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Two yellow-pigmented, Gram-stain-negative, aerobic, rod-shaped bacteria were isolated from the water of the hypersaline Chaka Salt Lake (strain SaA2.12T) and sediment of Qinghai Lake (strain LaA7.5T), PR China. According to the 16S rRNA phylogeny, the isolates belong to the genus Flavobacterium , showing the highest 16S rRNA sequence similarities to Flavobacterium arcticum SM1502T(97.6–97.7 %) and Flavobacterium suzhouense XIN-1T(96.5–96.6 %). Moreover, strains SaA2.12T and LaA7.5T showed 99.73 % 16S rRNA sequence similarity to each other. Major fatty acids, respiratory quinones and polar lipids detected in these isolates were iso-C15 : 0, menaquinone-6 and phosphatidylethanolamine, respectively. Strains SaA2.12T and LaA7.5T showed significant unique characteristics between them as well as between the closest phylogenetic members. The highest digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) values between SaA2.12T and its closest neighbours were 25.3 and 82.8 %, respectively; whereas these values (highest) between LaA7.5T and its closest members were 25.2 and 82.8 %, respectively. The dDDH and ANI values between strains SaA2.12T and LaA7.5T were calculated as 75.9 and 97.2 %, respectively. Therefore, based on polyphasic data, we propose that strain SaA2.12T represents a novel species with the name Flavobacterium salilacus sp. nov., with the type strain SaA2.12T (=KCTC 72220T=MCCC 1K03618T) and strain LaA7.5T as a subspecies within novel Flavobacterium salilacus with the name Flavobacterium salilacus subsp. altitudinum subsp. nov., with the type strain LaA7.5T (=KCTC 72806T=MCCC 1K04372T). These propositions automatically create Flavobacterium salilacus subsp. salilacus subsp. nov. with SaA2.12T (=KCTC 72220T=MCCC 1K03618T) as the type strain.

Tourism is a major economic and social activity of the present time. It is the temporary movement of people from their normal place of residence or work, mainly for pleasure. Due to the economic activities involved in the process of tourism, now it is emerged as an industry which is rapidly growing around the World. Tourism is the major source of foreign exchange earnings for many regions of the world. Tourism need to be addressed at the earliest as tourism has positive as well as negative impact on the cultural diversity, social standards, society and environment. The present study aimed to investigate the causal relationship between employment and income generation and tourist arrivals in district Srinagar of Jammu and Kashmir state. The results revealed that tourist arrivals accounts variation in the level of income and employment generation. Thus, tourism development has the potential to contribute to the economy of Srinagar district of Jammu and Kashmir State. Tourism is a major economic and social activity of the present time. It is the temporary movement of people from their normal place of residence or work, mainly for pleasure. Due to the economic activities involved in the process of tourism, now it is emerged as an industry which is rapidly growing around the World. Tourism is the major source of foreign exchange earnings for many regions of the world. Tourism need to be addressed at the earliest as tourism has positive as well as negative impact on the cultural diversity, social standards, society and environment. The present study aimed to investigate the causal relationship between employment and income generation and tourist arrivals in district Srinagar of Jammu and Kashmir state. The results revealed that tourist arrivals accounts variation in the level of income and employment generation. Thus, tourism development has the potential to contribute to the economy of Srinagar district of Jammu and Kashmir State.

The present study examined the impact of tourist arrivals on revenue generation. The results revealed that tourist arrivals accounts 51 per cent variation in revenue generation. Jammu and Kashmir State has a tremendous potential to become a major global tourist destination. Importance of tourism in J&K economy is known for decades now and its role in economic development has been an area of great interest from policy perspective. The tourism is being the key contributor in the economic development of J&K state. To understand the economic impact of tourism in the J&K state, present paper uses secondary sources of data and tries to examine the economic development such as tourist inflow, revenue generation.

BackgroundGraves' disease is routinely treated with antithyroid drugs, radioiodine, or surgery, but whether the choice of initial therapy influences long-term outcomes is uncertain. We evaluated cardiovascular morbidity and mortality according to the method and effectiveness of primary therapy in Graves' disease.MethodsIn this retrospective cohort study, we identified patients with hyperthyroidism, diagnosed between Jan 1, 1998, and Dec 31, 2013, from a thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) test register in south Wales, UK, and imported their clinical data into the All-Wales Secure Anonymised Information Linkage (SAIL) Databank (Swansea University, Swansea, UK). Patients with Graves' disease, defined by positive TRAb tests, were selected for the study, and their clinical data were linked with outcomes in SAIL. We had no exclusion criteria. Patients were matched by age and sex to a control population (1:4) in the SAIL database. Patients were grouped by treatment within 1 year of diagnosis into the antithyroid drug group, radioiodine with resolved hyperthyroidism group (radioiodine group A), or radioiodine with unresolved hyperthyroidism group (radioiodine group B). We used landmark Kaplan-Meier and Cox regression models to analyse the association of treatment with the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiovascular events (myocardial infarction, heart failure, ischaemic stroke, or death) with the landmark set at 1 year after diagnosis. We analysed the association between outcomes and concentration of TSH using Cox regression and outcomes and free thyroxine (FT4) concentration using restricted cubic-spline regression models.FindingsWe extracted patient-level data on 4189 patients (3414 [81·5%] females and 775 [18·5%] males) with Graves' disease and 16 756 controls (13 656 [81·5%] females and 3100 [18·5%] males). In landmark analyses, 3587 patients were in the antithyroid drug group, 250 were in radioiodine group A, 182 were in radioiodine group B. Patients had increased all-cause mortality compared with controls (hazard ratio [HR] 1·22, 95% CI 1·05–1·42). Compared with patients in the antithyroid drug group, mortality was lower among those in radioiodine group A (HR 0·50, 95% CI 0·29–0·85), but not for those in radioiodine group B (HR 1·51, 95% CI 0·96–2·37). Persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR 1·55, 95% CI 1·08–2·24). Spline regressions showed a positive non-linear relationship between FT4 concentrations at 1 year and all-cause mortality.InterpretationRegardless of the method of treatment, early and effective control of hyperthyroidism among patients with Graves' disease is associated with improved survival compared with less effective control. Rapid and sustained control of hyperthyroidism should be prioritised in the management of Graves' disease and early definitive treatment with radioiodine should be offered to patients who are unlikely to achieve remission with antithyroid drugs alone.FundingNational Institute for Social Care and Health Research, Wales.

Protein structure prediction is very important to gaining insights for diseases diagnostics, medical treatment, and human biology. Here, we present a technique to predict the protein structure from its amino acid composition (AAC) using the hybrid kernel support vector machine. First and foremost, data preprocessing is done to reduce the irrelevant and noisy data. Then, a multiple class feature selection is used to reduce data dimensionality. Then, to improve the accuracy of support vector machine classifier, a hybrid kernel function is generated by combining the radial basis function (RBF) and polynomial kernel. Lastly, training the hybrid kernel support vector machine using the preprocessed training dataset. We used 25PDB dataset, where the sequence similarity is below 40%. From the result analysis, it is evident that for high dimensional datasets, the proposed method performs best with respect to accuracy. Moreover, our proposed method outperforms many of the existing methods.

Saudi Arabia is experiencing depleting water level which ultimately leading to having reduced level of weed and crops farms. The ongoing practice of watering for all kind of weeds at farms is manual which is laborious and slow besides waste of unregulated use of water. Therefore, there arises the need of automated water control, making the automated watering system as the viable option for precision weed control system. This paper has presented the development of real-time automated water sprinkle system for the target weeding area. The technique of wavelet frequency is developed as a software interface using MATLAB program detecting need of water sprinkling from the pictures of the leaves obtained. Software-based results are applied to hardware for real-time grass detection and classification based on shape and density due to reason that the leaves may be wide open, shrunk and leaves those with curved in features. The real-time system is capable of thus deciding the proportionate amount of water needed to be sprinkled over the weeds using a purposely developed hardware system. The system can detect areas where more, more or less water is needed, through a high-accuracy connected camera.

This paper intends to know the influence of COVID‐19 on the stock markets and economic activities across the world. To achieve the purpose, daily panel data of 12 selective countries covering four continents from January to April 2020 have been collected. The impact on stock markets has been measured by applying the event study method, while the panel vector autoregressive model has been applied to measure the impact on economic activities. The stock index of each country, purchasing managers’ index, COVID‐19 variables, namely the number of lockdown days, restriction in internal movement, restriction in international travel, fiscal measure, and confirmed cases have been used. The study observes the serious negative impact of the pandemic on stock market returns. European stock markets are the worst sufferer compared to others. All pandemic variables have a negative impact on stock markets; moreover, lockdown days and restriction on movement have a negative impact on economic activities. This study considers such countries which significantly represent the world economy and are a serious victim of COVID‐19 pandemic. The outcome‐based recommendations will help governments, regulatory authority, and policymakers to combat the crisis in different dimensions.

