Misophonia in Children with Tic Disorders: A Case Series.
Misophonia is a condition characterized by the dislike or hatred (miso) of specific sounds (phonia) that results in an extreme emotional response. There has been growing interest in misophonia, with emerging evidence from neurodevelopmental populations and ongoing debate regarding the psychiatric classification and the mechanisms underlying this phenomenon. This is the first article to report on misophonic experiences and associated clinical characteristics in young people with tic disorders. In this article, we present the cases of 12 children and young people with tic disorders who have attended clinics in the United Kingdom and Italy who report misophonia. Misophonia was classified as a selective aversive response in accordance with the criteria proposed by Schröder. These cases support the view that a range of auditory stimuli may lead to negative/aversive emotional responses of varying degrees, with misophonia seeming to contribute to behavioral reactions. Among these, the most frequent was anger outbursts, followed by an increase in tics, trigger avoidance, repetition of the sound, and self-injurious behavior. No single treatment approach was effective, with some patients responding to cognitive behavioral therapies and others to pharmacological support. We postulate that misophonia could be an underestimated causative phenomenon for abrupt emotional dysregulation in individuals with tic disorders and should be considered as part of a comprehensive clinical assessment. This article presents findings of relevance to general discussions regarding the classification of misophonia, as well as the potential relationship between sensory abnormalities and the broader phenotype of tic disorders during development.


Big growth hormone (GH): conversion to small GH without peptide bond cleavage.
Mercaptoethanol treatment of big growth hormone (GH) obtained from human pituitary resulted in a 60% conversion to small GH. Further dissociation was obtained by combined treatment with the reducing agent plus urea. The results indicate that the existence of big GH is dependent upon the formation of inter-polypeptide chain disulfide bonds.


Reliability of the NEO Five Factor Inventory short form for assessing personality after stroke.
It is well recognized that an individual's personality characteristics influence their psychological adjustment after stroke. However, there is a lack of research on the reliability of personality inventories for stroke. This study primarily aimed to evaluate the reliability of the Neuroticism, Extroversion, Openness to Experience (NEO)-Five Factor Inventory (NEO-FFI) for assessing pre-morbid personality and personality changes after stroke. Further aims were to investigate changes in personality during the hospital-to-home transition period and examine associations between personality and mood. Forty participants with stroke (52.5% male, M age=65.55 years) were recruited at time of hospital discharge and completed the NEO-FFI, Centre for Epidemiologic Studies - Depression and Geriatric Anxiety Inventory. Significant others completed an informant version of the NEO-FFI. Stroke participants were re-assessed on the NEO-FFI at 1-month and 4-months post-discharge. Forty matched controls also completed the NEO-FFI. Internal consistency was adequate for the NEO-FFI (α=0.57-0.86), although low for agreeableness. There was fair to excellent concordance between self-rated and informant versions of the NEO-FFI (ICC=0.58-0.78). Significant positive associations were found between neuroticism and mood (r=0.50-0.68), and significant negative associations were found between extraversion and mood (r=-0.33-0.36) and agreeableness and anxiety (r=-0.43). Self-ratings of stroke participants on the NEO-FFI at discharge did not significantly differ from matched controls. Extraversion levels significantly decreased, and agreeableness levels significantly increased between discharge and 1- and 4-months post-discharge. Overall, the results support the reliability of the NEO-FFI for assessing personality characteristics in the context of stroke.


Surviving the Lunacy Act of 1890: English Psychiatrists and Professional Development during the Early Twentieth Century.
In recent decades, historians of English psychiatry have shifted their major concerns away from asylums and psychiatrists in the nineteenth century. This is also seen in the studies of twentieth-century psychiatry where historians have debated the rise of psychology, eugenics and community care. This shift in interest, however, does not indicate that English psychiatrists became passive and unimportant actors in the last century. In fact, they promoted Lunacy Law reform for a less asylum-dependent mode of psychiatry, with a strong emphasis on professional development. This paper illustrates the historical dynamics around the professional development of English psychiatry by employing Andrew Abbott's concept of professional development. Abbott redefines professional development as arising from both abstraction of professional knowledge and competition regarding professional jurisdiction. A profession, he suggests, develops through continuous re-formation of its occupational structure, mode of practice and political language in competing with other professional and non-professional forces. In early twentieth-century England, psychiatrists promoted professional development by framing political discourse, conducting a daily trade and promoting new legislation to defend their professional jurisdiction. This professional development story began with the Lunacy Act of 1890, which caused a professional crisis in psychiatry and led to inter-professional competition with non-psychiatric medical service providers. To this end, psychiatrists devised a new political rhetoric, 'early treatment of mental disorder', in their professional interests and succeeded in enacting the Mental Treatment Act of 1930, which re-instated psychiatrists as masters of English psychiatry.


Virtual endoscopic images by 3D FASE cisternography for neurovascular compression.
Three-dimensional fast asymmetric spin echo (3D FASE) cisternography provides high spatial resolution and excellent contrast as a water image acquisition technique. It is also useful for the evaluation of various anatomical regions. This study investigated the usefulness and limitations of virtual endoscopic images obtained by 3D FASE MR cisternography in the preoperative evaluation of patients with neurovascular compression. The study included 12 patients with neurovascular compression: 10 with hemifacial spasm and two with trigeminal neuralgia. The diagnosis was surgically confirmed in all patients. The virtual endoscopic images obtained were judged to be of acceptable quality for interpretation in all cases. The areas of compression identified in preoperative diagnosis with virtual endoscopic images showed good agreement with those observed from surgery, except in one case in which the common trunk of the anterior inferior cerebellar artery and posterior inferior cerebellar artery (AICA-PICA) bifurcated near the root exit zone of the facial nerve. The veins are displayed in some cases but not in others. The main advantage of generating virtual endoscopic images is that such images can be used for surgical simulation, allowing the neurosurgeon to perform surgical procedures with greater confidence.


The effectiveness of inpatient case management. Fact or fiction?
Production processes and service delivery in acute care hospitals can be fragmented. Inpatient case management has the potential to improve both processes and outcomes of hospital care. The author reports on 18 research studies that used inpatient case management as the treatment variable. These outcome studies, using case management, did not provide the evidence needed to address deficiencies in inpatient settings. However, these studies do provide clear direction for nurse administrators and nurse researchers to take concerning the next steps needed to address this critical issue.


The prevalence of Trichinella spiralis in foxes (Vulpes vulpes) and other game species in Denmark.
A survey of the rate of infection with Trichinella spiralis among game animals in Denmark is given with special regard to foxes. A total of 5084 foxes and 293 mustelidae were examined, most of them by a combined digestion and Baermann technique. Deep-frozen samples were examined by a method including digestion, filtration, and sedimentation. Four foxes were found infected (cf. Fig. 1). Three of them were shot inside or just outside a fenced area within which wild boars had previously been found infected. It is concluded that Trichinella infection in Danish free-living carnivores is very rare and that the prevalence in foxes is low compared to most European countries.


Comparison of cardiac and 60 Hz magnetically induced electric fields measured in anesthetized rats.
Extremely low frequency magnetic fields interact with an animal by inducing internal electric fields, which are in addition to the normal endogenous fields present in living animals. Male rats weighing about 560 g each were anesthetized with ketamine and xylazine. Small incisions were made in the ventral body wall at the chest and upper abdomen to position a miniature probe for measuring internal electric fields. The calibration constant for the probe size was 5.7 mm, with a flat response from at least 12 Hz to 20 kHz. A cardiac signal, similar to the normal electrocardiogram with a heart rate of about 250 bpm, was readily obtained at the chest. Upon analysis of its spectrum, the cardiac field detected by the probe had a broad maximum at 32-95 Hz. When the rats were exposed to a 1 mT, 60 Hz magnetic field, a spike appeared in the spectrum at 60 Hz. The peak-to-peak magnitudes of electric fields associated with normal heart function were comparable to fields induced by a 1 mT magnetic field at 60 Hz for those positions measured on the body surface (where induced fields were maximal). Within the body, or in different directions relative to the applied field, the induced fields were reduced (reaching zero at the center of the animal). The cardiac field increased near the heart, becoming much larger than the induced field. Thus, the cardiac electric field, together with the other endogenous fields, combine with induced electric fields and help to provide reference levels for the induced-field dosimetry of ELF magnetic field exposures of living animals.


Cost-effectiveness of photodynamic therapy for high-grade dysplasia in Barrett's esophagus.
Photodynamic therapy appears to be effective in ablating high-grade dysplasia in Barrett's esophagus. Our aim was to identify the most effective and cost-effective strategy for managing high-grade dysplasia in Barrett's esophagus without associated endoscopically visible abnormalities. By using decision analysis, the lifetime costs and benefits of 4 strategies for which long-term data exist were estimated by us: esophagectomy, endoscopic surveillance, photodynamic therapy, followed by esophagectomy for residual high-grade dysplasia; and photodynamic therapy followed by endoscopic surveillance for residual high-grade dysplasia. It was assumed by us that there was a 30% prevalence of cancer in high-grade dysplasia patients and a 77% efficacy of photodynamic therapy for high-grade dysplasia and early cancer. Esophagectomy cost 24,045 dollars, with life expectancy of 11.82 quality-adjusted life years. In comparison, photodynamic therapy followed by surveillance for residual high-grade dysplasia was the most effective strategy, with a quality-adjusted life expectancy of 12.31 quality-adjusted life years, but it also incurred the greatest lifetime cost (47,310 dollars) for an incremental cost-effectiveness of 47,410 dollars/quality-adjusted life years. The results were sensitive to post-surgical quality of life and survival, and to cancer prevalence if photodynamic therapy efficacy for cancer was less than 50%. Photodynamic therapy followed by endoscopic surveillance for residual high-grade dysplasia appears to be cost effective compared with esophagectomy for patients diagnosed with high-grade dysplasia in Barrett's esophagus. Clinical trials directly comparing these strategies are warranted.


Convenient one-pot synthesis of multisubstituted tetrahydropyrimidines via catalyst-free multicomponent reactions.
A novel and convenient one-pot synthesis of multisubstituted pyrimidine analogues via multicomponent reactions is disclosed. This catalyst-free domino reaction proceeded smoothly in good to excellent yields and offered several other advantages including short reaction time, a simple experimental workup procedure, and no toxic byproduct. In addition, the obtained products in our experiments are interesting nitrogen heterocyclic molecules containing alpha- and beta-amino acid blocks.


Mortality in the Emergency Department and the Effectiveness of Conventional Safety Event Reporting.
Background Patient mortality reviews identify care, system, and process deficiencies. Patient deaths undergo quarterly review in our academic emergency department (ED), whereas in other departments, mortality reviews are requested by the pronouncing physician within 24 hours. In the ED, individual physicians encounter barriers to 24-hour reviews, including feasibility, the perception of futility, re-exposure to traumatic events, and a high frequency of pre-hospital and non-preventable deaths. This quality review aimed to determine the preventable death rate, contributing factors to ED patient mortality, cases requiring further review, and the capture rate of individual case submissions into the patient safety reporting system. Methods A retrospective chart review was performed on all patient deaths occurring in our ED from July 2019 to February 2020. All patients 18 years or older who were pronounced dead in the ED during our data collection period were included. Patients declared deceased pre-hospital, on an inpatient floor, or in the operating room were excluded. Deaths were assessed for characteristics such as sex, presence of a pulse upon arrival, diagnostics and interventions performed, and whether the cause of death was traumatic or medical. Deaths were categorized on a 5-point Likert scale ranging from "not preventable" to "likely preventable." The presence or absence of contributing factors and the need for further review were recorded. Results Of the 166 reviewed cases, 87% (n=144) were non-preventable due to a terminal condition upon arrival, 12% (n=20) were non-preventable despite maximal efforts, 0.6% (n=1) were non-preventable despite a medical or systems error, and 0.6% (n=1) were possibly preventable due to a medical or systems error. No cases were definitively preventable. Only 1.2% (n=2) of cases required further safety review. In 55% (n=91) of cases, the patient arrived without a pulse. Medical deaths (60%, n=100) outnumbered traumatic deaths (39%, n=64). The most utilized diagnostic test was ultrasound (67%, n=111), and the most utilized intervention was advanced cardiac life support (59%, n=98). Conclusion There is a high prevalence of unpreventable deaths in the ED (99%, n=164). Only two cases (1.2%) were identified for further patient safety review. Standard safety event reporting practices correctly identified all possibly preventable ED deaths.


National and international guidelines for the diagnosis and treatment of asthma.
Excellent guidelines on the management of asthma are now available. The most comprehensive guidelines developed recently are the National Heart, Lung, and Blood Institute (NHLBI) Guidelines for the Diagnosis and Management of Asthma, the NHLBI/World Health Organization Global Initiative for Asthma, and the American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology Practice Parameters for the Diagnosis and Treatment of Asthma. The main purpose of such guidelines is to improve the quality of care for patients with asthma. This can only be accomplished, however, if these documents are used effectively.


Effect of MTA and Portland Cement on Fracture Resistance of Dentin.
Background and aims. It is important to evaluate the effects of endodontic materials on tooth structures to avoid endodontic treatment failure. The aim of the present study was to investigate the effect of mineral trioxide aggregates (MTA) and Portland cement (PC) on fracture resistance of dentin. Materials and methods. Thirty-six freshly extracted human single-rooted premolar teeth were selected. The crowns were removed and the roots were randomly divided into two experimental groups and one control group. The root samples were longitudinally divided into two halves and a dentin bar (2×2×10 mm) was cut from each root section for short-term (2weeks) and long-term (12 weeks) evaluations. The root sections in the experimental groups were exposed to MTA or PC, while keeping the control group specimens in physiologic saline. The fracture resistance of each specimen was measured using an Instron testing machine. The results were statistically analyzed using ANOVA, a post hoc Tukey test and paired t-test at 5% significance level. Results. The fracture resistance of MTA-treated specimens significantly increased between 2 and 12 weeks (P<0.05). After 12 weeks, MTA-treated specimens had the highest fracture resistance. In the PC group, the fracture resistance of specimens did not change significantly over time (P>0.05). Conclusion. The results showed that MTA increased the fracture resistance of root dentin, while PC had no significant effect on dentin fracture resistance.


Comparison of Diagnostic Methods and Sampling Sites for the Detection of Demodex musculi.
Demodex mites are microscopic, cigar-shaped, follicular mites often regarded as commensal microfauna in mammals. Although Demodex spp. can cause dermatologic disease in any immunocompromised mammal, they are rarely reported in laboratory mice. Recent identification of Demodex musculi in a colony of immunodeficient mice with dermatitis afforded us the opportunity to investigate the comparative sensitivity of 4 antemortem diagnostic techniques to detect D. musculi-superficial skin scrape (SSS), tape impression (TI), fur pluck (FP), and deep skin scrape (DSS)-which we performed on 4 anatomic sites (face, interscapular region [IS], caudal ventrum [CV], and caudal dorsum [CD]) in 46 mice. DSS had an overall detection rate of 91.1% (n = 112 tests), with the highest detection rates in IS (93.5%), CV (89.1%), and CD (90.0%). The detection rates for SSS (62.5%; n = 112 tests), TI (57.5%; n = 138 tests), and FP (62.7%; n = 158 tests) were all lower than for DSS. IS was the most reliable site. Results from combined FP and DSS samples collected from IS and CV yielded 100% detection, whereas the face was not a desirable sampling site due to inadequate sample quality and low detection rate. Demodex eggs and larvae were observed from FP more often than DSS (19.0% of 158 tests compared with 14.3% of 112 tests). In a subset of samples, an 18S rRNA PCR assay was equivalent to DSS for detection of mites (both 100%, n = 8). We recommend collecting samples from both IS and CV by both FP and DSS to assess for the presence of D. musculi and performing further studies to assess whether PCR analysis can be used as a diagnostic tool for the detection of Demodex mites in laboratory mice.


Risk Factors for Motorcycle-related Severe Injuries in a Medium-sized City in China.
Motorcycle vehicles are frequent in China, especially in the small and medium sized cities. Road traffic collisions involving motorcycles often result in severe injuries. We aimed to identify risk factors for severe injuries in inpatients sustaining motorcycle collisions. Patients with road traffic injuries involving motorcycles who presented to the neurosurgery and orthopedic departments of three major comprehensive hospitals in Shantou city were reviewed from October 2012 to June 2013. Data from 349 patients was investigated. Crash and injury characteristics were documented by interviewing patients, their family members, and their doctors. Binary logistic regression was used to determine risk factors for severe injuries. There were 253 males (72.49%) and 96 females (27.51%), with a male to female ratio of 2.64:1. The mean age was 38.21±17.32 years. One-hundred and fifty patients were in the severe injury group with a mean injury severity score (ISS) of 15.34±9.13. The simple and multiple logistic model showed that males, lack of safeguards, morning and night hours, non-urban areas, collision of a motorcycle with a cycle, ambulance transportation to hospital, admission to a neurosurgery department, lack of traffic control, unobstructed traffic, and poor visibility were all the risk factors. This research highlights some problems: less helmet wearing in motorcyclists and cyclists, rural injuries being more serious than urban ones, and head injuries being the main diagnosis in severe injuries. The result of this research is predictable. If the safety equipment is required to be used, such as helmets, and the traffic environment is improved, such as traffic flow, medical resources to injuries and deaths is seasonable, then traffic safety will be improved and accidents will be reduced.


Early resolution of increased nuchal translucency in a fetus with trisomy 18.
The normal timing for first-trimester nuchal translucency screening of aneuploidies is 10 to 14 weeks' gestation. We describe a fetus with trisomy 18 that presented at 11 weeks with increased nuchal thickness. Reevaluation at 12 and 13 weeks showed early return to normal of the increased nuchal measurement.


Instrumental factors in infrared microspectroscopy.
Instrumentation is the cornerstone of infrared microspectrometry (IMS) technology and the foundation for all applications. The fundamental factors in IMS systems are presented from the perspective of an instrument developer. While the current state of instrument development is presented, speculation of future development is also included. The goal of IMS instrumentation is to produce the highest signal-to-noise ratio (SNR) spectrum with the highest spectral resolution from the smallest sample area. Detector response, spectrometer efficiency, source brightness, wavelength range, microscope optics and sample definition are factors limiting IMS instrument performance. The current performance and future trends in IMS instrumentation are presented in this work.


Comparative analysis of the intestinal flora in type 2 diabetes and nondiabetic mice.
A relationship between type 2 diabetes mellitus (T2DM) and intestinal flora has been suggested since development of analysis technology for intestinal flora. An animal model of T2DM is important for investigation of T2DM. Although there are some animal models of T2DM, a comparison of the intestinal flora of healthy animals with that of T2DM animals has not yet been reported. The intestinal flora of Tsumura Suzuki Obese Diabetes (TSOD) mice was compared with that of Tsumura, Suzuki, Non Obesity (TSNO) mice in the present study. The TSOD mice showed typical type 2 diabetes symptoms, which were high-fat diet-independent. The TSOD and the TSNO mouse models were derived from the same strain, ddY. In this study, we compared the intestinal flora of TSOD mice with that if TSNO mice at 5 and 12 weeks of age. We determined that that the number of operational taxonomic units (OTUs) was significantly higher in the cecum of TSOD mice than in that of TSNO mice. The intestinal flora of the cecum and that of the feces were similar between the TSNO and the TSOD strains. The dominant bacteria in the cecum and feces were of the phyla Firmicutes and Bacteroidetes. However, the content of some bacterial species varied between the two strains. The percentage of Lactobacillus spp. within the general intestinal flora was higher in TSOD mice than in TSNO mice. In contrast, the percentages of order Bacteroidales and family Lachnospiraceae were higher in TSNO mice than in TSOD mice. Some species were observed only in TSOD mice, such as genera Turicibacter and SMB53 (family Clostridiaceae), the percentage of which were 3.8% and 2.0%, respectively. Although further analysis of the metabolism of the individual bacteria in the intestinal flora is essential, genera Turicibacter and SMB53 may be important for the abnormal metabolism of type 2 diabetes.


