Epidemic and molecular characterization of fluoroquinolone-resistant Shigella dysenteriae 1 isolates from calves with diarrhea.
The widespread distribution of antimicrobial-resistant Shigella has become a recurrent challenge in many parts of the developing world. Previous studies indicate that the host of Shigella has expanded from humans to animals. This study aimed to investigate the prevalence of fluoroquinolone resistance and associated molecular characterization of S. dysenteriae 1 isolated from calves. All 38 unduplicated S. dysenteriae 1 isolates were collected from calves in Gansu Province from October 2014 to December 2016. According to MLST and PFGE analysis, these isolates were separated into 4 and 28 genotypes, respectively. The most common STs identified were ST228 (34.21%, 13/38) and ST229 (39.47%, 15/38), which were first found in the present study. All isolates harbored virulence genes, and the incidence of the seven virulence genes were ipaH (100%), ipaBCD (92.11%), stx (73.68%), ial (57.89%), sen (28.95%), set1A and set1B (0%). According to the results of antimicrobial susceptibilities, 76.32% (29/38) were resistant to fluoroquinolone and showed multidrug resistance. In a study on the polymorphism of quinolone resistance-determining region (QRDR) of gyrA/B and parC/E genes, we identified two mutations in gyrA (Ser83 → Leu and Asp87 → Asn) and parC (Ser80 → Ile and Ser83 → Leu), respectively. Among them, 55.17% (16/29) of resistant strains had the gyrA point mutations (Ser83 → Leu) and parC point mutation (Ser83 → Leu). Moreover, 41.38% (12/29) of isolates had all five point mutations of gyrA and parC. In addition, the prevalence of the plasmid-mediated quinolone resistance (PMQR) determinant genes was also investigated. All 29 fluoroquinolone-resistant isolates were positive for the aac (6')-Ib-cr gene but negative for qepA, except for SD001. In addition, only 6 (20.69%, 6/29) isolates harbored the qnr gene, including two with qnrB (6.90%, 2/29) and four with qnrS (13.79%, 4/29). Given the increased common emergence of multidrug resistant isolates, uninterrupted surveillance will be necessary to understand the actual epidemic burden and control this infection.


Efficacy and safety of Barg-e-Sahajna (Moringa oleifera Lam.) in primary hypothyroidism.
Hypothyroidism is the most common disorder arising from hormone deficiency. It frequently affects women than men. The prevalence of overall hypothyroidism has been reported to be 4.8-11%. Levothyroxine is the treatment of choice for all types of hypothyroidism. The purpose of this pilot study was to evaluate the efficacy and safety of Barg-e-Sahajna (Leaves of Moringa oleifera Lam.) among diagnosed patients of primary hypothyroidism. This study was an open observational study. A total of 22 patients were screened, out of which 10 were excluded (did not meet inclusion criteria) and 2 refused to consent to be part of the study, rest 10 participants were enrolled after obtaining written informed consent finally 8 subjects completed the study and 2 are dropout in last follow up. The drug was given in the form of decoction at the dose of 5 g fresh leaves twice a day after meal for 45 days. The study effects on objective parameter thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were found extremely significant when compared before (16.62 ± 11.49, 132 ± 19.32, 9.28 ± 1.46) and after (4.75 ± 3.12, 150.37 ± 20.68, 11.84 ± 3.81) treatment with a significant decrease in serum TSH level (p<0.0246) and an increase in serum T3 (p<0.0005) and T4 (p<0.0438) levels. The results were analyzed using paired "t" test. The improvements in thyroid profiles (TSH, T3 and T4) after consuming 'Barg-e-Sahajna' show that the test drug is effective in primary hypothyroidism and the relief was considerable. No significant effect on safety parameters (serum-glutamic-oxaloacetic-transaminase [SGOT], serum glutamic-pyruvic transaminase [SGPT], blood urea, and serum creatinine) was observed. Therefore, it may be concluded that the Barg-e-Sahajna is preliminarily safe and effective in the management of primary hypothyroidism.


Data triangulation to estimate age-specific coverage of voluntary medical male circumcision for HIV prevention in four Kenyan counties.
Kenya is 1 of 14 priority countries in Africa scaling up voluntary medical male circumcision (VMMC) for HIV prevention following the recommendations of the World Health Organization and the Joint United Nations Programme on HIV/AIDS. To inform VMMC target setting, we modeled the impact of circumcising specific client age groups across several Kenyan geographic areas. The Decision Makers' Program Planning Tool, Version 2 (DMPPT 2) was applied in Kisumu, Siaya, Homa Bay, and Migori counties. Initial modeling done in mid-2016 showed coverage estimates above 100% in age groups and geographic areas where demand for VMMC continued to be high. On the basis of information obtained from country policy makers and VMMC program implementers, we adjusted circumcision coverage for duplicate reporting, county-level population estimates, migration across county boundaries for VMMC services, and replacement of traditional circumcision with circumcisions in the VMMC program. To address residual inflated coverage following these adjustments we applied county-specific correction factors computed by triangulating model results with coverage estimates from population surveys. A program record review identified duplicate reporting in Homa Bay, Kisumu, and Siaya. Using county population estimates from the Kenya National Bureau of Statistics, we found that adjusting for migration and correcting for replacement of traditional circumcision with VMMC led to lower estimates of 2016 male circumcision coverage especially for Kisumu, Migori, and Siaya. Even after addressing these issues, overestimation of 2016 male circumcision coverage persisted, especially in Homa Bay. We estimated male circumcision coverage in 2016 by applying correction factors. Modeled estimates for 2016 circumcision coverage for the 10- to 14-year age group ranged from 50% in Homa Bay to approximately 90% in Kisumu. Results for the 15- to 19-year age group suggest almost complete coverage in Kisumu, Migori, and Siaya. Coverage for the 20- to 24-year age group ranged from about 80% in Siaya to about 90% in Homa Bay, coverage for those aged 25-29 years ranged from about 60% in Siaya to 80% in Migori, and coverage in those aged 30-34 years ranged from about 50% in Siaya to about 70% in Migori. Our analysis points to solutions for some of the data issues encountered in Kenya. Kenya is the first country in which these data issues have been encountered because baseline circumcision rates were high. We anticipate that some of the modeling methods we developed for Kenya will be applicable in other countries.


Improved monitoring of inflammatory activity in patients with ulcerative colitis by combination of faecal tests for haemoglobin and calprotectin.
Faecal calprotectin (FC) tests and faecal immunological tests (FIT) for haemoglobin have been used to monitor disease activity in patients with ulcerative colitis (UC) but used alone they have some limitation concerning the predictive ability. We aimed to test if an FC test used in combination with FIT could improve the predictive ability. Consecutive out-patients with UC (n = 93) who were admitted for colonoscopy completed a single faecal sample before the start of bowel preparation. A quantitative CALPRO® calprotectin ELISA test and a qualitative FIT (cut-off < 40 ng/mL) were analyzed. An estimated Mayo score and a score of histological inflammation was performed blinded to the result of the faecal tests. The sensitivity, specificity, negative predictive value and positive predictive value for endoscopic inflammation (Mayo score > 1) was for FIT 85%, 83%, 96%, 57% and for FC > 186 µg/g 73%, 87%, 87%, 54%. Corresponding results for FIT*FC > 186 µg/g (at least one test positive) were 92%, 69%, 97%, 43%. For detecting moderate/severe histological inflammation the results were for FIT 69%, 79%, 92%, 43%, for FC > 75 µg/g 95%, 62%, 98%, 41%, and for FIT*FC > 75 µg/g 100%, 60%, 100%, 36%. None of the markers alone or in combination were useful to predict deep remission (Mayo score = 0 and no histological inflammation). We conclude that using the combination of an FC test and FIT shows minor improvement in predictive ability for inflammatory activity and remission in patients with UC.


Associations Between Aging-Related Changes in Grip Strength and Cognitive Function in Older Adults: A Systematic Review.
Grip strength and cognitive function reflect upper body muscle strength and mental capacities. Cross-sectional research has suggested that in old age these two processes are moderately to highly associated, and that an underlying common cause drives this association. Our aim was to synthesize and evaluate longitudinal research addressing whether changes in grip strength are associated with changes in cognitive function in healthy older adults. We systematically reviewed English-language research investigating the longitudinal association between repeated measures of grip strength and of cognitive function in community-dwelling older adults to evaluate the extent to which the two indices decline concurrently. We used four search engines: Embase, PsychINFO, PubMed, and Web of Science. Of 459 unique citations, 6 met our full criteria: 4 studies reported a longitudinal association between rates of change in grip strength and cognitive function in older adults, 2 of which reported the magnitudes of these associations as ranging from low to moderate; 2 studies reported significant cross-sectional but not longitudinal associations among rates of change. All studies concluded that cognitive function and grip strength declined, on average, with increasing age, although with little to no evidence for longitudinal associations among rates of change. Future research is urged to expand the study of physical and cognitive associations in old age using a within-person and multi-study integrative approach to evaluate the reliability of longitudinal results with greater emphasis on the magnitude of this association. CRD42016038544.


Meta-analysis of transcriptomic datasets identifies genes enriched in the mammalian circadian pacemaker.
The master circadian pacemaker in mammals is located in the suprachiasmatic nuclei (SCN) which regulate physiology and behaviour, as well as coordinating peripheral clocks throughout the body. Investigating the function of the SCN has often focused on the identification of rhythmically expressed genes. However, not all genes critical for SCN function are rhythmically expressed. An alternative strategy is to characterize those genes that are selectively enriched in the SCN. Here, we examined the transcriptome of the SCN and whole brain (WB) of mice using meta-analysis of publicly deposited data across a range of microarray platforms and RNA-Seq data. A total of 79 microarrays were used (24 SCN and 55 WB samples, 4 different microarray platforms), alongside 17 RNA-Seq data files (7 SCN and 10 WB). 31 684 MGI gene symbols had data for at least one platform. Meta-analysis using a random effects model for weighting individual effect sizes (derived from differential expression between relevant SCN and WB samples) reliably detected known SCN markers. SCN-enriched transcripts identified in this study provide novel insights into SCN function, including identifying genes which may play key roles in SCN physiology or provide SCN-specific drivers.


