Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer.
Aberrant DNA methylation is a crucial epigenetic regulator that is closely related to the occurrence and development of various cancers, including breast cancer (BC). The present study aimed to identify a novel methylation-based prognosis biomarker panel by integrally analyzing gene expression and methylation patterns in BC patients. DNA methylation and gene expression data of breast cancer (BRCA) were downloaded from The Cancer Genome Atlas (TCGA). R packages, including ChAMP, SVA, and MethylMix, were applied to identify the unique methylation-driven genes. Subsequently, these genes were subjected to Metascape for GO analysis. Univariant Cox regression was used to identify survival-related genes among the methylation-driven genes. Robust likelihood-based survival modeling was applied to define the prognosis markers. An independent data set (GSE72308) was used for further validation of our risk score system. A total of 879 DNA methylation-driven genes were identified from 765 BC patients. In the discovery cohort, we identified 50 survival-related methylation-driven genes. Finally, we built an eight-methylation-driven gene panel that serves as prognostic predictors. Our analysis of transcriptome and methylome variations associated with the survival status of BC patients provides a further understanding of basic biological processes and a basis for the genetic etiology in BC.


Influence of paid and unpaid work on psychophysiological stress responses of men and women.
Female labor force participation has increased considerably, but women's traditional responsibility for home and family has not changed accordingly. Although women's employment per se does not seem to have negative health consequences, studies show that stress from role conflicts and work overload is reflected in women's elevated psychophysiological arousal not only at work but also off work, which may induce psychosomatic symptoms (e.g., cardiovascular and musculoskeletal disorders). In addition, multiple role demands reduce women's possibilities to make a professional career on the same terms as men. Data emphasize the need for a new allocation of work functions between the sexes and the need for organizational changes leading to more influence and control over work to make it possible for both men and women to combine a qualified job with a meaningful family life.


Gold(I) Hydrides as Proton Acceptors in Dihydrogen Bond Formation.
Wavefunction and DFT calculations indicate that anionic dihydride complexes of AuI form strong to moderate directed Au-H⋅⋅⋅H bonds with one or two HF, H2 O and NH3 prototype proton donor molecules. The largely electrostatic interaction is influenced by relativistic effects which, however, do not increase the binding energy. Very weak Au⋅⋅⋅H associations-exhibiting a corresponding bond path-occur between neutral AuH and HF units, although ultimately F becomes the preferred donor atom in the most stable structure. Increasing the hydridicity of AuH by attachment of an electron donating NHC ligand effects Au-H⋅⋅⋅H bonding of moderate strength only with HF, whereas competing Au⋅⋅⋅H interactions dominate for H2 O and NH3 . Rare η2 coordinated and HX (X=F or OH) associated H2 complexes are produced during interaction with a single ion of stronger acidity, H2 F+ or H3 O+ . Theoretically, reaction of excess [AuH2 ]- as proton acceptor with H3 O+ or NH4+ in 3:1 or 4:1 ionic ratios, respectively, affords H⋅⋅⋅H bonded analogues of Eigen-type adducts. Outstanding analytical relationships between selected bonding parameters support the integrity of the results.


The Role of Cerebellum in Alzheimer's Disease: A Forgotten Research Corner.
Alzheimer's disease (AD) is a complex, heterogeneous, and progressive neurodegenerative dementia. Although the majority of AD research has primarily focused on disease-associated alterations of the cortex and hippocampus in the cerebrum, emerging evidence has highlighted the cerebellum's involvement in sleep, cognition, and AD. In this commentary, we discuss a recently published article in Alzheimer's and Dementia, which examines changes in cerebellar electrophysiology, sleep-wake cycles, and neuropathology in APPswe/PS1ΔE9 mice. We also explore the potential role of the cerebellum in AD, offering a fresh perspective on the study of cerebellar involvement in the disease.


A prospective study on postoperative pain after cataract surgery.
To evaluate postoperative pain and early recovery in cataract patients. A total of 201 patients who underwent elective first eye cataract extraction surgery were enrolled, and 196 were included in the final analysis. The study design was a single-center, prospective, follow-up study in a tertiary hospital in eastern Finland. Postoperative pain was evaluated with the Brief Pain Inventory at four time points: at baseline, and at 24 hours, 1 week, and 6 weeks postsurgery. Postoperative pain was relatively common during the first hours after surgery, as it was reported by 67 (34%) patients. After hospital discharge, the prevalence decreased; at 24 hours, 1 week, and 6 weeks, 18 (10%), 15 (9%) and 12 (7%) patients reported having ocular pain, respectively. Most patients with eye pain reported significant pain, with a score of ≥4 on a pain scale of 0-10, but few had taken analgesics for eye pain. Those who had used analgesics rated the analgesic efficacy of paracetamol and ibuprofen as good or excellent. Other ocular irritation symptoms were common after surgery; as a new postoperative symptom, foreign-body sensation was reported by 40 patients (22%), light sensitivity by 29 (16%), burning by 15 (8%), and itching by 15 (8%). Moderate or severe postoperative pain was relatively common after cataract surgery. Thus, all patients undergoing cataract surgery should be provided appropriate counseling on pain and pain management after surgery.


[Species from genus Eimeria observed in domestic rabbit (Oryctolagus cuniculus) feces raised at the Municipality of Campos dos Goytacazes in the State of Rio de Janeiro, Brazil].
This study was designed to identify species of the genus Eimeria from eleven rabbit meat breeders from Campos dos Goytacazes. Fecal samples were collected from rabbits with different health conditions and consintence of feces. The following species of Eimeria were identified: E. perforans; E. magna; E. coecicola; E. irresidua; E. media; E. flavescens; E. nagpurensis; E. intestinalis, E. exigua and E. stiedae. Parasites from this genus were detected in 81.82% (9) of the rabbit meat production sites, regardless of the management and hygiene conditions. In all cases the infection was always caused from more than one species of Eimeria.


Associating brain imaging phenotypes and genetic risk factors via a hypergraph based netNMF method.
Alzheimer's disease (AD) is a severe neurodegenerative disease for which there is currently no effective treatment. Mild cognitive impairment (MCI) is an early disease that may progress to AD. The effective diagnosis of AD and MCI in the early stage has important clinical significance. To this end, this paper proposed a hypergraph-based netNMF (HG-netNMF) algorithm for integrating structural magnetic resonance imaging (sMRI) of AD and MCI with corresponding gene expression profiles. Hypergraph regularization assumes that regions of interest (ROIs) and genes were located on a non-linear low-dimensional manifold and can capture the inherent prevalence of two modalities of data and mined high-order correlation features of the two data. Further, this paper used the HG-netNMF algorithm to construct a brain structure connection network and a protein interaction network (PPI) with potential role relationships, mine the risk (ROI) and key genes of both, and conduct a series of bioinformatics analyses. Finally, this paper used the risk ROI and key genes of the AD and MCI groups to construct diagnostic models. The AUC of the AD group and MCI group were 0.8 and 0.797, respectively.


Statistical basis of the Compton metabolic profile test.
The statistical basis of the Compton metabolic profile test is described and alternative methods for choosing animals for blood sampling are discussed. Recent modifications to the presentation of results, which facilitate interpretation, are described.


Sex differences in activation of the hypothalamic-pituitary-adrenal axis by methamphetamine.
Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activation is associated with changes in addiction-related behaviors. In this study, we tested whether sex differences in the acute effects of methamphetamine (MA) exposure involve differential activation of the HPA axis. Male and female mice were injected with MA (1 mg/kg) or saline for comparison of plasma corticosterone and analysis of the immediate early gene c-Fos in brain. There was a prolonged elevation in corticosterone levels in female compared to male mice. C-Fos was elevated in both sexes following MA in HPA axis-associated regions, including the hypothalamic paraventricular nucleus (PVN), central amygdala, cingulate, and CA3 hippocampal region. MA increased the number of c-Fos and c-Fos/glucocorticoid receptor (GR) dual-labeled cells to a greater extent in males than females in the cingulate and CA3 regions. MA also increased the number of c-fos/vasopressin dual-labeled cells in the PVN as well as the number and percentage of c-Fos/GR dual-labeled cells in the PVN and central amygdala, although no sex differences in dual labeling were found in these regions. Thus, sex differences in MA-induced plasma corticosterone levels and activation of distinct brain regions and proteins involved in HPA axis regulation may contribute to sex differences in acute effects of MA on the brain. Methamphetamine induces a prolonged plasma corticosterone response in females compared to males. This may be mediated by increased neural activation, involving a greater activation of glucocorticoid receptor-positive cells, in males in the CA3 and cingulate brain regions, which are involved in negative feedback functions. These findings indicate a sex difference in the neural regulation of methamphetamine-induced plasma corticosterone release.


Hemophagocytic lymphohistiocytosis associated with hepatosplenic T-cell lymphoma: case report.
Hepatosplenic T-cell lymphoma (HSTCL) is a rare non-Hodgkin lymphoma, marked by liver, spleen, and bone marrow sinusoidal infiltration, with an aggressive clinical course, which represents a difficult diagnostic task for clinicians and pathologists. Another equally severe and challenging condition is the hemophagocytic lymphohistiocytosis (also called hemophagocytic syndrome [HS]), which is often associated with hematologic malignancies and infectious diseases. The authors report the case of a 56-year-old woman diagnosed with HSTCL based on bone marrow aspirate flow cytometry and skin biopsy. The patient underwent a cycle of chemotherapy but the outcome was unfavorable with multiple organ failure. The laboratory analysis was consistent with HS. The autopsy confirmed both the remaining lymphoma in the pulmonary vessels and the hemophagocytic cells in the spleen and bone marrow.


Staphylococcus biofilm components as targets for vaccines and drugs.
Staphylococci have become the most common cause of nosocomial infections, especially in patients with predisposing factors such as indwelling or implanted foreign polymer bodies. The pathogenesis of foreign-body associated infections with S.aureus and S. epidermidis is mainly related to the ability of these bacteria to form thick, adherent multilayered biofilms. In a biofilm, staphylococci are protected against antibiotic treatment and attack from the immune system, thus making eradication of the infections problematic. This necessitates the discovery of novel prophylactic and therapeutic strategies to treat these infections. In this review, we provide an overview of staphylococcal biofilm components and discuss new possible approaches to controlling these persistent biofilm-dwelling bacteria.


Colorectal surgery in Italy. Criteria to identify the hospital units and the tertiary referral centers entitled to perform it.
Improving the quality and effectiveness of care is a key priority of any health policy. The outcomes of health care can be considered as indicators of effectiveness or quality. The scientific literature that evaluates the association between the volume of activity and the outcome of health interventions has greatly developed over the past decade, but, for practical reasons, ethical and social issues, a few randomized controlled studies were made to evaluate this association, although there are numerous observational studies of outcome and systematic reviews of the studies themselves. The colorectal surgery is the most studied area and it represents the ideal testing ground to determine the effectiveness of the quality indicators because of the high incidence of the disease and the wide spread in the territory of the structures that aim to tackle these issues. Numerous studies have documented an association between the large number of colo-rectal surgical procedures and the quality of results. In particular, the volume of activity is one of the characteristics of measurable process that can have a significant impact on the outcome of health care. In conclusion, the ability to use volume thresholds as a proxy for quality is very tempting but it is only part of reality. Infact, the volume-outcome relationship strictly depends on the type of cancer (colon vs rectum) and it appears somehow stronger for the individual surgeon than for the hospital; especially for the 5-year overall survival, operative mortality and number of permanent stoma.


Probing vaccine antigens against bovine mastitis caused by Streptococcus uberis.
Streptococcus uberis is a worldwide pathogen that causes intramammary infections in dairy cattle. Because virulence factors determining the pathogenicity of S. uberis have not been clearly identified so far, a commercial vaccine is not yet available. Different S. uberis strains have the ability to form biofilm in vitro, although the association of this kind of growth with the development of mastitis is unknown. The objective of this study was to evaluate the potential use as vaccine antigens of proteins from S. uberis biofilms, previously identified by proteomic and immunological analyses. The capability of eliciting a protective immune response by targeted candidates was assayed on a murine model. Sera from rabbits immunized with S. uberis biofilm preparations and a convalescent cow intra-mammary infected with S. uberis were probed against cell wall proteins from biofilm and planktonic cells previously separated by two-dimensional gel electrophoresis. Using rabbit immunized serum, two proteins were found to be up-regulated in biofilm cells as compared to planktonic cells; when serum from the convalescent cow was used, up to sixteen biofilm proteins were detected. From these proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fructose-biphosphate aldolase (FBA), and elongation factor Ts (EFTs) were chosen to be tested as vaccine antigen candidates. For this purpose, different groups of mice were immunized with the three recombinant-expressed proteins (each one formulated separately in a vaccine), and thereafter intraperitoneally challenged with S. uberis. The three proteins induced specific IgG antibodies, but a significant reduction of mortality was only observed in the groups of mice vaccinated with FBA or EFTs. These results suggest that FBA and EFTs might be considered as strong antigenic candidates for a vaccine against S. uberis bovine mastitis. Moreover, this is the first study to indicate that also in S. uberis, GAPDH, FBA and EFTs, as proteins detected in both cytoplasm and cell wall fractions, can play a second function (moonlighting), the latter being particularly involved in the virulence of such a pathogen organism.


A universal long-term flu vaccine may not prevent severe epidemics.
Recently, the promise of a new universal long-term flu vaccine has become more tangible than ever before. Such a vaccine would protect against very many seasonal and pandemic flu strains for many years, making annual vaccination unnecessary. However, due to complacency behavior, it remains unclear whether the introduction of such vaccines would maintain high and stable levels of vaccination coverage year after year. To predict the impact of universal long-term flu vaccines on influenza epidemics we developed a mathematical model that linked human cognition and memory with the transmission dynamics of influenza. Our modeling shows that universal vaccines that provide short-term protection are likely to result in small frequent epidemics, whereas universal vaccines that provide long-term protection are likely to result in severe infrequent epidemics. Influenza vaccines that provide short-term protection maintain risk awareness regarding influenza in the population and result in stable vaccination coverage. Vaccines that provide long-term protection could lead to substantial drops in vaccination coverage and should therefore include an annual epidemic risk awareness programs in order to minimize the risk of severe epidemics.


Evolutionary population genetics of promoters: predicting binding sites and functional phylogenies.
We study the evolution of transcription factor-binding sites in prokaryotes, using an empirically grounded model with point mutations and genetic drift. Selection acts on the site sequence via its binding affinity to the corresponding transcription factor. Calibrating the model with populations of functional binding sites, we verify this form of selection and show that typical sites are under substantial selection pressure for functionality: for cAMP response protein sites in Escherichia coli, the product of fitness difference and effective population size takes values 2NDeltaF of order 10. We apply this model to cross-species comparisons of binding sites in bacteria and obtain a prediction method for binding sites that uses evolutionary information in a quantitative way. At the same time, this method predicts the functional histories of orthologous sites in a phylogeny, evaluating the likelihood for conservation or loss or gain of function during evolution. We have performed, as an example, a cross-species analysis of E. coli, Salmonella typhimurium, and Yersinia pseudotuberculosis. Detailed lists of predicted sites and their functional phylogenies are available.


The Evaluation of Colorectal Cancer Risk in Serum by anti-DESMIN-conjugated CdTe/CdS Quantum Dots.
DESMIN is a novel prognostic predictor and therapeutic target for colorectal cancer (CRC). Enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence (ELC) assays are large-scale and highcost projects; therefore, it is necessary to develop a new, fast, and simple yet highly sensitive and specific method to detect DESMIN in serum. Semiconducting quantum dots (QDs) possess high fluorescence quantum yield, stability against photobleaching, and size-controlled luminescence properties, thus being utilized in photoelectrochemical tumor marker detection, especially in ameliorating the diagnostic value in complex biological ambient ionization. However, CdTe/CdS quantum dots (QDs) have not been applied in detecting DESMIN in serum. DESMIN in serum has been established using anti-DESMIN-conjugated CdTe/CdS quantum dots (QDs) and measurements. The assay sensitivity was determined by measurement of quenched fluorescence intensity of DESMIN at 0.1, 0.5, 1.0, 2.0, or 5.0 ng/mL in PBS or 0.25%, 0.5%, 1.0%, 2.0%, or 5% human serum diluted in PBS. The assay was optimized under different pH (7.00 - 7.40) for different reaction durations (10 - 60 minutes). The specificity of anti-DESMIN-QDs was determined by testing the interference of DESMIN activity with CEA, IgG, or AFP, each at 1 ng/mL. Under the optimized incubation time (30 minutes) at room temperature and optimal pH 7.1 - 7.2, a correlation between the decreased fluorescence intensity of anti-DESMIN-conjugated CdTe/CdS QDs and the concentration of DESMIN in the range from 0.05 to 100 ng/mL, was established. The sensitivity for the detection of DESMIN in the range from 0.05 to 100 ng/mL, with a detection limit of 0.02 ng/mL. The assay presented a high specificity because the anti-DESMIN-conjugated CdTe/CdS QDs only reacted with ABR1B10 in the sera in the presence of CEA, IgG or AFP. The immunofluorescence assay to detect DESMIN in serum using anti-DEMSIN-conjugated CdTe/ CdS QDs was fast and simple yet presented high sensitivity and specificity. Our method provides a promising tool for early prediction of CRC risk.


Enhancement by retinoic acid and dibutyryl cyclic adenosine 3':5'-monophosphate of the differentiation and gene expression of human neuroblastoma cells induced by interferon.
Human neuroblastoma cell lines are induced to differentiate and display neuronal phenotypes when treated with interferon (IFN)-alpha 2, retinoic acid (RA), or dibutyryl cyclic AMP (dbcAMP). We investigated the effects of combinations of these agents in induction-differentiation in the neuroblastoma cell line, NUB-6. The inductive effect of IFN-alpha 2 was markedly enhanced when used in combination with RA or dbcAMP. In parallel, RA or dbcAMP also enhanced the level of 2'-5'-oligoadenylate (2-5A) synthetase, and enzyme induced by IFNs and implicated in their biological action. The levels of another IFN-inducible enzyme, p68 kinase, were not enhanced by the combination treatments. The enhancement effects appeared to be exerted largely at the posttranscriptional level as both RA and dbcAMP stabilized IFN-induced 2-5A synthetase mRNA, resulting in increased enzyme activity. Thus, the 2-5A synthetase system is likely involved in mediating the IFN-alpha 2-induced differentiation of neuroblastoma cells and may also mediate the enhancement effects of RA and dbcAMP on IFN activity in these cells. These results also provide a rational basis for establishing a combination therapeutic approach for the treatment of neuroblastoma.


Air-stable flexible organic light-emitting diodes enabled by atomic layer deposition.
Organic light-emitting diodes (OLED) are an energy-efficient light source with many desirable attributes, besides being an important display of technology, but its practical application has been limited by its low air-stability. This study demonstrates air-stable flexible OLEDs by utilizing two atomic-layer-deposited (ALD) films: (1) a ZnO film as both a stable electron-injection layer (EIL) and as a gas barrier in plastics-based OLED devices, and (2) an Al2O3/ZnO (AZO) nano-laminated film for encapsulating the devices. Through analyses of the morphology and electrical/gas-permeation properties of the films, we determined that a low ALD temperature of 70 °C resulted in optimal EIL performance from the ZnO film and excellent gas-barrier properties [water vapor transmission rate (WVTR) <5 × 10(-4) g m(-2) day(-1)] from both the ZnO EIL and the AZO encapsulating film. The low-temperature ALD processes eliminated thermal damage to the OLED devices, which were severe when a 90 °C encapsulation process was used, while enabling them to achieve an air-storage lifetime of >10,000 h.


On the enthalpy of formation of Escherichia coli K-12 cells.
An examination is made of five methods for obtaining values of the enthalpy of formation of a unit mass of living Escherichia coli K-12 cells. The values obtained by these methods ranged from -88.95 kJ to -99.55 kJ, the gross average being 96.01 kJ, per unit carbon formula weight equivalent of living, hydrated cells. Although theoretically the growth of this organism in a microcalorimeter should provide the best value, the value obtained by this method (-88.95 kJ per UCFW equivalent) is not in close agreement with those of the other four methods, the values from which form a cluster averaging -97.8 +/- 1.0 kJ (-23.4 +/- 0.2 kcal)/UCFW equivalent. Calculations using this value indicate that the enthalpy change accompanying anabolism (as this is represented) is zero, or very nearly so, and that the heat of growth is that from catabolism alone.


Panoramic View Of Challenges And Opportunities For Primary Healthcare Systems In Pakistan.
Pakistan has a broad system of primary health care facilities to achieve mission of "Health for all". Over the last seven years health expenditure by government of Pakistan has been increased to attain this goal. This study was conducted with the aim to assess all blocks of service readiness (basic equipment, basic amenities, laboratory capacity, standard precautions and essential medicines) in public-primary health care facilities of tehsil Rawalpindi, Pakistan. A cross-sectional survey was carried out utilizing two separate structured questionnaires for basic health units and rural health centres. Information was collected from administrative heads along with other staff where required, of all public-primary health care facilities of Tehsil Rawalpindi. Data were analysed by using SPSS version.17. A total of 26 health facilities were assessed; only 56% BHUs had a sign board that was available in readable form. BHUs with women medical officer as administrative head constituted 52%. Backup for electricity and toilet were the most neglected areas. Basic amenities, standard precautions and laboratory capacity of Basic Health Units (BHUs) showed a clear deviation from standards and is thus a challenge for Pakistan's Primary Health care (PHC). On the other hand for Rural Health Centres (RHCs), most were on the way to meet expectations. Pakistan's government is undoubtedly putting efforts in order to achieve targets of primary healthcare but it needs better mainstreaming of political, institutional and social commitments with modified standards for PHC.


Plastic Surgery Diversity, Equity, and Inclusion Mentorship Program and Workshop: A Single Institution's Experience.
Several minority groups and students without home plastic surgery programs remain underrepresented in plastic surgery. To address these barriers, our division created the Plastic Surgery Diversity, Equity, and Inclusion Mentorship Program and Workshop. Students meeting at least one of the following eligibility criteria were invited in fall of 2020: medical student in years 1 though 3 or a research year who is (1) underrepresented in medicine, including African American, Hispanic/Latinx, Native American, Pacific Islander; (2) lesbian, gay, bisexual, transgender, or queer (LGBTQ); (3) first-generation low-income; or (4) does not have a plastic surgery residency program associated with their medical school. Students participated in quarterly meetings with their resident mentor and the annual hands-on workshop. The workshop was held on March 20, 2020, with both virtual and in-person participants. It included various didactic lectures, a suture laboratory, a resident panel, a social lunch hour, and extremity and head cadaver dissections with fracture plating. Twenty-four students attended the workshop. The course was rated 9.4 of 10 by students. The top met goals were gaining didactic plastic surgery knowledge (100%), exposure to a plastic surgery residency program (100%), resources to help overcome minority-specific barriers (96%), and technical skills such as suturing (96%). At the conclusion of the workshop, students had a significant increase in confidence in various aspects of plastic surgery knowledge and technical skills. The Plastic Surgery Diversity, Equity, and Inclusion Mentorship Program and Workshop demonstrated preliminary success in providing support for students underrepresented in medicine and students without home programs.


Regulatory network of GSK3-like kinases and their role in plant stress response.
Glycogen synthase kinase 3 (GSK3) family members are evolutionally conserved Ser/Thr protein kinases in mammals and plants. In plants, the GSK3s function as signaling hubs to integrate the perception and transduction of diverse signals required for plant development. Despite their role in the regulation of plant growth and development, emerging research has shed light on their multilayer function in plant stress responses. Here we review recent advances in the regulatory network of GSK3s and the involvement of GSK3s in plant adaptation to various abiotic and biotic stresses. We also discuss the molecular mechanisms underlying how plants cope with environmental stresses through GSK3s-hormones crosstalk, a pivotal biochemical pathway in plant stress responses. We believe that our overview of the versatile physiological functions of GSK3s and underlined molecular mechanism of GSK3s in plant stress response will not only opens further research on this important topic but also provide opportunities for developing stress-resilient crops through the use of genetic engineering technology.


Inactivation of MS2 bacteriophage by streamer corona discharge in water.
Electrical discharge processes are emerging as water treatment technologies applicable to both the degradation of organic contaminants as well as inactivation of pathogens. Particularly as a disinfection technology, electrical discharge processes do not produce toxic byproducts, and effectively inactivate a wide spectrum of microorganisms by multiple lethal actions generated by the formation of plasma channels. This study demonstrates the inactivation of a virus using the streamer corona discharge process (SCDP) with MS2 phage as a surrogate. A rapid inactivation of MS2 phage (i.e., approximately 4 log inactivation in 5 min) was observed in all experimental runs conducted. Discharge conditions such as applied voltage and storage capacitance significantly affected the inactivation efficiency of MS2 phage, whereas the influence of water quality parameters was minor. In order to elucidate the mechanism of MS2 phage inactivation, potentially lethal factors that can be generated by the SCDP were selected, and their roles in the inactivation of MS2 phage were examined. As a result, effects of UV radiation, chemical oxidants, and pulsed electric fields were found to be insignificant. The shockwave generated upon plasma channel formation appears to be the most important factor responsible for MS2 phage inactivation.


Relationship between previous treatments and onset of symptoms in patients with Whipple's disease.
The clinical features of Whipple's disease (WD) consist of arthropathy that precedes the involvement of other organs, such as the gastrointestinal tract, nervous system and heart. It has been shown that gastrointestinal manifestations can be precipitated by immunosuppressive therapy used to control the arthropathy. In the present study, we investigated the clinical features of the Italian population of patients affected by WD. The clinical histories of 22 patients with WD were reviewed. Relationship between previous treatments and onset of symptoms was analysed. 20/22 patients suffered from arthropathy that had started before gastrointestinal complaints; gastrointestinal symptoms were present in 18 patients and neurological involvement was found in 5. WD must always be taken into account in male patients with long-standing ill-defined arthropathy, and it should be ruled out before starting immunosuppressive or antibiotic treatment that can make correct diagnosis and management very difficult.


Use of Hoechst 33342 stain to evaluate live fresh and frozen bull sperm by computer-assisted analysis.
The objective of this research was to investigate possible procedures for evaluating living bull sperm stained with Hoechst 33342 while in a simple medium and in commonly used complex egg yolk-glycerol-Tris (EYGT) and whole milk-glycerol (WMG) extenders. The two semen extenders provide good cryoprotection, but the latter one virtually obscures the sperm. To evaluate sperm motion characteristics when static nonsperm particles are present, a new Hamilton Thorne epifluorescent optical system (UV) with a strobe light was developed for potential use with DNA-stained sperm. This system permitted examination for the first time of sperm motion characteristics in milk. In Experiment 1 (four bull semen replicates with five dye concentrations and three incubation times), 2.5 microg/ml of Hoechst 33342 stained live and dead sperm sufficiently in a modified Tyrode's solution to measure all sperm characteristics without depressing motility, which was validated by using phase-contrast to analyze stained and unstained controls. In Experiments 2a and 2b, each using semen from four bulls with a 5 x 5 factorial arrangement, it was determined that 40 to 60 microg/ml of dye in EYGT or WMG, with UV illumination for 20 minutes, was optimal. There was no detrimental effect on sperm motility. In Experiment 3, analyses of two ejaculates, from each of eight bulls, confirmed that motion characteristics of sperm in EYGT and WMG were not depressed when the sperm were stained with Hoechst 33342. These experiments demonstrate that the dye concentrations and exposure times developed for use with the new epifluorescent optics facilitate evaluating bull sperm frozen in particle-filled whole milk and should be useful for sperm evaluation of a variety of species when nonsperm particulate matter may otherwise interfere.


Prognostic significance of ventricular late potentials in the postmyocardial infarction period.
Ventricular late potentials in patients after myocardial infarction can be assumed to herald an increased risk of future sudden cardiac death or symptomatic sustained ventricular tachycardia. This holds particularly true for patients studied early after recent myocardial infarction whereas patients assessed later in the subsequent course have a substantially lesser incidence of arrhythmic events, probably due to intercurrent death of those at high risk. Of prognostic importance appears not only the presence but also the duration of late potentials. A meaningful role is also assumed by the extent of left ventricular functional impairment (EF less than 40%). However, in consideration of the complex mechanisms that can lead to sudden cardiac death, no single method predicts with high sensitivity the occurrence of a ventricular tachyarrhythmic event. Sudden cardiac death can be incurred on the basis of chronic electrophysiological abnormalities as a consequence of regional slow conduction in the border zone of a previous myocardial infarction precipitated by trigger factors such as spontaneous ventricular arrhythmias. Sudden cardiac death or symptomatic sustained ventricular tachycardia can also occur due to sudden and transient changes in the electrophysiological properties of the myocardium due to ischemia. Whether the combination of late potentials with clinical parameters such as ventricular arrhythmias detected in the ambulatory ECG and those induced with programmed electrical stimulation will lead to more accurate identification of patients at risk prerequisites further elucidation. Currently available literature indicates that in patients with late potentials, ventricular tachycardias can be induced more frequently by programmed electrical stimulation and that the combination of both phenomena confers a particularly high risk.


The use of assistive technologies among children with disabilities: the perception of parents of children with disabilities in Ghana.
Assistive technologies (ATs) are fundamental to the successful educational and societal inclusion of all children with disabilities. In particular, the use of ATs has been found to increase levels of independence in daily living and promote greater access to learning opportunities for children with disabilities. However, the knowledge base and baseline information on the use of ATs is limited in developing countries such as Ghana. In this study, we sought to explore the experiences of parents regarding the use of ATs by their children with disabilities in Ghana. We used a survey questionnaire consisting of both open- and closed-ended questions to explore the perspectives of parents with children with disabilities (n = 35) who were attending the rehabilitation unit of a referral hospital. Although participants acknowledged the benefits of ATs for the development and participation of their children in society, they noted barriers to the usage of ATs by their children. Among several barriers, parents mentioned that they lacked funds to purchase assistive devices. Some parents also mentioned the high cost of ATs and rehabilitation services. The need for government to include rehabilitation services and ATs in the National Health Insurance Scheme to ease the burden on participants and other implications of the findings for policymaking are extensively discussed. Implications for rehabilitationIn an environment where there is negative attitude towards children and parents with disabilities, ATs are expected to encourage the participation and acceptance in society.Although many participants were aware of the benefits of ATs to their children, they reported barriers to usage among their children with disabilities.This study shows that poverty, limited health facilities, unfriendly environment and stigmatisation were barriers encountered by parents.We conclude that the government should expand health and rehabilitation facilities to encourage access and participation.


Cell death mode switch from necrosis to apoptosis in brain.
In brain ischemia, cell destructive necrosis occurs in the core, which in turn links to cell death expansion in the vicinity. Apoptosis, on the other hand, occurs in the surroundings of the core, called the penumbra, several days later. As cells showing apoptosis disappear by microglial phagocytosis in the brain, cell death induced by ischemic stress should eventually be terminated. Thus, the authors propose the hypothesis that the cell death mode switch in the event of brain ischemia is an in vivo self-protective mechanism. The authors attempt to overview the current understanding of the molecular mechanisms of necrosis and apoptosis in relation to the ATP hypothesis, and also introduce novel mechanisms for an in vitro cell death mode switch.


[22q11 deletion syndrome: considerable phenotype variability].
22q11 deletion syndrome is one of the most frequent syndromes with an estimated prevalence of 1:2000-4000 live births. The syndrome is known to be associated with congenital cardiac malformations, hypocalcaemia and immunodeficiency. We present two cases with rhinopharyngeal insufficiency, cognitive impairment, developmental delay and behavioural problems. These symptoms are even more often associated with the syndrome than the former manifestations. Early diagnosis is important to prevent complications and provide proper support to patient and family.


Systemic increase in type I interferon activity in Sjögren's syndrome: a putative role for plasmacytoid dendritic cells.
In the salivary glands of primary Sjögren's syndrome (pSjS) patients, type I IFN activity is increased, but systemic levels of type I IFN proteins are rarely detected. This study focused on the systemic activity of type I IFN in pSjS, as well as the role of peripheral plasmacytoid dendritic cells (pDC). Monocytes obtained from pSjS patients showed an increased expression of 40 genes. Twenty-three of these genes (58%), including IFI27, IFITM1, IFIT3 and IFI44, were inducible by type I IFN. pSjS serum had an enhanced capability of inducing IFI27, IFITM1, IFIT3 and IFI44 in the monocytic cell line THP-1, likely due to the action of IFN-beta. This effect could be inhibited by blocking the type I IFN receptor, supporting a high type I IFN bioactivity in pSjS serum. In addition, circulatory pDC showed increased expression of CD40. This expression was correlated to the expression level of the type I IFN-regulated genes IFI27 and IFITM1 in monocytes of the same individual. This study indicates that the increased type I IFN activity observed in pSjS patients is not only a local but also a systemic phenomenon and points to pDC as a possible source of this activity.


Estimation of genetic parameters for carcass defects of Japanese Black cattle in Kagoshima.
Cattle exhibit a range of carcass defects, including blood splash (BLS), intramuscular edema (INE), muscle steatosis (MUS), bruising (BR), trim loss (TRL) and others (OTH). These defects lower the carcass value and can result in significant economic loss to producers. We estimated the incidence, relationship with inbreeding coefficients and genetic parameters of carcass defects in Japanese Black cattle using 561 619 carcass records from Kagoshima, Japan during April 1988 through March 2011. The defect incidence ranged from 0.22% for TRL to 5.73% for BR. The incidence of MUS and BR increased from 1.21% to 6.57% and from 1.06% to 9.31%, respectively. The incidence of INE peaked at 7.44% in 1999 and decreased thereafter. We observed a positive linear relationship between the defect incidence and the inbreeding coefficients in MUS, BR and TRL (P < 0.01). The heritabilities estimated by univariate animal model with Gibbs sampling for BLS, INE, MUS, BR and TRL were 0.24, 0.06, 0.18, 0.05 and 0.02, respectively. The contribution of farm variance to phenotypic variance was negligible (0.01 to 0.04). Significant genetic correlations of TRL were estimated with MUS (0.63) and BR (0.63). Our results suggest that genetic factors contribute to the incidence of BLS and MUS.


[Diagnosis of pancreatic diseases in childhood (author's transl)].
In many ways diagnosis of pancreatic disorders in children is difficult. Since pancreatic parameters are age-dependent, reliable laboratory parameters are not easily established. Children are less likely than adults to endure tolerance tests and invasive test methods should therefore be used only in special situations. Estimation of chymotrypsin in faeces seems to be an earlier indicator of pancreatic insufficiency than the PABA-peptide-test. A secretin-pancreozymin test can only be advised for first diagnosis after screening has repeatedly indicated pathological values and malabsorption has more or less been ruled out. A threefold rise in serum amylase values - matched for age - suggests pancreatitis and sonography should then be applied to obtain further clarification.


Children with sensorineural hearing loss after passing the newborn hearing screen.
To identify and describe the findings of children who passed their newborn hearing screen (NHS) and were subsequently found to have childhood hearing loss. Academic tertiary care center. Retrospective medical chart review. With approval of the institutional review board, hospital records were reviewed for children diagnosed as having hearing loss. We identified 923 children with hearing loss from 2001 to 2011. Patients who passed the NHS with subsequent hearing loss were included. Seventy-eight patients were included in our study. The suspicion of hearing loss in patients who passed the NHS was most often from parental concerns (n = 28 [36%]) and failed school hearing screens (n = 25 [32%]). Speech and language delay and failed primary care physician screens accounted for 17% and 12%, respectively. Configuration of the audiogram was bilateral symmetric (n = 42 [54%]), bilateral asymmetric (n = 16 [21%]), and unilateral (n = 20 [26%]) loss. Thirty-seven patients (47%) had severe or profound hearing loss. The etiology was unknown in 42 patients (54%); the remaining was attributed to genetics (n = 13 [17%]), anatomic abnormality (n = 11 [14%]), acquired perinatal (n = 9 [12%]), and auditory neuropathy (n = 3 [4%]). This is the largest study to characterize children with hearing loss who passed the NHS. In our review, parental concerns and school hearing screens were the most common method to diagnose hearing loss after passing the NHS. Families and primary care physicians may have a false sense of security when patients pass the NHS and overlook symptoms of hearing loss. This study raises the question whether further screens would identify hearing loss in children after passing the NHS.


Unraveling the electronic origin of a special feature in the triplet-minus-singlet spectra of carotenoids in natural photosystems.
The influence of carotenoid triplet states on the Qy electronic transitions of chlorophylls has been observed in experiments on light-harvesting complexes over the past three decades, but the interpretation of the resulting spectral feature in the triplet minus singlet (T-S) absorption spectra of photosystems is still debated, as the physical-chemical explanation of this feature has been elusive. Here, we resolve this debate, by explaining the T-S spectra of pigment complexes over the Qy-band spectral region through a comparative study of chlorophyll-carotenoid model dyads and larger pigment complexes from the main light harvesting complex of higher plants (LHCII). This goal is achieved by combining state-of-the-art time-dependent density functional theory with analysis of the relationship between electronic properties and nuclear structure, and by comparison to the experiment. We find that the special signature in the T-S spectra of both model and natural photosystems is determined by singlet-like triplet excitations that can be described as effective singlet excitations on chlorophylls influenced by a stable electronic triplet on the carotenoid. The comparison with earlier experiments on different light-harvesting complexes confirms our theoretical interpretation of the T-S spectra in the Qy spectral region. Our results indicate an important role for the chlorophyll-carotenoid electronic coupling, which is also responsible for the fast triplet-triplet energy transfer, suggesting a fast trapping of the triplet into the relaxed carotenoid structure. The gained understanding of the interplay between the electronic and nuclear structures is potentially informative for future studies of the mechanism of photoprotection by carotenoids.


Fatigue and sleep during cancer and chemotherapy: translational rodent models.
The frequent occurrence of fatigue and disturbed sleep in cancer survivors and the negative effect of these symptoms on quality of life and clinical outcome underscore the need to identify mechanisms that cause cancer-related fatigue, with a view toward developing more effective treatments for this problem. Human studies of fatigue and disturbed sleep are limited by high interindividual genetic and environmental variability, difficulties with behavioral or reporting compliance, and the subjective nature of the problems. Although animal models also must overcome the barrier of assessing fatigue and sleep disturbance in the absence of obvious objective clinical markers, animal studies are easier to control and standardize than are studies of people. Moreover, animal models are crucial to the identification and understanding of underlying disease mechanisms. This review describes the need for, the feasibility of, and several possible approaches to measuring fatigue in animal models of cancer and to relating such measures to disturbed sleep, immune function, and other potential mechanisms. Developing and using animal models to better understand fatigue and disturbed sleep related to cancer and its treatment has an enormous potential to expand the knowledge base and foster hypotheses necessary for the future development and testing of interventions.


Further Evaluation of Mechanisms Associated with the Antidepressantlike Signature of Scopolamine in Mice.
Conventional antidepressants lack efficacy for many patients (treatmentresistant depression or TRD) and generally take weeks to produce full therapeutic response in others. Emerging data has identified certain drugs such as ketamine as rapidly-acting antidepressants for major depressive disorder and TRD. Scopolamine, a drug used to treat motion sickness and nausea, has also been demonstrated to function as a rapidly-acting antidepressant. The mechanisms associated with efficacy in TRD patients and rapid onset of action have been suggested to involve a-Amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling. Since the work on these mechanisms with scopolamine has been limited, the present set of experiments was designed to further explore these mechanisms of action. Male, NIH Swiss mice demonstrated a robust and immediate antidepressant signature with ketamine or scopolamine when studied under the forced-swim test. The AMPA receptor antagonist NBQX prevented this antidepressant-like effect of scopolamine and ketamine. An orally-bioavilable mTOR inhibitor (AZD8055) also attenuated the antidepressant- like effects of scopolamine and ketamine. Scopolamine was also shown to augment the antidepressant- like effect of the selective serotonin reuptake inhibitor citalopram. When given in combination, scopolamine and ketamine acted synergistically to produce antidepressant-like effects. Although drug interaction data suggested that additional mechanisms might be at play, metabolomic analysis of frontal cortex and plasma from muscarinic M1+/+ and M1 -/- mice given scopolamine or vehicle did not reveal any hints as to the nature of these additional mechanisms of action. Overall, the data substantiate and extend the idea that AMPA and mTOR signaling pathways are necessary for the antidepressant-like effects of scopolamine and ketamine, mechanisms that appear to be of general significance for TRD therapeutic agents.


Health-engagement control strategies and 2-year changes in older adults' physical health.
This study examined the associations between older adults' daily physical symptoms (e.g., chest pain or difficulty breathing) and 2-year changes in chronic health problems (e.g., cardiovascular disease or cancer) and in functional problems (e.g., difficulty dressing or moving around at home). We reasoned that these associations depend on a person's active control processes aimed at counteracting physical health problems (i.e., health-engagement control strategies, or HECS). In particular, we hypothesized that high levels of HECS buffer the adverse effect of daily physical symptoms on increases in chronic and functional health problems. We found that daily physical symptoms were associated with declines in chronic and functional health among older adults who were not engaged in addressing their health problems, but not among their counterparts who reported high levels of HECS. These findings suggest that active control strategies play an important role in the maintenance of older adults' physical health.


[Bullosis in diabetics. Apropos of a new case].
Idiopathic bullae occurring in diabetics constitute an uncommon condition which may reveal the diabetes, announce its decompensation or represent a mere epiphenomenon. The authors report the case of a woman who experienced two episodes of idiopathic bullae: the first one disclosed the diabetes, the second one heralded its decompensation. Both episodes were preceded by painful paraesthesia. The bullae contained a clear and serous fluid and the separation was intradermal. Direct immunofluorescence with anti-fibrin serum only showed fluorescence in the lumen of the bulla and in subjacent dermal areas. Electron microscopy demonstrated that the tissue separation was at the base of the stratum corneum. Other clinical cases and pathogenetic theories found in the literature are reported. In contrast with other bullous diseases occurring in diabetics and often of poor prognosis, idiopathic bullae is a benign condition requiring no more than a symptomatic treatment.


Is there icosahedral ordering in liquid and undercooled metals?
The local structure of simple liquids is significantly different from that of corresponding crystalline systems. Signatures of fivefold local ordering have been previously found, but current knowledge is limited to pair distribution, leaving considerable uncertainty in the determination of the geometrical structure. New x-ray absorption experimental results on liquid and undercooled liquid copper, interpreted using an advanced data-analysis method based on multiple-scattering simulations, are shown to contain direct information on triplet correlations making feasible a reliable determination of the bond-angle distribution and fraction of nearly icosahedral configurations in liquids.


Cultural influences on caregiving burden: cases of Koreans and Americans.
This study compared cultural influences on caregiver burdens of Korean adult children and American adult children caring for parents with dementia, and identified culturally specific values, norms, and customs associated with low or high burden. The findings suggested that the low burden of the Korean caregivers was associated with extended family support and high filial responsibility while that of the American caregivers was related to the use of formal services and high gratification from caregiving. Obversely, the high burden of the Koreans was seen to be associated with limited formal services outside the family and low gratification from caregiving for in-laws while that of the Americans was suggested to be due to limited extended family support and low filial responsibility. Needs for culturally-appropriate interventions are discussed.


Detection of a novel single nucleotide polymorphism and imprinted status analysis of the Ras protein-specific guanine nucleotide-releasing factor 1 gene in domestic pigs.
The aim of this study was to determine the imprinting status of the Ras protein-specific guanine nucleotide-releasing factor 1 (Rasgrf1) gene in domestic pigs. In this study, a 228-bp partial sequence located in exon 14 and a 193-bp partial sequence located in exon 1 of the Rasgrf1 gene in domestic pigs were obtained. A novel single nucleotide polymorphism, a G/A transition, was identified in Rasgrf1 exon 14, and then the reciprocal Berkshire x Wannan black F1 hybrid model and the reverse transcription-polymerase chain reaction-restriction fragment length polymorphism method were used to detect the imprinting status of the porcine Rasgrf1 gene at the 1-day-old developmental stage. Imprinting analysis showed that, compared to the imprinted expression of the Rasgrf1 gene in mouse and rat, a variable imprinting status was observed in domestic pigs. In principle, the porcine Rasgrf1 gene was maternally expressed in the liver and small intestine, paternally expressed in the lung, and biallelically expressed in brain, heart, spleen, kidney, stomach, pancreas, fat, testis, ovary, longissimus dorsi, and pituitary tissues. In conclusion, our results indicated that the Rasgrf1 gene shows both species- and tissue-specific variation in imprinted expression.


Room-Temperature Lasing in Colloidal Nanoplatelets via Mie-Resonant Bound States in the Continuum.
Solid-state room-temperature lasing with tunability in a wide range of wavelengths is desirable for many applications. To achieve this, besides an efficient gain material with a tunable emission wavelength, a high quality-factor optical cavity is essential. Here, we combine a film of colloidal CdSe/CdZnS core-shell nanoplatelets with square arrays of nanocylinders made of titanium dioxide to achieve optically pumped lasing at visible wavelengths and room temperature. The all-dielectric arrays support bound states in the continuum (BICs), which result from lattice-mediated Mie resonances and boast infinite quality factors in theory. In particular, we demonstrate lasing from a BIC that originates from out-of-plane magnetic dipoles oscillating in phase. By adjusting the diameter of the cylinders, we tune the lasing wavelength across the gain bandwidth of the nanoplatelets. The spectral tunability of both the cavity resonance and nanoplatelet gain, together with efficient light confinement in BICs, promises low-threshold lasing with wide selectivity in wavelengths.


[Venous malformations in the head and neck should be treated].
Vascular lesions are tumours or malformations. Haemangioma is the most common tumour. It disappears at the age of seven. Malformations may be arterial, capillary, venous, arteriovenous, lymphatic or mixed. The vascular malformations do not disappear. There are several options for treating venous or lymphatic malformations. One of them is sclerosing therapy with Sotradecol by direct puncture. We have 15 years' experience of this method but present only the last 60 patients, treated between 1997 and 2001. Excellent or good results were seen in 59 patients. No permanent complications occurred. It is important to know the nomenclature and the different options for treatment as discussed in the International Society for the Study of Vascular Anomalies.


The histochemical localization of cholesterol in formalin-fixed and fresh frozen sections.
The premixed cholesterol reagent (acetic acid, sulphuric acid, ferric chloride and phosphoric acid) employed in a spectrophotometric method for serum cholesterol determinations was applied to frozen sections of various rat and rabbit tissues. The histochemical reaction was compared with the results obtained by the classical Schultz reaction. The same bluish-green color was observed after treatment of formalin-fixed and fresh cryostat sections incubated in 2.5% iron alum at 37 C for 3 days. The premixed cholesterol reagent is stable for years at room temperature if stored in a brown bottle and is thus readily available for routine use.


Using Delayed Toxicities to Re-evaluate Tolerability in Phase 2 Trials: A Case Example using Bortezomib.
In advanced stage patients enrolled in dose-finding trials, it is difficult to assess delayed toxicities because frequently patients discontinue after one or two cycles of treatment. Patients enrolled in phase 2 trials are typically followed longer to assess efficacy. Thus, their data may be useful for evaluating long-term tolerability. We illustrate this using as example two phase 2 bortezomib trials (total N = 172) conducted by SWOG. While treatment-related severe toxicity rates based on cycle 1 were acceptable (23% and 31%), they were notably higher over extended administration (37% and 70%). This additional information should be considered when designing subsequent trials.


Store brand formulas--a new alternative for bottle-feeding moms.
There are more infant formula options on the market today than ever before. Health care professionals must help mothers determine what type of formula to feed their child, such as an iron-fortified, milk-based formula or a soy-based formula. It is also key to realize that the Federal Food and Drug Administration tightly regulates infant formula so they are all nutritionally equivalent. The only significant difference among today's term formula options is price. Most leading retailers around the country carry a store brand of formula that bears the store's name, is made by Wyeth Nutritionals, regulated by the FDA, and available at a significant savings.


Synthesizing medical evidence: systematic reviews and metaanalyses.
Systematic reviews and metaanalyses have become increasingly popular ways of summarizing, and sometimes extending, existing medical knowledge. In this review the authors summarize current methods of performing metaanalyses, including the following: formulating a research question; performing a structured literature search and a search for trials not published in the formal medical literature; summarizing and, where appropriate, combining results from several trials; and reporting and presenting results. Topics such as cumulative and Bayesian metaanalysis and metaregression are also addressed. References to textbooks, articles, and Internet resources are also provided. The goal is to assist readers who wish to perform their own metaanalysis or to interpret critically a published example.


Predictors of recovery from post-deployment posttraumatic stress disorder symptoms in war veterans: The contributions of psychological flexibility, mindfulness, and self-compassion.
Posttraumatic stress disorder (PTSD) is a major challenge among war veterans. This study assessed the contribution of several interrelated, modifiable psychosocial factors to changes in PTSD symptom severity among combat-deployed post-9/11 Veterans. Data were drawn from a longitudinal study of predictors of mental health and functional outcomes among U.S. Iraq and Afghanistan war Veterans (N = 117). This study assessed the unique contribution of psychological flexibility, mindfulness, and self-compassion to PTSD recovery, after accounting for established predictors of PTSD chronicity, including combat exposure, alcohol use problems, and traumatic brain injury. PTSD symptom severity was assessed using a clinician-administered interview, and PTSD recovery was defined as the change in symptom severity from lifetime worst severity, measured at baseline, to current severity at one-year follow-up. A mindful awareness latent factor comprised of all three variables measured at baseline predicted PTSD recovery beyond the other predictors of PTSD chronicity (f2 = 0.30, large effect). Each construct predicted PTSD recovery when tested individually. When tested simultaneously, self-compassion, but not mindfulness or psychological flexibility, predicted PTSD recovery. These findings suggest that mindful awareness of emotional distress predicts recovery from PTSD symptoms in war veterans, which supports the utility mindfulness-based interventions in promoting post-trauma recovery.


Effects of a Single Water Molecule on the Reaction Barrier of Interstellar CO2 Formation Reaction.
The mechanism by which CO2 is formed in the interstellar space remains a mystery. The most likely reaction is collision between CO and OH; however, previous theoretical works have shown that the activation barrier for CO2 formation is high enough to prevent the reaction at the low thermal conditions of space (∼10 K). The effects of single water molecule on the reaction barrier of CO2 formation from reaction between CO and OH have been investigated here by means of ab initio calculation. The barrier height along the lowest-energy pathway in the reaction between CO and OH in the absence of the H2O molecule was calculated to be 2.3 kcal/mol when CCSD(T) energy corrections are combined with the MP2 basis set limit. In the case of the hydrated (H2O-CO-OH) system, the inclusion of a single H2O molecule into the system significantly decreased the barrier height to 0.2 kcal/mol. This suggests that CO2 can be formed when CO and OH react in the presence of H2O, even under thermal conditions as low as 10 K.


Liver transplantation in a patient with rapid onset parkinsonism-dementia complex induced by manganism secondary to liver failure.
Bilateral and symmetric globus-pallidus hyperintensities are observed on T1-weighted MRI in most of the patients with chronic liver failure, due to manganese accumulation. We report a 53-year-old man, with rapid onset parkinsonism-dementia complex associated with accumulation of manganese in the brain, secondary to liver failure. A brain MRI was performed and a high signal on T1-weighted images was seen on globus-pallidus, as well as on T2-weighted images on the hemispheric white-matter. He was referred to a liver-transplantation. The patient passed away on the seventh postoperative day. Our findings support the concept of the toxic effects of manganese on the globus-pallidus. The treatment of this form of parkinsonism is controversial and liver-transplantation should not be considered as first line treatment but as an alternative one.


Thermal stability of the DNA-binding domain of the Myb oncoprotein.
The DNA-binding domain of the c-myb protooncogene product consists of three homologous tandem repeats of 51-52 amino acids (denoted as R1, R2, and R3 from the N-terminal side). In order to analyze conformational and thermodynamic characteristics of the homologous repeats, we have examined the DNA-binding domain by circular dichroism (CD) and differential scanning calorimetry (DSC). The CD spectra for the three individual repeats are significantly different in the fine profiles, indicating subtle differences in their conformations. The melting analyses for the fragments show that the thermal stability of each fragment is different from one another, with the following order of stability: R1(Tm = 61 degrees C) approximately greater than R3(57 degrees C) >> R2(43 degrees C), where R2 is much less stable than the other repeats. The denaturing process for the whole DNA-binding domain, measured by DSC, is characterized by a very broad transition ranging from 30 to 80 degrees C. The denaturation curve can be fit well by a three-state transition with one intermediate state. The transition temperature for the native-to-intermediate transition coincides with the melting temperature of R2, indicating that the intermediate state corresponds to the unfolding of unstable R2. The CD spectrum of the whole domain is almost identical to the sum of the individual spectra. Thus, these results suggest that the individual repeats in the whole DNA-binding domain behave independently in terms of conformation and stability. The addition of DNA to the DNA-binding fragment drastically changed the melting profile, in which the broad transition curve was replaced by a sharp peak at 58 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)


Multivariate allometric scaling of men's world indoor rowing championship performance.
The World Indoor Rowing Championship (WIRC) is based on the time (T) to row a simulated 2500 m on a rowing ergometer. In the WIRC there are separate age categories but only two weight classes: light and heavyweight, thus penalizing those just heavier and those significantly lighter than the cut-off weight. Multivariate allometric scaling (MAS) provides an expression of performance free of the confounding effect of more than one scaling variable. We used MAS to scale T by height (H) and age (A) to create a new index of rowing performance, T*H(-a)*A(-b). Subjects were 148 male competitors from the 1995 WIRC. MAS indicated that T*H*A(-0.06) expresses T free of the confounding effect of H and A. We also scaled T only by H on those subjects, A < 40, (N = 109). Results showed that T*H is an optimal and particularly feasible scaling of T. Use of either convention dramatically changed race results. In conclusion, we recommend use of either the T.H (17 < or = A < or = 39) or T*H*A(-0.06) conventions to adjust WIRC performance in adult males.


Combined Interaction of Cellular and Extracellular Components Causes Genetic Cascade Activation in Breast Cancer Metastasis.
Breast cancer (BC) consists of malignant cells as well as surrounding nonmalignant cells - fibroblasts, macrophages, endothelial cells, lymphocytes, neutrophils, mesenchymal stem cells, and extracellular matrix (ECM). This surrounding stroma is referred to as the breast tumor microenvironment (BTME). The components of BTME interact with cancerous breast cells for the promotion of BC. The reciprocal cross talk between BTME and neoplastic breast cells, through the secretion of chemicals, growth factors, and chemokines, may lead to cell proliferation, migration, metastasis as well as immune response suppression. Multiple genetic loci, in association with stromal components, are linked to immunological stimuli to induce BC in ductal cells. These genes participate in tumor activation pathways and promote carcinogenesis via fibroblast, leukocyte, and endothelial-cell-mediated responses. The collaborative effect of the cellular components and BTME-associated genes plays vital role in tumor initiation and metastasis of breast cells. This process involves genes which cause degenerative changes in ECM leading to epithelial-mesenchymal transitions, which finally causes metastatic BC. This shows that metastatic BC results from combined activation of different cellular and extracellular components, and their activity is primarily controlled by activation of the genetic cascade. These components work simultaneously to cause metastatic BC.


Maternal erythrocyte fatty acid composition as a predictive marker for pregnancy health.
Pregnancy is accompanied by a surge in demand for fatty acids (FAs) in order to support maternal health, as well as fetal growth and development. Of particular demand is essential for long-chain polyunsaturated FAs. FAs are primarily obtained from dietary sources and are distributed in the body. In comparison with the use of self-reporting approaches, measuring the FA levels within different blood compartments can present a more accurate image of nutritional, and thus tissue, FA composition. Hence, the FA profile of plasma or serum is commonly used for physiological analyses. Nevertheless, plasma and serum FAs are not yet incorporated into cell membranes, and consequently may not be a suitable reflection of the FA status of body tissues. The evaluation of erythrocyte FA levels offers a superior possibility for the following reasons: the biological fluctuation of erythrocyte FA composition is low, phospholipids account for almost all the lipid content of erythrocytes, and the FA profiles of erythrocytes represent those of tissues. Here, we elaborate on whether the status of maternal erythrocyte FAs can serve as a prognostic biomarker for reproductive health and fetomaternal complications, including embryonic and fetoplacental development, gestational length, and preeclampsia. In addition, factors with the potential of altering the maternal erythrocyte FAs such as maternal diet, lifestyle habits, genetics, and body composition are discussed.


A genome-wide association study for a proxy of intermuscular fat level in the Italian Large White breed identifies genomic regions affecting an important quality parameter for dry-cured hams.
Intermuscular fat content in protected designations of origin dry-cured hams is a very important meat quality trait that affects the acceptability of the product by the consumers. An excess in intermuscular fat (defined as the level of fat deposition between leg muscles) is a defect that depreciates the final product. In this study we carried out a genome-wide association study for visible intermuscular fat (VIF) of hams in the Italian Large White pig breed. This trait was evaluated on the exposed muscles of green legs in 1122 performance-tested gilts by trained personnel, according to a classification scale useful for routine and cheap evaluation. All animals were genotyped with the Illumina PorcineSNP60 BeadChip. The genome-wide association study identified three QTL regions on porcine chromosome 1 (SSC1; accounting for ~79% of the SNPs below the 5.0E-04 threshold) and SSC2, two on SSC7 and one each on SSC3, SSC6, SSC9, SSC11, SSC13, SSC15, SSC16 and SSC17. The most significant SNP (ALGA0004143 on SSC1 at 77.3 Mb; PFDR < 0.05), included in the largest QTL region which spanned about 6.8 Mb on SSC1, is located within the glutamate ionotropic receptor kainate type subunit 2 (GRIK2) gene. Functional annotation of all genes included in QTL regions for VIF suggested that intermuscular fat in the Italian Large White breed is a complex trait apparently influenced by complex biological mechanisms also involving obesity-related processes. These QTL target mainly chromosome regions different from those affecting subcutaneous and intramuscular fat deposition.


[Recombinant expression of mutant human annexin V].
To mutate human annexin V gene and transform it to Pichia Pastoris for mutant human annexin V expression, so as to be purified as active annexin V with endogenous metal chelating site. The 5' and 3' end of native annexin V gene were mutated by specific primers. The mutant annexin V gene was inserted into pPIC9K and sequenced. The correct plasmid was linearized and transformed into Pichia Pastoris strain GS115 by electroporation. The transformants were selected from MD plates and cultured in BMGY medium and induced with methanol. The culture was centrifuged and the supernatant was analyzed by SDS-PAGE and silver staining. The binding activity of mutant human annexin V from culture supernatant was determined with phosphatidylserine exposed erythrocytes and fluorescein isothiocyanate-annexin V. The 5' end of native human annexin V gene was fused with GCAGGCGGCTGCGGCCAT coding sequence and 3' end 946-948 site TGT was mutated to AGC. Pichia Pastoris transformants secreted proteins of relative molecular mass 36 000 48 h after methanol induction. The concentration of this protein that inhibited 50% of the binding of fluorescein-annexin V was 4nmol/L. Highly-active recombinant mutant human annexin V with endogenous metal-chelating sites can be expressed in Pichia Pastoris system.


Pityriasis rosea-like eruption induced by isotretinoin.
Pityriasis rosea is a common, self-limited and inflammatory skin disease. The etiology is not clearly known. Viral agents, autoimmunity, psychogenic factors and drugs have all been suggested as risk factors. Isotretinoin is usually used in the treatment of resistant, nodulocytic acne. We present a case of pityriasis rosea-like eruption induced by isotretinoin. To our knowledge, this is the second clinical case of pityriasis rosea-like eruption induced by isotretinoin.


Anal carcinoma in mid-Norway 1970-2000.
The treatment of anal carcinoma changed from surgery to chemoradiotherapy 20-25 years ago. The aim of this observational study was to compare surgery with chemoradiotherapy with regard to side effects, local recurrence and survival during and after the implementation of a new treatment policy for anal carcinoma. The study includes all 111 patients with anal carcinoma diagnosed between 1970 and 2000 in mid-Norway. One hundred patients were treated with the intention to cure, and 11 patients received palliative treatment. Thirty-four patients were treated with surgery alone, and 57 patients with chemoradiotherapy. Among patients treated for cure, 17 patients (17%) developed local recurrence; ten patients (33%) in the surgically treated group and 4 (7%) in the chemoradiotherapy group (p = 0.15). Five year overall survival was 48% after surgery, compared to 78% after chemoradiotherapy (p = 0.004). Stage, age and treatment were all significant indicators of survival in uni- and multivariable analysis. Late side effects were moderate after combined therapy; only one patient preferred getting a stoma due to radiation damage of the anal sphincter. The change of strategy for anal cancer treatment from surgery to combined therapy has probably reduced local recurrence and improved survival. Side effects in this series of patients were minor after chemoradiotherapy compared to a permanent stoma after surgery.


Ectopic Pelvic Fibroid in a Woman With Uterine Agenesis and Mayer-Rokitansky-Küster-Hauser Syndrome.
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare disorder characterized by aplasia or hypoplasia of the uterus and vagina due to arrest in the development of the müllerian ducts. Women with this syndrome have the normal 46 XX karyotype, normal female secondary sex characteristics, and primary amenorrhea. Only a few cases have been described in the literature where a fibroid develops from a rudimentary, nonfunctioning uterus in patients with MRKH syndrome. In even rarer instances, a fibroid can develop in patients with a congenitally absent uterus.Here, we present the first reported case of an ectopic fibroid in association with congenital absence of a uterus found by ultrasound in a 66-year-old white female patient with MRKH syndrome and unilateral renal agenesis.


Smoking cessation research in primary care treatment centers: the SCRIPT-MS project.
Despite wide distribution of an evidence-based clinical practice guideline, the provision of treatment for tobacco use has been weak. The primary care setting is an ideal environment in which to implement the tobacco clinical practice guideline. It has been suggested that implementation of the guideline may be enhanced by adapting guideline recommendations into a stepped-care plus treatment-matching model; however, this model has yet to be tested. This article describes an ongoing investigation designed to evaluate (1) the feasibility of implementing this treatment model in a primary care environment, (2) efforts on identifying reasonable assessment methods, (3) primary care providers' use of assessment data, and (4) the relationships between predictors and outcomes under differing treatment "step" conditions in primary care settings. Six primary care clinics are participating in this study comparing usual care, brief clinical intervention, and enhanced clinical intervention conditions. The last of these conditions is hypothesized to produce the best and most cost-effective outcomes. Recruitment is expected to continue until January 2004, being 65% complete as of this writing. Follow-up contacts will continue until April 2005. Results should provide information that will contribute to the ongoing development of primary care-based tobacco intervention approaches.


Analysis of aortic area/height ratio in patients with thoracic aortic aneurysm and Type A dissection.
Significant proportions of aortic dissections occur at aortic diameters <5.5 cm. By indexing aortic area to height and correlating with absolute aortic diameter, we sought to identify those aneurysm patients with aortic diameters <5.5 cm who do not meet current size thresholds for surgery, yet with corresponding abnormal indexed aortic areas (IAAs) >10 cm2/m, are at increased risk of aortic complications. IAAs were calculated at 3 aortic locations in 187 aneurysm and 66 dissection patients operated on between 2010 and 2016 at our tertiary aortic centre. Proportions of patients with IAA >10 cm2/m, mean IAAs corresponding to aortic diameters <4.0 cm, 4.0-4.5 cm, 4.5-5.0 cm, 5.0-5.5 cm and >5.5 cm, and mean aortic diameters corresponding to IAAs 10-12 cm2/m, 12-14 cm2/m and >14 cm2/m were determined. Proportions of patients with abnormal IAAs were similar in both groups. In all, 49.1% of aneurysm patients with aortic diameters 4.5-5.0 cm, and 98.5% with aortic diameters 5.0-5.5 cm had abnormal IAAs. Out of 200 separate aneurysms with IAAs >10 cm2/m between the mid-sinus and mid-ascending aorta, 139 (69.5%) would not warrant surgery according to existing guidelines. Using the IAA, we identified a significant proportion of patients with thoracic aortic aneurysms who are at increased risk of aortic complications, despite current aortic guidelines not endorsing surgical intervention in this group. Our data suggests the IAA may be useful in preoperative risk evaluation and as a criterion for surgery.


Conceptualization and measurement of environmental exposure in epidemiology: accounting for activity space related to daily mobility.
A considerable body of literature has investigated how environmental exposures affect health through various pathways. These studies have generally adopted a common approach to define environmental exposures, focusing on the local residential environment, using census tracts or postcodes to delimit exposures. However, use of such administrative units may not be appropriate to evaluate contextual effets on health because they are generally not a 'true' representation of the environments to which individuals are exposed. Recent work has suggested that advances may be made if an activity-space approach is adopted. The present paper investigates how various disciplines may contribute to the refinement of the concept of activity space for use in health research. In particular we draw on seminal work in time geography, which provides a framework to describe individual behavior in space and time, and can help the conceptualization of activity space. In addition we review work in environmental psychology and social networks research, which provides insights on how people and places interact and offers new theories for improving the spatial definition of contextual exposures.


Effect of Mechanical Heterogeneity on the Structural Integrity of HTPB Propellant Grain.
To investigate the structural effects of the mechanical heterogeneity of Hydroxyl-terminated polybutadiene (HTPB) propellant grain under ignition pressurization, a gradient finite element method was proposed to evaluate its structural integrity. The heterogeneous mechanical properties of the propellant grain were constructed and assessed. The results demonstrate that the mechanical properties of the propellant grain are spatially variable when taking into account the effect of the load. The range of variation in the mechanical properties is related to the size of the load and its effect on the mechanical properties of the propellant. Two key parameters that affect the mechanical response of the grain are the non-uniform distribution of the modulus and the damage strain threshold. An increase in the propellant modulus leads to an increase in the stress response and a decrease in the strain response of the propellant grain under ignition pressurization. Meanwhile, an increase in the damage strain threshold improves the propellant's modulus in the linear elastic stage in a disguised form. This also leads to an increase in the stress response and a decrease in the strain response when the strain response exceeds the damage strain threshold. The safety factor, based on the equivalent strain failure criterion of the grain, directly depends on both the strain response of the propellant grain and the maximum elongation of the propellant. Furthermore, the change in the safety factor of two propellant grains is primarily affected by the maximum elongation of the propellant.


Understanding statistics. Putting p-values into perspective.
Understanding statistics can be one of the more difficult and daunting tasks facing the clinician attempting to understand and use the research literature. While the fundamental aim of including statistics in literature is to justify the conclusions and to enhance the information presented, all too often, statistics serve only to intimidate and alienate clinicians. There are two sources for this barrier to understanding: poor comprehension of statistics by clinicians, and inappropriate presentation of statistics by researchers. In the third of our papers on evidence-based practice and the clinician, some basic principles of statistics are introduced. Aspects such as the concepts of clinical and statistical significance are discussed, and an outline of the appropriate use of specific statistics is provided. The hope is that this will enable the clinician to better judge the applicability of statistical techniques as applied in the published literature. Some of the newer, more 'clinician friendly' statistical approaches are also presented. Finally some of the cheats and shortcuts commonly encountered in the presentation of research are discussed, and the methods for dealing with them are outlined.


A comparison of operative approaches and parameters predictive of success in multilevel arterial occlusive disease.
The correction of abnormal inflow alone in patients with multilevel arterial occlusive disease (MLAOD) may be inadequate to relieve limb-threatening ischemia. This study was undertaken to compare operative approaches and attempt to define preoperative parameters predictive of limb salvage in patients with MLAOD. The outcome after revascularization for 194 patients with limb-threatening ischemia MLAOD was assessed retrospectively. One hundred fifty-one patients initially underwent an inflow operation alone. Based on whether or not these patients required an outflow operation within one year, they were divided into two groups: group 1, no outflow operation (121 patients, 121 limbs), and group 2, outflow operation required for continued ischemic symptoms (30 patients, 30 limbs). A separate group of forty-three patients (43 limbs) underwent synchronous inflow-outflow operations, or multilevel revascularization, as their initial operative procedure (group 3). Perioperative complications and mortality rates did not differ between groups. Limb salvage rates were similar for groups 1 and 3, whereas in group 2, limb salvage rates were significantly reduced (p = 0.0184). Long-term limb salvage after an isolated inflow procedure was associated with lack of prior vascular reconstructions (p = 0.0002), the absence of tissue loss (p = 0.0019), and an infrageniculate angiographic runoff score of less than 6 (p = 0.054). In patients with limb-threatening MLAOD, synchronous inflow-outflow operations can be performed with resultant morbidity and mortality rates comparable with inflow alone. After an inflow operation, the approach of "expectant management" may ultimately compromise limb salvage if a subsequent outflow operation is required.


Impact of a teaching scholars program.
Researchers employ various approaches to evaluate teaching scholars programs (TSPs). We interviewed secondary beneficiaries of the TSP. During an interview, TSP graduates identified individuals and/or groups whom they felt were affected as a result of their TSP participation. At least one individual from each type of these identified beneficiaries was interviewed. Quantitative results were summarized descriptively and qualitative comments coded through a consensus process. Thirty-six (88%) of TSP participants were interviewed. From their responses, 50 beneficiaries were interviewed. Sixty-eight percent of beneficiaries identified that, as a result of TSP, the scholars became better teachers and educational scholars and enhanced educational scholarship, programs, teaching, mentoring, and leadership in departments. Eighty-nine percent identified educational projects emanating from their contact with the scholar. Beneficiaries validated that the TSP produced better teachers and scholars. The impact in scholarship validated the importance of completing a project as part of the TSP. TSP also enhanced networking and educational resources for departments.


Experimental evidence of coexisting periodic stochastic resonance and coherence resonance phenomena.
We report evidence of coexisting period stochastic resonance (PSR) and coherence resonance (CR) phenomena in an electrochemical cell. The anodic voltage (V) in the cell is chosen such that the anodic current (I) exhibits excitable fixed point behavior. Subsequently, the anodic voltage is modulated by an external perturbation that is a composite of a subthreshold periodic pulse signal and Gaussian white noise (GWN). As the amplitude of the GWN is increased, the regularity of the invoked dynamics is analyzed using normalized variance curve. The calculated resonance curve shows a double minima, implying the existence of two optimum noise levels where enhanced regularity of the induced spike sequence is detected. Numerical simulations corroborate experimental findings.