Widespread geographic distribution of oral Candida dubliniensis strains in human immunodeficiency virus-infected individuals.
Candida dubliniensis is a recently identified chlamydospore-positive yeast species associated with oral candidiasis in human immunodeficiency virus (HIV)-infected (HIV+) patients and is closely related to Candida albicans. Several recent reports have described atypical oral Candida isolates with phenotypic and genetic properties similar to those of C. dubliniensis. In this study 10 atypical chlamydospore-positive oral isolates from HIV+ patients in Switzerland, the United Kingdom, and Argentina and 1 isolate from an HIV-negative Irish subject were compared to reference strains of C. albicans and Candida stellatoidea and reference strains of C. dubliniensis recovered from Irish and Australian HIV+ individuals. All 11 isolates were phenotypically and genetically similar to and phylogenetically identical to C. dubliniensis. These findings demonstrate that the geographical distribution of C. dubliniensis is widespread, and it is likely that it is a significant constituent of the normal oral flora with the potential to cause oral candidiasis, particularly in immunocompromised patients.


Annual report: Surveillance of adverse events following immunisation in Australia, 2011.
This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) reported to the Therapeutic Goods Administration (TGA) for 2011, and describes reporting trends over the 12-year period 2000 to 2011. There were 2,327 AEFI records for vaccines administered in 2011, a decrease of 40% from 3,894 in 2010. The decrease in 2011 was attributable to a decline in reporting following seasonal influenza (2,354 to 483) and pandemic H1N1 (pH1N1) influenza vaccines (514 to 2). However, reporting rates for some other vaccines were higher in 2011 compared with 2010. The 13-valent pneumococcal conjugate vaccine (13vPCV) replaced the 7-valent pneumococcal conjugate vaccine (7vPCV) and was suspected of involvement in 236 AEFI cases (48 per 100,000 doses). An increase in the number of reports following rotavirus (from 40 to 56 per 100,000 doses), and the hexavalent infant vaccine (from 27 to 40 per 100,000 doses), may have been due at least in part to co-administration with 13vPCV. Reports following DTPa-IPV also increased (from 94 to 139 per 100,000 doses), continuing a trend since 2009. AEFI reports following receipt of the 23-valent pneumococcal vaccine also increased markedly in those aged ≥65 years, from 155 to 288 records. In response to the increase in reports following 23vPPV, boosters are no longer recommended for those without medical risk factors. The most commonly reported reactions were injection site reactions, fever, allergic reactions and malaise. Only 7% of all the reported adverse events were categorised as serious, as per the database definitions, although some events classified as non-serious may have caused severe illness. Three deaths were temporally associated with vaccination; however, all were attributed to causes other than vaccination. The increase in 2011 was predominately due to reports of injection site reactions (49% increase in 2011). Increases in some instances may also be partly attributable to an increasing propensity to report AEFI.


[Study on quantification method of non-starch polysaccharides in Dendrobium catenatum].
The non-starch polysaccharides,mainly composed of glucomannans,are the major bioactive compounds in Dendrobium catenatum. In order to evaluate the quality of the medicinal materials and guide the production and processing,a quantification method of non-starch polysaccharides was established by stems of D. catenatum C15 strain collected from the pear epiphytic cultivation. The non-starch polysaccharides were obtained by " water extraction,α-amylase pretreatment,and alcohol precipitation once" method. The contents of starches,non-starch polysaccharides and monosaccharides were analyzed. In addition,the system suitability was tested. Compared with method of the Chinese Pharmacopoeia( 2015 edition),the contents of total polysaccharides,glucose,and mannose were decreased by 20. 9%,58. 8% and 1. 6% respectively. The method effectively digested starch and retained non-starch polysaccharides,and the analysis result was accurate and repeatable. Therefore,it is suitable for the content measurement of non-starch polysaccharides of D. catenatum. Furthermore,it could be an alternative method for quality control of D. catenatum and a reference in the determination of non-starch polysaccharides in other starch-containing medicinal materials.


Diode Laser Excision of Blandin-Nuhn Mucocele.
The glands of Blandin and Nuhn are mixed mucous and serous glands that are embedded within the musculature of the anterior tongue ventrum. The differential diagnosis for lesions in that area is often challenging and includes other salivary and nonsalivary lesions. This affects decision-making, surgical management, and measures to prevent complications. Unlike conventional cold blade surgery, diode laser use may simplify such treatment.


Differential cholesterol uptake in liver cells: A role for PCSK9.
The clearance of low-density lipoprotein (LDL) particles from the circulation is regulated by the LDL receptor (LDLR) and proprotein convertase subtilisin/kexin 9 (PCSK9) interaction. Its disruption reduces blood cholesterol levels and delays atherosclerosis progression. Whether other members of the LDLR superfamily are in vivo targets of PCSK9 has been poorly explored. The aim of this work was to study the interaction between PCSK9 and members of the LDLR superfamily in the regulation of liver cholesterol homeostasis in an in vivo low-density lipoprotein receptor related protein 5 (LRP5) deficient mice model challenged with high-fat diet. Our results show that Wt and Lrp5-/- mice fed a hypercholesterolemic diet (HC) have increased cholesterol ester accumulation and decreased liver LDLR and LRP5 gene and protein expression. Very low-density lipoprotein receptor (VLDLR), LRP6, LRP2, and LRP1 expression levels were analyzed in liver samples and show that they do not participate in Lrp5-/- liver cholesterol uptake. Immunoprecipitation experiments show that LRP5 forms a complex with PCSK9 in liver-specific fat-storing stellate cells but not in structural HepG2 cells. Hepatic stellate cells silenced for LRP5 and/or PCSK9 expression and challenged with lipids show reduced cholesterol ester accumulation, indicating that both proteins are involved in lipid processing in the liver. Our results indicate that cholesterol esters accumulate in livers of Wt mice in a LDLR-family-members dependent manner as VLDLR, LRP2, and LRP6 show increased expression in HC mice. However, this increase is lost in livers of Lrp5-/- mice, where scavenger receptors are involved in cholesterol uptake. PCSK9 expression is strongly downregulated in mice livers after HC feeding. However PCSK9 and LRP5 bind in the cytoplasm of fat storing liver cells, indicating that this PCSK9-LRP5 interaction is cell-type specific and that both proteins contribute to lipid uptake.


Power laws prevail in medical ultrasound.
Major topics in medical ultrasound rest on the physics of wave propagation through tissue. These include fundamental treatments of backscatter, speed of sound, attenuation, and speckle formation. Each topic has developed its own rich history, lexicography, and particular treatments. However, there is ample evidence to suggest that power law relations are operating at a fundamental level in all the basic phenomena related to medical ultrasound. This review paper develops, from literature over the past 60 years, the accumulating theoretical basis and experimental evidence that point to power law behaviors underlying the most important tissue-wave interactions in ultrasound and in shear waves which are now employed in elastography. The common framework of power laws can be useful as a coherent overview of topics, and as a means for improved tissue characterization.


[Fate of the calcium-dense proximal fragment in scaphoid fracture].
A cohort study with retrolective and prolective collection of data was carried out 49 of 99 patients with scaphoid fractures, initially treated by plaster cast immobilization and having developed a proximal fragment with increased bone density were studied. More than half of these patients had a good or excellent result according to the modified score of Green and O'Brien 29 of 49 proximal fragments with increased bone density returned to normal density: 45 of 49 showed bony union, and 35 of 49 showed no signs of posttraumatic arthrosis. The appearance of stripes with increased bone density in plain X-rays indicated a problem in the process of fracture healing; the clinical interpretation, however, was difficult. Four patients were treated by percutaneous canulated screw (Streli). These fractures showed bony union, the fragment with increased bone density returned to normal in three of four patients. All of these patients had some remaining clinical problems.


A Memory of Early Life Physical Activity Is Retained in Bone Marrow of Male Rats Fed a High-Fat Diet.
Studies have reported opposing effects of high-fat (HF) diet and mechanical stimulation on lineage commitment of the bone marrow stem cells. Yet, how bone marrow modulates its gene expression in response to the combined effects of mechanical loading and a HF diet has not been addressed. We investigated whether early-life (before onset of sexual maturity at 6 weeks of age) voluntary physical activity can modulate the effects of a HF diet on male Sprague Dawley rats. In the bone marrow, early-life HF diet resulted in adipocyte hypertrophy and a pro-inflammatory and pro-adipogenic gene expression profile. The bone marrow of the rats that undertook wheel exercise while on a HF diet retained a memory of the early-life exercise. This memory lasted at least 60 days after the cessation of the voluntary exercise. Our results are consistent with the marrow adipose tissue having a unique response to HF feeding in the presence or absence of exercise.


Etiology and clinical characteristics of neonatal sepsis in different medical setting models: A retrospective multi-center study.
General hospitals admit lower gestational age neonates than maternal and child health care centers, therefore associated with a higher morbidity and mortality. This study aimed to assess the etiology and clinical characteristics of neonatal sepsis in different medical setting models. Neonates admitted to 5 tertiary medical centers, including one national general hospital, two maternal and child health care hospitals and two regional general hospitals, in central-south China with culture-proven sepsis between January 2010 and December 2019 were included in the study. We compared maternal and neonatal characteristics, pathogen distribution, treatment and neonatal outcomes among 3 different medical setting models in this retrospective cohort. We identified 757 episodes of culture-proven sepsis in 757 neonates. The predominant pathogens were coagulase-negative staphylococci, Klebsiella pneumoniae, Escherichia coli and Group B streptococci. A total of 683 neonates with detailed information were involved in further comparison; 54.6% were from the national general hospital, 35.9% were from the maternal and child health care hospital, and 9.5% were from the regional general hospital. Neonates in national and regional general hospitals had significantly lower gestational age and birthweight (P < 0.001). Patterns of pathogen distribution were different among these medical setting models. Early-onset sepsis was more common in maternal and child health care hospitals (61.4% vs. 42.1% vs. 46.7%, P < 0.001), while hospital-acquired late-onset sepsis was more common in national and regional general hospitals (32.7% vs. 33.3% vs. 11.4%, P < 0.001). The proportion of complications or comorbidities of neonates in maternal and child health care hospitals were significantly lower than neonates in national and regional general hospitals (P < 0.001). The case fatality rate was significantly higher in regional general hospitals (10.8% vs. 3.2% vs. 0.8%, P = 0.001). We report distinct patterns of clinical characteristics, pathogens and outcomes in patient subgroups with neonatal sepsis from national general hospital, maternal and child health care hospital and regional general hospital. It might have some implications for improvement of prevention, management and empirical antibiotic use in neonatal sepsis in different setting models, especially in resource-limited settings from middle and low-income countries.


Enantiomeric separation and detection by high-performance liquid chromatography-mass spectrometry of 2-arylpropionic acids derivatized with benzofurazan fluorescent reagents.
The enantiomneric separation and the detection of 2-arylpropionic acids after derivatization with the fluorescent reagents with a benzofurazan structure, (S)-(+)-4-(N,N- dimethylaminosulphonyl)-7-(3-aminopyrrolidin-1-yl)-2,1,3-ben zoxadiazole ((S)-DBD-Apy), (R)-(-)-4-nitro-7-(3-aminopyrrolidin-1-yl)-2,1,3- benzoxadiazole ((R)-NBD-Apy), 4-N,N-dimethylaminosulphonyl-7-piperazino-2,1,3-benzoxadi zole (DBD-PZ) and N-hydrazinoformylmethyl-N-methylamino-4,4- N,N-dimethylaminosulphonyl-2,1,3-benzoxadiazole (DBD-CO-Hz) by high-performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS) were examined. The diastereomeric derivatization with (S)-DBD-Apy or (R)-NBD-Apy and the separation on the reversed phase column afforded the high sensitivity. The separation on chiral stationary phase after non-chiral derivatization with DBD-PZ or DBD-CO-Hz provided less sensitivity. The signal-to-noise ratio of (S)-DBD-Apy-(S)-ketoprofen of 200:1 was observed for 12.5 picomole (pmol) injection and selected ion monitoring (SIM) of the quasi-molecular ion after splitting 1:7 before entering into the electrospray ion sources. As a result, the usefulness of these reagents for MS detection has been demonstrated.


Basic quality indicators for clinical care of patients with major depression, schizophrenia, and bipolar disorder.
To identify a set of indicators to monitor the quality of care for patients with major depression, schizophrenia, or bipolar disorder. A group of 10 experts selected the most automatically applicable indicators from a total of 98 identified in a previous study. Five online sessions and 5 discussion meetings were performed to select the indicators that met theoretical feasibility criteria automatically. Subsequently, feasibility was tested in a pilot study conducted in two hospitals of the Spanish Health Service. After evaluating its measurement possibilities in the Spanish Health Service, and the fulfillment of all the quality premises defined, 16 indicators were selected. Three were indicators of major depression, 5 of schizophrenia, 3 of bipolar disorder, and 5 indicators common to all three pathologies. They included measures related to patient safety, maintenance and follow-up of treatment, therapeutic adherence, and adequacy of hospital admissions. After the pilot study, 5 indicators demonstrated potential in the automatic generation of results, with 3 of them related to treatments (clozapine in schizophrenia, lithium for bipolar disorder, and valproate in women of childbearing age). Indicators support the monitoring of the quality of treatment of patients with major depression, schizophrenia, or bipolar disorder. Based on this proposal, each care setting can draw up a balanced scorecard adjusted to its priorities and care objectives, which will allow for comparison between centers.


Relations between physical and ecosystem service flows of freshwater are critical for water resource security in large dryland river basin.
Freshwater ecosystem services are the link between ecological systems and social systems, which is an important guarantee of the freshwater safety particularly in dryland regions. However, more quantitative research has been based on the freshwater ecosystem services of static situations, and less on the flow conditions. We established a comprehensive modeling framework for the analysis of water security pattern based on the physical flow (PF) and ecosystem service flow (ESF) of freshwater. The results for Yellow River Basin showed that the water-scarce area have reduced in the past two decades. The PF of freshwater relieves water stress on an average of 52.1 % of the static water in scarce areas per year. The problem in water-deficient areas meanly lies on the water supply side. These results highlight the importance of PF from the upstream to downstream, which is critical for formulating sustainable management strategies in safeguarding long-term regional freshwater resource security.


Clinical approach to the management of intractable epilepsy.
Resistance of seizures to anti-epileptic therapy may be due to patient error, or to physician diagnostic and/or treatment error, rather than being truly intractable epilepsy. Increased drug dosage, irrespective of blood levels, a change of drug, or the addition of a second drug, are variously indicated in truly resistant cases. The use of more than two drugs is better avoided, and in some cases reduction of treatment may improve seizure control while lessening side-effects. Repeated assessment of patients with refractory epilepsy is important, as causative or provocative factors may remain latent for long periods. Surgical therapy probably should be used more often and earlier than it now is for epilepsies that are medically intractable.


American Academy of Asthma, Allergy and Immunology--55th annual meeting. 26 February-3 March 1999, Orlando, FL, USA.
This was a particularly comprehensive gathering of investigators and clinicians interested in the field of allergy, asthma and immunology. The meeting presented information ranging from basic immunological research to the clinical trials of drugs already available for treatment in the US today. There were 984 original oral and poster presentations and over 100 symposia, seminars and workshops. The plenary sessions involved sections on allergic inflammation, immune modulation, chemokine receptors, the origins of asthma, the diagnosis and management of food and drug reactions, the environmental influences on allergic diseases, and dermatological diseases. There were approximately 500 faculty members who presented new data or participated in lectures, seminars or workshops.


Effect of cigarette filters on the chemical composition and in vitro biological activity of cigarette mainstream smoke.
The objective of this study was to evaluate the effects of cigarette filters on the chemical composition and toxicity of cigarette mainstream smoke. In this work, we used three types of cigarettes, including non-filter 2R4F cigarettes, cellulose acetate (CA)-filter 2R4F cigarettes, and carbon dual-filter 2R4F cigarettes. The cytotoxicity of TPM obtained from the filter cigarettes was not different from that of the non-filter cigarettes on an equal TPM basis. However, the EC50 value of GVP from carbon-filter cigarettes were 40.9 puffs/L, thereby indicating the cytotoxicity of these cigarettes was approximately 37% and 21% lower than non-filter and CA-filter cigarettes, respectively. The cytotoxicity of GVP was correlated with carbonyl components. The mutagenicity of TPM obtained from non-filter cigarettes, calculated on an equal TPM basis, was up to 30-40% lower than that of the filter cigarettes. When calculated on a per cigarette basis, the mutagenicity of CA or carbon-filter cigarettes was found to be 35% lower than that of the non-filter cigarettes. The results of chemical composition analyses revealed that the observed increase in aromatic amine compound yields on an equal TPM basis in filter cigarettes may be related with the mutagenic activity determined in Ames assays.


Congenital metatarsus varus. A suggestion for a possible mechanism and relation to other foot deformities.
The pathogenesis of metatarsus varus was investigated by a series of dissections of 14 normal feet of stillborn or infants who died during the perinatal period. The deformity could not be produced without the surgical incisions described below. A valgus position of the hindfoot was produced by maximal dorsiflexion of the foot. The deformity of the fore part of the foot could not be produced even by extreme traction on the tibialis anterior tendon even after capsulotomy of the first tarsometatarsal joint. Only extensive capsulotomies in the tarsometatarsal joints distal to the joint of Chopart made it possible to displace the bones into the position analogous to metatarsus varus. It is suggested that metatarsus varus may be a deformity which occurs on a maximally dorsiflexed foot and that the primary mechanism of the forefoot deformity is a subluxation in the fore part of the foot. Secondary contractures of the soft tissues, and adaptive bone changes offer a possible explanation for lack of spontaneous recovery as well as the difficulties encountered in treating late cases.


Quantitative pathological changes in the cerebellum of multiple system atrophy.
Multiple system atrophy (MSA) is a rare neurodegenerative disorder associated with parkinsonism, ataxia, and autonomic dysfunction. Its pathology is primarily subcortical comprising vacuolation, neuronal loss, gliosis, and α-synucleinimmunoreactive glial cytoplasmic inclusions (GCI). To quantify cerebellar pathology in MSA, the density and spatial pattern of the pathological changes were studied in α-synuclein-immunolabelled sections of the cerebellar hemisphere in 10 MSA and 10 control cases. In MSA, densities of Purkinje cells (PC) were decreased and vacuoles in the granule cell layer (GL) increased compared with controls. In six MSA cases, GCI were present in cerebellar white matter. In the molecular layer (ML) and GL of MSA, vacuoles were clustered, the clusters exhibiting a regular distribution parallel to the edge of the folia. Purkinje cells were randomly or regularly distributed with large gaps between surviving cells. Densities of glial cells and surviving neurons in the ML and surviving cells and vacuoles in the GL were negatively correlated consistent with gliosis and vacuolation in response to neuronal loss. Principal components analysis (PCA) suggested vacuole densities in the ML and vacuole density and cell losses in the GL were the main source of neuropathological variation among cases. The data suggest that: (1) cell losses and vacuolation of the GCL and loss of PC were the most significant pathological changes in the cases studied, (2) pathological changes were topographically distributed, and (3) cerebellar pathology could influence cerebral function in MSA via the cerebello-dentato-thalamic tract.


[Intravital bone imaging:osteoclast.]
Osteoclasts are bone-resorbing giant polykaryons that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursors. We have originally established an advanced imaging system for visualizing the in vivo behavior of mature osteoclasts in living bone tissues with intravital multiphoton microscopy. By means of this system, we could grasp the real time-course of osteoclastic bone resorption, and identified two distinct functional states of differentiated osteoclasts, 'bone-resorptive' and 'non-resorptive'. Intravital imaging also revealed that various biologic drugs acted directly on mature osteoclasts during inflammatory bone destruction. In this review, we show the latest data of intravital imaging of osteoclast dynamics.


Impacts of agroecological practices on soil microbial communities in experimental open-field vegetable cropping systems.
This study aimed to determine the impact of different agroecological practices on the composition and diversity of edaphic bacterial and fungal communities. We designed two experimental agroecological vegetable cropping systems and analyzed their effects on soil microbial communities by pyrosequencing the 16S and 18S ribosomal RNA genes. Our results highlighted modifications to the Operational Taxonomic Units in both experimental systems compared with bare soil, particularly for the phyla Actinobacteria, Ascomycota, Bacteroidetes, and Mucoromycota. Multidimensional scaling plots based on beta diversity showed a clear distinction between the two experimental systems for fungi, whereas differences were observed between bare soil and the two experimental systems for bacteria. Overall, the agroecological systems enhanced soil microbial diversity. We showed a distinction between the two experimental systems and bare soil, correlated with the high total N and total P contents in the agroecological systems. Both experimental systems promoted soil enrichment with certain essential minerals. The agroecological systems had a positive impact on soil microbial communities, particularly by promoting the development of beneficial soil bacteria like Actinobacteria. In the two experimental systems, changes in the quality and quantity of organic matter (i.e. mulch, vermicompost, plant diversity) could have modified the abundance and diversity of microbial communities.


Psychologic assessment technology for geriatric practice.
Psychologic assessment is an integral aspect of the comprehensive functional assessment of geriatric patients. Medical areas in which psychologic testing and evaluation can be of significant service in the diagnosis and formulation of treatment plans include psychiatric and neurologic disturbances, psychosomatic disorders, circulatory diseases (especially hypertension), diabetes, chronic pain, sexual dysfunctions, and gastrointestinal problems. In the effort to gain an understanding of the total patient, it is important to clarify the effect of physical condition on a person's psychologic reactions as well as the impact of psychologic states on his/her biologic status. This orientation is particularly important in dealing with elderly patients because the interaction between the physical and the psychologic in this age group is exceedingly strong and significant. Despite the fact that research in the psychology of the aged is of long standing, the attention given by clinical psychologists to the provision of services to geriatric patients has been quite limited until recently. Many psychologic tests have been developed during the past 70 years, but relatively few of them have been standardized for use with the aged. Of late, however, this has been changing. Several tests have been adapted, and some new ones have been organized with the needs and characteristics of the aged in mind. Closer attention has been paid to psychometric principles in the development of the tests, leading to the organization of useful norms and the demonstration of proper levels of reliability and validity. Accordingly, the state of the art of psychologic assessment of the aged is currently rather limited, but the outlook for the near future appears encouraging. In evaluating the condition of a geriatric patient, the clinical psychologist normally generates data through observations, testing, and interviewing. The resulting report covers the following areas: 1) adaptation to the examination and behavioral characteristics during the procedure, 2) cognitive functioning, 3) visual motor coordination and perception of spatial relationships, and 4) personality characteristics and mental health status. Data for the first area are normally derived by the examiner from observations and subjective impressions of the patient's behavior. For each of the other areas the information is obtained through standardized tests. In this discussion, some of the principal assessments that are currently available are reviewed and evaluated for their usefulness with the aged.


Sedges in the mist: A new species of Lepidosperma (Cyperaceae, Schoeneae) from the mountains of Tasmania.
The status of a putative new species of Lepidosperma from the mountains of south-western Tasmania, Australia, was investigated. Phenetic analysis (Flexible UPGMA Agglomerative Hierarchical Fusion and semi-strong hybrid multidimensional scaling) was conducted on a database derived from morphological and anatomical characters scored from herbarium material, culm anatomy slides and scanning electron micrographs of fruit. The results of the analysis support the recognition of a new species, here described as Lepidosperma monticola G.T.Plunkett & J.J.Bruhl. The distribution, habitat and conservation status are discussed.


Association between mtDNA haplogroups and skeletal fluorosis in Han population residing in drinking water endemic fluorosis area of northern China.
To investigate the association between mtDNA genetic information and the risk of SF, individuals were conducted in the drinking water endemic fluorosis area in northern China, sequenced the whole genome of mtDNA, identified the SNPs and SNVs, analyzed the haplogroups, and diagnosed SF, and then, the effect of mtDNA genetic information on the risk of SF was evaluated. We find that, D5 haplogroup and its specific SNPs reduced the risk, while the D4 haplogroup and its specific SNPs increased the risk of SF. The number of SNVs in coding regions of mitochondrial respiratory chain (MRC) is different between the controls and cases. This suggests that D5 haplogroup may play a protective role in the risk of SF, while the opposite is observed for the D4 haplogroup, this may relate to their specific SNPs. And SNVs that encode the MRC complex may also be associated with the risk of SF.


Development of a single nucleotide polymorphism genotyping microarray platform for the identification of bovine milk protein genetic polymorphisms.
The objective of this study was to develop and validate a fast method for typing the main mutations of bovine milk protein genes by using microarray technology. An approach based on the ligation detection reaction (LDR) and a universal array (UA) was used. Polymorphisms in both the coding and noncoding sequences of alpha(S1)-casein, beta-casein, kappa-casein, and beta-lactoglobulin genes were considered because of their well-known effects on milk composition and cheese production. A total of 22 polymorphic sites, corresponding to 21 different variants, were included in the diagnostic microarray. First, a multiplex PCR was developed to amplify all the DNA target sequences simultaneously. Second, the LDR-UA assay was implemented. The method was validated by analyzing 100 Italian Friesian DNA samples, which were also genotyped by conventional methods both at the protein level by means of milk isoelectrofocusing and at the molecular level using PCR-RFLP and PCR-single strand conformation polymorphism techniques. The genotypes obtained using the LDR-UA approach were in full agreement with those obtained by the conventional analyses. An important result of the LDR-UA assay was a more accurate genotyping of the different milk protein alleles than was found with conventional typing methods. At the kappa-casein gene, in fact, 4 samples were heterozygous (3 reference samples and 1 validation sample) for an allele coding for Thr(136) and Ala(148). This variant, which can be considered as the wild type of the genus Bos, is not usually identifiable by the conventional typing methods used. The multiplex PCR-LDR-UA approach developed provides for an accurate, inexpensive, and high-throughput assay that does not exhibit false positive or false negative signals, thus making it highly suitable for animal genotyping.


Molecular phylogenetics of the Neotropical fish family Prochilodontidae (Teleostei: Characiformes).
Migratory detritivores of the characiform family Prochilodontidae occur throughout the freshwaters of much of South America. Prochilodontids often form massive populations and many species achieve substantial body sizes; a combination that makes them one of the most commercially important fish groups on the continent. Their economic significance notwithstanding, prochilodontids have never been the subject of a comprehensive molecular phylogenetic analysis. Using three mitochondrial and three nuclear loci spanning all prochilodontid species, we generated a novel phylogenetic hypothesis for the family. Our results strongly support monophyly of the family and the three included genera. A novel, highly supported placement of Ichthyoelephas sister to the clade containing Prochilodus and Semaprochilodus diverges from a previous morphological hypothesis. Most previously hypothesized interspecific relationships are corroborated and some longstanding polytomies within Prochilodus and Semaprochilodus are resolved. The morphologically similar P. brevis, P. lacustris, P. nigricans and P. rubrotaeniatus are embedded within what is herein designated as the P. nigricans group. Species limits and distributions of these species are problematic and the group clearly merits taxonomic revision.


Tetraplegia after a tracheal resection procedure.
We describe a 27-year-old patient who was admitted to our hospital for a tracheal stenosis caused by an adenocystic carcinoma. A tracheal resection procedure was performed and the head was fixed to the anterior chest wall by two sutures. Postoperatively he became tetraplegic, from which he completely recovered after the sutures were removed. We think that the decreased blood flow in the arterial spinal artery with flexion of the neck in combination with hypotension was the direct cause of this major complication.


Comparison of the Effect of Intravenous Fentanyl with Low-Dose Ketamine on Pain Relief in Patients Taking Methadone and Suffering from Limb Fractures.
Given the significance of pain control in addicted patients and the prominence of not using opioids due to patient's drug dependence, the present study aimed at comparing and evaluating the effect of intravenous fentanyl with low-dose ketamine on pain relief in patients taking methadone and suffering from limb fractures. The present double-blind randomized clinical trial was performed on 100 patients taking methadone and suffering from limb fractures. The patients were divided into two groups receiving 1 μg/kg single dose of fentanyl and 0.3 mg/kg single dose of ketamine (low-dose ketamine). Patients' pain scores and the incidence rate of complications were recorded before the intervention, and 15, 30, and 60 min after drug administration and were then compared between the two groups. The mean pain score of patients 15 min after the intervention was significantly lower in the low-dose ketamine group with a mean of 2.50 ± 1.34 as compared with the fentanyl group with a mean of 7.10 ± 1.43 (P < 0.001). However, the mean pain score was not significantly different between the two groups 30 and 60 min after the intervention (P > 0.05). In addition, the incidence rate of complications was not significantly different between the two groups (P > 0.05). According to the results of this study, low-dose ketamine as compared with fentanyl relieves pain in the mentioned patients with a faster effect and in a shorter time although no difference can be found between the pain scores of the two groups 30 and 60 min after the intervention.


[MR tomography in staging of carcinomas of the uterus].
Magnetic resonance imaging (MRI) has proven to be a suitable imaging modality for the evaluation of uterine neoplasms. In contrast to computed tomography and ultrasound, MRI allows multiplanar observer-independent imaging of the whole female pelvis with high tissue-specific contrast. This article reviews the advantages and limitations of MRI in the staging of endometrial and cervical carcinoma, focusing on MRI with reference to other imaging modalities. New technical developments are discussed and an imaging approach for these tumor types is suggested.


Correlation between total urinary protein quantitation and random urine sample protein/creatinine ratio in children.
Random urine samples and 24-hour urine samples were obtained prospectively from 5 healthy children and 28 children with renal diseases, aged 2 to 14 years. The relationship between the random urine protein/creatinine ratio (Up/Ucr) and total daily protein excretion were studied. Protein concentrations were measured using a Coomassie blue binding technique. The Up/Ucr measured in 61 urine samples correlated closely with 24-hour urine protein excretion. In log-transformed data, the correlation was linear with a coefficient of 0.97 (log Up/Ucr mg/mmole = 0.786 + 1.018 logTP, TP in mg/h/M2). The Up/Ucr that coincided with a protein excretion of 4 mg/h/M2 was 25.1 mg/mmole (0.222 mg/mg) and of 40 mg/h/M2 was 261 mg/mmole (2.31 mg/mg). The results of our study indicate that Up/Ucr is an accurate estimate of quantitative protein excretion. In clinical practice this is a suitable method of quantification for proteinuria in patients with renal disease.


Does resting electroencephalograph asymmetry reflect a trait? an application of latent state-trait theory.
Recent research on brain asymmetry and emotion treated measures of resting electroencephalograph (EEG) asymmetry as genuine trait variables, but inconsistency in reported findings and modest retest correlations of baseline asymmetry are not consistent with this practice. The present study examined the alternative hypothesis that resting EEG asymmetry represents a superimposition of a traitlike activation asymmetry with substantial state-dependent fluctuations. Resting EEG was collected from 59 participants on 4 occasions of measurement, and data were analyzed in terms of latent state-trait theory. For most scalp regions, about 60% of the variance of the asymmetry measure was due to individual differences on a temporally stable latent trait, and 40% of the variance was due to occasion-specific fluctuations, but measurement errors were negligible. Further analyses indicated that these fluctuations might be efficiently reduced by aggregation across several occasions.


Biodegradation and saccharification of wood chips of Pinus strobus and Liriodendron tulipifera by white rot fungi.
Degradation and glucose production from wood chips of white pine (Pinus strobus) and tulip tree (Liriodendron tulipifera) by several white rot fungi were investigated. The highest weight losses from 4 g of wood chips of P. strobus and L. tulipifera by the fungal degradation on yeast extractmalt extract-glucose agar medium were 38% of Irpex lacteus and 93.7% of Trametes versicolor MrP 1 after 90 days, respectively. When 4 g of wood chips of P. strobus and L. tulipifera biodegraded for 30 days were treated with cellulase, glucose was recovered ot the highest values of 106 mg/g degraded wood by I. lacteus and 450 mg/g degraded wood by T. versicolor. The weight loss of 10 g of wood chip of L. tulipifera by T. versicolor on the nutrient non-added agar under the nonsterile conditions was 35% during 7 weeks of incubation, and the cumulative amount of glucose produced during this period was 239 mg without cellulase treatment. The activities of ligninolytic enzymes (lignin peroxidase, manganese peroxidase, and laccase) of fungi tested did not show a high correlation with degradation of the wood chips and subsequent glucose formation. These results suggest that the selection of proper wood species and fungal strain and optimization of glucose recovery are all necessary for the fungal pretreatment of woody biomass as a carbon substrate.


Single dose of betamethasone in combined medical treatment of secretory otitis media.
With the objective of evaluating the efficacy of cefixime and the combination of cefixime and betamethasone in the treatment of secretory otitis media (SOM), we enrolled 142 children 2 to 12 years old in a randomized, double-blind, placebo-controlled study. All children suffered from SOM, verified by otomicroscopy and tympanometry, of at least 3 months' duration. Active treatment was a 10-day course of cefixime with and without a single dose of 6 mg betamethasone. On hundred forty children were available for efficacy evaluation 14 to 23 days after the start of treatment. A statistically significant treatment effect was found in the group treated with cefixime plus betamethasone (n = 59), with a 44.1% cure rate as compared to 19.7% in the cefixime-treated group (n = 61; p < .005) and 5% in the placebo group (n = 20; p < .005). Relapse rates were high and no statistically differences between groups remained at last valid visit. Adverse events possibly or probably associated with active treatment were reported in 11 cases (9.2%). One patient reported a severe adverse event. No serious events occurred. The study did not show any significant long-term effect of cefixime treatment or any long-term treatment benefit with the addition of betamethasone to the antibiotic.


Simultaneous demonstration of glycogen and protein in glycosomes of cardiac tissue.
Cardiac conduction fibers fixed either in glutaraldehyde and OsO4 or treated additionally en bloc with uranyl acetate were studied in order to demonstrate the structure of glycosomes (protein-glycogen complex). Sections were stained histochemically by periodic acid-thiosemicarbazide-silver proteinate (PA--TSC--SP) for glycogen followed by uranyl acetate and lead citrate (U-Pb) for protein. In control sections periodic acid was replaced by hydrogen peroxide (H2O2). Glycogen appeared in all sections stained by PA-TSC-SP. Protein was poorly contrasted in periodic acid treated histochemical sections taken from fixed in glutaraldehyde and OsO4. Simultaneous staining of glycogen and protein was achieved in sections of tissue treated en bloc with uranyl acetate. This treatment revealed two classes of glycosomes: 1) glycosomes deposited freely in the cytoplasm whose structure was disintegrated after treatment with uranyl acetate: 2) glycosomes associated with other cellular structures that remained intact. Staining of glycogen and protein in the same section demonstrated for the first time the structure of intact glycosomes.


2D SiP2/h-BN for a Gate-Controlled Phototransistor with Ultrahigh Sensitivity.
Two-dimensional (2D) materials are extremely attractive for the construction of highly sensitive photodetectors due to their unique electronic and optical properties. However, developing 2D photodetectors with ultrahigh sensitivity for extremely low-light-level detection is still a challenge owing to the limitation of high dark current and low detectivity. Herein, a gate-controlled phototransistor based on 2D SiP2/hexagonal boron nitride (h-BN) was rationally designed and demonstrated ultrahigh sensitivity for the first time. With a back-gate device geometry, the SiP2/h-BN phototransistor exhibits an ultrahigh detectivity of 3.4 × 1013 Jones, which is one of the highest values among 2D material-based photodetectors. In addition, the phototransistor also shows a gate tunable responsivity of ≤43.5 A/W at a gate voltage of 30 V due to the photogating effect. The ultrahigh sensitivity of the SiP2-based phototransistor is attributed to the extremely low dark current suppressed by the phototransistor configuration and the improved photocurrent by using h-BN as a substrate to reduce charge scattering. This work provides a facile strategy for improving the detectivity of photodetectors and validates the great potential of 2D SiP2 phototransistors for ultrasensitive optoelectronic applications.


Distinctive signatures of recursion.
Although recursion has been hypothesized to be a necessary capacity for the evolution of language, the multiplicity of definitions being used has undermined the broader interpretation of empirical results. I propose that only a definition focused on representational abilities allows the prediction of specific behavioural traits that enable us to distinguish recursion from non-recursive iteration and from hierarchical embedding: only subjects able to represent recursion, i.e. to represent different hierarchical dependencies (related by parenthood) with the same set of rules, are able to generalize and produce new levels of embedding beyond those specified a priori (in the algorithm or in the input). The ability to use such representations may be advantageous in several domains: action sequencing, problem-solving, spatial navigation, social navigation and for the emergence of conventionalized communication systems. The ability to represent contiguous hierarchical levels with the same rules may lead subjects to expect unknown levels and constituents to behave similarly, and this prior knowledge may bias learning positively. Finally, a new paradigm to test for recursion is presented. Preliminary results suggest that the ability to represent recursion in the spatial domain recruits both visual and verbal resources. Implications regarding language evolution are discussed.


Choice of provider for out-patient treatment is not working.
In 2012, the coalition government introduced the legal right for National Health Service (NHS) patients in England to choose their mental healthcare provider for out-patient treatment. This was a significant step towards parity of care between mental and physical ill health, and NHS Improvement and NHS England have provided sensible guidance on its implementation. However, several factors prevent the system from working as it was intended: lack of awareness of the principle of patient choice for out-patient treatment; complacency from some trusts and commissioners; mental health trusts operating outside the e-referrals system; misuse of care pathways; lack of direct access by many general practitioners for out-of-area referrals; and delays in authorisation for funding. I describe how I have come to this conclusion and suggest some solutions. Declaration of interest The author is employed by a trust that potentially benefits from 'patient choice'.


Titration of PEEP by the arterial minus end-tidal carbon dioxide gradient.
It was shown in dogs that intrapulmonary physiologic shunt (Qsp/Qt), arterial oxygen tension (PaO2), total static respiratory compliance (CT), oxygen delivery (O2AV), cardiac output (Qt), and arterial minus end-tidal carbon dioxide gradient (PaCO2-PetCO2) undergo statistically significant deterioration when oleic acid is injected into the pulmonary artery. Positive end-expiratory pressure (PEEP) therapy reduced Qsp/Qt and PaCO2-PetCO2 gradient and increased PaO2. The CT did not show any consistent pattern of improvement with the application of PEEP. The Qt and the O2AV progressively decreased as PEEP was increased. The application of additional PEEP beyond that which minimized the PaCO2-PetCO2 gradient produced a statistically significant increase in the PaCO2-PetCO2 gradient, but this was not reflected by concomitant changes in Qsp/Qt or PaO2 in spite of a further decrease in Qt. Thus, the PaCO2-PetCO2 gradient may be a more sensitive indicator of excessive PEEP than is Qst/Qt or PaO2, since it should be smallest when there is maximal recruitment of perfused or functional gas units without overdistention of alveolar areas contributing to dead space. Also, the use of the PaCO2-PetCO2 gradient permits the rapid titration of PEEP without the need for a pulmonary artery catheter.


Cortical sources of Vernier acuity in the human visual system: An EEG-source imaging study.
Vernier acuity determines the relative position of visual features with a precision better than the sampling resolution of cone receptors in the retina. Because Vernier displacement is thought to be mediated by orientation-tuned mechanisms, Vernier acuity is presumed to be processed in striate visual cortex (V1). However, there is considerable evidence suggesting that Vernier acuity is dependent not only on structures in V1 but also on processing in extrastriate cortical regions. Here we used functional magnetic resonance imaging-informed electroencephalogram source imaging to localize the cortical sources of Vernier acuity in observers with normal vision. We measured suprathreshold and near-threshold responses to Vernier onset/offset stimuli at different stages of the visual cortical hierarchy, including V1, hV4, lateral occipital cortex (LOC), and middle temporal cortex (hMT+). These responses were compared with responses to grating on/off stimuli, as well as to stimuli that control for lateral motion in the Vernier task. Our results show that all visual cortical regions of interest (ROIs) responded to both suprathreshold Vernier and grating stimuli. However, thresholds for Vernier displacement (Vernier acuity) were lowest in V1 and LOC compared with hV4 and hMT+, whereas all visual ROIs had identical thresholds for spatial frequency (grating acuity) and for relative motion. The cortical selectivity of sensitivity to Vernier displacement provides strong evidence that LOC, in addition to V1, is involved in Vernier acuity processing. The robust activation of LOC might be related to the sensitivity to the relative position of features, which is common to Vernier displacement and to some kinds of texture segmentation.


[The learning needs of the cancer patient: a conceptual analysis].
This paper offers a conceptual analysis of the term "learning need" of a cancer population. This analysis was made according to the steps recommended by Wilson (1969). In order to properly understand the essential features of the learning need concept, it is defined by focusing on its characteristics: cognitive knowledge, affective knowledge, psychomotor knowledge and the notion of learning. For the sake of clarity, the expression "learning need" was analyzed by examining a group of closely related concepts: information need, desire to learn and search for information. Although it is often used, the boundary between these concepts is not clearly identified. Some of these concepts may even be confused for each other. The paper concludes by explaining the nature of the cancer patient's learning needs.


