Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 178
Filter
1.
Virusdisease ; 35(2): 321-328, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39071868

ABSTRACT

H9N2 avian Influenza virus subtype is highly neglected but have the potential to emerge as a next pandemic influenza virus, by either itself evolution or through the donation of genes to other subtype. So to understand the extent of H9N2 virus prevalence and associated risk factors in poultry of retail shops and their surrounding environment a cross sectional study was carried out. A total of 500 poultry tissue and 700 environmental samples were collected from 20 district of Madhya Pradesh. Virus isolation was carried out in egg inoculation and harvested allantoic fluid was tested for HA and further molecular confirmation of subtypes by RT-PCR using H9 specific primers. Prevalence was calculated and positive samples were statistically associated with observed risk factors using univariate and multivariate logistic regression analysis. A total of 9.4% and 9.7% prevalence in tissue samples and environmental samples has been reported respectively and out of 20 districts 10 (50%) were found positive for the virus. Out of 21 studied risk factors only two risk factors named as "keeping total number birds slaughtered per day" and "procuring birds from wholesaler" were found significantly associated with the H9N2 positivity in multivariate logistic regression analysis. This high level of H9N2 positivity in birds with no clinical manifestations providing a great opportunity for avian influenza virus for amplification, co-infection in other animals like dogs, cats, pigs and in human through genetic re-assortment that may lead to emergence of a novel influenza virus with high zoonotic potential. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-024-00865-y.

2.
AJNR Am J Neuroradiol ; 43(12): E46-E53, 2022 12.
Article in English | MEDLINE | ID: mdl-36456085

ABSTRACT

Magnetoencephalography, the extracranial detection of tiny magnetic fields emanating from intracranial electrical activity of neurons, and its source modeling relation, magnetic source imaging, represent a powerful functional neuroimaging technique, able to detect and localize both spontaneous and evoked activity of the brain in health and disease. Recent years have seen an increased utilization of this technique for both clinical practice and research, in the United States and worldwide. This report summarizes current thinking, presents recommendations for clinical implementation, and offers an outlook for emerging new clinical indications.


Subject(s)
Brain , Magnetoencephalography , Humans , Magnetoencephalography/methods , Brain/diagnostic imaging , Brain/physiology , Neuroimaging , Neurons , Magnetic Phenomena
3.
Proc Nutr Soc ; 81(1): 1-11, 2022 03.
Article in English | MEDLINE | ID: mdl-34726148

ABSTRACT

The liver is a key metabolic organ that undertakes a multitude of physiological processes over the course of a day, including intrahepatic lipid and glucose metabolism which plays a key role in the regulation of systemic lipid and glucose concentrations. It serves as an intermediary organ between exogenous (dietary) and endogenous energy supply to extrahepatic organs. Thus, perturbations in hepatic metabolism can impact widely on metabolic disease risk. For example, the accumulation of intra-hepatocellular TAG (IHTG), for which adiposity is almost invariably a causative factor may result in dysregulation of metabolic pathways. Accumulation of IHTG is likely due to an imbalance between fatty acid delivery, synthesis and removal (via oxidation or export as TAG) from the liver; insulin plays a key role in all of these processes.


Subject(s)
Insulin Resistance , Non-alcoholic Fatty Liver Disease , Fatty Acids/metabolism , Glucose/metabolism , Humans , Lipid Metabolism/physiology , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Obesity/metabolism
4.
Sci Rep ; 11(1): 19324, 2021 Sep 29.
Article in English | MEDLINE | ID: mdl-34588466

ABSTRACT

Detection of nitroaromatics employing greener techniques has been one of the most active research fields in chemistry. A series of triphenylamine (TPA) functionalized carboxylic acids were synthesized and characterized using various spectroscopic techniques including single-crystal X-ray diffraction analysis. The interaction of carboxylic acid-decorated TPAs with nitroaromatic compounds was photophysically explored using absorption and emission spectroscopy. Stern-Volmer plot accounts for the appreciable quenching constant of the TPA-acids. Density functional theory calculations were carried out to study the new compounds' frontier molecular orbital energy levels and the possible interactions with picrate anion and revealed an unusual charge transfer interaction between acids and picrate anion. The contact mode detection shows the TPA-acids can be used as dip-strip sensors for picric acid detection.

5.
Elife ; 102021 06 22.
Article in English | MEDLINE | ID: mdl-34155973

ABSTRACT

Semantic representations are processed along a posterior-to-anterior gradient reflecting a shift from perceptual (e.g., it has eight legs) to conceptual (e.g., venomous spiders are rare) information. One critical region is the anterior temporal lobe (ATL): patients with semantic variant primary progressive aphasia (svPPA), a clinical syndrome associated with ATL neurodegeneration, manifest a deep loss of semantic knowledge. We test the hypothesis that svPPA patients perform semantic tasks by over-recruiting areas implicated in perceptual processing. We compared MEG recordings of svPPA patients and healthy controls during a categorization task. While behavioral performance did not differ, svPPA patients showed indications of greater activation over bilateral occipital cortices and superior temporal gyrus, and inconsistent engagement of frontal regions. These findings suggest a pervasive reorganization of brain networks in response to ATL neurodegeneration: the loss of this critical hub leads to a dysregulated (semantic) control system, and defective semantic representations are seemingly compensated via enhanced perceptual processing.


Subject(s)
Aphasia, Primary Progressive/physiopathology , Nerve Degeneration/physiopathology , Neurons/physiology , Semantics , Temporal Lobe/physiopathology , Aged , Female , Humans , Male , Middle Aged
6.
Food Chem ; 341(Pt 2): 128646, 2021 Mar 30.
Article in English | MEDLINE | ID: mdl-33229161

ABSTRACT

Curcumin, together with demethoxycurcumin and bisdemethoxycurcumin as a whole called curcuminoids, is an active phytochemical constituent present in the turmeric. When it comes to their analysis, most will rely on UV-Visible spectroscopy, HPLC and LC-MS methods. Looking to improve productivity, time and simplicity, we are proposing a 1H NMR based approach for curcuminoids analysis and its applications to different geographical regions. In the present work, sample preparation protocol is reported for the simultaneous determination of curcuminoids using 1H NMR. For the quantification of curcuminoids, 6-7 ppm vinylic proton region in the 1H NMR spectrum was used, where acetone was observed as the suitable solvent in terms of curcuminoids solubility and proper resolution of peak. The result shows that curcumin (46.8-59.50%) was major among all varieties, followed by DMC (22.15-27.70%) and BDMC (17.52-30.29%) except in Andhrapradesh variety, where BDMC (30.29%) was more than DMC (22.89%). These studies were further supported by HPLC analysis.


Subject(s)
Curcuma/chemistry , Diarylheptanoids/chemistry , Proton Magnetic Resonance Spectroscopy/methods , Chromatography, High Pressure Liquid , Limit of Detection , Plant Extracts/chemistry , Reference Standards , Solvents/chemistry
7.
Acta Virol ; 64(3): 325-330, 2020.
Article in English | MEDLINE | ID: mdl-32985206

ABSTRACT

We investigated the experimental infection of two highly pathogenic avian influenza H5N1 viruses isolated from crow (A/crow/Assam/142119/2008) and chicken (A/chicken/Sikkim/151466/2009) in house crows (Corvus splendens). Both viruses caused infection in crows, where four out of six and three out of six crows succumbed to H5N1 infection within 11 days post challenge by crow and chicken viruses, respectively. The major clinical signs in crows were wing paralysis, circling and torticollis. The virus shedding detected from swabs was not persistent in both crow nor chicken viruses. Both viruses were isolated more frequently from oral swabs than from cloacal swabs. Both virus strains were isolated from brain, lungs, heart, liver, pancreas, spleen, large intestines of crows that succumbed to H5N1 infection. The surviving birds seroconverted in response to H5N1 virus infection. Microscopically, both viruses caused coagulative necrosis in pancreas and kidneys. Brain showed gliosis and neuronal degeneration. This experimental study highlights that crows could be infected with H5N1 viruses from different hosts with minor differences in pathogenicity. Therefore, it is imperative to carry out surveillance of highly pathogenic avian influenza H5N1 virus in synanthropic birds along with biosecurity measures to mitigate the H5N1 spread in poultry population. Keywords: chicken virus; crow virus; highly pathogenic avian influenza; house crows.


Subject(s)
Influenza A Virus, H5N1 Subtype/pathogenicity , Influenza in Birds/virology , Animals , Chickens , Crows , Influenza in Birds/pathology
8.
Int J Obstet Anesth ; 44: 3-12, 2020 11.
Article in English | MEDLINE | ID: mdl-32673965

ABSTRACT

BACKGROUND: Unless prevented, hypotension occurs in up to 80% of normotensive women undergoing spinal anaesthesia for caesarean delivery. Renin-angiotensin-aldosterone system genetic polymorphisms have been associated with hypertensive disease, but few studies investigated effects on blood pressure regulation under spinal anaesthesia. We postulated that these polymorphisms increased vasodilation and maternal hypotension during spinal anaesthesia. METHODS: A retrospective secondary analysis of data from four prospective trials with similar inclusion/exclusion criteria evaluating phenylephrine/ephedrine delivery systems during spinal anaesthesia for elective caesarean delivery. Angiotensin type-1 receptor (AT1R) (A1166C), angiotensin-converting enzyme (ACE) (I/D), and aldosterone synthase CYP11B2 (C344T) polymorphisms were identified from stored specimens. The associations between the polymorphisms and hypotension (systolic blood pressure <80% of baseline), and vasopressor use, were determined by univariable and multivariable regression. RESULTS: Of 556 patients, 378 (68.0%) had hypotension. The AC/CC genotypes of AT1R (A1166C) were associated with hypotension by univariable analysis (OR 2.70, 95% CI 1.38 to 5.28, P=0.004]) and multivariable analysis (OR 3.65, [95% CI 1.68 to 7.94, P=0.004]) after adjustment for age, race, intravenous fluid volume, and block height. No difference in vasopressor use or adverse maternal or fetal outcomes were noted. Baseline characteristics were similar, with the exception of higher baseline blood pressure, block height, and intravenous fluid volume in the hypotensive group. There was no significant association between ACE and CYP11B2 polymorphisms and hypotension. CONCLUSION: AC/CC genotypes of AT1R (A1166C) polymorphism were associated with maternal hypotension under spinal anaesthesia for caesarean delivery. An association with cardiovascular indices and high-risk parturients should be examined.


Subject(s)
Anesthesia, Obstetrical , Anesthesia, Spinal , Cesarean Section , Hypotension/genetics , Polymorphism, Genetic/genetics , Receptor, Angiotensin, Type 1/genetics , Renin-Angiotensin System/genetics , Adult , Cohort Studies , Female , Humans , Middle Aged , Mothers , Pregnancy , Prospective Studies , Retrospective Studies , Young Adult
9.
Ophthalmic Epidemiol ; 27(5): 344-353, 2020 10.
Article in English | MEDLINE | ID: mdl-32351148

ABSTRACT

PURPOSE: The integration of primary eyecare into existing primary healthcare systems requires simple yet effective tools that do not overburden the grass-root level worker. The objective of this study was to test the accuracy of a questionnaire-based tool administered by trained community-based rehabilitation volunteers (CBRVs) in identifying persons with visual disability, proportions accessing referral pathway and barriers to uptake of eyecare services. METHODS: CBRVs working in the urban-slum service area of a teaching hospital were trained in administering a questionnaire-based tool derived from the World Health Organization (WHO) "Training in the community for people with disabilities" to a responsible adult member of the household. Post-training, they screened and referred adults with perceived visual problems. This tool was tested against two reference standards: (i) history of visual disability elicited by ophthalmologist; (ii) pre-set visual acuity and diagnosis criteria. RESULTS: Ten CBRVs screened 950 individuals of whom 805 (84.7%) were examined by an optometrist and ophthalmologist. Sensitivity and specificity of this method were 75% (95% CI 72-78%), 95.8% (95% CI 94-98%) respectively, using history and 60.2% (95% CI 57-63%), 91.8% (95% CI 90-94%) using clinical criteria as reference standard. Referral pathway was used by 91/221 (41.2%) referred individuals. The commonest barriers to accessing eye care were 'did not feel the need' (32.2%) and 'busy with work/household responsibilities' (30.2%). CONCLUSIONS: This questionnaire-based tool administered by grass-root level health workers to a responsible adult member of the family may be a promising screening method for identification and appropriate referral of persons with visual disability in the community.


Subject(s)
Disabled Persons , Poverty Areas , Vision Disorders , Adult , Humans , India , Referral and Consultation , Vision Disorders/rehabilitation , Volunteers
10.
Anal Chim Acta ; 1093: 123-130, 2020 Jan 06.
Article in English | MEDLINE | ID: mdl-31735205

ABSTRACT

Accurate and rapid diagnosis of Influenza A viruses (IAVs) is challenging because of multiple strains circulating in humans and animal populations, and the emergence of new strains. In this study, we demonstrate a simple and rapid strategy for visual detection of multiple strains of IAVs (H1 to H16 subtypes) using peptide nucleic acid (PNA) as a biosensor and unmodified gold nanoparticles (AuNPs) as a reporter. The design principle of the assay is based on the color change on account of free PNA-induced aggregation of AuNPs in the presence of non-complementary viral RNA sequence and vice-versa. The assay could detect IAV RNA with a visual limit of detection of 2.3 ng. The quantification of RNA with a considerable accuracy on a simple spectrophotometer was achieved on plotting the PNA-induced colorimetric changes (absorption ratio of A640/A520) in the presence of a varying concentration of complementary RNA. As a proof-of-concept, the visual assay was validated on 419 avian clinical samples and receiver operating characteristic (ROC) curve analysis showed a high diagnostic specificity (96.46%, 95% CI = 93.8 to 98.2) and sensitivity (82.41%, 95% CI = 73.9 to 89.1) when RT-qPCR was used as reference test. Hence, the simplicity, rapidity, and universality of this strategy make it a potential candidate visual assay for clinical diagnosis and surveillance of IAVs, especially in the resource-limited settings. The proposed strategy establishes new avenues for developing a simple and rapid diagnostic system for viral infections and biomolecules.


Subject(s)
Biosensing Techniques/methods , Colorimetry/methods , Influenza A virus/isolation & purification , Peptide Nucleic Acids/chemistry , RNA, Viral/analysis , Animals , Birds/virology , Gold/chemistry , Limit of Detection , Metal Nanoparticles/chemistry , Nucleic Acid Hybridization , Peptide Nucleic Acids/genetics , Proof of Concept Study , RNA, Viral/genetics , ROC Curve
11.
J Forensic Dent Sci ; 10(1): 5-7, 2018.
Article in English | MEDLINE | ID: mdl-30122862

ABSTRACT

Children should be given the privilege to mature in a loving, supportive family environment that promotes the development of an individual to his/her full potential. The abuse and neglect of children is a problem that pervades all segments of society. Dentists/forensic odontologists are in a strategic position to recognize mistreated children. While the detection of dental care neglect is an obvious responsibility for dentists, other types of child abuse and neglect also may present themselves in the dental office. Once this information is known to the dentist, he/she can join physicians in protecting children from injury.

12.
J Appl Microbiol ; 124(2): 408-422, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29178633

ABSTRACT

AIMS: To enhance the antimicrobial and antibiofilm activity of norfloxacin against the planktonic and biofilm mode of growth in ESKAPE pathogens using chemically modified norfloxacin salts. METHODS AND RESULTS: Antimicrobial testing, synergy testing and time-kill curve analysis were performed to evaluate antibacterial effect of norfloxacin carboxylic acid salts against ESKAPE pathogens. In vivo efficacy to reduce bacterial bioburden was evaluated in zebrafish infection model. Crystal violet assay and live-dead staining were performed to discern antibiofilm effect. Membrane permeability, integrity and molecular docking studies were carried out to ascertain the mechanism of action. The carboxylic acid salts, relative to parent molecule norfloxacin, displayed two- to fourfold reduction in minimum inhibitory concentration against Staphylococcus aureus and Pseudomonas aeruginosa, in addition to displaying potent bacteriostatic effect against certain members of ESKAPE pathogens. In vivo treatments revealed that norfloxacin tartrate (SRIN2) reduced MRSA bioburden by greater than 1 log fold relative to parent molecule in the muscle tissue. In silico docking with gyrA of S. aureus showed increased affinity of SRIN2 towards DNA gyrase. The enhanced antibacterial effect of norfloxacin salts could be partially accounted by altered membrane permeability in S. aureus and perturbed membrane integrity in P. aeruginosa. Antibiofilm studies revealed that SRIN2 (norfloxacin tartrate) and SRIN3 (norfloxacin benzoate) exerted potent antibiofilm effect particularly against Gram-negative ESKAPE pathogens. The impaired colonization of both S. aureus and P. aeruginosa due to improved norfloxacin salts was further supported by live-dead imaging. CONCLUSION: Norfloxacin carboxylic acid salts can act as potential alternatives in terms of drug resensitization and reuse. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study shows that carboxylic acid salts of norfloxacin could be effectively employed to treat both planktonic- and biofilm-based infections caused by select members of ESKAPE pathogens.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Gram-Negative Aerobic Bacteria/drug effects , Gram-Negative Bacterial Infections/microbiology , Norfloxacin/pharmacology , Staphylococcus aureus/drug effects , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/growth & development , Acinetobacter baumannii/physiology , Animals , Anti-Bacterial Agents/chemistry , Carboxylic Acids/chemistry , Carboxylic Acids/pharmacology , Enterobacter/drug effects , Enterobacter/growth & development , Enterobacter/physiology , Enterococcus faecium/drug effects , Enterococcus faecium/growth & development , Enterococcus faecium/physiology , Escherichia coli/drug effects , Escherichia coli/growth & development , Escherichia coli/physiology , Gram-Negative Aerobic Bacteria/growth & development , Gram-Negative Aerobic Bacteria/physiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/growth & development , Klebsiella pneumoniae/physiology , Microbial Sensitivity Tests , Norfloxacin/chemistry , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & development , Pseudomonas aeruginosa/physiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/growth & development , Staphylococcus aureus/physiology
13.
RSC Adv ; 8(36): 20440-20449, 2018 May 30.
Article in English | MEDLINE | ID: mdl-35541670

ABSTRACT

Herein, we report the covalent functionalization of graphene oxide (GO) through ''click'' reaction and its applications towards ammonia sensing. This inimitable method of covalent functionalization involves linking GO with azide moiety and click coupling of different derivatives of aryl propargyl ether, which enhances the sensitivity towards ammonia. The functionalized GO were characterized using NMR, XRD, SEM, FT-IR, Raman, UV-Vis, TGA and DSC. Compared to pristine GO, the GO functionalized with Ar samples (GO-Ar) exhibit excellent room temperature ammonia sensing properties with good response/recovery characteristics. It has been observed that 2,3-difluoro and 2,3,4-trifluoro substituted aryl propargyl ether functionalized GO (GO-Ar2 and GO-Ar3) shows superior ammonia sensing with response/recovery of 63%/∼90% and 60%/100%, respectively at 20 ppm. The GO-Ar3 exhibits high sensitivity towards ammonia at 20-100 ppm. Computational studies supports the high sensitivity of GO-Ar towards ammonia due to its high adsorption energy.

