The effects of carbohydrate loading 48 hours before a simulated squash match.
The aim of this study was to ascertain whether a high carbohydrate diet in the days before movement patterns simulating a squash match would increase carbohydrate oxidation during the match, and alter physical performance. Nine New Zealand level squash players were recruited to complete a simulated squash match on two occasions: 1) following a 48-hr high carbohydrate (11.1g·kg-1); and 2) following a calorie-matched low carbohydrate (2.1 g·kg-1) diet. The interventions were assigned in a randomized, single-blind, cross-over design. The match simulation was designed to mimic a five-game match lasting approximately 1 hr. Performance was measured as time to complete each game. Expired respiratory gases and heart rate were continuously collected throughout the trial using a portable gas analysis system. Capillary blood glucose and lactate samples were obtained during a 90 s rest period between each game. Rating of perceived exertion was also recorded after each set. Respiratory exchange ratio was significantly higher during exercise following the high CHO diet (0.80 vs. 0.76) p < .001) and this was associated with significantly faster time to complete the games (2340 ± 189 s vs. 2416 ± 128 s, p = .036). Blood glucose and lactate concentrations were also significantly higher in the high carbohydrate condition (p = .038 and p = .021 respectively). These results suggest that ingestion of a diet high in carbohydrate (>10 g/kg body weight) preceding simulated competitive squash produces increased rates of carbohydrate oxidation and maintains higher blood glucose concentrations. These metabolic effects were associated with improved physical performance.


Piezo2 Expression in Mechanosensitive Dental Primary Afferent Neurons.
Mechanosensitive ion channels have been suggested to be expressed in dental primary afferent (DPA) neurons to transduce the movement of dentinal fluid since the proposal of hydrodynamic theory. Piezo2, a mechanosensitive, rapidly inactivating (RI) ion channel, has been recently identified in dorsal root ganglion (DRG) neurons to mediate tactile transduction. Here, we examined the expression of Piezo2 in DPA neurons by in situ hybridization, single-cell reverse transcriptase polymerase chain reaction, and whole-cell patch-clamp recordings. DPA neurons with Piezo2 messenger RNA (mRNA) or Piezo2-like currents were further characterized based on their neurochemical and electrophysiological properties. Piezo2 mRNA was found mostly in medium- to large-sized DPA neurons, with the majority of these neurons also positive for Nav1.8, CGRP, and NF200, whereas only a minor population was positive for IB4 and peripherin. Whole-cell patch-clamp recordings revealed Piezo2-like, RI currents evoked by mechanical stimulation in a subpopulation of DPA neurons. RI currents were pharmacologically blocked by ruthenium red, a compound known to block Piezo2, and were also reduced by small interfering RNA-mediated Piezo2 knockdown. Piezo2-like currents were observed almost exclusively in IB4-negative DPA neurons, with the current amplitude larger in capsaicin-insensitive DPA neurons than the capsaicin-sensitive population. Our findings show that subpopulation of DPA neurons is indeed mechanically sensitive. Within this subpopulation of mechanosensitive DPA neurons, we have identified the Piezo2 ion channel as a potential transducer for mechanical stimuli, contributing to RI inward currents. Piezo2-positive DPA neurons were characterized as medium- to large-sized neurons with myelinated A-fibers, containing nociceptive peptidergic neurotransmitters.


Minimal resonances in annular non-euclidean strips.
Differential growth processes play a prominent role in shaping leaves and biological tissues. Using both analytical and numerical calculations, we consider the shapes of closed, elastic strips which have been subjected to an inhomogeneous pattern of swelling. The stretching and bending energies of a closed strip are frustrated by compatibility constraints between the curvatures and metric of the strip. To analyze this frustration, we study the class of "conical" closed strips with a prescribed metric tensor on their center line. The resulting strip shapes can be classified according to their number of wrinkles and the prescribed pattern of swelling. We use this class of strips as a variational ansatz to obtain the minimal energy shapes of closed strips and find excellent agreement with the results of a numerical bead-spring model. We derive and test a surprising resonance condition for strips with minimal bending energy along the strip center line to exist.


Adult and Adolescent Disclosures of Child Sexual Abuse: A Comparative Analysis.
The recent attention focused on child sexual abuse (CSA) disclosure pathways has highlighted complex psychological processes that influence disclosure both for children and adults. Some authors have suggested that such processes may differ between children and adults yet few studies have examined distinct samples within the same study. This paper addresses this gap by exploring adolescent (n = 20) and adult (n = 10) experiences of disclosure of childhood sexual abuse. Interviews were conducted with both samples, using the same interview schedule and a comparative analysis was conducted of the key themes identified from a grounded theory analysis. Those themes that were found to be common to both samples included pressure cooker effect, telling would make it worse, and self-blame. Themes that were found to be more prevalent in the adolescent sample included police/court involvement, concern for other children, being asked, and peer influence. It is suggested that such potential differences reflect the changing social context over the past few decades which is characterised by increased awareness of sexual abuse as a crime and the risks of recidivism of offenders.


Patient satisfaction as an outcome of individualised nursing care.
The association between individualised nursing care and patient satisfaction has been previously found. However, there is a lack of studies examining this association between individualised care and patient satisfaction in a cross-cultural study. This study examines the association between individualised care and patient satisfaction in a sample of general surgical patients from five European countries. A cross-sectional design and survey method were used to collect data from general surgical patients (N = 1315, response rate 78%) in 72 inpatient wards in 26 general acute hospitals' in 2009 using self-completed questionnaires the Individualised Care Scale and the Patient Satisfaction Scale. Data were analysed using descriptive statistics, Pearson correlation coefficients and multiple stepwise regression analyses. Surgical patients reported that the care they received was only moderately individualised overall, but individuality was taken into account well in patients' clinical situation and decisional control over care. Patients were satisfied with their care, mostly with the technical aspects of care and least with the information given. There were between-country differences in patients' perceptions of individuality in care and patient satisfaction. A positive correlation between the level of individualised care received and patient satisfaction was found, confirming that individualised nursing care delivery influences patients' satisfaction with care and demonstrating that this quality of care indicator might be able to be used as a predictor of patient satisfaction, one outcome of care. The findings of this study strengthen previous results and further reporting the existence of a relationship and the positive correlation between individualised care and patient satisfaction. The results can inform administrative decisions and policy on introducing nursing approaches to care that would increase patient satisfaction.


Knowledge and behaviors of prevention of COVID-19 and the related factors in the rural population referred to the health centers: a cross-sectional study.
Observance of preventive behaviors is one of the main ways to break the coronavirus disease 2019 (COVID-19) chain of transmission. Therefore, the present study was conducted to determine the knowledge and behaviors of prevention of COVID-19 and the related factors in the rural population of Rasht city. In this cross-sectional study, 344 people of the population referred to health centers in Rasht city were included through multi-stage cluster random sampling. The data were collected using a three-part researcher-made questionnaire including individual-social factors, knowledge about the prevention of COVID-19, and the preventive behaviors against COVID-19. Data analysis was performed using the Kolmogorov-Smirnov and Shapiro-Wilk tests, Spearman's correlation coefficient, and multiple logistic regression analysis, by SPSS software version 16 at a significance level < 0.05. The mean total score of knowledge about COVID-19 was at a moderate level, and the preventive behaviors of COVID-19 were at a good level. There was no significant relationship between the scores of awareness and preventive behaviors of COVID-19 (rs=0.001, P = 0.998). Awareness of COVID-19 was higher in university-educated individuals and women. Also, women, individuals who had access to the Internet, those trained by health centers, and those who were visited by health workers at home had more preventive behaviors. Despite the lack of connection between knowledge and preventive behaviors, the villagers living in the suburbs of Rasht had a moderate level of knowledge and a good level of preventive behaviors of COVID-19. Appropriate educational interventions should be carried out to increase the awareness and performance of the rural residents.


[Pathomechanisms and hypothesis-guided therapeutic strategies for late-onset Alzheimer's disease].
Even though the clinical effectiveness of the presently used pharmaceutical therapy of sporadic Alzheimer Disease seems to be proven sufficient, their effective mechanisms are much less known or are disregarded in the evaluation of the clinical effects. However, it seems to be inevitable to know both clinical effect and effective mechanisms of pharmaceutics in order to be able to judge their adversity and benefit. In reference to the pharmaceutics implemented on sporadic AD in Germany, total different effective mechanisms are shown. In consideration of the shown pathomechanisms which have been recognized for sporadic AD, therapeutic rationales on application of Ginkgo biloba extract (EGb 761) and Memantine are evident. The application of acetylcholinesterase inhibitors, often looked on as agent of choice, is to be considered critically because of the danger of the occurrence of myopathological dysfunction, resp. the Gulf War Syndrome. Sophisticated and hastily advertised therapy strategies with statins or vaccination against beta A4 should not be used because of a lack of sufficient evidence based on the pathophysiological pattern of damage as known in sporadic AD. Future development must take in account that with sporadic AD aging influences cannot or can hardly be influenced. Therapeutic goals should consist to improve the cellular energy status and the membrane functioning.


[Staphylococcal infection in guinea pigs with enhanced delayed hypersensitivity induced by Staphylococcus aureus surface antigens].
A comparative study was made of the relationship between the DHS phenomenon and certain staphylococcal antigens and the intensity of infectious process in sublethal infection of guinea-pigs by Staphylococcus aureus. The protective effect, which was manifested by reduced amounts of staphylococcal colonies in spleen tissues and elevated level of lymphocytes, and neutrophil activation, correlated with DHS induced by surface antigens under study (cell wall, peptidoglycan, protein A). Incomplete combination or certain antigens induced DHS but did not increase the resistance to the following infection.


Long term exercise-derived exosomal LncRNA CRNDE mitigates myocardial infarction injury through miR-489-3p/Nrf2 signaling axis.
Myocardial infarction (MI) is a cardiovascular disease and troubles patients all over the world. Exosomes produced after long-term exercise training were discovered to mediate intercellular communication and alleviate MI-induced heart injury. However, the detailed roles of long-term exercise-derived exosomal long noncoding RNAs (LncRNAs) in MI remain uncovered. In this study, we collected and identified long-term exercise-derived exosomes, and established MI or hypoxia/reoxygenation (H/R) model after LncRNA colorectal neoplasia differentially expressed (CRNDE) depletion. This work proved that LncRNA CRNDE was highly expressed in long-term exercise-derived exosomes (p = 0.0078). CRNDE knockdown increased cardiomyocytes apoptosis and oxidative stress (p = 0.0036), and suppressed MI progress (p = 0.0005). CRNDE served as the sponge of miR-489-3p to affect Nrf2 expression (p = 0.0001). MiR-489-3p inhibition effectively reversed the effects of CRNDE depletion on hypoxia cardiomyocytes (p = 0.0002). These findings offered a promising therapeutic option for the treatment of MI.


Respiratory Pattern Analysis for Different Breathing Types and Recording Sensors in Healthy Subjects.
Accurate monitoring of respiratory activity can lead to early identification and treatment of possible respiratory failure. However, spontaneous breathing can vary considerably. To quantify this variability, this study aimed at comparing the breathing pattern characteristics obtained from several recording sensors during different breathing types. Respiratory activity was recorded with a pneumotachograph and two inductive plethysmographic bands, thoracic and abdominal, in 23 healthy volunteers (age 21.5±1.2 years, 13 females). The subjects were asked to breathe at their natural rate, in successive stages: first freely, then through their nose, nose and mouth, mouth alone, and finally deep and shallow. Both band signals were compared to the pneumotach-derived (gold standard) volume signal. The time series of inspiratory and expiratory duration, total cycle duration and tidal volume were estimated from each of these signals, and also from the sum of the thoracic and abdominal bands. This composite signal showed the highest correlation with the volume signal for almost all subjects, and also had a significantly higher correlation with those obtained from the gold standard volume, compared to either band. In general, breathing parameters increased from basal to nose-mouth breathing, had a minimum in shallow breathing and a maximum in deep breathing. Women exhibited a significantly longer exhalation phase than men during deep breathing, in the combined bands and the gold standard volume. In conclusion, variations in respiratory cycle morphology in different breathing types can be well captured by the simple addition of abdominal and thoracic band signals.Clinical Relevance- Breathing pattern variability can be identified by the combination of abdominal and thoracic bands.


Local control of extra-abdominal desmoid tumors: systematic review and meta-analysis.
The local control of desmoid tumors constitutes a continuing treatment dilemma due to its high recurrence rates. The purpose of this systematic review was to critically examine the current treatment of these rare tumors and to specifically evaluate the local failure and response rates of surgery, radiation and systemic therapy. We comprehensively searched the literature for relevant studies across Cinahl, Embase, Medline and the Cochrane databases. Articles were categorized as surgery, radiation, surgery + radiation and systemic therapy (including cytotoxic and non cytotoxic). Methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Pooled odd ratios (OR) for comparative studies and weighted proportions with 95% confidence intervals (CI) are reported. Thirty-five articles were included in the final analysis. Weighted mean local failure rates were 22% [95% CI (16-28%)], 35% [95% CI (26-44%)] and 28% [95% CI (18-39%)] for radiation alone, surgery alone and surgery + radiation respectively. In the analysis of comparative studies, surgery and radiation in combination had lower local failure rates than radiation alone [OR 0.7 (0.4, 1.2)] and surgery alone [OR 0.7 (0.4, 1.0)]. Weighted mean stable disease rates were 91% [95% CI (85-96%)] and 52% [95% CI (38-65%)] for non cytotoxic and cytotoxic chemotherapy respectively. The current evidence suggests that surgery alone has a consistently high rate of local recurrence in managing extra-abdominal desmoid tumors. Radiation therapy in combination with surgery improves local control rates. However, the limited data on systemic therapy for this rare tumor suggests the benefit of using both cytotoxic and non cytotoxic chemotherapy to achieve stable disease.


Persistent vestibular-ocular impairment following concussion in adolescents.
The current study investigated the role of persistent vestibular-ocular symptoms and impairment following sport-related concussion on recovery time and clinical outcomes among adolescents. Prospective cohort. 50 (F-22/M-28) adolescents aged 12-20 years completed a vestibular-ocular motor screening, neurocognitive assessment, and the Post-Concussion Symptom Scale (PCSS) at clinical assessments conducted at 0-10 and 11-21 days after concussion. Participants were assigned to: 1) persistent vestibular-ocular (PERSIST), 2) vestibular-ocular improvement (IMPROVE), or 3) no vestibular-ocular impairment (NONE) groups based on vestibular-ocular motor screening conducted during each assessment. A 3 (GROUP) X 2 (TIME) ANOVA was performed on neurocognitive and symptom scores, and a between-subjects ANOVA was performed for recovery time. 49 subjects were identified among the PERSIST (n=17), IMPROVE (n=12) and NONE (n=20) groups. There were no neurocognitive performance differences between groups at 0-10 days post-concussion, but groups differed on PCSS at 11-21 days (p=.001), with the PERSIST (29.0±24.9) group reporting higher symptoms than the NONE (5.45±10.0; p=.005) group. The PERSIST group took significantly longer to recover (34.9±11.6 days) than the NONE (22.9±14.9 days) group (p=.03). All groups improved on verbal (p<.001) and visual memory (p=.028), visual motor speed (p=.005), and reaction time (p=.004) from 0-10 to 11-20 days following SRC and no significant group by time interactions for cognitive scores identified. Persistent post-concussion vestibular-ocular symptoms and impairment may influence neurocognitive performance and clinical recovery following sport-related concussion.


In vivo evidence that TATA-binding protein/SL1 colocalizes with UBF and RNA polymerase I when rRNA synthesis is either active or inactive.
Here we show that the TATA-binding protein (TBP) is localized in the nucleoplasm and in the nucleolus of mammalian cells, consistent with its known involvement in transcription by RNA polymerase I, II, and III. In the nucleolus of actively growing cells, TBP colocalizes with upstream binding factor (UBF) and RNA polymerase I at the sites of rRNA transcription. During mitosis, when rRNA synthesis is down-regulated, TBP colocalizes with TBP-associated factors for RNA polymerase I (TAF(I)s), UBF, and RNA polymerase I on the chromosomal regions containing the rRNA genes. Treatment of cells with a low concentration of actinomycin D inhibits rRNA synthesis and causes a redistribution of the rRNA genes that become concentrated in clusters at the periphery of the nucleolus. A similar redistribution was observed for the major components of the rRNA transcription machinery (i.e., TBP, TAF(I)s, UBF, and RNA polymerase I), which still colocalized with each other. Furthermore, anti-TBP antibodies are shown to coimmunoprecipitate TBP and TAF(I)63 in extracts prepared from untreated and actinomycin D-treated cells. Collectively, the data indicate that in vivo TBP/promoter selectivity factor, UBF, and RNA polymerase I remain associated with both active and inactive rRNA genes.


Chemical constituents of the fruits of Morinda citrifolia (Noni) and their antioxidant activity.
Purification of a n-BuOH-soluble partition of the MeOH extract of Morinda citrifolia (Noni) fruits led to the isolation of two new iridoid glucosides, 6alpha-hydroxyadoxoside (1) and 6beta,7beta-epoxy-8-epi-splendoside (2), as well as 17 known compounds, americanin A (3), narcissoside (4), asperuloside, asperulosidic acid, borreriagenin, citrifolinin B epimer a, citrifolinin B epimer b, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, epi-dihydrocornin, d-glucose, d-mannitol, methyl alpha-d-fructofuranoside, methyl beta-d-fructofuranoside, nicotifloroside, and beta-sitosterol 3-O-beta-d-glucopyranoside. The structures of the new compounds were determined by spectroscopic data interpretation. Compound 4, borreriagenin, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, epi-dihydrocornin, methyl alpha-d-fructofuranoside, and methyl beta-d-fructofuranoside were isolated for the first time from M. citrifolia. The antioxidant activity was evaluated for all isolates in terms of both DPPH and ONOO(-) bioassays. The neolignan, americanin A (3), was found to be a potent antioxidant in these assays.


The clinical impacts of sleep apnea on mortality and allograft function in kidney transplant patients: A meta-analysis.
Sleep apnea (SA) is common in patients with advanced chronic kidney disease. However, its prevalence and clinical significance in kidney transplant patients are unknown. To demonstrate the clinical impacts of SA on kidney allograft and mortality from current evidence to date. Ovid -MEDLINE, EMBASE, and the Cochrane Library were searched for eligible publications. Kidney transplant recipients aged ≥ 18 years with SA were included. The outcomes included overall mortality, graft failure, and graft loss. Graft loss was attributed by either 1) graft failure requiring renal replacement therapy (RRT)or 2) death. Four observational studies (n = 5,259) were included in the meta-analyses. The mean age was 49.6 ± 0.4 years. Most patients were male (58.3%) and white (82.1%). Up to 25.1% had diabetes, 15.2% had SA, and 36.8% had history of smoking. The mean body mass index was 26.9 ± 0.9 kg/m2. With the mean follow-up duration of 14.4 ± 4.2 years, the pooled adjusted odds ratios (ORs) for graft failure and mortality among kidney transplant patients with SA were 1.061 (95% CI, 0.851 - 1.322; I2 = 41.3%) and 1.044 (95% CI, 0.853 - 1.278; I2 = 0%), respectively. The pooled adjusted OR for graft loss was 0.837 (95% CI, 0.597 - 1.173; I2 = 0%). On subgroup analyses, the ORs for graft failure were similar after adjusted by study year, country, study design, sample size, ethnicity, and sex. No potential publication bias was detected. With 14-year follow-up, SA in kidney transplant patients was not associated with worsening clinical and allograft outcomes, such as graft loss, graft failure, and mortality. However, additional observational studies are needed to confirm this finding.


Inter-species hybridization among Neotropical cats of the genus Leopardus, and evidence for an introgressive hybrid zone between L. geoffroyi and L. tigrinus in southern Brazil.
Natural hybrid zones between distinct species have been reported for many taxa, but so far, few examples involve carnivores or Neotropical mammals in general. In this study, we employed mitochondrial DNA (mtDNA) sequences and nine microsatellite loci to identify and characterize a hybrid zone between two Neotropical felids, Leopardus geoffroyi and L. tigrinus, both of which are well-established species having diverged from each other c. 1 million years ago. These two felids are mostly allopatric throughout their ranges in South America, with a narrow contact zone that includes southern Brazil. We present strong evidence for the occurrence of hybridization between these species and identify at least 14 individuals (most of them originating from the geographical contact zone) exhibiting signs of interspecific genomic introgression. The genetic structure of Brazilian L. tigrinus populations seems to be affected by this introgression process, showing a gradient of differentiation from L. geoffroyi correlated with distance from the contact zone. We also corroborate and extend previous findings of hybridization between L. tigrinus and a third related felid, L. colocolo, leading to an unusual situation for a mammal, in which the former species contains introgressed mtDNA lineages from two distinct taxa in addition to its own.


Regulating the regulators: understanding miRNA biogenesis and decay in adult skeletal muscles.
Maintaining cellular homeostasis necessitates precise control of gene expression, a process that molds both the transcriptome and proteome to adapt to internal and external changes effectively. MicroRNAs (miRNAs) are small RNAs (~ 22nucleotides) belonging to a broad family of non-coding RNAs and are important regulators of gene expression. While numerous studies have advanced our understanding of the common processes underlying miRNA biogenesis and function, individual cell types in diverse organisms have evolved distinct mechanisms for regulating them. In this current issue, Satoshi Oikawa and colleagues delve into the molecular dynamics of miRNAs in adult skeletal muscles. Their research introduces intriguing new inquiries for further investigations to uncover alternative mechanisms of miRNA biogenesis in skeletal muscle.


Stages as models of scene geometry.
Reconstruction of 3D scene geometry is an important element for scene understanding, autonomous vehicle and robot navigation, image retrieval, and 3D television. We propose accounting for the inherent structure of the visual world when trying to solve the scene reconstruction problem. Consequently, we identify geometric scene categorization as the first step toward robust and efficient depth estimation from single images. We introduce 15 typical 3D scene geometries called stages, each with a unique depth profile, which roughly correspond to a large majority of broadcast video frames. Stage information serves as a first approximation of global depth, narrowing down the search space in depth estimation and object localization. We propose different sets of low-level features for depth estimation, and perform stage classification on two diverse data sets of television broadcasts. Classification results demonstrate that stages can often be efficiently learned from low-dimensional image representations.


Immunohistochemical studies of the PrP(CJD) deposition in Creutzfeldt-Jakob disease.
The PrP(CJD) deposition in eight brains of sporadic Creutzfeldt-Jakob disease (CJD) was examined immunohistochemically using both hydrolytic autoclaving and formic acid pretreatment in order to understand the pathogenesis of CJD. Synaptic-type PrP immunoreactivity was revealed in the gray matter in all cases and had a tendency to be weaker in devastated areas in cases with a longer duration of illness. However, in one particular case with numerous prion plaques, the degeneration was relatively mild while PrP(CJD) immunoreactivity was intense despite the longest duration of illness among the examined cases. Deep layer accentuation of PrP(CJD) immunoreactivity was observed in the cerebral cortices in most cases. This staining pattern, however, disappeared in a burnt-out lesion exhibiting status spongiosus. The granular layer was damaged mostly in the cerebellum of the advanced cases. PrP(CJD) and synaptophysin immunoreactivities decreased as the tissue degeneration progressed. Interestingly, the Purkinje cells had no positivity for PrP(CJD) in all cases, although the neurons in relatively preserved cerebellum showed apparent positivity for synaptophysin. In the Ammon's horn and subiculum the neurons were well preserved despite the marked immunoreactivity for PrP(CJD) in all cases, although some cases demonstrated severe spongiform change. Approximately half of the cases showed intracytoplasmic inclusion body-like immunoreactivity for PrP(CJD) in neurons of the dentate nucleus. These findings suggest that PrP(CJD) deposition may be an event that precedes neuronal degeneration evolving from deeper layers of the cerebral cortex. Although the Ammon's horn and subiculum showed striking PrP(CJD) deposition and spongiform change, neuronal loss did not take place, suggesting that deposited PrP(CJD) itself seems not to be directly harmful to the neurons. Some investigators have assumed that microglia activated by PrP(CJD) plays an important role in neuronal degeneration. Considering this, we speculate that microglia in the Ammon's horn and subiculum may have a unique characteristic of not responding to PrP(CJD).


Admission Cognition and Function Predict Change in Physical Function Following Skilled Nursing Rehabilitation.
Many older adults are discharged from skilled nursing facilities (SNFs) at functional levels below those needed for safe, independent home and community mobility. There is limited evidence explaining this insufficient recovery. The purpose of this secondary analysis was to determine predictors of physical function change following SNF rehabilitation. Secondary analysis of a prospective observational cohort study. Across 4 SNFs, data were collected from 698 adults admitted for physical rehabilitation following an acute hospitalization. Physical function recovery was evaluated as change from admission to discharge in Short Physical Performance Battery (SPPB) scores (N = 698) and gait speed (n = 444). Demographic and clinical characteristics collected at admission served as potential predictors of physical function change. Following imputation, a standardized model selection estimator was calculated for predictors per physical function outcome. Predictor estimates and 95% CIs were calculated for each outcome model. Higher cognitive scores [standardized β (βSTD) = 0.11, 95% CI: 0.0004, 0.20] and higher activities of daily living (ADL) independence at admission (βSTD = 0.22, 95% CI: 0.05, 0.34) predicted greater SPPB change; higher SPPB scores at admission (βSTD = -0.26, 95% CI: -0.35, -0.14) predicted smaller SPPB change. Higher ADL independence at admission (βSTD = 0.17, 95% CI: 0.01, 0.37) predicted greater gait speed change; faster gait speed at admission (βSTD = -0.30, 95% CI: -0.44, -0.15) predicted smaller gait speed change. Admission cognition, ADL independence, and physical function predicted physical function change following post-hospitalization rehabilitation. Inverse findings for admission physical function and ADL independence predictors suggest independence with ADL is not necessarily aligned with mobility-related function. Findings highlight that functional recovery is multifactorial and requires comprehensive assessment throughout SNF rehabilitation.


Comparative expression of hCG β-genes in human trophoblast from early and late first-trimester placentas.
Human chorionic gonadotropin (hCG) displays a major role in pregnancy initiation and progression and is involved in trophoblast differentiation and fusion. However, the site and the type of dimeric hCG production during the first trimester of pregnancy is poorly known. At that time, trophoblastic plugs present in the uterine arteries disappear, allowing unrestricted flow of maternal blood to the intervillous space. The consequence is an important modification of the trophoblast environment, including a rise of oxygen levels from about 2.5% before 10 wk of amenorrhea (WA) to ∼8% after 12 WA. Two specific β-hCG proteins that differ from three amino acids have been described: type 1 (CGB7) and type 2 (CGB3, -5, and -8). Here, we demonstrated in situ and ex vivo on placental villi and in vitro in primary cultures of human cytotrophoblasts that type 1 and 2 β-hCG RNAs and proteins were expressed by trophoblasts and that these expressions were higher before blood enters in the intervillous space (8-9 vs. 12-14 WA). hCG was immunodetected in villous mononucleated cytotrophoblasts (VCT) and syncytiotrophoblast (ST) at 8-9 WA but only in ST at 12-14 WA. Furthermore, hCG secretion was fourfold higher in VCT cultures from 8-9 WA compared with 12-14 WA. Interestingly, VCT from 8-9 WA placentas were found to exhibit more fusion features. Taken together, we showed that type 1 and type 2 β-hCG are highly expressed by VCT in the early first trimester, contributing to the high levels of hCG found in maternal serum at this term.


Realtime photoacoustic microscopy in vivo with a 30-MHz ultrasound array transducer.
We present a novel high-frequency photoacoustic microscopy system capable of imaging the microvasculature of living subjects in realtime to depths of a few mm. The system consists of a high-repetition-rate Q-switched pump laser, a tunable dye laser, a 30-MHz linear ultrasound array transducer, a multichannel high-frequency data acquisition system, and a shared-RAM multi-core-processor computer. Data acquisition, beamforming, scan conversion, and display are implemented in realtime at 50 frames per second. Clearly resolvable images of 6-microm-diameter carbon fibers are experimentally demonstrated at 80 microm separation distances. Realtime imaging performance is demonstrated on phantoms and in vivo with absorbing structures identified to depths of 2.5-3 mm. This work represents the first high-frequency realtime photoacoustic imaging system to our knowledge.


Primary adrenal insufficiency caused by a novel mutation in DAX1 gene.
Adrenal hypoplasia congenita (AHC) is a rare disorder. The X-linked form is related to mutations in the DAX1 (NROB1) gene. Here, we report a newborn who had a novel hemizygous frameshift mutation in DAX1(c.543delA) and presented with primary adrenal failure that was initially misdiagnosed as congenital adrenal hyperplasia. This report highlights the value of genetic testing for definite diagnosis in children with primary adrenal failure due to abnormal adrenal gland development, providing the possibility both for presymptomatic, and in cases with a sibling with this condition, for prenatal diagnosis.


Is cestode infection intensity associated with decreased body condition in the Eurasian woodcock Scolopax rusticola?
The Eurasian woodcock Scolopax rusticola is a widespread woodland specialist and a widely harvested quarry species throughout its European wintering areas, including Britain. Woodcock are prone to cestodiasis, but prevalence levels and possible effects on body condition remain under-studied. We studied the prevalence, abundance and intensity of cestodiasis in 161 woodcock harvested in four British regions in December and January during two consecutive winters (2013/14 and 2014/15). Cestodiasis prevalence was 90%, and there was no difference in prevalence between birds harvested in Cornwall, Wessex, East Anglia and Scotland. High prevalence levels were explained by the fact that earthworms (Lumbricidae) are intermediate hosts for some cestode species and also the most important dietary component of woodcock. The distribution of cestodiasis in woodcock was aggregated, such that when using the total length of cestodes per sample to measure abundance, 65% of the birds had less than 80 cm. Cestodiasis abundance varied between sexes across regions but the intensity was not affected by region, sex, age or their interactions. The intensity of cestodiasis was positively correlated with fresh weight and pectoral mass, while no significant correlation was found with the abdominal fat pad. Our results suggest that, despite high prevalence levels and intensity of cestodiasis in woodcock, host body condition is not significantly affected and hence it is unlikely that cestodiasis has a major effect on woodcock population dynamics.


Maltese mushroom (Cynomorium coccineum L.) as source of oil with potential anticancer activity.
The present study aimed to examine the potential anticancer properties of fixed oil obtained from Maltese mushroom (Cynomorium coccineum L.), an edible, non-photosynthetic plant, used in traditional medicine of Mediterranean countries to treat various ailments and as an emergency food during the famine. We investigated the effect of the oil, obtained from dried stems by supercritical fractioned extraction with CO2, on B16F10 melanoma and colon cancer Caco-2 cell viability and lipid profile. The oil, rich in essential fatty acids (18:3n-3 and 18:2n-6), showed a significant growth inhibitory effect on melanoma and colon cancer cells. The incubation (24 h) with non-toxic oil concentrations (25 and 50 μg/mL) induced in both cancer cell lines a significant accumulation of the fatty acids 18:3n-3 and 18:2n-6 and an increase of the cellular levels of eicosapentaenoic acid (20:5n-3) with anticancer activity. Moreover, the oil exhibited the ability to potentiate the growth inhibitory effect of the antitumor drug 5-fluorouracil in Caco-2 cells and to influence the melanin content in B16F10 cells. The results qualify C. coccineum as a resource of oil, with potential benefits in cancer prevention, for nutraceutical and pharmaceutical applications.


Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) combine CpG oligodeoxynucletides as a novel therapeutic vaccine for chronic hepatitis B infection.
Hepatitis B virus infection is a non-cytopathic hepatotropic virus which can lead to chronic liver disease and hepatocellular carcinoma. Traditional therapies fail to provide sustained control of viral replication and liver damage in most patients. As an alternative strategy, immunotherapeutic approaches have shown promising efficacy in the treatment of chronic hepatitis B patients. Here, we investigated the efficacy of a novel therapeutic vaccine formulation consisting of two HBV antigens, HBsAg and HBcAg, and CpG adjuvant. This vaccine formulation elicits forceful humoral responses directed against HBsAg/HBcAg, and promotes a Th1/Th2 balance response against HBsAg and a Th1-biased response against HBcAg in both C57BL/6 and HBV transgenic mice. Vigorous cellular immune response was also detected in HBV transgenic mice, for a significantly higher number of HBs/HBc-specific IFN-γ secreting CD4+ and CD8+ T cells was generated. Moreover, vaccinated mice elicited significantly intense in vivo CTL attack, reduced serum HBsAg level without causing liver damage in HBV transgenic mice. In summary, this study demonstrates a novel therapeutic vaccine with the potential to elicit vigorous humoral and cellular response, overcoming tolerance in HBV transgenic mice.


Injuries to the elbow.
Presented is an outline of the anatomy, biomechanics and function of the elbow joint, as it relates to normal and sporting activities. A variety of elbow injuries, including fractures of the olecranon, radial head and distal humerus are presented with appropriate methods of treatment. The aim to return patients to early functional activity is stressed. Soft tissue and more chronic over-use problems are briefly discussed, and a treatment regimen presented. In general, elbow injuries which involve acute fractures, dislocations and ligament injuries should be treated aggressively, in order to achieve early functional mobility. The more chronic over-use elbow problems should be viewed with a certain caution, and results are not as predictable following treatment of such injuries and over-use problems.


A computational examination on the structure, spin-state energetics and spectroscopic parameters of high-valent Fe(IV)=NTs species.
The imidoiron(IV) species are relatively less explored compared to the oxoiron(IV) intermediates. Recently, generation and characterization of a novel imido/oxoiron(iv) species ([(N(4)Py)Fe(IV)=X](2+) X = NTs; 1, O; 2) has been reported with an S = 1 ground state. Although the ground state for 1 and 2 are the same, they are reported to be distinctly different in other aspects. Unlike the oxoiron(IV) species, the Fe(IV) and nitrene combination in 1 lead to eight different spin states. Bearing in mind the complexity arising here, we have undertaken a detailed DFT study on this transient intermediate and probed its electronic structure and bonding in comparison to the oxoiron(IV) unit. Our Molecular Orbital, Energy Decomposition Analysis, and Natural Bond Orbital analysis indicates a weaker σ and non-degenerate π* orbitals for 1 in comparison to a stronger σ and degenerate π* orbitals for 2. The implication of these intricate bonding differences in reactivity is discussed along with the computation of absorption and other spectral parameters. Our results broadly support the proposed S = 1 ground state for 1 and provides some useful insight into its electronic structure.


A novel general approach to eucaryotic mutagenesis functionally identifies conserved regions within the adenovirus 13S E1A polypeptide.
A new approach to the isolation of mutations in mammalian genes was developed which permits both the selection of infrequently occurring mutants that alter the cellular morphology of recipient cells and the rapid reisolation of the mutant gene. The adenovirus type 5 13S early region 1a (E1a) gene was mutagenized in vitro with sodium bisulfite and then efficiently transferred into cells with a retrovirus shuttle vector. Three classes of mutants of the 13S E1a gene product were isolated, each of which induced a distinct morphological alteration. The mutant E1a gene was reisolated from each cell line, and the precise nucleotide changes were determined. The E1a-induced morphological alterations were further examined by the construction of single and double point mutations within different regions of the polypeptides by utilizing the amino acid substitutions obtained from the original mutants. The results suggest that each of the three regions of highly conserved amino acids within the E1a 13S polypeptide has a distinct role in the alteration of cellular morphology and the activation of gene expression.


Immunocytochemical evidence for phorbol ester-induced directional translocations of protein kinase C in HL60, K562, CHO, and E7SKS cells: possible role in differentiation.
The effects of phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on the directions of protein kinase C (PKC) translocation in two leukemic cell lines (HL60 and K562) and two fibroblastic cell lines (CHO and E7SKS), related to their susceptibility to the differentiating effect of TPA, were examined. Immunocytochemical evidence indicated that TPA induced a redistribution (outward) of PKC to the plasma membrane in TPA-sensitive HL60 cells, whereas it caused a translocation (inward) of the enzyme to the nucleus or the perinuclear region in K562, CHO, and E7SKS cells, which are resistant to TPA in terms of cell growth and differentiation. Immunoblot analysis of the nuclear proteins from K562 cells revealed that TPA induced an increase in the amount of immunoreactive proteins. TPA, however, did not increase the amount of these immunoreactive species in nuclei isolated from CHO and E7SKS cells, indicating that the translocated PKC was associated only with perinuclear structures of the TPA-treated cells. It is suggested that directional redistribution of PKC to the plasma membrane, as opposed to the nuclear and perinuclear region, might represent an early event required for the TPA-induced differentiation and maturation of HL60 cells.


Widespread regulation of gene expression in the Drosophila genome by the histone acetyltransferase dTip60.
The MYST histone acetyltransferase (HAT) dTip60 is part of a multimeric protein complex that unites both HAT and chromatin remodeling activities. Here, we sought to gain insight into the biological functions of dTip60. Strong ubiquitous dTip60 knock-down in flies was lethal, whereas knock-down in the wing imaginal disk led to developmental defects in the wing. dTip60 localized to the nucleus in early embryos and was present in a large number of interbands on polytene chromosomes. Genome-wide expression analysis upon depletion of dTip60 in cell culture showed that it regulated a large number of genes in Drosophila, among which those with chromatin-related functions were highly enriched. Surprisingly, a significant portion of these genes were upregulated upon dTip60 loss, indicating that dTip60 has repressive as well as activating functions. dTip60 protein was directly located at promoter regions of a subset of repressed genes, suggesting a direct role in gene repression. Comparison of the gene expression signature of dTip60 downregulation with that of histone deacetylase inhibition with trichostatin A revealed a significant correlation, suggesting that the dTip60 complex recruits an HDAC-containing complex to regulate gene expression in the Drosophila genome.


Speciation has a spatial scale that depends on levels of gene flow.
Area is generally assumed to affect speciation rates, but work on the spatial context of speciation has focused mostly on patterns of range overlap between emerging species rather than on questions of geographical scale. A variety of geographical theories of speciation predict that the probability of speciation occurring within a given region should (1) increase with the size of the region and (2) increase as the spatial extent of intraspecific gene flow becomes smaller. Using a survey of speciation events on isolated oceanic islands for a broad range of taxa, we find evidence for both predictions. The probability of in situ speciation scales with island area in bats, carnivorous mammals, birds, flowering plants, lizards, butterflies and moths, and snails. Ferns are an exception to these findings, but they exhibit high frequencies of polyploid and hybrid speciation, which are expected to be scale independent. Furthermore, the minimum island size for speciation correlates across groups with the strength of intraspecific gene flow, as is estimated from a meta-analysis of published population genetic studies. These results indicate a general geographical model of speciation rates that are dependent on both area and gene flow. The spatial scale of population divergence is an important but neglected determinant of broad-scale diversity patterns.


Cutaneous and lingual papules as a sign of beta 2 microglobulin-derived amyloidosis in a long-term hemodialysis patient.
Although hemodialysis has permitted long-term survival of patients with renal failure, beta 2 microglobulin-derived amyloidosis is a serious complication occurring most commonly in long-term hemodialysis patients. Orthopedic manifestations are quite common, but cutaneous and lingual manifestations are relatively uncommon. We report a 56-year-old patient with lichenoid plaque type of skin eruptions and lingual papules caused by beta 2 microglobulin-derived amyloidosis. Immunohistochemical study showed that amyloid deposits were positive for anti-beta 2 microglobulin antibody, but negative for anti-advanced glycation end products antibody (anti-CML and CLE antibody). We discuss the histological and the clinical features of skin manifestations of beta 2 microglobulin-derived amyloidosis.


[Ketoconazole and clindamycin efficacy vs oral clindamycin in premature membranes rupture prevention].
Vulvovaginitis is one of the main causes of premature membrane rupture. To evaluate effectiveness of a combination of ketoconazole (400 mg) and clindamycin (100 mg) in vaginal tablets, compared with clindamicyn alone (600 mg/daily) orally, for six days, to prevent premature membrane rupture in patients with vulvovaginitis. Longitudinal, prospective, comparative, randomized, double-blind, double-dummy study in patients older than 18 years, during them third trimester of normoevolutive pregnancy with symptomatic vulvovaginitis. Patients were monitored as out patient. Genital secretion culture and fresh studies were made. Signs and symptoms were evaluated in regular intervals: 4, 7 and 11 days. Pregnancy control was performed every three weeks, until childbirth or premature membrane rupture. 105 patients were included: 53 in the group of ketoconazole and clindamicyn (1), and 52 in the group of clindamycin alone (2). Symptoms were similar in both groups of treatment, without statistically significant differences. A case of group 2 has premature membrane rupture (p = 0.495). C. albicans was cultured in 35% of group 2 and in 11% of group 2. No adverse events with treatments were reported. The combination of ketoconazole and cindamycin was effective to prevent premature membrane rupture in patients with vulvovaginitis.


Estimations of production yields for selection of a practical optimal optical coating design.
Modern design approaches enable one to construct a series of theoretical designs with excellent spectral properties for almost all optical coating design problems. Selection of a practical optimal design among a variety of possible theoretical designs becomes a key issue. We demonstrate how preproduction estimations of expected production yields can be used for selection of a practical optimal design. The question of reliability of such estimations is also addressed.


