A nearby long gamma-ray burst from a merger of compact objects.

Gamma-ray bursts (GRBs) are flashes of high-energy radiation arising from energetic cosmic explosions. Bursts of long (greater than two seconds) duration are produced by the core-collapse of massive stars1, and those of short (less than two seconds) duration by the merger of compact objects, such as two neutron stars2. A third class of events with hybrid high-energy properties was identified3, but never conclusively linked to a stellar progenitor. The lack of bright supernovae rules out typical core-collapse explosions4-6, but their distance scales prevent sensitive searches for direct signatures of a progenitor system. Only tentative evidence for a kilonova has been presented7,8. Here we report observations of the exceptionally bright GRB 211211A, which classify it as a hybrid event and constrain its distance scale to only 346 megaparsecs. Our measurements indicate that its lower-energy (from ultraviolet to near-infrared) counterpart is powered by a luminous (approximately 1042 erg per second) kilonova possibly formed in the ejecta of a compact object merger.

Very-high-frequency oscillations in the main peak of a magnetar giant flare.

Magnetars are strongly magnetized, isolated neutron stars1-3 with magnetic fields up to around 1015 gauss, luminosities of approximately 1031-1036 ergs per second and rotation periods of about 0.3-12.0 s. Very energetic giant flares from galactic magnetars (peak luminosities of 1044-1047 ergs per second, lasting approximately 0.1 s) have been detected in hard X-rays and soft γ-rays4, and only one has been detected from outside our galaxy5. During such giant flares, quasi-periodic oscillations (QPOs) with low (less than 150 hertz) and high (greater than 500 hertz) frequencies have been observed6-9, but their statistical significance has been questioned10. High-frequency QPOs have been seen only during the tail phase of the flare9. Here we report the observation of two broad QPOs at approximately 2,132 hertz and 4,250 hertz in the main peak of a giant γ-ray flare11 in the direction of the NGC 253 galaxy12-17, disappearing after 3.5 milliseconds. The flare was detected on 15 April 2020 by the Atmosphere-Space Interactions Monitor instrument18,19 aboard the International Space Station, which was the only instrument that recorded the main burst phase (0.8-3.2 milliseconds) in the full energy range (50 × 103 to 40 × 106 electronvolts) without suffering from saturation effects such as deadtime and pile-up. Along with sudden spectral variations, these extremely high-frequency oscillations in the burst peak are a crucial component that will aid our understanding of magnetar giant flares.

Assessing the Relative Importance of Satellite-Detected Methane Superemitters in Quantifying Total Emissions for Oil and Gas Production Areas in Algeria.

Methane emissions from oil and gas production provide an important contribution to global warming. We investigate 2020 emissions from the largest gas field in Algeria, Hassi R'Mel, and the oil-production-dominated area Hassi Messaoud. We use methane data from the high-resolution (20 m) Sentinel-2 instruments to identify and estimate emission time series for 11 superemitters (including 10 unlit flares). We integrate this information in a transport model inversion that uses methane data from the coarser (7 km × 5.5 km) but higher-precision TROPOMI instrument to estimate emissions from both the 11 superemitters (>1 t/h individually) and the remaining diffuse area source (not detected as point sources with Sentinel-2). Compared to a bottom-up inventory for 2019 that is aligned with UNFCCC-reported emissions, we find that 2020 emissions in Hassi R'Mel (0.16 [0.11-0.22] Tg/yr) are lower by 53 [24-73]%, and emissions in Hassi Messaoud (0.22 [0.13-0.28] Tg/yr) are higher by 79 [4-188]%. Our analysis indicates that a larger fraction of Algeria's methane emissions (∼75%) come from oil production than national reporting suggests (5%). Although in both regions the diffuse area source constitutes the majority of emissions, relatively few satellite-detected superemitters provide a significant contribution (24 [12-40]% in Hassi R'Mel; 49 [27-71]% in Hassi Messaoud), indicating that mitigation efforts should address both. Our synergistic use of Sentinel-2 and TROPOMI can produce a unique and detailed emission characterization of oil and gas production areas.

Peripheral Tubercular Neuritis.

Peripheral neuropathy can affect sensory, motor, or autonomic nerves and manifest with a variety of symptoms. Tuberculosis as a major infectious disease that often affects many organs of the body. However, primary involvement of peripheral nerves is unusual. Peripheral neuropathy in patients with tuberculosis often is associated with other comorbidities, such as immunocompromised states, diabetes mellitus, malnutrition, and some antitubercular medications. This report describes the rare finding of peripheral tubercular neuritis with caseating abscesses of right median and radial nerve in a healthy 24-year man.

Comparison of Reverse Sural Artery Fasciocutaneous Flap in Soft Tissue Reconstruction Between above Ankle and Below Ankle Defect.

Background Fasciocutaneous reverse sural artery flap is a popular option to treat soft tissue defects in the distal leg, ankle, and foot region. Objective To compare the results of sural artery flap reconstruction between the above ankle and below ankle soft tissue defect. Method It was a retrospective study of sural flap reconstruction of varied etiology for the defect grouped as above ankle and below ankle operated over a period of five years. Flap and graft take-up, rate of primary healing, margin necrosis, and complications were the assessed outcome variables. Result There were a total of 37 patients, 17 cases of the above ankle and 20 cases of below ankle sural flap reconstruction analyzed in the study. Road traffic accident was the most common cause and the mean size of the defect was 40.70 cm2 . The overall flap take-up rate was 94.6%, partial margin necrosis was in 6 patients, and > 50% flap necrosis was in 2 cases. The rate of primary healing, margin necrosis and mean healing time were 17 (100%) vs 12 (60%), 0 vs 8 cases (6 margin necrosis and 2 cases of > 50% of flap necrosis), and 20.04 days vs 22.50 days respectively in the above ankle and below ankle flap reconstruction groups. These differences were statistically significant. Conclusion Fasciocutaneous reverse sural artery flap is an excellent choice for reconstruction of the defect at the distal leg and around the ankle region with a high success rate. Below ankle flap reconstruction showed a higher rate of margin necrosis, longer healing time, and less rate of primary healing as compared to the above ankle group.

Synthesis, radiolabeling, and pre-clinical evaluation of [44Sc]Sc-AAZTA conjugate PSMA inhibitor, a new tracer for high-efficiency imaging of prostate cancer.

PURPOSE: The aim of this work was to demonstrate the suitability of AAZTA conjugated to PSMA inhibitor (B28110) labeled with scandium-44 as a new PET tracer for diagnostic imaging of prostate cancer. BACKGROUND: Nowadays, scandium-44 has received significant attention as a potential radionuclide with favorable characteristics for PET applications. A polyaminopolycarboxylate heptadentate ligand based on a 1,4-diazepine scaffold (AAZTA) has been thoroughly studied as chelator for Gd3+ ions for MRI applications. The excellent results of the equilibrium, kinetic, and labeling studies led to a preliminary assessment of the in vitro and in vivo behavior of [44Sc][Sc-(AAZTA)]- and two derivatives, i.e., [44Sc][Sc (CNAAZTA-BSA)] and [44Sc][Sc (CNAAZTA-cRGDfK)]. RESULTS: B28110 was synthesized by hybrid approach, combining solid-phase peptide synthesis (SPPS) and solution chemistry to obtain high purity (97%) product with an overall yield of 9%. Subsequently, the radioactive labeling was performed with scandium-44 produced from natural calcium target in cyclotron, in good radiochemical yields (RCY) under mild condition (pH 4, 298 K). Stability study in human plasma showed good RCP% of [44Sc]Sc-B28110 up to 24 h (94.32%). In vivo PET/MRI imaging on LNCaP tumor-bearing mice showed high tracer accumulation in the tumor regions as early as 20 min post-injection. Ex vivo biodistribution studies confirmed that the accumulation of 44Sc-PSMA-617 was two-fold lower than that of the radiolabeled B28110 probes. CONCLUSIONS: This work demonstrated the suitability of B28110 for the complexation with scandium-44 at room temperature and the high performance of the resulting new tracer based on AAZTA chelator for the diagnosis of prostate cancer using PET.

Oncological outcomes and stoma-free survival following TaTME, a prospective cohort study.