14.
Zoonoses Public Health ; 65(1): e243-e247, 2018 02.
Article in English | MEDLINE | ID: mdl-28941132

ABSTRACT

Highly pathogenic avian influenza viruses (HPAIV) of H5N1 subtype are a major global threat to poultry and public health. Export of poultry products, such as chicken and duck meat, is a known source for the cross-boundary spread of HPAI H5N1 viruses. Humans get infected with HPAI H5N1 viruses either by close contact with infected poultry or through consumption of fresh/undercooked poultry meat. Skeletal muscle is the largest soft tissue in chicken that has been shown to contain virus during systemic HPAIV infection and supports productive virus infection. However, the time between infection of a chicken with H5N1 virus and presence of virus in muscle tissue is not yet known. Further, it is also not clear whether chicken infected with low doses of H5N1 virus that cause non-fatal subclinical infections continue to accumulate virus in skeletal muscle. We investigated the amount and duration of virus detection in skeletal muscle of chicken experimentally infected with different doses (102 , 103 and 104 EID50 ) of a HPAI H5N1 virus. Influenza viral antigen could be detected as early as 6 hr after infection and live virus was recovered from 48 hr after infection. Notably, chicken infected with lower levels of HPAI H5N1 virus (i.e., 102 EID50 ) did not die acutely, but continued to accumulate high levels of H5N1 virus in skeletal muscle until 6 days post-infection. Our data suggest that there is a potential risk of human exposure to H5N1 virus through meat from clinically healthy chicken infected with a low dose of virus. Our results highlight the need to implement rigorous monitoring systems to screen poultry meat from H5N1 endemic countries to limit the global spread of H5N1 viruses.


Subject(s)
Chickens , Influenza A Virus, H5N1 Subtype/isolation & purification , Influenza in Birds/virology , Muscle, Skeletal/virology , Animals , Humans , Muscle, Skeletal/pathology , Risk Factors , Zoonoses
15.
Zoonoses Public Health ; 65(1): e124-e129, 2018 02.
Article in English | MEDLINE | ID: mdl-29115743

ABSTRACT

Low pathogenic avian influenza virus (LPAIV) exhibits an ecological climax with the aquatic ecosystem. The most widely prevalent subtype of LPAIV is H9N2. Wild aquatic birds being the natural reservoirs and ducks, the "Trojan horses" for Avian Influenza Virus (AIV), can contaminate the natural water bodies inhabited by them. The virus can persist in the contaminated water from days to years depending upon the environmental conditions. Various aquatic species other than ducks can promote the persistence and transmission of AIV; however, studies on the role of aquatic fauna in persistence and transmission of avian influenza virus are scarce. This experiment was designed to evaluate the survivability of H9N2 LPAIV in water with and without Atyopsis moluccensis (bamboo shrimp) for a period of 12 days. The infectivity and amount of virus in water were calculated and were found to be significantly higher in water with A. moluccensis than in water without A. moluccensis. The study also showed that A. moluccensis can accumulate the virus mechanically which can infect chicken eggs up to 11 days. The virus transmission potential of A. moluccensis requires further studies.


Subject(s)
Decapoda/virology , Influenza A Virus, H9N2 Subtype , Animals , Disease Reservoirs , Host-Pathogen Interactions , Microbial Viability , RNA, Viral/genetics , RNA, Viral/metabolism , Time Factors , Virus Replication , Water , Water Microbiology
16.
Sci Rep ; 7(1): 10916, 2017 09 07.
Article in English | MEDLINE | ID: mdl-28883500

ABSTRACT

Advanced structural characterisation techniques which are rapid to use, non-destructive and structurally definitive on the nanoscale are in demand, especially for a detailed understanding of extended-defects and their influence on the properties of materials. We have applied the electron backscatter diffraction (EBSD) technique in a scanning electron microscope to non-destructively characterise and quantify antiphase domains (APDs) in GaP thin films grown on different (001) Si substrates with different offcuts. We were able to image and quantify APDs by relating the asymmetrical intensity distributions observed in the EBSD patterns acquired experimentally and comparing the same with the dynamical electron diffraction simulations. Additionally mean angular error maps were also plotted using automated cross-correlation based approaches to image APDs. Samples grown on substrates with a 4° offcut from the [110] do not show any APDs, whereas samples grown on the exactly oriented substrates contain APDs. The procedures described in our work can be adopted for characterising a wide range of other material systems possessing non-centrosymmetric point groups.

