Surgical mask to prevent influenza transmission in households: a cluster randomized trial

Background

Facemasks and respirators have been stockpiled during pandemic preparedness. However, data on their effectiveness for limiting transmission are scarce. We evaluated the effectiveness of facemask use by index cases for limiting influenza transmission by large droplets produced during coughing in households.

Methodology and Principal Findings

A cluster randomized intervention trial was conducted in France during the 2008–2009 influenza season. Households were recruited during a medical visit of a household member with a positive rapid influenza A test and symptoms lasting less than 48 hours. Households were randomized either to the mask or control group for 7 days. In the intervention arm, the index case had to wear a surgical mask from the medical visit and for a period of 5 days. The trial was initially intended to include 372 households but was prematurely interrupted after the inclusion of 105 households (306 contacts) following the advice of an independent steering committee. We used generalized estimating equations to test the association between the intervention and the proportion of household contacts who developed an influenza-like illness during the 7 days following the inclusion. Influenza-like illness was reported in 24/148 (16.2%) of the contacts in the intervention arm and in 25/158 (15.8%) of the contacts in the control arm and the difference between arms was 0.40% (95%CI: −10% to 11%, P = 1.00). We observed a good adherence to the intervention. In various sensitivity analyses, we did not identify any trend in the results suggesting effectiveness of facemasks.

Conclusion

This study should be interpreted with caution since the lack of statistical power prevents us to draw formal conclusion regarding effectiveness of facemasks in the context of a seasonal epidemic.

Trial Registration

clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00774774","term_id":"NCT00774774"}}NCT00774774     

AKTIP interacts with ESCRT I and is needed for the recruitment of ESCRT III subunits to the midbody

To complete mitosis, the bridge that links the two daughter cells needs to be cleaved. This step is carried out by the endosomal sorting complex required for transport (ESCRT) machinery. AKTIP, a protein discovered to be associated with telomeres and the nuclear membrane in interphase cells, shares sequence similarities with the ESCRT I component TSG101. Here we present evidence that during mitosis AKTIP is part of the ESCRT machinery at the midbody. AKTIP interacts with the ESCRT I subunit VPS28 and forms a circular supra-structure at the midbody, in close proximity with TSG101 and VPS28 and adjacent to the members of the ESCRT III module CHMP2A, CHMP4B and IST1. Mechanistically, the recruitment of AKTIP is dependent on MKLP1 and independent of CEP55. AKTIP and TSG101 are needed together for the recruitment of the ESCRT III subunit CHMP4B and in parallel for the recruitment of IST1. Alone, the reduction of AKTIP impinges on IST1 and causes multinucleation. Our data altogether reveal that AKTIP is a component of the ESCRT I module and functions in the recruitment of ESCRT III components required for abscission.     

Mycobiota associated with insect galleries in walnut with thousand cankers disease reveals a potential natural enemy against Geosmithia morbida

Thousand Cankers Disease (TCD) affects Juglans and Pterocarya species. This disease poses not only a major threat to the nut and timber industries but also to native stands of walnut trees. Galleries created by Pityophthorus juglandis (vector) are colonized by the fungus Geosmithia morbida (causal agent of necrosis). It is unknown if other fungi colonizing these galleries might act antagonistically towards G. morbida. The objectives of this study were to: (1) characterize the fungal community associated with TCD-infected trees and (2) develop a pilot study addressing their potential antagonism towards G. morbida. We collected non-Geosmithia fungi from ten TCD-infected walnut trees from California and Tennessee. Four hundred and fifty-seven isolates, representing sixty-five Operational Taxonomic Units (99 % ITS similarity) were obtained. Fungal communities were found to be highly diverse. Ophiostoma dominated the communities associated with TCD-compromised trees from California, whereas Trichoderma dominated TCD-compromised trees in Tennessee. Six Trichoderma isolates showed varying levels of antagonism against three isolates of G. morbida, suggesting potential applications for the biological control of TCD. Furthermore, results from this study contribute to the growing knowledge about the observed differential disease development between the western and eastern USA and could overall impact our understanding of TCD etiology.     

Rosuvastatin protects isolated hearts against ischemia-reperfusion injury: role of Akt-GSK-3β, metabolic environment,and mitochondrial permeability transition pore

Journal of Physiology and Biochemistry - The cardioprotective activity of rosuvastatin (R) is yet to be known. The objective of this study was to research whether R perfusion before global ischemia...     

Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection

Activation of innate immune cells by Trypanosoma cruzi-derived molecules such as GPI anchors and DNA induces proinflammatory cytokine production and host defense mechanisms. In this study, we demonstrate that DNA from T. cruzi stimulates cytokine production by APCs in a TLR9-dependent manner and synergizes with parasite-derived GPI anchor, a TLR2 agonist, in the induction of cytokines by macrophages. Compared with wild-type animals, T. cruzi-infected Tlr9(-/-) mice displayed elevated parasitemia and decreased survival. Strikingly, infected Tlr2(-/-)Tlr9(-/-) mice developed a parasitemia equivalent to animals lacking MyD88, an essential signaling molecule for most TLR, but did not show the acute mortality displayed by MyD88(-/-) animals. The enhanced susceptibility of Tlr9(-/-) and Tlr2(-/-)Tlr9(-/-) mice was associated with decreased in vivo IL-12/IFN-gamma responses. Our results reveal that TLR2 and TLR9 cooperate in the control of parasite replication and that TLR9 has a primary role in the MyD88-dependent induction of IL-12/IFN-gamma synthesis during infection with T. cruzi.     

The α-Helical Region in p24γ2 Subunit of p24 Protein Cargo Receptor Is Pivotal for the Recognition and Transport of Glycosylphosphatidylinositol-anchored Proteins

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are group of proteins that depend on p24 cargo receptors for their transport from the endoplasmic reticulum to the Golgi apparatus. The GPI anchor is expected to act as a sorting and transport signal, but so far little is known about the recognition mechanism. In the present study we investigate the GPI-AP transport in cell knockdown of p24γ, the most diverse p24 subfamily. Knockdown of p24γ₂ but not of other p24γ family members impaired the transport of a reporter GPI-AP. Restoration of the knockdown-induced phenotype using chimeric constructs between p24γ₂ and the related p24γ₁ further implied a role of the α-helical region of p24γ₂ but not its GOLD domain in the specific binding of GPI-APs. We conclude that motifs in the membrane-adjacent α-helical region of p24γ₂ are involved in recognition of GPI-APs and are consequently responsible for the incorporation of these proteins into coat protein complex II-coated transport vesicles.     

Mitochondrial dysfunction and the inflammatory response

Inflammation has been linked to multiple degenerative and acute diseases as well as the aging process. Moreover, mitochondrial alterations play a central role in these processes. Mitochondria have an important role in pro-inflammatory signaling; similarly, pro-inflammatory mediators may also alter mitochondrial function. Both of these processes increase mitochondrial oxidative stress, promoting a vicious inflammatory cycle. Additionally, damage-associated molecular patterns derived from mitochondria could contribute to inflammasome formation and caspase-1 activation, while alterations in mitochondrial autophagy may cause inflammation. Strategies aimed at controlling excessive oxidative stress within mitochondria may represent both preventive and therapeutic interventions in inflammation.     

Early Gag Immunodominance of the HIV-Specific T-Cell Response during Acute/Early Infection Is Associated with Higher CD8+ T-Cell Antiviral Activity and Correlates with Preservation of the CD4+ T-Cell Compartment

The important role of the CD8⁺ T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8⁺ T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8⁺ T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4⁺ T-cell set points were observed in PHI subjects with higher HIV-specific CD8⁺ T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1β (MIP-1β). All together, this study underscores the importance of CD8⁺ T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection.     

Biodistribution of sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) in an oral cancer model

Boron neutron capture therapy (BNCT) is based on selective accumulation of ¹⁰B carriers in tumor followed by neutron irradiation. We previously proved the therapeutic success of BNCT mediated by the boron compounds boronophenylalanine and sodium decahydrodecaborate (GB-10) in the hamster cheek pouch oral cancer model. Based on the clinical relevance of the boron carrier sodium borocaptate (BSH) and the knowledge that the most effective way to optimize BNCT is to improve tumor boron targeting, the specific aim of this study was to perform biodistribution studies of BSH in the hamster cheek pouch oral cancer model and evaluate the feasibility of BNCT mediated by BSH at nuclear reactor RA-3. The general aim of these studies is to contribute to the knowledge of BNCT radiobiology and optimize BNCT for head and neck cancer. Sodium borocaptate (50 mg ¹⁰B/kg) was administered to tumor-bearing hamsters. Groups of 3–5 animals were killed humanely at nine time-points, 3–12 h post-administration. Samples of blood, tumor, precancerous pouch tissue, normal pouch tissue and other clinically relevant normal tissues were processed for boron measurement by optic emission spectroscopy. Tumor boron concentration peaked to therapeutically useful boron concentration values of 24–35 ppm. The boron concentration ratio tumor/normal pouch tissue ranged from 1.1 to 1.8. Pharmacokinetic curves showed that the optimum interval between BSH administration and neutron irradiation was 7–11 h. It is concluded that BNCT mediated by BSH at nuclear reactor RA-3 would be feasible.     

Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and mutated in patients affected by autosomal dominant hearing impairment (DFNA4)

Myosins have been implicated in various motile processes, including organelle translocation, ion-channel gating, and cytoskeleton reorganization. Different members of the myosin superfamily are responsible for syndromic and nonsyndromic hearing impairment in both humans and mice. MYH14 encodes one of the heavy chains of the class II nonmuscle myosins, and it is localized within the autosomal dominant hearing impairment (DFNA4) critical region. After demonstrating that MYH14 is highly expressed in mouse cochlea, we performed a mutational screening in a large series of 300 hearing-impaired patients from Italy, Spain, and Belgium and in a German kindred linked to DFNA4. This study allowed us to identify a nonsense and two missense mutations in large pedigrees, linked to DFNA4, as well as a de novo allele in a sporadic case. Absence of these mutations in healthy individuals was tested in 200 control individuals. These findings clearly demonstrate the role of MYH14 in causing autosomal dominant hearing loss and further confirm the crucial role of the myosin superfamily in auditive functions.