ICQ (I seek you) and adolescents: a quantitative study in Hong Kong.
The Hong Kong Government and the education sector encourage the whole population-from toddlers to senior citizens-to utilize information technology, and many do. Yet there are no studies exploring the patterns of adolescents using ICQ (I seek you) in Asian countries. This study was done in Hong Kong, which has the greatest number of ICQ users. A quantitative approach was adopted by administering self-constructed questionnaires to the students of one high school. One hundred and forty-seven adolescents volunteered to participate. The key findings of the study are (1) most of the adolescents have been using ICQ for 1-4 years; (2) most fit one of two patterns of use: either 2 or 3 days per week, or more than 5 days per week; (3) they spend less than 3 h per day on ICQ; (4) the main reasons for using ICQ are entertainment, relaxation, and socializing; and (5) parents are concerned about possible negative impacts on their children's academic performance because of using ICQ. Two main implications are drawn: proper use of ICQ can minimize parental distress and encourage adolescents to be less sedentary.


A provisional gene regulatory atlas for mouse heart development.
Congenital Heart Disease (CHD) is one of the most common birth defects. Elucidating the molecular mechanisms underlying normal cardiac development is an important step towards early identification of abnormalities during the developmental program and towards the creation of early intervention strategies. We developed a novel computational strategy for leveraging high-content data sets, including a large selection of microarray data associated with mouse cardiac development, mouse genome sequence, ChIP-seq data of selected mouse transcription factors and Y2H data of mouse protein-protein interactions, to infer the active transcriptional regulatory network of mouse cardiac development. We identified phase-specific expression activity for 765 overlapping gene co-expression modules that were defined for obtained cardiac lineage microarray data. For each co-expression module, we identified the phase of cardiac development where gene expression for that module was higher than other phases. Co-expression modules were found to be consistent with biological pathway knowledge in Wikipathways, and met expectations for enrichment of pathways involved in heart lineage development. Over 359,000 transcription factor-target relationships were inferred by analyzing the promoter sequences within each gene module for overrepresentation against the JASPAR database of Transcription Factor Binding Site (TFBS) motifs. The provisional regulatory network will provide a framework of studying the genetic basis of CHD.


[Endogenous opiates, palatability and control of food intake].
Endogenous opiate or opioïds are peptidic neuromodulators which bind with specific receptors (mu, kappa, delta, etc), and thus control numerous physiological process, mainly pain and food intake (FI). Endogenous or exogenous agonists of opioïd receptors increase FI. Antagonists decrease it. However several results indicate discrepancies. The anorectic activity of antagonists is different of the activity of classical anorexigenic drugs since inhibition of opioïd receptors did not induce long term change of body weight. The analysis of the neurophysiological action of the opioïd system on FI can explain this apparent discrepancy. Opioïds act on the short term control of FI modulating the rewarding properties of alimentary stimuli: agonist increase and antagonists decrease it. Such an action correspond to a control of food palatability or, in human, to a control of the sensory pleasure/displeasure associated with food stimuli. Opioïd system does not seem to directly act on body weigh regulation.


Memory Classifiers for Robust ECG Classification against Physiological Noise.
The development of sophisticated machine learning algorithms has made it possible to detect critical health conditions like cardiac arrhythmia, directly from electrocardiogram (ECG) recordings. Large-scale machine learning models, like deep neural networks, are well known to underperform when subjected to small perturbations which would not pose a challenge to physicians. This is a hurdle that needs to be removed to facilitate wide-scale adoption. We find this to be true even for models trained using data-augmentation schemes.In this paper, we show that using memory classifiers it is possible to attain a boost in robustness using expert-informed features. Memory classifiers combine standard deep neural network training with a domain knowledge-guided similarity metric to boost the robustness of classifiers. We evaluate the performance of the models against naturally occurring physiological perturbations, specifically electrode movement, muscle artifact, and baseline wander noise. Our approach demonstrates improved robustness across all evaluated noises for an average improvement in F1 score of 3.13% compared to models using data augmentation techniques.Clinical relevance- This approach improves the robustness of deep learning methods in safety-critical medical applications.


Alpha-1 adrenoceptor hyperresponsiveness in three neuropathic pain states: complex regional pain syndrome 1, diabetic peripheral neuropathic pain and central pain states following spinal cord injury.
The pathophysiology of the pain associated with complex regional pain syndrome, spinal cord injury and diabetic peripheral neuropathy is not known. The pain of complex regional pain syndrome has often been attributed to abnormal sympathetic nervous system activity based on the presence of vasomotor instability and a frequently reported positive response, albeit a temporary response, to sympathetic blockade. In contrast, the pain below the level of spinal cord injury and diabetic peripheral neuropathy are generally seen as deafferentation phenomena. Each of these pain states has been associated with abnormal sympathetic nervous system function and increased peripheral alpha-1 adrenoceptor activity. This increased responsiveness may be a consequence of alpha-1 adrenoceptor postsynaptic hypersensitivity, or alpha-2 adrenoceptor presynaptic dysfunction with diminished noradrenaline reuptake, increased concentrations of noradrenaline in the synaptic cleft and increased stimulation of otherwise normal alpha-1 adrenoceptors. Plausible mechanisms based on animal research by which alpha-1 adrenoceptor hyperresponsiveness can lead to chronic neuropathic-like pain have been reported. This raises the intriguing possibility that sympathetic nervous system dysfunction may be an important factor in the generation of pain in many neuropathic pain states. Although results to date have been mixed, there may be a greater role for new drugs which target peripheral alpha-2 adrenoceptors (agonists) or alpha-1 adrenoceptors (antagonists).


Tissue characterization of intracranial tumors by MR imaging. In vivo evaluation of T1- and T2-relaxation behavior at 1.5 T.
The main purpose of this in vivo study was to provide a detailed description of the T1- and T2-relaxation processes in intracranial tumors at 1.5 T. A total of 100 patients were investigated. Optimal experimental conditions were carefully observed, including the use of long TR values. T1 determination was based on a partial saturation inversion recovery sequence covering 12 or 6 data points. T2 determination involved a multiple spin echo sequence with 32 echoes. Calculations included biexponential analysis of the 12-point T1 data and all T2 data obtained. The results were evaluated in accordance with histopathology. The T1- and the T2-relaxation times of the prevailing tumor types were significantly different (p less than 0.0005). However, biologic scatter and overlap between tumor types were considerable. In particular, no discrimination between benign and malignant tumor growth was possible. Biexponential evaluation did not increase the specificity, although a biexponential relaxation behavior was recognized in 37% of the T2 curves. The results indicate that tissue heterogeneity is responsible for most of the scatter in the relaxation times. It is concluded that tissue characterization by MR imaging, based solely on relaxation time measurements, seems to be of no value in the differentiation of intracranial tumors.


A longitudinal study of depression and gestational diabetes in pregnancy and the postpartum period.
Depression and glucose intolerance commonly co-occur among non-pregnant individuals; however, the temporal relationship between gestational diabetes (GDM) and depression during pregnancy and the postpartum period is less understood. Our objective was to assess longitudinal associations between depression early in pregnancy and GDM risk, as well as GDM and subsequent risk of postpartum depression. Data came from the prospective National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort (2009-2013), and had been collected at 12 US clinical centres. Pregnant women without psychiatric disorders, diabetes or other chronic conditions before pregnancy were followed throughout pregnancy (n = 2477). Only women with GDM and matched controls were followed up at 6 weeks postpartum (n = 162). GDM was ascertained by a review of the medical records. Depression was assessed in the first (8-13 gestational weeks) and second (16-22 weeks) trimesters and at 6 weeks postpartum using the Edinburgh Postnatal Depression Scale. Postpartum depression was defined as a depressive symptom score ≥10 or antidepressant medicine use after delivery. RR and 95% CI were adjusted for pre-pregnancy BMI and other risk factors. GDM was considered to be the outcome for the first set of analyses, with depression in the first and second trimesters as the exposures. Postpartum depression was considered as the outcome for the second set of analyses, with GDM as the exposure. Overall, comparing the highest and lowest quartiles of first-trimester depression scores, the scores from the highest quartile were associated with a significant twofold (95% CI 1.06, 3.78) increased risk of GDM, but this was attenuated to 1.72-fold (95% CI 0.92, 3.23) after adjustment; the second-trimester results were similar. The risk was stronger and significant in both trimesters among non-obese women (p for trend 0.02 and 0.01, respectively), but null for obese women. Women with persistently high depression scores in both trimesters had the greatest risk of GDM (highest vs lowest quartile in both trimesters: adjusted RR 3.21, 95% CI 1.00, 10.28). GDM was associated with an adjusted 4.62-fold (95% CI 1.26, 16.98) increased risk of subsequent postpartum depression. This prospective study demonstrates a modest association between depressive symptoms early in pregnancy and an increased risk of incident GDM, as well as between GDM and subsequent postpartum depression risk, highlighting pregnancy and the postpartum period as an important susceptible time window during the life course for the interplay between depression and glucose intolerance phenotypes. GDM risk associated with elevated depressive symptoms was particularly high among non-obese women and women with symptoms persisting across the first two trimesters of pregnancy.


Using the systematic review methodology to evaluate factors that influence the persistence of influenza virus in environmental matrices.
Understanding factors that influence persistence of influenza virus in an environment without host animals is critical to appropriate decision-making for issues such as quarantine downtimes, setback distances, and eradication programs in livestock production systems. This systematic review identifies literature describing persistence of influenza virus in environmental samples, i.e., air, water, soil, feces, and fomites. An electronic search of PubMed, CAB, AGRICOLA, Biosis, and Compendex was performed, and citation relevance was determined according to the aim of the review. Quality assessment of relevant studies was performed using criteria from experts in virology, disease ecology, and environmental science. A total of 9,760 abstracts were evaluated, and 40 appeared to report the persistence of influenza virus in environmental samples. Evaluation of full texts revealed that 19 of the 40 studies were suitable for review, as they described virus concentration measured at multiple sampling times, with viruses detectable at least twice. Seven studies reported persistence in air (six published before 1970), seven in water (five published after 1990), two in feces, and three on surfaces. All three fomite and five air studies addressed human influenza virus, and all water and feces studies pertained to avian influenza virus. Outcome measurements were transformed to half-lives, and resultant multivariate mixed linear regression models identified influenza virus surviving longer in water than in air. Temperature was a significant predictor of persistence over all matrices. Salinity and pH were significant predictors of persistence in water conditions. An assessment of the methodological quality review of the included studies revealed significant gaps in reporting critical aspects of study design.


Lymphokine-activated killer (LAK) cell purging of leukemic bone marrow: range of activity against different hematopoietic neoplasms.
Natural killer cells activated in vitro by incubation with IL-2 display a broad range of cytolytic activity against neoplastic cells. These lymphokine-activated killer (LAK) cells can discriminate between neoplastic and normal bone marrow cells and may represent a useful means of purging bone marrow prior to autologous transplantation. We demonstrate that LAK cells can successfully remove four distinctly different malignant hematopoietic cell types from normal bone marrow grafts. The LAK purging technique is capable of a 2-3 log10 reduction in tumor cells in the bone marrow graft without compromising hematological recovery or survival. Our results also suggest, however, that an inhibitory effect on stem cell function by allogeneic LAK cells exists, and this form of purging may be used only if greater levels of bone marrow are transferred in an allogeneic setting. The ability to detect and eliminate malignant cells in bone marrow prior to use for autologous transplantation suggests that LAK cells, alone or in conjunction with current methods of bone marrow purging, could be useful for the in vitro treatment of bone marrow in patients who require high-dose chemotherapy and autologous bone marrow transplantation.


[Pathogenetic correlation between chronic pancreatitis and pancreatic carcinoma].
The autopsy material from the Institute of Pathology of the Faculty of Medicine of the Humboldt University (Charité) in Berlin for the years 1970 to 1984 was analyzed with respect to the presence of pancreatic carcinoma and a long history of chronic, non-obstructive pancreatitis. A total of 20,515 adult sections were reviewed. 331 (1.6%) of these had carcinoma of the exocrine pancreas. 75 pancreata were dissected in tail-to-head direction into 10 blocks. In 12 (16%) of them a chronic non-obstructive pancreatitis or pancreatic scarring as a result of pancreatitis could be demonstrated histologically. The possibility of a relationship between pancreatitis and pancreatic carcinoma is considered, in particular with respect to pre-malignant changes and latency of the latter. Comprehensive analysis and evaluation of the present study material, together with a critical evaluation of the literature, support the viewpoint that long-term, chronic pancreatitis and pancreatic carcinoma have a common pathogenic basis and that chronic pancreatitis may be regarded as an antecedent event for the neoplasm.


Charcot Arthropathy of the Digit: A Report of 2 Cases.
Charcot arthropathy (CA) is a progressive degenerative joint disease typically affecting lower extremity weight-bearing joints, with only a few cases reported in the fingers. We present 2 cases of interphalangeal joint CA: the long finger distal interphalangeal joint in a 73-year-old man with severe carpal tunnel syndrome and the ring finger proximal interphalangeal joint of a 71-year-old woman with diabetic neuropathy. Two cases of CA of the digits were treated with splinting with resolution of symptoms and no wound complications.


Exosome-templated nanoplasmonics for multiparametric molecular profiling.
Exosomes are nanoscale vesicles distinguished by characteristic biophysical and biomolecular features; current analytical approaches, however, remain univariate. Here, we develop a dedicated platform for multiparametric exosome analysis-through simultaneous biophysical and biomolecular evaluation of the same vesicles-directly in clinical biofluids. Termed templated plasmonics for exosomes, the technology leverages in situ growth of gold nanoshells on vesicles to achieve multiselectivity. For biophysical selectivity, the nanoshell formation is templated by and tuned to distinguish exosome dimensions. For biomolecular selectivity, the nanoshell plasmonics locally quenches fluorescent probes only if they are target-bound on the same vesicle. The technology thus achieves multiplexed analysis of diverse exosomal biomarkers (e.g., proteins and microRNAs) but remains unresponsive to nonvesicle biomarkers. When implemented on a microfluidic, smartphone-based sensor, the platform is rapid, sensitive, and wash-free. It not only distinguished biomarker organizational states in native clinical samples but also showed that the exosomal subpopulation could more accurately differentiate patient prognosis.


Neonatal brain volume as a marker of differential susceptibility to parenting quality and its association with neurodevelopment across early childhood.
Parenting quality is associated with child cognitive and executive functions (EF), which are important predictors of social and academic development. However, children vary in their susceptibility to parenting behaviors, and the neurobiological underpinnings of this susceptibility are poorly understood. In a prospective longitudinal study, we examined whether neonatal total brain volume (TBV) and subregions of interest (i.e., hippocampus (HC) and anterior cingulate gyrus (ACG)) moderate the association between maternal sensitivity and cognitive/EF development across early childhood. Neonates underwent a brain magnetic resonance imaging scan. Their cognitive performance and EF was characterized at 2.0 ± 0.1 years (N = 53) and at 4.9 ± 0.8 years (N = 36) of age. Maternal sensitivity was coded based on observation of a standardized play situation at 6-mo postpartum. Neonatal TBV moderated the association between maternal sensitivity and 2-year working memory as well as all 5-year cognitive outcomes, suggesting that the positive association between maternal sensitivity and child cognition was observed only among children with large or average but not small TBV as neonates. Similar patterns were observed for TBV-corrected HC and ACG volumes. The findings suggest that larger neonatal TBV, HC and ACG may underlie susceptibility to the environment and affect the degree to which parenting quality shapes long-term cognitive development.


Antibody and antigen contact residues define epitope and paratope size and structure.
A total of 111 Ag-Ab x-ray crystal structures of large protein Ag epitopes and paratopes were analyzed to inform the process of eliciting or selecting functional and therapeutic Abs. These analyses illustrate that Ab contact residues (CR) are distributed in three prominent CR regions (CRR) on L and H chains that overlap but do not coincide with Ab CDR. The number of Ag and Ab CRs per structure are overlapping and centered around 18 and 19, respectively. The CR span (CRS), a novel measure introduced in this article, is defined as the minimum contiguous amino acid sequence containing all CRs of an Ag or Ab and represents the size of a complete structural epitope or paratope, inclusive of CR and the minimum set of supporting residues required for proper conformation. The most frequent size of epitope CRS is 50-79 aa, which is similar in size to L (60-69) and H chain (70-79) CRS. The size distribution of epitope CRS analyzed in this study ranges from ~20 to 400 aa, similar to the distribution of independent protein domain sizes reported in the literature. Together, the number of CRs and the size of the CRS demonstrate that, on average, complete structural epitopes and paratopes are equal in size to each other and similar in size to intact protein domains. Thus, independent protein domains inclusive of biologically relevant sites represent the fundamental structural unit bound by, and useful for eliciting or selecting, functional and therapeutic Abs.


Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells.
Exposure to polycyclic aromatic hydrocarbons (PAHs) has been positively associated with prostate cancer, but knowledge of the formation of PAH-DNA adducts and related genotoxic events in prostatic cells is limited. In the present study, benzo[a]pyrene (BaP), a potent mutagenic PAH, formed significant levels of DNA adducts in cell lines derived from human prostate carcinoma. When analyzing the effect of BaP on the induction of CYP1 enzymes participating in the metabolic activation of PAHs in LNCaP cells, we found that BaP induced expression of CYP1A1 and CYP1A2, but not CYP1B1 enzyme. Despite a significant amount of DNA adducts being formed by BaP and, to a lesser extent also by another strong genotoxin, dibenzo[a,l]pyrene, neither apoptosis nor cell-cycle arrest were induced in LNCaP cells. LNCaP cells were not sensitized to the induction of apoptosis by PAHs even through inhibition of the phosphoinositide-3-kinase/Akt pro-survival pathway. The lack of apoptosis was not due a disruption of expression of pro-apoptotic and pro-survival members of the Bcl-2 family of apoptosis regulators. In contrast to other genotoxic stimuli, genotoxic PAHs failed to induce DNA double-strand breaks, as illustrated by the lack of phosphorylation of histone H2AX or checkpoint kinase-2. BaP did not activate p53, as evidenced by the lack of p53 accumulation, phosphorylation at Ser15, or induction of p53 transcriptional targets. Taken together, although genotoxic PAHs produced significant levels of DNA adducts in a model of human prostate carcinoma cells, they did not activate the mechanisms leading to elimination of cells with significant damage to DNA, presumably due to their failure to activate the p53-dependent DNA damage response.


[Differentiation of strains of bovine infectious rhinotracheitis virus using restriction analysis].
The virus of infectious rhinotracheitis of cattle (BHV-1) causes the respiratory diseases, encephalitis, vulvovaginitis, abortions, etc. in sensitive animals. The attempts to differentiate the viral strains by virology and serology methods were unsuccessful. The restriction analysis makes possible to divide the strains into the three main groups designated BHV-1.1, BHV-1.2 and BHV-1.3. Majority of authors note the lack of correlation between the restriction pattern of DNA and the syndromes caused by the strains of the first and second groups while all the representatives of the third group were isolated in case of meningoencephalitis. The restriction analysis of BHV-1 strains isolated in the USSR by restriction endonucleases EcoRI, BamHI, HpaI and ClaI is presented. The obtained results show the absence of correlation between the restriction pattern of the strain and the syndrome caused by the viruses of all three groups. The representatives of the group BHV-1.3 that are not associated with the neurological syndrome are isolated for the first time.


Differential expression of the human ST5 gene in HeLa-fibroblast hybrid cell lines mediated by YY1: evidence that YY1 plays a part in tumor suppression.
Through a mutational analysis of a differentially regulated enhancer, we present evidence that supports a role for the transcription factor YY1 in tumor suppression in HeLa/fibroblast somatic cell hybrids. The human ST5 gene was previously shown to be expressed as three RNA species, 4.6, 3.1 and 2.8 kb in length. Whereas the two larger species are expressed at similar levels in all cell lines examined, the 2.8 kb mRNA is expressed specifically in non-tumorigenic hybrids. In this study, the basis for the differential expression of this mRNA species was investigated. The message was shown to originate from a promoter located within an intron of the ST5 gene. An enhancer located approximaely 1500 nt upstream of the start site was required for cell type specific expression. Mutational analysis of this enhancer revealed an AP1 site and five YY1 sites which were necessary for full enhancer activity. Levels of YY1 DNA binding activity were found to be as much as 6-fold higher in the non-tumorigenic cells relative to the tumorigenic cells, while AP1 activity was similar in both cell types. These results suggest that a signaling pathway targeting YY1 may play an important role in tumor suppression in HeLa-fibroblast hybrids.


Spectrum of EEG Abnormalities in COVID-19 Patients.
Neurologic involvement is commonly reported in coronavirus disease (COVID-19) patients. The published literature regarding the COVID-19-related neurophysiological findings, including the EEG findings, is still quite limited. The objective of this study was to evaluate the EEG findings in patients with a COVID-19 infection and look for a possible correlations and prognosis. This is an inpatient hospital-based retrospective observational study. All admitted COVID-19 patients undergoing an EEG study between January 1, 2020 and June 30, 2021 were included in this study. EEG was ordered by the primary intensive care physician or a neurologist taking part in the clinical care of patients. Sixty-six EEG studies in 57 patients were included. Mean age was 62.2 ± 16.3 years with male predominance (65%). Encephalopathy (70%) was the most common indication for an EEG. Background EEG abnormalities were seen in most of the patients (92.4%) with severe abnormalities correlating with the prognosis of the patient. Epileptiform discharges were only seen in 7.5% of the EEGs, with majority of the discharges arising from the frontal region. Mortality reported was high (47%). Nonspecific diffuse background EEG abnormalities are commonly seen in COVID-19 patients. Epileptiform discharges are less common but mostly originate from frontal region. Most of these patients also had an abnormal neuroimaging. The significance of this peculiar finding needs further research. Nonspecific background EEG changes are common in COVID-19 patients. Among epileptiform discharges, focal epileptiform discharges arising from the frontal region were common, usually associated with an abnormal neuroimaging.


Temporal Trends in Incidence and Outcomes of Acute Pancreatitis in Hospitalized Patients in the United States From 2002 to 2013.
We sought to examine temporal trends in incidence and outcomes of acute pancreatitis (AP) in hospitalized adult patients in the United States. Subjects were obtained from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database using International Classification of Diseases, Ninth Revision, Clinical Modification codes for the years 2002-2013. Incidence of AP, all-cause mortality, cost, and duration of hospitalization were assessed. We identified 4,791,802 cases of AP. A significant increase in the incidence of AP was observed from 9.48 cases per 1000 hospitalizations in 2002 to 12.19 per 1000 hospitalizations in 2013 (P < 0.001). In-hospital mortality decreased from 2.99 cases per 100 cases in 2002 to 2.04 cases per 100 cases in 2013 (P < 0.001). Mean length of stay decreased from 6.99 (standard deviation [SD], 9.37) days in 2002 to 5.74 (SD, 7.94) days in 2013 (P < 0.001). Cost of hospitalization increased from $27,827 (SD, $54,556) in 2002 to $49,772 (SD, $106,205) in 2013 (P < 0.001). Hospital admissions for AP in adults increased significantly in the United States from 2002 to 2013. In-hospital all-cause mortality and mean length of stay significantly decreased. In contrast, total cost of hospitalization rose.


Vision therapy/orthoptics for symptomatic convergence insufficiency in children: treatment kinetics.
To evaluate the kinetics of change in symptoms and signs of convergence insufficiency (CI) during 12 weeks of treatment with commonly prescribed vision therapy/orthoptic treatment regimens. In a randomized clinical trial, 221 children aged 9 to 17 years with symptomatic CI were assigned to home-based pencil push-ups (HBPP), home-based computer vergence/accommodative therapy and pencil push-ups (HBCVAT+), office-based vergence/accommodative therapy with home reinforcement (OBVAT), or office-based placebo therapy with home reinforcement (OBPT). Symptoms and signs were measured after 4, 8, and 12 weeks of treatment. The outcome measures were the mean CI Symptom Survey (CISS), near point of convergence (NPC), positive fusional vergence (PFV), and proportions of patients who were classified as successful or improved based on a composite measure of CISS, NPC, and PFV. Only the OBVAT group showed significant improvements in symptoms between each visit (p < 0.001). Between weeks 8 and 12, all groups showed a significant improvement in symptoms. Between-group differences were apparent by week 8 (p = 0.037) with the fewest symptoms in the OBVAT group. For each group, the greatest improvements in NPC and PFV were achieved during the first 4 weeks. Differences between groups became apparent by week 4 (p < 0.001), with the greatest improvements in NPC and PFV in the OBVAT group. Only the OBVAT group continued to show significant improvements in PFV at weeks 8 and 12. The percentage of patients classified as "successful" or "improved" based on our composite measure increased in all groups at each visit. The rate of improvement is more rapid for clinical signs (NPC and PFV) than for symptoms in children undergoing treatment for CI. OBVAT results in a more rapid improvement in symptoms, NPC and PFV, and a greater percentage of patients reaching pre-determined criteria of success when compared with HBPP, HBCVAT+, or OBPT.


Perspectives on symptom control in patients receiving community palliative care.
To remain at home, terminally ill cancer patients need good symptom control and support from informal carers. Few studies have explored the influence of informal carers on symptom control and vice versa. This qualitative case study was carried out in a specialist palliative care service (SPCS) to explore the reasons why patients were admitted for inpatient care. Ten patients were systematically selected and the main carer and health professionals involved in their care were invited to participate. Semi-structured, audiotape recorded interviews were conducted and a thematic analysis performed on the transcripts, using the 'Framework' approach. The results highlight the vital role that carers play in the assessment and management of symptoms in the community. However, carers reported difficulties in knowing what to monitor, how to interpret symptoms accurately and when to inform a professional. It was also reported that medication was not taken as it was prescribed and a number of reasons were given.


Distinctive disruption patterns of white matter tracts in Alzheimer's disease with full diffusion tensor characterization.
To characterize the white matter structural changes at the tract level and tract group level, comprehensive analysis with 4 metrics derived from diffusion tensor imaging (DTI), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD), was conducted. Tract groups, namely limbic, commissural, association, and projection tracts, include white matter tracts of similar functions. Diffusion tensor imaging data were acquired from 61 subjects (26 Alzheimer's disease [AD], 11 subjects with amnestic mild cognitive impairment [aMCI], and 24 age-matched controls). An atlas-based approach was used to survey 30 major cerebral white matter tracts with the measurements of FA, MD, AxD, and RD. Regional cortical atrophy and cognitive functions of AD patients were also measured to correlate with the structural changes of white matter. Synchronized structural changes of cingulum bundle and fornix, both of which are part of limbic tract group, were revealed. Widespread yet distinctive structural changes were found in limbic, commissural, association, and projection tract groups between control and AD subjects. Specifically, FA, MD, and RD of limbic tracts, FA, MD, AxD, and RD of commissural tracts, MD, AxD, and RD of association tracts, and MD and AxD of projection tracts are significantly different between AD patients and control subjects. In contrast, the comparison between aMCI and control subjects shows disruption only in the limbic and commissural tract groups of aMCI subjects. MD values of all tract groups of AD patients are significantly correlated to cognitive functions. Difference between AD and control and that between aMCI and control indicates a progression pattern of white matter disruption from limbic and commissural tract group to other tract groups. High correlation between FA, MD, and RD measurements from limbic tracts and cortical atrophy suggests the disruption of the limbic tract group is caused by the neuronal damage.


Agents of change: how do complementary and alternative medicine providers play a role in health behavior change?
Recent investigations indicate that complementary and alternative medicine (CAM) use may be conducive to health behavior change. The goal of this study was to investigate how this change occurs. Using Social Cognitive Theory and Self-determination Theory as guiding frameworks, we surveyed a convenience sample of 216 CAM consumers abouttheir CAM therapy and iors and conducted focus groups with 36 CAM consumers. Consumers reported encouragement from providers and improved energy resulting from treatments as reasons for making health behavior changes. Multivariate analysis showed that increased odds of self-reported dietary change were significantly associated with increasing body awareness as a result of therapy, endorsing the statement that sustained improvement for their health conditions required self-care, using an acupuncturist, and being 44 years or younger. Comparable results were found for exercise change, except using an acupuncturist was a significant negative predictor and age was not significant. Focus group findings echoed these themes. This initial investigation into how CAM providers may play a role in health behavior change suggests that provider support, increased responsibility for one's health, and the CAM treatments themselves contribute to behavior change, although additional research in this area is warranted.


Subnormal concentrations of serum cobalamin (vitamin B12) in cats with gastrointestinal disease.
The present study sought to determine the spectrum of diseases associated with subnormal concentrations of serum cobalamin in cats undergoing investigation of suspected gastrointestinal problems. The solid-phase boil radioassay (RA) for cobalamin employed in the present study was immunologically specific, precise, and accurate, with a sensitivity of 15 pg/mL. The RA yielded results that strongly correlated with those obtained by bioassay (Spearmann rho = .805; P < .0001), although the absolute values were lower for the RA. Forty-nine of 80 serum samples submitted during the period of January 1996-January 1998 had cobalamin concentrations below the reference range for healthy cats (range 900-2,800 pg/mL; mean +/- SD, 1,775 +/- 535 pg/mL; n = 33). Cats with subnormal cobalamin concentrations (mean +/- SD; 384 +/- 272 pg/mL, range 3-883 pg/mL) were middle-aged or older and were presented for weight loss. diarrhea, vomiting, anorexia, and thickened intestines. Definitive diagnoses in 22 cats included inflammatory bowel disease (IBD), intestinal lymphoma, cholangiohepatitis or cholangits, and pancreatic inflammation. Serum concentrations of cobalamin were particularly low in cats with intestinal lymphoma, three-fifths of whom also had subnormal serum concentrations of folate (< 9 ng/mL). The simultaneous presence of disease in the intestines, pancreas, or hepatobiliary system in many cats made it difficult to determine the cause of subnormal cobalamin concentrations. The circulating half-life of parenteral cyanocobalamin was shorter in 2 cats with IBD (5 days) than in 4 healthy cats (12.75 days). The presence of subnormal serum concentrations of cobalamin in 49 of 80 cats evaluated suggests that the measurement of serum cobalamin may be a useful indirect indicator of enteric or pancreatic disease in cats. The rapid depletion of circulating cobalamin in cats suggests that cats may be highly susceptible to cobalamin deficiency. However, the relationship of subnormal serum cobalamin concentrations to cobalamin deficiency and the effect of cobalamin deficiency on cats remain to be determined.


Role of cell walls in the bioaccessibility of lipids in almond seeds.
Certain nutrients and phytochemicals in almonds may confer protection against cardiovascular disease, but little is known about factors that influence their bioavailability. A crucial and relevant aspect is the amount of these dietary components available for absorption in the intestine, which is a concept referred to as bioaccessibility. We investigated the role played by cell walls in influencing the bioaccessibility of intracellular lipid from almond seeds. Quantitative analyses of nonstarch polysaccharides (NSPs) and phenolic compounds of cell walls were performed by gas-liquid chromatography and HPLC, respectively. In a series of experiments, the effects of mechanical disruption, chewing, and digestion on almond seed microstructure and intracellular lipid release were determined. In the digestibility study, fecal samples were collected from healthy subjects who had consumed diets with or without almonds. Almond seeds and fecal samples were examined by microscopy to identify cell walls and intracellular lipid. Cell walls were found to be rich in NSPs, particularly arabinose-rich polysaccharides, with a high concentration of phenolic compounds detected in the seed coat cell wall. During disruption of almond tissue by mechanical methods or chewing, only the first layer of cells at the fractured surface was ruptured and able to release lipid. In fecal samples collected from subjects consuming the almond diet, we observed intact cotyledonary cells, in which the cell walls encapsulated intracellular lipid. This lipid appeared susceptible to colonic fermentation once the cotyledonary cell walls were breached by bacterial degradation. The cell walls of almond seeds reduce lipid bioaccessibility by hindering the release of lipid available for digestion.


Systematic Review of the Effects of Ultraviolet Radiation on Markers of Metabolic Dysfunction.
Emerging findings suggest that exposure to ultraviolet wavelengths of sunlight modulates metabolic function. Here we review the metabolic effects of exposure to ultraviolet radiation (UVR), focusing on the effects of phototherapies (that administer UVR), and advice to increase sun exposure in individuals enrolled in clinical trials and intervention studies. We identified 25 studies in which the effects of UVR on metabolic outcomes were examined, including: narrowband ultraviolet B phototherapy (nbUVB, n = 12); psoralen ultraviolet A phototherapy (n = 4); other types of UVR phototherapy (n = 5); and sun exposure advice (n = 5). Most studies recruited a small number of participants (≤100), who were middle-aged individuals undergoing treatment for psoriasis flare, with phototherapy or sun exposure advice administered for ≤12 weeks. Data obtained at baseline were usually compared with an endpoint following treatment with UVR, for a limited number of outcomes. There were few studies in which markers of glucose metabolism were assessed, with some beneficial effects of sun exposure (but not phototherapy) reported. LDL-cholesterol levels were lower in individuals receiving sun exposure advice, while treatment with nbUVB reduced blood concentrations of inflammatory markers (C-reactive protein and interleukin-6). Future studies should focus on determining whether the effects of these interventions change with time, and if they are dependent on the source of UVR (i.e. phototherapy or sun exposure) and wavelength(s) of light administered. Furthermore, studies need to measure a variety of (clinical) markers of glucose metabolism, adiposity and inflammation, control for factors such as skin type and sex, and stratify participants for metabolic disease diagnosis.


Screening, morphological and molecular characterization of fungi producing cystathionine γ-lyase.
The potency for production of cystathionine γ-lyase (CGL) by the fungal isolates was screened. Among the tested twenty-two isolates, Aspergillus carneus was the potent CGL producer (6.29 U/mg), followed by A. ochraceous (6.03 U/mg), A. versicolor (2.51 U/mg), A. candidus (2.12 U/mg), A. niveus and Penicillium notatum (2.0 U/mg). The potent six isolates producing CGL was characterized morphologically, A. carneus KF723837 was further molecularly characterized based on the sequence of 18S-28S rDNA. Upon sulfur starvation, the yield of A. carneus extracellular CGL was increased by about 1.7- and 4.1-fold comparing to non-sulfur starved and L-methionine free medium, respectively. Also, the uptake of L-methionine was duplicated upon sulfur starvation, assuming the activation of specific transporters for L-methionine and efflux of CGL. Also, the intracellular thiols and GDH activity of A. carneus was strongly increased by S starvation, revealing the activation of in vivo metabolic antioxidant systems. Upon irradiation of A. carneus by 2.0 kGy of γ-rays, the activity of CGL was increased by two-fold, regarding to control, with an obvious decreases on its yield upon further doses. Practically, CGL activity from the solid A. carneus cultures, using rice bran as substrate, was increased by 1.2-fold, comparing to submerged cultures, under optimum conditions.


The mouse bioassay for the detection of estrogenic activity in rodent diets: I. A standardized method for conducting the mouse bioassay.
A standardized procedure was developed for conducting the mouse bioassay for detecting estrogenic activity in rodent diets. Studies were conducted with CD-1 mice to determine the appropriate weaning age and length of bioassay period. Uterine growth curves were generated from mice weaned at 15 days of age and fed a negative control diet until 28 days of age. These mice showed slow regular increases in uterine weights from 15 22 days of age followed by rapid uterine growth in some mice from 24 to 28 days of age. Estrogenic bioassays using female mice weaned at 15 days of age and fed the positive control diets containing 4 or 6 ppb diethylstilbestrol (DES) demonstrated significant (P less than 0.05) increases in uterine weight and in uterus to body weight (U:BW) ratios over those of mice fed the negative control diet without DES for 5, 7 or 9 days after weaning. In contrast, mice weaned at 17 days of age showed significant (P less than 0.05) increases in uterine weight and in U:BW ratios only at 5 days after weaning. Six ppb DES was required in the positive control diet to produce a 1.5 fold increase in the U:BW ratio over those of mice fed the negative control diet. It was concluded that mice should be weaned at 15 days of age and that the bioassay period should be terminated at 7 days, when the mice are 22 days old, for best reproducible results. The criteria for a valid bioassay should include the demonstration of a significant statistical increase in the U:BW ratios of mice fed the DES positive diet over those of mice fed the negative control diet.


Estimates of the number of US women who could benefit from tamoxifen for breast cancer chemoprevention.
The Breast Cancer Prevention Trial demonstrated that tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer among women at elevated risk for the disease. The U.S. Food and Drug Administration (FDA) subsequently approved tamoxifen for women aged 35 years or older with a 5-year breast cancer risk of 1.67% or higher for breast cancer chemoprevention. However, tamoxifen use has been associated with adverse outcomes, and not all eligible women have a positive benefit/risk ratio. We used weighted data from the year 2000 National Health Interview Survey Cancer Control Module to estimate the total number of U.S. women, aged 35-79 years, who were eligible for tamoxifen chemoprevention based on the FDA eligibility criteria. We also estimated the numbers of white and black women who would benefit from tamoxifen chemoprevention on the basis of a positive benefit/risk index developed by Gail et al. Of the 65,826,074 women aged 35-79 years without reported breast cancer in the United States in 2000, 10,232 816 women (15.5%, 95% confidence interval [CI] = 14.7% to 16.3%) would be eligible for tamoxifen chemoprevention. The percentage of U.S. women who would be eligible varied dramatically by race, with 18.7% (95% CI = 17.8% to 19.7%) of white women, 5.7% (95% CI = 4.3% to 7.5%) of black women, and 2.9% (95% CI = 2.1% to 3.9%) of Hispanic women being eligible. Of the 50,104,829 white U.S. women aged 35-79 years, 2,431,911 (4.9%, 95% CI = 4.3% to 5.4%) would have a positive benefit/risk index for tamoxifen chemoprevention. Of the 7,481,779 black U.S. women aged 35-79 years, only 42,768 (0.6%, 95% CI = 0.2% to 1.3%) would have a positive benefit/risk index. Among white women, 28,492 (95% CI = 24,693 to 32,292) breast cancers would be prevented or deferred if those women who have a positive net benefit index took tamoxifen over the next 5 years. A substantial percentage of U.S. women would be eligible for tamoxifen chemoprevention according to FDA criteria, but a much smaller percentage would have an estimated net benefit. Nevertheless, this latter percentage corresponds to more than two million women.


Preliminary Results of Laser Ablation during In Vivo Experiments: Comparison of Thermal Effects Obtained with Bare and Diffuser Tip Applicators.
This work is a step towards the analysis of the effect of different laser applicator tips used for laser ablation of liver for in vivo experiments. As the thermal outcome of this minimally invasive treatment for tumors depends upon the interaction between the tissue and the light, the emission pattern of the laser applicator has a key role in the shape and size of the final treated region. Hence, we have compared two different laser applicators: a bare tip fiber (emitting light from the tip and forward) and a diffuser tip fiber (emitting light at 360° circumferentially from the side of the fiber). The experiments have been carried out percutaneously in a preclinical scenario (anesthetized pigs), under computed tomography (CT) guidance. The thermal effects of the two applicators have been assessed in terms of real-time temperature distribution, by means of an array of 40 fiber Bragg grating (FBG) sensors, and in terms of cavitation and ablation volumes, measured through CT post-temperature due to breathing motion has been analyzed and filtered out. Results show that the maximum temperature reached 50.5 °C for the bare tip fiber experiment (measured at 6.24 mm distance from the applicator) and 60.9 °C for the diffuser tip fiber experiment (measured at 5.23 mm distance from the applicator). The diffuser tip fiber allowed to achieve a more symmetrical heat distribution than the bare tip fiber, and without cavitation volume.Clinical Relevance-This work shows the analysis of the thermal effects of different laser fiber tips to improve laser ablation treatment. The results obtained in the preclinical scenario well represent the expected clinical outcome in the treatment of hepatic tumors. Moreover, these findings can be applied to other fields in which laser ablation is the optimal therapeutic choice, such as neurosurgery.