BACKGROUND: Transanal TME (TaTME) was introduced to improve access to the pelvis in difficult cases (male sex, obesity and mid to low rectal cancers) and reduce the risk of anastomotic leak by avoiding cross stapling. In April 2018 the Norwegian hospital to whom all local; recurrences for rectal cancer are referred reported an unexpected rise in early multifocal local recurrences of 9.5% following TaTME compared with 3.4% following conventional TME leading to a nationwide moratorium on the procedure and ending, in an editorial published on the British Journal of Surgery in August 2020, by saying that other countries should consider the issue in the context of local practices and results. There are limited data concerning oncological outcomes of TaTME compared to conventional TME. The aim of this study was to report perioperative and oncological outcomes for patients with rectal cancer treated with TaTME in a high-volume, experienced UK centre. METHODS: From January 2015 to January 2020 consecutive patients with histologically confirmed rectal cancer having TaTME at Worcestershire Royal Hospital NHS were prospectively entered into an online international registry. Patients were followed according to local protocol with clinical examination, tumour markers, endoscopy and radiology. RESULTS: Seventy patients underwent TaTME for rectal cancer. The median distance of the tumour from the anorectal junction was 4 cm (IQR 2-5). The mesorectal margin was involved in 20 (1%) patients, all of whom received neoadjuvant chemoradiotherapy. Overall survival was 94% at a median follow-up of 15 months (IQR 9-31 months). Distant recurrence occurred in 12 (17%) of patients at a median of 14 months (IQR 10-17 months). The 18-month stoma-free survival rate was 66%. CONCLUSIONS: A local recurrence rate of 5.7% supports the oncological safety of TaTME for rectal cancer.

Endophytes enhance the production of root alkaloids ajmalicine and serpentine by modulating the terpenoid indole alkaloid pathway in Catharanthus roseus roots.

AIM: The aim of this study was to identify and characterize promising endophytes capable of enhancing the content of root alkaloids ajmalicine and serpentine in low alkaloid yielding genotype of Catharanthus roseus cultivar Prabal and the possible mechanisms involved. METHOD AND RESULT: Of the four strains isolated from alkaloid-rich genotype of C. roseus cultivar Dhawal, endophytic strains CATDLF5 (Curvularia sp.) and CATDLF6 (Choanephora infundibulifera) enhanced serpentine content by 211·7-337·6%, while CATDRF2 (Aspergillus japonicus) and CATDS5 (Pseudomonas sp.) increased the content of ajmalicine by 123·4-203·8% in cultivar Prabal. Upregulated expression of key genes, geraniol 10-hydroxylase, tryptophan decarboxylase and strictosidine synthase involved in terpenoid indole alkaloid (TIA) biosynthetic pathway was observed in endophyte inoculated plants. Upregulated Octadecanoid-derivative Responsive Catharanthus AP2/ERF domain transcription activators like ORCA3 while, and downregulation of transcriptional repressor, ZCTs (Cys2/His2-type zinc finger protein family) enhanced the expression of genes for secondary metabolite production in endophyte-inoculated plants. CONCLUSION: The present work concluded that the selected endophytes of C. roseus can enhance the ajmalicine and serpentine contents by modulating the expression of structural and regulatory genes of TIA biosynthetic pathway in root. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytes can play an important role to enhance in planta content of pharmaceutically important alkaloids in C. roseus and can therefore be useful in reducing the cost of production of important alkaloids.

Prescription Pattern Monitoring and Off-label Use of Medicines in the Pediatric Department at Tertiary Care Teaching Hospital.