The ability of probiotic bacteria to colonise the target site is considered of utmost importance and used for preliminary screening of potential probiotic candidates. Thirty-eight vaginal Lactobacillus strains isolated from healthy women and characterised by 16S RNA sequencing were assessed for colonisation characteristics including adherence to human vaginal epithelial cells, auto-aggregation and hydrophobicity. No significant difference in adherence (P = 0.384), auto-aggregation (P = 0.282) and hydrophobicity (P = 0.084) abilities between Lactobacillus species was observed, however, significant difference in colonisation characteristics between strains of the same species was noted (P < 0.001). We identified seven Lactobacillus strains that may serve as best candidates for vaginal probiotic development.

Fungi are a prospective resource of bioactive compounds, but conventional methods of drug discovery are not effective enough to fully explore their metabolic potential. This study aimed to develop an easily attainable method to elicit the metabolic potential of fungi using Aspergillus nidulans laeA as a transcription regulation tool. In this study, functional analysis of Aspergillus nidulans laeA (AnLaeA) and Aspergillus sp. Z5 laeA (Az5LaeA) was done in the fungus Aspergillus sp. Z5. Heterologous AnLaeA-and native Az5LaeA-overexpression exhibited similar phenotypic effects and caused an increase in production of a bioactive compound diorcinol in Aspergillus sp. Z5, which proved the conserved function of this global regulator. In particular, heteroexpression of AnLaeA showed a significant impact on the expression of velvet complex genes, diorcinol synthesis-related genes, and different transcription factors (TFs). Moreover, heteroexpression of AnLaeA influenced the whole genome gene expression of Aspergillus sp. Z5 and triggered the upregulation of many genes. Overall, these findings suggest that heteroexpression of AnLaeA in fungi serves as a simple and easy method to explore their metabolic potential. In relation to this, AnLaeA was overexpressed in the fungus Penicillium sp. LC1-4, which resulted in increased production of quinolactacin A.

A novel bacterium designated SSM4.2T was isolated from seaweed of Gouqi Island, which is the center of the Zhoushan fishing ground in the East China Sea. Strain SSM4.2T was Gram-stain-negative, bright yellow-pigmented, short rod-shaped, non-flagellated, non-spore forming, aerobic and motile by gliding. Growth was observed at 4–37 °C (optimum 25–30 °C), pH 6.0–8.0 (optimum pH 7.0) and 0–2.0% (w/v) NaCl (optimum 0%) concentration. The strain was catalase- and oxidase-positive. Menaquinone-6 (MK-6) was found as the sole respiratory quinone and zeaxanthin as the main carotenoid pigment. The predominant fatty acids (≥ 10%) were iso-C15:0, iso-C15:1 G, iso-C17:0 3-OH and summed feature 3 (C16:1 ω7c /C16:1 ω6c). The major polar lipid was phosphatidylethanolamine (PE). The genome size was 5.7 Mbp. The DNA G + C content was 34.1 mol%. 16S rRNA gene sequence revealed that strain SSM4.2T belongs to the genus Flavobacterium and shares high-sequence similarity with F. limi KACC 18851T (98.1%), F. hydrophilum KACC 19591T (97.6%), F. defluvii KCTC 12612T (97.1%), F. cheongpyeongense KACC 19592T (97.0%) and F. fluviatile KCTC 52446T (96.9%). Strain SSM4.2T had 73.2–84.6% average nucleotide identity and 19.1–29.4% digital DNA-DNA hybridization values with its closest type strains. Based on its phenotypic, chemotaxonomic, phylogenetic and genomic features, strain SSM4.2T represents a novel species of the genus Flavobacterium, for which the name Flavobacterium ajazii sp. nov. is proposed. The type strain is SSM4.2T (= KCTC 72807T = MCCC 1K04370T).

OBJECTIVE The activation of effector immune cells at the cervicovaginal mucosa (CVM) might influence the cervical HIV load and thus the secondary transmission; however, limited information is available about the innate effector cells at CVM during HIV infection. In this study, we quantified and assessed the activation of the effector immune cells at the CVM of HIV-infected women with different disease outcomes: nonprogressive HIV disease (LTNPs) and chronic HIV-infected (CHI) and their relationship with cervical viral shedding. METHOD The phenotype and frequency of cytobrush-derived effector immune cells like natural killer cells, T cells, and dendritic cells and their degranulation status (CD107a expression as a surrogate marker of activation) was determined using flow cytometry in age-matched HIV- infected and uninfected women and their association with cervical HIV load was determined. RESULT The frequencies of dendritic cells, CD56, CD56 natural killer cell subsets were similar in both the study groups and also within the HIV-infected women with and without progressive disease. The frequencies of CD56CD16 natural killer cells (P = 0.04) and degranulating CD56 natural killer cells were significantly higher among HIV-infected women (P

Analyzing the situation in Dhaka, Bangladesh before the national election of 2014, this paper explores the consequences of political hostility on street-connected children using qualitative methods...

The antithyroid drugs, Carbimazole, Methimazole, and Propylthiouracil remain the mainstay of Graves' disease management in pregnancy. A series of Clinical Practice Guidelines aimed at optimising fetal and maternal outcomes in women with Graves' disease have been published in recent years. Areas covered: This review examines existing guideline recommendations on antithyroid drug management of Graves' disease in pregnancy. Expert commentary: Recent guidelines have been shaped by expanding knowledge of the adverse effect profiles of antithyroid drugs on the developing fetus. A core management strategy is to limit fetal exposure to excess thyroid hormones and to curtail adverse drug effects through effective preconception and peri-conception management. Propylthiouracil is the recommended treatment in the first trimester of pregnancy but there is uncertainty regarding antithyroid drug choices in women who continue to require treatment in later pregnancy. Further studies are needed to fully evaluate the risks of congenital anomalies following intrauterine thionamide exposure.

Camellia sinensis is being used for decades for its therapeutic efficacies against physiological problems and microbial infections. This study was undertaken to investigate the antibacterial and antifungal potential of aqueous extract of Camellia sinensis. Antibacterial activity was determined by disc and well diffusion assay. MIC and MBC were calculated by broth dilution method. Miles and Misra technique was used to find out colony forming unit per/ml. All the test organisms revealed a diverse range of vulnerability against aqueous extract. Among Gram positive, MRSA showed to be the most sensitive with least MIC and MBC while among Gram-negative Pseudomonas aeruginosa exhibited the highest sensitivity. In Miles and Misra, a progressive decline in log of CFU/ml was observed. In time-kill assay, a decline was noted in the viable count of S.aureus after exposure to 18% aqueous extract of Camellia sinensis. In the present study aqueous extract of Camellia sinensis found to be effective against Gram positive, Gram negative and fungi. The most important finding of this study is its aqueous extract inhibitory effect against drug-resistant microorganisms e.g. MRSA and P. aeruginosa and Candida albicans.

Introduction: Pyrexia of unknown origin (PUO) is often a diagnostic challenge. Common causes currently reported include non-infectious inflammatory disorders (NIID) (30.6%), infections (23.1%), malignancy (10.7%) and miscellaneous (12.4%). However, 23.1% remain undiagnosed despite extensive investigations. Fever is a component of subacute thyroiditis (SAT) in 28-83% of subjects reported in the literature. But its presentation as a PUO is reported only in a handful of subjects. Case Presentation: A 71-year-old Asian male presented with evening fevers of 2-3 weeks duration. He had no accompanying sweats, cough, breathlessness, or weight loss. He had a past history of TB, polio, hydatid cyst and hypertension for which he was on treatment. He was a teetotaler. Several family members living in his native land had active TB and he visited them often. Clinical examination at initial presentation was unremarkable. He interrupted investigations to go back to Asia, and became unwell for over 6 weeks with evening fevers and sweating, a weight loss of over 7 kg, and a poor appetite. At this point he had no neck pain, palpitations or bowel abnormalities. Clinical examination continued to be normal upon his return to the UK and in the Endocrine Clinic. Investigations: Investigations were done to exclude (a) infections - There was no growth of pathogenic organisms in repeated blood, urine and sputum cultures. Screening tests for TB, hepatitis, and glandular fever were negative. Blood screens for malarial parasites, amoebic and Brucella serology, and stools examination and culture were also negative. Echocardiography was normal. (b) Malignancy - Urine Bence Jones proteins and serum protein electrophoresis were normal. Bone marrow examination was suggestive of Leishmaniasis but a PCR test excluded this diagnosis. Humoral markers of malignancy were negative. CT scans of the thorax, abdomen and pelvis were normal and did not show any evidence of visceral abnormalities (c) NIID - CRP 120, ESR 130, with blood tests consistent with iron deficiency. Autoimmune screening for dsDNA, ANA, ANCA were negative. Upon return to the UK a PET/CT scan showed the diffuse tracer uptake in both thyroid lobes and changes consistent with a large left lobe. Free thryroxine was 28pmol/l (reference range 9-19.1), and TSH was undetectable (

Modern mobile phones have a powerful processing unit that can perform multiple operations simultaneously. But the main constrain is the processing power and energy required to drive it. Cloud computing has come as a blessing for the mobile computing as it possesses a vast resource, high storage capacity and high processing power. In Mobile Cloud Computing (MCC), computation is offloaded to the cloud, cloud processes the data and generates information; and sends it back to the mobile device. Probability of offloading depends on line bandwidth, line length, size of data, processing speed of mobile, processing speed of cloud, storage and energy capacity of mobile etc. This paper presents a model for efficient data offloading decision, depending on the total execution time of a task when the data computation happens in the mobile and when it is offloaded to the cloud. An algorithm has been proposed here on data offloading decision. As thus an equation has been proposed to observe the probability of offloading process.

Hypoadrenalism (primary and secondary) affects 4/10,000 individuals.[1][1] But the commonest cause of hypothalamo-pituitary-adrenal axis suppression is exogenous steroid use, and about 1% of the UK population are on such therapy.[2][2] These steroid-treated subjects have a higher incidence of

Uncorrected thyroid dysfunction in pregnancy has well-recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre-empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves' disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy.

Heavy metals are ubiquitous in nature, thus constituting a serious environmental problem in many countries. Due to their toxicity, there is an obvious need to determine them at trace levels. Zinc is essential for many cellular processes, including DNA synthesis, transcription, and translation, but excess can be toxic. To analyze the uptake and metabolism of zinc in Escherichia coli , a high affinity FRET (Fluorescence Resonance Energy Transfer)–based nanosensor was developed using the cyanobacterial metallothionein SmtA flanked by CFP (cyan fluorescent protein) and YFP (yellow fluorescent protein). The chimeric sensor protein was expressed in E. coli BL21 (DE3) and purified by affinity chromatography. Following binding of zinc, FRET ratio increased with increasing the Zn 2+ concentration. Affinity mutants were constructed with binding constants ranging from 50 μM to 1 mM. In vitro analysis with bacterially purified sensor showed that it is specific for Zn 2+ and responds only weakly to Cd 2+ with no response for other biological metal ions. Moreover, the sensor activity in vitro was stable with extreme changes in pH. In vivo analysis of nanosensor response in E. coli showed that free Zn 2+ accumulate in the bacterial cells and is slowly metabolized.

The influence of 10 different rootstocks was investigated for evaluating the most suitable rootstock for table grape cultivar Fantasy Seedless. The growth performance, photosynthesis, biochemical composition, and primary nutrients’ status of the scion after grafting were investigated in ‘Fantasy Seedless’ grafted on 10 different rootstocks. The studies on vegetative parameters revealed that the rootstock influences the vegetative growth thereby increasing the photosynthesis of a vine. The rootstock influenced the changes in biochemical constituents in the grafted vine thus helping the vine to store enough food material. The grafted vines exhibited variations in primary nutrients status highlighting the scope for selection of better rootstock for sustainable nutrition management.

Nowadays, various drugs on the market are becoming more and more resistant to numerous diseases, thus declining their efficacy for treatment purposes in human beings. Antibiotic resistance is one among the top listed threat around the world which eventually urged the discovery of new potent drugs followed by an increase in the number of deaths caused by cancer due to chemotherapy resistance as well. Accordingly, marine cyanobacteria, being the oldest prokaryotic microorganisms belonging to a monophyletic group, have proven themselves as being able to generate pharmaceutically important natural products. They have long been known to produce distinct and structurally complex secondary metabolites including peptides, polyketides, alkaloids, lipids, and terpenes with potent biological properties and applications. As such, this review will focus on recently published novel compounds isolated from marine cyanobacteria along with their potential bioactivities such as antibacterial, antifungal, anticancer, anti-tuberculosis, immunosuppressive and anti-inflammatory capacities. Moreover, various structural classes, as well as their technological uses will also be discussed.

One of the crucial determinants for successful administration of lactobacilli to the vaginal niche is the use of appropriate Lactobacillus species. In this cross-sectional study 54 human immunodeficiency virus (HIV)-negative and 76 HIV-positive antiretroviral treatment-naive women were evaluated for culturable vaginal lactobacilli and their association with genital HIV-1 shedding. Lactobacillus species were identified by 16S rDNA sequencing while cervical and plasma HIV-1 viral load was determined by Abbott real-time PCR. Lactobacilli were isolated in 77.8 % HIV-negative and 73.7 % HIV-positive women. The mean log10 plasma and cervical HIV-1 viral loads (RNA copies ml−1) were 3.73±1.02 and 2.85±0.32 respectively. We observed that presence of L. crispatus, L. gasseri or L. jensenii species was associated with undetectable cervical HIV-1 (P=0.046) and reduced genital HIV-1 shedding (P=0.048) compared to other species. Our findings endorse using Lactobacillus-based strategies to aid the prevention of HIV-1 transmission among Indian women, however confirmation by future prospective studies is indeed warranted.

Glioblastoma multiforme (GBM) is the deadliest form of heterogeneous brain cancer. It affects an enormous number of patients every year and the survival is approximately 8 to 15 months. GBM has driven by complex signaling pathways and considered as a most challenging to treat. Standard treatment of GBM includes surgery, radiation therapy, chemotherapy and also the combined treatment. This review article described inter and intra- tumor heterogeneity of GMB. In addition, recent chemotherapeutic agents, with their mechanism of action have been defined. FDA-approved drugs also been focused over here and most importantly highlighting some natural and synthetic and novel anti- glioma agents, that are the main focus of researchers nowadays.

Word document (62Â KB). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA statement. This file contains a 27-item checklist of recommended items to include in a systematic review and meta-analysis. (DOC 62Â kb)

Background Suboptimal thyroid hormone therapy including under-replacement and over-replacement is common amongst patients with hypothyroidism. This is a significant health concern as affected patients are at risk of adverse cardiovascular or metabolic consequences. Despite a growing body of evidence on the effects of various factors on thyroid hormone replacement, a systematic appraisal of the evidence is lacking. This review aims to appraise and quantify the extent to which clinical, behavioural and pharmacogenomic factors affect levothyroxine therapy in patients with primary hypothyroidism. Methods/design The databases Web of Science, Cochrane Library, EMBASE and PubMed will be searched. Patients must be adults over the age of 18 years, suffering from primary hypothyroidism including overt and subclinical hypothyroidism and receiving levothyroxine treatment. Studies in children, pregnant women and patients with secondary or tertiary hypothyroidism will not be included. We will also exclude studies focused on forms of thyroid hormone replacement therapy other than levothyroxine. The primary outcome is to quantify the effect of clinical, behavioural and pharmacogenomic factors on thyroid stimulating hormone (TSH) levels. Secondary outcomes are the effect these factors have on thyroxine (T4) and triiodothyronine (T3) levels, mortality, morbidity, quality of life, treatment complications, adverse effects, physical and social functioning. Studies will be screened through reading the title, abstract and then full text. Two reviewers will independently extract the data and select articles, and a third reviewer will be consulted if there is any disagreement. We will undertake a meta-analysis of studies in which there is a defined intervention or exposure, patients are receiving levothyroxine for hypothyroidism, there is an appropriate control group of levothyroxine treated patients that are not exposed to the intervention, and the primary outcome is determined by serum TSH levels. Studies will comprise of randomised controlled trials as well as observational data. Eligible studies will be assessed for bias using the risk of bias tool available in the Cochrane handbook 2011, and the quality of evidence will be judged according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A flow diagram describing the data search will be created according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis: The PRISMA statement. A narrative synthesis will be undertaken in the description of the data, and summary tables will be created of the results. Discussion This review will be the first systematic review of this nature. The evidence synthesised will be useful to general practitioners in their management of hypothyroidism. Findings will be disseminated at conferences and in professional and peer-reviewed journals. Systematic review registration PROSPERO CRD42015027211 Electronic supplementary material The online version of this article (doi:10.1186/s13643-017-0457-z) contains supplementary material, which is available to authorized users.

