Middle East respiratory syndrome

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention

Perceptions of Massage Therapists Participating in a Randomized Controlled Trial

Background: Clinical practice and randomized trials often have disparate aims, despite involving similar interventions. Attitudes and expectancies of practitioners influence patient outcomes, and there is growing emphasis on optimizing provider–patient relationships. In this study, we evaluated the experiences of licensed massage therapists involved in a randomized controlled clinical trial using qualitative methodology.Methods: Seven massage therapists who were interventionists in a randomized controlled trial participated in structured interviews approximately 30 minutes in length. Interviews focused on their experiences and perceptions regarding aspects of the clinical trial, as well as recommendations for future trials. Transcribed interviews were analyzed for emergent topics and themes using standard qualitative methods.Results: Six themes emerged. Therapists discussed 1) promoting the profession of massage therapy through research, 2) mixed views on using standardized protocols, 3) challenges of sham interventions, 4) participant response to the sham intervention, 5) views on scheduling and compensation, and 6) unanticipated benefits of participating in research.Conclusions: Therapists largely appreciated the opportunity to promote massage through research. They demonstrated insight and understanding of the rationale for a clinical trial adhering to a standardized protocol. Evaluating the experiences and ideas of complementary and alternative medicine practitioners provides valuable insight that is relevant for the implementation and design of randomized trials

Modeling the Measurements of Cochlear Microcirculation and Hearing Function after Loud Noise

Objective: Recent findings support the crucial role of microcirculatory disturbance and ischemia for hearing impairment especially after noise-induced hearing loss (NIHL). The aim of this study was to establish an animal model for in vivo analysis of cochlear microcirculation and hearing function after a loud noise to allow precise measurements of both parameters in vivo. Study Design: Randomized controlled trial. Setting: Animal study. Subjects and Methods: After assessment of normacusis (0 minutes) using evoked auditory brainstem responses (ABRs), noise (106-dB sound pressure level [SPL]) was applied to both ears in 6 guinea pigs for 30 minutes while unexposed animals served as controls. In vivo fluorescence microscopy of the stria vascularis capillaries was performed after surgical exposure of 1 cochlea. ABR measurements were derived from the contralateral ear. Results: After noise exposure, red blood cell velocity was reduced significantly by 24.3% (120 minutes) and further decreased to 44.5% at the end of the observation (210 minutes) in contrast to stable control measurements. Vessel diameters were not affected in both groups. A gradual decrease of segmental blood flow became significant (38.1%) after 150 minutes compared with controls. Hearing thresholds shifted significantly from 20.0 ± 5.5 dB SPL (0 minutes) to 32.5 ± 4.2dB SPL (60 minutes) only in animals exposed to loud noise. Conclusion: With regard to novel treatments targeting the stria vascularis in NIHL, this standardized model allows us to analyze in detail cochlear microcirculation and hearing function in vivo

Adenovirus DNA in Guthrie cards from children who develop acute lymphoblastic leukaemia (ALL)

Aims: The aim of this thesis was to increase understanding of how molecular processes influence the development and risk assessment of childhood leukemia. Studies I and II investigates whether a specific virus infection in utero could be involved in a “first hit” in leukemogenesis. Studies III and IV examine whether alterations in protein expression from cell cycle regulating genes may predict a relapse in children with myeloid malignancies undergoing hematopoietic stem cell transplantation (HSCT). Background: Genetic alterations, analyzed at time of diagnosis in children who develop leukemia, have been traced back to neonatal dried blood spots (DBS). This suggests that the majority of chromosome translocations occur in utero during fetal hematopoiesis, generating a “first hit”. A “second hit” is then required to generate a leukemic clone. Today, experiments in vitro, animal models, and clinical observations have revealed that several viruses are oncogenic and capable of initiating a genetic alteration. Smith M postulated the theory that an in utero infection might be the “first hit”, causing genetic aberrations that could later lead to the development of the leukemic clone, which is supported by the early age of onset and space-time clustering data, based on time, place of birth, and diagnosis. Leukemia develops as a result of hematopoietic or lymphoid tissue with uncontrolled cell division. Normally cell division is controlled by the cell cycle, the network of which is complex with numerous regulating proteins both up and down stream, but also containing several feedback loops. The important regulators of this process are tumor suppressor genes, essential for normal cell proliferation and differentiation as well as for controlling DNA integrity. Errors in these genes or their protein expression affect the ability of the cell to check for DNA damage, thus tumors may occur. Proteins from these genes could serve as prognostic markers and predict relapse. Methods: In studies I and II we investigated neonatal DBS by PCR for the presence of adenovirus DNA (243 samples) and the three newly discovered polyomaviruses (50 samples) from children who later developed leukemia but also from controls (486 and 100 samples respectively). In studies III and IV we explored the expression of one (p53) respectively four (p53, p21, p16 and PTEN) cell cycle regulating proteins in bone marrow at diagnosis as well as pre and post HSCT in myeloid malignancies in children. We retrospectively collected clinical data and bone marrow samples from 33 children diagnosed with chronic myeloid malignancies (MDS, JMML and CML), 34 children diagnosed with AML as well as 55 controls. The samples were prepared by tissue micro array (TMA) as well as immunohistochemistry and examined for protein expression in a light microscope. Results: In study I we detected adenovirus DNA in only two patients who later developed leukemia, but in none of the controls. In study II all the samples were negative for KIPyV, WUPyV and MCPyV DNA in both patients and controls. In study III we found an overexpression of p53 protein at diagnosis that significantly predicted relapse after HSCT in children with rare chronic myeloid malignancies. In study IV a significantly higher p53 expression was found in the relapse compared to the non-relapse group at six months post HSCT in children with AML, suggesting that p53 may be used as prognostic markers for predicting a relapse. In addition, the calculated cut off level for p53 at diagnosis (study III) and at six months (study IV) post HSCT was approximately 20%, which indicates that a p53 expression over 20% may predict relapse in children with myeloid malignancies. Conclusion: Although we did not find an association between adenoviruses or the three newly discovered polyomaviruses and the development of childhood leukemia, a virus could still be involved in this process; the virus may have escaped detection, other new viruses could be involved or a virus could precipitate the “second hit”. We suggest that evaluation of p53 protein expression may be used as a supplement to regular prognostic markers both pre and post HSCT. To further evaluate this, a prospective multicenter study has been started

