Discovery of Gamma Rays from the Quiescent Sun with HAWC.

We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5-2.6 TeV spectrum is well fit by a power law, dN/dE=A(E/1 TeV)^{-γ}, with A=(1.6±0.3)×10^{-12} TeV^{-1} cm^{-2} s^{-1} and γ=3.62±0.14. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.

PHEOCHROMOCYTOMA, THE GREAT MASQUERADER, PRESENTING AS REVERSIBLE CARDIOMYOPATHY: PRIMUM NON NOCERE.

Background: Pheochromocytoma, the great masquerader, can have a varied spectrum of clinical manifestations. It can often cause a diagnostic challenge despite the availability of modern investigation modalities. Case: We present the case of a 38-year-old male who presented with uncontrolled hypertension for the past 10 years and heart failure for one year. The diagnosis of pheochromocytoma was missed in the initial setting, leading to a biopsy of the retroperitoneal mass. Fortunately, the patient survived the procedure. Subsequently, with the involvement of a multi-disciplinary team, he was optimized for surgery under strict cardiac monitoring. After the complete excision of the tumour, he showed significant improvement not only in his clinical symptoms but also in his cardiac status. Conclusions: This case emphasizes the age-old medical phrase of 'Primum non nocere or first, do no harm'. Any invasive procedure in a pheochromocytoma can lead to a massive release of catecholamines causing a hypertensive crisis, pulmonary oedema, and even cardiac arrest. Any young patient presenting with hypertension or heart failure should be investigated for secondary causes. Cardiomyopathy due to pheochromocytoma is because of catecholamine overload and usually reverses or improves after curative surgery.

Neutrophil to lymphocyte ratio as a prognostic marker for non-metastatic renal cell carcinoma - does it add to what we already know?

AIM: To study the correlation of pre-operative neutrophil to lymphocyte ratio (NLR) with pathological stage, Fuhrman grade, sarcomatoid differentiation, tumor necrosis and lymph node positivity and its prognostic role in non-metastatic renal cell carcinoma (non-mRCC). MATERIALS AND METHODS: This retro-prospective, observational study was done at a tertiary care center in Mumbai, India. All patients with non-mRCC from July 2015 to April 2018 were included. Patients with co-existing systemic infection, prior immunotherapy, and long-term steroids were excluded. NLR closest to surgery, but within one month prior to surgery was used. Patients were stratified as NLR ≥ 3.0 or < 3. NLR was correlated with known prognostic factors by Pearson's correlation. RESULTS: 113 patients, aged 18-81 years (83 males and 30 females) were included. 75% had clear cell RCC. 62% had stage 1 disease. 58% patients had Fuhrman Grade 2. 10 patients had lymph node metastasis, 6 had sarcomatoid differentiation, 40 had tumor necrosis. The NLR was < 3 in 72 patients. Statistically significant correlation between NLR and tumor stage (p = 0.0054) as well as NLR and tumor necrosis (p = 0.0128) was shown. CONCLUSIONS: NLR correlates significantly with higher T stage and tumor necrosis. NLR may be integrated with well-established prognostic markers to improve the accuracy of prognostic scores.

ITSN1 regulates SAM68 solubility through SH3 domain interactions with SAM68 proline-rich motifs.

SAM68 is an mRNA-binding protein involved in mRNA processing in the nucleus that forms membraneless compartments called SAM68 Nuclear Bodies (SNBs). We found that intersectin 1 (ITSN1), a multidomain scaffold protein harboring five soluble SH3 domains, interacts with SAM68 proline-rich motifs (PRMs) surrounded by self-adhesive low complexity domains. While SAM68 is poorly soluble in vitro, the interaction of ITSN1 SH3 domains and mRNA with SAM68 enhances its solubility. In HeLa cells, the interaction between the first ITSN1 SH3 domain (SH3A) and P0, the N-terminal PRM of SAM68, induces the dissociation of SNBs. In addition, we reveal the ability of another SH3 domain (SH3D) of ITSN1 to bind to mRNAs. ITSN1 and mRNA may thus act in concert to promote SAM68 solubilization, consistent with the absence of mRNA in SNBs in cells. Together, these results support the notion of a specific chaperoning of PRM-rich SAM68 within nuclear ribonucleoprotein complexes by ITSN1 that may regulate the processing of a fraction of nuclear mRNAs, notably SAM68-controlled splicing events related to higher neuronal functions or cancer progression. This observation may also serve as a putative model of the interaction between other PRM-rich RBPs and signaling proteins harboring SH3 domains.

