Canonical Spin Glass and the Anomalous Hall Effect in a Centrosymmetric Ferrimagnet.
Centrosymmetric ferro/ferrimagnets provide an ideal arena for fundamental research due to their fascinating magnetic and structural characters. In this work, the Co0.8MnSn compound with a single hexagonal phase was successfully synthesized, and the magnetic phase transition and magnetic and electronic properties have been systematically investigated. Interestingly, Arrott plots and normalized magnetic entropy changes derived from the isothermal magnetizing curves may imply the first-order nature of the magnetic ordering transition around TC ∼ 121 K. The AC susceptibility analysis and detailed nonequilibrium dynamical studies (including magnetic aging, rejuvenation, and memory effects) reveal the canonical spin-glass state of Co0.8MnSn at lower temperature. Further, negative magnetoresistance and the anomalous Hall effect dominated by a commonly intrinsic term are obtained. Moreover, the field-dependent AC susceptibility data indicated that complicated and nontrivial magnetic spin textures should exist in the compound. These studies may open up further research opportunities in exploring emergent physical phenomena and potential applications in centrosymmetric magnets.


Elastic rubber strips to heal large wounds of the body wall.
Closure of large wounds is a difficult surgical challenge. This article reports on the effective closure of large surgical wounds using elastic rubber strips. One to 3 circular elastic rubber strips were sutured by applying moderate tension to the opposite edges of 30 large wounds in 28 patients. The strips were sutured in a successive "X" fashion by crossing one over the other. These rubber strips were replaced when they ruptured or after their tension had reduced because of the closure of the wounds. Complete closure of the wounds was achieved with no further need for any surgical procedure or device. One patient with laparostomy and colostomy presented with difficulty on adapting the colostomic bag, and the rubber strips were removed. The rubber strip had little effect on a large wound of the skull. In the late postoperative follow-up, 3 of the 15 closed laparostomies developed incisional hernias, and all these patients were subjected to hernioplasties with good results. The use of circular elastic rubber strips maintained at moderate tension is a simple, effective, and inexpensive surgical option for healing large wounds. It is readily available at any hospital and requires no extensive surgical experience.


Folding probabilities: a novel approach to folding transitions and the two-dimensional Ising-model.
The theoretical concept of folding probability, p(fold), has proven to be a useful means to characterize the kinetics of protein folding. Here, we illustrate the practical importance of p(fold) and demonstrate how it can be determined theoretically. We derive a general analytical expression for p(fold) and show how it can be estimated from simulations for systems where the transition rates between the relevant microstates are not known. By analyzing the Ising model we are able to determine the scaling behavior of the numerical error in the p(fold) estimate as function of the number of analyzed Monte Carlo runs. We apply our method to a simple, newly developed protein folding model for the formation of alpha helices. It is demonstrated that our technique highly parallelizes the calculation of p(fold) and that it is orders of magnitude more efficient than conventional approaches.


Tarsometatarsal bone remodelling after subtalar arthroereisis.
Subtalar arthroereisis has been described for the treatment of flexible juvenile flatfoot. However, the mechanism responsible for deformity correction has not yet been investigated adequately. The aim of this study was to document the effect of subtalar arthroereisis on the tarsometatarsal bone morphology. We retrospectively reviewed the clinical and radiological data of 26 patients (45 feet) with juvenile flexible flatfoot deformity treated by subtalar arthroereisis at our department between 2000 and 2018. Radiological evaluation included angular measurements of tarsometatarsal bone morphology as well as hindfoot and midfoot alignment. Mean radiographic follow-up was 19.4 months (sd 8.8; 12 to 41). A significant change of angular measurements of tarsometatarsal bone morphology was found after subtalar arthroereisis (p < 0.001). While there was an increase of the distal medial cuneiform angle (DMCA) and the medial cuneo-first metatarsal angle on the anteroposterior view, a decrease of the naviculo-medial cuneiform angle and the medial cuneo-first metatarsal angle was seen on the lateral view. Furthermore, we found significant improvements of all hindfoot and midfoot alignment parameters except the lateral tibio-calcaneal angle and the calcaneal pitch angle (p < 0.001). Our data support the theory of tarsometatarsal bone remodelling, which may contribute to the effect of subtalar arthroereisis for the treatment of flexible juvenile flatfoot. IV.


Intervention in the Late Stages of Congestive Heart Failure Prospects in the 1990s.
The human heart is a brilliant example of biological engineering. Its four engineering components, when properly integrated, is a marvel of a rugged, high performance, self regulating biological pump. The components of the heart are conduction system (rate control), coronary circulation (fuel supply), valves (directional flow) and muscle (power and force). The breakdown of any component part and failure of proper system integration leads to reduced pumping performance and appearance of clinical symptoms. Effective treatment exits for the failure of three of these components - valve repair and/or replacement; coronary artery bypass, angioplasty or pharmacologic intervention; and pacemakers and drugs for conduction problems.


Capillary pressure as related to water holding in polyacrylamide and chicken protein gels.
The ability of food gels to hold water affects product yield and organoleptic quality. Most researchers believe that water is held by capillarity such that gels having smaller mean pore diameter and a more hydrophilic surface hold water more tightly. To date, however, only qualitative evidence relating pore size to water holding (WH) properties has been provided. The present study sought to provide quantitative confirmation of this hypothesis. Scanning electron microscopy coupled with image analysis was used to measure pore size, and water contact angle with the gel surface was measured by the captive bubble method, in both model polyacrylamide gels and heat-induced protein (minced chicken breast) gels. These were related to water lost during cooking of meat pastes to form gels (cooking loss (CL)), as well as water lost upon centrifugation (expressible water (EW)) or by capillary suction (CSL) of all prepared gels, as inverse measures of WH. As predicted by the Young-Laplace equation for calculating capillary pressure, the presumed mechanism of WH, gels with lower water losses exhibited a more hydrophilic surface (smaller contact angle). Yet, both lower CL and CSL correlated with larger mean pore diameter of gels, not smaller as had been expected. Polyacrylamide gels varied more in WH than did prepared meat gels, yet only the capillary suction method was sensitive enough to detect these differences. The ability of gels to hold water is important for economics of processing, food quality, and food safety. This study investigated the prevailing theory for how gels hold water, capillarity. Both the pore sizes of gel microstructures and the degree of hydrophilicity of the polymers comprising each gel were quantitatively assessed and related to water holding (WH) properties, and this was the first report using such methodologies. It appeared that the degree of hydrophilicity was much more important explaining WH properties than pore size, and that future research of this kind should be carried out.


[Joint replacement quality index: the perspective of resident physicians].
Joint replacement is an established therapy for arthrosis. The quality index for joint replacement (knee and hip) should include screening for quality of patient-centred care in hospitals providing replacements, on the basis of administrative data. The quality index summarizes 16 inpatient and posthospital complications (indicators). The aim of the study was to evaluate this quality index from the medical practitioner's viewpoint. Four semistructured focus groups with 11 family physicians and 8 orthopaedic/trauma surgeons were conducted. The discussions were recorded, transcribed and analysed qualitatively according to Mayring. Infections and the revision of a total joint arthroplasty have been weighted as the most important indicators from the existing quality indicators. Between the participants some differences regarding the relevance of the indicators thrombosis and pulmonary embolism occurred. These indicators were weighted as more important by family physicians than orthopedic/trauma surgeons. For eight of the indicators, imprecision in words/meaning was criticized. In an open-ended second section, 20 new indicators within the areas complications, management and overall sector communication were identified. Major amendments of the quality index for the joint replacement are necessary. The knowledge gained from this study may serve as a basis for this development.


Painful Passages: Traumatic Experiences and Post-Traumatic Stress among Immigrant Latino Adolescents and their Primary Caregivers.
Using data from a stratified random sample of 281 foreign-born adolescents and their parents, this study provides data on migration-related trauma exposures and examines how the migration process influences the risk of experiencing trauma and developing Post-Traumatic Stress Disorder (PTSD). We find that 29% of foreign-born adolescents and 34% of foreign-born parents experienced trauma during the migration process. Among those that experienced trauma, 9% of adolescents and 21% of their parents were at risk for PTSD. Pre-migration poverty combined with clandestine entry into the US increased the risk of trauma and the subsequent development of PTSD symptoms. Post-migration experiences of discrimination and neighborhood disorder further exacerbated this risk, while social support and familism mitigated it. Our results emphasize the importance of understanding how factors prior to, during, and after migration combine to influence the health of immigrants.


Do the correlates of screen time and sedentary time differ in preschool children?
Preschool children can spend up to 12 h a day in sedentary time and few meet current recommendations for screen time. Little is known about ecological correlates that could be targeted to decrease specific versus total sedentary behaviour. This study examined whether the correlates of screen time and sedentary time differ in preschool boys and girls. Parents participating in the HAPPY Study in 2008/09 in Melbourne, Australia reported their child's usual screen time and potential individual, social and physical environment correlates. Children wore ActiGraph GT1M accelerometers for eight days to objectively assess sedentary time (<100 counts.min-1). Multivariable linear regression analyses were performed, stratified by sex and controlling for child age, preschool/childcare attendance and clustering by centre of recruitment. Correlates significantly associated with screen time or sedentary time in individual models (p < 0.05) were included in final combined models. Children were sedentary for 301.1 (SD 34.1) minutes/day and spent 108.5 (SD 69.6) minutes/day in screen time. There were no sex differences in screen or sedentary time. In the final models, sleep duration was inversely associated with girls' sedentary time and boys' screen time. The only other consistent correlates for boys and girls were parental self-efficacy to limit screen time and screen time rules, which were inversely associated with screen time for both sexes. Parents reporting that they get bored watching their child play was inversely associated and maternal television viewing was positively associated with boys' screen time. Paternal age was positively associated with boys' sedentary time. Maternal ethnicity was inversely associated and paternal education, child preferences for sedentary behaviour, and parental concerns about child's physical activity and sedentary behaviour were positively associated with girls' screen time. The modifiable correlates of total sedentary and screen time identified in this study could be targeted in interventions to reduce these behaviours. With correlates differing for screen and sedentary time, and between boys and girls, interventions may also benefit from including behaviour- and sex-specific strategies.


Cation-π Interaction Trigger Supramolecular Hydrogelation of Peptide Amphiphiles.
As an important noncovalent interaction, cation-π interaction plays an essential role in a broad area of biology and chemistry. Despite extensive studies in protein stability and molecular recognition, the utilization of cation-π interaction as a major driving force to construct supramolecular hydrogel remains uncharted. Here, a series of peptide amphiphiles are designed with cation-π interaction pairs that can self-assemble into supramolecular hydrogel under physiological condition. The influence of cation-π interaction is thoroughly investigated on peptide folding propensity, morphology, and rigidity of the resultant hydrogel. Computational and experimental results confirm that cation-π interaction could serve as a major driving force to trigger peptide folding, resultant β-hairpin peptide self-assembled into fibril-rich hydrogel. Furthermore, the designed peptides exhibit high efficacy on cytosolic protein delivery. As the first case of using cation-π interactions to trigger peptide self-assembly and hydrogelation, this work provides a novel strategy to generate supramolecular biomaterials.


A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension.
The primary objective of this study was to compare the antihypertensive efficacy and safety of intravenously administered nicardipine with that of intravenous nitroprusside (SNP) in patients with severe hypertension. The study was conducted in 121 patients with severe hypertension (diastolic blood pressure [BP] > 120 mm Hg, or systolic BP > 200 mm Hg). Patients were randomized to receive intravenous nicardipine or SNP. Drugs were administered according to a predetermined dosing schedule for a 10 to 12 h period. Sixty-one patients were randomized to intravenous nicardipine and 60 to SNP. Pretreatment BP values for the nicardipine and SNP groups were 217/128 mm Hg and 219/128 mm Hg, respectively. Therapeutic response (diastolic BP < 100 mm Hg, or a decrease of > 15 mm Hg; systolic BP < 180 mm Hg, or a decrease of > 20 mm Hg) was achieved in 98% (60/61) of patients treated with nicardipine and 93% (56/60) of patients treated with SNP. The mean decreases in systolic and diastolic BP were 61 mm Hg and 40 mm Hg after 4 h of nicardipine, and 59 mm Hg and 38 mm Hg after 4 h of SNP. The mean increases in heart rate also were similar in both groups (nicardipine, 12 beats/min; SNP 10 beats/min). The mean numbers of dose adjustments per hour required to maintain the BP reductions were lower (P < .01) in the nicardipine-treated patients (0.5 +/- 0.1 times per hour) than in the SNP-treated patients (1.5 +/- 0.2 times per hour).(ABSTRACT TRUNCATED AT 250 WORDS)


A spectrophotometric method for determination of catalase activity in small tissue samples.
A simple and rapid method for determination of catalase activity in small tissue samples is described. Using a new approach, we have exploited the peroxidatic function of catalase for the determination of enzyme activity. The method was based on the reaction of the enzyme with methanol in the presence of an optimal concentration of hydrogen peroxide. The formaldehyde produced was measured spectrophotometrically with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald) as a chromogen. With this method, a detection limit of 12.5 ng of purified catalase from bovine liver was possible, and it was successfully applied to microgram amounts of mouse liver and pancreatic islet homogenates. The catalase activity in liver was about 50 times higher than that in pancreatic islets.


Corneal development associated with eyelid opening.
The development of the cornea as a tissue initiates as early as five weeks in the human embryo. This development continues gradually until the time of eyelid opening, which is associated with major developmental changes. These events, most easily observed in rodents, which are born with closed eyelids, include alterations in the rate of cell proliferation in the epithelium, stroma and endothelium; differentiation of the epithelium; appearance of a tear film and tear-film-associated proteins; and swelling and thinning of the stroma. Eyelid opening is also associated with numerous alterations in gene expression. These events are the subject of this review. Readers are directed to the article by Wolosin et al., also in this volume, for an in-depth discussion of early corneal development.


Inter-species variability of haplamine metabolism and identification of its phase I metabolites from liver microsomes.
Haplamine, a pyranoquinoline alkaloid, was isolated from the genus Haplophyllum. The inter-species variability of haplamine metabolism was determined by reversed phase high performance liquid chromatography (HPLC) with UV detection. Microsomes from the liver of rats, mice, rabbits, guinea-pigs and humans were incubated with haplamine. After incubation, samples were extracted with a mixture of ethyl acetate and isopropyl alcohol (90 : 10; v/v). Haplamine and its metabolites were separated by HPLC using Nucleosil C18 Nautilus (5 microm) connected with a precolumn of the same type. The HPLC mobile phase consisted of water (A) and a mixture of methanol and acetonitrile (85 : 15; v/v) (B) used in a gradient mode (17 to 27 % B for 10 min, 27 to 90 % B for 37 min, 90 to 17 % B for 3 min, and finally 17 % B for 3 min) at 1 mL/min. Quantitative and qualitative results showed significant inter-species differences in haplamine metabolism. Qualitative similarities were found between guinea-pigs, rabbits, and humans. The metabolites were isolated by HPLC and identified by GC/MS after silylation. The phase I metabolites identified in human liver microsomes were TRANS/CIS-3,4-dihydroxy-9-O-desmethylhaplamine, TRANS/CIS-3,4-dihydroxyhaplamine and 9-O-desmethylhaplamine.


STI571 sensitizes nasopharyngeal carcinoma cells to cisplatin: sustained activation of ERK with improved growth inhibition.
Previously, we demonstrated that c-kit and stem cell factors (SCF) commonly co-expressed in primary and metastatic nasopharyngeal carcinomas (NPC), and in HONE-1 NPC cells with tyrosine autophosphorylation of c-kit. These findings suggest that the SCF/c-kit signaling may contribute to pathogenesis of NPC. Therefore, the efficacy of STI571 treatment alone and when combined with cisplatin on HONE-1 cells were evaluated. STI571 induced growth inhibition at the IC50 concentration (14.9 microM). When the concentration was at or higher than 30 microM, the induction of cell apoptosis was observed. The effects of STI571 were shown to be mediated by the sustained activation of ERK but did not involve the inhibition of c-kit signal activity. When the STI571 (5 microM) and cisplatin (5 microg/ml) treatments were combined, there were further inductions of ERK activation resulting in obviously enhanced growth inhibition and induction of cell apoptosis. In a xenograft model, STI571 (50 mg/kg/day) showed only a limited ability to inhibit HONE-1 cell growth, but when combined with cisplatin (3 mg/kg/twice a week) treatment, there was a significant improvement in growth inhibition compared with STI571 or cisplatin treatment alone. Our results provide experimental support for the advanced NPC therapeutic trials using the combined STI571 and cisplatin treatment.


Biological variation and reference change value of the estimated glomerular filtration rate in humans: A systematic review and meta-analysis.
Knowledge of the biological variation of serum or plasma creatinine (Cr) and the estimated glomerular filtration rate (eGFR) is important for understanding disease dynamics in Chronic Kidney Disease (CKD). The aim of our study was to determine the magnitude of random fluctuation of eGFR by determining its reference change value (RCV). We performed a systematic review and meta-analysis of studies on biological variation of Cr. Relevant studies were identified by systematic literature search on PubMed. Additional studies were retrieved from the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Biological Variation Database. Random-effects meta-analysis was conducted to derive an overall estimate of intra-individual variation of creatinine (CVICr). Based on our estimate of CVICr and RCV for Cr, the RCV for the eGFR was determined. Among identified studies, 37 met our inclusion criteria. Meta-analysis of all studies yielded a CVICr of 5.2% (95% confidence interval [CI] 4.6-5.8%), however high between-study heterogeneity (I 2 = 82.3%) was found. Exclusion of outliers led to a significant reduction of heterogeneity while still including 85% of all studies and resulted in a slightly lower CVICr of 5.0% (95% CI 4.7-5.4%). Assuming an analytical variation of CVA 1.1%, we found an overall RCV for eGFR of ±16.5%. After exclusion of outlier studies, we found a minimum conservative RCV for eGFR of ±12.5%. The RCV of the eGFR represents a valuable tool for clinicians to discern true changes in kidney function from random fluctuation.


Service of Remembrance: a comprehensive cancer center's response to bereaved family members.
Comprehensive cancer centers that offer an array of clinical trials and treatment options often experience significant patient mortality rates. Bereavement resources may not be routinely incorporated into the service delivery model in these specialty hospitals. In response, an interdisciplinary team at one cancer center proposed, planned, and implemented an annual Service of Remembrance. The incorporation of music, poetry, and visual arts was important in designing a program that would provide a meaningful, spiritual experience. A community artist who designed an interactive memorial art piece played a pivotal role. This article outlines the process of institutional culture change and describes future challenges in the implementation of this type of bereavement service.


[Changes in peripheral blood flow during the acute period of severe cranio-cerebral injury (quantitative study)].
The results of a quantitative investigation of the circulation rate and peripheral vascular resistance effected by the method of venous occlusive plethysmography in 37 patients with severe cerebro-cranial injuries are reported. A correlative dependance of changes in the peripheral hemodynamics on the clinical manifestations of a traumatic brain lesion was disclosed. At this juncture three types of the peripheral blood flow changes that corresponded to the syndromes observed were recognized, namely: infra-axial, supra-axial and, pre-eminently, hemispheral ones. The grossest alterations were seen to occur in the case of the infra-axial syndrome of the affection, which manifested themselves in a steep decline of the circulation rate and an appreciable increase of the peripheral vascular resistance.


Navigating Identities: Subtle and Public Agency of Bicultural Gay Youth.
Young people who discover their sexual attraction to people of the same sex often go through a period of ambivalence or distress, especially when they grow up in an environment that condemns homosexuality. The Dutch sociopolitical context makes the expression of same-sex desires among those with non-Dutch roots even more complicated and risky, as prevailing schemes of interpretation render the two identities incompatible. This study explores the expressions of same-sex desires and identities as well as the different forms of agency of bicultural gay youth. In-depth interviews with 14 young adults reveal how young people negotiate bicultural identities in Dutch society that brings to the fore complexities in managing diverse sexual identities and strong religious and cultural affiliations in tandem. Their strategies have the effect of questioning dominant discourses and transcend the oppositional dichotomy between sexual and ethnic forms of sociocultural otherness.


