Optical Coherence Tomography-Based Positive Predictors of Eplerenone Therapy in Chronic Central Serous Chorioretinopathy: A Retrospective Study.

PURPOSE: This study aimed to investigate optical coherence tomography (OCT) biomarkers as potential predictors of treatment response in chronic central serous chorioretinopathy (CSCR). MATERIALS AND METHODS: It was a retrospective cohort study that included 42 patients with chronic CSCR. After complete ocular and hematological examinations, all patients received 50 mg/day of oral eplerenone for three months and were followed for at least six months. All participants were divided into two groups: Group 1 participants with a positive response to treatment (complete resolution of subretinal fluid (SRF) at six months) and Group 2 poor responders (moderate or less than 50% reduction in SRF from baseline). The primary outcome measure was the resolution of SRF, and various OCT biomarkers like central macular thickness (CMT), pigment epithelial detachments (PED), double-layer sign, elongation of the photoreceptor's outer segment, the integrity of the external limiting membrane, the integrity of the ellipsoid zone, hyperreflective foci in the outer segment, and subretinal deposits in the SRF were assessed. RESULTS: The mean age was 41.33 ± 10.75 years, and 34 participants were male. Thirty-seven (88.1%) of the participants had good responses to eplerenone, with the mean height of SRF decreasing significantly from a maximum of 269.74 µm to a minimum of 21.86 µm at six months (p<0.001). The mean CMT decreased from the first visit time point to the third visit time (p<0.001). Logistic regression analysis assessed the absence of PED and double-layer signs associated with a good response. CONCLUSION: The eplerenone therapy seems to be efficient for chronic CSCR, and OCT can be an invaluable aid to the treating physician.

Current Concepts and Recent Updates of Optical Biometry- A Comprehensive Review.

One of the most recent advancements in the field of cataract surgery is optical biometry. With the advent of optical biometry ocular measurements are now simpler, quicker, and more precise. The devices have made intraocular lens (IOL) power calculations easier in difficult situations too, such as in cases with extremes of axial lengths, silicone filled eyes, cataract surgery in post-keratoplasty eyes, post Laser-Assisted in Situ Keratomileusis (LASIK) eyes, etc. The gold standard for IOL power calculation in the present day is by the use of optical biometry devices. The anatomical measurements by these devices are highly precise and because of these measurements and the incorporation of various IOL power calculation formulas the optical biometry devices give the accurate power and the post-operative visual outcome is highly satisfactory among the patients. The growing use of these devices has made cataract the most commonly performed refractive surgical procedure nowadays. In the current scenario, optical biometry has widespread acceptance in almost all countries and has many advantages over ultrasound or immersion biometry. Cataract surgeons can obtain easy and reliable measurements from these devices. Refractive surprises have also decreased considerably with their use. This article will comprehensively review the principles of the various optical biometry devices, the parameters used in each of the devices, the advantages and disadvantages, and add more like what all this article will add.

Monotherapy with topical Natamycin to treat Scedosporium keratomycosis: A rare case from Central India.

Keratomycosis is common in Indian subcontinent. Diagnosis of the causal agent and successful management is a challenge for the clinician. Scedosporium is a rare fungus species, and it is relatively rare in causing keratomycosis. We report the case of a 29-year-old male who presented with complaints of redness, watering, and white lesion over his left eye. He sustained an injury in the left eye with vegetative matter. Corneal scraping was sent for potassium hydroxide staining and culture; fungal colony was seen in culture. Colony characters on Sabouraud dextrose agar and lactophenol cotton blue enabled a diagnosis of Scedosporium species. The patient was treated with topical Natamycin 5%, and complete resolution was seen at the end of 4 weeks. This case report highlights good response of keratitis caused by Scedosporium to topical Natamycin therapy.

Digital society social interactions and trust analysis model.

During unprecedented events such as COVID-19, the fabric of society comes under stress and all stakeholders want to increase the predictability of the future and reduce the ongoing uncertainties. In this research, an attempt has been made to model the situation in which the sentiment "trust" is computed so as to map the behaviour of society. However, technically, the purpose of this research is not to determine the "degree of trust in society" as a consequence of some specific emotions or sentiments that the community is experiencing at any particular time. This project is concerned with the construction of a computational model that can assist in improving our understanding of the dynamics of digital societies, particularly when it comes to the attitude referred to as "trust." The digital society trust analysis (D.S.T.A.) model that has been provided is simple to configure and simple to implement. It includes many previous models, such as standing models, Schelling's model of segregation, and tipping points, in order to construct models for understanding the dynamics of a society reeling under the effects of a COVID-19 pandemic, misinformation, fake news, and other sentiments that impact the behaviour of the different groups.

Oxidative Stress Mediates the Fetal Programming of Hypertension by Glucocorticoids.

The field of cardiovascular fetal programming has emphasized the importance of the uterine environment on postnatal cardiovascular health. Studies have linked increased fetal glucocorticoid exposure, either from exogenous sources (such as dexamethasone (Dex) injections), or from maternal stress, to the development of adult cardiovascular pathologies. Although the mechanisms are not fully understood, alterations in gene expression driven by altered oxidative stress and epigenetic pathways are implicated in glucocorticoid-mediated cardiovascular programming. Antioxidants, such as the naturally occurring polyphenol epigallocatechin gallate (EGCG), or the superoxide dismutase (SOD) 4-hydroxy-TEMPO (TEMPOL), have shown promise in the prevention of cardiovascular dysfunction and programming. This study investigated maternal antioxidant administration with EGCG or TEMPOL and their ability to attenuate the fetal programming of hypertension via Dex injections in WKY rats. Results from this study indicate that, while Dex-programming increased blood pressure in male and female adult offspring, administration of EGCG or TEMPOL via maternal drinking water attenuated Dex-programmed increases in blood pressure, as well as changes in adrenal mRNA and protein levels of catecholamine biosynthetic enzymes phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), dopamine beta hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), in a sex-specific manner. Furthermore, programmed male offspring displayed reduced antioxidant glutathione peroxidase 1 (Gpx1) expression, increased superoxide dismutase 1 (SOD1) and catalase (CAT) expression, and increased pro-oxidant NADPH oxidase activator 1 (Noxa1) expression in the adrenal glands. In addition, prenatal Dex exposure alters expression of epigenetic regulators histone deacetylase (HDAC) 1, 5, 6, 7, 11, in male and HDAC7 in female offspring. These results suggest that glucocorticoids may mediate the fetal programming of hypertension via alteration of epigenetic machinery and oxidative stress pathways.

Pathway mapping of leukocyte transcriptome in influenza patients reveals distinct pathogenic mechanisms associated with progression to severe infection.

BACKGROUND: Influenza infections produce a spectrum of disease severity, ranging from a mild respiratory illness to respiratory failure and death. The host-response pathways associated with the progression to severe influenza disease are not well understood. METHODS: To gain insight into the disease mechanisms associated with progression to severe infection, we analyzed the leukocyte transcriptome in severe and moderate influenza patients and healthy control subjects. Pathway analysis on differentially expressed genes was performed using a topology-based pathway analysis tool that takes into account the interaction between multiple cellular pathways. The pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. RESULTS: 107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. Severe influenza was associated with upregulation in several neutrophil-related pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (NET) formation. The degree of upregulation in neutrophil-related pathways were significantly higher in severely infected patients compared to moderately infected patients. Severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation such as CD4+ T-cell co-stimulation, CD8+ T cell and Natural Killer (NK) cells effector functions. Apoptosis pathways were also downregulated in severe influenza patients compare to moderate and healthy controls. CONCLUSIONS: These findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection.

Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection.

Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817-0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy.

Medial patellofemoral ligament reconstruction using an autograft or allograft for patellar dislocation: a systematic review.

PURPOSES: The purpose of this study is to review the use of an allograft or autograft in medial patellofemoral ligament (MPFL) reconstruction. MATERIALS AND METHODS: Various electronic databases were searched for relevant articles published from January 2000 to September 2017 that evaluated clinical outcomes of MPFL reconstruction using an autograft or allograft. Data search, extraction, analysis, and quality assessments were performed based on Cochrane Collaboration guidelines. RESULTS: The study of 21 autografts and one allograft was included in this review. Although direct comparative studies were unavailable, the Kujala score and subjective results were reported in the majority of these studies. While the use of an autograft for MPFL reconstruction yielded satisfactory clinical outcomes with few perioperative complications, no new outcome has been drawn from the use of allografts. CONCLUSIONS: Although many studies have shown favorable clinical results for MPFL reconstruction using an autograft, the clinical results of MPFL reconstruction using an allograft have not yet been sufficient to achieve meaningful clinical results due to low levels of evidence. Direct comparisons were not conducted because there were very few studies on allografts; thus, further research in this area should be performed in the future.

