Severe cutaneous reactions to captopril and enalapril; histological study and comparison with early mycosis fungoides.
A severe non-dose related skin eruption attributable to treatment with captopril was recently reported: this is distinct from the dose related rashes that have been widely described. Ultrastructural and immunohistochemical studies were carried out to determine in detail the histological features of this eruption: the histological appearances were similar to those found in early mycosis fungoides, so that this disease was erroneously diagnosed in one case. Unlike most other complications resulting from treatment with Captopril, an indistinguishable rash can result from treatment with enalapril, a newer angiotensin converting enzyme inhibitor.


Genetic association of fetal-hemoglobin levels in individuals with sickle cell disease in Tanzania maps to conserved regulatory elements within the MYB core enhancer.
Common genetic variants residing near upstream regulatory elements for MYB, the gene encoding transcription factor cMYB, promote the persistence of fetal hemoglobin (HbF) into adulthood. While they have no consequences in healthy individuals, high HbF levels have major clinical benefits in patients with sickle cell disease (SCD) or β thalassemia. Here, we present our detailed investigation of HBS1L-MYB intergenic polymorphism block 2 (HMIP-2), the central component of the complex quantitative-trait locus upstream of MYB, in 1,022 individuals with SCD in Tanzania. We have looked at 1022 individuals with HbSS or HbS/β(0) in Tanzania. In order to achieve a detailed analysis of HMIP-2, we performed targeted genotyping for a total of 10 SNPs and extracted additional 528 SNPs information from a genome wide scan involving the same population. Using MACH, we utilized the existing YRI data from 1000 genomes to impute 54 SNPs situated within HIMP-2. Seven HbF-increasing, low-frequency variants (β > 0.3, p < 10(-5), f ≤ 0.05) were located in two partially-independent sub-loci, HMIP-2A and HMIP-2B. The spectrum of haplotypes carrying such alleles was diverse when compared to European and West African reference populations: we detected one such haplotype at sub-locus HMIP-2A, two at HMIP-2B, and a fourth including high-HbF alleles at both sub-loci ('Eurasian' haplotype clade). In the region of HMIP-2A a putative functional variant (a 3-bp indel) has been described previously, but no such candidate causative variant exists at HMIP-2B. Extending our dataset through imputation with 1000 Genomes, whole-genome-sequence data, we have mapped peak association at HMIP-2B to an 11-kb region around rs9494145 and rs9483788, flanked by two conserved regulatory elements for MYB. Studies in populations from the African continent provide distinct opportunities for mapping disease-modifying genetic loci, especially for conditions that are highly prevalent there, such as SCD. Population-genetic characteristics of our cohort, such as ethnic diversity and the predominance of shorter, African-type haplotypes, can add to the power of such studies.


Treatment for family members in crisis after critical injury.
A sudden critical injury produces a great amount of stress within a family. Families faced with this experience require treatment to modify the stress of the situation, receive and comprehend information, maintain patterns of adequate family functioning, use effective coping skills, and provide positive support to the patient. Specific questions discussed include: Who are family members? Why treat family members who are in crisis? What areas should be included in family assessment? What treatments are effective for families? What family outcomes can be expected? A clinical case study is used to describe assessment areas and initial treatments for family in crisis after one of their members is critically injured.


A mutagenesis-derived Lrp5 mouse mutant with abnormal retinal vasculature and low bone mineral density.
Familial exudative vitreoretinopathy (FEVR) is caused by mutations in the genes encoding low-density lipoprotein receptor-related protein (LRP5) or its interacting partners, namely frizzled class receptor 4 (FZD4) and norrin cystine knot growth factor (NDP). Mouse models for Lrp5, Fzd4, and Ndp have proven to be important for understanding the retinal pathophysiology underlying FEVR and systemic abnormalities related to defective Wnt signaling. Here, we report a new mouse mutant, tvrm111B, which was identified by electroretinogram (ERG) screening of mice generated in the Jackson Laboratory Translational Vision Research Models (TVRM) mutagenesis program. ERGs were used to examine outer retinal physiology. The retinal vasculature was examined by in vivo retinal imaging, as well as by histology and immunohistochemistry. The tvrm111B locus was identified by genetic mapping of mice generated in a cross to DBA/2J, and subsequent sequencing analysis. Gene expression was examined by real-time PCR of retinal RNA. Bone mineral density (BMD) was examined by peripheral dual-energy X-ray absorptiometry. The tvrm111B allele is inherited as an autosomal recessive trait. Genetic mapping of the decreased ERG b-wave phenotype of tvrm111B mice localized the mutation to a region on chromosome 19 that included Lrp5. Sequencing of Lrp5 identified the insertion of a cytosine (c.4724_4725insC), which is predicted to cause a frameshift that disrupts the last three of five conserved PPPSPxS motifs in the cytoplasmic domain of LRP5, culminating in a premature termination. In addition to a reduced ERG b-wave, Lrp5tvrm111B homozygotes have low BMD and abnormal features of the retinal vasculature that have been reported previously in Lrp5 mutant mice, including persistent hyaloid vessels, leakage on fluorescein angiography, and an absence of the deep retinal capillary bed. The phenotype of the Lrp5tvrm111B mutant includes abnormalities of the retinal vasculature and of BMD. This model may be a useful resource to further our understanding of the biological role of LRP5 and to evaluate experimental therapies for FEVR or other conditions associated with LRP5 dysfunction.


Strong coupling between surface plasmon polaritons and Sulforhodamine 101 dye.
We demonstrate a strong coupling between surface plasmon polaritons and Sulforhodamine 101 dye molecules. Dispersion curves for surface plasmon polaritons on samples with a thin layer of silver covered with Sulforhodamine 101 molecules embedded in SU-8 polymer are obtained experimentally by reflectometry measurements and compared to the dispersion of samples without molecules. Clear Rabi splittings, with energies up to 360 and 190 meV, are observed at the positions of the dye absorption maxima. The split energies are dependent on the number of Sulforhodamine 101 molecules involved in the coupling process. Transfer matrix and coupled oscillator methods are used to model the studied multilayer structures with a great agreement with the experiments. Detection of the scattered radiation after the propagation provides another way to obtain the dispersion relation of the surface plasmon polaritons and, thus, provides insight into dynamics of the surface plasmon polariton/dye interaction, beyond the refrectometry measurements.PACS: 42.50.Hz, 33.80.-b, 78.67.-n.


Are neuropathological conditions relevant to ethylmercury exposure?
Mercury and mercurial compounds are among the environmentally ubiquitous substances most toxic to both wildlife and humans. Once released into the environment from both natural and anthropogenic sources, mercury exists mainly as three different molecular species: elemental, inorganic, and organic. Potential health risks have been reported from exposure to all forms; however, of particular concern for human exposure relate to the potent neurotoxic effects of methylmercury (MeHg), especially for the developing nervous system. The general population is primarily exposed to MeHg by seafood consumption. In addition, some pharmaceuticals, including vaccines, have been, and some continue to be, a ubiquitous source of exposure to mercurials. A significant controversy has been whether the vaccine preservative ethylmercury thiosalicylate, commonly known as thimerosal, could cause the development of autism. In this review, we have discussed the hypothesis that exposure to thimerosal during childhood may be a primary cause of autism. The conclusion is that there are no reliable data indicating that administration of vaccines containing thimerosal is a primary cause of autism. However, one cannot rule out the possibility that the individual gene profile and/or gene-environment interactions may play a role in modulating the response to acquired risk by modifying the individual susceptibility.


Supercontinuum-based 10-GHz flat-topped optical frequency comb generation.
The generation of high-repetition-rate optical frequency combs with an ultra-broad, coherent and smooth spectrum is important for many applications in optical communications, radio-frequency photonics and optical arbitrary waveform generation. Usually, nonlinear broadening techniques of comb-based sources do not provide the required flatness over the whole available bandwidth. Here we present a 10-GHz ultra-broadband flat-topped optical frequency comb (> 3.64-THz or 28 nm bandwidth with ~365 spectral lines within 3.5-dB power variation) covering the entire C-band. The key enabling point is the development of a pre-shaping-free directly generated Gaussian comb-based 10-GHz pulse train to seed a highly nonlinear fiber with normal dispersion profile. The combination of the temporal characteristics of the seed pulses with the nonlinear device allows the pulses to enter into the optical wave-breaking regime, thus achieving a smooth flat-topped comb spectral envelope. To further illustrate the high spectral coherence of the comb, we demonstrate high-quality pedestal-free short pulse compression to the transform-limited duration.


Coffee Consumption and Cardiovascular Health.
Coffee is the most widely consumed beverage worldwide and is only second to water drinking and is consumed by 83% of adults in the United States. The long-held controversy regarding the association of coffee consumption with an increased incidence of cardiovascular diseases (CVDs) and hypertension has been reversed by several recent prospective cohort studies and meta-analyses, which have demonstrated that coffee consumption is not associated with increased incidence of CVDs and hypertension and instead it could have a beneficial effect. To get a better understanding of the effects of coffee consumption on cardiovascular health, a Medline search of the English language literature was conducted from 2010 to early 2015 and 25 pertinent reports with information on the effects of coffee drinking, the incidence of CVDs, and hypertension and its mechanism of action were selected for inclusion in this commentary. These studies have shown either a neutral or beneficial effect of coffee on cardiovascular health. In conclusion, coffee is safe to drink by both normal subjects and by those with preexisting CVDs and hypertension.


Reactive haemophagocytic syndrome in adult-onset Still's disease: a report of six patients and a review of the literature.
To examine the prevalence and characteristics of patients with reactive haemophagocytic syndrome (RHS) complicating adult-onset Still's disease (AOSD). Of 50 patients with AOSD fulfilling Yamaguchi and Fautrel criteria followed in our department, clinical and laboratory data, course and treatment of six patients with histologically proven RHS and without any obvious cause other than AOSD were retrospectively recorded. RHS led to AOSD in two cases, whereas it appeared after a mean duration of 3.5 years from onset of AOSD in the other cases. The main symptoms were fever (n = 6), polyarthralgias or myalgias (n = 4), lymphadenopathy or splenomegaly (n = 3), pharyngitis (n = 3), rash (n = 3), pleuritis (n = 3), hepatomegaly (n = 1), normal or low leucocyte count (n = 4), anaemia (n = 6), lymphocytopenia (n = 6), thrombocytopenia (n = 4), hyperbasophilic lymphocytes (n = 2), abnormal liver function tests (n = 6) and increased serum triglyceride level (n = 6). Serum ferritin concentration was constantly increased (>10,000 microg/l in five cases, with <5-35% in glycosylated form). Two patients presented with coagulopathy. Treatment comprised corticosteroids (n = 4) and intravenous immunoglobulins (n = 3), whereas prednisone was unchanged in one case. One death due to pneumonia occurred 15 days after RHS. With a follow-up ranging from 2 to 7.5 years, the other patients were in remission with prednisone plus etanercept (n = 1), prednisone plus methotrexate (n = 1), low-dose prednisone (n = 2) or without treatment (n = 1). RHS is not uncommon in AOSD. It should be evoked in a patient with AOSD in the absence of hyperleucocytosis, thrombocytopenia, lymphopenia and coagulopathy, or in the presence of high serum ferritin and triglyceride levels.


A high risk of hepatitis C infection among Egyptian blood donors: the role of parenteral drug abuse.
To determine the prevalence and risk factors of hepatitis C virus (HCV) infection among Egyptian blood donors, 188 consecutive adult blood donors from four hospitals and one temporary donor center located in Cairo, Egypt were evaluated. Sera were tested for HCV antibodies (anti-HCV) using second-generation enzyme-linked immunosorbent assay (ELISA) test kits. Sera that were repeatedly reactive by ELISA were further verified by a second-generation recombinant immunoblot assay (RIBA). Antibodies to HCV were detected by RIBA in 26.6% of the blood donors, which is higher than the 10-19% prevalence of antibody found in other studies of Egyptian blood donors. A history of selling blood (odds ratio [OR] = 12.1) and the use of illicit parenteral drugs (OR = 2.5) were significantly associated with anti-HCV seropositivity after controlling for age and gender. These data indicate that the use of illicit drugs may be one reason for high levels of reported HCV infection among Egyptian blood donors. These findings also indicate that Egyptian blood donors should be screened for anti-HCV and individuals who have a history of drug abuse should be deferred from donating blood.


Cardiac adaptive mechanisms of Tibetan antelope (Pantholops hodgsonii) at high altitudes.
To identify cardiac mechanisms that contribute to adaptation to high altitudes in Tibetan antelope (Pantholops hodgsonii). 9 male Tibetan antelope and 10 male Tibetan sheep (Ovis aries). Tibetan antelope and Tibetan sheep inhabiting a region with an altitude of 4,300 m were captured, and several cardiac variables were measured. Expression of genes for atrial natriuretic peptide, brain natriuretic peptide, and calcium-calmodulin-dependent protein kinase II δ was measured via real-time PCR assay. Ratios of heart weight to body weight for Tibetan antelope were significantly greater than those of Tibetan sheep, but ratios of right-left ventricular weights were similar. Mean ± SD baseline heart rate (26.33 ± 6.15 beats/min) and systolic arterial blood pressure (97.75 ± 9.56 mm Hg) of antelope were significantly lower than those of sheep (34.20 ± 6.57 beats/min and 130.06 ± 17.79 mm Hg, respectively). The maximum rate of rise in ventricular pressure in antelope was similar to that in Tibetan sheep, but after exposure to air providing a fraction of inspired oxygen of 14.6% or 12.5% (ie, hypoxic conditions), the maximum rate of rise in ventricular pressure of the antelope increased significantly to 145.1% or 148.1%, respectively, whereas that of the sheep decreased to 68.4% or 70.5%, respectively. Gene expression of calcium-calmodulin-dependent protein kinase II δ and atrial natriuretic peptide, but not brain natriuretic peptide, in the left ventricle of the heart was significantly higher in antelope than in sheep. Hearts of the Tibetan antelope in this study were well adapted to high-altitude hypoxia as shown by higher heart weight ratios, cardiac contractility in hypoxic conditions, and expression of key genes regulating cardiac contractility and cardiac hypertrophy, compared with values for Tibetan sheep.


Detecting and reacting to change: the effect of exposure to narrow categorizations.
The ability to detect a change, to accurately assess the magnitude of the change, and to react to that change in a commensurate fashion are of critical importance in many decision domains. Thus, it is important to understand the factors that systematically affect people's reactions to change. In this article we document a novel effect: decision makers' reactions to a change (e.g., a visual change, a technology change) were systematically affected by the type of categorizations they encountered in an unrelated prior task (e.g., the response categories associated with a survey question). We found that prior exposure to narrow, as opposed to broad, categorizations improved decision makers' ability to detect change and led to stronger reactions to a given change. These differential reactions occurred because the prior categorizations, even though unrelated, altered the extent to which the subsequently presented change was perceived as either a relatively large change or a relatively small one.


Laparoscopic renal cryosurgery: the Northwestern experience.
Laparoscopic renal cryosurgery provides a minimally invasive alternative for the treatment of small renal lesions of undefined malignant potential. We report on our series of patients treated with laparoscopic renal cryosurgery. Fifteen patients underwent laparoscopic renal cryoablation of peripheral, exophytic unifocal renal lesions. Patients were managed with a 4-port transperitoneal approach for anteromedial tumors and 3 to 4-port retroperitoneal approach for posterolateral tumors. All lesions were biopsied and sent to pathology for permanent section. A 4.8 mm cryoprobe (CMS cryoprobe, 4.8 mm x 2 cm x 40 cm, Cryomedical Sciences Inc., Ewing, New Jersey) was placed into the tumor using visual and ultrasonographic guidance, and a double freeze-passive thaw cycle was performed. The iceball was extended at least 1 cm beyond the tumor margin under ultrasound guidance. Followup biopsies were performed on all consenting patients with renal cell carcinoma at least 3 months after cryosurgery was performed. Laparoscopic renal cryosurgery was successfully performed on all 15 patients (6 male and 9 female). Of the 15 patients 10 had renal cell carcinoma. Mean age was 68.5 years (range 49 to 86). Mean tumor size was 2.15 cm (range 1.2 to 3.2) and mean estimated blood loss was 67 cc (range 15 to 125). There were 2 perioperative complications. Mean hospital stay was 3.5 days (range 1 to 11). Patients returned to work after 16.5 days (range 7 to 28). Radiographic followup revealed stable cryoablative lesions in all patients. Mean radiographic followup was 453 days (range 147 to 816). Mean preoperative creatinine was 1.25 mg/dl (range 0.8 to 4.3) and mean postoperative creatinine obtained 1 month postoperatively was 1.36 (range 0.8 to 4.8). There was 1 treatment failure, although another patient had a positive biopsy outside the ablated area. The failure occurred in the largest tumor treated (3.2 cm) and was due to incomplete treatment of the periphery of the lesion. The other patient had a successfully treated tumor but a positive followup biopsy due to multifocal papillary renal cell carcinoma and required nephrectomy. Laparoscopic renal cryosurgery appears to be a safe and effective minimally invasive alternative for the treatment of small renal masses. Careful selection of patients with lesions that are less than 3.0 cm and close monitoring of the iceball is necessary to treat these patients successfully.


Lateralization of the posterior parietal cortex for internal monitoring of self- versus externally generated movements.
Internal monitoring or state estimation of movements is essential for human motor control to compensate for inherent delays and noise in sensorimotor loops. Two types of internal estimation of movements exist: self-generated movements, and externally generated movements. We used functional magnetic resonance imaging to investigate differences in brain activity for internal monitoring of self- versus externally generated movements during visual occlusion. Participants tracked a sinusoidally moving target with a mouse cursor. On some trials, vision of either target (externally generated) or cursor (self-generated) movement was transiently occluded, during which subjects continued tracking by estimating current position of either the invisible target or cursor on screen. Analysis revealed that both occlusion conditions were associated with increased activity in the presupplementary motor area and decreased activity in the right lateral occipital cortex compared to a control condition with no occlusion. Moreover, the right and left posterior parietal cortex (PPC) showed greater activation during occlusion of target and cursor movements, respectively. This study suggests lateralization of the PPC for internal monitoring of internally versus externally generated movements, fully consistent with previously reported clinical findings.


Healthcare professional and patient codesign and validation of a mechanism for service users to feedback patient safety experiences following a care transfer: a qualitative study.
To develop and validate a mechanism for patients to provide feedback on safety experiences following a care transfer between organisations. Qualitative study using participatory methods (codesign workshops) and cognitive interviews. Workshop data were analysed concurrently with participants, and cognitive interviews were thematically analysed using a deductive approach based on the developed feedback mechanism. Expert patients (n=5) and healthcare professionals (n=11) were recruited purposively to develop the feedback mechanism in 2 workshops. Workshop 1 explored principles underpinning safety feedback mechanisms, and workshop 2 included the practical development of the feedback mechanism. Final design and content of the feedback mechanism (a safety survey) were verified by workshop participants, and cognitive interviews (n=28) were conducted with patients. Workshop participants identified that safety feedback mechanisms should be patient-centred, short and concise with clear signposting on how to complete, with an option to be anonymous and balanced between positive (safe) and negative (unsafe) experiences. The agreed feedback mechanism consisted of a survey split across 3 stages of the care transfer: departure, journey and arrival. Care across organisational boundaries was recognised as being complex, with healthcare professionals acknowledging the difficulty implementing changes that impact other organisations. Cognitive interview participants agreed the content of the survey was relevant but identified barriers to completion relating to the survey formatting and understanding of a care transfer. Participatory, codesign principles helped overcome differences in understandings of safety in the complex setting of care transfers when developing a safety survey. Practical barriers to the survey's usability and acceptability to patients were identified, resulting in a modified survey design. Further research is required to determine the usability and acceptability of the survey to patients and healthcare professionals, as well as identifying how governance structures should accommodate patient feedback when relating to multiple health or social care providers.


APP metabolism regulates tau proteostasis in human cerebral cortex neurons.
Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.


Current Understanding of Physicochemical Mechanisms for Cell Membrane Penetration of Arginine-rich Cell Penetrating Peptides: Role of Glycosaminoglycan Interactions.
Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet. Alternatively, CPPs favorably bind in a charge density- dependent manner to negatively charged, sulfated glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate, which are abundant on the cell surface and are involved in many biological functions. We have recently demonstrated that the interaction of CPPs with sulfated GAGs plays a critical role in their direct cell membrane penetration: the favorable enthalpy contribution drives the high-affinity binding of arginine-rich CPPs to sulfated GAGs, initiating an efficient cell membrane penetration. The favorable enthalpy gain is presumably mainly derived from a unique property of the guanidino group of arginine residues forming multidentate hydrogen bonding with sulfate and carboxylate groups in GAGs. Such interactions can be accompanied with charge neutralization of arginine-rich CPPs, promoting their partition into cell membranes. This review summarizes the current understanding of the physicochemical mechanism for lipid membrane penetration of CPPs, and discusses the role of the GAG interactions on the cell membrane penetration of CPPs.


If, Why, and When Subjective Well-Being Influences Health, and Future Needed Research.
We review evidence on whether subjective well-being (SWB) can influence health, why it might do so, and what we know about the conditions where this is more or less likely to occur. This review also explores how various methodological approaches inform the study of the connections between subjective well-being and health and longevity outcomes. Our review of this growing literature indicates areas where data are substantial and where much more research is needed. We conclude that SWB can sometimes influence health, and review a number of reasons why it does so. A key open question is when it does and does not do so-in terms of populations likely to be affected, types of SWB that are most influential (including which might be harmful), and types of health and illnesses that are most likely to be affected. We also describe additional types of research that are now much needed in this burgeoning area of interest, for example, cross-cultural studies, animal research, and experimental interventions designed to raise long-term SWB and assess the effects on physical health. This research area is characterised both by potentially extremely important findings, and also by pivotal research issues and questions.


Psychosocial assessment and repetition of self-harm: the significance of single and multiple repeat episode analyses.
Self-harm is a common reason for presentation to the Emergency Department. An important question is whether psychosocial assessment reduces risk of repeated self-harm. Repetition has been investigated with survival analysis using various models, though many are not appropriate for recurrent events. Survival analysis was used to investigate associations between psychosocial assessment following an episode of self-harm and subsequent repetition, including (i) one repeat, and (ii) recurrent repetition (≤5 repeats) using (a) an independent episodes model, and (b) a stratified episodes model based on a conditional risk set. Data were from the Multicentre Study on Self-harm in England, 2000 to 2007. Psychosocial assessment following an index episode of self-harm was associated with a 51% (95% CI 42%-58%) decreased risk of a repeat episode in persons with no psychiatric treatment history, and 26% (95% CI 8%-34%) decreased risk in those with a treatment history. For recurrent repetition, assessment was associated with a 57% (95% CI 51%-63%) decreased risk of repetition assuming independent episodes, and 13% (95% CI 1%-24%) decreased risk accounting for ordering and correlation of episodes by the same person (stratified episodes model). All models controlled for age, gender, method, history of self-harm, and centre differences. Some missing data on psychiatric treatment for non-assessed patients. Psychosocial assessment appeared to be beneficial in reducing the risk of repetition, especially in the short-term. Findings for recurrent repetition were highly dependent on model assumptions. Analyses should fully account for ordering and correlation of episodes by the same person.


Crossmodal change blindness between vision and touch.
Change blindness is the name given to people's inability to detect changes introduced between two consecutively-presented scenes when they are separated by a distractor that masks the transients that are typically associated with change. Change blindness has been reported within vision, audition, and touch, but has never before been investigated when successive patterns are presented to different sensory modalities. In the study reported here, we investigated change detection performance when the two to-be-compared stimulus patterns were presented in the same sensory modality (i.e., both visual or both tactile) and when one stimulus pattern was tactile while the other was presented visually or vice versa. The two to-be-compared patterns were presented consecutively, separated by an empty interval, or else separated by a masked interval. In the latter case, the masked interval could either be tactile or visual. The first experiment investigated visual-tactile and tactile-visual change detection performance. The results showed that in the absence of masking, participants detected changes in position accurately, despite the fact that the two to-be-compared displays were presented in different sensory modalities. Furthermore, when a mask was presented between the two to-be-compared displays, crossmodal change blindness was elicited no matter whether the mask was visual or tactile. The results of two further experiments showed that performance was better overall in the unimodal (visual or tactile) conditions than in the crossmodal conditions. These results suggest that certain of the processes underlying change blindness are multisensory in nature. We discuss these findings in relation to recent claims regarding the crossmodal nature of spatial attention.


Impact of Age on Change in Self-Image 5 Years After Complex Spinal Fusion (≥5 Levels).
Spinal deformities that require ≥5 fusion levels are difficult and challenging for both the surgeon and patient. Corrections of moderate to severe deformities have been shown to improve patient-reported outcomes (PROs), and provide patients with a better quality of life. Self-image is an important PRO because it sheds insight into the patient's perception of health, as well as serving as a proxy of satisfaction for patients with spine deformity undergoing corrective surgery. However, with an aging population, the impact of age on long-term change in self-image is unknown. The aim of this study is to determine the effects of age on self-image 5 years after undergoing an elective complex spinal fusion (≥5 levels). This was a retrospective analysis of prospectively collected data of 55 adult patients (≥18 years old) undergoing ≥5 levels of spinal fusion to the sacrum with iliac fixation from January 2002 to December 2008. Patients were grouped by age: young (<60 years old) and older (≥60 years old). Patient demographics, comorbidities, preoperative variables (sagittal and Cobb angles) and postoperative complication rates were collected. All patients had prospectively collected outcome measures and a minimum of 5 years follow-up. PRO instrument SRS-22r (function, self-image, mental health, and pain) was completed before surgery then at follow-up (at least 5 years after surgery). The primary outcome investigated in this study was the change in self-image after surgery. Baseline characteristics and preoperative variables were similar in both cohorts. There were no significant differences in intraoperative variables, including the mean ± standard deviation number of fusion levels between the cohorts (young, 11.2 ±4.3 vs. older, 12.1 ± 4.0; P = 0.42). Complication rates were similar between the cohorts, with no significant differences in the types of complications (young, 29.63% vs. older, 25.0%; P = 0.77). There were no significant differences in preoperative and follow-up PROs between the cohorts. The mean ± standard deviation preoperative and follow-up self-image scores were (young, 2.35±0.58 vs. older, 2.68 ± 0.64; P = 0.51) and (young, 3.82 ± 0.63 vs. older, 3.51 ± 0.94), respectively. There were no significant differences in the change of function, mental health, or pain between the cohorts. However, the younger cohort experienced a significantly greater overall change in self-image than did the older cohort (young, 1.49 ± 0.87 vs. older, 0.70±1.14; P = 0.01). Our study suggests that age significantly affects the perception of self-image after deformity correction surgery; with younger patients reporting a greater change from baseline in self-image after surgery. Further studies are necessary to corroborate our observed findings.


Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial.
Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and bevacizumab-naive second-line metastatic colorectal cancer. We assessed continued use of bevacizumab plus standard second-line chemotherapy in patients with metastatic colorectal cancer progressing after standard first-line bevacizumab-based treatment. In an open-label, phase 3 study in 220 centres in Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, the Netherlands, Norway, Portugal, Saudi Arabia, Spain, Sweden, and Switzerland, patients (aged ≥18 years) with unresectable, histologically confirmed metastatic colorectal cancer progressing up to 3 months after discontinuing first-line bevacizumab plus chemotherapy were randomly assigned in a 1:1 ratio to second-line chemotherapy with or without bevacizumab 2·5 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7·5 mg/kg every 3 weeks, intravenously). The choice between oxaliplatin-based or irinotecan-based second-line chemotherapy depended on the first-line regimen (switch of chemotherapy). A combination of a permuted block design and the Pocock and Simon minimisation algorithm was used for the randomisation. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00700102. Between Feb 1, 2006, and June 9, 2010, 409 (50%) patients were assigned to bevacizumab plus chemotherapy and 411 (50%) to chemotherapy alone. Median follow-up was 11·1 months (IQR 6·4-15·6) in the bevacizumab plus chemotherapy group and 9·6 months (5·4-13·9) in the chemotherapy alone group. Median overall survival was 11·2 months (95% CI 10·4-12·2) for bevacizumab plus chemotherapy and 9·8 months (8·9-10·7) for chemotherapy alone (hazard ratio 0·81, 95% CI 0·69-0·94; unstratified log-rank test p=0·0062). Grade 3-5 bleeding or haemorrhage (eight [2%] vs one [<1%]), gastrointestinal perforation (seven [2%] vs three [<1%]), and venous thromboembolisms (19 [5%] vs 12 [3%]) were more common in the bevacizumab plus chemotherapy group than in the chemotherapy alone group. The most frequently reported grade 3-5 adverse events were neutropenia (65 [16%] in the bevacizumab and chemotherapy group vs 52 [13%] in the chemotherapy alone group), diarrhoea (40 [10%] vs 34 [8%], respectively), and asthenia (23 [6%] vs 17 [4%], respectively). Treatment-related deaths were reported for four patients in the bevacizumab plus chemotherapy group and three in the chemotherapy alone group. Maintenance of VEGF inhibition with bevacizumab plus standard second-line chemotherapy beyond disease progression has clinical benefits in patients with metastatic colorectal cancer. This approach is also being investigated in other tumour types, including metastatic breast and non-small cell lung cancers. F Hoffmann-La Roche.


Caffeine supplementation does not affect match activities and fatigue resistance during match play in young football players.
Abstract The study examined the effect of caffeine supplementation on match activities and development of fatigue during a football match. In a randomised, double-blind cross-over design, two experimental football games separated by 7 days were organised between the junior teams of two professional football clubs (17.6 ± 1.1 years (±s), 71.7 ± 6.9 kg, 13.9% ± 5.0% body fat). The players ingested either a capsule of 6 mg · kg-1 b.w. caffeine or placebo (dextrose) 65 min prior to the matches. Match activities were assessed using the ZXY match analysis system, and a Yo-Yo intermittent recovery test-level 2 (Yo-Yo IR2) was conducted immediately post-game. Heart rate was monitored throughout the game, and blood samples were obtained at baseline, half-time and after the game. There were no differences between caffeine and placebo regarding total distance covered (10,062 ± 916 vs 9854 ± 901 m), high-intensity running (557 ± 178 vs 642 ± 240 m), sprinting distance (109 ± 58 vs 112 ± 69 m) or acceleration counts (123 ± 31 vs 126 ± 24). In both trials, players displayed lower (P < 0.05) values in total distance and acceleration counts in the last 15 min compared to all other 15-min periods of the matches. Post-game Yo-Yo IR2 performance was not different between game trials (caffeine: 829 ± 322 m; placebo 819 ± 289 m). In conclusion, oral caffeine administration does not appear to have an ergogenic effect in young football players during match play.


