Aflatoxin M1 Contamination Levels in Cheeses Sold in Isfahan Province, Iran.
Aflatoxin M1 (AFM1)-contaminated dairy products pose serious human health risks, causing liver and renal failure if consumed. They are also related to decreased milk and egg production in infected animals. This study investigated the AFM1 contamination levels in cheeses sold in Isfahan province, Iran, by enzyme-linked immunosorbent assay (ELISA). A total of 100 white cheese samples were randomly collected from supermarkets in Isfahan province and after extraction using dichloromethane were prepared for the ELISA. Of the 100 samples, 52 (52%) were contaminated by AFM1, at levels ranging from 50.2 to 424.4 ng/kg. The remaining 48% of the samples had undetectable AFM1 levels (< 50 ng/kg). Based on the standard limit set by the European Commission and Iran, 8% (8/100) of the AFM1-positive samples (with concentrations between 250.2 and 424.4 ng/kg) had levels higher than the permissible value of 250 ng/kg. Although the percentage of cheese samples in Isfahan province with AFM1 levels exceeding the national permissible limit was low, the examination of cheeses and the milk used for their production is nevertheless important for ensuring public health. Furthermore, optimum storage conditions of animal feed should be ensured, and livestock nutrition must be monitored for the presence of AFM1 and other aflatoxins.


Time-resolved studies of femtosecond-laser induced melt dynamics.
This work presents time-resolved images of femtosecond-laser-induced melt dynamics in 60 nm gold films on glass substrates. Melt dynamics induced by laser radiation with focus diameters of 6 μm and 8 μm (FWHM) at constant laser fluence is investigated with a temporal resolution of 10 ns. In both cases, the formation of the microbumps and gold jets takes at least 250 ns. It is shown that the formation process can be compared to jetting behavior induced by cavitation bubbles near a free liquid surface. This is confirmed by SEM illustrating a re-entrant spike through a hole in the microbump.


Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin.
Alexander T. Shulgin is widely thought of as the 'father' of +/-3,4-methylenedioxymethamphetamine (MDMA). This paper re-assesses his role in the modern history of this drug. We analysed systematically Shulgin's original publications on MDMA, his publications on the history of MDMA and his laboratory notebook. According to Shulgin's book PIHKAL (1991), he synthesized MDMA in 1965, but did not try it. In the 1960s Shulgin also synthesized MDMA-related compounds such as 3,4-methylenedioxyamphetamine (MDA), 3-methoxy-4,5-methylenedioxyamphetamine (MMDA) and 3,4-methylenedioxyethylamphetamine (MDE), but this had no impact on his rediscovery of MDMA. In the mid-1970s Shulgin learned of a 'special effect' caused by MDMA, whereupon he re-synthesized it and tried it himself in September 1976, as confirmed by his laboratory notebook. In 1977 he gave MDMA to Leo Zeff PhD, who used it as an adjunct to psychotherapy and introduced it to other psychotherapists. Shulgin was not the first to synthesize MDMA, but he played an important role in its history. It seems plausible that he was so impressed by its effects that he introduced it to psychotherapist Zeff in 1977. This, and the fact that in 1978 he published with David Nichols the first paper on the pharmacological action of MDMA in humans, explains why Shulgin is sometimes (erroneously) called the 'father' of MDMA.


Safety and efficacy of adalimumab (D2E7) in Crohn's disease patients with an attenuated response to infliximab.
Although infliximab is highly effective in the treatment of Crohn's disease (CD), attenuated response to infliximab may develop over time in a subgroup of patients. The aim of our study was to examine the safety and efficacy of adalimumab (D2E7), a fully humanized anti-TNF-alpha Ab, in CD patients who had experienced an attenuated response to infliximab. Fifteen patients with active CD who experienced an attenuated response to infliximab were treated with adalimumab over a 6-month period. Patients, received a loading dose of 80 mg subcutaneously followed by 40 mg every 2 wk. The clinical response to adalimumab was classified as complete response, partial response, or nonresponse. Two patients received the loading dose of adalimumab but did not have adequate follow-up evaluations. Of the remaining 13 patients, 7 (54%) had a complete response, 4 (31%) had a partial response, and 2 (15%) were nonresponders. In six patients, the maintenance dose was increased in order to maintain clinical response. Eight of 11 (73%) patients on concurrent corticosteroids were able to discontinue or significantly decrease the dose of the steroids. Adalimumab was well tolerated without signs or symptoms of allergic reaction except in two patients who developed an injection site reaction. Our preliminary data suggest that adalimumab may be a safe and effective therapy for patients with CD who have experienced an attenuated response to infliximab.


Childhood cancer research in Oxford II: The Childhood Cancer Research Group.
We summarise the work of the Childhood Cancer Research Group, particularly in relation to the UK National Registry of Childhood Tumours (NRCT). The Group was responsible for setting up and maintaining the NRCT. This registry was based on notifications from regional cancer registries, specialist children's tumour registries, paediatric oncologists and clinical trials organisers. For a large sample of cases, data on controls matched by date and place of birth were also collected. Significant achievements of the Group include: studies of aetiology and of genetic epidemiology; proposals for, and participation in, international comparative studies of these diseases and on a classification system specifically for childhood cancer; the initial development of, and major contributions to, follow-up studies of the health of long-term survivors; the enhancement of cancer registration records by the addition of clinical data and of birth records. The Group made substantial contributions to the UK government's Committee on Medical Aspects of Radiation in the Environment. An important part of the ethos of the Group was to work in collaboration with many other organisations and individuals, both nationally and internationally: many of the Group's achievements described here were the result of such collaborations.


Fast second-harmonic generation frequency-resolved optical gating using only a pulse shaper.
In many ultrafast contexts, a collinear pulse-shaping frequency-resolved optical gating (FROG) technique is desired. Some applicable techniques already exist, but they suffer from one of two issues: either they require many time points to allow for Fourier filtering, or they do not yield a traditional FROG trace. To overcome these issues, we propose and demonstrate a fast new phase-cycled FROG technique using a pulse shaper.


Human metapneumovirus epidemiological and evolutionary patterns in Coastal Kenya, 2007-11.
Human metapneumovirus (HMPV) is an important global cause of severe acute respiratory infections in young children and the elderly. The epidemiology of HMPV in sub-Saharan Africa is poorly described and factors that allow its recurrent epidemics in communities not understood. We undertook paediatric inpatient surveillance for HMPV in Kilifi County Hospital (KCH) of Coastal Kenya between 2007 and 2011. Nasopharyngeal samples collected from children aged 1 day-59 months admitted with severe or very severe pneumonia, were tested for HMPV using real-time polymerase chain reaction (RT-PCR). Partial nucleotide sequences of the attachment (G) and fusion (F) surface proteins of positive samples were determined and phylogenetically analyzed. HMPV was detected in 4.8 % (160/3320) of children [73.8 % (118/160) of these less than one year of age], ranging between 2.9 and 8.8 % each year over the 5 years of study. HMPV infections were seasonal in occurrence, with cases predominant in the months of November through April. These months frequently coincided with low rainfall, high temperature and low relative humidity in the location. Phylogenetic analysis of partial F and G sequences revealed three subgroups of HMPV, A2 (74 %, 91/123), B1 (3.2 %, 4/123) and B2 (22.8 %, 28/123) in circulation, with subgroup A2 predominant in majority of the epidemic seasons. Comparison of G sequences (local and global) provided a greater phylogenetic resolution over comparison of F sequences and indicated presence of probable multiple G antigenic variants within the subgroups due to differences in amino acid sequence, encoded protein length and glycosylation patterns. The present study reveals HMPV is an important seasonal contributor to respiratory disease hospitalization in coastal Kenya, with an evolutionary pattern closely relating to that of respiratory syncytial virus.


Phase I study of the selective Aurora A kinase inhibitor MLN8054 in patients with advanced solid tumors: safety, pharmacokinetics, and pharmacodynamics.
This phase I trial examined the safety, pharmacokinetics, and pharmacodynamics of MLN8054, an oral, selective, small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received increasing doses of MLN8054 in 28-day cycles until dose-limiting toxicity (DLT) was seen in ≥2 of 3-6 patients in a cohort. For the 10-mg and 20-mg cohorts, treatment was administered once daily on days 1 to 5 and 8 to 12. Patients in later cohorts (25, 35, 45, 55, 60, 70, and 80 mg/day) were treated four times daily on days 1 to 14, with the largest dose at bedtime (QID-14D) to mitigate benzodiazepine-like effects possibly associated with peak plasma concentrations. Patients (n = 43) received a median of 1 cycle (range, 1-10). DLT of somnolence was first noted in the 20-mg cohort. Two DLTs of somnolence (n = 1) and transaminitis (n = 1) were seen at QID-14D 80 mg. Grade 2 oral mucositis (n = 1), predicted to be a mechanistic effect, was observed only at QID-14D 80 mg. MLN8054 exposure levels were roughly linear with dose; terminal half-life was 30 to 40 hours. Pharmacodynamic analyses of skin and tumor mitotic indices, mitotic cell chromosome alignment, and spindle bipolarity provided evidence of Aurora A inhibition. MLN8054 dosing for 10 to 14 days in 28-day cycles was feasible. Somnolence and transaminitis were DLTs. Pharmacodynamic analyses in mitotic cells of both skin and tumor provided proof of mechanism for Aurora A kinase inhibition. A more potent, selective, second-generation Aurora A kinase inhibitor, MLN8237, is in clinical development.


Gambling in Brazil: lifetime prevalences and socio-demographic correlates.
Gambling has experienced world-wide growth. The current study is the first national survey into household gambling conducted in a developing country. The sample was a three-stage probabilistic one designed to cover individuals 14 years old or older, of both genders and from all regions of the national territory; 325 census sectors were visited, including rural areas. DSM-IV-based instruments were used to assess problem and pathological gambling; individuals were asked to estimate their monthly gambling expenditure. The lifetime prevalences were: pathological gambling 1.0%, and problem gambling 1.3%. Maximum gambling expenditure corresponded to 5.4% of the household income for social gamblers, 16.9% for problem gamblers and 20.0% for pathological gamblers. The male:female ratio among adults for pathological gambling was 3.2:1. The data suggest the existence of two subgroups of pathological gamblers, one younger (33.9±4.19) and severe (7 or more DSM-IV criteria), another older (47.8±6.01) and less severe (5-6 criteria). In a multinomial logistic regression, problematic gambling was associated with gender, age, education, employment, region of origin and living in metropolitan areas. The data suggest that feeling active and socially inserted protects against problematic gambling. Individuals who are young, male, unemployed or not currently pursuing further education may be at special risk for severe pathological gambling.


Novel functions of the ubiquitin-independent proteasome system in regulating Xenopus germline development.
In most species, early germline development occurs in the absence of transcription with germline determinants subject to complex translational and post-translational regulations. Here, we report for the first time that early germline development is influenced by dynamic regulation of the proteasome system, previously thought to be ubiquitously expressed and to serve 'housekeeping' roles in controlling protein homeostasis. We show that proteasomes are present in a gradient with the highest levels in the animal hemisphere and extending into the vegetal hemisphere of Xenopus oocytes. This distribution changes dramatically during the oocyte-to-embryo transition, with proteasomes becoming enriched in and restricted to the animal hemisphere and therefore separated from vegetally localized germline determinants. We identify Dead-end1 (Dnd1), a master regulator of vertebrate germline development, as a novel substrate of the ubiquitin-independent proteasomes. In the oocyte, ubiquitin-independent proteasomal degradation acts together with translational repression to prevent premature accumulation of Dnd1 protein. In the embryo, artificially increasing ubiquitin-independent proteasomal degradation in the vegetal pole interferes with germline development. Our work thus reveals novel inhibitory functions and spatial regulation of the ubiquitin-independent proteasome during vertebrate germline development.


Propane and propane-water interactions: a study at cryogenic temperatures.
The phase transition of solid propane and a propane-water mixture under ultrahigh vacuum has been investigated using reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption mass spectrometry (TPD-MS). Here, the investigation is divided into two sections: the phase transition of pure propane and the interaction of propane with water. RAIR spectra of pure propane reveal an unknown crystalline phase at 50 K (phase I), which gradually converts to a known crystalline phase (phase II) at higher temperature. This conversion is associated with certain kinetics. Co-deposition of water and propane restricts the amorphous to crystalline phase transition, while sequential deposition (H2O@C3H8; propane over predeposited water) does not hinder it. For an alternative sequential deposition (C3H8@H2O; water over predeposited propane), the phase transition is hindered due to diffusional mixing within the given experimental time, which is attributed to the reason behind the restricted phase transition.


Phylogenetic study of Catapyrenium s. str. (Verrucariaceae, lichen-forming Ascomycota) and related genus Placidiopsis.
The current classification of what used to be called Catapyrenium comprises eight genera belonging to distinct lineages in the Verrucariaceae. Previous phylogenetic studies have shown that the redefined genus Catapyrenium (Catapyrenium s. str.) is monophyletic and sister of Placidiopsis within the Staurothele group, but this relationship was based on only two species from each genus. We conducted a phylogenetic study of Catapyrenium and Placidiopsis as currently delimited to evaluate the monophyly of each genus and infer infrageneric relationships. An initial family level phylogenetic analysis based on the nuLSU locus and implementing a backbone constraint tree (with both weighted maximum parsimony and bootstrap maximum likelihood approaches) was performed to infer phylogenetic placements of Catapyrenium and Placidiopsis taxa not included in previous molecular systematic studies. The results of this analysis were used to define the ingroup for a second phylogenetic analysis based on nuITS and nuLSU and centered on Catapyrenium s. str. and Placidiopsis. Placidiopsis was found to be monophyletic, whereas Catapyrenium s. str. was not. Catapyrenium dactylinum was found to be closely related to Placopyrenium caeruleopulvinum and Placopyrenium stanfordii, all of which were closely related to Placocarpus schaereri and Verrucula. In addition we found genus Placopyrenium to be polyphyletic. The resulting trees confirmed that Catapyrenium s. str. (excluding C. dactylinum) and Placidiopsis constitute two sister monophyletic entities. The data do not support Placidiopsis cinerascens and P. tenella as two distinct species because no characters can be used to distinguish them. Thus P. tenella is here reduced to synonymy with P. cinerascens.


White matter hyperintensities in dementia of Alzheimer's type and in healthy subjects without cerebrovascular risk factors. A magnetic resonance imaging study.
T2-weighted (0.5 T) magnetic resonance images were used to study the prevalence of subcortical white matter hyperintensities (WMHIs) in 22 patients with dementia of Alzheimer's type (DAT), 20 age-matched older healthy control subjects, and 10 younger healthy control subjects. Exclusionary criteria for all groups included cerebrovascular risk factors. All subjects had Hachinski Ischemic Index scores of less than 2 and computed tomographic scans showing no infarct. The WMHIs were classified as periventricular WMHIs or deep WMHIs and graded 0 through 3 (0 indicated absent, and 3, severe). For the group with DAT and older control subjects, periventricular WMHIs and deep WMHIs were graded 2 or 3 in fewer than 17% and 27% of subjects, respectively, whereas in the younger control subjects, all ratings were grade 1 or less. Serum cholesterol and systolic blood pressure values, although within the normal range, were elevated significantly in older control subjects when compared with those in younger control subjects. No significant differences in WMHI ratings, blood pressure, cholesterol, or triglyceride levels were found between patients with DAT and age-matched control subjects. Systolic blood pressure levels correlated with the severity of periventricular WMHIs only in older control subjects. Age correlated with periventricular WMHIs and deep WMHIs within both the older control subjects and the patients with DAT. There was no significant correlation between WMHIs and the severity of dementia in the group with DAT. These results suggest that, in subjects screened for cerebrovascular risk factors, WMHIs are rare and occur with identical frequency in patients with DAT as in age-matched healthy control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


The role of next generation sequencing in infection prevention in human parainfluenza virus 3 infections in immunocompromised patients.
Respiratory viral infections are a significant problem in patients with hematologic malignancies. We report a cluster of HPIV 3 infections in our myeloma patients, and describe the utility of next generation sequencing (NGS) to identify transmission linkages which can assist in infection prevention. To evaluate the utility of NGS to track respiratory viral infection outbreaks and delineate between community acquired and nosocomial infections in our cancer units. Retrospective chart review conducted at a single site. All patients diagnosed with multiple myeloma who developed symptoms suggestive of upper respiratory tract infection (URTI) or lower respiratory tract infection (LRTI) along with a respiratory viral panel (RVP) test positive for HPIV 3 between April 1, 2016, to June 30, 2016, were included. Sequencing was performed on the Illumina MiSeq™. To gain understanding regarding community strains of HPIV 3 during the same season, we also performed NGS on HPIV3 strains isolated from pediatric cases. We saw a cluster of 13 cases of HPIV3 infections in the myeloma unit. Using standard epidemiologic criteria, 3 cases were considered community acquired, 7 cases developed infection during treatment in the cancer infusion center, while an additional 3 developed infections during hospital stay. Seven patients required hospitalization for a median duration of 20days. NGS enabled sensitive discrimination of the relatedness of the isolates obtained during the outbreak and provided evidence for source of transmission. Two hospital onset infections could be tracked to an index case; the genome sequences of HPIV 3 strains from these 3 patients only differed by a single nucleotide. NGS offers a significantly higher discriminatory value as an epidemiologic tool, and can be used to gather real-time information and identification of transmission linkages to assist in infection prevention in immunocompromised patients.


Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis.
The benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration. We pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson. Recurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1). Effects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.


Resequencing microarray method for molecular diagnosis of human arboviral diseases.
Resequencing DNA microarray (RMA) technology uses probes designed to identify a panel of viral sequences. It can be used for detecting emerging viruses by revealing the nucleotide polymorphisms within the target of interest. As a new tool for molecular diagnosis of arbovirus infection, high density PathogenID v2.0 RMA (PID2-RMA) was assessed for the detection and genetic analysis of dengue, West Nile, and Chikungunya viruses in spiked blood samples or sera from individuals infected with dengue virus. Viral RNAs extracted from biological samples were retrotranscribed into cDNA and amplified using the Phi 29 polymerase-based method. This amplified cDNA was used for hybridization on PID2-RMA. A good specificity of RMA-based detection was demonstrated using a panel of arboviruses including Dengue, West Nile and Chikungunya viruses. This technology was also efficient for the detection and genetic analysis of the different serotypes of dengue virus in sera of infected patients. Furthermore, the mixing of dengue, West Nile and Chikungunya prototype viruses within a single sample of human blood did not interfere with the sensitivity of PID2-RMA. Our data show that high density PID2-RMA was suitable for the identification of medically important arboviruses. It appears to be particularly adapted to the genetic analysis of dengue, West Nile, and Chikungunya viruses in urgent clinical situations where the rapid identification and characterization of the pathogen is essential.


Efficacy and safety of pregabalin in alcohol dependence.
Pregabalin is a new anxiolytic that selectively binds to the alpha2-delta subunit of voltage-gated calcium channels, inhibiting release of excessive levels of excitatory neurotransmitters. In this open-label trial we aimed to investigate the efficacy of pregabalin on alcoholism indices in detoxified alcohol-dependent subjects. Reduction of cravings, psychiatric symptom improvements, and the evaluation of safety parameters were the secondary endpoints. Thirty-one alcohol-dependent patients were consecutively recruited and screened for the study. Twenty detoxified patients received pregabalin starting at 50 mg/day (orally) in the first week, gradually increasing to a flexible dose of 150-450 mg/day. Subjects were assessed at the beginning of the treatment, and after 2, 8 and 16 weeks. Craving (visual analogue scale, Obsessive and Compulsive Drinking Scale [OCDS]) and withdrawal (Clinical Institute Withdrawal Assessment for Alcohol [CIWA-Ar]) rating scales were applied; psychiatric symptoms were evaluated through the Symptom Check List-90-Revised (SCL-90-R). Out of the twenty patients who received the study drug, 15 completed the study procedures: 10 remained totally alcohol-free for the duration of the study, five relapsed. An additional four patients dropped out during the study, and one stopped taking medication due to adverse events. A significant progressive reduction of both craving and withdrawal symptomatology were observed. Safety parameters did not show any significant variation during treatment. Pregabalin shows promise as a treatment for alcohol dependence. Although limited by a low number of participants and by the open design, this is the first study concerning the efficacy and safety of pregabalin in current alcoholics. In these patients pregabalin was effective and well tolerated. Additional research is needed to explore the clinical relevance of these findings.


GWAS risk factors in Parkinson's disease: LRRK2 coding variation and genetic interaction with PARK16.
Parkinson's disease (PD) is a multifactorial movement disorder characterized by progressive neurodegeneration. Genome-wide association studies (GWAS) have nominated over fifteen distinct loci associated with risk of PD, however the biological mechanisms by which these loci influence disease risk are mostly unknown. GWAS are only the first step in the identification of disease genes: the specific causal variants responsible for the risk within the associated loci and the interactions between them must be identified to fully comprehend their impact on the development of PD. In the present study, we first attempted to replicate the association signals of 17 PD GWAS loci in our series of 1381 patients with PD and 1328 controls. BST1, SNCA, HLA-DRA, CCDC62/HIP1R and MAPT all showed a significant association with PD under different models of inheritance and LRRK2 showed a suggestive association. We then examined the role of coding LRRK2 variants in the GWAS association signal for that gene. The previously identified LRRK2 risk mutant p.M1646T and protective haplotype p.N551K-R1398H-K1423K did not explain the association signal of LRRK2 in our series. Finally, we investigated the gene-gene interaction between PARK16 and LRRK2 that has previously been proposed. We observed no interaction between PARK16 and LRRK2 GWAS variants, but did observe a non-significant trend toward interaction between PARK16 and LRRK2 variants within the protective haplotype. Identification of causal variants and the interactions between them is the crucial next step in making biological sense of the massive amount of data generated by GWAS studies. Future studies combining larger sample sizes will undoubtedly shed light on the complex molecular interplay leading to the development of PD.


Retinotopic organization and functional subdivisions of the human lateral geniculate nucleus: a high-resolution functional magnetic resonance imaging study.
Functional magnetic resonance imaging (fMRI) has provided intriguing insights into the topography and functional organization of visual cortical areas in the human brain. However, little is known about the functional anatomy of subcortical nuclei. Here, we used high-resolution fMRI (1.5 x 1.5 x 2 mm3) at 3 tesla to investigate the retinotopic organization of the human lateral geniculate nucleus (LGN). The central 15 degrees of the visual field were mapped using periodic flickering checkerboard stimuli that evoked a traveling wave of activity. The contralateral visual hemifield was represented with the lower field in the medial-superior portion and the upper field in the lateral-inferior portion of each LGN. The horizontal meridian was significantly overrepresented relative to the vertical meridian. The fovea was represented in posterior and superior portions, with increasing eccentricities represented more anteriorly. The magnification of the fovea relative to the periphery was similar to that described for human primary visual cortex. The magnocellular regions of the LGN were distinguished based on their sensitivity to low stimulus contrast and tended to be located in its inferior and medial portions. Our results demonstrate striking similarities in the topographic organization of the macaque and human LGN and support accounts of a constant magnification from the retina through the cortex in both species.


Stability analysis for grating-tuned strong-external-feedback semiconductor lasers.
We give a simple stability analysis within the scope of steady-state solution for the grating-tuned strong-external-feedback semiconductor lasers. In our model, a fluctuation in the refractive index of an active medium through the coupling of carrier density will cause another fluctuation in the refractive index. If the latter is always smaller than the former, the fluctuation will be damped, and therefore the corresponding operating point of the laser is stable. Our analysis indicates that there are various stable and unstable operating-frequency ranges for various reflectivities of the internal facet of the laser diode. In addition, it agrees well with the experimental results and explains the bistability of threshold gain versus operating frequency.


Characterization of CF4/CF3Br binary mixture adsorption on hydrophobic/hydrophilic surfaces via atomistic MD simulation.
Molecular dynamics simulations of multilayer adsorption of binary mixtures of two tetrasubstituted halomethanes (CF(4) and CF(3)Br) on two very different substrates (graphite vs hydroxylated SiO(2)) were performed for three different bulk compositions (40%, 50%, and 60% CF(4)) and over a range of temperatures from 80 to 200 K. The goal of these simulations was to investigate in depth how these factors affect film structure, layer composition, lateral arrangement, and molecular orientation in the first adsorbed layer on each substrate. In line with a previous study of single-component adsorption on these surfaces, mixtures adsorbed on the hydroxylated SiO(2) surface show stable number density profiles that are largely independent of temperature, up to 160 K. This level of stability is essentially absent in the case of adsorption on graphite, which show densities and surface populations that are largely dependent on overall film composition, molecular orientation, and adsorbate-substrate interactions, in addition to system temperature. Further, the composition of the first adsorbed layer at each solid surface appears to be influenced by the choice of substrate, with CF(3)Br the majority component at the graphite surface for all compositions and temperatures, while the first adsorbed layer on hydroxylated SiO(2) more clearly mirrors the overall film composition at temperatures below 160 K.


Boswellic acid protects against Bisphenol-A and gamma radiation induced hepatic steatosis and cardiac remodelling in rats: role of hepatic PPAR-α/P38 and cardiac Calcineurin-A/NFATc1/P38 pathways.
Bisphenol-A (BPA) and gamma-radiation are two risky environmental pollutants that human beings are exposed to in everyday life and consequently they threaten human health via inducing oxidative stress, inflammation, and eventually tissue damage. This study aims at appraising the protective effect of Boswellic Acid (BA) (250 mg/kg/day, orally) administration on BPA (150 mg/kg/day, i.p) and γ-irradiation (IR) (3 Gy/week for 4 weeks up to cumulative dose of 12 Gy/experimental course) for 4 weeks-induced damage to liver and heart tissues of rats. The present results indicated a significant improvement against damage induced by BPA and IR revealed in biochemical investigations (hepatic PPAR-α/P38 and cardiac ET-1/Calcineurin-A/NFATc1/P38) and histopathological examination of liver and heart. It could be concluded that BA possesses a protective effect against these two deleterious environmental pollutants which attracted major global concerns due to their serious toxicological impact on human health.


Education on the consequences of traumatic brain injury for children and adolescents with TBI and families/caregivers: a systematic scoping review.
To examine the breadth of education or training on the consequences of traumatic brain injury (TBI) for children and adolescents with TBI and their families/caregivers. Systematic scoping review of literature published through July 2018 using eight databases and education, training, instruction, and pediatric search terms. Only studies including pediatric participants (age <18) with TBI or their families/caregivers were included. Six independent reviewers worked in pairs to review abstracts and full-text articles independently, and abstracted data using a REDCap database. Forty-two unique studies were included in the review. Based on TBI injury severity, 24 studies included persons with mild TBI (mTBI) and 18 studies focused on moderate/severe TBI. Six studies targeted the education or training provided to children or adolescents with TBI. TBI education was provided primarily in the emergency department or outpatient/community setting. Most studies described TBI education as the main topic of the study or intervention. Educational topics varied, such as managing TBI-related symptoms and behaviors, when to seek care, family issues, and returning to work, school, or play. The results of this scoping review may guide future research and intervention development to promote the recovery of children and adolescents with TBI.


Generalized spectral decomposition: a theory and practice to spectral reconstruction.
The generalized spectral decomposition (GSD) theorem is introduced, and the generalized fundamental stimulus and metameric black are analyzed to show how they convey the valuable features in terms of color information. The suggestion would be considered as the generalization of Cohen and Kappauf's matrix R theory and its later application in parameric correction by Fairman. The GSD theorem provides a modular model whose arguments can be elaborately set up for high-performance spectral recovery. It is also shown that the suggested methods for spectral decomposition and/or spectral reconstruction proposed by different researchers could be considered as special cases of GSD.


Electrical characteristics and photocurrent spectral response of Si nanowires p-i-n junctions.
P-i-n junctions were fabricated along Si nanowires (SiNWs) via the conventional top-down approach using optical lithography. Each device comprises 500 identical SiNWs connected in parallel, and each SiNW has triangular cross-section with dimensions of ~6 nm (base) by ~8 nm (height). The photodiodes exhibit very good rectifying electrical characteristics with a low reverse bias current of ~0.2 fA per SiNW. The photocurrent spectral response exhibits three peaks between 400 nm to 700 nm, which arise due to local optical field enhancement associated with diffraction by the periodic SiNW array and interference in an air/SiO2/Si cavity.


Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy.
The standard palliative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) is gemcitabine-based chemotherapy; however, PDAC still presents a major therapeutic challenge. The aims of this study were to investigate the expression pattern of genes involved in gemcitabine sensitivity in resected PDAC tissues and to determine correlations of gene expression with treatment outcome. We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 70 patients with PDAC. Of the 70 patients, 40 received gemcitabine-based adjuvant chemotherapy (AC). We measured hENT1, dCK, CDA, RRM1, and RRM2 messenger RNA (mRNA) levels by quantitative real-time reverse transcription-polymerase chain reaction and determined the combined score (GEM score), based on the expression levels of hENT1, dCK, RRM1, and RRM2, to investigate the association with survival time. By determining the expression levels of these genes in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytologic specimens, we investigated the feasibility of individualized chemotherapy. High dCK (P = .0067), low RRM2 (P = .003), and high GEM score (P = .0003) groups had a significantly longer disease-free survival in the gemcitabine-treated group. A low GEM score (<2) was an independent predictive marker for poor outcome to gemcitabine-based AC as shown by multivariate analysis (P = .0081). Altered expression levels of these genes were distinguishable in microdissected neoplastic cells from EUS-FNA cytologic specimens. Quantitative analyses of hENT1, dCK, RRM1, and RRM2 mRNA levels using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytologic specimens may be useful in predicting the gemcitabine sensitivity of patients with PDAC.


The zebrafish genome encodes the largest vertebrate repertoire of functional aquaporins with dual paralogy and substrate specificities similar to mammals.
Aquaporins are integral membrane proteins that facilitate the transport of water and small solutes across cell membranes. These proteins are vital for maintaining water homeostasis in living organisms. In mammals, thirteen aquaporins (AQP0-12) have been characterized, but in lower vertebrates, such as fish, the diversity, structure and substrate specificity of these membrane channel proteins are largely unknown. The screening and isolation of transcripts from the zebrafish (Danio rerio) genome revealed eighteen sequences structurally related to the four subfamilies of tetrapod aquaporins, i.e., aquaporins (AQP0, -1 and -4), water and glycerol transporters or aquaglyceroporins (Glps; AQP3 and AQP7-10), a water and urea transporter (AQP8), and two unorthodox aquaporins (AQP11 and -12). Phylogenetic analyses of nucleotide and deduced amino acid sequences demonstrated dual paralogy between teleost and human aquaporins. Three of the duplicated zebrafish isoforms have unlinked loci, two have linked loci, while DrAqp8 was found in triplicate across two chromosomes. Genomic sequencing, structural analysis, and maximum likelihood reconstruction, further revealed the presence of a putative pseudogene that displays hybrid exons similar to tetrapod AQP5 and -1. Ectopic expression of the cloned transcripts in Xenopus laevis oocytes demonstrated that zebrafish aquaporins and Glps transport water or water, glycerol and urea, respectively, whereas DrAqp11b and -12 were not functional in oocytes. Contrary to humans and some rodents, intrachromosomal duplicates of zebrafish AQP8 were water and urea permeable, while the genomic duplicate only transported water. All aquaporin transcripts were expressed in adult tissues and found to have divergent expression patterns. In some tissues, however, redundant expression of transcripts encoding two duplicated paralogs seems to occur. The zebrafish genome encodes the largest repertoire of functional vertebrate aquaporins with dual paralogy to human isoforms. Our data reveal an early and specific diversification of these integral membrane proteins at the root of the crown-clade of Teleostei. Despite the increase in gene copy number, zebrafish aquaporins mostly retain the substrate specificity characteristic of the tetrapod counterparts. Based upon the integration of phylogenetic, genomic and functional data we propose a new classification for the piscine aquaporin superfamily.


Construction of a helper-free recombinant adenovirus that expresses polyomavirus large T antigen.
Adenovirus-polyomavirus recombinant viruses were constructed in vitro by inserting a hybrid transcription unit composed of the adenovirus type 2 major late promoter and the early coding region of polyomavirus into the adenovirus type 5 vector Ad5 delta E1/dl309. The vector lacks the E1a and E1b transcription units and contains a unique restriction endonuclease cleavage site in their place. The polyomavirus genomic insert contained a small deletion which precluded the synthesis of functional small and middle T antigen but allowed for the synthesis of large T antigen. One recombinant virus, Ad5PyR39, which contained the hybrid transcription unit in the opposite transcriptional orientation from the overall direction of late-gene transcription, was studied in detail. Ad5PyR39 replicated efficiently without a helper virus in human 293 cells and expressed hybrid mRNAs of the expected size and composition that were translated to yield large T antigen. The large T antigen synthesized in 293 cells was the same size as that produced in mouse 3T6 cells lytically infected with polyomavirus, and this protein bound efficiently and specifically to the large-T-antigen-binding sites in polyomavirus DNA. Moreover, the large T antigen encoded by the recombinant virus proved capable of catalyzing the replication in mouse 3T6 cells of a plasmid containing the polyomavirus origin for DNA replication. Comparison of the amount of large T antigen produced in 3T6 cells infected with polyomavirus with that in 293 cells infected with Ad5PyR39, under optimal conditions for each system, revealed at least a fivefold greater yield of the protein on a per cell basis in the latter system compared with the former. Ad5PyR39 should prove to be useful to isolate large quantities of functional polyomavirus large T antigen for structural and biochemical studies.


Survival among women with cancer of the uterine cervix: influence of marital status and social class.
The aim was to investigate whether the survival of women with cancer of the uterine cervix is associated with their marital status and social class. The study was a survey of survival up to 5 years from diagnosis of women with cancer of the cervix registered in the South Thames Cancer Registry, using Cox regression to adjust for marital status, social class, age, and stage at registration. Because of deficiencies in social class data held by the Registry (social class was assigned in only 51% of cases, as opposed to 93% for marital status), the findings were compared with survival data from the OPCS Longitudinal Study. During the period of study (1977-81) the South Thames Cancer Registry covered a female population of about 3.5 million in the south east of England. Data on 1728 women were analysed. MEASUREMENTS AND AND MAIN RESULTS: Apparent differences in crude survival by marital status and social class were examined. These were found to be accounted for by adjustment for age and stage. The better survival of those whose social class was unknown was found to be an artefact of the way in which cancer registries assign social class, but this did not appear to bias registry based studies of social class survival seriously. (1) After adjusting for age, factors affecting survival in women with cancer of the cervix, such as stage at presentation or host resistance, appear to be similarly distributed in the different marital status and social class groups; (2) for cervical cancer, the marked social class gradient and unusual marital status distribution found in cross sectional mortality data reflect the incidence of the disease, not differences in survival; (3) explanations for these patterns in incidence and mortality data are to be found in the aetiology of the disease.


An experimental test of the causes of small-scale phenotypic differentiation in a population of great tits.
Phenotypic differentiation between populations is thought to occur mainly at spatial scales where gene-flow is restricted and selection regimes differ. However, if gene flow is nonrandom, dispersal may reinforce, rather than counteract, evolutionary differentiation, meaning that differences occurring over small scales might have a genetic basis. The purpose of this study was to determine the cause of differences in mean phenotype between two parts of a population of great tits Parus major, separated by <3 km. We conducted a partial cross-fostering experiment between two contrasting parts of this population to separate genetic and environmental sources of variation, and to test for gene-environment interaction. We found strong environmental effects on nestling size, mass and condition index, with nestlings reared in a low density part of the population being larger, heavier and in better condition, than those in a high density part, irrespective of their origin. In addition, we found smaller, but significant, differences in nestling condition and shape associated with the areas that birds originated from, suggesting the presence of genetic differences between parts of this population. There was no evidence of gene-environment interaction for any character. This experiment is thus consistent with previous analyses suggesting that differences between parts of this population had evolved recently, apparently due to phenotype-dependent dispersal, and indicates that population differentiation can be maintained over small spatial scales despite extensive dispersal.


Mechanisms involved in down-regulation of intestinal IgA in rats by high cocoa intake.
Previous studies have shown that rat intestinal immunoglobulin A (IgA) concentration and lymphocyte composition of the intestinal immune system were influenced by a highly enriched cocoa diet. The aim of this study was to dissect the mechanisms by which a long-term high cocoa intake was capable of modifying gut secretory IgA in Wistar rats. After 7 weeks of nutritional intervention, Peyer's patches, mesenteric lymph nodes and the small intestine were excised for gene expression assessment of IgA, transforming growth factor β, C-C chemokine receptor-9 (CCR9), interleukin (IL)-6, CD40, retinoic acid receptors (RARα and RARβ), C-C chemokine ligand (CCL)-25 and CCL28 chemokines, polymeric immunoglobulin receptor and toll-like receptors (TLR) expression by real-time polymerase chain reaction. As in previous studies, secretory IgA concentration decreased in intestinal wash and fecal samples after cocoa intake. Results from the gene expression showed that cocoa intake reduced IgA and IL‑6 in Peyer's patches and mesenteric lymph nodes, whereas in small intestine, cocoa decreased IgA, CCR9, CCL28, RARα and RARβ. Moreover, cocoa-fed animals presented an altered TLR expression pattern in the three compartments studied. In conclusion, a high-cocoa diet down-regulated cytokines such as IL-6, which is required for the activation of B cells to become IgA-secreting cells, chemokines and chemokine receptors, such as CCL28 and CCR9 together with RARα and RARβ, which are involved in the gut homing of IgA-secreting cells. Moreover, cocoa modified the cross-talk between microbiota and intestinal cells as was detected by an altered TLR pattern. These overall effects in the intestine may explain the intestinal IgA down-regulatory effect after the consumption of a long-term cocoa-enriched diet.


Prolonged sitting at work is associated with a favorable time course of low-back pain among blue-collar workers: a prospective study in the DPhacto cohort.
Objective Low-back pain (LBP) is a massive health problem. Sitting at work has been suggested to be both a risk and protective factor for LBP. Thus, the objective of this study was to investigate the association between total and temporal patterns of objectively measured sitting duration and individual time course of LBP. Methods The analysis was performed among 665 participants from the DPhacto cohort of mainly blue-collar workers. Sitting at work was measured by accelerometry at baseline, expressed in total duration and temporal pattern [% of working time spent in brief bursts (≤5 minutes), moderate (>5 - ≤20 minutes) and prolonged periods (>20 minutes)] of sitting. Time course of LBP (0-10 scale) were collected by monthly text messages across one year. Linear mixed models were applied to investigate the association, adjusting for potential confounders. Results Significant negative associations between sitting duration at work and adjusted time course of LBP were found; total sitting (B -0.01, 95% CI -0.01- -0.004), brief bursts (B -0.01, 95% CI -0.02- -0.01), moderate (B -0.01, 95% CI -0.01- -0.008) and prolonged periods (B -0.01, 95% CI -0.02- -0.01). Meaning, a 5-minute increase of sitting at work will correspond to a decrease in one year time course of LBP by -0.05 points. Conclusion Longer duration of total and temporal sitting periods at work was significantly associated with a favorable time course of LBP. This finding shows sitting at work to be beneficial for LBP, among populations of mainly blue-collar workers, by protecting from LBP aggravation.


Promoting physical activity interventions in communities with poor health and socio-economic profiles: A process evaluation of the implementation of a new walking group scheme.
Walking groups have known health benefits but may not operate in communities with the greatest health needs, leading to the potential for increasing health inequity. This study examined the process of implementing a new volunteer led walking group scheme in a deprived community in England with poor physical activity, health and socio-economic indicators. Documentary evidence and semi-structured interviews with stakeholders and volunteer walk leaders undertaken at the beginning and end of the funding period were analysed thematically. It was found that utilising community-based assets, forming collaborative partnerships with health and non-health organisations and ongoing sustainability issues were all factors that affected the scheme's effective implementation. Passive recruitment methods and mass publicity did not attract participants who were representative of their community. The findings firstly suggest the necessity of identifying and mobilising community based assets at the 'grass roots' in deprived communities during the preparatory stage to access those in greatest need and to plan and build capacity. Secondly, the findings highlight the key role that health professionals have in referring those in poorest health and the inactive into walking interventions. In the new era of fiscally constrained public health embedded within local authorities these findings are pertinent in supporting the utilisation of local assets to address entrenched physical inactivity and inequity within deprived communities.


Exercise-Based Stroke Rehabilitation: Clinical Considerations Following the COVID-19 Pandemic.
Background. The COVID-19 pandemic attributable to the severe acute respiratory syndrome virus (SARS-CoV-2) has had a significant and continuing impact across all areas of healthcare including stroke. Individuals post-stroke are at high risk for infection, disease severity, and mortality after COVID-19 infection. Exercise stroke rehabilitation programs remain critical for individuals recovering from stroke to mitigate risk factors and morbidity associated with the potential long-term consequences of COVID-19. There is currently no exercise rehabilitation guidance for people post-stroke with a history of COVID-19 infection. Purpose. To (1) review the multi-system pathophysiology of COVID-19 related to stroke and exercise; (2) discuss the multi-system benefits of exercise for individuals post-stroke with suspected or confirmed COVID-19 infection; and (3) provide clinical considerations related to COVID-19 for exercise during stroke rehabilitation. This article is intended for healthcare professionals involved in the implementation of exercise rehabilitation for individuals post-stroke who have suspected or confirmed COVID-19 infection and non-infected individuals who want to receive safe exercise rehabilitation. Results. Our clinical considerations integrate pre-COVID-19 stroke (n = 2) and COVID-19 exercise guidelines for non-stroke populations (athletic [n = 6], pulmonary [n = 1], cardiac [n = 2]), COVID-19 pathophysiology literature, considerations of stroke rehabilitation practices, and exercise physiology principles. A clinical decision-making tool for COVID-19 screening and eligibility for stroke exercise rehabilitation is provided, along with key subjective and physiological measures to guide exercise prescription. Conclusion. We propose that this framework promotes safe exercise programming within stroke rehabilitation for COVID-19 and future infectious disease outbreaks.


Manganese doped fluorescent paramagnetic nanocrystals for dual-modal imaging.
In this work, dual-modal (fluorescence and magnetic resonance) imaging capabilities of water-soluble, low-toxicity, monodisperse Mn-doped ZnSe nanocrystals (NCs) with a size (6.5 nm) below the optimum kidney cutoff limit (10 nm) are reported. Synthesizing Mn-doped ZnSe NCs with varying Mn(2+) concentrations, a systematic investigation of the optical properties of these NCs by using photoluminescence (PL) and time resolved fluorescence are demonstrated. The elemental properties of these NCs using X-ray photoelectron spectroscopy and inductive coupled plasma-mass spectroscopy confirming Mn(2+) doping is confined to the core of these NCs are also presented. It is observed that with increasing Mn(2+) concentration the PL intensity first increases, reaching a maximum at Mn(2+) concentration of 3.2 at% (achieving a PL quantum yield (QY) of 37%), after which it starts to decrease. Here, this high-efficiency sample is demonstrated for applications in dual-modal imaging. These NCs are further made water-soluble by ligand exchange using 3-mercaptopropionic acid, preserving their PL QY as high as 18%. At the same time, these NCs exhibit high relaxivity (≈2.95 mM(-1) s(-1)) to obtain MR contrast at 25 °C, 3 T. Therefore, the Mn(2+) doping in these water-soluble Cd-free NCs are sufficient to produce contrast for both fluorescence and magnetic resonance imaging techniques.


Consultation techniques using shared decision making for patients with cancer and their families.
This article elucidates the nursing consultation techniques in shared decision making (SDM) for patients with cancer and their family members. Descriptive data (207 records) from the nurse-led SDM consultation facility and content analysis were used to extract the nursing consultation techniques. In addition, the order in which these techniques were used to structure the SDM process for patients with cancer was identified. The author extracted eight categories pertaining to nurse consultation techniques for the SDM process: sharing feelings, helping to identify the focus of the consultations, helping to devise a personalized recovery plan, providing information in accordance with the patient's responses, supporting the patient to understand the information provided, ensuring continued treatment and care, strengthening the patient support system, and exploring possibilities on the basis of patient needs. The identified logical order in which these techniques were applied may be useful as a guide to systematic decision-making support.


The plasma peptides of sepsis.
A practical strategy to discover sepsis specific proteins may be to compare the plasma peptides and proteins from patients in the intensive care unit with and without sepsis. The aim was to discover proteins and/or peptides that show greater observation frequency and/or precursor intensity in sepsis. The endogenous tryptic peptides of ICU-Sepsis were compared to ICU Control, ovarian cancer, breast cancer, female normal, sepsis, heart attack, Alzheimer's and multiple sclerosis along with their institution-matched controls, female normals and normal samples collected directly onto ice. Endogenous tryptic peptides were extracted from individual sepsis and control EDTA plasma samples in a step gradient of acetonitrile for random and independent sampling by LC-ESI-MS/MS with a set of robust and sensitive linear quadrupole ion traps. The MS/MS spectra were fit to fully tryptic peptides within proteins using the X!TANDEM algorithm. The protein observation frequency was counted using the SEQUEST algorithm after selecting the single best charge state and peptide sequence for each MS/MS spectra. The protein observation frequency of ICU-sepsis versus ICU Control was subsequently tested by Chi square analysis. The average protein or peptide log10 precursor intensity was compared across disease and control treatments by ANOVA in the R statistical system. Peptides and/or phosphopeptides of common plasma proteins such as ITIH3, SAA2, SAA1, and FN1 showed increased observation frequency by Chi square (χ2 > 9, p < 0.003) and/or precursor intensity in sepsis. Cellular gene symbols with large Chi square values from tryptic peptides included POTEB, CTNNA1, U2SURP, KIF24, NLGN2, KSR1, GTF2H1, KIT, RPS6KL1, VAV2, HSPA7, SMC2, TCEB3B, ZNF300, SUPV3L1, ADAMTS20, LAMB4, MCCC1, SUPT6H, SCN9A, SBNO1, EPHA1, ABLIM2, cB5E3.2, EPHA10, GRIN2B, HIVEP2, CCL16, TKT, LRP2 and TMF1 amongst others showed increased observation frequency. Similarly, increased frequency of tryptic phosphopeptides were observed from POM121C, SCN8A, TMED8, NSUN7, SLX4, MADD, DNLZ, PDE3B, UTY, DEPDC7, MTX1, MYO1E, RXRB, SYDE1, FN1, PUS7L, FYCO1, USP26, ACAP2, AHI1, KSR2, LMAN1, ZNF280D and SLC8A2 amongst others. Increases in mean precursor intensity in peptides from common plasma proteins such as ITIH3, SAA2, SAA1, and FN1 as well as cellular proteins such as COL24A1, POTEB, KANK1, SDCBP2, DNAH11, ADAMTS7, MLLT1, TTC21A, TSHR, SLX4, MTCH1, and PUS7L among others were associated with sepsis. The processing of SAA1 included the cleavage of the terminal peptide D/PNHFRPAGLPEKY from the most hydrophilic point of SAA1 on the COOH side of the cystatin C binding that was most apparent in ICU-Sepsis patients compared to all other diseases and controls. Additional cleavage of SAA1 on the NH2 terminus side of the cystatin binding site were observed in ICU-Sepsis. Thus there was disease associated variation in the processing of SAA1 in ICU-Sepsis versus ICU controls or other diseases and controls. Specific proteins and peptides that vary between diseases might be discovered by the random and independent sampling of multiple disease and control plasma from different hospital and clinics by LC-ESI-MS/MS for storage in a relational SQL Server database and analysis with the R statistical system that will be a powerful tool for clinical research. The processing of SAA1 may play an unappreciated role in the inflammatory response to Sepsis.


Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1.
Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that stimulates monocyte recruitment when injected into tissues of healthy animals. However, the function of this chemokine in models with preexisting inflammation is not known. Therefore, MCP-1 was superfused over the mesentery of naive rats or rats with chronic adjuvant-induced vasculitis. MCP-1 elicited increased leukocyte transendothelial migration in adjuvant-immunized rats compared with naive animals. Surprisingly, histology revealed that neutrophils constituted the majority of leukocytes recruited in adjuvant-immunized animals. In vitro, MCP-1 was also able to induce chemotaxis of neutrophils isolated from adjuvant-immunized rats but not from naive rats. Flow cytometry revealed novel expression of the CC chemokine receptors CCR1 and CCR2 on neutrophils from adjuvant-immunized animals. In naive animals, an antibody against CD18 blocked leukocyte adhesion and emigration in response to MCP-1. In adjuvant-immunized animals, leukocyte adhesion was reduced by antibodies against the alpha4-integrin but not by antibodies against CD18. However, the CD18 antibody did block emigration. To our knowledge, this study is the first to show increased sensitivity to a CC chemokine in a model with preexisting inflammation, and altered leukocyte recruitment profiles in response to MCP-1. It also demonstrates that CD18 is required for chemokine-induced leukocyte transendothelial migration, independent of its known role in mediating firm adhesion. J. Clin. Invest. 103:1269-1276 (1999).


"Your brain can't wait": perspectives of children and adolescents with acquired brain injury and their parents on physical rehabilitation during the subacute phase.
Physical interventions during subacute rehabilitation have potential to improve functional recovery. This study explored the perspectives of children and adolescents with acquired brain injury (ABI) and their parents with respect to physical rehabilitation during the subacute phase. Thirteen children and adolescents with ABI and their parents were included and interviewed using semi-structured interviews. Interview transcripts were analysed using inductive thematic analysis approach. Six themes were identified: 1) beliefs of physical rehabilitation, 2) content of physical rehabilitation, 3) tailored care, 4) impact of context, 5) communication and 6) transition. The importance of intensive physical practice was widely supported. The positive can-do mentality was emphasised to create an atmosphere of hope, meaning that every effort would be made to achieve maximum recovery. Intensive involvement of parents is considered essential during subacute rehabilitation including an open and mutual dialogue about the focus of rehabilitation, therapy goals and future participation in their own environment. Our findings highlight the need for an intensive rehabilitation approach, tailored to the individual's needs. The perspectives of children and adolescents and their parents in our study contribute to a better understanding of factors that are important for optimal recovery through physical rehabilitation during the subacute phase.


Healthcare utilization and clinical outcomes after catheter ablation of atrial flutter.
Atrial flutter ablation is associated with a high rate of acute procedural success and symptom improvement. The relationship between ablation and other clinical outcomes has been limited to small studies primarily conducted at academic centers. We sought to determine if catheter ablation of atrial flutter is associated with reductions in healthcare utilization, atrial fibrillation, or stroke in a large, real world population. California Healthcare Cost and Utilization Project databases were used to identify patients undergoing atrial flutter ablation between 2005 and 2009. The adjusted association between atrial flutter ablation and healthcare utilization, atrial fibrillation, or stroke was investigated using Cox proportional hazards models. Among 33,004 patients with a diagnosis of atrial flutter observed for a median of 2.1 years, 2,733 (8.2%) underwent catheter ablation. Atrial flutter ablation significantly lowered the adjusted risk of inpatient hospitalization (HR 0.88, 95% CI 0.84-0.92, p<0.001), emergency department visits (HR 0.60, 95% CI 0.54-0.65, p<0.001), and overall hospital-based healthcare utilization (HR 0.94, 95% CI 0.90-0.98, p = 0.001). Atrial flutter ablation was also associated with a statistically significant 11% reduction in the adjusted hazard of atrial fibrillation (HR 0.89, 95% CI 0.81-0.97, p = 0.01). Risk of acute stroke was not significantly reduced after ablation (HR 1.09, 95% CI 0.81-1.45, p = 0.57). In a large, real world population, atrial flutter ablation was associated with significant reductions in hospital-based healthcare utilization and a reduced risk of atrial fibrillation. These findings support the early use of catheter ablation for the treatment of atrial flutter.


The impact of e-prescribing on prescriber and staff time in ambulatory care clinics: a time motion study.
Electronic prescribing has improved the quality and safety of care. One barrier preventing widespread adoption is the potential detrimental impact on workflow. We used time-motion techniques to compare prescribing times at three ambulatory care sites that used paper-based prescribing, desktop, or laptop e-prescribing. An observer timed all prescriber (n = 27) and staff (n = 42) tasks performed during a 4-hour period. At the sites with optional e-prescribing >75% of prescription-related events were performed electronically. Prescribers at e-prescribing sites spent less time writing, but time-savings were offset by increased computer tasks. After adjusting for site, prescriber and prescription type, e-prescribing tasks took marginally longer than hand written prescriptions (12.0 seconds; -1.6, 25.6 CI). Nursing staff at the e-prescribing sites spent longer on computer tasks (5.4 minutes/hour; 0.0, 10.7 CI). E-prescribing was not associated with an increase in combined computer and writing time for prescribers. If carefully implemented, e-prescribing will not greatly disrupt workflow.


Pseudotype formation of murine leukemia virus with the G protein of vesicular stomatitis virus.
Mixed infection of a cell by vesicular stomatitis virus (VSV) and retroviruses results in the production of progeny virions bearing the genome of one virus encapsidated by the envelope proteins of the other. The mechanism for the phenomenon of pseudotype formation is not clear, although specific recognition of a viral envelope protein by the nucleocapsid of an unrelated virus is presumably involved. In this study, we used Moloney murine leukemia virus (MoMLV)-based retroviral vectors encoding the gene for neomycin phosphotransferase to investigate the interaction between the VSV G protein and the retroviral nucleocapsid during the formation of MoMLV(VSV) pseudotypes. Our results show that VSV G protein can be incorporated into the virions of retrovirus in the absence of other VSV-encoded proteins or of retroviral envelope protein. Infection of hamster cells by MoMLV(VSV) pseudotypes gave rise to neomycin phosphotransferase-resistant colonies, and addition of anti-VSV serum to the virus preparations completely abolished the infectivity of MoMLV(VSV) pseudotypes. It should be possible to use existing mutants of VSV G protein in the system described here to identify the signals that are important for the formation of MoMLV(VSV) pseudotypes.


Right ventricular end-diastolic stiffness heralds right ventricular failure in monocrotaline-induced pulmonary hypertension.
Recent studies suggest right ventricular (RV) stiffness is important in pulmonary hypertension (PH) prognosis. Smaller stroke volume (SV) variation after a certain RV end-diastolic pressure (EDP) respiratory variation as assessed by spectral transfer function (STF) may identify RV stiffness. Our aim was to evaluate RV stiffness in monocrotaline (MCT)-induced PH progression and to validate STF gain between EDP and SV as marker of stiffness. Seven-week-old male Wistar rats randomly injected with 60 mg/kg MCT or vehicle were divided into three groups (n = 12 each) according to cardiac index (CI): controls (Ctrl), preserved CI (MCT pCI), and reduced CI (MCT rCI). All underwent RV pressure-volume (PV) evaluation 24-34 days after MCT, under halogenate anesthesia and constant positive-pressure ventilation. End-diastolic stiffness (βi), end-systolic elastance (Eesi), arterial elastance for indexed volumes (Eai), and preload recruitable stroke work (PRSW) were obtained and beat-to-beat fluctuations during ventilation assessed by STF. Eai was the strongest determinant of CI, alongside βi but not PRSW. MCT rCI showed impaired ventricular-vascular coupling (VVC) and higher βi, along with low end-diastolic pressure (EDP) and stroke volume index (SVi) STF gain, denoting impaired preload reserve. On multivariate analysis βi and not Eesi correlated with EDP-SVi STF gain (P < 0.001). Receiver-operating characteristics (ROC) curve analysis of EDP-SVi STF gain showed an area under curve of 0.84 for βi prediction (P = 0.002). Afterload, impaired VVC and RV stiffness are major players in RV failure. RV stiffness can be assessed by STF gain analysis of respiratory fluctuations between EDP and SVi, which may constitute a prognostic tool in PH.


Identification and Application of Gene Expression Signatures Associated with Lifespan Extension.
Several pharmacological, dietary, and genetic interventions that increase mammalian lifespan are known, but general principles of lifespan extension remain unclear. Here, we performed RNA sequencing (RNA-seq) analyses of mice subjected to 8 longevity interventions. We discovered a feminizing effect associated with growth hormone regulation and diminution of sex-related differences. Expanding this analysis to 17 interventions with public data, we observed that many interventions induced similar gene expression changes. We identified hepatic gene signatures associated with lifespan extension across interventions, including upregulation of oxidative phosphorylation and drug metabolism, and showed that perturbed pathways may be shared across tissues. We further applied the discovered longevity signatures to identify new lifespan-extending candidates, such as chronic hypoxia, KU-0063794, and ascorbyl-palmitate. Finally, we developed GENtervention, an app that visualizes associations between gene expression changes and longevity. Overall, this study describes general and specific transcriptomic programs of lifespan extension in mice and provides tools to discover new interventions.


Prosthetic lower extremity hemodialysis access grafts have satisfactory patency despite a high incidence of infection.
Prosthetic arteriovenous grafts (AVGs) in the lower extremity represent a useful alternative for hemodialysis vascular access when all upper limb access sites have been used or in some patients when freedom of both hands is necessary during dialysis. Reported complications include an increased risk of infection and limb ischemia. This study evaluated our experience with the patency outcomes and complication rates of polytetrafluoroethylene (PTFE) AVGs placed in the thigh. A retrospective outcomes analysis was performed of all femoral AVGs inserted between January 1992 and July 2007. Data were obtained by review of medical records for patient demographics, comorbidities, and AVG-related outcomes. Patency, complication rates, and risk factors for infection were determined. A total of 153 prosthetic AVGs were placed in 127 patients (63 men). Mean patient age was 52.7 ± 16.3 years. Median follow-up was 25 months (range, 1-169 months). The most common underlying renal disease was glomerulonephritis in 27 (21%). Hypertension and coronary artery disease were common comorbidities, respectively, in 49 (39%) and 23 patients (18%). The primary and secondary AVG patency rates at 12 months were 53.9% and 75.3%, respectively, and 2- and 5-year patency rates were, respectively, 39.6% and 19.3% (primary) and 63.8% and 50.6% (secondary). The mean AVG survival for all cases was 31.6 months (range, 0-149 months). Surgical thrombectomy was required in 82 (54%), and 22 AVGs (14%) required surgical revision for stenosis. Infection occurred in 41 AVGs (27%), and limb ischemia occurred in 2 (1.3%). Statistical analysis did not reveal a significant risk factor for infection. Femoral AVGs are a suitable alternative to upper limb vascular access, with acceptable primary and secondary patency rates. Infection occurred in approximately one-quarter of cases, whereas steal was uncommon.


Expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and the methylation patterns at the KvDMR1 and H19/IGF2 imprinting control regions is conserved between human and bovine.
Beckwith-Wiedemann syndrome (BWS) is a loss-of-imprinting pediatric overgrowth syndrome. The primary features of BWS include macrosomia, macroglossia, and abdominal wall defects. Secondary features that are frequently observed in BWS patients are hypoglycemia, nevus flammeus, polyhydramnios, visceromegaly, hemihyperplasia, cardiac malformations, and difficulty breathing. BWS is speculated to occur primarily as the result of the misregulation of imprinted genes associated with two clusters on chromosome 11p15.5, namely the KvDMR1 and H19/IGF2. A similar overgrowth phenotype is observed in bovine and ovine as a result of embryo culture. In ruminants this syndrome is known as large offspring syndrome (LOS). The phenotypes associated with LOS are increased birth weight, visceromegaly, skeletal defects, hypoglycemia, polyhydramnios, and breathing difficulties. Even though phenotypic similarities exist between the two syndromes, whether the two syndromes are epigenetically similar is unknown. In this study we use control Bos taurus indicus X Bos taurus taurus F1 hybrid bovine concepti to characterize baseline imprinted gene expression and DNA methylation status of imprinted domains known to be misregulated in BWS. This work is intended to be the first step in a series of experiments aimed at determining if LOS will serve as an appropriate animal model to study BWS. The use of F1 B. t. indicus x B. t. taurus tissues provided us with a tool to unequivocally determine imprinted status of the regions of interest in our study. We found that imprinting is conserved between the bovine and human in imprinted genes known to be associated with BWS. KCNQ1OT1 and PLAGL1 were paternally-expressed while CDKN1C and H19 were maternally-expressed in B. t. indicus x B. t. taurus F1 concepti. We also show that in bovids, differential methylation exists at the KvDMR1 and H19/IGF2 ICRs. Based on these findings we conclude that the imprinted gene expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and the methylation patterns at the KvDMR1 and H19/IGF2 ICRs are conserved between human and bovine. Future work will determine if LOS is associated with misregulation at these imprinted loci, similarly to what has been observed for BWS.


Molecular recognition of insulin by a synthetic receptor.
The discovery of molecules that bind tightly and selectively to desired proteins continues to drive innovation at the interface of chemistry and biology. This paper describes the binding of human insulin by the synthetic receptor cucurbit[7]uril (Q7) in vitro. Isothermal titration calorimetry and fluorescence spectroscopy experiments show that Q7 binds to insulin with an equilibrium association constant of 1.5 × 10(6) M(-1) and with 50-100-fold selectivity versus proteins that are much larger but lack an N-terminal aromatic residue, and with >1000-fold selectivity versus an insulin variant lacking the N-terminal phenylalanine (Phe) residue. The crystal structure of the Q7·insulin complex shows that binding occurs at the N-terminal Phe residue and that the N-terminus unfolds to enable binding. These findings suggest that site-selective recognition is based on the properties inherent to a protein terminus, including the unique chemical epitope presented by the terminal residue and the greater freedom of the terminus to unfold, like the end of a ball of string, to accommodate binding. Insulin recognition was predicted accurately from studies on short peptides and exemplifies an approach to protein recognition by targeting the terminus.


Evaluation of two enzyme immunoassays for detecting Helicobacter pylori in stool specimens of dyspeptic patients after eradication therapy.
The aim of the current study was to assess the reliability of two enzyme immunoassays in detecting the Helicobacter pylori status of stool specimens of Turkish dyspeptic patients in the post-treatment period. Forty-eight patients with non-ulcer dyspepsia who were positive for H. pylori underwent a 1 week regimen of triple therapy. Stool samples of patients were obtained 2 and 6 weeks after eradication therapy and a [13C]urea breath test was performed 6 weeks after therapy in order to assess the reliability of mAb-based (Amplified IDEIA HpStAR, DakoCytomation) and polyclonal-antiserum-based (Premier Platinum HpSA, Meridian Diagnostics) stool antigen test kits and to compare their diagnostic accuracies. Using a minimum cutoff OD450 value of 0.19 for Amplified IDEIA HpStAR and 0.16 for Premier Platinum HpSA the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of the tests were determined 2 and 6 weeks after completion of eradication therapy. At both the second and the sixth week in the post-treatment period the diagnostic accuracy of Amplified IDEIA HpStAR was significantly better than the Premier Platinum's (75% versus 50%, S2=6.4; P=0.011, and 90% versus 69%, S2=6.316; P=0.012, respectively). In light of these findings the mAb-based Amplified IDEIA HpStAR has a high diagnostic accuracy for H. pylori infection in Turkish dyspeptic patients 6 weeks after completion of eradication therapy.


Insight into the biology of Mycobacterium mucogenicum and Mycobacterium neoaurum clade members.
Nontuberculous mycobacteria, NTM, are of growing concern and among these members of the Mycobacterium mucogenicum (Mmuc) and Mycobacterium neoaurum (Mneo) clades can cause infections in humans and they are resistant to first-line anti-tuberculosis drugs. They can be isolated from different ecological niches such as soil, tap water and ground water. Mycobacteria, such as Mmuc and Mneo, are classified as rapid growing mycobacteria, RGM, while the most familiar, Mycobacterium tuberculosis, belongs to the slow growing mycobacteria, SGM. Modern "omics" approaches have provided new insights into our understanding of the biology and evolution of this group of bacteria. Here we present comparative genomics data for seventeen NTM of which sixteen belong to the Mmuc- and Mneo-clades. Focusing on virulence genes, including genes encoding sigma/anti-sigma factors, serine threonine protein kinases (STPK), type VII (ESX genes) secretion systems and mammalian cell entry (Mce) factors we provide insight into their presence as well as phylogenetic relationship in the case of the sigma/anti-sigma factors and STPKs. Our data further suggest that these NTM lack ESX-5 and Mce2 genes, which are known to affect virulence. In this context, Mmuc- and Mneo-clade members lack several of the genes in the glycopeptidolipid (GLP) locus, which have roles in colony morphotype appearance and virulence. For the M. mucogenicum type strain, MmucT, we provide RNASeq data focusing on mRNA levels for sigma factors, STPK, ESX proteins and Mce proteins. These data are discussed and compared to in particular the SGM and fish pathogen Mycobacterium marinum. Finally, we provide insight into as to why members of the Mmuc- and Mneo-clades show resistance to rifampin and isoniazid, and why MmucT forms a rough colony morphotype.


Profiling early lung immune responses in the mouse model of tuberculosis.
Tuberculosis (TB) is caused by the intracellular bacteria Mycobacterium tuberculosis, and kills more than 1.5 million people every year worldwide. Immunity to TB is associated with the accumulation of IFNγ-producing T helper cell type 1 (Th1) in the lungs, activation of M.tuberculosis-infected macrophages and control of bacterial growth. However, very little is known regarding the early immune responses that mediate accumulation of activated Th1 cells in the M.tuberculosis-infected lungs. To define the induction of early immune mediators in the M.tuberculosis-infected lung, we performed mRNA profiling studies and characterized immune cells in M.tuberculosis-infected lungs at early stages of infection in the mouse model. Our data show that induction of mRNAs involved in the recognition of pathogens, expression of inflammatory cytokines, activation of APCs and generation of Th1 responses occurs between day 15 and day 21 post infection. The induction of these mRNAs coincides with cellular accumulation of Th1 cells and activation of myeloid cells in M.tuberculosis-infected lungs. Strikingly, we show the induction of mRNAs associated with Gr1+ cells, namely neutrophils and inflammatory monocytes, takes place on day 12 and coincides with cellular accumulation of Gr1+ cells in M.tuberculosis-infected lungs. Interestingly, in vivo depletion of Gr1+ neutrophils between days 10-15 results in decreased accumulation of Th1 cells on day 21 in M.tuberculosis-infected lungs without impacting overall protective outcomes. These data suggest that the recruitment of Gr1+ neutrophils is an early event that leads to production of chemokines that regulate the accumulation of Th1 cells in the M.tuberculosis-infected lungs.


[Schizophrenia and Wilson's disease].
An 18 year-old male first presented a clinical picture of acute psychosis with two recurrences at ages 22 and 23. The diagnosis made at that time was paranoid schizophrenia. Twelve years after his first psychiatric hospitalization, it was discovered that he was suffering from Wilson's disease. In retrospect, the clinical picture was atypical, notably with an important neurologic involvement mainly parkinsonism almost uncontrollable and aggravated with neuroleptics. The chelating treatment with d-penicillamine resulted in partial improvement of the neurological involvement because the extrapyramidal and neurovegetative symptoms persisted. The psychiatric symptoms improved with fewer neuroleptics than during the 12 previous years. However, neuroleptics had to be continued because of the delay in diagnosing the illness, which diminished the efficiency of the single chelating treatment. The clinical presentation and therapeutic response of this patient strongly suggest a link between the cerebral intoxication by copper and the psychiatric symptoms.


Immunosuppression and monocyte subsets.
Monocytes are critical in innate immunity and transplantation. Three monocyte subsets exist, CD14(++)CD16(-), CD14(++)CD16(+) and CD14(+)CD16(++) monocytes; cell counts of CD14(++)CD16(+) and CD14(+)CD16(++) monocytes are increased in pre-transplant chronic kidney disease. Interestingly, the effect of immunosuppressants on monocyte heterogeneity has not been well studied. The impact of immunosuppressants on monocyte subsets was studied: (i) in 152 kidney transplant (KTx) recipients to characterize subset distribution in the steady state, (ii) in patients after autologous (n = 10) versus allogenic (n = 9) haematopoietic stem cell transplantation (HSCT) to analyse monocyte subset development and (iii) in an in vitro model to compare the effect of immunosuppressants on monocyte subset biology. In KTx, steroid intake was associated with higher total, CD14(++)CD16(-) and CD14(++)CD16(+) monocyte counts, but fewer CD14(+)CD16(++) monocytes, whereas intake of mycophenolate, calcineurin inhibitors (CNI) and mammalian target of rapamycin inhibitors (mTORI) did not affect monocyte (subset) counts. In linear regression analysis, only steroid intake was a significant determinant of monocyte (subset) counts: total monocytes (β = 0.331; P < 0.001), CD14(++)CD16(-) monocytes (β = 0.374; P < 0.001), CD14(++)CD16(+) monocytes (β = 0.221; P = 0.010) and CD14(+)CD16(++) monocytes (β = -0.169; P = 0.049). After HSCT, CD14(++)CD16(-) monocytes were the first to arise, followed by CD14(++)CD16(+) and later by CD14(+)CD16(++) monocytes. Monocyte subset distribution did not differ significantly in patients after allogenic compared with autologous transplantation. CNI, mycophenolate and methotrexate did not influence monocyte subset development, but modified surface receptor expression (CCR2, HLA-DR, ENG, TEK and TLR4) in allogenic HSCT. Chronic low-dose steroids are associated with monocytosis and higher counts of CD14(++)CD16(-) and of proinflammatory CD14(++)CD16(+) monocytes.


Element specific determination of the magnetic properties of two macrocyclic tetranuclear 3d-4f complexes with a Cu3Tb core by means of X-ray magnetic circular dichroism (XMCD).
We apply X-ray magnetic circular dichroism to study the internal magnetic structure of two very promising star shaped macrocyclic complexes with a CuII3TbIII core. These complexes are rare examples prepared with a macrocyclic ligand that show indications of SMM (Single Molecule Magnet) behavior, and they differ only in ring size: one has a propylene linked macrocycle, [CuII3TbIII(LPr)(NO3)2(MeOH)(H2O)2](NO3)·3H2O (nickname: Cu3Tb(LPr)), and the other has the butylene linked analogue, [CuII3TbIII(LBu)(NO3)2(MeOH)(H2O)](NO3)·3H2O (nickname: Cu3Tb(LBu)). We analyze the orbital and spin contributions to the Cu and Tb ions quantitatively by applying the spin and orbital sum rules concerning the L2 (M4)/L3 (M5) edges. In combination with appropriate ligand field simulations, we demonstrate that the Tb(iii) ions contribute with high orbital magnetic moments to the magnetic anisotropy, whereas the ligand field determines the easy axis of magnetization. Furthermore, we confirm that the Cu(ii) ions in both molecules are in a divalent valence state, the magnetic moments of the three Cu ions appear to be canted due to 3d-3d intramolecular magnetic interactions. For Cu3Tb(LPr), the corresponding element specific magnetization loops reflect that the Cu(ii) contribution to the overall magnetic picture becomes more important as the temperature is lowered. This implies a low value for the 3d-4f coupling.


Recent developments and future prospects of SPECT myocardial perfusion imaging.
Myocardial perfusion SPECT imaging is the most commonly performed functional imaging for assessment of coronary artery disease. High diagnostic accuracy and incremental prognostic value are the major benefits while suboptimal spatial resolution and significant radiation exposure are the main limitations. Its ability to detect hemodynamic significance of lesions seen on multidetector CT angiogram (MDCTA) has paved the path for a successful marriage between anatomical and functional imaging modalities in the form of hybrid SPECT/MDCTA system. In recent years, there have been enormous efforts by industry and academia to develop new SPECT imaging systems with better sensitivity, resolution, compact design and new reconstruction algorithms with ability to improve image quality and resolution. Furthermore, expected arrival of Tc-99m-labeled deoxyglucose in next few years would further strengthen the role of SPECT in imaging hibernating myocardium. In view of these developments, it seems that SPECT would enjoy its pivotal role in spite of major threat to be replaced by fluorine-18-labeled positron emission tomography perfusion and glucose metabolism imaging agents.


Prevalence and patterns of Moringa oleifera use among HIV positive patients in Zimbabwe: a cross-sectional survey.
Supplementation of conventional medicines with herbs is increasing globally, including among people infected with HIV. Yet there is little data systematically describing the prevalence and patterns of this supplementation and on which counseling scripts can be based. Moringa oleifera is an herb found in the tropics and sub-tropics commonly used for medicinal and nutritional purposes. This survey determined the prevalence and patterns of use of M. oleifera among HIV positive patients. The study was a cross-sectional survey. HIV-infected adults were enrolled from an opportunistic infections clinic of a referral hospital. Using a previously piloted researcher administered questionnaire; patients who reported to the clinic over three months were interviewed about their use of herbal medicines. The focus was on M. oleifera use, and included plant part, dosage, prescribers and the associated medical conditions. Sixty-eight percent (68%) of the study participants consumed M. oleifera. Of these, 81% had commenced antiretroviral drugs. Friends or relatives were the most common source of a recommendation for use of the herb (69%). Most (80%) consumed M. oleifera to boost the immune system. The leaf powder was mainly used, either alone or in combination with the root and/or bark. M. oleifera supplementation is common among HIV positive people. Because it is frequently prescribed by non-professionals and taken concomitantly with conventional medicine, it poses a potential risk for herb-drug interactions. Further experimental investigations into its effect on drug metabolism and transport would be useful in improving clinical outcome of HIV positive patients.


Comparative analysis of the human type 1a and bovine type 1 papillomavirus genomes.
The DNA sequences of the genomes of the bovine type 1 and human type 1a papillomaviruses were compared. The overall organization of both genomes is very similar. Three areas of maximal homology were found in the L1 and E1/E2 genes, and at the beginning of L2. The conservation of homologous amino acid sequences encoded in the open reading frames argues that these segments represent real genes or exons. Within these segments, however, only certain domains of the putative proteins are preferentially conserved. Two polypeptide chains show homologous arrangement of the cysteine residue clusters Cys-X-X-Cys, despite a lack of conservation of the rest of the amino acid sequence. A significant sequence divergence in a region where the three reading frames are open suggests that papillomavirus genomes have evolved not solely by accumulation of point mutations. Conserved sequences were also found in the noncoding region, and their possible involvement in regulation of viral gene expression is discussed.


Measurement of macular pigment optical density in a healthy Chinese population sample.
Macular pigment may protect against age-related macular degeneration (AMD) by its capacity to absorb blue light and scavenge free radicals. Current information on human macular pigment density has been largely from studies on Caucasian populations. The purpose of this study was to assess macular pigment density and its determinant factors in a Chinese population sample. Macular pigment optical density (MPOD) was measured in a healthy Chinese population using heterochromatic flicker photometry (HFP). Participants received a standard ophthalmic examination, and only subjects who were confirmed not to have any eye diseases except mild age-related cataract were included in the study. Demographic and lifestyle data and general health status were recorded by questionnaire. A total of 281 unrelated healthy Chinese individuals, including 96 males and 185 females, with ages ranging from 17 to 85 years, participated in the study. The mean and standard deviation of MPOD levels were 0.56 ± 0.19, 0.49 ± 0.18, 0.36 ± 0.15, and 0.19 ± 0.12, respectively, at 0.25°, 0.5°, 1.0°, and 1.75° eccentricity points. A significant age-related decline in MPOD was observed at 0.25° (P = 0.014). Females tended to have relatively lower levels of MPOD than males at 0.25° (P = 0.21), 0.5° (P = 0.025), and 1.0° (P = 0.16). No statistically significant association of MPOD was observed with body mass index or smoking status. Macular pigment density measured by HFP tended to decline with aging in this healthy Chinese population sample. Females may have lower levels of MPOD than males.


The Danger of Walking with Socks: Evidence from Kinematic Analysis in People with Progressive Multiple Sclerosis.
Multiple sclerosis (MS) is characterized by gait impairments and severely impacts the quality of life. Technological advances in biomechanics offer objective assessments of gait disabilities in clinical settings. Here we employed wearable sensors to measure electromyography (EMG) and body acceleration during walking and to quantify the altered gait pattern between people with progressive MS (PwPMS) and healthy controls (HCs). Forty consecutive patients attending our department as in-patients were examined together with fifteen healthy controls. All subjects performed the timed 10 min walking test (T10MW) using a wearable accelerator and 8 electrodes attached to bilateral thighs and legs so that body acceleration and EMG activity were recorded. The T10MWs were recorded under three conditions: standard (wearing shoes), reduced grip (wearing socks) and increased cognitive load (backward-counting dual-task). PwPMS showed worse kinematics of gait and increased muscle coactivation than controls at both the thigh and leg levels. Both reduced grip and increased cognitive load caused a reduction in the cadence and velocity of the T10MW, which were correlated with one another. A higher coactivation index at the thigh level of the more affected side was positively correlated with the time of the T10MW (r = 0.5, p < 0.01), Expanded Disability Status Scale (EDSS) (r = 0.4, p < 0.05), and negatively correlated with the cadence (r = -0.6, p < 0.001). Our results suggest that excessive coactivation at the thigh level is the major determinant of the gait performance as the disease progresses. Moreover, demanding walking conditions do not influence gait in controls but deteriorate walking performances in PwPMS, thus those conditions should be prevented during hospital examinations as well as in homecare environments.


A framework for studying perceptions of rural healthcare staff and basic ICT support for e-health use: an Indian experience.
Current research observes that electronic healthcare has various advantages, such as easy recording, retrieval, and sharing of patient data anytime and anywhere while providing data privacy. Almost all developed countries currently practice e-health. On the other hand, many developing countries still rely on traditional paper-based healthcare systems that are quite vulnerable to data loss, loss of patients' privacy due to nonsecured data sharing, and mandatory consumption of physical space to store patients' records as stacks of files. India is a developing country that broadly applies a traditional healthcare system. Unfortunately, no studies have been conducted to identify precise reasons why e-health solutions have not been adopted in the Indian primary health centers (PHCs). To fill the research gap, this work is an attempt to propose a complete framework that includes (1) a systematic survey of available resources at the level of healthcare staffs' perceptions toward using e-health and basic information communication technology (ICT) supports at the organizational level and (2) a mathematical model to engineer significant factors for analysis of overall preparedness of the health centers. Healthcare administrators (Block Medical Officer of Health) from each PHC (n = 10) and in total 50 healthcare staff (e.g., doctors, nurses, pharmacists, and midwives) participated in the study. Initially, a systematic survey was conducted to explore the possible factors at the individual (e.g., healthcare personnel) and organizational (e.g., healthcare administration) levels. A questionnaire was generated to capture the data based on the factors identified. The collected data were mathematically modeled to run regressions with significance tests examining the effects of these factors on the level of satisfaction of the end users. The result shows that basic ICT for support at the organizational levels is significantly lacking to implement e-health in these PHCs, although healthcare staffs are ready to use it. Proper measures have to be adopted mostly at the organizational level, such as improving basic ICT support before what will in all probability be a successful implementation and practice of e-health in Indian PHCs.


Identifying MRI markers associated with early response following laser ablation for neurological disorders: preliminary findings.
There is a renewed interest in MR-guided laser interstitial thermal therapy (LITT) as a minimally invasive alternative to craniotomy for local treatment of various brain tumors and epilepsy. LITT allows for focused delivery of laser energy monitored in real time by MRI, for precise ablation of the lesion. Although highly promising, the long-term effects of laser ablation as a viable treatment option for neurological disorders have yet to be rigorously studied and quantified. In this work, we present a quantitative framework for monitoring per-voxel thermal-induced changes post-LITT over time on multi parametric MRI. We demonstrate that voxel-by-voxel quantification of MRI markers over time can enable a careful and accurate (a) characterization of early LITT-related changes (if and when they are exaggerated and when they subside), and (b) identification and monitoring of MRI markers that potentially allow for better quantification of response to LITT therapy. The framework was evaluated on two distinct cohorts of patients (GBM, epilepsy), who were monitored post-LITT at regular time-intervals via multi-parametric MRI. On a cohort of six GBM studies we found that (a) it may be important for the initial treatment-related changes to subside to more reliably capture MRI markers relating to tumor recurrence, and (b) T1w MRI and T2-GRE may better differentiate changes that may correspond to tumor recurrence from patients with no recurrence, as compared to T2w-MRI, and FLAIR. Similarly, our preliminary analysis of four epilepsy studies suggests that (a) early LITT changes (attributed to swelling, edema) appear to subside within 4-weeks post-LITT, and (b) ADC may be more reflective of early treatment changes (up to 1 month), while T1w may be more reflective of early delayed treatment changes (1 month, 3 months), while T2-w and T2-FLAIR appeared to be more sensitive to late treatment related changes (6-months post-LITT) compared to the other MRI protocols under evaluation.