AUTOMATED DETECTION OF MALARIAL RETINOPATHY USING TRANSFER LEARNING.

Cerebral Malaria (CM) is a severe neurological syndrome of malaria mainly found in children and is associated with highly specific retinal lesions. The manifestation of these indications of CM in the retina is called malarial retinopathy (MR). All patients showing clinical signs of CM are commonly diagnosed and treated accordingly; however, 23% of them are misdiagnosed as they suffer from another infection with identical clinical symptoms. Due to these underlying symptoms, the false positive cases may go untreated and could result in death of the patients. A diagnostic test is needed that is highly specific in order to reduce false positives. The purpose of this study to demonstrate a technique based on a transfer learning technique using images from three different retinal cameras to identify the hemorrhages and whitening lesions in the retina which can accurately identify the patients with MR. The MR detection model gives a specificity of 100% and a sensitivity of 90% with an AUC of 0.98. The algorithm demonstrates the potential of accurate MR detection with a low-cost retinal camera.

Quercetin loaded chitosan tripolyphosphate nanoparticles accelerated cutaneous wound healing in Wistar rats.

Previous studies have shown that quercetin on topical application improved cutaneous wound healing in rats, but hydrophobic nature and less skin penetration limits its potential as topical healing agent. Therefore, present study was planned to investigate wound healing potential of chitosan based quercetin nanoparticles. Quercetin loaded nanoparticles were synthesized by ionic gelation method and characterized by various standard techniques. A 2 × 2 cm2 square shaped wound was created on the thoraco-lumbar part of rats. Wounded rats were divided into 6 groups namely, gel (20%), blank nanoparticle (0.16%), bulk quercetin (0.3%), quercetin nanoparticles (0.03%), quercetin nanoparticles (0.1%) and quercetin nanoparticles (0.3%) treated groups. Different formulations of quercetin nanoparticles were applied on the wounds for the duration of study and healing tissues were collected on 7th, 14th and 21st day to study various parameters. Quercetin loaded nanoparticles were 361.16 ± 9.72 nm size and spherical in shape. We observed quercetin nanoparticles (0.03%) treatment caused marked reduction in the tumor necrosis factor-alpha, whereas expressions of interleukin 10, vascular endothelial growth factor and transforming growth factor beta1 was increased significantly with treatment. The granulation tissue of quercetin nanoparticles (0.03%) treated group showed better quality healing and maturity as supported by the increased blood vessels density, decreased inflammatory cells, increased number of myofibroblasts, deposition and arrangement of collagen fibers and re-epithelialization. In conclusion, quercetin nanoparticles (0.03%) treatment significantly improved wound healing by modulation of cytokines and growth factors involved in inflammatory and proliferative phases of wound healing.

Constraints on Lorentz Invariance Violation from HAWC Observations of Gamma Rays above 100 TeV.

Because of the high energies and long distances to the sources, astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV). Superluminal LIV enables the decay of photons at high energy. The high altitude water Cherenkov (HAWC) observatory is among the most sensitive gamma-ray instruments currently operating above 10 TeV. HAWC finds evidence of 100 TeV photon emission from at least four astrophysical sources. These observations exclude, for the strongest of the limits set, the LIV energy scale to 2.2×10^{31} eV, over 1800 times the Planck energy and an improvement of 1 to 2 orders of magnitude over previous limits.