[Bimodal changes in germinability of pea seeds under the influence of low doses of gamma-radiation].
Pea seeds (cv. 'Nemchinovskii-85', harvest of 2002, 80%-germination percentage) were exposed to gamma-radiation with doses ranging from 19 cGy to 100 Gy. One week after the irradiation with doses of 19 cGy and 3 Gy. the germination percentage decreased to 58 and 45%, respectively; at doses of 7 and 10 Gy it was 73 and 70% respectively. At greater doses (25, 50, and 100 Gy), germination percentage decreased in proportion. Anomalous changes in seed germination percentage (as a function of irradiation dose) were caused by the redistribution of irradiated seeds between fractions I and II. The measurements of room temperature phosphorescence in air-dry seeds and the phosphorescence of endogenous porphyrines of imbibing seeds showen that the germination decrease after the irradiation with low doses (19 cGy and 3 Gy) was caused by the increase in the number of weak seeds of fraction II, which had high rates of water uptake and suffered from hypoxia under seed coat. Some of these seeds suffocated from hypoxia, and other seeds produced seedlings with morphological defects (such seeds were considered incapable of germination). During storage of seeds irradiated at doses 19 cGy-10 Gy, the recovery of germination percentage (after its initial decrease) was caused by the decrease in seed number in fraction II. The subsequent germination decrease was caused by seed death. The higher was the irradiation dose, the faster were changes in germination percentage during storage of irradiated seeds. Bimodal changes in pea seed germination with the increase of y-irradiation dose has apparently the same origin as the changes in seed germination during accelerated ageing.


Measuring health-related quality of life in patients with irritable bowel syndrome: can less be more?
This study assessed the ability of a brief, well-validated generic health-related quality of life (HRQOL) measure to characterize the symptom burden of patients with irritable bowel syndrome (IBS) with reference to a large survey of U.S. community-living adults. One hundred four Rome II diagnosed patients with IBS completed measures of pain, psychological dysfunction (neuroticism, somatization, distress, abuse), and HRQOL (SF-36, IBS-QOL, CDC HRQOL-4) during baseline assessment of a National Institutes of Health-funded clinical trial. The four-item CDC HRQOL-4 assesses global health and the number of days in the past 30 days resulting from poor physical health, poor mental health, and activity limitation. Patients with IBS averaged 15 of 30 days with poor physical or mental health. These average overall unhealthy days exceeded those of respondents with arthritis, diabetes, heart disease/stroke, cancer, and class III obesity (body mass index > or =40 kg/m2) from the U.S. survey. Fifteen percent of patients identified musculoskeletal disorders, not IBS symptoms, as the major cause of their activity limitation. Overall unhealthy days among patients with IBS varied directly with IBS symptom severity, abuse, pain, and psychological distress. Controlling for personality variables that influence perception and reporting HRQOL did not diminish the statistical significance of associations between the CDC HRQOL-4 and other study measures. The CDC HRQOL-4 is a psychometrically sound, rapid, and efficient instrument whose HRQOL profile reflects the symptom burden of moderate-to-severe IBS, is sensitive to treatment effects associated with cognitive behavior therapy, and is not a proxy for personality variables identified as potential confounders of HRQOL. HRQOL is related to but not redundant with psychological distress.


Magnetic resonance assessment of cerebral perfusion in depressed cardiac patients: preliminary findings.
The authors investigated the links between depression, cardiac disease, and microcirculatory cerebral blood flow (CBF). A magnetic resonance imaging technique based on arterial spin tagging was used to estimate microcirculatory CBF in depressed (N = 5) and comparison (N = 14) elderly subjects with coronary artery disease. Signal intensity ratios corresponding to relative microcirculatory CBF were calculated for four regions on two axial images through the upper and lower halves of the lateral ventricles. On the superior image, estimates of microcirculatory CBF were statistically significantly lower on the left side in the depressed subjects than in the nondepressed group. When the ratios in the superior and inferior images were averaged, the depressed subjects had lower values for both left periventricular regions of interest and the parietal region. Despite the small study group and indirect estimates of blood flow, these preliminary findings suggest that a relative cerebral hypoperfusion may underlie depression in elderly cardiac patients.


Ultrasound Imaging Characterization of Soft Tissue Dynamics of the Seated Human Body.
To characterize the dynamics of internal soft organs and external anatomical structures, this paper presents a system that combines medical ultrasound imaging with an optical tracker and a vertical exciter that imparts whole-body vibrations on seated subjects. The spatial and temporal accuracy of the system was validated using a phantom with calibrated internal structures, resulting in 0.224 mm maximum root-mean-square (r.m.s.) position error and 13 ms maximum synchronization error between sensors. In addition to the dynamics of the head and sternum, stomach dynamics were characterized by extracting the centroid of the stomach from the ultrasound images. The system was used to characterize the subject-specific body dynamics as well as the intrasubject variabilities caused by excitation pattern (frequency up-sweep, down-sweep, and white noise, 1-10 Hz), excitation amplitude (1 and 2 m/s2 r.m.s.), seat compliance (rigid and soft), and stomach filling (empty and 500 mL water). Human subjects experiments (n = 3) yielded preliminary results for the frequency response of the head, sternum, and stomach. The method presented here provides the first detailed in vivo characterization of internal and external human body dynamics. Tissue dynamics characterized by the system can inform design of vehicle structures and adaptive control of seat and suspension systems, as well as validate finite element models for predicting passenger comfort in the early stages of vehicle design.


Scattered-wave-packet formalism with applications to barrier scattering and quantum transistors.
The scattered wave formalism developed for a quantum subsystem interacting with reservoirs through open boundaries is applied to one- or two-dimensional barrier scattering and quantum transistors. The total wave function is divided into incident and scattered components. Markovian outgoing wave boundary conditions are imposed on the scattered or total wave function by either the ratio or polynomial methods. For barrier scattering problems, accurate time-dependent transmission probabilities are obtained through the integration of the modified time-dependent Schrödinger equations for the scattered wave function. For quantum transistors, the time-dependent transport is studied for a quantum wave packet propagating through the conduction channel of a field effect transistor. This study shows that the scattered wave formalism significantly reduces computational effort relative to other open boundary methods and demonstrates wide applications to quantum dynamical processes.


Depressive symptoms, insulin resistance, and risk of diabetes in women at midlife.
To examine depression and 3-year change in insulin resistance and risk of diabetes and whether associations vary by race. We analyzed data from 2,662 Caucasian, African-American, Hispanic, Japanese-American, and Chinese-American women without a history of diabetes from the Study of Women's Health Across the Nation. We estimated regression coefficients and odds ratios to determine whether depression (Center for Epidemiological Studies Depression Scale score > or =16) predicted increases in homeostasis model assessment of insulin resistance (HOMA-IR) and greater risk of incident diabetes, respectively, over 3 years. Mean baseline HOMA-IR was 1.31 (SD 0.86) and increased 0.05 units per year for all women (P <0.0001). A total of 97 incident cases of diabetes occurred. Depression was associated with absolute levels of HOMA-IR (P <0.04) but was unrelated to changes in HOMA-IR; associations did not vary by race. The association between depression and HOMA-IR was eliminated after adjustment for central adiposity (P=0.85). Depression predicted a 1.66-fold greater risk of diabetes (P <0.03), which became nonsignificant after adjustment for central adiposity (P=0.12). We also observed a depression-by-race interaction (P <0.05) in analyses limited to Caucasians and African Americans, the only groups with enough diabetes cases to reliably test this interaction. Race-stratified models showed that depression predicted 2.56-fold greater risk of diabetes in African Americans only, after risk factor adjustment (P=0.008). Depression is associated with higher HOMA-IR values and incident diabetes in middle-aged women. These associations are mediated largely through central adiposity. However, African-American women with depression experience increased risk of diabetes independent of central adiposity and other risk factors.


Relation between psychosomatic disturbances and job stress in video display unit operators.
Some psychosomatic disturbances have been related to protracted video display unit (VDU) use at work, and they may be associated with job stress. This study aimed at assessing the association between psychosomatic disturbances with job-related and subjective stress in 990 VDU. Job stress was evaluated by Karasek's Questionnaire, psychological job demands and job decision latitude scores were calculated. Workers were assigned to four categories: high-strain job, low-strain job, active job, and passive job. Subjective perception of stress was evaluated with the Rapid Stress Assessment Scale. None of the psychosomatic disturbances investigated were associated with higher psychological job demands scores, whereas many of them were significantly related to lower job decision latitude scores and high-strain jobs. All psychosomatic disturbances were significantly associated with personal stress. Logistic regression confirms the protective role of job decision latitude on headache, fatigue, intestinal gas, disturbed sleep and the significant role of subjective stress on all psychosomatic disturbances studied. Whereas subjective stress is harmful, job decision latitude is a protective factor for several psychosomatic disturbances reported by VDU operators. Improvement in the job decision latitude might be a preventive specific measure in work planning to reduce possible stress-related disorders.


Multiple versus single dose natural surfactant extract for severe neonatal respiratory distress syndrome.
This section is under preparation and will be included in the next issue. To compare the effect of multiple doses of natural surfactant extract to single doses of natural surfactant extract in premature infants with established respiratory distress syndrome. Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn infant; publication type, clinical trials), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal hand searching in the English language. Randomized controlled trials comparing a policy of multiple doses of natural surfactant extract to a policy of single doses of natural surfactant extract in premature infants with respiratory distress syndrome were considered for this review. Data on clinical outcomes including pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage (all intraventricular hemorrhage and severe intraventricular hemorrhage), chronic lung disease, retinopathy of prematurity, and mortality were excerpted by the primary reviewer (R. Soll). Data were analyzed according to the standards of the Neonatal Cochrane Review Group. Two randomized controlled trials of multiple vs. single dose natural surfactant extract in infants with established respiratory distress syndrome were identified. Meta-analysis of these trials suggests a reduction in the risk of pneumothorax (typical relative risk 0.51, 95% CI 0.30, 0.88; typical risk difference-0.09, 95% CI -0.15, -0. 02) and a trend towards a reduction in mortality (typical relative risk 0.63, 95% CI 0.39, 1.02; typical risk difference -0.07, 95% CI -0.14, 00.00). No complications associated with multiple dose treatment are reported in the identified trials. In infants with established respiratory distress, a policy of multiple doses of natural surfactant extract results in greater improvements regarding oxygenation and ventilatory requirements, a decreased risk of pneumothorax and a trend toward improved survival. The ability to give multiple doses of surfactant to infants with ongoing respiratory insufficiency leads to improved clinical outcome and appears to be the most effective treatment policy.


