Equal volumes of high and low intensity of eccentric exercise in relation to muscle damage and performance.
We examined differences in muscle damage and muscle performance perturbations in relation to the same volumes of high (HI) and low intensity (LI) of eccentric exercise. Untrained young healthy men (n = 12) underwent 2 isokinetic quadriceps eccentric exercise sessions, 1 on each randomly selected leg, separated by a 2-week interval. In the first session subjects performed HI exercise (i.e., 12 sets of 10 maximal voluntary efforts). In the second session, volunteers were subjected to continuous exercise of LI (50% of peak torque) until the total work done was approximately equal to that generated during HI. Muscle damage (serum creatine kinase concentration [CK], delayed onset of muscle soreness, and range of motion) and muscle performance (eccentric [EPT] and isometric peak torque [IPT]) indicators were assessed pre-exercise and 24, 48, 72, and 96 hours postexercise. Compared to baseline data, changes in muscle damage indicators were significantly different (p < 0.05) at almost all postexercise time points in both conditions. However, apart from the significant elevation of CK at 24 hours after HI (p < 0.05), no other significant differences were observed between the 2 exercise conditions (p > 0.05). The main finding in relation to muscle performance was that decrements following HI exercise were significantly greater (p < 0.05) compared to LI. Compared with baseline data, the EPT values following HI and LI exercise were as follows: 24 hours, 72.1% vs. 92%; 48 hours, 81.9% vs. 94.8%; 72 hours, 77.7% vs. 100.6%; 96 hours, 86.8% vs. 107.9%. The corresponding data for IPT were as follows: 24 hours, 86.4% vs. 102.8%; 48 hours, 84.2% vs. 107%; 72 hours, 84.8% vs. 109.2%; 96 hours, 86.8% vs. 114.4%. These results indicate that matching volumes of HI and LI eccentric exercise have similar effects on muscle damage, but HI has a more prominent effect on muscle performance.


Application of life course trajectory methods to public health data: A comparison of sequence analysis and group-based multi-trajectory modeling for modelling childhood adversity trajectories.
There is increasing awareness of the importance of modelling life course trajectories to unravel how social, economic and health factors relate to health over time. Different methods have been developed and applied in public health to classify individuals into groups based on characteristics of their life course. However, the application and results of different methods are rarely compared. We compared the application and results of two methods to classify life course trajectories of individuals, i.e. sequence analysis and group-based multi-trajectory modeling (GBTM), using public health data. We used high-resolution Danish nationwide register data on 926,160 individuals born between 1987 and 2001, including information on the yearly occurrence of 7 childhood adversities in 2 dimensions (i.e. family poverty and family dynamics). We constructed childhood adversity trajectories from 0 to 15 years by applying (1) sequence analysis using optimal matching and cluster analysis using Ward's method and (2) GBTM using logistic and zero-inflated Poisson regressions. We identified 2 to 8 cluster solutions using both methods and determined the optimal solution for both methods. Both methods generated a low adversity, a poverty, and a consistent or high adversity cluster. The 5-cluster solution using sequence analysis additionally included a household psychiatric illness and a late adversity cluster. The 4-group solution using GBTM additionally included a moderate adversity cluster. Compared with the solution obtained through sequence analysis, the solution obtained through GBTM contained fewer individuals in the low adversity cluster and more in the other clusters. We find that the two methods generate qualitatively similar solutions, but the quantitative distributions of children over the groups are different. The method of choice depends on the type of data available and the research question of interest. We provide a comprehensive overview of important considerations and benefits and drawbacks of both methods.


Linkage and evolutionary diversification of developmentally regulated multigene families: tandem arrays of the 401/18 chorion gene pair in silkmoths.
The coordinately expressed silkmoth chorion genes, 401 and 18, are closely linked as a pair, in divergent orientation. Analysis of overlapping clones (chromosomal "walk") demonstrated that each of the multiple copies of this gene pair is embedded within a larger deoxyribonucleic acid unit, which is tandemly repeated in a few arrays or possibly a single array. Southern analysis and examination of clones from a single individual moth demonstrated that the repeat units are extensively polymorphic in restriction sites, length, and possibly number, no differential amplification was evident during choriogenesis. Intron and 5'-flanking sequences were shown to be specific for the 401/18 gene pair and not to be present elsewhere in the genome. The spatial distribution of variations in the genes and their flanking sequences were examined.


FADD at the Crossroads between Cancer and Inflammation.
Initially described as an adaptor molecule for death receptor (DR)-mediated apoptosis, Fas-associated death domain (FADD) was later implicated in nonapoptotic cellular processes. During the last decade, FADD has been shown to participate and regulate most of the signalosome complexes, including necrosome, FADDosome, innateosome, and inflammasome. Given the role of these signaling complexes, FADD has emerged as a new actor in innate immunity, inflammation, and cancer development. Concomitant to these new roles, a surprising number of mechanisms deemed to regulate FADD functions have been identified, including post-translational modifications of FADD protein and FADD secretion. This review focuses on recent knowledge of the biological roles of FADD, a pleiotropic molecule having multiple partners, and its impact in cancer, innate immunity, and inflammation.


The metabolic regulation in immune cells and pathogenesis of systemic lupus erythematosus ∼toward new therapeutic applications∼.
The importance of cellular metabolism has long been known as Warburg effect; cancer cells are characterized by mitochondrial defect that shifts towards aerobic glycolysis. Recently, many reports have revealed that immune metabolism is a key factor for controlling immune cell proliferation and differentiation. Resting lymphocytes generate energy through oxidative phosphorylation and fatty acid oxidation, whereas activated lymphocytes rapidly shift to glycolysis. Especially in T cells, more precise mechanism of regulating metabolism have been clarified on differentiation from naïve T cells to effector T cells. Similar studies have also been carried out to characterize B cell and myeloid cell metabolism. Metabolic regulation is considered to be particularly important in autoimmune diseases. Metabolic changes in these diseases might not only reflect the chronic activated immune-status but also associated with their pathogenesis. Here, we review what is known on the altered metabolism in systemic lupus erythematosus (SLE), mainly focusing on T cells and B cells, and how they contribute to SLE pathogenesis. We also discuss how immune metabolic defects can become targets of future SLE therapy.


Expression pattern of the Ets-related transcription factor Elf-1.
Members of the Ets family of winged helix-loop-helix transcription factors play important roles in the development and function of multiple mammalian cell lineages. Elf-1 is an Ets-related transcription factor that is expressed at high levels in T cells and is known to regulate the expression of several T cell genes, including the granulocyte-macrophage colony stimulating factor (GM-CSF) gene, the interleukin-2 receptor alpha subunit (IL-2Ralpha) gene, and the CD4 gene. In the studies described in this report, we have characterized the pattern of expression of Elf-1 in the developing mouse embryo and in adult mouse tissues as well as in multiple immortalized human and murine cell lines. Elf-1 is expressed at high levels throughout thymocyte development, with equivalent levels of Elf-1 expression seen in all subsets of maturing thymocytes and T cells. Somewhat surprisingly, however, Elf-1 is also expressed at high levels in epithelial cells lining the oral cavity, the lung, the CNS, and the gastrointestinal and urinary tracts as well as in the skin of the developing mouse embryo and at lower levels in the adult mouse testis and liver. Western blot analyses of a large number of immortalized cell lines demonstrated high-level Elf-1 expression in T and B lymphocyte and macrophage cell lines as well as in two prostate carcinoma cell lines. Low-level expression was observed in fibroblasts, embryonic stem cells, and myoblasts. Taken together, our data suggest that in addition to its role in regulating T cell development and function, Elf-1 may regulate gene expression in the B cell and myelomonocytic lineages, as well as in multiple epithelial cell types during murine embryonic development.


Single-cell sequencing of head and neck carcinoma: Transcriptional landscape and prognostic model based on malignant epithelial cell features.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the development of novel therapeutic strategies for HNSCC requires a profound understanding of tumor cells and the tumor microenvironment (TME). Additionally, HNSCC has a poor prognosis, necessitating the use of genetic markers for predicting clinical outcomes in HNSCC. In this study, we performed single-cell sequencing analysis on tumor tissues from seven HNSCC patients, along with one adjacent normal tissue. Firstly, the analysis of epithelial cell clusters revealed two clusters of malignant epithelial cells, characterized by unique gene expression patterns and dysregulated signaling pathways compared to normal epithelial cells. Secondly, the examination of the TME unveiled extensive crosstalk between fibroblasts and malignant epithelial cells, potentially mediated through ligand-receptor interactions such as COL1A1-SDC1, COL1A1-CD44, and COL1A2-SDC1. Furthermore, transcriptional heterogeneity was observed in immune cells present in the TME, including macrophages and dendritic cells. Finally, leveraging the gene expression profiles of malignant epithelial cells, we developed a prognostic model comprising six genes, which we validated using two independent datasets. These findings shed light on the heterogeneity within HNSCC tumors and the intricate interplay between malignant cells and the TME. Importantly, the developed prognostic model demonstrates high efficacy in predicting the survival outcomes of HNSCC patients.


The efficacy of functional communication therapy for chronic aphasic patients.
Twelve weeks of therapy emphasizing functional communication content was conducted twice weekly in a group setting for seven chronic aphasic patients whose average post-onset time was 97.9 months. Porch Index of Communicative Abilities (PICA) test scores did not change significantly as a result of this treatment. Communicative Abilities in Daily Living (CADL) test scores, however, revealed statistically significant improvement in post-treatment performances. A final administration of CADL tests six weeks after cessation of functional communication treatment indicated that the positive change in CADL scores had been maintained.


Calbindin D28K and parvalbumin gene expression in rat embryonic ventral forebrain grafts.
The present study characterizes expression of calbindin D28K (CB-D28K) and parvalbumin (PV) in ventral forebrain (VFB) grafts placed in the neocortex of adult rats bearing quisqualic acid lesions to the nucleus basalis magnocellularis. Three to nine months after transplantation surgery, rats were killed for in situ hybridization with probes to CB-D28K or PV and for immunohistochemistry with antibodies to CB-D28K or PV. In addition, an antibody to choline acetyltransferase (ChAT) was used to characterize the cholinergic component in the graft and an antibody to tyrosine hydroxylase (TH) to explore catecholaminergic innervation of the graft. Quantitative analysis of CB-D28K and PV messenger ribonucleic acid (mRNA) was based on counts of silver grains generated by emulsion autoradiography. Cells expressing CB-D28K mRNA were significantly larger than such cells in the adult VFB and the mean number of silver grains per cell was significantly greater than to such cells in the adult VFB. The level of CB-D28K mRNA expression as calculated by ratio of silver grains per unit area was also significantly increased. Quantification of PV mRNA showed no significant differences between the cells in the graft and in the adult VFB. In order to begin to interpret these findings, a comparison was made with such cells in the VFB of developing rats. Brain sections were sampled from embryonic day 17 and postnatal days 1, 5, 12, 19 and adult (6-12 months of age). Cells expressing CB-D28K mRNA were detected in ventral forebrain from postnatal day 5 and cells expressing PV mRNA were detected in ventral forebrain from postnatal day 19. In the course of normal development of the ventral forebrain, no CB-D28K cells were found that were as large or expressed such high levels of CB-D28K mRNA as observed in the grafts. We conclude that changes in grafted cells expressing CB-D28K do not reflect an arrest of developmental processes. TH immunohistochemistry revealed lack of catecholaminergic innervation of the graft, whereas adult mediolateral septal cells that express CB-D28K receive such innervation in addition to other neurotransmitter inputs. Imbalance in neurotransmitter inputs to grafted cells expressing CB-D28K is discussed as a possible factor in their increased size and gene expression.


[Table method of the component expansion of phenotypic variance based on correlations between relatives].
Tables are proposed which allow to ease and unify calculations of component partitioning of the phenotype variance based on the "least squares methods". Combinations of additive and dominant genetic components and four common environmental ones are considered. To use tables, information is needed about correlations among following types of relatives: 1) MZ and DZ twins, parent-offspring; 2) siblings, parent-offspring, second degree relatives; 3) the first variant and sibling; 4) the third variant and second degree relatives.


FOXO3 encodes a carcinogen-activated transcription factor frequently deleted in early-stage lung adenocarcinoma.
The FOXO family of transcription factors elicits cell cycle arrest, apoptosis, and resistance to various physiologic and pathologic stresses relevant to sporadic cancer, such as DNA damage and oxidative stress. Although implicated as tumor suppressors, FOXO genetic inactivation has not been observed in human cancer. In an investigation of the two major types of non-small cell lung cancer, here, we identify the FOXO3 gene as a novel target of deletion in human lung adenocarcinoma (LAC). Biallelic or homozygous deletion (HD) of FOXO3 was detected in 8 of 33 (24.2%) mostly early-stage LAC of smokers. Another 60.6% of these tumors had losses of FOXO3 not reaching the level of HD (hereafter referred to as sub-HD). In contrast, no HD of FOXO3 was observed in 19 lung squamous cell carcinoma. Consistent with the deletion of FOXO3 were corresponding decreases in its mRNA and protein levels in LAC. The potential role of FOXO3 loss in LAC was also investigated. The carcinogen (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) is strongly implicated as a cause of human lung cancer. Here, we show that FOXO3a is functionally activated and augments the level of caspase-dependent apoptosis in cells exposed to this DNA-damaging carcinogen. These results implicate FOXO3 as a suppressor of LAC carcinogenesis, a role frequently lost through gene deletion.


Evaluation of in vitro antimicrobial susceptibility of Bacillus anthracis strains isolated during anthrax outbreaks in Italy from 1984 to 2017.
Anthrax, caused by Bacillus anthracis, is a non-contagious infectious disease that affects a wide range of animal species (primarily ruminants) including humans. Due to the often-fatal outcome in humans, quick administration of definitely effective antimicrobials is crucial either as prophylaxis or as a clinical case therapy. In this study, 110 B. anthracis strains, temporally, geographically, and genetically different, isolated during anthrax outbreaks in Italy from 1984 to 2017, were screened using a broth microdilution method to determine their susceptibility to 16 clinically relevant antimicrobial agents. The strains were isolated from various matrices (human, animal, and environmental samples) and were representative of thirty distinct genotypes previously identified by 15-loci multiple-locus variable-number of tandem repeats analysis. The antimicrobials tested were gentamicin, ceftriaxone, streptomycin, penicillin G, clindamycin, chloramphenicol, vancomycin, linezolid, cefotaxime, tetracycline, erythromycin, rifampin, amoxicillin, ciprofloxacin, doxycycline, and trimethoprim. All isolates were susceptible to most of the tested antimicrobials, with the exception of trimethoprim for which all of them showed high minimal inhibitory concentration values. An intermediate level of susceptibility was recorded for ceftriaxone and cefotaxime. Although the Centers for Disease Control and Prevention recommend the use of doxycycline, ciprofloxacin, penicillin G, and amoxicillin for treatment of human cases and for post-exposure prophylaxis to anthrax spores, this study shows a high degree of in vitro susceptibility of B. anthracis to many other antimicrobials, suggesting the possibility of an alternative choice for prophylaxis and therapy.


Unkinking The Kinked: A Rare Intussusception In The Paediatric Emergency Department.
Intussusception is the introversion of the proximal intestinal loop into the distal downstream part of the intestinal loop, leading to gut wall oedema and restriction of blood supply. A high index of suspicion is required to diagnose it timely. Mostly infants aged less than a year are vulnerable to this surgical emergency presenting mostly with abdominal distension, vomiting, reluctance to feed and bright red jelly-like stools which, if left unrecognised, may result in the development of ischaemic portion of the gut and catastrophic outcomes. We present the case of a 60-day-old baby who presented in the Paediatric Emergency Department with progressive abdominal distension and bloody stools. Abdominal X-ray showed dilated bowel and ultrasound imaging showed a target sign positive for intussusception. The baby was rushed to the operating room (OR) due to delayed presentation, where an uneventful exploratory laparotomy was performed. Acute intestinal intussusception remains a cause of low morbidity and mortality rates if recognised earlier.


Safety of fully automatic external defibrillation by untrained lay rescuers in the presence of a bystander.
Automated external defibrillators (AEDs) are becoming increasingly available in public places to be used by citizens in case of cardiac arrest. Most AEDs are semi-automatic (SAEDs), but some are fully automatic (FAEDs) and there is ongoing debate and concern that they may lead to inadvertent shocks to rescuers or bystanders because the timing of the shock is not controlled by the rescuer. We therefore compared the behaviour of untrained citizens using an FAED or an SAED in a simulated cardiac arrest scenario. One hundred and seventy-six laypeople were randomised to use an FAED or an SAED (Lifepak CR+, Medtronic, Redmond, USA) in a simulated cardiac arrest scenario on a manikin (Ambu, Denmark) where a bystander was touching the victim's upper arm. Each rescuer's performance was recorded on video and analysed afterwards using a modified Cardiff Score. The rescuer or the bystander was considered unsafe if either of them touched the victim during shock delivery. Eleven cases could not be analysed because of technical problems. Fifteen participants violated the protocol making further analysis impossible. Of the remaining 150 participants, 68 used the FAED and 82 used the SAED. The rescuers were safe in 97/150 (65%) cases, without a difference between FAED and SAED. The bystander was safe in 25/68 (37%) cases in the FAED group versus 19/82 (23%) in the SAED group (p=0.07). Combined safety of both rescuer and bystander was observed in 23/68 (34%) cases in the FAED group versus 15/82 (18%) in the SAED group (p=0.03). Safety was not compromised when untrained lay rescuers used an FAED compared with an SAED. The observation of overall safer behaviour by FAED users in the presence of bystanders may be related to the additional instructions provided by the FAED, and the reduced interaction of the rescuer with the bystander when using the SAED.


A cohesive effort to assess the suitability and disparity of carbon nanotubes for water treatment.
Population growth, industrialization, and the extensive use of chemicals in daily life have all contributed to an increase in waste generation and an intensified release of organic pollutants into the aquatic environment. To ensure the quality of water (including natural resources), the removal of these pollutants from wastewater has become a challenging task for scientific community. Conventional physical, chemical, and biological treatment methods are commonly used in combinations and are not very effective. Recently, carbon nanotubes (CNTs) emerged as the most reliable and adaptable choice for efficient water treatment due to their extraordinary material properties appearing as a single-step solution for water treatment. High surface area, exceptional porosities, hollow and layered structures, and ease of chemical activation and functionalization are some properties which makes it excellent adsorption material. Hence, this review paper discusses the recent advances in the synthesis, purification, and functionalization of CNTs for water and wastewater treatment. In addition, this study also also provides a quick overview of CNTs-based advance technologies employed in water treatment and carefully assesses the benefits versus risks during large-scale water treatment. Furthermore, it concludes that identified risks to the environment and human health cannot be easily ignored and strict regulatory requirements are a must for producing low-cost innoxious CNTs.


Intraoperative ultrasonography of the biliary tract using saline as a contrast agent: a fast and accurate technique to identify complex biliary anatomy.
Intraoperative assessment of biliary tract anatomy is relevant for a number of benign and malignant hepatobiliary diseases. During biliary reconstruction, drainage of all relevant bile ducts is imperative to prevent atrophy of undrained segment, cholangitis and secondary biliary cirrhosis. Intraoperative cholangiography, though widely used for intraoperative imaging of the biliary tract, involves heavy equipment use, radiation risk and has a limited role in the evaluation of isolated segmental bile ducts. We evaluated the use of a novel technique of intraoperative ultrasonography of the biliary tract using normal saline as a contrast agent. It involves injecting saline in any part of the biliary system while performing real-time intraoperative 2-dimensional ultrasonography. This procedure was carried out in intraoperative situations to delineate complex biliary anatomy involving segmental bile ducts. Excellent image quality was obtained in the form of opacification and demarcation of the liver segment to which the duct belongs. The flow of saline microbubbles was clearly visible on real-time ultrasound images, leading to accurate identification of the duct. Intraoperative ultrasonography with saline as a contrast agent can accurately identify small isolated segmental bile ducts and help in surgery of the biliary tract. It is a simple and inexpensive technique that can be performed with minimal resources.


Mood and cognitive side effects of interferon-alpha therapy.
The central nervous system side effects associated with interferon-alpha (IFN-alpha) therapy, including depression and cognitive changes, can compromise otherwise effective immunotherapy. The term "depression" has multiple meanings ranging from a feeling of sadness to a neuropsychiatric disorder with defined diagnostic criteria. A syndrome of mood disturbance with memory impairment, cognitive slowing, and impaired executive function is common with IFN-alpha therapy and is consistent with mild subcortical dementia. Cognitive deficits and mood disorder may occur independently, and in some cases depression is a reactive phenomenon. Risk factors for development of IFN-alpha neurotoxicity include duration of treatment, high-dose therapy, and prior cranial irradiation or neurologic illness. Past or current psychiatric illness also may put the patient at risk. Subtypes of major depression are associated with neuroendocrine and neurochemical alterations that are consistent with the observed activities of IFN-alpha. This may provide insight into the etiology of IFN-alpha neurotoxicity, as well as possible interventions. Assessment of the neuropsychiatric status of patients treated with IFN-alpha should be a standard of care. Possible pharmacologic interventions to decrease the neurotoxicity associated with IFN-alpha therapy include antidepressants, psychostimulants, and opioid antagonists. Preliminary clinical and research experience suggests that it is possible to effectively palliate IFN-alpha toxicity.


Inactivation of basolateral amygdala specifically eliminates palatability-related information in cortical sensory responses.
Evidence indirectly implicates the amygdala as the primary processor of emotional information used by cortex to drive appropriate behavioral responses to stimuli. Taste provides an ideal system with which to test this hypothesis directly, as neurons in both basolateral amygdala (BLA) and gustatory cortex (GC)-anatomically interconnected nodes of the gustatory system-code the emotional valence of taste stimuli (i.e., palatability), in firing rate responses that progress similarly through "epochs." The fact that palatability-related firing appears one epoch earlier in BLA than GC is broadly consistent with the hypothesis that such information may propagate from the former to the latter. Here, we provide evidence supporting this hypothesis, assaying taste responses in small GC single-neuron ensembles before, during, and after temporarily inactivating BLA in awake rats. BLA inactivation (BLAx) changed responses in 98% of taste-responsive GC neurons, altering the entirety of every taste response in many neurons. Most changes involved reductions in firing rate, but regardless of the direction of change, the effect of BLAx was epoch-specific: while firing rates were changed, the taste specificity of responses remained stable; information about taste palatability, however, which normally resides in the "Late" epoch, was reduced in magnitude across the entire GC sample and outright eliminated in most neurons. Only in the specific minority of neurons for which BLAx enhanced responses did palatability specificity survive undiminished. Our data therefore provide direct evidence that BLA is a necessary component of GC gustatory processing, and that cortical palatability processing in particular is, in part, a function of BLA activity.


DGAT1 overexpression in muscle by in vivo DNA electroporation increases intramyocellular lipid content.
In adipose tissue, the microsomal enzyme 1,2-acyl CoA:diacylglyceroltransferase-1 (DGAT1) plays an important role in triglyceride storage. Because DGAT1 is expressed in skeletal muscle as well, we aimed to directly test the effect of DGAT1 on muscular triglyceride storage by overexpressing DGAT1 using in vivo DNA electroporation. A pcDNA3.1-DGAT1 construct in saline was injected in the left tibialis anterior muscle of rats, followed by the application of eight transcutaneous pulses, using the contralateral leg as sham-electroporated control. Electroporation of the DGAT1 construct led to significant overexpression of the DGAT1 protein. The functionality of DGAT1 overexpression is underscored by the pronounced diet-responsive increase in intramyocellular lipid (IMCL) storage. In chow-fed rats, DGAT1-positive myocytes showed significantly higher IMCL content compared with the control leg, which was almost devoid of IMCL (1.99 +/- 1.13% vs. 0.017 +/- 0.014% of total area fraction; P <0.05). High-fat feeding increased IMCL levels in both DGAT1-positive and control myocytes, resulting in very high IMCL levels in DGAT1-overexpressing myocytes (4.96 +/- 1.47% vs. 0.80 +/- 0.14%; P <0.05). Our findings indicate that DGAT1 contributes to the storage of IMCL and that in vivo DNA electroporation is a promising tool to examine the functional consequences of altered gene expression in mature skeletal muscle.


[Antibiotic resistance of blood culture isolates in Buskerud in 1994 and 1998].
The increase of antimicrobial resistance has caused general concern world-wide. There is a high risk that this development will also occur in Norway. Several efforts have been made to prevent the emergence of antimicrobial resistance. A national surveillance programme for antimicrobial resistance has been started, and new legislation has made resistance surveillance programmes compulsory in every Norwegian hospital. Local surveillance of resistance is among the most important measures. We have undertaken surveillance of all blood culture isolates from the County of Buskerud in 1994 and 1998. Detection of antibiotic resistance-patterns were undertaken for all blood culture isolates in the two years using disc diffusion method (Rosco diagnostics, Taastrup, Denmark). We also looked at the consumption of antimicrobial agents in Buskerud Central Hospital in 1998. A total of 628 isolates from 572 patients were included in the study, 279 isolates from 1994 and 349 from 1998. We still have low occurrence of resistance in Buskerud, and there has been no significant increase during the four-year period. The low prevalence of antibiotic resistance reflects the restrictive antibiotic policy in Norway. Therefore, we find it important to continue this policy and to continue close surveillance of the development of antibiotic resistance.


Breast carcinoma in young women.
To estimate the incidence of breast carcinoma and survival in patients younger than 25 years old, and to describe presenting clinical signs and symptoms of breast cancer in this age group. A population-based descriptive study and case review in Olmsted County, Minnesota, was conducted using the resources of the Rochester Epidemiology Project. Participants were Olmsted County girls and women younger than 25 years old with histopathologically confirmed breast carcinoma diagnosed between 1935 and 2005. Nonresidents who presented to a medical facility within Olmsted County during this time period were included in some portions of the analysis. Main outcome measures were age-adjusted incidence, 5-year survival, and clinical presentation of breast carcinoma in girls and women younger than 25 years of age. With four breast carcinomas observed in Olmsted County residents over 1,201,539 person-years, the annual age-adjusted incidence of breast cancer in this population was 3.2 per million (95% confidence interval, 0.1-6.2). All four cancers occurred in the 20- to 24-year age group (age-specific incidence, 16.2 per million). Eight additional cases of breast carcinoma were identified in nonresidents. Delay in diagnosis was common. All had at least one feature worrisome for an aggressive neoplasm identified in their clinical history, on physical examination or by imaging. Breast carcinoma in young women is very rare, associated with delayed diagnosis, and usually associated with concerning features requiring biopsy. III.


Living environment matters: relationships between neighborhood characteristics and health of the residents in a Dutch municipality.
Characteristics of an individual alone cannot exhaustively explain all the causes of poor health, and neighborhood of residence have been suggested to be one of the factors that contribute to health. However, knowledge about aspects of the neighborhood that are most important to health is limited. The main objective of this study was to explore associations between certain features of neighborhood environment and self-rated health and depressive symptoms in Maastricht (The Netherlands). A large amount of routinely collected neighborhood data were aggregated by means of factor analysis to 18 characteristics of neighborhood social and physical environment. Associations between these characteristics and self-rated health and presence of depressive symptoms were further explored in multilevel logistic regression models adjusted for individual demographic and socio-economic factors. The study sample consisted of 9,879 residents (mean age 55 years, 48 % male). Residents of unsafe communities were less likely to report good health (OR 0.88 95 % CI 0.80-0.97) and depressive symptoms (OR 0.81 95 % CI 0.69-0.97), and less cohesive environment was related to worse self-rated health (OR 0.81 95 % CI 0.72-0.92). Residents of neighborhoods with more car traffic nuisance and more disturbance from railway noise reported worse mental health (OR 0.79 95 % CI 0.68-0.92 and 0.85 95 % CI 0.73-0.99, respectively). We did not observe any association between health and quality of parking and shopping facilities, facilities for public or private transport, neighborhood aesthetics, green space, industrial nuisance, sewerage, neighbor nuisance or satisfaction with police performance. Our findings can be used to support development of integrated health policies targeting broader determinants of health. Improving safety, social cohesion and decreasing traffic nuisance in disadvantaged neighborhoods might be a promising way to improve the health of residents and reduce health inequalities.


Clinical Mass Spectrometry Discovered Human IgG Sialylation as a Potential Biosignature for Kidney Function.
Immunoglobulin G (IgG) N-glycosylation was discovered to have an association with inflammation status, which has the potential to be a novel biomarker for kidney diseases. In this study, we applied an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to plasma and urine samples from 57 individuals with different levels of kidney function. Natural abundances of total IgG, IgG1, IgG2, and IgG3 subclasses in plasma showed positive correlations to the estimated glomerular filtration rates (eGFRs). Eighteen IgG glycopeptides also showed positive correlations. In contrast, higher IgG amounts were found in urine samples from participants with lower eGFR values. After normalizing IgG glycopeptides from plasma to their respective protein amounts, H4N4F1S1-IgG1 (r = 0.37, p = 0.0047, significant) and H5N4F1S1-IgG1 (r = 0.25, p = 0.063, marginally significant) were the two glycopeptides that still had positive correlations with eGFRs. The results showed that the UHPLC-MS/MS method is capable of investigating IgG profiles, and monitoring IgG and glycosylation patterns is worthy of further clinical application for kidney disease.


Engagement of adolescents in a health communications program to prevent noncommunicable diseases: Multiplicadores Jóvenes, Lima, Peru, 2011.
Several risk factors for noncommunicable diseases (NCDs), including obesity, are associated with behaviors established in infancy that persist throughout adolescence and adulthood. As such, adolescents should be engaged in the design and implementation of NCD prevention strategies. In Lima, Peru's capital, the proportion of adolescents aged 15 to 19 is 9.3% of the city's population, and school enrollment rates are high. The prevalence of excess weight in Peruvian adolescents is 14.2%, and prevalence has not declined in recent years. Also recently, NCDs and their risk factors have gained more attention in public health and policy areas, with regulatory action focusing on healthful nutrition to address obesity and related NCDs. The Multiplicadores Jóvenes (Young Multipliers) project was conducted among adolescents aged 15 to 17 from 9 public secondary schools in peri-urban areas of Lima, Peru. The project provided basic communication tools and knowledge of NCD prevention and public health research to adolescents during 16 weekly participatory sessions to enable them to design and disseminate healthful lifestyle promotion messages to their school peers. Thirty of 45 participants finished the program. Seven communications campaigns were designed and implemented in schools, reaching 1,200 students. The participants gained motivation, increased knowledge, and developed communication skills that were combined to implement healthful lifestyle promotion campaigns. Engaging young people in public health promotion activities was feasible and advantageous for the design of tailored prevention-related content and its dissemination among peers.


Responses of fibers in medial longitudinal fasciculus (MLF) of alert monkeys during horizontal and vertical conjugate eye movements evoked by vestibular or visual stimuli.
Extracellular recordings were obtained from 37 histologically identified MLF fibers near the trochlear nucleus in alert monkeys trained to perform a visual tracking task and subjected to adequate horizontal and vertical vestibular stimulation. The behavioral paradigm permitted independent quantitative assessment of a fiber's response to eye or head movements. 2. According to their discharge pattern, almost all MLF fibers were placed in one of two classes: 1) Horizontal burst-tonic fibers (n = 20). During both vestibular and visually evoked eye movements, burst-tonic fibers discharged in strict relation to horizontal eye movements, exhibiting a burst of activity prior to on-direction saccades and steady firing related to horizontal eye position during fixations. 2) Vertical vestibular plus eye-position fibers (n = 14). Vertical fibers discharged in relation to vertical head velocity in the absence of eye movements and in relation to vertical eye position in the absence of head movement, and paused with saccades in any direction. 3. The quantitative similarity of horizontal burst-tonic fiber discharge to that of ipsilateral medial rectus oculomotoneurons suggests that burst-tonic fibers provide the major excitatory synaptic drive to medial rectus motoneurons during conjugate eye movements of vestibular or visual origin. 4. The discharge pattern of vertical vestibular plus eye-position fibers is significantly different from that of oculomotoneurons, suggesting that additional neural processing of vertical fiber information must occur in the mesencephalon. 5. The functional dichotomy of horizontal and vertical MLF fibers and their contrasting discharge patterns provide new evidence for the anatomic and functional separation of horizontal and vertical eye movement mechanisms in the pons and mesencephalon, respectively.


Lack of association of C-reactive protein and coronary calcium by electron beam computed tomography in postmenopausal women: implications for coronary artery disease screening.
We sought to test the hypothesis that C-reactive protein, a marker of inflammation, would correlate positively with coronary calcium, a marker of atherosclerosis, in postmenopausal women. High sensitivity testing for C-reactive protein (hsCRP) has recently been shown in large population studies to predict cardiac events in asymptomatic postmenopausal women. Coronary calcification determined by electron beam computerized tomography (EBCT) has also been suggested to be predictive of cardiac events in women. We performed hsCRP testing and determined calcium scores by EBCT in 172 asymptomatic postmenopausal women (mean age: 64.5 +/- 7.9 years) at risk for cardiac disease. Risk factors were determined by history, physical, electrocardiogram, exercise testing, and lipoprotein profiles. Calcium scores ranged from 0 to 2,618. For analysis, calcium scores were divided into three groups; none (0 to 10), minimal (>10 to 50), and significant (>50). Overall, there was no significant positive relationship between hsCRP level and calcium score. Specifically, the hsCRP levels (mg/dl) were 0.24 +/- 0.43, 0.33 +/- 0.47 and 0.17 +/- 0.32 (medians 0.11, 0.15, and 0.06) for women with none, minimal, and significant coronary calcification, respectively. In subgroup analysis, a similar lack of positive association was observed after stratification by smoking status and by hormone replacement therapy use, two factors known to increase hsCRP. In contrast to our a priori hypothesis, we found no evidence of a positive association between hsCRP and calcium score by EBCT. These data thus raise the possibility that hsCRP and EBCT calcium score reflect different pathologic processes, an issue with implications for coronary artery disease screening.


Clinical outcome of Maggot Debridement Therapy followed by Negative Pressure Wound Therapy for chronic hand wound with Multi-Drug Resistant Organism infection: Two cases and review of the literature.
The advancement in science and research has led to development of medical maggots which feed exclusively on dead tissue. Medical maggots have three important functions namely debridement, disinfection, and stimulation of wound healing. The modern use of medical maggots now goes by the term "Maggot Debridement Therapy" (MDT) for use in wound management. MDT is still used infrequently due to the effectiveness of surgical debridement and antibiotics for treatment of wound infection. Lately, there was emergence of Multi-Drug Resistant Organism (MDRO) likely due to inappropriate antibiotics usage. Maggot secretions have been shown to be effective in inhibiting some MDRO, for example, Methicillin-resistant Staphylococcus aureus, thus making MDT an attractive option for wounds with MDRO. We report two patients with multiple medical comorbidities, diagnosed with serious MDRO Diabetic Hand Infections treated with three cycles of MDT followed by Negative Pressure Wound Therapy.


Clarifying workforce flexibility from a division of labor perspective: a mixed methods study of an emergency department team.
The need for greater flexibility is often used to justify reforms that redistribute tasks through the workforce. However, "flexibility" is never defined or empirically examined. This study explores the nature of flexibility in a team of emergency doctors, nurse practitioners (NPs), and registered nurses (RNs), with the aim of clarifying the concept of workforce flexibility. Taking a holistic perspective on the team's division of labor, it measures task distribution to establish the extent of multiskilling and role overlap, and explores the behaviors and organizational conditions that drive flexibly. The explanatory sequential mixed methods study was set in the Fast Track area of a metropolitan emergency department (ED) in Sydney, Australia. In phase 1, an observational time study measured the tasks undertaken by each role (151 h), compared as a proportion of time (Kruskal Wallis, Mann-Whitney U), and frequency (Pearson chi-square). The time study was augmented with qualitative field notes. In phase 2, 19 semi-structured interviews sought to explain the phase 1 observations and were analyzed thematically. The roles were occupationally specialized: "Assessment and Diagnosis" tasks consumed the largest proportion of doctors' (51.1%) and NPs' (38.1%) time, and "Organization of Care" tasks for RNs (27.6%). However, all three roles were also multiskilled, which created an overlap in the tasks they performed. The team used this role overlap to work flexibly in response to patients' needs and adapt to changing demands. Flexibility was driven by the urgent and unpredictable workload in the ED and enabled by the stability provided by a core group of experienced doctors and nurses. Not every healthcare team requires the type of flexibility found in this study since that was shaped by patient needs and the specific organizational conditions of the ED. The roles, tasks, and teamwork that a team requires to "be flexible" (i.e., responsive and adaptable) are highly context dependent. Workforce flexibility therefore cannot be defined as a particular type of reform or role; rather, it should be understood as the capacity of a team to respond and adapt to patients' needs within its organizational context. The study's findings suggest that solutions for a more flexible workforce may lay in the organization of healthcare work.


Effect of weight loss on muscle fiber type, fiber size, capillarity, and succinate dehydrogenase activity in humans.
To examine the effects of weight loss on muscle oxidative properties, nine obese subjects (body mass index, 34 +/- 1.5) had muscle biopsies before and after weight loss and weight stabilization. Weight loss ranged from 13-32 kg and represented 20.8 +/- 2.1% of initial weight. After weight loss, there was no change in the proportions of oxidative (type I and type IIa) fibers and also no change in mean fiber cross-sectional area, whereas there was a small, but significant, decrease in the relative interstitial space (P < 0.05). However, weight loss resulted in a 32 +/- 6% (mean +/- SEM) increase in capillary/fiber ratio and a 54% increase in capillary density (P < 0.05). In addition, there was a 41 +/- 13% increase in succinate dehydrogenase (SDH) activity (P < 0.05). This increase in muscle capillarization and SDH activity was seen in all fiber types, even the relatively lower oxidative type IIx fibers. There was a strong correlation between the change in capillary/fiber ratio and the change in SDH activity (r = 0.82; P < 0.02). Thus, weight loss resulted in no change in muscle fiber type or cross-sectional area, but produced increases in capillary/fiber ratio, capillary density, and SDH activity, suggesting an increase in muscle oxidative capacity.


Establishing Minimal Clinically Important Difference in Sleep Outcomes after Spinal Cord Stimulation in Patients with Chronic Pain Disorders.
As one of the most common medical conditions for which patients seek medical care, chronic pain can be debilitating. The relationship between chronic pain and sleep is thought to be bidirectional, suggesting that treatment of one can be beneficial to the other. There is mounting evidence that spinal cord stimulation (SCS) improves aspects of sleep. How meaningful that is to patients' lives has not been ascertained. The aim of the current study was to further elucidate the effect of SCS on sleep by examining the relationship between pain outcome measures with the insomnia severity index (ISI) and to establish the minimally clinical important difference (MCID), which is defined as the smallest noticeable change that an individual perceives as clinically significant. We prospectively collected ISI, Epworth sleepiness scale (ESS), Numerical Rating Scale, McGill Pain Questionnaire-Short Form, Oswestry Disability Index, Beck Depression Inventory, and Pain Catastrophizing Scale data both pre- and postoperatively for chronic pain patients who underwent SCS placement and had long-term outcomes. The ISI is a well-studied questionnaire used to assess an individual's level of insomnia. We correlated the ESS and ISI with pain outcome measures in sixty-four patients at a mean follow-up of 9.8 ± 2.9 months. The ISI showed correlations with disability as measured through the Oswestry Disability Index (p = 0.014) and depression as measured through the Beck Depression Inventory (p = 0.024). MCID values for the ISI were calculated using both anchor- and distribution-based methods. The minimal detectable change method resulted in an MCID of 2.4 points, standard error of measurement resulted in an MCID of 2.6 points, and the change difference resulted in an MCID of 2.45. The receiver operating characteristic method yielded an MCID of 0.5-point change with an area under the curve of 0.61. This study successfully established MCID ranges for the ISI outcome measure to help gauge improvement in insomnia after SCS. The ISI has ample evidence of its validity in assessment of insomnia, and MCID values of 2.4-2.6 correlate with improvement in disability and depression in our patients.


T₁ mapping detects pharmacological retardation of diffuse cardiac fibrosis in mouse pressure-overload hypertrophy.
Diffuse interstitial fibrosis is present in diverse cardiomyopathies and associated with poor prognosis. We investigated whether magnetic resonance imaging-based T1 mapping could quantify the induction and pharmacological suppression of diffuse cardiac fibrosis in murine pressure-overload hypertrophy. Mice were subjected to transverse aortic constriction or sham surgery. The angiotensin receptor blocker losartan was given to half the animals. Cine-magnetic resonance imaging performed at 7 and 28 days showed hypertrophy and remodeling and systolic and diastolic dysfunction in transverse aortic constriction groups as expected. Late gadolinium-enhanced magnetic resonance imaging revealed focal signal enhancement at the inferior right ventricular insertion point of transverse aortic constriction mice concordant with the foci of fibrosis in histology. The extracellular volume fraction, calculated from pre- and postcontrast T1 measurements, was elevated by transverse aortic constriction and showed direct linear correlation with picrosirius red collagen volume fraction, thus confirming the suitability of extracellular volume fraction as an in vivo measure of diffuse fibrosis. Treatment with losartan reduced left ventricular dysfunction and prevented increased extracellular volume fraction, indicating that T1 mapping is sensitive to pharmacological prevention of fibrosis. Magnetic resonance imaging can detect diffuse and focal cardiac fibrosis in a clinically relevant animal model of pressure overload and is sensitive to pharmacological reduction of fibrosis by angiotensin receptor blockade. Thus, T1 mapping can be used to assess antifibrotic therapeutic strategies.


Long-term follow-up of patients with cutaneous T-cell lymphoma treated with extracorporeal photochemotherapy.
Few studies have assessed the long-term outcome of patients with cutaneous T-cell lymphoma (CTCL) treated with extracorporeal photochemotherapy (ECP). Our objective was to assess the efficacy, safety, and survival of a cohort of patients with refractory T-cell lymphoma in various stages of cutaneous involvement who were treated with ECP. Twenty patients who had received at least 6 months of ECP between September 1988 and April 1991 were reevaluated and the data analyzed statistically to obtain outcome data through December 1995. A complete response (disappearance of all lesions) was obtained in five patients (25%) and a partial response (disappearance of at least 50% of lesions) in five patients (25%). Of the 10 responders, seven (70%) were weaned from ECP. Two of seven patients had a relapse. Ten patients (50%) showed no response to ECP. No statistically significant differences between responders and nonresponders were found with respect to demographic, clinical, or laboratory variables. Seven patients died of causes directly related to CTCL and two patients died of unrelated causes. Median survival time for the entire cohort was 96 months (range, 16 to 152 months). An assessment of early response after 6 to 8 months of ECP had a sensitivity of 100% and a specificity of 90% for predicting long-term (> 4 years) outcome. Adverse effects were minimal. ECP is a safe effective alternative therapy for CTCL that is refractory to other therapies; it can induce a long-term, disease-free remission in a minority of patients. Response in the first 6 to 8 months of treatment predicts long-term outcome.


[A.M. Fiamberti and 'psycosurgery'].
A.M. Fiamberti has been the Director of Psychiatric Hospital in Varese from its opening to 1964, allowing the structure to gain an important role in the history of Psychiatric Hospitals in Northen Italy in 20th century. Fiamberti has been the 'inventor' of a discussed therapeutical technique of 'psycosurgery' he began to use in 1937. The article analyzes the history and characters of this surgical technique at the light of testimonies in contemporary journals and reviews.


A novel metered dose transdermal spray formulation for oxybutynin.
The objective of the present work was to develop a metered dose spray formulation for transdermal delivery of oxybutynin and to carry out the in vitro characterization of the optimized formulation. Oxybutynin release from a series of ethanol/acetone/methylal based formulations was assessed in vitro and the developed formulation was used for delivery from a metered dose spray. Various qualitative and quantitative parameters like spray pattern, particle size distribution, pH, evaporation time, pump seal efficiency test, average weight per metered dose, content per spray and content uniformity were evaluated. The different film forming agents were assessed and carbopol (0.5%) and lutrol (0.1%) were found to give good clarity of solution, evaporation rate, spray pattern and tackiness of the film. Diffusion studies of the optimized formulations through the semipermeable membrane showed the release of drug to the extent of almost 50% over a period of 24 h. Stability studies were conducted as per ICH guidelines and indicated that formulations were stable. Skin irritation studies were performed using rabbit as an animal model. The results obtained show that the metered dose transdermal spray formulation can be a promising and innovative therapeutic system for the transdermal administration of oxybutynin.


Association of cytochrome P4502E1 and NAD(P)H:quinone oxidoreductase 1 genetic polymorphisms with susceptibility to large artery atherosclerotic ischemic stroke: a case-control study in the Turkish population.
Stroke, a major cause of death and disability, is described as interruption or severe reduction of blood flow in cerebral arteries. Oxidative stress plays an important role in the pathogenesis of atherosclerosis and carotid atherosclerosis is a risk factor for stroke. Combination of multiple environmental and genetic risk factors is thought to increase stroke. Therefore, investigation of the polymorphisms of enzymes is of crucial importance to determine the molecular etiology of the disease. To test this hypothesis, we performed a case-control study in which we compared the distribution of CYP2E1 and NQO1 genotypes between 245 large artery atherosclerotic ischemic stroke patients and 145 controls, using PCR-RFLP. A significant difference was observed between stroke patients and controls with respect to the CYP2E1*5B genotype (odds ratio; OR 8.069, P = 0.011) and allele (OR 7.876, P = 0.011) distribution. However, this polymorphism was not a significant predictor of disease status in logistic regression analysis. NQO1*2 polymorphism genotype distribution was significantly different between patients and controls (P = 0.027) and heterozygote *1*2 genotype was found to be a protective factor against large artery atherosclerotic ischemic stroke in logistic regression analysis (OR 0.562, P = 0.018). This is the first study conducted regarding the association of CYP2E1 and NQO1 genetic polymorphisms and large artery atherosclerotic ischemic stroke risk in Turkish population.


Determination of promethazine in serum by liquid chromatography.
We describe a procedure for the liquid-chromatographic determination of promethazine in low-nanogram concentrations in serum. Triflupromazine is used as the internal standard. The method is based on a single extraction of promethazine from serum with hexane and subsequent derivatization with trichloroethyl chloroformate. Analytical recovery of promethazine is about 90%. The lower limit of detection is 1 microgram/L when a 2.0-mL aliquot of serum is assayed. Our data illustrate the practicability of the method for bioavailability studies after oral or rectal administration of promethazine hydrochloride.


Sex hormone effects in non-pregnant rat and human myometrium.
To study effects of sex hormones on spontaneous contractility and on the effects of depolarizing agent potassium chloride (KCl), M-cholinoceptor and prostaglandin receptor agonists on non-pregnant rat and human uterine tissues. Uterine rings from ovariectomized rats treated with sex hormones or placebo, and uterine strips from premenopausal and postmenopausal women were equilibrated in Krebs buffer (t=37 degrees C, pH approximately 7.4) for isometric tension recordings. Spontaneous contractile activity and contractions in response to KCl, eicosanoids, and acetylcholine were compared. In tissues from ovariectomized rats, spontaneous contractility was increased, while KCl-induced contractions were decreased. Treatment with 17beta-estradiol, but not progesterone, inhibited spontaneous contractions, but potentiated KCl evoked contractions. Treatment with 17beta-estradiol did not influence responses to prostanoids in ovariectomized rats, while treatment with both sex hormones restored decreased the responses. Spontaneous contractility and responses to KCl were less in uterine tissues from postmenopausal versus premenopausal women. Hormone replacement therapy partly restored the responses to KCl, prostanoids, and acetylcholine. Ovarian steroids modulate spontaneous contractile activity, responses to depolarization, prostanoids and M-cholinoceptor activation in non-pregnant rat and human uterine tissues in vitro.


The organization of local and distant functional connectivity in the human brain.
Information processing in the human brain arises from both interactions between adjacent areas and from distant projections that form distributed brain systems. Here we map interactions across different spatial scales by estimating the degree of intrinsic functional connectivity for the local (<or=14 mm) neighborhood directly surrounding brain regions as contrasted with distant (>14 mm) interactions. The balance between local and distant functional interactions measured at rest forms a map that separates sensorimotor cortices from heteromodal association areas and further identifies regions that possess both high local and distant cortical-cortical interactions. Map estimates of network measures demonstrate that high local connectivity is most often associated with a high clustering coefficient, long path length, and low physical cost. Task performance changed the balance between local and distant functional coupling in a subset of regions, particularly, increasing local functional coupling in regions engaged by the task. The observed properties suggest that the brain has evolved a balance that optimizes information-processing efficiency across different classes of specialized areas as well as mechanisms to modulate coupling in support of dynamically changing processing demands. We discuss the implications of these observations and applications of the present method for exploring normal and atypical brain function.


Amplified Photoacoustic Signal and Enhanced Photothermal Conversion of Polydopamine-Coated Gold Nanobipyramids for Phototheranostics and Synergistic Chemotherapy.
Light-responsive nanoprobes were suffering from the threat of high-dose laser irradiation, and it was important for constructing new nanoprobes for safe and efficient phototheranostics. Here, polydopamine (PDA)-coated gold nanobipyramids (AuNBPs@PDA) were synthesized for amplified photoacoustic (PA) signal and enhanced photothermal conversion with low-dose laser irradiation and then doxorubicin (DOX)-loaded AuNBPs@PDA-DOX nanoprobes were constructed for PA imaging-guided synergistic photothermal therapy (PTT) and chemotherapy. The AuNBPs@PDA nanoparticles possessed higher photothermal conversion efficiency (42.07%) and stronger PA signal than those of AuNBP nanoparticles, and the AuNBPs@PDA-DOX nanoprobes showed dual-responsive DOX release of pH and photothermal stimulation. With low-dose laser irradiation (1.0 W/cm2) and low-concentration AuNBPs@PDA-DOX (60 μg/mL), the 4T1 cell viability was reduced to about 5%, owing to the combination of PTT and chemotherapy, compared with 42.3% of single chemotherapy and 25.3% of single PTT. Moreover, by modeling 4T1 tumor-bearing nude mice, in vivo PA imaging was achieved and the tumors were completely inhibited, demonstrating the excellent synergistic effect of PTT/chemotherapy. Therefore, the developed AuNBPs@PDA-DOX nanoprobes can be used for phototheranostics and synergistic chemotherapy, achieving low-dose laser irradiation and high-efficient visualized theranostics.


A reexamination of information theory-based methods for DNA-binding site identification.
Searching for transcription factor binding sites in genome sequences is still an open problem in bioinformatics. Despite substantial progress, search methods based on information theory remain a standard in the field, even though the full validity of their underlying assumptions has only been tested in artificial settings. Here we use newly available data on transcription factors from different bacterial genomes to make a more thorough assessment of information theory-based search methods. Our results reveal that conventional benchmarking against artificial sequence data leads frequently to overestimation of search efficiency. In addition, we find that sequence information by itself is often inadequate and therefore must be complemented by other cues, such as curvature, in real genomes. Furthermore, results on skewed genomes show that methods integrating skew information, such as Relative Entropy, are not effective because their assumptions may not hold in real genomes. The evidence suggests that binding sites tend to evolve towards genomic skew, rather than against it, and to maintain their information content through increased conservation. Based on these results, we identify several misconceptions on information theory as applied to binding sites, such as negative entropy, and we propose a revised paradigm to explain the observed results. We conclude that, among information theory-based methods, the most unassuming search methods perform, on average, better than any other alternatives, since heuristic corrections to these methods are prone to fail when working on real data. A reexamination of information content in binding sites reveals that information content is a compound measure of search and binding affinity requirements, a fact that has important repercussions for our understanding of binding site evolution.


Molecularly imprinted polymers in capillary electrochromatography: recent developments and future trends.
The developments in molecularly imprinted polymer (MIP)-based capillary electrochromatography (CEC) achieved during the past years are reviewed in this article. The MIP is prepared using a templated polymerization reaction and results in a material with a high selectivity towards a predetermined target. The selectivity of the MIP is comparable to that of the biological antibodies, however, the MIP is much more stable and is thus able to withstand extremely harsh conditions in terms of pH, temperature, and organic solvents. The high selectivity and stability of the MIP made it an interesting candidate for application as stationary phase sorbent in chromatography. However, due to slow kinetics the efficiency of the early MIP columns, which were predominantly applied in high-performance liquid chromatography (HPLC), were limited. The use of CEC was thought to improve the efficiency of the MIP-based separation system. The small dimensions of the capillary format employed in CEC have put demands on the polymer systems which have resulted in the development of many different polymer formats. Thus, this need for novel MIP formats for applications in CEC has contributed a lot to the general development of MIP formats as well as to the knowledge in MIP synthesis and characteristics.


Diastereoselective Friedel-Crafts alkylation of indoles with chiral alpha-phenyl benzylic cations. Asymmetric synthesis of anti-1,1,2-triarylalkanes.
The reactions of chiral benzyl carbocations bearing alpha-phenyl substituents with N-sulfonylated indoles afford 1,1,2-triarylalkanes with anti-selectivities. This outcome is a reversal of facial diastereoselectivity relative to Bach's alpha-alkyl-bearing benzyl cations. The reactions are promoted by either a Brønsted acid (TFA) or Lewis acid (BF3.OEt2), offering differential diastereoselectivities and reactivities. The electronic properties of both reacting partners strongly influence the reaction rates and the product diastereoselectivities and appear to operate under kinetic control. This chemistry provides an efficient access to sterically congested tetrasubstituted ethanes.


Quantitative Assessment of Single-Image Super-Resolution in Myocardial Scar Imaging.
Single-image super resolution is a process of obtaining a high-resolution image from a set of low-resolution observations by signal processing. While super resolution has been demonstrated to improve image quality in scaled down images in the image domain, its effects on the Fourier-based image acquisition technique, such as MRI, remains unknown.We performed high-resolution ex vivo late gadolinium enhancement (LGE) magnetic resonance imaging (0.4 × 0.4 × 0.4 mm3) in postinfarction swine hearts (n = 24). The swine hearts were divided into the training set (n = 14) and the test set (n = 10), and in all hearts, low-resolution images were simulated from the high-resolution images. In the training set, super-resolution dictionaries with pairs of small matching patches of the high- and low-resolution images were created. In the test set, super resolution recovered high-resolution images from low-resolution images using the dictionaries. The same algorithm was also applied to patient LGE (n = 4) to assess its effects. Compared with interpolated images, super resolution significantly improved basic image quality indices (P < 0.001). Super resolution using Fourier-based zero padding achieved the best image quality. However, the magnitude of improvement was small in images with zero padding. Super resolution substantially improved the spatial resolution of the patient LGE images by sharpening the edges of the heart and the scar. In conclusion, single-image super resolution significantly improves image errors. However, the magnitude of improvement was relatively small in images with Fourier-based zero padding. These findings provide evidence to support its potential use in myocardial scar imaging.


Alcohol withdrawal syndrome: mechanisms, manifestations, and management.
The alcohol withdrawal syndrome is a well-known condition occurring after intentional or unintentional abrupt cessation of heavy/constant drinking in patients suffering from alcohol use disorders (AUDs). AUDs are common in neurological departments with patients admitted for coma, epileptic seizures, dementia, polyneuropathy, and gait disturbances. Nonetheless, diagnosis and treatment are often delayed until dramatic symptoms occur. The purpose of this review is to increase the awareness of the early clinical manifestations of AWS and the appropriate identification and management of this important condition in a neurological setting.


Pattern of neuropathic pain induced by topical capsaicin application in healthy subjects.
Human experimental pain models are widely used to study drug effects under controlled conditions, but they require further optimization to better reflect clinical pain conditions. To this end, we measured experimentally induced pain in 110 (46 men) healthy volunteers. The quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain) was applied on untreated ("control") and topical capsaicin-hypersensitized ("test") skin. Z-transformed QST-parameter values obtained at the test site were compared with corresponding values published from 1236 patients with neuropathic pain using Bayesian statistics. Subjects were clustered for the resemblance of their QST pattern to neuropathic pain. Although QST parameter values from the untreated site agreed with reference values, several QST parameters acquired at the test site treated with topical capsaicin deviated from normal. These deviations resembled in 0 to 7 parameters of the QST pattern observed in patients with neuropathic pain. Higher degrees (50%-60%) of resemblance to neuropathic QST pattern were obtained in 18% of the subjects. Inclusion in the respective clusters was predictable at a cross-validated accuracy of 86.9% by a classification and regression tree comprising 3 QST parameters (mechanical pain sensitivity, wind-up ratio, and z-transformed thermal sensory limen) from the control sites. Thus, we found that topical capsaicin partly induced the desired clinical pattern of neuropathic pain in a preselectable subgroup of healthy subjects to a degree that fuels expectations that experimental pain models can be optimized toward mimicking clinical pain. The subjects, therefore, qualify for enrollment in analgesic drug studies that use highly selected cohorts to enhance predictivity for clinical analgesia.


ranchSATdb: A Genome-Wide Simple Sequence Repeat (SSR) Markers Database of Livestock Species for Mutant Germplasm Characterization and Improving Farm Animal Health.
Microsatellites, also known as simple sequence repeats (SSRs), are polymorphic loci that play an important role in genome research, animal breeding, and disease control. Ranch animals are important components of agricultural landscape. The ranch animal SSR database, ranchSATdb, is a web resource which contains 15,520,263 putative SSR markers. This database provides a comprehensive tool for performing end-to-end marker selection, from SSRs prediction to generating marker primers and their cross-species feasibility, visualization of the resulting markers, and finding similarities between the genomic repeat sequences all in one place without the need to switch between other resources. The user-friendly online interface allows users to browse SSRs by genomic coordinates, repeat motif sequence, chromosome, motif type, motif frequency, and functional annotation. Users may enter their preferred flanking area around the repeat to retrieve the nucleotide sequence, they can investigate SSRs present in the genic or the genes between SSRs, they can generate custom primers, and they can also execute in silico validation of primers using electronic PCR. For customized sequences, an SSR prediction pipeline called miSATminer is also built. New species will be added to this website's database on a regular basis throughout time. To improve animal health via genomic selection, we hope that ranchSATdb will be a useful tool for mapping quantitative trait loci (QTLs) and marker-assisted selection. The web-resource is freely accessible at https://bioinfo.usu.edu/ranchSATdb/.


Gross deletions and translocations in human genetic disease.
Translocations and gross deletions constitute an important cause of both cancer and inherited disease. Such gene rearrangements are non-randomly distributed in the human genome as a consequence of selection for growth advantage and/or the inherent potential of some DNA sequences to be frequently involved in breakage and recombination. Chromosomal rearrangements are generated by a variety of recombinational processes, each characterised by mechanism-specific DNA sequence features. Various types of recombinogenic motifs have been shown to promote non-homologous end joining whilst direct repeats may mediate homologous recombination. In addition, repetitive sequence elements can facilitate the formation of secondary structure between DNA ends at translocation or gross deletion breakpoints, and in so doing, may play a role in illegitimate recombination. Although results from DNA breakpoint studies are broadly consistent with a role for homologous unequal recombination in deletion mutagenesis and a role for non-homologous recombination in the generation of translocations, homologous recombination and non-homologous end joining are unlikely to be mutually exclusive mechanisms. Thus, chromosomal rearrangements will often represent the net result of multiple highly complex molecular interactions that are not always readily explicable.


Research Progress on the Correlation Between Vitamin D and Neurological Disorders.
To review the correlation between vitamin D (VD) and several common neurological disorders with the aim of providing directions and ideas for using VD to treat neurological disorders. VD, 1,25-dihydroxyvitamin D3, stroke, epilepsy, and cognitive dysfunction were used as keywords. The PubMed and Embase databases were searched for articles published from 2010 to 2021. The inclusion criteria were as follows: clear introduction of the research sample, detailed explanation of the sample selection in the research, intervention, and control measures, and available odds ratio and 95% confidence interval. The exclusion criteria were as follows: duplicate reports, defects in research design and poor quality, incomplete data and unclear results, and unmodifiable errors in the statistical method. Initially, 1,360 articles were retrieved from the PubMed and Embase databases. Finally, 81 articles were included, 76 of which were published within the last 5 years. VD deficiency is very common in the population and is associated with a variety of neurological diseases. VD, a neuroactive steroid, plays an important role in the protection of the central nervous system. In contrast, stroke can cause epilepsy and varying degrees of changes in cognitive function. Furthermore, seizure and epilepsy can cause changes in cognitive function. The degree of alteration in cognitive function affects the occurrence and progression of stroke and epilepsy. Therefore, VD can be used for the comprehensive treatment of neurological diseases.


The differentiation state of the Schwann cell progenitor drives phenotypic variation between two contagious cancers.
Contagious cancers are a rare pathogenic phenomenon in which cancer cells gain the ability to spread between genetically distinct hosts. Nine examples have been identified across marine bivalves, dogs and Tasmanian devils, but the Tasmanian devil is the only mammalian species known to have given rise to two distinct lineages of contagious cancer, termed Devil Facial Tumour 1 (DFT1) and 2 (DFT2). Remarkably, DFT1 and DFT2 arose independently from the same cell type, a Schwann cell, and while their ultra-structural features are highly similar they exhibit variation in their mutational signatures and infection dynamics. As such, DFT1 and DFT2 provide a unique framework for investigating how a common progenitor cell can give rise to distinct contagious cancers. Using a proteomics approach, we show that DFT1 and DFT2 are derived from Schwann cells in different differentiation states, with DFT2 carrying a molecular signature of a less well differentiated Schwann cell. Under inflammatory signals DFT1 and DFT2 have different gene expression profiles, most notably involving Schwann cell markers of differentiation, reflecting the influence of their distinct origins. Further, DFT2 cells express immune cell markers typically expressed during nerve repair, consistent with an ability to manipulate their extracellular environment, facilitating the cell's ability to transmit between individuals. The emergence of two contagious cancers in the Tasmanian devil suggests that the inherent plasticity of Schwann cells confers a vulnerability to the formation of contagious cancers.


Association of insulin resistance with polymorphic variants of Clock and Bmal1 genes: A case-control study.
Background: Little information is available in the literature for the correlation of insulin resistance (IR) and CLOCK gene polymorphism in Chinese population. This study aimed to investigate the relationship of HOMA-IR (homeostasis model assessment of insulin resistance) to polymorphic variants of Clock and Bmal1 genes in Chinese patients with essential hypertension.Methods: A total of 334 outpatients with essential hypertension (103 patients of HOMA-IR positive and 231 patients of HOMA-IR negative) were recruited to analyze Clock T3111C and Bmal1 A1420G genotypes with DNA sequencing approach.Results: Waist circumference, body mass index, glycated hemoglobin, total cholesterol, triglyceride, and plasminogen activator inhibitor-1 were significantly increased, while high-density lipoprotein cholesterol was significantly decreased in patients with HOMA-IR positive (P < .05-0.001 vs. patients with HOMA-IR negative). Twenty-four-hour ambulatory blood pressure monitoring showed that 24-h mean systolic blood pressure (SBP), especially nightime SBP, was higher in patients with HOMA-IR positive (P < .05 vs. patients with HOMA-IR negative). Notably, compared with the negative group, the distribution frequency of C allele of Clock T3111C and GG genotype of Bmal1 A1420G were significantly higher in the HOMA-IR positive group (29.1 vs. 10.8% P < .000 and 43.7 vs. 27.7% P = .007, respectively). Logistic regression analysis showed that C allele of Clock T3111C (OR = 4.128, CI 95% 2.313-7.368, p = .000) and GG genotype of Bmal1 A1420G (OR = 1.983, CI 95% 1.117-3.521, p = .019) were independent risk factors for potential HOMA-IR in Chinese patients with essential hypertension.Conclusion: Our results indicated that Chinese hypertensive patients with C allele of Clock T3111C or GG genotype of Bmal1 A1420G might be susceptible to IR and are more likely to develop high nighttime SBP.


Comparative genomics and association analysis identifies virulence genes of Cercospora sojina in soybean.
Recently, a new strain of Cercospora sojina (Race15) has been identified, which has caused the breakdown of resistance in most soybean cultivars in China. Despite this serious yield reduction, little is known about why this strain is more virulent than others. Therefore, we sequenced the Race15 genome and compared it to the Race1 genome sequence, as its virulence is significantly lower. We then re-sequenced 30 isolates of C. sojina from different regions to identifying differential virulence genes using genome-wide association analysis (GWAS). The 40.12-Mb Race15 genome encodes 12,607 predicated genes and contains large numbers of gene clusters that have annotations in 11 different common databases. Comparative genomics revealed that although these two genomes had a large number of homologous genes, their genome structures have evolved to introduce 245 specific genes. The most important 5 candidate virulence genes were located on Contig 3 and Contig 1 and were mainly related to the regulation of metabolic mechanisms and the biosynthesis of bioactive metabolites, thereby putatively affecting fungi self-toxicity and reducing host resistance. Our study provides insight into the genomic basis of C. sojina pathogenicity and its infection mechanism, enabling future studies of this disease. Via GWAS, we identified five candidate genes using three different methods, and these candidate genes are speculated to be related to metabolic mechanisms and the biosynthesis of bioactive metabolites. Meanwhile, Race15 specific genes may be linked with high virulence. The genes highly prevalent in virulent isolates should also be proposed as candidates, even though they were not found in our SNP analysis. Future work should focus on using a larger sample size to confirm and refine candidate gene identifications and should study the functional roles of these candidates, in order to investigate their potential roles in C. sojina pathogenicity.


[Extracorporeal membrane oxygenation (ECMO) in the newborn infant and the child with intractable respiratory failure].
Extracorporeal membrane oxygenation (ECMO) has become a nearly standard treatment for neonates with refractory hypoxemic respiratory failure due to various disease. Even though in the non-neonatal age the experience is less extensive, an increased widespread interest on the possible applications in children with severe life-threatening respiratory or cardiovascular insufficiency is well documented in the literature. General contraindications include presence of active bleeding, underlying lethal disease, congenital malformations, or severe brain damage. Whilst in the neonatal population common entry criteria have been widely accepted, the identification of precise parameters capable to predict mortality and thus indicating an ECMO support in older patients are still lacking. At present, nonetheless, more than 10.000 newborns and 1.000 children with severe respiratory insufficiency at high mortality risk have received an ECMO treatment, with a survival rate of more than 80% and 50%, respectively. The initial results of our ECMO program for both neonatal and pediatric patients with refractory respiratory failure are encouraging, both in terms of mortality and morbidity, and they will be briefly discussed.


[Exposure therapy for anxiety disorders in a psychiatric ward].
Exposure treatment is efficient as a treatment for some anxiety disorders. Briefly described, it consists in letting the patient expose himself to an anxiety-inducing situation without running away from it. In the author's experience, this mode of treatment is too seldom used. This article exemplifies conditions in which this form of therapy can be useful. The method is easily learnt by general practitioners. The article describes the treatment of five patients with these psychiatric diagnoses: agoraphobia, social phobia, compulsive disorder, and post-traumatic stress disorder.


Respiratory muscle activity after spontaneous, neostigmine- or sugammadex-enhanced recovery of neuromuscular blockade: a double blind prospective randomized controlled trial.
The use of neostigmine after neuromuscular blockade (NMB) has been associated with postoperative respiratory complications. In previous studies, we found lower diaphragmatic activity after neostigmine reversal of NMB, compared to sugammadex. It is still unclear whether the adequate use of neostigmine guarantees normal respiratory muscle function after NMB. In this study, we wanted to assess the effect of commonly used degrees of NMB and their possible reversal strategies on respiratory muscle activity after the return of normal neuromuscular transmission. This is a randomized, controlled, parallel-group, single-centre, double-blind study in patients scheduled for intracranial surgery at a tertiary academic hospital in Belgium. All participants received target controlled propofol/remifentanil anesthesia and were randomized into one of five groups, receiving either a shallow NMB with no reversal (shallow/saline), a shallow NMB with sugammadex reversal (shallow/sugammadex), a moderate NMB with neostigmine reversal (moderate/neostigmine), a moderate NMB with sugammadex reversal (moderate/sugammadex), or a deep NMB with sugammadex reversal (deep/sugammadex). Primary and secondary outcome parameters were diaphragm and intercostal electromyographic (EMG) activity at the moment of resumed spontaneous breathing activity, defined as a maximal interval of 10 min after the first spontaneous breath. For the five groups, a total of 55 patients could be included in the final analysis. Median time of spontaneous breathing analyzed was 5 min (IQR 3-9.5 min). Both the moderate/sugammadex and the moderate/neostigmine groups had lower levels of diaphragm EMG compared to the shallow/sugammadex group. The moderate/neostigmine group had lower levels of intercostal EMG activity compared to the shallow/saline group. In this study, the depth of neuromuscular blockade and type of reversal strategy impacts respiratory muscle activity at the moment of resumed spontaneous breathing and recovery of neuromuscular blockade. Both groups that received moderate NMB had lower levels of diaphragm EMG, compared to the shallow NMB group with sugammadex reversal. Compared to the shallow NMB group with no reversal, the moderate NMB with neostigmine reversal group had lower intercostal EMG activity. Clinicaltrials.gov NCT01962298 on October 9, 2013 and EudraCT 2013-001926-25 on October 10, 2013.


Infection and food: a factor in sudden infant death syndrome?
Despite the identification of risk factors for sudden infant death syndrome (SIDS) and decreased SIDS rates in many countries, there is still no coherent, widely accepted, mechanistic explanation for SIDS. As an extension of our work on the infectious aetiology of SIDS, we have explored the prediction that infectious agents might reach susceptible infants and babies, via particular sources of food. In this ecological study, we demonstrated significant correlations between SIDS rates and exposure to meat from some sources, and we propose that more detailed studies be carried out.


Telemedicine: follow the money modalities.
Until the late 1990s,e private and public third-party payers generally did not have explicit policies to pay for telehealth services. The Balanced Budget Act of 1997 signaled a significant change in Medicare payment policies opening the door for telemedicine reimbursement. This article traces the development of current Medicare telemedicine payment policies, beginning with the BBA of 1997 and including current medicare payment legislation. Issues related to telemedicine payment by both Medicare and other third party payers are presented; implication for the future, and the role of the nursing community are discussed.


Measuring the impact of emergency medical services (EMS) on out-of-hospital cardiac arrest survival in a developing country: A key metric for EMS systems' performance.
Out-of-hospital cardiac arrest (OHCA) can be used to evaluate the overall performance of the emergency medical services' (EMS) system. This study assessed the impact of EMS on OHCA survival rates in a setting where the prehospital system is underdeveloped.A retrospective chart review was carried out over a 5-year period of all adult OHCA patients admitted to the emergency department (ED) of a tertiary care center in Lebanon.A total of 271 patients with OHCA (179 [66.1%] men, mean age of 69.9 [standard deviation = 15.0 years] were enrolled. The most common OHCA location was residence/home (58.7%). The majority of arrests were witnessed (51.7%) with 6.1% witnessed by EMS; 211 patients (75.6%) were transported to the ED by EMS. Prehospital cardiopulmonary resuscitation (CPR) was done by EMS for 43.2% of the patients, whereas only 4.4% received CPR from a family member/bystander. Prehospital automated external defibrillator use was documented in 1.5% of cases in the prehospital setting. Only 2 patients had return of spontaneous circulation prior to ED arrival. Most patients (96.7%) were resuscitated in the ED. Patients presented to the ED mostly in asystole (79.3%). Forty-three patients (15.9%) survived to hospital admission and 13 (4.8%) were discharged alive with over half of them (53.8%) had a good neurological outcome upon discharge (cerebral performance category 1 or 2).Survival of EMS-treated OHCA victims in Lebanon is not as expected. Medical oversight of EMS activities is needed to link EMS activities to clinical outcomes and improve survival from cardiac arrest in Lebanon.


Friendship and internalizing symptoms among children and adolescents with ASD.
Anxiety and depression are common among children and adolescents with autism spectrum disorders (ASD), highlighting a need to identify factors that protect against these symptoms. Among typically developing children, friendships are protective, and lead to better emotional outcomes. The current study examined a large, well-characterized sample of children and adolescents with ASD to examine the relations among friendship, ASD symptom severity, and anxiety/depression. Rates of anxiety/depression were high in this sample. Greater ASD severity was associated with fewer symptoms of anxiety/depression, lower IQ, and poorer number and/or quality of reciprocal friendships. Surprisingly, children with no or very poor dyadic relationships experienced less anxiety than those with existing, but limited, friendships. Implications and directions for future research are discussed.


Preservation of hepatic phenotype in lentiviral-transduced primary human hepatocytes.
Lentiviral vectors effectively transduce both dividing and non-dividing cells and stably integrate into the genome of the host cell. In this study, we evaluated the usefulness of a lentiviral system for genetic modulation of primary human hepatocyte cultures. Infection with GFP-expressing lentivectors shows that Huh7 and HepG2 cell lines, as well as primary cultures of human hepatocytes, are efficiently transduced by lentiviral vectors. Real-time RT-PCR analyses demonstrate that infection with lentivectors does not alter hepatic hallmarks such as the expression of the nuclear receptors CAR, PXR, RXR alpha, or HNF4 alpha, or expression of the secretory protein, albumin. Additionally, infected hepatocytes retain the capacity for CYP3A4 induction in response to treatment with phenobarbital, a uniquely sensitive indicator of hepatic differentiation status. Lentivectors may be used for both over-expression and knockdown analyses in primary hepatocytes, as demonstrated in this study by >200-fold CAR over-expression and knockdown of CAR to less than 40% of endogenous levels, with corresponding effects on CYP2B6 expression. In summary, lentiviral vectors provide a novel methodology by which primary human hepatocytes may be stably genetically manipulated, with minimal effects on the differentiated hepatic phenotype. These approaches offer considerable advantage over current methodologies, providing a valuable alternative for use in pharmacological and toxicological investigations involving primary human hepatocyte models and potentially for cell-based therapeutics to treat hepatic dysfunction in vivo.


Laser Acupuncture for Postoperative Pain Management in Cats.
The aim of this study was to evaluate laser acupuncture as an adjuvant for postoperative pain management in cats. Twenty cats, undergoing ovariohysterectomy, were sedated with intramuscular (IM) ketamine (5 mg kg(-1)), midazolam (0.5 mg kg(-1)), and tramadol (2 mg kg(-1)). Prior to induction of anaesthesia, the subjects were randomly distributed into two groups of 10 cats: Laser: bilateral stomach 36 and spleen 6 acupoints were stimulated with infrared laser; no acupuncture was applied. Anaesthesia was induced using intravenous propofol (4 mg kg(-1)) and maintained with isoflurane. Postoperative analgesia was evaluated by a blinded assessor for 24 h following extubation using the Dynamic Interactive Visual Analogue Scale and Multidimensional Composite Pain Scale. Rescue analgesia was provided with IM tramadol (2 mg kg(-1)), and the pain scores were reassessed 30 min after the rescue intervention. If the analgesia remained insufficient, meloxicam (0.2 mg kg(-1) IM, single dose) was administered. Data were analyzed using t-tests, the Mann-Whitney test, and the Friedman test (P < 0.05). The pain scores did not differ between groups. However, postoperative supplemental analgesia was required by significantly more cats in the CONTROL (5/10) compared with the Laser group (1/10) (P = 0.038). Laser acupuncture reduced postoperative analgesic requirements in cats undergoing ovariohysterectomy.


Differences in nutritional status and activities of daily living and mobility in elderly hospitalized patients with heart failure.
This study aims to examine the effect of differences in nutritional status on activities of daily living (ADL) and mobility recovery of hospitalized elderly patients with heart failure (HF). From among 377 consecutive HF patients who underwent rehabilitation at one acute-care hospital from January 2013 to August 2015, those who were aged ≥ 65 years could walk with assistance before hospitalization and who were hospitalized for the first time were included in this retrospective cohort study. Exclusion criteria were pacemaker surgery during hospitalization, change to other departments, death during hospitalization, and unmeasured ADL. We investigated patient characteristics, basic attributes, Geriatric Nutritional Risk Index (GNRI), ADL [motor Functional Independence Measure (motor FIM)], and Rivermead Mobility Index (RMI). Of these 377 patients, 96 met the inclusion criteria and were divided into the low GNRI group (n = 38, 83.5 ± 8.3 years, 44.7% male) and high GNRI group (n = 58, 81.0 ± 6.6 years, 55.2%). Patient characteristics and the difference between motor ADL and motility recovery and nutrition data were analysed with unpaired t-test, χ2 test, and two-way analysis of covariance. In comparing the two groups, the following parameters were significantly lower in the low GNRI group than in the high GNRI group: body mass index (18.7 ± 2.2 vs. 23.2 ± 2.7 kg/m2 , P < 0.01), albumin (3.4 ± 0.4 vs. 3.8 ± 0.4 g/dL, P < 0.01), diabetes mellitus ratio (21.1% vs. 50.0%, P < 0.01), RMI at discharge (6.8 ± 2.6 vs. 8.2 ± 2.2, P = 0.01), and motor FIM at discharge (67.2 ± 19.5 vs. 75.6 ± 13.3, P = 0.02). RMI showed a significant group and term main effect and interaction effect (P < 0.05). Motor FIM showed a significant main effect of group and term (P < 0.05), and no significant interaction effect. Low nutritional status in hospitalized elderly HF patients affected their recovery of mobility but did not appear to affect the recovery of ADL.


Suppression of idiotypic specificities in adult mice by administration of antiidiotypic antibody.
It has previously been shown that there are extensive idiotypic cross-reactions among antiphenylarsonate antibodies of A/J mice. The present work indicates that administration, into normal, adult A/J mice, of rabbit antiidiotypic antibody directed to A/J antiphenylarsonate antibody suppresses almost completely the subsequent production of antibody of the corresponding idiotype. No effect was noted on the formation of antibodies to the protein carrier or of antiphenylarsonate antibody of a different idiotype. The data are consistent with central suppression of production of the idiotypic antibody mediated through interaction with immunoglobulin receptors on lymphocytes.


Alcohol drinking and mortality among men enrolled in an American Cancer Society prospective study.
We studied whether moderate alcohol drinkers have a lower total and coronary heart disease (CHD) mortality than nondrinkers. Among 276,802 U.S. men aged 40-59 enrolled in 1959 in an American Cancer Society prospective study, 42,756 deaths, 18,771 from CHD, occurred during the following 12 years (3% of the cohort was lost to follow-up). Using nondrinkers (55.3% of the cohort) as a reference category, age- and smoking-stratified relative risks (RR) of total mortality were 0.88 for occasional drinkers, 0.84 for those drinking 1 drink per day, 0.93, 1.02, 1.08, 1.22, and 1.38 for those drinking 2, 3, 4, 5, and 6 or more drinks per day, respectively. RRs of CHD mortality were 0.86, 0.79, 0.80, 0.83, 0.74, 0.85, and 0.92, respectively. Multivariate analysis failed to identify other confounders. No changes in RRs were introduced by excluding subjects with poor health or history of chronic disease at enrollment (32.8% of the cohort) or excluding subjects who died during the first 6 years of follow-up. These data indicate an apparent protective effect of moderate alcohol intake on CHD mortality that cannot be attributed to the inclusion of subjects with CHD or related diseases into the nondrinker category.


Morphological and molecular characterization of Globodera populations from Oregon and Idaho.
An unusual population of cyst nematode was found in soils collected from a Powell Butte, OR field with a cropping history including potato, wheat, other crops, and significant weed presence. These nematodes could not be placed with certainty into any known species and exhibited some unique morphological features in some specimens. Compared with Globodera pallida, the cyst body length was slightly longer and the second-stage juvenile stylet length was slightly shorter. In some individuals, the J2 stylet knob height was greater and the tail annules were more prominent than in G. pallida, and the tail abruptly narrowed, with a slight constriction near the posterior third of the hyaline terminus. Compared with G. rostochiensis, the hyaline tail terminus had a larger number of refractive bodies, and cysts of this population had a smaller Granek's ratio and fewer cuticular ridges between the anus and vulva. In some individuals, the tail termini of second-stage juveniles were more bluntly pointed, and the stylet knobs were more anteriorly directed with greater height. Unlike G. tabacum, the cyst wall often lacked a network-like pattern and, in some individuals, the juvenile tail terminus distinctly narrowed after a constriction. Molecularly, the population was distinct from G. pallida, G. rostochiensis, and G. tabacum. Multiplex polymerase chain reaction of the internal transcribed spacer (ITS) rDNA region gave results similar to G. tabacum; however, ITS restriction fragment length polymorphism patterns were observed to have individual bands in common with G. rostochiensis and G. pallida. Phylogenetic analysis based on ITS1 and -2 rDNA sequences showed greatest similarity to populations from Argentina and Chile; together, they form a moderately supported clade, distinct from G. rostochiensis, G. tabacum, G. "mexicana," European type G. pallida, and several G. pallida populations from South America.