Multiple Galactic Sources with Emission Above 56 TeV Detected by HAWC.

We present the first catalog of gamma-ray sources emitting above 56 and 100 TeV with data from the High Altitude Water Cherenkov Observatory, a wide field-of-view observatory capable of detecting gamma rays up to a few hundred TeV. Nine sources are observed above 56 TeV, all of which are likely galactic in origin. Three sources continue emitting past 100 TeV, making this the highest-energy gamma-ray source catalog to date. We report the integral flux of each of these objects. We also report spectra for three highest-energy sources and discuss the possibility that they are PeVatrons.

Carriage of Class 1 integrons and molecular characterization of intI1 gene in multidrug-resistant Salmonella spp. isolates from broilers.

AIM: The present study was conducted with the following aims: (i) To screen the Salmonella spp. isolates recovered from suspected cases of fowl typhoid for carriage of Class 1 integrons and analyze their association with antimicrobial resistance and (ii) to carry out molecular characterization and phylogenetic analysis of Class 1 integron-integrase (intI1) gene. MATERIALS AND METHODS: A total of 43 Salmonella isolates were subjected to polymerase chain reaction (PCR) assay to determine the presence of Class1 intI1. Differences between different serotypes in relation to their carriage of integrons and the differences between strains containing or not containing an integron and being resistant to different antimicrobials were analyzed by Fisher exact test using STATA™ (StataCorp, College Station, TX). Phylogenetic analysis was carried out using MEGA6 software. RESULTS: Out of 43 isolates, 40 (93.02%) were found positive for Class 1 integrons. 35/40 (87.5%) intI1-positive isolates were multidrug resistance (MDR) (resistant to ≥4 antibiotics), which support the hypothesis of an association between the presence of Class 1 integrons and emerging MDR in Salmonella. There was no significant difference among isolates resistant to different antimicrobials in Class 1 integron carrying isolates and the Class 1 integron negative isolates (p<0.05). Further, there was no significant difference among different serotypes in respect of their carriage of Class 1 integrons. CONCLUSION: It can be concluded that the high prevalence of Class 1 integrons indicates a high potential of Salmonella isolates for horizontal transmission of antimicrobial genes, especially among Gram-negative organisms.

Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

Publisher Correction: Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

In this Letter, owing to a production error, the penultimate version of the PDF was published. The HTML version was always correct. The PDF has been corrected online.

Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star)1-3. Two jets of ionized matter with a bulk velocity of approximately 0.26c (where c is the speed of light in vacuum) extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets2,4-8. SS 433 differs from other microquasars (small-scale versions of quasars that are present within our own Galaxy) in that the accretion is believed to be super-Eddington9-11, and the luminosity of the system is about 1040 ergs per second2,9,12,13. The lobes of W50 in which the jets terminate, about 40 parsecs from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed14-16. At higher energies (greater than 100 gigaelectronvolts), the particle fluxes of γ-rays from X-ray hotspots around SS 433 have been reported as flux upper limits6,17-20. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons that are interacting with the ambient gas. Here we report teraelectronvolt γ-ray observations of the SS 433/W50 system that spatially resolve the lobes. The teraelectronvolt emission is localized to structures in the lobes, far from the centre of the system where the jets are formed. We have measured photon energies of at least 25 teraelectronvolts, and these are certainly not Doppler-boosted, because of the viewing geometry. We conclude that the emission-from radio to teraelectronvolt energies-is consistent with a single population of electrons with energies extending to at least hundreds of teraelectronvolts in a magnetic field of about 16 microgauss.

Chest wall resection and reconstruction for Rosai-Dorfman disease masquerading as a chest wall sarcoma.

Rosai-Dorfman disease (RDD) is a rare benign histiocytic proliferative disease that can present as a pseudotumour of soft tissue. We describe the first chest wall resection and reconstruction.

Th1/Th2 immune responses and oxidative stress in caprine flea allergy dermatitis.

Flea allergy dermatitis (FAD) is the common, often neglected skin disease of goats caused mainly by Ctenocephalides felis. This study aimed to evaluate the immuno-oxidative pathobiology of FAD in goats. Twelve goats from the same herd were divided into two groups of six animals each. The group I (FAD) included animals with natural flea infestation and severe dermatitis lesions. The group II (Healthy control) animals were free from any parasitic infestation. To assess the pathological changes, the markers of oxidative stress (lipid peroxidation, reduced glutathione and total antioxidant capacity), and immune status (Tumour necrosis factor alpha, Interleukin 10, Transforming growth factor beta 1 and Th1/Th2 cytokine ratio) were evaluated from the blood and the serum samples. Remarkable oxidative stress and severe inflammatory response with Th2 cytokine dominance were observed in flea infested animals. Highly antigenic agents of fleas, either secretory or excretory or structural, induced severe inflammatory responses and significant oxidative stress in caprine FAD. Massive release of cytokines may be responsible for severe skin inflammation and lesions in FAD in contrast to other Th2 dominant ectoparasitic skin conditions of goats'.

Molecular prevalence and haemato-biochemical profile of canine monocytic ehrlichiosis in dogs in and around Hisar, Haryana, India.

The present study was planned to investigate the molecular prevalence of canine monocytic ehrlichiosis (CME) in dogs in and around Hisar and to evaluate the haemato-biochemical profile for its better management. A total of 60 dogs presented to Medicine Section, TVCC, LUVAS, Hisar with the history of naturally acquired tick infestation and clinical signs consistent with CME were screened on the basis of blood smear examination, followed by molecular detection by nested PCR assay targeting a portion of 16S rRNA gene of Ehrlichia canis. Nested PCR detected 18 cases positive for E. canis with estimated 30% percent positivity as compared to 8.33% (5 out of 60) by blood smear examination. These 18 dogs confirmed for CME by nested PCR were assessed for clinical and haemato-biochemical profile. Breed-wise prevalence indicated maximum number of cases in Labrador retriever, followed by Pug, Rottweiler and German shepherd dog with more number of cases in male dogs. Age-wise prevalence revealed highest number of cases in more than 1 year age group, followed by 6 months to 1 year age group and least in less than 6 months aged dogs. Pyrexia, anorexia and pale to congested mucous membranes were the main clinical signs observed, followed by lethargy, vomiting. Less common clinical signs were epistaxis, lymphadenomegaly, hind limb weakness, malena, ocular discharge, followed by haematuria, corneal opacity, nasal discharge and coughing, icterus, dermal petechiae and ecchymoses. The haematological profile revealed macrocytic hypochromic anaemia, thrombocytopenia, normal leucocyte count with relative lymphocytosis, monocytosis and neutropenia. Serum biochemistry revealed significant rise in values of ALT, AST, GGT, bilirubin total, bilirubin indirect, alkaline phosphatase and A/G ratio in affected dogs as compared to healthy control, suggesting the hepatic dysfunction. The lipid metabolites and kidney function parameters were non-significantly altered from those of healthy control. A high positivity for E. canis detected by nested PCR in dogs in and around Hisar suggests the endemicity of the disease in dogs' population in this region and warrants the screening for the disease in suspected dogs by this technique as compared to routine blood smear examination. The presented haemato-biochemical profile may be useful in presumptive diagnosis of the disease in dogs and their better clinical management.

Spastin regulates VAMP7-containing vesicles trafficking in cortical neurons.

Alteration of axonal transport has emerged as a common precipitating factor in several neurodegenerative disorders including Human Spastic Paraplegia (HSP). Mutations of the SPAST (SPG4) gene coding for the spastin protein account for 40% of all autosomal dominant uncomplicated HSP. By cleaving microtubules, spastin regulates several cellular processes depending on microtubule dynamics including intracellular membrane trafficking. Axonal transport is fundamental for the viability of motor neurons which often have very long axons and thus require efficient communication between the cell body and its periphery. Here we found that the anterograde velocity of VAMP7 vesicles, but not that of VAMP2, two vesicular-SNARE proteins implicated in neuronal development, is enhanced in SPG4-KO neurons. We showed that this effect is associated with a slight increase of the level of acetylated tubulin in SPG4-KO neurons and correlates with an enhanced activity of kinesin-1 motors. Interestingly, we demonstrated that an artificial increase of acetylated tubulin by drugs reproduces the effect of Spastin KO on VAMP7 axonal dynamics but also increased its retrograde velocity. Finally, we investigated the effect of microtubule targeting agents which rescue axonal swellings, on VAMP7 and microtubule dynamics. Our results suggest that microtubule stabilizing agents, such as taxol, may prevent the morphological defects observed in SPG4-KO neurons not simply by restoring the altered anterograde transport to basal levels but rather by increasing the retrograde velocity of axonal cargoes.

Comparative analysis of midgut bacterial communities in three aedine mosquito species from dengue-endemic and non-endemic areas of Rajasthan, India.

Dengue viruses are transmitted to humans through the bites of infected female aedine mosquitoes. Differences in the composition and structure of bacterial communities in the midguts of mosquitoes may affect the vector's ability to transmit the disease. To investigate and analyse the role of midgut bacterial communities in viral transmission, midgut bacteria from three species, namely Stegomyia aegypti (= Aedes aegypti), Fredwardsius vittatus (= Aedes vittatus) and Stegomyia albopicta (= Aedes albopictus) (all: Diptera: Culicidae), from dengue-endemic and non-endemic areas of Rajasthan, India were compared. Construction and analyses of six 16S rRNA gene libraries indicated that Serratia spp.-related phylotypes dominated all clone libraries of the three mosquito species from areas in which dengue is not endemic. In dengue-endemic areas, phylotypes related to Aeromonas, Enhydrobacter spp. and uncultivated bacterium dominated the clone libraries of S. aegypti, F. vittatus and S. albopicta, respectively. Diversity indices analysis and real-time TaqMan polymerase chain reaction assays showed bacterial diversity and abundance in the midguts of S. aegypti to be higher than in the other two species. Significant differences observed among midgut bacterial communities of the three mosquito species from areas in which dengue is and is not endemic, respectively, may be related to the vectorial capacity of mosquitoes to carry dengue viruses and, hence, to the prevalence of disease in some areas.

Cost analysis of gentamicin-impregnated collagen sponges in preventing sternal wound infection post cardiac surgery.

OBJECTIVE: The use of antibiotic-impregnated sponges (Collatamp) during cardiac surgery is controversial. We analysed the cost-effectiveness of its selective use in patients at high-risk of sternal wound infection (SWI). METHOD: Postoperative costs were analysed in two groups of patients undergoing heart surgery between 2011 and 2013: those with SWI (group 1) and in high-risk patients without SWI (group 2). The potential cost of gentamicin-impregnated collagen sponges (GCS) use in high-risk patients was compared with our current practice. RESULTS: We identified 1,251 patients with at least one recognised risk factor for developing SWI in this period. Of these, 18 developed SWI (incidence 1.4%). The median postoperative cost per patient without SWI was £9,617. The additional cost per patient incurred by SWI was £4,860.75. The annual additional cost for treating patients with SWI was £43,749. With a 50% reduction in SWI, the annual additional cost of treating these patients would be reduced to £21,873. The cost of GCS is £80 per patient. Adding this to £21,873 gives a potential total cost of £71,913 in the treated high-risk cohort. CONCLUSION: In our practice the annual cost of treating SWI in high-risk patients without use of GCS is lower than the annual cost of using GCS in all high-risk patients (£43,749 versus £71,913) if it produces a 50% reduction in SWI. The reduction in the incidence of SWI poses no economic benefit when the cost of the product is factored in.