Effect of tea and other dietary factors on iron absorption.
Iron deficiency is a major world health problem, that is, to a great extent, caused by poor iron absorption from the diet. Several dietary factors can influence this absorption. Absorption enhancing factors are ascorbic acid and meat, fish and poultry; inhibiting factors are plant components in vegetables, tea and coffee (e.g., polyphenols, phytates), and calcium. After identifying these factors their individual impact on iron absorption is described. Specific attention was paid to the effects of tea on iron absorption. We propose a calculation model that predicts iron absorption from a meal. Using this model we calculated the iron absorption from daily menus with varying amounts of enhancers and inhibitors. From these calculations we conclude that the presence of sufficient amounts of iron absorption enhancers (ascorbic acid, meat, fish, poultry, as present in most industrialized countries) overcomes inhibition of iron absorption from even large amounts of tea. In individuals with low intakes of heme iron, low intakes of enhancing factors and/or high intakes of inhibitors, iron absorption may be an issue. Depletion of iron stores enhances iron absorption, but this effect is not adequate to compensate for the inhibition of iron absorption in such an inadequate dietary situation. For subjects at risk of iron deficiency, the following recommendations are made. Increase heme-iron intake (this form of dietary iron present in meat fish and poultry is hardly influenced by other dietary factors with respect to its absorption); increase meal-time ascorbic acid intake; fortify foods with iron. Recommendations with respect to tea consumption (when in a critical group) include: consume tea between meals instead of during the meal; simultaneously consume ascorbic acid and/or meat, fish and poultry.


Obesity and obstructive sleep apnea: pathogenic mechanisms and therapeutic approaches.
Obstructive sleep apnea is a common disorder whose prevalence is linked to an epidemic of obesity in Western society. Sleep apnea is due to recurrent episodes of upper airway obstruction during sleep that are caused by elevations in upper airway collapsibility during sleep. Collapsibility can be increased by underlying anatomic alterations and/or disturbances in upper airway neuromuscular control, both of which play key roles in the pathogenesis of obstructive sleep apnea. Obesity and particularly central adiposity are potent risk factors for sleep apnea. They can increase pharyngeal collapsibility through mechanical effects on pharyngeal soft tissues and lung volume, and through central nervous system-acting signaling proteins (adipokines) that may affect airway neuromuscular control. Specific molecular signaling pathways encode differences in the distribution and metabolic activity of adipose tissue. These differences can produce alterations in the mechanical and neural control of upper airway collapsibility, which determine sleep apnea susceptibility. Although weight loss reduces upper airway collapsibility during sleep, it is not known whether its effects are mediated primarily by improvement in upper airway mechanical properties or neuromuscular control. A variety of behavioral, pharmacologic, and surgical approaches to weight loss may be of benefit to patients with sleep apnea, through distinct effects on the mass and activity of regional adipose stores. Examining responses to specific weight loss strategies will provide critical insight into mechanisms linking obesity and sleep apnea, and will help to elucidate the humoral and molecular predictors of weight loss responses.


Association of one-point glucocorticoid-free status with chronic damage and disease duration in systemic lupus erythematosus: a cross-sectional study.
It is still unclear how glucocorticoids (GCs) affect the long-term clinical course of patients with SLE. The objective of this study is to explore the factors associated with GC-free treatment status. Using data from the lupus registry of nationwide institutions, GC dose at registration was compared between short, middle and long disease durations of <5, 5-20 and ≥20 years, respectively. After excluding patients who never used GC, we evaluated the relationship between GC-free status and chronic damage using Systemic Lupus International Collaborating Clinics Damage Index. GC doses at enrolment of the 1019 patients were as follows: GC-free in 101 (10%); 0<prednisolone (PSL) ≤5 mg/day in 411 (40%); 5<PSL ≤7.5 in 169 (17%); 7.5<PSL ≤10 in 194 (19%) and PSL≥10 in 144 (14%) patients. Of the patients who were not currently using GCs, patients who never used GC more frequently had short disease duration (66% with short, 23% with middle and 17% with long disease duration, p=0.00029). Univariate analysis of patients who underwent GC treatment showed that patients without GCs exhibited older age, lower disease activity, less immunosuppressant and hydroxychloroquine use and higher C3 levels. Among patients with a disease duration of ≥20 years, GC-free status was more frequent in patients without chronic damage (11% vs 4%, p=0.023). After adjusting for age, sex and disease activity, no chronic damage accrual was associated with GC-free status (OR 3.6, 95% CI 1.1 to 11.3). Even in the patients with long disease duration, one-point GC-free treatment status might be related to no chronic damage accrual.


Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from a national, population-based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: AusDiab).
Serum 25-hydroxyvitamin D [25(OH)D] concentration has been inversely associated with the prevalence of metabolic syndrome (MetS), but the relationship between 25(OH)D and incident MetS remains unclear. We evaluated the prospective association between 25(OH)D, MetS, and its components in a large population-based cohort of adults aged 25 yr or older. We used baseline (1999-2000) and 5-yr follow-up data of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Of the 11,247 adults evaluated at baseline, 6,537 returned for follow-up. We studied those without MetS at baseline and with complete data (n = 4164; mean age 50 yr; 58% women; 92% Europids). We report the associations between baseline 25(OH)D and 5-yr MetS incidence and its components, adjusted for age, sex, ethnicity, season, latitude, smoking, family history of type 2 diabetes, physical activity, education, kidney function, waist circumference (WC), and baseline MetS components. A total of 528 incident cases (12.7%) of MetS developed over 5 yr. Compared with those in the highest quintile of 25(OH)D (≥34 ng/ml), MetS risk was significantly higher in people with 25(OH)D in the first (<18 ng/ml) and second (18-23 ng/ml) quintiles; odds ratio (95% confidence interval) = 1.41 (1.02-1.95) and 1.74 (1.28-2.37), respectively. Serum 25(OH)D was inversely associated with 5-yr WC (P < 0.001), triglycerides (P < 0.01), fasting glucose (P < 0.01), and homeostasis model assessment for insulin resistance (P < 0.001) but not with 2-h plasma glucose (P = 0.29), high-density lipoprotein cholesterol (P = 0.70), or blood pressure (P = 0.46). In Australian adults, lower 25(OH)D concentrations were associated with increased MetS risk and higher WC, serum triglyceride, fasting glucose, and insulin resistance at 5 yr. Vitamin D supplementation studies are required to establish whether the link between vitamin D deficiency and MetS is causal.


Isolated tuberculosis of C2 spinous process.
Isolated tuberculosis (TB) of posterior elements is extremely rare. Only few cases are reported in literature but none described isolated spinous process involvement in the absence of disease process in any other part of the body. The authors report a case of isolated tuberculous involvement of C2 spinous process, which to the best of our knowledge, is first such case report. A case report of isolated C2 spinous process TB. Sixteen-year-old girl presented with two-month history of slow growing, painless lump at the back of her neck without any other symptoms. X-ray showed erosion of C2 spinous process. MRI also suggested an abscess. Patient underwent incision and drainage of abscess and debridement of involved bone. Cultures and histopathology confirmed TB. Patient responded to antituberculous therapy. Posterior element TB is a rare condition but in countries where TB is common, its possibility should always be considered. Isolated TB of parts of posterior elements can occur in absence of disease elsewhere.


Differences in the in vivo effects of cuprizone on superoxide dismutase activity in rat liver cytosol and mitochondrial intermembrane space.
Through aerobic NBT2+ photoreduction in the absence or in the presence of 10(-4) M EDTA and through o-dianisidine photooxidation superoxide dismutase (SOD) activity was differentiated as enzymatic and nonenzymatic. SOD activity in cytosol and mitochondrial matrix was enzymatic, while 50% of the SOD activity in the intermembrane space was nonenzymatic. Cuprizone inhibited by 40% the cytosolic SOD activity and by more than 50% the nonenzymatic SOD activity in intermembrane space without, however, changing the enzymatic SOD activity in the latter fraction. Single copper injection increased enzymatic SOD activity: the cuprizone-inhibited cytosolic dismutase activity restored to normal and the unaltered dismutase activity in the intermembrane space exceeded that in the controls.


THE RELATIONSHIP BETWEEN SERUM LEVEL OF MALONDIALDEHYDE AND PROGRESSION OF COLORECTAL CANCER.
- The purpose of the study was to assess the level of serum malondialdehyde (MDA) concentration and its association with the stage and histopathologic sizes of colorectal cancer (CRC). One hundred and two patients having undergone surgical treatment of CRC between January 2014 and December 2015 were included in this cross-sectional study. The patients were divided into four groups (stage I-IV) according to the TNM classification. Control group included 30 subjects with no signs of malignancy and inflammatory diseases. In each patient, preoperative blood samples were obtained for determination of MDA concentration by ELISA immunoassay. Serum levels of MDA were progressively increased in patients with CRC, reaching the highest value in the fourth stage of CRC. Serum concentrations of MDA were significantly higher in pT4 group as compared with pT3 and pT2 groups of CRC patients (p<0.01). Significantly higher levels of MDA were found in the N1 and N2 groups of CRC patients as compared with N0 group, as well as in patients with metastatic disease as compared with those without metastasis (p<0.001). In conclusion, the progression of CRC is associated with a significant increase in serum MDA levels.


Ethical considerations in the study of online illness narratives: a qualitative review.
This aim of the review was to describe differences in ethical approaches to research on Internet communication during illness and to report conclusions drawn relevant to a proposed narrative analysis of parent blogs of childhood illness. As the study of the online expression of illness experiences becomes more expansive, discussion of related ethical issues is central to promoting research trustworthiness and rigour. Ethical considerations are central to the patient-provider relationship. The EBSCO Host, CINAHL, Medline, Communication & Mass Media Complete, and Google Scholar databases were searched from January 1990 to September 2009 using the terms 'Internet research and ethics', 'Internet research, illness and ethics' and 'blog, Internet research and ethics'. Of the 4114 references found, 21 met the inclusion criteria for the review. The review was designed to be a comprehensive assessment of the concepts analysed and the qualitative research measures taken concerning ethics in Internet research across formats. Three main approaches to ethical conduct in Internet research on illness experiences were found: human subjects, representation and open source approaches. The personal and sensitive nature of online illness narratives demand their consideration in health care as 'human subjects' research. The best hope for ethical treatment of author-participants is the creation of a comprehensive plan for addressing any and all potential ethical conflicts that may arise in the collection, analysis and reporting of data, taking into consideration rapid changes in technology.


Neonatal respiratory morbidity after elective cesarean section.
The objective of this study was to examine the rate of respiratory morbidity in neonates delivered by elective cesarean delivery (ECD) at term, with a definite confirmation of gestational age (GA) by 1st-trimester ultrasound. Consecutive women carrying a singleton pregnancy and undergoing ECD at term (>38 1/7 weeks), confirmed by 1st-trimester ultrasound, were included in the study group. Multiple gestations, cesarean section (CS) in labor, CS performed after rupture of membranes and induced deliveries were excluded. The control group included women with a singleton pregnancy at term (>38 1/7 weeks) who delivered spontaneously. This group of women was randomly selected during the study period. The study group included 277 women delivered by ECD. The control group consisted of 311 women. Five newborns in the study group and none in the control group were admitted to the neonatal intensive care unit (NICU) due to respiratory disorders (p < 0.02). Excluding diabetic women did not change the results. On multivariate analysis, no other factors were found to independently influence the risk of respiratory complications. In our study, the rate of respiratory morbidity was found to be significantly higher in neonates delivered by ECD compared to those delivered vaginally. The fact that GA was confirmed by 1st-trimester ultrasound makes iatrogenic prematurity an unlikely sole cause for this excess morbidity.


Ileocecal involvement in intestinal Behçet's disease and Crohn's disease: comparison of clinicopathological and immunophenotypic features.
Intestinal Behçet's disease (BD) predominantly affects the ileocecal region and is currently diagnosed based on endoscopic features and clinical manifestations. It is difficult to distinguish between intestinal BD and Crohn's disease (CD) due to similar patient populations, gastrointestinal involvement, extraintestinal manifestations, and long-term recurrent course. In this study we aimed to compare the clinicopathological and immunophenotypic features of intestinal BD to CD. The medical and pathological records of 29 cases of intestinal BD and 120 cases of CD diagnosed at Sir Run Run Shaw Hospital were retrospectively analyzed. Immunohistochemistry for CD3, CD20, FOXP3, myeloperoxidase, and quantitative analysis of the infiltrating inflammatory cells was conducted. Intestinal BD with ileocecal ulcer had a higher incidence of abdominal pain and a higher erythrocyte sedimentation rate than CD, while chronic diarrhea was more common in CD. Excessive neutrophils in the mucosal lamina propria, neutrophilic exudate on the ulcer surface, and prominent lymphocytic infiltration in ulcer tissues were statistically more frequent in intestinal BD than in CD. The numbers of FOXP3+ T cells, CD3+ T cells, and CD20+ B cells in biopsy tissue from intestinal BD were significantly higher than CD, but the ratio of FOXP3+ T cells to CD3+ T cells was not statistically different. Besides the typical clinical and endoscopic findings, diagnostic biopsies from the ileocecal region in intestinal BD show some histological and immunophenotypic features that are different from CD, which may be useful in distinguishing these two entities.


Factors influencing the use of episiotomy during vaginal delivery in South Eastern Nigeria.
Given considerable evidence that routine episiotomy increases maternal morbidity and without evidence to support maternal or neonatal benefit, has episiotomy use changed among health care providers? To date, very limited information exists relating to the past and current practice of episiotomy in many developing countries. To determine the prevalence of episiotomy at Aba in South Eastern Nigeria, examine factors influencing the performance of episiotomy and document complications associated with the procedure. A hospital based retrospective study. The Abia State University Teaching Hospital (ABSUTH), Aba in South Eastern Nigeria, from January 2001 to December 2005. Four thousand, one hundred and seventy two mothers who delivered vaginally within the study period. There were 1877 episiotomies, for an episiotomy rate of 45%. Ninety per cent of the primigravid parturients had episiotomy. Women undergoing episiotomy were younger (mean age 24.7 years; range 16-37) than women without episiotomy (mean age 28.5 years, range 20-43). When controlled for parity and maternal age, other risk factors were occipito-posterior position, vacuum extraction, forceps delivery, vaginal breech delivery, and a history of Caesarean section. Episiotomy use was also associated with major perineal lacerations and increased length of hospital stay. The episiotomy rate of 45 per 100 vaginal deliveries in this study is obviously higher than evidence-based recommendations for optimal patient care. A policy of systematic reduction in the incidence of episiotomy can be pursued in this hospital. Greater attention needs to be paid to selection of women to undergo episiotomy.


Thalamic Glioblastoma: Clinical Presentation, Management Strategies, and Outcomes.
Thalamic glioblastomas (GBMs) represent a significant neurosurgical challenge. In view of the low incidence of these tumors, outcome data and management strategies are not well defined. To identify the natural history and factors associated with survival in patients with thalamic glioblastoma. A retrospective review of all patients with thalamic glioblastoma over a 10-yr period was performed. Presenting clinical, radiological, and outcome data were collected. Chi-squared and Fisher's exact tests were used to compare clinical characteristics across tumor groups. Cox proportional hazard models were utilized to investigate variables of interest with regard to overall survival. Fifty-seven patients met inclusion criteria, with a median age of 53 and median Karnofsky Performance Scale (KPS) score of 80. The most common presenting symptoms were weakness, confusion, and headache. Hydrocephalus was present in 47% of patients preoperatively. Stereotactic biopsy was performed in 47 cases, and 10 patients underwent craniotomy. The median overall survival was 12.2 mo. Higher KPS, younger age, and cerebrospinal fluid (CSF) diversion were correlated with better overall survival univariately, respectively, while the presence of language deficits at initial presentation was associated with poorer survival. In multivariate analysis, the only significant predictor of survival was presenting KPS. The overall survival of patients with thalamic glioblastoma is comparable to unresectable lobar supratentorial GBMs. Younger patients and those with good presenting functional status had improved survival. Midbrain involvement by the tumor is not a negative prognostic factor. Improved therapies are needed, and patients should be considered for early trial involvement and aggressive upfront therapy.


DataView: A Tutorial Tool for Data Analysis. Template-based Spike Sorting and Frequency Analysis.
DataView is a Windows program for viewing and analyzing digital data derived from analog signals using A/D acquisition systems. It is primarily designed for research neuroscientists, but its low (or zero) cost makes it a suitable tool for giving students hands-on experience of analysis techniques. It is supplied with many examples of pre-recorded data and also has facilities to allow tutors to use their own - or indeed their students' - experimental results as the dataset for analysis. This article illustrates the use of DataView with a brief tutorial on template-based spike sorting and frequency analysis. The DataView manual contains detailed instructions and sample datasets for a wide range of other analytical and data-manipulation techniques.


Cross-sectional average length of life by parity: Country comparisons.
This study aims to present an alternative measure of fertility-cross-sectional average length of life by parity (CALP)-which: (1) is a period fertility indicator using all available cohort information; (2) captures the dynamics of parity transitions; and (3) links information on fertility quantum and timing together as part of a single phenomenon. Using data from the Human Fertility Database, we calculate CALP for 12 countries in the Global North. Our results show that women spend the longest time at parity zero on average, and in countries where women spend comparatively longer time at parity zero, they spend fewer years at parities one and two. The analysis is extended by decomposing the differences in CALPs between Sweden and the United States, revealing age- and cohort-specific contributions to population-level differences in parity-specific fertility patterns. The decomposition illustrates how high teenage fertility in the United States dominates the differences between these two countries in the time spent at different parities.


Phrynosoma intraepidermal receptor: A dorsal intraepidermal mechanoreceptor in horned lizards (Phrynosoma; Phrynosomatidae; Reptilia).
Horned lizards of seven species have intraepidermal sensory receptors on many dorsal body scales, some limb scales, and on head scales (supra- and infralabial, eyelid edges, frontal facing surfaces, and mental chin). These dome-shape scale receptors usually occur singly on keeled scales. Frequently, several receptor-bearing scales are grouped around an enlarged, receptor-bearing spine scale, thus forming multiple-scale complexes. Each dome-shape scale organ is delimited by a circular groove (figured in stereoscopic SEM). Ultrastructural examination of these receptors in Phrynosoma modestum shows them to have characteristics of reptilian intraepidermal mechanoreceptors. Each dome-shape scale organ is covered by thinned α- and β-layers of epidermal keratin. The β-layer forms a thickened ring immediately outside the circular groove and is very thin within the groove. The epidermal portion of the domed receptor contains columnar cells with numerous desmosomal connections. Myelinated nerve fibers and melanophore processes traverse these columnar cells, extending upward from a dermal papilla to just below the α-layer of the dome-shape receptor. Distally, the nerve fibers enlarge to form discoidal nerve terminals, which are surrounded by desmosomes, forming a tonofibrillar basket. Dome-shape scale receptors may function to: (1) detect contact with objects during forward locomotion, (2) locate attacking ants on the lizard's skin and/or, during subterranean burrowing, (3) determine depth below the surface, or (4) sense vibrations through the soil from surface predators or surface rainfall. © 1996 Wiley-Liss. Inc.


Mitochondrial Calcium Dysregulation Contributes to Dendrite Degeneration Mediated by PD/LBD-Associated LRRK2 Mutants.
Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of late-onset familial Parkinson's disease (PD), with clinical features of motor and cognitive dysfunction indistinguishable from sporadic PD. Calcium dysregulation plays an important role in PD pathogenesis, but the mechanisms of neurodegeneration remain unclear. Recent reports indicate enhanced excitatory neurotransmission in cortical neurons expressing mutant LRRK2, which occurs before the well-characterized phenotype of dendritic shortening. As mitochondria play a major role in the rapid buffering of cytosolic calcium, we hypothesized that altered mitochondrial calcium handling contributes to dendritic retraction elicited by the LRRK2-G2019S and -R1441C mutations. In primary mouse cortical neurons, we observed increased depolarization-induced mitochondrial calcium uptake. We found that expression of mutant LRRK2 elicited transcriptional upregulation of the mitochondrial calcium uniporter (MCU) and the mitochondrial calcium uptake 1 protein (MICU1) with no change in levels of the mitochondrial calcium antiporter NCLX. Elevated MCU and MICU1 were also observed in LRRK2-mutated patient fibroblasts, along with increased mitochondrial calcium uptake, and in postmortem brains of sporadic PD/PDD patients of both sexes. Transcriptional upregulation of MCU and MICU1 was caused by activation of the ERK1/2 (MAPK3/1) pathway. Inhibiting ERK1/2 conferred protection against mutant LRRK2-induced neurite shortening. Pharmacological inhibitors or RNAi knockdown of MCU attenuated mitochondrial calcium uptake and dendritic/neuritic shortening elicited by mutant LRRK2, whereas expression of a constitutively active mutant of NCLX that enhances calcium export from mitochondria was neuroprotective. These data suggest that an increased susceptibility to mitochondrial calcium dysregulation contributes to dendritic injury in mutant LRRK2 pathogenesis.SIGNIFICANCE STATEMENT Cognitive dysfunction and dementia are common features of Parkinson's disease (PD), causing significant disability. Mutations in LRRK2 represent the most common known genetic cause of PD. We found that PD-linked LRRK2 mutations increased dendritic and mitochondrial calcium uptake in cortical neurons and familial PD patient fibroblasts, accompanied by increased expression of the mitochondrial calcium transporter MCU. Blocking the ERK1/2-dependent upregulation of MCU conferred protection against mutant LRRK2-elicited dendrite shortening, as did inhibiting MCU-mediated calcium import. Conversely, stimulating the export of calcium from mitochondria was also neuroprotective. These results implicate increased susceptibility to mitochondrial calcium overload in LRRK2-driven neurodegeneration, and suggest possible interventions that may slow the progression of cognitive dysfunction in PD.


Quantitative analysis of methylation defects and correlation with clinical characteristics in patients with pseudohypoparathyroidism type I and GNAS epigenetic alterations.
Pseudohypoparathyroidism type I (PHP-I) includes two main subtypes, PHP-Ia and -Ib. About 70% of PHP-Ia patients, who show Albright hereditary osteodystrophy (AHO) associated with resistance toward multiple hormones (PTH/TSH/GHRH/gonadotropins), carry heterozygous mutations in the α-subunit of the stimulatory G protein (Gsα) exons 1-13, encoded by the guanine nucleotide binding-protein α-stimulating activity polypeptide 1 (GNAS), whereas the majority of PHP-Ib patients, who classically display hormone resistance limited to PTH and TSH with no AHO sign, have methylation defects in the imprinted GNAS cluster. Recently methylation defects have been detected also in patients with PHP and different degrees of AHO, indicating a molecular overlap between the two forms. The objectives of the study were to collect patients with the following characteristics: clinical PHP-I (with or without AHO), no mutation in Gsα coding sequence, but the presence of GNAS methylation alterations and to investigate the existence of correlations between the degree of the epigenetic defect and the severity of the disease. We quantified GNAS methylation alterations by both PCR-pyrosequencing and methylation specific-multiplex ligation-dependent probe amplification assay in genomic DNA from 63 patients with PHP-I and correlated these findings with clinical parameters (age at diagnosis; calcium, phosphorus, PTH, TSH levels; presence or absence of each AHO sign). By both approaches, the degree of the imprinting defect did not correlate with the onset of the disease, the severity of endocrine resistances, or with the presence/absence of specific AHO signs. Similar molecular alterations may lead to a broad spectrum of diseases, from isolated PTH resistance to complete PHP-Ia, and the degree of methylation alterations does not reflect or anticipate the severity and the type of different PHP/AHO manifestations.


Risk factors for weight faltering in infancy according to age at onset.
The aim of this study was to identify risk factors for failure to thrive (FTT) or weight faltering according to age of onset. The study is part of a Danish longitudinal population study of early risk mechanisms in child psychiatric disorders, The Copenhagen Child Cohort, which consists of a birth cohort of 6090 children born during the year 2000 and followed prospectively from birth. Weight faltering/FTT was defined as slow conditional weight gain, and divided into subtypes according to age of onset in the first year of life: birth to 2 weeks, 2 weeks to 4 months, and 4-8 months. Regardless of the age of onset, slow weight gain was found to be strongly associated with feeding problems, but the risk factors involved differed according to age of onset. Thus, onset within the first weeks of life clearly differed from faltering later on, the former being strongly associated with low birthweight and gestational age, with single parenthood and with mother having smoked during pregnancy. Onset between 2 weeks and 4 months was associated with congenital disorders and serious somatic illness, and with deviant mother-child relationship, whereas, onset between 4 and 8 months seemed to represent a group of children with feeding problems arising de novo in otherwise healthy children. In conclusion, weight faltering in infancy is clearly associated with contemporary measured feeding problems, but the risk mechanisms involved differ in early vs. late onset.


An alternative index for assessing profile similarity in bioequivalence trials.
In a typical bioequivalence trial, summary measures of the plasma concentration versus time profile are used to compare two formulations of a drug product. Commonly used measures include area under the curve (AUC), maximum plasma concentration (C(max)) and time to maximum concentration (T(max)). Equivalence of these summary measures, in general, does not guarantee equivalence of the entire profile. Rescigno and Chinchilli and Elswick propose indices which measure profile similarity, but can be overly sensitive to unimportant differences and are not easily interpreted pharmacologically. We propose an alternative index based on smoothing the relative difference between bioavailability profiles. This provides a method for assessing bioequivalence over the entire profile which has a familiar interpretation and can be tuned to provide a compromise between the insensitivity to pattern differences of summary measures and the oversensitivity of pointwise comparisons.


Bird Species Involved in West Nile Virus Epidemiological Cycle in Southern Québec.
Despite many studies on West Nile Virus (WNV) in the US, including the reservoir role of bird species and the summer shifts of the Culex mosquito, feeding from birds to mammals, there have been few equivalent studies in the neighboring regions of Canada where WNV is endemic. Here, a priority list of bird species likely involved in WNV transmission in the greater Montréal area is constructed by combining three sources of data: (i) from WNV surveillance in wild birds (2002-2015); (ii) blood meal analysis of Culex pipiens-restuans (CPR), the primary enzootic vectors of WNV in the region, collected from surveillance in 2008 and 2014; (iii) literature review on the sero-prevalence/host competence of resident birds. Each of these data sources yielded 18, 23 and 53 species, and overall, 67 different bird species were identified as potential WNV amplifiers/reservoirs. Of those identified from CPR blood meals, Common starlings, American robins, Song sparrows and House sparrows ranked the highest and blood meal analysis demonstrated a seasonal shift in feed preference from birds to mammals by CPR. Our study indicates that there are broad similarities in the ecology of WNV between our region and the northeastern US, although the relative importance of bird species varies somewhat between regions.


[Extended spinal decompression using an anterior approach in the treatment of myelopathies caused by cervical arthrosis].
Forty-five patients suffering from severe myelopathy due to cervical spondylosis with stenosis of the spinal canal were treated by anterior decompression extending over three levels or more. In eight instances, the decompression was the only surgical procedure: in 37 instances, there was associated bone graft. No severe complications were noted. The clinical results were assessed, using the Nurick scale. The average follow-up was four years. No patient was made worse. Twelve were completely relieved, 21 were improved and 12 were unchanged. The authors conclude that this technique is worthwhile. Grafting should be done only in cases where there is post-operative instability. After a review of the literature, the authors conclude that anterior resection of the vertebral bodies is more reliable than extensive laminectomy.


Impact of different inspiratory flow patterns on arterial C02-tension.
Ventilation with decelerating inspiratory flow is known to reduce the dead space fraction and to decrease PaCO2. Constant inspiratory flow with an end-inspiratory pause (EIP) is also known to increase the removal of CO2. The aim of the study was to elucidate the effect of the pause/no-flow period while both the pattern and rate of inspiratory flow was unchanged, and when the lung was ventilated with sufficient PEEP to prevent end-expiratory collapse. Surfactant depleted piglets were assigned to decelerating or constant inspiratory flow with 24 breaths per minute (bpm) or 12 bpm, or to constant flow, without and with an end-inspiratory pause of 25%. By adding an EIP the total time without active inspiratory flow of the respiratory cycle was kept unchanged. Gas exchange, airway pressures, functional residual capacity (using sulfurhexafluoride) and haemodynamics (thermo-dye indicator dilution technique) were measured. Irrespective of ventilatory frequency, PaCO2 was lower and serial dead space reduced with decelerating flow, compared with constant inspiratory flow. With an end-inspiratory pause added to constant inspiratory flow, serial dead space was reduced but did not decrease PaCO2. The results of this study corroborate the assumption that total time without active inspiratory flow is important for arterial CO2-tension.


A nanoscale parametric feedback oscillator.
We describe and demonstrate a new oscillator topology, the parametric feedback oscillator (PFO). The PFO paradigm is applicable to a wide variety of nanoscale devices and opens the possibility of new classes of oscillators employing innovative frequency-determining elements, such as nanoelectromechanical systems (NEMS), facilitating integration with circuitry and system-size reduction. We show that the PFO topology can also improve nanoscale oscillator performance by circumventing detrimental effects that are otherwise imposed by the strong device nonlinearity in this size regime.


The effects of adding lactococcal proteinase on the growth rate of Lactococcus lactis in milk depend on the type of enzyme.
Increasing the proteolytic activity of Lactococcus lactis cultures in milk by adding the corresponding proteinase resulted in a stimulation of the growth rate regardless of the strain and the type of proteinase, demonstrating that the rate of casein degradation was responsible for the growth rate limitation of L. lactis in milk. However, the stimulation was only transient, and the reduction in growth rate in the poststimulation phase depended on the type of cell envelope proteinase. When a PI-type proteinase was added, three causes were involved in the subsequent reduction in growth rate: degradation of the added proteinase, repression of the proteolytic activity expressed by the cells, and competition for peptide uptake. When a PIII-type proteinase was added, the cessation of stimulation was due to the autoproteolysis of the added enzyme only.


Preferential expression of alpha B-crystallin in astrocytic elements of neuroectodermal tumors.
Recently the authors have identified a major component of Rosenthal fibers as alpha B-crystallin, a major lens protein. In the current study the authors investigated the expression of alpha B-crystallin in four cultured glioma cell lines and in 115 human neuroectodermal tumors. alpha B-crystallin was expressed differentially by those glioma cell lines, but not by neuroblastoma cell lines. Northern blot analysis revealed two distinct messages for alpha B-crystallin in C-6, whereas only a single message in U-373MG and G26-24. In human surgical specimens positive immunostaining was frequently observed in the following brain tumors: pilocytic astrocytoma of the juvenile type, anaplastic astrocytoma, glioblastoma multiforme, and subependymal giant cell astrocytoma. The astrocytic elements of mixed oligoastrocytomas, glioblastomas with sarcomatous components, and gangliogliomas were likewise strongly stained. In contrast, little immunoreactivity was observed in ependymal and choroid plexus tumors. Thus, alpha B-crystallin is mainly expressed by astrocytic tumors among neuroectodermal neoplasms, without regard to the presence of Rosenthal fibers.


Comparing Outcomes of Sub-Total Cholecystectomy Versus Open Cholecystectomy as Bailout Procedures for the Difficult Gallbladder.
Although laparoscopic cholecystectomy is one of the most common operations performed, there is no consensus on the best surgical approach when inflammation obscures hepatocystic anatomy in severe cholecystitis. Traditionally, this situation triggered conversion to open cholecystectomy (COC); however, in recent decades, alternative approaches have been described. We compared outcomes of bailout procedures for severe cholecystitis, primarily focusing on COC versus laparoscopic subtotal cholecystectomy (LSTC). Retrospective review comparing outcomes of intended laparoscopic cholecystectomy cases that were converted to bailout procedures between 2015-2020 at a single institution. Bailout procedures were categorized into LSTC and COC groups. Demographics, clinical presentation, time to surgery, operative indications, operative duration, and post-operative outcomes were compared using independent sample t-tests with Welch-Satterthwaite correction or Wilcoxon rank-sum tests (continuous variables) or Fisher's exact/χ2 tests. A P-value of less than .05 was considered significant. Final analysis included 158 subjects: 55 LSTC and 99 COC. Patient demographics and clinical presentations were similar between groups. LSTC had shorter operative time, fewer ICU admissions, and shorter length of stay than COC (P < .05). There were 9 (9.2%) cases of ileus, 4 (4.0%) cases of post-operative bleeding, and 2 (2.0%) cases of bile duct injury in COC. There was 1 (1.8%) case of ileus, 1 (1.8%) case of post-operative bleeding, and no bile duct injury in LSTC. LSTC was associated with fewer complications than COC, which had higher rates of biliary injury, bleeding, ileus, ICU admission, and longer hospital stay.


Somatic mosaicism for Friedreich's ataxia GAA triplet repeat expansions in the central nervous system.
Most patients with Friedreich's ataxia (FRDA) carry expanded GAA repeats in both homologues of the frataxin gene on chromosome 9. We determined the size of the GAA repeats in autopsied samples from the CNS of six FRDA patients. We observed heterogeneity of repeat sizes in different CNS regions, indicative of extensive mitotic instability. Samples from the same CNS subdivision (e.g., cortex, thalamus) contained a similar mixture of alleles, suggesting that the pattern of repeat size mosaicism reflects the developmental history of each sample. Regional differences in repeat size could not account for the characteristic distribution of pathology in FRDA, which appears instead to be related to the pattern of frataxin expression.


Atypical Presentation of a Sequestered Posterolateral Disc Fragment.
Sequestered disc fragments typically occur ventrally but can also migrate dorsally or intradurally. At times, atypical disc herniations can be misinterpreted on imaging as other lesions, such as neoplasms, hematomas, or abscesses. We present an uncommon case of a patient presenting with cauda equina syndrome secondary to an enhancing sequestered disc fragment mimicking a tumor.


Decrease in the Generation of Amyloid-β Due to Salvianolic Acid B by Modulating BACE1 Activity.
Generation and accumulation of the amyloid-β (Aβ) peptide after proteolytic processing of the full length amyloid precursor protein (FL-APP) by β-secretase (β-site APP cleaving enzyme or BACE1) and γ-secretase are the main causal factors of Alzheimer's disease (AD). Thus, inhibition of BACE1, a rate-limiting enzyme in the production of Aβ, is an attractive therapeutic approach for the treatment of AD. Recent studies suggest that salvianolic acid B (Sal B) is isolated from the radix of Salvia miltiorrhiza Bunge, a Chinese herbal medicine commonly used for the treatment of cardiovascular, cerebrovascular and liver diseases in China. In this study, we discovered that Sal B acted as a BACE1 modulator and reduced the level of secreted Aβ in two different Swedish APP (SwedAPP) mutant cell lines. Using N2a-mouse and H4- human neuroglioma cell lines expressing SwedAPP, it was demonstrated that Sal B significantly and dose-dependently decreased the generation of extracellular Aβ, soluble APPβ (by-product of APP cleaved by BACE1), and intracellular C-terminal fragment β from APP without influencing α-secretase and γ-secretase activity and the levels of FL-APP. In addition, using protein-docking, we determined the potential conformation of Sal B on BACE1 docking and revealed the interactions of Sal B with the BACE1 catalytic center. The docking provides a feasible explanation for the experimental results, especially in terms of the molecular basis of Sal B's action. Our results indicate that Sal B is a BACE1 inhibitor and, as such, is a promising candidate for the treatment of AD.


KGF pretreatment decreases B7 and granzyme B expression and hastens repair in lungs of mice after allogeneic BMT.
We investigated keratinocyte growth factor (KGF) as a pretreatment therapy for idiopathic pneumonia syndrome (IPS) generated as a result of lung damage and allogeneic T cell-dependent inflammatory events occurring in the early peri-bone marrow (BM) transplant (BMT) period. B10.BR (H2(k)) recipient mice were transplanted with C57BL/6 (H2(b)) BM with spleen cells after lethal irradiation with and without cyclophosphamide conditioning with and without subcutaneous KGF pretreatment. KGF-pretreated mice had fewer injured alveolar type II (ATII) cells at the time of BMT and exhibited ATII cell hyperplasia at day 3 post-BMT. The composition of infiltrating cells on day 7 post-BMT was not altered by KGF pretreatment, but the frequencies of cells expressing the T-cell costimulatory molecules B7.1 and B7.2 and mRNA for the cytolysin granzyme B (usually increased in IPS) were decreased by KGF. Sera from KGF-treated mice had increases in the Th2 cytokines interleukin (IL)-4, IL-6, and IL-13 4 days after cessation of KGF administration (i.e., at the time of BMT). These data suggest that KGF hinders IPS by two modes: 1) stimulation of alveolar epithelialization and 2) attenuation of immune-mediated injury as a consequence of failure to upregulate cytolytic molecules and B7 ligand expression and the induction of anti-inflammatory Th2 cytokines in situ.


Choosing when choices are limited: The role of perceived afforded choice and autonomy in prisoners' well-being.
Although prison life is generally characterized by little choice and autonomy, there exists considerable variation in the number and type of choices offered to different prisoners. Based on self-determination theory, which maintains that perceived afforded choice and autonomy are of crucial importance for individuals' psychological functioning, we investigated the relation between choice, autonomy satisfaction, and subjective quality of life among prisoners. We drew on quantitative cross-sectional data gathered among 156 Belgian prisoners (Mage = 38.60, 88.5% men). Participants filled out questionnaires measuring perceived afforded choice, autonomy satisfaction, and quality of life. The main hypotheses were tested using structural equation modeling. Results showed that perceived afforded choice related to higher subjective quality of life within prison. This relation was partially accounted for by elevated levels of autonomy satisfaction. Supplementary analyses revealed that the benefit of choice emerged regardless of participants' valuation of choice, and that perceived afforded choice with regard to daytime activities (i.e., leisure activities, work, and education) yielded the strongest effect. Collectively, results suggest that enhancing perceived afforded choice and autonomy satisfaction may provide important avenues for promoting prisoner quality of life. These findings are discussed in light of the growing focus on strength-based approaches and psychological well-being within the prison context. (PsycINFO Database Record


A pilot study to determine the effect of trunk and hip focused neuromuscular training on hip and knee isokinetic strength.
The objective was to determine the effect of trunk focused neuromuscular training (TNMT) on hip and knee strength. The hypothesis was that TNMT would increase standing isokinetic hip abduction, but not knee flexion/extension, strength. 21 high-school female volleyball players (14 TMNT, mean age 15.4 (1.4) years, weight 170.5 (5.0) cm, height 64.1 (8.5) kg and 7 controls, mean age 16.0 (1.7) years, height 173.4 (10.0) cm, weight 63.9 (5.3) kg; p>0.05) were recruited to participate in this study. The 14 TNMT subjects participated in a TNMT protocol (twice weekly) over a 10 week period in addition to their standard once-weekly off-season strength training. Standing isokinetic hip abduction strength and seated knee flexion/extension strength were measured before and after TNMT. A significant interaction of group and time was observed. The TNMT group increased isokinetic hip abduction strength approximately 15% (13.5% in the dominant leg: mean (SD) 46.6 (10.1) to 52.9 (11.4) foot-pounds and 17.1% in the non-dominant leg: 46.1 (10.4) to 54.0 (10.7) foot-pounds; p = 0.01). There was no difference in the control group in pre-test versus post-test measures. Post-test results also indicated no effect of TNMT on isokinetic knee extension (p = 0.57) or knee flexion (p = 0.57) strength. Ten weeks of TNMT increased standing hip abduction strength in female athletes. Increased hip abduction strength and recruitment may improve the ability of female athletes to increase control of lower limb alignment and decrease knee loads resulting from increased trunk displacement during sports activities.


The prospective relationship between distress tolerance and cigarette smoking expectancies in adolescence.
The current study examined the prospective relationship between distress tolerance (DT) and positive and negative cigarette smoking outcome expectancies, which are reliable predictors of the onset and maintenance of smoking behaviors. Data from a longitudinal study (N = 204) examining risk behaviors in adolescence were used to assess whether DT predicts individual differences in rate of change in smoking outcome expectancies over 4 annual assessment waves through adolescence. Adolescents (mean age at first wave: 13.03 years; SD = 0.88 years) completed a behavioral task assessing DT at baseline and a self-report measure of adolescent smoking expectancies annually across 4 years. Latent growth curve models were estimated to test our hypotheses. Results showed that DT at baseline did not significantly predict initial levels of negative affect reduction (NAR) expectancies, but NAR expectancies increased more quickly over time for adolescents with lower DT. Moreover, as hypothesized, DT did not prospectively predict significant changes in smoking expectancies outside of the domain of NAR, including negative physical feelings, negative social impression, and boredom reduction expectancies. These findings suggest that DT is a useful indicator of adolescent expectancies about the consequences of cigarette smoking, particularly those focused on reducing negative affect. Thus, DT may be an important target for preventing smoking initiation among adolescents via this putative mechanism. Theoretical and clinical implications are discussed within the context of observed effect sizes. (PsycINFO Database Record


Come from away: Best practices in mini-sabbaticals for the development of young investigators: a White Paper by the SEQUIN (mini-Sabbatical Evaluation and QUality ImprovemeNt) Group.
Mini-sabbaticals are formal short-term training and educational experiences away from an investigator's home research unit. These may include rotations with other research units and externships at government research or regulatory agencies, industry and non-profit programs, and training and/or intensive educational programs. The National Institutes of Health have been encouraging training institutions to consider offering mini-sabbaticals, but given the newness of the concept, limited data are available to guide the implementation of mini-sabbatical programs. In this paper, we review the history of sabbaticals and mini-sabbaticals, report the results of surveys we performed to ascertain the use of mini-sabbaticals at Clinical and Translational Science Award hubs, and consider best practice recommendations for institutions seeking to establish formal mini-sabbatical programs.


An efficient biological pathway layout algorithm combining grid-layout and spring embedder for complicated cellular location information.
Graph drawing is one of the important techniques for understanding biological regulations in a cell or among cells at the pathway level. Among many available layout algorithms, the spring embedder algorithm is widely used not only for pathway drawing but also for circuit placement and www visualization and so on because of the harmonized appearance of its results. For pathway drawing, location information is essential for its comprehension. However, complex shapes need to be taken into account when torus-shaped location information such as nuclear inner membrane, nuclear outer membrane, and plasma membrane is considered. Unfortunately, the spring embedder algorithm cannot easily handle such information. In addition, crossings between edges and nodes are usually not considered explicitly. We proposed a new grid-layout algorithm based on the spring embedder algorithm that can handle location information and provide layouts with harmonized appearance. In grid-layout algorithms, the mapping of nodes to grid points that minimizes a cost function is searched. By imposing positional constraints on grid points, location information including complex shapes can be easily considered. Our layout algorithm includes the spring embedder cost as a component of the cost function. We further extend the layout algorithm to enable dynamic update of the positions and sizes of compartments at each step. The new spring embedder-based grid-layout algorithm and a spring embedder algorithm are applied to three biological pathways; endothelial cell model, Fas-induced apoptosis model, and C. elegans cell fate simulation model. From the positional constraints, all the results of our algorithm satisfy location information, and hence, more comprehensible layouts are obtained as compared to the spring embedder algorithm. From the comparison of the number of crossings, the results of the grid-layout-based algorithm tend to contain more crossings than those of the spring embedder algorithm due to the positional constraints. For a fair comparison, we also apply our proposed method without positional constraints. This comparison shows that these results contain less crossings than those of the spring embedder algorithm. We also compared layouts of the proposed algorithm with and without compartment update and verified that latter can reach better local optima.


[Intensive psychopharmacologic therapy of slowly-progressive schizophrenia].
The authors analyze the results of psychopharmacotherapy of 120 patients with slowly progressive schizophrenia characterized by a high resistance to the treatment. Two new methods of the intensive therapy of such conditions (discrete and daily intravenous drip of tranquilizers in conjunction with low doses of neuroleptics) are described. The pharmacological and pharmacokinetic substantiation of each of the two techniques is presented. Clinical indications for their use have been elaborated.


Dupuytren's contracture: a retrospective database analysis to assess clinical management and costs in England.
Dupuytren's disease is a fibro-proliferative disorder affecting ~3-5% of the UK population. Current surgical treatments for Dupuytren's contracture (DC) include fasciectomy and fasciotomy. We assessed the clinical management of DC in England over a 5-year period; associated NHS costs were assessed for a 1-year period. Hospital Episode Statistics were extracted from April 2003 to March 2008 for patients with Palmar Fascial Fibromatosis (ICD10=M720) and DC-related procedures. Variables included demographics, OPCS, patient status and physician specialty. To estimate 2010-2011 costs, HRG4 codes and the National Schedule of Tariff 2010-11-NHS Trusts were applied to the 2007-2008 period. Over 5 years, 75,157 DC admissions were recorded; 64,506 were analyzed. Mean admissions per year were 12,901 and stable. Day cases increased from 42% (2003-2004) to 62% (2007-2008). The percent of patients having two or more admissions per year increased from 5.5% in 2003-2004 to 26.1% in 2007-2008. Between 2003 and 2007, 91% of procedures were Fasciectomy. Revision of Fasciectomy and Fasciotomy each accounted for ~4%; Amputation for 1%. In 2007, classification was extended to identify Digital Fasciectomy, its Revision and Dermofasciectomy. In 2007-2008, admissions were: 70% Palmar Fasciectomy, 16% Digital Fasciectomy, 1.3% Other Fasciectomy, 4.4% Revision of Palmar Fasciectomy, 1.3% Revision of Digital Fasciectomy, 3.8% Division of Palmar Fascia, 2.6% Dermofasciectomy and 1.1% Amputation. 79% of cases were overseen by trauma and orthopaedic surgeons, 19% by plastic surgeons. Mean (±SD) inpatient hospital length of stay was 1.5 (±1.4) days in 2003-2004 and 1.0 (±1.3) days in 2007-2008. Total estimated costs for 1 year (2010-2011) were £41,576,141. Per-patient costs were £2,885 (day case) and £3,534 (inpatient). Costs ranged from £2,736 (day-case Fasciectomy) to £9,210 (day-case Revision Digital). Between 2003 and 2008, fasciectomy was the most common surgical procedure for DC in England. While procedure rates and physician specialties varied little, there was a reversal in surgical venue: inpatient operations decreased as day-case procedures increased. The change is likely due to economic trends and changes to the healthcare system. Estimated costs for 2010-2011 varied by procedure type and patient status. These findings can be used to understand clinical management of DC and guide healthcare policy.


Fission yeast dim1(+) encodes a functionally conserved polypeptide essential for mitosis.
In a screen for second site mutations capable of reducing the restrictive temperature of the fission yeast mutant cdc2-D217N, we have isolated a novel temperature-sensitive mutant, dim1-35. When shifted to restrictive temperature, dim1-35 mutant cells arrest before entry into mitosis or proceed through mitosis in the absence of nuclear division, demonstrating an uncoupling of proper DNA segregation from other cell cycle events. Deletion of dim1 from the Schizosaccharomyces pombe genome produces a lethal G2 arrest phenotype. Lethality is rescued by overexpression of the mouse dim1 homolog, mdim1. Likewise, deletion of the Saccharomyces cerevisiae dim1 homolog, CDH1, is lethal. Both mdim1 and dim1(+) are capable of rescuing lethality in the cdh1::HIS3 mutant. Although dim1-35 displays no striking genetic interactions with various other G2/M or mitotic mutants, dim1-35 cells incubated at restrictive temperature arrest with low histone H1 kinase activity. Morevoer, dim1-35 displays sensitivity to the microtubule destabilizing drug, thiabendazole (TBZ). We conclude that Dim1p plays a fundamental, evolutionarily conserved role as a protein essential for entry into mitosis as well as for chromosome segregation during mitosis. Based on TBZ sensitivity and failed chromosome segregation in dim1-35, we further speculate that Dim1p may play a role in mitotic spindle formation and/or function.


[Neurobehavioral effects of explosion exposure on acute and chronic traumatic brain injury in rats].
Objective: To explore the effect of nerve injury in rats by neurobehavioral experiments, in order to provide a model and idea for further clarification of the traumatic brain injury mechanism under explosion exposure. Methods: From May 2021 to August 2022, 160 SPF male rats were randomly divided into four groups, including control group, 60 kPa group (low intensity group), 90 kPa group (medium intensity group) and 120 kPa group (high intensity group). The blast induced traumatic brain injury (bTBI) model of rats was established by using the shock tube platform to simulate the shock wave parameters of the explosion overpressure of 60 kPa, 90 kPa and 120 kPa. Acute observation was carried out after 24 h and 7 d of explosive exposure, and chronic recovery observation was carried out after 28 d and 90 d. The time effect of shock wave brain injury in different situations was discussed by open field, light dark test, active avoidance test. Finally, the results of brain injury in rats were detected by pathological tissue staining. Results: After 24 h explosion exposure, compared with the control group, the rest time of rats in low and high intensity groups increased, the total movement distance decreased, and the number of visits to the camera obscura decreased, with statistical significance (P<0.05). After 7 days of exposure, compared with the control group, the rest time of rats in high intensity group increased, and the number of visits to the obscura decreased, with statistical significance (P<0.05). After 28 and 90 days of exposure, compared with the control group, there were no significant differences in rest time, total exercise distance and times of visiting the camera obscura in all intensity groups (P>0.05). After 24 h of explosive exposure, compared with the control group, the cell morphology of rats in each intensity group was normal, and no inflammatory cell infiltration was observed. Conclusion: In the acute phase (24 h) of blast exposure, rats have no desire to explore the outside world, and shock wave exposure may damage the neurological function of rats.


The role of orienting in vibrissal touch sensing.
Rodents, such as rats and mice, are strongly tactile animals who explore the environment with their long mobile facial whiskers, or macrovibrissae, and orient to explore objects further with their shorter, more densely packed, microvibrissae. Although whisker motion (whisking) has been extensively studied, less is known about how rodents orient their vibrissal system to investigate unexpected stimuli. We describe two studies that address this question. In the first we seek to characterize how adult rats orient toward unexpected macrovibrissal contacts with objects and examine the microvibrissal exploration behavior following such contacts. We show that rats orient to the nearest macrovibrissal contact on an unexpected object, progressively homing in on the nearest contact point on the object in each subsequent whisk. Following contact, rats "dab" against the object with their microvibrissae at an average rate of approximately 8 Hz, which suggests synchronization of microvibrissal dabbing with macrovibrissal motion, and an amplitude of 5 mm. In study two, we examine the role of orienting to tactile contacts in developing rat pups for maintaining aggregations (huddles). We show that young pups are able to orient to contacts with nearby conspecifics before their eyes open implying an important role for the macrovibrissae, which are present from birth, in maintaining contact with conspecifics. Overall, these data suggest that orienting to tactile cues, detected by the vibrissal system, plays a crucial role throughout the life of a rat.


Reactive evaporation in ionized gases.
By conventional reactive evaporation techniques, films with a certain deviation from stochiometric composition and, therefore, increased absorptance and dielectric losses were obtained. By ionization of the residual gas a considerable increase of reactivity has been achieved. The construction of a discharge tube with a region of high current density for ionization is described. The tube was arranged inside a bell jar. The ionized gas emerged from a nozzle in the wall of the tube directly into the high vacuum region. Production parameters for SiO(2), SiO(x)N(y), and TiO(2) films were evaluated. On unheated substrates SiO(2) films, which are practically free of absorptance down to 190 nm, and TiO(2) films with refractive indices up to 2.3, were obtained.


Plasmid-encoded Pgp3 is a major virulence factor for Chlamydia muridarum to induce hydrosalpinx in mice.
Hydrosalpinx induction in mice by Chlamydia muridarum infection, a model that has been used to study C. trachomatis pathogenesis in women, is known to depend on the cryptic plasmid that encodes eight genes designated pgp1 to pgp8. To identify the plasmid-encoded pathogenic determinants, we evaluated C. muridarum transformants deficient in the plasmid-borne gene pgp3, -4, or -7 for induction of hydrosalpinx. C. muridarum transformants with an in-frame deletion of either pgp3 or -4 but not -7 failed to induce hydrosalpinx. The deletion mutant phenotype was reproduced by using transformants with premature termination codon insertions in the corresponding pgp genes (to minimize polar effects inherent in the deletion mutants). Pgp4 is known to regulate pgp3 expression, while lack of Pgp3 does not significantly affect Pgp4 function. Thus, we conclude that Pgp3 is an effector virulence factor and that lack of Pgp3 may be responsible for the attenuation in C. muridarum pathogenicity described above. This attenuated pathogenicity was further correlated with a rapid decrease in chlamydial survival in the lower genital tract and reduced ascension to the upper genital tract in mice infected with C. muridarum deficient in Pgp3 but not Pgp7. The Pgp3-deficient C. muridarum organisms were also less invasive when delivered directly to the oviduct on day 7 after inoculation. These observations demonstrate that plasmid-encoded Pgp3 is required for C. muridarum survival in the mouse genital tract and represents a major virulence factor in C. muridarum pathogenesis in mice.


Epistasis between loci on chromosomes 2 and 6 influences human height.
Human height is a typical and important complex trait, which is determined by both actions and interactions of multiple genes. Although an increasing number of genes or genomic regions have been discovered for their independent effects on height variation, no study has been performed to identify genes or loci that interact to control the trait. This study aimed to search for potential genomic regions that harbor interactive genes underlying human height. Here with a sample containing 3726 Caucasians, the largest one ever obtained from a single population of the same ethnicity among genetic linkage studies of human complex traits, we performed variance component linkage analyses of height based on a two-locus epistatic model. We examined pairwise genetic interaction among three regions, 9q22, 6p21, and 2q21, which achieved significant or suggestive linkage signals for height in our recent whole genome scan. Significant genetic interaction between 6p21 and 2q21 was detected, with 2q21 achieving a maximum LOD score of 3.21 (P = 0.0035) under the epistatic model, compared with a maximum LOD score of 1.63 under a two-locus additive model. Interestingly, 6p21 contains a cluster of candidate genes for skeletal growth, suggesting a mechanism whereby 2q21 regulates height through 6p21. By providing the first evidence for genetic interaction underlying human height variation, this study further delineated the genetic architecture of human height and contributed to the genetic dissection of human complex traits in general.


Tracheostomy in children admitted to paediatric intensive care.
Tracheostomy is a common intervention for adults admitted to intensive care; many are performed early and most are percutaneous. Our study aimed to elucidate current practice and indications for children in the UK admitted to paediatric intensive care and undergoing tracheostomy. A questionnaire covering unit guidelines, practice, and the advantages and disadvantages of tracheostomy was sent to all UK paediatric intensive care units (PICUs) participating in the Paediatric Intensive Care Audit Network (PICANet). These results were combined with data from PICANet on all children in the UK reported to have had a tracheostomy performed during a PICU admission between 2005 and 2009 inclusive. Over 5 years, 1613 children had tracheostomies performed during their PICU admission (2.05% of all admissions). The death rate was 5.58% with tracheostomy versus 4.72% overall, but differences were not significant when risk-adjusted using the Paediatric Index of Mortality 2 (PIM2). All 29 units participating in PICANet responded to the survey. Prolonged invasive ventilation was an indication for tracheostomy in 25/29 units, but the definition varied between 14 and 90 days, and most respondents considered timing on an individual basis. Children undergoing tracheostomy during PICU admission account for 9% of PICU bed days in the UK. In contrast with current adult UK practice, tracheostomy for children admitted to intensive care is infrequent, performed late following admission and usually surgical. Practice varies significantly. The death rate for children having a tracheostomy performed was not significantly higher than for children admitted to PICU who did not undergo tracheostomy.


H3N2 Canine Influenza Virus Infection in a Dog.
In 2015, H3N2 canine influenza emerged in dogs in the greater Chicago area. During this time, a 10-year-old German Shepherd dog presented to the referring veterinarian with lethargy and coughing that quickly progressed to death. This report describes the macroscopic and microscopic lesions and the molecular testing performed to identify the novel North American H3N2 strain of canine influenza. The larynx, pharynx, and trachea were covered by a fibrinonecrotic membrane. Bilaterally, the lungs had multifocal subpleural necrosis of the caudal lung lobes with hemorrhage, congestion, and pulmonary edema. Staphylococcus pseudointermedius was isolated from the lung. Mycoplasma cynos was identified by real-time polymerase chain reaction from nasal passages, oropharynx, larynx, trachea, and cranial lung lobes. The neuraminidase gene sequence from the influenza virus isolated obtained from this dog had ≥98% homology to the strain circulating in the Chicago area.


Ecological drivers of antipredator defenses in carnivores.
Mammals have evolved several morphological and behavioral adaptations to reduce the risk of predation, but we know little about the ecological factors that favor their evolution. For example, some mammalian carnivores have the ability to spray noxious anal secretions in defense, whereas other species lack such weaponry but may instead rely on collective vigilance characteristic of cohesive social groups. Using extensive natural history data on 181 species in the order Carnivora, we created a new estimate of potential predation risk from mammals and birds of prey and used comparative phylogenetic methods to assess how different sources of predation risk and other ecological variables influence the evolution of either noxious weaponry or sociality in this taxon. We demonstrate that the evolution of enhanced spraying ability is favored by increased predation risk from other mammals and by nocturnality, but the evolution of sociality is favored by increased predation risk from birds of prey and by diurnality, which may allow for enhanced early visual detection. These results suggest that noxious defenses and sociality are alternative antipredator strategies targeting different predator guilds under different lighting conditions.


Determination of two wound healing components in Streptocaulon juventas (Lour.) Merr.: periplogenin and digitoxigenin.
Streptocaulon juventas (Lour.) Merr. (SJ) is an herbal medicine can promote wound healing. Cardiac glycosides, especially periplogenin, digitoxigenin, and their glycosides were the main constituents of SJ. We aim to establish a method for the simultaneous determination of periplogenin and digitoxigenin in SJ and evaluate the wound healing activities of these two components. UPLC-QqQ-MS/MS was used for the determination of periplogenin and digitoxigenin. Meanwhile, rats were subjected to full-thickness skin resection on the back to investigate the wound healing effects of periplogenin and digitoxigenin. The content of periplogenin and digitoxigenin in 13 batches of SJ extracts ranged from 43.26 to 97.15 μg/g and 18.04 to 55.55 μg/g, respectively. Periplogenin and digitoxigenin significantly increased the rate of wound healing in rats, increased the content of hydroxyproline in wound tissue, and improved the pathological state of wound skin tissue.


Discovering candidate SNPs for resilience breeding of red clover.
Red clover is a highly valuable crop for the ruminant industry in the temperate regions worldwide. It also provides multiple environmental services, such as contribution to increased soil fertility and reduced soil erosion. This study used 661 single nucleotide polymorphism (SNP) markers via targeted sequencing using seqSNP, to describe genetic diversity and population structure in 382 red clover accessions. The accessions were selected from NordGen representing red clover germplasm from Norway, Sweden, Finland and Denmark as well as from Lantmännen, a Swedish seed company. Each accession was represented by 10 individuals, which was sequenced as a pool. The mean Nei's standard genetic distance between the accessions and genetic variation within accessions were 0.032 and 0.18, respectively. The majority of the accessions had negative Tajima's D, suggesting that they contain significant proportions of rare alleles. A pairwise FST revealed high genetic similarity between the different cultivated types, while the wild populations were divergent. Unlike wild populations, which exhibited genetic differentiation, there was no clear differentiation among all cultivated types. A principal coordinate analysis revealed that the first principal coordinate, distinguished most of the wild populations from the cultivated types, in agreement with the results obtained using a discriminant analysis of principal components and cluster analysis. Accessions of wild populations and landraces collected from southern and central Scandinavia showed a higher genetic similarity to Lantmännen accessios. It is therefore possible to link the diversity of the environments where wild populations were collected to the genetic diversity of the cultivated and wild gene pools. Additionally, least absolute shrinkage and selection operator (LASSO) models revealed associations between variation in temperature and precipitation and SNPs within genes controlling stomatal opening. Temperature was also related to kinase proteins, which are known to regulate plant response to temperature stress. Furthermore, the variation between wild populations and cultivars was correlated with SNPs within genes regulating root development. Overall, this study comprehensively investigated Nordic European red clover germplasm, and the results provide forage breeders with valuable information for further selection and development of red clover cultivars.


Developmental and geographic variation in stress hormones in wild Belding's ground squirrels (Spermophilus beldingi).
Extensive research has been conducted on the role of glucocorticoids in regulating growth, mobilizing energy, responding to stressors and modulating learning and memory. However, little is known about the production of corticoids during early development in free-living animals, particularly during sensitive periods of acquisition of important behaviors. In a four-year study of Belding's ground squirrels, Spermophilus beldingi, a non-invasive assay of glucocorticoids was used to quantify age and population differences among juveniles from three California locations. Fecal-cortisol metabolites are elevated during a short period when juveniles first emerge aboveground from their natal burrows at about 4 weeks of age. This period of cortisol elevation coincides with when young are learning survival behaviors such as anti-predator responses and foraging strategies. Population differences in juvenile cortisol levels, which may reflect local variation in habitat quality and predator environments, were not evident until 2 weeks after emergence. Elevated cortisol at the age of emergence was also observed in juveniles born and reared in captivity without exposure to typical stressors that occur around the age of emergence. These results indicate that corticoids are regulated during early development, and the possible functions of age-related corticoid levels are discussed, including mobilization of glucose for natal emergence and later facilitation of growth and energy storage during the short summer before hibernation. In some species, elevated corticoids can also facilitate learning and memory, and current work is exploring whether the higher cortisol observed in all three S. beldingi populations just after emergence function to promote rapid acquisition of survival behaviors.


Female-favorable attenuation of coronary myogenic constriction via reciprocal activations of epoxyeicosatrienoic acids and nitric oxide.
Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid via CYP/epoxygenases, which are catabolized by soluble epoxide hydrolase (sEH) and known to possess cardioprotective properties. To date, the role of sEH in the modulation of pressure-induced myogenic response/constriction in coronary arteries, an important regulatory mechanism in the coronary circulation, and the issue as to whether the disruption of the sEH gene affects the myogenic response sex differentially have never been addressed. To this end, experiments were conducted on male (M) and female (F) wild-type (WT) and sEH-knockout (KO) mice. Pressure-diameter relationships were assessed in isolated and cannulated coronary arteries. All vessels constricted in response to increases in intraluminal pressure from 60 to 120 mmHg. Myogenic vasoconstriction was significantly attenuated, expressed as an upward shift in the pressure-diameter curve of vessels, associated with higher cardiac EETs in M-KO, F-WT, and F-KO mice compared with M-WT controls. Blockade of EETs via exposure of vessels to 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) prevented the attenuated myogenic constriction in sEH-KO mice. In the presence of 14,15-EEZE, pressure-diameter curves of females presented an upward shift from those of males, exhibiting a sex-different phenotype. Additional administration of N(ω)-nitro-l-arginine methyl ester eliminated the sex difference in myogenic responses, leading to four overlapped pressure-diameter curves. Cardiac sEH was downregulated in F-WT compared with M-WT mice, whereas expression of endothelial nitric oxide synthase and CYP4A (20-HETE synthase) was comparable among all groups. In summary, in combination with NO, the increased EET bioavailability as a function of genetic deletion and/or downregulation of sEH accounts for the female-favorable attenuation of pressure-induced vasoconstriction.


Emergence of non-serotype b encapsulated Haemophilus influenzae as a cause of pediatric meningitis in northwestern Ontario.
Before the introduction of the conjugate vaccine, Haemophilus influenzae serotype b (Hib) was the leading cause of bacterial meningitis in children. Although successful in reducing Hib cases, the vaccine confers no protection against other serotypes of H influenzae, such as a (Hia), or f (Hif). The emergence of invasive disease caused by non-Hib in northwestern Ontario (38 cases between 2002 and 2008) with predominance of Hia was previously reported by the authors. At that time, no cases of pediatric meningitis caused by H influenzae were recorded in the region. Continued surveillance identified 12 new cases of invasive non-Hib between January 2009 and July 2011. Among these cases, three young children developed meningitis with severe complications caused by Hia or Hif. The present article describes these cases along with the characteristics of recent H influenzae isolates from the region, (ie, their genetic background and antibiotic sensitivity). The findings point to the clonal nature of circulating Hia strains as well as to an increase in frequency and severity of pediatric invasive H influenzae infections in northwestern Ontario.


The influence of native nephrectomy on the incidence of recurrent disease following renal transplantation for primary glomerulonephritis.
Factors influencing the incidence of recurrent glomerulonephritis following renal transplantation are poorly understood. Bilateral pretransplant native nephrectomy has been advocated to reduce the likelihood of recurrence after renal transplant. However, there is significant morbidity of native nephrectomy in the uremic population. Therefore, we sought to determine the effect of pretransplant native nephrectomy on the incidence of recurrent primary glomerulonephritis and the attendant risk of graft failure due to recurrent disease. Three hundred sixty-four consecutive cadaveric (n = 214), living-related (n = 137), and living-unrelated (n = 13) renal transplants were performed in 319 patients with a diagnosis of primary glomerulonephritis. Specific diagnoses included were focal segmental glomerulosclerosis (FSGS), rapidly progressive glomerulonephritis/idiopathic crescentic glomerulonephritis (RPGN/ICG), IgA nephropathy (IgA), mesangioproliferative glomerulonephritis, type I and II (MPG), anti-glomerular basement membrane nephritis (anti-GBM), and membranous glomerulonephritis (MGN). Rates of recurrence and graft loss were compared between patients treated with bilateral native nephrectomy (n = 61) and those who were not (n = 303). Bilateral nephrectomy did not prevent or delay the onset of recurrent glomerulonephritis in the renal allograft. In fact, there was a significantly increased five- and ten-year risk of recurrence in patients undergoing pretransplant nephrectomy vs. no nephrectomy (25.2% and 42% vs. 13.9% and 19.4%, P < 0.02, respectively). The increased rate of recurrence was evident in the CAD/LUD recipients, but not in recipients of LRD transplants. Of the specific diseases, FSGS and MGN recurred more commonly (20.2% and 20.3%, respectively). A detrimental effect of pretransplant nephrectomy on recurrence rates and incidence of graft loss due to recurrent disease independent of other variables could be demonstrated only for FSGS patients. Based on these findings, we no longer recommend native nephrectomy in the prospective renal transplant recipient at high risk for developing recurrent glomerulonephritis.


Rates of COVID-19-related Outcomes in Cancer compared to non-Cancer Patients.
Cancer patients are a vulnerable population postulated to be at higher risk for severe COVID-19 infection. Increased COVID-19 morbidity and mortality in cancer patients may be attributable to age, comorbidities, smoking, healthcare exposure, and cancer treatments, and partially to the cancer itself. Most studies to date have focused on hospitalized patients with severe COVID-19, thereby limiting the generalizability and interpretability of the association between cancer and COVID-19 severity. We compared outcomes of SARS-CoV-2 infection in 323 patients enrolled prior to the pandemic in a large academic biobank (n=67 cancer patients and n=256 non-cancer patients). After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer was independently associated with higher odds of hospitalization (OR 2.16, 95% CI 1.12-4.18) and 30-day mortality (OR 5.67, CI 1.49-21.59). These associations were primarily driven by patients with active cancer. These results emphasize the critical importance of preventing SARS-CoV-2 exposure and mitigating infection in cancer patients.


[Nucleotide and oligonucleotide derivatives--a research tool of molecular biology].
The work of the authors are discussed, that they have been engaged in since the late forties, on synthesis and investigation of mono- and oligonucleotide derivatives. One class of mixed biopolymers (mono (oligo) nucleotides) is used to demonstrate the effect of covalent and noncovalent intramolecular interactions on the character of various protein-nucleic acid contacts. General approaches to creating regioselective reagents are outlined, that can be widely used for modification of both proteins and nucleic acids. Designing and application of some of such reagents is analyzed.


GOAP: a generalized orientation-dependent, all-atom statistical potential for protein structure prediction.
An accurate scoring function is a key component for successful protein structure prediction. To address this important unsolved problem, we develop a generalized orientation and distance-dependent all-atom statistical potential. The new statistical potential, generalized orientation-dependent all-atom potential (GOAP), depends on the relative orientation of the planes associated with each heavy atom in interacting pairs. GOAP is a generalization of previous orientation-dependent potentials that consider only representative atoms or blocks of side-chain or polar atoms. GOAP is decomposed into distance- and angle-dependent contributions. The DFIRE distance-scaled finite ideal gas reference state is employed for the distance-dependent component of GOAP. GOAP was tested on 11 commonly used decoy sets containing 278 targets, and recognized 226 native structures as best from the decoys, whereas DFIRE recognized 127 targets. The major improvement comes from decoy sets that have homology-modeled structures that are close to native (all within ∼4.0 Å) or from the ROSETTA ab initio decoy set. For these two kinds of decoys, orientation-independent DFIRE or only side-chain orientation-dependent RWplus performed poorly. Although the OPUS-PSP block-based orientation-dependent, side-chain atom contact potential performs much better (recognizing 196 targets) than DFIRE, RWplus, and dDFIRE, it is still ∼15% worse than GOAP. Thus, GOAP is a promising advance in knowledge-based, all-atom statistical potentials. GOAP is available for download at http://cssb.biology.gatech.edu/GOAP.


[Trophic function of phytophagous rotifers (Rotatoria). Experiment and modelling].
Three predator-dependent trophic functions have been fitted to experimental data on individual ration of two phytophagous rotifers (Brachionus calyciflorus and Philodina acuticornis) in laboratory monocultures of microalgae (Chlorella vulgaris Beyer, Scenedesmus quadricauda Brev. and Synechocistis sp.). The best fit was obtained with theoretical dependence proposed in that generalises the Arditi-Ginzburg ratio-dependent trophic function, approaching the Holling type II expression when either predator or prey density becomes low. At the same time the obtained results suggest that the original ratio-dependent function of Arditi-Ginzburg can be effectively used for modelling trophic interactions in the considered systems, because individual ration of rotifers is determined by the ratio of microalgae to consumer abundances.


Dynamic Relational Group Psychotherapy: A Neurobiologically Informed Model of Change.
In this article we introduce a preliminary, neurobiologically informed model of group therapy that links the timing and nature of specific group interventions with hypothesized changing neurobiological needs of the group. We suggest that the observed phases of group development reflect an underlying reorganization of neuronal circuitry that occurs as members progress through a hierarchically organized treatment, and that this reorganization involves the integration and homeostatic rebalancing of subcortical and neural networks. Our preliminary Dynamic Relational model suggests that an understanding of the neurobiological processes involved in group development may help inform and direct effective group-based psychotherapy interventions.


Quantitative analysis of gene expression in a single cell by qPCR.
We developed a quantitative PCR method featuring a reusable single-cell cDNA library immobilized on beads for measuring the expression of multiple genes in a single cell. We used this method to analyze multiple cDNA targets (from several copies to several hundred thousand copies) with an experimental error of 15.9% or less. This method is sufficiently accurate to investigate the heterogeneity of single cells.


Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts.
Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FUra) selectively in tumors through the intermediate metabolite 5'-deoxy-5-fluorouridine (5'-dFUrd, doxifluridine). 5'-dFUrd is metabolized to 5-FUra by thymidine phosphorylase (dThdPase) located in high levels in various types of solid tumors from patients, whereas 5-FUra generated is catabolized to dihydrofluorouracil by dihydropyrimidine dehydrogenase (DPD). The present study investigated whether the efficacy of capecitabine and its intermediate metabolite 5'-dFUrd correlates with levels of these enzymes in various human cancer xenograft models. Capecitabine and 5'-dFUrd were highly effective and inhibited tumor growth by more than 50% in 18 of 24 xenograft lines (75%) and 15 of 24 xenograft lines (63%), respectively, whereas 5-FUra and a mixture of tegafur and uracil were effective only in 1 of 24 (4.2%) and 5 of 24 (21%), respectively. The efficacy of capecitabine correlated with dThdPase activity. However, capecitabine was effective even in tumors with lower levels of dThdPase if DPD levels were also lower. In contrast, it was not as effective even in tumors with sufficient levels of dThdPase if DPD levels were very high. The efficacy of capecitabine consequently correlated very well with and depended on the ratio of these two enzymes in tumors. These results indicate that capecitabine might exert its efficacy through 5-FUra generated in tumor tissues but not through that generated in normal organs. On the other hand, there was no correlation between the efficacy of a mixture of tegafur and uracil and these enzyme activities in tumors. The efficacy of capecitabine would be optimized by selecting patients who have tumors with a high ratio of dThdPase to DPD activities.


Immune monitoring in organ transplantation using neopterin.
Transplantation has become an established and successful therapy. Rejections and infections are the principal immune-related complications in the post-transplant course. A reliable and early diagnosis is necessary to prevent graft failure and patient morbidity. Despite the immunologic nature of these complications the diagnostic procedures still rely on functional tests and organ biopsies. Non-invasive monitoring remains to be one of the major goals in transplant medicine. Neopterin is a sensitive marker of the cellular immune response. It reflects the activation of macrophages and can be easily measured in serum, plasma, urine or other body fluids. This review summarises studies on the diagnostic value of neopterin in transplant medicine. Based on these results key factors for immune monitoring in regard to neopterin are evaluated. In particular the unspecificity of diagnostic immune markers, the kinetics of the immune response, the importance of adjustment of neopterin to kidney function, and quantitative differences in immune pathways against viruses and allografts are discussed. Reflecting these points a concept to use neopterin for non-invasive immune monitoring in the clinical routine is presented. This approach calculates probabilities for specific post-transplant complications based on daily measurements of neopterin, a combination with the acute phase reactant amyloid A, and a modification of the likelihood ratio concept.


Detection and quantitative analysis of human herpesvirus in pilocytic astrocytoma.
We investigated the hypothetical role of human herpesviruses (HHVs) in tumour formation of the cerebellum. Thirty-five samples of pilocytic astrocytoma and 10 control samples of cerebellum from patients who died of unrelated diseases were examined. Presence of the 8 known HHVs was first studied using specific real-time quantitative Polymerase Chain Reaction (qPCR) targeting viral DNA polymerase. HHV's DNA polymerase was found present in 20 samples (7 controls, 13 astrocytomas) and was absent in 25 samples (3 controls, 22 astrocytomas). DNA polymerase of Epstein-Barr Virus (EBV) was present in 16 samples, 7/10 controls (70%) and 9/35 astrocytomas (26%). HHV-1 and Varicella-Zoster virus were detected only twice and HHV-2, Cytomegalovirus, HHV-7 and HHV-8, only once. HHV-6 was not detected. In all cases, the gene copy numbers of DNA polymerase were low (<100/100 ng DNA). A second approach was to search for novel HHVs, using consensus-degenerated hybrid oligonucleotide primers (CODEHOP) PCR: no sequence indicative of a new HHV was detected. In summary, EBV was the most frequent HHV detected in pilocytic astrocytoma, but at very low levels. According to the actually accepted threshold the results suggest that EBV cannot be considered responsible for tumorigenesis of pilocytic astrocytoma.


Willingness to take drugs to prevent serious chronic diseases.
The aim of this study was to determine an individual's willingness to take a preventive therapy for each of two chronic diseases (type 2 diabetes [T2D] and dementia) when provided with varying likelihoods of acquiring the disease. After reading a description of two chronic diseases (i.e. T2D and dementia), 345 student volunteers at McMaster University rated their likelihood of taking a drug that could halve their chance of developing each disease, assuming a 1-year risk of developing the disease of 50%, 25%, and 10%. A five-point Likert scale was used to collect responses. Assuming an annual incidence of 50%, 27% of respondents were neither likely nor very likely to take a therapy that halved the annual incidence of T2D and 13% were neither likely nor very likely to take a therapy that halved the annual incidence of dementia. Higher quoted incidence rates of the disease and a personal history of a chronic illness significantly increased willingness to take such therapy. A high proportion of young educated adults have ambivalent or negative attitudes regarding the use of pharmacological therapy to prevent serious health outcomes even when the absolute 1-year risk of these outcomes is very high.


Green's function for a spherical dielectric discontinuity and its application to simulation.
We present rapidly convergent expressions for the Green's function of the Poisson equation for spherically symmetric systems where the dielectric constant varies discontinuously in the radial direction. These expressions are used in Monte Carlo simulations of various electrolyte systems, and their efficiency is assessed. With only the leading term of the expansion included, a precision of the polarization energy of 0.01 kJ mol(-1) or better was achieved, which is smaller than the statistical uncertainty of a typical simulation. The inclusion of the dielectric inhomogeneity leads to a 2.5-fold increase of the computational effort, which is modest for this type of model. The simulations are performed on six types of systems having either (i) a uniform surface charge distribution, (ii) a uniform volume charge distribution, or (iii) mobile ions, which were neutralized by mobile counterions. The ion density distributions are investigated for different dielectric conditions. These spatial distributions are discussed in terms of the importance of (i) the direct mean-field Coulomb interaction, (ii) the surface charge polarization at the dielectric discontinuity, and/or (iii) the change in the attractive Coulomb correlations.


Numb-/low Enriches a Castration-Resistant Prostate Cancer Cell Subpopulation Associated with Enhanced Notch and Hedgehog Signaling.
Purpose: To elucidate the role and molecular mechanism of Numb in prostate cancer and the functional contribution of Numb-/low prostate cancer cells in castration resistance.Experimental Design: The expression of Numb was assessed using multiple Oncomine datasets and prostate cancer tissues from both humans and mice. The biological effects of the overexpression and knockdown of Numb in human prostate cancer cell lines were investigated in vitro and in vivo In addition, we developed a reliable approach to distinguish between prostate cancer cell populations with a high or low endogenous expression of Numb protein using a Numb promoter-based lentiviral reporter system. The difference between Numb-/low and Numbhigh prostate cancer cells in the response to androgen-deprivation therapy (ADT) was then tested. The likely downstream factors of Numb were analyzed using luciferase reporter assays, immunoblotting, and quantitative real-time PCR.Results: We show here that Numb was downregulated and negatively correlated with prostate cancer advancement. Functionally, Numb played an inhibitory role in xenograft prostate tumor growth and castration-resistant prostate cancer development by suppressing Notch and Hedgehog signaling. Using a Numb promoter-based lentiviral reporter system, we were able to distinguish Numb-/low prostate cancer cells from Numbhigh cells. Numb-/low prostate cancer cells were smaller and quiescent, preferentially expressed Notch and Hedgehog downstream and stem-cell-associated genes, and associated with a greater resistance to ADT. The inhibition of the Notch and Hedgehog signaling pathways significantly increased apoptosis in Numb-/low cells in response to ADT.Conclusions: Numb-/low enriches a castration-resistant prostate cancer cell subpopulation that is associated with unregulated Notch and Hedgehog signaling. Clin Cancer Res; 23(21); 6744-56. ©2017 AACR.


Management of spontaneous dissection of the cervical carotid artery.
This manuscript reviews the management of patients with spontaneous dissection of the cervical internal carotid artery (sICAD). Recommendations are not based on controlled-randomized trials, but on case-control and observational, hospital-based studies, and case reports. Vascular risk factors seem to be as prevalent in patients with sICAD as in age-matched, healthy volunteers. Stroke prevention includes the treatment of vascular risk factors and the administration of oral aspirin, which may be as effective as anticoagulation. The few available data indicate that most patients with sICAD causing severe stenosis or occlusion, or an aneurysm can be treated conservatively. Patients with sICAD were not excluded in the intravenous controlled-randomized thrombolysis trials with tissue plasminogen activator, but were excluded in the intraarterial controlled-randomized thrombolysis trials. Taking the few published case series and reports on thrombolysis in patients with sICAD into consideration, intravenous thrombolysis may be beneficial, whereas it remains unclear whether intraarterial thrombolysis is useful.


Nonconventional ventilation techniques.
Mechanical ventilation is one of the most important life support tools in the ICU, but it may also be harmful by causing ventilator-induced lung injury (VILI) and other deleterious effects. Advances in ventilator technology have allowed the introduction of numerous ventilator modes in an effort to improve gas exchange, reduce the risk of VILI, and finally improve outcome. In this review, we will summarize the studies evaluating some of the nonconventional ventilation techniques and discuss their possible use in clinical practice. Proportional assist ventilation and neurally adjusted ventilator assist are able to improve patient-ventilator synchrony, possibly sleep, and may be better tolerated than pressure support ventilation; both integrate the physiological concept of respiratory variability like noisy ventilation. Experimental or short-term clinical studies have shown physiological benefits with the application of biphasic pressure modes. Some of the automated weaning algorithms may reduce time spent on ventilator and decrease ICU stay, especially in a busy environment. Apart from the physiological and clinical attractiveness demonstrated in animals and small human studies, most of the nonconventional ventilator modes must prove their clinical benefits in large prospective trials before being applied in daily clinical practice.


Family aspects of trichotillomania.
This paper reports on the utilization of family system concepts in the understanding and treatment of trichotillomania. The paper discusses family interactional aspects of trichotillomania in four families as well as a description of assessment, intervention and follow-up procedures used with each family group.


Differences in open field behavior between heterozygous and homozygous negative gilts for the RYR(1) gene.
A test widely used to assess fear and novelty responses in domestic species is the open field. The aim of this study was to investigate the effect of RYR(1) genotype on open field behavior in growing pigs. The study subjected 15 heterozygous (Nn) and 15 RYR(1)-free (NN) gilts of 19 weeks of age to 3 replicates of an open field test 2 days apart from each other. The study measured the number of grid lines crossed and defecation score in the test arena. There was a significant individual correlation among the 3 replicates of the test, both for number of grid lines crossed and defecation score (p <.05). RYR(1) genotype had a significant effect on number of grid lines crossed, with NN gilts showing more overall activity than Nn gilts (p <.05). The study observed no significant differences in defecation score between genotypes. This result suggests that the RYR(1) genotype may have an effect on the appraisal of novelty. Thus, it would be interesting to take this factor into account when using this methodology to assess fear responses in pigs and in interpreting the results with respect to welfare.