Postural function in idiopathic normal pressure hydrocephalus before and after shunt surgery: a controlled study using computerized dynamic posturography (EquiTest).
Postural dysfunction is one of the major features of idiopathic normal pressure hydrocephalus (iNPH). With computerized dynamic posturography (CDP) balance can be assessed objectively. The primary aim of this study was to describe the postural function in iNPH patients pre- and post-operatively in comparison with healthy individuals (HI) using CDP. Thirty-five patients (16 M, 19 F) with a mean age of 73 (range 49-81) with iNPH, and sixteen HI (7 M, 9 F) aged 73 (62-89) were included. iNPH patients were operated on with a ventriculo-peritoneal shunt. Patients and HI were tested regarding motor function, balance and cognition. CDP, EquiTest (NeuroCom International, Clackamas, OR), was performed before and three months after shunt surgery and twice in HI, with a three-month interval. Pre-operatively, the 35 patients had poorer balance measured with the Sensory Organizing Test (SOT) score in every condition (p=0.01 in SOT 1 and p<0.001 in SOT 2-6) compared to the HI. The greatest difference was in test conditions measuring mainly vestibular function, where loss of balance (LOB) was frequent. Twenty patients were evaluated three months after shunt surgery and 18/20 (90%) of them were considered shunt responders, with a mean improvement of motor score of 26% (range 5-67%). There was an improvement post-operatively in the weighted composite SOT score (p<0.05) but no significant change in any of the SOT conditions. LOB was not significantly reduced in any of the test conditions. CDP showed that the patients had a poorer balance than the HI. The greatest difference was in SOT 5-6, indicating that the postural disturbance is of primarily central vestibular origin. There was a slight improvement of balance post-operatively.


Analysis of fetal biometric measurements in the last 30 years.
To compare fetal biometric measurements with standard growth charts for ultrasound parameters existing from the last 30 years. A preliminary prospective study. Artemisia Mean Centre of Perinatal Diagnosis, Rome,Italy. A cross sectional study involving 1000 pregnant women with uncomplicated singleton pregnancy between 14(th) and 41(th) weeks of gestation from 1 January to 30 June 2008. All recruited pregnant women enrolled had an abdominal ultrasonography for fetal biometry. For each measurement, regression models were fitted to estimate the mean and SD. The results were compared with existing references from the last 30 years using Student's T distribution. Moreover, neonatal weights were obtained from 1977 to 2008 by ISTAT. One thousand normal fetuses from pregnant women, between 22(th) and 23(th) weeks, between 32(th) and 33(th) weeks and at 38(th) week, were thoroughly measured. THERE WERE SIGNIFICANT DIFFERENCES FROM THE COMPARISON WITH OUR DATA FOR EACH GESTATIONAL AGE: femur length and homer length, abdominal circumference, head circumference and occipitofrontal diameter were longer than all parameters of existing references from the last 30 years. The analysis of neonatal weights on ISTAT data from 1977 to 2007 demonstrated a significant increment through the years. Fetus is grown up across the years. It is necessary to modify the standard growth charts for ultrasound parameters existing from the last 30 years with actually fetal biometric measurements. It is helpful for a correct clinical approach and for an appropriate management mother-fetus.


The costs of dominance: testosterone, cortisol and intestinal parasites in wild male chimpanzees.
Male members of primate species that form multi-male groups typically invest considerable effort into attaining and maintaining high dominance rank. Aggressive behaviors are frequently employed to acquire and maintain dominance status, and testosterone has been considered the quintessential physiological moderator of such behaviors. Testosterone can alter both neurological and musculoskeletal functions that may potentiate pre-existing patterns of aggression. However, elevated testosterone levels impose several costs, including increased metabolic rates and immunosuppression. Cortisol also limits immune and reproductive functions. To improve understanding of the relationships between dominance rank, hormones and infection status in nonhuman primates, we collected and analyzed 67 fecal samples from 22 wild adult male chimpanzees (Pan troglodytes schweinfurthii) at Ngogo, Kibale National Park, Uganda. Samples were analyzed for cortisol and testosterone levels as well as intestinal parasite prevalence and richness. 1,700 hours of observation data were used to determine dominance rank of each animal. We hypothesized that dominance rank would be directly associated with fecal testosterone and cortisol levels and intestinal parasite burden. Fecal testosterone (but not cortisol) levels were directly associated with dominance rank, and both testosterone and cortisol were directly associated with intestinal parasite richness (number of unique species recovered). Dominance rank was directly associated with helminth (but not protozoan) parasite richness, so that high ranking animals had higher testosterone levels and greater helminth burden. One preliminary interpretation is that the antagonist pleiotropic effects of androgens and glucocorticoids place a cost on attaining and maintaining high dominance rank in this species. Because of the costs associated with elevated steroid levels, dominance status may be an honest signal of survivorship against helminth parasites.


Fuzhuan Brick Tea Polysaccharides Attenuate Metabolic Syndrome in High-Fat Diet Induced Mice in Association with Modulation in the Gut Microbiota.
An increasing amount of evidence suggests that the gut microbiota composition and structure contribute to the pathophysiology of metabolic syndrome (MS), which has been put forward as a new target in the treatment of diet-induced MS. In this work, we aimed to investigate effects of Fuzhuan brick tea polysaccharides (FBTPS) on MS and gut microbiota dysbiosis in high-fat diet (HFD) fed mice and to further investigate whether its attenuation of MS is related to the modulation of gut microbiota. The results showed that FBTPS intervention could significantly attenuate metabolic syndrome in HFD-induced mice. Based on results of sequencing, FBTPS treatment could increase the phylogenetic diversity of HFD-induced microbiota. FBTPS intervention could significantly restore the HFD-induced increases in relative abundances of Erysipelotrichaceae, Coriobacteriaceae, and Streptococcaceae. Spearman's correlation analysis showed that 44 key OTUs were negatively or positively associated with MS. Our results suggested that FBTPS could serve as a novel candidate for prevention of MS in association with the modulation of gut microbiota.


[Absnece of amyloid protein in the organs of normal mice].
The immunomorphological Coons' method (its indirect variant) was used to discover specific amyloid protein AA in the organs of mice with experimental amyloidosis and normal mice (adult, newborn, embryo). The use of pure antiprotein-AA-antibodies allowed to reveal the minimal deposits of amyloid protein at the earliest stages of amyloidogenesis. The organs of normal mice (adult, newborn, embryo) did not contain this protein.


Acute reciprocal changes distant from the site of spinal osteotomies affect global postoperative alignment.
Introduction. Three-column vertebral resections are frequently applied to correct sagittal malalignment; their effects on distant unfused levels need to be understood. Methods. 134 consecutive adult PSO patients were included (29 thoracic, 105 lumbar). Radiographic analysis included pre- and postoperative regional curvatures and pelvic parameters, with paired independent t-tests to evaluate changes. Results. A thoracic osteotomy with limited fusion leads to a correction of the kyphosis and to a spontaneous decrease of the unfused lumbar lordosis (-8°). When the fusion was extended, the lumbar lordosis increased (+8°). A lumbar osteotomy with limited fusion leads to a correction of the lumbar lordosis and to a spontaneous increase of the unfused thoracic kyphosis (+13°). When the fusion was extended, the thoracic kyphosis increased by 6°. Conclusion. Data from this study suggest that lumbar and thoracic resection leads to reciprocal changes in unfused segments and requires consideration beyond focal corrections.


Generating genius: how an Alzheimer's drug became considered a 'cognitive enhancer' for healthy individuals.
Donepezil, an acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease, has been widely cited in media and bioethics literature on cognitive enhancement (CE) as having the potential to improve the cognitive ability of healthy individuals. In both literatures, this claim has been repeatedly supported by the results of a small study published by Yesavage et al. in 2002 on non-demented pilots (30-70 years old). The factors contributing to this specific interpretation of this study's results are unclear. We examined print media and interdisciplinary bioethics coverage of this small study, aiming to provide insight into how evidence from research may be shaped within different discourses, potentially influencing important policy, ethics, and clinical decisions. Systematic qualitative content analysis was used to examine how this study was reported in 27 media and 22 bioethics articles. Articles were analyzed for content related to: (1) headlines and titles; (2) colloquialisms; and, (3) accuracy of reporting of the characteristics and results of the study. In media and bioethics articles referencing this small study, strong claims were made about donepezil as a CE drug. The majority of headlines, titles, and colloquialisms used enhancement language and the majority of these suggest that donepezil could be used to enhance intellectual ability. Further, both literatures moved between reporting the results of the primary study and magnifying the perceived connection between these results and the CE debate that was alluded to in the primary study. Specific descriptions of the results overwhelmingly reported an improvement in performance on a flight simulator, while more general statements claimed donepezil enhanced cognitive performance. Further, a high level of reporting accuracy was found regarding study characteristics of the original study, but variable levels of accuracy surrounded the presentation of complex characteristics (i.e., methods) or contentious properties of the CE debate (i.e., initial health status of the study subjects). Hyped claims of CE effects cannot be completely accounted for by sheer inaccuracy in reporting. A complex interaction between the primary and secondary literature, and expectations and social pressures related to CE appears to drive enthusiastic reports.


Multilevel Lumbar Stenosis Caused by Large Tophi Involving Both Spinal Canal and Posterior Spinal Elements: A Rare Case Report and Literature Review.
Tophus is a characteristic manifestation of gout entering the chronic phase, which usually deposits in the joints of the extremities, skin mucosa, etc. A gout tophus that involves the spine causing spinal stenosis is rare and it can be misdiagnosed as a spinal tumor preoperatively. We report the case of a 35-year-old man who presented with lumbar stenosis symptoms, and suffered multiple-site gout tophi involvement throughout his body. Radiographic examinations showed that the large tophi infiltrated the posterior elements of the spine and encroached the lumbar spinal canal, resulting in neurologic compression from the second to the fifth lumbar level. Urate could be observed on a dual-energy computed tomography. A posterior-based procedure was performed to eradicate the tophi and stabilize the spine. Finally, urate crystal was confirmed by postoperative pathological examination. Here, the clinical manifestations, radiological, pathological and surgical features for this case are reported.


Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung.
mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody-binding titers also decreased in bronchoalveolar lavage (BAL). Four days after Delta challenge, the virus was unculturable in BAL, and subgenomic RNA declined by ∼3-log10 compared with control animals. In nasal swabs, sgRNA was reduced by 1-log10, and the virus remained culturable. Anamnestic antibodies (590-fold increased titer) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.


APC/CFZR-1 Controls SAS-5 Levels To Regulate Centrosome Duplication in Caenorhabditis elegans.
As the primary microtubule-organizing center, centrosomes play a key role in establishing mitotic bipolar spindles that secure correct transmission of genomic content. For the fidelity of cell division, centrosome number must be strictly controlled by duplicating only once per cell cycle. Proper levels of centrosome proteins are shown to be critical for normal centrosome number and function. Overexpressing core centrosome factors leads to extra centrosomes, while depleting these factors results in centrosome duplication failure. In this regard, protein turnover by the ubiquitin-proteasome system provides a vital mechanism for the regulation of centrosome protein levels. Here, we report that FZR-1, the Caenorhabditis elegans homolog of Cdh1/Hct1/Fzr, a coactivator of the anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase, functions as a negative regulator of centrosome duplication in the C. elegans embryo. During mitotic cell division in the early embryo, FZR-1 is associated with centrosomes and enriched at nuclei. Loss of fzr-1 function restores centrosome duplication and embryonic viability to the hypomorphic zyg-1(it25) mutant, in part, through elevated levels of SAS-5 at centrosomes. Our data suggest that the APC/CFZR-1 regulates SAS-5 levels by directly recognizing the conserved KEN-box motif, contributing to proper centrosome duplication. Together, our work shows that FZR-1 plays a conserved role in regulating centrosome duplication in C. elegans.


Prevalence of Hypertension and Associated Factors Among Adults in Debre Berhan Town, North Shoa Zone, Ethiopia, 2020.
Hypertension is a serious medical condition that significantly increases the risks of heart, brain, kidney, and other diseases. The prevalence is highest in Africa (27%) and lowest in America (18%). Hypertension is a major reason for premature death worldwide; this is why it will become a targeted non-communicable disease by 2025. To assess the prevalence of hypertension and associated factors among adults in Debre Berhan town, Amhara region, Ethiopia. A community-based cross-sectional study was conducted among 680 participants who were selected by a systematic sampling technique. Data were checked, cleaned, and entered into Epi-data then exported to SPSS-23 for analysis. Hosmer-Lemeshow test was used to check the model fitness. Binary logistic regression analysis was used to see the association between dependent and independent variables. All variables with p <0.25 were taken into the multivariable model to minimize the possible confounders. The multi collinearity test was carried out to see the correlation between independent variables by using a variance inflation factor (VIF). The odds ratio along with 95% CI were estimated to measure the strength of association and to identify factors associated with hypertension using multivariable logistic regression. Descriptive statistics in the form of tables, figures, percent with measure of central tendency and dispersion with multivariable analysis were used to report the findings and to identify the factors associated with the outcome variable at a p<0.05. Among 680 participants, the prevalence of hypertension was 27.5%. Sex, being male (AOR: 1.77, 95% CI: 1.12-2.81), alcohol consumption (AOR: 2.76: 95% CI: 1.87-4.05), physical exercise (AOR: 2.17, 95% CI: 1.28-3.71), being overweight (AOR: 1.99, 95% CI: 1.11-3.58), and family history of hypertension (AOR: 2.10, 95% CI: 1.43-3.08) were found to be significantly associated with hypertension. Prevalence of hypertension in Debre Berhan town was relatively high compared with other studies. So, it is necessary to emphasize intervention in the community for behavioral change, in order to minimize alcohol consumption and to encourage adoption of regular physical exercise, with the existing health system and partners working on hypertension.


Sex differences in the age-related decrease of spontaneous baroreflex function in healthy individuals.
The baroreflex is a powerful physiological mechanism for rapidly adjusting heart rate in response to changes in blood pressure. Spontaneous baroreflex sensitivity (BRS) has been shown to decrease with age. However, studies of sex differences in these age-related changes are rare. Here we investigated several markers of spontaneous baroreflex function in a large sample of healthy individuals. Cardiovascular signals were recorded in the supine position under carefully controlled resting conditions. After quality control, n = 980 subjects were divided into five age groups [age < 30 yr (n = 612), 30-39 yr (n = 140), 40-49 yr (n = 95), 50-59 yr (n = 61), and >60 yr (n = 72)]. Spontaneous baroreflex function was assessed in the time domain (bradycardic and tachycardic slope) and in the frequency domain in the low- and high-frequency band (LF-α, HF-α) applying the transfer function. General linear models showed a significant effect of factor age (P < 0.001) and an age × sex interaction effect (P < 0.05) on each indicator of the baroreflex function. Simple main effects showed a significantly higher BRS as indicated by tachycardic slope, LF-α and HF-α in middle-aged women compared with men (30-39 yr) and higher LF-α, bradycardic and tachycardic slope in men compared with women of the oldest age group (>60 yr). Changes in BRS over the lifespan suggest that baroreflex function declines more slowly but earlier in life in men than in women. Our findings could be linked to age-related changes in major sex hormone levels, suggesting significant implications for diverse cardiovascular outcomes and the implementation of targeted preventive strategies.NEW & NOTEWORTHY In this study, we demonstrate that the age-related decrease of spontaneous baroreflex sensitivity is different in men and women by analyzing resting state cardiovascular data of a large sample of healthy individuals.


Impact of various types of near work and time spent outdoors at different times of day on visual acuity and refractive error among Chinese school-going children.
Various types of near work have been suggested to promote the incidence and progression of myopia, while outdoor activity appears to prevent or retard myopia. However, there is a lack of consensus on how to interpret these results and translate them into effective intervention strategies. This study examined the association between visual acuity and time allocated to various activities among school-going children. Population-based survey of 19,934 students in grade 4 and 5 from 252 randomly selected rural primary schools in Northwest China in September 2012. This survey measured visual acuity and collected self-reported data on time spent outdoors and time spent doing various types of near activities. Prolonged (>60 minutes/day) computer usage (-0.025 LogMAR units, P = .011) and smartphone usage (-0.041 LogMAR units, P = .001) were significantly associated with greater refractive error, while television viewing and after-school study were not. For time spent outdoors, only time around midday was significantly associated with better uncorrected visual acuity. Compared to children who reported no midday time outdoors, those who spent time outdoors at midday for 31-60 minutes or more than 60 minutes had better uncorrected visual acuity by 0.016 LogMAR units (P = .014) and 0.016 units (P = .042), respectively. Use of smart phones and computers were associated with declines in children's vision, while television viewing was not. Statistically significant associations between outdoor time at midday and reduced myopia may support the hypothesis that light intensity plays a role in the protective effects of outdoor time.


Euthanasia in Belgium: legal, historical and political review.
This article describes and evaluates the Belgian euthanasia experience by considering its practice and policy, both before and after the formal decriminalisation of euthanasia in 2002. The pre-legal practice of euthanasia, the evolution of euthanasia legislation, criticism of this legislation, the influence of politics, and later changes to the 2002 Act on Euthanasia are discussed, as well as the subject of euthanasia of minors and the matter of organ procurement. It is argued that the Belgian euthanasia experience is characterised by political expedition, and that the 2002 Act and its later amendments suffer from practical and conceptual flaws. Illegal euthanasia practices remain a live concern in Belgium, something which nations who are seeking to decriminalise euthanasia should consider.


Contributions of depressive mood and circulating inflammatory markers to coronary heart disease in healthy European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).
Data on the possible association between depressive disorders and inflammatory markers are scarce and inconsistent. We investigated whether subjects with depressive mood had higher levels of a wide range of inflammatory markers involved in coronary heart disease (CHD) incidence and examined the contribution of these inflammatory markers and depressive mood to CHD outcome. We built a nested case-referent study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study of healthy middle-aged men from Belfast and France. We considered the baseline plasma sample from 335 future cases (angina pectoris, nonfatal myocardial infarction, coronary death) and 670 matched controls (2 controls per case). Depressive mood characterized men whose baseline depression score (13-item modification of the Welsh depression subscale) was in the fourth quartile (mean score, 5.75; range, 4 to 12). On average, men with depressive mood had 46%, 16%, and 10% higher C-reactive protein, interleukin-6, and intercellular adhesion molecule-1 levels, respectively, independently of case-control status, social characteristics, and classic cardiovascular risk factors; no statistical difference was found for fibrinogen. The odds ratios of depressive mood for CHD were 1.35 (95% CI, 1.05 to 1.73) in univariate analysis and 1.50 (95% CI, 1.04 to 2.15) after adjustment for social characteristics and classic cardiovascular risk factors. The latter odds ratio remained unchanged when each inflammatory marker was added separately, and in this analysis, each inflammatory marker contributed significantly to CHD event risk. These data support an association of depressive mood with inflammatory markers and suggest that depressive mood is related to CHD even after adjustment for these inflammatory markers.


Sex chromosome evolution and Haldane's rule.
Haldane observed that where interspecies hybrids show sex differences in sex ratio or fertility, it is always heterogametic sex which is affected. Many hypotheses have been advanced to explain Haldane's rule, but it is difficult to find a unifying explanation that will accommodate male and female heterogamety, and explains why fertility, especially, is affected. Here we propose that asymmetry can be accounted for by interactions involved in determining male dimorphisms or fertility between genes which diverged from allele pairs on the X and Y. Failure of one or more heterospecific interactions will render the male sterile. Similar arguments may be made for other groups with male or female heterogamety, and the argument can be extended to account for Y- (or W-) autosome interactions.


Microbiology challenges and opportunities in the circular economy.
Our knowledge and understanding of micro-organisms have led to the development of safe food, clean water, novel foods, antibiotics, vaccines, healthier plants, animals and soils, and more, which feeds into the United Nations Sustainable Development Goals (UN SDGs). The circular economy can contribute to the UN SDGs and micro-organisms are central to circular nutrient cycles. The circular economy as described by the Ellen MacArthur foundation has two halves, i.e. technical and biological. On the technical side, non-biological resources enter manufacturing paths where resource efficiency, renewable energy and design extend the life of materials so that they are more easily reused and recycled. Biological resources exist on the other half of the circular economy. These are used to manufacture products such as bioplastics and paper. The conservation of nature's stocks, resource efficiency and recycling of materials are key facets of the biological half of the circular economy. Microbes play a critical role in both the biological and technical parts of the circular economy. Microbes are key to a functioning circular economy, where natural resources, including biological wastes, are converted by microbes into products of value and use for society, e.g. biogas, bioethanol, bioplastics, building block chemicals and compost for healthy soils. In more recent times, microbes have also been seen as part of the tool kit in the technical side of the circular economy, where microbial enzymes can degrade plastics and microbes can convert those monomers to value-added products.


Encapsulation Capacity of β-Cyclodextrin Stabilized Silver Nanoparticles towards Creatinine Enhances the Colorimetric Sensing of Hydrogen Peroxide in Urine.
The β-cyclodextrin shell of synthesized silver nanoparticles (βCD-AgNPs) are found to enhance the detection of hydrogen peroxide in urine when compared to the Horse Radish Peroxidase assay kit. Nanoparticles are confirmed by the UV-Vis absorbance of their localized surface plasmonic resonance (LSPR) at 384 nm. The mean size of the βCD-AgNPs is 53 nm/diameter; XRD analysis shows a face-centered cubic structure. The crystalline structure of type 4H hexagonal nature of the AgNPs with 2.4 nm β-CD coating onto is confirmed using aberration corrected high-resolution transmission electron microscopy (HRTEM). A silver atomic lattice at 2.50 Å and 2.41 Å corresponding to (100) and (101) Miller indices is confirmed using the HRTEM. The scope of βCD-AgNPs to detect hydrogen peroxide (H2O2) in aqueous media and human urine is investigated. The test is optimized by examining the effect of volumes of nanoparticles, the pH of the medium, and the kinetic and temperature effect on H2O2 detection. The βCD-AgNPs test is used as a refined protocol, which demonstrated improved sensitivity towards H2O2 in urine compared to the values obtained by the Horse Radish Assay kit. Direct assessment of H2O2 by the βCD-AgNPs test presented always with a linear response in the nM, μM, and mM ranges with a limit of detection of 1.47 nM and a quantitation limit of 3.76 nM. While a linear response obtained from 1.3 to 37.3 nmoles of H2O2/mole creatinine with a slope of 0.0075 and regression coefficient of 0.9955 when the βCD-AgNPs is used as refined test of creatinine. Values ranging from 34.62 ± 0.23 nmoles of H2O2/mole of creatinine and 54.61 ± 1.04 nmoles of H2O2/mole of creatinine when the matrix is not diluted and between 32.16 ± 0.42 nmoles of H2O2/mole of creatinine and 49.66 ± 0.80 nmoles of H2O2/mole of creatinine when the matrix is twice diluted are found in freshly voided urine of seven apparent healthy men aged between 20 and 40 years old.


Ranging of male Oropsylla montana fleas via male California ground squirrel (Spermophilus beecheyi) juveniles.
We asked if fleas more frequently remain on those California ground squirrels (Spermophilus beecheyi) that are likely to emigrate from their natal nest. In Camp Ohlone, Alameda County, California, juvenile male squirrels were infested with more fleas (Oropsylla montana) than were juvenile females, and juveniles of both sexes were infested with more fleas (O. montana and Hoplopsyllus anomalus) than adults. There was no difference between the adult sexes in the number of fleas. The disproportionate infestation of male juveniles was accounted for almost exclusively by male O. montana. Greater activity on the part of juvenile males did not account for this difference; the activity of male and female juveniles was very similar. As yearlings, male squirrels established home ranges at greater distances from the natal burrow than did females. Remaining on ranging male squirrels might help male fleas find nonsibling mates in new nests, whereas female fleas might tend to stay in the natal nest in order to assure their progeny of its resources. Flea behavior, modified by characteristics of the host that are sex-specific and predictive of future traits, such as the tendency to range, may thus determine the nature and extent of infestations in juvenile squirrels.


Quantitative MRI Characterization of the Extremely Preterm Brain at Adolescence: Atypical versus Neurotypical Developmental Pathways.
Background Extremely preterm (EP) birth is associated with higher risks of perinatal white matter (WM) injury, potentially causing abnormal neurologic and neurocognitive outcomes. MRI biomarkers distinguishing individuals with and without neurologic disorder guide research on EP birth antecedents, clinical correlates, and prognoses. Purpose To compare multiparametric quantitative MRI (qMRI) parameters of EP-born adolescents with autism spectrum disorder, cerebral palsy, epilepsy, or cognitive impairment (ie, atypically developing) with those without (ie, neurotypically developing), characterizing sex-stratified brain development. Materials and Methods This prospective multicenter study included individuals aged 14-16 years born EP (Extremely Low Gestational Age Newborns-Environmental Influences on Child Health Outcomes Study, or ELGAN-ECHO). Participants underwent 3.0-T MRI evaluation from 2017 to 2019. qMRI outcomes were compared for atypically versus neurotypically developing adolescents and for girls versus boys. Sex-stratified multiple regression models were used to examine associations between spatial entropy density (SEd) and T1, T2, and cerebrospinal fluid (CSF)-normalized proton density (nPD), and between CSF volume and T2. Interaction terms modeled differences in slopes between atypically versus neurotypically developing adolescents. Results A total of 368 adolescents were classified as 116 atypically (66 boys) and 252 neurotypically developing (125 boys) participants. Atypically versus neurotypically developing girls had lower nPD (mean, 557 10 × percent unit [pu] ± 46 [SD] vs 573 10 × pu ± 43; P = .04), while atypically versus neurotypically developing boys had longer T1 (814 msec ± 57 vs 789 msec ± 82; P = .01). Atypically developing girls versus boys had lower nPD and shorter T2 (eg, in WM, 557 10 × pu ± 46 vs 580 10 × pu ± 39 for nPD [P = .006] and 86 msec ± 3 vs 88 msec ± 4 for T2 [P = .003]). Atypically versus neurotypically developing boys had a more moderate negative association between T1 and SEd (slope, -32.0 msec per kB/cm3 [95% CI: -49.8, -14.2] vs -62.3 msec per kB/cm3 [95% CI: -79.7, -45.0]; P = .03). Conclusion Atypically developing participants showed sexual dimorphisms in the cerebrospinal fluid-normalized proton density (nPD) and T2 of both white matter (WM) and gray matter. Atypically versus neurotypically developing girls had lower WM nPD, while atypically versus neurotypically developing boys had longer WM T1 and more moderate T1 associations with microstructural organization in WM. © RSNA, 2022 Online supplemental material is available for this article.


Unstable fractures and dislocations of the pelvic ring--results of treatment in relation to the severity of injury.
Between 1968 and 1984, III patients were treated for unstable fractures of the pelvic ring. Cause, incidence, accompanying local lesions, mortality, Injury Severity Score (ISS) and mode of treatment were retrospectively analysed. ISS and mortality were closely correlated. The overall mortality was 19% and the average ISS 53. The mortality of the conservatively treated patients was 21.8%, for the operative group the mortality was 8.3%, while the ISS was the same in both groups. From these results we conclude that unstable pelvic fractures, which are almost invariably associated with other serious injuries, should be treated aggressively by external and/or internal fixation.


Biological role of tyrosinase related protein and its biosynthesis and transport from TGN to stage I melanosome, late endosome, through gene transfection study.
Tyrosinase-related protein (TRP)-1 is one of the most abundant melanosomal glycoproteins involved in melanogenesis. This report summarizes our recent research efforts related to the biological role and biosynthesis of TRP-1 and its transport from TGN (trans-Golgi network) to the stage I melanosome. Our UV irradiation and tyrosinase and TRP-1 cDNA co-transfection studies indicated that human TRP-1 is involved in not only melanogenesis but also prevention of melanocyte death, which may occur during biosynthesis of melanin pigment in the presence of tyrosinase. Furthermore, a coordinated gene interaction was indicated between tyrosinase and TRP-1, resulting in upregulation of mRNA and protein expression of LAMP (lysosome-associated membrane protein)-1 that would directly prevent the tyrosinase-mediated programmed cell death of melanocytes. Similar to tyrosinase, however, TRP-1 appears to require a molecular chaperone, calnexin, which we have cloned recently. Our cDNA transfection study of tyrosinase with calnexin showed clearly the necessity of calnexin in order to have efficient, functional activity of melanosomal glycoprotein, especially tyrosinase. Once glycosylation is completed, TRP-1 will be transported from TGN to the stage I melanosome. At this stage, TRP-1 will have its own target signal, in particular, tyrosine-rich leucine residues in cytoplasmic tail. Our TRP-1 cDNA transfection and immunoelectron microscopy study shows that TRP-1 will be transported through small vesicles, probably non-clathrin-coated type, to large vacuoles, identical to the MPR (mannose-6-phosphate receptor)-positive, late endosomes. In this transport process a low molecular weight G-protein, rab-7, was isolated from the purified melanosomal protein on 2D-PAGE and identified by subsequent sequencing and PCR amplification. Confocal microscopy with double immunostaining and immunoelectron microscopy confirmed the co-localization of rab-7 and TRP-1 in the melanosomes with early stages of maturation (I-HI). Furthermore, this process will also be regulated by phosphatidylinositol 3-kinase (PI-3 kinase).


Performance of Traditional Pretest Probability Estimates in Stable Patients Undergoing Myocardial Perfusion Imaging.
The yield of myocardial perfusion imaging is low in contemporary patients with suspected coronary artery disease (CAD) selected based on American College of Cardiology Foundation/American Heart Association pretest probability estimate. We compared traditional pretest estimates of CAD probability with the prevalence of abnormal myocardial perfusion single-photon emission computed tomography (MPS). This was a cohort study from a single academic center. Consecutive stable patients without known CAD referred for stress MPS for suspected CAD between 2004 and 2011 were identified (n=15 777). Angina typicality was determined using standard criteria. Abnormal MPS perfusion was defined as a summed stress score ≥4, ischemia as summed stress score ≥4 and summed difference score ≥2, and extensive ischemia as summed difference score ≥8 using a standard, 17-segment model of the left ventricle. The pretest probability of CAD was determined using the American College of Cardiology Foundation/American Heart Association criteria. Overall, 14% (n=2177) of patients had abnormal MPS of whom 11% (n=1698) had ischemia and 4% (n=684) extensive ischemia. In patients with chest pain who underwent treadmill MPS (n=4764), only 27% reported angina on the treadmill. Typical angina was associated with the highest prevalence for positive MPS (33% in men and 14% in women), ischemia (30% in men and 12% in women), and extensive ischemia (22% in men and 4% in women) when compared with other symptom categories. Prevalence of MPS abnormality was substantially lower than expected based on pretest probability estimates across most sex and age groups. In multivariable analysis, the pretest probability estimate was not an independent predictor of abnormal MPS. Traditional estimates of pretest probability of CAD are not predictive of MPS perfusion abnormality and overestimate its prevalence in stable patients.


Epoxynemanione A, nemanifuranones A-F, and nemanilactones A-C, from Nemania serpens, an endophytic fungus isolated from Riesling grapevines.
Ten polyketide specialized metabolites, epoxynemanione A, nemanifuranones A-F, and nemanilactones A-C, were isolated from the culture filtrate of Nemania serpens (Pers.) Grey (1821), an endophytic fungus from a Riesling grapevine (Vitis vinifera) found in Canada's Niagara region. Additionally, four known metabolites 2-(hydroxymethyl)-3-methoxy-benzoic acid, phyllostine, 5-methylmellein and a nordammarane triterpenoid were isolated. A related known metabolite 2,3-dihydro-2-hydroxy-2,4-dimethyl-5-trans-propenylfuran-3-one has also been included for structural and biological comparison to the nemanifuranones. The latter was isolated from the culture filtrates of Mollisia nigrescens, an endophytic fungus from the leaves and stems of lowbush blueberry (Vaccinium angustifolium) found in the Acadian forest of Nova Scotia, Canada. Their structures were elucidated based on 1D and 2D NMR, HRESIMS measurements, X-ray crystallographic analysis of nemanifuranone A, the nordammarane triterpenoid and 2,3-dihydro-2-hydroxy-2,4-dimethyl-5-trans-propenylfuran-3-one compounds, and comparison of NOE and vicinal 1H-1H coupling constants to literature data for relative stereochemical assignments. Nemanifuranone A possesses a rare C2 hemiacetal and was active against both Gram-negative and Gram-positive bacteria.


[Neurochemical mechanisms of depression-like behavior in WAG/Rij rats].
Behavior in the light-dark choice, open-field, sucrose consumption/preference and forced swimming tests, monoamines and their metabolites level in 6 brain structures (prefrontal cortex, nucleus accumbens, striatum, hypothalamus, hippocampus, amygdala), and density of D2-like dopamine receptors in 21 brain regions were studied in WAG/Rij and Wistar rats. WAG/Rij rats exhibited symptoms of depression-like behavior such as increased immobility in the forced swim test and decreased sucrose consumption/preference (anhedonia). Substantial changes in behavior indicating increased anxiety in WAG/Rij rats were not revealed. Neurochemical abnormalities suggesting hypofunction of the mesolimbic dopaminergic brain system were found in "depressive" WAG/Rij rats compared with "normal" Wistar rats: decreased levels of noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine in the nucleus accumbens, and increased density of D2-like dopamine receptors in the nucleus accumbens and ventral tegmental area. Reduced levels of dopamine were also observed in the prefrontal cortex and striatum. No substantial changes in the content of monoamines and their metabolites have been revealed in the hypothalamus, hippocampus and amygdala as well as in the content ofserotonin and its metabolite 5-hydroxyindolacetic acid in all studied brain structures with the exception of increased level ofserotonin in the amygdala. Results suggest that hypofunction of the mesolimbic dopaminergic brain system (nucleus accumbens) is a neurochemical mechanism of depression-like behavior in WAG/Rij rats.


Assessing Cognitive Skills in Early Childhood Education Using a Bilingual Early Language Learner Assessment Tool.
In this article, we propose that basic cognitive skills may be fostered and assessed in early childhood educational (pre-K) settings using a technology-based approach to assessment. BELLA (Bilingual English Language Learner Assessment), designed for use with both monolingual (English or Spanish speaking) and bilingual (English and Spanish speaking) children, is designed to attend to cognitive skill development in addition to (pre-)academic knowledge. Specifically, BELLA assesses analytical, creative, and practical thinking in 3-5-year-old children through unique item content and delivery. BELLA is among the first tablet-based pre-K assessments designed to assess cognitive skills needed for the era of the Anthropocene.


Recent advances in cotton genomics.
Genome research promises to promote continued and enhanced plant genetic improvement. As a world's leading crop and a model system for studies of many biological processes, genomics research of cottons has advanced rapidly in the past few years. This article presents a comprehensive review on the recent advances of cotton genomics research. The reviewed areas include DNA markers, genetic maps, mapped genes and QTLs, ESTs, microarrays, gene expression profiling, BAC and BIBAC libraries, physical mapping, genome sequencing, and applications of genomic tools in cotton breeding. Analysis of the current status of each of the genome research areas suggests that the areas of physical mapping, QTL fine mapping, genome sequencing, nonfiber and nonovule EST development, gene expression profiling, and association studies between gene expression and fiber trait performance should be emphasized currently and in near future to accelerate utilization of the genomics research achievements for enhancing cotton genetic improvement.


"Dirty like a Tenant": Migration and Embodied Dispositions in Malawi.
Much has been written about how structural (e.g. colonialism) and social (e.g. gender) determinants shape embodied health outcomes. However, little attention has been paid to the ways that marginalized populations become complicit in their own oppression. Ethnographic data collected over two years at a rural public hospital in Malawi show that the tobacco political economy produces significant intra-rural inequalities that result in the exclusion of migrant farm workers, called "tenants," from HIV care. Using an analytical framework informed by Bourdieu's concepts of social field and habitus, I illustrate how social inequalities persist unchallenged, even by the most disadvantaged people.


Selection and Transmission of Antibiotic-Resistant Bacteria.
Ever since antibiotics were introduced into human and veterinary medicine to treat and prevent bacterial infections there has been a steady selection and increase in the frequency of antibiotic resistant bacteria. To be able to reduce the rate of resistance evolution, we need to understand how various biotic and abiotic factors interact to drive the complex processes of resistance emergence and transmission. We describe several of the fundamental factors that underlay resistance evolution, including rates and niches of emergence and persistence of resistant bacteria, time- and space-gradients of various selective agents, and rates and routes of transmission of resistant bacteria between humans, animals and other environments. Furthermore, we discuss the options available to reduce the rate of resistance evolution and/ or transmission and their advantages and disadvantages.


Analysis of the coupled flows of aluminum and copper in household air conditioning system.
The global "copper-poor and aluminum-rich" situation has made the possibility of "copper saving with aluminum" an important topic. This study established a framework for analyzing multiple substances' coupled flows at the product level based on material flow analysis (MFA), and took the household air conditioning system of the Chinese mainland in 2020 as an example to characterize the coupled flows of aluminum and copper. The results showed that the system consumed 0.69 million tons of aluminum and 2.10 million tons of copper, and discharged 0.17 million tons of aluminum and 0.43 million tons of copper to the environment cumulatively to achieve 13.2 million terajoules of final heat exchanged and serve 1.24 billion square meters during lifetime in mainland China alone, secondary aluminum and copper accounted for only 22.61% and 24.83% of the total consumption, and the in-use stocks increased by 0.19 million tons of aluminum and 0.70 million tons of copper. The external dependency of copper ore was 92.83%, which was significantly higher than the 44.29% of bauxite. The comprehensive utilization efficiency of copper reached 77.88%, which was slightly higher than the 70.80% of aluminum. The conclusion indicates that under the premise of meeting use requirements, promoting "replacing copper with aluminum" can improve the stability and safety of China's material supply chain, but there is a need to further boost the production efficiency of aluminum in primary production.


Synthesis of Carotenoids of Industrial Interest in the Photosynthetic Bacterium Rhodopseudomonas palustris : Bioengineering and Growth Conditions.
Rhodopseudomonas palustris is a purple photosynthetic bacterium that accumulates in the inner membrane the photosynthetic pigment spirilloxanthin, formed from lycopene. Here, we describe the procedures used to successfully engineer Rps. palustris strains to reroute the production of lycopene toward the synthesis of ß-carotene or canthaxanthin. The crtCD genes specifically involved in spirilloxanthin were replaced by crtY and crtW genes from Bradyrhizobium ORS278 to synthesize ß-carotene and (or) canthaxanthin, two pigments of industrial interest. Since the synthesis of canthaxanthin depends on the presence of oxygen, the procedure to optimize their production is also proposed. By modulating the light and oxygen during the growth process, a single species of photosynthetic bacteria, with an efficient growth rate, produces various carotenoids of economical interest.


Reduced relative volume in motor and attention regions in developmental coordination disorder: A voxel-based morphometry study.
Developmental coordination disorder (DCD) is a prevalent childhood movement disorder, impacting the ability to perform movement skills at an age appropriate level. Although differences in grey matter (GM) volumes have been found in related developmental disorders, no such evidence has been linked with DCD to date. This cross-sectional study assessed structural brain differences in children with and without DCD. High-resolution structural images were acquired from 44 children aged 7.8-12 years, including 22 children with DCD (≤16th percentile on MABC-2; no ADHD/ASD), and 22 typically developing controls (≥20th percentile on MABC-2). Structural voxel-based morphology analysis was performed to determine group differences in focal GM volumes. Children with DCD were found to have significant, large, right lateralised reductions in grey matter volume in the medial and middle frontal, and superior frontal gyri compared to controls. The addition of motor proficiency as a covariate explained the between-group GM volume differences, suggesting that GM volumes in motor regions are reflective of the level of motor proficiency. A positive correlation between motor proficiency and relative GM volume was also identified in the left posterior cingulate and precuneus. GM volume reductions in premotor frontal regions may underlie the motor difficulties characteristic of DCD. It is possible that intervention approaches targeting motor planning, attention, and executive functioning processes associated with the regions of reduced GM volume may result in functional improvements in children with DCD.


Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies.
To review, summarise, and compare the evidence for effectiveness of screening sigmoidoscopy and screening colonoscopy in the prevention of colorectal cancer occurrence and deaths. Systematic review and meta-analysis of randomised controlled trials and observational studies. PubMed, Embase, and Web of Science. Two investigators independently extracted characteristics and results of identified studies and performed standardised quality ratings. Randomised controlled trials and observational studies in English on the impact of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality in the general population at average risk. For screening sigmoidoscopy, four randomised controlled trials and 10 observational studies were identified that consistently found a major reduction in distal but not proximal colorectal cancer incidence and mortality. Summary estimates of reduction in distal colorectal cancer incidence and mortality were 31% (95% confidence intervals 26% to 37%) and 46% (33% to 57%) in intention to screen analysis, 42% (29% to 53%) and 61% (27% to 79%) in per protocol analysis of randomised controlled trials, and 64% (50% to 74%) and 66% (38% to 81%) in observational studies. For screening colonoscopy, evidence was restricted to six observational studies, the results of which suggest tentatively an even stronger reduction in distal colorectal cancer incidence and mortality, along with a significant reduction in mortality from cancer of the proximal colon. Indirect comparisons of results of observational studies on screening sigmoidoscopy and colonoscopy suggest a 40% to 60% lower risk of incident colorectal cancer and death from colorectal cancer after screening colonoscopy even though this incremental risk reduction was statistically significant for deaths from cancer of the proximal colon only. Compelling and consistent evidence from randomised controlled trials and observational studies suggests that screening sigmoidoscopy and screening colonoscopy prevent most deaths from distal colorectal cancer. Observational studies suggest that colonoscopy compared with flexible sigmoidoscopy decreases mortality from cancer of the proximal colon. This added value should be examined in further research and weighed against the higher costs, discomfort, complication rates, capacities needed, and possible differences in compliance.


Relative importance of heat-labile enterotoxin in the causation of severe diarrheal disease in the gnotobiotic piglet model by a strain of enterotoxigenic Escherichia coli that produces multiple enterotoxins.
Enterotoxigenic Escherichia coli (ETEC) strains that produce multiple enterotoxins are important causes of severe dehydrating diarrhea in human beings and animals, but the relative importance of these enterotoxins in the pathogenesis is poorly understood. Gnotobiotic piglets were used to study the importance of heat-labile enterotoxin (LT) in infection with an ETEC strain that produces multiple enterotoxins. LT(-) (DeltaeltAB) and complemented mutants of an F4(+) LT(+) STb(+) EAST1(+) ETEC strain were constructed, and the virulence of these strains was compared in gnotobiotic piglets expressing receptors for F4(+) fimbria. Sixty percent of the piglets inoculated with the LT(-) mutant developed severe dehydrating diarrhea and septicemia compared to 100% of those inoculated with the nalidixic acid-resistant (Nal(r)) parent and 100% of those inoculated with the complemented mutant strain. Compared to piglets inoculated with the Nal(r) parent, the mean rate of weight loss (percent per hour) of those inoculated with the LT(-) mutant was 67% lower (P < 0.05) and that of those inoculated with the complemented strain was 36% higher (P < 0.001). Similarly, piglets inoculated with the LT(-) mutant had significant reductions in the mean bacterial colony count (CFU per gram) in the ileum; bacterial colonization scores (square millimeters) in the jejunum and ileum; and clinical pathology parameters of dehydration, electrolyte imbalance, and metabolic acidosis (P < 0.05). These results indicate the significance of LT to the development of severe dehydrating diarrhea and postdiarrheal septicemia in ETEC infections of swine and demonstrate that EAST1, LT, and STb may be concurrently expressed by porcine ETEC strains.


Neuromusculoskeletal thermography: a valuable diagnostic tool?
The use of neuromusculoskeletal thermography is rapidly increasing. Recent studies have begun to document the types of diagnostic and other clinically useful information which may be derived from the procedure. This paper provides a review and summary of current research and a comparison with myelography, computerized tomography, electromyography and clinical and surgical findings in cases of presumed musculoskeletal pain syndromes. The importance of diagnostic sensitivity, specificity, positive and negative predictive value, and accuracy (validity) are discussed. In general, the literature reports high sensitivity and negative predictive value, but lower specificity and positive predictive value. The implications of these findings are examined in regard to clinical case management, with emphasis on potential usefulness to chiropractors. Although thermography appears to be a promising diagnostic tool, there remain a number of threats to the scientific validity of current research which must be accounted for in future work.


Minimally important differences of EORTC QLQ-C30 scales in patients with lung cancer or malignant pleural mesothelioma - Interpretation guidance derived from two randomized EORTC trials.
A minimally important difference (MID) is the smallest difference in quality of life (QoL) perceived as relevant by patients or clinicians. MIDs aid interpretation of QOL data in research and clinical practice. We aimed to determine MIDs for the EORTC QLQ-C30 for patients with lung cancer or malignant pleural mesothelioma. Data were drawn from two EORTC-sponsored randomized clinical trials (RCTs): a three-arm RCT of two cisplatin-based treatments and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer, and an RCT comparing cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma. MIDs for interpreting within-group change and between-group differences in change over time were computed using anchor-based approaches, for improvements and deteriorations separately. Distribution-based approaches provided corroborative evidence. The combined data from the trials comprised 730 patients. Available data allowed us to determine 8/14 anchor-based MIDs for EORTC scales for improvements, and 9/14 MIDs for deterioration. Furthermore, we provided distribution-based estimates for all 14 QLQ-C30 scales. Most MIDs for improvements ranged between 5 and 10, for both within-group and between-group differences. Outliers were appetite loss and constipation, with MIDs up to 15 score points. MIDs were slightly larger for within-group deterioration, ranging from -5 to - 15, with the largest for Nausea/vomiting (-1 to 4) and Appetite loss (-1 to 5). MIDs for between-group differences in deterioration ranged from - 4 (Physical, Role, and Social functioning, and Global quality of life) to -9 (Nausea/vomiting, Appetite loss and Constipation). MIDs vary over scales and for between- versus within-group comparisons; this must be taken into account when interpreting changes. Nevertheless, the majority of MIDs range between 5 and 10 score points, in line with previously used thresholds for QLQ-C30. These findings and those from other tumor-specific MID analyses will inform a planned consensus process identifying commonalities and differences across tumor sites.


Synthesis of Masarimycin, a Small Molecule Inhibitor of Gram-Positive Bacterial Growth.
Peptidoglycan (PG) in the cell wall of bacteria is a unique macromolecular structure that confers shape, and protection from the surrounding environment. Central to understanding cell growth and division is the knowledge of how PG degradation influences biosynthesis and cell wall assembly. Recently, the metabolic labeling of PG through the introduction of modified sugars or amino acids has been reported. While chemical interrogation of biosynthetic steps with small molecule inhibitors is possible, chemical biology tools to study PG degradation by autolysins are underdeveloped. Bacterial autolysins are a broad class of enzymes that are involved in the tightly coordinated degradation of PG. Here, a detailed protocol is presented for preparing a small molecule probe, masarimycin, which is an inhibitor of N-acetylglucosaminidase LytG in Bacillus subtilis, and cell wall metabolism in Streptococcus pneumoniae. Preparation of the inhibitor via microwave-assisted and classical organic synthesis is provided. Its applicability as a tool to study Gram-positive physiology in biological assays is presented.


Intramyocardial Dissecting Hematoma after Acute Myocardial Infarction-Echocardiographic Features and Clinical Outcome.
Intramyocardial dissecting hematoma (IDH) after acute myocardial infarction (MI) is a rare form of subacute cardiac rupture and hence management uncertainties. The objective of this study was to describe the clinical course of a small series of IDH patients and to review the available evidence for managing similar cases. Eight IDH patients from our center had echocardiographic, coronary angiographic and clinical outcome data reviewed. PubMed was also searched for IDH following MI. Cases were divided into three groups and compared according to the dissection location. In our 8 patients, 3 had septal, 1 right ventricular (RV), and 4 left ventricular (LV) dissection. Five were medically treated and 3 surgically repaired. Reviewing the literature revealed 68 IDH patients, of mean age 66 ± 10 years, 43 males. The percentage of IDH involving the LV free wall, septal, and RV free wall were 47%, 26.5%, and 26.5%, respectively. In the cohort as a whole, mortality was not different between surgically and medically treated patients (33.3% vs. 54.3%, P = 0.08), neither based on the IDH location (P = 0.49). While surgical and medical treatment of the LV free wall (20.0% vs. 40.9%, P = 0.25) and septal (46.2% vs. 60.0%, P = 0.60) were not different, surgical repair of RV free wall had significantly better survival (30.0% vs. 87.5%, P = 0.015). The LVEF (P = 0.82), mitral regurgitation (P = 0.49) failed to predict mortality. While survival following medical and surgical treatment of LV IDH is not different, patients with RV free wall dissection benefit significantly from surgical repair.


A pilot community-based randomized comparison of speech generating devices and the picture exchange communication system for children diagnosed with autism spectrum disorder.
A pilot community-based randomized controlled trial was conducted to compare the effects of the Picture Exchange Communication System (PECS) to a teaching sequence using a high-tech Speech Generating Device (SGD) to teach social communication behaviors. The two approaches were compared to evaluate the effectiveness of the newer, more high-tech intervention using technology to improve social and communicative behavior of children diagnosed with Autism Spectrum Disorder. A total of 35 school-age children were randomized to either a high-tech (SGD device) or low-tech (PECS cards) form of Augmentative and Alternative Communication (AAC). Study participants received 4 months of communication training delivered in their classrooms, and the primary outcome measures of the trial were several functional communication skills emphasized in the PECS teaching sequence. Results indicated that both high-tech and low-tech AAC approaches resulted in significant improvements in communication, and that these improvements did not differ significantly between the two approaches. These findings support the use of high-tech AAC, and highlight the need for evidence-based guidelines for its use as well as evaluation with individuals with a range impairments and disabilities. Autism Research 2018, 11: 1701-1711. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study compared the effectiveness of a free and open-source app for teaching social and communicative behavior to children with autism spectrum disorder (ASD) to traditional picture card approaches. Thirty-five children with ASD were randomized to a picture card or app-based intervention and both treatment approaches resulted in significant improvements in social and communicative behavior. These data indicated that both "high-tech" and "low-tech" interventions were effective for improving behavior and that there was not a significant difference between the two approaches.


The cloning and sequencing of the virion protein genes from a British isolate of porcine respiratory coronavirus: comparison with transmissible gastroenteritis virus genes.
Previous analysis of porcine respiratory coronavirus (PRCV) mRNA species showed that mRNAs 2 and 3 were smaller than the corresponding transmissible gastroenteritis virus (TGEV) mRNA species (Page et al. (1991) J. Gen. Virol. 72, 579-587). Sequence analysis showed that mRNA 3 was smaller due to the presence of a new putative RNA-leader binding site upstream of the PRCV ORF-3 gene. However, this observation did not explain the deletion observed in PRCV mRNA 2. Polymerase chain reaction (PCR) was used to generate cDNA from the 3' coding region of the putative polymerase gene to the poly (A) tail of PRCV for comparison to the equivalent region from TGEV. The PRCV S protein was found to consist of 1225 amino acids, which had 98% similarity to the TGEV S protein. However, the PRCV S gene contained a 672 nucleotide deletion, corresponding to 224 amino acids (residues 21 to 245 in TGEV S protein), 59 nucleotides downstream of the S gene initiation codon. The PRCV genome from the ORF-3 gene to the poly (A) tail was sequenced for comparison to TGEV in order to identify other potential differences between the two viruses. Four ORFs were identified that showed 98% similarity to the TGEV ORF-4, M, N and ORF-7 genes. No other deletions or any PRCV specific sequences were identified.


Smartphone Addiction and Interpersonal Competence of Nursing Students.
Interpersonal competence is an important capacity for nurses. Recently, the advent of smartphones has instigated considerable changes in daily life. Because smartphone has multiple functions, people tend to use them for numerous activities, often leading to addictive behavior. This cross-sectional study performed a detailed analysis of smartphone addiction subscales and social support related to interpersonal competence of nursing students. Overall, 324 college students were recruited at Catholic University in Seoul, Korea from Feb 2013 to Mar 2013. Participants completed a self-reported questionnaire, which included scales that measured smartphone addiction, social support, interpersonal competence, and general characteristics. Path analysis was used to evaluate structural relations between subscales of smartphone addictions, social support, and interpersonal competence. The effect of cyberspace-oriented relationships and social support on interpersonal competence were 1.360 (P=.004) and 0.555 (P<.001), respectively. Cyberspace-oriented relationship, which is a smartphone addiction subscale, and social support were positively correlated with interpersonal competence of nursing students, while other smartphone addiction subscales were not related to nursing student interpersonal competence. Therefore, effective smartphone teaching methods be developed to enhance nursing student motivation.


Immune Activation Modulation via Magnetically Localized Bacteria Based Micro/Bio Robot (BBMBR).
Understanding tumor's microenvironment is one of the key factors in the cancer therapy. Especially, from the perspective of immunotherapy, immune desert or cold tumor is referred as significantly downregulated T cell in-filtration due to lack of immune surveillance in the tumor microenvironment. There are many studies are dedicated to convert cold tumor to hot tumor for enhancing the efficacy of immunotherapy. In this study, we suggested selective immune activation system through the spatiotemporal control of the bacteria as an immune boosting agent. To this end, we have developed bacteria-based micro/bio robot system (BBMBR) by attaching bacteria with magnetic nanoparticles (MNP) so that the localization can be controlled through the magnetic field. The biomanufacturing results showed that BBMBR includes 6.6 ± 1.54 MNP attached and the presence ratio of bacteria-MNP out of total bacteria population reached 75.2 ± 3.37%. Spatial controllability experiments have shown that rotational and translation localization has been controlled as intended. The function of the immune modulation system through BBMBR was confirmed through experiments that magnetically driven BBMBR localization induced localized immune activation. M1-phenotype differentiation of macrophage cells were quantified CD80 staining, and overall immune response level was evaluated through IL-6 measurements. As the distance from the activation point increased, the population of M1 differentiated macrophages decreased, and when the movement of BBMBR was magnetically restricted, overall immune activation was found to be regulated downward. Proposed BBMBR and immune modulation framework could introduce a powerful new paradigm in cancer treatment by improving the localization controllability of immune-boosting agent and the spatial immune activation strategies.


How to deal with undetectable and low measurable serum thyroglobulin levels in the follow-up of patients with differentiated thyroid carcinoma?
Serum thyroglobulin (Tg) was measured in 52 patients 3 months to 15 years (mean 5.3 years) after thyroidectomy with or without subsequent radioablation for differentiated thyroid carcinoma, before and after the interruption of suppressive thyroxine (T4) replacement therapy for 5 weeks. Whole body scintigraphy was carried out at the end of the T4 withdrawal period. Serum Tg was undetectable (less than 3 micrograms/l) in 38 patients on T4 therapy, in 18 the scintigraphy showed a minimal accumulation in the neck region and in 20 no uptake anywhere after withdrawal of T4. In the former group Tg rose in 10 patients to 4-21 micrograms/l when off T4 which seemed to correspond to the normal tissue left in situ, in the latter group Tg rose only in 2 patients to 5 and 21 micrograms/l, respectively. Two patients out of 14 with detectable Tg on T4 had pulmonary metastases as uncovered by whole body scintigraphy (in one of them Tg rose from 12 micrograms/l on T4 to 1200 micrograms/l off T4) and 6 patients were suspected for having recidual cancer tissue (2 patients had a negative scintigraphy) because the Tg rose (66-215 micrograms/l) over the upper limit of the reference range (less than 50 micrograms/l) after T4 withdrawal. In conclusion, in the follow-up of patients with differentiated thyroid carcinoma no routine scans are needed as long as serum Tg remains undetectable but further examinations are shortly warranted when detectable Tg is obtained during T4 suppression.


Overweight in midlife is related to lower cognitive function 30 years later: a prospective study with longitudinal assessments.
To examine if the body mass index (BMI) in midlife is related to cognitive function 30 years later in a dementia-free sample. BMI was reported in 1963 at age 50-60 years, and cognitive abilities were examined 30 years later in a longitudinal design with 5 measurement occasions at 2-year intervals (n = 417). The cognitive abilities examined included tests of long-term memory, short-term memory, speed, verbal and spatial ability. Multilevel modeling adjusting for demographic and lifestyle factors, and relevant diseases showed that a higher BMI in midlife predicted lower test performance 30 years later. Significant associations between BMI and level of performance were found in all cognitive abilities; however, a higher midlife BMI was not associated with steeper cognitive decline. Our results indicate that midlife overweight is related to lower overall cognitive function in old age. The fact that BMI-related effects were noted in mean-level cognitive performance, whereas only one ability showed differences in slopes, suggests that the negative effect of overweight has an onset before the entry into very old age.


Handover and transport of critically ill children: An integrative review.
The handover and transport of critically ill pediatric patients requires communication amongst multiple disciplines. Poor communication is a leading cause of sentinel events and human factors affect handover and transport. To synthesize published data on pediatric handover and transport and identify gaps to provide direction for future investigation. Integrative literature review. Forty research studies were reviewed and revealed the following themes: risk for patient complications, standardized communication, and specialized teams and teamwork were associated with improved outcomes. No articles were identified regarding transportation of critically ill pediatric patients from the emergency room to the intensive care unit. There was a knowledge gap in best practices in handover and transport within the unique subsets of the pediatric population including neonate, toddler, school-aged, and adolescents. Research supported a combined approach of specialized teams using standardized communication in the handover and transport of the pediatric patient to improve outcomes. Further study is warranted on interprofessional (team to team) handover practices, select subsets of the pediatric population, and the handover and transport of critically ill patients from the emergency room to the intensive care unit.


The resilience of neighborhood social processes: A case study of the 2011 Brisbane flood.
Social disorganization theories position neighborhood social capital and collective efficacy as key social processes that should facilitate community resilience in the aftermath of disaster. Yet limited evidence demonstrates that these social processes are themselves resilient with some studies showing that disaster can fracture even once cohesive neighborhoods. In this paper we assess the stability of neighborhood level collective efficacy and social capital before and after a disaster. We use multilevel structural equation modeling and draw on census and longitudinal survey data collected from over 4000 residents living in 148 neighborhoods in Brisbane, Australia before and after a significant flood event. We examine what happens to social capital and collective efficacy in flooded and non-flooded neighborhoods and assess whether demographic shifts are associated with change and/or stability in these processes. We find strong evidence that these processes operate similarly across flooded and not flooded communities. Our findings also reveal significant stability for our measures of social capital across time, while collective efficacy increases post flood across all neighborhoods, but more so in flooded neighborhoods. Neighborhood demographics have limited effect on patterns of stability or change in these social processes. We discuss the theoretical and practical implications of these findings for our understanding of neighborhood resilience in the wake of disaster.


Neuropeptide Y action in the rat hippocampal slice: site and mechanism of presynaptic inhibition.
Neuropeptide Y (NPY), the most abundant peptide in mammalian CNS, has been shown to inhibit excitatory neurotransmission presynaptically at the stratum radiatum-CA1 synapse in the in vitro rat hippocampal slice. We examined the site and mechanism of this inhibition in a series of in vitro intra- and extracellular recordings in areas CA1 and CA3, the source of much of the excitatory synaptic input to the CA1 neurons. NPY's inhibitory action at the stratum radiatum-CA1 synapse was unaffected by high concentrations of the antagonists bicuculline, theophylline, or atropine, suggesting that it does not act by stimulating the release of the known presynaptic inhibitory transmitters GABA, adenosine, or ACh, respectively. Bath application of 10(-6) NPY, a concentration that strongly inhibited the stratum radiatum-CA1 synapse had no effect on CA3 neuron resting potential, input resistance or action potential amplitude, threshold, or duration. NPY also does not alter the amplitude or duration of the prolonged CA3 action potentials evoked in the presence of TTX, tetraethyl-ammonium, and elevated external Ca2+ or those evoked in the presence of TTX and Ba2+ ions. NPY therefore does not alter the passive or active properties of the somata of the presynaptic CA3 neurons. Neither the afferent fiber volley of the Schaffer collaterals in stratum radiatum of area CA1 nor the excitability of the CA3 terminals in CA1 was affected by NPY application. However, application of the transient K+ current blocker, 4-aminopyridine (4-AP) at concentrations of 10 and 50 microM, completely abolished the action of 10(-6) M NPY on the stratum radiatum-CA1 excitatory synaptic potentials. This action of 4-AP could be reversed by reducing extracellular Ca2+ concentrations from a control level of 1.5 to 0.7 mM (in 10 microM 4-AP) and to 0.5 mM (in 50 microM 4-AP). The evidence suggests that NPY inhibits excitatory synaptic transmission at the Schaffer collateral-CA1 synapse by acting directly at the terminal to reduce a Ca2+ influx.


The Nasal Fracture Algorithm: A Case for Protocol-Driven Management to Optimize Care and Resident Work Hours.
Since the initiation of resident duty hour restrictions, significant controversy has arisen regarding its impact on surgical resident training. We reviewed a singular facet of the otolaryngology residency experience, nasal bone fracture management, to identify if treatment standardization would improve care and efficiency. For 1 year, otolaryngology consults for isolated nasal fractures were analyzed to assess consultation trends, rate of intervention, and resident work hour utilization. Following a review of the literature, an evidence-based algorithm for management of nasal fractures was developed. Analysis revealed a potential improvement in intervention rate from 20% to 100% with utilization of the algorithm, with an 84% decrease in overall emergency room and inpatient consultations. Sixty-three hours of otherwise lost resident time would be gained. In the setting of Accreditation for Graduate Medical Education duty hour restrictions, implementation of protocol-driven management may result in a decrease in work hours and serve as a model for more efficient otolaryngology care.


Three-dimensional analysis of the intrinsic anatomy of the metatarsal bones.
Knowledge of the anatomy of the forefoot is important for understanding its mechanical pathology and developing specific surgical procedures. The aim of this study was to quantify 3-dimensional morphological parameters, which were proposed for the characterization of the metatarsal intrinsic anatomy. Thirty-five metatarsal bones prepared from 7 cadaver specimens were analyzed according to a new 3-dimensional computer-aided (CA) methodology. Manual and CA measurement techniques were compared. The reality of an intrinsic axial torsion of the metatarsals was underlined with mean values between 3.2 degrees and 57.7 degrees. Using the CA method, the reliability was excellent (intraclass correlation coefficient, 0.98) and significantly better than the manual method (P < .1E-12). With specific consideration of the second metatarsal intrinsic morphology, we emphasized its mechanical function. These results reflect the possibilities of CA systems. These data, which were carried out on specific anatomical characteristics of the metatarsal bones, can improve the metatarsalgia surgical procedures.


How to improve fuzzy-neural system modeling by means of qualitative simulation.
The main problem in efficiently building robust fuzzy-neural models of nonlinear systems lies in the difficulty to define a "meaningful" fuzzy rule-base. Our approach to the solution of such a problem is based on a hybrid method which integrates fuzzy systems with qualitative models. We introduce qualitative models to exploit the available, although incomplete, a priori physical knowledge on the system with the goal to infer, through qualitative simulation, all of its possible behaviors.We show here that a rule-base, which captures all of the distinctions in the system states, is automatically generated by encoding the knowledge of the system dynamics described by the outcomes of its qualitative simulation. Such a rule-base properly initializes a fuzzy identifier, which is then tuned to a set of experimental data. Our method has shown good performance when applied both as a predictor and as a simulator.


Systematic review of interventions to promote social-emotional development in young children with or at risk for disability.
This systematic review synthesized the research on interventions used by occupational therapy practitioners to promote social-emotional development in young children (birth-5 yr) with or at risk for disabilities. After a comprehensive search of the research literature, 23 studies were reviewed and then synthesized into five themes: (1) touch-based interventions to enhance calming and parent-infant bonding, (2) relationship-based interventions to promote positive caregiver-child interactions, (3) joint attention interventions, (4) naturalistic preschool interventions to promote peer-to-peer engagement, and (5) instruction-based interventions to teach children appropriate social behaviors. The interventions for infants primarily involved coaching parents in specific strategies to promote positive interactions; interventions for preschool-age children typically involved encouraging peer support, instructing children, and applying naturalistic behavioral techniques to develop higher-level social competence. The studies demonstrated low to moderate positive effects for interventions used by occupational therapy practitioners to improve social-emotional development across ages, diagnoses, and settings.


Arabidopsis TAF15b Localizes to RNA Processing Bodies and Contributes to snc1-Mediated Autoimmunity.
In both animals and plants, messenger (m)RNA export has been shown to contribute to immune response regulation. The Arabidopsis nuclear protein MOS11, along with the nucleoporins MOS3/Nup96/SAR3 and Nup160/SAR1 are components of the mRNA export machinery and contribute to immunity mediated by nucleotide binding leucine-rich repeat immune receptors (NLR). The human MOS11 ortholog CIP29 is part of a small protein complex with three additional members: the RNA helicase DDX39, ALY, and TAF15b. We systematically assessed the biological roles of the Arabidopsis homologs of these proteins in toll interleukin 1 receptor-type NLR (TNL)-mediated immunity using reverse genetics. Although mutations in ALY and DDX39 did not result in obvious defects, taf15b mutation partially suppressed the autoimmune phenotypes of a gain-of-function TNL mutant, snc1. An additive effect on snc1 suppression was observed in mos11-1 taf15b snc1 triple mutant plants, suggesting that MOS11 and TAF15b have independent functions. TAF15b-GFP fusion protein, which fully complemented taf15b mutant phenotypes, localized to nuclei similarly to MOS11. However, it was also targeted to cytosolic granules identified as processing bodies. In addition, we observed no change in SNC1 mRNA levels, whereas less SNC1 protein accumulated in taf15b mutant, suggesting that TAF15b contributes to SNC1 homeostasis through posttranscriptional mechanisms. In summary, this study highlights the importance of posttranscriptional RNA processing mediated by TAF15b in the regulation of TNL-mediated immunity.


Genomic landscape of adenoid cystic carcinoma of the breast.
Adenoid cystic carcinoma (AdCC) is a rare type of triple-negative breast cancer (TNBC) characterized by the presence of the MYB-NFIB fusion gene. The molecular underpinning of breast AdCCs other than the MYB-NFIB fusion gene remains largely unexplored. Here we sought to define the repertoire of somatic genetic alterations of breast AdCCs. We performed whole-exome sequencing, followed by orthogonal validation, of 12 breast AdCCs to determine the landscape of somatic mutations and gene copy number alterations. Fluorescence in situ hybridization and reverse-transcription PCR were used to define the presence of MYB gene rearrangements and MYB-NFIB chimeric transcripts. Unlike common forms of TNBC, we found that AdCCs have a low mutation rate (0.27 non-silent mutations/Mb), lack mutations in TP53 and PIK3CA and display a heterogeneous constellation of known cancer genes affected by somatic mutations, including MYB, BRAF, FBXW7, SMARCA5, SF3B1 and FGFR2. MYB and TLN2 were affected by somatic mutations in two cases each. Akin to salivary gland AdCCs, breast AdCCs were found to harbour mutations targeting chromatin remodelling, cell adhesion, RNA biology, ubiquitination and canonical signalling pathway genes. We observed that, although breast AdCCs had rather simple genomes, they likely display intra-tumour genetic heterogeneity at diagnosis. Taken together, these findings demonstrate that the mutational burden and mutational repertoire of breast AdCCs are more similar to those of salivary gland AdCCs than to those of other types of TNBCs, emphasizing the importance of histological subtyping of TNBCs. Furthermore, our data provide direct evidence that AdCCs harbour a distinctive mutational landscape and genomic structure, irrespective of the disease site of origin.


Use of Lipotransfer in Scleroderma.
Lipotransfer for soft tissue filling is a well-established plastic and aesthetic surgical technique. Elective fat grafting is considered a safe and well-tolerated procedure. Coleman and others have reported that fat grafting may have tissue regenerative properties and not only serve as a soft tissue filler. There have been reports from our group and others that it may improve fibrosis secondary to many different pathological aetiologies including scleroderma, burn injury, lichen sclerosis, graft vs host disease, and radiation. The mechanism of action remains unclear but has been postulated that is adipose derived stem cells (ADSCs) related. Lipoaspirate has been characterised and shown to contain several cell populations including fibroblasts, endothelial cells, and ADSCs. The ADSCs have shown to secrete angiogenic, immunodulatory, and antiapoptotic factors as well as proliferate and differentiate into different cell types similarly to other stem cell sources. We have shown that ADSCs are functionally different in scleroderma patients but despite this lipotransfer produces a significant reversal in the effects of fibrosis in these patients. The advantage of lipoaspirate containing a valuable source of regenerative properties, ease of access, isolation, and processing may serve a significant future role in the treatment of fibrotic conditions.


CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alphaIIbbeta3 in platelets.
Second messenger-mediated inside-out activation of integrin alphaIIbbeta3 is a key step in platelet aggregation. We recently showed strongly impaired but not absent alphaIIbbeta3-mediated aggregation of CalDAG-GEFI-deficient platelets activated with various agonists. Here we further evaluated the roles of CalDAG-GEFI and protein kinase C (PKC) for alphaIIbbeta3 activation in platelets activated with a PAR4 receptor-specific agonist, GYPGKF (PAR4p). Compared with wild-type controls, platelets treated with the PKC inhibitor Ro31-8220 or CalDAG-GEFI-deficient platelets showed a marked defect in aggregation at low (< 1mM PAR4p) but not high PAR4p concentrations. Blocking of PKC function in CalDAG-GEFI-deficient platelets, how-ever, strongly decreased aggregation at all PAR4p concentrations, demonstrating that CalDAG-GEFI and PKC represent separate, but synergizing, pathways important for alphaIIbbeta3 activation. PAR4p-induced aggregation in the absence of CalDAG-GEFI required cosignaling through the Galphai-coupled receptor for ADP, P2Y12. Independent roles for CalDAG-GEFI and PKC/Galphai signaling were also observed for PAR4p-induced activation of the small GTPase Rap1, with CalDAG-GEFI mediating the rapid but reversible activation of this small GTPase. In summary, our study identifies CalDAG-GEFI and PKC as independent pathways leading to Rap1 and alphaIIbbeta3 activation in mouse platelets activated through the PAR4 receptor.


Studies of the interaction between Rad52 protein and the yeast single-stranded DNA binding protein RPA.
The RFA1 gene encodes the large subunit of the yeast trimeric single-stranded DNA binding protein replication protein A (RPA), which is known to play a critical role in DNA replication. A Saccharomyces cerevisiae strain carrying the rfa1-44 allele displays a number of impaired recombination and repair phenotypes, all of which are suppressible by overexpression of RAD52. We demonstrate that a rad52 mutation is epistatic to the rfa1-44 mutation, placing RFA1 and RAD52 in the same genetic pathway. Furthermore, two-hybrid analysis indicates the existence of interactions between Rad52 and all three subunits of RPA. The nature of this Rad52-RPA interaction was further explored by using two different mutant alleles of rad52. Both mutations lie in the amino terminus of Rad52, a region previously defined as being responsible for its DNA binding ability (U. H. Mortenson, C. Beudixen, I. Sunjeuaric, and R. Rothstein, Proc. Natl. Acad. Sci. USA 93:10729-10734, 1996). The yeast two-hybrid system was used to monitor the protein-protein interactions of the mutant Rad52 proteins. Both of the mutant proteins are capable of self-interaction but are unable to interact with Rad51. The mutant proteins also lack the ability to interact with the large subunit of RPA, Rfa1. Interestingly, they retain their ability to interact with the medium-sized subunit, Rfa2. Given the location of the mutations in the DNA binding domain of Rad52, a model incorporating the role of DNA in the protein-protein interactions involved in the repair of DNA double-strand breaks is presented.


Advances in the discovery of fatty acid amide hydrolase inhibitors: what does the future hold?
Fatty acid amide hydrolase (FAAH) is a membrane-bound enzyme, that inactivates endogenous signaling lipids of the fatty acid amide family, including the endocannabinoid anandamide (N-arachidonoylethanolamine, AEA). The latter compound has been shown to regulate a number of important pathophysiological conditions in humans, like feeding, obesity, immune response, reproductive events, motor coordination, and neurological disorders. Hence, direct manipulation of the endocannabinoid tone is thought to have therapeutic potential. A new opportunity to develop effective drugs may arise from multi-target directed ligand (MTDL) strategies, which brings the concept that a single compound can recognize different targets involved in the cascade of pathophysiological events. This review reports the latest advances in the development of new single targeted and dual-targeted FAAH inhibitors over the past 5 years. In recent years, several FAAH inhibitors have been synthesized and investigated, yet to date none of them has reached the market as a systemic drug. Due to the diligence of inherent redundancy and robustness in many biological networks and pathways, multitarget inhibitors present a new prospect in the pharmaceutical industry for treatment of complex diseases.


High levels of PROM1 (CD133) transcript are a potential predictor of poor prognosis in medulloblastoma.
The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have been performed. The aims of our study were to evaluate the expression profile of the PROM1 gene in medulloblastoma and to assess its possible role as a prognostic factor. The PROM1 gene expression was evaluated by quantitative- polymerase chain reaction on 45 medulloblastoma samples by using specific dye-labeled probe systems. A significantly higher expression of PROM1 was found both in patients with poorer prognosis (P= .007) and in those with metastasis (P= .03). Kaplan-Meier analysis showed that both overall survival (OS) and progression-free survival (PFS) were shorter in patients with higher PROM1 mRNA levels than in patients with lower expression, even when the desmoplastic cases were excluded (P= .0004 and P= .002, for OS and PFS for all cases, respectively; P= .002 and P= .008 for OS and PFS for nondesmoplastic cases, respectively). Cox regression model demonstrated that PROM1 expression is an independent prognostic factor (hazard ratio, 4.56; P= .008). The result was validated on an independent cohort of 42 cases by microarray-based analysis (P= .019). This work suggests that high mRNA levels of PROM1 are associated with poor outcome in pediatric medulloblastoma. Furthermore, high PROM1 expression levels seem to increase the likelihood of metastases. Such results need to be confirmed in larger prospective series to possibly incorporate PROM1 gene expression into risk classification systems to be used in the clinical setting.


Double dart technique of instillation of triamcinolone in ganglion over the wrist.
Ganglia are the most common benign cystic swellings found over both the dorsal and volar aspects of the wrist. In spite of technical advancement, both operative and non-operative interventions achieve more or less similar results. Complete evacuation of gelatinous fluid followed with intra cystic instillation of triamcinolone has given encouraging results. To assess the efficacy and safety of drainage of cyst and instillation of triamcinolone in wrist ganglion. A prospective study was conducted on patients with simple ganglion cysts on the wrist. Total of 219 patients underwent this study. Out of this, 105 patients underwent the aspiration of the cyst fluid followed by intracystic instillation of triamcinolone, and 114 patients underwent surgical excision of wrist ganglia. Two years follow up was done for recurrence. Most ganglia of wrist occurred in the extensor aspect. Complications noted among the surgically excised group were post operative pain and restricted mobility of wrist with a recurrence rate of 21.5%. Instillation of Triamcinolone into the ganglion yielded early resolution with a low recurrence of 8.4%. Intracystic instillation of triamcinolone after complete evacuation of cyst fluid is a simple and effective technique for treatment of ganglion.


Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders.
Segmental duplications at breakpoints (BP4-BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities. DNA samples from 1445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children's Hospital Boston and DNA samples from 1441 individuals with autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4-BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4-BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4-BP5 covers approximately 1.5 Mb (chr15:28.719-30.298 Mb) and includes six reference genes and 1 miRNA gene, while the smaller duplications cover approximately 500 kb (chr15:28.902-29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. The phenotype of chromosome 15q13.2q13.3 BP4-BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying aetiology of this syndrome.


Airway responsiveness after acute exposure to urban particulate matter 1648 in a DO11.10 murine model.
Enhanced airway responsiveness (AR) is a well-established characteristic of asthma that epidemiological evidence has linked with inhalation of ambient particulate matter (PM). To determine whether acute exposure to urban particulate matter PM1648 can exacerbate airway responsiveness and alter the early inflammatory state, a unique murine model was created using DO11.10 mice, transgenic for a T cell receptor recognizing ovalbumin(323-339). Because these mice are sensitive to ovalbumin, immunization procedures involving adjuvant or long aerosolization procedures are not necessary and, therefore, allow for the study of an acute AR response to particulate and antigen in young animals. AR was assessed by barometric whole body plethysmography and measured by enhanced pause (Penh). PM1648 and ovalbumin were administered intranasally 72 and 4 h before to AR assessment, respectively. A dose-response relationship between PM1648 and Penh was determined, and doses at or above 500 microg had Penh values significantly higher than saline controls. Penh values of control particle titanium dioxide (TiO(2)) were similar to saline controls demonstrating no nonspecific particulate effect on AR. Lung lavage at time of AR assessment showed no significant inflammation due to particulate exposure or ovalbumin alone; however, PM1648/ovalbumin and TiO(2)/ovalbumin combinations resulted in significant neutrophilia. In addition, treatment with polymyxin B to remove surface-bound endotoxin did not significantly affect Penh levels. These results indicate that PM1648 specifically increases AR in a dose-dependent manner and that this exacerbation is not a direct response to increased neutrophil concentration, particle-bound endotoxin or nonspecific particle effects.


Glial Cell Line-Derived Neurotrophic Factor-Transfected Placenta-Derived Versus Bone Marrow-Derived Mesenchymal Cells for Treating Spinal Cord Injury.
BACKGROUND Placenta-derived mesenchymal stem cells (PMSCs) were isolated from placenta and had differentiation and self-renewal potential. We transfected PMSCs with glial cell line-derived neurotrophic factor (GDNF) and compared their effect for repairing spinal cord injury (SCI) with that of GDNF-transfected bone marrow-derived mesenchymal stem cell (BMSC). MATERIAL AND METHODS The PMSCs were isolated from Sprague-Dawley rat placenta; BMSCs were isolated from Sprague-Dawley rat thigh bone marrow. Primary cultured BMSCs and PMSCs were uniformly spindle-shaped. Flow cytometry indicated that both cell types were CD29- and CD90-positive and CD34- and CD45-negative, confirming that they were MSCs. The PMSCs and BMSCs were transfected with recombinant lentivirus containing the GDNF gene in vitro. PMSC and BMSC viability was increased after transfection, and GDNF expression was increased until 10 d after transfection. SCI was created in the rats (n=64) and was repaired using transfected PMSCs and BMSCs or untransfected PMSCs and BMSCs. RESULTS The transfected PMSCs and BMSCs repaired the SCI. Flow cytometry, histology, immunohistochemical, kinesiology properties, and Basso-Beattie-Bresnahan locomotion score measurements determined no significant difference between transfected PMSCs and BMSCs at 7, 14, and 21 d post-transplantation (P>0.05); the injury healed better in transfected PMSCs and BMSCs than in untransfected PMSCs and BMSCs (P<0.05). CONCLUSIONS MSCs have similar biology characteristics and capacity for SCI repair to BMSCs and can be used as a new resource for treating SCI.


No evidence for unethical amnesia for imagined actions: A failed replication and extension.
In a recent study, Kouchaki and Gino (2016) suggest that memory for unethical actions is impaired, regardless of whether such actions are real or imagined. However, as we argue in the current study, their claim that people develop "unethical amnesia" confuses two distinct and dissociable memory deficits: one affecting the phenomenology of remembering and another affecting memory accuracy. To further investigate whether unethical amnesia affects memory accuracy, we conducted three studies exploring unethical amnesia for imagined ethical violations. The first study (N = 228) attempts to directly replicate the only study from Kouchaki and Gino (2016) that includes a measure of memory accuracy. The second study (N = 232) attempts again to replicate these accuracy effects from Kouchaki and Gino (2016), while including several additional variables meant to potentially help in finding the effect. The third study (N = 228) is an attempted conceptual replication using the same paradigm as Kouchaki and Gino (2016), but with a new vignette describing a different moral violation. We did not find an unethical amnesia effect involving memory accuracy in any of our three studies. These results cast doubt upon the claim that memory accuracy is impaired for imagined unethical actions. Suggestions for further ways to study memory for moral and immoral actions are discussed.