Paleontologic Technique for Defining Ancient Pole Positions.
Taxonomnic diversity gradients appear to offer a quantitative paleontologic technique for obtaining ancient positions of the rotational pole of the earth. Statistical analysis of a model based on the taxonomic diversity of Recent planktonic foramninifera shows a close relationship to the latitudinal temperature gradient and, thus permits location of the pole. A similar analysis for Permian orthotetaceid brachiopods suggests a pole near the present position. A vailable data on diversity fit a present earth mizodel better than one based on Permian paleomagnetic results and thus suggest that it may be necesary to consider a model for the earth's magnetic field which does not require coincidence of the magnetic and rotational poles.


Populism, Exclusion, Post-truth. Some Conceptual Caveats Comment on "The Rise of Post-truth Populism in Pluralist Liberal Democracies: Challenges for Health Policy".
In their editorial, Speed and Mannion identify two main challenges "the rise of post-truth populism" poses for health policy: the populist threat to inclusive healthcare policies, and the populist threat to well-designed health policies that draw on professional expertise and research evidence. This short comment suggests some conceptual clarifications that might help in thinking through more profoundly these two important issues. It argues that we should approach right-wing populism as a combination of a populist down/up (people/elite) axis with an exclusionary nationalist in/out (member/non-member) axis. And it raises some questions regarding the equation between populism, demagogy and the rejection of expertise and scientific knowledge.


Wake Up Safe and root cause analysis: quality improvement in pediatric anesthesia.
In 2006, the Quality and Safety Committee of the Society for Pediatric Anesthesia initiated a quality improvement project for the specialty of pediatric anesthesiology that ultimately resulted in the development of Wake Up Safe (WUS), a patient safety organization that maintains a registry of de-identified, serious adverse events. The ultimate goal of WUS is to implement change in processes of care that improve the quality and safety of anesthetic care provided to pediatric patients nationwide. Member institutions of WUS submit data regarding the types and numbers of anesthetics performed and information pertaining to serious adverse events. Before a member institution submits data for any serious adverse event, 3 anesthesiologists who were not involved in the event must analyze the event with a root cause analysis (RCA) to identify the causal factor(s). Because institutions across the country use many different RCA methods, WUS educated its members on RCA methods in an effort to standardize the analysis and evaluate each serious adverse event that is submitted. In this review, we summarize the background and development of this patient safety initiative, describe the standardized RCA method used by its members, demonstrate the use of this RCA method to analyze a serious event that was reported, and discuss the ways WUS plans to use the data to promote safer anesthetic practices for children.


[Isolation of staphylococcal enterotoxin type B and a study of its physicochemical, biological and immunological properties].
The homogeneous preparation of type B staphylococcal enterotoxin (SEB) has been obtained by its adsorption from the culture fluid on amberlite, elution, isoelectric focusing in the ampholine system and gel filtration in a column packed with Sephadex G-25. The isolated SEB component is a thermostable protein, homogeneous in its antigenic composition and according to the results of disc electrophoresis in acrylamide gel. Its molecular weight is 28,000 daltons with pI equal to 8.6 (the main component), 8.0 and 8.25 (the minor components). All the forms are immunochemically identical. The minimum enterotoxic dose of SEB for cats is 3-5 micrograms per kg of body weight. The biological activity of the enterotoxin disappears under the action of 6 M urine. Monospecific antiserum to SEB with a precipitating antibody titer of 1:64 has been obtained.


The role of repeat angiography in the management of pelvic fractures.
Angiographic embolization has emerged as the treatment modality of choice for bleeding pelvic fractures. The purpose of this study is to identify potential indicators for ongoing pelvic hemorrhage despite initial therapeutic or non-diagnostic angiography. The trauma registry of a Level I trauma center was used to identify patients with pelvic fractures between January 2000 and June 2002. Records were reviewed for demographics, severity of injury, hemodynamic status, initial and subsequent base deficit, blood and fluid requirements, length of stay, and mortality. Statistical analysis was performed using Student's t test, and univariate and multivariate analysis, significance was assigned to p < or = 0.05. During the study period, 678 patients had pelvic fractures. Angiography was performed in 31 (4.6%) of these patients. Arterial hemorrhage was diagnosed initially on 16 (51.6%) patients requiring embolization. Three (18.8%) of these embolized patients required repeat angiography and embolization due to ongoing pelvic hemorrhage. Of the initial 15 patients with negative angiograms, five (33.3%) had repeat angiograms due to continued hypotension and acidosis. Four (80.0%) of these five patients were found to have arterial hemorrhage requiring embolization. Of the seven (22.6%) patients requiring repeat angiography for control of ongoing pelvic hemorrhage, three independent factors were predictive: continued or recurrent hypotension (SBP < 90), absence of intra-abdominal injury, and persistent base deficit of 10 for greater than 6 hours. The presence of all three independent predictors was associated with a 97% probability of pelvic bleeding (p = 0.001). Angiographic embolization is highly effective in controlling arterial bleeding associated with pelvic fractures. However, repeat angiography should be performed in patients with pelvic fractures with ongoing evidence of hemorrhage demonstrated by persistent base deficit and hypotension once other potential sources of bleeding have been excluded.


Culture and phenotype of activated T-cells from patients with type I diabetes mellitus.
Blood T-cells from 28 patients with type I (insulin-dependent) diabetes (IDDM) of variable duration were examined for the Tac antigen by immunofluorescence, and for proliferation in the presence of interleukin 2 (IL 2). The mean percentage of Tac+ cells in patients whose IDDM was of less than 2-yr duration was 6.2% compared with 2% in patients whose IDDM was of 3 or more years' duration, or in healthy controls. The percentage of Tac+ cells in the patients' blood correlated positively with the amount of thymidine uptake in a 24-h culture of blood mononuclear cells and with the percentage of T-cell blasts generated in a 6-day culture. The patients' T-cell blasts stained with OKT 4 or OKT 8, suggesting that each of these subsets is present in the activated T-cell population in the patients' blood. The T-cell blasts did not show specificity for pork insulin in an antigen restimulation assay. There was no correlation between increased Tac+ cells and the presence or absence of islet cell antibodies. If T-cell activation in IDDM occurs as a result of recognition of islet cell antigens, our results suggest that both HLA-DR-restricted (OKT 4+) and A-, B-, and C-restricted (OKT 8+) T-cell subsets contribute.


CPC: assess the protein-coding potential of transcripts using sequence features and support vector machine.
Recent transcriptome studies have revealed that a large number of transcripts in mammals and other organisms do not encode proteins but function as noncoding RNAs (ncRNAs) instead. As millions of transcripts are generated by large-scale cDNA and EST sequencing projects every year, there is a need for automatic methods to distinguish protein-coding RNAs from noncoding RNAs accurately and quickly. We developed a support vector machine-based classifier, named Coding Potential Calculator (CPC), to assess the protein-coding potential of a transcript based on six biologically meaningful sequence features. Tenfold cross-validation on the training dataset and further testing on several large datasets showed that CPC can discriminate coding from noncoding transcripts with high accuracy. Furthermore, CPC also runs an order-of-magnitude faster than a previous state-of-the-art tool and has higher accuracy. We developed a user-friendly web-based interface of CPC at http://cpc.cbi.pku.edu.cn. In addition to predicting the coding potential of the input transcripts, the CPC web server also graphically displays detailed sequence features and additional annotations of the transcript that may facilitate users' further investigation.


Medical negligence in orthopaedic surgery: a review of 130 consecutive medical negligence reports.
Payments by the NHS Litigation Authority continue to rise each year, and reflect an increase in successful claims for negligence against NHS Trusts. Information about the reasons for which Trusts are sued in the field of trauma and orthopaedic surgery is scarce. We analysed 130 consecutive cases of alleged clinical negligence in which the senior author had been requested to act as an expert witness between 2004 and 2006, and received information on the outcome of 97 concluded cases from the relevant solicitors. None of the 97 cases proceeded to a court hearing. Overall, 55% of cases were abandoned by the claimants' solicitors, and the remaining 45% were settled out of court. The cases were settled for sums ranging from pound 4500 to pound 2.7 million, the median settlement being pound 45,000. The cases that were settled out of court were usually the result of delay in treatment or diagnosis, or because of substandard surgical technique.


Constitutively active PTH/PTHrP receptor specifically expressed in osteoblasts enhances bone formation induced by bone marrow ablation.
Bone is maintained by continuous bone formation by osteoblasts provided by proliferation and differentiation of osteoprogenitors. Parathyroid hormone (PTH) activates bone formation, but because of the complexity of cells in the osteoblast lineage, how these osteoprogenitors are regulated by PTH in vivo is incompletely understood. To elucidate how signals by PTH in differentiated osteoblasts regulate osteoprogenitors in vivo, we conducted bone marrow ablation using Col1a1-constitutively active PTH/PTHrP receptor (caPPR) transgenic mice. These mice express caPPR specifically in osteoblasts by using 2.3 kb Col1a1 promoter and showed higher trabecular bone volume under steady-state conditions. In contrast, after bone marrow ablation, stromal cells recruited from bone surface extensively proliferated in the marrow cavity in transgenic mice, compared to limited proliferation in wild-type mice. Whereas de novo bone formation was restricted to the ablated area in wild-type mice, the entire marrow cavity, including not only ablated area but also outside the ablated area, was filled with newly formed bone in transgenic mice. Bone mineral density was significantly increased after ablation in transgenic mice. Bone marrow cell culture in osteogenic medium revealed that alkaline phosphatase-positive area was markedly increased in the cells obtained from transgenic mice. Furthermore, mRNA expression of Wnt-signaling molecules such as LRP5, Wnt7b, and Wnt10b were upregulated after marrow ablation in bone marrow cells of transgenic mice. These results indicate that constitutive activation of PTH/PTHrP receptor in differentiated osteoblasts enhances bone marrow ablation-induced recruitment, proliferation, and differentiation of osteoprogenitors.


Comparison of consumer derived evidence with an omaha system evidence-based practice guideline for community dwelling older adults.
Consumer involvement in healthcare is critical to support continuity of care for consumers to manage their health while transitioning from one care setting to another. Validation of evidence-based practice (EBP) guideline by consumers is essential to achieving consumer health goals over time that is consistent with their needs and preferences. The purpose of this study was to compare an Omaha System EBP guideline for community dwelling older adults with consumer-derived evidence of their ongoing needs, resources, and strategies after home care discharge. All identified problems were relevant for all patients except for Neglect and Substance use. Ten additional problems were identified from the interviews, five of which affected at least 10% of the participants. Consumer derived evidence both validated and expanded EBP guidelines; thus further emphasizing the importance of consumer involvement in the delivery of home healthcare.


Rational approach to implementation of prostate cancer antigen 3 into clinical care.
Prostate cancer antigen 3 (PCA3) encodes a prostate-specific messenger ribonucleic acid (mRNA) that serves as the target for a novel urinary molecular assay for prostate cancer detection. The objective of the current study was to evaluate the ability of PCA3, added to measurements of serum prostate-specific antigen (PSA), to predict cancer detection by extended template biopsy. Between September 2006 and December 2007, whole urine samples were collected after attentive digital rectal examinations from 187 men before they underwent ultrasound-guided, 12-core prostate biopsy in a urology outpatient clinic. Urine PCA3/PSA mRNA ratio scores were measured within 1 month, and serum PSA was measured within 6 months prior to biopsy. Those measurements were related to cancer-positive biopsies. Overall, 87 of 187 biopsies (46.5%) were positive for cancer. The sensitivity and specificity of a PCA3 score > or =35 for positive biopsy were 52.9% and 80%, respectively, and the positive and negative predictive values were 69.7% and 66.1%, respectively. By using receiver operating characteristic curve analysis, PSA alone resulted in an area under the curve (AUC) of 0.63 for prostate cancer detection; whereas a combined PSA and PCA3 score resulted in an AUC of 0.71. The likelihood of prostate cancer detection rose with increasing PCA3 score ranges (P > .0001), providing possible PCA3 score parameters for stratification into groups at low risk, moderate risk, high risk, and very high risk for a positive biopsy. Adding PCA3 to serum PSA improved prostate cancer prediction. The use of PCA3 in a clinical setting may help to stratify patients according to their risk for biopsy and cancer detection, although a large-scale validation study will be needed to address assay standardization, optimal cutoff values, and appropriate patient populations.


Socioeconomic deprivation and rheumatoid disease: what lessons for the health service? ERAS Study Group. Early Rheumatoid Arthritis Study.
To assess how socioeconomic deprivation influences the presentation, treatment, and outcome of patients with rheumatoid arthritis (RA). Three year follow up of 869 consecutive patients with RA from nine hospital rheumatology clinics, with patients categorised by the Carstairs deprivation score of their enumeration district of residence. Outcomes included Health Assessment Questionnaire (HAQ), joint and pain scores, grip strength, functional grade, radiological evidence of bony erosions, and medical/surgical interventions. Patients from more deprived enumeration districts presented with more severe disease as judged by the HAQ score and joint scores. An increase from the 5th to the 95th centile of the Carstairs distribution was associated with an odds ratio of 1.87 (95% confidence interval (95% CI) 1.31 to 2.66) for an above-median HAQ score and 1.77 (95% CI 1.23 to 2.54) for an above-median joint score. Statistically non-significant deprivation trends were seen with erythrocyte sedimentation rate, pain score, and grip strength. By three years, despite no important differences in clinical management, socioeconomic differentials had worsened or remained unchanged such that clear deprivation trends were then seen in HAQ (p=0.002) and joint scores (p=0.001), in grip strength (p=0. 008), and in functional grade (p=0.003). The association between deprivation and HAQ at three years was present after adjustment for age, sex, treatment centre, and HAQ at presentation (adjusted odds ratio 1.74, 95% CI 1.1 to 2.74). Socioeconomic deprivation was associated with a worse clinical course of rheumatoid disease, and this effect was already apparent at presentation, but not with systematic differentials in its treatment. This suggests that individual susceptibility and lifestyle factors contribute to socioeconomic differentials in outcome, an observation that has implications for clinical management.


Transition Milestones, Psychological Distress, and Suicidal Ideation Among Transgender Adults: A Structural Equation Analysis.
This paper examines the relationships among transition milestones (i.e., transition-related events in transgender persons' lives that demarcate their life circumstances before vs. afte a milestone was reached), psychological distress, and suicidal ideation in a large sample of transgender adults. Data from the 2015 U.S. National Transgender Survey were used to examine 11 specific transition milestones in a sample of 27,715 transgender Americans aged 18 or older. The Kessler-6 scale was used to measure psychological distress and a dichotomous measure of suicidal ideation during the past year was the other main outcome measure. Covariates in the multivariate analysis included demographic measures, variables assessing support and discrimination, and 11 transition milestones. Bivariate analyses revealed that, in almost all instances, reaching specific transition milestones led to reduced psychological distress and diminished odds of suicidal ideation. Multivariate analysis revealed that psychological distress was a strong predictor of suicidal ideation, but transition milestones were not retained in the final model. Structural equation analysis showed that three specific transition milestones (namely, changing one's name and/or gender on legal documents, taking gender-affirming hormones, having had any gender-conforming surgical procedures) influenced suicidal ideation indirectly, through their direct impact on psychological distress. Reaching specific transition milestones plays an important role in many transgender adults' lives, and may be highly beneficial in helping them to reduce psychological distress. This, in turn, is likely to have a positive impact upon their likelihood of contemplating suicide.


PHROG: A Multimodal Feature for Place Recognition.
Long-term place recognition in outdoor environments remains a challenge due to high appearance changes in the environment. The problem becomes even more difficult when the matching between two scenes has to be made with information coming from different visual sources, particularly with different spectral ranges. For instance, an infrared camera is helpful for night vision in combination with a visible camera. In this paper, we emphasize our work on testing usual feature point extractors under both constraints: repeatability across spectral ranges and long-term appearance. We develop a new feature extraction method dedicated to improve the repeatability across spectral ranges. We conduct an evaluation of feature robustness on long-term datasets coming from different imaging sources (optics, sensors size and spectral ranges) with a Bag-of-Words approach. The tests we perform demonstrate that our method brings a significant improvement on the image retrieval issue in a visual place recognition context, particularly when there is a need to associate images from various spectral ranges such as infrared and visible: we have evaluated our approach using visible, Near InfraRed (NIR), Short Wavelength InfraRed (SWIR) and Long Wavelength InfraRed (LWIR).


Supporting Safety in Health Care Transformations.
Health care is in dramatic transformation due to the rapid development and massive implementation of (high- and low-tech) technologies. But not all transformations are as intended. Research in health transformation has disclosed new sources of risk and unpredictability, which require more research and organizational adjustment, i.e. learning. However, unintended consequences and effects occur at different levels of interaction and collaboration, requiring corresponding adjustment and learning strategies. - On the background of an ethnographic study of support-work in surgery in different Danish hospitals, this paper analyses cognitive-socio-technical health care practices as learning ecologies, giving special attention to the intentional and unintentional roles of technologies herein and their context dependency. The paper argues for an increased awareness of support at different contextual levels of use, presenting three examples from the study as learning cases. The three cases exemplify instances of disruption of the workflow and the collaboration among clinicians. They display how these instances are taken as challenges requiring learning at different levels in order to live up to the overall purpose, which is to reestablish safety - in the team and for the patient.


Biochemical properties of membranes isolated from calcium-depleted rabbit hearts.
The purpose of this study was to define the biochemical properties of sarcolemma from the calcium-depleted rabbit heart. Calcium repletion after calcium-free perfusion results in irreversible damage to the heart (calcium paradox). No difference was found in specific activity of the Na+ -Ca++ antiporter in a crude preparation of sarcolemmal vesicles that was isolated from calcium-depleted hearts, compared with control perfused hearts. Likewise, the passive calcium efflux from sarcolemmal vesicles, preloaded with calcium via the Na+ -Ca++ antiporter, showed rates that were identical with control values. This indicates that the sarcolemma calcium permeability is not affected by calcium-free perfusion of the heart. Na+,K+ -ATPase activity in sarcolemma isolated from calcium-depleted hearts was reduced by 75% (P less than 0.005) compared with the control activity. Sarcolemmal phosphoproteins, whether produced by endogenous cyclic AMP- or calcium-calmodulin-dependent protein kinase, were not altered by calcium-free perfusion of the heart. The content of an important calcium-binding site in the myocardial cell, the sialic acid residues, was also estimated. Only a long period (60 minutes) of calcium-free perfusion resulted in a significant decrease (by 68%, P less than 0.025) of sialic acid content in the homogenate but not in the sarcolemma preparation. In hearts that were reperfused for 15 minutes with a normal calcium concentration (1.3 mM), sarcolemmal Na+,K+ -ATPase remained depressed and calcium permeability was still unchanged. It is possible that the sarcolemma isolation method selected a distinct part of the sarcolemma from the calcium-depleted and repleted heart that had no modified glycocalyx and permeability barriers to calcium ions, and that another part of the sarcolemma with altered properties was lost during the isolation procedure. Another possibility is that reconstitution processes during isolation affected membrane permeability properties. The results of the Na+,K+ -ATPase measurements provide evidence that the net calcium gain of the cells after calcium repletion may be associated, in part, with a loss in ability of the sarcolemma to remove calcium from the cytosol.


Natural variation of canine parvovirus.
Canine parvovirus was first recognized during 1978. Analysis of isolates collected since its emergence revealed that viruses circulating after 1980 were antigenically different from earlier isolates. Monoclonal antibodies clearly distinguished the two strains, some being specific for either the old or the new viruses. Restriction enzyme analysis of viral DNA's showed that the post-1980 viruses were similar to earlier isolates, but some restriction site differences were present in the new strain. These results suggest that the canine parvoviruses infecting dogs in the seven areas of the United States that were sampled derive from a variant virus that replaced the original strain during 1980.


Co-deposition towards mussel-inspired antifouling and antibacterial membranes by using zwitterionic polymers and silver nanoparticles.
Bacterial attachment and the subsequent colonization on the surfaces of bio-materials usually result in biofilm formation, and thus lead to implant failure, inflammation and so on. Herein, a novel mussel-inspired antibacterial and antifouling membrane was designed via co-deposition of polydopamine (PDA) and a zwitterionic polymer, followed by incorporating bactericidal silver nanoparticles (Ag NPs). Polyethyleneimine-graft-sulfobetaine methacrylate (PEI-SBMA) was firstly co-deposited onto a polyethersulfone (PES) membrane surface via crosslinking with PDA to construct an antifouling surface. Then, Ag NPs were in situ synthesized on the membrane surface without adding any external reducing agents. Elemental and morphological surface analyses confirmed the successful co-deposition of PEI-SBMA onto the PES surface and the successful reduction of silver ions by the PDA layer. In addition, the PEI-SBMA could significantly reduce Ag NP aggregation, and the modified surface exhibited sustained bactericidal activity and effective inhibition of bacterial adhesion. This demonstrated that the proposed approach was straightforward to fabricate mussel-inspired antifouling and antibacterial membranes, which showed great potential to be used in biomedical fields.


A bio-electromechanical imaging technique with combined electrical impedance and ultrasound tomography.
Electrical impedance tomography (EIT) seeks to image the electrical conductivity of an object using electrical impedance measurement data at its periphery. Ultrasound reflection tomography (URT) is an imaging modality that is able to generate images of mechanical properties of the object in terms of acoustic impedance changes. Both URT and EIT have the potential to be used in various medical applications. In this paper we focus on breast tumour detection. Both URT and EIT belong to soft field tomography and suffer from the small amounts of available data and the inherently ill-posed nature of the inverse problems. These facts result in limited achievable reconstruction accuracy and resolution. A dual bio-electromechanical tomography system using ultrasound and electrical tomography is proposed in this paper to improve the detection of the small-size tumour. Data fusion techniques are implemented to combine the EIT/URT data. Based on simulations, we demonstrate the improvement of detection of small size anomalies and improved depth detection compared to single modality soft field tomography.


Two-Dimensional Field-Effect Transistor Sensors: The Road toward Commercialization.
The evolutionary success in information technology has been sustained by the rapid growth of sensor technology. Recently, advances in sensor technology have promoted the ambitious requirement to build intelligent systems that can be controlled by external stimuli along with independent operation, adaptivity, and low energy expenditure. Among various sensing techniques, field-effect transistors (FETs) with channels made of two-dimensional (2D) materials attract increasing attention for advantages such as label-free detection, fast response, easy operation, and capability of integration. With atomic thickness, 2D materials restrict the carrier flow within the material surface and expose it directly to the external environment, leading to efficient signal acquisition and conversion. This review summarizes the latest advances of 2D-materials-based FET (2D FET) sensors in a comprehensive manner that contains the material, operating principles, fabrication technologies, proof-of-concept applications, and prototypes. First, a brief description of the background and fundamentals is provided. The subsequent contents summarize physical, chemical, and biological 2D FET sensors and their applications. Then, we highlight the challenges of their commercialization and discuss corresponding solution techniques. The following section presents a systematic survey of recent progress in developing commercial prototypes. Lastly, we summarize the long-standing efforts and prospective future development of 2D FET-based sensing systems toward commercialization.


Development of obliterative bronchiolitis in a murine model of orthotopic lung transplantation.
Orthotopic lung transplantation in rats was first reported by Asimacopoulos and colleagues in 1971 (1). Currently, this method is well accepted and standardized not only for the study of allo-rejection but also between syngeneic strains for examining mechanisms of ischemia-reperfusion injury after lung transplantation. Although the application of the rat and other large animal model (2) contributed significantly to the elucidation of these studies, the scope of those investigations is limited by the scarcity of knockout and transgenic rats. Due to no effective therapies for obliterative bronchiolitis, the leading cause of death in lung transplant patients, there has been an intensive search for pre-clinical models that replicate obliterative bronchiolitis. The tracheal allograft model is the most widely used and may reproduce some of the histopathologic features of obliterative bronchiolitis (3). However, the lack of an intact vasculature with no connection to the recipient's conducting airways, and incomplete pathologic features of obliterative bronchiolitis limit the utility of this model (4). Unlike transplantation of other solid organs, vascularized mouse lung transplants have only recently been reported by Okazaki and colleagues for the first time in 2007 (5). Applying the basic principles of the rat lung transplant, our lab initiated the obliterative bronchiolitis model using minor histoincompatible antigen murine orthotopic single-left lung transplants which allows the further study of obliterative bronchiolitis immunopathogenesis(6).


Predictors of quality of life in young adults with congenital heart disease.
The aim of this study was to identify medical and psychosocial risk factors for impaired health-related quality of life (HRQoL) and poor psychological adjustment (PA) in young adults with congenital heart disease (CHD). A group of 188 patients (43% females, ages 18-30 years) with various types of CHD and 139 age-matched healthy controls (57% females) completed questionnaires assessing HRQoL, PA, social support, significant life events in the past year, education level, civil status, and employment status. Medical variables were retrieved from the patients' hospital records. Patients reported worse physical HRQoL than controls but similar mental HRQoL and PA. Female CHD patients showed worse physical and mental HRQoL and poorer PA than males. In CHD patients, a lower educational level and lower physical exercise capacity predicted lower physical HRQoL, but complexity of CHD was not related to HRQoL or PA. Less social support was associated with lower mental HRQoL and poorer PA in CHD patients. Young adults with CHD have impaired physical HRQoL but normal mental HRQoL and PA. Lower physical exercise capacity, female sex, less social support, and lower educational level predict an unfavourable quality of life and PA. This subgroup of patients should be monitored more closely and provided with special psychosocial care to improve long-term outcome.


Circadian variation of the response of T cells to antigen.
Circadian clocks regulate many important aspects of physiology, and their disturbance leads to various medical conditions. Circadian variations have been found in immune system variables, including daily rhythms in circulating WBC numbers and serum concentration of cytokines. However, control of immune functional responses by the circadian clock has remained relatively unexplored. In this study, we show that mouse lymph nodes exhibit rhythmic clock gene expression. T cells from lymph nodes collected over 24 h show a circadian variation in proliferation after stimulation via the TCR, which is blunted in Clock gene mutant mice. The tyrosine kinase ZAP70, which is just downstream of the TCR in the T cell activation pathway and crucial for T cell function, exhibits rhythmic protein expression. Lastly, mice immunized with OVA peptide-loaded dendritic cells in the day show a stronger specific T cell response than mice immunized at night. These data reveal circadian control of the Ag-specific immune response and a novel regulatory mode of T cell proliferation, and may provide clues for more efficient vaccination strategies.


Relationship between pNG2, an Emr plasmid in Corynebacterium diphtheriae, and plasmids in aerobic skin coryneforms.
Erythromycin-resistant (Emr) coryneforms from cutaneous lesions and erythromycin-susceptible (Ems) coryneforms from normal skin sites were screened for plasmids. Approximately one-third of the 40 isolates carried one or more plasmids ranging in mass from 2.5 to 36 megadaltons, all exhibiting different restriction enzyme digest patterns. In contrast, only Corynebacterium diphtheriae strains comprising a single cohort of apparently identical Emr, pNG2-carrying isolates have been identified as plasmid carriers. Homology was demonstrated between pNG2 and a number of fragments in restriction enzyme digests of plasmids from both Emr and Ems skin coryneforms under high-stringency conditions. However, none was detected between pNG2 and the genomic or plasmid DNAs of Emr staphylococci or streptococci isolated concurrently with the Emr coryneforms. One coryneform plasmid, pNG34, exhibited extensive homology with pNG2, and many comigrating fragments were observed. Very little relationship was observed between C. diphtheriae and the skin coryneforms when their genomic DNAs were hybridized. The origin and presence of pNG2 in Emr C. diphtheriae is discussed in relation to these findings.


The nutritional requirements of methicillin-dependent and -resistant strains of Pediococcus cerevisiae.
A new methicillin-dependent and -resistant substrain (called MRD) of Pediococcus cerevisiae was developed by serial passages followed by replica-plating. Other methicillin-resistant, but not -dependent, substrains were isolated after treatment of the same parent strain with a mutagen. A methicillin-independent partial revertant, still resistant to the drug, was isolated from the original methicillin-dependent and -resistant substrain (CRD) developed several years ago. The requirements of some of these strains for acetate, vitamins and amino acids were compared. All except the parent methicillin-sensitive strain required pantothenate for growth, but no other consistent differences were found. The parent, but not strain CRD, grew without lysine added to the medium, though 19 other amino acids were needed by each strain. Both of these strains fermented glucose to lactate (mainly the L-isomer) in the absence or presence of methicillin.


Lymphedema of the extremities: prospects of microsurgical treatment.
Presented herein is an experience with the treatment of 60 patients with lymphedema of the extremities, who had undergone transplantation of "lymphatic flaps". The treatment success is analyzed in both free microsurgical autotransplantation of tissue complexes (52 patients) containing intact lymphatic structures and in transposition (8 patients). The authors evaluate the potential of radio-nuclide diagnostic techniques for quantification of the effectiveness of surgical treatment. After transplantation and transposition of different types of "lymphatic flaps" good results were obtained in 36 (60%) patients. The prospects of the use of "lymphatic flaps" are assessed from the standpoint of the current concepts related to the surgical treatment of lymphedema of the extremities.


The mystery of the shroud of turin challenges 20th-century science.
On the face of it, the very idea that the linen cloth in which Jesus Christ was wrapped in the tomb should have survived to this day would seem incredible. It demands even more of human credulity that the cloth bears a photographic likeness which would seem to be that of Jesus as he lay in the tomb. [From The Shroud of Turin by IAN WILSON].


[Influencing factors in the leakage of liposome and arabinoside cytosine (ARA-C) entrapped in liposomes in treatment of L1210 mouse leukemia].
Ara-c entrapped into multilamella vesicles (MLV's) composed of PC:C (2:1) (phosphotidylcholine, cholesterol) or PC:SM (1:4) (sphingomyelin) was incubated in the simple salt medium at 37 degrees C for one hour. Its leakage from the liposomes was 5.6-17.6% but, in the presence of serum, the leakage was 35.7-49.1%. Having been incubated at 37 degrees C overnight, the leakage significantly increased but the leakage rate was the highest within the 1st hour. When ara-c entrapped into reverse evaporation vesicles (REV's) composed of PC:C (2:1) or PC:SM (1:4) was incubated in the simple salt medium at 37 degrees C for one hour, its leakage was 2.4-4.1% but, in the presence of serum, the leakage was 10.9-8.2%. When the liposomes were incubated at 37 degrees C overnight, the leakage gradually increased. Whether in the presence of serum or not, the leakage from REV's was much less than that from MLV's. There was no effect on the survival of L1210 leukemia mice when free ara-c was injected intraperitoneally once at the dose of 10 mg/kg, but when the same dose was given for five times, the increase rate in life span was 43.2--51.3%. When ara-c, entrapped into MLV's or REV's composed of PC:C (2:1) and PC:SM (1:4), was given at the dose of 10 mg/kg only once, the effect of intraperitoneal injection was more marked than that of intravenous injection. No effect was observed when free ara-c was continuously infused at the dose of 2 mg/kg once everyday for five days.(ABSTRACT TRUNCATED AT 250 WORDS)


Lesion contrast enhancement in medical ultrasound imaging.
Methods for improving the contrast-to-noise ratio (CNR) of low-contrast lesions in medical ultrasound imaging are described. Differences in the frequency spectra and amplitude distributions of the lesion and its surroundings can be used to increase the CNR of the lesion relative to the background. Automated graylevel mapping is used in combination with a contrast-weighted form of frequency-diversity speckle reduction. In clinical studies, the techniques have yielded mean CNR improvements of 3.2 dB above ordinary frequency-diversity imaging and 5.6 dB over sharper conventional images, with no post-processing graylevel mapping.


Delayed Muscle Activity in Stroke Survivors with Upper-Limb Hemiparesis.
Stroke is the leading cause of disability worldwide, and nearly 80% of stroke survivors suffer from upper-limb hemiparesis. Myoelectric exoskeletons can restore dexterity and independence to stroke survivors with upper-limb hemiparesis. However, the ability of patients to dexterously control myoelectric exoskeletons is limited by an incomplete understanding of the electromyographic (EMG) hallmarks of hemiparesis, such as muscle weakness and spasticity. Here we show that stroke survivors with upper-limb hemiparesis suffer from delayed voluntary muscle contraction and delayed muscle relaxation. We quantified the time constants of EMG activity associated with initiating and terminating voluntary hand grasps and extensions for both the paretic and non-paretic hands of stroke survivors. We found that the initiation and termination time constants were greater on the paretic side for both hand grasps and hand extensions. Notably, the initiation time constant during hand extension was approximately three times longer for the paretic hand than for the contralateral non-paretic hand (0.618 vs 0.189 s). We also show a positive correlation between the initiation and termination time constants and clinical scores on the Modified Ashworth Scale. The difficulty stroke survivors have in efficiently modulating their EMG presents a challenge for appropriate control of assistive myoelectric devices, such as exoskeletons. This work constitutes an important step towards understanding EMG differences after stroke and how to accommodate these EMG differences in assistive myoelectric devices. Real-time quantitative biofeedback of EMG time constants may also have broad implications for guiding rehabilitation and monitoring patient recovery.Clinical Relevance- After a stroke, muscle activity changes, and these changes make it difficult to use muscle activity to drive assistive and rehabilitative technologies. We identified slower muscle contraction and muscle relaxation as a key difference in muscle activity after a stroke. This quantifiable difference in muscle activity can be used to develop better assistive technologies, guide rehabilitation, and monitor patient recovery.


Trends in mortality from sporadic Creutzfeldt-Jakob disease in France 1992-7.
This study examined trends in mortality from sporadic Creutzfeldt-Jakob disease in France for 1992-7 by age, genotype at the codon 129 of the prion protein gene, and geographical area. Case ascertainment was based on notifications by neurologists, neuropathologists, and laboratories; 324 deaths from definite or probable Creutzfeldt-Jakob disease were registered during the study period. The yearly number of deaths increased significantly between 1992 and 1997. The rise was higher for older age groups. It was also higher in those who were homozygous for valine compared with other genotypes. Eighteen departments (geographical administrative areas) out of 95 showed a significant increase in the number of deaths from sporadic Creutzfeldt-Jakob disease. Intensive epidemiological surveillance is a likely explanation for the apparent increase in the number of sporadic cases of Creutzfeldt-Jakob disease over the 1992-7 period, particularly in older age groups and in departments with low mortality rate at the beginning of the study period. Intensive surveillance may also have led to a better identification of atypical valine homozygous cases.


Endoscopic carpal tunnel release.
Open carpal tunnel release has been the standard treatment of carpal tunnel syndrome for the past three decades. Since its introduction in the late 1980s, endoscopic carpal tunnel release has generated excitement and controversy. Two basic techniques have developed: the single portal and the double portal. Data from many clinical series and cadaver studies are available for review. The endoscopic carpal tunnel release offers several advantages over the standard open technique, including less scar tenderness, earlier return to work and activities of daily living, and earlier return of pinch and grip strength. Endoscopic carpal tunnel release may be safer than many of the new "mini" open techniques. The indications and threshold for surgery are the same in both techniques. The major contraindications are rheumatoid arthritis, mass lesions, and repeat surgery. Many adjunctive procedures done with open carpal tunnel release such as exploration of the motor branch, release of Guyon's canal, epineurotomy or neurolysis, and flexor tenosynovectomy are unnecessary. With proper training and equipment, endoscopic carpal tunnel release can be done safely, with complication rates comparable to those for the open technique and with high patient satisfaction.


A measure of parent engagement: plan appropriateness, partnering, and positive outcome expectancy in pediatric rehabilitation sessions.
To examine the psychometric properties of a parent-report measure of engagement in pediatric rehabilitation. 113 parents (of children 4 months to 18 years, varying in diagnoses) were recruited from standard outpatient/inpatient, early intervention, and life skills programs, sampled from different sites in Canada, the US, and Australia. Parents completed the Pediatric Rehabilitation Intervention Measure of Engagement-Parent version (PRIME-P) twice, after two therapy sessions approximately two weeks apart. Analyses examined factor structure, internal consistency, and test-retest reliability, and assessed construct validity hypotheses concerning participant characteristics and contextual factors. The resulting 11-item PRIME-P has three factors capturing engagement in terms of Plan Appropriateness, Partnering, and Positive Outcome Expectancy. The factors displayed strong internal consistency and test-retest reliability (Partnering demonstrated slightly weaker test-retest reliability). Construct validity was shown by significant associations between the PRIME-P scales and parents' presence versus absence during the sessions, as well as service providers' years of experience. The PRIME-P captures parent engagement as a multifaceted construct involving appropriateness of the therapy plan, a sense of active partnership in the intervention process, and an expectation for a positive outcome. The PRIME-P has promise for research, clinical practice, and educational purposes.IMPLICATIONS FOR REHABILITATIONThe PRIME-P is a psychometrically sound tool that fills a gap in how researchers and practitioners can measure the engagement of parents in the therapy process.To enhance parent engagement, service providers can encourage collaboration in planning, foster a sense of working in partnership, and convey a sense of hope.The findings point to the need to pay attention to parents' beliefs about the therapy plan and outcomes, in addition to their behavioral involvement.The PRIME-P is a promising tool for pediatric rehabilitation that can be used to investigate the role of a crucial, yet poorly understood variable in the therapy process.


Increased survivin expression contributes to apoptosis-resistance in IPF fibroblasts.
Fibroblasts perform critical functions during the normal host response to tissue injury, but the inappropriate accumulation and persistent activation of these cells results in the development of tissue fibrosis. The mechanisms accounting for the aberrant accumulation of fibroblasts during fibrotic repair are poorly understood, although evidence supports a role for fibroblast resistance to apoptosis as a contributing factor. We have shown that TGF-β1 and endothelin-1 (ET-1), soluble mediators implicated in fibrogenesis, promote fibroblast resistance to apoptosis. Moreover, we recently found that ET-1 induced apoptosis resistance in normal lung fibroblasts through the upregulation of survivin, a member of the Inhibitor of Apoptosis (IAP) protein family. In the current study, we sought to determine the role of survivin in the apoptosis resistance of primary fibroblasts isolated from the lungs of patients with Idiopathic Pulmonary Fibrosis (IPF), a fibrotic lung disease of unclear etiology for which there is no definitive therapy. First, we examined survivin expression in lung tissue from patients with IPF and found that there is robust expression in the fibroblasts residing within fibroblastic foci (the "active" lesions in IPF which correlate with mortality). Next, we show that survivin expression is increased in fibroblasts isolated from IPF lung tissue compared to cells from normal lung tissue. Consistent with a role in fibrogenesis, we demonstrate that TGF-β1 increases survivin expression in normal lung fibroblasts. Finally, we show that inhibition of survivin enhances susceptibility of a subset of IPF fibroblasts to apoptosis. Collectively, these findings suggest that increased survivin expression represents one mechanism contributing an apoptosis-resistant phenotype in IPF fibroblasts.