Molecular basis of structure and function of the microvillus membrane of intestinal epithelial cells

Correlation of molecular structure with biochemical functions of the plasma membrane of the microvilli of intestinal epithelial cells has been investigated by biochemical and electron microscopic procedures. Repeating particles, measuring approximately 60 &#197;in diameter, were found on the surface of the microvilli membrane which had been isolated or purified from rabbit intestinal epithelial cells and negatively stained with phosphotungstic acid. These particles were proved to be inherent components of the microvillus membrane, attached to the outer surface of its trilaminar structure, and were designated as the elementary particles of the microvilli of intestinal epithelial cells. Biochemical and electron microscopic identification of these elementary particles has been carried out by isolation of the elementary particles with papain from the isolated microvillus membrane, followed by purification of the particles by chromatographies on DEAE-cellulose and Sephadex columns. The partially purified particles containing invertase and leucine aminopeptidase are similar in size and structure to those of the elementary particles in the microvillus membrane. Evidence indicates that each of the elementary particles coincide with or include an enzyme molecule such as disaccharidase or peptidase, which carry out the terminal hydrolytic digestion of carbohydrates and proteins, respectively, on the surface of the microvillus membrane. Magnesium ionactivated adenosine triphosphatase and alkaline phosphatase cannot be solubilized with papain but remains in the smooth-surface membrane after the elementary particles have been removed. Cytochemical electron microscopic observation revealed that the active site of magnesium ion-activated adenosine triphosphatase is localized predominantly in the inner surface of the trilaminar structure of the microvillus membrane.</p

Polyploidization as a Retraction Force in Plant Genome Evolution: Sequence Rearrangements in Triticale

BACKGROUND: Polyploidization is a major evolutionary process in plants where hybridization and chromosome doubling induce enormous genomic stress and can generate genetic and epigenetic modifications. However, proper evaluation of DNA sequence restructuring events and the precise characterization of sequences involved are still sparse. METHODOLOGY/PRINCIPAL FINDINGS: Inter Retrotransposons Amplified Polymorphism (IRAP), Retrotransposons Microsatellite Amplified Polymorphism (REMAP) and Inter Simple Sequence Repeat (ISSR) largely confirmed the absence of any intraspecific variation in wheat, rye and triticale. The comparative analysis of banding profiles between wheat and rye inbred lines revealed 34% of monomorphic (common to both parental species) bands for the ten different primer combinations used. The analysis of triticale plants uncovered nearly 51% of rearranged bands in the polyploid, being the majority of these modifications, due to the loss of rye bands (83%). Sequence analysis of rye fragments absent in triticale revealed for instance homology with hydroxyproline-rich glycoproteins (HRGP), a protein that belongs to a major family of inducible defence response proteins. Conversely, a wheat-specific band absent in triticale comprises a nested structure of copia-like retrotransposons elements, namely Claudia and Barbara. Sequencing of a polyploid-specific band (absent in both parents) revealed a microsatellite related sequence. Cytological studies using Fluorescent In Situ Hybridization (FISH) with REMAP products revealed a widespread distribution of retrotransposon and/or microsatellite flanking sequences on rye chromosomes, with a preferential accumulation in heterochromatic sub-telomeric domains. CONCLUSIONS/SIGNIFICANCE: Here, we used PCR-based molecular marker techniques involving retrotransposons and microsatellites to uncover polyploidization induced genetic restructuring in triticale. Sequence analysis of rearranged genomic fragments either from rye or wheat origin showed these to be retrotransposon-related as well as coding sequences. Further FISH analysis revealed possible chromosome hotspots for sequence rearrangements. The role of chromatin condensation on the origin of genomic rearrangements mediated by polyploidization in triticale is also discussed

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial

The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC