37 research outputs found
Psychoeducation and the family burden in schizophrenia: a randomized controlled trial
Abstract Background The majority of patients with schizophrenia live with their relatives in Pakistan, thereby families experience a considerable burden. We aimed to study the impact of psychoeducation on the burden of schizophrenia on the family in a randomised controlled trial. Methods A total of 108 patients with schizophrenia and their family members from the outpatient department of a teaching hospital in Lahore, Pakistan were randomised. Both groups received psychotropic drugs but one group received psychoeducation in addition. Family burden was assessed at the time of recruitment and at 6 months post intervention. Results In all, 99 patients and their relatives completed the treatment. There was significant reduction in burden at post-intervention assessment in the psychoeducation group based on intention to treat analysis. Conclusion Family psychoeducation can be an important intervention for patients with schizophrenia in Pakistan.</p
Homozygous Deletion of Six Olfactory Receptor Genes in a Subset of Individuals with Beta-Thalassemia
Progress in the functional studies of human olfactory receptors has been largely hampered by the lack of a reliable experimental model system. Although transgenic approaches in mice could characterize the function of individual olfactory receptors, the presence of over 300 functional genes in the human genome becomes a daunting task. Thus, the characterization of individuals with a genetic susceptibility to altered olfaction coupled with the absence of particular olfactory receptor genes will allow phenotype/genotype correlations and vindicate the function of specific olfactory receptors with their cognate ligands. We characterized a 118 kb ÎČ-globin deletion and found that its 3âČ end breakpoint extends to the neighboring olfactory receptor region downstream of the ÎČ-globin gene cluster. This deletion encompasses six contiguous olfactory receptor genes (OR51V1, OR52Z1, OR51A1P, OR52A1, OR52A5, and OR52A4) all of which are expressed in the brain. Topology analysis of the encoded proteins from these olfactory receptor genes revealed that OR52Z1, OR52A1, OR52A5, and OR52A4 are predicted to be functional receptors as they display integral characteristics of G-proteins coupled receptors. Individuals homozygous for the 118 kb ÎČ-globin deletion are afflicted with ÎČ-thalassemia due to a homozygous deletion of the ÎČ-globin gene and have no alleles for the above mentioned olfactory receptors genes. This is the first example of a homozygous deletion of olfactory receptor genes in human. Although altered olfaction remains to be ascertained in these individuals, such a study can be carried out in ÎČ-thalassemia patients from Malaysia, Indonesia and the Philippines where this mutation is common. Furthermore, OR52A1 contains a Îł-globin enhancer, which was previously shown to confer continuous expression of the fetal Îł-globin genes. Thus, the hypothesis that ÎČ-thalassemia individuals, who are homozygous for the 118 kb deletion, may also have an exacerbation of their anemia due to the deletion of two copies of the Îł-globin enhancer element is worthy of consideration
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PS18kh: A New Tidal Disruption Event with a Non-axisymmetric Accretion Disk
We present the discovery of PS18kh, a tidal disruption event discovered at the center of SDSS J075654.53+341543.6 (d â 322 Mpc) by the Pan-STARRS Survey for Transients. Our data set includes pre-discovery survey data from Pan-STARRS, the All-sky Automated Survey for Supernovae, and the Asteroid Terrestrial-impact Last Alert System as well as high-cadence, multiwavelength follow-up data from ground-based telescopes and Swift, spanning from 56 days before peak light until 75 days after. The optical/UV emission from PS18kh is well-fit as a blackbody with temperatures ranging from T â 12,000 K to T â 25,000 K and it peaked at a luminosity of L â 8.8 Ă 10 erg s . PS18kh radiated E = (3.45 ± 0.22) Ă 10 erg over the period of observation, with (1.42 ± 0.20) Ă 10 erg being released during the rise to peak. Spectra of PS18kh show a changing, boxy/double-peaked Hα emission feature, which becomes more prominent over time. We use models of non-axisymmetric accretion disks to describe the profile of the Hα line and its evolution. We find that at early times the high accretion rate leads the disk to emit a wind which modifies the shape of the line profile and makes it bell-shaped. At late times, the wind becomes optically thin, allowing the non-axisymmetric perturbations to show up in the line profile. The line-emitting portion of the disk extends from r ⌠60r to an outer radius of r ⌠1400r and the perturbations can be represented either as an eccentricity in the outer rings of the disk or as a spiral arm in the inner disk. 43 -1 50 50 in g out
Epigenetic Mechanisms Regulate Stem Cell Expressed Genes Pou5f1 and Gfra1 in a Male Germ Cell Line