Local level of TGF-β1 determines the effectiveness of dexamethasone through regulating the balance of Treg/Th17 cells in TNBS-induced mouse colitis.
Transforming growth factor β1 (TGF-β1) has a crucial role in regulating the balance of type 17 T-helper cells (Th17) and T regulatory cells (Tregs) that are involved in the pathogenesis of inflammatory bowel disease, while the function of local TGF-β1 in this process has remained to be fully elucidated. The present study investigated the effects of different local TGF-β1 levels on the Treg/Th17 balance and on the dexamethasone efficacy in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Various TGF-β1 levels in colon tissue were achieved by enema delivery of a high, medium or low amount of adenovirus expressing TGF-β1 (107, 108 or 109 pfu, denoted as AdTGF-1, AdTGF-2 and AdTGF-3, respectively). Dexamethasone further decreased colon damage and myeloperoxidase activity in TNBS mice receiving AdTGF-1 and AdTGF-2. When AdTGF-1 was administered, dexamethasone enhanced its effect by reducing interferon (IFN)-γ and increasing interleukin (IL)-10 production. In TNBS mice receiving AdTGF-2, the increase in IFN-γ, tumor necrosis factor-α, IL-6, IL-17 and IL-23 was significantly prevented by dexamethasone treatment. In comparison with the lower doses, AdTGF-3 exerted the opposite effect on regulating the cytokine production in TNBS mice, which was not affected by dexamethasone treatment. In mesenteric lymph nodes, AdTGF-1 prevented the TNBS-induced reduction of Tregs and IL-10, and potentially increased the efficacy of dexamethasone. In addition, dexamethasone further decreased the levels of activated caspase3 in TNBS mice receiving adenoviral TGF-β1, particularly in the AdTGF-1 group. The activation of the p38 mitogen-activated protein kinase/c-Jun N-terminal kinase/c-Jun pathway was significantly inhibited by a low amount of TGF-β1 administered to TNBS-treated mice, which was further decreased by dexamethasone. The present study provided evidence that the therapeutic effect of dexamethasone may depend on the local levels of TGF-β1 in TNBS-induced colitis and may be mediated, at least partially, through promoting the differentiation of Tregs and thus altering the balance of pro- and anti-inflammatory cytokines.


Management of Diabetes Mellitus in Normal Renal Function, Renal Dysfunction and Renal Transplant Recipients, Focusing on Glucagon-Like Peptide-1 Agonist: A Review Based upon Current Evidence.
Diabetes Mellitus (DM) is a leading cause of both Cardiovascular Disease (CVD) and End-stage Renal Disease (ESRD). After 2008, there has been much evidence presented, and recently the guidelines for sugar control have changed to focus on being more disease orientated. GLP-1 Receptor Agonists (GLP-1R) and sodium glucose cotransporter-2 inhibitors are suggested as the first line towards fighting all DM, CVD and ESRD. However, the benefits of GLP-1R in organ transplantation recipients remain very limited. No clinical trials have been designed for this particular population. GLP-1R, a gastrointestinal hormone of the incretin family, possesses antidiabetic, antihypertensive, anti-inflammatory, anti-apoptotic and immunomodulatory actions. There are few drug-drug interactions, with delayed gastric emptying being the major concern. The trough level of tacrolimus may not be significant but should still be closely monitored. There are some reasons which support GLP-1R in recipients seeking glycemic control. Post-transplant DM is due to an impaired β-cell function and glucose-induced glucagon suppression during hyperglycemia, which can be reversed by GLP-1R. GLP-1R infusion tends to relieve immunosuppressant related toxicity. Until now, in some cases, glycemic control and body weight reduction can be anticipated with GLP-1R. Additional renal benefits have also been reported. Side effects of hypoglycemia and gastrointestinal discomfort were rarely reported. In conclusion, GLP-1R could be implemented for recipients while closely monitoring their tacrolimus levels and any potential side effects. Any added benefits, in addition to sugar level control, still require more well-designed studies to prove their existence.


Thermal Pain in Teeth: Electrophysiology Governed by Thermomechanics.
Thermal pain arising from the teeth is unlike that arising from anywhere else in the body. The source of this peculiarity is a long-standing mystery that has begun to unravel with recent experimental measurements and, somewhat surprisingly, new thermomechanical models. Pain from excessive heating and cooling is typically sensed throughout the body through the action of specific, heat sensitive ion channels that reside on sensory neurons known as nociceptors. These ion channels are found on tooth nociceptors, but only in teeth does the pain of heating differ starkly from the pain of cooling, with cold stimuli producing more rapid and sharper pain. Here, we review the range of hypotheses and models for these phenomena, and focus on what is emerging as the most promising hypothesis: pain transduced by fluid flowing through the hierarchical structure of teeth. We summarize experimental evidence, and critically review the range of heat transfer, solid mechanics, fluid dynamics, and electrophysiological models that have been combined to support this hypothesis. While the results reviewed here are specific to teeth, this class of coupled thermomechanical and neurophysiological models has potential for informing design of a broad range of thermal therapies and understanding of a range of biophysical phenomena.


Hepatitis C virus antibody titers associated with cognitive dysfunction in an asymptomatic community-based sample.
Hepatitis C virus (HCV) infection is associated with cognitive dysfunction in clinic-based studies. The risk could be attributed to factors such as antiviral medications, substance abuse, or coincidental infection. The aim was to evaluate cognitive function in relation to HCV antibody titers in a community-based sample of asymptomatic individuals at low risk for substance abuse. Adults were ascertained from a community in Mansoura, Egypt, where HCV is endemic (n = 258). Cognitive performance was evaluated using the Arabic version of the Penn Computerized Neurocognitive Battery. Substance abuse and psychopathology were also assessed. Antibodies to HCV and Toxoplasma gondii (TOX), a common protozoan that can affect cognition, were estimated using serological IgG assays. The prevalence of HCV and TOX infection was 17.6% and 52.9%, respectively. HCV antibody titers were significantly associated with worse function in four cognitive tests for accuracy and three tests for speed, after adjusting for covariates (p < .05, beta coefficients, 2.1-3.2). TOX antibody titers were associated with impaired accuracy in one test. The association between HCV antibody titers and cognitive impairment is not mediated by antiviral treatment or substance abuse in this sample. Whether HCV has a causal role in the cognitive dysfunction should be investigated.


Effects of Alcohol on Postoperative Adhesion Formation in Ischemic Myocardium and Pericardium.
Postoperative formation of adhesions increases risk of complications during cardiac reoperations. We previously demonstrated that swine supplemented with vodka had a significant reduction in adhesions at sternotomy after previous thoracotomy. This follow-up study was conducted to determine reproducibility and the mechanism for adhesion reduction in swine supplemented with ethanol. An ameroid constrictor was placed in the left circumflex in 14 male Yorkshire swine to induce chronic myocardial ischemia through left minithoracotomy. Animals were supplemented postoperatively with ethanol (45 g ETOH, n = 7) or sucrose (80 g SUC, n = 7) for 7 weeks, followed by a reoperative median sternotomy. The ETOH group had significantly fewer adhesions, thinner pericardial thickness, decreased intramyocardial fibrosis, and decreased myocardial collagen deposition compared with the SUC group. In the myocardium, ETOH animals had decreased expression of proadhesion proteins focal adhesion kinase, paxillin, integrin-β1, transforming growth factor-β1 and phosphorylated SMAD and increased expression of adhesion breakdown proteins matrix metalloproteinase (MMP) 1, MMP2, MMP3, and MMP9 compared with SUC animals. However in the pericardium, ETOH animals had increased expression of proadhesion proteins focal adhesion kinase, paxillin, phosphorylated paxillin, vinculin, integrin-β1, tumor necrosis factor-α, transforming growth factor-β, and phosphorylated SMAD3, and decreased expression of adhesion breakdown proteins MMP1, MMP3, MMP9, and plasmin compared with SUC animals. Alcohol supplementation substantially reduced postoperative pericardial adhesion formation, attenuated pericardial thickening, and reduced myocardial fibrosis in response to chronic ischemia. Alcohol supplementation modulates adhesion protein and MMP/tissue inhibitor of metalloproteinase expression, favoring a profile associated with reduced pericardial adhesions. These results suggest that the myocardium is the driving factor in reducing pericardial adhesions and mediating the postoperative healing process.


Genetic screening in C. elegans identifies rho-GTPase activating protein 6 as novel HERG regulator.
The human ether-a-go-go related gene (HERG) constitutes the pore forming subunit of I(Kr), a K(+) current involved in repolarization of the cardiac action potential. While mutations in HERG predispose patients to cardiac arrhythmias (Long QT syndrome; LQTS), altered function of HERG regulators are undoubtedly LQTS risk factors. We have combined RNA interference with behavioral screening in Caenorhabditis elegans to detect genes that influence function of the HERG homolog, UNC-103. One such gene encodes the worm ortholog of the rho-GTPase activating protein 6 (ARHGAP6). In addition to its GAP function, ARHGAP6 induces cytoskeletal rearrangements and activates phospholipase C (PLC). Here we show that I(Kr) recorded in cells co-expressing HERG and ARHGAP6 was decreased by 43% compared to HERG alone. Biochemical measurements of cell-surface associated HERG revealed that ARHGAP6 reduced membrane expression of HERG by 35%, which correlates well with the reduction in current. In an atrial myocyte cell line, suppression of endogenous ARHGAP6 by virally transduced shRNA led to a 53% enhancement of I(Kr). ARHGAP6 effects were maintained when we introduced a dominant negative rho-GTPase, or ARHGAP6 devoid of rhoGAP function, indicating ARHGAP6 regulation of HERG is independent of rho activation. However, ARHGAP6 lost effectiveness when PLC was inhibited. We further determined that ARHGAP6 effects are mediated by a consensus SH3 binding domain within the C-terminus of HERG, although stable ARHGAP6-HERG complexes were not observed. These data link a rhoGAP-activated PLC pathway to HERG membrane expression and implicate this family of proteins as candidate genes in disorders involving HERG.


[Clinical efficacy and bacteriological studies of clarithromycin and cefdinir against group A beta-hemolytic streptococcal tonsillopharyngitis].
The clinical efficacy and safety of clarithromycin (CAM) and cefdinir (CFDN) were evaluated in 65 pediatric outpatients with group A beta-hemolytic streptococcal tonsillopharyngitis. Treatment was "effective" or better in 26 (78.8%) children receiving CAM and in 27 (87.1%) receiving CFDN based on antigen clearance and the "Criteria for Evaluation in Clinical Trials of Antibacterial Agents in Children" proposed by Japan Society of Chemotherapy (p = NS). The causative organisms were eradicated in 94.7% and 93.8% of subjects in the CAM and CFDN groups, respectively (p = NS). Adverse drug reactions were limited to moderate diarrhea in one patient in each group, and subsided during treatment. Causative organisms exhibited good susceptibility to CAM and CFDN. These results suggest excellent efficacy, safety and usefulness of CAM and CFDN in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitsis in children.