Background Off-label use means the use, concerning dosage, indication, route of administration, or age, of pharmaceutical products which are beyond the terms of the product license. For regulatory bodies and physicians, the global challenge is to achieve optimum pediatric drug therapy. Objective This prospective observational work was carried out in the paediatric department to evaluate the prescribing pattern of medicines and to identify the use of off-label drugs. Method A cross-sectional study was carried in 200 paediatric patients of ages between 0 and 12 years at the paediatric outpatient department of Universal College of Medical Sciences, Bhairahawa. Data were collected by reviewing the prescription paper and the required information was recorded using a structured data collection sheet prepared for study. The prescribing pattern was assessed by using the World Health Organization (WHO) Prescription Indicators and off-label use was assessed using the WHO Children Formulary 2010. Result Among 413 total prescriptions, only 5.56% of drugs were found to be prescribed by generic name, 16.7% of prescriptions were found to be antibiotic and 57.62% of prescribed drugs were from essential drug list. Out of 413 prescribed drugs, 16.46% of drugs were found to be off-label. The maximum extent of off-label prescribing was 51.47% in the child, followed by infants (42.6%) and neonates (5.8%). Fexofenadine; antihistaminic (23.56%), Amoxicillin+clavulanic acid; antibiotic (22.06%) had higher off-label use. Off-label dose (71.8%) was the most common cause of off-label prescribing. Conclusion Off-label prescribing among pediatric patients is common.More eminence data on the safety and efficacy of off-label medicines must be generated to rationalize paediatric pharmacotherapy.

Role of HAMP Genetic Variants on Pathophysiology of Iron Deficiency Anemia.

Hepcidin is a 25-amino acid peptide hormone produced by hepatocytes and plays a key role in body iron metabolism. Hepcidin deficiency is the cause of iron overload in hereditary hemochromatosis, iron-loading anemia, and its excess is associated with anemia of inflammation, chronic disease and iron deficiency anemia (IDA). The aims of this study was to evaluate HAMP gene mutation, namely IVS2 + 1(-G) (c.148-150 + 1del) and Gly71 Asp (c.212G > A (rs104894696) association with iron status in IDA conditions. Our study participants were 500 IDA patients and 550 age and sex-matched healthy controls. Hepcidin, ferritin and CRP analysis was done by ELISA method while ESR analysis was done according to Wintrobe method. CBC analysis was done by auto-analyzer. Two mutations in the HAMP genes were analysed by PCR RFLP method. Among the IDA patients, 7 were heterozygous for Met50del IVS2 + 1(-G) mutation. Nine IDA patients were heterozygous for G71D G-A mutation and homozygous were not identified in both mutations.Controls were showing heterozygous frequency 1.8 and 2.1% of Met50del IVS2 + 1(-G) and G71D G-A mutations respectively. Mutation of HAMP (Met50del IVS2 + 1(-G) and G71D G-A) were clinically associated with IDA and act as modulator of disease.

ACC deaminase-containing plant growth-promoting rhizobacteria protect Papaver somniferum from downy mildew.

AIMS: The aim of this study was to determine whether ACC (1-aminocyclopropane-1-carboxylic acid) deaminase-containing bacterial treatments could enhance the tolerance of poppy (Papaver somniferum L.) plants against biotic stress of downy mildew caused by Peronospora sp. METHODS AND RESULTS: Three different genotypes of P. somniferum, that is, Sampada, J-16 and I-14 were included in the experiment. The ACC deaminase-containing bacteria Pseudomonas putida (WPTe) reduced the downy mildew disease severity and significantly improved the growth and yield of P. somniferum plants. The chlorophyll content, photosynthetic rate, stomatal conductance and transpiration rate were modulated upon WPTe treatments in the poppy plants. We observed reduced synthesis of ethylene precursor (ACC) and abscisic acid (ABA), and enhanced production of indole acetic acid (IAA) in P. somniferum plants upon WPTe treatments. Moreover, WPTe treatment reduced proline and lipid peroxidation in plant leaves. CONCLUSION: These results highlight that the ACC deaminase-containing plant growth-promoting rhizobacteria (PGPR) enhance the tolerance of P. somniferum plant against downy mildew. SIGNIFICANCE AND IMPACT OF THE STUDY: ACC deaminase-containing PGPR may be used against phytopathogens which apart from protecting the plants from the disease could also be useful in reducing ethylene-induced damages in the event of abiotic stresses.

Prevalence of Factor V Leiden-G1691A and MTHFR-C677T Thrombosis Gene Modifier in Iron Deficiency Anemia: A Pathophysiological Effect in Indian Isolates.

Normal iron levels are required to prevent thrombocytosis by inhibiting thrombopoiesis. Thrombocytosis is usually associated with a mild iron deficiency and is the result of a lack of inhibition of thrombopoiesis. Study participants were 430 iron deficiency anemia (IDA) patients. Ten (10) mL of venous blood were collected for the subjects. Ferritin analysis was done by ELISA method while Hemogram analysis was done by auto-analyzer. Factor V Leiden, PRTG20210A, and MTHFR C677T genotype analysis was performed by PCR-RFLP method. Among the patients, 9 were heterozygous (G>A) and 2 were homozygous (A>A) carrier of FV Leiden; while 20 were heterozygous (C>T) and 3 were homozygous (T>T) for MTHFR polymorphism. None of the patient was identified with PT mutation. Patients with thrombosis gene marker had lower hemoglobin, mean corpuscular volume, mean corpuscular haemoglobin levels, and mean corpuscular hemoglobin concentration than patients without thrombosis gene marker. Serum ferritin was elevated in subject with the absence of thrombosis gene markers. Our data suggest a high impact of inherited hypercoagulability risk factors in the pathogenesis of IDA and its complications.

Restless legs syndrome and pregnancy: prevalence, possible pathophysiological mechanisms and treatment.

Restless legs syndrome (RLS) is a common sleep disorder that may be associated with pregnancy. Studies have found that the prevalence of RLS among pregnant women ranged from 10 to 34%. Typically, there is complete remission of symptoms soon after parturition; however, in some patients, they may continue postpartum. RLS has been shown to be associated with a number of complications in pregnancy including preeclampsia and increased incidence of Cesarean sections. Although multiple hypotheses have been proposed to explain this association, each individual hypothesis cannot completely explain the whole pathogenesis. Present understanding suggests that a strong family history, low serum iron and ferritin level, and high estrogen level during pregnancy might play important roles. Vitamin D deficiency and calcium metabolism may also play a role. Medical treatment of RLS during pregnancy is difficult and challenging considering the risks to mother and fetus. However, in some cases, the disease may be severe enough to require treatment.

Using CRP to predict anastomotic leakage after open and laparoscopic colorectal surgery: is there a difference?

AIM: C-reactive protein (CRP) has proven to be a useful adjunct in early diagnosis of anastomotic leak (AL) after colorectal surgery. It would be of considerable value to examine whether modality of surgery has influence upon postoperative CRP serum levels and their predictive value in the diagnosis of AL. METHODS: All patients undergoing elective colorectal surgery with anastomosis were enrolled into a prospective database between 2011 and 2014. AL was defined with strict operative and radiological criteria. Outcomes between open and laparoscopic resections were assessed statistically and Receiver Operating Characteristic (ROC) curve analysis performed. RESULTS: Seven hundred twenty-seven patients with an intestinal anastomosis were identified including 468 laparoscopic procedures (468/727; 64 %). There were 58 anastomotic leaks (58/727; 7.9 %) of which 29 (6.2 %) were laparoscopic and 29 (11.2 %) were open. Mean CRP levels were significantly higher in patients after open surgery compared with laparoscopic both with AL (p = 0.013), and without (p = 0.02). ROC curve analysis revealed postoperative day 3 (cut-off CRP 209) and day 4 (cut-off CRP 123.5) to be most predictive of leak in the open group with an area under the curve (AUC) 0.794 (sensitivity 80 %, specificity 80 %) and AUC 0.806 (sensitivity 94 %, specificity 60 %), respectively. In the laparoscopic group, day 2 proved to be the most accurate day for detection of leak with a cut-off CRP of 146.5 showing 75 % sensitivity and a 70 % specificity (AUC 0.766). CONCLUSION: CRP levels are higher after open surgery compared with laparoscopic surgery, both with and without AL. AL generates a significant detectable increase in CRP within 2-4 days after surgery.

In human alleles specific variation of MTHFR C677T and A1298C associated "risk factor" for the development of ovarian cancer.

Etiopathology of tumor biology is highly complex and ovarian cancer is one of the important gynaecological neoplasia associated with high risk of mortality rate. Methlenetetrahydrofolate reductase (MTHFR) mutation are commonly linked to folate metabolism with increased risk factor for the development of neural tube defects, recurrent pregnancy loss and development of several type of cancer but genetic interaction between two alleles of MTHFR has been poorly defined in ovarian cancer in India. Hence, present study becomes imperative with the aim to assess the alleles frequency of MTHFR (C677T & A1298C) gene polymorphism using PCR based RFLP analysis. The O.R at 95% confidence interval (C.I.) was computed between cases and their respective controls to determine "risk factor". Interestingly, our findings reveals highly significant (p < 0.001) difference in heterozygous (CT) condition of C677T allele by computing odd ratio (0.12 at 95% C.I, 0.021-0.0428; P for trend = 0.001) in controls and (0.34 at 95% C.I, 0.074-1.530; P for trend = 0.198) cases, suggesting that three time increase the "risk factor" for genetic susceptibility of MTHFR "T" allele for the development of ovarian carcinoma.

Entomological and serological investigation of Japanese encephalitis in endemic area of eastern Uttar Pradesh, India.

BACKGROUND & OBJECTIVES: Japanese encephalitis virus (JEV), a mosquito borne pathogen, is one of the major causes of viral encephalitis in eastern Uttar Pradesh, India. The objective of this work was to evaluate the entomological based virological surveillance of Japanese encephalitis (JE) in the highly endemic area of eastern Uttar Pradesh. METHODS: The study was carried out during September 2010 to March 2013 in Gorakhpur district of Uttar Pradesh. A total of 251 adult mosquito pools and 64 water samples containing larvae were collected from the District of Gorakhpur. Water pH, turbidity, and oxygen level were analyzed for vector breeding index (BI). In addition, 393 serum/cerebrospinal fluid (CSF) samples of acute encephalitis syndrome (AES) suspected cases were collected from the district hospital. RESULTS: The various Culex species found included, Cx. quinquefasciatus (26.83%), Cx. vishnui (22.29%), Cx. pseudovishnui (20.73%), Cx. tritaeniorhynchus (12.71%), Cx. whitmorei (9.04%), and Cx. gelidus (8.25%). Highest minimum infection rate (MIR) was calculated for Cx. tritaeniorhynchus (2.32), followed by Cx. vishnui (1.98) and Cx. pseudovishnui (0.71). All the larvae samples were negative for JEV. The mean number larvae of Cx. tritaeniorhynchus and Cx. pseudovishnui was negatively correlated with pH (r = - 0.45 and r = - 0.63) and turbidity (r = - 0.30 and r = - 0.37). In contrast, positive correlation was observed in case of Cx. quinquefasciatus. A total of 41 clinical samples were found positive for JEV by IgM ELISA. The rainfall was significantly associated with Japanese encephalitis incidence and showed positive correlation to disease transmission (p = 0.02, r = 0. 66). INTERPRETATION & CONCLUSION: The findings showed the rapid dissemination of JEV within a population, facilitated by different species of Culex in the region. As JE is a vaccine-preventable disease, an immunization programme, an effective vector control strategy and application of standard hygiene practices in these endemic areas could result in a considerable reduction in morbidity and mortality due to JE.

Toll-like receptors and CD40 modulate each other's expression affecting Leishmania major infection.

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and results in innate immune system activation that results in elicitation of the adaptive immune response. One crucial modulator of the adaptive immune response is CD40. However, whether these molecules influence each other's expression and functions is not known. Therefore, we examined the effects of TLRs on CD40 expression on macrophages, the host cell for the protozoan parasite Leishmania major. While polyinosinic-polycytidylic acid [poly (I:C)], a TLR-3 ligand, lipopolysaccharide (LPS), a TLR-4 ligand, imiquimod, a TLR-7/8 ligand and cytosine-phosphate-guanosine (CpG), a TLR-9 ligand, were shown to enhance CD40 expression, CD40 stimulation enhanced only TLR-9 expression. Therefore, we tested the synergism between CD40 and CpG in anti-leishmanial immune response. In Leishmania-infected macrophages, CpG was found to reduce CD40-induced extracellular stress-regulated kinase (ERK)1/2 activation; with the exception of interleukin (IL)-10, these ligands had differential effects on CD40-induced IL-1α, IL-6 and IL-12 production. CpG significantly enhanced the anti-leishmanial function of CD40 with differential effects on IL-4, IL-10 and interferon (IFN)-γ production in susceptible BALB/c mice. Thus, we report the first systematic study on CD40-TLR cross-talk that regulated the experimental L. major infection.