Lactate dehydrogenase-elevating virus infection: an experimental model of immune microenvironment modulation.
Lactate dehydrogenase-elevating virus (LDV), a mouse arterivirus, is characterized by a lifelong viremia, despite antiviral innate and adaptative immune response. It induces strong modifications of the host immune microenvironment, including macrophage and natural killer cell activation, secretion of pro-inflammatory cytokines, modulation of T helper cell differentiation and polyclonal activation of B-lymphocytes. This modification of the immune microenvironment results in the protection against some diseases such as allergies, graft-versus-host reaction, experimental autoimmune encephalitis, and growth of some tumors. In contrast, it exacerbates other pathologies such as endotoxin shock and autoantibody-mediated autoimmune diseases. Thus, LDV infection provides an interesting model to understand the consequences of viral infections on pathogenic mechanisms and to define new therapeutic approaches.


Effect of absolute and relative loading on muscle activity during stable and unstable squatting.
The purpose of this investigation was to determine the effect of stable and unstable conditions on one repetition maximum strength and muscle activity during dynamic squatting using absolute and relative loading. Ten recreationally weight-trained males participated in this study (age = 24.1 +/- 2.0 y, height = 178.0 +/- 5.6 cm, body mass = 83.7 +/- 13.4 kg, 1RM/body mass = 1.53 +/- 0.31), which involved two laboratory sessions separated by 1 wk. Linear position transducers were used to track bar displacement while subjects stood on a force plate for all trials. Vastus lateralis (VL), biceps femoris (BF) and erector spinae (L1) muscle activity (average integrated EMG [IEMG]) was also recorded during all trials. During the first session subjects complete a one repetition maximum test in a stable dynamic squat (S1RM = 128.0 +/- 31.4 kg) and an unstable dynamic squat (U1RM = 83.8 +/- 17.3 kg) in a randomized order with a 30-min rest period between conditions. The second session consisted of the performance of three trials each for 12 different conditions (unstable and stable squats using three different absolute loads [six conditions] and unstable and stable squats using three different relative loads [six conditions]). Results revealed a statistically significant difference between S1RM and U1RM values (P < or = .05). The stable trials resulted in the same or a significantly higher value for VL, BF and L1 muscle activity in comparison with the unstable trials for all twelve conditions. Unstable squatting is of equal or less (depending on the loading condition) benefit to improving or maximizing muscle activity during resistance exercise.


Thermoacoustic tomography forward modeling with the spectral element method.
A thermoacoustic tomography (TAT) forward solver based on the spectral element method (SEM) with perfectly matched layer absorbing boundary condition has been developed. The TAT forward solver is intended to model acoustically inhomogeneous media with high accuracy in the frequency domain. The high-order basis functions used in the SEM are Gauss-Lobatto-Legendre (GLL) polynomials. Due to the orthogonality of the GLL basis functions and GLL quadrature integration, the mass matrix is diagonal and the stiffness matrix is sparse. Thus, the proposed method greatly reduces the memory requirement and computational time in comparison with the conventional finite element method (FEM). Numerical results show that the high-order SEM is able to achieve the same accuracy as the FEM but with a much smaller number of unknowns. Therefore, the TAT forward solver based on SEM is able to simulate a large-scale and realistic TAT problem.


An incomplete pentalogy of Cantrell.
Pentalogy of Cantrell is a rare entity of congenital defects involving the abdominal wall, sternum, diaphragm, pericardium and heart. The complete pentalogy and its variants have been described in the literature. We report a 47-day-old girl with an incomplete pentalogy of Cantrell presenting with congenital absence of the sternum, congenital heart defects, and an epigastric hernia. Two even rarer expressions of this disorder, tricuspid atresia type IIc and asymmetric kidneys, were also found. The patient was successfully managed with palliative pulmonary artery banding as preparation for a modified Fontan operation when she is older. We report this rare case, and discuss the pathologic findings and surgical strategy.


Eye movement correlates of acquired central dyslexia.
Based on recent progress in theory and measurement techniques, the analysis of eye movements has become one of the major methodological tools in experimental reading research. Our work uses this approach to advance the understanding of impaired information processing in acquired central dyslexia of stroke patients with aphasia. Up to now there has been no research attempting to analyze both word-based viewing time measures and local fixation patterns in dyslexic readers. The goal of the study was to find out whether specific eye movement parameters reflect pathologically preferred segmental reading in contrast to lexical reading. We compared oral reading of single words of normal controls (n=11) with six aphasic participants (two cases of deep, surface and residual dyslexia each). Participants were asked to read aloud lines of target words differing in length and frequency. Segmental reading was characterized by deviant spatial distribution of saccadic landing positions with initial fixations located mainly at the beginning of the word, while lexical readers showed the normative 'preferred landing positions' left to the center of the words. Contrary to expectation, word length did not distinguish between segmental and lexical readers, while word frequency showed the expected effect for lexical readers only. Their mean fixation duration was already prolonged during first pass reading reflecting their attempts of immediate access to lexical information. After first pass reading, re-reading time was significantly increased in all participants with acquired central dyslexia due to their exceedingly higher monitoring demands for oral reading.


HIF-1 alpha is required for solid tumor formation and embryonic vascularization.
The transcriptional response to lowered oxygen levels is mediated by the hypoxia-inducible transcription factor (HIF-1), a heterodimer consisting of the constitutively expressed aryl hydrocarbon receptor nuclear translocator (ARNT) and the hypoxic response factor HIF-1alpha. To study the role of the transcriptional hypoxic response in vivo we have targeted the murine HIF-1alpha gene. Loss of HIF-1alpha in embryonic stem (ES) cells dramatically retards solid tumor growth; this is correlated with a reduced capacity to release the angiogenic factor vascular endothelial growth factor (VEGF) during hypoxia. HIF-1alpha null mutant embryos exhibit clear morphological differences by embryonic day (E) 8.0, and by E8.5 there is a complete lack of cephalic vascularization, a reduction in the number of somites, abnormal neural fold formation and a greatly increased degree of hypoxia (measured by the nitroimidazole EF5). These data demonstrate the essential role of HIF-1alpha in controlling both embryonic and tumorigenic responses to variations in microenvironmental oxygenation.


Poly(3-hydroxybutyrate)/ZnO bionanocomposites with improved mechanical, barrier and antibacterial properties.
Poly(3-hydroxybutyrate) (PHB)-based bionanocomposites incorporating different contents of ZnO nanoparticles were prepared via solution casting technique. The nanoparticles were dispersed within the biopolymer without the need for surfactants or coupling agents. The morphology, thermal, mechanical, barrier, migration and antibacterial properties of the nanocomposites were investigated. The nanoparticles acted as nucleating agents, increasing the crystallization temperature and the degree of crystallinity of the matrix, and as mass transport barriers, hindering the diffusion of volatiles generated during the decomposition process, leading to higher thermal stability. The Young's modulus, tensile and impact strength of the biopolymer were enhanced by up to 43%, 32% and 26%, respectively, due to the strong matrix-nanofiller interfacial adhesion attained via hydrogen bonding interactions, as revealed by the FT-IR spectra. Moreover, the nanocomposites exhibited reduced water uptake and superior gas and vapour barrier properties compared to neat PHB. They also showed antibacterial activity against both Gram-positive and Gram-negative bacteria, which was progressively improved upon increasing ZnO concentration. The migration levels of PHB/ZnO composites in both non-polar and polar simulants decreased with increasing nanoparticle content, and were well below the current legislative limits for food packaging materials. These biodegradable nanocomposites show great potential as an alternative to synthetic plastic packaging materials especially for use in food and beverage containers and disposable applications.


Binding sites for carrier-immobilized carbohydrates in the kidney: implication for the pathogenesis of Henoch-Schönlein purpura and/or IgA nephropathy.
Henoch-Schönlein purpura is a common vasculitis of childhood affecting the skin, joints, gastrointestinal tract, and kidney. The mesangial deposition of IgA1 is the most critical factor for the prognosis of patients with this disease. The aberrant glycosylation of the IgA1 subclass with the absence of terminally located galactose and presence of only alpha-N-acetylgalactosamine in O-linked oligosaccharides in the hinge region of IgA1 represents a prominent difference from the normal IgA1. These alterations prompt the supposition that the sugar part may guide IgA deposition by recognition of endogenous lectins on the mesangium. Owing to the limited knowledge about the expression of carbohydrate-binding sites in the human kidney we initiated the study of this aspect with a class of tools which are suitable to map the lectinome of cells. Employing biotinylated neoglycoconjugates, glycosaminoglycans, and sulphated polysaccharides we monitored the presence of accessible carbohydrate-binding sites in control kidneys represented by tumour-free areas of kidneys with Grawitz tumour and in biopsies from patients with Henoch-Schönlein purpura-associated IgA nephropathy. Using frozen sections, no expression of any tested carbohydrate-binding site(s) was observed in the endothelial and the mesangial cells in glomeruli of the control kidneys as well as in the biopsies from Henoch-Schönlein purpura IgA nephropathic kidneys, in contrast to the tubules. The N-acetylgalactosamine-binding sites were expressed only in the inner layer of Bowman's capsule of 20% of glomeruli of the control kidney from one patient with Grawitz tumour and one biopsy from a patient with Henoch-Schönlein purpura-associated IgA nephropathy. However, the macrophages in the glomeruli of patients with IgA nephropathy and interstitial macrophages from both studied groups, i.e. without and with IgA nephropathy, harbour capacity to recognize carrier-immobilized alpha-N-acetylgalactosamine. Access to this binding site for the neoligand conjugate can be blocked by the monoclonal antibody MEM-18 recognizing CD14 antigen. The possibility for a participation of macrophage deposition of IgA1 in mesangium via a lectin mechanism involving this binding capacity warrants further studies.


Detection of mutations in SF3B1, EIF1AX and GNAQ in primary orbital melanoma by candidate gene analysis.
Ocular melanoma is a rare but often deadly malignancy that arises in the uvea (commonest primary site), conjunctiva or the orbit. Primary orbital melanoma (POM) is exceedingly rare, with approximately 60 cases reported to date. Despite recent advances in our understanding of the genetics of primary uveal and conjunctival melanomas, this information is lacking for POM. DNA was extracted from 12 POM tissues, with matched germline DNA (where available). MLPA was conducted to detect chromosomal alterations and Sanger sequencing used to identify point mutations in candidate melanoma driver genes (BRAF, NRAS, KRAS, GNA11, GNAQ), and other genes implicated in melanoma prognosis (EIF1AX, SF3B1). Immunohistochemistry was performed to analyse BAP1 nuclear expression. MLPA detected copy number alterations in chromosomes 1p, 3, 6 and 8. Sequencing of melanoma driver genes revealed GNAQ (p.Q209L) mutations in two samples; although it is possible that these samples represent extraocular spread of an occult uveal melanoma. A recurrent mutation in SF3B1 (p.R625H) was observed in indolent, but not aggressive, tumours; a mutation in EIF1AX (p.N4S) was detected in one patient with non-aggressive disease. EIF1AX and SF3B1 mutations appear have a role in determining the clinical course of POM and detection of these changes could have clinical significance. Further in depth analysis of this rare group using differing 'omic technologies will provide novel insights into tumour pathogenesis.


