Over-expression of Topoisomerase II Enhances Salt Stress Tolerance in Tobacco

Topoisomerases are unique enzymes having an ability to remove or add DNA supercoils and untangle the snarled DNA. They can cut, shuffle and religate DNA strands and remove the torsional stress during DNA replication, transcription or recombination events. In the present study, we over-expressed topoisomerase II (TopoII) in tobacco (Nicotiana tabaccum) and examined its role in growth and development as well as salt (NaCl) stress tolerance. Several putative transgenic plants were generated and the transgene integration and expression was confirmed by PCR and Southern blot analyses, and RT-PCR analysis respectively. Percent seed germination, shoot growth and chlorophyll content revealed that transgenic lines over-expressing the NtTopoIIα-1 gene exhibited enhanced tolerance to salt (150 and 200 mM NaCl) stress. Moreover, over-expression of TopoII lead to the elevation in proline and glycine betaine levels in response to both concentrations of NaCl as compared to wild-type. In response to NaCl stress, TopoII over-expressing lines showed reduced lipid peroxidation derived malondialdehyde (MDA) generation. These results suggest that TopoII plays a pivotal role in salt stress tolerance in plants

Contemporary management of primary parapharyngeal space tumors

The parapharyngeal space is a complex anatomical area. Primary parapharyngeal tumors are rare tumors and 80% of them are benign. A variety of tumor types can develop in this location; most common are salivary gland neoplasm and neurogenic tumors. The management of these tumors has improved greatly owing to the developments in imaging techniques, surgery, and radiotherapy. Most tumors can be removed with a low rate of complications and recurrence. The transcervical approach is the most frequently used. In some cases, minimally invasive approaches may be used alone or in combination with a limited transcervical route, allowing large tumors to be removed by reducing morbidity of expanded approaches. An adequate knowledge of the anatomy and a careful surgical plan is essential to tailor management according to the patient and the tumor. The purpose of the present review was to update current aspects of knowledge related to this more challenging area of tumor occurrence.Peer reviewe

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Role of Trichoderma harzianum in mitigating NaCl stress in Indian mustard (Brassica juncea L) through antioxidative defense system

Salinity stress affected crop production of more than 20% of irrigated land globally. In the present study the effect of different concentrations of NaCl (0, 100, and 200 mM) on growth, physio-biochemical attributes, antioxidant enzymes, oil content, etc. in Brassica juncea and the protective role of Trichoderma harzianum (TH) was investigated. Salinity stress deteriorates growth, physio-biochemical attributes, that ultimately leads to decreased biomass yield in mustard seedlings. Higher concentration of NaCl (200 mM) decreased the plant height by 33.7%, root length by 29.7% and plant dry weight (DW) by 34.5%. On the other hand, supplementation of TH to NaCl treated mustard seedlings showed elevation by 13.8, 11.8, and 16.7% in shoot, root length and plant DW respectively as compared to plants treated with NaCl (200 mM) alone. Oil content was drastically affected by NaCl treatment; however, TH added plants showed enhanced oil percentage from 19.4 to 23.4% in the present study. NaCl also degenerate the pigment content and the maximum drop of 52.0% was recorded in Chl. ‘a’. Enhanced pigment content was observed by the application of TH to NaCl treated plants. Proline content showed increase by NaCl stress and maximum accumulation of 59.12% was recorded at 200 mM NaCl. Further enhancement to 70.37% in proline content was recorded by supplementation of TH. NaCl stress (200 mM) affirms the increase in H2O2 by 69.5% and MDA by 36.5%, but reduction in the accumulation is recorded by addition of TH to mustard seedlings. 200 mM NaCl elevated SOD, POD, APX, GR, GST, GPX, GSH, and GSSG in the present study. Further enhancement was observed by the application of TH to the NaCl fed seedlings. NaCl stress suppresses the uptake of important elements in both roots and shoots, however, addition of TH restored the elemental uptake in the present study. Mustard seedlings treated with NaCl and TH showed restricted Na uptake as compared to seedlings treated with NaCl alone. In conclusion, TH proved to be very beneficial in imparting resistance to the mustard plants against NaCl stress through improved uptake of essential elements, modulation of osmolytes and antioxidants

Translaryngeal ultrasound in thyroid surgery: state of the art review

BACKGROUND: Clinical voice assessment prior to thyroid and parathyroid surgery is essential, but the paradigm of indirect laryngoscopy (IDL), when indicated, has been challenged by the risk of aerosolised SARS-Cov-2 during endoscopy of the aerodigestive tract. Translaryngeal ultrasound (TLUS) to assess the vocal cords has been proposed as a safe, non-invasive and sensitive alternative. The aim of this review was to verify TLUS as a viable tool for perioperative laryngeal assessment. METHOD: A literature review was performed using Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials and Scopus with the following search strategy: (vocal cord OR vocal fold OR glottic OR glottis OR vocal ligaments OR rima glottidis) AND (ultras* OR sonograph* OR echography OR echotomography). RESULTS: Fifteen studies were included in this review. All studies compared TLUS to IDL in visualizing the vocal cords in adults. Ten studies compared pre-operative TLUS to IDL where 50.6-100% of vocal cords were successfully visualized. Nine studies compared post-operative TLUS to IDL and reported visualization between 39.6% and 100%. Pre- and post-operative negative predictive values ranged from 60% to 100%. CONCLUSION: Whilst promising, successful visualization of the cords is limited by inter-user variability, older age and male gender. Thus, we see the role of TLUS as an alternative to IDL in the post-operative setting in the young patient following uncomplicated surgery with a normal voice on clinical examination, to confirm recurrent laryngeal nerve integrity while minimizing the risk of aerosolization

Comprehensive energy, economic and thermal comfort assessments for the passive energy retrofit of historical buildings - A case study of a late nineteenth-century Victorian house renovation in the UK

This paper aims to evaluate the energy-saving potential, affordability and thermal comfort performance of various passive building retrofit measures for a historical building (late nineteenthcentury Victorian house) renovation. Three types of interior passive retrofit measures (i.e. internal wall insulation, glazing upgrade and airtightness improvement), classified as traditional and advanced measures, are further grouped into 63 retrofit combinations. In order to evaluate the performance of these defined retrofit combinations, five assessment indicators are proposed, including energy reduction rate, specific initial cost, discounted payback period, space volume reduction rate, and indoor thermal comfort. Under three internal space reduction scenarios with a space reduction rate of 5.2%, 2.6% and 1.3%, these combinations are evaluated and compared, and the most favourable combinations are determined to achieve multiple objectives (maximum energy saving, most cost-effective and most energy-efficient). The influence of the most favourable retrofit combinations on the internal thermal comfort level improvement is also dynamically evaluated using the EnergyPlus simulation tool. The final recommended passive retrofit combination consists of vacuum insulation windows, gypsum air infiltration reduction, and 2cm thickness of Polyisocyanurate (PIR) panels, with 51.8% of primary energy reduction, a specific initial investment of £144.71/m2 and a discounted payback period of 18 years