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1.  The extracellular matrix protects Pseudomonas aeruginosa biofilms by limiting the penetration of tobramycin 
Environmental microbiology  2013;15(10):2865-2878.
SUMMARY
Biofilm cells are less susceptible to antimicrobials than their planktonic counterparts. While this phenomenon is multifactorial, the ability of the biofilm matrix to reduce antibiotic penetration into the biofilm is thought to be of limited importance, as previous studies suggest that antibiotics move fairly rapidly through biofilms. In this study, we monitored the transport of two clinically relevant antibiotics, tobramycin and ciprofloxacin, into non-mucoid P. aeruginosa biofilms. To our surprise, we showed that the positively charged antibiotic tobramycin is sequestered to the biofilm periphery, while the neutral antibiotic ciprofloxacin readily penetrated. We provide evidence that tobramycin in the biofilm periphery both stimulated a localized stress response and killed bacteria in these regions, but not in the underlying biofilm. Although it is unclear which matrix component binds tobramycin, its penetration was increased by the addition of cations in a dose-dependent manner, which led to increased biofilm death. These data suggest that ionic interactions of tobramycin with the biofilm matrix limit its penetration. We propose that tobramycin sequestration at the biofilm periphery is an important mechanism in protecting metabolically active cells that lie just below the zone of sequestration.
doi:10.1111/1462-2920.12155
PMCID: PMC4045617  PMID: 23751003
2.  Shrinking lung syndrome in systemic lupus erythematosus-scleroderma overlap 
Shrinking lung syndrome (SLS) is a infrequently reported manifestation of systemic lupus erythematosus (SLE). Reported prevalence of SLS is about 0.5% in SLE patients. Pathogenesis is not fully understood and different therapeutic modalities have been employed with variable results, as only 77 cases of SLS have been documented in literature. SLS in SLE-Scleroderma overlap has not been reported yet. We report a patient of SLE - scleroderma overlap presenting with dyspnea, intermittent orthopnea and pleuritic chest pain. Evaluation revealed elevated hemidiaphragms and severe restrictive defect. She was eventually diagnosed as a case of SLS. This case report is a reminder to the medical fraternity that SLS although a rare complication must be thought of in the special subset of patients of SLE having respiratory symptoms.
doi:10.4103/0970-2113.142152
PMCID: PMC4220329  PMID: 25378855
Scleroderma; scleroderma shrinking lung syndrome; systemic lupus erythematosus
3.  Conditions Associated with the Cystic Fibrosis Defect Promote Chronic Pseudomonas aeruginosa Infection 
Rationale: Progress has been made in understanding how the cystic fibrosis (CF) basic defect produces lung infection susceptibility. However, it remains unclear why CF exclusively leads to chronic infections that are noninvasive and highly resistant to eradication. Although biofilm formation has been suggested as a mechanism, recent work raises questions about the role of biofilms in CF.
Objectives: To learn how airway conditions attributed to CF transmembrane regulator dysfunction could lead to chronic infection, and to determine if biofilm-inhibiting genetic adaptations that are common in CF isolates affect the capacity of Pseudomonas aeruginosa to develop chronic infection phenotypes.
Methods: We studied P. aeruginosa isolates grown in agar and mucus gels containing sputum from patients with CF and measured their susceptibility to killing by antibiotics and host defenses. We also measured the invasive virulence of P. aeruginosa grown in sputum gels using airway epithelial cells and a murine infection model.
Measurements and Main Results: We found that conditions likely to result from increased mucus density, hyperinflammation, and defective bacterial killing could all cause P. aeruginosa to grow in bacterial aggregates. Aggregated growth markedly increased the resistance of bacteria to killing by host defenses and antibiotics, and reduced their invasiveness. In addition, we found that biofilm-inhibiting mutations do not impede aggregate formation in gel growth environments.