Long-term modulation of type L pyruvate kinase activity in young and mature rats.
The regulation of type L pyruvate kinase concentrations in liver of young (35-45 days old) and adult (60-85 days old) rats starved and re-fed a 71% sucrose diet was investigated. Re-feeding is accompanied by an increase in the enzyme level in liver determined kinetically and immunologically. A constant ratio of kinetic activity to immunological activity was observed under all conditions examined, indicating that activity changes are the result of a regulation of synthesis or degradation and not an interconversion between kinetically active and inactive forms of the enzyme. Synthesis of pyruvate kinase was directly examined by using hepatocytes isolated from starved and re-fed rats. A stimulation of pyruvate kinase synthesis is observed on re-feeding. This increase in synthesis of pyruvate kinase is retained by the isolated hepatocyte for up to 7h in the absence of hormonal stimuli. Administration of glucagon (1mum) to the isolated hepatocytes had no influence on synthesis of pyruvate kinase and no evidence for a glucagon-directed degradation of the enzyme was found. Re-feeding the rat was followed by a transient increase in the synthesis of pyruvate kinase. The peak rate of synthesis was observed before a detectable increase in the enzyme concentration. After a rapid synthesis period, a new steady-state level of the enzyme was achieved and synthesis rates declined. The time course and magnitude for the response to the sucrose diet was dependent on the age of the rat. In young rats, an increase in pyruvate kinase synthesis is observed within 6h and peak synthesis occurs at 11h after re-feeding sucrose. The peak synthesis rate for pyruvate kinase for young rats represents approx. 1% of total protein synthesis. With adult rats, increased pyruvate kinase synthesis is not observed for 11h, with peak synthesis occurring at 24h after re-feeding. In the older rats, peak pyruvate kinase synthesis constitutes greater than 4% of total protein synthesis. Continued re-feeding of the adult rat beyond 24h is accompanied by a decline of pyruvate kinase synthesis to approx. 1.5% of total protein synthesis. The concentration of the enzyme, however, does not decline during this period, suggesting that control of pyruvate kinase degradation as well as synthesis occurs.


Hypnosis, attachment, and oxytocin:an integrative perspective (1.).
This article considers links between clinical hypnosis, attachment theory, and oxytocin. First, it proposes that commonalities between clinical hypnosis and attachment theory may improve our understanding of the hypnotherapeutic process. Then, it suggests that an integrative model unifying clinical hypnosis and attachment theory may constitute a link between clinical hypnosis and a neurobiological factor such as oxytocin. Finally, it discusses the implications of these hypotheses for clinical practice and future researches.


Medical management in the acute hip fracture patient: a comprehensive review for the internist.
Each year, more than 250,000 Americans will suffer a broken hip from a fall from no more than standing height. The National Osteoporosis Foundation estimates that more than 500,000 acute hip fractures will occur annually by the year 2040. The costs associated with this healthcare phenomenon are staggering and will continue to increase with an aging population.Hospitalists routinely comanage orthopedic patients as either consultants or as primary physicians in the hospital setting. A unique set of problems exists in this population. Among them are perioperative cardiac risk, perioperative anemia from acute blood loss, venous thromboembolism prophylaxis, and problems with the timing of surgery. It is imperative that hospitalists understand the orthopedic surgeon's point of view in managing these particular problems and become familiar with the evidence supporting or refuting treatment modalities related to these subject areas. In addition, an understanding of the anatomy and surgical options and complications related to each type of fracture allows the hospitalist to become familiar with postoperative rehabilitation needs. It cannot be overstated that addressing hip fracture prevention must be a part of every patient's perioperative care because the incidence of a repeat fracture is significant. Morbidity related to the fracture and comorbidities also need close examination.This article aims to provide a solid understanding of the issues associated with the acute hip fracture population to enhance practice and allow for the best outcome for patients.


ampC gene expression in promoter mutants of cefoxitin-resistant Escherichia coli clinical isolates.
Reverse transcriptase polymerase chain reaction was used to determine the amount of overexpression of the ampC gene in 52 cefoxitin-resistant Escherichia coli clinical isolates that had previously characterized mutations in their ampC promoter/attenuator regions. The results showed that mutations that create a consensus -35 box (TTGACA) are the most important factor in strengthening the ampC promoter, followed by base pair insertions that increase the distance between the -35 and -10 boxes to 17 or 18 bp. Mutations in the -10 box are of lesser importance and those in the attenuator region appear to have little effect on ampC expression. Three strains overexpress ampC due to the effect of insertion elements located in the ampC promoter regions. Further, the data show that there is no correlation between ampC overexpression and the minimum inhibition concentration of cefoxitin in clinical isolates. Overall, the data indicate that a combination of ampC promoter mutations and other strain-specific factors combine to contribute to the magnitude of cefoxitin resistance in E. coli.


Persistent hyperprolactinemia and bilateral galactocele in a male infant.
Galactocele is a benign breast lesion, usually occurring in nursing women. This lesion is a rare cause of breast enlargement in children. In this paper we describe the case of an infant with hyperprolactinemia (which persisted throughout 15 years of clinical observation) and bilateral galactocele. We speculate that a congenital midline defect in our patient might have impaired the normal dopaminergic inhibitory tone on pituitary lactotroph cells, thus leading to an increased prolactin secretion by the pituitary gland; this, in turn, might have favored the development of the galactocele.


Inhibitory effects of ubiquitination of synoviolin by PADI4.
Rheumatoid arthritis (RA) is a chronic inflammatory articular disease that is characterized by synovial hyperplasia. A number of signaling pathways are associated with the development and induced symptoms of RA. Notably, patients with RA have increased protein citrullination and generation of auto‑antibodies against citrullinated proteins. Genome wide association studies have revealed that peptidyl‑arginine deiminase 4 (PADI4) is an enzyme implicated in citrullination in the RA synovium. Autoantibodies targeting citrullinated proteins are used as diagnostic markers in patients with RA. The functions associated with citrullinated proteins are thought to induce autoimmunity, however, the regulatory mechanisms of citrullination via PADI4 are unclear. The group has previously cloned an E3 ubiquitin ligase, synoviolin (SYVN1), from the RA synovium, demonstrating that SYVN1 serves critical roles in synovial hyperplasia. The data indicated that the endoplasmic reticulum (ER) associated degradation system, which involves SYVN1, may have important roles in the proliferation of synoviocytes. In addition, ubiquitination by SYVN1 is associated with fibrosis, inflammation and cytokine production via the regulation of ER stress signals and quality control of proteins. The present study investigated the crosstalk between the representative post‑translational signaling processes, citrullination and ubiquitination. The results revealed that PADI4 interacted with SYVN1 directly and that overexpression of PADI4 suppressed the ubiquitination of proteins. Thus, a reduction in ER stress induced by PADI4 may abrogate the initiation of chronic RA by suppressing the proliferative signals of RA synoviocytes.


Effect of initial COD concentration, nutrient addition, temperature and microbial acclimation on anaerobic treatability of broiler and cattle manure.
In this study, anaerobic treatability and biogas generation potential of broiler and cattle manure were investigated. For this purpose, seven sets of anaerobic batch reactor experiments were performed using broiler and cattle manure and their mixtures in five different ratios (100% broiler; 75% broiler, 25% cattle; 50% broiler, 50% cattle; 25% broiler, 75% cattle; 100% cattle). These manure mixtures had two different initial chemical oxygen demand (COD) (12,000 and 53,500 mg/l) concentrations. The effects of initial COD concentration, nutrient and trace metal supplementation, microbial acclimation and digestion temperature were investigated. Results revealed that the efficiency of total COD removal was 32.0-43.3% and 37.9-50% for initial COD concentrations of 12,000 and 53,500 mg/l, respectively. The biogas yields observed for initial COD concentrations of 12,000 and 53,500 mg/l were 180-270 and 223-368 ml gas/g COD added, respectively. A decrease in biogas yield was observed as the fraction of broiler manure increased in mixture of broiler and cattle manure at initial COD values of 53,500 mg/l.


Reinforcing operants other than abstinence in drug abuse treatment: an effective alternative for reducing drug use.
This study examines the effectiveness of using vouchers to reinforce either the provision of urine samples testing negative for illicit drugs (UA group) or the completion of objective, individually defined, treatment-plan-related tasks (TP group). A third group was assigned to the clinic's standard treatment (STD group). Participants were randomly assigned to groups after a 6-week baseline-stabilization period. Urine specimens were collected thrice weekly throughout the study. In the UA condition, participants earned $5 (U.S. dollars) in vouchers for each drug-free urine submitted. In the TP condition, participants earned up to $15 in vouchers per week for demonstrating completion of treatment plan tasks assigned by their counselors. Contingencies were in effect for 12 weeks, after which all participants received the clinic's standard treatment. Urinalysis results indicate that the TP intervention was significantly more effective in reducing illicit drug use than either the UA or STD interventions. These effects were maintained with a trend toward continuing improvement for the TP groups even after contingencies were discontinued.


Aberration effects in an optical measuring microscope.
The effects of aberrations on the accuracy and repeatability of critical dimension measurements made with an optical microscope are examined theoretically and practically. Aberrations in microscope objectives are studied to determine their effects on the image profiles of narrow ($#x2248;2-microAm) line objects, such as the geometries on integrated circuits. A diffraction theory model is developed and used to investigate the effects of the primary aberrations. Microscope objectives from different manufacturers are examined, and agreement between the theoretical and practical image intensity profiles is demonstrated. It is concluded that the aberrations in many commercially available objective lenses introduce significant errors into semiconductor geometry measurements.