Summary TSH receptor antibodies (TRAbs) are the pathological hallmark of Graves’ disease, present in nearly all patients with the disease. Euthyroid Graves’ ophthalmopathy (EGO) is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves’ ophthalmopathy (GO) was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves’ disease. Learning points Euthyroid Graves’ ophthalmopathy can present initially with negative thyroid-specific autoantibodies. Patients with suggestive symptoms of ophthalmopathy should be carefully evaluated for GO with imaging studies even when thyroid function and autoantibodies are normal. Patients with EGO can develop thyroid dysfunction within 4 years of follow-up underpinning the need for long-term follow-up and continued patient and physician vigilance in patients who have been treated for EGO.

Carbon (C) and nitrogen (N) are two essential elements that influence plant growth and development. The C and N metabolic pathways influence each other to affect gene expression, but little is known about which genes are regulated by interaction between C and N or the mechanisms by which the pathways interact. In the present investigation, proteome analysis of N-efficient and N-inefficient Indian mustard, grown under varied combinations of low-N, sufficient-N, ambient [CO2], and elevated [CO2] was carried out to identify proteins and the encoding genes of the interactions between C and N. Two-dimensional gel electrophoresis (2-DE) revealed 158 candidate protein spots. Among these, 72 spots were identified by matrix-assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF). The identified proteins are related to various molecular processes including photosynthesis, energy metabolism, protein synthesis, transport and degradation, signal transduction, nitrogen metabolism and defense to oxidative, water and heat stresses. Identification of proteins like PII-like protein, cyclophilin, elongation factor-TU, oxygen-evolving enhancer protein and rubisco activase offers a peculiar overview of changes elicited by elevated [CO2], providing clues about how N-efficient cultivar of Indian mustard adapt to low N supply under elevated [CO2] conditions. This study provides new insights and novel information for a better understanding of adaptive responses to elevated [CO2] under N deficiency in Indian mustard.

Adrenal incidentalomas (AIs) are mostly benign and nonsecretory. Management algorithms lack sensitivity when assessing malignant potential, although functional status is easier to assess. We present a subject whose AI was a retroperitoneal leiomyosarcoma (RL).Case Presentation. A woman on warfarin with SLE and the antiphospholipid syndrome, presented with left loin pain. She was normotensive and clinically normal. Ultrasound scans demonstrated left kidney scarring, but CT scans revealed an AI. MRI scans later confirmed the AI without significant fat and no interval growth. Cortisol after 1 mg dexamethasone, urinary free cortisol and catecholamines, plasma aldosterone renin ratio, and 17-hydroxyprogesterone were within the reference range. Initially, adrenal haemorrhage was diagnosed because of warfarin therapy and the acute presentation. However, she underwent adrenalectomy because of interval growth of the AI. Histology confirmed an RL. The patient received adjuvant radiotherapy.Discussion. Our subject presented with an NSAI. However, we highlight the following: (a) the diagnosis of adrenal haemorrhage in this anticoagulated woman was revised because of interval growth; (b) the tumour, an RL, was relatively small at diagnosis; (c) this subject has survived well over 60 months despite an RL perhaps because of her acute presentation and early diagnosis of a small localised tumour.

Oral cavity functions as an early indicator for a variety of systemic diseases. Early and accurate diagnosis of these underlying systemic disorders entails thorough examination of the oral mucosa, gingiva, teeth, tongue and other oral tissues. Although gingival changes may be related to local factors in the oral cavity, it can also be an expression of systemic conditions such as blood dyscrasias, endocrinal imbalance, and nutritional deficiencies. Leukemia, a malignancy of white blood cells is a dreadful disease, which, if not diagnosed properly and treated early may result in significant morbidity and mortality. Oral changes may be the first and only presenting signs in leukemic patients. This paper aims to throw light on an interesting case of acute leukemia diagnosed on the basis of oral signs and emphasizes the importance of thorough oral examination to identify the threatening condition.