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Purpose: Healthy corneas resist colonization by virtually all microbes yet contact lens wear can predispose the cornea to sight-threatening infection with Pseudomonas aeruginosa . Here, we explored how lens wear changes corneal epithelium transcriptional responses to P. aeruginosa and its impact on bacterial gene expression., Methods: Male and female C57BL/6J mice were fitted with a contact lens on one eye for 24 h. After lens removal, corneas were immediately challenged for 4 h with P. aeruginosa . A separate group of naïve mice were similarly challenged with bacteria. Bacteria-challenged eyes were compared to uninoculated naive controls as was lens wear alone. Total RNA-sequencing determined corneal epithelium and bacterial gene expression., Results: Prior lens wear profoundly altered the corneal response to P. aeruginosa , including: upregulated pattern-recognition receptors ( tlr3, nod1 ), downregulated lectin pathway of complement activation ( masp1 ), amplified upregulation of tcf7 , gpr55, ifi205, wfdc2 (immune defense) and further suppression of efemp1 (corneal stromal integrity). Without lens wear, P. aeruginosa upregulated mitochondrial and ubiquinone metabolism genes. Lens wear alone upregulated axl, grn, tcf7, gpr55 (immune defense) and downregulated Ca2 + -dependent genes necab1, snx31 and npr3 . P. aeruginosa exposure to prior lens wearing vs. naïve corneas upregulated bacterial genes of virulence ( popD ), its regulation ( rsmY , PA1226) and antimicrobial resistance ( arnB , oprR )., Conclusion: Prior lens wear impacts corneal epithelium gene expression altering its responses to P. aeruginosa and how P. aeruginosa responds to it favoring virulence, survival and adaptation. Impacted genes and associated networks provide avenues for research to better understand infection pathogenesis.

Caloric restriction improves metabolic health but is often complicated by bone loss. We studied bone parameters in humans during a 10-day fast and identified candidate metabolic regulators of bone turnover. Pro-collagen 1 intact N-terminal pro-peptide (P1NP), a bone formation marker, decreased within 3 days of fasting. Whereas dual-energy x-ray absorptiometry measures of bone mineral density were unchanged after 10 days of fasting, high-resolution peripheral quantitative CT demonstrated remodeling of bone microarchitecture. Pathway analysis of longitudinal metabolomics data identified one-carbon metabolism as fasting dependent. In cultured osteoblasts, we tested the functional significance of one-carbon metabolites modulated by fasting, finding that methionine - which surged after 3 days of fasting - affected markers of osteoblast cell state in a concentration-dependent manner, in some instances exhibiting a U-shaped response with both low and high concentrations driving putative antibone responses. Administration of methionine to mice for 5 days recapitulated some fasting effects on bone, including a reduction in serum P1NP. In conclusion, a 10-day fast in humans led to remodeling of bone microarchitecture, potentially mediated by a surge in circulating methionine. These data support an emerging model that points to a window of optimal methionine exposure for bone health.

Regenerative peripheral nerve interface (RPNI) surgery has been demonstrated to be an effective tool as an interface for neuroprosthetics. Additionally, it has been shown to be a reproducible and reliable strategy for the active treatment and for prevention of neuromas. The purpose of this article is to provide a comprehensive review of RPNI surgery to demonstrate its simplicity and empower reconstructive surgeons to add this to their armamentarium. This article discusses the basic science of neuroma formation and prevention, as well as the theory of RPNI. An anatomic review and discussion of surgical technique for each level of amputation and considerations for other etiologies of traumatic neuromas are included. Lastly, the authors discuss the future of RPNI surgery and compare this with other active techniques for the treatment of neuromas., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Within epithelial cells, Pseudomonas aeruginosa depends on its type III secretion system (T3SS) to escape vacuoles and replicate rapidly in the cytosol. Previously, it was assumed that intracellular subpopulations remaining T3SS-negative (and therefore in vacuoles) were destined for degradation in lysosomes, supported by data showing vacuole acidification. Here, we report in both corneal and bronchial human epithelial cells that vacuole-associated bacteria can persist, sometimes in the same cells as cytosolic bacteria. Using a combination of phase-contrast, confocal, and correlative light-electron microscopy (CLEM), we also found they can demonstrate biofilm-associated markers: cdrA and cyclic-di-GMP (c-di-GMP). Vacuolar-associated bacteria, but not their cytosolic counterparts, tolerated the cell-permeable antibiotic ofloxacin. Surprisingly, use of mutants showed that both persistence in vacuoles and ofloxacin tolerance were independent of the biofilm-associated protein CdrA or exopolysaccharides (Psl, Pel, alginate). A T3SS mutant (Δ exsA ) unable to escape vacuoles phenocopied vacuole-associated subpopulations in wild-type PAO1-infected cells, with results revealing that epithelial cell death depended upon bacterial viability. Intravital confocal imaging of infected mouse corneas confirmed that P. aeruginosa formed similar intracellular subpopulations within epithelial cells in vivo . Together, these results show that P. aeruginosa differs from other pathogens by diversifying intracellularly into vacuolar and cytosolic subpopulations that both contribute to pathogenesis. Their different gene expression and behavior (e.g., rapid replication versus slow replication/persistence) suggest cooperation favoring both short- and long-term interests and another potential pathway to treatment failure. How this intracellular diversification relates to previously described "acute versus chronic" virulence gene-expression phenotypes of P. aeruginosa remains to be determined. IMPORTANCE Pseudomonas aeruginosa can cause sight- and life-threatening opportunistic infections, and its evolving antibiotic resistance is a growing concern. Most P. aeruginosa strains can invade host cells, presenting a challenge to therapies that do not penetrate host cell membranes. Previously, we showed that the P. aeruginosa type III secretion system (T3SS) plays a pivotal role in survival within epithelial cells, allowing escape from vacuoles, rapid replication in the cytoplasm, and suppression of host cell death. Here, we report the discovery of a novel T3SS-negative subpopulation of intracellular P. aeruginosa within epithelial cells that persist in vacuoles rather than the cytoplasm and that tolerate a cell-permeable antibiotic (ofloxacin) that is able to kill cytosolic bacteria. Classical biofilm-associated markers, although demonstrated by this subpopulation, are not required for vacuolar persistence or antibiotic tolerance. These findings advance our understanding of how P. aeruginosa hijacks host cells, showing that it diversifies into multiple populations with T3SS-negative members enabling persistence while rapid replication is accomplished by more vulnerable T3SS-positive siblings. Intracellular P. aeruginosa persisting and tolerating antibiotics independently of the T3SS or biofilm-associated factors could present additional challenges to development of more effective therapeutics.

Aims and Objective: The aim of the present study was to ascertain the reliability of using salivary glucose in diagnosing and monitoring the blood glucose levels in type 1 diabetic patients and also to evaluate the salivary glucose in fasting and postprandial states and correlate with the blood glucose levels and hemoglobin A1c values., Materials and Methods: The study was conducted on 79 Type 1 diabetic patients and 100 healthy controls. The blood and salivary glucose levels were evaluated in both study and control groups using glucose-oxidase peroxidase method., Results: There was significantly higher level of salivary glucose in diabetics than in controls. There was a positive moderate-to-strong correlation between stimulated and unstimulated salivary glucose to blood glucose in both fasting and postprandial states. The cutoff values for stimulated and unstimulated fasting salivary glucose was 5.8 mg/dl and 5.6 mg/dl, respectively. The cutoff value for stimulated and unstimulated salivary glucose in postprandial state was 10.3 mg/dl and 9.5 mg/dl, respectively., Conclusion: Salivary glucose appears to be a reliable biofluid to assess the blood glucose levels and can be a reliable alternative to blood glucose in Type 1 diabetes mellitus patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Pharmacy and Bioallied Sciences.)

Background: Antimicrobial resistance (AMR) is a global public health threat. The indiscriminate use of antibiotics in the animal health sector contributes to increasing rates of AMR and studies involving dairy farmers in India have found knowledge levels regarding antibiotics and AMR to be very low. The purpose of this study was to assess different methods to raise awareness and knowledge about AMR and antibiotic use among dairy farmers, paravets (veterinary assistants), and veterinarians., Materials and Methods: The study was conducted in September-December of 2018 in some parts of Haryana, Assam, Karnataka, and West Bengal. It had two parts: an intervention meeting (September-October 2018) which consisted of focus group discussions (FGD) with farmers, key informant interviews (KII) with veterinary professionals along with distribution of information packages, and then a follow-up survey (November-December 2018). The villages were randomly allocated to either one of the four intervention approaches (1-FGD/KII and information package on AMR; 2-FGD/KI and information on animal health; 3- FGD/KII and information package on animal health plus information on AMR; or 4- only the FGD/KII). A follow-up survey was done to assess the effect of interventions., Results: In total, 274 dairy farmers and 51 veterinary professionals (21 veterinarians and 30 paravets) participated in the follow-up survey. Many of the farmers and veterinary professionals who participated in the follow-up survey had been part of the intervention meetings. The average knowledge score of farmers was 7.8. It was found that the knowledge score was higher amongst farmers who had participated in the intervention meetings ( p < 0.05), had received intervention approach 2 ( p = 0.03) or approach 3 ( p = 0.01), and amongst female farmers ( p = 0.03) compared to male. The veterinary professionals had good knowledge but lacked interest in training the farmers about antimicrobial resistance., Conclusion: Our research demonstrated that a higher percentage of farmers and veterinary professionals who attended the intervention meeting had improved knowledge. Dairy farmers should be regularly educated on antibiotic usage and how to avoid misusing them. Also, veterinary experts should be provided with tools and strategies to educate farmers on the use of antimicrobials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sharma, Mutua, Deka, Shome, Bandyopadhyay, Shome, Kumar, Grace, Dey and Lindahl.)

Background and Aims: Moderate to severe postburn contractures (PBCs) of the neck lead to multiple areas of difficulty in airway management. Awake flexible fiberscope guided intubation with cuffed endotracheal tube (ETT) is considered the "gold standard" for securing the airway in these cases. Supraglottic airway devices (SADs), if at all used, are used either as rescue devices or as conduits for ETT. This case series looks at the possibility of using SADs as a planned airway securing device in these cases., Material and Methods: We managed 24 cases of moderate to severe PBC neck using six types of pre shaped SADs as the first choice airway device. These SADs were placed after either airway topicalization (19 cases) or general anesthesia (GA) (5 cases). Once SAD placement was confirmed, all the patients received GA and muscle relaxant. Tests for proper placement and function and fiberscopy (conducted in four cases) were performed at various times during the procedure. The SADs were removed once the patients were fully awake., Results: SADs could be placed in one attempt in all the cases. The time taken to hand over the patients to surgeons was 12-20 min. SADs maintained their proper placement and function in spite of changing airway dimensions during contracture release. The patients tolerated the SADs well right until the time they were fully awake. The SADs could be successfully removed on the operation table in all the cases., Conclusion: Pre shaped SADs secure the airway quickly and are free from the risk of intraoperative displacements and allow uneventful emergence in moderate and severe PBC neck cases and need to be considered as the first choice in these cases., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Anaesthesiology Clinical Pharmacology.)

Blind nasal intubation (BNI) has been around for over a century now. Many clinicians advocate it as an "old-is-gold" skill, which can be performed without any adjuncts in cases where visualization of larynx is a problem. Even today, BNI not only comes handy in resource-limited centers, it may also come to the rescue of airway managers in well-equipped centers. However, in the century since it was first described, there have been other major developments in the field of airway management and BNI as a skill has taken a backseat when it comes to a priority order. More so because it is limited by modalities to teach and train as most of the available manikins, which are otherwise phenomenal when it comes to imitating anatomy and overall attention to detail of a human airway, suffer terribly in one basic aspect needed to teach, train, and learn BNI-"they" cannot breathe! Attempts have been made to fabricate some manikins on these lines. But what if they can not only breathe but breathe out CO 2 as well! We describe a simple method whereby we created a "CO 2 breathing" manikin and tested it in an Airway Management Workshop with 105 participants, and then evaluated it under controlled conditions in 20 volunteers. We got very encouraging results and realized that our manikin makes the teaching and training of BNI very interesting and attractive by simulating the actual clinical scenario. We feel that it has the potential of reinventing the valuable skill of BNI., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Anaesthesiology Clinical Pharmacology.)

Background and Aims: The supraglottic airway devices (SADs) that allow direct (without an intermediary device like Aintree or airway exchange catheters) tracheal intubation can be invaluable for field use in conditions ideally managed by intubation. Whilst fiberscope-guided intubation is the method of choice, if these 'direct-intubation' SADs could provide high success rates for blind tracheal intubation, their scope of use can increase tremendously. Our study assesses intubating laryngeal mask airway (ILMA), i-gel and Ambu AuraGain for blind tracheal intubation in adults., Material and Methods: Ninety adults undergoing elective surgery were randomized into three equal groups. After induction of anesthesia, the group-specific SAD was inserted and on achieving adequate ventilation, blind tracheal intubation was attempted over two attempts. Success rates and time of achieving adequate device placement and tracheal intubation through these were evaluated. Data were analyzed using SPSS version 17.0 and P < 0.05 was considered statistically significant., Results: All three devices could achieve adequate ventilation within two allowed attempts. Successful tracheal intubation rates were significantly better with ILMA than i-gel on first attempt (87% vs. 27%, P < 0.001) and after second attempt that was supplemented with optimization maneuvers (100% vs. 40%, P < 0.001). No patient could be intubated through Ambu AuraGain within two attempts. Time taken for successful tracheal intubation did not differ significantly ( P = 0.205) with ILMA or i-gel., Conclusion: Out of ILMA, I-gel and Ambu AuraGain, ILMA is the best device for blind tracheal intubation in adults with normal airways., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Anaesthesiology Clinical Pharmacology.)

Bacterial lipases play important roles during infection. The Staphylococcus aureus genome contains several genes that encode well-characterized lipases and several genes predicted to encode lipases or esterases for which the function has not yet been established. In this study, we sought to define the function of an uncharacterized S. aureus protein, and we propose the annotation S. aureus lipase 3 (SAL3) (SAUSA300&#95;0641). We confirmed that SAL3 is a lipase and that it is surface associated and secreted through an unknown mechanism. We determined that SAL3 specifically hydrolyzes short chain (4-carbon and fewer) fatty acids and specifically binds negatively charged lipids including phosphatidic acid, phosphatidylinositol phosphate, and phosphatidylglycerol, which is the most abundant lipid in the staphylococcal cell membrane. Mutating the catalytic triad S66-A, D167-A, S168-A, and H301-A in the recombinant protein abolished lipase activity without altering binding to host lipid substrates. Taken together we report the discovery of a novel lipase from S. aureus specific to short chain fatty acids with yet to be determined roles in host pathogen interactions., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: Postoperative upper airway complications are frequently encountered with the use of supraglottic airway devices (SADs). Cuff pressure is one of the risk factors for upper airway complications with SADs. Among SADs, i-gel has shown lesser incidence. The effect of different cuff pressures on the incidence of postoperative upper airway complications is not known with Ambu AuraGain and nor has Ambu AuraGain been compared with i-gel in this regard. So, we undertook this study., Methods: A total of 200 patients undergoing elective laparoscopic surgery were randomised into 3 groups based on the SAD used and intra-cuff pressure: i-gel (IG) ( n = 66); Ambu AuraGain at 25 cmH 2 O cuff pressure (AL) ( n = 67); and Ambu AuraGain at 60 cmH 2 O cuff pressure (AH) ( n = 67). The oropharyngeal leak pressures (OLPs) were measured after insertion and generation of carboperitoneum. An observer who was blind to the intraoperative details assessed the patients for two postoperative days for sore throat, dysphagia, dysphonia, or any other upper airway complications., Results: The OLPs before and after carboperitoneum in the 3 groups were (IG-24.22 ± 7.87 and 28.31 ± 8.52, AL-24.40 ± 5.84 and 26.94 ± 5.93, AH-25.02 ± 5.02 and 28.91 ± 5.6) cmH 2 O ( P = 0.747 and P = 0.231). The overall incidence of postoperative sore throat among the 3 groups was: IG-5.7%, AL-14.9%, and AH-17.9%; P = 0.135. Dysphagia was seen only with Ambu AuraGain at high pressure in 4 patients (5.97%) ( P = 0.017)., Conclusion: Limiting cuff pressure in Ambu AuraGain to 25, as against 60 cmH 2 O, does not affect the OLP but has the potential of reducing the incidence of dysphagia., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Anaesthesia.)

Assessment of airway is recommended by every airway guideline to ensure safe airway management. Numerous unifactorial and multifactorial tests have been used for airway assessment over the years. However, there is none that can identify all the difficult airways. The reasons for the inadequacy of these methods of airway assessment might be their dependence on difficult to remember and apply mnemonics and scores, inability to identify all the variations from the "normal", and their lack of stress on evaluating the non-patient factors. Airway Management Foundation (AMF) experts and members have been using a different approach, the AMF Approach, to overcome these problems inherent to most available models of airway assessment. This approach suggests a three-step model of airway assessment. The airway manager first makes the assessment of the patient through focused history, focused general examination, and focused airway assessment using the AMF "line of sight" method. The AMF "line of sight" method is a non-mnemonic, non-score-based method of airway assessment wherein the airway manager examines the airway along the line of sight as it moves over the airway and notes down all the variations from the normal. Assessment of non-patient factors follows next and finally there is assimilation of all the information to help identify the available, difficult, and impossible areas of the airway management. The AMF approach is not merely intubation centric but also focuses on all other methods of securing airway and maintaining oxygenation. Airway assessment in the presence of contagion like COVID-19 is also discussed., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Anaesthesiology Clinical Pharmacology.)

Sneathia amnii is a poorly characterized emerging pathogen that has been implicated in amnionitis and urethritis. We found that S. amnii damages fetal membranes, and we identified and purified a cytotoxic exotoxin that lyses human red blood cells and damages cells from fetal membranes. The gene appears to be cotranscribed with a second gene that encodes a protein with identity to two-partner system transporters, suggesting that it is the "A," or secreted component of a type Vb system. The toxin is 1,881 amino acids with a molecular weight of approximately 200 kDa. It binds to red blood cell membranes and forms pores with a diameter of 2.0 to 3.0 nm, resulting in osmolysis. Because it appears to be the "A" or passenger component of a two-partner system, we propose to name this novel cytotoxin/hemolysin CptA for cytopathogenic toxin component A. IMPORTANCE Sneathia amnii is a very poorly characterized emerging pathogen that can affect pregnancy outcome and cause urethritis and other infections. To date, nothing is known about its virulence factors or pathogenesis. We have identified and isolated a cytotoxin, named CptA for cytopathogenic toxin, component A, that is produced by S. amnii CptA is capable of permeabilizing chorionic trophoblasts and lysing human red blood cells and, thus, may play a role in virulence. Except for small domains conserved among two-partner secretion system passenger proteins, the cytotoxin exhibits little amino acid sequence homology to known toxins. In this study, we demonstrate the pore-forming activity of this novel toxin., (Copyright © 2020 American Society for Microbiology.)

Diet is major modifiable risk factor for cardiovascular disease that can influence the immune status of the individual and contribute to persistent low-grade inflammation. In recent years, there has been an increased appreciation of the role of polyunsaturated fatty acids (PUFA) in improving immune function and reduction of systemic inflammation via the modulation of pattern recognition receptors (PRR) on immune cells. Extensive research on the use of bioactive lipids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and their metabolites have illustrated the importance of these pro-resolving lipid mediators in modulating signaling through PRRs. While their mechanism of action, bioavailability in the blood, and their efficacy for clinical use forms an active area of research, they are found widely administered as marine animal-based supplements like fish oil and krill oil to promote health. The focus of this review will be to discuss the effect of these bioactive fatty acids and their metabolites on immune cells and the resulting inflammatory response, with a brief discussion about modern methods for their analysis using mass spectrometry-based methods.

Arachidonic acid metabolites resulting from the cyclooxygenase (COX), lipoxygenase, and cytochrome P450 oxidase enzymatic pathways play pro- and anti-inflammatory roles in allergic airway inflammation (AAI) and asthma. Expression of COX-2 and soluble epoxide hydrolase (sEH) are elevated in allergic airways and their enzymatic products (e.g., prostaglandins and diols of epoxyeicosatrienoic acids, respectively) have been shown to participate in the pathogenesis of AAI. Here, we evaluated the outcome of inhibiting the COX-2 and sEH enzymatic pathways with a novel dual inhibitor, PTUPB, in A. alternata -induced AAI. Allergen-challenged mice were administered with 10 or 30 mg/kg of PTUPB, celecoxib (selective COX-2 inhibitor), t -TUCB (selective sEH inhibitor) or vehicle daily by gavage and evaluated for various features of AAI. PTUPB and t -TUCB at 30 mg/kg, but not celecoxib, inhibited eosinophilic infiltration and significantly increased levels of anti-inflammatory EETs in the lung tissue of allergen-challenged mice. t -TUCB significantly inhibited allergen-induced IL-4 and IL-13, while a less pronounced reduction was noted with PTUPB and celecoxib. Additionally, t -TUCB markedly inhibited eotaxin-2, an eosinophil-specific chemokine, which was only marginally reduced by PTUPB and remained elevated in celecoxib-treated mice. PTUPB or t -TUCB administration reversed allergen-induced reduction in levels of various lipid mediators in the lungs, with only a minimal effect noted with celecoxib. Despite the anti-inflammatory effects, PTUPB or t -TUCB did not reduce allergen-induced airway hyperresponsiveness (AHR). However, development of structural changes in the allergic airways, such as mucus hypersecretion and smooth muscle hypertrophy, was significantly inhibited by both inhibitors. Celecoxib, on the other hand, inhibited only airway smooth muscle hypertrophy, but not mucus hypersecretion. In conclusion, dual inhibition of COX-2 and sEH offers no additional advantage relative to sEH inhibition alone in attenuating various features associated with A. alternata -induced AAI, while COX-2 inhibition exerts only moderate or no effect on several of these features. Dual sEH/COX-2 inhibition may be useful in treating conditions where eosinophilic inflammation co-exists with pain-associated inflammation., (Copyright © 2019 Dileepan, Rastle-Simpson, Greenberg, Wijesinghe, Kumar, Yang, Hwang, Hammock, Sriramarao and Rao.)

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unrelated donor SCT, or autologous SCT. Blood samples were taken following conditioning and prior to transplant on day 0 and the plasma was comprehensively characterized with respect to its lipidome and metabolome via liquid chromatography/mass spectrometry (LCMS) and gas chromatography/mass spectrometry (GCMS). A pro-inflammatory metabolic profile was observed in patients who eventually developed GVHD. Five potential pre-transplant biomarkers, 2-aminobutyric acid, 1-monopalmitin, diacylglycerols (DG 38:5, DG 38:6), and fatty acid FA 20:1 demonstrated high sensitivity and specificity towards predicting post-transplant GVHD. The resulting predictive model demonstrated an estimated predictive accuracy of risk stratification of 100%, with area under the curve of the ROC of 0.995. The likelihood ratio of 1-monopalmitin (infinity), DG 38:5 (6.0), and DG 38:6 (6.0) also demonstrated that a patient with a positive test result for these biomarkers following conditioning and prior to transplant will be at risk of developing GVHD. Collectively, the data suggest the possibility that pre-transplant metabolic signature may be used for risk stratification of SCT recipients with respect to development of alloreactivity.

The metabolic changes that accompany changes in Cardiopulmonary testing (CPET) and heart failure biomarkers (HFbio) are not well known. We undertook metabolomic and lipidomic phenotyping of a cohort of heart failure (HF) patients and utilized Multiple Regression Analysis (MRA) to identify associations to CPET and HFBio test performance (peak oxygen consumption (Peak VO2), oxygen uptake efficiency slope (OUES), exercise duration, and minute ventilation-carbon dioxide production slope (VE/VCO2 slope), as well as the established HF biomarkers of inflammation C-reactive protein (CRP), beta-galactoside-binding protein (galectin-3), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP)). A cohort of 49 patients with a left ventricular ejection fraction < 50%, predominantly males African American, presenting a high frequency of diabetes, hyperlipidemia, and hypertension were used in the study. MRA revealed that metabolic models for VE/VCO2 and Peak VO2 were the most fitted models, and the highest predictors' coefficients were from Acylcarnitine C18:2, palmitic acid, citric acid, asparagine, and 3-hydroxybutiric acid. Metabolic Pathway Analysis (MetPA) used predictors to identify the most relevant metabolic pathways associated to the study, aminoacyl-tRNA and amino acid biosynthesis, amino acid metabolism, nitrogen metabolism, pantothenate and CoA biosynthesis, sphingolipid and glycerolipid metabolism, fatty acid biosynthesis, glutathione metabolism, and pentose phosphate pathway (PPP). Metabolite Set Enrichment Analysis (MSEA) found associations of our findings with pre-existing biological knowledge from studies of human plasma metabolism as brain dysfunction and enzyme deficiencies associated with lactic acidosis. Our results indicate a profile of oxidative stress, lactic acidosis, and metabolic syndrome coupled with mitochondria dysfunction in patients with HF tests poor performance. The insights resulting from this study coincides with what has previously been discussed in existing literature thereby supporting the validity of our findings while at the same time characterizing the metabolic underpinning of CPET and HFBio., Competing Interests: The authors have declared that no competing interests exist.

Parry Romberg Syndrome or Progressive Hemifacial Atrophy is a rare disease usually affecting one side of face with loss of soft and hard tissues. The disease appears suddenly and is usually self-limiting in 2-10 years time. The loss of soft and hard tissue leads to aesthetic and functional deficits which are compounded by the presence of associated symptoms like neuralgia, migraine, epilepsy and ocular involvement. The degree of deformity depends on the age at which the disease manifests first; the younger the age, the more severe the deformity. These patients undergo severe psychological trauma and social problems. The exact etiology is not known, and treatment is largely cosmetic. A report of three cases and a literature review is presented.

Pathological conditions can give rise to calcifications within oral mucosa representing either a local or systemic disturbance. Inflammation, trauma, debris acting as nidus and vascular lesions have been attributed as principal causes for occurrence of calcifications within the oral mucosa. Occurrence of multiple calcified thrombi (phleboliths) is considered pathognomonic for hemangiomas and vascular malformations in the oral and maxillofacial region. Isolated occurrence of phlebolith in oral mucosa though very rare, especially without any underlying vascular lesions, can be diagnostically challenging. Either a traumatic association at that site or a hemangioma of childhood that has regressed once the individual became an adult are the possible explanations suggested for the occurrence of these unique solitary phleboliths. Histologically, an "onion-ring"-like concentric lamellar fibrosis around a central core with varying amounts of calcifications and presence of minute vascular channels within or around calcified lamellae is characteristic for phlebolith. There is a high propensity for misdiagnosing solitary phlebolith located in sites like the buccal mucosa where various other pathologic soft-tissue calcifications, such as sialoliths, calcified lymph nodes, traumatic myositis ossificans, etc. can occur and they too appear radiopaque in radiographs. Besides, the absence of any associated underlying vascular lesion adds to the mispercep-tion. In such cases, histopathological examination with routine hematoxylin and eosin staining alone may not be sufficient to determine the accurate diagnosis. Allied clinical history and immunohistochemistry can aid to arrive at the final diagnosis. We report such a case of nonvascular lesion-associated solitary phlebolith in the right buccal mucosa of a healthy 49-year-old male patient and discuss its differential diagnosis with emphasis on histological presentation.

Introduction: Cranial defects may arise due to trauma, infection, surgical ablation or errors in development. Restoration of such defects is important for esthetics, function and morale of the patient. Several materials are available. Each has its advantages and disadvantages. Search is on for an ideal material. Autogenous grafts remain the gold standard in reconstruction of such defects. However, the morbidity associated with their harvest, additional time required, the need for a second surgical site and the limited supply has led to the search for newer substitutes. Although many materials are available today including biologic and non biologic substitutes, there is still no consensus about the best material. In this article we describe our use of calcium phosphate cements for reconstruction of hemispherical cranial defects., Materials and Methods: Cases requiring reconstruction of hemispherical cranial defects (more than 15 cm in any dimension) were selected for study. After exposing the defect under GA, titanium mesh was adapted to the defect for support. Then the calcium phosphate cement was prepared and injected on the mesh to establish good contour. The alloplastic insert in each patient was evaluated for: (a) Immediate post-operative complications (b) Restoration of contour and soft tissue support (c) New bone formation ascertained on HRCT at the end of 2 years. Patients were examined on postoperative first week, at 3 and at 6 months. High resolution computed tomography scans were taken at 2 years postop. There were two female and three male patients., Results: There were no complications in the post operative period. The general condition of the patients improved post operatively. Even though the cements maintained their contour at 2 years, there were no signs of bone formation within the cement., Conclusion: Calcium phosphate cement is a good bone substitute for use in cranioplasty. In defects requiring mechanical strength, it should be supported by a titanium mesh. It retains the contour but is not replaced by bone even after 2 years.

Aim: To investigate and record the palatal changes in individuals habituated to reverse chutta smoking in rural coastal Andhra population., Materials and Methods: Sixty individuals out of whom 47 females and 13 males habituated to reverse smoking with no other tobacco and alcohol habits and no other systemic disturbances were selected. The palatal changes were recorded by six examiners. Database were searched for the following terms "reverse smokers," "nicotina palatini" and "palatal lesions.", Results: The mean and percentage prevalence of the each lesion recorded and agreed by six examiners among 60 subjects showed presence of 87.77% hyperpigmented areas, 64.44% depigmented areas, 51.66% excrescences, 32.22% potentially malignant lesions and 9.72% frank ulcerations., Conclusion: Reverse smoking is an endemic tobacco habit still practiced in the coastal rural Andhra Pradesh. It is a well-established and socially acceptable habit among adult females. The changes recorded clinically shows characteristic features that are unique among this population group.

Unlabelled: Helicobacter pylori is a microaerophilic organism, which colonizes in the gastric mucosa. Its role in etiology and development of acute and chronic gastritis and peptic ulcer diseases is scientifically proved. Oral cavity especially supragingival, subgingival plaque and so forth simulate the same microaerophilic environment favorable for the growth of this bacterium., Aim: Detection of H. pylori simultaneously in the oral cavity and gastric mucosa of patients suffering from gastric pathologies., Objectives: To detect H. pylori in the oral cavity and gastric mucosa using endoscopy, urease test and real-time polymerase chain reaction (PCR) (urease A gene). Determining its association and corelation with patient demographics, oral hygiene maintenance and periodontal disease status., Materials and Methods: Endoscopic examination, oral findings oral hygiene index-simplified (OHI-S) and community periodontal index and treatment needs (CPITN) indices were recorded. Antral biopsies and supragingival plaque samples were taken from 56 dyspeptic adult patients. The collected samples were subjected to histological examination, urease broth test and urease A gene amplification using real-time PCR., Result: H. pylori was detected in the supragingival plaque of individuals with H. pylori-induced gastric diseases using rapid urease test and real-time PCR analysis. Occurrence of same strain of H. pylori simultaneously in plaque and gastric mucosa was observed. Positive correlation was obtained between the collected indices and quantity of H. pylori colonization.

The present study describes the beneficial effects of potential probiotic E. coli 16 (pUC8:16gfp) expressing Vitreoscilla hemoglobin (vgb) gene, associated with bacterial respiration under microaerobic condition, on gastrointestinal (GI) colonization and its antioxidant activity on carbon tetrachloride (CCl4) induced toxicity in Charles Foster rats. In vitro, catalase activity in E. coli 16 (pUC8:16gfp) was 1.8 times higher compared to E. coli 16 (pUC-gfp) control. In vivo, E. coli 16 (pUC8:16gfp) not only was recovered in the fecal matter after 70 days of oral administration but also retained antibacterial activities, whereas E. coli 16 (pUC-gfp) was not detected. Oral administration of 200 and 500 μL/kg body weight of CCl4 to rats at weekly interval resulted in elevated serum glutamyl pyruvate transaminase (SGPT) and serum glutamyl oxalacetate transaminase (SGOT) levels compared to controls. Rats prefed with E. coli 16 (pUC8:16gfp) demonstrated near to normal levels for SGPT and SGOT, whereas the liver homogenate catalase activity was significantly increased compared to CCl4 treated rats. Thus, pUC8:16gfp plasmid encoding vgb improved the growth and GI tract colonization of E. coli 16. In addition, it also enhanced catalase activity in rats harboring E. coli 16 (pUC8:16gfp), thereby preventing the absorption of CCl4 to GI tract.

Background: Despite the recent major changes in vascular and general surgery training, there has been a paucity of literature examining the effect of these changes on training and surgical outcomes. Amputations represent a common cross-section in core competencies for general surgery and vascular surgery trainees. This study evaluates the effect of trainee participation on outcomes after above-knee and below-knee amputations., Methods: The American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) database (2005 to 2010) was queried using Current Procedural Terminology codes (American Medical Association, Chicago, Ill) for below-knee amputation (27880, 27882) and above knee-amputation (27590, 27592). Resident involvement was defined using the NSQIP variable and was narrowed to postgraduate year 1 to 5. Variables associated with resident involvement were identified, and mortality, morbidity, intraoperative transfusion, and operative time (75th percentile vs the bottom three quartiles) were evaluated as distinct categoric end points in logistic regression. Included in the model were variables with a P value <.1 on χ(2) or independent t-test, as appropriate. Significance was defined at P < .05., Results: Residents were involved in 6587 of 11,038 amputations (62%). After adjustment for preoperative and intraoperative factors on logistic regression, there was a significant increase in major morbidity (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.14-1.42; P < .001), intraoperative transfusion (OR, 1.78; 95% CI, 1.50-2.11; P < .001), and operative time (OR, 1.64 95% CI, 1.46-1.84; P < .001) in resident cases., Conclusions: Resident involvement was associated with increased odds of major morbidity after amputation and also with increased operative time and risk for intraoperative transfusions., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Venous thromboembolism is a national health concern. Up to 58% of patients suffering from major multisystem trauma will experience venous thromboembolism if no measures are taken to prevent it. Of those, 10% to 30% will be fatal. The appropriate use of lower extremity compression, anticoagulation, and the use of inferior vena cava (IVC) filters has helped reduce the overall morbidity and mortality from this disease. The development of lower-profile devices and the ability to retrieve IVC filters has led to a liberalization of their use. The majority of the filters used today have achieved U.S. Food and Drug Administration approval through the 510K mechanism (approval based on prior similar devices rather than safety studies of the proposed device), and therefore, no rigorous investigations have been performed on them. Initially seeming safe, a recent increase in reports of filter migration, vena cava perforation, and vena cava thrombosis has prompted the Food and Drug Administration to ask for more information on their patterns of use, safety, efficacy, and retrievability. This report details some of the available data on the subject of IVC filters and the discussion surrounding the topic of prophylactic IVC filters in trauma patients., (Copyright © 2013 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Various local flaps have been used for reconstruction of developmental and post surgical soft tissue defects of maxillofacial region. They include nasolabial flap, palatal pedicled flap, buccal fat pad, temporalis muscle and fascia flap. An ideal flap for all indications is yet to be found. Our experience with free dermal fat graft in the correction of deformities associated with Parry Romberg syndrome and oral submucous fibrosis is presented.

Maintenance of hemodialysis access for end-stage renal disease continues to be a major challenge for vascular surgeons, nephrologists, and primary care physicians. This case report highlights the complication and treatment of lower extremity central venous stenosis, allowing continued dialysis access for a patient with limited remaining fistula options. This stenosis resulted from the prolonged use of a lower extremity central venous catheter. This case highlights the importance of imaging the central veins in obstruction of lower extremity fistulas. Once detected, as in the upper extremity, this can be effectively treated using balloon dilation and stenting., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Mice deficient in the Polycomb repressor Bmi1 develop numerous abnormalities including a severe defect in stem cell self-renewal, alterations in thymocyte maturation and a shortened lifespan. Previous work has implicated de-repression of the Ink4a/Arf (also known as Cdkn2a) locus as mediating many of the aspects of the Bmi1(-/-) phenotype. Here we demonstrate that cells derived from Bmi1(-/-) mice also have impaired mitochondrial function, a marked increase in the intracellular levels of reactive oxygen species and subsequent engagement of the DNA damage response pathway. Furthermore, many of the deficiencies normally observed in Bmi1(-/-) mice improve after either pharmacological treatment with the antioxidant N-acetylcysteine or genetic disruption of the DNA damage response pathway by Chk2 (also known as Chek2) deletion. These results demonstrate that Bmi1 has an unexpected role in maintaining mitochondrial function and redox homeostasis and indicate that the Polycomb family of proteins can coordinately regulate cellular metabolism with stem and progenitor cell function.

EphB4, a member of the largest family of receptor tyrosine kinases, is normally expressed on endothelial and neuronal cells. Although aberrant expression of EphB4 has been reported in several human tumors, including breast cancer, its functional significance is not understood. We report here that EphB4 is expressed in 7 of 12 (58%) human breast cancer specimens and 4 of 4 (100%) breast tumor cell lines examined. Overexpression of EphB4 in breast cancer cells was driven by gene amplification and by the erbB family of receptors via activation of Janus tyrosine kinase-signal transducers and activators of transcription and protein kinase B. The aberrantly expressed receptor was phosphorylated by its natural ligand, EphrinB2, and signaled via the protein kinase B pathway. Targeted knockdown of EphB4 expression by small interference RNA (and antisense oligodeoxynucleotides (ODNs)) led to dose-dependent reduction in cell survival, increased apoptosis, and sensitization to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Antisense ODN-mediated EphB4 knockdown resulted in reduced tumor growth in a murine tumor xenograft model. Antisense ODN-treated tumors were 72% smaller than control tumors at 6 weeks, with an 86% reduction in proliferating cells, 15-fold increase in apoptosis, and 44% reduction in tumor microvasculature. Our data indicate that biologically active EphB4 functions as a survival factor in breast cancer and is a novel target for therapy.

We have used in vivo 31P-nuclear magnetic resonance spectroscopy to study the changes in high-energy phosphates following hyperthermia. Immediately after heating, there is a fall in adenosine triphosphate and apparent intracellular pH and an increase in inorganic phosphate. Following sublethal heating (40 degrees for 15 min), these changes were partial, and they resolved over the subsequent 45 hr. With tumors given severe hyperthermia (47 degrees for 15 min), there was complete disappearance of adenosine triphosphate, with no recovery by 24 hr posttreatment. Qualitatively similar effects were seen after heating of normal leg muscle. The degree of fall of the adenosine triphosphate/inorganic phosphate concentration ratio was directly proportional to the heat dose and to thermal cell kill. 31P-Nuclear magnetic resonance spectroscopy may be useful in thermal dosimetry and treatment evaluation following hyperthermia.