Repeatability and validity of cell and fluid-phase measurements in nasal fluid: a comparison of two methods of nasal lavage.
There is little information on the repeatability of cell counts and fluid-phase measurements in nasal fluid obtained by different methods of nasal lavage. To compare the repeatability and validity of total and differential cell counts and eosinophil cationic protein (ECP) in nasal secretions obtained by two methods of nasal lavage. Twelve healthy subjects and twelve subjects with clinically stable allergic rhinitis were randomly assigned to two nasal lavages (separated by 48 h), by one of two methods in the first week and by the second method in the following week. One method was a modification of the method described by Greiff et al. and Grunberg and coworkers and the other was that described by Naclerio and coworkers. Both methods of nasal lavage gave poorly repeatable eosinophil counts and ECP in normal subjects but better repeatability in subjects with rhinitis. The modified Greiff/Grunberg method gave higher and more repeatable total cell count and, in subjects with rhinitis, more reproducible ECP levels compared with the Naclerio Both methods were able to discriminate between healthy and rhinitic subjects: mean +/- SD eosinophil percentage count and eosinophil cationic protein differences were 4.5 +/- 4% (P < 0.05) and 24.5 +/- 46.9 microg/L (P < 0.05), respectively, with the modified method and 7.0 +/- 4% (P < 0.05) and 26.9 +/- 68 microg/L (P < 0.05), respectively, with the Naclerio method. Both methods are valid and discriminate between normal and rhinitic subjects. In subjects with rhinitis, although the repeatability of eosinophil counts is similar by both methods, the modified Greiff/Grunberg method gives more reproducible ECP measurements, compared with the Naclerio method.


Internal climate variability and projected future regional steric and dynamic sea level rise.
Observational evidence points to a warming global climate accompanied by rising sea levels which impose significant impacts on island and coastal communities. Studies suggest that internal climate processes can modulate projected future sea level rise (SLR) regionally. It is not clear whether this modulation depends on the future climate pathways. Here, by analyzing two sets of ensemble simulations from a climate model, we investigate the potential reduction of SLR, as a result of steric and dynamic oceanographic affects alone, achieved by following a lower emission scenario instead of business-as-usual one over the twenty-first century and how it may be modulated regionally by internal climate variability. Results show almost no statistically significant difference in steric and dynamic SLR on both global and regional scales in the near-term between the two scenarios, but statistically significant SLR reduction for the global mean and many regions later in the century (2061-2080). However, there are regions where the reduction is insignificant, such as the Philippines and west of Australia, that are associated with ocean dynamics and intensified internal variability due to external forcing.


Challenges of identifying asian women for breast cancer screening.
To emphasize the need for multiple data sources to develop a comprehensive list of potential respondents for a study of breast cancer screening behavior among Asian American women. Descriptive, pilot. An urban Michigan county. 616 Chinese women age 40 and older. Comparison of multiple data sources, including lists from membership directories of local Chinese organizations, a commercial survey company, health promotion events, and brief telephone interviews. Of the 616 eligible women, 32% were identified through the membership directories of local Chinese organizations, 28% from a list obtained from the survey company, 22% from telephone directories, 10% from the attendance lists of health promotion events, and 8% from more than one source. Multiple sources are required to obtain a comprehensive list for specialized populations. Every data source has its advantages and disadvantages. The use of diverse sources helps to offset the limitations of each individual one. Identifying potential participants from specialized populations represents a major issue for clinicians and researchers in nursing and other health-related disciplines. Strategies exist to facilitate the process.


The Mirror Neurons Network in Aging, Mild Cognitive Impairment, and Alzheimer Disease: A functional MRI Study.
The aim of the current study is to investigate the integrity of the Mirror Neurons (MN) network in normal aging, Mild Cognitive Impairment (MCI), and Alzheimer disease (AD). Although AD and MCI are considered "cognitive" diseases, there has been increasing recognition of a link between motor function and AD. More recently the embodied cognition hypothesis has also been developed: it postulates that a part of cognition results from the coupling between action and perception representations. MN represent a neuronal population which links perception, action, and cognition, therefore we decided to characterize MN functioning in neurodegenerative cognitive decline. Three matched groups of 16 subjects (normal elderly-NE, amnesic MCI with hippocampal atrophy and AD) were evaluated with a focused neuropsychological battery and an fMRI task specifically created to test MN: that comprised of an observation run, where subjects were shown movies of a right hand grasping different objects, and of a motor run, where subjects observed visual pictures of objects oriented to be grasped with the right hand. In NE subjects, the conjunction analysis (comparing fMRI activation during observation and execution), showed the activation of a bilateral fronto-parietal network in "classical" MN areas, and of the superior temporal gyrus (STG). The MCI group showed the activation of areas belonging to the same network, however, parietal areas were activated to a lesser extent and the STG was not activated, while the opposite was true for the right Broca's area. We did not observe any activation of the fronto-parietal network in AD participants. They did not perform as well as the NE subjects in all the neuropsychological tests (including tests of functions attributed to MN) whereas the MCI subjects were significantly different from the NE subjects only in episodic memory and semantic fluency. Here we show that the MN network is largely preserved in aging, while it appears involved following an anterior-posterior gradient in neurodegenerative decline. In AD, task performance decays and the MN network appears clearly deficient. The preservation of the anterior part of the MN network in MCI could possibly supplement the initial decay of the posterior part, preserving cognitive performance.


Interleukin-1 beta: a putative mediator of HPA axis hyperactivity in major depression?
There is extensive evidence that major depression, and particularly melancholia, is characterized by hypothalamic-pituitary-adrenal (HPA) axis hyperactivity as well as systemic immune activation, which may be accompanied by increased interleukin-1 beta production. Interleukin-1 beta is known to enhance HPA axis activity during an immune response. This study investigated whether interleukin-1 beta production is related to HPA axis activity in depressed subjects. The subjects were 28 inpatients with major or minor depression and 10 normal comparison subjects. The authors measured 1) the subjects' cortisol levels after an overnight 1-mg dexamethasone suppression test (DST) and 2) mitogen-stimulated supernatant interleukin-1 beta production by peripheral blood mononuclear cells. Statistically significant positive correlations between interleukin-1 beta production and post-DST cortisol values were found in the study group as a whole and in the depressed and normal subgroups separately. It is suggested that constituents of the immune response (such as interleukin-1 beta) in major depression may contribute to HPA axis hyperfunction in that illness.


Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway.
In the present study, we aim to elucidate the roles of caveolin-1(Cav-1), a 22 kDa protein in plasma membrane invaginations, in modulating neuronal differentiation of neural progenitor cells (NPCs). In the hippocampal dentate gyrus, we found that Cav-1 knockout mice revealed remarkably higher levels of vascular endothelial growth factor (VEGF) and the more abundant formation of newborn neurons than wild type mice. We then studied the potential mechanisms of Cav-1 in modulating VEGF signaling and neuronal differentiation in isolated cultured NPCs under normoxic and hypoxic conditions. Hypoxic embryonic rat NPCs were exposed to 1% O₂ for 24 h and then switched to 21% O₂ for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O₂. Compared with normoxic NPCs, hypoxic NPCs had down-regulated expression of Cav-1 and up-regulated VEGF expression and p44/42MAPK phosphorylation, and enhanced neuronal differentiation. We further studied the roles of Cav-1 in inhibiting neuronal differentiation by using Cav-1 scaffolding domain peptide and Cav-1-specific small interfering RNA. In both normoxic and hypoxic NPCs, Cav-1 peptide markedly down-regulated the expressions of VEGF and flk1, decreased the phosphorylations of p44/42MAPK, Akt and Stat3, and inhibited neuronal differentiation, whereas the knockdown of Cav-1 promoted the expression of VEGF, phosphorylations of p44/42MAPK, Akt and Stat3, and stimulated neuronal differentiation. Moreover, the enhanced phosphorylations of p44/42MAPK, Akt and Stat3, and neuronal differentiation were abolished by co-treatment of VEGF inhibitor V1. These results provide strong evidence to prove that Cav-1 can inhibit neuronal differentiation via down-regulations of VEGF, p44/42MAPK, Akt and Stat3 signaling pathways, and that VEGF signaling is a crucial target of Cav-1. The hypoxia-induced down-regulation of Cav-1 contributes to enhanced neuronal differentiation in NPCs.


LRP1 modulates the microglial immune response via regulation of JNK and NF-κB signaling pathways.
Neuroinflammation is characterized by microglial activation and the increased levels of cytokines and chemokines in the central nervous system (CNS). Recent evidence has implicated both beneficial and toxic roles of microglia when over-activated upon nerve injury or in neurodegenerative diseases, including Alzheimer's disease (AD). The low-density lipoprotein receptor-related protein 1 (LRP1) is a major receptor for apolipoprotein E (apoE) and amyloid-β (Aβ), which play critical roles in AD pathogenesis. LRP1 regulates inflammatory responses in peripheral tissues by modulating the release of inflammatory cytokines and phagocytosis. However, the roles of LRP1 in brain innate immunity and neuroinflammation remain unclear. In this study, we determined whether LRP1 modulates microglial activation by knocking down Lrp1 in mouse primary microglia. LRP1-related functions in microglia were also assessed in the presence of LRP1 antagonist, the receptor-associated protein (RAP). The effects on the production of inflammatory cytokines were measured by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Potential involvement of specific signaling pathways in LRP1-regulated functions including mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) were assessed using specific inhibitors. We found that knocking down of Lrp1 in mouse primary microglia led to the activation of both c-Jun N-terminal kinase (JNK) and NF-κB pathways with corresponding enhanced sensitivity to lipopolysaccharide (LPS) in the production of pro-inflammatory cytokines. Similar effects were observed when microglia were treated with LRP1 antagonist RAP. In addition, treatment with pro-inflammatory stimuli suppressed Lrp1 expression in microglia. Interestingly, NF-κB inhibitor not only suppressed the production of cytokines induced by the knockdown of Lrp1 but also restored the down-regulated expression of Lrp1 by LPS. Our study uncovers that LRP1 suppresses microglial activation by modulating JNK and NF-κB signaling pathways. Given that dysregulation of LRP1 has been associated with AD pathogenesis, our work reveals a critical regulatory mechanism of microglial activation by LRP1 that could be associated with other AD-related pathways thus further nominating LRP1 as a potential disease-modifying target for the treatment of AD.


[Effect of the inhibition of "NADH-diaphorase" activity on the ultrastructural localization of 3 beta-hydroxysteroid dehydrogenase].
The NADH-ferricyanide oxidoreductase ("NADH-diaphorase") activity can be inhibited selectively with 0.5 mM p-chloromercuribenzoate, and the reduction of the potassium ferricyanide can be restored with an exogenous electron carrier (PMS). These operations do not affect the localization of the final precipitate of copper ferrocyanide which results from 3beta-hydroxysteroid dehydrogenase activity.


Low dosage promethazine and loratadine negatively affect neuromotor function.
Determine how the sedating antihistamine promethazine and non-sedating antihistamine loratadine at a dose of 10mg influence voluntary and involuntary motor processes in the hours following ingestion and the morning after ingestion. Eight healthy young adults were recruited into a human double-blind, placebo-controlled, three-way crossover study. Neuromotor function was examined using a battery of controlled reaction time, postural tremor, and heart rate variability measures. Neuromotor function was assessed 4 times for each of the promethazine, loratadine and placebo interventions; pre-ingestion, 1h post-ingestion, 2h post-ingestion, and the following day. Self-perceived levels of drowsiness increased only after ingestion of promethazine. However, both antihistamines had negative effects on simple reaction time, choice reaction time, the RMS and peak power amplitude of postural tremor, and autonomic cardiac regulation. The presence of selective neuromotor deficits following ingestion of promethazine and loratadine suggest that sedating and non-sedating antihistamines alter neuromotor function. It is possible that the H(1) antagonists used in this study have antimuscarinic effects, which may impact on the central dopaminergic system that plays a role in modulating several CNS processes associated with movement. Antihistamines are one of the most commonly procured over-the-counter medications. The current study suggests that taking non-sedating antihistamines to avoid the adverse drug reaction of drowsiness may not avoid unwanted motor control side-effects.


Needle cricothyrotomy.
Needle cricothyrotomy with percutaneous translaryngeal ventilation (PTLV) can be a life-saving procedure when an emergency airway is needed. Needle cricothyrotomy is preferred over surgical cricothyrotomy in infants and young children. Appropriate ventilatory parameters using a high-flow oxygen source and an adequate expiratory time (inhalation-exhalation ratio) may limit the complications of barotrauma and allow for a more extended time of ventilation. Preliminary reports suggest that PTLV may be also useful in the endotracheal intubation of patients who have a difficult or failed airway and may help prevent aspiration, although further studies are needed. The emergency physician should be familiar with the indications, contraindications, complications, and procedure of this type of rescue airway, which is also used to ventilate patients during elective laryngeal surgery.


Beta-glucuronidase activity in saliva: relationship to clinical periodontal parameters.
Beta-glucuronidase (betaG) in gingival crevicular fluid (GCF), a marker of neutrophil influx into the crevicular environment, has previously been shown to be correlated with periodontal clinical parameters at individual sites (probing depth and clinical attachment level). Furthermore, elevated levels of betaG were found to be a risk factor for periodontal attachment loss. Analysis of betaG in saliva may be a measure of crevicular neutrophil influx for the whole mouth. The purpose of this cross-sectional study was to evaluate the relationship between betaG activity in saliva and periodontal clinical parameters in subjects demonstrating various levels of periodontal disease. The study population consisted of 380 subjects (108 males and 272 females). A sample of unstimulated whole saliva and a venous blood sample were obtained from each subject, and a periodontal examination, which included measurement of probing depth (PD), attachment level (AL), and gingival index (GI) was performed. The unmodified saliva samples were frozen at -20 degrees C and analyzed for betaG activity. The blood samples were analyzed for number of white blood cells, neutrophils, monocytes, lymphocytes, and platelets. Statistical analysis was conducted to determine the association between salivary betaG activity and the whole-mouth clinical periodontal parameters, complete blood count, smoking status, and age. Highly significant correlations between salivary betaG activity and mean probing depth (MPD), mean gingival index (MGI), and the number of sites with probing depth > or = 5 mm were found. When subjects were divided into tertiles based on their MPD and MGI, elevated salivary betaG activity was detected in subjects in the 2 upper tertiles. Logistic regression modeling was used to determine which of the clinical or laboratory parameters were able to identify patients with at least 4 sites with PD > or = 5 mm. Salivary betaG activity > or = 100 produced an odds ratio (OR) of 3.77. In comparison, current and former smokers had an OR of 3.15 and 2.29, respectively. CONLCUSIONS: The results suggest that a significant association exists between periodontal clinical parameters and salivary betaG activity. Due to the non-invasive and simple nature of saliva collection, this association should be studied to determine its usefulness as a screening test for periodontitis, and a means of monitoring the response to treatment.


An Integrative in silico Study to Discover Key Drivers in Pathogenicity of Focal and Segmental Glomerulosclerosis.
Focal and segmental glomerulosclerosis (FSGS) is a clinical-pathologic condition marked by segmental and localized glomerular damages. Despite investigations, the molecular mechanisms behind FSGS development remain to be more clarified. By a comprehensive analysis of an FSGS-related array set, the aim of this study was to unravel the top pathways and molecules involved in the pathogenesis of this disorder. FSGS-related microarray dataset (GSE129973) from the Gene Expression Omnibus database was quality checked, analyzed, and its differentially expressed genes (DEGs) (log2 fold change > 1) were used for the construction of a protein-protein interaction (PPI) network (STRING). The degree of centrality was considered to select the hub molecules in the network. The weighted gene co-expression network analysis (WGCNA) was utilized to construct co-expression modules. Hub molecules were selected based on module membership and gene significance values in the disease's most correlated module. After spotting the key molecules considering both strategies, their expression pattern was checked in other FSGS microarray datasets. Gene ontology and Reactome pathway enrichment analyses were performed on the DEGs of the related module. After quality checking, normalization, and analysis of the dataset, 5,296 significant DEGs, including 2,469 upregulated and 2,827 downregulated DEGs were identified. The WGCNA algorithm clustered the DEGs into nine independent co-expression modules. The disease most correlated module (black module) was recognized and considered for further enrichment analysis. The immune system, cell cycle, and vesicle-mediated transports were among the top enriched terms for the identified module's DEGs. The immune system, cell cycle, and vesicle-mediated transports were among the top enriched terms for the black module's DEGs. The key molecules (BMP-2 and COL4A1) were identified as common hub molecules extracted from the two methods of PPI and the co-expressed networks. The two identified key molecules were validated in other FSGS datasets, where a similar pattern of expression was observed for both the genes. Two hub molecules (BMP-2 and COL4A) and some pathways (vesicle-mediated transport) were recognized as potential players in the pathogenesis of FSGS.


Carbonic anhydrase 2-like in the giant clam, Tridacna squamosa: characterization, localization, response to light, and possible role in the transport of inorganic carbon from the host to its symbionts.
The fluted giant clam, Tridacna squamosa, lives in symbiosis with zooxanthellae which reside extracellularly inside a tubular system. Zooxanthellae fix inorganic carbon (Ci) during insolation and donate photosynthate to the host. Carbonic anhydrases catalyze the interconversion of CO2 and HCO3-, of which carbonic anhydrase 2 (CA2) is the most ubiquitous and involved in many biological processes. This study aimed to clone a CA2 homolog (CA2-like) from the fleshy and colorful outer mantle as well as the thin and whitish inner mantle of T. squamosa, to determine its cellular and subcellular localization, and to examine the effects of light exposure on its gene and protein expression levels. The cDNA coding sequence of CA2-like from T. squamosa comprised 789 bp, encoding 263 amino acids with an estimated molecular mass of 29.6 kDa. A phenogramic analysis of the deduced CA2-like sequence denoted an animal origin. CA2-like was not detectable in the shell-facing epithelium of the inner mantle adjacent to the extrapallial fluid. Hence, CA2-like is unlikely to participate directly in light-enhanced calcification. By contrast, the outer mantle, which contains the highest density of tertiary tubules and zooxanthellae, displayed high level of CA2-like expression, and CA2-like was localized to the tubule epithelial cells. More importantly, exposure to light induced significant increases in the protein abundance of CA2-like in the outer mantle. Hence, CA2-like could probably take part in the increased supply of inorganic carbon (Ci) from the host clam to the symbiotic zooxanthellae when the latter conduct photosynthesis to fix Ci during light exposure.


Challenges of the phase I drug development in non-small cell lung cancer.
In this article, the challenges and strategies of phase 1 drug development for lung cancer are discussed. These include the use of precise dose determinations via statistical modelling, the improved selection of patients based on genetic or molecular biomarkers, relevant pharmacokinetic and pharmacodynamic analyses, and the early evaluation of efficacy. The application of molecular tumor profiling for individualizing therapy is increasingly seen in phase I trials. Finally, the implication of a shift towards multi-institutional trials and centralized study management are discussed.


Expression of human erythropoietin in cultured tobacco cells.
Human erythropoietin (Epo) cDNA was engineered for expression in cultured tobacco cells (Nicotiana tabacum L. cv. BY2). Two plasmid DNAs were constructed: pCEP, which contained Epo cDNA under control of the cauliflower mosaic virus-derived 35S RNA promoter and terminator, and pNSEP, which contained signal sequence-deleted Epo cDNA under control of the 35S RNA promoter and terminator. By using the electroporation method, each of these plasmid DNAs was transferred into the protoplasts of BY2 cells together with a plasmid, pNR35, which conferred G418-resistance on the cells. Four G418-resistant clones were obtained from protoplasts transfected with pNSEP and pNR35, and only one of them, named 11N, survived in suspension culture. Integration of pNSEP DNA into the genome of 11N cells was confirmed by Southern blot and PCR analyses. Production of Epo mRNA was shown by Northern blot analysis. Epo protein was shown to be expressed in 11N cells by colorimetric enzyme immunoassay. The productivity of Epo in the 11N cells (1 pg/g of wet cells) was very low.


