Chandra Observations of Eight Sources Discovered by INTEGRAL

We report on 0.3-10 keV observations with the Chandra X-ray Observatory of eight hard X-ray sources discovered within 8 degrees of the Galactic plane by the INTEGRAL satellite. The short (5 ks) Chandra observations of the IGR source fields have yielded very likely identifications of X-ray counterparts for three of the IGR sources: IGR J14091-6108, IGR J18088-2741, and IGR J18381-0924. The first two have very hard spectra in the Chandra band that can be described by a power-law with photon indices of Gamma = 0.6+/-0.4 and -0.7(+0.4)(-0.3), respectively (90% confidence errors are given), and both have a unique near-IR counterpart consistent with the Chandra position. IGR J14091-6108 also displays a strong iron line and a relatively low X-ray luminosity, and we argue that the most likely source type is a Cataclysmic Variable (CV), although we do not completely rule out the possibility of a High Mass X-ray Binary. IGR J18088-2741 has an optical counterpart with a previously measured 6.84 hr periodicity, which may be the binary orbital period. We also detect five cycles of a possible 800-950 s period in the Chandra light curve, which may be the compact object spin period. We suggest that IGR J18088-2741 is also most likely a CV. For IGR J18381-0924, the spectrum is intrinsically softer with Gamma = 1.5(+0.5)(-0.4), and it is moderately absorbed, nH = (4+/-1)e22 cm-2. There are two near-IR sources consistent with the Chandra position, and they are both classified as galaxies, making it likely that IGR J18381-0924 is an Active Galactic Nucleus (AGN). For the other five IGR sources, we provide lists of nearby Chandra sources, which may be used along with further observations to identify the correct counterparts, and we discuss the implications of the low inferred Chandra count rates for these five sources.Comment: Accepted by ApJ, 14 page

GEMINI near-infrared spectroscopic observations of young massive stars embedded in molecular clouds

K-band spectra of young stellar candidates in four southern hemisphere clusters have been obtained with the near-infrared spectrograph GNIRS in Gemini South. The clusters are associated with IRAS sources that have colours characteristic of ultracompact HII regions. Spectral types were obtained by comparison of the observed spectra with those of a NIR library; the results include the spectral classification of nine massive stars and seven objects confirmed as background late-type stars. Two of the studied sources have K-band spectra compatible with those characteristic of very hot stars, as inferred from the presence of Civ, Niii, and Nv emission lines at 2.078 micron, 2.116 micron, and 2.100 micron respectively. One of them, I16177 IRS1, has a K-band spectrum similar to that of Cyg OB2 7, an O3If* supergiant star. The nebular K-band spectrum of the associated UC Hii region shows the s-process [Kriii] and [Seiv] high excitation emission lines, previously identified only in planetary nebula. One young stellar object (YSO) was found in each cluster, associated with either the main IRAS source or a nearby resolved MSX component, confirming the results obtained from previous NIR photometric surveys. The distances to the stars were derived from their spectral types and previously determined JHK magnitudes; they agree well with the values obtained from the kinematic method, except in the case of IRAS15408-5356, for which the spectroscopic distance is about a factor two smaller than the kinematic value.Comment: This is the version that will be published by the Montly Notices of the Royal Astronomical Societ

Central nervous system stimulation therapies in phantom limb pain: a systematic review of clinical trials

Phantom limb pain is a chronic pain syndrome that is difficult to cope with. Despite neurostimulation treatment is indicated for refractory neuropathic pain, there is scant evidence from randomized controlled trials to recommend it as the treatment choice. Thus, a systematic review was performed to analyze the efficacy of central nervous system stimulation therapies as a strategy for pain management in patients with phantom limb pain. A literature search for studies conducted between 1970 and September 2020 was carried out using the MEDLINE and Embase databases. Principles of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline were followed. There were a total of 10 full-text articles retrieved and included in this review. Deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and motor cortex stimulation were the treatment strategies used in the selected clinical trials. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation were effective therapies to reduce pain perception, as well as to relieve anxiety and depression symptoms in phantom limb pain patients. Conversely, invasive approaches were considered the last treatment option as evidence in deep brain stimulation and motor cortex stimulation suggests that the value of phantom limb pain treatment remains controversial. However, the findings on use of these treatment strategies in other forms of neuropathic pain suggest that these invasive approaches could be a potential option for phantom limb pain patients

Proteomic profiling of stallion spermatozoa suggests changes in sperm metabolism and compromised redox regulation after cryopreservation

Proteomic technologies allow the detection of thousands of proteins at the same time, being a powerful technique to reveal molecular regulatory mechanisms in spermatozoa and also sperm damage linked to low fertility or specific biotechnologies. Modifications induced by the cryopreservation in the stallion sperm proteome were studied using UHPLC/MS/MS. Ejaculates from fertile stallions were collected and split in two subsamples, one was investigated as fresh (control) samples, and the other aliquot frozen and thawed using standard procedures and investigated as frozen thawed subsamples. UHPLC/MS/MS was used to study the sperm proteome under these two distinct conditions and bioinformatic enrichment analysis conducted. Gene Ontology (GO) and pathway enrichment analysis were performed revealing dramatic changes as consequence of cryopreservation. The terms oxidative phosphorylation, mitochondrial ATP synthesis coupled electron transport and electron transport chain were significantly enriched in fresh samples (P = 5.50 × 10−12, 4.26 × 10−8 and 7.26 × 10–8, respectively), while were not significantly enriched in frozen thawed samples (P = 1). The GO terms oxidation reduction process and oxidoreductase activity were enriched in fresh samples and the enrichment was reduced in frozen thawed samples (1.40 × 10−8, 1.69 × 10−6 versus 1.13 × 10−2 and 2-86 × 10−2 respectively). Reactome pathways (using human orthologs) significantly enriched in fresh sperm were TCA cycle and respiratory electron transport (P = 1.867 × 10−8), Respiratory electron transport ATP synthesis by chemiosmosis coupling (P = 2.124 × 10−5), Citric acid cycle (TCA cycle)(P = 8.395 × 10−4) Pyruvate metabolism and TCA cycle (P = 3.380 × 10−3), Respiratory electron transport (P = 2.764 × 10−2) and Beta oxidation of laurolyl-CoA to decanoyl CoA-CoA (P = 1.854 × 10−2) none of these pathways were enriched in thawed samples (P = 1). We have provided the first detailed study on how the cryopreservation process impacts the stallion sperm proteome. Our findings identify the metabolic proteome and redoxome as the two key groups of proteins affected by the procedure. Significance: In the present manuscript we investigated how the cryopreservation of stallion spermatozoa impacts the proteome of these cells. This procedure is routinely used in horse breeding and has a major impact in the industry, facilitating the trade of genetic material. This is still a suboptimal biotechnology, with numerous unresolved problems. The limited knowledge of the molecular insults occurring during cryopreservation is behind these problems. The application and development of proteomics to the spermatozoa, allow to obtain valuable information of the specific mechanisms affected by the procedure. In this paper, we report that cryopreservation impacts numerous proteins involved in metabolism regulation (mainly mitochondrial proteins involved in the TCA cycle, and oxidative phosphorylation) and also affects proteins with oxidoreductase activity. Moreover, specific proteins involved in the sperm-oocyte interaction are also affected by the procedure. The information gathered in this study, opens interesting questions and offer new lines of research for the improvement of the technology focusing the targets here identified, and the specific steps in the procedure (cooling, toxicity of antioxidants etc.) to be modified to reduce the damage

Biomimetic Ca-P coatings Incorporating bisphosphonates produced on starch-based degradable biomaterials

In this study, sodium clodronate, a well-known therapeutic agent from the family of bisphosphonates (BPs), is incorporated in a biomimetic calcium phosphate (CaP) coating, previously formed on the surface of a starch-based biomaterial by a sodium silicate methodology, as a strategy to develop a site-specific drug delivery system for bone tissue regeneration applications. The effects on the resulting CaP coatings were evaluated in terms of morphology, chemistry, and structure. The dissolution of Ca and P from the coating and the release profiles of sodium clodronate was also assessed. As a preliminary approach, this first study also aimed at evaluating the effects of this BP on the viability of a human osteoblastic cell line since there is still little information available on the interaction between BPs and this type of cells. Sodium clodronate was successfully incorporated, at different doses, in the structure of a biomimetic CaP layer previously formed by a sodium silicate process. This type of BPs had a stimulatory effect on osteoblastic activity, particularly at the specific concentration of 0.32 mg/mL. It is foreseen that these coatings can, for instances, be produced on the surface of degradable polymers and then used for regulating the equilibrium on osteoblastic/osteoclastic activity, leading to a controlled regenerative effect at the interface between the biomaterial and bone

Lightning Impulse Current Tests on Conductive Fabrics

Submitted to "Journal of Industrial Textiles"The large amount of electric current associated to lightning discharges is hazardous for living beings, equipment, structures and buildings. To protect those targets against lightning are used Lightning Protection Systems (LPS). However, there are some temporary outdoor activities and backcountry places where an adequate LPS cannot be set up mainly due to the large dimensions of its components and its heavy weight. On the search of light weight lightning protection materials that can be used as part of special LPS, we research some types of electroconductive fabrics by applying high lightning impulse currents in laboratory. The fabric samples checked were pieces of 10 cm x 10 cm: two rip-stop type, a plain-weave, a non-woven and a carbon-impregnated polymeric, all of them obtained commercially. Under laboratory conditions, these samples were subject to subsequent lightning impulse currents registering the voltage and current signals. Optical and scanning electron microscope inspections were performed after tests. Despite some changes visualized as marks left on the fabric surface, the results show that investigated conductive textiles can endure ground currents produced by atmospheric lightning since they withstand the several applied laboratory lightning impulse currents. The outcomes suggest that the weave pattern of the conductive fabric influences the lightning current tolerance, enabling some conductive fabrics to be used in heavy-current applications and as part of personal LPS for outdoor, backcountry and mobile shelters, particularly when lightweight and portability are mandatory

