Pseudomonas aeruginosa associated pulmonary infections and in vitro amplification virulent rhamnolipid (rhlR) gene / Infecções pulmonares associadas a Pseudomonas aeruginosa e gene ramnolipídeo virulento (rhlR) da amplificação in vitro

Background: Pseudomonas aeruginosa is a common opportunistic pathogenic bacterium with the ability to develop a strong communication pathway by quorum sensing system and different virulent factors. Among the various important secretions of P. aeruginosa rhamnolipid is important biological detergent, believed to be involved in the development of the biofilm and intercellular communication. It readily dissolves the lung surfactants that are then easily catalyzed by the phospholipases and in this way is involved in the acute pulmonary infection. Objective: research work was designed to investigate virulence and gene associated with virulence in P. aeruginosa responsible for pulmonary infections. Methods: In current study polymerase chain reaction (PCR) was used for the detection of the rhlR (rhamnolipid encoding) gene of isolated strains. A number of assays were performed that ensured its virulent behavior. Disc diffusion method was used to check its antibiotic resistance. Isolated strains were resistant to a number of antibiotics applied. Result: It was found that males are more prone to respiratory infections as compared to females. Male members with age of 44-58 and 59-73 are at a higher risk, while females with age of 44-58 are also at a risk of pulmonary infections. Antibiotic resistance was observed by measuringzone of inhibition in strains GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 and GCU-SG-M6. GCU-SG-M2 was resistant to fluconazole (FLU), clarithromycin (CLR), cefixime (CFM) and Penicillin (P10). No zone of inhibition was observed. But it showed unusual diffused zone around the Ak and MEM antibiotic discs. rhl R gene and 16s rRNA gene were characterized and analyzed. Conclusion: Findings from current study would help[...].

Antecedentes: Pseudomonas aeruginosa é uma bactéria patogênica oportunista comum, com a capacidade de desenvolver uma forte via de comunicação pelo sistema de detecção de quorum e diferentes fatores virulentos. Entre as várias secreções importantes de P. aeruginosa rhamnolipid, há um importante detergente biológico, que se acredita estar envolvido no desenvolvimento do biofilme e na comunicação intercelular. Dissolve rapidamente os surfactantes pulmonares que são facilmente catalisados pelas fosfolipases e, dessa maneira, estão envolvidos na infecção pulmonar aguda. Objetivo: O trabalho de pesquisa foi desenhado para investigar a virulência e o gene associado à virulência em P. aeruginosa responsável por infecções pulmonares. Métodos: No presente estudo, a reação em cadeia da polimerase (PCR) foi utilizada para a detecção do gene rhlR (codificação ramnolipídeo) de cepas isoladas. Foram realizados vários ensaios que garantiram seu comportamento virulento. O método de difusão em disco foi utilizado para verificar sua resistência a antibióticos. As estirpes isoladas foram resistentes a vários antibióticos aplicados. Resultado: Verificou-se que os homens são mais propensos a infecções respiratórias em comparação às mulheres. Membros do sexo masculino com idade entre 44 e 58 e 59 e 73 anos correm maior risco, enquanto mulheres com idade entre 44 e 58 anos também correm risco de infecções pulmonares. A resistência aos antibióticos foi observada medindo a zona de inibição nas cepas GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 e GCU-SG-M6. O GCU-SG-M2 foi resistente ao fluconazol (FLU), claritromicina (CLR), cefixima (CFM) e penicilina (P10). Nenhuma zona de inibição foi observada. Mas se notou uma zona difusa incomum ao redor dos discos antibióticos Ak e MEM. Os genes rhl R e 16s rRNA foram caracterizados e analisados. Conclusão: As conclusões do presente estudo ajudariam a aumentar a conscientização sobre a resistência a antibióticos de, [...].

Pseudomonas aeruginosa associated pulmonary infections and in vitro amplification virulent rhamnolipid (rhlR) gene

Abstract Background Pseudomonas aeruginosa is a common opportunistic pathogenic bacterium with the ability to develop a strong communication pathway by quorum sensing system and different virulent factors. Among the various important secretions of P. aeruginosa rhamnolipid is important biological detergent, believed to be involved in the development of the biofilm and intercellular communication. It readily dissolves the lung surfactants that are then easily catalyzed by the phospholipases and in this way is involved in the acute pulmonary infection. Objective research work was designed to investigate virulence and gene associated with virulence in P. aeruginosa responsible for pulmonary infections. Methods In current study polymerase chain reaction (PCR) was used for the detection of the rhlR (rhamnolipid encoding) gene of isolated strains. A number of assays were performed that ensured its virulent behavior. Disc diffusion method was used to check its antibiotic resistance. Isolated strains were resistant to a number of antibiotics applied. Result It was found that males are more prone to respiratory infections as compared to females. Male members with age of 44-58 and 59-73 are at a higher risk, while females with age of 44-58 are also at a risk of pulmonary infections. Antibiotic resistance was observed by measuring zone of inhibition in strains GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 and GCU-SG-M6. GCU-SG-M2 was resistant to fluconazole (FLU), clarithromycin (CLR), cefixime (CFM) and Penicillin (P10). No zone of inhibition was observed. But it showed unusual diffused zone around the Ak and MEM antibiotic discs. rhl R gene and 16s rRNA gene were characterized and analyzed. Conclusion Findings from current study would help in raising awareness about antibiotic resistance of P. aeruginosa, and also the sequence of rhl R gene can be used as the diagnostic marker sequence to identify the virulent rhl R gene sequence from the samples when isolated from sputum of Pneumonia patients.

Resumo Antecedentes Pseudomonas aeruginosa é uma bactéria patogênica oportunista comum, com a capacidade de desenvolver uma forte via de comunicação pelo sistema de detecção de quorum e diferentes fatores virulentos. Entre as várias secreções importantes de P. aeruginosa rhamnolipid, há um importante detergente biológico, que se acredita estar envolvido no desenvolvimento do biofilme e na comunicação intercelular. Dissolve rapidamente os surfactantes pulmonares que são facilmente catalisados pelas fosfolipases e, dessa maneira, estão envolvidos na infecção pulmonar aguda. Objetivo O trabalho de pesquisa foi desenhado para investigar a virulência e o gene associado à virulência em P. aeruginosa responsável por infecções pulmonares. Métodos No presente estudo, a reação em cadeia da polimerase (PCR) foi utilizada para a detecção do gene rhlR (codificação ramnolipídeo) de cepas isoladas. Foram realizados vários ensaios que garantiram seu comportamento virulento. O método de difusão em disco foi utilizado para verificar sua resistência a antibióticos. As estirpes isoladas foram resistentes a vários antibióticos aplicados. Resultado Verificou-se que os homens são mais propensos a infecções respiratórias em comparação às mulheres. Membros do sexo masculino com idade entre 44 e 58 e 59 e 73 anos correm maior risco, enquanto mulheres com idade entre 44 e 58 anos também correm risco de infecções pulmonares. A resistência aos antibióticos foi observada medindo a zona de inibição nas cepas GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 e GCU-SG-M6. O GCU-SG-M2 foi resistente ao fluconazol (FLU), claritromicina (CLR), cefixima (CFM) e penicilina (P10). Nenhuma zona de inibição foi observada. Mas se notou uma zona difusa incomum ao redor dos discos antibióticos Ak e MEM. Os genes rhl R e 16s rRNA foram caracterizados e analisados. Conclusão As conclusões do presente estudo ajudariam a aumentar a conscientização sobre a resistência a antibióticos de P. aeruginosa e, também, a sequência do gene rhl R pode ser usada como sequência de diagnóstico para identificar a sequência virulenta do gene rhl R das amostras quando isoladas do escarro de pacientes com pneumonia.

Pseudomonas aeruginosa associated pulmonary infections and in vitro amplification virulent rhamnolipid (rhlR) gene / Infecções pulmonares associadas a Pseudomonas aeruginosa e gene ramnolipídeo virulento (rhlR) da amplificação in vitro

Background: Pseudomonas aeruginosa is a common opportunistic pathogenic bacterium with the ability to develop a strong communication pathway by quorum sensing system and different virulent factors. Among the various important secretions of P. aeruginosa rhamnolipid is important biological detergent, believed to be involved in the development of the biofilm and intercellular communication. It readily dissolves the lung surfactants that are then easily catalyzed by the phospholipases and in this way is involved in the acute pulmonary infection. Objective: research work was designed to investigate virulence and gene associated with virulence in P. aeruginosa responsible for pulmonary infections. Methods: In current study polymerase chain reaction (PCR) was used for the detection of the rhlR (rhamnolipid encoding) gene of isolated strains. A number of assays were performed that ensured its virulent behavior. Disc diffusion method was used to check its antibiotic resistance. Isolated strains were resistant to a number of antibiotics applied. Result: It was found that males are more prone to respiratory infections as compared to females. Male members with age of 44-58 and 59-73 are at a higher risk, while females with age of 44-58 are also at a risk of pulmonary infections. Antibiotic resistance was observed by measuring zone of inhibition in strains GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 and GCU-SG-M6. GCU-SG-M2 was resistant to fluconazole (FLU), clarithromycin (CLR), cefixime (CFM) and Penicillin (P10). No zone of inhibition was observed. But it showed unusual diffused zone around the Ak and MEM antibiotic discs. rhl R gene and 16s rRNA gene were characterized and analyzed. Conclusion: Findings from current study would help in raising awareness about antibiotic resistance of P. aeruginosa, and also the sequence of rhl R gene can be used as the diagnostic marker sequence to identify the virulent rhl R gene sequence from the samples when isolated from sputum of Pneumonia patients.

Antecedentes: Pseudomonas aeruginosa é uma bactéria patogênica oportunista comum, com a capacidade de desenvolver uma forte via de comunicação pelo sistema de detecção de quorum e diferentes fatores virulentos. Entre as várias secreções importantes de P. aeruginosa rhamnolipid, há um importante detergente biológico, que se acredita estar envolvido no desenvolvimento do biofilme e na comunicação intercelular. Dissolve rapidamente os surfactantes pulmonares que são facilmente catalisados pelas fosfolipases e, dessa maneira, estão envolvidos na infecção pulmonar aguda. Objetivo: O trabalho de pesquisa foi desenhado para investigar a virulência e o gene associado à virulência em P. aeruginosa responsável por infecções pulmonares. Métodos: No presente estudo, a reação em cadeia da polimerase (PCR) foi utilizada para a detecção do gene rhlR (codificação ramnolipídeo) de cepas isoladas. Foram realizados vários ensaios que garantiram seu comportamento virulento. O método de difusão em disco foi utilizado para verificar sua resistência a antibióticos. As estirpes isoladas foram resistentes a vários antibióticos aplicados. Resultado: Verificou-se que os homens são mais propensos a infecções respiratórias em comparação às mulheres. Membros do sexo masculino com idade entre 44 e 58 e 59 e 73 anos correm maior risco, enquanto mulheres com idade entre 44 e 58 anos também correm risco de infecções pulmonares. A resistência aos antibióticos foi observada medindo a zona de inibição nas cepas GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCUSG-M2, GCU-SG-M1 e GCU-SG-M6. O GCU-SG-M2 foi resistente ao fluconazol (FLU), claritromicina (CLR), cefixima (CFM) e penicilina (P10). Nenhuma zona de inibição foi observada. Mas se notou uma zona difusa incomum ao redor dos discos antibióticos Ak e MEM. Os genes rhl R e 16s rRNA foram caracterizados e analisados. Conclusão: As conclusões do presente estudo ajudariam a aumentar a conscientização sobre a resistência a antibióticos de P. aeruginosa e, também, a sequência do gene rhl R pode ser usada como sequência de diagnóstico para identificar a sequência virulenta do gene rhl R das amostras quando isoladas do escarro de pacientes com pneumonia.

Children with Heterozygous Familial Hypercholesterolemia in the United States: Data from the Cascade Screening for Awareness and Detection-FH Registry.

OBJECTIVE: To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry. STUDY DESIGN: This is a cross-sectional analysis of 493 participants aged <18 years with heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments. RESULTS: Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals. CONCLUSIONS: Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.

Longitudinal low density lipoprotein cholesterol goal achievement and cardiovascular outcomes among adult patients with familial hypercholesterolemia: The CASCADE FH registry.

BACKGROUND AND AIMS: There are limited data from the US on outcomes of patients in specialty care for familial hypercholesterolemia (FH). METHODS: CASCADE FH Registry data were analyzed to assess longitudinal changes in medication usage, in low density lipoprotein cholesterol (LDL-C) levels, and the rate of major adverse cardiovascular events (MACE (myocardial infarction, coronary revascularization, stroke or transient ischemic attack) in adults with FH followed in US specialty clinics. RESULTS: The cohort consisted of 1900 individuals (61% women, 87% Caucasian), with mean age of 56 ±â€¯15 years, 37% prevalence of ASCVD at enrollment, mean pretreatment LDL-C 249 ±â€¯68 mg/dl, mean enrollment LDL-C 145 mg/dl and 93% taking lipid lowering therapy. Over follow up of 20 ±â€¯11 months, lipid lowering therapy use increased (mean decrease in LDL-C of 32 mg/dl (p < 0.001)). Only 48% of participants achieved LDL-C < 100 mg/dl and 22% achieved LDL-C < 70 mg/dl; ASCVD at enrollment was associated with greater likelihood of goal achievement. MACE event rates were almost 6 times higher among patients with prior ASCVD compared to those without (4.6 vs 0.8/100 patient years). Also associated with incident MACE were markers of FH severity and conventional ASCVD risk factors. CONCLUSIONS: With care in FH specialized clinics, LDL-C decreased, but LDL-C persisted >100 mg/dl in 52% of patients. High ASCVD event rates suggest that adults with FH warrant designation as having an ASCVD risk equivalent. Earlier and more aggressive therapy of FH is needed to prevent ASCVD events.

Characterization of Breast Lesions Using a Novel Combined Approach of Ultrasonography and Elastography Prior to Invasive Procedures: Are New Age Modalities Set to Replace the Diagnostic Giant?

Objective The goal of this study was to evaluate the diagnostic yield of B-mode ultrasound and ultrasound elastography used alone and in combination for differentiating breast lesions into benign and malignant. Materials and methods Eighty-five patients were investigated with B-mode ultrasonography and elastography and provided a Breast Imaging Reporting, and Data System (BI-RADS) score based on ultrasonography, strain ratio, and elastography score (ES) based on elastography. Each lesion was then evaluated by a combination method, combining BI-RADS with strain ratio and BI-RADS with elastography score. Each modality was assessed for the successful detection and characterization of the lesion and whether combining ultrasonography B-mode imaging with strain elastography improves diagnosis and is reliable enough to replace invasive procedures such as biopsy that have been the mainstay of diagnosis. Results Of 85 lesions, 23 lesions (27%) were found to be malignant, and 62 lesions (72.9%) were benign. When used alone, BI-RADS had 100.0% sensitivity, 13% specificity, 50% and 100% positive and negative predictive values (respectively), and 72.9% accuracy. BI-RADS results were then combined with strain ratio (SR) and ES. BI-RADS with SR had 91.3% sensitivity, 95.2% specificity, 87.5% and 96.7% positive and negative predictive values (respectively), and 94.1% accuracy. Similarly, BI-RADS with ES had 91.3% sensitivity, 93.5% specificity, 84.0% and 96.7% positive and negative predictive values, and 92.9% accuracy. Conclusions The combination method performs better at diagnosing breast lesions than BI-RADS alone and can be used as an early and preliminary basis for diagnosis and in settings where invasive procedures cannot be performed. Combining strain elastography and BI-RADS also help characterize which lesions are better suited for biopsy, leading to a decline in unnecessary invasive procedures.

Novel technique using tensor fascia lata graft to reconstruct a floor of mouth postablative defect from invasive ectopic papillary carcinoma of the thyroglossal duct tract.

We describe a rare case of ectopic papillary thyroid cancer in the thyroglossal duct tract invading the floor-of-mouth musculature. The postablative defect was reconstructed with a bone-anchored tensor fascia lata graft to resuspend the floor of mouth to the mandible as a neogeniohyoid sling, enabling maintenance of a functional tongue position for normal speech and swallowing. This reconstruction should be considered when suprahyoid musculature is resected without breaching the oral lining.

Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel.

Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.

Health disparities among adult patients with a phenotypic diagnosis of familial hypercholesterolemia in the CASCADE-FH™ patient registry.

BACKGROUND AND AIMS: Most familial hypercholesterolemia (FH) patients remain undertreated, and it is unclear what role health disparities may play for FH patients in the US. We sought to describe sex and racial/ethnic disparities in a national registry of US FH patients. METHODS: We analyzed data from 3167 adults enrolled in the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE-FH) registry. Logistic regression was used to evaluate for disparities in LDL-C goals and statin use, with adjustments for covariates including age, cardiovascular risk factors, and statin intolerance. RESULTS: In adjusted analyses, women were less likely than men to achieve treated LDL-C of <100 mg/dL (OR 0.68, 95% CI, 0.57-0.82) or ≥50% reduction from pretreatment LDL-C (OR 0.79, 95% CI, 0.65-0.96). Women were less likely than men to receive statin therapy (OR, 0.60, 95% CI, 0.50-0.73) and less likely to receive a high-intensity statin (OR, 0.60, 95% CI, 0.49-0.72). LDL-C goal achievement also varied by race/ethnicity: compared with whites, Asians and blacks were less likely to achieve LDL-C levels <100 mg/dL (Asians, OR, 0.47, 95% CI, 0.24-0.94; blacks, OR, 0.49, 95% CI, 0.32-0.74) or ≥50% reduction from pretreatment LDL-C (Asians, OR 0.56, 95% CI, 0.32-0.98; blacks, OR 0.62, 95% CI, 0.43-0.90). CONCLUSIONS: In a contemporary US population of FH patients, we identified differences in LDL-C goal attainment and statin usage after stratifying the population by either sex or race/ethnicity. Our findings suggest that health disparities contribute to the undertreatment of US FH patients. Increased efforts are warranted to raise awareness of these disparities.

US physician practices for diagnosing familial hypercholesterolemia: data from the CASCADE-FH registry.

BACKGROUND: In the US familial hypercholesterolemia (FH), patients are underidentified, despite an estimated prevalence of 1:200 to 1:500. Criteria to identify FH patients include Simon Broome, Dutch Lipid Clinic Network (DLCN), or Make Early Diagnosis to Prevent Early Deaths (MEDPED). The use of these criteria in US clinical practices remains unclear. OBJECTIVE: To characterize the FH diagnostic criteria applied by US lipid specialists participating in the FH Foundation's CASCADE FH (CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia) patient registry. METHODS: We performed an observational, cross-sectional analysis of diagnostic criteria chosen for each adult patient, both overall and by baseline patient characteristics, at 15 clinical sites that had contributed data to the registry as of September 8, 2015. A sample of 1867 FH adults was analyzed. The median age at FH diagnosis was 50 years, and the median pretreatment low-density lipoprotein cholesterol (LDL-C) value was 238 mg/dL. The main outcome was the diagnostic criteria chosen. Diagnostic criteria were divided into five nonexclusive categories: "clinical diagnosis," MEDPED, Simon Broome, DLCN, and other. RESULTS: Most adults enrolled in CASCADE FH (55.0%) received a "clinical diagnosis." The most commonly used formal criteria was Simon-Broome only (21%), followed by multiple diagnostic criteria (16%), MEDPED only (7%), DLCN only (1%), and other (0.5%), P < .0001. Of the patients with only a "clinical diagnosis," 93% would have met criteria for Simon Broome, DLCN, or MEDPED based on the data available in the registry. CONCLUSIONS: Our findings demonstrate heterogeneity in the application of FH diagnostic criteria in the United States. A nationwide consensus definition may lead to better identification, earlier treatment, and ultimately CHD prevention.

Treatment Gaps in Adults With Heterozygous Familial Hypercholesterolemia in the United States: Data From the CASCADE-FH Registry.

BACKGROUND: Cardiovascular disease burden and treatment patterns among patients with familial hypercholesterolemia (FH) in the United States remain poorly described. In 2013, the FH Foundation launched the Cascade Screening for Awareness and Detection (CASCADE) of FH Registry to address this knowledge gap. METHODS AND RESULTS: We conducted a cross-sectional analysis of 1295 adults with heterozygous FH enrolled in the CASCADE-FH Registry from 11 US lipid clinics. Median age at initiation of lipid-lowering therapy was 39 years, and median age at FH diagnosis was 47 years. Prevalent coronary heart disease was reported in 36% of patients, and 61% exhibited 1 or more modifiable risk factors. Median untreated low-density lipoprotein cholesterol (LDL-C) was 239 mg/dL. At enrollment, median LDL-C was 141 mg/dL; 42% of patients were taking high-intensity statin therapy and 45% received >1 LDL-lowering medication. Among FH patients receiving LDL-lowering medication(s), 25% achieved an LDL-C <100 mg/dL and 41% achieved a ≥50% LDL-C reduction. Factors associated with prevalent coronary heart disease included diabetes mellitus (adjusted odds ratio 1.74; 95% confidence interval 1.08-2.82) and hypertension (2.48; 1.92-3.21). Factors associated with a ≥50% LDL-C reduction from untreated levels included high-intensity statin use (7.33; 1.86-28.86) and use of >1 LDL-lowering medication (1.80; 1.34-2.41). CONCLUSIONS: FH patients in the CASCADE-FH Registry are diagnosed late in life and often do not achieve adequate LDL-C lowering, despite a high prevalence of coronary heart disease and risk factors. These findings highlight the need for earlier diagnosis of FH and initiation of lipid-lowering therapy, more consistent use of guideline-recommended LDL-lowering therapy, and comprehensive management of traditional coronary heart disease risk factors.

Differential S-nitrosylation of proteins in Alzheimer's disease.

Numerous studies have provided evidence regarding the involvement of protein S-nitrosylation in the progression of Alzheimer's disease (AD) pathology and its implication in the formation and accumulation of misfolded protein aggregates. The identification of S-nitrosylated proteins can be a major step toward the understanding of mechanisms leading to neuronal degeneration. The present study targeted S-nitrosylated proteins in AD hippocampus, substantia nigra and cortex using the following work-flow that combines S-nitrosothiol-specific antibody detection, classical biotin switch method labeled with fluorescence dye followed by electrospray ionization quadrupole time of flight tandem MS (ESI-QTOF MS/MS) identification. Endogenous nitrosocysteines were identified in 45 proteins, mainly involved in metabolism, signaling pathways, apoptosis and redox regulation as assigned by REACTOME and KEGG pathway database analysis. Superoxide dismutase (SOD2) [Mn], fructose-bisphosphate aldolase C (ALDOC) and voltage-dependent anion-selective channel protein 2 (VDAC2) showed differential S-nitrosylation signal, not previously reported in AD regions. Extensive neuronal atrophy with increased protein S-nitrosylation in AD regions is also evident from immunofluorescence studies using S-nitrosocysteine antibody. A number of plausible cysteine modification sites were predicted via Group-based Prediction System-S-nitrosothiols (GPS-SNO) 1.0 while STRING 8.3 analysis revealed functional annotations in the modified proteins. The findings are helpful in characterization of functional abnormalities and may facilitate the understanding of molecular mechanisms and biological function of S-nitrosylation in AD pathology.

Tuberculous cervical lymphadenitis in a patient with laryngeal carcinoma.

OBJECTIVE: We report an extremely rare presentation of concomitant tuberculous cervical lymphadenitis in a patient with carcinoma of the larynx. CASE REPORT: A 66-year-old man presented with a nine-month history of hoarseness. He was found to have an exophytic lesion over the posterior half of the right vocal fold. He also had a palpable right jugulodigastric node. Biopsy of the vocal fold lesion revealed invasive squamous cell carcinoma. Histological analysis of an excision biopsy specimen from the lymph node was highly suggestive of tuberculosis. On further assessment of the slides, one acid-fast bacillus was seen. The patient was treated with radiotherapy to the larynx and concomitant anti-tuberculosis chemotherapy. Five months following treatment, there was no sign of laryngeal cancer recurrence; however, the patient continued to have a productive cough and night sweats. CONCLUSION: To our knowledge, this is the first report of a laryngeal carcinoma with concurrent tuberculous cervical lymphadenitis. In the face of an unhelpful fine needle aspiration cytology examination, an assumption of metastatic neck disease could have been made. Subsequent surgical and/or oncological intervention would have been highly inappropriate, with potentially catastrophic effects. This case highlights the importance of proper diagnosis, and emphasises the fact that tuberculosis should always be borne in mind in the differential diagnosis.