Predicting in-hospital mortality in pneumonia-associated septic shock patients using a classification and regression tree: a nested cohort study.

BACKGROUND: Pneumonia complicated by septic shock is associated with significant morbidity and mortality. Classification and regression tree methodology is an intuitive method for predicting clinical outcomes using binary splits. We aimed to improve the prediction of in-hospital mortality in patients with pneumonia and septic shock using decision tree analysis. METHODS: Classification and regression tree models were applied to all patients with pneumonia-associated septic shock in the international, multicenter Cooperative Antimicrobial Therapy of Septic Shock database between 1996 and 2015. The association between clinical factors (time to appropriate antimicrobial therapy, severity of illness) and in-hospital mortality was evaluated. Accuracy in predicting clinical outcomes, sensitivity, specificity, and area under receiver operating curve of the final model was evaluated in training (n = 2111) and testing datasets (n = 2111). RESULTS: The study cohort contained 4222 patients, and in-hospital mortality was 51%. The mean time from onset of shock to administration of appropriate antimicrobials was significantly higher for patients who died (17.2 h) compared to those who survived (5.0 h). In the training dataset (n = 2111), a tree model using Acute Physiology and Chronic Health Evaluation II Score, lactate, age, and time to appropriate antimicrobial therapy yielded accuracy of 73% and area under the receiver operating curve 0.75. The testing dataset (n = 2111) had accuracy of 69% and area under the receiver operating curve 0.72. CONCLUSIONS: Overall mortality (51%) in patients with pneumonia complicated by septic shock is high. Increased time to administration of antimicrobial therapy, Acute Physiology and Chronic Health Evaluation II Score, serum lactate, and age were associated with increased in-hospital mortality. Classification and regression tree methodology offers a simple prognostic model with good performance in predicting in-hospital mortality.

Fungicidal versus fungistatic therapy of invasive Candida infection in non-neutropenic adults: a meta-analysis.

The purpose of this study was to determine whether fungicidal versus fungistatic pharmacotherapy of invasive candidiasis/candidemia yields superior outcomes. Data sources included MEDLINE (1966-June 2017), EMBASE (1980-June 2017), PubMed (1966-June 2017), Global Health-Ovid (inception to June 2017), LILACS Virtual Health Library (inception to June 2017) and the Cochrane Central Register of Controlled Trials (to 2nd quarter 2017). The ClinicalTrial.gov database, the SCOPUS database, SIGLE (System for Information on Grey Literature) and Google Scholar were also utilised to search for relevant studies. Randomised studies of any pharmacotherapy of invasive candidiasis including candidemia using a fungicidal (amphotericin B or echinocandin compound) versus a fungistatic (triazole) compound in adolescent or adult non-neutropenic patients. Eight studies met the inclusion criteria. Pooled odds ratios demonstrated an advantage of fungicidal therapy with respect to early therapeutic success (OR 1.61, 95% CI 1.27-2.03, p < 0.0001, I2 = 0%) and persistence or recurrence of infection (OR 0.51, 95% CI 0.35-0.74, p = 0.0005, I2 = 0%) but no advantage for late survival (OR 0.97, 95% CI 0.77-1.21, p = 0.77, I2 = 0%). Fungicidal therapy of invasive candidiasis and candidemia is associated with a higher probability of early therapeutic success and decreased probability of persistent or recurrent infection. However, there is no improvement in survival.

Inflammatory Signaling in Hypertension: Regulation of Adrenal Catecholamine Biosynthesis.

The immune system is increasingly recognized for its role in the genesis and progression of hypertension. The adrenal gland is a major site that coordinates the stress response via the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal system. Catecholamines released from the adrenal medulla function in the neuro-hormonal regulation of blood pressure and have a well-established link to hypertension. The immune system has an active role in the progression of hypertension and cytokines are powerful modulators of adrenal cell function. Adrenal medullary cells integrate neural, hormonal, and immune signals. Changes in adrenal cytokines during the progression of hypertension may promote blood pressure elevation by influencing catecholamine biosynthesis. This review highlights the potential interactions of cytokine signaling networks with those of catecholamine biosynthesis within the adrenal, and discusses the role of cytokines in the coordination of blood pressure regulation and the stress response.

Culture-Negative Septic Shock Compared With Culture-Positive Septic Shock: A Retrospective Cohort Study.

OBJECTIVES: To determine the clinical characteristics and outcomes of culture-negative septic shock in comparison with culture-positive septic shock. DESIGN: Retrospective nested cohort study. SETTING: ICUs of 28 academic and community hospitals in three countries between 1997 and 2010. SUBJECTS: Patients with culture-negative septic shock and culture-positive septic shock derived from a trinational (n = 8,670) database of patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with culture-negative septic shock (n = 2,651; 30.6%) and culture-positive septic shock (n = 6,019; 69.4%) were identified. Culture-negative septic shock compared with culture-positive septic shock patients experienced similar ICU survival (58.3% vs 59.5%; p = 0.276) and overall hospital survival (47.3% vs 47.1%; p = 0.976). Severity of illness was similar between culture-negative septic shock and culture-positive septic shock groups ([mean and SD Acute Physiology and Chronic Health Evaluation II, 25.7 ± 8.3 vs 25.7 ± 8.1]; p = 0.723) as were serum lactate levels (3.0 [interquartile range, 1.7-6.1] vs 3.2 mmol/L [interquartile range, 1.8-5.9 mmol/L]; p = 0.366). As delays in the administration of appropriate antimicrobial therapy after the onset of hypotension increased, patients in both groups experienced congruent increases in overall hospital mortality: culture-negative septic shock (odds ratio, 1.56; 95% CI [1.47-1.66]; p < 0.0001) and culture-positive septic shock (odds ratio, 1.65; 95% CI [1.59-1.71]; p < 0.0001). CONCLUSIONS: Patients with culture-negative septic shock behave similarly to those with culture-positive septic shock in nearly all respects; early appropriate antimicrobial therapy appears to improve mortality. Early recognition and eradication of infection is the most obvious effective strategy to improve hospital survival.

The impact of obesity in cirrhotic patients with septic shock: A retrospective cohort study.

BACKGROUND & AIMS: The prevalence of obesity in cirrhosis is rising. The impact of obesity in critically ill cirrhotic patients with sepsis/septic shock has not been evaluated. This study aimed to examine the relationship between obesity and mortality in cirrhotic patients admitted to the intensive care unit with septic shock. METHODS: A retrospective cohort study of all cirrhotic patients with septic shock (n = 362) and a recorded body mass index (BMI) from an international, multicentre (CATSS) database (1996-2015) was performed. Patients were classified by BMI as per WHO categories. Primary outcome was in-hospital mortality. Multivariate logistic regression analyses were carried out to determine independent associations with outcome. RESULTS: In this analysis, mean age was 56.4 years, and 62% were male. Median BMI was 26.3%, and 57.7% were overweight/obese. In-hospital mortality was 71%. Obese patients were more likely to have comorbidities of cardiac disease, lung disease and diabetes. Compared to survivors (n = 105), non-survivors (n = 257) had significantly higher MELD and APACHEII scores and higher requirements for renal replacement therapy and mechanical ventilation (P < .03 for all). Using multivariable logistic regression, increase in BMI (OR 1.07, P = .034), time delay to appropriate antimicrobials (OR 1.16 per hour, P = .003), APACHEII (OR 1.12 per unit, P = .008) and peak lactate (OR 1.15, P = .028) were independently associated with in-hospital mortality. CONCLUSIONS: Septic shock in cirrhosis carries a high mortality. Increased BMI is common in critically ill cirrhotic patients and independently associated with increased in-hospital mortality.

A novel immune biomarker IFI27 discriminates between influenza and bacteria in patients with suspected respiratory infection.

Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with in vitro experiments using well-established infection models.We identified a single-gene biomarker, IFI27, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. In vitro studies showed that IFI27 was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. In vivo studies confirmed that IFI27 was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), IFI27 displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections.IFI27 represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory infection.

Cardiac phenylethanolamine N-methyltransferase: localization and regulation of gene expression in the spontaneously hypertensive rat.

Phenylethanolamine N-methyltransferase (PNMT) is the terminal enzyme in the catecholamine biosynthetic pathway responsible for adrenaline biosynthesis. Adrenaline is involved in the sympathetic control of blood pressure; it augments cardiac function by increasing stroke volume and cardiac output. Genetic mapping studies have linked the PNMT gene to hypertension. This study examined the expression of cardiac PNMT and changes in its transcriptional regulators in the spontaneously hypertensive (SHR) and wild type Wistar-Kyoto (WKY) rats. SHR exhibit elevated levels of corticosterone, and lower levels of the cytokine IL-1ß, revealing systemic differences between SHR and WKY. PNMT mRNA was significantly increased in all chambers of the heart in the SHR, with the greatest increase in the right atrium. Transcriptional regulators of the PNMT promoter show elevated expression of Egr-1, Sp1, AP-2, and GR mRNA in all chambers of the SHR heart, while protein levels of Sp1, Egr-1, and GR were elevated only in the right atrium. Interestingly, only AP-2 protein-DNA binding was increased, suggesting it may be a key regulator of cardiac PNMT in SHR. This study provides the first insights into the molecular mechanisms involved in the dysregulation of cardiac PNMT in a genetic model of hypertension.

Inflammatory impact of IFN-γ in CD8+ T cell-mediated lung injury is mediated by both Stat1-dependent and -independent pathways.

Influenza infection results in considerable pulmonary pathology, a significant component of which is mediated by CD8(+) T cell effector functions. To isolate the specific contribution of CD8(+) T cells to lung immunopathology, we utilized a nonviral murine model in which alveolar epithelial cells express an influenza antigen and injury is initiated by adoptive transfer of influenza-specific CD8(+) T cells. We report that IFN-γ production by adoptively transferred influenza-specific CD8(+) T cells is a significant contributor to acute lung injury following influenza antigen recognition, in isolation from its impact on viral clearance. CD8(+) T cell production of IFN-γ enhanced lung epithelial cell expression of chemokines and the subsequent recruitment of inflammatory cells into the airways. Surprisingly, Stat1 deficiency in the adoptive-transfer recipients exacerbated the lung injury that was mediated by the transferred influenza-specific CD8(+) T cells but was still dependent on IFN-γ production by these cells. Loss of Stat1 resulted in sustained activation of Stat3 signaling, dysregulated chemokine expression, and increased infiltration of the airways by inflammatory cells. Taken together, these data identify important roles for IFN-γ signaling and Stat1-independent IFN-γ signaling in regulating CD8(+) T cell-mediated acute lung injury. This is the first study to demonstrate an anti-inflammatory effect of Stat1 on CD8(+) T cell-mediated lung immunopathology without the complication of differences in viral load.

Non-pulmonary infections but not specific pathogens are associated with increased risk of AKI in septic shock.

INTRODUCTION: Little is known regarding the relationship between the anatomic infection site and etiologic pathogen with the occurrence of acute kidney injury (AKI) in severe infections. We set out to determine the association between the site of infection, type of pathogen in septic shock and occurrence of AKI. METHODS: Using a large, international multicenter database that included data from 28 academic and community hospitals, we retrospectively analyzed adult (age >18 years) cases of septic shock occurring between January 1996 and December 2008. Early acute kidney injury (AKI) was classified by the RIFLE criteria at or within 24 h of shock diagnosis. Multivariate logistic regression was used to determine the association between the infection site/microbial pathogen and occurrence of AKI. Analyses were adjusted for demographics, illness severity, comorbidities and intensive care unit interventions (partial adjustment) ± site of infection and microbial pathogen (full adjustment). RESULTS: After exclusions, 4,493 cases from potentially eligible patients in the database were included in the analytic cohort of whom 3,298 (73.4 %) experienced AKI. Patients with AKI were older (p < 0.0001), had a higher mean Acute Physiology and Chronic Health Evaluation score (p < 0.0001), and had greater laboratory and hemodynamic abnormalities. The most common site of infection among septic shock patients with AKI was the lung (34.5 %), followed by gastrointestinal (GI) (26.2 %) and urinary (15.3 %) sources. Likewise, the most common infecting organism among septic shock patients with AKI was E. coli (23.9 %) followed by S. aureus (GI) (16.1 %) and other enterobacteriaceae (15.7 %). There was a large degree of variability in the occurrence of AKI based on the site of infection and the pathogen in unadjusted analysis (p < 0.0001), which persisted with partial (excluding infection site and microbial pathogen grouping) adjustment (p < 0.0001). Fully adjusted multivariate analysis showed significant variations in AKI only in relation to the anatomic source of infection, with non-pulmonary infections having higher risk than pulmonary infections. The pathogen group/pathogen had no significant independent impact on AKI. CONCLUSION: This study demonstrates that the presence of septic AKI varies significantly based on the site of infection but not the type of causative organism.

Association between source of infection and hospital mortality in patients who have septic shock.

RATIONALE: Mortality caused by septic shock may be determined by a systemic inflammatory response, independent of the inciting infection, but it may also be influenced by the anatomic source of infection. OBJECTIVES: To determine the association between the anatomic source of infection and hospital mortality in critically ill patients who have septic shock. METHODS: This was a retrospective, multicenter cohort study of 7,974 patients who had septic shock in 29 academic and community intensive care units in Canada, the United States, and Saudi Arabia from January 1989 to May 2008. MEASUREMENTS AND MAIN RESULTS: Subjects were assigned 1 of 20 anatomic sources of infection based on clinical diagnosis and/or isolation of pathogens. The primary outcome was hospital mortality. Overall crude hospital mortality was 52% (21-85% across sources of infection). Variation in mortality remained after adjusting for year of admission, geographic source of admission, age, sex, comorbidities, community- versus hospital-acquired infection, and organism type. The source of infection with the highest standardized hospital mortality was ischemic bowel (75%); the lowest was obstructive uropathy-associated urinary tract infection (26%). Residual variation in adjusted hospital mortality was not explained by Acute Physiology and Chronic Health Evaluation II score, number of Day 1 organ failures, bacteremia, appropriateness of empiric antimicrobials, or adjunct therapies. In patients who received appropriate antimicrobials after onset of hypotension, source of infection was associated with death after adjustment for both predisposing and downstream factors. CONCLUSIONS: Anatomic source of infection should be considered in future trial designs and analyses, and in development of prognostic scoring systems.

Antiapoptotic actions of methyl gallate on neonatal rat cardiac myocytes exposed to H2O2.

Reactive oxygen species trigger cardiomyocyte cell death via increased oxidative stress and have been implicated in the pathogenesis of cardiovascular diseases. The prevention of cardiomyocyte apoptosis is a putative therapeutic target in cardioprotection. Polyphenol intake has been associated with reduced incidences of cardiovascular disease and better overall health. Polyphenols like epigallocatechin gallate (EGCG) can reduce apoptosis of cardiomyocytes, resulting in better health outcomes in animal models of cardiac disorders. Here, we analyzed whether the antioxidant N-acetyl cysteine (NAC) or polyphenols EGCG, gallic acid (GA) or methyl gallate (MG) can protect cardiomyocytes from cobalt or H2O2-induced stress. We demonstrate that MG can uphold viability of neonatal rat cardiomyocytes exposed to H2O2 by diminishing intracellular ROS, maintaining mitochondrial membrane potential, augmenting endogenous glutathione, and reducing apoptosis as evidenced by impaired Annexin V/PI staining, prevention of DNA fragmentation, and cleaved caspase-9 accumulation. These findings suggest a therapeutic value for MG in cardioprotection.

Influenza A induced cellular signal transduction pathways.

Influenza A is a negative sense single stranded RNA virus that belongs to the Orthomyxoviridae Family. This enveloped virus contains 8 segments of viral RNA which encodes 11 viral proteins. Influenza A infects humans and is the causative agent of the flu. Annually it infects approximately 5% to 15% of the population world wide and results in an estimated 250,000 to 500,000 deaths a year. The nature of influenza A replication results in a high mutation rate which results in the need for seasonal vaccinations. In addition the zoonotic nature of the influenza virus allows for recombination of viral segments from different strains creating new variants that have not been encountered before. This type of mutation is the method by which pandemic strains of the flu arises. Infection with influenza results in a respiratory illness that for most individuals is self limiting. However in susceptible populations which include individuals with pre-existing pulmonary or cardiac conditions, the very young and the elderly fatal complications may arise. The most serious of these is the development of viral pneumonia which may be accompanied by secondary bacterial infections. Progression of pneumonia leads to the development of acute respiratory distress syndrome (ARDS), acute lung injury (ALI) and potentially respiratory failure. This progression is a combined effect of the host immune system response to influenza infection and the viral infection itself. This review will focus on molecular aspects of viral replication in alveolar cells and their response to infection. The response of select innate immune cells and their contribution to viral clearance and lung epithelial damage will also be discussed. Molecular aspects of antiviral response in the cells in particular the protein kinase RNA dependent response, and the oligoadenylate synthetase RNAse L system in relation to influenza infection.