Survey of the prevalence of warble fly larvae in market cattle in Great Britain.
A survey of warble-infested 'fat' cattle in 57 selected livestock markets in Great Britain was carried out during June 1972 and during May each year from 1973 to 1984. The annual total number of cattle inspected varied from 41,587 to 60,481. The level of infestation increased from 22.3 per cent in 1972 to 38.0 per cent in 1976 and then declined slightly to 34.3 per cent in 1978. Following the introduction of legislation and the warble fly eradication campaign in 1978 there was a rapid decrease to 8.6 per cent infestation by 1979 and by 1984 the level was less than 0.02 per cent.


[Indralin--a novel effective radioprotector during irradiation by high-energy protons].
Experiments with 120 mongrel dogs were aimed at the assessment of radio protective strength of indralin and local shielding of the pelvic marrow from 2.5 Gy, and also their concurrent use for the dogs irradiated by protons (240 MeV) at absolutely lethal and over-lethal 4 Gy and 5 Gy. Clinical observations, hematological investigations and ECG analysis of survived animals were conducted 4.5 years post the irradiation. Dogs that remained healthy following 3.5 to 4.5 years since the irradiation were sacrificed for pathomorphological investigations. The radioprotective effect of local shielding against 4 Gy was weak while this effect of intramuscular indralin (10, 20, 40 mg/kg of body) was significant reaching 50 to 67.7%. The concurrent use of two methods had, apparently, potentiated the 100% radioprotection of the animals irradiated by overlethal 5 Gy. Blood investigations of the survived dogs every 2-4 months evidenced that complete recovery of the total leukocyte count had taken 9 to 13 months. Also, dogs' pregnancy in 9-10 months since the beginning of irradiation pointed to maintenance of fertility and the ability to parturiate 2 or 3 times yielding 5-6 live cubs. Necropsy of the dogs did not reveal gross macroscopic structural changes of visceral organs or tissues. Seven out of 27 sacrificed dogs had benign tumors infrequent in intact dogs at this age.


History of Pharmacy Museum of the Faculty of Pharmacy University of Belgrade.
History of Pharmacy Museum at the Faculty of Pharmacy University of Belgrade was founded in Belgrade in 1952, thanks to many pharmacists and historians, but especially to Mr Andrija Mirković (Mpharm). His precious private collection of antiquities, which he donated to the Faculty of Pharmacy in Belgrade, subsequently a basic one for the Museum foundation, included apothecary vessels, apparatuses, manuscripts and books dated back to the XVI century. Furthermore, there were included many other antiquities, books and manuscripts from pharmacies on the territory of former Yugoslavia, mostly from Serbia, so the entire Museum collection comprises various apothecary vessels: 700 ceramic, wooden, glass, porcelain and halide glass jars, as well as the XIX century exhibits from Pravitelstvena Apoteka (the first state-owned pharmacy in Serbia, which operated between 1836-1859). The Museum collection of accessories and vessels is completed with a library and precious archive materials. The library itself includes the original manuscripts as well as the colour offprint of some manuscripts, and printed works; mostly scientific books, textbooks, journals and pharmacopoeias with drug tax lists. Some printed books dating back to the Late Middle Ages are very rare and precious, such as Curio's Medicina Salernitana (1612) and the Ruel's version of Dioscorides' De materia medica. This entire collection is considered a unique one in Serbia for its variety and greatness, representing a precious source for studying the History of Pharmacy and Pharmaceutical Ethics (as a subject was included into the Faculty's curriculum since 1952 and cancelled recently in 2008).


Carbonate-mediated Mars-van Krevelen mechanism for CO oxidation on cobalt-doped ceria catalysts: facet-dependence and coordination-dependence.
Carbonate intermediates have been reported to play an active role in CO oxidation over ceria-based catalysts in recent experimental studies. However, the detailed CO oxidation mechanism involving carbonate intermediates over ceria-based catalysts remains obscure. In this work, we carried out systematic density functional theory calculations corrected by on-site Coulomb interactions (DFT+U) to investigate the complete CO oxidation mechanism involving carbonate intermediates over cobalt-doped CeO2 catalysts, aiming to unravel how the carbonate participates in CO oxidation and shed light on the underlying factors that control the carbonate-mediated reaction mechanism. A novel carbonate-mediated Mars-van Krevelen (M-vK) mechanism was proposed, in which the carbonate acts as an active intermediate rather than a spectator and can react with CO to form CO2. This carbonate-mediated M-vK mechanism is facet-dependent because it is predominant on the (110) surface whereas the conventional M-vK mechanism is more favorable on (111) and (100) surfaces. The origin of facet-dependence was discussed by analyzing the geometric and electronic structures. It is found that the negatively charged bent CO2- intermediate formed on the (110) surface plays a critical role in the carbonate-mediated M-vK mechanism, whereas the formation of a neutral linear CO2 intermediate on (111) and (100) surfaces hinders the carbonate-mediated M-vK mechanism. The surface oxygen vacancy hinders the formation of carbonate intermediates, indicating that the carbonate-mediated M-vK mechanism is also vacancy-dependent. The formation of carbonate intermediates on different metal (Ti, V, W, Mo and Re) doped CeO2(110) surfaces was studied and the results indicate that the coordination environment of the dopant species is a key factor that determines the carbonate-mediated M-vK mechanism. This study provides atomic-scale insights into the reaction mechanism involving carbonate intermediates and the structure-mechanism relationship for CO oxidation over cobalt-ceria catalysts.


Pharmacotherapy and adjunctive treatment for idiopathic pulmonary fibrosis (IPF).
Idiopathic pulmonary fibrosis (IPF) is an advancing and fatal lung disease with increasing incidence and prevalence. Nintedanib and pirfenidone were approved by the FDA for the treatment of IPF in 2014 based on positive phase 3 trials, and both of these antifibrotic drugs are conditionally recommended in the 2015 ATS/ERS/JRS/ALAT Clinical Practice Guideline. Although an improvement over previously suggested therapies, their capacity to reduce, but not completely arrest or improve, lung function over time presents an opportunity for novel or add-on pharmacologic agents. The purpose of this review is to deliver a brief overview of the results of phase 3/4 IPF trials with pirfenidone and nintedanib, as well as highlight encouraging results of phase 1/2 trials with novel therapies. Long-term studies indicate that pirfenidone and nintedanib are effective IPF treatments, with acceptable safety and tolerability. The combination of pirfenidone and nintedanib appear safe. Promising results have recently been made public for several phase 2 trials with novel targets, including the autotaxin-lysophosphatidic acid (ATX/LPA) pathway, connective tissue growth factor (CTGF), pentraxin-2, G protein-coupled receptor agonists/antagonists, αvβ6 integrin, and galectin-3. Results of treatments directed at gastro-esophageal reflux in patients with IPF have also been published. Currently, monotherapy with pirfenidone or nintedanib is the mainstay of pharmacological treatment for IPF. Innovative therapies along with combinations of pharmacological agents hold great promise for the future.


Differential Co-Occurring Patterns Between Depressive Symptomatology and Sleep-Wake-Related Disturbances in Mood Disorders.
This study aimed to elucidate the various co-occurring patterns of depressive symptomatology and sleep-wake-related disturbances (SWRDs) in patients with mood disorders. Individuals in non-acute states of major depressive disorder or bipolar disorder were recruited. The Beck Depression Inventory II (BDI-II) was utilized to evaluate depressive symptoms. BDI-II items were classified into three domains: cognitive, affective, and somatic. Between-domain differences with various SWRDs were examined. Latent class analysis was used to empirically classify participants using BDI-II items as indicator variables. Co-occurring patterns between domains of BDI-II items and SWRDs were re-examined in each subgroup to elucidate inter-individual differences. In total, 657 participants were enrolled. Of participants, 66.8% were female, and 52.4% were diagnosed with major depressive disorder. Each BDI-II domain exhibited different co-occurring patterns. The somatic domain was most likely to co-occur with various SWRDs. Three subgroups were derived from latent class analysis and were designated as poor sleep quality and high insomnia (n=150), poor sleep quality and moderate insomnia (n=248), and poor sleep quality and low insomnia (n=159). The group with more severe insomnia presented with more severe depressive and anxiety symptoms. The three subgroups further differed in co-occurring patterns. From the low insomnia to high insomnia group, the associations with various SWRDs appeared in the sequence of somatic, affective, and cognitive domains. Co-occurring patterns between domains of depressive symptomatology with various SWRDs differ and may vary among individuals.


Teaching Home-Based Primary Care.
Despite the growing homebound population and the development of innovative models of care that work to bring care to people in their homes, home visits are not a routine part of education for many healthcare providers. This manuscript describes the experience of Mount Sinai Visiting Doctors teaching home-based primary care to learners of various disciplines and reports the results of a survey performed to assess trainee experience. Mount Sinai Visiting Doctors is the largest academic home-based primary care program in the country and trainees of various disciplines have nearly 1,700 contact days annually of directly supervised clinical teaching. In order to improve trainee education and meet our practice needs, trainees: 1) independently conduct urgent visits, 2) carry longitudinal panels of homebound patients, and 3) perform subspecialist consultations. Mount Sinai Visiting Doctors has exposed thousands of trainees to home-based primary care in the past 20 years and trainees report positive reviews of their experiences. As the need to train future providers in home-based primary care grows, we will be challenged to provide trainees with adequate exposure to multidisciplinary teams and to teach about the importance of continuity of care.


Correlation of bcl-2, p53, and MIB-1 expression with ependymoma grade and subtype.
In this study, we report our results on the proliferative activity of ependymomas as determined by MIB-1 (also known as Ki-67) immunohistochemical analysis, and we compare our results with those obtained by immunolabeling with monoclonal antibodies to p53 and bcl-2 proteins to assess whether expression correlated with ependymoma subtype or tumor grade. The study included 4 myxopapillary ependymomas (Grade I of the World Health Organization [WHO] scale), 10 subependymomas (WHO Grade I), 17 ependymomas (WHO Grade II), 2 papillary ependymomas (WHO grade II), and 4 anaplastic ependymomas (WHO Grade III). The MIB-1 proliferation index was significantly higher in tumors diagnosed as anaplastic ependymoma (P < .001), with a moderate level of correlation (Kendall's tau-b = 0.557, asymptotic standard error = 108). In addition, one ependymoma (WHO Grade II) not considered overtly anaplastic by routine histologic criteria showed a high MIB-1 labeling index, suggesting that the MIB-1 proliferation index might be a more objective indicator of tumor grade. The remaining WHO Grade I and Grade II ependymomas showed low proliferative activity. bcl-2 oncoprotein expression was identified in all of the four myxopapillary and in both papillary ependymomas. An additional observation was the correlation of p53 expression with increasing WHO grade. These data suggest that high MIB-1 and p53 immunolabeling might be objective indicators of high grade in ependymomas that do not otherwise meet routine histologic criteria for high-grade ependymoma. Subsequent clinicopathologic analyses will be important in assessing whether these markers are useful as independent predictors of survival.


The cross-script length effect: further evidence challenging PDP models of reading aloud.
The interaction between length and lexical status is one of the key findings used in support of models of reading aloud that postulate a serial process in the orthography-to-phonology translation (B. S. Weekes, 1997). However, proponents of parallel models argue that this effect arises in peripheral visual or articulatory processes. The authors addressed this possibility using the special characteristics of the Serbian and Japanese writing systems. Experiment 1 examined length effects in Serbian when participants were biased to interpret phonologically bivalent stimuli in the alphabet in which they are words or in the alphabet in which they are nonwords (i.e., the visual characteristics of stimuli were held constant across lexical status). Experiment 2 examined length effects in Japanese kana when words were presented in the kana script in which they usually appear or in the script in which they do not normally appear (i.e., the phonological characteristics of stimuli were held constant across lexical status). Results in both cases showed a larger length effect when stimuli were treated as nonwords and thus offered strong support to models of reading aloud that postulate a serial component.


Video absorbtiometry in diagnostic cytology: description of a new technique and a preliminary statistical evaluation.
Cytological specimens from 21 patients were examined using digital video microscopy. The staining characteristics of cells incubated with hydroquinone and the tetrazolium stain MTT were analysed using a novel procedure that is independent of morphological features and relies on characteristics of the frequency distribution of the localised (pixel) absorbances of the cellular images. The properties of the distribution of absorbances were assessed by a number of procedures. Comparisons were made of nine malignant and 12 non-malignant cytological samples, obtained mainly from pleural and peritoneal fluid. The data showed significant differences between the sets of samples which may be of value in cytological diagnosis. In the material examined all the malignant samples exhibited a positive skewness with the alpha-3 test (the mean alpha-3 value being greater than 0.5); this was true in only two of 12 non-malignant samples. This analytical technique, which is largely independent of morphology, magnification, and absolute absorbance values, seems to hold promise for the simplification and automation of cytological screening procedures.


Treatment strategies for carotid artery aneurysms.
The aim of this paper was to present single centre experience in the treatment of extra cranial carotid artery aneurysms (ECCA) and to analyze results discussing different treatment modalities. The study analyzed 60 patients with 62 ECCA treated surgically at the Clinic for vascular and endovascular surgery, Serbian Clinical Center (Belgrade) in the period between 1985 and 2013. Treatment strategy was individually selected and demographic, morphologic, intraoperative and postoperative data were collected. Thirty-day operative mortality was 3.3% and completely stroke related. Besides two fatal strokes one additional was registered making total number of 3 (4.8%) postoperative strokes. Only one (1.6%) early graft thrombosis has been found. The 30-day-patency rate was 98.4%. During the same period seven local complications were found: three (4.8%) hemorrhage and four (6.4%) cranial nerves injuries. In all cases of hemorrhage successful re-intervention was performed without any consequences. Cranial nerves injuries included transient contusions of hypoglossal (2) and superior laryngeal nerve (2). The etiology, location, and morphology of an ECCA are determining selection of appropriate therapy. Large or tortuous aneurysms, as well as aneurysms involving common carotid or proximal internal carotid artery, are also absolutely indicated to open surgical therapy. Aneurysms which involve the distal internal carotid artery and false anastomotic aneurysms are best managed with endovascular techniques. The ligature is indicated for the treatment of external carotid aneurysms, mycotic aneurysms with local infection and in ruptured ECCA with uncontrolled bleeding.


The Role of Metabolism in Toxicity of Polycyclic Aromatic Hydrocarbons and their Non-genotoxic Modes of Action.
Polycyclic aromatic hydrocarbons (PAHs) represent a class of widely distributed environmental pollutants that have been primarily studied as genotoxic compounds. Their mutagenicity/genotoxicity largely depends on their oxidative metabolism leading to the production of dihydrodiol epoxide metabolites, as well as additional metabolites contributing to oxidative DNA damage, such as PAH quinones. However, both parental PAHs and their metabolites, including PAH quinones or hydroxylated PAHs, have been shown to produce various types of non-genotoxic effects. These include e.g., activation of the aryl hydrocarbon receptor and/or additional nuclear receptors, activation of membrane receptors, including tyrosine kinases and G-protein coupled receptors, or activation of intracellular signaling pathways, such as mitogen-activated protein kinases, Akt kinase and Ca2+-dependent signaling. These pathways may, together with the cellular DNA damage responses, modulate cell proliferation, cell survival or cell-to-cell communication, thus contributing to the known carcinogenic effects of PAHs. In the present review, we summarize some of the known non-genotoxic effects of PAHs, focusing primarily on those that have also been shown to be modulated by PAH metabolites. Despite the limitations of the available data, it seems evident that more attention should be paid to the discrimination between the potential non-genotoxic effects of parental PAHs and those of their metabolites. This may provide further insight into the mechanisms of toxicity of this large and diverse group of environmental pollutants.


Participant food and activity costs in a translational Diabetes Prevention Program.
The Diabetes Prevention Program (DPP) and its translational adaptations have been shown to be effective. However, individual-level economic impacts, such as the out-of-pocket costs borne by participants due to involvement in these programs have not been consistently and thoroughly evaluated. As cost is an important consideration that will impact the willingness of individuals to participate in such programs, this study examined direct monetary costs to participants in the Group Lifestyle Balance (GLB) DPP. Older adults (n = 134, mean age 62.8 years) with body mass index (BMI) ≥24 kg/m2 and prediabetes and/or metabolic syndrome participated in this GLB intervention, with two-thirds randomized to begin the intervention immediately and one-third functioning as a control for 6 months before receiving the entire intervention. Food and activity time and costs borne by participants were measured by self-report at baseline and after 6 months. Significant improvements in clinical metabolic measures, weight, and physical activity levels were achieved after 6 months in the intervention group compared both with baseline and the controls. Food costs did not increase among intervention participants. Costs related to physical activity did not change consistently over the course of the intervention. This DPP-GLB lifestyle intervention was effective in reducing risk factors for Type 2 diabetes mellitus among a diverse group of older participants without significantly increasing their out-of-pocket costs for food or physical activity over the course of the intervention. These results should help reduce concerns of individuals who are hesitant to participate in similar programs due to costs. The clinical trial registration number of this study is NCT01050205.


Change in the Shrinkage Forces of Composite Resins According to Controlled Deflection.
The aim of this study was to investigate how the polymerization shrinkage forces of composite resins change with change in deflection. Five composites, SDR (Dentsply Caulk, Milford, DE, USA), EcuSphere-Shape (DMG, Hamburg, Germany), Tetric N-Ceram Bulk Fill (Ivoclar Vivadent, Schaan, Liechtenstein), CLEARFIL AP-X (Kuraray Noritake Dental Inc., Sakazu, Kurashiki, Okayama, Japan), and Filtek Z350 XT (3M Dental Products, St Paul, MN, USA), were tested in this experiment. The polymerization shrinkage forces of the composites were measured using a custom-made tooth-deflection-mimicking device and software (R&B Inc, Daejon, Korea). In all measurements, six modes were tested: maximum-deflection, zero-deflection, and four deflection-controlled modes. For each deflection mode, the shrinkage forces were recorded continuously every 0.1 second for 180 seconds. Polymerization shrinkage and flexural modulus were also measured. Eight specimens of each material were allocated for each test. For each material, six groups of shrinkage force values were compared using one-way ANOVA and Tukey post hoc tests at a 95% confidence level. The polymerization shrinkage force of each material in each of the six deflection modes was analyzed with 95% confidence using one-way ANOVA and Tukey post hoc tests. The relationship between the force measured in the six deflection modes and the linear polymerization shrinkage and flexural modulus was analysed with 95% confidence using Pearson correlation analysis. For each material, the following held true: the shrinkage force was highest in zero-deflection mode, the force decreased as deflection increased, and the smallest force appeared in maximum-deflection mode (p<0.05). There was a high negative correlation between allowable deflection and shrinkage force in all materials.


The wheat proteins puroindoline-a and alpha1-purothionin induce nodal swelling in myelinated axons.
The effects of two basic cysteine-rich lipid-binding proteins isolated from wheat seedlings, puroindoline-a and alpha1-purothionin, were studied on single frog myelinated axons stained with the fluorescent dye FM1-43 using confocal laser scanning microscopy. During exposure to either puroindoline-a or alpha1-purothionin (10 and 100 microM) a marked swelling of nodes of Ranvier was observed, provided NaCl was present in the external solution. It is suggested that these proteins increase the internal osmolality by forming pores in the axonal membrane and induce water influx to compensate for such an increase. Moreover, in the presence of alpha1-purothionin (100 microM), the intensity of the axonal staining with FM1-43 was increased. It is the first time, to our knowledge, that basic proteins containing domains of a cysteine-rich repeated motif are reported to produce swelling and water movements across neuronal cell membranes.


Genome sequences of cluster GA phages Phonegingi and Dropshot.
Bacteriophages Phonegingi and Dropshot were isolated from soil in North Carolina using the host Microbacterium foliorum. Both phages have siphovirus morphologies. Based on gene content similarity to one another and to other actinobacteriophages, both phages are assigned to phage cluster GA.


Incidence and clinical manifestations of adenoviral infection among children undergoing allogeneic stem cell transplantation.
Adenoviral infection in children undergoing stem cell transplantation is associated with significant morbidity and mortality. Identification of adenoviral infection by polymerase chain reaction from blood facilitates accurate and rapid diagnosis and surveillance. The incidence of adenoviral infection among children undergoing SCT in Israel is not known. To estimate the incidence of adenoviral infection in pediatric SCT patients and to characterize the morbidity associated with proven infection. Blood samples obtained weekly from children who underwent allogeneic SCT were retrospectively tested for adenovirus using standard PCR. A total of 657 samples collected from 32 patients were examined. Correlation was made between the presence of adenovirus in samples and clinical records. Of the 32 patients 4 had adenoviral infection by PCR (12.5%). Clinical disease was present in all four patients concurrent with positive PCR. Gastrointestinal complaints and abnormal hepatocellular enzymes were uniformly present. One patient died due to disseminated disease. T cell depletion was a significant risk factor for adenoviral infection (P = 0.03). In the patient population studied, the incidence of adenoviral infection in children undergoing SCT was 12.5%. The combination of gastrointestinal symptoms and abnormal hepatocellular enzymes should raise the suspicion of adenoviral infection, especially when occurring during the first few months after SCT.


[Changes in regional hemodynamics indices in patients with open-angle glaucoma].
Changes in the hemodynamic parameters of the eye were examined in patients with primary open-angle glaucoma (OAG) in the well developed and far advanced stages with moderately increased (up to 32 mm Hg) and high (33 mm Hg and higher) pressure before and after surgery. Computer-aided vacuum ophthalmodynamometer was used with a sucking cup calibrated for two levels of ophthalmic tone, whose external diameter was 13 mm and funnel angle 60 degrees. A total of 59 patients (82 eyes) aged 50 to 84 years were examined, control group consisted of 18 patients (36 eyes). Mean dynamic pressure in the orbital artery and perfusion pressure were measured, and the orbital-brachial coefficient estimated. Progressive decrease of perfusion pressure was paralleled by increase of the mean dynamic pressure in the orbital artery in patients with stages Iic and IIIb OAG and by its decrease in those with stage IIIc OAG. Such changes of the hemodynamics are explained by the compensatory work of the ocular bloodflow autoregulation mechanism in the first case and its failure in the second. After regression analysis, linear equations of the relationship between changes in the mean dynamic pressure and intraocular pressure were calculated. After surgery, changes in the hemodynamic parameters were followed up for 12 months in 27 eyes with well-developed condition and for 6 months in 13 eyes with far advanced condition.


Laboratory Result Reference Ranges Stratified for Patient-Reported Sex and Ethnicity Are More Closely Associated With Postoperative Outcomes Than Currently Used Reference Ranges: A Retrospective Data Analysis.
A single laboratory range for all individuals may fail to take into account underlying physiologic differences based on sex and genetic factors. We hypothesized that laboratory distributions differ based on self-reported sex and ethnicity and that ranges stratified by these factors better correlate with postoperative mortality and acute kidney injury (AKI). Results from metabolic panels, complete blood counts, and coagulation panels for patients in outpatient encounters were identified from our electronic health record. Patients were grouped based on self-reported sex (2 groups) and ethnicity (6 groups). Stratified ranges were set to be the 2.5th/97.5th percentile for each sex/ethnic group. For patients undergoing procedures, each patient/laboratory result was classified as normal/abnormal using the stratified and nonstratified (traditional) ranges; overlap in the definitions was assessed between the 2 classifications by looking for the percentage of agreement in result classifications of normal/abnormal using the 2 methods. To assess which definitions of normal are most associated with adverse postoperative outcomes, the odds ratio (OR) for each outcome/laboratory result pair was assessed, and the frequency that the confidence intervals of ORs for the stratified versus nonstratified range did not overlap was examined. Among the 300 unique combinations (race × sex × laboratory type), median proportion overlap (meaning patient was either "normal" or "abnormal" for both methodologies) was 0.86 [q1, 0.80; q3, 0.89]. All laboratory results except 6 overlapped at least 80% of the time. The frequency of overlap did not differ among the racial/ethnic groups. In cases where the ORs were different, the stratified range was better associated with both AKI and mortality (P < .001). There was no trend of bias toward any specific sex/ethnic group. Baseline "normal" laboratory values differ across sex and ethnic groups, and ranges stratified by these groups are better associated with postoperative AKI and mortality as compared to the standard reference ranges.


Intrapericardial cisplatin combined with oral colchicine resulted in long term control of malignant pericardial effusion in the course of metastatic renal cancer.
Background Neoplastic pericardial effusion (NPE) represents a common cause of morbidity and mortality in patient with cancer. NPE presents frequently as cardiac tamponade, requiring urgent pericardiocentesis or pericardiotomy, with subsequent pericardial fluid drainage. Despite high effectiveness of such procedures, the recurrence of effusion is noted in 30- 60% of patients. Intrapericardial therapy with cisplatin was found to be effective in NPE due to lung and breast cancer. Its role in cardiac tamponade due to renal cancer is unknown. Case presentation We presented 82-year-old man with renal cancer who was admitted to the Intensive Care Unit because of threatening pericardial tamponade due to NPE . Urgent subxiphoid pericardiotomy was performed with subsequent evacuation of 1000ml of bloody fluid. On the inner surface of the pericardium several pink nodules were found. Histological examination revealed carcinoma clarocellulare. In view of the persistent high drainage of the pericardium, intrapericardial cisplatin therapy was performed. The first day after surgery colchicine 0.5 mg/day/po was also introduced. No side effects of this treatment were observed. The patient died 12- month later due to cancer progression and cachexia. No recurrence of pericardial effusion was observed. Conclusion This is the first case study demonstrating long-term efficacy and safety of intrapericardial cisplatin combined with oral colchicine in NPE due to metastatic renal cell carcinoma.


Binding energy and specificity in the catalytic mechanism of yeast aldose reductases.
Derivatives of d-xylose and d-glucose, in which the hydroxy groups at C-5, and C-5 and C-6 were replaced by fluorine, hydrogen and azide, were synthesized and used as substrates of the NAD(P)H-dependent aldehyde reduction catalysed by aldose reductases isolated from the yeasts Candida tenuis, C. intermedia and Cryptococcus flavus. Steady-state kinetic analysis showed that, in comparison with the parent aldoses, the derivatives were reduced with up to 3000-fold increased catalytic efficiencies (k(cat)/K(m)), reflecting apparent substrate binding constants (K(m)) decreased to as little as 1/250 and, for d-glucose derivatives, up to 5.5-fold increased maximum initial rates (k(cat)). The effects on K(m) mirror the relative proportion of free aldehyde that is available in aqueous solution for binding to the binary complex enzyme-NAD(P)H. The effects on k(cat) reflect non-productive binding of the pyranose ring of sugars; this occurs preferentially with the NADPH-dependent enzymes. No transition-state stabilization energy seems to be derived from hydrogen-bonding interactions between enzyme-NAD(P)H and positions C-5 and C-6 of the aldose. In contrast, unfavourable interactions with the C-6 group are used together with non-productive binding to bring about specificity (6-10 kJ/mol) in a series of d-aldoses and to prevent the reaction with poor substrates such as d-glucose. Azide introduced at C-5 or C-6 destabilizes the transition state of reduction of the corresponding hydrogen-substituted aldoses by approx. 4-9 kJ/mol. The total transition state stabilization energy derived from hydrogen bonds between hydroxy groups of the substrate and enzyme-NAD(P)H is similar for all yeast aldose reductases (yALRs), at approx. 12-17 kJ/mol. Three out of four yALRs manage on only hydrophobic enzyme-substrate interactions to achieve optimal k(cat), whereas the NAD(P)H-dependent enzyme from C. intermedia requires additional, probably hydrogen-bonding, interactions with the substrate for efficient turnover.


Characterization of Tetracycline Hydrochloride Compounded in a Miracle Mouthwash Formulation.
Miracle mouthwash (MMW) is a commonly prescribed oral formulation compounded with varying active ingredients, depending on purpose of treatment. Due to patient-to-patient customization, the solubility, stability, and solid-state characteristics of the active ingredients may not be known after compounding. This study found that the common antibiotic, tetracycline hydrochloride (HCl), compounded in MMW formulations that contained dexamethasone elixir and diphenhydramine, underwent significant physical-chemical changes. Simulated patient conditions demonstrated appreciable fluctuations from the target content of 50 mg tetracycline HCl per teaspoon over 15 days. The lowest tetracycline content sampled was 32.5 mg, while the highest content sampled was 53.0 mg. Although tetracycline HCl went into solution after compounding, tetracycline did not remain in solution. In fact, the amount of tetracycline in solution declined exponentially, with over two-thirds of tetracycline precipitating out within the first day of compounding and 14% remaining in solution after 15 days. Crystals that formed within the MMW formulation were analyzed using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and powder X-ray diffraction (PXRD), which confirmed a solvent-mediated phase transformation of tetracycline HCl to tetracycline hexahydrate. For tetracycline in solution, pH had a significant effect on chemical degradation. Therefore, tetracycline HCl compounded in MMW formulations can have significant physical-chemical stability changes, possibly impacting patient dosing.


The combination of bortezomib with chemotherapy to treat relapsed/refractory acute lymphoblastic leukaemia of childhood.
Achieving complete remission (CR) in childhood relapsed/refractory acute lymphoblastic leukaemia (ALL) is a difficult task. Bortezomib, a proteasome inhibitor, has in vitro activity against ALL blasts. A phase I-II trial, reported by the Therapeutic Advances in Childhood Leukaemia and Lymphoma (TACL) consortium, demonstrated that bortezomib with chemotherapy has acceptable toxicity and remarkable activity in patients with relapsed ALL failing 2-3 previous regimens. We evaluated bortezomib in combination with chemotherapy in 30 and 7 children with B-cell precursor (BCP) and T-cell ALL, respectively. Bortezomib (1·3 mg/m2 /dose) was administered intravenously on days 1, 4, 8, and 11. Chemotherapy agents were the same as those used in the TACL trial, consisting of dexamethasone, doxorubicin, vincristine and pegylated asparaginase. Three patients (8·1%) died due to infections. Twenty-seven patients (72·9%) achieved CR or CR with incomplete platelet recovery (CRp). Fourteen had minimal residual disease (MRD) lower than 0·1%. Twenty-two of 30 BCP-ALL patients (73·3%) and 5/7 patients (71%) with T-cell ALL achieved CR/CRp. The 2-year overall survival (OS) is 31·3%; CR/CRp patients with an MRD response had a remarkable 2-year OS of 68·4%. These data confirm that the combination of bortezomib with chemotherapy is a suitable/effective option for childhood relapsed/refractory ALL.


Chromosome 16q loss--a genetic key to the understanding of breast carcinogenesis.
In the last decade the concepts of breast cancer dedifferentiation and progression have undergone a significant and substantial change. In the past it was widely believed that the detailed associations between genetic and morphological changes defined in the Vogelstein model of colorectal cancer pathogenesis could be transferred to breast carcinogenesis. A multitude of studies seemed to verify this a priori hypothesis. However, with the introduction of global screening techniques, predominantly at the DNA level, it became obvious that this linear model might be oversimplified for breast cancer. It is now widely accepted that losses of chromosomal 16q characterize in-situ and invasive breast cancer tumours with predominantly low tumour grade and estrogen receptor (ER) positivity (luminal breast cancers). In contrast, high grade breast cancers of the HER2, the basal or the non expressor phenotype with 16q-losses are rarely seen and in consequence a concept of multiple, parallel pathways with defined precursor lesions emerged. As a consequence, it became obvious that the hunt for oncogenes/tumour suppressor genes in invasive breast cancer is pathway specific. Whereas high grade breast cancers have been relatively well characterized by several recurrent changes in oncogenes/tumour suppressor genes located on various chromosomal regions (e.g. egfr, p53, HER2), the characterization of a 16q-specific tumour suppressor gene in ER-positive breast cancer is still a tremendous challenge. This review will focus on the role of 16q in breast cancer and aims to give insights into actual research efforts, e.g. alternative explanations in order to unravel the central role of 16q in breast cancer.


CRISPR-PN2: a flexible and genome-aware platform for diverse CRISPR experiments in parasitic nematodes.
Parasitic nematodes represent a significant threat to human health, causing diseases of major socioeconomic importance worldwide. Central to controlling infections of parasitic nematodes is a more detailed molecular picture of host specificity, parasite activation and immune suppression. CRISPR technology holds huge potential for researchers in the field of parasitic nematology, as it provides a powerful genetic tool to dissect questions in parasite biology. To expedite the development of CRISPR technology in parasitic nematodes, software is required to facilitate the design of effective and specific sgRNA sequences. Here, the author introduces CRISPR-PN2, a comprehensive web-based platform that provides flexible use control over the automated design of specific gRNA sequences for CRISPR experiments in parasitic nematodes.


Bubbles trapped in a fluidized bed: Trajectories and contact area.
This work investigates the dynamics of bubbles in a confined, immersed granular layer submitted to an ascending gas flow. In the stationary regime, a central fluidized zone of parabolic shape is observed, and the bubbles follow different dynamics: either the bubbles are initially formed outside the fluidized zone and do not exhibit any significant motion over the experimental time or they are located inside the fluidized bed, where they are entrained downwards and are, finally, captured by the central air channel. The dependence of the air volume trapped inside the fluidized zone, the bubble size, and the three-phase contact area on the gas injection flow rate and grain diameter are quantified. We find that the volume fraction of air trapped inside the fluidized region is roughly constant and of the order of 2%-3% when the gas flow rate and the grain size are varied. Contrary to intuition, the gas-liquid-solid contact area, normalized by the air injected into the system, decreases when the flow rate is increased, which may have significant importance in industrial applications.


Nuclear receptor profile in calvarial bone cells undergoing osteogenic versus adipogenic differentiation.
Nuclear receptors (NRs) are key regulators of cell function and differentiation. We examined NR expression during osteogenic versus adipogenic differentiation of primary mouse calvarial osteoblasts (MOBs). MOBs were cultured for 21 days in osteogenic or adipogenic differentiation media. von Kossa and Oil Red O staining, and qRT-PCR of marker genes and 49 NRs were performed. PCR amplicons were subcloned to establish correct sequences and absolute standard curves. Forty-three NRs were detected at days 0-21. Uncentered average linkage hierarchical clustering identified four expression clusters: NRs (1) upregulated during osteogenic, but not adipogenic, differentiation, (2) upregulated in both conditions, with greater upregulation during adipogenic differentiation, (3) upregulated equally in both conditions, (4) downregulated during adipogenic, but not osteogenic, differentiation. One-way ANOVA with contrast revealed 20 NRs upregulated during osteogenic differentiation and 12 NRs upregulated during adipogenic differentiation. Two-way ANOVA demonstrated that 18 NRs were higher in osteogenic media, while 9 NRs were higher in adipogenic media. The time effect revealed 16 upregulated NRs. The interaction of condition with time revealed 6 NRs with higher expression rate during adipogenic differentiation and 3 NRs with higher expression rate during osteogenic differentiation. Relative NR abundance at days 0 and 21 were ranked. Basal ranking changed at least 5 positions for 13 NRs in osteogenic media and 9 NRs in adipogenic media. Osteogenic and adipogenic differentiation significantly altered NR expression in MOBs. These differences offer a fingerprint of cellular commitment and may provide clues to the underlying mechanisms of osteogenic versus adipogenic differentiation.


Lubricin: Its Presence in Repair Cartilage following Treatment with Autologous Chondrocyte Implantation.
To determine if lubricin was present in the surface layer of repair cartilage formed after autologous chondrocyte implantation (ACI). Forty-three biopsies of repair tissue were taken from patients who had been treated with ACI 8 to 68 months previously (mean of 18.0 ± 14.4 months); 30 had flaps of periosteum and 13 of Chondro-Gide(®). Cryopreserved sections were stained with hematoxylin and eosin, toluidine blue, and immunostained for lubricin and type II collagen. The quality of repair tissue was scored via OsScore, and clinical improvement in patients was assessed via change in Lysholm score. Normal/control cartilage was studied for comparison (n = 5). Patients' Lysholm scores improved from 48.1 ± 17 preoperatively to 69.5 ± 21.5 posttreatment. The thickness of repair tissue was 2.9 ± 1.7 mm compared with 2.3 ± 0.6 mm for control cartilage, with an OsScore of 6.7 ± 1.6 (8.9 ± 1.2 for controls). Ninety-eight percent of biopsies had staining for lubricin, with 84% having some in the surface layer (60% of periosteal treated and 100% of Chondro-Gide treated). The improvement in Lysholm score was not significantly different in patients with lubricin present at the surface compared with those without. Lubricin was present in almost all samples of repair tissue formed post ACI, often in the surface layer, resembling the distribution that is seen in normal cartilage. The presence of lubricin in the upper layer is likely to have implications for the functioning of the tissue because, via its mucin-like repeats, it appears capable of reducing the friction that could arise in articulating joints.


Integration of negative emotional experience versus suppression: addressing the question of adaptive functioning.
Integrative emotion regulation is defined as the ability to experience negative emotions, explore their sources, and use this exploration for volitional regulation of behavior. Empirical research on integrative regulation is quite scarce and relies mainly on self-reports. The present research comprised 2 studies exploring the behavioral, emotional, and cognitive consequences of integrative emotion regulation and suppression of emotion, in relation to a fear-eliciting film. Study 1 examined associations between emotion regulation types (self-reported) and defensive versus nondefensive emotional processing (coded from postfilm open-ended written texts) in 80 Israeli college students. In Study 2, we manipulated the emotion regulation types by assigning 120 Israeli college students to integrative, suppressive, and control (neutral) conditions and exposing them twice to the same fear-eliciting film, 72 hr apart. We hypothesized that in the second exposure to the film, participants who were instructed to practice integrative regulation would benefit more than participants in the other 2 groups in terms of lower arousal level related to an experience of fear (measured by skin conductance, physical observation, and self-report) and better cognitive capacity (on a recall test). In general, the results supported our hypotheses. In comparison to suppression, integrative regulation was associated with less defensive written expression in the first study and with lower arousal and better cognitive recall in the second study. Hence, current outcomes provide some support for the assumption that taking interest in and accepting one's negative emotions is linked with less defensive processing of negative experiences and with better functioning.


Phosphatidic acid-phosphatidylethanolamine interaction and apocytochrome c translocation across model membranes.
The translocation of apocytochrome c (apocyt.c) across large unilamellar vesicles (LUVs) constructed from mixtures of anionic and zwitterionic phospholipids, phosphatidylethanolamine (PE) and phosphatidylcholine (PC), has been studied. It was shown that the import ratio of horse heart apocyt.c in LUVs composed of phosphatidic acid (PA) combined with PE and PC (62+/-10%) was much higher than that in LUVs made of PE and PC plus any other acidic phospholipid species (20+/-5%). This feature was shared by tuna heart and chicken heart apocyt.c. In addition, the greater efficiency of the PA/PE/PC system versus others in facilitating apocyt.c translocation was maintained using synthetic anionic phospholipids with the same acyl chains. Besides, apocyt.c induces more leakage of entrapped fluorescein sulphonate (FS) from the interior of PA/PC/PE vesicles compared with phosphatidylglycerol (PG)/PC/PE ones. By measuring the intrinsic fluorescence emission spectrum and the accessibility of the preprotein to the fluorescence quencher, acrylamide, differences could be detected in the conformational changes of apocyt.c as a consequence of its interaction with PA/PE/PC and PG/PE/PC vesicles, respectively. Particularly notable is that PE is indispensable for the PA/PE/PC system to most efficiently facilitate apocyt.c translocation across the model membranes. With the fraction of PE increasing from 0 to 30 mol%, the translocation efficiency of apocyt.c as well as its ability to induce FS efflux was significantly enhanced in PA-containing LUVs, whereas this was not observed in the case of replacement of PA by PG or phosphatidylserine. It is also interesting to note that in LUVs containing PA, dioleoyl-PE, but not dielaidoyl-PE, can exert such influences, indicative of the role of non-bilayer formation propensity. On the basis of these results it is postulated that PA might increase the bilayer-destabilizing effects of PE, and hence increase the translocation efficiency of apocyt.c and its leakage-induction ability.


Return to Galileo? The Inquisition of the International Narcotic Control Board.
Nearly 400 years after Galileo Galilei of Florence was arraigned and convicted of suspected heresy by the ten member Congregation of the Holy Office (Inquisition), the International Narcotic Control Board (INCB) is similarly inserting itself into matters pertaining to innovations in healthcare and the public health response to addiction throughout the world. Like that earlier Inquisition of 1633 that convicted Galileo of heresy for holding that the sun is the centre of the universe with the earth revolving around it (in contradiction to church doctrine of the time) the INCB and its thirteen-member panel, now rails against any evidence out of sync with the established doctrine of the war on drugs--particularly those innovations in public health called harm reduction. The latest healthcare and harm reduction practices to attract the ire of the INCB Inquisition are elements of Canada's most effective and innovative measures to minimize the harms of drugs in Vancouver--supervised injection facilities and, recently, the potential establishment of supervised inhalation rooms--along with the long established practice of providing safer mouthpieces for pulmonary inhalation in British Columbia. This is particularly significant as it comes in the midst of a crucial battle between municipal and provincial authorities in BC with the federal government in Ottawa, which seems determined to undermine all the most effective HR programs that are the result of years of steady local and governmental support in Vancouver and now threatens to derail all these programs and spread doubt about their usefulness despite the overwhelmingly positive findings of serous research.