Conclusions: Our findings suggest that conditions associated with several CF pathogenesis hypotheses could cause the noninvasive and resistant infection phenotype, independently of the bacterial functions needed for biofilm formation.
doi:10.1164/rccm.201312-2142OC
PMCID: PMC4225830  PMID: 24467627
cystic fibrosis; chronic infection; Pseudomonas aeruginosa; biofilm
4.  Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria 
Science (New York, N.Y.)  2011;334(6058):982-986.
Bacteria become highly tolerant to antibiotics when nutrients are limited. The inactivity of antibiotic targets caused by starvation-induced growth arrest is thought to be a key mechanism producing tolerance (1). Here we show that the antibiotic tolerance of nutrient-limited and biofilm Pseudomonas aeruginosa is mediated by active responses to starvation, rather than by the passive effects of growth arrest. The protective mechanism is controlled by the starvation-signaling stringent response (SR), and our experiments link SR–mediated tolerance to reduced levels of oxidant stress in bacterial cells. Furthermore, inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics, and markedly enhanced the efficacy of antibiotic treatment in experimental infections.
doi:10.1126/science.1211037
PMCID: PMC4046891  PMID: 22096200
5.  Pharmacognostical study and establishment of quality parameters of aerial parts of Costus speciosus-a well known tropical folklore medicine 
Objective
To evaluate the diagnostic pharmacognostical characters of Costus speciosus (aerial parts) along with their physico-chemical parameters and fluorosence analysis.
Method
The pharmacognostical characters were determined in terms of macroscopy, microscopy, powder microscopy, leaf constant, fluorescence analysis and preliminary phytochemical investigation.
Results
The findings of macroscopy revealed that leaves elliptic to oblong or oblong-lancoelate, thick, spirally arranged, with stem clasping sheaths up to 4 cm, flowers large, white, cone-like terminal spikes, with bright red bracts. Transverse section of leaflet showed the presence of cuticularised epidermis with polygonal cells on adaxial surface and bluntly angled cells on abaxial surface of lamina, mesophyll cells differentiated in to single layered palisade cells on each surface and 2-3 layered spongy parenchyma, unicellular and uniseriate multicellular covering trichomes, paracytic stomata and vascular bundles surrounded by sclerenchymatous multicellular sheath. Preliminary phytochemical screening exhibited the presence of various phytochemical groups like alkaloids, glycosides, steroids, phenolic constituents. Further, the leaf constants, powder microscopy and fluorescence characteristics indicated outstanding results from this investigation
Conclusions
Various pharmacognostical and physico-chemical parameters have pivotal roles in identification, authentication and establishment of quality parameters of the species.
doi:10.12980/APJTB.4.2014C1103
PMCID: PMC3994359  PMID: 25182951
Costus speciosus; Quality control; Physico-chemical parameters; Microscopy; Fluorescence analysis
6.  Bacterial Decolorization of Textile Azo Dye Acid Orange by Staphylococcus hominis RMLRT03 
Toxicology International  2014;21(2):160-166.
A bacterial strain RMLRT03 with ability to decolorize textile dye Acid Orange dye was isolated from textile effluent contaminated soil of Tanda, Ambedkar Nagar, Uttar Pradesh (India). The decolorization studies were performed in Bushnell and Haas medium (BHM) amended with Acid Orange dye. The bacterial strain was identified as Staphylococcus hominis on the basis of 16S rDNA sequence. The bacterial strain exhibited good decolorization ability with glucose and yeast extract supplementation as cosubstrate in static conditions. The optimal condition for the decolorization of Acid Orange dye by Staphylococcus hominis RMLRT03 strain were at pH 7.0 and 35°C in 60 h of incubation. The bacterial strain could tolerate high concentrations of Acid Orange dye up to 600 mg l-1. The high decolorizing activity under natural environmental conditions indicates that the bacterial strain has practical application in the treatment of dye containing wastewaters.
doi:10.4103/0971-6580.139797
PMCID: PMC4170557  PMID: 25253925
16S rDNA; BHM; cosubstrate; decolorization; textile dye
7.  Clinical Significance and Molecular Characterization of Nonsporulating Molds Isolated from the Respiratory Tracts of Bronchopulmonary Mycosis Patients with Special Reference to Basidiomycetes 
Journal of Clinical Microbiology  2013;51(10):3331-3337.