Serum cholesterol and impulsivity in a large sample of healthy young men.
Studies that have investigated the association between cholesterol levels and impulsivity are relatively few in number and have yielded equivocal results. In this study, we investigated the relationship between impulsivity, depression and serum lipids [total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides] in a large sample (N=2051) of healthy young men who were remarkably homogeneous in terms of age, educational level, and socioeconomic conditions. Depression was assessed using the depression scale of the Minnesota Multiphasic Personality Inventory-2, and impulsivity was measured using the impulse control scale of the Big Five Questionnaire (BFQ). We found that subjects with a low serum cholesterol, defined as the lowest tenth of the total cholesterol distribution (< or =3.7 mmol/l), scored significantly lower on the impulse control scale of the BFQ. There was no significant association between depression and cholesterol concentrations. In addition, in a multiple regression model, both lower levels of total cholesterol and higher levels of HDL cholesterol emerged as significant predictors of impulsivity. However, since the regression model accounted for only 0.6% of the variance in the score on the impulse control scale of the BFQ, the biological significance of these correlations was negligible. Taken together, these findings suggest that, in healthy young men, a relationship between cholesterol and impulsivity emerges only when the statistical analysis focuses on subjects with very low levels of cholesterol.


Narrative-Informed, Emotion-Focused Psychotherapy in Synchronous, Online Chat Groups for Adolescents and Young Adults with Cancer: A Proof-of-Concept Study.
Few, scalable, evidence-based psychosocial interventions exist for adolescent and young adult cancer survivors (AYAs, 18-39 years old). Using an existing, facilitated, online synchronous chat group-plus-education model (OSG+E), we replaced their educational workbook with an AYA-created film to stimulate an age-specific, emotion-focused group discussion (OSG+V). This randomized proof-of-concept trial compared the two models' content suitability, group processes, and feasibility over 9 months in 34 male and female AYAs with a range of cancers. AYAs rated the OSG + V model more suitable, cohesive, and as having higher levels of important group processes than the OSG+E. A larger randomized trial is feasible for this AYA-appropriate, emotion-focused OSG + V model.


Meckel's diverticulum: possible detection by combining pentagastrin with histamine H2 receptor blocker.
A Meckel's scan was performed on a 7-yr-old boy because of rectal bleeding. He was premedicated with pentagastrin (6 micrograms/kg subcutaneously) followed by 259 MBq (7 mCi) [99mTc]pertechnetate intravenously. The study was essentially negative. Because of persistent rectal bleeding and a strong clinical suspicion of a Meckel's, a repeat study was performed 6 wk later. He received pentagastrin as before, but this time was also given a histamine H2 receptor blocker (zantac). A Meckel's diverticulum was clearly evident.


The prevalence of insomnia in multiple sclerosis: A meta-analysis.
Insomnia is a common complaint for adults with multiple sclerosis and can severely impact health-related quality of life. Point prevalence estimates of insomnia are, however, difficult to determine in this population due to the use of different measurement tools as well as the highly variable clinical presentation of multiple sclerosis. This review consolidates the current evidence base to provide a global estimate of insomnia disorders and symptoms in multiple sclerosis, with consideration of both measurement and sample issues. A comprehensive review of the PUBMED, EMBASE, PsycINFO and CINAHL databases from database inception until January 31st, 2023 identified 1649 records, of which 34 (7636 participants total) were eligible for inclusion. Findings were meta-analysed using a random-effects model. Estimates based on self-reported symptoms (52%, CI: 44%-59%) were significantly higher than those obtained by diagnostic tools (22%, CI: 16%-29%). Gender was identified as a potential moderator, with women more likely to report insomnia than men. One in two adults with multiple sclerosis endorse symptoms of poor sleep quality and daytime sleepiness, with 1 in 5 diagnosed with an insomnia disorder. Future research is needed to enhance understanding of these comorbid conditions, including the trajectory of insomnia with disease progression. PROSPERO registration number CRD42021281524.


Escherichia coli and the Emergence of Molecular Biology.
The creation of the "Phage group" by M. Delbrück, S. E. Luria, and A. D. Hershey in 1940 at Cold Spring Harbor played a crucial role in the development of molecular biology. In the 1940s, working with Escherichia coli and its viruses, Luria and Delbrück discovered the spontaneous nature of bacterial mutations and Hershey described recombination in bacteriophages and demonstrated with M. Chase that the genetic material that infects bacteria is DNA. At the same time, S. Benzer defined the structure of a functional genetic unit and J. Lederberg and E. Tatum discovered sexual recombination between bacteria. Some years later, Lederberg's group discovered extrachromosomal particles, the plasmids, and a novel way of genetic transfer through bacteriophages, called transduction. In 1949, at the Pasteur Institute in Paris, A. Lwoff uncovered the mechanism of lysogeny. Shortly afterwards, F. Jacob and E. Wollman unraveled the mechanism of the sexual process in E. coli and established the circularity of the bacterial chromosome. In the 1960s, J. Monod and F. Jacob, by genetic analysis of the E. coli lactose system, proposed the operon model for gene regulation and introduced the concept of messenger RNA. The elucidation of the double helix structure of DNA in 1953 by F. Crick and J. Watson had major consequences: the establishment of the copying mechanism (Meselson and Stahl), the discovery of the nature of the genetic code (S. Brenner) leading to its deciphering. E. coli and its phages were instrumental in the development of recombinant DNA technology based on the discovery of the restriction-modification system by W. Arber.


Alteration of the oral and gut microbiota in patients with Kawasaki disease.
Kawasaki disease (KD) is a multi-systemic vasculitis that primarily affects children and has an unknown cause. Although an increasing number of studies linking the gut microbiota with KD, the unchallengeable etiology of KD is not available. Here, we obtained fecal and oral samples from KD patients and healthy controls, and then we use high-throughput sequencing to examine the diversity and composition of microbiota. Results showed that both in the gut and oral microbiota, the diversity of KD patients was significantly lower than that of the healthy controls. In the gut microbiota, a higher abundance of Enterococcus (40.12% vs less than 0.1%), Bifidobacterium (20.71% vs 3.06%), Escherichia-Shigella (17.56% vs 0.61%), Streptococcus (5.97% vs 0.11%) and Blautia (4.69% vs 0.1%) was observed in the KD patients, and enrichment of Enterococcus in the patients was observed. In terms of oral microbiota, the prevalence of Streptococcus (21.99% vs 0.1%), Rothia (3.02% vs 0.1%), and Escherichia-Shigella (0.68% vs 0.0%) were significantly higher in the KD patients, with the enrichment of Streptococcus and Escherichia-Shigella. Additionally, significant differences in microbial community function between KD patients and healthy controls in the fecal samples were also observed, which will affect the colonization and reproduction of gut microbiota. These results suggested that the dysbiosis of gut and oral microbiota are both related to KD pathogenesis, of which, the prevalence of Enterococcus in the gut and higher abundance of Streptococcus and Escherichia-Shigella in the oral cavity will be a potential biomarker of the KD. Overall, this study not only confirms that the disturbance of gut microbiota is a causative trigger of KD but also provides new insight into the oral microbiota involved in KD pathogenesis.


Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review.
The analysis of the 2017 Cochrane review reveals flaws, which means that contrary to its findings, there is no evidence that graded exercise therapy is effective. Because of the failure to report harms adequately in the trials covered by the review, it cannot be said that graded exercise therapy is safe. The analysis of the objective outcomes in the trials provides sufficient evidence to conclude that graded exercise therapy is an ineffective treatment for myalgic encephalomyelitis/chronic fatigue syndrome.


Exploiting graph kernels for high performance biomedical relation extraction.
Relation extraction from biomedical publications is an important task in the area of semantic mining of text. Kernel methods for supervised relation extraction are often preferred over manual feature engineering methods, when classifying highly ordered structures such as trees and graphs obtained from syntactic parsing of a sentence. Tree kernels such as the Subset Tree Kernel and Partial Tree Kernel have been shown to be effective for classifying constituency parse trees and basic dependency parse graphs of a sentence. Graph kernels such as the All Path Graph kernel (APG) and Approximate Subgraph Matching (ASM) kernel have been shown to be suitable for classifying general graphs with cycles, such as the enhanced dependency parse graph of a sentence. In this work, we present a high performance Chemical-Induced Disease (CID) relation extraction system. We present a comparative study of kernel methods for the CID task and also extend our study to the Protein-Protein Interaction (PPI) extraction task, an important biomedical relation extraction task. We discuss novel modifications to the ASM kernel to boost its performance and a method to apply graph kernels for extracting relations expressed in multiple sentences. Our system for CID relation extraction attains an F-score of 60%, without using external knowledge sources or task specific heuristic or rules. In comparison, the state of the art Chemical-Disease Relation Extraction system achieves an F-score of 56% using an ensemble of multiple machine learning methods, which is then boosted to 61% with a rule based system employing task specific post processing rules. For the CID task, graph kernels outperform tree kernels substantially, and the best performance is obtained with APG kernel that attains an F-score of 60%, followed by the ASM kernel at 57%. The performance difference between the ASM and APG kernels for CID sentence level relation extraction is not significant. In our evaluation of ASM for the PPI task, ASM performed better than APG kernel for the BioInfer dataset, in the Area Under Curve (AUC) measure (74% vs 69%). However, for all the other PPI datasets, namely AIMed, HPRD50, IEPA and LLL, ASM is substantially outperformed by the APG kernel in F-score and AUC measures. We demonstrate a high performance Chemical Induced Disease relation extraction, without employing external knowledge sources or task specific heuristics. Our work shows that graph kernels are effective in extracting relations that are expressed in multiple sentences. We also show that the graph kernels, namely the ASM and APG kernels, substantially outperform the tree kernels. Among the graph kernels, we showed the ASM kernel as effective for biomedical relation extraction, with comparable performance to the APG kernel for datasets such as the CID-sentence level relation extraction and BioInfer in PPI. Overall, the APG kernel is shown to be significantly more accurate than the ASM kernel, achieving better performance on most datasets.


Optimization of a method for deactivation of platelet-activating factor:acetylhydrolase in serum for use in in-vitro fertilization culture media.
Embryos produced by in-vitro fertilization (IVF) may produce less platelet-activating factor (PAF) than is optimal for development. It was previously shown that supplementation of culture media with PAF results in a significant increase in pregnancy rate. Human embryos are often cultured in media supplemented with serum containing the enzyme PAF:acetylhydrolase (PAF:AH; EC 18.104.22.168), which hydrolyses PAF to its inactive form, lyso-PAF. Thus, effective supplementation of media with PAF requires inactivation of this enzyme. In this study we examine the efficacy of the methods of PAF:AH deactivation used for PAF supplementation of IVF culture medium. When the effectiveness of a commonly used acid treatment protocol (pH 3.0 at room temperature for 5 min) was examined, it was found that it was not completely effective for the majority of sera. When synthetic PAF was added to 18 serum samples which had been acid treated, five had 90-100% of the original PAF remaining after 24 h (showing that the acid treatment was effective), eight had from 10-90% of the original PAF remaining after 24 h, and five samples had 0-10%. The extent to which PAF:AH was susceptible to deactivation was not associated with the activity in the serum prior to treatment, the serum oestradiol concentration, or the cause of infertility. The period of acidification and the incubation temperature were assessed to develop a new acid-treatment protocol (20 min acid treatment at 37 degrees C) which was able to deactivate PAF:AH effectively in all sera (53/53) examined. A trial was performed to assess the effect of acid treatment of serum for 5 min at room temperature compared with the new protocol (20 min at 37 degrees C) on IVF outcome, following PAF supplementation of IVF culture medium. Oocyte recovery, fertilization and embryo development rates were equivalent for both groups and approximately equal numbers of embryos were transferred or cryopreserved. Pregnancy rates were not significantly different (14.6 versus 20.0%) for the two treatments, with a trend towards a higher pregnancy rate with the new acid-treatment protocol. The results show that this new procedure for acid treatment of serum in combination with PAF supplementation does not have detrimental effects on embryos and their pregnancy outcome and is therefore suitable for use in IVF.


Therapeutic Inhibition of miR-33 Promotes Fatty Acid Oxidation but Does Not Ameliorate Metabolic Dysfunction in Diet-Induced Obesity.
miR-33 has emerged as an important regulator of lipid homeostasis. Inhibition of miR-33 has been demonstrated as protective against atherosclerosis; however, recent studies in mice suggest that miR-33 inhibition may have adverse effects on lipid and insulin metabolism. Given the therapeutic interest in miR-33 inhibitors for treating atherosclerosis, we sought to test whether pharmacologically inhibiting miR-33 at atheroprotective doses affected metabolic parameters in a mouse model of diet-induced obesity. High-fat diet (HFD) feeding in conjunction with treatment of male mice with 10 mg/kg control anti-miR or anti-miR33 inhibitors for 20 weeks promoted equivalent weight gain in all groups. miR-33 inhibitors increased plasma total cholesterol and decreased serum triglycerides compared with control anti-miR, but not compared with PBS-treated mice. Metrics of insulin resistance were not altered in anti-miR33-treated mice compared with controls; however, respiratory exchange ratio was decreased in anti-miR33-treated mice. Hepatic expression of miR-33 targets Abca1 and Hadhb were derepressed on miR-33 inhibition. In contrast, protein levels of putative miR-33 target gene SREBP-1 or its downstream targets genes Fasn and Acc were not altered in anti-miR33-treated mice, and hepatic lipid accumulation did not differ between groups. In the adipose tissue, anti-miR33 treatment increased Ampk gene expression and markers of M2 macrophage polarization. We demonstrate in a mouse model of diet-induced obesity that therapeutic silencing of miR-33 may promote whole-body oxidative metabolism but does not affect metabolic dysregulation. This suggests that pharmacological inhibition of miR-33 at doses known to reduce atherosclerosis may be a safe future therapeutic.


The effect of nedocromil sodium on human airway epithelial cell-induced eosinophil chemotaxis and adherence to human endothelial cell in vitro.
Although some studies have shown that long-term treatment of asthmatics with nedocromil sodium can reduce airway hyperresponsiveness and improve symptoms and lung function, the mechanisms underlying its effects are not well understood. We have investigated the effect of nedocromil sodium on eosinophil chemotaxis, eosinophil adherence to human endothelial cells and release of soluble intercellular adhesion molecule-1 (sICAM-1) from endothelial cells, induced by conditioned medium collected from cultured human bronchial epithelial cells. Conditioned medium significantly increased eosinophil chemotaxis from a baseline median value of 2.1 (range 1.9-4.5) cells-high power field(-1) (HPF) to 10.5 (range 7.8-12.3) cells-HPF(-1) (p<0.05). Similarly, conditioned medium significantly increased eosinophil adherence to endothelial cells from a baseline value of 9 (range 8-12)% to 23 (range 21-30)% (p<0.05). Nedocromil sodium, at 10(-5) M concentration, significantly attenuated the eosinophil chemotaxis and adherence induced by conditioned medium. Conditioned medium also significantly increased the release of sICAM-1 from endothelial cells, from a baseline value of 11.5 (range 8.1-15.4) pg x microg(-1) protein to 67.6 (range 55.6-73.5) pg x microg(-1) protein (p<0.05). This was significantly attenuated by anti-tumour necrosis factor-alpha (TNF-alpha), anti-interleukin-1beta (IL-1beta) and 10(-5) M nedocromil sodium. These findings suggest that human bronchial epithelial cell-derived mediators may potentiate eosinophil activity, and that this can be modulated by nedocromil sodium, suggesting a possible mechanism underlying its anti-inflammatory effect.


Physical activity for paediatric rheumatic diseases: standing up against old paradigms.
Over the past 50 years it has become clear that physical inactivity is associated with chronic disease risk. For several rheumatic diseases, bed rest was traditionally advocated as the best treatment, but several levels of evidence support the imminent paradigm shift from the prescription of bed rest to physical activity in individuals with paediatric rheumatic diseases, in particular juvenile systemic lupus erythematosus, juvenile idiopathic arthritis, juvenile fibromyalgia, and juvenile dermatomyositis. Increasing levels of physical activity can alleviate several symptoms experienced by patients with paediatric rheumatic diseases, such as low aerobic fitness, pain, fatigue, muscle weakness and poor health-related quality of life. Moreover, the propensity of patients with paediatric rheumatic diseases to be hypoactive - often due to social self-isolation, overprotection, and fear and/or ignorance on the part of parents, teachers and health practitioners - can be detrimental to general disease symptoms and function. In support of this rationale, a growing number of studies have demonstrated that the systemic benefits of exercise training clearly outweigh the risks in these diseases. In this sense, health professionals are advised to assess, track and fight against physical inactivity and sedentary behaviour on a routine basis, as they are invaluable health risk parameters in rheumatology.


[Experiences with Ketalar anesthesia in gynecological and obstetrical operations].
The authors' experience with Ketalar anaesthesia applied in 483 cases has been described. The effect of the narcotic on the cardiovascular system, respiration and acid-base household is analysed in details. As stated by the authors, the narcotic is well applicable in obstetrical and gynecological small operations. By appropriate preparation the occurence of side effects can be reduced. With Shirodkar operations increase of the uterine tonus can be prevented by protective premedication. Ketalar is not recommended for the introduction of anaesthesia in cases of Caesarean section as it may increase the incidence of neonatal asphyxia.


Performance evaluation of a distance learning program.
This paper presents a performance metric which uses a single number to characterize the response time for a non-deterministic client-server application operating over the Internet. When applied to a Macintosh-based distance learning application called the Digital Anatomist Browser, the metric allowed us to observe that "A typical student doing a typical mix of Browser commands on a typical data set will experience the same delay if they use a slow Macintosh on a local network or a fast Macintosh on the other side of the country accessing the data over the Internet." The methodology presented is applicable to other client-server applications that are rapidly appearing on the Internet.


The effectiveness of various biofiltration substrates in removing bacteria, endotoxins, and dust from ventilation system exhaust from a chicken hatchery.
The objective of this study was to evaluate the effectiveness of various organic and organic-mineral biofilter media in purifying ventilation exhaust from a chicken hatchery room. Three different substrates were tested. Efficiency levels for the removal of dust, gram-negative bacteria, and bacterial endotoxin were recorded. The microbiological properties of the substrates were also studied. All of the biofilter substrates were highly effective in removing gram-negative bacteria, moderately effective in reducing dust levels, and only slightly effective in removing endotoxin. The substrate that was most efficient in retaining bioaerosols was the organic-mineral medium containing 20% halloysite, 40% compost, and 40% peat, which generally had at least satisfactory efficiency values for removing all of the contaminants tested.


A comparative study of serum alpha 1-microglobulin and beta 2-microglobulin levels in cancerous and other diseases.
The levels of serum alpha 1-microglobulin in 60 normal persons and in 191 patients suffering from a variety of benign and malignant disorders were determined by an enzyme immunoassay, and these values were compared with the levels of beta 2-microglobulin. A discrepancy between the serum levels of these proteins was found in hepatobiliary disorders; that is, an increased serum level of beta 2-microglobulin was observed in 73.9%, while in only 4.3% was there an elevation of alpha 1-microglobulin. In particular, alpha 1-microglobulin levels in patients with liver cirrhosis were well below the normal range, while beta 2-microglobulin levels were elevated. Elevated levels of both proteins were noted in patients with some impairments of renal function, particularly in chronic renal failure, and in immunological diseases. In 81 patients with neoplastic diseases, a high alpha 1-microglobulin value was found in only 15 patients (16.4%), while a high beta 2-microglobulin value in 62 patients (76.5%). The serum levels of both alpha 1-microglobulin and beta 2-microglobulin were especially high in plasma cell dyscrasia with Bence Jones protein, but other neoplastic diseases were mostly associated with beta 2-microglobulin elevation alone.


[Psychotherapeutic group intervention for patients in the second half of life].
Mental disorders in the elderly often influence their social and physical wellbeing. Depression and anxiety disorders may frequently be found in elderly patients with chronic diseases; however, we now know that this patient group may benefit from psychotherapy. The psychotherapeutic group "40 plus" provides a supportive group intervention for physically and psychically impaired patients in their second half of life. The group intervention allows them to recognize and to activate their resources, as well as the interaction between physical disorders and psychosocial burdens and possible influential aspects to be perceived. An evaluation of 64 patients who participated in this group intervention showed a significant improvement of depression, psychosocial burdens and somatization. The concept of the group "40 plus" presented here may therefore be seen as to effectively bridge a gap in the health care of the elderly.


