White matter hyperintensity volume modifies the association between CSF vascular inflammatory biomarkers and regional FDG-PET along the Alzheimer's disease continuum.

In older adults with abnormal levels of Alzheimer's disease neuropathology, lower cerebrospinal fluid (CSF) vascular endothelial growth factor (VEGF) levels are associated with lower [¹8F]-fluorodeoxyglucose positron emission tomography (FDG-PET) signal, but whether this association is (1) specific to VEGF or broadly driven by vascular inflammation, or (2) modified by vascular risk (e.g., white matter hyperintensities [WMHs]) remains unknown. To address this and build upon our past work, we evaluated whether 5 CSF vascular inflammation biomarkers (vascular cell adhesion molecule 1, VEGF, C-reactive protein, fibrinogen, and von Willebrand factor)-previously associated with CSF amyloid levels-were related to FDG-PET signal and whether WMH volume modified these associations in 158 Alzheimer's Disease Neuroimaging Initiative participants (55-90 years old, 39 cognitively normal, 80 mild cognitive impairment, 39 Alzheimer's disease). We defined regions both by cortical boundary and by the 3 major vascular territories: anterior, middle, and posterior cerebral arteries. We found that WMH volume had interactive effects with CSF biomarkers (VEGF and C-reactive protein) on FDG-PET throughout the cortex in both vascular territories and conventionally defined regions of interest.

Mitochondrial DNA variation in Alzheimer's disease reveals a unique microprotein called SHMOOSE.

Mitochondrial DNA variants have previously associated with disease, but the underlying mechanisms have been largely elusive. Here, we report that mitochondrial SNP rs2853499 associated with Alzheimer's disease (AD), neuroimaging, and transcriptomics. We mapped rs2853499 to a novel mitochondrial small open reading frame called SHMOOSE with microprotein encoding potential. Indeed, we detected two unique SHMOOSE-derived peptide fragments in mitochondria by using mass spectrometry-the first unique mass spectrometry-based detection of a mitochondrial-encoded microprotein to date. Furthermore, cerebrospinal fluid (CSF) SHMOOSE levels in humans correlated with age, CSF tau, and brain white matter volume. We followed up on these genetic and biochemical findings by carrying out a series of functional experiments. SHMOOSE acted on the brain following intracerebroventricular administration, differentiated mitochondrial gene expression in multiple models, localized to mitochondria, bound the inner mitochondrial membrane protein mitofilin, and boosted mitochondrial oxygen consumption. Altogether, SHMOOSE has vast implications for the fields of neurobiology, Alzheimer's disease, and microproteins.

Testing a convolutional neural network-based hippocampal segmentation method in a stroke population.

As stroke mortality rates decrease, there has been a surge of effort to study poststroke dementia (PSD) to improve long-term quality of life for stroke survivors. Hippocampal volume may be an important neuroimaging biomarker in poststroke dementia, as it has been associated with many other forms of dementia. However, studying hippocampal volume using MRI requires hippocampal segmentation. Advances in automated segmentation methods have allowed for studying the hippocampus on a large scale, which is important for robust results in the heterogeneous stroke population. However, most of these automated methods use a single atlas-based approach and may fail in the presence of severe structural abnormalities common in stroke. Hippodeep, a new convolutional neural network-based hippocampal segmentation method, does not rely solely on a single atlas-based approach and thus may be better suited for stroke populations. Here, we compared quality control and the accuracy of segmentations generated by Hippodeep and two well-accepted hippocampal segmentation methods on stroke MRIs (FreeSurfer 6.0 whole hippocampus and FreeSurfer 6.0 sum of hippocampal subfields). Quality control was performed using a stringent protocol for visual inspection of the segmentations, and accuracy was measured as volumetric correlation with manual segmentations. Hippodeep performed significantly better than both FreeSurfer methods in terms of quality control. All three automated segmentation methods had good correlation with manual segmentations and no one method was significantly more correlated than the others. Overall, this study suggests that both Hippodeep and FreeSurfer may be useful for hippocampal segmentation in stroke rehabilitation research, but Hippodeep may be more robust to stroke lesion anatomy.

Sex is a defining feature of neuroimaging phenotypes in major brain disorders.

Sex is a biological variable that contributes to individual variability in brain structure and behavior. Neuroimaging studies of population-based samples have identified normative differences in brain structure between males and females, many of which are exacerbated in psychiatric and neurological conditions. Still, sex differences in MRI outcomes are understudied, particularly in clinical samples with known sex differences in disease risk, prevalence, and expression of clinical symptoms. Here we review the existing literature on sex differences in adult brain structure in normative samples and in 14 distinct psychiatric and neurological disorders. We discuss commonalities and sources of variance in study designs, analysis procedures, disease subtype effects, and the impact of these factors on MRI interpretation. Lastly, we identify key problems in the neuroimaging literature on sex differences and offer potential recommendations to address current barriers and optimize rigor and reproducibility. In particular, we emphasize the importance of large-scale neuroimaging initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analyses consortium, the UK Biobank, Human Connectome Project, and others to provide unprecedented power to evaluate sex-specific phenotypes in major brain diseases.

Regional relationships between CSF VEGF levels and Alzheimer's disease brain biomarkers and cognition.

Vascular endothelial growth factor (VEGF) is a complex signaling protein that supports vascular and neuronal function. Alzheimer's disease (AD) -neuropathological hallmarks interfere with VEGF signaling and modify previously detected positive associations between cerebral spinal fluid (CSF) VEGF and cognition and hippocampal volume. However, it remains unknown 1) whether regional relationships between VEGF and glucose metabolism and cortical thinning exist, and 2) whether AD-neuropathological hallmarks (CSF Aß, t-tau, p-tau) also modify these relationships. We addressed this in 310 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (92 cognitively normal, 149 mild cognitive impairment, 69 AD; 215 CSF Aß+, 95 CSF Aß-) with regional cortical thickness and cognition measurements and 158 participants with FDG-PET. In Aß + participants (CSF Aß42 ≤ 192 pg/mL), higher CSF VEGF levels were associated with greater FDG-PET signal in the inferior parietal, and middle and inferior temporal cortices. Abnormal CSF amyloid and tau levels strengthened the positive association between VEGF and regional FDG-PET indices. VEGF also had both direct associations with semantic memory, as well as indirect associations mediated by regional FDG-PET signal to cognition.

Demonstration of the protective effect of ghrelin in the livers of rats with cisplatin toxicity.

Despite the various and newly developed chemotherapeutic agents in recent years, cisplatin is still used very frequently as a chemotherapeutic agent, even though cisplatin has toxic effects on many organs. The aim of our study is to show whether ghrelin reduces the liver toxicity of cisplatin in the rat model. Twenty-eight male Sprague Dawley albino mature rats were chosen to be utilized in the study. Group 1 rats (n = 7) were taken as the control group, and no medication was given to them. Group 2 rats (n = 7) received 5 mg/kg/day cisplatin and 1 ml/kg/day of 0.9% NaCl, Group 3 rats (n = 7) received 5 mg/kg/day cisplatin and 10 ng/kg/day ghrelin, Group 4 rats (n = 7) received 5 mg/kg/day cisplatin and 20 ng/kg/day ghrelin for 3 days. Glutathione, malondialdehyde (MDA), superoxide dismutase (SOD), plasma alanine aminotransferase (ALT) levels, and liver biopsy results were measured in rats. It was determined that, especially in the high-dose group, the MDA, plasma ALT, and SOD levels increased less in the ghrelin group as compared to the cisplatin group, and the glutathione level decreased slightly with a low dose of ghrelin, while it increased with a higher dose. In histopathological examination, it was determined that the toxic effect of cisplatin on the liver was reduced with a low dose of ghrelin, and its histopathological appearance was similar to normal liver tissue when given a high dose of ghrelin. These findings show that ghrelin, especially in high doses, can be used to reduce the toxic effect of cisplatin.

White matter hyperintensities and their relationship to cognition: Effects of segmentation algorithm.

White matter hyperintensities (WMHs) are brain white matter lesions that are hyperintense on fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) scans. Larger WMH volumes have been associated with Alzheimer's disease (AD) and with cognitive decline. However, the relationship between WMH volumes and cross-sectional cognitive measures has been inconsistent. We hypothesize that this inconsistency may arise from 1) the presence of AD-specific neuropathology that may obscure any WMH effects on cognition, and 2) varying criteria for creating a WMH segmentation. Manual and automated programs are typically used to determine segmentation boundaries, but criteria for those boundaries can differ. It remains unclear whether WMH volumes are associated with cognitive deficits, and which segmentation criteria influence the relationships between WMH volumes and clinical outcomes. In a sample of 260 non-demented participants (ages 55-90, 141 males, 119 females) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we compared the performance of five WMH segmentation methods, by relating the WMH volumes derived using each method to both clinical diagnosis and composite measures of executive function and memory. To separate WMH effects on cognition from effects related to AD-specific processes, we performed analyses separately in people with and without abnormal cerebrospinal fluid amyloid levels. WMH volume estimates that excluded more diffuse, lower-intensity lesions were more strongly correlated with clinical diagnosis and cognitive performance, and only in those without abnormal amyloid levels. These findings may inform best practices for WMH segmentation, and suggest that AD neuropathology may mask WMH effects on clinical diagnosis and cognition.

Early seizures and temporal lobe trauma predict post-traumatic epilepsy: A longitudinal study.

OBJECTIVE: Injury severity after traumatic brain injury (TBI) is a well-established risk factor for the development of post-traumatic epilepsy (PTE). However, whether lesion location influences the susceptibility of seizures and development of PTE longitudinally has yet to be defined. We hypothesized that lesion location, specifically in the temporal lobe, would be associated with an increased incidence of both early seizures and PTE. As secondary analysis measures, we assessed the degree of brain atrophy and functional recovery, and performed a between-group analysis, comparing patients who developed PTE with those who did not develop PTE. METHODS: We assessed early seizure incidence (n = 90) and longitudinal development of PTE (n = 46) in a prospective convenience sample of patients with moderate-severe TBI. Acutely, patients were monitored with prospective cEEG and a high-resolution Magnetic Resonance Imaging (MRI) scan for lesion location classification. Chronically, patients underwent a high-resolution MRI, clinical assessment, and were longitudinally monitored for development of epilepsy for a minimum of 2 years post-injury. RESULTS: Early seizures, occurring within the first week post-injury, occurred in 26.7% of the patients (n = 90). Within the cohort of subjects who had evidence of early seizures (n = 24), 75% had a hemorrhagic temporal lobe injury on admission. For longitudinal analyses (n = 46), 45.7% of patients developed PTE within a minimum of 2 years post-injury. Within the cohort of subjects who developed PTE (n = 21), 85.7% had a hemorrhagic temporal lobe injury on admission and 38.1% had early (convulsive or non-convulsive) seizures on cEEG monitoring during their acute ICU stay. In a between-group analysis, patients with PTE (n = 21) were more likely than patients who did not develop PTE (n = 25) to have a hemorrhagic temporal lobe injury (p < 0.001), worse functional recovery (p = 0.003), and greater temporal lobe atrophy (p = 0.029). CONCLUSION: Our results indicate that in a cohort of patients with a moderate-severe TBI, 1) lesion location specificity (e.g. the temporal lobe) is related to both a high incidence of early seizures and longitudinal development of PTE, 2) early seizures, whether convulsive or non-convulsive in nature, are associated with an increased risk for PTE development, and 3) patients who develop PTE have greater chronic temporal lobe atrophy and worse functional outcomes, compared to those who do not develop PTE, despite matched injury severity characteristics. This study provides the foundation for a future prospective study focused on elucidating the mechanisms and risk factors for epileptogenesis.

Epidemiology of seasonal influenza in the Middle East and North Africa regions, 2010-2016: Circulating influenza A and B viruses and spatial timing of epidemics.

BACKGROUND: There is a limited knowledge regarding the epidemiology of influenza in Middle East and North Africa. OBJECTIVES: We described the patterns of influenza circulation and the timing of seasonal epidemics in countries of Middle East and North Africa. METHODS: We used virological surveillance data for 2010-2016 from the WHO FluNet database. In each country, we calculated the median proportion of cases that were caused by each virus type and subtype; determined the timing and amplitude of the primary and secondary peaks; and used linear regression models to test for spatial trends in the timing of epidemics. RESULTS: We included 70 532 influenza cases from seventeen countries. Influenza A and B accounted for a median 76.5% and 23.5% of cases in a season and were the dominant type in 86.8% and 13.2% of seasons. The proportion of influenza A cases that were subtyped was 85.9%, while only 4.4% of influenza B cases were characterized. For most countries, influenza seasonality was similar to the Northern Hemisphere, with a single large peak between January and March; exceptions were the countries in the Arabian Peninsula and Jordan, all of which showed clear secondary peaks, and some countries had an earlier primary peak (in November-December in Bahrain and Qatar). The direction of the timing of influenza activity was east to west and south to north in 2012-2013 and 2015-2016, and west to east in 2014-2015. CONCLUSIONS: The epidemiology of influenza is generally uniform in countries of Middle East and North Africa, with influenza B playing an important role in the seasonal disease burden.

The success of the different eradication therapy regimens for Pseudomonas aeruginosa in cystic fibrosis.

WHAT IS KNOWN AND OBJECTIVE: Antibiotic therapy aimed at eradicating Pseudomonas aeruginosa (Pa), and improved regimens to treat chronic Pa infection have played a major role in increasing the median survival of patients with cystic fibrosis (CF). However, different clinical centres use varying eradication regimens. The aim of this study was to evaluate the efficacy of multiple eradication treatments against initial Pa infection and to determine the factors affecting the treatment success. METHODS: This study was conducted at the Hacettepe University Department of Pediatric Pulmonology. We examined the demographic, clinical and microbiological data of 146 CF patients with first Pa isolation in sputum culture from all 630 patients with CF studied. We aimed to identify the factors that affected the eradication of Pa infection and assessed the success rates of the different eradication protocols used. RESULTS AND DISCUSSION: The mean age of the patients was 71·5 months (2 months-29 years) when Pa was first isolated; the mean duration from CF diagnosis to first Pa isolation was 40 months. The most common treatment choices consisted of 2 weeks of intravenous ceftazidim-amikacin for severe exacerbation or 3 months of inhaled gentamycin combined with 3 weeks of oral ciprofloxacin for mild exacerbation in asymptomatic patients. With these treatment regimens, eradication was observed in 47 patients (32%), intermittent colonization in 42 patients (28%) and chronic colonization in 57 patients (40%). Forced expiratory volume in 1 s decline was statistically significant in patients with chronic colonization (P = 0·006). Being older than 2 years of age or having symptoms at the first Pa isolation was negatively associated with the treatment success. WHAT IS NEW AND CONCLUSION: Early antibiotic treatment for Pa can eradicate the bacteria, prevent or delay the development of chronic colonization and improve the general health status. The acquisition of Pa at an older age and having symptoms at first isolation negatively affected the success of eradication. The use of intravenous antibiotics may increase the efficacy of therapy. Inhaled tobramycin for Pa eradication was approved for reimbursement in Turkey from August 2014. The relatively low eradication rate may be explained by a lack of reimbursement for inhaled tobramycin and colistin in our country during the study period.