The Indirect Effect of Holistic Career Values on Work Engagement: A Longitudinal Study Spanning Two Decades.
In contrast to earlier assumptions that the "ideal worker" should embrace traditional notions of career success, there is growing recognition that possessing holistic career values may be beneficial in the work domain as well. However, there is little empirical evidence to support this argument. We hypothesised that individuals who at the time of their university graduation possessed holistic career values would display stronger personal life satisfaction 20 years later, which in turn would enhance their work engagement (i.e. an individual's perceptions of the extent to which the work environment possesses engaging characteristics). Data from a longitudinal study of 158 university students who completed two questionnaires, one in 1992 and the other 20 years later, supported our hypotheses. We found that individuals who possessed holistic career values displayed stronger personal life satisfaction 20 years later, which in turn enhanced their work engagement. We further found that this indirect effect of holistic career values on work engagement (through personal life satisfaction) is conditionally moderated by work-family interference. Cultivating a holistic career perspective among employees is beneficial for both employee well-being (i.e. personal life satisfaction) and the flourishing of their organisations (i.e. work engagement).


Transforming growth factor beta-1 (TGF-β1) stimulates collagen synthesis in cultured rainbow trout cardiac fibroblasts.
Cold acclimation of rainbow trout, Oncorhynchus mykiss, causes collagen to increase within the extracellular matrix (ECM) of the myocardium, while warm acclimation has the opposite effect. The mechanism responsible for this remodelling response is not known. In mammals, transforming growth factor beta-1 (TGF-β1) stimulates collagen deposition within the myocardial ECM. Therefore, we hypothesized that TGF-β1 regulates trout myocardial ECM turnover and predicted that TGF-β1 would induce collagen deposition in cultured rainbow trout cardiac fibroblasts. We found that treatment of trout cardiac fibroblasts with 15 ng ml-1 human recombinant TGF-β1 caused an increase in total collagen at 48 and 72 h and an increase in collagen type I protein after 7 days. We also found that TGF-β1 treatment caused an increase in the transcript abundance of tissue inhibitor of metalloproteinase 2 (timp-2) and matrix metalloproteinase 9 (mmp-9) at 24 h. Cells treated with TGF-β1 also had lower levels of the gene transcript for mmp-2 after 48 h and higher levels of the gene transcript for collagen type I α1 (col1a1) after 72 h. These changes in gene expression suggest that the increase in collagen deposition is due to a decrease in the activity of matrix metalloproteinases and an increase in collagen synthesis. Together, these results indicate that TGF-β1 is a regulator of ECM composition in cultured trout cardiac fibroblasts and suggest that this cytokine may play a role in regulating collagen content in the trout heart during thermal acclimation.


The Misestimation of Uncertainty in Affective Disorders.
Our knowledge about the state of the world is often incomplete, making it difficult to select the best course of action. One strategy that can be used to improve our ability to make decisions is to identify the causes of our ignorance (i.e., why an unexpected event might have occurred) and use estimates of the uncertainty induced by these causes to guide our learning. Here, we explain the logic behind this process and describe the evidence that human learners use estimates of uncertainty to sculpt their learning. Finally, we describe recent work suggesting that misestimation of uncertainty is involved in the development of anxiety and depression and describe how these ideas may be advanced.


Day surgery regional anesthesia in children: safety and improving outcomes, do they make a difference?
The objective of this review is to provide an overview of recent developments in pediatric regional anesthesia and elucidate outcomes as it relates to patient safety and overall satisfaction. Since the inception of the Pediatric Regional Anesthesia Network database, the acquisition of data has enabled the pediatric anesthesiologist to extrapolate results and translate them into useful outcomes. Despite the growing trend to provide regional anesthesia in the pediatric population, there continues to be a paucity of available research studies to evaluate outcomes of various regional nerve blocks. This review serves as a conduit to explore the most recent data available, in each regional anesthetic technique, as it relates to outcomes such as analgesia, patient safety and satisfaction. Despite the limited number of randomized controlled trials evaluating the safety of individual regional anesthetic techniques, the growing body of data, such as presented in the Pediatric Regional Anesthesia Network database, suggests a high degree of safety in performing various regional anesthetic modalities. Modern medicine should continue to embrace the use of regional anesthesia, particularly in the ambulatory setting, to reduce perioperative pain and improve patient outcomes.


Neuropathology of acquired immunodeficiency syndrome (AIDS): an autopsy review.
In the brains and spinal cords of 153 adult patients dying with acquired immunodeficiency syndrome (AIDS) at New York and Memorial Hospitals a subacute encephalitis with multinucleated cells was present in 28% of all patients. This encephalitis was characterized by multinucleated cells primarily located in the white matter and associated with myelin pallor and sparse infiltrates of rod cells, macrophages, gemistocytic astrocytes and lymphocytes. The incidence per 12 month period ranged from 0 to 43% and significantly increased between 1983-84 (14%) and 1984-85 (43%). Recent virologic and pathologic studies suggest that this encephalitis may be caused by direct LAV/HTLV-III infection of the central nervous system (CNS). Cytomegalovirus encephalomyelitis and toxoplasmosis were the most common opportunistic infections (26% and 10%, respectively). Progressive multifocal leukoencephalopathy, herpes simplex ventriculitis, varicella-zoster leukoencephalitis and fungal infections were infrequent (less than 3% each). A nonspecific encephalitis with microglial nodules and with mild white matter changes occurred in 17%, vacuolar myelopathy in 29% and CNS lymphoma in 6%. Less than 20% of patients had either normal brains or terminal metabolic encephalopathies. This survey shows that neuropathologic complications of AIDS are frequent. Infections are the most common complication and are caused by probable LAV/HTLV-III infection, or by opportunistic organisms.


Antibiotic prescribing for adults with acute cough/lower respiratory tract infection: congruence with guidelines.
European guidelines for treating acute cough/lower respiratory tract infection (LRTI) aim to reduce nonevidence-based variation in prescribing, and better target and increase the use of first-line antibiotics. However, their application in primary care is unknown. We explored congruence of both antibiotic prescribing and antibiotic choice with European Respiratory Society (ERS)/European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for managing LRTI. The present study was an analysis of prospective observational data from patients presenting to primary care with acute cough/LRTI. Clinicians recorded symptoms on presentation, and their examination and management. Patients were followed up with self-complete diaries. 1,776 (52.7%) patients were prescribed antibiotics. Given patients' clinical presentation, clinicians could have justified an antibiotic prescription for 1,915 (71.2%) patients according to the ERS/ESCMID guidelines. 761 (42.8%) of those who were prescribed antibiotics received a first-choice antibiotic (i.e. tetracycline or amoxicillin). Ciprofloxacin was prescribed for 37 (2.1%) and cephalosporins for 117 (6.6%). A lack of specificity in definitions in the ERS/ESCMID guidelines could have enabled clinicians to justify a higher rate of antibiotic prescription. More studies are needed to produce specific clinical definitions and indications for treatment. First-choice antibiotics were prescribed to the minority of patients who received an antibiotic prescription.


Lectins from Triticum vulgaris and Limax flavus are universal antagonists of botulinum neurotoxin and tetanus toxin.
Lectins from Anguilla anguilla, Artocarpus integrifolia, Canavalia ensiformis, Datora stramonium, Glycine max, Limax flavus, Ricinus communis and Triticum vulgaris were tested for their abilities to antagonize the binding of botulinum neurotoxin and tetanus toxin to rat brain membranes and to antagonize the ability of these toxins to block neuromuscular transmission in mouse phrenic nerve-hemidiaphragm preparations. Lectins from Limax flavus and Triticum vulgaris, both of which have affinity for sialic acid, were antagonists of the various serotypes of botulinum neurotoxin and tetanus toxin. When tested against the high affinity binding site for botulinum neurotoxin type B, the lectin from Limax flavus had a Ki of 3.1 x 10(-7) M and the lectin from Triticum vulgaris had a Ki of 3.75 x 10(-7) M. When tested against the high affinity binding site for tetanus toxin, the lectins from Limax flavus and Triticum vulgaris had Ki values of 1.5 x 10(-7) and 1 x 10(-6) M, respectively. In all cases the lectins behaved as competitive antagonists. In reverse experiments, neither botulinum toxin nor tetanus toxin was a very effective antagonist of lectin binding to brain membranes. Studies on isolated neuromuscular preparations showed that the lectin from Triticum vulgaris did not affect transmission at concentrations of 10(-6) to 10(-3) M, but at a concentration of 3 x 10(-5) M the lectin produced highly statistically significant antagonism of the neuromuscular blocking properties of botulinum neurotoxin types A, B, C, D, E and F as well as tetanus toxin. The lectin did not antagonize beta-bungarotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)


Enterotoxigenic Escherichia coli Adhesin-Toxoid Multiepitope Fusion Antigen CFA/I/II/IV-3xSTaN12S-mnLTG192G/L211A-Derived Antibodies Inhibit Adherence of Seven Adhesins, Neutralize Enterotoxicity of LT and STa Toxins, and Protect Piglets against Diarrhea.
Enterotoxigenic Escherichia coli (ETEC) strains are a leading cause of children's diarrhea and travelers' diarrhea. Vaccines inducing antibodies to broadly inhibit bacterial adherence and to neutralize toxin enterotoxicity are expected to be effective against ETEC-associated diarrhea. 6×His-tagged adhesin-toxoid fusion proteins were shown to induce neutralizing antibodies to several adhesins and LT and STa toxins (X. Ruan, D. A. Sack, W. Zhang, PLoS One 10:e0121623, 2015, https://doi.org/10.1371/journal.pone.0121623). However, antibodies derived from His-tagged CFA/I/II/IV-2xSTaA14Q-dmLT or CFA/I/II/IV-2xSTaN12S-dmLT protein were less effective in neutralizing STa enterotoxicity and were not evaluated in vivo for efficacy against ETEC diarrhea. Additionally, His-tagged proteins are considered less desirable for human vaccines. In this study, we produced a tagless adhesin-toxoid MEFA (multiepitope fusion antigen) protein, enhanced anti-STa immunogenicity by including a third copy of STa toxoid STaN12S, and examined antigen immunogenicity in a murine model. Moreover, we immunized pregnant pigs with the tagless adhesin-toxoid MEFA protein and evaluated passive antibody protection against STa+ or LT+ ETEC infection in a pig challenge model. Results showed that tagless adhesin-toxoid MEFA CFA/I/II/IV-3xSTaN12S-mnLTR192G/L211A induced broad antiadhesin and antitoxin antibody responses in the intraperitoneally immunized mice and the intramuscularly immunized pigs. Mouse and pig serum antibodies significantly inhibited adherence of seven colonization factor antigen (CFA) adhesins (CFA/I and CS1 to CS6) and effectively neutralized both toxins. More importantly, suckling piglets born to the immunized mothers acquired antibodies and were protected against STa+ ETEC and LT+ ETEC diarrhea. These results indicated that tagless CFA/I/II/IV-3xSTaN12S-mnLTR192G/L211A induced broadly protective antiadhesin and antitoxin antibodies and demonstrate that this adhesin-toxoid MEFA is a potential antigen for developing broadly protective ETEC vaccines.


Fossil land mammal from antarctica.
A fossil land mammal, apparently the first found in Antarctica, belongs to the extinct marsupial family Polydolopidae. The fossils were recovered from rocks about 40 million years old on Seymour Island, in the northern Antarctic Peninsula. The newly discovered marsupials support theories that predicted their former presence in Antarctica and strengthen proposals that Australian marsupials perhaps originated from South American species that dispersed across Antarctica when Australia still was attached to it, prior to 56 million years ago.


Microbial degradation of street dust polycyclic aromatic hydrocarbons in microcosms simulating diffuse pollution of urban soil.
Diffuse pollution with polycyclic aromatic hydrocarbons (PAHs) of topsoil in urban regions has caused increasing concerns in recent years. We simulated diffuse pollution of soil in microcosms by spiking sandy topsoil (A-horizon) and coarse, mineral subsoil (C-horizon) with street dust (PM63) isolated from municipal street sweepings from central Copenhagen. The microbial communities adapted to PAH degradation in microcosms spiked with street dust in both A-horizon and C-horizon soils, in spite of low PAH-concentrations. The increased potential for PAH degradation was demonstrated on several levels: by slowly diminishing PAH-concentrations, increased mineralization of 14C-PAHs, increasing numbers of PAH degraders and increased prevalence of nah and pdo1 PAH degradation genes, i.e. the microbial communities quickly adapted to PAH degradation. Three- and 4-ring PAHs from the street dust were biodegraded to some extent (10-20%), but 5- and 6-ring PAHs were not biodegraded in spite of frequent soil mixing and high PAH degradation potentials. In addition to biodegradation, leaching of 2-, 3- and 4-ring PAHs from the A-horizon to the C-horizon seems to reduce PAH-levels in surface soil. Over time, levels of 2-, 3- and 4-ring PAHs in surface soil may reach equilibrium between input and the combination of biodegradation and leaching. However, levels of the environmentally critical 5- and 6-ring PAHs will probably continue to rise. We presume that sorption to black carbon particles is responsible for the persistence and low bioaccessibility of 5- and 6-ring PAHs in diffusely polluted soil.


Application of the industrial hygiene hierarchy of controls to prioritize and promote safer methods of pest control: a case study.
In 2005, the California Department of Public Health, Occupational Health Branch (OHB) investigated an incident of pesticide exposure and identified 27 vineyard workers who became ill due to drift of cyfluthrin, a pesticide being applied to a neighboring orange field to control katydids. Another pest, citrus thrips, was also present in the field. We investigated safer alternatives for katydid and thrips control to prevent illness due to pesticide exposure and used the industrial hygiene hierarchy of controls to prioritize the control methods. OHB evaluated factors that contributed to pesticide exposure and identified safer alternatives by conducting literature reviews on katydid and thrips control, drift prevention technology, and other relevant topics, and by interviewing integrated pest management advisors, conventional and organic growers, equipment manufacturers, county agricultural commissioners, pest control advisors, regulatory agencies, and others. We prioritized methods using the industrial hygiene hierarchy of controls. We identified safer pest control practices that incorporated hazard elimination, chemical substitution, engineering controls, and administrative controls, including employer policies and government regulations.


Association between problematic internet use, socio-demographic variables and obesity among European adolescents.
Overweight of children and adolescents continues to be an important and alarming global public health problem. As the adolescent's time spent online has increased, problematic internet use (PIU) potentially leads to negative health consequences. This study aimed to examine the relation between PIU and overweight/obesity among adolescents in seven European countries and assess the effect of demographic and lifestyle factors recorded in the European Network for Adolescent Addictive Behaviour (EU NET ADB) survey (www.eunetadb.eu). A cross-sectional school-based survey of 14- to 17-year-old adolescents was conducted in seven European countries: Germany, Greece, Iceland, the Netherlands, Poland, Romania and Spain. Anonymous self-completed questionnaires included sociodemographic data, internet usage characteristics, school achievement, parental control and the Internet Addiction Test. Associations between overweight/obesity and potential risk factors were investigated by logistic regression analysis, allowing for the complex sample design. The study sample consisted of 10 287 adolescents aged 14-17 years. 12.4% were overweight/obese, and 14.1% presented with dysfunctional internet behavior. Greece had the highest percentage of overweight/obese adolescents (19.8%) and the Netherlands the lowest (6.8%). Male sex [odds ratio (OR) = 2.89, 95%CI: 2.46-3.38], heavier use of social networking sites (OR = 1.26, 95%CI: 1.09-1.46) and residence in Greece (OR = 2.32, 95%CI: 1.79-2.99) or Germany (OR = 1.48, 95%CI: 1.12-1.96) were independently associated with higher risk of overweight/obesity. A greater number of siblings (OR = 0.79, 95%CI: 0.64-0.97), higher school grades (OR = 0.74, 95%CI: 0.63-0.88), higher parental education (OR = 0.89, 95%CI: 0.82-0.97) and residence in the Netherlands (OR = 0.49, 95%CI: 0.31-0.77) independently predicted lower risk of overweight/obesity. The results indicate an association of overweight/obesity with PIU and suggest the importance of formulating preventive public health policies that target physical health, education and sedentary online lifestyle early in adolescence with special attention to boys.


Microfluidic-assisted fabrication of carriers for controlled drug delivery.
The microfluidic technique has brought unique opportunities toward the full control over the production processes for drug delivery carriers, owing to the miniaturisation of the fluidic environment. In comparison to the conventional batch methods, the microfluidic setup provides a range of advantages, including the improved controllability of material characteristics, as well as the precisely controlled release profiles of payloads. This review gives an overview of different fluidic principles used in the literature to produce either polymeric microparticles or nanoparticles, focusing on the materials that could have an impact on drug delivery. We also discuss the relations between the particle size and size distribution of the obtained carriers, and the design and configuration of the microfluidic setups. Overall, the use of microfluidic technologies brings exciting opportunities to expand the body of knowledge in the field of controlled drug delivery and great potential to clinical translation of drug delivery systems.


Effects of Exercise on Carotid Arterial Wall Thickness in Obese Pediatric Populations: A Meta-Analysis of Randomized Controlled Trials.
In pediatric populations, the use of carotid intima-media thickness (IMT) as a marker of cardiovascular risk has increased. However, previous studies examining the effects of exercise training on arterial structure and function in obese children and adolescents have shown inconsistent findings. The primary aim of this systematic review and meta-analysis is to expand on the current body of literature by providing a quantitative estimate of the change in carotid IMT following exercise training as well as to provide an exploratory analysis of potential moderators associated with the variation in response to an exercise training intervention in overweight and obese youth. A computerized search was made using three databases. The analysis was restricted to studies that examined the effect of exercise interventions on carotid IMT in pediatric obesity (6-18-year-olds). Hedges' g and 95% confidence intervals (CIs) were calculated. Six randomized controlled trials (303 youths) were included. Exercise was associated with a small-to-moderate but significant reduction in carotid IMT (g = -0.306; 95% CI -0.540 to -0.072; p = 0.011). Likewise, exercise program duration per week significantly influenced the effect of exercise on carotid IMT (β = -0.060; p = 0.015). Exercise seems to reduce carotid IMT in childhood obesity. Therefore, encouraging obese pediatric individuals to become physically active can lead to favorable changes in the arterial wall.


Construction of an Infant Neurological International Battery (Infanib) for the assessment of neurological integrity in infancy.
In this article, we describe the construction of an instrument for the assessment of the neurological integrity of infants. In a follow-up program for infants from the neonatal intensive care unit, 365 evaluations of 308 infants were made by using a 32-item battery with items from four methods. Factor analyses were used for data analyses, which yielded a 20-item instrument with five factors. We named the instrument the Infant Neurological International Battery (Infanib). The Infanib has sufficient reliability for clinical and research purposes. We have formed scoring sheets, which permit clinical use of the instrument. Cut points are recommended for the separation of infants with normal, transiently abnormal, and abnormal neurologic development. The quantified scoring system enables comparison of infants on item scores, subscores (factor scores), and total scores. It also permits entry of these scores in the computer so that more complex descriptions are possible of the relationship of the neurological assessment of infants both to earlier (eg, birth) and later variables (eg, cerebral palsy, cognitive function, and school performance).


scanPAV: a pipeline for extracting presence-absence variations in genome pairs.
The recent technological advances in genome sequencing techniques have resulted in an exponential increase in the number of sequenced human and non-human genomes. The ever increasing number of assemblies generated by novel de novo pipelines and strategies demands the development of new software to evaluate assembly quality and completeness. One way to determine the completeness of an assembly is by detecting its Presence-Absence variations (PAV) with respect to a reference, where PAVs between two assemblies are defined as the sequences present in one assembly but entirely missing in the other one. Beyond assembly error or technology bias, PAVs can also reveal real genome polymorphism, consequence of species or individual evolution, or horizontal transfer from viruses and bacteria. We present scanPAV, a pipeline for pairwise assembly comparison to identify and extract sequences present in one assembly but not the other. In this note, we use the GRCh38 reference assembly to assess the completeness of six human genome assemblies from various assembly strategies and sequencing technologies including Illumina short reads, 10× genomics linked-reads, PacBio and Oxford Nanopore long reads, and Bionano optical maps. We also discuss the PAV polymorphism of seven Tasmanian devil whole genome assemblies of normal animal tissues and devil facial tumour 1 (DFT1) and 2 (DFT2) samples, and the identification of bacterial sequences as contamination in some of the tumorous assemblies. The pipeline is available under the MIT License at https://github.com/wtsi-hpag/scanPAV. Supplementary data are available at Bioinformatics online.


Malachite green toxicity assessed on Asian catfish primary cultures of peripheral blood mononuclear cells by a proteomic analysis.
The potential genotoxic and carcinogenic properties reported for malachite green (MG) and the frequent detection of MG residues in fish and fish products, despite the ban of MG, have recently generated great concern. Additional toxicological data are required for a better understanding of the mechanism of action and a more comprehensive risk assessment for the exposure of fish to this fungicide. To date, the use of fish peripheral blood mononuclear cells (PBMCs) has not been exploited as a tool in the assessment of the toxicity of chemicals. However, PBMCs are exposed to toxicants and can be easily collected by blood sampling. The present study aims at better understanding the effects of MG by a proteomic analysis of primary cultured PBMC from the Asian catfish, Pangasianodon hypophthalmus, exposed to MG. The two lowest concentrations of 1 and 10 ppb were selected based on the MTS (water soluble tetrazolium salts) cytotoxicity test. Using a proteomic analysis (2D-DIGE), we showed that 109 proteins displayed significant changes in abundance in PBMC exposed during 48 h to MG. Most of these proteins were successfully identified by nano LC-MS/MS and validated through the Peptide and Protein Prophet of Scaffold™ software, but only 19 different proteins were considered corresponding to a single identification per spot. Our data suggest that low concentrations of MG could affect the mitochondrial metabolic functions, impair some signal transduction cascades and normal cell division, stimulate DNA repair and disorganize the cytoskeleton. Altogether, these results confirm that the mitochondrion is a target of MG toxicity. Further studies on the identified proteins are needed to better understand the mechanisms of MG toxicity in fish produced for human consumption.


Oxidant-induced glutathionylation at protein disulfide bonds.
Disulfide bonds are a key determinant of protein structure and function, and highly conserved across proteomes. They are particularly abundant in extracellular proteins, including those with critical structural, ligand binding or receptor function. We demonstrate that oxidation of protein disulfides induces polymerization, and results in oxygen incorporation into the former disulfide via thiosulfinate generation. These intermediates, which have half-lives of several hours in vitro, undergo secondary reactions that cleave the disulfide bond, by irreversible hydrolysis to sulfinic and sulfonic acids, or reaction with thiols in a process that yields thiolated proteins (e.g. glutathionylated species in the case of reaction with glutathione). The adducts have been characterized by mass spectrometry (as ions corresponding to the addition of 306 and 712 Da for addition of one and two glutathione molecules, respectively) and immunoblotting. These modifications can be induced by multiple biologically-important oxidants, including HOCl, ONOOH, and H2O2, and on multiple proteins, demonstrating that this is a common disulfide modification pathway. Addition of glutathione to give glutathionylated proteins, can be reversed by reducing systems (e.g. tris(2-carboxyethyl)phosphine), but this does not repair the original disulfide bond. Exposure of human plasma to these modifying agents increases protein glutathionylation, demonstrating potential in vivo relevance. Overall these data provide evidence for a novel and facile route to glutathionylated proteins involving initial oxidation of a disulfide to a thiosulfinate followed by rapid reaction with GSH ('oxidant-mediated thiol-disulfide exchange'). These data elucidate a novel pathway for protein glutathionylation that may have significant implications for redox biology and cell signaling.


Numerical compression schemes for proteomics mass spectrometry data.
The open XML format mzML, used for representation of MS data, is pivotal for the development of platform-independent MS analysis software. Although conversion from vendor formats to mzML must take place on a platform on which the vendor libraries are available (i.e. Windows), once mzML files have been generated, they can be used on any platform. However, the mzML format has turned out to be less efficient than vendor formats. In many cases, the naïve mzML representation is fourfold or even up to 18-fold larger compared with the original vendor file. In disk I/O limited setups, a larger data file also leads to longer processing times, which is a problem given the data production rates of modern mass spectrometers. In an attempt to reduce this problem, we here present a family of numerical compression algorithms called MS-Numpress, intended for efficient compression of MS data. To facilitate ease of adoption, the algorithms target the binary data in the mzML standard, and support in main proteomics tools is already available. Using a test set of 10 representative MS data files we demonstrate typical file size decreases of 90% when combined with traditional compression, as well as read time decreases of up to 50%. It is envisaged that these improvements will be beneficial for data handling within the MS community.


Changes in the Rumen Microbiota of Cows in Response to Dietary Supplementation with Nitrate, Linseed, and Saponin Alone or in Combination.
Dietary supplementation with linseed, saponins, and nitrate is a promising methane mitigation strategy in ruminant production. Here, we aimed to assess the effects of these additives on the rumen microbiota in order to understand underlying microbial mechanisms of methane abatement. Two 2-by-2 factorial design studies were conducted simultaneously, which also allowed us to make a broad-based assessment of microbial responses. Eight nonlactating cows were fed diets supplemented with linseed or saponin in order to decrease hydrogen production and nitrate to affect hydrogen consumption; also, combinations of linseed plus nitrate or saponin plus nitrate were used to explore the interaction between dietary treatments. Previous work assessed effects on methane and fermentation patterns. Rumen microbes were studied by sequencing 18S and 16S rRNA genes and ITS1 amplicons. Methanogen activity was monitored by following changes in mcrA transcript abundance. Nitrate fed alone or in combination in both studies dramatically affected the composition and structure of rumen microbiota, although impacts were more evident in one of the studies. Linseed moderately modified only bacterial community structure. Indicator operational taxonomic unit (OTU) analysis revealed that both linseed and nitrate reduced the relative abundance of hydrogen-producing Ruminococcaceae Linseed increased the proportion of bacteria known to reduce succinate to propionate, whereas nitrate supplementation increased nitrate-reducing bacteria and decreased the metabolic activity of rumen methanogens. Saponins had no effect on the microbiota. Inconsistency found between the two studies with nitrate supplementation could be explained by changes in microbial ecosystem functioning rather than changes in microbial community structure.IMPORTANCE This study aimed at identifying the microbial mechanisms of enteric methane mitigation when linseed, nitrate, and saponins were fed to nonlactating cows alone or in a combination. Hydrogen is a limiting factor in rumen methanogenesis. We hypothesized that linseed and saponins would affect hydrogen producers and nitrate would affect hydrogen consumption, leading to reduced methane production in the rumen. Contrary to what was predicted, both linseed and nitrate had a deleterious effect on hydrogen producers; linseed also redirected hydrogen consumption toward propionate production, whereas nitrate stimulated the growth of nitrate-reducing and, hence, hydrogen-consuming bacterial taxa. This novel knowledge of microbial mechanisms involved in rumen methanogenesis provides insights for the development and optimization of methane mitigation strategies.


Taxanes in the adjuvant treatment of breast cancer.
Adjuvant chemotherapy clearly demonstrates a reduction in mortality in breast cancer. However, the added benefit from the addition of taxanes remains uncertain. Paclitaxel and its cousin docetaxel have proven activity in the treatment of metastatic breast cancer. Toxicity has been tolerable when taxanes are used as single agents or in combination with anthracyclines. Several clinical trials are currently underway evaluating the role of taxanes in the adjuvant setting. Preliminary results from large phase III studies are promising; however, mature data are required before conclusions can be drawn. This article reviews the trials currently underway, evaluating the efficacy, dosage, scheduling, and regimens of taxanes in the adjuvant treatment of breast cancer.


The state of stroke services across the globe: Report of World Stroke Organization-World Health Organization surveys.
Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization-World Health Organization-Lancet Neurology Commission on Stroke conducted a survey of the status of stroke services in low and middle-income countries (LMICs) compared to high-income countries. Using a validated World Stroke Organization comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across World Health Organization regions and economic strata. The World Health Organization also conducted a survey of non-communicable diseases in 194 countries in 2019. Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys, and participation in research) were reported in low-income countries than high-income countries. The overall global score for prevention was 40.2%. Stroke units were present in 91% of high-income countries in contrast to 18% of low-income countries (p < 0.001). Acute stroke treatments were offered in ∼ 60% of high-income countries compared to 26% of low-income countries (p = 0.009). Compared to high-income countries, LMICs provided less rehabilitation services including in-patient rehabilitation, home assessment, community rehabilitation, education, early hospital discharge program, and presence of rehabilitation protocol. There is an urgent need to improve access to stroke units and services globally especially in LMICs. Countries with less stroke services can adapt strategies from those with better services. This could include establishment of a framework for regular monitoring of stroke burden and services, implementation of integrated prevention activities and essential acute stroke care services, and provision of interdisciplinary care for stroke rehabilitation.


Relations of Facial Nerve With Retromandibular Vein in Human Fetuses.
The relationship of facial nerve (FN) and its branches with the retromandibular vein (RMV) has been described in adults, whereas there is no data in the literature regarding this relationship in fetuses. The study was conducted to evaluate the anatomic relationships of these structures on 61 hemi-faces of fetuses with a mean age of 26.5 ± 4.9 weeks with no visible facial abnormalities. The FN trunk was identified at its emergence at the stylomastoid foramen. It was traced till its ramification within the parotid gland. In 46 sides, FN trunk ramified before crossing RMV and ran lateral to it, while in 8 sides FN trunk ramified on the lateral aspect of the RMV. In 3 sides, FN trunk ramified after crossing the RMV at its medial aspect. In only 1 side, FN trunk trifurcated as superior, middle, and inferior divisions and RMV lied anterior to FN trunk, lateral to superior division, medial to middle and inferior divisions. In 2 sides, FN trunk bifurcated as superior and inferior divisions. Retromandibular vein was located anterior to FN trunk, medial to superior division, lateral to inferior division in both of them. In 1 side, RMV ran medial to almost all branches, except the cervical branch of FN. Variability in the relationship of FN and RMV in fetuses as presented in this study is thought to be crucial in surgical procedures particularly in early childhood.


Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes.
The human gut microbiota supplies its host with essential nutrients, including B-vitamins. Using the PubSEED platform, we systematically assessed the genomes of 256 common human gut bacteria for the presence of biosynthesis pathways for eight B-vitamins: biotin, cobalamin, folate, niacin, pantothenate, pyridoxine, riboflavin, and thiamin. On the basis of the presence and absence of genome annotations, we predicted that each of the eight vitamins was produced by 40-65% of the 256 human gut microbes. The distribution of synthesis pathways was diverse; some genomes had all eight biosynthesis pathways, whereas others contained no de novo synthesis pathways. We compared our predictions to experimental data from 16 organisms and found 88% of our predictions to be in agreement with published data. In addition, we identified several pairs of organisms whose vitamin synthesis pathway pattern complemented those of other organisms. This analysis suggests that human gut bacteria actively exchange B-vitamins among each other, thereby enabling the survival of organisms that do not synthesize any of these essential cofactors. This result indicates the co-evolution of the gut microbes in the human gut environment. Our work presents the first comprehensive assessment of the B-vitamin synthesis capabilities of the human gut microbiota. We propose that in addition to diet, the gut microbiota is an important source of B-vitamins, and that changes in the gut microbiota composition can severely affect our dietary B-vitamin requirements.


Alternative Therapies in the Treatment of Atrial Fibrillation.
Atrial fibrillation (AF) is the most common clinical arrhythmia and represents a major social and economic problem. The number of subjects with AF is constantly increasing as a result of aging and improved survival in several cardiac and non-cardiac diseases. Patients with AF are often symptomatic, have a reduced physical capacity and are at high risk for thromboembolic events. Moreover, AF is associated with increased mortality and independent of the management, based either on rhythm or rate control strategy. The safety and efficacy of most anti-arrhythmic drugs are questionable. Increasing attention has therefore been addressed to evaluate the possible therapeutic and/or preventive effects of forms of treatment coming from ancient medical traditions of Far East, like acupuncture and yoga. In traditional Chinese medicine, acupuncture has been found effective in managing patients with paroxysmal supraventricular tachycardia. Recently, also in the Western literature, reports have been published supporting the clinical efficacy of acupuncture to treat arterial hypertension and to reduce chest pain. Other studies have evaluated the effects of acupuncture and other methods of Eastern Medicine, i.e., Qigong, Tai Chi Chuan and Yoga, in the treatment of cardiac illnesses associated with supraventricular arrhythmias. Two reports on the effects of acupuncture in preventing or reducing the rate of AF recurrences in patients with persistent or paroxysmal AF have been recently reported . Another ancient traditional eastern form of therapy and prevention, i.e., yoga, has been recently shown to reduce episodes of atrial fibrillation and improve the symptoms of anxiety and depression often associated with this arrhythmia. Growing evidence indicates that acupuncture and yoga are safe, without any pro-arrhythmic effect and with limited cost. All these factors should be considered when evaluating the efficacy of therapeutic intervention for an epidemic disease such as AF.


Optical phase shifting with acousto-optic devices.
A novel optical phase-shifting method based on a well-known acousto-optic interaction is proposed. By using a pair of acousto-optic modulators (AOMs) and properly aligning them, we construct an optical phase shifter that can directly control the phase of a collimated beam. The proposed phase shifter is insensitive to the polarization of the incident beam when polarization-insensitive AOMs are used, and no calibration is necessary. The proposed approach is confirmed with experimental results.


Development of an Illustrated Guide to Techniques of Dressing Application in the Patient With Burns.
Burns are complex, difficult-to-treat wounds associated with high rates of morbidity and mortality. The aim of this study is to develop and validate an illustrated guide to techniques of dressing application for use in the initial management of the patient with burn wounds. The construction of the illustrated guide was based on a literature review conducted of publications between 2001 to 2017 in MEDLINE/PubMed, Scientific Electronic Library Online, Cochrane Library, and Google Scholar. No similar work was found in the literature. Standardized photographs were taken using a manikin to illustrate the step-by-step procedures. The content validity of the illustrated guide was assessed by a panel of 7 burn specialists through a questionnaire in the search for a consensus opinion according to the Delphi technique. The questionnaire assessed 3 main components: Objective, Structure and Presentation, and Relevance of the guide. The final version of the illustrated guide showed an excellent overall content validity index (CVI) of 0.99. The CVI was 1.0 for the component Objective, 0.98 for Structure and Presentation, and 1.0 for Relevance. The guide has 79 pages, 86 illustrations, and 10 chapters on techniques of dressing application for patients with burn wounds. Topics including material preparation, gowning and gloving procedures, and techniques of dressing application for different parts of the body were addressed. An illustrated guide for dressing application in burn wounds was developed and validated for content by an expert panel.


Investigating pressure bandaging for snakebite in a simulated setting: bandage type, training and the effect of transport.
The clinical evidence base for the use of pressure bandaging in snakebite is limited. We aimed to investigate if pressure bandages (PB) generated and maintained presumptive optimal pressures in a simulated setting. A total of 96 subjects were recruited, 78 health professionals and 18 from the general public. Participants were asked to apply PB with crepe and with an elasticized bandage without instruction. A paediatric blood pressure cuff attached to a pressure transducer was used to measure the pressure generated. PB application with elasticized bandages was repeated by 36 participants (18 general public and 18 health professionals) with feedback on pressures attained, and reassessment on the sixth subsequent attempt. Pressure was also measured under correctly applied bandages during an ambulance ride. The median pressure generated under crepe bandages was 28 mmHg (interquartile range [IQR]: 17-42 mmHg) compared with 47 mmHg (IQR 26-83 mmHg) with elasticized bandages, with most subgroups applying the elasticized bandage closer to the estimated optimal pressure (55-70 mmHg). Following training, the median pressure for the 36 participants was 65 mmHg (IQR 56-71 mmHg), closer to the optimal range than initial attempts. On initial bandaging, 5/36 (14%) participants achieved optimal pressure range with elasticized bandages, compared with 18/36 (50%) after training (P = 0.002). Crepe bandages initially correctly applied did not maintain desired pressure during ambulance transport on urban roads over 30 min. Elasticized bandages maintained pressure. PB was poorly done by the general public and health professionals. Crepe bandages rarely generated optimal pressures compared with elasticized bandages, but training did improve participants' ability to apply elasticized bandages. PB recommendations should be modified to specify appropriate bandage types.


Unexpected kidney-restricted role for IL-17 receptor signaling in defense against systemic Candida albicans infection.
Kidney injury is a frequent outcome in patients with disseminated Candida albicans fungal infections. IL-17 receptor (IL-17R) signaling is critical for renal protection against disseminated candidiasis, but the identity and function of IL-17-responsive cells in mediating renal defense remains an active area of debate. Using BM chimeras, we found that IL-17R signaling is required only in nonhematopoietic cells for immunity to systemic C. albicans infection. Since renal tubular epithelial cells (RTEC) are highly responsive to IL-17 in vitro, we hypothesized that RTEC might be the dominant target of IL-17 activity in the infected kidney. We generated mice with a conditional deletion of IL-17 receptor A (Il17ra) in RTEC (Il17raΔRTEC). Strikingly, Il17raΔRTEC mice showed enhanced kidney damage and early mortality following systemic infection, very similar to Il17ra-/- animals. Increased susceptibility to candidiasis in Il17raΔRTEC mice was associated with diminished activation of the renal protective Kallikrein-kinin system (KKS), resulting in reduced apoptosis of kidney-resident cells during hyphal invasion. Moreover, protection was restored by treatment with bradykinin, the major end-product of KKS activation, which was mediated dominantly via bradykinin receptor b1. These data show that IL-17R signaling in RTEC is necessary and likely sufficient for IL-17-mediated renal defense against fatal systemic C. albicans infection.


There's More than Meets the Eye: Complex Associations of Daily Pain, Physical Symptoms, and Self-Efficacy with Activity in Middle and Older Adulthood.
Participation in activities is associated with a range of positive outcomes in adulthood. Research has shown that pain and physical symptoms are associated with less activity in older adults, whereas higher self-efficacy is associated with more activity. Such research tends to examine cross-sectional or long-term between-person change, limiting the opportunity to explore dynamic within-person processes that unfold over shorter time periods. This study aimed to (1) replicate previous between-person associations of self-efficacy with engagement in activity and (2) examine whether daily variation in pain, physical symptoms, and self-efficacy corresponded with daily within-person variation in different types of activity. We predicted that participants would engage in less activity on days when they experienced more pain or physical symptoms than their average (a negative within-person association) and that participants would engage in more activity on days when self-efficacy was higher than average (a positive within-person association). This study used an online diary study to assess self- reported daily pain, physical symptoms, self-efficacy, and engagement in activity among 185 adults aged 51-84 years for up to 7 days. Multilevel modelling was used to examine whether between-person (average) and daily within-person variability in pain, physical symptoms, and self-efficacy were associated with social, physical, and mental activity. In line with previous research, between-person self-efficacy was positively associated with social and physical activity. Supporting the hypotheses, within-person self-efficacy was also positively associated with social and physical activity. The results for pain and physical symptoms were less consistent. Between-person pain was positively associated with social activity. Age interactions indicated that within-person pain was negatively associated with social activity and positively associated with physical activity among older adults. Within-person physical symptoms were positively related to social and mental activity. Stable individual differences as well as short-term within-person variation in physical and psychological functioning are associated with day-to-day variation in activity. Between-person associations did not always reflect within-person associations (e.g., for pain). These complex associations may be influenced by a range of factors including the type of activity and how it is defined (e.g., specific activities and their difficulty), the type of physical symptoms experienced, and age.


First Report of Alternaria alternata Causing Leaf Spot on Aloe vera in Louisiana.
Aloe vera (L.) Burm. f. is a perennial succulent plant that is grown worldwide mainly for medicinal and cosmetic uses. In the USA, it is mainly cultivated in some southern states to produce aloe gel for the cosmetic industry (3), and in Louisiana it is also sold commercially as an ornamental. During the summer of 2011, several A. vera plants infected with leaf spots were observed on the campus of Louisiana State University, Baton Rouge. Large, necrotic, sunken, circular to oval, dark brown spots were present on both surfaces of the leaves. Infected leaf tissue pieces were surface disinfested with 1% NaOCl solution for 1 min and plated on potato dextrose agar (PDA). Plates were incubated at 28°C in the dark for 4 days. A dark olivaceous fungus with profuse golden brown, branched, and septate hyphae was consistently isolated from the infected tissue on PDA. The fungus produced conidia with longitudinal and transverse septa, and was morphologically identified as an Alternaria sp. (4). Conidia were produced in long chains, pale to light brown, obpyriform, with a beak (6.0 μm long), one to seven transverse and up to three longitudinal septa, and measured 10 to 45 μm long × 7 to 18 μm wide. Conidiophores were straight, septate, light to olive golden brown with conidial scar, and measured 35 to 100 μm long × 2 to 5 μm wide. Genomic DNA from a single-spored isolate was extracted and the internal transcribed spacer (ITS1-5.8s-ITS2) regions were amplified and sequenced using primers ITS1 and ITS4. BLASTn analysis of a 486-bp sequence (GenBank Accession No. JQ409455) resulted in 100% homology with A. alternata strain DHMJ16 (GenBank Accession No. JN986768) from China and several other Alternaria spp. The fungus was identified as A. alternata based on mycelial and conidia characters after being grown under standard, previously described conditions (4). Pathogenicity tests were carried out by inoculating six potted aloe plants with 0.5-cm diameter discs taken from a 6-day-old culture grown on PDA. Four discs were placed on the upper surface of each of the bottom leaves of every plant. Inoculated plants were individually covered with a plastic bag and maintained in a greenhouse for 1 week at 25 ± 2°C. Six control plants received only agar plugs. Seven days after inoculation, necrotic leaf spots were observed on the inoculated plants and A. alternata was reisolated from these spots. No leaf spots were observed on control plants. To the best of our knowledge, this is the first report of leaf spot caused by A. alternata on A. vera in Louisiana. Several outbreaks of the disease have been reported in Pakistan and India as damaging aloe gel production in those countries (1,2). An outbreak of this disease in Louisiana could represent a serious issue for the state's A. vera ornamental commerce. References: (1) R. Bajwa et al. Can. J. Plant Pathol. 32:490, 2010. (2) A. Kamalakannan et al. Australas. Plant Dis. Notes 3:110, 2008. (3) T. Reynolds. Aloes: The Genus Aloe. CRC Press, Boca Raton, FL, 2004. (4) E. G. Simmons. Alternaria: An Identification Manual: Fully Illustrated and with Catalogue Raisonné 1796-2007. CBS Fungal Biodiversity Centre, Utrecht, The Netherlands, 2007.


Impact on rats from acute intratracheal inhalation exposures to WTC dusts.
Background: Studies have revealed the increased incidence of health disorders in First Responders (FR) who were at Ground Zero over the initial 72 hr after the World Trade Center (WTC) collapses. Previous studies in rats exposed to WTC dusts using exposure scenarios that mimicked FR mouthbreathing showed exposure led to altered expression of genes whose products could be involved in lung ailments. Nevertheless, it was uncertain if repeated exposures (as occurred in earliest days post-disaster) might have given rise to long-term changes in the lungs/other organs, in white blood cell (WBC) profiles, and/or systemic expression of select (mostly immune-related) proteins.Methods: To examine this, rats were exposed on 2 consecutive days (2 hr/d, intratracheal inhalation) to WTC dusts and then examined over a 1-yr period thereafter. At select times post-exposure, organ (lung, heart, liver, kidney, spleen) weights, WBC profiles, and blood levels of a variety of proteins were evaluated.Results: The study showed that over the 1-yr period, there were nominal effects on organ weights (absolute, index) as a result of the dust exposures. There were significant changes (relative to in naïve rats) in WBC profiles, with exposed rats having increased monocyte-macrophage and decreased lymphocyte percentages. The study also found that dust exposure led to significant systemic increases in many proteins, including MCP-1, RANTES, MMP-9, RAGE, and Galectin-3.Conclusions: These results provide further support for our longstanding hypothesis that the WTC dusts could potentially have acted as direct inducers of many of the health effects that have been seen in the exposed FR.


Correspondence Between Cytomegalovirus Immunoglobulin-G Levels Measured in Saliva and Serum.
Human cytomegalovirus (HCMV) infects more than 80% of the global population. While mostly asymptomatic, HCMV infection can be serious among the immunocompromised, and it is implicated in chronic disease pathophysiology in adulthood. Large-scale minimally invasive HCMV screening could advance research and public health efforts to monitor infection prevalence and prevent or mitigate downstream risks associated with infection. We examine the utility of measuring HCMV immunoglobulin-G (IgG) levels in saliva as an index of serum levels. Matched serum and saliva samples from healthy adults (N = 98; 44% female; 51% white) were assayed for HCMV IgG, total salivary protein, and salivary markers related to oral inflammation, blood, and tissue integrity. We examine the serum-saliva association for HCMV IgG and assess the influence of participant characteristics and factors specific to the oral compartment (e.g., oral inflammation) on HCMV IgG levels and cross-specimen relations. We found a robust serum-saliva association for HCMV IgG with serum antibody levels accounting for >60% of the variance in salivary levels. This relation remained after adjusting for key demographic and oral immune-related variables. Compared to the serum test, the salivary HCMV IgG test had 51% sensitivity and 97% specificity. With improvements in assay performance and sample optimization, HCMV antibody levels in oral fluids may be a useful proxy for serum levels.


The role of cognitive schemata in the development of posttraumatic stress disorder: results of cross-sectional and longitudinal studies.
There are two theories (by Horowitz and by Foa) which attempt at explaining the process of posttraumatic stress disorder (PTSD) development by information dissonance. The purpose of the present study was to verify these theories via cross-sectional and longitudinal studies. The study based on a cross-sectional design was performed on a representative group of Polish firefighters. The study using a longitudinal protocol was conducted among police officers. The level of PTSD was assessed using the Questionnaire for PTSD Measurement (K-PTSD). The sense of coherence (SOC) was measured with the Polish adaptation of the Orientation to Life Questionnaire by A. Antonovsky. In the cross-sectional study, the correlation coefficients between K-PTSD and SOC were -0.35 (p < 0.001) in the group of firefighters and -0.47 (p < 0.001) in that of police officers. In the longitudinal study, the relationship between SOC and PTSD symptoms appeared to be curvilinear and had the U-letter shape. Therefore, we used ANOVA for statistical analysis. Unfortunately, the F(2.31) = 1.900 and p > 0.05 indicated that the tendency we observed was not statistically significant. We would like to propose two possible explanations for the difference in the relationships between SOC and PTSD symptoms obtained in the studies employing the cross-sectional and the longitudinal protocols.


High-Convexity Tightness Predicts the Shunt Response in Idiopathic Normal Pressure Hydrocephalus.
Although neuroimaging plays an important role in the diagnosis of idiopathic normal pressure hydrocephalus, its predictive value for response to shunt surgery has not been established. The purpose of the current study was to identify neuroimaging markers that predict the shunt response of idiopathic normal pressure hydrocephalus. Sixty patients with idiopathic normal pressure hydrocephalus underwent presurgical brain MR imaging and clinical evaluation before and 1 year after shunt surgery. The assessed MR imaging features included the Evans index, high-convexity tightness, Sylvian fissure dilation, callosal angle, focal enlargement of the cortical sulci, bumps in the lateral ventricular roof, and deep white matter and periventricular hyperintensities. The idiopathic normal pressure hydrocephalus grading scale total score was used as a primary clinical outcome measure. We used measures for individual symptoms (ie, the idiopathic normal pressure hydrocephalus grading scale subdomain scores, such as gait, cognitive, and urinary scores), the Timed Up and Go test, and the Mini-Mental State Examination as secondary clinical outcome measures. The relationships between presurgical neuroimaging features and postoperative clinical changes were investigated by using simple linear regression analysis. To identify the set of presurgical MR imaging features that best predict surgical outcomes, we performed multiple linear regression analysis by using a bidirectional stepwise method. Simple linear regression analyses demonstrated that presurgical high-convexity tightness, callosal angle, and Sylvian fissure dilation were significantly associated with the 1-year changes in the clinical symptoms. A multiple linear regression analysis demonstrated that presurgical high-convexity tightness alone predicted the improvement of the clinical symptoms 1 year after surgery. High-convexity tightness is a neuroimaging feature predictive of shunt response in idiopathic normal pressure hydrocephalus.


Stress-related hormones and glycinebetaine interplay in protection of photosynthesis under abiotic stress conditions.
Plants subjected to abiotic stresses such as extreme high and low temperatures, drought or salinity, often exhibit decreased vegetative growth and reduced reproductive capabilities. This is often associated with decreased photosynthesis via an increase in photoinhibition, and accompanied by rapid changes in endogenous levels of stress-related hormones such as abscisic acid (ABA), salicylic acid (SA) and ethylene. However, certain plant species and/or genotypes exhibit greater tolerance to abiotic stress because they are capable of accumulating endogenous levels of the zwitterionic osmolyte-glycinebetaine (GB). The accumulation of GB via natural production, exogenous application or genetic engineering, enhances plant osmoregulation and thus increases abiotic stress tolerance. The final steps of GB biosynthesis occur in chloroplasts where GB has been shown to play a key role in increasing the protection of soluble stromal and lumenal enzymes, lipids and proteins, of the photosynthetic apparatus. In addition, we suggest that the stress-induced GB biosynthesis pathway may well serve as an additional or alternative biochemical sink, one which consumes excess photosynthesis-generated electrons, thus protecting photosynthetic apparatus from overreduction. Glycinebetaine biosynthesis in chloroplasts is up-regulated by increases in endogenous ABA or SA levels. In this review, we propose and discuss a model describing the close interaction and synergistic physiological effects of GB and ABA in the process of cold acclimation of higher plants.