Predisposing factors for primary acquired nasolacrimal duct obstruction.
Pathological origin of primary acquired nasolacrimal duct obstruction (PANDO) is considered as inflammation of unknown causes; however, specific predisposing factors have not been fully addressed to date. In an institutional setting, background factors of 45 patients with PANDO were compared to those in 67 control subjects. The control subjects were persons with senile cataract, representing the non-pathological general population. The evaluated background factors were inflammatory medical histories (infectious conjunctivitis and allergic conjunctivitis and/or rhinitis), previously reported factors (POAG and topical timolol), and a novel factor proposed in the current study (exposure to swimming pool). Data were extracted from the patients through interview based on a standardized questionnaire as well as from their clinical records. After adjustment for age and gender, a history of infectious conjunctivitis was more common in the PANDO group than in the control group (55.6 % vs 32.8 %, P = 0.0027), and regular attendance to indoor swimming pools was also more common in the PANDO group (33.3 % vs 0 %, P < 0.0001). Furthermore, when age- and gender- matched subjects were selected, a history of conjunctivitis and swimming pool exposure were independently associated with the development of PANDO (P = 0.022 and P < 0.0001 respectively). On the other hand, the frequencies of histories of POAG, topical timolol, and allergic conjunctivitis and/or rhinitis were similar between the two groups. Histories of infectious conjunctivitis and swimming pool exposure could be associated with the development of PANDO, although the pathogenesis of this condition has been considered as inflammation of unknown causes.


Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) levels in patients with overt and subclinical hyperthyroidism: effects of treatment.
Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) has been shown to increase in parallel with platelet activation in acute ischaemic and thrombotic diseases. There has been no study evaluating SCUBE1 levels in patients with overt hyperthyroidism (OHyper) and subclinical hyperthyroidism (SHyper), conditions which are known to show impairment of both endothelial and platelet function. This study sought to evaluate SCUBE1 concentrations in patients with SHyper and OHyper, and assessed the effects of antithyroid drug (ATD) therapy on circulating SCUBE1 levels. Forty-five untreated patients with OHyper, 20 untreated patients with SHyper and 30 age- and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters were evaluated in all patients before and after treatment. Compared with the control subjects, SCUBE1 levels were significantly increased in patients with SHyper and OHyper (P < 0·0001 and P = 0·002, respectively). SCUBE1 levels were not significantly different in patients with OHyper compared with patients with SHyper. There was no significant correlation between serum thyroid hormones and SCUBE1 levels. Plasma SCUBE1 levels decreased significantly in both OHyper and SHyper after ATD treatment (P < 0·05). Increased SCUBE1 levels in both SHyper and OHyper patients may reflect increased platelet activation and possible endothelial dysfunction, which might augment the risk for atherosclerotic and atherothrombotic complications. SCUBE1 may be used as a reliable marker of endothelial damage in hyperthyroidism, especially in the subclinical period.


Phanerozoic pO2 and the early evolution of terrestrial animals.
Concurrent gaps in the Late Devonian/Mississippian fossil records of insects and tetrapods (i.e. Romer's Gap) have been attributed to physiological suppression by low atmospheric pO2 Here, updated stable isotope inputs inform a reconstruction of Phanerozoic oxygen levels that contradicts the low oxygen hypothesis (and contradicts the purported role of oxygen in the evolution of gigantic insects during the late Palaeozoic), but reconciles isotope-based calculations with other proxies, like charcoal. Furthermore, statistical analysis demonstrates that the gap between the first Devonian insect and earliest diverse insect assemblages of the Pennsylvanian (Bashkirian Stage) requires no special explanation if insects were neither diverse nor abundant prior to the evolution of wings. Rather than tracking physiological constraint, the fossil record may accurately record the transformative evolutionary impact of insect flight.


Global distribution of malocclusion traits: A systematic review.
Considering that the available studies on prevalence of malocclusions are local or national-based, this study aimed to pool data to determine the distribution of malocclusion traits worldwide in mixed and permanent dentitions. An electronic search was conducted using PubMed, Embase and Google Scholar search engines, to retrieve data on malocclusion prevalence for both mixed and permanent dentitions, up to December 2016. Out of 2,977 retrieved studies, 53 were included. In permanent dentition, the global distributions of Class I, Class II, and Class III malocclusion were 74.7% [31 - 97%], 19.56% [2 - 63%] and 5.93% [1 - 20%], respectively. In mixed dentition, the distributions of these malocclusions were 73% [40 - 96%], 23% [2 - 58%] and 4% [0.7 - 13%]. Regarding vertical malocclusions, the observed deep overbite and open bite were 21.98% and 4.93%, respectively. Posterior crossbite affected 9.39% of the sample. Africans showed the highest prevalence of Class I and open bite in permanent dentition (89% and 8%, respectively), and in mixed dentition (93% and 10%, respectively), while Caucasians showed the highest prevalence of Class II in permanent dentition (23%) and mixed dentition (26%). Class III malocclusion in mixed dentition was highly prevalent among Mongoloids. Worldwide, in mixed and permanent dentitions, Angle Class I malocclusion is more prevalent than Class II, specifically among Africans; the least prevalent was Class III, although higher among Mongoloids in mixed dentition. In vertical dimension, open bite was highest among Mongoloids in mixed dentition. Posterior crossbite was more prevalent in permanent dentition in Europe.


Low communication high performance ab initio density matrix renormalization group algorithms.
There has been recent interest in the deployment of ab initio density matrix renormalization group (DMRG) computations on high performance computing platforms. Here, we introduce a reformulation of the conventional distributed memory ab initio DMRG algorithm that connects it to the conceptually simpler and advantageous sum of the sub-Hamiltonian approach. Starting from this framework, we further explore a hierarchy of parallelism strategies that includes (i) parallelism over the sum of sub-Hamiltonians, (ii) parallelism over sites, (iii) parallelism over normal and complementary operators, (iv) parallelism over symmetry sectors, and (v) parallelism within dense matrix multiplications. We describe how to reduce processor load imbalance and the communication cost of the algorithm to achieve higher efficiencies. We illustrate the performance of our new open-source implementation on a recent benchmark ground-state calculation of benzene in an orbital space of 108 orbitals and 30 electrons, with a bond dimension of up to 6000, and a model of the FeMo cofactor with 76 orbitals and 113 electrons. The observed parallel scaling from 448 to 2800 central processing unit cores is nearly ideal.


An analysis of the effect of synovial capillary distribution upon trans-synovial concentration profiles and exchange.
Recent morphometric studies of synovium lining the rabbit knee showed that capillaries extend to greater than 200 microns below the synovial surface; that a proportion of the superficial capillaries are fenestrated; and that the numerical density of the capillaries varies with depth ( Knight & Levick , 1983, 1984). Such observations raised the question 'Down to what depth do capillaries contribute significantly to the diffusional flux of a small extracellular solute (e.g. sulphate) into the joint cavity?' This problem was addressed by a mathematical model of trans-synovial diffusion. The periarticular tissue was considered as a stack of thin slices (delta chi = 2.5 microns), each of known depth and capillary population. An expression for interstitial concentration normal to the surface was derived from the Fick diffusion equations and the mass-balance equation for each slice. Morphometric values were substituted into the area and distance terms of the Fick equation. A range of values was explored for two permeability terms, namely Df/Di (diffusivity across unit fenestral matrix relative to that across unit interstitial matrix) and PS/Q (permeability-surface area product/blood flow for synovial fenestrated capillaries); the ranges lay between the estimated extreme values. Steady-state concentrations and transcapillary fluxes at each depth were obtained by iterative calculation on a microcomputer. The thickness of tissue from which 80% of the joint influx arose (T0.8) was 7-13 microns for diffusion-limited transcapillary exchange (PS/Q = 0.05; Df/Di = 1-0.3); or 9-17 microns for flow-limited exchange (PS/Q = 5; Df/Di = 1-0.03) in areolar synovium, which is the most extensive tissue. The relative independence of the results from the permeability conditions was due to the dominant effect of a peak in capillary density just below the synovial surface. The resistance of the capillary endothelial wall as a fraction of total blood-joint barrier resistance was calculated to be 0.18-0.80 in areolar synovium under conditions of diffusion-limited exchange.


Clinical spectrum of fascicular tachycardia.
Ventricular tachycardia spreading from the anterior or posterior division of the left bundle branch is generally called fascicular tachycardia (FT). We will present our experience with FT, a type of ventricular tachycardia not necessarily implying the absence of heart disease and/or sensitivity to selective antiarrhythmic drugs, but only particular routes of left ventricular depolarization. Since 1981 we have had the opportunity to study 10 cases of FT (nine men and one woman; aged 28-77 years, mean ± SD 55 ± 18.6 years) by means of echocardiography, coronary angiography (seven cases), endomyocardial biopsy (five cases), signal-averaged electrocardiogram (SAECG, nine patients), electrophysiological and electropharmacological evaluation. Seven patients had paroxystic, extrastimulus inducible FT that was sensitive to verapamil given intravenously (group A); three patients, on the other hand, showed repetitive or incessant FT, not modifiable by stimulation techniques and sensitive to class 1 antiarrhythmic drugs (group B). Patients presented histologic substrates ranging from the absence of heart disease to previous myocardial infarction or myocarditis. FT spontaneously disappeared within 2 years in group B, while frequently persisted in the long term in group A. FT is not a homogeneous group of ventricular tachycardia, as patients may differ according to clinical presentation, mechanisms that are involved in the genesis of the arrhythmia and natural history; the histologic substrate is highly variable, ranging from the total absence of heart disease to severe forms of myocardial involvement.


Nonstarter lactobacilli isolated from soft and semihard Argentinean cheeses: genetic characterization and resistance to biological barriers.
Nonstarter lactic acid bacteria isolated from Argentinean cheeses were identified and characterized by focusing on their resistance to biological barriers, along with other physiological features of potential interest, in the search for future probiotic organisms. Lactobacilli were enumerated and isolated from semihard and soft cheeses made with multistrain Streptococcus thermophilus starters. Lactobacilli counts in 1-week-old cheeses were between 10(5) and 10(7) CFU/g and then reached 10(7) CFU/ g in all 1-month samples, while streptococci were always above 10(9) CFU/g. A total number of 22 lactobacilli isolates were retained, identified, and characterized by in vitro tests. Species identity was determined by carbohydrate metabolism and species-specific PCR assays. Genetic diversity was explored by random amplified polymorphic DNA (RAPD) PCR analysis. The Lactobacillus strains were assigned to the species L. casei, L. plantarum, L. rhamnosus, L. curvatus, L. fermentum, and L. perolens. All the strains studied tolerated 25 ppm of lysozyme, and most of them showed resistance to 0.3% bile. After incubation in gastric solution (pH 2.0), counts decreased by several log units, ranging from 3.2 to 7.0. The strains were able to grow in the presence of bile salts, but only three isolates were capable of deconjugation. The nonstarter lactobacilli that were assayed fermented the prebiotic substrates (especially lactulose and inulin). Some strains showed high cell hydrophobicity and beta-galactosidase activity, as well as inhibitory activity against pathogenic bacteria. It was concluded that most of the lactobacilli isolated in this study demonstrated resistance to biological barriers and physiological characteristics compatible with probiotic properties, which make them suitable for further research in in vivo studies aimed at identifying new probiotic organisms.