Nonsporulating molds (NSMs), especially basidiomycetes, have predominantly been reported as human pathogens responsible for allergic and invasive disease. Their conventional identification is problematic, as many isolates remain sterile in culture. Thus, inconclusive culture reports might adversely affect treatment decisions. The clinical significance of NSMs in pulmonary mycoses is poorly understood. We sequenced the internal transcribed spacer (ITS) region and D1/D2 domain of the larger subunit (LSU) of 52 NSMs isolated from respiratory specimens. The basidiomycetes were the predominant NSMs, of which Schizophyllum commune was the most common agent in allergic bronchopulmonary mycosis (ABPM), followed by Ceriporia lacerata in invasive fungal disease. Porostereum spadiceum, Phanaerochaete stereoides, Neosartorya fischeri, and Marasmiellus palmivorus were the other molds observed. Application of ITS and LSU region sequencing identified 92% of the isolates. The antifungal susceptibility data revealed that all basidiomycetes tested were susceptible to amphotericin B and resistant to caspofungin, fluconazole, and flucytosine. Except for 3 isolates of S. commune and a solitary isolate of M. palmivorus, all basidiomycetes had low MICs for itraconazole, posaconazole, and voriconazole. Basidiomycetes were isolated from patients with ABPM, invasive pulmonary mycosis/pneumonia, or fungal balls. In addition, the majority of the basidiomycetes were isolated from patients with chronic respiratory disorders who were sensitized to one of the basidiomycetous fungi and demonstrated precipitating antibodies against the incriminating fungi, indicating an indolent tissue reaction. Thus, isolation of basidiomycetes from the lower respiratory tract could be significant, and it is important to monitor these patients in order to prevent subsequent lung damage.
doi:10.1128/JCM.01486-13
PMCID: PMC3811655  PMID: 23903552
8.  Role of Decompression in Late Presentation of Cervical Spinal Cord Disorders 
Asian Spine Journal  2014;8(2):183-189.
Study Design
Prospective study conducted at Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, India.
Purpose
To show the efficacy of decompression in the late presentation of cervical spinal cord disorders.
Overview of Literature
Studies by various authors have shown that early spinal decompression results in better neurological outcomes.
Methods
From January 2003 to January 2005, 11 of the 41 patients with cervical spinal cord compression, meeting the inclusion criteria, underwent anterior decompression; interbody graft placement and stabilization by anterior cervical locking plate. The neurologic and functional outcomes were recorded.
Results
Five patients had spinal cord injury and 6 patients had compressive cervical myelopathy. Complications included 1 death and 1 plate loosening. No patient lost their preoperative neurological status. One patient had no improvement, 2 patients showed full recovery. The mean follow-up is 28.3 month. At the of rehabilitation, 6 were able to walk without support), 2 could walk with support, and 1 needed a wheelchair. The average American Spinal Injury Association motor score on admission to the hospital, 32.8 (standard deviation [SD], 30.5); admission to rehabilitation, 38.6 (SD, 32.4); discharge from rehabilitation, 46.2 (SD, 33.7). The most recent follow-up was 64.0 (SD, 35.3).
Conclusions
The anterior approach for cervical decompression allows for adequate decompression. This decompression is the best chance offered in even late reported cases, including posttraumatic cases where there is no evidence of cord transactions. The use of anterior cervical plates reduces the chances of graft loosening, extruding, or collapsing.
doi:10.4184/asj.2014.8.2.183
PMCID: PMC3996343  PMID: 24761201
Cervical vertebrae; Neglected disease; Quadriparesis; Surgical decompression
9.  Curcumin Modulates α-Synuclein Aggregation and Toxicity 
ACS Chemical Neuroscience  2012;4(3):393-407.
In human beings, Parkinson’s disease (PD) is associated with the oligomerization and amyloid formation of α-synuclein (α-Syn). The polyphenolic Asian food ingredient curcumin has proven to be effective against a wide range of human diseases including cancers and neurological disorders. While curcumin has been shown to significantly reduce cell toxicity of α-Syn aggregates, its mechanism of action remains unexplored. Here, using a series of biophysical techniques, we demonstrate that curcumin reduces toxicity by binding to preformed oligomers and fibrils and altering their hydrophobic surface exposure. Further, our fluorescence and two-dimensional nuclear magnetic resonance (2D-NMR) data indicate that curcumin does not bind to monomeric α-Syn but binds specifically to oligomeric intermediates. The degree of curcumin binding correlates with the extent of α-Syn oligomerization, suggesting that the ordered structure of protein is required for effective curcumin binding. The acceleration of aggregation by curcumin may decrease the population of toxic oligomeric intermediates of α-Syn. Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases.
doi:10.1021/cn3001203
PMCID: PMC3605819  PMID: 23509976
Curcumin; α-synuclein; amyloid; oligomers; toxicity; Parkinson’s disease
10.  Molecular Characterization and In Vitro Antifungal Susceptibility Profile of Schizophyllum commune, an Emerging Basidiomycete in Bronchopulmonary Mycoses 
Schizophyllum commune (n = 30) showed lowest geometric mean MICs of isavuconazole (0.19 μg/ml), itraconazole (0.2 μg/ml), voriconazole (0.24 μg/ml), and amphotericin B (0.29 μg/ml) and high geometric mean MICs of fluconazole (19.39 μg/ml) and flucytosine (17.28 μg/ml). Five cases (of 8) of allergic bronchopulmonary mycosis that were treated with itraconazole had no recrudescence after 6 to 24 months of follow-up. One case each of invasive pulmonary mycosis and fungal ball were treated successfully with voriconazole and itraconazole.
doi:10.1128/AAC.02619-12
PMCID: PMC3716139  PMID: 23507274
11.  Proteomic profiling of serum samples from chikungunya-infected patients provides insights into host response 
Clinical proteomics  2013;10(1):14.
Background
Chikungunya is a highly debilitating febrile illness caused by Chikungunya virus, a single-stranded RNA virus, which is transmitted by Aedes aegypti or Aedes albopictus mosquito species. The pathogenesis and host responses in individuals infected with the chikungunya virus are not well understood at the molecular level. We carried out proteomic profiling of serum samples from chikungunya patients in order to identify molecules associated with the host response to infection by this virus.
Results
Proteomic profiling of serum obtained from the infected individuals resulted in identification of 569 proteins. Of these, 63 proteins were found to be differentially expressed (≥ 2-fold) in patient as compared to control sera. These differentially expressed proteins were involved in various processes such as lipid metabolism, immune response, transport, signal transduction and apoptosis.
Conclusions
This is the first report providing a global proteomic profile of serum samples from individuals infected with the chikungunya virus. Our data provide an insight into the proteins that are involved as host response factors during an infection. These proteins include clusterin, apolipoproteins and S100A family of proteins.
doi:10.1186/1559-0275-10-14
PMCID: PMC3879382  PMID: 24124767
iTRAQ; Quantitative proteomics; Arthritis; Hyponatremia; Neuropathology
12.  New Clonal Strain of Candida auris, Delhi, India 
Emerging Infectious Diseases  2013;19(10):1670-1673.
A new clonal strain of Candida auris is an emerging etiologic agent of fungemia in Delhi, India. In 12 patients in 2 hospitals, it was resistant to fluconazole and genotypically distinct from isolates from South Korea and Japan, as revealed by M13 and amplified fragment length polymorphism typing.
doi:10.3201/eid1910.130393
PMCID: PMC3810747  PMID: 24048006
Candida auris; fungemia; M13 fingerprinting; AFLP; antifungal susceptibility; India; fungi; parasitic diseases
13.  Reconstruction of post-traumatic long bone defect with vascularised free fibula: A series of 28 cases 
Introduction:
The severe long bone defects usually follow high-energy trauma and are often associated with a significant soft-tissue injury. The goal of management of these open long bone defects is to provide stable fixation with maintenance of limb length and soft-tissue coverage. The purpose of this article is to present the clinic-radiological outcome, complications and treatment of post-traumatic long bone defect with vascularised fibula transfer.
Materials and Methods:
Retrospective records of 28 patients were analysed who presented with post-traumatic long bone defects and in whom reconstruction with vascularised free fibula was done. Demographic data were recorded and clinical and radiological assessment was done.
Results:
Out of 28 patients in whom vascularised free fibula transfer was carried out three flaps were lost while non-union occur in three patients. Three patients developed a stress fracture of transferred free fibula in the post-operative period. Few of the patients experienced some problems in the donor leg; however, all of them improved in subsequent follow-up.
Discussion:
It is clearly evident from this study that timing of surgery plays an important role in the micro-vascular reconstruction in trauma cases. All the complication like flap loss, non-union or delayed union occur in patients in whom reconstruction was delayed.
Conclusion:
The free vascularised fibula graft is a viable method for the reconstruction of skeletal defects of more than 6 cm, especially in cases of scarred and avascular recipient sites or in patients with combined bone and soft-tissue defects. Results are best when the reconstruction is done within 1 week of trauma.
doi:10.4103/0970-0358.122013
PMCID: PMC3897102  PMID: 24459347
Long bone defect; post-traumatic; vascularised free fibula
14.  Clinical Significance of Filamentous Basidiomycetes Illustrated by Isolates of the Novel Opportunist Ceriporia lacerata from the Human Respiratory Tract 
Journal of Clinical Microbiology  2013;51(2):585-590.
The filamentous basidiomycete Ceriporia lacerata, an agent of white rot on wood, has never been reported in human disease and its clinical significance is not yet known. We describe 4 patients with respiratory diseases where C. lacerata was implicated in a wide spectrum of clinical manifestations ranging from saprobic colonization to fungal pneumonia. The isolates did not show the morphological characteristics that facilitate recognition of filamentous basidiomycetes, such as the presence of clamp connections, spicules along hyphae, or fruiting bodies. The identity of the mold was confirmed by sequencing the internal transcribed spacer 1 and 4 (ITS-1 and ITS-4) and D1/D2 regions of the rRNA gene. All of the isolates exhibited the lowest MICs of posaconazole and isavuconazole (MIC range, 0.06 to 0.125 μg/ml), followed by itraconazole (MIC range, 0.06 to 0.5 μg/ml), voriconazole (MIC range, 0.125 to 0.5 μg/ml), and amphotericin B (MIC range, 0.25 to 1 μg/ml). The infections reported here occurred in patients with preexisting lung damage induced by tuberculosis or chronic obstructive pulmonary disease. Chronic, sometimes fatal infections by the ascomycete Aspergillus fumigatus and the basidiomycete Schizophyllum commune are well established in the presence of an anatomical pulmonary defect or in the background of immunodeficiency. It is postulated that C. lacerata, a novel opportunist basidiomycete, may be involved in similar pathological processes.
doi:10.1128/JCM.02943-12
PMCID: PMC3553890  PMID: 23241374
15.  Time Course Study of Delayed Wound Healing in a Biofilm-Challenged Diabetic Mouse Model 
Wound Repair and Regeneration  2012;20(3):342-352.
Bacterial biofilm has been shown to play a role in delaying wound healing of chronic wounds, a major medical problem that results in significant healthcare burden. A reproducible animal model could be very valuable for studying the mechanism and management of chronic wounds. Our previous work demonstrated that Pseudomonas aeruginosa (PAO1) biofilmchallenge on wounds in diabetic (db/db) mice significantly delayed wound healing. In this wound time course study, we further characterize the bacterial burden, delayed wound healing and certain aspects of the host inflammatory response in the PAO1 biofilm-challenged db/db mouse model. PAO1 biofilms were transferred onto 2 day old wounds created on the dorsal surface of db/db mice. Control wounds without biofilm-challenge healed by 4 weeks, consistent with previous studies; none of the biofilm-challenged wounds healed by 4 weeks; 64% of the biofilm-challenged wounds healed by 6 weeks; and all of the biofilm-challenged wounds healed by 8 weeks. During the wound healing process, P. aeruginosa were gradually cleared from the wounds while the presence of S. aureus (part of the normal mouse skin flora) increased. Scabs from all unhealed wounds contained 107 P. aeruginosa, which was 100 fold higher than the counts isolated from wound beds (i.e. 99% of the P. aeruginosa was in the scab). Histology and genetic analysis showed proliferative epidermis, deficient vascularization and increased inflammatory cytokines. Hypoxia inducible factor (HIF) expression increased 3 fold in 4 week wounds. In summary, our study demonstrates that biofilm-challenged wounds typically heal in approximately 6 weeks, at least 2 weeks longer than non biofilm-challenged normal wounds. These data suggest that this delayed wound healing model enables the in vivo study of bacterial biofilm responses to host defenses and the effects of biofilms on host wound healing pathways. It may also be used to test anti-biofilm strategies the treatment of chronic wounds.
doi:10.1111/j.1524-475X.2012.00793.x
PMCID: PMC3349451  PMID: 22564229
Pseudomonas aeruginosa; biofilm; wound infection; keratinocytes; inflammatory response; gene expression
16.  First Human Case of Pulmonary Fungal Ball Due to a Perenniporia Species (a Basidiomycete) 
Journal of Clinical Microbiology  2012;50(11):3786-3791.
Perenniporia species are basidiomycetes, resupinate shelf fungi responsible for white rot decay of wood. Here, we report for the first time an intracavitary pulmonary fungal ball due to a species of Perenniporia that has not been recognized so far as a human pathogen. The fungus was identified by sequencing of the partial ribosomal operon of a culture from a clinical specimen.
doi:10.1128/JCM.01863-12
PMCID: PMC3486195  PMID: 22895039
17.  Future Directions in Early Cystic Fibrosis Lung Disease Research 
Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled “Future Research Directions in Early CF Lung Disease” on September 21–22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene–environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.
doi:10.1164/rccm.201111-2068WS
PMCID: PMC3360572  PMID: 22312017
cystic fibrosis; airway disease; innate immunity; microbiology; genetics
18.  Tuberculosis of greater trochanter presenting as avulsion fracture of greater trochanter-A case report 
Isolated tuberculosis of greater trochanteris unusual and clinical presentation is often vague. Isolated fracture of greater trochanter is also rare. We are reporting a case of tuberculosis of greater trochanter in adult female with radiological presentation in form of avulsion fracture of greater trochanter which has not be reported in literature till now to our knowledge.
doi:10.1016/S2222-1808(13)60062-6
PMCID: PMC4027276
Tuberculosis greater trochanter; Greater trochanter fracture
19.  Infection With Cryptosporidium hominis Provides Incomplete Protection of the Host Against Cryptosporidium parvum 
The Journal of Infectious Diseases  2012;205(6):1019-1023.
Cryptosporidium hominis and Cryptosporidium parvum, which infect humans equally, are genetically/antigenically almost identical. It remains unclear, however, whether infection with C. hominis protects against C. parvum. Gnotobiotic piglets were used to investigate cross-protection. After ≥3 days of recovery from C. hominis infection, the piglets were completely protected against subsequent challenge with C. hominis but only partially against challenge with C. parvum, as compared with age-matched control animals challenged with either species. In conclusion, C. hominis–specific immunity was sufficient to completely protect against challenge with the same species but insufficient to provide the same level of protection against C. parvum.
doi:10.1093/infdis/jir874
PMCID: PMC3415952  PMID: 22279124
20.  Analysis of ventilatory ratio as a novel method to monitor ventilatory adequacy at the bedside 
Critical Care  2013;17(1):R34.
Introduction
Due to complexities in its measurement, adequacy of ventilation is seldom used to categorize disease severity and guide ventilatory strategies. Ventilatory ratio (VR) is a novel index to monitor ventilatory adequacy at the bedside. VR=(V˙Emeasured×PaCO2measured)/(V˙Epredicted×PaCO2ideal). V˙Epredicted is 100 mL.Kg-1.min-1 and PaCO2ideal is 5 kPa. Physiological analysis shows that VR is influenced by dead space (VD/VT) and CO2 production (V˙CO2). Two studies were conducted to explore the physiological properties of VR and assess its use in clinical practice.
Methods
Both studies were conducted in adult mechanically ventilated ICU patients. In Study 1, volumetric capnography was used to estimate daily VD/VT and measure V˙CO2 in 48 patients. Simultaneously, ventilatory ratio was calculated using arterial blood gas measurements alongside respiratory and ventilatory variables. This data was used to explore the physiological properties of VR. In Study 2, 224 ventilated patients had daily VR and other respiratory variables, baseline characteristics, and outcome recorded. The database was used to examine the prognostic value of VR.
Results
Study 1 showed that there was significant positive correlation between VR and VD/VT (modified r = 0.71) and V˙CO2 (r = 0.14). The correlation between VR and VD/VT was stronger in mandatory ventilation compared to spontaneous ventilation. Linear regression analysis showed that VD/VT had a greater influence on VR than V˙CO2 (standardized regression coefficient 1/1-VD/VT: 0.78, V˙CO2: 0.44). Study 2 showed that VR was significantly higher in non-survivors compared to survivors (1.55 vs. 1.32; P < 0.01). Univariate logistic regression showed that higher VR was associated with mortality (OR 2.3, P < 0.01), this remained the case after adjusting for confounding variables (OR 2.34, P = 0.04).
Conclusions
VR is an easy to calculate bedside index of ventilatory adequacy and appears to yield clinically useful information.
doi:10.1186/cc12541
PMCID: PMC4057449  PMID: 23445563
21.  PLUNC: a multifunctional surfactant of the airways 
Biochemical Society transactions  2011;39(4):1012-1016.
PLUNC (palate, lung and nasal epithelium clone) protein is an abundant secretory product of epithelia throughout the mammalian conducting airways. Despite its homology with the innate immune defence molecules BPI (bactericidal/permeability-increasing protein) and LBP (lipopolysaccharide-binding protein), it has been difficult to define the functions of PLUNC. Based on its marked hydrophobicity and expression pattern, we hypothesized that PLUNC is an airway surfactant. We found that purified recombinant human PLUNC exhibited potent surfactant activity by several different measures, and experiments with airway epithelial cell lines and primary cultures indicate that native PLUNC makes a significant contribution to the overall surface tension in airway epithelial secretions. Interestingly, we also found that physiologically relevant concentrations of PLUNC-inhibited Pseudomonas aeruginosa biofilm formation in vitro without acting directly as a bactericide. This finding suggests that PLUNC protein may inhibit biofilm formation by airway pathogens, perhaps through its dispersant properties. Our data, along with reports from other groups on activity against some airway pathogens, expand on an emerging picture of PLUNC as a multifunctional protein, which plays a novel role in airway defences at the air/liquid interface.
doi:10.1042/BST0391012
PMCID: PMC3572202  PMID: 21787339
biofilm; conducting airway; innate immunity; palate; lung and nasal epithelium clone (PLUNC); surfactant
23.  Clonal Expansion and Emergence of Environmental Multiple-Triazole-Resistant Aspergillus fumigatus Strains Carrying the TR34/L98H Mutations in the cyp51A Gene in India 
PLoS ONE  2012;7(12):e52871.
Azole resistance is an emerging problem in Aspergillus which impacts the management of aspergillosis. Here in we report the emergence and clonal spread of resistance to triazoles in environmental Aspergillus fumigatus isolates in India. A total of 44 (7%) A. fumigatus isolates from 24 environmental samples were found to be triazole resistant. The isolation rate of resistant A. fumigatus was highest (33%) from soil of tea gardens followed by soil from flower pots of the hospital garden (20%), soil beneath cotton trees (20%), rice paddy fields (12.3%), air samples of hospital wards (7.6%) and from soil admixed with bird droppings (3.8%). These strains showed cross-resistance to voriconazole, posaconazole, itraconazole and to six triazole fungicides used extensively in agriculture. Our analyses identified that all triazole-resistant strains from India shared the same TR34/L98H mutation in the cyp51 gene. In contrast to the genetic uniformity of azole-resistant strains the azole-susceptible isolates from patients and environments in India were genetically very diverse. All nine loci were highly polymorphic in populations of azole-susceptible isolates from both clinical and environmental samples. Furthermore, all Indian environmental and clinical azole resistant isolates shared the same multilocus microsatellite genotype not found in any other analyzed samples, either from within India or from the Netherlands, France, Germany or China. Our population genetic analyses suggest that the Indian azole-resistant A. fumigatus genotype was likely an extremely adaptive recombinant progeny derived from a cross between an azole-resistant strain migrated from outside of India and a native azole-susceptible strain from within India, followed by mutation and then rapid dispersal through many parts of India. Our results are consistent with the hypothesis that exposure of A. fumigatus to azole fungicides in the environment causes cross-resistance to medical triazoles. The study emphasises the need of continued surveillance of resistance in environmental and clinical A. fumigatus strains.
doi:10.1371/journal.pone.0052871
PMCID: PMC3532406  PMID: 23285210
24.  Photochemical Functionalization of Polymer Surfaces for Microfabricated Devices 
Herein we report the topochemical modification of polymer surfaces with perfluorinated aromatic azides. The aryl azides, which have quaternary amine or aldehyde functional groups, were linked to the surface of the polymer by UV irradiation. The polymer substrates used in this study were cyclic olefin copolymer (COC) and poly(methylmethacrylate) (PMMA). These substrates were characterized before and after modification, using reflection-absorption infrared spectroscopy (RAIRS), sessile water contact angle measurements, and X-ray photoelectron spectroscopy (XPS). Analysis of the surface confirmed the presence of an aromatic groups with aldehyde or quaternary amine functionality. Enzyme immobilization and patterning onto polymer surfaces were studied using confocal microscopy. Enzymatic digests were carried out on modified probes manufactured from thermoplastic substrates and the resulting peptide analysis was completed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
doi:10.1021/la7033577
PMCID: PMC3529600  PMID: 18294015
25.  Evaluation of anti-arthritic potential of the methanolic extract of the aerial parts of Costus speciosus 
Objective:
Costus speciosus Koen. (Keu, Crape ginger), an ornamental plant, widely distributed in India is traditionally used as astringent, aphrodisiac, purgative, anthelmintic, depurative, febrifuge and expectorant. The plant is also used in rheumatism, dropsy, urinary diseases and jaundice. The purpose of this study is to evaluate the anti-arthritic activity of the methanolic extract of the aerial parts of Costus speciosus (CS) in experimental animal models.
Materials and Methods:
The powdered drug was subjected to successive solvent extraction, with solvents in increasing order of polarity to obtain the methanolic extract of the aerial parts of the plant. CS was evaluated for anti-arthritic action by Freund's adjuvant induced arthritis test in adult Albino rats (150-200 gm). Rats were injected 0.1 ml of complete Freund's adjuvant into the planter region of the left hind paw. Statistical analysis was performed using One way analysis of variance (ANOVA) followed by Bonferonni test. P<0.05 was considered statistically significant.
Results:
The methanolic extract of CS in doses of 400 and 800 mg/kg showed 75.50% and 68.33% protection against increase in paw edema, respectively. CS showed dose-dependent action in all the experimental models.
Conclusion:
The present study indicates that CS has significant anti-arthritic properties.
doi:10.4103/0975-9476.104443
PMCID: PMC3545241  PMID: 23326092
Arthritis; Costus speciosus; diclofenac sodium; Freund's complete adjuvant; paw volume

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