Mammographic texture and risk of breast cancer by tumor type and estrogen receptor status.
Several studies have shown that mammographic texture features are associated with breast cancer risk independent of the contribution of breast density. Thus, texture features may provide novel information for risk stratification. We examined the association of a set of established texture features with breast cancer risk by tumor type and estrogen receptor (ER) status, accounting for breast density. This study combines five case-control studies including 1171 breast cancer cases and 1659 controls matched for age, date of mammogram, and study. Mammographic breast density and 46 breast texture features, including first- and second-order features, Fourier transform, and fractal dimension analysis, were evaluated from digitized film-screen mammograms. Logistic regression models evaluated each normalized feature with breast cancer after adjustment for age, body mass index, first-degree family history, percent density, and study. Of the mammographic features analyzed, fractal dimension and second-order statistics features were significantly associated (p < 0.05) with breast cancer. Fractal dimensions for the thresholds equal to 10% and 15% (FD_TH_10 [corrected] and FD_TH_15) [corrected] were associated with an increased risk of breast cancer while thresholds from 60% to 85% (FD_TH_60 to FD_TH_85) [corrected] were associated with a decreased risk. Increasing the FD_TH_75 [corrected] and Energy feature values were associated with a decreased risk of breast cancer while increasing Entropy was associated with an increased [corrected] risk of breast cancer. For example, 1 standard deviation increase of FD_TH_75 [corrected] was associated with a 13% reduced risk of breast cancer (odds ratio = 0.87, 95% confidence interval 0.79-0.95). Overall, the direction of associations between features and ductal carcinoma in situ (DCIS) and invasive cancer, and estrogen receptor positive and negative cancer were similar. Mammographic features derived from film-screen mammograms are associated with breast cancer risk independent of percent mammographic density. Some texture features also demonstrated associations for specific tumor types. For future work, we plan to assess risk prediction combining mammographic density and features assessed on digital images.


[Correlations between the indicators of EEG and REG in children with serous meningitis].
Investigation of the bioelectrical activity and cerebral blood content has shown different changes in the baseline EEGs and REGs in children with acute serous meningitis. The visual assessment of the EEGs revealed in 52% of cases paroxysmal activity, diminished regularity of the dominant rhythm, etc. The findings of the cross-correlation analysis indicated impairment of the space-time organization of the potentials: there was a reduction in the functional activity of the anterior associative structures, particularly in the left hemisphere, and lagging of the electrical processes in the frontal zones of the right hemisphere from potentials of other centres. Changes in the cross-correlational functions of biopotentials were attended by alterations in the REG parameters, in particular by a decreased amplitude of the pulse wave, elevated vascular tone and increased interhemispherical asymmetry. The role of intracranial hypertension in the genesis of identified disorders is discussed.


Isolating the effect of major depression on obesity: role of selection bias.
There is suggestive evidence that rates of major depression have risen markedly in the U.S. concurrent with the rise in obesity. The economic burden of depression, about USD100 billion annually, is under-estimated if depression has a positive causal impact on obesity. However, virtually the entire existing literature on the connection between the two conditions has examined merely whether they are significantly correlated, sometimes holding constant a limited set of demographic factors. This study assesses whether, and the extent to which, the positive association between the two conditions reflects a causal link from major depression to higher BMI and obesity. Individual-level data from three nationally-representative studies are utilized: (i) National Comorbidity Survey-Replication (N=3,229); (ii) National Longitudinal Survey of Youth-1979 (N=21,365); and (iii) Behavioral Risk Factor Surveillance System (N=2,858,973). Dependent variables include body mass index (BMI) and a dichotomous indicator for overweight or obese. We measure diagnosed major depression based on DSM-IV criteria and the CES Depression scale. While contemporaneous effects are considered, the study primarily focuses on the effects of past and lifetime depression to bypass reverse causality and further assess the role of non-random selection on unobservable factors. The effects of past and lifetime depression on obesity are estimated based on: (i) models that control for an extensive set of typically-unobserved factors, including parental history, family background, parental investments, risk-taking, and use of anti-depressants and other prescription medications; (ii) constrained selection models; and (iii) models controlling for family fixed effects. There are expectedly no significant or substantial effects of current depression on BMI or overweight/obesity, given that BMI is a stock that changes relatively slowly over time. Results also do not support a causal interpretation among males. However, among females, estimates indicate that past or lifetime diagnosis of major depression raises the probability of being overweight or obese by about seven percentage points. Results also suggest that this effect appears to plausibly operate through shifts in food consumption and physical activity. Unadjusted differences document a strong correlation between depression and obesity, both cross-sectionally and temporally. However, it remains unclear how much of this association is consistent with a causal link from depression to obesity and how much of it is being driven by non-random selection. We find evidence that past and lifetime depression raises the probability of being overweight or obese among females. We estimate that this higher risk of overweight and obesity among females could potentially add about 10% (or USD9.7 billion) to the estimated economic burden of depression. Estimates from this study suggest that the rising trend in obesity partly underlies the reported increased prevalence of depression, at least among women. Public health interventions which reduce major depression among women could therefore also further promote public health by reducing overweight and obesity. While this study points to some preliminary evidence that the effect of depression on obesity appears to operate through shifts in diet and physical activity, more research is required to inform the proximate and distant mediating pathways. Though this study focuses on gender differentials, differences based on race/ethnicity and educational status would further inform heterogeneous responses across individuals and population subgroups.


Prediction of methylphenidate treatment outcome in adults with attention-deficit/hyperactivity disorder (ADHD).
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent mental disorder of childhood, which often persists in adulthood. Methylphenidate (MPH) is one of the most effective medications to treat ADHD, but also few adult patients show no sufficient response to this drug. In this paper, we give an overview regarding genetic, neuroimaging, clinical and other studies which have tried to reveal the reasons for non-response in adults with ADHD, based on a systematic literature search. Although MPH is a well-established treatment for adults with ADHD, research regarding the prediction of treatment outcome is still limited and has resulted in inconsistent findings. No reliable neurobiological markers of treatment response have been identified so far. Some findings from clinical studies suggest that comorbidity with substance use disorders and personality disorders has an impact on treatment course and outcome. As MPH is widely used in the treatment of adults with ADHD, much more work is needed regarding positive and negative predictors of long-term treatment outcome in order to optimize the pharmacological treatment of adult ADHD patients.


Detection of microsporidia by indirect immunofluorescence antibody test using polyclonal and monoclonal antibodies.
During a screening for monoclonal antibodies (MAbs) to the microsporidian Encephalitozoon hellem, three murine hybridoma cell lines producing strong enzyme-linked immunosorbent assay (ELISA) reactivities were cloned twice, were designated C12, E9, and E11, and were found to secrete MAbs to the immunoglobulin M isotype. On subsequent ELISAs, the three MAbs reacted most strongly to E. hellem, and they reacted somewhat less to Encephalitozoon cuniculi and least to Nosema corneum, two other microsporidian species. The MAbs produced values of absorbance against microsporidia that were at least three times greater than reactivities obtained with control hybridoma supernatants or with uninfected host cell proteins used as antigens. By Western blot immunodetection, the three MAbs detected three E. hellem antigens with relative molecular weights (M(r)s) of 62, 60, and 52 when assayed at the highest supernatant dilutions producing reactivity. At lower dilutions, the MAbs detected additional proteins with M(r)s of 55 and 53. By using indirect immunofluorescence antibody staining, the MAbs, as well as hyperimmune polyclonal murine antisera raised against E. cuniculi and E. hellem, were able to detect formalin-fixed, tissue culture-derived E. cuniculi and E. hellem and two other human microsporidia, Enterocytozoon bieneusi and Septata intestinalis, in formalin-fixed stool and urine, respectively. E. bieneusi, however, stained more intensely with the polyclonal antisera than with the MAbs. Neither the MAbs nor the hyperimmune murine polyclonal antibodies detected Cryptosporidium, Giardia, Trichomonas, or Isospora spp. At higher concentrations, the polyclonal antisera did stain N. corneum and yeast cells. The background staining could be absorbed with Candida albicans. These results demonstrate that polyclonal antisera to E. cuniculi and E. hellem, as well as MAbs raised against E. hellem, can be used for indirect immunofluorescence antibody staining to detect several species of microsporidia known to cause opportunistic infections in AIDS patients.


Folding of the amino-terminal domain of apolipoprotein B initiates microsomal triglyceride transfer protein-dependent lipid transfer to nascent very low density lipoprotein.
The initial assembly of apolipoprotein B100 (apoB) into lipoprotein particles occurs cotranslationally. To examine steps required to initiate this process, the intracellular folding and assembly of the amino-terminal 28% of apoB (apoB28) was examined using several criteria including nonreducing gel electrophoresis, sensitivity to dithiothreitol (DTT)-mediated reduction, and buoyant density gradient centrifugation. In hepatoma cells, after a 1-min pulse with radiolabeled amino acids, labeled apoB28 migrated during gel electrophoresis in the folded position and was resistant to reduction in vivo with 2 mM DTT. A similar rate and extent of folding was observed in Chinese hamster ovary cells, a microsomal triglyceride transfer protein (MTP)-negative cell line that can neither lipidate nor efficiently secrete apoB28. Amino-terminal folding of apoB28 was essential for its subsequent intracellular lipidation as apoB28 synthesized in hepatoma cells under reducing conditions remained lipid poor (d > 1.25 g/ml) and was retained intracellularly. Upon DTT removal, reduced apoB28 underwent a process of rapid (t1/2 approximately 2 min) post-translational folding followed by a slower process of MTP-dependent lipidation. As with the cotranslational assembly pathway, post-translational lipidation of apoB28 displayed a strict dependence upon amino-terminal folding. We conclude that: 1) folding of the amino-terminal disulfide bonded domain of apoB is achieved prior to the completion of translation and is independent of MTP and events associated with buoyant lipoprotein formation and 2) domain-specific folding of apoBs amino-terminal region is required to initiate MTP-dependent lipid transfer to nascent apoB in the hepatic endoplasmic reticulum.


Visualization and Validation of The Microstructures in The Airway Wall in vivo Using Diffractive Optical Coherence Tomography.
At present, there is no available method to study the in vivo microstructures of the airway wall (epithelium, smooth muscle, adventitia, basement membrane, glands, cartilage). Currently, we rely on ex vivo histologic evaluation of airway biopsies. To overcome this obstacle, we have developed an endoscopic ultrahigh-resolution diffractive optical coherence tomography (OCT) system, operating at a wavelength of 800 nm, to non-invasively study the in vivo microstructures of the airway wall. Prior to human study, validation of diffractive OCT's ability to quantitate airway microstructural components is required. To validate and demonstrate the accuracy of this OCT system, we used an ovine model to image small airways (∼ 2 mm in diameter). Histologic samples and correlated OCT images were matched. The cross-sectional area of the airway wall, lumen, and other microstructures were measured and compared. A total of 27 sheep were studied from which we identified 39 paired OCT-histology airway images. We found strong correlations between the OCT and the histology measurements of the airway wall area and the microstructural area measurements of the epithelium, basement membrane, airway smooth muscle, glands, cartilage, and adventitia. The correlations ranged from r=0.61 (p<0.001) for the epithelium to r=0.86 (p<0.001) for the adventitia with the correlation between the OCT and the histology measurements for the entire airway wall of r=0.76 (p<0.001). Given the high degree of correlation, these data validate the ability to acquire and quantify in vivo microscopic level imaging with this newly developed 800nm ultra-high resolution diffractive OCT system.


A comparison of microarray databases.
Microarray technology has become one of the most important functional genomics technologies. A proliferation of microarray databases has resulted. It can be difficult for researchers exploring this technology to know which bioinformatics systems best meet their requirements. In order to obtain a better understanding of the available systems, a survey and comparative analysis of microarray databases was undertaken. The survey included databases that are currently available, as well as databases that should become available in early 2001. Databases fall into three categories: (i) those that can be installed locally, (ii) those available for public data submission and (iii) those available for public query. Developers of microarray gene-expression databases were asked questions regarding the scope and availability of their database, its system requirements, its future compliance with MGED (Microarray Gene Expression Database) standards, and its associated analytical tools. Participants included AMAD (Stanford/Berkeley/UCSF), ArrayExpress (EBI), ChipDB (MIT/Whitehead), GeneX (NCGR), GeNet (Silicon Genetics), GeneDirector (BioDiscovery), GEO (NCBI), GXD (Jackson Laboratory), mAdb (NCI), maxdSQL (University of Manchester), NOMAD (UCSF), RAD (University of Pennsylvania) and SMD (Stanford University). Other database developers were contacted but data was not available at the time of manuscript preparation. Each database fulfils a different role, reflecting the widely varying needs of microarray users.


Progression of cartilage degradation, bone resorption and pain in rat temporomandibular joint osteoarthritis induced by injection of iodoacetate.
Osteoarthritis (OA) is an important subtype of temporomandibular disorders. A simple and reproducible animal model that mimics the histopathologic changes, both in the cartilage and subchondral bone, and clinical symptoms of temporomandibular joint osteoarthritis (TMJOA) would help in our understanding of its process and underlying mechanism. To explore whether injection of monosodium iodoacetate (MIA) into the upper compartment of rat TMJ could induce OA-like lesions. Female rats were injected with varied doses of MIA into the upper compartment and observed for up to 12 weeks. Histologic, radiographic, behavioral, and molecular changes in the TMJ were evaluated by light and electron microscopy, MicroCT scanning, head withdrawal threshold test, real-time PCR, immunohistochemistry, and TUNEL assay. The intermediate zone of the disc loosened by 1 day post-MIA injection and thinned thereafter. Injection of an MIA dose of 0.5 mg or higher induced typical OA-like lesions in the TMJ within 4 weeks. Condylar destruction presented in a time-dependent manner, including chondrocyte apoptosis in the early stages, subsequent cartilage matrix disorganization and subchondral bone erosion, fibrosis, subchondral bone sclerosis, and osteophyte formation in the late stages. Nociceptive responses increased in the early stages, corresponding to severe synovitis. Furthermore, chondrocyte apoptosis and an imbalance between anabolism and catabolism of cartilage and subchondral bone might account for the condylar destruction. Multi-level data demonstrated a reliable and convenient rat model of TMJOA could be induced by MIA injection into the upper compartment. The model might facilitate TMJOA related researches.


Quantification of radiotracer uptake with a dedicated breast PET imaging system.
Tomographic breast imaging techniques can be used to quantify radiotracer uptake in breast and tumor tissue. However, physical processes common to PET imaging can confound accurate quantification. In this investigation, we assessed the effects of these phenomena and tested correction schemes for our new positron emission mammography-tomography system (PEM-PET). The PEM-PET scanner utilizes two sets of rotating planar detector heads. Each unit consists of a 4 x 3 array of Hamamatsu H8500 flat panel position sensitive photomultipliers coupled to a 96 x 72 array of 2 x 2 x 15 mm3 LYSO detector elements (pitch = 2.1 mm). Image reconstruction is performed with a 3D-OSEM algorithm parallelized to run on a multiprocessor computer system. The reconstructed field-of-view is 15 x 15 x 15 cm3. Much of the testing procedures were based on NEMA-NU2/2001 protocols. Count rate losses due to pulse pile-up, image contamination due to acceptance of random coincidences and Compton scatter, and image artifacts produced by photon attenuation were measured. It was found that the system was susceptible to count rate losses when moderate levels of radiation were present in the scanner due to the current design of the event trigger electronics. Application of corrections for Compton scattering, photon attenuation and dead time resulted in improved estimations of 18F concentration in simplified phantom studies. Results from these preliminary studies indicate that the PEM-PET scanner will be useful for the quantification of radiotracer uptake in breast tumors, possibly facilitating early assessment of cancer treatments.


Legal problems and principles in discharge planning: implications for social work.
While not immutable, legal principles are among the more sturdy and commanding guides of our professional behavior toward patients. By protecting privacy and autonomy inherent in the Patients Bill of Rights, legal principles shore up what is vulnerable and fearful in the patient's approach to making sense out of their plight.


The prediction of above-average participation in volunteerism: a test of the theory of planned behavior and the volunteers functions inventory in older Australian adults.
In the present prospective study of 81 older volunteers from a nonprofit organization in Australia, the authors compared the predictive utility of I. Ajzen's (1988) theory of planned behavior with that of E. G. Clary and M. Snyder's (1991) functional approach to volunteering. The authors mailed questionnaires to 385 volunteers in two waves of data collection. The first wave measured theory-of-planned-behavior variables and functional-approach variables. The second wave measured self-reported volunteering behavior for the previous month. Regression analyses supported both the theory of planned behavior and the functional approach; the theory of planned behavior accounted for a significantly larger proportion of variance in above-average participation in self-reported volunteerism. The findings of the present study provided some support for both the theory of planned behavior and the functional approach as models of self-reported volunteerism.


A matter of life and death.
Cases concerning the withdrawal or withholding of artificial nutrition and hydration from patients in a vegetative or minimally conscious state raise difficult medical, legal and ethical questions including the diagnosis and classification of disorders of consciousness, the legal processes to be followed, and the legal and ethical principles to be applied when making decisions. There is also an issue as to whether it is necessary or appropriate for such decisions to be taken by judges. This article, based on a lecture given in Oxford in October 2016, considers a number of these issues and concludes that any consideration of the question from the patient's point of view must include an objective analysis of what is in his or her best interests, as well as subjective expressions of wishes and feelings. Whilst noting that it has been suggested that applications to the court should be confined to those cases where there is a dispute as to whether withdrawal of artificial nutrition and hydration (ANH) would be in the patient's best interests, the author proposes that, until such time as we have greater clarity and understanding about the disorders of consciousness, and about the legal and ethical principles to be applied, there remains a need for independent oversight and that applications to the court should continue to be obligatory in all cases where the withdrawal of ANH is proposed, at least for the time being.


[Experience in long-term therapy of active rheumatoid arthritis with leflunomide].
To study therapeutic potential of a novel basic drug leflunomide in suppression of activity and progression of rheumatoid arthritis (RA). Leflunomide efficacy was investigated in a 36 month trial including 50 patients with moderate and high activity RA. Monthly registrations were made of the articular syndrome quantitative parameters (Richi's index, number of painful and swollen joints, severity of pain and general condition of the patient), morning stiffness duration, ESR, CRP, RF. Leflunomide efficacy was assessed by EULAR and ACR criteria. Dynamics of the extrajoint manifestations observed in 70% patients before therapy were examined clinically and by device tests. Speed of progression of erosive arthritis was quantified by a modified Sharp's method in hand and foot joints, carpal bones each 6 months. Arava tolerance was controlled clinically and by laboratory tests. Leflunomide was found effective in 94% RA patients. A rapid (within the first month) and significant improvement in parameters of articular syndrome and CRP level was observed. To month 4 of therapy 1/5 patients achieved remission by EULAR criteria, to month 12--1/3 patients. By ACR criteria, 6-month leflunomide treatment produced good and exellent results in 71% patients which persisted up to the 36th month of therapy. The effect was better in shorter history of RA, moderate RA, in the absence of osteolyses and ankyloses. Leflunomide significantly reduced RF concentration in the serum, suppressed extrajoint RA manifestations (except Sjogren's syndrome). The mean number of new joint erosions for 6 consecutive months was 2.93 +/- 3.2, 1.41 +/- 1.8, 0.78 +/- 2.0 (median 0), while progression coefficient corresponded to slow progression to the treatment month 18. No new erosions occurred after 12 months of arava treatment in 41% patients and after 18 months--in 62%. Leflunomide is well tolerated. The drug was discontinued because of cutaneous pruritus and diarrhea in 5 and 1 patients, respectively.


Self-referenced sensor utilizing extra-ordinary optical transmission from metal nanoslits array.
We report the first self-referenced sensor based on the extraordinary optical transmission (EOT) of metal-nanoslits array in the near-infra-red (NIR) telecommunication window of the electromagnetic spectrum. The nanoslits array shows two enhanced transmission peaks, out of which one shows a red shift with an increase in the refractive index of the analyte medium, while the other remains fixed. We demonstrate the detection of small amounts of water in ethanol using the nanoslits array chip. The present study might be useful in developing ultra-small biosensor chips integrated to optical fibers for online monitoring and remote sensing applications.


Atrial fibrillation and congestive heart failure: a two-way street.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical cardiology, particularly in patients with heart failure. Its prevalence increases with the degree of left ventricular dysfunction and severity of heart failure symptoms. The development of AF in the setting of heart failure has been shown to result in increased mortality. Studies thus far indicate that rhythm control with antiarrhythmic drug therapy or catheter ablation offers both symptomatic and probably survival advantage in patients with heart failure and AF. In patients with permanent AF, the effects of restoring a regular ventricular response with atrioventricular junction ablation followed by biventricular pacing remain to be shown. In the current manuscript, we will review the proposed mechanisms of increased morbidity and mortality associated with AF and the current treatment options including the roles of radiofrequency ablation and pacing.


Evolutionary Connectionism: Algorithmic Principles Underlying the Evolution of Biological Organisation in Evo-Devo, Evo-Eco and Evolutionary Transitions.
The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term "evolutionary connectionism" to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions.


Multiple myeloma presenting with high-output heart failure and improving with anti-angiogenesis therapy: two case reports and a review of the literature.
Common manifestations of multiple myeloma include osteolytic lesions, cytopenias, hypercalcemia, and renal insufficiency. Patients may also exhibit heart failure which is often associated with either past therapy or cardiac amyloidosis. A less recognized mechanism is high-output heart failure. Diuretic therapy in this setting has little efficacy in treating the congested state. Furthermore, effective pharmacotherapy has not been established. We report two patients with multiple myeloma and high-output heart failure who failed diuretic therapy. The patients were given dexamethasone in conjunction with lenalidomide and thalidomide, respectively. Shortly thereafter, each patient demonstrated a significant improvement in symptoms. This is the first report of successful treatment of multiple myeloma-induced high-output failure via the utilization of these agents. Two patients with multiple myeloma were evaluated for volume overload. The first was a 50-year-old man with refractory disease. Magnetic resonance imaging demonstrated diffuse marrow replacement throughout the pelvis. Cardiac catheterization conveyed elevated filling pressures and a cardiac output of 15 liters/minute. He quickly decompensated and required mechanical ventilation. The second patient was a 61-year-old man recently diagnosed with multiple myeloma and volume overload. Skeletal survey demonstrated numerous lytic lesions throughout the pelvis. His cardiac catheterization also conveyed elevated filling pressures and a cardiac output of 10 liters/minute. Neither patient responded to diuretic therapy and they were subsequently started on dexamethasone plus lenalidomide and thalidomide, respectively. The first patient's brisk diuresis allowed for extubation within 48 hours after the first dose. He had a net negative fluid balance of 15 liters over 10 days. The second patient also quickly diuresed and on repeat cardiac catheterization, his cardiac output had normalized to 4.7 liters/minute. Multiple myeloma can cause high-output failure. The mechanism is likely extensive bony involvement causing innumerable intramedullary arteriovenous fistulas. Diuretic therapy is not effective in treating this condition. Lenalidomide and thalidomide, both of which inhibit angiogenesis, seem to be viable treatment options. Based on the rapid and effective results seen in these two patients, a potential novel mechanism of 'pharmacologic fistula ligation' with these agents may be the most effective way to treat this presentation.


Cocaine Exposure and Children's Self-Regulation: Indirect Association via Maternal Harshness.
This study examined the association between prenatal cocaine exposure and children's self-regulation at 3 years of child age. In addition to direct effects of prenatal cocaine exposure on children's self-regulation, we hypothesized there would be indirect associations between cocaine exposure and self-regulation via higher maternal harshness and poor autonomic regulation in infancy. The sample consisted of 216 mother-infant dyads recruited at delivery from local area hospitals (116 cocaine-exposed, 100 non-exposed). Infant autonomic regulation was measured at 7 months of age during an anger/frustration task, maternal harshness was coded from observations of mother-toddler interactions at 2 years of age, and children's self-regulation was measured at 3 years of age using several laboratory paradigms. Contrary to hypotheses, there were no direct associations between maternal cocaine use during pregnancy and children's self-regulation. However, results from testing our conceptual model including the indirect effects via maternal harshness or infant parasympathetic regulation indicated that this model fit the data well, χ(2) (23) = 34.36, p > 0.05, Comparative Fit Index = 0.95, RMSEA = 0.05. Cocaine using mothers displayed higher intensity of harshness toward their toddlers during lab interactions across a variety of tasks at 2 years of age (β = 0.23, p < 0.05), and higher intensity of harshness at 2 years was predictive of lower self-regulation at 3 years (β = -0.36, p < 0.01). Maternal cocaine use was also predictive of a non-adaptive increase in respiratory sinus arrhythmia (RSA) from baseline to the negative affect task, but RSA change in infancy was not predictive of self-regulation at 3 years. RESULTS are supportive of animal models indicating higher aggression among cocaine treated dams, and indicate that higher maternal harshness among cocaine using mothers is predictive of child self-regulatory outcomes in the preschool period.


Novel LIMK2 Inhibitor Blocks Panc-1 Tumor Growth in a mouse xenograft model.
LIM kinases (LIMKs) are important cell cytoskeleton regulators that play a prominent role in cancer manifestation and neuronal diseases. The LIMK family consists of two homologues, LIMK1 and LIMK2, which differ from one another in expression profile, intercellular localization, and function. The main substrate of LIMK is cofilin, a member of the actin-depolymerizing factor (ADF) protein family. When phosphorylated by LIMK, cofilin is inactive. LIMKs play a contributory role in several neurodevelopmental disorders and in cancer growth and metastasis. We recently reported the development and validation of a novel LIMK inhibitor, referred to here as T56-LIMKi, using a combination of computational methods and classical biochemistry techniques. Here we report that T56-LIMKi inhibits LIMK2 with high specificity, and shows little or no cross-reactivity with LIMK1. We found that T56-LIMKi decreases phosphorylated cofilin (p-cofilin) levels and thus inhibits growth of several cancerous cell lines, including those of pancreatic cancer, glioma and schwannoma. Because the most promising in-vitro effect of T56-LIMKi was observed in the pancreatic cancer cell line Panc-1, we tested the inhibitor on a nude mouse Panc-1 xenograft model. T56-LIMKi reduced tumor size and p-cofilin levels in the Panc-1 tumors, leading us to propose T56-LIMKi as a candidate drug for cancer therapy.


Biomechanical Properties of Common Carotid Arteries Assessed by Circumferential 2D Strain and β Stiffness Index in Patients With Ankylosing Spondylitis.
Ankylosing spondylitis (AS) is associated with an elevated risk of cardiovascular disease (CVD) related to atherosclerosis, preceded by arterial stiffness. We aimed to examine common carotid artery (CCA) biomechanical properties using ultrasound to calculate β stiffness index (indicating arterial stiffness) and, a more recently developed technique, 2-dimensional (2D) speckle tracking strain (indicating arterial motion and deformation, strain) to (1) compare with age- and sex-matched controls, and (2) analyze relationships between strain and stiffness with disease characteristics and traditional risk factors for CVD in patients with AS. In this cross-sectional study, a cohort of 149 patients with AS, mean age 55.3 ± 11.2 years, 102 (68.5%) men, and 146 (98%) HLA-B27-positive, were examined. Bilateral CCA were examined for circumferential 2D strain and β stiffness index. A subgroup of 46 patients was compared with 46 age- and sex-matched controls, both groups without hypertensive disease, diabetes, myocardial infarction, or stroke. Mean bilateral circumferential 2D strain was lower in AS patients compared with controls (7.9 ± 2.6% vs 10.3 ± 1.9%, P < 0.001), whereas mean bilateral β stiffness index was higher (13.1 ± 1.7 mmHg/mm vs 12.3 ± 1.3 mmHg/mm, P = 0.02). In multivariable linear regression analyses, strain was associated with age, erythrocyte sedimentation rate, history of anterior uveitis, and treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARD) and/or biological DMARD (R2 0.33), while stiffness was associated with age (R2 0.19). Both CCA circumferential 2D strain and β stiffness index differed between patients with AS and controls. Strain was associated with AS-related factors and age, whereas only age was associated with stiffness, suggesting that the obtained results reflect different pathogenic vascular processes.


Porcine circovirus type 2 (PCV2) infection decreases the efficacy of an attenuated classical swine fever virus (CSFV) vaccine.
The Lapinized Philippines Coronel (LPC) vaccine, an attenuated strain of classical swine fever virus (CSFV), is an important tool for the prevention and control of CSFV infection and is widely and routinely used in most CSF endemic areas, including Taiwan. The aim of this study was to investigate whether PCV2 infection affects the efficacy of the LPC vaccine. Eighteen 6-week-old, cesarean-derived and colostrum-deprived (CDCD), crossbred pigs were randomly assigned to four groups. A total of 10(5.3) TCID50 of PCV2 was experimentally inoculated into pigs through both intranasal and intramuscular routes at 0 days post-inoculation (dpi) followed by LPC vaccination 12 days later. All the animals were challenged with wild-type CSFV (ALD stain) at 27 dpi and euthanized at 45 dpi. Following CSFV challenge, the LPC-vaccinated pigs pre-inoculated with PCV2 showed transient fever, viremia, and viral shedding in the saliva and feces. The number of IgM(+), CD4(+)CD8-CD25(+), CD4(+)CD8(+)CD25(+), and CD4(-)CD8(+)CD25(+) lymphocyte subsets and the level of neutralizing antibodies against CSFV were significantly higher in the animals with LPC vaccination alone than in the pigs with PCV2 inoculation/LPC vaccination. In addition, PCV2-derived inhibition of the CSFV-specific cell proliferative response of peripheral blood mononuclear cells (PBMCs) was demonstrated in an ex vivo experiment. These findings indicate that PCV2 infection decreases the efficacy of the LPC vaccine. This PCV2-derived interference may not only allow the invasion of wild-type CSFV in pig farms but also increases the difficulty of CSF prevention and control in CSF endemic areas.


Tuberculous meningitis in adults: review of 61 cases.
Tuberculosis is still a major cause of serious illness in developing countries. The objective of this study was to assess the clinical, laboratory, radiological and prognostic features of tuberculous meningitis (TBM) in immuncompetent adult patients. Sixty-one patients with confirmed or presumed TBM seen over a 12-year period at the Neurology Department of Bakirköy Research and Training Hospital for Psychiatric and Neurological Disease, Istanbul, Turkey, were analyzed retrospectively. Patients were grouped according to the severity of meningitis on admission (stages I, II and III). They were also divided into two groups according to the presence of paradoxical response (progressive increase of lymphocytes or increase of polymorphonuclear cells instead of lymphocytes) in CSF samples. A combination of five antituberculosis drugs was used in the 1st month of treatment. Patients received antituberculosis therapy for at least 12 months. The outcome of the patients was defined on the basis of the 12-month Barthel index (BI) score (BI < 12 poor; BI >/= 12 good). For statistical analysis death was included in the poor outcome group. Paradoxical response in CSF findings was seen in 20 patients. There was no statistically significant difference between the outcome of the patients with and without CSF paradoxical response; however, new tuberculomas developed more frequently in the first group (p < 0.05). The overall mortality was 27.8%. Stage of disease was found to be independently associated with the 12-month outcome (OR 7.2; 95% CI 1.7-30.3, p = 0.007). In developing countries such as Turkey, tuberculosis is still an important public health issue. Early suspicion and appropriate long-term antituberculosis therapy together with corticosteroids may reduce mortality and morbidity in TBM patients.


Hospital structures guidelines for coping with snowstorms.
When a snowstorm not only paralyzes a community but also isolates its hospital or hospitals, contingency plans and procedures ensure the effective administration and operation of a health care facility during the emergency. In retrospect, Massachusetts General Hospital, Boston, has developed specific policies, procedures, and mechanisms to identify and deal with logistical and organizational problems that MGH experienced during the 1978 blizzard.


Pathology and morphology of Ichthyophonus hoferi in naturally infected fishes off the Swedish west coast.
The pathology and morphology of Ichthyophonus hoferi was studied in naturally infected Atlantic herring Clupea harengus, in sprat Sprattus sprattus, and in flounder Pleuronectes flesus from the west coast of Sweden. The pathogen was found in all organs examined, with the intensity of infection varying in different organs of the different fish species. Two main phases in the life of infecting parasites were identified, 'active' and 'passive', the latter being able to switch to active. The active phase of the infection in herring was usually accompanied by a lean and slender appearance of the body, a drastic decrease in intestinal fat, emaciation of the somatic muscles, swelling of the visceral organs, poor quality of flesh texture and a distinctive off-odour. The most characteristic macroscopic sign of ichthyophonosis in herring and flounder was the occurrence of creamy white nodules on the heart. The infection causes a chronic systemic granulomatous inflammation. The nature of the granulomatous inflammation was host- and tissue-dependent. The pathogenicity of the parasite in its active form and the side effects of host defence cells were also reflected in dramatic tissue damage and loss of structure and function of the infected organs. Three kinds of spores were identified: 'un-developing spore', 'developing spore' and 'plasmodio-spore'. The formation and spread of 'plasmodia', from plasmodio-spores, as a secondary infection agent is documented. Transmission electron microscopy revealed I. hoferi to be multinucleated, containing different organelles and structures. These included a cell wall, an undulating cell membrane, a thin paramural endoplasm, an endoplasmic reticulum, polymorphic but usually spherical mitochondria with short tubulo-vesicular cristae, dictyosomes with plate-like cristernae, large electron-dense lipid droplets and electron-lucid vacuoles, probably containing glycogen.


Regression of Epstein-Barr virus-induced B-cell transformation in vitro involves virus-specific CD8+ T cells as the principal effectors and a novel CD4+ T-cell reactivity.
T-cell memory to Epstein-Barr virus (EBV) was first demonstrated through regression of EBV-induced B-cell transformation to lymphoblastoid cell lines (LCLs) in virus-infected peripheral blood mononuclear cell (PBMC) cultures. Here, using donors with virus-specific T-cell memory to well-defined CD4 and CD8 epitopes, we reexamine recent reports that the effector cells mediating regression are EBV latent antigen-specific CD4+ and not, as previously assumed, CD8+ T cells. In regressing cultures, we find that the reversal of CD23+ B-cell proliferation was always coincident with an expansion of latent epitope-specific CD8+, but not CD4+, T cells; furthermore CD8+ T-cell clones derived from regressing cultures were epitope specific and reproduced regression when cocultivated with EBV-infected autologous B cells. In cultures of CD4-depleted PBMCs, there was less efficient expansion of these epitope-specific CD8+ T cells and correspondingly weaker regression. The data are consistent with an effector role for epitope-specific CD8+ T cells in regression and an auxiliary role for CD4+ T cells in expanding the CD8 response. However, we also occasionally observed late regression in CD8-depleted PBMC cultures, though again without any detectable expansion of preexisting epitope-specific CD4+ T-cell memory. CD4+ T-cell clones derived from such cultures were LCL specific in gamma interferon release assays but did not recognize any known EBV latent cycle protein or derived peptide. A subset of these clones was also cytolytic and could block LCL outgrowth. These novel effectors, whose antigen specificity remains to be determined, may also play a role in limiting virus-induced B-cell proliferation in vitro and in vivo.


Combined effects of hydrostatic pressure, temperature, and pH on the inactivation of spores of Clostridium perfringens type A and Clostridium sporogenes in buffer solutions.
To develop a spore inactivation strategy, the effect of 15-min hydrostatic pressure treatments (550 and 650 MPa) at 55 and 75 degrees C in citric acid buffer (4.75 and 6.5 pH) on spores of 5 isolates of Clostridium perfringens type A carrying the gene that encodes the C. perfringens enterotoxin (cpe) on the chromosome (C-cpe), 4 isolates carrying the cpe gene on a plasmid (P-cpe), and 2 strains of C. sporogenes were investigated. Treatments at 650 MPa, 75 degrees C and pH 6.5 were moderately effective against spores of P-cpe (approximately 3.7 decimal reduction, DR) and C. sporogenes (approximately 2.1 DR) but not for C-cpe (approximately 1.0 DR) spores. Treatments at pH 4.75 were moderately effective against spores of P-cpe (approximately 3.2 DR) and C. sporogenes (approximately 2.5 DR) but not of C-cpe (approximately 1.2 DR) when combined with 550 MPa at 75 degrees C. However, when pressure was raised to 650 MPa under the same conditions, high inactivation of P-cpe (approximately 5.1 DR) and C. sporogenes (approximately 5.8 DR) spores and moderate inactivation of C-cpe (approximately 2.8 DR) spores were observed. Further advances in high-pressure treatment strategies to inactivate spores of cpe-positive C. perfringens type A and C. sporogenes more efficiently are needed.


Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients.
To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus (HCV) liver transplant (LT) recipients. We retrospectively compared the liver biopsies of well-matched HCV LT recipients under calcineurin inhibitors (CNI group, n = 21) and mycophenolate (MMF group, n = 15) monotherapy, with those patients who successfully withdrawn immunosuppression (IS) therapy from at least 3 years (TOL group, n = 10). To perform the well-matched analysis, all HCV transplanted patients from December 1993 were screened. Only those HCV patients who reached the following criteria were considered for the analysis: (1) at least 3 years of post-operative follow-up; (2) patients with normal liver graft function under low dose CNI monotherapy (CNI group); (3) patients with normal liver graft function under antimetabolite (Micophenolate Mofetil or coated mycophenolate sodium) monotherapy (MMF group); and (4) recipients with normal liver function without any IS. We excluded from the analysis recipients who were IS free or under monotherapy for < 36 mo, recipients with cirrhosis or with unstable liver function tests. Thirty six recipients were enrolled in the study. Demographics, clinical data, time after LT and baseline liver biopsies were comparable in the three groups. After six years of follow-up, there was no worsening of hepatic fibrosis in the MMF group (2.5 ± 1.5 Ishak Units vs 2.9 ± 1.7 Ishak Units, P = 0.5) and TOL group (2.7 ± 10.7 vs 2.5 ± 1.2, P = 0.2). In contrast, a significant increase in the fibrosis score was observed in the CNI group (2.2 ± 1.7 vs 3.9 ± 1.6, P = 0.008). The yearly fibrosis progression rate was significantly worse in the CNI group (0.32 ± 0.35) vs MMF group (0.03 ± 0.31, P = 0.03), and TOL group (-0.02 ± 0.27, P = 0.02). No differences have been reported in grading scores for CNI group (2.79 ± 1.9, P = 0.7), MMF group (3.2 ± 1.5, P = 0.9) and TOL group (3.1 ± 1.4, P = 0.2). Twenty four patients were treated with low dose ribavirin (8 TOL, 7 MMF, 9 CNI). The hepatitis C titers were comparable in the three groups. No episodes of rejection have been reported despite differences of liver function test in the three groups during the observational period. IS withdrawal and MMF monotherapy is safe and seems to be associated with the slowest fibrosis progression in HCV LT recipients.


Effect and Mechanism of TL1A Expression on Epithelial-Mesenchymal Transition during Chronic Colitis-Related Intestinal Fibrosis.
Recent evidences reveal that epithelial to mesenchymal transition (EMT) exacerbates the process of intestinal fibrosis. Tumor necrosis factor-like ligand 1A (TL1A) is a member of the tumor necrosis family (TNF), which can take part in the development of colonic inflammation and fibrosis by regulating immune response or inflammatory factors. The purpose of this study was to elucidate the possible contribution of TL1A in onset and progression of intestinal inflammation and fibrosis through EMT. Colonic specimens were obtained from patients with inflammatory bowel disease (IBD) and control individuals. The expression levels of TL1A and EMT-related markers in intestinal tissues were evaluated. Furthermore, the human colorectal adenocarcinoma cell line, HT-29, was stimulated with TL1A, anti-TL1A antibody, or BMP-7 to assess EMT process. In addition, transgenic mice expressing high levels of TL1A in lymphoid cells were used to further investigate the mechanism of TL1A in intestinal fibrosis. High levels of TL1A expression were detected in the intestinal specimens of patients with ulcerative colitis and Crohn's disease and were negatively associated with the expression of an epithelial marker (E-cadherin), while it was positively associated with the expression of interstitial markers (FSP1 and α-SMA). Transgenic mice with high expression of TL1A were more sensitive to dextran sodium sulfate and exhibited severe intestinal inflammation and fibrosis. Additionally, the TGF-β1/Smad3 pathway may be involved in TL1A-induced EMT, and the expression of IL-13 and EMT-related transcriptional molecules (e.g., ZEB1 and Snail1) was increased in the intestinal specimens of the transgenic mice. Furthermore, TL1A-induced EMT can be influenced by anti-TL1A antibody or BMP-7 in vitro. TL1A participates in the formation and process of EMT in intestinal fibrosis. This new knowledge enables us to better understand the pathogenesis of intestinal fibrosis and identify new therapeutic targets for its treatment.


Synthesis and Electrochemistry of Novel Dumbbell-Shaped Bis-pyrazolino[60]fullerene Derivatives Formed Using Microwave Radiation.
The design of covalently linked [60]fullerene dimers has gained increased attention, as the linked electron donors or acceptors are in close proximity to the surface of the C60, providing a valuable approach to novel molecular electronic devices. Herein, new compounds involving C60 dumbbells covalently connected by the π-conjugated system from azobenzene and diaryl ether linkers were synthesized following the bifunctional cycloaddition reactions to C60 using microwave radiation. The structural identity of the fullerene dimers has been determined using spectroscopic techniques including Fourier transform infrared (FT-IR), matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF), and NMR spectroscopy, and the photophysical and the electrochemical properties for the new dumbbells have been examined using UV-vis spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and square wave voltammetry. Both new dimers show electronic interaction with the fullerene cage and higher electron affinity than the pristine C60.


Demographics of Pediatric OHCA Survivors With Postdischarge Diseases: A National Population-Based Follow-Up Study.
Background: Postdischarge diseases (PDDs) have been reported for adult survivors of out-of-hospital cardiac arrest (OHCA). However, the detailed demographics of pediatric OHCA survivors with PDDs are not well-documented, and information regarding functional survivors is particularly limited. We aimed to report detailed information on the PDDs of survivors of traumatic and non-traumatic pediatric OHCA using a national healthcare database. Methods: We retrospectively obtained data from the Taiwan government healthcare database (2011-2015). Information on the demographics of traumatic and non-traumatic pediatric OHCA survivors (<20 years) was obtained and reported. The patients who survived to discharge (survivors) and those classified as functional survivors were followed up for 1 year for the analysis of newly diagnosed PDDs. The time from discharge to PDD diagnosis was also reported. Results: A total of 2,178 non-traumatic and 288 traumatic OHCA pediatric cases were included. Among the non-traumatic OHCA survivors (n = 374, survival rate = 17.2%), respiratory tract (n = 270, 72.2%), gastrointestinal (n = 187, 50.0%), and neurological diseases (n = 167, 49.1%) were the three most common PDD categories, and in these three categories, the majority of PDDs were atypical/influenza pneumonia, non-infective acute gastroenteritis, and generalized/status epilepsy, respectively. Among the traumatic OHCA survivors (n = 21, survival rate = 7.3%), respiratory tract diseases (n = 17, 81.0%) were the most common, followed by skin or soft tissue (n = 14, 66.7%) diseases. Most functional survivors still suffered from neurological and respiratory tract diseases. Most PDDs, except for skin or soft tissue diseases, were newly diagnosed within the first 3 months after discharge. Conclusions: Respiratory tract (pneumonia), neurological (epilepsy), and skin or soft tissue (dermatitis) diseases were very common among both non-traumatic and traumatic OHCA survivors. More importantly, most PDDs, except for skin or soft tissue diseases, were newly diagnosed within the first 3 months after discharge.


High-speed optical measurement for the drumhead vibration.
A high-speed optical measurement for the vibrating drumhead is presented and verified by experiment. A projected sinusoidal fringe pattern on the measured drumhead is dynamically deformed with the membrane vibration and grabbed by a high-speed camera. The shape deformation of the drumhead at each sampling instant can be recovered from this sequence of obtained fringe patterns. The membrane vibration of Chinese drum has been measured with a high speed sampling rate of 1,000 frames/sec. and a standard deviation of 0.075 mm. The restored vibration of the drumhead is also presented in an animation.


Cell-free translation of virion RNA from nondefective and transformation-defective Rous sarcoma viruses.
Nondefective and transformation-defective virion subunit RNAs from two strains of Rous sarcoma virus (RSV) were translated in cell-free systems derived from Krebs IIA ascites cells, wheat germ, and L-cells. In each case the predominant viral-specific product was a polypeptide of molecular weight 76,000 that is related to the internal viral group-specific antigens, as judged by immunoprecipitation with monospecific antisera and tryptic peptide fingerprinting. No difference could be detected between the translation products of 35S RNA from nondefective and transformation-defective RSV virions, nor of 35S RNA from different strains of RSV. The 76,000-molecular-weight polypeptide synthesized in response to 35S RNA in vitro was labeled with formyl-methionine from initiator tRNA. Models for viral protein synthesis are discussed in the light of these results, and arguments positioning the group-specific antigen gene at the 5' end of the 35S RNA are presented.


Sex-Dependent Effects of Chronic Circadian Disruption in AβPP/PS1 Mice.
Chronic disruption of the circadian timing system, often reflected as a loss of restful sleep, also includes myriad other pathophysiological effects. The current study examined how chronic circadian disruption (CD) could contribute to pathology and rate of progression in the AβPP/PS1 mouse model of Alzheimer's disease (AD). A chronic CD was imposed until animals reached 6 or 12 months of age in AβPP/PS1 and C57BL/6J control mice. Home cage activity was monitored for a period of 3-4 weeks prior to the endpoint along with a single timepoint measure of glucose sensitivity. To assess long term effects of CD on the AD phenotype, animals were re-entrained to a no disruption (ND) schedule just prior to the endpoint, after which a Morris water maze (MWM) was used to assess spatial learning and memory. Dampening of nighttime activity levels occurred in disrupted animals, and female animals demonstrated a greater adaptability to CD. Diminished arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) levels in the suprachiasmatic nucleus (SCN) of 12-month male AβPP/PS1 exposed to the CD paradigm were observed, potentially accounting for the diminished re-entrainment response. Similarly, CD worsened performance in the MWM in 12-month male AβPP/PS1 animals, whereas no effect was seen in females. Collectively, these findings show that exposure to chronic CD impairs circadian behavioral patterns and cognitive phenotypes of AβPP/PS1 mouse model in a sex-dependent manner.


Proteomic analysis of low dose arsenic and ionizing radiation exposure on keratinocytes.
Human exposure to arsenic and ionizing radiation (IR) occur environmentally at low levels. While the human health effects of arsenic and IR have been examined separately, there is little information regarding their combined effects at doses approaching environmental levels. Arsenic toxicity may be affected by concurrent IR especially given their known individual carcinogenic actions at higher doses. We found that keratinocytes responded to either low dose arsenic and/or low dose IR exposure, resulting in differential proteomic expression based on 2-DE, immunoblotting and statistical analysis. Seven proteins were identified that passed a rigorous statistical screen for differential expression in 2-DE and also passed a strict statistical screen for follow-up immunoblotting. These included: alpha-enolase, epidermal-fatty acid binding protein, heat shock protein 27, histidine triad nucleotide-binding protein 1, lactate dehydrogenase A, protein disulfide isomerase precursor, and S100A9. Four proteins had combined effects that were different than would be expected based on the response to either individual toxicant. These data demonstrate a possible reaction to the combined insult that is substantially different from that of either separate treatment. Several proteins had different responses than what has been seen from high dose exposures, adding to the growing literature suggesting that the cellular responses to low dose exposures are distinct.


Relation of contrast nephropathy to adverse events in pulmonary emboli patients diagnosed with contrast CT.
Limited data exist on the incidence of contrast induced nephropathy (CIN) and its impact on in-hospital prognosis of patients diagnosed with acute pulmonary embolism (APE) using contrast computerized tomography pulmonary angiography (CTPA). In this study, we examined the frequency of nephropathy after CTPA in APE patients and its link to in-hospital adverse outcomes. This was a retrospective study of 189 patients (mean age 67+16years, 48% male) with APE who underwent CTPA. CIN was defined as a≥0.5mg/dl and/or ≥25% increase in serum creatinine levels >48hours after CTPA. Patients were divided into two groups according to the presence or absence of CIN to compare clinical characteristics, risk factors, and in-hospital adverse events. Twenty-four (13%) of the patients were diagnosed with CIN. Patients with CIN were older (73±17 vs. 67±15years, P=.01) and had higher rates of heart failure (17% vs. 6%, P=.04). Preexisting renal dysfunction and advanced age were found to be independent predictors of CIN (OR: 4.2, 95% CI: 1.5-11.9, P=.006; OR: 3.2, 95% CI: 1.1-9.8, P=.03 respectively). The in-hospital adverse event rate was significantly higher in patients with CIN (16.7% vs. 2.4%, P=.001). A multivariate analysis revealed CIN as an independent predictor of in-hospital adverse event rate (OR: 6.1, 95%CI: 1.2-29.3, P=.02). CIN is associated with a higher in-hospital adverse event rate in APE patients diagnosed using CTPA. This is first large study to focus specifically on CIN in patients diagnosed with APE using CTPA.


Focusing of beams into subwavelength area in an inhomogeneous medium.
Propagation and focusing of nonparaxial Gaussian beams with spherical wavefront in a graded-index medium are investigated using quantum-theoretical method of coherent states. Explicit expressions for the trajectory and width of a beam taking into account all correction terms to the paraxial approximation have been obtained. Electromagnetic field distributions in longitudinal and lateral directions are simulated. Diffraction of strongly focused high-aperture wave beams is investigated theoretically. The ratio of intensities of evanescent and propagating fields is calculated for different values of focused spot.


Adapting Helping Babies Breathe into a Virtual Curriculum: Methods, Results, and Lessons Learned.
Introduction. The Helping Babies Breathe (HBB) curriculum is an established, effective method to combat neonatal mortality. The COVID-19 pandemic has disrupted in-person HBB training sessions worldwide, portending deficits in the dissemination of this important intervention. Methods. A pilot study to compare in-person versus virtual HBB training among US-based pediatric and family medicine residents. Two HBB master trainers condensed the curriculum into an abbreviated course that was offered to 14 learners in-person (n = 6) and virtually via Zoom (n = 8). A standardized 10-item survey was administered before and after the session to measure reported self-efficacy of critical elements of HBB. Difference of difference analysis was performed to detect differences in post vs pre-training results among the 2 groups using STATA MP 15. Results. All learners showed improvement in preparedness, assessment, and skills subcomponents of self-efficacy with no notable differences based on the type of learning medium. At baseline, in-person learners had a 7-point higher self-efficacy score (69.7) in comparison to virtual learners (62.8; P = .26). After training, the confidence score improved significantly; by 14.3 units for in-person learners (P = .01) and 12.9 for virtual learners (P = .04). There was no statistically significant difference in improvement between the 2 groups (P = .67). Furthermore, all learners passed the post-training knowledge assessment. Discussion. Virtual learning of HBB may be an alternative option in the setting of resource and travel limitations. Future work needs to assess possible differences in attainment of assessment skills and retention of the HBB curriculum among virtual learners.


Terrestrial reproduction and parental care drive rapid evolution in the trade-off between offspring size and number across amphibians.
The trade-off between offspring size and number is central to life history strategies. Both the evolutionary gain of parental care or more favorable habitats for offspring development are predicted to result in fewer, larger offspring. However, despite much research, it remains unclear whether and how different forms of care and habitats drive the evolution of the trade-off. Using data for over 800 amphibian species, we demonstrate that, after controlling for allometry, amphibians with direct development and those that lay eggs in terrestrial environments have larger eggs and smaller clutches, while different care behaviors and adaptations vary in their effects on the trade-off. Specifically, among the 11 care forms we considered at the egg, tadpole and juvenile stage, egg brooding, male egg attendance, and female egg attendance increase egg size; female tadpole attendance and tadpole feeding decrease egg size, while egg brooding, tadpole feeding, male tadpole attendance, and male tadpole transport decrease clutch size. Unlike egg size that shows exceptionally high rates of phenotypic change in just 19 branches of the amphibian phylogeny, clutch size has evolved at exceptionally high rates in 135 branches, indicating episodes of strong selection; egg and tadpole environment, direct development, egg brooding, tadpole feeding, male tadpole attendance, and tadpole transport explain 80% of these events. By explicitly considering diversity in parental care and offspring habitat by stage of offspring development, this study demonstrates that more favorable conditions for offspring development promote the evolution of larger offspring in smaller broods and reveals that the diversity of parental care forms influences the trade-off in more nuanced ways than previously appreciated.


Comparison of Diagnostic Potential of Narrow Band Imaging Bronchoscopy Over White Light Bronchoscopy in Lung Cancer.
Worldwide, lung cancer is the largest contributor to new cancer diagnoses and to death from cancer. Narrow band imaging (NBI) is a novel bronchoscopic technique which enables detailed examination of submucosal microcapillary grid and showed great potential in early detection of malignant lesions of the bronchial mucosa. The aim of this study was to compare diagnostic potential of NBI bronchoscopy over white light (WL) bronchoscopy in lung cancer. We enrolled 187 patients having clinical and radiologic findings highly suspicious of lung cancer. Patients were further divided into 2 groups: NBI group (n=102), and control WL group (n=85). Bronchoscopy examination was performed with respective visualization modes and all pathologic lesions were biopsied and histologically confirmed. On NBI bronchoscopy, malignancy was suspected in 69 patients, of whom 62 had malignancy, and 33 patients were suspected of inflammation, of whom 32 had inflammation and only 1 patient had malignancy. Under WL bronchoscopy, 54 patients were suspected of malignancy, of whom 36 had malignancy, and 31 patients were suspected of inflammation, of whom 23 had inflammatory disease and 8 had malignancy. NBI bronchoscopy had sensitivity 98.1%, specificity 82.05%, positive predictive value 89.86% and negative predictive value 96.97% in comparison to standard WL bronchoscopy which had sensitivity 81.82%, specificity 56.10%, positive predictive value 66.67% and negative predictive value 74.19%. NBI bronchoscopy demonstrated better results in comparison to WL bronchoscopy. The presence of pathologic vascularization of the tumor helps to better identify the malignant process. Inflammatory changes in the mucosa can be easily differentiated from malignant changes by the appearance of vessels.


Cardiac MRI in common marmosets revealing age-dependency of cardiac function.
The aim of this study was to establish a feasible and robust magnetic resonance imaging protocol for the quantitative assessment of cardiac function in marmosets and to present normal values of cardiac function across different ages from young adult, middle-aged, to very old clinically healthy animals. Cardiac MRI of 33 anesthetized marmosets at the age of 2-15 years was performed at 9.4 T using IntraGate-FLASH that operates without any ECG-triggering and breath holding. Normalized to post-mortem heart weight, the left ventricular end-diastolic volume (LV-EDV) was significantly reduced in older marmosets. The LV end-systolic volume (LV-ESV) and the LV stroke volume (LV-SV) showed a similar trend while the LV ejection fraction (LV-EF) and wall thickening remained unchanged. Similar observations were made for the right ventricle. Moreover, the total ventricular myocardial volume was lower in older monkeys while no significant difference in heart weight was found. In conclusion, IntraGate-FLASH allowed for quantification of left ventricular cardiac function but seems to underestimate the volumes of the right ventricle. Although less strong and without significant sex differences, the observed age related changes were similar to previously reported findings in humans supporting marmosets as a model system for age related cardiovascular human diseases.


Hyperbaric oxygen therapy reduces apoptosis after spinal cord injury in rats.
Hyperbaric oxygen therapy (HBOT) protects brain tissue from inflammatory injury by suppressing mitochondrial apoptotic pathways. However, its neuroprotective mechanism via anti-apoptosis in spinal cord injury (SCI) is still unclear. In our study, Male Sprague-Dawley rats were randomly divided into three groups: sham-operated (SH), SCI model, and SCI + HBOT. Rats in each group were randomly divided into four sub-groups in a time-dependent manner (1 day, 3 days, 7 days and 14 days after surgery). Expression of adaptor molecule apoptosis-associated speck-like protein (ASC) and caspase-3 was evaluated at the indicated time after injury. Our data showed that HBOT downregulated expression of ASC in SCI rats at the mRNA and protein levels. HBOT mitigated caspase-3 release in injured spinal cord tissue. We conclude that HBOT prevents inflammation apoptosis after SCI, likely through suppression of ASC and caspase-3.


Regulation of very-low-density-lipoprotein lipid secretion in hepatocyte cultures derived from diabetic animals.
Hepatocytes were derived from 2-3-day streptozotocin-diabetic rats and maintained in culture for up to 3 days. Compared with similar cultures from normal animals, these hepatocytes secreted less very-low-density-lipoprotein (VLDL) triacylglycerol, but the decrease in the secretion of VLDL non-esterified and esterified cholesterol was not so pronounced. This resulted in the secretion of relatively cholesterol-rich VLDL particles by the diabetic hepatocytes. Addition of insulin for a relatively short period (24 h) further decreased the low rates of VLDL triacylglycerol secretion from the diabetic hepatocytes. The secretion of VLDL esterified and non-esterified cholesterol also declined. These changes occurred irrespective of whether or not exogenous fatty acids were present in the culture medium. Little or no inhibitory effect of insulin was observed after longer-term (24-48 h) exposure to the hormone. Both dexamethasone and a mixture of lipogenic precursors (lactate plus pyruvate) stimulated VLDL triacylglycerol and cholesterol secretion, but not to the levels observed in hepatocytes from normal animals. The low rate of hepatic VLDL secretion in diabetes contrasts with the increase in whole-body VLDL production rate. This suggests that the intestine is a major source of plasma VLDL in insulin-deficient diabetes.


Phase Aberration and Attenuation Effects on Acoustic Radiation Force-Based Shear Wave Generation.
Elasticity is measured by shear wave elasticity imaging (SWEI) methods using acoustic radiation force to create the shear waves. Phase aberration and tissue attenuation can hamper the generation of shear waves for in vivo applications. In this study, the effects of phase aberration and attenuation in ultrasound focusing for creating shear waves were explored. This includes the effects of phase shifts and amplitude attenuation on shear wave characteristics such as shear wave amplitude, shear wave speed, shear wave center frequency, and bandwidth. Two samples of swine belly tissue were used to create phase aberration and attenuation experimentally. To explore the phase aberration and attenuation effects individually, tissue experiments were complemented with ultrasound beam simulations using fast object-oriented C++ ultrasound simulator (FOCUS) and shear wave simulations using finite-element-model (FEM) analysis. The ultrasound frequency used to generate shear waves was varied from 3.0 to 4.5 MHz. Results: The measured acoustic pressure and resulting shear wave amplitude decreased approximately 40%-90% with the introduction of the tissue samples. Acoustic intensity and shear wave displacement were correlated for both tissue samples, and the resulting Pearson's correlation coefficients were 0.99 and 0.97. Analysis of shear wave generation with tissue samples (phase aberration and attenuation case), measured phase screen, (only phase aberration case), and FOCUS/FEM model (only attenuation case) showed that tissue attenuation affected the shear wave generation more than tissue aberration. Decreasing the ultrasound frequency helped maintain a focused beam for creation of shear waves in the presence of both phase aberration and attenuation.


In vitro interactions between primycin and different statins in their effects against some clinically important fungi.
The in vitro antifungal activities of primycin (PN) and various statins against some opportunistic pathogenic fungi were investigated. PN completely inhibited the growth of Candida albicans (MIC 64 microg ml(-1)) and Candida glabrata (MIC 32 microg ml(-1)), and was very effective against Paecilomyces variotii (MIC 2 microg ml(-1)), but had little effect on Aspergillus fumigatus, Aspergillus flavus or Rhizopus oryzae (MICs >64 microg ml(-1)). The fungi exhibited different degrees of sensitivity to the statins; fluvastatin (FLV) and simvastatin (SIM) exerted potent antifungal activities against a wide variety of clinically important fungal pathogens. Atorvastatin, rosuvastatin and lovastatin (LOV) had a slight effect against all fungal isolates tested, whereas pravastatin was completely ineffective. The in vitro interactions between PN and the different statins were investigated using a standard chequerboard titration method. When PN was combined with FLV, LOV or SIM, both synergistic and additive effects were observed. The extent of inhibition was higher when these compounds were applied together, and the concentrations of PN and the given statin needed to block fungal growth completely could be decreased by several dilution steps. Similar interactions were observed when the variability of the within-species sensitivities was investigated.