We present a 70-year-old female patient who had the history of hypertension and presented with massive haemoptysis. She had been complaining of cough with expectoration and mild streaking of blood in sputum for about 3 days with only crepts in right infrascapular and infra-axillary regions as positive clinical findings. Bronchoscopy revealed a cauliflower-like lesion in the upper- right lobe bronchus; bronchial aspirate showed occasional colonies of gram positive filamentous bacteria surrounded by neutrophils. The Trucut biopsy showed sheets of neutrophils with colonies of filamentous bacteria consistent with actinomycotic infection. She was started on intravenous benzyl penicillin 20 million units 6 hourly. She recovered with no further bouts of hemoptysis and was discharged on amoxicillin + clavulanic acid in a stable condition and she remained under similar condition for more than a year on follow up. Actinomycosis is a rare disease caused by a harmless commensal species, Actinomyces. Diagnosis of actinomycosis is a challenging situation, and more so, very few cases causing hemoptysis have come to light so far.
Actinomycosis; Hemoptysis; Bronchoscopy
Covered self expandable metallic airway stents (SEMS) have been used for benign tracheal stenosis, post intubation tracheal stenosis, tracheal burn or trauma, tracheo-broncho-malacia, and extrinsic compression of trachea. Their placement is considered to be permanent, with open surgery the only way to remove the stent, though there are few cases reports of their removal with the bronchoscope, but the complications after their removal are very high. In our patient, one and a half years after placement of SEMS, she developed cough with dyspnoea, video bronchoscopy showed stenosis above the level of stent with granulation tissue inside the stent, stent fracture in lower part and stent migration to right main bronchus, thus she had all conceivable complications of stent placement. The stent was removed with the help of rigid bronchoscope under general anaesthesia. She was discharged the following day. The case is being reported because it was unique in having all the possible complications of stent placement, and rare as we could take out the stent in Toto. Thirdly, the stent could be removed without any complication.
Granulation tissue inside the stent; stenosis above the stent; stent fracture; stent migration
The incidence of tracheo-esophageal (TO) fistula is on the rise, especially after palliative management for esophageal malignancies. We report a case of cancer of esophagus who after chemotherapy and radiotherapy developed TO fistula. Placement of an esophageal stent helped him in taking food orally, but his cough and dyspnoea continued to worsen. Fibreoptic bronchoscopy demonstrated a severely compressed trachea secondary to protrusion of esophageal stent which responded very well to an Ultraflex-covered tracheal stent and the patient achieved relief from cough and dyspnoea.
Fibreoptic bronchoscopy; tracheo-esophageal fistula; Ultraflex stent
Hemoptysis is defined as the spitting of blood derived from the lungs or bronchial tubes as a result of pulmonary or bronchial hemorrhage. There is a large chunk of patients with hemoptysis who do not respond to conservative treatment including use of cough suppressants, antibiotics, vitamin C, hemostatics, and anxiolytics. The advanced management of such a situation is bronchial artery embolization (BAE) or open thoracic surgery, which is often not possible. We have attempted a cheap, effective, and safe alternative in the form of intrabronchial instillation of glue (n-butyl cyanoacrylate) under vision with the help of a therapeutic video bronchoscope (OLYMPUS T-180). The glue is instilled through a polyethylene catheter placed through the working channel of the video bronchoscope.
Hemoptysis; video bronchoscopy; glue therapy; n-butyl cyanoacrylate (glue)
Genitourinary histoplasmosis is very rare and to our knowledge only four cases of epididymal histoplasmosis and nine cases of prostatic histoplasmosis have been reported in literature. We hereby report a case of a middle-aged male, who presented three years after renal transplant, with complaints of fever, pain, and swelling in the scrotum. Imaging disclosed an enlarged right epididymis with prostatic and retrotrigonal abscess, suggesting tuberculosis infection. However, histopathology of the epididymal biopsy revealed histoplasmosis, and the drained pus on culture confirmed infection with Histoplasma capsulatum.
Epididymis; histoplasmosis; prostate
Bronchopleural fistula (BPF) is a communication between the pleural space and bronchial tree.
Materials and Methods:
A series of 9 cases are reported where BPF was identified and managed with intrabronchial instillation of glue (N-butyl-cyanoacrylate) through a video bronchoscope.
Out of 9 patients the BPF was successfully sealed in 8 cases (88.88%). In 1 patient of postpneumonectomy, the fistula was big, that is >8 mm who had a recurrence after the procedure. In one case of pyopneumothorax the leak reduced slowly and it took us 14 days to remove the intercostal drainage tube. Rest of the patients had a favorable outcome. No complications were observed in a follow-up of 6 months.
In our opinion, it is a cost-effective, viable, and safe alternative compared with costly, time-consuming, and high-risk surgical procedures.
Bronchopleural fistula; intercostal drainage tube; N-butyl cyanoacrylate glue; video bronchoscopy
Hemoptysis is a very common symptom in the practice of pulmonary physicians of India. We present a case of uncontrolled hemoptysis managed with bronchial artery embolization. Bronchial artery embolization is an effective treatment for patients with hemoptysis. Serious complications are rare, but may occur if the arterial supply to other structures is compromised.
Bronchial artery embolization; bronchogenic carcinoma; fiber optic bronchoscopy; hemoptysis
A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis.
Background: Stenotrophomonas maltophilia infection is gaining importance as an important cause of nosocomial pneumonia due to its characteristic inherent resistance to many broad- spectrum antibiotics. In this study we evaluated the demographic, clinical and microbiological profile of patients with lower respiratory tract infection due to Stenotrophomonas maltophilia.
Materials and Methods: A retrospective analysis of 33 patients diagnosed with Stenotrophomonas maltophilia lower respiratory tract infections during a period of two years from 2012 - 2013 was done.
Results: The predominant predisposing factor observed was mechanical ventilation in 17(51.5%) cases. Fluoroquinolones were the most effective antibiotic (26;78.8%) followed by trimethoprim-sulfamethoxazole (24;72.7%). Among the 19 patients treated with proper antibiotic, 13(68.4%) showed clinical improvement. Among the 14 patients who did not receive appropriate antibiotic for Stenotrophomonas maltophilia infection, 8(57.1%) showed improvement. Two (6%) had blood culture positive for Stenotrophomonas maltophilia. Mortality rate was 21.2%.
Stenotrophomonas maltophilia is emerging as an important nosocomial pathogen with increased risk in patients on mechanical ventilation in ICU. Empiric therapy should include agents active against S.maltophilia such as newer flouroquinolones and trimethoprim-sulfamethoxazole.
Antimicrobial drug resistance; Quinolones; Stenotrophomonas maltophilia; Trimethoprim-sulfamethoxazole
Increases in serum creatinine (ΔSCr) from baseline signify acute kidney injury (AKI) but offer little granular information regarding its characteristics. The 10th Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) suggested that combining AKI biomarkers would provide better precision for AKI course prognostication.
This study investigated the value of combining a functional damage biomarker (plasma cystatin C [pCysC]) with a tubular damage biomarker (urine neutrophil gelatinase-associated lipocalin [uNGAL]), forming a composite biomarker for prediction of discrete characteristics of AKI.
Data from 345 children after cardiopulmonary bypass (CPB) were analyzed. Severe AKI was defined as Kidney Disease Global Outcomes Initiative stages 2 to 3 (>100% ΔSCr) within 7 days of CPB. Persistent AKI lasted >2 days. SCr in reversible AKI returned to baseline ≤48 h after CPB. The composite of uNGAL (>200 ng/mg urine Cr = positive [+]) and pCysC (>0.8 mg/l = positive [+]), uNGAL+/pCysC+, measured 2 h after CPB initiation, was compared to ΔSCr increases of ≤50% for correlation with AKI characteristics by using predictive probabilities, likelihood ratios (LR), and area under the curve receiver operating curve (AUC-ROC) values.
Severe AKI occurred in 18% of patients. The composite uNGAL+/pCysC+ demonstrated a greater likelihood than ΔSCr for severe AKI (+LR: 34.2 [13.0:94.0] vs. 3.8 [1.9:7.2]) and persistent AKI (+LR: 15.6 [8.8:27.5] versus 4.5 [2.3:8.8]). In AKI patients, the uNGAL−/pCysC+ composite was superior to ΔSCr for prediction of transient AKI. Biomarker composites carried greater probability for specific outcomes than ΔSCr strata.
Composites of functional and tubular damage biomarkers are superior to ΔSCr for predicting discrete characteristics of AKI.
Acute Dialysis Quality Initiative; acute kidney injury phenotypes; biomarker combinations; cardiac surgery; functional acute kidney injury; pediatric acute kidney injury
This study investigates involvement of β-catenin signalling in regulation of p-glycoprotein (p-gp) expression in endothelial cells derived from brain vasculature. Pharmacological interventions that enhance or that block β-catenin signalling were applied to primary rat brain endothelial cells and to immortalized human brain endothelial cells, hCMEC/D3, nuclear translocation of β-catenin being determined by immunocytochemistry and by western blot analysis to confirm effectiveness of the manipulations. Using the specific glycogen synthase kinase-3 (GSK-3) inhibitor 6-bromoindirubin-3′-oxime enhanced β-catenin and increased p-gp expression including activating the MDR1 promoter. These increases were accompanied by increases in p-gp-mediated efflux capability as observed from alterations in intracellular fluorescent calcein accumulation detected by flow cytometry. Similar increases in p-gp expression were noted with other GSK-3 inhibitors, i.e. 1-azakenpaullone or LiCl. Application of Wnt agonist [2-amino-4-(3,4-(methylenedioxy) benzylamino)-6-(3-methoxyphenyl)pyrimidine] also enhanced β-catenin and increased transcript and protein levels of p-gp. By contrast, down-regulating the pathway using Dickkopf-1 or quercetin decreased p-gp expression. Similar changes were observed with multidrug resistance protein 4 and breast cancer resistance protein, both known to be present at the blood–brain barrier. These results suggest that regulation of p-gp and other multidrug efflux transporters in brain vasculature can be influenced by β-catenin signalling.
β-catenin; breast cancer resistant protein; glycogen synthase kinase-3; multidrug resistance protein 4; p-glycoprotein; brain endothelial cells
Acute kidney injury (AKI) research in the past decade has mostly focused upon development of a standard AKI definition, validation of early novel biomarkers to predict AKI prior to serum creatinine rise and predict AKI severity, and assessment of aspects of renal replacement therapies and their impact on survival. Given the independent association between AKI and mortality in the acute phase, such focus makes imminent sense. More recently, the recognition that AKI is associated with subsequent development of chronic kidney disease and end-stage renal disease, with the attendant increase in mortality, has led to interest in the clinical epidemiology and the mechanistic understanding of renal recovery after an AKI episode in critically ill patients. We review the current knowledge surrounding renal recovery after an AKI episode, including renal replacement therapy initiation timing and modality impact, biomarker assessment and mechanistic targets to guide potential future clinical trials.
To evaluate the advantages and disadvantages of pre-approval requirements for safety data to detect cardiovascular (CV) risk contained in the December 2008 U.S. Food and Drug Administration (FDA) guidance for developing type 2 diabetes drugs compared with the February 2008 FDA draft guidance from the perspective of diabetes population health.
We applied the incremental net health benefit (INHB) framework to quantify the benefits and risks of investigational diabetes drugs using a common survival metric (life-years [LYs]). We constructed a decision analytic model for clinical program development consistent with the requirements of each guidance and simulated diabetes drugs, some of which had elevated CV risk. Assuming constant research budgets, we estimate the impact of increased trial size on drugs investigated. We aggregate treatment benefit and CV risks for each approved drug over a 35-year horizon under each guidance.
The quantitative analysis suggests that the December 2008 guidance adversely impacts diabetes population health. INHB was −1.80 million LYs, attributable to delayed access to diabetes therapies (−0.18 million LYs) and fewer drugs (−1.64 million LYs), but partially offset by reduced CV risk exposure (0.02 million LYs). Results were robust in sensitivity analyses.
The health outcomes impact of all potential benefits and risks should be evaluated in a common survival measure, including health gain from avoided adverse events, lost health benefits from delayed or forgone efficacious products, and impact of alternative policy approaches. Quantitative analysis of the December 2008 FDA guidance for diabetes therapies indicates that negative impact on patient health will result. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
INHB; benefit; risk; CV; evaluation; pharmacoepidemiology
Fatty acids are integral mediators of energy storage, membrane formation and cell signaling. The pathways that orchestrate uptake of fatty acids remain incompletely understood. Expression of the integrin ligand Mfge8 is increased in human obesity and in mice on a high-fat diet, but its role in obesity is unknown. We show here that Mfge8 promotes the absorption of dietary triglycerides and the cellular uptake of fatty acid and that Mfge8-deficient (Mfge8−/−) mice are protected from diet-induced obesity, steatohepatitis and insulin resistance. Mechanistically, we found that Mfge8 coordinates fatty acid uptake through αvβ3 integrin– and αvβ5 integrin–dependent phosphorylation of Akt by phosphatidylinositide-3 kinase and mTOR complex 2, leading to translocation of Cd36 and Fatp1 from cytoplasmic vesicles to the cell surface. Collectively, our results imply a role for Mfge8 in regulating the absorption and storage of dietary fats, as well as in the development of obesity and its complications.
Plant essential oils are complex mixtures of volatile organic compounds, which play indispensable roles in the environment, for the plant itself, as well as for humans. The potential biological information stored in essential oil composition data can provide an insight into the silent language of plants, and the roles of these chemical emissions in defense, communication and pollinator attraction. In order to decipher volatile profile patterns from a global perspective, we have developed the ESSential OIL DataBase (EssOilDB), a continually updated, freely available electronic database designed to provide knowledge resource for plant essential oils, that enables one to address a multitude of queries on volatile profiles of native, invasive, normal or stressed plants, across taxonomic clades, geographical locations and several other biotic and abiotic influences. To our knowledge, EssOilDB is the only database in the public domain providing an opportunity for context based scientific research on volatile patterns in plants. EssOilDB presently contains 123 041 essential oil records spanning a century of published reports on volatile profiles, with data from 92 plant taxonomic families, spread across diverse geographical locations all over the globe. We hope that this huge repository of VOCs will facilitate unraveling of the true significance of volatiles in plants, along with creating potential avenues for industrial applications of essential oils. We also illustrate the use of this database in terpene biology and show how EssOilDB can be used to complement data from computational genomics to gain insights into the diversity and variability of terpenoids in the plant kingdom. EssOilDB would serve as a valuable information resource, for students and researchers in plant biology, in the design and discovery of new odor profiles, as well as for entrepreneurs—the potential for generating consumer specific scents being one of the most attractive and interesting topics in the cosmetic industry.
Database URL: http://nipgr.res.in/Essoildb/
Although the circuit mediating contextual fear conditioning has been extensively described, the precise contribution that specific anatomical nodes make to behavior has not been fully elucidated. To clarify the roles of the dorsal hippocampus (DH), basolateral amygdala (BLA), and medial prefrontal cortex (mPFC) in contextual fear conditioning, activity within these regions was mapped using cellular compartment analysis of temporal activity using fluorescence in situ hybridization (catFISH) for Arc mRNA. Rats were delay-fear conditioned or immediately shocked (controls) and thereafter reexposed to the shocked context to test for fear memory recall. Subsequent catFISH analyses revealed that in the DH, cells were preferentially reactivated during the context test, regardless of whether animals had been fear conditioned or immediately shocked, suggesting that the DH encodes spatial information specifically, rather then the emotional valence of an environment. In direct contrast, neuronal ensembles in the BLA were only reactivated at test if animals had been fear conditioned, suggesting that the amygdala specifically tracks the emotional properties of a context. Interestingly, Arc expression in the mPFC was consistent with both amygdala- and hippocampus-like patterns, supporting a role for the mPFC in both fear and contextual processing. Collectively, these data provide crucial insight into the region-specific behavior of neuronal ensembles during contextual fear conditioning and demonstrate a dissociable role for the hippocampus and amygdala in processing the contextual and emotional properties of a fear memory.
amygdala; Arc; catFISH; contextual fear; hippocampus; prefrontal cortex
Primary Angiosarcoma of the skin of the foot is very rare. Angiosarcoma is typically treated with resection and wide-field postoperative radiation therapy. Chemotherapy and radiation therapy have also been used. Regardless of the treatment, the risk of local and distant relapse remains high for this disease. We present a case of an elderly patient who developed cutaneous angiosarcoma of the foot. It posed as a diagnostic dilemma at presentation. Chronic lymphedema was a possible predisposing factor. Given his age, preexisting renal dysfunction, refusal of surgery, and preference not to receive chemotherapy, the patient was ultimately treated with definitive radiotherapy. We present this case because of its rare site, unique presentation and delay in diagnosis of the condition, and attainment of an excellent response to radiation at the time of follow-up. We also review the current literature on this topic.
Chronic overnutrition drives complex adaptations within both professional metabolic and bystander tissues that, despite intense investigation, are still poorly understood. Xu et al. (2013) now describe the unexpected ability of adipose tissue macrophages to buffer lipids released from obese adipocytes in a manner independent of inflammatory macrophage activation.
Rationale: Several studies suggest that nasal nitric oxide (nNO)
measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure
and interpretation have not been standardized.
Objectives: To use a standard protocol for measuring nNO to establish a
disease-specific cutoff value at one site, and then validate at six other sites.
Methods: At the lead site, nNO was prospectively measured in individuals
later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or
DNAH11 mutations (n = 6); and in 78 healthy and 146 disease
control subjects, including individuals with asthma (n = 37), cystic fibrosis (n
= 77), and chronic obstructive pulmonary disease (n = 32). A
disease-specific cutoff value was determined, using generalized estimating equations
(GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals
enrolled for evaluation for possible PCD.
Measurements and Main Results: At the lead site, nNO values in PCD (mean
± standard deviation, 20.7 ± 24.1 nl/min; range, 1.5–207.3 nl/min)
only rarely overlapped with the nNO values of healthy control subjects (304.6 ±
118.8; 125.5–867.0 nl/min), asthma (267.8 ± 103.2; 125.0–589.7
nl/min), or chronic obstructive pulmonary disease (223.7 ± 87.1;
109.7–449.1 nl/min); however, there was overlap with cystic fibrosis (134.0
± 73.5; 15.6–386.1 nl/min). The disease-specific nNO cutoff value was
defined at 77 nl/minute (sensitivity, 0.98; specificity, >0.999). At six other
sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed
Conclusions: Using a standardized protocol in multicenter studies, nNO
measurement accurately identifies individuals with PCD, and supports its usefulness
as a test to support the clinical diagnosis of PCD.
primary ciliary dyskinesia; Kartagener syndrome; ciliopathy; axoneme
Centrality of a node measures its relative importance within a network. There are a number of applications of centrality, including inferring the influence or success of an individual in a social network, and the resulting social network dynamics. While we can compute the centrality of any node in a given network snapshot, a number of applications are also interested in knowing the potential importance of an individual in the future. However, current centrality is not necessarily an effective predictor of future centrality. While there are different measures of centrality, we focus on degree centrality in this paper. We develop a method that reconciles preferential attachment and triadic closure to capture a node's prominence profile. We show that the proposed node prominence profile method is an effective predictor of degree centrality. Notably, our analysis reveals that individuals in the early stage of evolution display a distinctive and robust signature in degree centrality trend, adequately predicted by their prominence profile. We evaluate our work across four real-world social networks. Our findings have important implications for the applications that require prediction of a node's future degree centrality, as well as the study of social network dynamics.
Group A Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children (<5 years) worldwide. Although rotavirus vaccines have been successfully administered in many countries, in India the introduction of rotavirus vaccine in national immunization program was approved in 2014. Since high disease burden and large number of genetic variants have been reported from low income countries including India, monitoring of rotavirus was initiated prior to implementation of the vaccine in the region.
A total number of 3,582 stool samples were collected from an urban slum community in Kolkata, among which 1,568 samples were obtained from children of ≤5 years of age, with moderate to severe diarrhoea and 2,014 samples were collected from age-sex matched healthy neighbourhood controls. Rotavirus positive samples were typed by multiplex semi-nested PCR and nucleotide sequencing. Circulating strains were phylogenetically analyzed.
Among 1,568 children with diarrhoea, 395 (25.2%), and among 2,014 asymptomatic children, 42 (2%) were rotavirus positive. G1P was identified as the most common strain (32%) followed by G9P (16.9%), G2P (13.5%) and G9P (10.75%). G12 strains with combinations of P, P and P comprised 11.9% of total positive strains. The rest (<10%) were rare and uncommon strains like G1P, G1P, G2P and animal-like strains G4P, G6P and G11P. The 42 rotavirus positive samples from asymptomatic children revealed common genotypes like G1, G2 and G9.
This community based case-control study showed increased predominance of genotype G9 in Kolkata. It also confirmed co-circulation of a large number of genetic variants in the community. Asymptomatic rotavirus positive children though low in number can also be a source of dispersal of infection in the community. This study provides background information to the policy makers for implementation of rotavirus vaccines in this region.