18.
Ann R Coll Surg Engl ; 98(8): e171-e172, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27490988

ABSTRACT

We present a case that we believe to be the largest mixed germ cell testicular tumour reported in the United Kingdom. A 23-year-old male was admitted to our urology department with a large scrotal swelling. The patient was found to have a giant left testicular tumour and a solitary lung metastasis at presentation. He underwent an emergency radical orchidectomy and subsequently received four cycles of bleomycin, etoposide and cisplatin chemotherapy. Four months after starting treatment, the tumour markers had normalised and a repeat staging computed tomography showed no active disease. The tumour reached that size because of the patient's failure to seek medical attention due to fear and embarrassment.


Subject(s)
Carcinoma, Embryonal/diagnosis , Endodermal Sinus Tumor/diagnosis , Testicular Neoplasms/diagnosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Embryonal/pathology , Carcinoma, Embryonal/surgery , Combined Modality Therapy , Endodermal Sinus Tumor/pathology , Endodermal Sinus Tumor/surgery , Humans , Lung Neoplasms/secondary , Male , Orchiectomy , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery , Young Adult
19.
Ann R Coll Surg Engl ; 98(6): e94-6, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27055408

ABSTRACT

Introduction Adenomas of the parathyroid gland typically present with symptoms of hyperparathyroidism, manifested by fatigue, bone pain, abdominal pain, weakness, dyspepsia, nephrolithiasis and skeletal bone disease. Here, we describe, for the first time, a case of a non-functioning benign tumour of the parathyroid gland presenting as vocal-cord paralysis. Case History A 49-year-old male presented with a 10-week history of dysphonia and the feeling of having 'something stuck in my throat'. History-taking elicited no other associated symptoms. Flexible nasal endoscopy demonstrated paralysis of the left vocal cord. Computed tomography of the neck revealed a cystic lesion, 18mm in diameter adjacent to the oesophagus. After more rigorous tests, a neck exploration, left hemithyroidectomy, excision of the left paratracheal mass and level-VI neck dissection was undertaken, without incident to the patient or surgical team. Histology was consistent with a parathyroid adenoma. Conclusions This case emphasises the importance of including adenomatous disease of the parathyroid gland in the differential diagnosis despite normal parathyroid status as a cause of vocal cord palsy.


Subject(s)
Adenoma/diagnosis , Parathyroid Neoplasms/diagnosis , Vocal Cord Paralysis/etiology , Diagnosis, Differential , Dysphonia/etiology , Humans , Male , Middle Aged
20.
Leukemia ; 30(6): 1311-9, 2016 06.
Article in English | MEDLINE | ID: mdl-26854024

ABSTRACT

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.


Subject(s)
Enteropathy-Associated T-Cell Lymphoma/metabolism , Janus Kinases/metabolism , Receptors, G-Protein-Coupled/metabolism , STAT Transcription Factors/metabolism , Signal Transduction , Adult , Aged , Aged, 80 and over , Cell Survival/drug effects , Cells, Cultured , Enteropathy-Associated T-Cell Lymphoma/pathology , Female , GTP-Binding Protein alpha Subunit, Gi2/genetics , Gene Expression Profiling , Humans , Janus Kinase 3/genetics , Male , Middle Aged , Mutation , Protein Kinase Inhibitors/pharmacology , STAT5 Transcription Factor/genetics , Signal Transduction/drug effects , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL