Defense versus growth trade-offs: Insights from glucosinolates and their catabolites.

Specialized metabolites are a structurally diverse group of naturally occurring compounds that facilitate plant-environment interactions. Their synthesis and maintenance in plants is overall a resource-demanding process that occurs at the expense of growth and reproduction and typically incurs several costs. Evidence emerging on different specialized compounds suggests that they serve multiple auxiliary functions to influence and moderate primary metabolism in plants. These new functionalities enable them to mediate trade-offs from defenses to growth and also to offset their production and maintenance costs in plants. Recent research on glucosinolates (GSLs), which are specialized metabolites of Brassicales, demonstrates their emerging multifunctionalities to fine-tune plant growth and development under variable environments. Herein, we present findings from the septennium on individual GSLs and their catabolites (GHPs) per se, that work as mobile signals within plants to mediate precise regulations of their primary physiological functions. Both GSLs and GHPs calibrate growth-defense trade-off interactions either synergistically or directly when they function as storage compounds, abiotic stress alleviators, and one-to-one regulators of growth pathways in plants. We finally summarize the overall lessons learned from GSLs and GHPs as a model and raise the most pressing questions to address the molecular-genetic intricacies of specialized metabolite-based trade-offs in plants.

Eumycetoma of the Foot due to Fusarium solani in a Person with Diabetes Mellitus: Report of a Case and Review of Literature.

Eumycetomas are chronic suppurative granulomas caused by fungi characterised by invasive tumefactive lesions, sinuses and discharging grains. Herein, we describe a case of pedal eumycetoma due to Fusarium solani sensu stricto in a person with diabetes mellitus. A 45-year-old gentleman presented with an insidious onset swelling over his right foot with nodules and discharging grains. He had received itraconazole and anti-tuberculous therapy elsewhere, without response. Re-evaluation included a biopsy which confirmed eumycetoma and newly diagnosed diabetes. Surgical excision followed by histopathological, microbiological and multigene sequencing analyses [translation elongation factor, calmodulin and internal transcribed spacer region of rDNA] of the mould on culture were performed. Histopathology revealed septate fungal hyphae amidst a dense inflammatory infiltrate (Splendore-Hoeppli) reaction. Oral voriconazole was started and good glycemic control attained. Tissue growth sequences showed > 99% similarity with Fusarium solani sensu stricto. Antifungal susceptibility testing showed lowest MIC to voriconazole (0.5 mg/L). The patient showed excellent response to combined therapeutic modality with a near-complete resolution in size of lesion and obliteration of sinuses following 4 months of therapy and is planned for prolonged voriconazole therapy till complete radiological resolution. Diabetes predisposes to fungal infections of foot but eumycetomas are uncommon. Combined surgery and antifungals can improve morbidity and avoid amputations.

Normative data for insulin-like growth factor-1 (IGF-1) in healthy children and adolescents from India.

BACKGROUND: Serum IGF-1 is an important biochemical tool to diagnose and monitor GH-related disorders. However, ethnic-specific Indian data following consensus criteria for the establishment of normative data, are not available. Our objective was to generate chronological age (CA)-, bone age (BA)- and Tanner stage-specific normative data for IGF-1 in healthy Indian children and adolescents. METHODS: A cross-sectional epidemiological study was conducted in schools and the community, which enrolled apparently healthy children and adolescents with robust exclusion criteria. The outcome measure was serum IGF-1 assessed using an electro-chemiluminescence immunoassay (ECLIA). The 2.5th, 5th, 10th, 25th, 50th (median), 75th, 90th, 95th, and 97.5th centiles for IGF-1 were estimated using generalized additive models. RESULTS: We recruited 2226 apparently healthy participants and following exclusion, 1948 (1006 boys, 942 girls) were included in the final analysis. Girls had median IGF-1 peak at CA of 13 years (321.7 ng/mL), BA of 14 years (350.2 ng/mL) and Tanner stage IV (345 ng/mL), while boys had median IGF-1 peak at CA of 15 years (318.9 ng/mL) BA of 15 years (340.6 ng/mL) and Tanner stage III (304.8 ng/mL). Girls had earlier rise, peak and higher IGF-1 values. The reference interval (2.5th-97.5th percentile) was broader during peri-pubertal ages, indicating a higher physiological variability. CONCLUSION: This study provides ethnicity-specific normative data on serum IGF-1 and will improve the diagnostic utility of IGF-1 in the evaluation and management of growth disorders in Indian children and adolescents.

POEMS syndrome: an unusual cause of exuberant callus formation.

Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Together, they lead to angiogenesis-osteogenesis coupling and hence bone healing by callus formation. Of these growth factors, vascular endothelial growth factor is of particular interest because of its ability to induce neovascularisation (angiogenesis) and osteoclast invasion in soft callus. Hyperplastic callus can be seen in metabolic bone disease, endocrine disease and in patients with traumatic brain injury, but has not been described so far in polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome. This report is a case of POEMS syndrome with unusual presentation in the form of exuberant callus formation at fracture sites.

Metabolic bone disease heralding the diagnosis of Wilson's disease.

We report a short-statured, young man in his 20s presenting with bilateral cataract, recurrent kidney stones, history of refractory rickets and bone deformity. He had been consuming calcium and vitamin D supplements and had been operated for cataract and renal stone disease, prior to reporting in our clinic without any significant laboratory or clinical improvement. The patient was diagnosed as having Fanconi's syndrome attributable to Wilson's disease. This patient highlights that in case of resistant rickets, a high index of suspicion must be invoked for Wilson's disease. Timely recognition of this entity results in prompt ministrations and prevention of disability.

Body fat patterning in lean Asian Indians with diabetes: Case-control study.

AIM: To perform body fat patterning in Asian-Indian individuals with T2D. METHODS: A total of 53 patients with recent-onset diabetes and 106 non-diabetic controls were included from screened 261 individuals. Data was divided into 2 groups; overweight/obese [(BMI ≥23 kg/m2); 45 diabetic, 84 non-diabetic] and lean [(BMI <23 kg/m2); 8 diabetic, 22 non-diabetic]. Anthropometry (weight, height, BMI, waist, hip circumference, waist-hip ratio) and lipids, adiponectin and hsCRP were measured. Body composition (BC) was assessed by bioimpedance analysis (BIA) and Dual Energy X-ray absorptiometry (DEXA). We analyzed the association of visceral adipose tissue (VAT) with anthropometric measures to identify predictors of diabetes. RESULTS: Total body fat percentage was comparable between patients with T2D and non-diabetic controls in both, obese [35.0 ± 9.1% vs 36.8 ± 8.4%, p = 0.29 (BIA), 40.1 ± 6.7 vs 46.6 ± 4.1%, p = 0.052 (DEXA) and lean [25.1 ± 5.6% vs 26.0 ± 6.7%, p = 0.74 (BIA), 35.3 ± 4.8% vs 34.1 ± 6.3%, p = 0.72 (DEXA) study group. Individuals of T2D (obese or lean) had significantly higher visceral fat rating (BIA), VAT area, volume, mass and VAT corrected for total body fat percentage (DEXA). Obese T2D had lower muscle mass (57.0 ± 6.4% vs 60.0 ± 5.5%, p = 0.03) than obese controls. Intra-abdominal visceral fat (IAVF) [(VFR, VAT (mass/area/volume) and VAT mass corrected for body fat)] had the best sensitivity (71%) for incident diabetes. CONCLUSION: Higher Intra-abdominal visceral fat and not total body fat is associated with incident diabetes independent of BMI. IAVF estimation by either BIA or DEXA should be performed to predict diabetes especially in lean individuals.

Normative Data on Dehydroepiandrosterone Sulphate (DHEAS) and its Attributes in Healthy Indian Children and Adolescents.

Dehydroepiandrosterone sulphate (DHEAS), the biochemical indicator of adrenarche and pubarche, is of paramount importance in the evaluation of puberty-related disorders. The reference range of DHEAS should be ethnicity, age, sex, pubarche and Tanner stage specific. Anthropometry, puberty assessment and hormonal parameters were estimated using electrochemiluminescence assay. Bone age was estimated using the BoneXpert software. Of 2191 healthy Indian children aged 5-18 y screened at Chandigarh, 1919 were included in the final analysis (994 boys). The median DHEAS levels at pubarche stage P2 were 82.10 (55.0-129.0) g/dl in girls and 132.50 (95.12-205.50) g/dl in boys. By ROC analysis, the level of DHEAS at pubarche was 63.7 g/dl (sensitivity 72.6%, specificity 64.4%) in girls and 82.2 g/dl (sensitivity 81.8%, specificity 68.8%) in boys. The median age at adrenarche was 9.5 y in both sexes. On multivariate regression analysis; bone age, body mass index (BMI), gonadal steroids, and insulin-like growth factor-1 (IGF-1) significantly correlated with serum DHEAS levels in either sex.

Perioperative Management for Non-Thyroidal Surgery in Thyroid Dysfunction.

Thyroid hormone exerts effects across all organ systems. Hence, patients with thyroid dysfunction are at a risk of numerous complications. The stresses encountered during the perioperative period may exacerbate underlying thyroid disorders, potentially precipitating decompensation, and even death. Thus, it is of the utmost importance for the clinician to comprehend the mechanisms by which thyroid disease may complicate surgery and postoperative recovery and to optimize the status of thyrotoxic and hypothyroid patients. This article describes the adverse effects of thyroid dysfunction in patients undergoing nonthyroid surgery and recommends treatment approaches aimed at appropriate build-up to decrease perioperative risk.

Multifocal Multisystem Langerhans Cell Histiocytosis Involving Pituitary Masquerading as Crohn's Disease: A Case Report and Review of the Literature.

Background/Objective. We present a case of Langerhans cell histiocytosis (LCH) with gastrointestinal involvement masquerading as inflammatory bowel disease (IBD) in a patient who initially had features of central diabetes insipidus (CDI). Case Report. A 19-year-old male presented at 14 years of age with central diabetes insipidus. He subsequently developed panhypopituitarism and sellar-suprasellar mass, the biopsy of which was inconclusive. Secondary causes for hypophysitis were ruled out. Five years later, he developed perianal pus discharging sinuses, positive ASCA, and sacroiliitis. Rectal ulcer biopsy showed nonspecific inflammation and necrosis. Hence, he was managed as inflammatory bowel disease (IBD). Due to nonresponsiveness of symptoms, doubt about diagnosis was invoked and rectal ulcer biopsy was repeated, which then showed infiltration by Langerhans cells. Hence, he was diagnosed with LCH and showed resolution of symptoms on initiating steroids and vinblastine. Discussion. Gastrointestinal involvement by LCH is unusual and only rarely has represented a prominent clinical manifestation. In most cases, such involvement suggests widespread multisystem disease. Its distinctive morphologic and immunohistochemical features allow LCH to be distinguished from other inflammatory infiltrations found in mucosal biopsy specimens. Conclusion. Preceding CDI and hypopituitarism may predict LCH in patients with IBD-like diseases.

Thyroid eye disease with concurrent orbital lymphoma: a radiological surprise.

Summary: Thyroid eye disease (TED) is the most common extra-thyroidal manifestation in Graves' disease (GD). Additional/concurrent/synchronous pathologies may be present, especially in elderly patients who present with atypical features such as non-axial (or eccentric) proptosis, absence of lid lag and restricted superior extra-ocular movements. A 70-year-old female presented with progressive proptosis of her left eye and diplopia. She was diagnosed with GD a year prior and initiated on carbimazole. On examination, she had eccentric proptosis, restricted superior extra-ocular movements and a palpable mass in the supero-temporal quadrant of the left eye. Her T3 (1.33 ng/mL) and T4 (8.85 µg/dL) were normal with carbimazole. Thyroid-stimulating hormone (TSH)-receptor antibody was positive (3.15 IU/L, reference range <1.75). MRI revealed an enhancing lesion infiltrating the left superior rectus, with concurrent characteristic muscle belly involvement bilaterally. Orbital biopsy showed atypical lymphoid cells (CD20+), suggesting marginal zone lymphoma. CT thorax and abdomen, fluorodeoxyglucose-positron emission tomography and bone marrow examination were normal. The patient was administered orbital radiotherapy for her localised lymphoma and carbimazole was continued. TED is the most common cause of orbital involvement overall and in GD. However, additional or alternative pathology may be present which requires evaluation. MRI can be a useful adjunct in these patients. Orbital lymphoma needs to be staged with workup for disseminated disease. Radiotherapy is the treatment of choice for localized disease. The index case provides evidence for synchronous presentation of dual pathology and highlights the importance of astute clinical examination as well as keeps a low threshold for MRI in selected cases. Learning points: Thyroid eye disease can co-exist with other ocular pathology, especially in elderly individuals. Eccentric proptosis, absent lid lag and restriction of eye movements (suggesting tendon involvement) should alert towards the presence of alternative pathology. Orbital imaging using MRI not only has greater sensitivity in diagnosing radiologically bilateral disease in patients who have unilateral involvement clinically but is also useful to identify concurrent neoplasms.

Bladder cancer with pioglitazone: A case-control study.