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

Comparison of Figulla Flex® and Amplatzer™ devices for atrial septal defect closure: A meta-analysis

Background: Atrial septal defect (ASD) is one of the most common congenital heart diseases. Percutaneousclosure is the preferred treatment, but certain complications remain a concern. The most common devices are AMPLATZER™ (ASO) (St. Jude Medical, St. Paul, MN, USA) and Figulla Flex® septal occluders (FSO) (Occlutech GmbH, Jena, Germany). The present study aimed to assess main differences in outcomes.Methods: A systematic search in Pubmed and Google scholarship was performed by two independent reviewers for any study comparing ASO and FSO. Searched terms were “Figulla”, “Amplatzer”, and “atrial septal defect”. A random-effects model was used.Results: A total of 11 studies including 1770 patients (897 ASO; 873 FSO) were gathered. Baseline clinical and echocardiographic characteristics were comparable although septal aneurysm was more often reported in patients treated with ASO (32% vs. 25%; p = 0.061). Success rate (94% vs. 95%; OR: 0.81; 95% CI: 0.38–1.71; p = 0.58) and peri-procedural complications were comparable. Procedures were shorter, requiring less fluoroscopy time with an FSO device (OR: 0.59; 95% CI: 0.20–0.97; p = 0.003). Although the global rate of complications in long-term was similar, the ASO device was associated with a higher rate of supraventricular arrhythmias (14.7% vs. 7.8%, p = 0.009).Conclusions: Percutaneous closure of ASD is a safe and effective, irrespective of the type of device. No differences exist regarding procedural success between the ASO and FSO devices but the last was associated to shorter procedure time, less radiation, and lower rate of supraventricular arrhythmias in follow-up. Late cardiac perforation did not occur and death in the follow-up was exceptional

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

Acknowledgements The iHARP database was funded by unrestricted grants from Mundipharma International Ltd and Research in Real-Life Ltd; these analyses were funded by an unrestricted grant from Teva Pharmaceuticals. Mundipharma and Teva played no role in study conduct or analysis and did not modify or approve the manuscript. The authors wish to direct a special appreciation to all the participants of the iHARP group who contributed data to this study and to Mundipharma, sponsors of the iHARP group. In addition, we thank Julie von Ziegenweidt for assistance with data extraction and Anna Gilchrist and Valerie L. Ashton, PhD, for editorial assistance. Elizabeth V. Hillyer, DVM, provided editorial and writing support, funded by Research in Real-Life, Ltd.Peer reviewedPublisher PD

Heightened immune response to autocitrullinated porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is characterised by autoimmunity to citrullinated proteins, and there is increasing epidemiologic evidence linking Porphyromonas gingivalis to RA. P gingivalis is apparently unique among periodontal pathogens in possessing a citrullinating enzyme, peptidylarginine deiminase (PPAD) with the potential to generate antigens driving the autoimmune response. Objectives: To examine the immune response to PPAD in patients with RA, individuals with periodontitis (PD) and controls (without arthritis), confirm PPAD autocitrullination and identify the modified arginine residues. Methods: PPAD and an inactivated mutant (C351A) were cloned and expressed and autocitrullination of both examined by immunoblotting and mass spectrometry. ELISAs using PPAD, C351A and another P gingivalis protein arginine gingipain (RgpB) were developed and antibody reactivities examined in patients with RA (n=80), individuals with PD (n=44) and controls (n=82). Results: Recombinant PPAD was a potent citrullinating enzyme. Antibodies to PPAD, but not to Rgp, were elevated in the RA sera (median 122 U/ml) compared with controls (median 70 U/ml; p<0.05) and PD (median 60 U/ml; p<0.01). Specificity of the anti-peptidyl citrullinated PPAD response was confirmed by the reaction of RA sera with multiple epitopes tested with synthetic citrullinated peptides spanning the PPAD molecule. The elevated antibody response to PPAD was abolished in RA sera if the C351A mutant was used on ELISA. Conclusions: The peptidyl citrulline-specific immune response to PPAD supports the hypothesis that, as a bacterial protein, it might break tolerance in RA, and could be a target for therapy