Benefit of continuous kidney replacement therapy for managing tumor lysis syndrome in children with hematologic malignancies.
Tumor lysis syndrome (TLS) is often diagnosed in children with hematological malignancies and can be life threatening due to metabolic disturbances. Continuous renal replacement therapy (CKRT) can reverse these disturbances relatively quickly when conventional medical management fails. Our objective was to investigate the benefit of CKRT in the management of TLS in children admitted to the intensive care unit with hematologic malignancies. In addition, we sought to assess risk factors for acute kidney injury (AKI) in the setting of TLS. Retrospective review of all children admitted to the intensive care unit with TLS who received CKRT from January 2012 to August 2022. Among 222 children hospitalized with TLS from January 2012 to August 2022, 20 (9%) underwent CKRT to manage TLS in the intensive care unit. The patients' median age was 13 years (range 3-17 y), and most were males (18/20). T-cell acute lymphoblastic leukemia was the most common diagnosis (n=10), followed by acute myeloid leukemia (n=4), Burkitt lymphoma (n=4), and B-cell acute lymphoblastic leukemia (n=2). Five patients required mechanical ventilation, and 2 required vasopressors. The most common indication for CKRT was hyperphosphatemia, followed by, hyperuricemia, and hyperkalemia. All metabolic abnormalities corrected within 12 h of initiation of CKRT. CKRT courses were brief, with a median duration of 2 days (range 1-7 days). Having higher serum phosphorus levels 12 h preceding CKRT was significantly associated with severe acute kidney injury (AKI). The median phosphorus level was 6.4 mg/dL in children with no/mild AKI and 10.5 mg/dL in children with severe AKI (p=0.0375). Serum uric acid levels before CKRT were not associated with AKI. All children survived to hospital discharge, and the one-year survival rate was 90%. CKRT is safe in children with hematologic malignancies with severe TLS and reverses metabolic derangements within 6-12 h. Most patients had AKI at the initiation of CKRT but did not require long-term kidney replacement therapy. Hyperphosphatemia before initiation of CKRT is associated with higher risk of AKI.


Effect of 2-chloroethanol on hepatic microsomal enzymes in the rat.
The effect of 2-chloroethanol on the activities of hepatic microsomal enzymes in the rat has been studied. A significant reduction in activities of drug-metabolizing enzymes (aminopyrine N-demethylase, coumarin 3-hydroxylase) and a marked decrease of glucose 6-phosphatase were seen in both sexes given dose levels of 20 mg/kg sc daily for 7 days. Inosine diphosphatase activity remained unaltered. In male rats given 3 or 10 mg/kg, a trend in the inhibition of drug metabolism was found. A single dose of 50 mg/kg caused no apparent change in the activities of the enzymes measured.


Alveolar ridge preservation using a bioactive glass particulate graft in extraction site defects.
This article describes the application of a bioactive glass particulate graft and placement of an expanded polytetrafluoroethylene barrier into extraction sites to preserve the residual ridge and to develop the site prior to fixed prosthetic replacement. Extraction site development can enhance and facilitate the position and shape of the pontics while maximizing the natural contour of the soft tissues.


[Leukocyte depletion of blood products and anti-HLA immunization].
HLA alloimmunization and subsequent refractoriness to platelet transfusions are frequent complications of transfusion therapy in patients with hematologic malignancies. Contaminating leukocytes in red cell and platelet concentrates are responsible for primary HLA alloimmunization. In many clinical trials, it has been demonstrated that the use of leukocyte-poor blood products prepared by filtration could reduce HLA-alloimmunization from 40% to 15%. The immunogenic level cannot be determined accurately, but the previous studies show that a residual contamination below 1.10(6) leukocytes was efficient to prevent primary alloimmunization. Leukocyte depletion does not avoid secondary responses in patients having an history of pregnancies or transfusions. The UV-B irradiation of platelet concentrates, in combination with filtration, should further reduce alloimmunization in these presensitized patients.


Surface functionalization of methotrexate-loaded chitosan nanoparticles with hyaluronic acid/human serum albumin: Comparative characterization and in vitro cytotoxicity.
The active tumor targeting ligands, hyaluronic acid (HA) and human serum albumin (HSA), are considered promising targeting moieties of drug carriers for cancer therapy. The chitosan nanoparticles loaded with methotrexate (MTX-CsNPs) were employed as the core for subsequent coating process. HA and HSA coating solutions were used at different concentrations. The effect of different HA Mw (1000, 360, 10kDa) was also investigated. The coated MTX-CsNPs was characterized proving the success of surface functionalization. The antitumor activity of the prepared MTX-CsNPs was evaluated on MCF-7 breast cancer cell lines. Results showed that both 360 and 10kDa HA allowed for successful HA adsorption, while its Mw and concentration determined negative charge density. HSA coating was accompanied by a slight increase in nanoparticles (NPs) size and a final positive surface charge. The in vitro cytotoxicity proved that HA and HSA coated MTX-CsNPs improved the antitumor activity compared to uncoated NPs and free drug.


The characteristics analysis of intestinal microecology on cerebral infarction patients and its correlation with apolipoprotein E.
Cerebral infarction (CI) is associated with high rates of disability, mortality, and death in China, but its mechanism is unclear. Therefore, early diagnosis of CI and determining its mechanism are very important. Intestinal microecology is thought to be related to cardiovascular and cerebrovascular diseases. We hypothesized that intestinal microecology is also related to CI and that the intestinal microecology in the stool of CI patients differs from that in healthy people.Fecal samples of healthy subjects and CI patient (all n = 10) and we investigated the intestinal microecology of CI patient and healthy people stool by 16 seconds sequencing and analyzed relative abundance and diversity of microorganisms by unweighted pair-group method with arithmetic mean analysis (UPGMA) and principal co-ordinates analysis (PCoA). We also measured apolipoprotein E (ApoE) levels in the serum by ELISA assay and analyzed the correlation between ApoE and intestinal flora.We found that the relative structure and diversity of intestinal microecology was significantly different between the stools of CI patients and healthy people. At the class level, Gammaproteobacteria was increased and Bacteroidia was decreased in CI patient stool. We found a correlation between ApoE in the serum and Bacteroidia and Gammaproteobacteria species.We considered the intestinal flora can be used as an indicator of CI and the up-regulation of ApoE may be the potential mediate for intestinal microecology contribute to CI.


[Ethical dilemmas in health].
It is difficult to speak of ethic dilemmas in a society that has relativism as the oficial philosophical and political doctrine, i.e., stable values and behavior references, are denied, both in health care and in any other area of human knowledge. In the field of medical sciences it is even pretended to pass from the observational methodology to a field of manipulation and manipulability. It is the very Ethic that is presented as a dilemma. In these conditions one needs to know the lines of thought that are defended, to replace and make disappear the stable ethic references: ecletism, historicism, scientificism, pragmatism, and nihilism itself, that lead to the 'new ethic paradigm', that has created by itself a pseudo-spirituality. The truth is we are adrift in the 'Ethic of Convenience' which changes according to the majorities. In this setting the way to go is to rediscover the abandoned ethic values: only with an objective ethic, with sound references and foundations, it is possible to re-establish and perfect the patient-physician relationship, for a better social health. And this begins with the ethic problem of human life.


Key Insights into Hand Biomechanics: Human Grip Stiffness Can Be Decoupled from Force by Cocontraction and Predicted from Electromyography.
We investigate the relation between grip force and grip stiffness for the human hand with and without voluntary cocontraction. Apart from gaining biomechanical insight, this issue is particularly relevant for variable-stiffness robotic systems, which can independently control the two parameters, but for which no clear methods exist to design or efficiently exploit them. Subjects were asked in one task to produce different levels of force, and stiffness was measured. As expected, this task reveals a linear coupling between force and stiffness. In a second task, subjects were then asked to additionally decouple stiffness from force at these force levels by using cocontraction. We measured the electromyogram from relevant groups of muscles and analyzed the possibility to predict stiffness and force. Optical tracking was used for avoiding wrist movements. We found that subjects were able to decouple grip stiffness from force when using cocontraction on average by about 20% of the maximum measured stiffness over all force levels, while this ability increased with the applied force. This result contradicts the force-stiffness behavior of most variable-stiffness actuators. Moreover, we found the thumb to be on average twice as stiff as the index finger and discovered that intrinsic hand muscles predominate our prediction of stiffness, but not of force. EMG activity and grip force allowed to explain 72 ± 12% of the measured variance in stiffness by simple linear regression, while only 33 ± 18% variance in force. Conclusively the high signal-to-noise ratio and the high correlation to stiffness of these muscles allow for a robust and reliable regression of stiffness, which can be used to continuously teleoperate compliance of modern robotic hands.


KL-6 mucin expression in carcinoma of the ampulla of Vater: association with cancer progression.
To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater. Ampullary carcinoma tissues were collected from 38 patients who underwent pancreatoduodenectomy or local resection. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. Positive staining of ampullary carcinoma cells was observed in 26 (68.4%) cases. Staining was not found in the surrounding non-cancer regions of the ampullary tissues. Remarkable KL-6 expression was observed in invasive carcinoma cells in pancreatic and duodenal tissues and in metastatic carcinoma cells in lymph nodes. Positive KL-6 expression was related to lymph node metastasis (P = 0.020), pancreatic invasion (P = 0.016), duodenal invasion (P = 0.034), and advanced stage of TNM clinical classification (P = 0.010). Survival analysis showed that positive expression of KL-6 was related to a poorer prognosis (P = 0.029). The aberrant expression of KL-6 mucin is significantly related to unfavorable behaviors of carcinoma of the ampulla of Vater.