BACKGROUND: Varied reports suggest a contentious relationship of bladder malignancy with pioglitazone in patients with type 2 diabetes. AIM: To study an association (prevalence and predictors) of bladder malignancy with pioglitazone therapy in Asian-Indian type 2 diabetes patients. METHOD: In this observational multicenter study, type 2 diabetic patients attending out-patient diabetes-clinic were evaluated. A detailed history of anti-diabetic medication, dose, duration, pioglitazone usage, time since initiation of pioglitazone, physical examination, biochemical tests and details pertaining to prevalent neuropathy, retinopathy and nephropathy were recorded. Details of bladder cancer or any malignancy (if present), time since diagnosis, risk factors for bladder cancer and histopathology records were noted. The study cohort was divided into two groups-pioglitazone ever users (Group A) and never users (Group B). RESULTS: A total of 8000 patients were screened out of which 1560 were excluded. Among 6440 included patients, 1056 (16.3%) patients were in group A and 5384 (83.6%) group B. Patients on pioglitazone were older (59.1 vs 57.7 years, p < 0.001), had longer duration of diabetes (12.7 vs 10.6 years, p < 0.001) with poor glycemic control (HbA1c 8.5 vs 8.3%, p < 0.01). A total of 74 patients had prevalent bladder cancer [16 (1.5%) in Group A and 58 in Group B (1.0%)]. Prevalent bladder cancer was not significantly greater in ever-users (odds ratio OR = 1.29, 95% confidence interval CI, 0.83-2.00) compared to never-users (odds ratio OR = 0.94, 95% confidence interval CI, 0.834-1.061) of pioglitazone (p = 0.207). However, history of hematuria in pioglitazone-users; while older age (>58 year), history of smoking and hematuria in the whole cohort were significant associated with bladder cancer. In the entire study cohort, 254 patients; 3.5% of males (128 out of 3575) and 4.6% of females (126 out of 2713) developed any malignancy. Age was significantly associated with prevalent malignancy in people with diabetes (odds ratio OR 1.036, 95% confidence interval CI: 1.022-1.051, p = 0.00) on multivariate forward regression. CONCLUSION: Pioglitazone use in Asian-Indians is not associated with an increased bladder cancer risk. However, pioglitazone should be restricted in individuals with history of hematuria. Age more than 58 years is a significant risk factor for development of any malignancy, particularly bladder cancer.

A comprehensive Vis-NIRS equation for rapid quantification of seed glucosinolate content and composition across diverse Brassica oilseed chemotypes.

The globally cultivated Brassica crops contain high deliverable concentrations of health-promoting glucosinolates. Development of a Visible-Near InfraRed Spectroscopy (Vis-NIRS) calibration to profile different glucosinolate components from 641 diverse Brassica juncea chemotypes was attempted in this study. Principal component analysis of HPLC-determined glucosinolates established the distinctiveness of four B. juncea populations used. Subsequently, modified partial least square regression based population-specific and combined Vis-NIRS models were developed, wherein the combined model exhibited higher coefficient of determination (R2; 0.81-0.97) for eight glucosinolates and higher ratio of prediction determination (RPD; 2.42-5.35) for seven glucosinolates in B. juncea populations. Furthermore, range error ratio (RER > 4) for twelve and RER > 10 for eight glucosinolates make the combined model acceptable for screening and quality control. The model also provided excellent prediction for aliphatic glucosinolates in four oilseed Brassica species. Overall, our work highlights the potential of Vis-NIR spectroscopy in estimating glucosinolate content in the economically important Brassica oilseeds.

Antimicrobial food packaging: potential and pitfalls.

Nowadays food preservation, quality maintenance, and safety are major growing concerns of the food industry. It is evident that over time consumers' demand for natural and safe food products with stringent regulations to prevent food-borne infectious diseases. Antimicrobial packaging which is thought to be a subset of active packaging and controlled release packaging is one such promising technology which effectively impregnates the antimicrobial into the food packaging film material and subsequently delivers it over the stipulated period of time to kill the pathogenic microorganisms affecting food products thereby increasing the shelf life to severe folds. This paper presents a picture of the recent research on antimicrobial agents that are aimed at enhancing and improving food quality and safety by reduction of pathogen growth and extension of shelf life, in a form of a comprehensive review. Examination of the available antimicrobial packaging technologies is also presented along with their significant impact on food safety. This article entails various antimicrobial agents for commercial applications, as well as the difference between the use of antimicrobials under laboratory scale and real time applications. Development of resistance amongst microorganisms is considered as a future implication of antimicrobials with an aim to come up with actual efficacies in extension of shelf life as well as reduction in bacterial growth through the upcoming and promising use of antimicrobials in food packaging for the forthcoming research down the line.