Male fertility is declining and an underlying cause may be due to environment-epigenetic interactions in developing sperm, yet nothing is known of how the epigenome controls gene expression in sperm development. Histone methylation and acetylation are dynamically regulated in spermatogenesis and are sensitive to the environment. Our objectives were to determine how histone H3 methylation and acetylation contribute to the regulation of key genes in spermatogenesis. A germ cell line, GC-1, was exposed to either the control, or the chromatin modifying drugs tranylcypromine (T), an inhibitor of the histone H3 demethylase KDM1 (lysine specific demethylase 1), or trichostatin (TSA), an inhibitor of histone deacetylases, (HDAC). Quantitative PCR (qPCR) was used to identify genes that were sensitive to treatment. As a control for specificity the Myod1 (myogenic differentiation 1) gene was analyzed. Chromatin immunoprecipitation (ChIP) followed by qPCR was used to measure histone H3 methylation and acetylation at the promoters of target genes and the control, Myod1. Remarkably, the chromatin modifying treatment specifically induced the expression of spermatogonia expressed genes Pou5f1 and Gfra1. ChIP-qPCR revealed that induction of gene expression was associated with a gain in gene activating histone H3 methylation and acetylation in Pou5f1 and Gfra1 promoters, whereas CpG DNA methylation was not affected. Our data implicate a critical role for histone H3 methylation and acetylation in the regulation of genes expressed by spermatogonia â here, predominantly mediated by HDAC-containing protein complexes
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Multi-messenger observations of a binary neutron star merger
On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transientâs position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta
Vampires in the village Ćœrnovo on the island of KorÄula: following an archival document from the 18th century
SrediĆĄnja tema rada usmjerena je na raĆĄÄlambu spisa pohranjenog u DrĆŸavnom arhivu u Mlecima (fond: Capi del Consiglio deâ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na dogaÄaj iz 1748. godine u korÄulanskom selu Ćœrnovo, kada su mjeĆĄtani â vjerujuÄi da su se pojavili vampiri â oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te reÄeni dogaÄaj analizira u ĆĄirem druĆĄtvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio deâ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Ćœrnove on the island of KorÄula in Croatia opened tombs on the local cemetery in the fear of the vampires treating.
This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions
DAF-2 as a Model for Human Insulin Receptoropathies
Human exome sequencing has dramatically increased the rate of identification of disease-associated polymorphisms. However, examining the functional consequences of those variants has created an analytic bottleneck. Insulin-like signaling in has long provided a model to assess consequences of human insulin signaling mutations, but this has not been evaluated in the context of current genetic tools. We have exploited strains derived from the Million Mutation Project (MMP) and gene editing to explore further the evolutionary relationships and conservation between the human and insulin receptors. Of 40 MMP alleles analyzed in the insulin-like receptor gene DAF-2, 35 exhibited insulin-like signaling indistinguishable from wild-type animals, indicating tolerated mutations. Five MMP alleles proved to be novel dauer-enhancing mutations, including one new allele in the previously uncharacterized C-terminus of DAF-2 CRISPR-Cas9 genome editing was used to confirm the phenotypic consequence of six of these DAF-2 mutations and to replicate an allelic series of known human disease mutations in a highly conserved tyrosine kinase active site residue, demonstrating the utility of for directly modeling human disease. Our results illustrate the challenges associated with prediction of the phenotypic consequences of amino acid substitutions, the value of assaying mutant isoform function , and how recently developed tools and resources afford the opportunity to expand our understanding even of highly conserved regulatory modules such as insulin signaling. This approach may prove generally useful for modeling phenotypic consequences of candidate human pathogenic mutations in conserved signaling and developmental pathways.Some strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by National Institutes of Health (NIH) Office of Research Infrastructure Programs (P40 OD010440). This work utilized the computational resources of the NIH High Performing Computation (HPC) Biowulf cluster. This work was supported by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. D.A.B. was supported by the NIH Oxford-Cambridge Scholars Program. R.K.S. was supported by the Wellcome Trust [grant number WT098498], and the United Kingdom National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre