Sphingolipids Mediate Differential Echinocandin Susceptibility in Candida albicans and Aspergillus nidulans

The cell wall synthesis-inhibiting echinocandins, including caspofungin and micafungin, play important roles in the treatment of candidiasis and aspergillosis. Previous studies revealed that, in the haploid yeast Candida glabrata, sphingolipid biosynthesis pathway mutations confer caspofungin reduced susceptibility (CRS) but micafungin increased susceptibility (MIS). Here, we describe one Candida albicans strain (of 10 tested) that similarly yields CRS-MIS mutants at relatively high frequency. Mutants demonstrated increased levels of long-chain bases (sphingolipid pathway intermediates) and, unique to this strain, loss of His104/Pro104 heterozygosity in the TSC13-encoded enoyl reductase. CRS-MIS was similarly observed in a C. albicans homozygous fen1Δ fen12Δ laboratory strain and in diverse wild-type strains following exogenous long-chain-base treatment. Analogous to these results, CRS-MIS was demonstrated in an Aspergillus nidulans basA mutant encoding defective sphingolipid C₄-hydroxylase and in its wild-type parent exposed to long-chain bases. Sphingolipids likely modulate echinocandin interaction with their Fks membrane target in all susceptible fungi, with potential implications for optimizing therapy with existing antifungals and the development of novel agents.     

Mechanical and Tribological Behavior of Mechanically Alloyed Ni-TiC Composites Processed via Spark Plasma Sintering

Titanium carbide (TiC) reinforced nickel (Ni) matrix composites were processed via mechanical alloying (MA) followed by spark plasma sintering (SPS) process. Mechanical alloying has gained special attention as a powerful non-equilibrium process for fabricating amorphous and nanocrystalline materials, whereas spark plasma sintering (SPS) is a unique technique for processing dense and near net shape bulk alloys with homogenous microstructure. TiC reinforcement varied from 5 to 50 wt.% into nickel matrix to investigate its effect on the microstructure and mechanical behavior of Ni-TiC composites. All Ni-TiC composites powder was mechanically alloyed using planetary high energy ball mill with 400 rpm and ball to powder ratio (BPR) 15:1 for 24 h. Bulk Ni-TiC composites were then sintered via SPS process at 50 MPa pressure and 900–1200 °C temperature. All Ni-TiC composites exhibited higher microhardness and compressive strength than pure nickel due to the presence of homogeneously distributed TiC particles within the nickel matrix, matrix grain refinement, and excellent interfacial bonding between nickel and TiC reinforcement. There is an increase in Ni-TiC composites microhardness with an increase in TiC reinforcement from 5 to 50 wt.%, and it reaches the maximum value of 900 HV for Ni-50TiC composites.     

Guidelines for prevention of hospital acquired infections

These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments.     

Comparison of post-operative ICU sedation between dexmedetomidine and propofol in Indian population

Context:

Critically ill patients requiring mechanical ventilation frequently need sedatives and analgesics to facilitate their care. Dexmedetomidine, a short-acting alpha-2-agonist, possesses anxiolytic, anesthetic, hypnotic, and analgesic properties.

Aims:

The objective of this study was to evaluate the efficacy and safety of dexmedetomidine in comparison to propofol in the management of sedation for post-operative intensive care unit (ICU) patients, as a sedative agent.

Settings and Design:

Teaching hospital, A phase III, prospective, open, randomized and comparative.

Materials and Methods:

Thirty patients who were ambulatory and who required the post-operative mechanical ventilation or post-operative sedation were enrolled, in which 15 patients received Dexmedetomidine and remaining 15 patients received propofol. All these patients were treated for the period of 8 to 24 h.

Statistical Analysis Used:

Data were analyzed using Student''s t-test and Chi-square test. The value of P < 0.05 was considered as statistically significant.

Results:

Demographic data were comparable. Pulse rate, respiratory rate and blood pressure were comparable. Depth of sedation and extubation time were similar. To maintain analgesia throughout the study period, patients receiving propofol infusions required significantly more analgesics than patients receiving Dexmedetomidine.

Conclusions:

Dexmedetomidine appears to be a safe and acceptable ICU sedative agent when both the clinician''s and patient''s perspectives are considered.     

Mechanistic insight into the improved Li ion conductivity of solid polymer electrolytes

Polymer based solid electrolytes (SEs) are envisaged as futuristic components of safer solid state energy devices. But the semi-crystalline nature and slow dynamics of the host polymer matrix are found to hamper the ion transport through the solid polymer network and hence solid state devices are still far beyond the scope of practical application. In this study, we unravel the synergistic roles of Li salt (LiClO₄) and two different polymers – polyethylene oxide (PEO) and polydimethyl siloxane (PDMS), in the Li ion transport through their solid blend based electrolyte. A detailed study using dielectric spectroscopy and thermo-mechanical analysis is conducted to understand the tunability of the PEO chain dynamics with LiClO₄ and the mechanism of hopping of Li ions by forming ion pairs with oxygen dipoles on the PEO backbone is established. Despite the lack of PDMS''s capability to solvate ions and promote ion transport directly, its proper mixing within the PEO host matrix is demonstrated to enhance ion transport due to the influence of PDMS on the segmental dynamics of PEO. A detailed molecular dynamics study supported by experimental validation suggests that even inert polymers can affect the dynamics of the active host matrix and increase ion transport, leading to next generation high ionic conductivity solid matrices, and opens new avenues in designing polymer based transparent electrolytes.

The studies shown here prove that both the Li salt and ‘inert-polymer’ mixing have paramount importance in the tunability of Li ion conductivity in solid electrolytes for batteries.     

Correlation of human S100A12 (EN-RAGE) and high-sensitivity C-reactive protein as gingival crevicular fluid and serum markers of inflammation in chronic periodontitis and type 2 diabetes

Objective

The aim of the present study was to evaluate the levels and correlation of human S100A12 and high-sensitivity C-reactive protein (hs-CRP) in gingival crevicular fluid (GCF) and serum in chronic periodontitis (CP) subjects with and without type 2 diabetes mellitus (DM).

Materials and methods

A total of 44 subjects were divided into three groups: group 1 had 10 periodontally healthy subjects, group 2 consisted of 17 CP subjects and group 3 had 17 type 2 DM subjects with CP. GCF and serum levels of human S100A12 and hs-CRP were quantified using enzyme-linked immunosorbent assay and immunoturbidimetric analysis, respectively. The clinical outcomes evaluated were gingival index, probing depth and clinical attachment level and the correlations of the two inflammatory mediators with clinical parameters were evaluated.

Results

Both human S100A12 and hs-CRP levels increased from group 1 to group 2 to group 3. The GCF and serum values of both these inflammatory mediators correlated positively with each other and with the periodontal parameters evaluated (p < 0.05).

Conclusion

Human S100A12 and hs-CRP can be considered as possible GCF and serum markers of inflammatory activity in CP and DM.     

Fabrication of maxillary single complete denture in a patient with deranged mandibular occlusal plane: A case report

Construction of a single complete denture (SCD) is a challenging clinical situation especially when the opposing natural dentition is not in a normal plane of occlusion. Mal-aligned, tilted or supra-erupted teeth in the opposing arch are some of the problems that should be corrected to achieve a balanced occlusion in patients who require SCD. Achieving harmonious occlusal plane is a primary objective of any restorative procedure to facilitate natural mandibular movements and ease of mastication. Establishment of normal occlusal plane in opposite arch is pre-requisite to maintain the stability of the SCD. This clinical report describes restoration of mandibular teeth (with severe attrition and deranged occlusion) by establishing normal plane of occlusion with the help of custom made occlusal plane template (OPT) followed by construction of a complete denture in maxillary arch.     

Echocardiography for Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy. The prevalence of phenotypic expression, in the absence of another systemic or cardiac disease causing increased left ventricular (LV) wall thickness, is estimated to be 1:500. The frequency of clinical presentation is far less, highlighting the need for a non-invasive diagnostic imaging tool. Echocardiography is readily available and allows for structural characterization and hemodynamic assessment of the hypertrophic heart and to screen patients at-risk for HCM, such as first degree relatives of affected individuals, and differentiate HCM from the athletic heart. Echocardiography can also be used to assess for anatomic abnormalities of the mitral valve apparatus that may exacerbate LV outflow track obstruction and to further risk stratify patients during exercise. Finally, echocardiography plays an integral role in guiding alcohol septal ablation procedures.     

Validation of the GRACE score for prognosis in Indian patients with acute coronary syndromes

AimTo validate the global registry of acute coronary events (GRACE) score in acute coronary syndromes (ACS) patients and study its angiographic correlation.Methods and resultsTwo-hundred and thirty-five ACS patients were studied for the combined endpoint of all-cause in-hospital mortality and non-fatal infarction/reinfarction. We tested the predictive accuracy of the composite GRACE score using the receiver operating characteristics (ROC) curve.Lower systolic blood pressure (SBP) (odds ratio [OR] 7.93, P=0.005), ST-segment deviation (OR 7.79, P=0.02) and cardiac biomarker positivity (OR > 6.52, P=0.01) were significantly associated with events. Serum creatinine > 1.4 mg/dL showed a trend towards statistical significance (OR 4.14, P=0.05), whereas age > 50 years (OR 3.62, P=not significant [NS]) and Killips class 4 (OR 2.71, P=NS) showed good association. The best value for predicting events was a GRACE score of > 217 and these patients were more likely to have double/triple vessel disease (P = 0.0009). The C statistic for the GRACE score was 0.75.ConclusionHigher GRACE score predicts in-hospital events and more severe angiographic coronary artery disease (CAD).     

Aneurysmally dilated major aorto-pulmonary collateral in tetralogy of Fallot

Haemodynamically significant systemic-to-pulmonary artery collaterals may present as a cause of cardiorespiratory compromise in tetralogy of Fallot (TOF) with pulmonary atresia. We present here a case of TOF with pulmonary atresia with aneurysmally dilated aorto-pulmonary collateral causing compression over trachea, presenting as dry irritating cough who died suddenly with haemoptysis probably due to rupture of hypertrophied bronchial collaterals or direct erosion of large major aorto-pulmonary collateral arteries (MAPCA) into the respiratory tract.