Epidemiology of Hospital Admissions with Influenza during the 2013/2014 Northern Hemisphere Influenza Season: Results from the Global Influenza Hospital Surveillance Network.

BACKGROUND: The Global Influenza Hospital Surveillance Network was established in 2012 to obtain valid epidemiologic data on hospital admissions with influenza-like illness. Here we describe the epidemiology of admissions with influenza within the Northern Hemisphere sites during the 2013/2014 influenza season, identify risk factors for severe outcomes and complications, and assess the impact of different influenza viruses on clinically relevant outcomes in at-risk populations. METHODS: Eligible consecutive admissions were screened for inclusion at 19 hospitals in Russia, Turkey, China, and Spain using a prospective, active surveillance approach. Patients that fulfilled a common case definition were enrolled and epidemiological data were collected. Risk factors for hospitalization with laboratory-confirmed influenza were identified by multivariable logistic regression. FINDINGS: 5303 of 9507 consecutive admissions were included in the analysis. Of these, 1086 were influenza positive (534 A(H3N2), 362 A(H1N1), 130 B/Yamagata lineage, 3 B/Victoria lineage, 40 untyped A, and 18 untyped B). The risk of hospitalization with influenza (adjusted odds ratio [95% confidence interval]) was elevated for patients with cardiovascular disease (1.63 [1.33-2.02]), asthma (2.25 [1.67-3.03]), immunosuppression (2.25 [1.23-4.11]), renal disease (2.11 [1.48-3.01]), liver disease (1.94 [1.18-3.19], autoimmune disease (2.97 [1.58-5.59]), and pregnancy (3.84 [2.48-5.94]). Patients without comorbidities accounted for 60% of admissions with influenza. The need for intensive care or in-hospital death was not significantly different between patients with or without influenza. Influenza vaccination was associated with a lower risk of confirmed influenza (adjusted odds ratio = 0.61 [0.48-0.77]). CONCLUSIONS: Influenza infection was detected among hospital admissions with and without known risk factors. Pregnancy and underlying comorbidity increased the risk of detecting influenza virus in patients hospitalized with influenza-like illness. Our results support influenza vaccination as a measure for reducing the risk of influenza-associated hospital admission.

Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination?

INTRODUCTION: Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. METHODS: This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. RESULTS: 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. DISCUSSION: Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate.

Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study.

INTRODUCTION: Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000. METHODS: Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data. We calculated the proportion of influenza cases due to type B and Victoria and Yamagata lineages in each country and season; tested the correlation between proportion of influenza B and maximum weekly influenza-like illness (ILI) rate during the same season; determined the frequency of vaccine mismatches; and described the age distribution of cases by virus type. RESULTS: The database included 935 673 influenza cases (2000-2013). Overall median proportion of influenza B was 22·6%, with no statistically significant differences across seasons. During seasons where influenza B was dominant or co-circulated (>20% of total detections), Victoria and Yamagata lineages predominated during 64% and 36% of seasons, respectively, and a vaccine mismatch was observed in ≈25% of seasons. Proportion of influenza B was inversely correlated with maximum ILI rate in the same season in the Northern and (with borderline significance) Southern hemispheres. Patients infected with influenza B were usually younger (5-17 years) than patients infected with influenza A. CONCLUSION: Influenza B is a common disease with some epidemiological differences from influenza A. This should be considered when optimizing control/prevention strategies in different regions and reducing the global burden of disease due to influenza.

The Global Influenza Hospital Surveillance Network (GIHSN): a new platform to describe the epidemiology of severe influenza.

BACKGROUND: Influenza is a global public health problem. However, severe influenza only recently has been addressed in routine surveillance. OBJECTIVES: The Global Influenza Hospital Surveillance Network (GIHSN) was established to study the epidemiology of severe influenza in consecutive seasons in different countries. Our objective is to describe the GIHSN approach and methods. METHODS: The GIHSN uses prospective active surveillance to identify consecutive influenza admissions in permanent residents of well-defined geographic areas in sites around the world. A core common protocol is followed. After consent, data are collected on patient characteristics and clinical outcomes, respiratory swabs are obtained, and the presence of influenza virus and subtype or lineage is ascertained by polymerase chain reaction. Data are collated and analyzed at the GIHSN coordination center. RESULTS: The GIHSN has run its activities for two consecutive influenza seasons, 2012-2013 and 2013-2014, and hospitals in Brazil, China, France, Russian Federation, Turkey, and Spain have been involved in one or both seasons. Consistency on the application of the protocol and heterogeneity for the first season have been addressed in two previous publications. During both seasons, 19 677 eligible admissions were recorded; 11 843 (60%) were included and tested, and 2713 (23%) were positive for influenza: 991 (37%) A(H1N1); 807 (30%) A(H3N2); 583 (21%) B/Yamagata; 56 (2%) B/Victoria and 151 (6%) influenza A; and 125 (5%) influenza B were not characterized. CONCLUSIONS: The GIHSN is a platform that provides information on severe influenza worldwide, applying a common core protocol and a consistent case definition.

Longitudinal quantification and visualization of intracerebral haemorrhage using multimodal magnetic resonance and diffusion tensor imaging.

OBJECTIVE: To demonstrate a set of approaches using diffusion tensor imaging (DTI) tractography whereby pathology-affected white matter (WM) fibres in patients with intracerebral haemorrhage (ICH) can be selectively visualized. METHODS: Using structural neuroimaging and DTI volumes acquired longitudinally from three representative patients with ICH, the spatial configuration of ICH-related trauma is delineated and the WM fibre bundles intersecting each ICH lesion are identified and visualized. Both the extent of ICH lesions as well as the proportion of WM fibres intersecting the ICH pathology are quantified and compared across subjects. RESULTS: This method successfully demonstrates longitudinal volumetric differences in ICH lesion load and differences across time in the percentage of fibres which intersect the primary injury. CONCLUSIONS: Because neurological conditions such as intracerebral haemorrhage (ICH) frequently exhibit pathology-related effects which lead to the exertion of mechanical pressure upon surrounding tissues and, thereby, to the deformation and/or displacement of WM fibres, DTI fibre tractography is highly suitable for assessing longitudinal changes in WM fibre integrity and mechanical displacement.

First-year results of the Global Influenza Hospital Surveillance Network: 2012-2013 Northern hemisphere influenza season.

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) was developed to improve understanding of severe influenza infection, as represented by hospitalized cases. The GIHSN is composed of coordinating sites, mainly affiliated with health authorities, each of which supervises and compiles data from one to seven hospitals. This report describes the distribution of influenza viruses A(H1N1), A(H3N2), B/Victoria, and B/Yamagata resulting in hospitalization during 2012-2013, the network's first year. METHODS: In 2012-2013, the GIHSN included 21 hospitals (five in Spain, five in France, four in the Russian Federation, and seven in Turkey). All hospitals used a reference protocol and core questionnaire to collect data, and data were consolidated at five coordinating sites. Influenza infection was confirmed by reverse-transcription polymerase chain reaction. Hospitalized patients admitted within 7 days of onset of influenza-like illness were included in the analysis. RESULTS: Of 5034 patients included with polymerase chain reaction results, 1545 (30.7%) were positive for influenza. Influenza A(H1N1), A(H3N2), and both B lineages co-circulated, although distributions varied greatly between coordinating sites and over time. All age groups were affected. A(H1N1) was the most common influenza strain isolated among hospitalized adults 18-64 years of age at four of five coordinating sites, whereas A(H3N2) and B viruses were isolated more often than A(H1N1) in adults ≥65 years of age at all five coordinating sites. A total of 16 deaths and 20 intensive care unit admissions were recorded among patients with influenza. CONCLUSIONS: Influenza strains resulting in hospitalization varied greatly between coordinating sites and over time. These first-year results of the GIHSN are relevant, useful, and timely. Due to its broad regional representativeness and sustainable framework, this growing network should contribute substantially to understanding the epidemiology of influenza, particularly for more severe disease.

2012-2013 Seasonal influenza vaccine effectiveness against influenza hospitalizations: results from the global influenza hospital surveillance network.

BACKGROUND: The effectiveness of currently licensed vaccines against influenza has not been clearly established, especially among individuals at increased risk for complications from influenza. We used a test-negative approach to estimate influenza vaccine effectiveness (IVE) against hospitalization with laboratory-confirmed influenza based on data collected from the Global Influenza Hospital Surveillance Network (GIHSN). METHODS AND FINDINGS: This was a multi-center, prospective, active surveillance, hospital-based epidemiological study during the 2012-2013 influenza season. Data were collected from hospitals participating in the GIHSN, including five in Spain, five in France, and four in the Russian Federation. Influenza was confirmed by reverse transcription-polymerase chain reaction. IVE against hospitalization for laboratory-confirmed influenza was estimated for adult patients targeted for vaccination and who were swabbed within 7 days of symptom onset. The overall adjusted IVE was 33% (95% confidence interval [CI], 11% to 49%). Point estimates of IVE were 23% (95% CI, -26% to 53%) for influenza A(H1N1)pdm09, 30% (95% CI, -37% to 64%) for influenza A(H3N2), and 43% (95% CI, 17% to 60%) for influenza B/Yamagata. IVE estimates were similar in subjects <65 and ≥65 years of age (35% [95% CI, -15% to 63%] vs.31% [95% CI, 4% to 51%]). Heterogeneity in site-specific IVE estimates was high (I2 = 63.4%) for A(H1N1)pdm09 in patients ≥65 years of age. IVE estimates for influenza B/Yamagata were homogenous (I2 = 0.0%). CONCLUSIONS: These results, which were based on data collected from the GIHSN during the 2012-2013 influenza season, showed that influenza vaccines provided low to moderate protection against hospital admission with laboratory-confirmed influenza in adults targeted for influenza vaccination. In this population, IVE estimates against A(H1N1)pdm09 were sensitive to age group and study site. Influenza vaccination was moderately effective in preventing admissions with influenza B/Yamagata for all sites and age groups.

Short-term levosimendan treatment protects rat testes against oxidative stress

The objective of this study was to evaluate the effect of short-term levosimendan exposure on oxidant/antioxidant status and trace element levels in the testes of rats under physiological conditions. Twenty male Wistar albino rats were randomly divided into two groups of 10 animals each. Group 1 was not exposed to levosimendan and served as control. Levosimendan (12 µg/kg) diluted in 10 mL 0.9% NaCl was administered intraperitoneally to group 2. Animals of both groups were sacrificed after 3 days and their testes were harvested for the determination of changes in tissue oxidant/antioxidant status and trace element levels. Tissue malondialdehyde (MDA) was significantly lower in the levosimendan group (P < 0.001) than in the untreated control group and superoxide dismutase and glutathione peroxidase (GSH-Px) levels were significantly higher in the levosimendan group (P < 0.001). Carbonic anhydrase, catalase and GSH levels were not significantly different from controls. Mg and Zn levels of testes were significantly higher (P < 0.001) and Co, Pb, Cd, Mn, and Cu were significantly lower (P < 0.001) in group 2 compared to group 1. Fe levels were similar for the two groups (P = 0.94). These results suggest that 3-day exposure to levosimendan induced a significant decrease in tissue MDA level, which is a lipid peroxidation product and an indicator of oxidative stress, and a significant increase in the activity of an important number of the enzymes that protect against oxidative stress in rat testes.