesized that the distribution of host-seeking larvae among habitat types post-pasture vacation would reflect habitat use patterns of WTD, and in turn, affect the subsequent rate of pasture infestation by CFT. Methods We adapted a spatially explicit, individual-based model to simulate interactions among SCFT, cattle, and WTD as a tool to investigate the potential effects of WTD habitat use preferences on the efficacy of a pasture vacation. We parameterized the model to represent conditions typical of rangelands in south Texas, USA, simulated a 1-year pasture vacation under different assumptions regarding WTD habitat use preferences, and summarized effects on efficacy through (1) time post-vacation to reach 100% of pre-vacation densities of host-seeking larvae, and (2) the ecological conditions that resulted in the lowest host-seeking larval densities following pasture vacation. Results Larval densities at the landscape scale varied seasonally in a similar manner over the entire simulation period, regardless of WTD habitat use preferences. Following the removal of cattle, larval densities declined sharply to < 100 larvae/ha. Following the return of cattle, larval densities increased to > 60% of pre-vacation densities ≈ 21 weeks post-vacation, and reached pre-vacation levels in less than a year. Trends in larval densities in different habitat types paralleled those at the landscape scale over the entire simulation period, but differed quantitatively from one another during the pasture vacation. Relative larval densities (highest to lowest) shifted from (1) wood/shrub, (2) grass, (3) mixed-brush during the pre-vacation period to (1) mixed-brush, (2) wood/shrub, (3) grass or (1) wood/shrub, (2) mixed-brush, (3) grass during the post-vacation period, depending on WTD habitat use preferences. Conclusions By monitoring WTD-driven shifts in distributions of SCFT host-seeking larvae among habitat types during simulated pasture vacation experiments, we were able to identify potential SCFT refugia from which recrudescence of infestations could originate. Such information could inform timely applications of acaricides to specific refugia habitats immediately prior to the termination of pasture vacations. Graphical Abstract