Long Term Health-Related Quality of Life with Differentiated Thyroid Cancer in Goiter Endemic Area.

Health related quality of life (HRQOL) is a multidimensional concept that encompasses the patient's perceptions of his or her physical, emotional, social, and cognitive functions. Despite DTC patients' long survival, HRQOL has been shown to be lower than in the general population. There is a scarcity of data on HRQOL in thyroid cancer in the Indian population and especially goiter endemic area. As a result, the authors conducted a health-related quality of life survey in patients managed at their center in Northern India's Sub-Himalayan region using two widely accepted questionnaires. Adults with differentiated thyroid cancer who had surgery with or without radio-iodine ablation and had recovered for at least 6 months were assessed using health quality of life surveys, the QLQ-C30 and QLQ-THY34 of the European Organization for Research and Treatment of Cancer Quality of Life Group. The survey was completed by 57 adults with a mean age of 45.64 ± 15.64 years. The average time between the survey and treatment was 13.3 ± 10.8 months. After surgery, the QLQ-C30 found a significant reduction in insomnia, appetite loss, constipation, diarrhea, and financial difficulties, whereas radio-iodine ablation significantly improved global health status. The QLQ-THY34 found a significant increase in symptoms such as voice concerns, hair problems, dry mouth, shoulder functioning, tingling, and worrying after surgery, with a significant improvement in swallowing and job impact symptoms. The surgical extent had no impact. The quality of life for people with differentiated thyroid cancer in goiter-endemic areas is similar to that of other areas. However, the limited number of subjects in the study warrants further large sample size longitudinal study to understand the exact Health-related quality of life in thyroid cancer in endemic area.

Complete Second Branchial Fistula: A Rare Entity.

Second branchial anomalies like branchial cyst, sinus or fistula are common lateral neck masses in pediatric age group but it is rare to encounter complete branchial fistula with external as well as internal openings. We present a case of 16 yrs old female patient with complete Branchial fistula which was diagnosed with the help of CT fistulogram and thereafter taken up for surgical excision of fistula under general anaesthesia. Histopathology confirmed the diagnosis of branchial fistula. In case of lateral neck mass with external opening in pediatric age group strong possibility of diagnosis of branchial fistula should be kept, timely management of the case improves the quality of life.

Clinical and Mycologic Characteristics of Emerging Mucormycosis Agent Rhizopus homothallicus.

We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02-0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03-16], itraconazole [0.03-16], posaconazole [0.03-8], and isavuconazole [0.03-16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus.

Covid 19 Associated Idiopathic Intracranial Hypertension and Acute Vision loss.

Headache is a frequent complaint in COVID-19 while intracranial hypertension leading to acute vision loss is unusual. A 49-years-old female presented with persistent headache and vision loss and was found Covid 19 positive. Investigations suggested Covid 19 associated intracranial hypertension. She improved with medical management but again presented with acute vision loss. The visual loss was managed by endoscopic optic nerve fenestration surgery. She had significant recovery in vision during follow up period. Persistent headache in Covid 19 should have a high index of suspicion for idiopathic intracranial hypertension to avoid irreversible vision loss.

High expression of aldehyde dehydrogenase 1 and tissue necrosis factor alpha may relate to chronic infection of buffalo mammary gland.

Aldehyde dehydrogenase 1 (ALDH1) and hepatocyte nuclear factor 4A (HNF4A) are the putative mammary stem cell markers. Tissue necrosis factor alpha (TNFA) is involved in inflammation-associated carcinogenesis and cell proliferation. In this study, the gene expression profile of ALDH1, HNF4A and TNFA of buffalo mammary tissue using real-time quantitative PCR (RT-qPCR). Analysis of RT-qPCR data revealed that the relative expression (log2 fold change) of ALDH1 and TNFA during mastitis (vs. lactation) was increased (P < .05) by 2.98 and 4.71, respectively. The relative expression (log2 fold change; -7.39) of stem cell marker, HNF4A was decreased (P < .05) during mastitis. Histological analysis of mammary tissue during mastitis showed thickening of stroma and occasionally hyperplasia, predominantly in prepubertal and non-lactating animals. Although, the level of expression of these genes may vary, depending upon the physiological stage of the animals, however expression of ALDH1 and TNFA was high during mastitis. A systematic study on large samples of buffalo mammary tissue with appropriate comparisons needs to be evaluated with these markers for prognosis of buffalo mammary health.

Physico-chemical, hydration, cooking, textural and pasting properties of different adzuki bean (Vigna angularis) accessions.

Physico-chemical, hydration, cooking, textural and pasting properties of thirteen adzuki bean (Vigna angularis) accessions were studied. Protein and ash content ranged from 18.82 to 24.52% and 2.02 to 7.03%, respectively. Bulk density and seed weight of the adzuki seed ranged from 0.76 to 1.00 g/mL and 74.87 to 148.20 g/1000 seeds, respectively. Hydration capacity, swelling capacity and cooking time ranged from 0.05 to 0.12 g/seed, 0.04 to 0.15 mL/seed and 48.67 to 74.33 min, respectively. Different accessions showed significant variations in their physicochemical, cooking, hydration and texture properties. Swelling capacity showed significantly positive correlation with L* value. Hardness of soaked grain varied ranged between 68.67 and 120.25 N and had significant positive correlation with gumminess and chewiness. The springiness and chewiness of cooked seeds showed highly significant positive correlation. Peak viscosity, breakdown viscosity, final viscosity, setback viscosity and pasting temperature of adzuki bean flour ranged from 1979 to 2373 cP, 45 to 183 cP, 2954 to 4004 cP, 931 to 1666 cP and 75.02 to 78.27 °C, respectively. Peak viscosity and breakdown viscosity were negatively correlated to amylose content while setback viscosity showed positive correlation.

Ultrasound assisted extraction of polyphenols and their distribution in whole mung bean, hull and cotyledon.

In this study, extraction of polyphenols using different solvents (acetone, ethanol, methanol and water) with ultrasound and conventional method from whole mung bean (WMB), hull and cotyledon was conducted. Total phenolic content (TPC), total flavonoids content (TFC), total antioxidant activities (TAA), ferric reducing power (FRP) and DPPH radical scavenging activity were determined. Ultrasound treated extracts exhibited higher TPC, TFC, TAA, FRP and DPPH in different mung bean fractions than CSE. Among the solvents, acetone showed better TPC, TFC, TAA, FRP and DPPH. Hull had significantly higher TPC, TFC, TAA, FRP and DPPH than WMB and cotyledon. Sinapic acid (SA) was the major polyphenol in different fractions. Acetone extract of hull showed high polyphenol content. SA, ferulic acid, catechin, p-coumaric acid, resveratrol, quercetin and luteolin were the major contributors to antioxidant activity of acetone extract. Mung bean hull contained the maximum polyphenols and acetone was observed to be the best extraction medium for polyphenols in combination with ultrasound.

Effect of canning on color, protein and phenolic profile of grains from kidney bean, field pea and chickpea.

The aim of the present study was to evaluate the effect of canning on color, protein and phenolic profile of grains of kidney bean, field pea and chickpea varieties/accession. Color of grains of different pulses was enhanced after canning. Grains L* (lightness) decreased while a* (redness to yellowness) and b* (greenness to blueness) increased after canning in all the pulses. Protein profiling of grains of different pulses after canning revealed that kidney bean and chickpea, respectively, had the least and the most thermally susceptible polypeptides. Kidney bean and chickpea showed higher Percentage washed drained weight (PWDW) than field pea. Pulse with more grain hardness and PWDW showed higher degree of grain splitting during canning. Grain splitting was also higher in dark colored accessions/varieties as compared to the light colored. Ferulic acid was the most predominant compound present in raw grains of different pulses. Raw kidney bean grains showed higher accumulation of catechin, chlorogenic, protocatechuic acid, p-coumaric acid and ferulic acid than those of chickpea and field pea. Canning caused reduction in all the phenolic compounds except gallic acid and most prominent effect of canning on protocatechuic acid, chlorogenic and ferulic acid was observed.

Successive Reduction Dry Milling of Normal and Waxy Corn: Grain, Grit, and Flour Properties.

Dry milling of different corn types resulted in varied proportions of germ, pericarp, grit and flour. Grit and flour produced during different reduction stages varied in particle size and chemical constituents, hence applications in food industry. In this study, recovery of different fractions and variation in physicochemical and pasting properties of grit and flour fractions obtained during 3 successive reduction dry millings of 2 normal (African tall, HQPM1) and 1 waxy corn (IC 550353) were evaluated. Waxy corn grains had the highest L*, a*, b*, ash, fat, and protein content and the lowest weight. Waxy and African tall gave the highest recovery of germ and pericarp, respectively. Waxy corn showed lower grit and flour recovery as compared to normal corn. Flour fractions showed higher L* and lower a* and b* values than grit fractions. Particle size of grit and flour fractions ranged from 840 to 982 µm and 330 to 409 µm, respectively. Fractions with larger particle size showed lower L* value. The b* value showed positive correlation with yellow pigment content. Grit and flour from the 1st reduction stage showed higher ash and fat content. Protein content was correlated positively with ash content and negatively with L* value. Grit and flour fractions with higher protein content had lower pasting viscosities. Pasting viscosities were higher for flours than their corresponding grits. Protein profiling of grit and flour fractions from different stages showed quantitative and qualitative differences in medium (22, 28, and 35 kDa) and low molecular weight (16, 17, and 19 kDa) polypeptides and were related to grit and flour yield.

Immunomodulatory activity of orphan drug Elmiron® in female B6C3F1/N mice.

Interstitial cystitis (IC) is a chronic disorder characterized by bladder discomfort and urinary urgency in the absence of identifiable infection. Despite the expanding use in IC treatment and other chronic conditions, the effects of Elmiron® treatment on immune system remain unknown. Therefore, female B6C3F1/N mice were orally administered Elmiron® daily for 28-days at doses of 63, 125, 250, 500 or 1000mg/kg to evaluate its immunomodulatory effects. Mice treated with Elmiron® had a significant increase in absolute numbers of splenic macrophages (63, 500 and 1000mg/kg) and natural killer (NK) cells (250 and 1000mg/kg). Elmiron® treatment did not affect the humoral immune response or T cell proliferative response. However, innate immune responses such as phagocytosis by liver macrophages (1000mg/kg) and NK cell activity were enhanced (500 and 1000mg/kg). Further analysis using a disease resistance model showed that Elmiron®-treated mice demonstrated significantly increased anti-tumor activity against B16F10 melanoma cells at the 500 and 1000mg/kg doses. Collectively, we conclude that Elmiron® administration stimulates the immune system, increasing numbers of specific cell populations and enhancing macrophage phagocytosis and NK cell activity in female B6C3F1/N mice. This augmentation may have largely contributed to the reduced number of B16F10 melanoma tumors.

Evaluation of propargyl alcohol toxicity and carcinogenicity in F344/N rats and B6C3F1/N mice following whole-body inhalation exposure.

Propargyl alcohol (PA) is a high production volume chemical used in synthesis of many industrial chemicals and agricultural products. Despite the potential for prolonged or accidental exposure to PA in industrial settings, the toxicity potential of PA was not well characterized. To address the knowledge gaps relevant to the toxicity profile of PA, the National Toxicology Program (NTP) conducted 2-week, 14-week and 2-year studies in male and female F344/N rats and B6C3F1/N mice. For the 2-week inhalation study, the rats and mice were exposed to 0, 31.3, 62.5, 125, 250 or 500ppm. Significant mortality was observed in both rats and mice exposed to ≥125ppm of PA. The major target organ of toxicity in both mice and rats was the liver with exposure-related histopathological changes (250 and 500ppm). Based on the decreased survival in the 2-week study, the rats and mice were exposed to 0, 4, 8, 16, 32 or 64ppm of PA in the 14-week study. No treatment-related mortality was observed. Mean body weights of male (≥8ppm) and female mice (32 and 64ppm) were significantly decreased (7-16%). Histopathological changes were noted in the nasal cavity, and included suppurative inflammation, squamous metaplasia, hyaline droplet accumulation, olfactory epithelium atrophy, and necrosis. In the 2-year inhalation studies, the rats were exposed to 0, 16, 32 and 64ppm of PA and the mice were exposed to 0, 8, 16 and 32ppm of PA. Survival of male rats was significantly reduced (32 and 64ppm). Mean body weights of 64ppm male rats were significantly decreased relative to the controls. Both mice and rats showed a spectrum of non-neoplastic changes in the nose. Increased neoplastic incidences of nasal respiratory/transitional epithelial adenoma were observed in both rats and mice. The incidence of mononuclear cell leukemia was significantly increased in male rats and was considered to be treatment-related. In conclusion, the key findings from this study indicated that the nose was the primary target organ of toxicity for PA. Long term inhalation exposure to PA led to nonneoplastic changes in the nose, and increased incidences of respiratory/transitional epithelial adenomas in both mice and rats. Increased incidences of harderian gland adenoma may also have been related to exposure to PA in male mice.

Inosine-containing RNA is a novel innate immune recognition element and reduces RSV infection.

During viral infections, single- and double-stranded RNA (ssRNA and dsRNA) are recognized by the host and induce innate immune responses. The cellular enzyme ADAR-1 (adenosine deaminase acting on RNA-1) activation in virally infected cells leads to presence of inosine-containing RNA (Ino-RNA). Here we report that ss-Ino-RNA is a novel viral recognition element. We synthesized unmodified ssRNA and ssRNA that had 6% to16% inosine residues. The results showed that in primary human cells, or in mice, 10% ss-Ino-RNA rapidly and potently induced a significant increase in inflammatory cytokines, such as interferon (IFN)-ß (35 fold), tumor necrosis factor (TNF)-α (9.7 fold), and interleukin (IL)-6 (11.3 fold) (p<0.01). Flow cytometry data revealed a corresponding 4-fold increase in influx of neutrophils into the lungs by ss-Ino-RNA treatment. In our in vitro experiments, treatment of epithelial cells with ss-Ino-RNA reduced replication of respiratory syncytial virus (RSV). Interestingly, RNA structural analysis showed that ss-Ino-RNA had increased formation of secondary structures. Our data further revealed that extracellular ss-Ino-RNA was taken up by scavenger receptor class-A (SR-A) which activated downstream MAP Kinase pathways through Toll-like receptor 3 (TLR3) and dsRNA-activated protein kinase (PKR). Our data suggests that ss-Ino-RNA is an as yet undescribed virus-associated innate immune stimulus.

Protein kinase R is a novel mediator of CD40 signaling and plays a critical role in modulating immunoglobulin expression during respiratory syncytial virus infection.

Effective immunoglobulin responses play a vital role in protection against most pathogens. However, the molecular mediators and mechanisms responsible for signaling and selective expression of immunoglobulin types remain to be elucidated. Previous studies in our laboratory have demonstrated that protein kinase R (PKR) plays a crucial role in IgE responses to double-stranded RNA (dsRNA) in vitro. In this study, we show that PKR plays a critical role in IgG expression both in vivo and in vitro. PKR(-/-) mice show significantly altered serum IgG levels during respiratory syncytial virus (RSV) infection. IgG2a expression is particularly sensitive to a lack of PKR and is below the detection level in mock- or RSV-infected PKR(-/-) mice. Interestingly, we show that upon activation by anti-CD40 and gamma interferon (IFN-γ), B cells from PKR(-/-) mice show diminished major histocompatibility complex class II (MHC II), CD80, and CD86 levels on the cell surface compared to wild-type (WT) mice. Our data also show that PKR is necessary for optimal expression of adhesion molecules, such as CD11a and ICAM-1, that are necessary for homotypic aggregation of B cells. Furthermore, in this report we demonstrate for the first time that upon CD40 ligation, PKR is rapidly phosphorylated and activated, indicating that PKR is an early and novel downstream mediator of CD40 signaling pathways.

Critical role of MARCO in crystalline silica-induced pulmonary inflammation.

Chronic exposure to crystalline silica can lead to the development of silicosis, an irreversible, inflammatory and fibrotic pulmonary disease. Although, previous studies established the macrophage receptor with collagenous structure (MARCO) as an important receptor for binding and uptake of crystalline silica particles in vitro, the role of MARCO in regulating the inflammatory response following silica exposure in vivo remains unknown. Therefore, we determined the role of MARCO in crystalline silica-induced pulmonary pathology using C57Bl/6 wild-type (WT) and MARCO(-/-) mice. Increased numbers of MARCO(+) pulmonary macrophages were observed following crystalline silica, but not phosphate-buffered saline and titanium dioxide (TiO(2)), instillation in WT mice, highlighting a specific role of MARCO in silica-induced pathology. We hypothesized that MARCO(-/-) mice will exhibit diminished clearance of silica leading to enhanced pulmonary inflammation and exacerbation of silicosis. Alveolar macrophages isolated from crystalline silica-exposed mice showed diminished particle uptake in vivo as compared with WT mice, indicating abnormalities in clearance mechanisms. Furthermore, MARCO(-/-) mice exposed to crystalline silica showed enhanced acute inflammation and lung injury marked by increases in early response cytokines and inflammatory cells compared with WT mice. Similarly, histological examination of MARCO(-/-) lungs at 3 months post-crystalline silica exposure showed increased chronic inflammation compared with WT; however, only a small difference was observed with respect to development of fibrosis as measured by hydroxyproline content. Altogether, these results demonstrate that MARCO is important for clearance of crystalline silica in vivo and that the absence of MARCO results in exacerbations in innate pulmonary immune responses.

Differential binding of inorganic particles to MARCO.

Alveolar macrophages (AM) in the lung have been documented to play pivotal roles in inflammation and fibrosis (silicosis) following inhalation of crystalline silica (CSiO(2)). In contrast, exposure to either titanium dioxide (TiO(2)) or amorphous silica (ASiO(2)) is considered relatively benign. The scavenger receptor macrophage receptor with collagenous structure (MARCO), expressed on AM, binds and internalizes environmental particles such as silica and TiO(2). Only CSiO(2) is toxic to AM, while ASiO(2) and TiO(2) are not. We hypothesize that differences in induction of pathology between toxic CSiO(2) and nontoxic particles ASiO(2) and TiO(2) may be related to their differential binding to MARCO. In vitro studies with Chinese hamster ovary (CHO) cells transfected with human MARCO and mutants were conducted to better characterize MARCO-particulate (ASiO(2), CSiO(2), and TiO(2)) interactions. Results with MARCO-transfected CHO cells and MARCO-specific antibody demonstrated that the scavenger receptor cysteine-rich (SRCR) domain of MARCO was required for particle binding for all the tested particles. Only TiO(2) required divalent cations (viz., Ca(+2) and/or Mg(+2)) for binding to MARCO, and results from competitive binding studies supported the notion that TiO(2) and both the silica particles bound to different motifs in SRCR domain of MARCO. The results also suggest that particle shape and/or crystal structure may be the determinants linking particle binding to MARCO and cytotoxicity. Taken together, these results demonstrate that the SRCR domain of MARCO is required for particle binding and that involvement of different regions of SRCR domain may distinguish downstream events following particle binding.

Silica binding and toxicity in alveolar macrophages.

Inhalation of the crystalline form of silica is associated with a variety of pathologies, from acute lung inflammation to silicosis, in addition to autoimmune disorders and cancer. Basic science investigators looking at the mechanisms involved with the earliest initiators of disease are focused on how the alveolar macrophage interacts with the inhaled silica particle and the consequences of silica-induced toxicity on the cellular level. Based on experimental results, several rationales have been developed for exactly how crystalline silica particles are toxic to the macrophage cell that is functionally responsible for clearance of the foreign particle. For example, silica is capable of producing reactive oxygen species (ROS) either directly (on the particle surface) or indirectly (produced by the cell as a response to silica), triggering cell-signaling pathways initiating cytokine release and apoptosis. With murine macrophages, reactive nitrogen species are produced in the initial respiratory burst in addition to ROS. An alternative explanation for silica toxicity includes lysosomal permeability, by which silica disrupts the normal internalization process leading to cytokine release and cell death. Still other research has focused on the cell surface receptors (collectively known as scavenger receptors) involved in silica binding and internalization. The silica-induced cytokine release and apoptosis are described as the function of receptor-mediated signaling rather than free radical damage. Current research ideas on silica toxicity and binding in the alveolar macrophage are reviewed and discussed.