Glycerol and Methylglyoxal Metabolism.
The metabolic connection between glycerol and methylglyoxal (MG) is principally that DHAP, which is an intermediate in the aerobic breakdown of glycerol, is also the major precursor of MG, being the substrate for methylglyoxal synthase (MGS). The synthesis of MG is a consequence of unbalanced metabolism related either to a limitation for phosphate or to excessive carbon flux through the pathways that have the capacity to generate significant pools of DHAP. Cells producing MG produce a poison as an intermediate strategy for survival of metabolic imbalance. Indeed the panoply of metabolic regulation in this sector of catabolism can be seen as a strategy to avoid death by self-poisoning. Glycerol entry into Escherichia coli and Salmonella enterica serovar Typhimurium is facilitated by the aquaglyceroporin, GlpF. A homologous protein in serovar Typhimurium, PduF, facilitates the entry of 1,2-propanediol (Ppd) and is part of the Ppd metabolic pathway. MGS catalyzes the elimination of phosphate from DHAP, forming an enzyme-bound enediol(ate) intermediate that is released from the enzyme, followed by release of inorganic phosphate. The enzyme is highly specific for DHAP. Multiple MG detoxification pathways are found in both E. coli and serovar Typhimurium, but the dominant pathway is the GSH-dependent glyoxalase III system. The KefB and KefC systems have evolved to provide protection during detoxification of electrophiles. KefB and KefC are GSH-gated K+ efflux systems that are activated by the formation and binding of glutathione adducts that are generated during detoxification.


Insulin glargine in type 2 diabetes in everyday clinical practice: 7 years experience.
Insulin therapy is often essential in people with type 2 diabetes mellitus (T2DM) but is typically not initiated early enough or aggressive enough, leading to worsening of glycaemic control and the majority of people staying above recommended haemoglobin A(1c) (HbA(1c)) targets of <7%. The extensive clinical experience gained with insulin glargine, in particular, the low risk of hypoglycaemia and consistent improvements in HbA(1c), suggests that insulin glargine can be initiated aggressively to help patients reach such HbA(1c) targets. However, many clinicians may be unaware of how easy it is to initiate insulin glargine. Indeed, the once-daily injection of insulin glargine plus once-daily measurement of blood glucose should provide little difficulty for patients. In the current review, the options for the initiation of insulin glargine in T2DM and how the patient can become more involved in management of their diabetes are discussed. The advantages of insulin glargine in randomized controlled trials and how these have translated into everyday clinical practice are also discussed.


How well do antenatal clinic (ANC) attendees represent the general population? A comparison of HIV prevalence from ANC sentinel surveillance sites with a population-based survey of women aged 15-49 in Cambodia.
The purpose of this study was to evaluate whether HIV-1 prevalence among antenatal clinic (ANC) attendees in Cambodia provided a reasonable estimate of HIV-1 prevalence among all women 15-49 years. METHODS Antenatal clinic attendees in five HIV sentinel surveillance sites (five provinces) were selected by consecutive sampling (n = 1695). The population survey of females by household was carried out in the same five areas. Household females aged 15-49 years were selected using a three-stage cluster sampling design (n = 3066). Serum-based HIV ELISA testing was done for both ANC attendees and household females. The HIV prevalence for ANC attendees and household females were compared by age group and urban versus rural location. The overall prevalence of HIV-1 infection among ANC attendees (1.62%, 95% CI : 1.26-1.98) was similar to the overall prevalence obtained from the general population of household females (1.24%, 95% CI : 0.92-1.55) in the same catchment areas in Cambodia. In the rural areas, the overall HIV prevalence among ANC attendees (2.18%, 95% CI : 1.59-2.77) was significantly higher than among the household females (0.86%, 95% CI : 0.49-1.23) after adjustment for age distribution and education level. In the 15-24 age group in rural areas, the HIV prevalence of ANC women was 2.71% (95% CI : 0.96-4.46) compared with 0.77% (95% CI : 0.02-1.53) in household females. Although ANC data can be used to estimate trends over time, it should be realized that ANC data may overestimate the actual prevalence in the younger age group in rural areas in Cambodia.


Using MALDI-TOF-MS to test Staphylococcus aureus-infected vitreous.
This study aimed to establish a method for testing Staphylococcus aureus in the vitreous of endophthalmitis with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), which is simple, fast, and sensitive. S. aureus at different numbers was either mixed with homogenized vitreous or inoculated in porcine eyes for culturing, followed by homogenization. The homogenized vitreous samples, with or without centrifugation, were stained with Gram and Coomassie Blue (CBB) dyes and cultured with blood agar. The pellet of the vitreous mixture was analyzed with MALDI-TOF-MS. The minimum detectable levels of S. aureus in H2O and in the pellet of homogenized vitreous were 9.0 × 103 (positive rate, 22.2%) and 1.0 × 104 CFU/μl (positive rate, 11.1%), respectively. In the vitreous samples inoculated with S. aureus and cultured for 12 h, the number of S. aureus increased in a dose-dependent manner to the number of bacteria in the inoculate. In the supernatant of the homogenized vitreous, there were traces of bacteria identified with Gram staining. On the blood agar plates, the supernatant grew a few colonies, while the pellet grew intensive colonies. The vitreous fragments that were stained with CBB were displayed in the supernatants, in small numbers, and in the pellets. When the inoculated number was 1.0 × 104 CFU/μl or higher, the bacteria in the vitreous pellets could be identified in all samples (100%, n = 9). However, bacteria could be detected in only two out of nine spots of pellets (22.2%) if the number of inoculated S. aureus was 1.0 × 103 CFU/μl. A method for testing S. aureus directly from vitreous samples of endophthalmitis by the combination of easy extraction methods and a MALDI-TOF- MS assay was provided. This rapid identification method is easily adaptable for use in clinical routine and can help reduce the delay in diagnosis, allowing for earlier therapeutic intervention in patients.


Decreased GABA(A) benzodiazepine binding site densities in postmortem brains of Cloninger type 1 and 2 alcoholics.
Ethanol modulates the GABA(A) receptor to cause sedative, anxiolytic and hypnotic effects that are qualitatively similar to benzodiazepines and barbiturates. The aim of this study was to explore if GABA(A) receptor density is altered in post-mortem brains of anxiety-prone Cloninger type 1 and socially hostile type 2 alcoholic subtypes when compared to controls. The GABA(A) binding site density was measured by whole-hemisphere autoradiography with tritium labeled flunitrazepam ([(3)H]flunitrazepam) from 17 alcoholic (nine type 1, eight type 2) and 10 non-alcoholic post-mortem brains, using cold flumazepam as a competitive ligand. A total of eight specific brain areas were examined. Alcoholics displayed a significantly (p < 0.001, bootstrap type generalizing estimating equations model) reduced [(3)H]flunitrazepam binding site density when compared to controls. When localized, type 2 alcoholics displayed a significantly (p ≤ 0.05) reduced [(3)H]flunitrazepam binding site density in the internal globus pallidus, the gyrus dentatus and the hippocampus, whereas type 1 alcoholics differed from controls in the internal globus pallidus and the hippocampus. While previous reports have demonstrated significant alterations in dopaminergic and serotonergic receptors between type 1 and type 2 alcoholics among these same subjects, we observed no statistically significant difference in [(3)H]flunitrazepam binding site densities between the Cloninger type 1 and type 2 alcoholics.


Effect of washing on the post-thaw quality of cryopreserved ram epididymal spermatozoa.
The aim of the study was to evaluate the effect of washing on the post-thaw quality of ram cauda epididymal spermatozoa (P1: Unwashed, P2: Washed). Fresh testicles of adult healthy slaughtered rams were collected and transported to the laboratory in an ice chest, where they were weighed, and cauda epididymides were separated. These cauda epididymides were used for recovery of spermatozoa in tris-citric acid fructose buffer by incision method. Spermatozoa samples showing ≥70% progressive motility were pooled and processed further. The mean values (±standard error) of various parameters such as the percentage of sperm motility, live sperm, intact acrosome, and hypo-osmotic swelling test (HOST) reacted spermatozoa were recorded. In this experiment, the percent sperm motility, live spermatozoa, and intact acrosome both at pre-freeze and post-thaw were higher (p>0.05) in P1 than P2. However, the post-thaw percent HOST reacted spermatozoa was slightly higher (p>0.05) for P2 than P1. Washing of cauda epididymal spermatozoa has no significant adverse effect on the quality during cryopreservation. Therefore, this processing method can be applied wherever necessary before the extension of the recovered spermatozoa sample in different ram extenders.


Potential Clinical Utility and Feasibility of Combined Left Atrial Appendage Closure and Positioning of Miniaturized Pacemaker Through a Single Right Femoral Vein Access.
This study assessed the clinical utility and feasibility of concomitant of combined left atrial appendage (LAA) closure and positioning of miniaturized pacemaker (Micra TPS). All consecutive patients who underwent VVI-PM implant from November 2015 to October 2016 were considered. VVI-PM implant was conducted either using transvenous approach or by positioning Micra TPS. In selected patients with concomitant contraindication to OAC, Micra TPS was combined with LAA occlusion ("combined approach"), performed in general anesthesia and guided by multimodality imaging; procedural and follow-up data of these specific patients were registered. Sixty patients were treated with VVI-PM implant. Six patients (10.0%) presented OAC contraindication, of which 4 (6.7%) were eligible for the "combined procedure"; 2 of 4 of these patients presented chronic hemodialysis-dependent renal failure. The combined approach was successful in all 4 patients without intra- or periprocedural complications. No adverse events linked to the combined approach occurred during mid-term follow-up (7.5, interquartile range 5.0 to 7.9 months). In conclusion, VVI-PM indication and concomitant contraindication to OAC is not uncommon; in selected patients, combined LAA closure and positioning of Micra TPS may be a feasible therapeutic option.


The effect of relative distance enlargement on visual acuity in the visually impaired.
Prescribing magnification is typically based on distance or near visual acuity. This presumes a constant minimum angle of visual resolution with working distance and therefore enlargement of an object moved to a shorter working distance (relative distance enlargement). This study examines this premise in a visually impaired population. Distance letter visual acuity was measured prospectively for 380 low vision patients (distance visual acuity between 0.3 and 2.1 logMAR) over the age of 57 years, along with near word visual acuity at an appropriate distance for near lens additions from +4 D to +20 D. Demographic information, the disease causing low vision, contrast sensitivity, visual field and psychological status were also recorded. Distance letter acuity was significantly related to (r = 0.84) but on average 0.1 +/- 0.2 logMAR better (1 +/- 2 lines on a logMAR chart) than near word acuity at 25 cm with a +4 D lens addition. In 39.8 per cent of patients, near word acuity was more than 0.1 logMAR worse than distance letter acuity. In 11.0 per cent of subjects, near visual acuity was more than 0.1 logMAR better than distance letter acuity. The group with near word acuity worse than distance letter acuity also had lower contrast sensitivity. The group with near word acuity better than distance letter acuity was less likely to have age-related macular degeneration. Smaller print size could be read by reducing working distance (achieved by using higher near lens additions) in 86.1 per cent, although not by as much as predicted by geometric progression in 14.5 per cent. Although distance letter and near word acuity are highly related, they are on average 1 logMAR line different and this varies significantly between individuals. Near word acuity did not increase linearly with relative distance enlargement in approximately one in seven visually impaired, suggesting that the measurement of visual resolution over a range of working distances will assist appropriate prescribing of magnification aids.


[Extracorporeal photochemotherapy as prevention of graft rejection, coupled with declining infectious complications rates in urological patients].
This study presents results of extracorporeal photochemotherapy (EPCT) application in 24 renal allograft recipients (RAR), who suffered chronic kidney disease (CKD) caused by urological diseases. The comparison group treated only with chemical immunosuppression comprised 24 recipients who received transplants from the same donors as intervention group patients. It was found that EPCT reduces not only the number of RAR rejections, but also the incidence of infectious complications. The effectiveness of EFHT was confirmed by clinical, laboratory and immunological data, and by protocol biopsy results. Possible mechanisms of preservation of anti-infectious protection in the setting of chemical immunosuppression when using EPCT are discussed.


Protrusive tongue strength in people with severely weak tongues.
The purpose of the study was to quantify tongue protrusion force and compare its characteristics between participants with severely weak tongues and those with normal lingual strength. The sample consisted of 11 participants with severe lingual strength deficits and 11 age- and sex-matched participants with normal lingual strength. Tongue force was evaluated quantitatively using the Forling instrument, and the average force, maximum force, average force application rate, and area under the graphic curve were analysed. These parameters were compared between the groups. In the participants with severely weak tongues, the average and the maximum forces in N (Newton) were 2.03 ± 1.17 and 3.56 ± 1.77, respectively. The average force application rate in N/s (Newton per second) was 1.25 and the area under the graphic curve in Ns (Newton times second) was 18.6. The values of the participants with normal lingual strength were, respectively, 13.27 ± 6.15 N, 18.91 ± 7.95 N, 10.46 N/s, and 108.08 Ns. All parameters analysed differed significantly between the groups. The data collected could aid speech-language pathologists in diagnosing problems related to tongue force.


Nodular Thyroid Disease and Thyroid Cancer in the Era of Precision Medicine.
The management of thyroid nodules, one of the main clinical challenges in endocrine clinical practice, is usually straightforward. Although the most important concern is ruling out malignancy, there are grey areas where uncertainty is frequently present: the nodules labelled as indeterminate by cytology and the extent of therapy when thyroid cancer is diagnosed pathologically. There is evidence that the current available precision medicine tools (from all the "-omics" to molecular analysis, fine-tuning imaging or artificial intelligence) may help to fill present gaps in the future. We present here a commentary on some of the current challenges faced by endocrinologists in the field of thyroid nodules and cancer, and illustrate how precision medicine may improve their diagnostic and therapeutic capabilities in the future.


[A case with multiple myeloma in which serum forms gel precipitation upon exposure to air].
We present the case of a 69-years-old man who was admitted to hospital with multiple myeloma. IgG-kappa type monoclonal protein was detected in the serum. When we separated the serum obtained from blood sample of the patient and the lid of the collecting tube was opened, the patient's serum became gelled immediately. When the lid of the collecting tube remained closed, the patient's serum did not become gelled even at 4 degrees C. Moreover, the gelled serum of the patient did not resolve at 56 degrees C. Taken together, these results indicated that gel formation of the patient's serum may not be due to cryoglobulin. It was found that the pH of the patient's serum elevated to pH 8.0 quickly after exposed to air. It was also found that the patient's serum, but not the sera of other IgG-kappa multiple myeloma patients, became gelled as soon as PBS of pH 8.0 was added. These results highly suggest that the patient's serum becomes gelled at pH 8.0. However, the isoelectric focusing of isolated precipitation in the patient showed fractions around the pH 8.5-8.7 zone, which was different from the pH at which the precipitation began to form. We think that this may be the first report of a multiple myeloma patient whose serum becomes gelled after exposed to air.


Prophylatic use of IV nalmefene to prevent epidural opioid-induced pruritus: A multicenter, randomized clinical trial.
The incidence of pruritus from neuraxial opioids is about 60%. Pruritus causes discomfort and decreases the quality of recovery. This randomized double-blinded clinical trial was aimed to evaluate the prophylactic effects of a single dose IV nalmefene on the incidence and severity of epidural opioid-induced pruritus within 24 h after surgeries. A two-center, randomized, double blinded, controlled clinical trial. The study was conducted from March 2022 to February 2023 at two tertiary care hospitals in China. Patients aged between 18 and 80 years-old who underwent elective surgeries and received epidural analgesia intra- and post-operatively were screened for study enrollment. A total of 306 patients were enrolled, 302 patients underwent randomization and 296 patients were included in the final analysis. The nalmefene group was prophylactically given 0.5 μg/kg nalmefene intravenously while the control group was given the same volume of saline. The primary endpoint was the incidence of pruritus within 24 h after surgeries. The secondary endpoints included time of the first patient-reported pruritus, severity of pruritus after surgeries, severity of acute pain scores after surgeries and other anesthesia/analgesia related side effects. Pruritus occurred in 51 of the 147 (34.69%) patients in the control group and 35 of the 149 (23.49%) patients in the nalmefene group (odds ratio, 0.58; 95% CI, 0.35 to 0.96; P = 0.034) within 24 h postoperatively. Nalmefene group demonstrated delayed onset of pruritus, reduced severity of pruritus and decreased vomiting within 24 h after surgery. There were no significant differences in postoperative analgesia and the incidence of other anesthesia/analgesia associated side effects. A single dose of 0.5 μg/kg nalmefene intravenously significantly reduced the incidence and severity of epidural-opioid induced pruritus within 24 h after surgery without affecting the efficacy of epidural analgesia. Chinese Clinical Trial Registry (www.chictr.org.cn) and the registration number is ChiCTR2100050463. Registered on August 27th, 2021.


Phenotypic and molecular characteristics of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in slaughterhouse pig-related workers and control workers in Guangdong Province, China.
Pig farmers and veterinarians have high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) due to the occupational livestock exposure, while few reported this association on slaughterhouse workers. We conducted this cross-sectional study to explore the phenotypic and molecular characteristics of S. aureus and MRSA in slaughterhouse pig-related workers and control workers in Guangdong Province, China. Participants were interviewed and provided two nasal swabs. Swabs were tested for S. aureus, and isolates were further tested for antimicrobial susceptibility, virulence genes and multi-locus sequence typing. Compared with control workers, pig-related workers have significantly higher prevalence of MRSA carriage (adjusted odd ratio (aOR) 3·70, 95% CI 1·63-8·40). The proportions of MRSA resistant to clindamycin, erythromycin, tetracycline or chloromycetin were significantly higher in pig-related workers than in control workers. The predominant phenotypes of S. aureus were resistant to penicillin, clindamycin, erythromycin and tetracycline. Three MRSA CC9 isolates with livestock-associated characteristics (resistance to tetracycline and absence of immune evasion cluster (IEC) genes) were detected in pig-related workers but not in control workers. For human-associated CCs (CC7, CC59, CC6, and CC188), there was no significant difference in IEC profile or antimicrobial resistance between the groups. These findings reveal that there may be a potential risk for livestock-to-human transmission of LA-MRSA and human-to-human transmission of human-associated MRSA.


Mutations of CREBBP and SOCS1 are independent prognostic factors in diffuse large B cell lymphoma: mutational analysis of the SAKK 38/07 prospective clinical trial cohort.
Recently, the mutational background of diffuse large B cell lymphoma (DLBCL) has been revealed, identifying specific genetic events that drive lymphomagenesis. However, the prognostic value of these mutations remains to be determined. Prognostic biomarkers in DLBCL are urgently needed, since the current clinical parameter-based factors (e.g., International Prognostic Index (IPI)) are insufficient, particularly in identifying patients with poor prognosis who might benefit from alternative treatments. We investigated the prognostic value of somatic mutations in DLBCL in a clinical trial (NCT00544219) patient cohort homogenously treated with six cycles of rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP), followed by two cycles of R (R-CHOP-14). The primary endpoint was event-free survival (EFS) at 2 years. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Targeted high-throughput sequencing (HTS) of tumor genomic DNA was performed on all exons or hotspots of 68 genes frequently mutated in B cell lymphomas. Mutational data was correlated with the endpoints to identify prognostic associations. Targeted HTS detected somatic mutations in 71/76 (93%) of investigated cases. The most frequently mutated genes were KMT2D, SOCS1, GNA13, and B2M. Survival analysis revealed that CREBBP- and EP300-mutated cases had significantly worse OS, PFS, and EFS. In addition, ATM mutations predicted worse outcomes for all three clinical endpoints in germinal center B cell-like DLBCL. In contrast, SOCS1 mutations were associated with better PFS. On multivariable analysis taken into account IPI and failure to achieve complete remission, CREBBP and EP300 mutations remained significant to predict worse OS, PFS, and EFS. Targeted mutation analysis of a uniformly treated prospective clinical trial DLBCL cohort identifies tumor-based genetic prognostic markers that could be useful in the clinical management of such patients. ClinicalTrials.gov NCT00544219.


Appropriate initial antibiotic therapy in hospitalized patients with gram-negative infections: systematic review and meta-analysis.
The rapid global spread of multi-resistant bacteria and loss of antibiotic effectiveness increases the risk of initial inappropriate antibiotic therapy (IAT) and poses a serious threat to patient safety. We conducted a systematic review and meta-analysis of published studies to summarize the effect of appropriate antibiotic therapy (AAT) or IAT against gram-negative bacterial infections in the hospital setting. MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched until May 2014 to identify English-language studies examining use of AAT or IAT in hospitalized patients with Gram-negative pathogens. Outcomes of interest included mortality, clinical cure, cost, and length of stay. Citations and eligible full-text articles were screened in duplicate. Random effect models meta-analysis was used. Fifty-seven studies in 60 publications were eligible. AAT was associated with lower risk of mortality (unadjusted summary odds ratio [OR] 0.38, 95 % confidence interval [CI] 0.30-0.47, 39 studies, 5809 patients) and treatment failure (OR 0.22, 95 % CI 0.14-0.35; 3 studies, 283 patients). Conversely, IAT increased risk of mortality (unadjusted summary OR 2.66, 95 % CI 2.12-3.35; 39 studies, 5809 patients). In meta-analyses of adjusted data, AAT was associated with lower risk of mortality (adjusted summary OR 0.43, 95 % CI 0.23-0.83; 6 studies, 1409 patients). Conversely, IAT increased risk of mortality (adjusted summary OR 3.30, 95 % CI 2.42-4.49; 16 studies, 2493 patients). A limited number of studies suggested higher cost and longer hospital stay with IAT. There was considerable heterogeneity in the definition of AAT or IAT, pathogens studied, and outcomes assessed. Using a large set of studies we found that IAT is associated with a number of serious consequences,including an increased risk of hospital mortality. Infections caused by drug-resistant, Gram-negative organisms represent a considerable financial burden to healthcare systems due to the increased costs associated with the resources required to manage the infection, particularly longer hospital stays. However, there were insufficient data that evaluated AAT for the outcome of costs among patients with nosocomialGram-negative infections. IAT in hospitalized patients with Gram-negative infections is associated with adverse outcomes. Technological advances for rapid diagnostics to facilitate AAT along with antimicrobial stewardship, surveillance, infection control, and prevention is needed.


Environmental differences in substrate mechanics do not affect sprinting performance in sand lizards (Uma scoparia and Callisaurus draconoides).
Running performance depends on a mechanical interaction between the feet of an animal and the substrate. This interaction may differ between two species of sand lizard from the Mojave Desert that have different locomotor morphologies and habitat distributions. Uma scorparia possesses toe fringes and inhabits dunes, whereas the closely related Callisaurus draconoides lacks fringes and is found on dune and wash habitats. The present study evaluated whether these distribution patterns are related to differential locomotor performance on the fine sand of the dunes and the course sand of the wash habitat. We measured the kinematics of sprinting and characterized differences in grain size distribution and surface strength of the soil in both habitats. Although wash sand had a surface strength (15.4±6.2 kPa) that was more than three times that of dune sand (4.7±2.1 kPa), both species ran with similar sprinting performance on the two types of soil. The broadly distributed C. draconoides ran with a slightly (22%) faster maximum speed (2.2±0.2 m s(-1)) than the dune-dwelling U. scorparia (1.8±0.2 m s(-1)) on dune sand, but not on wash sand. Furthermore, there were no significant differences in maximum acceleration or the time to attain maximum speed between species or between substrates. These results suggest that differences in habitat distribution between these species are not related to locomotor performance and that sprinting ability is dominated neither by environmental differences in substrate nor the presence of toe fringes.


Weekend hospitalisations and post-operative complications following urgent surgery for ulcerative colitis and Crohn's disease.
There is increasing complexity in the management of patients with acute severe exacerbation of inflammatory bowel disease [IBD; Crohn's disease (CD), ulcerative colitis (UC)] with frequent requirement for urgent surgery. To determine whether a weekend effect exists for IBD care in the United States. We used data from the Nationwide Inpatient Sample (NIS) 2007, the largest all-payer hospitalisation database in the United States. Discharges with a diagnosis of CD or UC who underwent urgent intestinal surgery within 2 days of hospitalisation were identified using the appropriate ICD-9 codes. The independent effect of admission on a weekend was examined using multivariate logistic regression adjusting for potential confounders. Our study included 7,112 urgent intestinal surgeries in IBD patients, 21% of which occurred following weekend admissions. There was no difference in disease severity between weekend and weekday admissions. Post-operative complications were more common following weekend than weekday hospitalisations in UC [odds ratio (OR) 1.71, 95% confidence interval (CI) 1.01-2.90]. The most common post-operative complication was post-operative infections (Weekend 30% vs. weekday 20%, P = 0.04). The most striking difference between weekend and weekday hospitalisations was noted for needing repeat laparotomy (OR 11.5), mechanical wound complications (OR 10.03) and pulmonary complications (OR 2.22). In contrast, occurrence of any post-operative complication in CD was similar between weekday and weekend admissions. Patients with UC hospitalised on a weekend undergoing urgent surgery within 2 days have an increased risk for post-operative complications, in particular mechanical wound complications, need for repeat laparotomy and post-operative infections.


Ophthalmologic sequelae of thermal burns over ten years at the Alfred Hospital.
To study the ocular outcomes of facial burns over a 10-year period at the Alfred Hospital; in particular, to investigate the impact of 3 variables (grading of burn, use of prophylactic ocular surface lubrication, and timing of ophthalmologic referral) on the requirements for eyelid surgery. A retrospective review of patients admitted to the Alfred Hospital (from October 1990 to October 2000) after thermal burns with facial, eyelid, and ocular involvement. Sixty-six patients were identified with facial burns involving the lids or eyes, having been admitted over a 10-year period. Of these 66, 7 died of complications of the burns and 12 required eye or eyelid surgery. Of those patients treated with prophylactic ocular surface lubrication, the rate of ocular surgery was 18.4% as opposed to 30% when no prophylaxis was used. The higher the percentage of total burn, the later the referral was made. Of those with severe eyelid burns, 100% had eyelid surgery and 50% of moderate burns had eyelid surgery. Sixty percent of moderate eyelid burns that required surgery did not receive prophylaxis. Thirty-four of 66 patients had acute corneal involvement, but only 3 eyes of 118 had long-term corneal morbidity. The requirement for eyelid surgery was closely related to the severity of the eyelid burn. The presence of an acute corneal burn with epithelial loss was not a poor prognosticator. The use of prophylactic ocular surface lubrication may provide early corneal protection, thereby minimizing ulceration in patients who may otherwise have required surgery, especially in those with mild to moderate exposure. Prompt ophthalmologic examination and the early use of prophylactic ocular surface lubrication for the cornea are associated with less need for eyelid surgery in patients with moderate eyelid burns.


Legg-Calvé-Perthes disease: classifications and prognostic factors.
Legg-Calvé-Perthes Disease (LCPD) represents idiopathic avascular necrosis of femoral head in pediatric population. Indications for treatment depend mostly on prognosis about femoral head sphericity and hip congruence at the end of growth. The aim of this review is to highline prognostic factors of LCPD. Bibliographic search in PubMed allowed selection of 33 articles concerning prognostic factors and/or classification of LCPD. Clinical factors of poor prognosis are overweight, female sex, age exceeding 6 years old, and lack of hip abduction. Radiologically, Herring's classification is consensual because of its high prognostic value and very good reproducibility. The other signs of femoral head "at-risk" and the assessment of the reduction in abduction of the femoral head in the acetabulum are also prognostic of late evolution. MRI seems to be a future tool in assessing the fate of hips in LCPD. It is likely that a better understanding of LCPD etiology would precise the prognosis of this disease.


The osteopontin gene +1239A/C single nucleotide polymorphism is associated with type 1 diabetes mellitus in the Italian population.
Secreted phosphoprotein 1, also known as Osteopontin (Opn), is a proinflammatory cytokine involved in the TH1 response and is highly expressed in the islets and pancreatic lymph nodes of non-obese diabetic mice before the onset of diabetes. In humans, typing of the +1239A/C single nucleotide polymorphism (SNP) in the 3UTR of the Opn gene (SPP1) showed that +1239C carriers displayed higher Opn serum levels than +1239A homozygotes and a higher risk of developing autoimmune/lymphoproliferative syndrome, multiple sclerosis, and systemic lupus erythematosus. The aim of this work is to evaluate whether +1239A/C is also associated with type 1 diabetes mellitus (T1DM). We typed +1239A/C in an initial cohort of 184 T1DM patients and 361 controls, and confirmed our data in a second cohort of 513 patients and 857 controls. In both cohorts, +1239C carriers displayed a significantly higher risk of T1DM than +1239A homozygotes (combined cohorts: OR=1.63, 95 percent CI: 1.34-1.97). Clinical analysis did not detect any differences between patients carrying or not +1239C in terms of gender distribution and age at T1DM diagnosis. These data suggest that SPP1 variants marked by +1239C are associated with T1DM development in the Italian population. The predisposing effect may depend on its effect on Opn levels.


Organizational facilitators and barriers for participation in workplace health promotion in healthcare: A qualitative interview study among nurses.
There is evidence for the positive effects of workplace health promotion (WHP) for nurses. Although this highly stressed target group also actively desires WHP, the number of participants is low. Individual reasons play a role in the decision to engage in WHP activities, yet it is interesting to consider which organizational factors a company could address to improve participation. In this regard, the question arises of what organizational factors facilitate participation in WHP activities from the perspective of nurses in inpatient care facility (ICF), outpatient care service (OCS), and acute care hospitals (ACH). Sixteen semi-structured interviews were conducted in different care settings between May and September 2021. Questions about everyday working life, WHP activities, and organizational framework conditions were asked. The results show that there is a wide range of influencing factors at the organizational level, some overall settings, and others setting-specific. High workload and the fit of WHP activities with shift times were particularly inhibiting overall settings. A negative association with the employer worked as a barrier in ICF and ACH. When implementing WHP activities, it can be useful to consider organizational facilitators and barriers to promote sustainable and attractive WHP activities and higher participation rates in the different settings of nursing.


Lesions of the basal amygdala block expression of conditioned fear but not extinction.
Although the role of the amygdala in acquisition of conditioned fear is well established, there is debate concerning the intra-amygdala circuits involved. The lateral nucleus of the amygdala (LA) is thought to be an essential site of plasticity in fear conditioning. The LA has both direct and indirect [via the basal nuclei; basal amygdala (BA)] projections to the central nucleus (Ce) of the amygdala, an essential output for fear behaviors. Lesions of the LA or Ce prevent acquisition of conditioned freezing to a conditioned stimulus, but BA lesions do not, suggesting that the BA is not normally involved in fear conditioning. If true, posttraining BA lesions should also have no effect. Replicating previous studies, we found that rats given electrolytic BA lesions before training acquired conditioned fear normally. They also showed normal long-term retention and extinction of conditioned fear. Unexpectedly, BA lesions made after training completely blocked expression of conditioned fear. Despite this deficit, lesioned rats were able to learn a new tone-shock association. Thus, although the LA-Ce system is sufficient for fear acquisition in the absence of the BA, it is not sufficient when the BA is present, suggesting that the BA is an important site of plasticity in fear conditioning. The pattern of lesion deficits we observed (after but not before training) might be explained by homeostatic mechanisms that balance plasticity over multiple inputs, regulating the influence of the BA and LA onto Ce output neurons.


The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells.
MicroRNAs (miRNAs) are short (21-23nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors. Here we show that the two RNA-binding proteins, p72 and KHSRP, both with known roles in promoting miRNA biogenesis, regulate the protein level of human Ago2 in transformed human cells. We determined that p72 and KHSRP influence Ago2 stability by regulating miRNA levels in the cell and that loss of p72/KHSRP results in a decrease of unloaded Ago2.


Time-frequency analysis of the surface EMG during maximum height jumps under altered-G conditions.
Surface electromyographic (SEMG) signals are often used to study motor control during human movement. Typically, the SEMG signal is used to determine when the muscle was on or off during the movement. However, determining the time-based frequency content of the SEMG signal in conjunction with the time-history of the movement may provide us with more insight into how the motion is organized. We collected SEMG from 4 muscles, (soleus, vasti, gluteus maximus, hamstrings) while subjects performed jumping and sit-to-stand tasks under altered g-environments. The experiment was performed on the Dynamic Environmental Simulator at Wright Patterson AFB, OH. The subjects performed the tasks at 1.0, 1.2, 1.4, 1.6, and 1.8 g. The SEMG signals were then analyzed using a continuous discrete wavelet transform based on a 4-coefficient Daubechie wavelet. Our initial results show that although the time-history of muscle activation patterns during movements do not always vary significantly at different g levels, the frequency content does change, with more high frequency activation at low g levels, and more low frequency activation at higher g levels. One possible explanation for the difference in frequency activation is fatigue of fast twitch fibers during the experiment. These differences were not apparent from the time-history activation patterns, and are difficult to interpret from standard FFT manipulations.


Sleep abnormalities in patients with brain stem lesions.
Seven patients with "locked-in" syndrome were studied by prolonged polygraphic recordings. Severe alterations in the sleep pattern were observed in five patients who had bilateral extensive pontine lesions resulting in tetraplegia, facial and pseudobulbar paralysis, and absence of conjugate horizontal gaze. Rapid eye movement (REM) sleep was entirely absent while non-rapid eye movement (NREM) sleep was absent, reduced, or altered. The remaining two patients, both of whom had relative sparing of horizontal gaze and apparently either no or minimal pontine tegmental involvement, showed both REM and NREM sleep with only a minimal alteration in the sleep pattern. The study suggests that, in human beings as in animals, pontine structures near the midline are essential for control of sleep states.


Long-term results of extracorporeal shockwave therapy and core decompression in osteonecrosis of the femoral head with eight- to nine-year follow-up.
This study analyzed the long-term outcomes of extracorporeal shockwave therapy (ESWT) and core decompression for early osteonecrosis of the femoral head (ONFH) with 8- to 9-year follow-up. The study cohort consisted of 48 patients with 57 hips including 23 patients with 29 hips in the ESWT group and 25 patients with 28 hips in the surgical group. Patients in ESWT group received shockwave therapy to the affected hip. Patients in surgical group underwent core decompression and autogenous cancellous bone and allogenous fibular graft. The average length of follow-up was 103.5 ± 3.4 (ranged 93-106) months and 104.5 ± 4.3 (ranged 95-108) months for the ESWT and the surgical group, respectively. The evaluations included clinical assessment for pain and function, X-ray and MRI of the affected hips. The overall clinical results were 76% good or fair and 24% poor for the ESWT group; and 21% good or fair and 79% poor for the surgical group. THA was performed in 3% and 21% at one year, 10% and 32% at 2 years and 24% and 64% at 8-9 years for ESWT and the surgical group respectively. Significant differences in pain and Harris hip scores were observed at different time intervals favoring the ESWT group. There was a trend of decrease in the size of the lesion in the ESWT group when compared with the surgical group. ESWT appears to be more effective than core decompression and bone grafting for early ONFH with 8- to 9-year long-term follow-up.


[Successful surgical treatment of an extrasinusal dural arteriovenous fistula located in the lateral wall of the cavernous sinus: a case report].
We report the successful surgical treatment of a dural arteriovenous fistula(AVF)located in the lateral wall of the cavernous sinus. A 44-year-old woman presented with facial numbness in the left V3 area. Magnetic resonance imaging showed a flow void sign around the sphenoid ridge on a T2-weighted image. Digital subtraction angiography(DSA)demonstrated a dural AVF that was supplied by feeding arteries from the C4 portion of the left internal carotid artery. Without sinus enhancement, the draining vein flowed directly through the superficial sylvian vein into the vein of Labbé. Following treatment of the dural AVF located in the anterior cranial fossa, we ligated the draining vein at the penetrating point in the intradural region using surgical management. Intraoperative findings showed that the shunt point was located in the left lateral wall of the cavernous sinus. The postoperative course was uneventful and DSA showed no evidence of the AVF. The patient was discharged with no neurological deficits. Few studies have reported the use of direct surgery alone for the treatment of dural AVFs located in the cavernous sinus with a perfusion pattern as in this case.


Ruthenium-Catalyzed Enantioselective Hydrogenation of Phenanthridine Derivatives.
The first asymmetric hydrogenation of phenanthridines catalyzed by chiral cationic ruthenium diamine complexes has been developed with up to 92% ee and full conversions. The choice of the counteranion of the catalyst was found to be critical for achieving high enantioselectivity. In addition, the obtained 5,6-dihydrophenanthridine could be used as a chiral hydride donor for organocatalytic asymmetric transfer hydrogenation.


Advances in venous surgery: SEPS and phlebectomy for chronic venous insufficiency.
Chronic venous insufficiency (CVI) and its complications of chronic pain, intractable ulceration, and infection are important conditions to treat by modern surgical techniques. As early as the 1930s, perforating veins with outward flow were implicated in the pathogenesis of this condition. Recognition that such outward flow promotes leukocyte adhesion and activation as the principal microcirculatory cause for the cutaneous changes has explained the importance of perforating vein interruption? Because of disability of CVI, surgeons and patients reluctantly tolerated the open Linton perforator interruption operation with its morbid knee-to-ankle incisions. It was tolerated because it worked. Modifications to reduce the morbidity of the procedure eliminated two of the three incisions used in the explorations of the 1930s. Other modifications such as DePalma's modification of the incisions further reduced wound complications. However, the most significant surgical alteration was to utilize the endoscopic techniques introduced in Europe by Fischer and Hauer. Very quickly it was obvious that the endoscopic technique minimized postoperative complications. Application of endoscopic perforator interruption to varicose vein surgery validated the safety of the procedure but did not contribute to knowledge about treating CVI.


Cationic RAFT polymerization using ppm concentrations of organic acid.
A metal-free, cationic, reversible addition-fragmentation chain-transfer (RAFT) polymerization was proposed and realized. A series of thiocarbonylthio compounds were used in the presence of a small amount of triflic acid for isobutyl vinyl ether to give polymers with controlled molecular weight of up to 1×10(5) and narrow molecular-weight distributions (Mw /Mn <1.1). This "living" or controlled cationic polymerization is applicable to various electron-rich monomers including vinyl ethers, p-methoxystyrene, and even p-hydroxystyrene that possesses an unprotected phenol group. A transformation from cationic to radical RAFT polymerization enables the synthesis of block copolymers between cationically and radically polymerizable monomers, such as vinyl ether and vinyl acetate or methyl acrylate.


Characterization of Mood Instability through Bipolar Disorders: A cluster-analytic approach using weekly prospective life-chart methodology.
BackgroundThe aim of this study was to characterize mood instability (MI) in Bipolar Disorder (BD) and to investigate potential differences between subtype I and II. MethodsLife-charts from weekly mood ratings of 90 patients were used to compute: weeks spent with symptoms, number of episodes, and MI. Regression analyses were conducted to assess the relationship between BD subtype and MI adjusting by all potential confounding factors. Hierarchical cluster analysis was performed to determine the appropriate number of clusters that described the data and to assign subjects to a specific cluster based on their MI. We then compared clusters on clinical and psychosocial outcomes. ResultsMedian follow-up was 5 years (IQR: 3.6-7.9). Patients spent 15.2%, 5%, and 3% of follow-up with depressive, manic, and mixed symptoms, respectively. BD type II presented higher MI (β = 1.83, 95% CI: 0.66-3.00) and subsydromal symptoms than BD type I patients. No differences in functioning or recurrences were found between subtypes. Differences in MI between the two clusters mimicked those between type I and II but enhanced (β = 3.86, 95%CI -4.72, -2.66). High MI (n = 43) patients presented poorer functioning and higher recurrences compared to Low MI patients (n = 43). ConclusionBD type II presented higher MI and subsyndromal symptoms than BD type I patients. However, these differences did not translate into clinically relevant outcomes. A classification based on MI may provide useful clinical insights.


Synthesis, Properties, and Semiconducting Characteristics of BF2 Complexes of β,β-Bisphenanthrene-Fused Azadipyrromethenes.
Three novel π-extended BF2 complexes of β,β-bisphenanthrene-fused azadipyrromethenes containing nine fused rings have been synthesized on the basis of a tandem Suzuki coupling reaction on readily available 2,6-dibromoazaBODIPYs followed by an intramolecular oxidative aromatic coupling mediated by iron(III) chloride. These resultant BF2 complexes exhibit strong absorption (extinction coefficients up to 2.4 × 105 M-1 cm-1) and emission in the near-infrared (NIR) range (790-816 nm) with excellent photo and thermal stabilities. The hole mobility of the thin-film field-effect transistors of these dyes fabricated by a solution process reaches up to 0.018 cm2 V-1 s-1.