Critical appraisal of data used to infer record UVI in the tropical andes.
When the data sets that suggested record high UVI values at Mt Licancabur, and Laguna Blanca, Bolivia are reviewed in full, we find that the reported peak values are incorrect, probably due to instrumental problems. These affect the UVB, UVA and PAR channels at different times and different solar zenith angles, with distinct diurnal patterns in each case. The outliers are consistent with errors that would result from build-up of ice or snow on the surface of the entrance dome, combined with incomplete baffling of light within the integrating spheres that form the entrance optic of these instruments, but we cannot unequivocally attribute them to this cause. The analysis shows that for all three channels, cloud enhancements over clear-sky values by a factor of ∼4 or more would be required to explain their highest values. Such repeated enhancements are not physically plausible and are more than twice those previously observed in the UV region. Further, at the time of peak reported UVB, the UVA cloud enhancement factor was less than 1.2 (i.e., UVA radiation was increased by less than 20% over clear-sky values), which implies that to explain the high UVB values, an atmospheric ozone amount (∼25 DU) far below the minimum ever observed would be required. The analysis also shows that the algorithm to convert from UVB to UVI is incorrect, and that if the correct algorithm had been used, the peak UVI values would have been even larger than reported. Disregarding the obviously incorrect measurements, the highest realistic values near solar noon from this dataset are in the range UVI = 25 ± 5, which is in agreement with previous estimates in the region.


MicroRNA-155 is essential for the optimal proliferation and survival of plasmablast B cells.
A fast antibody response can be critical to contain rapidly dividing pathogens. This can be achieved by the expansion of antigen-specific B cells in response to T-cell help followed by differentiation into plasmablasts. MicroRNA-155 (miR-155) is required for optimal T-cell-dependent extrafollicular responses via regulation of PU.1, although the cellular processes underlying this defect are largely unknown. Here, we show that miR-155 regulates the early expansion of B-blasts and later on the survival and proliferation of plasmablasts in a B-cell-intrinsic manner, by tracking antigen-specific B cells in vivo since the onset of antigen stimulation. In agreement, comparative analysis of the transcriptome of miR-155-sufficient and miR-155-deficient plasmablasts at the peak of the response showed that the main processes regulated by miR-155 were DNA metabolic process, DNA replication, and cell cycle. Thus, miR-155 controls the extent of the extrafollicular response by regulating the survival and proliferation of B-blasts, plasmablasts and, consequently, antibody production.


Improved long-term durability of allogeneic heart valves in the orthotopic sheep model.
Frozen cryopreservation (FC) with the vapour phase of liquid nitrogen storage (-135°C) is a standard biobank technique to preserve allogeneic heart valves to enable a preferable allograft valve replacement in clinical settings. However, their long-term function is limited by immune responses, inflammation and structural degeneration. Ice-free cryopreserved (IFC) valves with warmer storage possibilities at -80°C showed better matrix preservation and decreased immunological response in preliminary short-term in vivo studies. Our study aimed to assess the prolonged performance of IFC allografts in an orthotopic pulmonary sheep model. FC (n = 6) and IFC (n = 6) allografts were transplanted into juvenile Merino sheep. After 12 months of implantation, functionality testing via 2-dimensional echocardiography and histological analyses was performed. In addition, multiphoton autofluorescence imaging and Raman microspectroscopy analysis were applied to qualitatively and quantitatively assess the matrix integrity of the leaflets. Six animals from the FC group and 5 animals from the IFC group were included in the analysis. Histological explant analysis showed early inflammation in the FC valves, whereas sustainable, fully functional, devitalized acellular IFC grafts were obtained. IFC valves showed excellent haemodynamic data with fewer gradients, no pulmonary regurgitation, no calcification and acellularity. Structural remodelling of the leaflet matrix structure was only detected in FC-treated tissue, whereas IFC valves maintained matrix integrity comparable to that of native controls. The collagen crimp period and amplitude and elastin structure were significantly different in the FC valve cusps compared to IFC and native cusps. Collagen fibres in the FC valves were less aligned and straightened. IFC heart valves with good haemodynamic function, reduced immunogenicity and preserved matrix structures have the potential to overcome the known limitations of the clinically applied FC valve.


Smell and Taste Disorders Resulting from Cancer and Chemotherapy.
Malnutrition is common in both adult and pediatric patients undergoing treatment for cancer. Patients commonly attribute difficulties maintaining food intake to an altered taste developed during treatment. This review summarizes what is known about taste and smell dysfunction in patients with undergoing chemotherapy as their main treatment modality. Self-reported taste and smell alterations are prevalent in upwards of 86% of cancer patients. There is some evidence for decreased taste sensitivity in cancer patients when assessed using common gustatory tests. In some patients, taste and smell alterations may continue well after their cancer treatment has been completed. Such disorders can increase distress, reduce appetite and contribute towards poor nutritional status in cancer patients. There remain no effective interventions for improving the appetite or nutritional intake of patients with cancer experiencing taste and smell changes. There is a lack of consistency in assessment methodologies for measuring taste and smell changes in cancer patients and we therefore recommend that future work use well-established methods. Research should also take into account the role of food hedonics, food flavor and texture in assessing the association between taste dysfunction, poor oral intake and malnutrition in cancer patients. Both adult and child cancer patients should be counselled on the potential impact taste and smell dysfunction can have on their appetite and oral intake.


Increments in ischaemia time induces microvascular complications in the DIEP flap for breast reconstruction.
The deep inferior epigastric artery perforator (DIEP) flap is currently one of the preferred methods of autologous breast reconstruction. As a microsurgical flap, it is subjected to ischaemia-reperfusion injury and no reflow phenomenon, both of which are influenced by prolonged ischaemia times. In this work, we review the rates of microvascular complications according to ischaemia times in patients submitted to DIEP flap breast reconstruction. A retrospective review of 182 patients submitted to breast reconstruction with DIEP flap was conducted. Patients were first classified according to ischaemia time percentiles 25, 50, 75 and 100 comparing the rates of microvascular complications using Fisher's exact test. Next, patients were separated in two groups above and below P(50). Using Student's t-test and Fisher's exact test, univariate analysis was conducted to compare all demographic and surgical variables as well as complications between these groups. Finally, multivariate analysis using binary logistic regression was performed to determine whether or not ischaemia time was an independent risk factor for microvascular complications. Flap success rate was 97%. Eighteen flaps (9.5%) presented some form of microvascular event. Higher rates of complications were observed as ischaemia time increased (p < 0.05). On multivariate analysis, ischaemia time was found to be an independent risk factor for microvascular complications (odds ratio (OR) 3.81, p = 0.03). Flaps with ischaemia longer than 1.5-2 h were observed to be at higher risk of developing some form of vascular compromise. Ischaemia time is an independent risk factor for microvascular complications in the DIEP flap for breast reconstruction. Keeping such time to the minimum necessary and avoiding needless delays is likely to improve flap survival.


Homocysteine thiolactone disposal by human arterial endothelial cells and serum in vitro.
Previous work with cultured mammalian cells and perfused laboratory animals suggested to us that hydrolysis of homocysteine thiolactone was catalyzed in these systems. We confirmed this finding by measuring the sulfhydryl-releasing activity of cultured endothelial cells from human umbilical arteries in homocysteine thiolactone solution, pH 7.4, 37 degrees C. The reaction was vigorous and stereospecific and showed saturation kinetics (Km values for L- and D,L-homocysteine thiolactone were 3.9 and 8.2 mmol/l, respectively, and Vmax values were 10.75 and 10.1 mumol/min/10(9) cells, respectively). L-Homocysteine thiolactone was quantitatively converted to homocysteine, as measured by amino acid analysis. Human serum also accelerated the elimination of homocysteine thiolactone, although in this process, the majority of the newly formed sulfhydryl-containing product was precipitable by sulfosalicylic acid, indicating likely homocysteinylation of serum proteins. However, approximately 38% of the sulfhydryl-containing product was not precipitated, and because thiolactone elimination stereospecifically favored the L-enantiomer, a possible subsidiary role for serum-catalyzed hydrolysis of the thiolactone was suggested. No homocysteine thiolactone could be found in serum samples from six patients with acute myocardial infarction, three patients with cystathionine beta-synthase deficiency, and six normal subjects. Thus, humans have active vascular systems for elimination of homocysteine thiolactone, a process that could be responsible for an absence of the compound in serum.


Expression of the thermogenic nuclear hormone receptor coactivator PGC-1alpha is reduced in the adipose tissue of morbidly obese subjects.
Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha) is an accessory protein which can potentiate the transcriptional activation function of many nuclear hormone receptors. Its tissue distribution and physiological studies suggest that its principal in vivo roles are to promote cold-induced thermogenesis, mitochondrial biogenesis, hepatic gluconeogenesis, and fatty acid beta-oxidation. It is expressed in the white adipose tissue of both humans and rodents, and in rodents it has been suggested to mediate in part the leptin-induced conversion of white adipocytes from fat storing to fat oxidising cells. In this study, quantitative real-time PCR has been used in human tissue to demonstrate that (1) PGC1alpha mRNA levels in subcutaneous fat are three-fold lower in morbidly obese than in slim subjects; (2) there are no differences in PGC1alpha mRNA between omental and subcutaneous mature adipocytes; (3) there is a robust induction of PGC1alpha expression during subcutaneous human preadipocyte differentiation ex vivo. Whether low PGC1alpha expression is a prelude to the development of obesity, or a consequence of that obesity, attempts to upregulate endogenous white adipose tissue expression may prove a valuable new avenue to explore in obesity therapy.


Oxidation of maltose and trehalose during prolonged moderate-intensity exercise.
The aim of the present study was to compare the effects of trehalose (TRE) and maltose (MAL) ingestion on exogenous carbohydrate oxidation rates and blood metabolite responses during prolonged moderate-intensity cycling exercise. Nine trained subjects performed three randomly assigned bouts of exercise separated by at least 1 wk. Each trial consisted of 150 min of cycling at 55% of maximal power output (Wmax) while ingesting a solution providing either 1.1 g x min(-1) TRE, 1.1 g x min(-1) MAL, or water (WAT). Total carbohydrate oxidation rates were significantly higher (P < 0.05) in both the MAL (2.09 +/- 0.18 g x min(-1)) and TRE (1.92 +/- 0.32 g x min(-1)) trials compared with the WAT trial (1.62 +/- 0.28 g x min(-1)). Peak exogenous carbohydrate oxidation was significantly higher in the MAL trial compared with the TRE trial (1.01 +/- 0.24 and 0.73 +/- 0.22 g x min(-1), respectively, P < 0.05). The MAL trial resulted in significantly reduced endogenous carbohydrate oxidation rates compared with the WAT trial (1.20 +/- 0.25 and 1.62 +/- 0.28 g x min(-1), respectively, P < 0.05). When compared with the WAT trial, total fat oxidation for the same period was significantly reduced in both carbohydrate trials (0.91 +/- 0.19, 0.68 +/- 0.19, and 0.79 +/- 0.19 g x min(-1) for WAT, MAL, and TRE, respectively, P < 0.05) and tended to be lower in MAL compared with TRE (P < 0.06). Both solutions maintained high plasma glucose concentrations. MAL had a "sparing" effect on endogenous carbohydrate stores. The reduced exogenous carbohydrate oxidation rate of TRE compared to MAL is probably due to a reduced enzymatic hydrolysis rate within the small intestine, causing a slower availability.


Environmental neurotoxin interaction with proteins: Dose-dependent increase of free and protein-associated BMAA (β-N-methylamino-L-alanine) in neonatal rat brain.
β-Methylamino-L-alanine (BMAA) is implicated in the aetiology of neurodegenerative disorders. Neonatal exposure to BMAA induces cognitive impairments and progressive neurodegenerative changes including intracellular fibril formation in the hippocampus of adult rats. It is unclear why the neonatal hippocampus is especially vulnerable and the critical cellular perturbations preceding BMAA-induced toxicity remains to be elucidated. The aim of this study was to compare the level of free and protein-associated BMAA in neonatal rat brain and peripheral tissues after different exposures to BMAA. Ultra-high performance liquid chromatography-tandem mass spectrometry analysis revealed that BMAA passed the neonatal blood-brain barrier and was distributed to all studied brain areas. BMAA was also associated to proteins in the brain, especially in the hippocampus. The level in the brain was, however, considerably lower compared to the liver that is not a target organ for BMAA. In contrast to the liver there was a significantly increased level of protein-association of BMAA in the hippocampus and other brain areas following repeated administration suggesting that the degradation of BMAA-associated proteins may be lower in neonatal brain than in the liver. Additional evidence is needed in support of a role for protein misincorporation in the neonatal hippocampus for long-term effects of BMAA.


Analysis of interactive continence health information on the Web.
The purpose of this study was to describe interactive information about continence health promotion for women that is available on Web sites identified by popular search engines or health/medical search engines or that is available on community-based or select health organizations' Web sites. We used a variety of search services to search the Web for sites that disseminated information about continence health for women, for example, urinary incontinence, urine loss, and bladder problems. Two reviewers initially evaluated sites to determine if an interactive feature that provided individualized feedback was present. Web sites that had an interactive-with-feedback feature were further examined to delineate the purpose of the site and other descriptive characteristics. We evaluated each site according to content pertaining to continence health information. Most major search engines located more than 100,000 Web sites in the initial search; narrowing the search terms with the words "and women" decreased the number of sites. Only 13 sites with interactive-with-feedback features were located for further evaluation. E-mail was the most common interactive feature; none of the sites contained comprehensive information on continence health promotion. Web sites exist and are informative in terms of continence health promotion, but they lack an emphasis on self-care and sufficient information to promote it. The functionality of computer technology and the Web has not been maximized for the purpose of delivering continence health information.


Experience of primary care among homeless individuals with mental health conditions.
The delivery of primary care to homeless individuals with mental health conditions presents unique challenges. To inform healthcare improvement, we studied predictors of favorable primary care experience among homeless persons with mental health conditions treated at sites that varied in degree of homeless-specific service tailoring. This was a multi-site, survey-based comparison of primary care experiences at three mainstream primary care clinics of the Veterans Administration (VA), one homeless-tailored VA clinic, and one tailored non-VA healthcare program. Persons who accessed primary care service two or more times from July 2008 through June 2010 (N = 366) were randomly sampled. Predictor variables included patient and organization characteristics suggested by the patient perception model developed by Sofaer and Firminger (2005), with an emphasis on mental health. The primary care experience was assessed with the Primary Care Quality-Homeless (PCQ-H) questionnaire, a validated survey instrument. Multiple regression identified predictors of positive experiences (i.e. higher PCQ-H total score). Significant predictors of a positive experience included a site offering tailored service design, perceived choice among providers, and currently domiciled status. There was an interaction effect between site and severe psychiatric symptoms. For persons with severe psychiatric symptoms, a homeless-tailored service design was significantly associated with a more favorable primary care experience. For persons without severe psychiatric symptoms, this difference was not significant. This study supports the importance of tailored healthcare delivery designed for homeless persons' needs, with such services potentially holding special relevance for persons with mental health conditions. To improve patient experience among the homeless, organizations may want to deliver services that are tailored to homelessness and offer a choice of providers.


Cultural challenges and barriers through the voices of nurses.
To discover and describe challenges and barriers perceived by nurses in providing culturally competent care in their day-to-day encounters with diverse patient populations. Nurses are challenged in today's healthcare environment to provide culturally competent care to a diverse patient population. To provide patient- and family-centred care, nurses must first acknowledge patient's and family's cultural differences, be willing to incorporate patient's and family's beliefs within the healthcare treatment plan, and respect the values and lifeways of differing cultures. Qualitative description with thematic analysis was used to describe nurses' perceptions of barriers and challenges in providing culturally competent care. The qualitative component of the study was part of a larger research study that used a prospective, cross-sectional, descriptive survey. Participants responded to two open-ended questions about potential challenges and barriers to providing culturally competent health care. Nurses were recruited in a south-eastern state in the USA. Research surveys were mailed to 2000 nurses throughout the state using a stratified sampling method. Three hundred and seventy-four nurses participated in the study. Three themes emerged from the qualitative description: great diversity, lack of resources, and prejudices and biases. The provision of culturally competent patient- and family-centred care is an ethical imperative and professional mandate. Describing nurses' perspectives on challenges and barriers to providing culturally competent care is the first step in helping to redesign care delivery practices. Challenges to providing culturally competent care included diversity in patient populations, lack of resources to provide culturally competent care and biases/prejudices. Strategies to address these challenges in the areas of nursing education, nursing research and nursing policy were proposed.


Molecular mechanism of apoptosis induction by resveratrol, a natural cancer chemopreventive agent.
In efforts to identify naturally occurring compounds that act as protective agents, resveratrol, a phytoalexin existing in wine, has attracted much interest because of its diverse pharmacological characteristics. Considering that apoptosis induction is the most potent defense approach for cancer treatment, we have tried to summarize our present understanding of apoptosis induction by resveratrol based on the two major apoptosis pathways.


Comparison of analgesic effects of nimesulide, paracetamol, and their combination in animal models.
To compare the analgesic activity of nimesulide and paracetamol alone and their combination in animal models for the degree of analgesia and the time course of action. Analgesia was studied in albino rats using formalin test and in albino mice using writhing test and the radiant heat method. For each test, four groups of six animals each were orally fed with a single dose of nimesulide, paracetamol, and combination of nimesulide + paracetamol and gum acacia as control, respectively. In all the three test models, all three drug treatments showed significant analgesia (P < 0.001) as compared to control, but there was no significant difference in the analgesia produced by either drugs alone or in combination. The radiant heat method demonstrated a quicker onset and longer duration of action with nimesulide, whereas writhing test showed a quicker onset of action with paracetamol. In formalin test, greater degree of analgesia was seen with individual drugs than that of the combination, though this difference was not statistically significant. Nimesulide and paracetamol combination offers no advantage over nimesulide alone or paracetamol alone, either in terms of degree of analgesia or onset of action. Therefore, our study supports the reports claiming irrationality of the fixed dose combination of nimesulide and paracetamol.


Trophic ecology of northern Australia's terapontids: ontogenetic dietary shifts and feeding classification.
The diets of 21 terapontid species from freshwater environments in northern Australia were investigated to determine the similarity and dissimilarity among species and the extent of any ontogenetic shifts. Distinct ontogenetic dietary shifts occurred in all species for which sufficient data were available, with many species passing through several discrete trophic categories during their life histories. Diets of all juvenile terapontids were similar, mainly comprising aquatic insects and zooplankton. Larger size classes of terapontids diverged into a broad spectrum of feeding groups comprising carnivorous dietary modes (including piscivory and lepidophagy), omnivory (including frugivory and consumption of allochthonous prey), herbivory and detritivory. The results indicate that the terapontids represent Australia's most trophically diverse freshwater fish family.


Natural history of multiple sclerosis symptoms.
The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is a database that contains information from over 35,000 patient volunteers on symptom severity in 11 domains commonly affected in multiple sclerosis (MS): mobility, hand function, vision, fatigue, cognition, bowel/bladder function, sensory, spasticity, pain, depression, and tremor/coordination. The Registry affords a unique opportunity to study the frequency and severity of domain-specific impairment in a contemporary, mostly treated MS cohort over the course of the disease. The objective of this work was to calculate symptom prevalence in each of the 11 domains for years 0 to 30 from symptom onset. The resulting "symptom prevalence tables" demonstrate that a majority of participants perceive at least some degree of impairment in most domains as early as the first year of disease. The severity of impairment increases with disease duration across all domains, but the patterns of disability accumulation differ. The symptom prevalence tables illustrate the magnitude of perceived impact of the disease and highlight the extent of unmet need in symptomatic management. The tables are easy to use and allow MS patients and their clinicians to compare an individual's own impairment in any of the 11 domains to that of NARCOMS participants with the same disease duration.


Study on Coagulation Kinetics of Disk-like Particles under Simple Shear Flow.
In this study, a theoretical study is carried out on the collision of two disk-like particles to understand the coagulation of disk-like particles suspended in liquid under a shear flow. The diameter of the particle is fixed at 2 μm while the length is varied so that the aspect ratio (length/diameter) varies from 0.1 to 0.4. The liquid viscosity is changed from 0.01 to 1 Pa s. The minimum Peclet number is 10, and the Brownian motion is considered to be negligible. Both hydrodynamic and van der Waals interactions are included in tracking the position and the orientation of each particle. The Hamaker constant is fixed at 1.06 × 10-20 J. The boundary integral formulation is used to calculate the hydrodynamic interaction. To obtain the kinetic constant of coagulation, the time-independent orientation distribution function for a particle is obtained under the noninteracting condition. The kinetic constant of coagulation is obtained by considering the presence of collision between two particles initially separated by a long distance, the orientations of two particles, and the flux of the liquid flow. The result shows that the kinetic constant of coagulation is reduced to approximately 1/3 of the value for the noninteracting particles when the viscosity is 1 Pa·s. As collision modes, side-side, face-edge, side-edge, and edge-edge are considered. The edge-edge mode is frequently observed in the given range of the aspect ratio. The collision mode does not change much from the noninteracting case except for the side-side mode.


Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK.
Melanogenesis plays a critical role in the protection of skin against external stresses such as ultraviolet irradiation and oxidative stressors. This study was aimed to investigate the effects of cannabidiol on melanogenesis and its mechanisms of action in human epidermal melanocytes. We found that cannabidiol increased both melanin content and tyrosinase activity. The mRNA levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP) 1, and TRP2 were increased following cannabidiol treatment. Likewise, cannabidiol increased the protein levels of MITF, TRP 1, TRP 2, and tyrosinase. Mechanistically, we found that cannabidiol regulated melanogenesis by upregulating MITF through phosphorylation of p38 mitogen-activated protein kinase (MAPK) and p42/44 MAPK, independent of cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling. In addition, the melanogenic effect of cannabidiol was found to be mediated by cannabinoid CB1 receptor, not by CB2 receptor. Taken together, these findings indicate that cannabidiol-induced melanogenesis is cannabinoid CB1 receptor-dependent, and cannabidiol induces melanogenesis through increasing MITF gene expression which is mediated by activation of p38 MAPK and p42/44 MAPK. Our results suggest that cannabidiol might be useful as a protective agent against external stresses.


Effect of D168V mutation in NS3/4A HCV protease on susceptibilities of faldaprevir and danoprevir.
Hepatitis C virus (HCV) is a serious cause of liver inflammation, cirrhosis and the development of hepatocellular carcinoma. Its NS3/4A serine protease functions to cleave a specific peptide bond, which is an important step in HCV replication. Thus the NS3/4A protease has become one of the main drug-targets in the design and development of anti-HCV agents. Unfortunately, high mutation rates in HCV have been reported due to the lack of RNA proofreading activity resulting in drug resistance. Herein, all-atom molecular dynamics simulations were employed to understand and illustrate the effects of the NS3/4A D168V mutation on faldaprevir (FDV) and danoprevir (DNV) binding efficiency. The D168V mutation was shown to interrupt the hydrogen bonding network of Q80R155D168R123 embedded in the extended S2 and partial S4 subsites of the NS3 protein and as a result the R123 side chain was displaced and moved out from the binding pocket. By means of MM/PBSA and MM/GBSA binding free energy calculations, the FDV and DNV binding affinities were shown to be significantly reduced by ∼10-15 kcal mol-1 and ∼4-9 kcal mol-1 relative to the wild-type complexes, respectively, which somewhat agrees with the experimental resistance folds.


Efficacy of ozone as a fungicidal and detoxifying agent of aflatoxins in peanuts.
Peanut contamination by fungi is a concern of processors and consumers owing to the association of these micro-organisms with quality deterioration and aflatoxin production. In this study the fungicidal and detoxifying effects of ozone on aflatoxins in peanuts was investigated. Peanut kernels were ozonated at concentrations of 13 and 21 mg L⁻¹ for periods of 0, 24, 48, 72 and 96 h. Ozone was effective in controlling total fungi and potentially aflatoxigenic species in peanuts, with a reduction in colony-forming units per gram greater than 3 log cycles at the concentration of 21 mg L⁻¹ after 96 h of exposure. A reduction in the percentage of peanuts with internal fungal populations was also observed, particularly after exposure to ozone at 21 mg L⁻¹. A reduction in the concentrations of total aflatoxins and aflatoxin B1 of approximately 30 and 25% respectively was observed for kernels exposed to ozone at 21 mg L⁻¹ for 96 h. It was concluded that ozone is an important alternative for peanut detoxification because it is effective in controlling potentially aflatoxigenic fungi and also acts in the reduction of aflatoxin levels in kernels.


Cohort profile: Children in Need Census (CIN) records of children referred for social care support in England.
The Children in Need Census (CIN) is a case-based administrative dataset on children referred to social care services in England. CIN includes information on the 'needs' of children, and whether they received social care support. Local and national government bodies in England currently use CIN for evaluation purposes. Data are accessible to researchers under certain conditions, allowing researchers to investigate the health implications of adverse childhood experiences. However, CIN suffers from lack of metadata, meaning it can be challenging for researchers to process and interpret data, particularly if researchers are unfamiliar with the English children's social care system. To address this issue, we provide the background to CIN and describe the available data from 2008 to 2016. CIN is derived from case records held by English local authorities on all children referred to children's social care for a 'needs assessment', regardless of whether they are eventually assessed as 'in need of social care support'. Local authorities submit these case records to the UK Department for Education for collation. CIN holds information on an estimated 2.76 million children from October 2008 to March 2016. Since 2013/2014, just under 900 000 children have been recorded in the CIN annually, equivalent to around 8% of children in England (annual prevalence). Approximately, 650 000 children enter or renter the dataset each year, equivalent to 5% of children in England (annual incidence). Of the estimated 2.76 million children in the data, 50% are male and 47% female. 45% are referred to children's social care services due to abuse or neglect. 10.7% of children in CIN went onto a child protection plan, meaning they were judged to be (at risk of) suffering significant harm. CIN data collection is annual and ongoing. Data from the most recent census period typically become available for researchers in the following Spring.


Verification of intraovum transmission of a microsporidium of vertebrates: Pseudoloma neurophilia infecting the Zebrafish, Danio rerio.
Direct transmission from parents to offspring, referred to as vertical transmission, occurs within essentially all major groups of pathogens. Several microsporidia (Phylum Microsporidia) that infect arthropods employ this mode of transmission, and various lines of evidence have suggested this might occur with certain fish microsporidia. The microsporidium, Pseudoloma neurophilia, is a common pathogen of the laboratory zebrafish, Danio rerio. We previously verified that this parasite is easily transmitted horizontally, but previous studies also indicated that maternal transmission occurs. We report here direct observation of Pseudoloma neurophilia in the progeny of infected zebrafish that were reared in isolation, including microscopic visualization of the parasite in all major stages of development. Histological examination of larval fish reared in isolation from a group spawn showed microsporidian spores in the resorbing yolk sac of a fish. Infections were also observed in three of 36 juvenile fish. Eggs from a second group spawn of 30 infected fish were examined using a stereomicroscope and the infection was observed from 4 to 48 hours post-fertilization in two embryos. Intraovum infections were detected in embryos from 4 of 27 pairs of infected fish that were spawned based on qPCR detection of P. neurophilia DNA. The prevalence of intraovum infections from the four spawns containing infected embryos was low (∼1%) based on calculation of prevalence using a maximum likelihood analysis for pooled samples. Parasite DNA was detected in the water following spawning of 11 of the infected pairs, suggesting there was also potential for extraovum transmission in these spawning events. Our study represents the first direct observation of vertical transmission within a developing embryo of a microsporidian parasite in a vertebrate. The low prevalence of vertical transmission in embryos is consistent with observations of some other fish pathogens that are also readily transmitted by both vertical and horizontal routes.


Differential scanning calorimetry predicts the critical quality attributes of amorphous glibenclamide.
Selection of a crystallinity detection tool that is able to predict the critical quality attributes of amorphous formulations is imperative for the development of process control strategies. The main aim of this study was to determine the crystallinity detection tool that best predicts the critical quality attributes (i.e. physical stability and dissolution behaviour) of amorphous material. Glibenclamide (model drug) was milled for various durations using a planetary mill and characterised using Raman spectroscopy and differential scanning calorimetry (DSC). Physical stability studies upon storage at 60°C/0% RH and dissolution studies (non-sink conditions) were performed on the milled glibenclamide samples. Different milling durations were needed to render glibenclamide fully amorphous according to Raman spectroscopy (60min) and onset of crystallisation using DSC (150min). This could be due to the superiority of DSC (onset of crystallisation) in detecting residual crystallinity in the samples milled for between 60 and 120min, which were not detectable with Raman spectroscopy. The physical stability upon storage and dissolution behaviour of the milled samples improved with increased milling duration and plateaus were reached after milling for certain periods of time (physical stability - 150min; dissolution - 120min). The residual crystallinity which was detectable with DSC (onset of crystallisation), but not with Raman spectroscopy, adversely affected the critical quality attributes of milled glibenclamide samples. In addition, mathematical simulations were performed on the dissolution data to determine the solubility advantages of the milled glibenclamide samples and to describe the crystallisation process that occurred during dissolution in pH7.4 phosphate buffer. In conclusion, the onset of crystallisation obtained from DSC measurements best predicts the critical quality attributes of milled glibenclamide samples and mathematical simulations based on the solvent-mediated crystallisation model were successfully performed on the dissolution data.


The thyroid hormone receptor-associated protein TRAP220 is required at distinct embryonic stages in placental, cardiac, and hepatic development.
Recent work indicates that thyroid hormone receptor-associated protein 220 (TRAP220), a subunit of the multiprotein TRAP coactivator complex, is essential for embryonic survival. We have generated TRAP220 conditional null mice that are hypomorphic and express the gene at reduced levels. In contrast to TRAP220 null mice, which die at embryonic d 11.5 (E11.5), hypomorphic mice survive until E13.5. The reduced expression in hypomorphs results in hepatic necrosis, defects in hematopoiesis, and hypoplasia of the ventricular myocardium, similar to that observed in TRAP220 null embryos at an earlier stage. The embryonic lethality of null embryos at E11.5 is due to placental insufficiency. Tetraploid aggregation assays partially rescues embryonic development until E13.5, when embryonic loss occurs due to hepatic necrosis coupled with poor myocardial development as observed in hypomorphs. These findings demonstrate that, for normal placental function, there is an absolute requirement for TRAP220 in extraembryonic tissues at E11.5, with an additional requirement in embryonic tissues for hepatic and cardiovascular development thereafter.


Phase measurements with wide-aperture interferometers.
An interferogram produced by wide-aperture interferometers is studied both theoretically and experimentally. The fringe spacing is shown to increase nonlinearly with the numerical aperture and the fringe envelope to become narrower as the numerical aperture is increased. Phase measurements with wide-aperture interferometers therefore require calibration, and the phase can be measured only over a limited range. A calibration is given for accurate phase measurements, and the range over which the phase can be measured is calculated. Experimental measurements are presented and compared with theory.


State of the evidence: Cannabinoids and cancer pain-A systematic review.
Cannabinoids are widely used to alleviate intractable symptoms such as pain, nausea, and muscle spasticity. The purpose of this review was to ascertain the current state of the science regarding use of cannabinoids for cancer pain. Four electronic databases were searched for randomized control trials of cannabinoids and cancer pain. Studies included examined the analgesic effects of cannabinoids for cancer pain. Methodological quality was assessed using the Jadad scale. Eight randomized control trials met the inclusion criteria for review. Most trials found analgesic effects from cannabinoids when compared to placebo, although not all associations reached statistical significance. The analgesic effects of cannabinoids were also limited by dose-dependent side effects. Side effects most commonly reported were changes in cognition, sedation, and dizziness. There is evidence that cannabinoids are effective adjuvants for cancer pain not completely relieved by opioid therapy, but there is a dearth of high-quality studies to support a stronger conclusion. Cannabinoids appear to be safe in low and medium doses. Methodological limitations of the trials limited the ability to make sound conclusions. Further research is warranted before efficacy, safety, and utility of cannabinoids for cancer pain can be determined.


The Microbial Rosetta Stone Central Agricultural Database: An Information Resource on High-Consequence Plant Pathogens.
Microbial pathogens of humans, animals, and plants can serve as potential agents of biowarfare, bioterrorism, and biocrime. Previously, the Microbial Rosetta Stone (MRS) Central database, an easily accessible informational resource tool, was developed to assist law enforcement personnel in the event of a disease investigation by providing key information on pathogens of concern. Although the database already contained information on a few high-profile plant pathogens, the coverage was insufficient considering the large number of plant pathogens that pose a threat, not only to agricultural production but also to natural plant resources such as forests and rangelands. In this project, 100 plant pathogens of high consequence were selected for study, existing literature on these agents was reviewed, and both the sources and key pathogen information provided therein were curated in the new Agricultural Database (AgDB), an accessory to the existing MRS Central Database. Chosen for inclusion in the MRS Central AgDB were plant pathogens having significant potential for damage to U.S. agricultural and natural ecosystems. The selection process included review of several previously developed plant-pathogen threat lists and recommendations from experts within the U.S. plant biosecurity community. Pathogen information was collected by searching a number of relevant literature databases, sites on the World Wide Web, and other resources. For inclusion in the MRS, the information was curated into categories: pathogen taxonomy, nomenclature synonyms, disease symptoms and geographic distribution, plant hosts, insect vectors, detection and diagnostic methods, laboratory and field protocols, sample collection, and epidemiology. The resulting AgDB enhances the MRS Central Database by summarizing and linking key information on high-threat plant diseases and their causal agents to relevant scientific literature and internet resources. The AgDB contains critical, key information on high-consequence plant pathogens, curated in a format that is readily accessible and easily searched. The resource enhances the existing MRS Central Database and provides law enforcement, forensic, and investigative personnel with an additional tool with which to respond to microbial emergencies, particularly those affecting the agricultural and environmental sectors.


Some aspects of intracellular parasitism.
In intracellular parasitism the host cell is a true and hospitable host. The parasite does not have to break in the door. It has subtle ways of inducing the host to open the door and welcome it in. One of the exciting fields in the future of parasitology is to find out what these ways are and why they are sometimes so highly specific that the cell that invites one parasite in will not open the door to another closely related species. Once inside, the parasite not only exploits nutrients already available in the cell, and the cell's energy-yielding system, but it further induces the cell to assist actively in its nutrition. Like a bandit who has cajoled his way in, the parasite now forces his host to prepare a banquet for him. Finally it may destroy its host cell, as in most of the associations I have described herein, or it may stimulate its host cell to abnormal increase in size or to have an altered metabolism with the formation of new products. Or it may even contribute some positive benefit to the host cell or to the multicellular organism of which the cell is a part, so that the two kinds of organisms then live together in a state of mutualism or symbiosis (26).


CellSaic, A Cell Aggregate-Like Technology Using Recombinant Peptide Pieces for MSC Transplantation.
In the field of stem cell therapy, research on the application of mesenchymal stem cells (MSCs) has flourished because of the various functions. On the other hand, research on the method of cell transplantation has developed from the administration of cell suspensions to cell-sheet engineering and 3D technology. In the trend, a cell transplantation platform named CellSaic, which is a combination of xeno-free recombinant scaffolds in a cell aggregate-like shape, was developed. CellSaic is the cell transplantation platform that can prevent the central necrosis within cell aggregates by arranging the cells and petaloid pieces of recombinant peptide (RCP) in a mosaic. The prevention of central necrosis is the most significant advantage over other 3D culture systems. This review details the unique characteristics of CellSaic including safety examination results and describes its future application for MSC transplantation. Particularly, in the application of MSCs, it has been reported that the MSC CellSaics increased the effect on improving various symptoms compared with MSCs only in the application of the therapy to inflammatory bowel disease (IBD), cerebral infarction, bone cartilage regeneration in joints, and islet transplantation. In accordance with the "One Health" concept, it is anticipated that this technology is expected to contribute to companion animal therapy and human therapy in the future.


Unified framework for automated iris segmentation using distantly acquired face images.
Remote human identification using iris biometrics has high civilian and surveillance applications and its success requires the development of robust segmentation algorithm to automatically extract the iris region. This paper presents a new iris segmentation framework which can robustly segment the iris images acquired using near infrared or visible illumination. The proposed approach exploits multiple higher order local pixel dependencies to robustly classify the eye region pixels into iris or noniris regions. Face and eye detection modules have been incorporated in the unified framework to automatically provide the localized eye region from facial image for iris segmentation. We develop robust postprocessing operations algorithm to effectively mitigate the noisy pixels caused by the misclassification. Experimental results presented in this paper suggest significant improvement in the average segmentation errors over the previously proposed approaches, i.e., 47.5%, 34.1%, and 32.6% on UBIRIS.v2, FRGC, and CASIA.v4 at-a-distance databases, respectively. The usefulness of the proposed approach is also ascertained from recognition experiments on three different publicly available databases.


QT interval prolongation associated with amiodarone use in Cipto Mangunkusumo Hospital, Jakarta.
To evaluate the incidence of QTc interval prolongation associated with the use of amiodarone, as well as factors that influence its occurrence. This was a descriptive retrospective study conducted from November 2010 until December 2011 using medical record of patients at ICCU Cipto Mangunkusumo Hospital from 2004-2011. Four groups of patients were included: (1) patients receiving amiodarone and other drugs causing which can cause QTc prolongation, (2) patients receiving amiodarone and other drug not causing QTc prolongation, (3) patients receiving drugs which can cause causing QTc prolongation, (4) patients not receiving amiodarone, nor other drugs which can cause causing QTc prolongation (served as control group). Difference of QTc interval within the same group was analyzed with paired t-test or Wilcoxon matched-pairs test. Between groups comparison were performed with Kruskal Wallis test. The influence of other factors (sex, age, heart failure, liver disorder, electrolyte imbalance) on QTc prolongation was analyzed using multiple regression. QTc interval prolongation in groups 1, 2, and 3 were respectively 65.5%, 63.3%, 56.6%, which were significantly different from control group (24.4%); Hypernatremia and hypertension were revealed as significant risk factor for QTc prolongation. Mortality occurred in 3, 4, and 4 patients in group 1, 2, and 3 respectively, and none in group 4. QTc interval prolongation occurred in association with amiodarone and other drugs known to prolong QTc interval. Hypernatremia and hypertension were shown as significant influencing factor of QTc interval prolongation.


The one-target advantage: advanced preparation or online processing?
The one-target advantage refers to a shorter movement time for one- target aiming movements, in comparison to aiming attempts followed by a second movement. Theoretical explanations of the one-target advantage vary in the extent to which they attribute this phenomenon to prior planning or to online control mechanisms. In this research, we attempted to gain insight into the control of sequential aiming movements by manipulating the availability of online feedback during this first or second movement component. When the participants vision was occluded during the first movement (Experiment 1) or during the second movement (Experiment 2), their performance was affected, showing that vision was important for online control of the movement sequence. A one-target advantage was found when the second movement was in the same direction as the first, but not when it was reversed with respect to the home button. Both prior planning and online control processes contribute to the one-target advantage. The degree to which these processes are important for limb control depends on the specific task demands


Prevention of tumour cell apoptosis associated with sustained protein kinase B phosphorylation is more sensitive to regulation by insulin signalling than stimulation of proliferation and extracellular signal-regulated kinase.
Insulin controls blood glucose while insulin-like growth factor (IGF) 1 is an important growth factor. Interestingly, both hormones have overlapping bioactivities and can activate the same intracellular signal transduction cascades. Growth control (mainly by IGF1) and metabolic function (predominantly by insulin) are believed to depend on activation of extracellular signal-regulated kinases (ERKs) 1/2 and protein kinase B (Akt/PKB), respectively. Therefore, insulin analogues that are used to normalize blood glucose are tested for their ability to preferentially activate Akt/PKB but not ERK1/2 and mitogenesis. Growth hormone, IGF1, and hyperinsulinemia are associated with increased risk of growth progression of some cancer types. To test if continuous exposure to insulin can favour tumour growth, we studied insulin/IGF1-dependent activation of ERK1/2 and Akt/PKB by Western blotting, inhibition of apoptosis by ELISA, and induction of proliferation by [3H]-thymidine incorporation in Saos-2/B10 osteosarcoma cells. IGF1 and insulin both induced proliferation and prevented apoptosis effectively. Regulation of apoptosis was far more sensitive than regulation of proliferation. IGF1 and insulin activated PKB (Akt/PKB) rapidly and consistently maintained its phosphorylation. Activation of ERK1/2 was only observed in response to IGF1. Loss of p-Akt/PKB (but not of p-ERK1/2) was associated with increased apoptosis, and protection from apoptosis was lost when activation of Akt/PKB was inhibited. These findings in Saos-2/B10 cells were also replicated in the A549 cell line, originally derived from a human lung carcinoma. Therefore, IGF1 and insulin more likely (at lower concentrations) enhance tumour cell survival than proliferation, via activation and maintenance of phosphatidylinositol 3-kinase activity and p-Akt/PKB.


Selective activity of the histone deacetylase inhibitor AR-42 against leukemia stem cells: a novel potential strategy in acute myelogenous leukemia.
Most patients with acute myelogenous leukemia (AML) relapse and die of their disease. Increasing evidence indicates that AML relapse is driven by the inability to eradicate leukemia stem cells (LSC). Thus, it is imperative to identify novel therapies that can ablate LSCs. Using an in silico gene expression-based screen for compounds evoking transcriptional effects similar to the previously described anti-LSC agent parthenolide, we identified AR-42 (OSU-HDAC42), a novel histone deacetylase inhibitor that is structurally similar to phenylbutyrate, but with improved activity at submicromolar concentrations. Here, we report that AR-42 induces NF-κB inhibition, disrupts the ability of Hsp90 to stabilize its oncogenic clients, and causes potent and specific cell death of LSCs but not normal hematopoietic stem and progenitor cells. Unlike parthenolide, the caspase-dependent apoptosis caused by AR-42 occurs without activation of Nrf-2-driven cytoprotective pathways. As AR-42 is already being tested in early clinical trials, we expect that our results can be extended to the clinic.


Photodynamic therapy for neovascular age-related macular degeneration.
In neovascular age-related macular degeneration, new vessels grow under the retina, distorting vision and leading to scarring. This is further exacerbated if the blood vessels leak. Photodynamic therapy, originally used in cancer treatment, has been investigated as a way to treat the neovascular membranes without affecting the retina. The aim of this review is to examine the effects of photodynamic therapy in the treatment of neovascular age-related macular degeneration. We searched for trials in the Cochrane Central Register of Controlled Trials - CENTRAL (which includes the Cochrane Eyes and Vision Group trials register) on the Cochrane Library (Issue 4 2002), MEDLINE (1966 to November 2002) and EMBASE (1980 to November 2002). We used the Science Citation Index to search for reports that cited relevant study reports. We contacted experts in the field and we searched the reference lists of relevant studies for further trial reports. We included randomised trials of photodynamic therapy in people with choroidal neovascularisation due to age-related macular degeneration. Two reviewers extracted the data independently. Relative risks were combined using a fixed effect model after testing for heterogeneity using a chi-square test. Two published trials were identified that randomised 948 participants to verteporfin therapy compared to 5% dextrose in water. Both trials were performed by the same investigators using largely the same clinical centres and funded by manufacturers of verteporfin. Outcome data were available at 12 and 24 months after the first treatment. Participants received on average five treatments over two years. The relative risk of losing three or more lines of visual acuity at 24 months comparing the intervention with the control group was 0.77 (95% confidence interval 0.69 to 0.87). The relative risk of losing six or more lines of visual acuity at 24 months comparing the intervention with the control group was 0.62 (95% confidence interval 0.50 to 0.76). The results at 12 months were similar to those at 24 months. Photodynamic therapy in people with choroidal neovascularisation due to age-related macular degeneration is effective in preventing visual loss. Outcomes and potential adverse effects of this treatment should be monitored closely. Further independent trials of Verteporfin are required to establish that the effects seen in this study are consistent and to determine important questions not yet addressed, particularly relating to quality of life and cost.


Pterostilbene is equally potent as resveratrol in inhibiting 12-O-tetradecanoylphorbol-13-acetate activated NFkappaB, AP-1, COX-2, and iNOS in mouse epidermis.
Resveratrol, a phytoalexin present in grapes, has been reported to inhibit multistage mouse skin carcinogenesis. Recent studies showed that topically applied resveratrol significantly inhibited cyclooxygenase-2 (COX-2) expression and activation of nuclear factor-kappaB (NF-kappaB) induced by tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis. The aim of the present study was to further explore the effect of resveratrol on TPA-induced signaling pathways in mouse epidermis and to compare with its dimethylether, pterostilbene. Resveratrol and pterostilbene significantly reduced activator protein 1 (AP-1) and NF-kappaB activation. In the case of AP-1, the binding of c-Jun subunit was particularly affected, while only slight effect on c-Fos binding to TPA-responsive element (AP-1 binding consensus sequence) (TRE) site was observed. Both stilbenes inhibited the activation of NF-kappaB by blocking the translocation of p65 to the nucleus and increasing the retention of IkappaBa in the cytosol. The latter might be related to decreased activity of IkappaB kinase and/or proteasome 20S. Reduced activation of transcription factors decreased the expression and activity of COX-2 and inducible nitric oxide synthase (iNOS). In most assays, pterostilbene was either equally or significantly more potent than resveratrol. Pterostilbene might show higher biological activity due to its possible better bioavailability, since substitution of hydroxy with methoxy group increases lipophilicity.


Na+ -Ca2+ exchanger (NCX3) knock-out mice display an impairment in hippocampal long-term potentiation and spatial learning and memory.
Long-term potentiation (LTP) depends on the coordinated regulation of an ensemble of proteins related to Ca(2+) homeostasis, including Ca(2+) transporters. One of the major players in the regulation of intracellular Ca(2+) ([Ca(2+)](i)) homeostasis in neurons is the sodium/calcium exchanger (NCX), which represents the principal mechanism of Ca(2+) clearance in the synaptic sites of hippocampal neurons. Because NCX3, one of the three brain isoforms of the NCX family, is highly expressed in the hippocampal subfields involved in LTP, we hypothesized that it might represent a potential candidate for LTP modulation. To test this hypothesis, we first examined the effect of ncx3 gene ablation on NCX currents (I(NCX)) and Ca(2+) homeostasis in hippocampal neurons. ncx3(-/-) neurons displayed a reduced I(NCX), a higher basal level of [Ca(2+)](i), and a significantly delayed clearance of [Ca(2+)](i) following depolarization. Furthermore, measurement of field EPSPs, recorded from the CA1 area, revealed that ncx3(-/-) mice had an impaired basal synaptic transmission. Moreover, hippocampal slices from ncx3(-/-) mice exhibited a worsening in LTP compared with congenic ncx3(+/+). Consistently, immunohistochemical and immunoblot analysis indicated that in the hippocampus of ncx3(-/-) mice both Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) expression and the phosphoCaMKIIα/CaMKIIα ratio were significantly reduced compared with ncx3(+/+). Interestingly, ncx3(-/-) mice displayed a reduced spatial learning and memory performance, as revealed by the novel object recognition, Barnes maze, and context-dependent fear conditioning assays. Collectively, our findings demonstrate that the deletion of the ncx3 gene in mice has detrimental consequences on basal synaptic transmission, LTP regulation, spatial learning, and memory performance.


A protein phosphorylation module patterns the Bacillus subtilis spore outer coat.
Assembly of the Bacillus subtilis spore coat involves over 80 proteins which self-organize into a basal layer, a lamellar inner coat, a striated electrodense outer coat and a more external crust. CotB is an abundant component of the outer coat. The C-terminal moiety of CotB, SKRB , formed by serine-rich repeats, is polyphosphorylated by the Ser/Thr kinase CotH. We show that another coat protein, CotG, with a central serine-repeat region, SKRG , interacts with the C-terminal moiety of CotB and promotes its phosphorylation by CotH in vivo and in a heterologous system. CotG itself is phosphorylated by CotH but phosphorylation is enhanced in the absence of CotB. Spores of a strain producing an inactive form of CotH, like those formed by a cotG deletion mutant, lack the pattern of electrondense outer coat striations, but retain the crust. In contrast, deletion of the SKRB region, has no major impact on outer coat structure. Thus, phosphorylation of CotG by CotH is a key factor establishing the structure of the outer coat. The presence of the cotB/cotH/cotG cluster in several species closely related to B. subtilis hints at the importance of this protein phosphorylation module in the morphogenesis of the spore surface layers.


Red cell extensional recovery and the determination of membrane viscosity.
A theory of membrane viscoelasticity developed by Evans and Hochmuth in 1976 is used to analyze the time-dependent recovery of an elongated cell. Before release, the elongated cell is the static equilibrium where external forces are balanced by membrane elastic force resultants. Upon release, the cell recovers its initial shape with a time-dependent exponential behavior characteristic of the viscoelastic solid model. It is shown that the model describes the time-dependent recovery process very well for a time constant in the range of 0.1-0.13 s. The time constant is the ratio membrane surface viscosity eta:membrane surface elasticity mu. Measurements for the shear modulus mu of 0.006 dyne/cm give a value for the surface viscosity of red cell membrane as a viscoelastic solid material of eta = mu tc = (6-8) X 10(-4) poise . cm.


Nanoscale Spatiotemporal Diffusion Modes Measured by Simultaneous Confocal and Stimulated Emission Depletion Nanoscopy Imaging.
The diffusion dynamics in the cellular plasma membrane provide crucial insights into molecular interactions, organization, and bioactivity. Beam-scanning fluorescence correlation spectroscopy combined with super-resolution stimulated emission depletion nanoscopy (scanning STED-FCS) measures such dynamics with high spatial and temporal resolution. It reveals nanoscale diffusion characteristics by measuring the molecular diffusion in conventional confocal mode and super-resolved STED mode sequentially for each pixel along the scanned line. However, to directly link the spatial and the temporal information, a method that simultaneously measures the diffusion in confocal and STED modes is needed. Here, to overcome this problem, we establish an advanced STED-FCS measurement method, line interleaved excitation scanning STED-FCS (LIESS-FCS), that discloses the molecular diffusion modes at different spatial positions with a single measurement. It relies on fast beam-scanning along a line with alternating laser illumination that yields, for each pixel, the apparent diffusion coefficients for two different observation spot sizes (conventional confocal and super-resolved STED). We demonstrate the potential of the LIESS-FCS approach with simulations and experiments on lipid diffusion in model and live cell plasma membranes. We also apply LIESS-FCS to investigate the spatiotemporal organization of glycosylphosphatidylinositol-anchored proteins in the plasma membrane of live cells, which, interestingly, show multiple diffusion modes at different spatial positions.


Oligosaccharides and Complex Carbohydrates: A New Paradigm for Cranberry Bioactivity.
Cranberry is a well-known functional food, but the compounds directly responsible for many of its reported health benefits remain unidentified. Complex carbohydrates, specifically xyloglucan and pectic oligosaccharides, are the newest recognized class of biologically active compounds identified in cranberry materials. Cranberry oligosaccharides have shown similar biological properties as other dietary oligosaccharides, including effects on bacterial adhesion, biofilm formation, and microbial growth. Immunomodulatory and anti-inflammatory activity has also been observed. Oligosaccharides may therefore be significant contributors to many of the health benefits associated with cranberry products. Soluble oligosaccharides are present at relatively high concentrations (~20% w/w or greater) in many cranberry materials, and yet their possible contributions to biological activity have remained unrecognized. This is partly due to the inherent difficulty of detecting these compounds without intentionally seeking them. Inconsistencies in product descriptions and terminology have led to additional confusion regarding cranberry product composition and the possible presence of oligosaccharides. This review will present our current understanding of cranberry oligosaccharides and will discuss their occurrence, structures, ADME, biological properties, and possible prebiotic effects for both gut and urinary tract microbiota. Our hope is that future investigators will consider these compounds as possible significant contributors to the observed biological effects of cranberry.


An Overview of the Use of Equine Collagen as Emerging Material for Biomedical Applications.
Type I collagen has always aroused great interest in the field of life-science and bioengineering, thanks to its favorable structural properties and bioactivity. For this reason, in the last five decades it has been widely studied and employed as biomaterial for the manufacture of implantable medical devices. Commonly used sources of collagen are represented by bovine and swine but their applications are limited because of the zoonosis transmission risks, the immune response and the religious constrains. Thus, type-I collagen isolated from horse tendon has recently gained increasing interest as an attractive alternative, so that, although bovine and porcine derived collagens still remain the most common ones, more and more companies started to bring to market a various range of equine collagen-based products. In this context, this work aims to overview the properties of equine collagen making it particularly appealing in medicine, cosmetics and pharmaceuticals, as well as its main biomedical applications and the currently approved equine collagen-based medical devices, focusing on experimental studies and clinical trials of the last 15 years. To the best of our knowledge, this is the first review focusing on the use of equine collagen, as well as on equine collagen-based marketed products for healthcare.


Patterns of parental relatedness and pup survival in the grey seal (Halichoerus grypus).
Levels of parental relatedness can affect offspring survival and susceptibility to disease. We investigated parental relatedness of live and dead Halichoerus grypus pups between and within island populations and between possible causes of mortality. Nine microsatellites were used to calculate internal relatedness (IR) and standardized mean d2. We find that pups with higher than average levels of IR have significantly lower survival and that this varied between island populations and that certain loci contributed to the effect more than others. Although, there were no significant differences between causes of mortality, peritonitis, infection and stillborn had the highest levels of IR. These results provide evidence that parental relatedness is an important determinant of pre-weaning pup survival in the grey seal and that this may vary with cause of mortality given a larger sample size.


Global mapping of transposon location.
Transposable genetic elements are ubiquitous, yet their presence or absence at any given position within a genome can vary between individual cells, tissues, or strains. Transposable elements have profound impacts on host genomes by altering gene expression, assisting in genomic rearrangements, causing insertional mutations, and serving as sources of phenotypic variation. Characterizing a genome's full complement of transposons requires whole genome sequencing, precluding simple studies of the impact of transposition on interindividual variation. Here, we describe a global mapping approach for identifying transposon locations in any genome, using a combination of transposon-specific DNA extraction and microarray-based comparative hybridization analysis. We use this approach to map the repertoire of endogenous transposons in different laboratory strains of Saccharomyces cerevisiae and demonstrate that transposons are a source of extensive genomic variation. We also apply this method to mapping bacterial transposon insertion sites in a yeast genomic library. This unique whole genome view of transposon location will facilitate our exploration of transposon dynamics, as well as defining bases for individual differences and adaptive potential.


The impact of backboard size and orientation on sternum-to-spine compression depth and compression stiffness in a manikin study of CPR using two mattress types.
To explore how backboard orientation and size impact chest compressions during cardiopulmonary resuscitation (CPR). Experiments were conducted on a full-body CPR training manikin using a custom-built simulator. Two backboards of different sizes were tested in longitudinal (head to toe) and latitudinal (side to side) directions to assess the impact of size and orientation on chest compressions during CPR. The net sternum-to-spine displacement, combined mattress and sternal displacement as well as the axial reaction force were measured during each test. The difference in net compression depth between the larger and smaller backboards ranged between 0.08±0.30 cm and 1.47±0.13 cm, while the difference in back support stiffness varied between 103.7±211 N/cm and 688.1±180.3 N/cm. The difference in net compression depth between the longitudinal and latitudinal backboard orientations ranged from 0.07±0.32 cm to 0.34±0.18 cm, while for the back support stiffness the difference was between 13.4±50.0 N/cm and 592.2±211.0 N/cm. The effect of backboard size on chest compression (CC) performance during CPR was found to be significant with the larger backboard producing deeper chest compressions and higher back support stiffness than the smaller backboard. The impact of backboard orientation was found to depend on the size of the backboard and type of mattress used. Clinicians should be aware that although a smaller backboard may be easier for rescuers to manipulate, it does not provide as effective back support or produce as deep chest compressions as a larger backboard.


Hazard quotient profiles used as a risk assessment tool for PFOS and PFOA serum levels in three distinctive European populations.
Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) blood levels are commonly used as biomarkers of human environmental exposure to these compounds. Many biomonitoring studies indicate 100% detection for PFOS and PFOA thus justifying a concern of possible risk for the most exposed individuals. This study addresses the predictive value of hazard quotients (HQs) calculated on the basis of serum PFOS and PFOA in male and female populations of reproductive age in Greenland, Poland and Ukraine. Overall, 2026 results of PFOS and PFOA serum concentrations (589 males, 1437 females) were obtained from the INUENDO database. HQs were calculated from the actual biomonitoring results and literature-based animal data linking toxicological outcomes and critical PFOS/PFOA serum levels. HQs for serum PFOS were calculated based on Points of Departure (PoD) at 13μgmL(-1) (cynomolgus monkeys, 183days, changes in THS and T3) and for PFOA at 7.1μgmL(-1) serum (male rats, 90days, hepatocellular necrosis, increased liver weight). Uncertainty factors were applied to reflect interspecies differences and human variability. Serum HQs were expressed as a ratio relative to the point of departure for each PFOS and PFOA. Only in the three cases of males in Greenland were there serum PFOS levels showing HQ values exceeding 1, so indicating that such serum levels may be of concern. The mean serum concentration of PFOS was significantly higher in male than in female populations. Despite significant differences between HQ profiles for PFOS and PFOA in donors from Greenland, Poland and Ukraine, the concentrations of these perfluoroalkylated compounds do not indicate a cause for concern, except for the three aforementioned cases from Greenland. This study demonstrates that the HQ approach can help to interpret human biomonitoring data and thus serve as a valuable tool in further risk assessment priority settings and may also be used as a basis for taking decisions in risk management.


Proprioceptive control of multijoint movement: bimanual circle drawing.
Proprioception is used by the central nervous system (CNS) in the control of the spatial and temporal characteristics of single joint and multiple joint movement. The present study addressed the role of proprioception in the control of bilateral cyclical movements of the limbs. Normal blindfolded human subjects drew circles simultaneously and symmetrically with the two arms (16 cm diameter, 1 /s) upon two digitizing tablets. In selected trials, vibration (60-70 Hz) was applied to the tendon of the biceps and/or anterior deltoid muscles of the dominant arm to distort the proprioceptive information from muscle spindle afferents. One goal of this study was to identify whether tendon vibration influenced the spatial characteristics of circles drawn by the vibrated, dominant arm and the non-vibrated, non-dominant arm. A second goal was to determine the effect of vibration on the temporal coupling between the two arms during circle drawing. The results revealed that tendon vibration affected the spatial characteristics of circles drawn by the vibrated arm in a manner similar to that previously found for unilateral circle drawing. During bimanual circle drawing, vibration had only a minimal effect on the spatial characteristics of the non-vibrated, non-dominant arm. Temporal interlimb coupling was quantified by the relative phasing between the arms. Without tendon vibration, the dominant arm led the non-dominant arm. Vibration of the dominant arm increased the average phase lead. In a first control experiment, vibration of the non-dominant arm decreased the phase lead of the dominant arm, or even reversed it to a non-dominant arm phase lead. In a second control experiment, the subjects performed the bimanual circle-drawing task with vision of only the vibrated arm, in which case there was no spatial distortion of the circles drawn by the vibrated arm, but the phase relation between the two arms was still shifted as if vision were completely unavailable. It was concluded that, in bimanual movements such as these, the spatial and temporal characteristics of movement are controlled independently. Whereas the spatial characteristics of hand movement seem to be controlled unilaterally, the temporal characteristics of interlimb coupling appear to be controlled by proprioceptive information from both limbs, possibly by a proprioceptive triggering mechanism.


Cholestanol accelerates α-synuclein aggregation and spreading by activating asparagine endopeptidase.
Cerebrotendinous xanthomatosis (CTX), an autosomal recessive disorder characterized by high levels of cholestanol in the blood and accumulation of cholestanol in multiple tissues, especially the brain, often presents in parkinsonism. However, it remains unknown whether cholestanol plays a role in the pathogenesis of sporadic Parkinson's disease (PD). Here, we show that the levels of serum cholestanol in patients with sporadic PD are higher than those in control participants. Cholestanol activates the protease asparagine endopeptidase (AEP) and induces the fragmentation of α-synuclein (α-syn) and facilitates its aggregation. Furthermore, cholestanol promotes the spreading of α-syn pathology in a mouse model induced by intrastriatal injection of α-syn fibrils. KO of AEP or administration of an AEP inhibitor ameliorates α-syn pathology, degeneration of the nigrostriatal dopaminergic pathway, and PD-like motor symptoms. These results not only indicate that cholestanol contributes to the aggregation and spreading of α-syn by activating AEP but also reveal an opportunity for treating PD with AEP inhibitors.


Morbillivirus glycoprotein expression induces ER stress, alters Ca2+ homeostasis and results in the release of vasostatin.
Although the pathology of Morbillivirus in the central nervous system (CNS) is well described, the molecular basis of neurodegenerative events still remains poorly understood. As a model to explore Morbillivirus-mediated CNS dysfunctions, we used canine distemper virus (CDV) that we inoculated into two different cell systems: a monkey cell line (Vero) and rat primary hippocampal neurons. Importantly, the recombinant CDV used in these studies not only efficiently infects both cell types but recapitulates the uncommon, non-cytolytic cell-to-cell spread mediated by virulent CDVs in brain of dogs. Here, we demonstrated that both CDV surface glycoproteins (F and H) markedly accumulated in the endoplasmic reticulum (ER). This accumulation triggered an ER stress, characterized by increased expression of the ER resident chaperon calnexin and the proapoptotic transcription factor CHOP/GADD 153. The expression of calreticulin (CRT), another ER resident chaperon critically involved in the response to misfolded proteins and in Ca(2+) homeostasis, was also upregulated. Transient expression of recombinant CDV F and H surface glycoproteins in Vero cells and primary hippocampal neurons further confirmed a correlation between their accumulation in the ER, CRT upregulation, ER stress and disruption of ER Ca(2+) homeostasis. Furthermore, CDV infection induced CRT fragmentation with re-localisation of a CRT amino-terminal fragment, also known as vasostatin, on the surface of infected and neighbouring non-infected cells. Altogether, these results suggest that ER stress, CRT fragmentation and re-localization on the cell surface may contribute to cytotoxic effects and ensuing cell dysfunctions triggered by Morbillivirus, a mechanism that might potentially be relevant for other neurotropic viruses.


The effect of maximum bite force on marginal bone loss of mini-implants supporting a mandibular overdenture: a randomized controlled trial.
To evaluate the effect of maximum bite force (mBF) on marginal bone loss (MBL) around mini-implants in edentulous patients wearing mandibular overdentures with two retention systems: ball and bar. Forty-five totally edentulous patients were selected from a public health center. All of them received two mini-implants (1.8 x 15 mm; Sendax) in the anterior mandible using a minimally invasive technique. A single randomization was performed to allocate the patients in two groups. Group I (n=22) received two single ball-type mini-implants and Group II (n=23) received two mini-implants splinted with a prefabricated bar. The mBF was recorded using a press-sensitive sheet Dental Prescale (Fuji) and MBL using standardized radiographs of each mini-implant at the baseline and 5, 7, 10, and 15 months after surgery; the values were compared between groups. Two members of Group I failed to complete the study, decreasing the number of participants to 20. There was no relationship between the mBF and the MBL of the mini-implants (Spearman's rhor(s)=0.147; P=0.378). At the 15-month follow-up, the average mBF for Group I (ball) was 247.53 +/- 132.91 N and that of Group II (bar) only 203.23 +/- 76.85 N (Mann-Whitney test; P=0.586). The MBL values were also higher for Group I (1.40 +/- 1.02 mm) than Group II (0.84 +/- 0.66 mm) during the entire 15-month follow-up period (Mann-Whitney test; P=0.077). No relationship was found between mBF and MBL for patients wearing overdentures retained on mini-implants using bar or ball attachment systems.


Enhanced imaging of choroidal vasculature by high-penetration and dual-velocity optical coherence angiography.
Dual-beam-scan Doppler optical coherence angiography (DB-OCA) with a 1-μm-wavelength probe is demonstrated for improved in vivo choroidal angiograms of the human eye. This method utilizes two scanning beams with spatial and temporal separation on the retina, and provides two measurable velocity ranges. The method achieves higher sensitivity to very low velocity flows than conventional Doppler optical coherence tomography. Moreover, longer wavelengths allowing greater penetration, enhanced visualization of choroidal vessels is verified with en-face projection images of the Doppler shift squared. Specifically, better choroidal vasculature visibility is achieved at a wavelength of 1 μm than at 840 nm.


Resurfacing of pitted facial acne scars using Er:YAG laser with ablation and coagulation mode.
Although the conventional, short-pulsed erbium: yttrium-aluminum-garnet (Er:YAG) laser provides substantial clinical improvement for pitted, facial acne scars, it shows less effective hemostasis and limited residual thermal effect in the dermis. Recently, dual-mode Er:YAG laser systems with both ablation and coagulation modes have been developed. The purpose of this study was to evaluate the clinical and histologic effects of resurfacing pitted, facial acne scars with a dual-mode Er:YAG laser. Twenty patients with pitted facial acne scars underwent laser resurfacing using a computerized-scanning, dual-mode Er:YAG laser. All patients had Fitzpatrick skin types ranging III-V. Initially, the epidermis was removed in two passes using the ablative settings. This step was followed by two passes in a mixed ablation and coagulation mode, to produce further ablation and controlled, residual thermal damage. A final pass in a ablation mode was used to remove necrotic tissue. Laser overlapping was approximately 30%. The results of laser treatment were evaluated for the degree of clinical improvement, duration of erythema, pigmentary change, and any adverse events at two weeks, one month, and three months. In two patients, skin biopsies were obtained at the following intervals: immediately and two weeks postoperatively for histologic examination. There was a 75% average clinical improvement observed in pitted, facial acne scars after laser treatment. Complete wound healing occurred between six and eight days. On histologic examination, complete re-epithelialization was observed at two weeks. Erythema occurred in all patients after laser treatment and lasted longer than three months in 10 patients (50%). Postinflammatory hyperpigmentation occurred in 12 patients (60%) two to four weeks after laser treatment and lasted longer than three months in one patient (5%). One patient (5%) experienced mild hypopigmention. Mild to moderate, postoperative acne flare-up occurred in seven patients (35%). No other adverse effects were observed. In conclusion, resurfacing with a dual-mode Er:YAG laser is a safe and effective treatment modality for pitted, facial acne scars.


Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose.
SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Single dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.


Proteomic study of amyloid beta (25-35) peptide exposure to neuronal cells: Impact on APE1/Ref-1's protein-protein interaction.
The genotoxic, extracellular accumulation of amyloid β (Aβ) protein and subsequent neuronal cell death are associated with Alzheimer's disease (AD). APE1/Ref-1, the predominant apurinic/apyrimidinic (AP) endonuclease and essential in eukaryotic cells, plays a central role in the base excision repair (BER) pathway for repairing oxidized and alkylated bases and single-strand breaks (SSBs) in DNA. APE1/Ref-1 is also involved in the redox activation of several trans-acting factors (TFs) in various cell types, but little is known about its role in neuronal functions. There is emerging evidence for APE1/Ref-1's role in neuronal cells vulnerable in AD and other neurodegenerative disorders, as reflected in its nuclear accumulation in AD brains. An increase in APE1/Ref-1 has been shown to enhance neuronal survival after oxidative stress. To address whether APE1/Ref-1 level or its association with other proteins is responsible for this protective effect, we used 2-D proteomic analyses and identified cytoskeleton elements (i.e., tropomodulin 3, tropomyosin alpha-3 chain), enzymes involved in energy metabolism (i.e., pyruvate kinase M2, N-acetyl transferase, sulfotransferase 1c), proteins involved in stress response (i.e., leucine-rich and death domain, anti-NGF30), and heterogeneous nuclear ribonucleoprotien-H (hnRNP-H) as being associated with APE1/Ref-1 in Aβ(25-35)-treated rat pheochromocytoma PC12 and human neuroblastoma SH-SY5Y cell lines, two common neuronal precursor lines used in Aβ neurotoxicity studies. Because the levels of some of these proteins are affected in the brains of AD patients, our study suggests a neuroprotective role for APE1/Ref-1 via its association with those proteins and modulating their cellular functions during Aβ-mediated neurotoxicity.


Can Grid Cell Ensembles Represent Multiple Spaces?
The way grid cells represent space in the rodent brain has been a striking discovery, with theoretical implications still unclear. Unlike hippocampal place cells, which are known to encode multiple, environment-dependent spatial maps, grid cells have been widely believed to encode space through a single low-dimensional manifold, in which coactivity relations between different neurons are preserved when the environment is changed. Does it have to be so? Here, we compute, using two alternative mathematical models, the storage capacity of a population of grid-like units, embedded in a continuous attractor neural network, for multiple spatial maps. We show that distinct representations of multiple environments can coexist, as existing models for grid cells have the potential to express several sets of hexagonal grid patterns, challenging the view of a universal grid map. This suggests that a population of grid cells can encode multiple noncongruent metric relationships, a feature that could in principle allow a grid-like code to represent environments with a variety of different geometries and possibly conceptual and cognitive spaces, which may be expected to entail such context-dependent metric relationships.


Characterization of interface properties of fluids by evaporation of a capillary bridge.
The surface properties between two non-miscible fluids are key elements to understand mass transfer, chemistry and bio-chemistry at interfaces. In this paper, surface properties are investigated in evaporating and non-evaporating conditions. A capillary bridge between two large plates (similar to a Hele-Shaw cell) is considered. The temporal evolution of surface forces and mass transfers due to evaporation of the liquid are measured. The force depends on surface properties of the substrate. It is adhesive in the wetting case and repulsive in the non-wetting case. The force is also shown to depend linearly on the volume of the capillary bridge F ∝ V 0 and inversely to the height of the bridge. Modelling is performed to characterize both surface force and evaporation properties of the capillary bridge. The evaporation is shown to be diffusion driven and is decoupled from the bridge mechanics.


Detection of colorectal lesions by using autofluorescence colonoscopy in acromegalics and their relation to serum growth hormone and insulin-like growth factor-1 levels.
Acromegalics have an increased risk of colorectal neoplasm. The aim of this study was to establish the association between acromegaly and colorectal lesions. The study included 51 patients with active acromegaly: 30 women and 21 men (average age 52.95 +/- 13.49 years). Growth hormone (GH), insulin-like growth factor I (IGF-I), prolactin (PRL), thyreothropin (TSH), thyroxine (FT4) were measured in the serum when patients were hospitalized for their first diagnosis of acromegaly, before starting the treatment. All patients underwent colonoscopy--in the first phase conventional in white light; in the second phase fluorescence colonoscopy. Autofluorescence of colonic mucosa was assessed by illumination with monochromatic light. Green fluorescence is characteristic for normal colonic mucose, whereas red fluorescence occur in pathological lesions. Material to histopathological examination was taken from every pathological colorectal lesion. Using conventional colonoscopy we detected colonic polyps in 21 acromegalic patients (41.17%). Polyps with red fluorescence were found in 7 (13.7%) acromegalics and with green fluorescence in 16 (31.37%) cases of these patients. Histological diagnoses of colorectal lesions are adenoma, hyperplastic and inflammatic polyps. The number of colorectal polyps was dependent on IGF-I, fT4 and sex. Acromegaly is associated with high prevalence of colorectal pathology, mainly hyperplastic polyp and adenoma. There is a relationship between number of colorectal polyps and serum IGF-I levels in acromegaly. Adenomas and hyperplastic polyps were associated with higher levels of IGF-I.


Critical limits of pressure-flow relation in the human brain.
This study was designed to determine the minimal mean flow velocity and pressure-flow relation necessary to preserve human consciousness. Passive upright tilt provocation was used in conjunction with transcranial Doppler in 80 patients with a history of syncope of unknown etiology. Cerebral blood flow velocity, blood pressure, and heart rate were monitored noninvasively. Forty patients remained asymptomatic, and the rest had clinically induced true syncope or premonitory symptoms. In the asymptomatic group, there was a 23 +/- 16% (p = 0.000) drop in mean flow velocity, but no significant changes in systolic and diastolic blood pressures. In the symptomatic patients, there was a 58 +/- 14% (p = 0.000) drop in mean flow velocity, 37 +/- 23% (p = 0.000) fall in systolic pressure, and 31 +/- 20% (p = 0.000) fall in diastolic pressure. In 80% of symptomatic patients, the critical lower limit of mean flow velocity was at -50% of resting baseline while patients were lying supine. The symptomatic group had lower mean flow velocity and blood pressure responses as compared with the asymptomatic group. The slope and intercept values of the pressure (y axis) to flow velocity (x axis) regression curves indicate a greater degree of impaired autoregulation in the symptomatic group (y = 0.529 x-6.11, r2 = 0.108, p = 0.038) as compared with the asymptomatic (y = 0.317 x + 0.966, r2 = 0.14, p = 0.017). The critical lower limit of cerebral perfusion lies at 50% below baseline supine mean flow velocity.


A curious case of disseminated cysticercosis in an immunocompetent adult.
Cysticercosis is an infection with the larval stage of Taenia Solium which is estimated to affect over 50 million people worldwide. We report a case of disseminated cysticercosis in an immunocompetent 68-year-old male who presented with back pain, presumed to be musculoskeletal in nature initially. Magnetic-resonance-imaging of the lumbar spine revealed intramuscular (paraspinous and psoas muscles) cysts, innumerable small cystic lesions bilaterally throughout the cerebellar and cerebral hemispheres, midbrain, and right ventricle suggestive of cysticercosis. Treatment with albendazole with dexamethasone for 3 months led to resolution of the cysts with complete resolution of symptoms. Despite its importance, current data on prevalence of this infection, disease burden and the incidence of hospitalization remains incomplete. Mandatory reporting of diagnosis would enable complete understanding of epidemiology of the disease. In this case we have emphasized the importance of early diagnosis of a systemic condition that could have caused serious implications if left untreated.


Myofascial face pain. Clinical characteristics of those with regional vs. widespread pain.
The authors conducted a study to determine whether there are differences in salient clinical characteristics between patients who have both myofascial face pain, or MFP, and comorbid fibromyalgia, or FM, and patients who have MFP but not FM. The authors enrolled in the study 162 female subjects who had histories of MFP. In physical examinations at the time of initial consultation, they recorded facial pain signs and symptoms. At the research interview follow-up (seven years post-consultation), participants were screened for a lifetime history of FM and other health problems. In addition, psychiatric interviewers conducted the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised, to assess each patient's history of depression and other psychiatric disorders. Of the 162 participants, 38 (23.5 percent) reported a history of FM. At the time of treatment for MFP, both the FM and non-FM groups had similar signs and symptoms of MFP. At the time of the research interview follow-up, participants with FM histories were significantly less likely than those without FM histories to report that they were free of MFP. On recall, those with FM histories reported experiencing more symptoms of MFP. Those with FM histories also were more likely to have had major depression and to report somatization symptoms. Finally, those who had FM more commonly had a history of facial pain's interference with social and occupational functioning and had more severe pain than did those without FM. Patients who have MFP and a history of widespread pain suggestive of FM are likely to have more persistent and debilitating MFP and to have higher rates of depression and somatization symptoms than those who have no history of widespread pain.


Origin of Bragg reflection peaks splitting in gratings fabricated using a multiple order phase mask.
We have studied the effect of waveguide alignment on the reflection spectrum of Bragg gratings fabricated using a multiple order phase mask. We have demonstrated that splitting of certain Bragg peaks observed in earlier experiments reported in literature is caused by formation of the gratings with different periodicities in the waveguide tilted with respect to the phase mask plane due to the interference of non-symmetrical diffraction orders. Analytical expressions for spectral separation of the split peaks have been derived and verified against the experimental data recently presented in literature. The analytical predictions were also confirmed by numerical simulations of intensity distributions behind the multiple order diffraction grating and its projection on the tilted waveguide.


An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry.
Fast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity may be a useful endophenotype for studying the genetics of disorders characterized by neural hyperexcitability, including substance use disorders (SUDs). However, the genetic underpinnings of fast beta EEG have not previously been studied in a population of African-American ancestry (AA). In a sample of 2382 AA individuals from 482 families drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a genome-wide association study (GWAS) on resting-state fast beta EEG power. To further characterize our genetic findings, we examined the functional and clinical/behavioral significance of GWAS variants. Ten correlated single-nucleotide polymorphisms (SNPs) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10-8. The most significantly associated SNP, rs11720469 (β: -0.124; P<4.5 × 10-9), is also an expression quantitative trait locus for BCHE (butyrylcholinesterase), expressed in thalamus tissue. Four of the genome-wide SNPs were also associated with Diagnostic and Statistical Manual of Mental Disorders Alcohol Dependence in COGA AA families, and two (rs13093097, rs7428372) were replicated in an independent AA sample (Gelernter et al.). Analyses in the AA adolescent/young adult (offspring from COGA families) subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h). Converging findings presented in this study provide support for the role of genetic variants within 3q26 in neural and behavioral disinhibition. These novel genetic findings highlight the importance of including AA populations in genetics research on SUDs and the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.


Cytotoxic and genotoxic effect of methanolic flower extract from Gentiana asclepiadea on COS 1 cells.
The purpose of this study was to assess whether a methanol extract isolated from the flower of Gentiana asclepiadea had potential cytotoxic or genotoxic effect on COS 1 (monkey kidney) cell line. Five various concentrations of the extract were investigated for cytotoxicity and genotoxicity and to determine non-cytotoxic and non-genotoxic concentrations suitable for utilization in pharmacology and medicine. Cytotoxicity was determined using the proliferation (growth activity) and the plating efficiency (colony forming ability) assays after 24 hour incubation of COS 1 cells with different concentrations of methanolic flower extract from G. asclepiadea. To assess potential genotoxicity, the comet assay or SCGE (Single-Cell Gel Electrophoresis) was used. We found that only the highest (5 and 25 mg/ml) concentrations of the extract revealed cytotoxic and genotoxic effect. We have also determined concentrations that stimulated cell growth (0.25 mg/ml) and colony forming ability (0.25-2.5 mg/ml) and did not exhibit genotoxic effect (0.25-2.5 mg/ml). We found out that extract of G. asclepiadea was neither cytotoxic nor genotoxic in a wide range of concentrations (0.25-2.5 mg/ml) and thus can be used to further investigate potential beneficial usage in pharmacology and medicine.