A CDC6 protein-binding peptide selected using a bacterial two-hybrid-like system is a cell cycle inhibitor.
Peptides or small molecules able to modulate protein-protein interactions hold promise as tools with which to probe and manipulate biological pathways. An important issue in this nascent field is to evaluate different methods with which to search libraries for molecules that modulate the function of specific target proteins. One strategy is to screen libraries for molecules that bind specifically to a protein known to be critical in the pathway of interest, with the expectation that the molecules isolated will recognize regions of the target protein important for its function and thereby exhibit biological activity. Here, a peptide library was screened using a two-hybrid-like system for molecules able to bind human CDC6 protein (CDC6p), required for the initiation of DNA replication in eukaryotic cells. From a collection of over a million peptides, a single species that exhibited good affinity and specificity for binding CDC6p was obtained. When expressed in human cells, the peptide inhibited cell cycle progression and exhibited other properties expected of a CDC6p inhibitor. This approach, which does not require detailed knowledge of the mechanism of action of a protein target, may be generally useful for isolating peptides capable of manipulating biological pathways.


4D-QSAR study of HEPT derivatives by electron conformational-genetic algorithm method.
In this work, the EC-GA method, a hybrid 4D-QSAR approach that combines the electron conformational (EC) and genetic algorithm optimization (GA) methods, was applied in order to explain pharmacophore (Pha) and predict anti-HIV-1 activity by studying 115 compounds in the class of 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio) thymine (HEPT) derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs). The series of NNRTIs were partitioned into four training and test sets from which corresponding quantitative structure-activity relationship (QSAR) models were constructed. Analysis of the four QSAR models suggests that the three models generated from the training and test sets used in previous works yielded comparable results with those of previous studies. Model 4, the data set of which was partitioned randomly into two training and test sets with 11 descriptors, including electronical and geometrical parameters, showed good statistics both in the regression (r2(training) )= 0.867, r2test = 0.923) and cross-validation (q (2) = 0.811, q2(ext1) = 0.909, q2(ext2) = 0.909) for the training set of 80 compounds and the test set of 27 compounds. The prediction of the anti-HIV-1 activity of HEPT compounds by means of the EC-GA method allowed for a quantitatively consistent QSAR model. In addition, eight novel compounds never tested experimentally have been designed theoretically using model 4.


Immunoprofile of mucinous non-neoplastic cyst of the pancreas.
A recently described mucinous non-neoplastic cyst (MNNC) of the pancreas is a benign cyst and should be distinguished from mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm (IPMN) due to different management and prognosis. The immunoprofile of MNNC has not been well studied. Twenty-three MNNCs diagnosed on surgical resection were retrieved. Immunohistochemical (IHC) staining was performed on surgically resected specimen. Sixteen IPMN and 15 MCN cases were also retrieved for comparison. Cyst fluid carcinoembryonic antigen and amylase concentrations were retrieved. MNNCs were randomly located in the pancreas and were either unilocular or multilocular cysts that were lined by a single layer of bland columnar or cuboidal mucinous cells and supported by paucicellular stroma. The glandular epithelial cells were diffusely positive for CK7 (100%) and PDX-1 (65%); focally positive for CD10 (superficial, 65%), CD99 (basally, 100%), CDX-2 (17%), and CK20 (4%); and negative for MUC2. Only rare stromal cells in the cyst wall were weakly positive for estrogen receptor or progesterone receptor in only 6% of cases and negative for inhibin. These results were also compared with the immunoprofile of IPMN and MCN. Although MNNC shares some IHC markers with IPMN or MCN, an IHC panel can help distinguish MNNC from IPMN or MCN. The results suggest that MNNC is different from IPMN and MCN.


Oral etoposide in small-cell lung cancer.
Etoposide can be administered orally. On the average, the bioavailability of etoposide administered in a soft gelatin capsule is approximately 50%. For both the oral and intravenous (IV) routes, there is a significant amount of inter- and intrapatient variability. In spite of the variability, clinical studies show that oral etoposide is clearly active in small-cell lung carcinoma (SCLC). In addition, combination chemotherapy studies using etoposide have yielded toxicity equivalent to IV administered programs such as CAV (cyclophosphamide, doxorubicin, vincristine). Oral etoposide has been used in several large combination chemotherapy studies safely and with clear efficacy.


Comparison of Annoyance from Railway Noise and Railway Vibration.
The aim of this study is to compare vibration exposure to noise exposure from railway traffic in terms of equal annoyance, i.e., to determine when a certain noise level is equally annoying as a corresponding vibration velocity. Based on questionnaire data from the Train Vibration and Noise Effects (TVANE) research project from residential areas exposed to railway noise and vibration, the dose response relationship for annoyance was estimated. By comparing the relationships between exposure and annoyance for areas both with and without significant vibration exposure, the noise levels and vibration velocities that had an equal probability of causing annoyance was determined using logistic regression. The comparison gives a continuous mapping between vibration velocity in the ground and a corresponding noise level at the facade that are equally annoying. For equivalent noise level at the facade compared to maximum weighted vibration velocity in the ground the probability of annoyance is approximately 20% for 59 dB or 0.48 mm/s, and about 40% for 63 dB or 0.98 mm/s.


Challenging traditional beliefs: microsurgery for arteriovenous malformations of the basal ganglia and thalamus.
Arteriovenous malformations of the basal ganglia and thalamus are often managed with radiosurgery or observation, without consideration of microsurgery. Given the devastating effects of hemorrhage from these lesions, the accumulating evidence that they bleed more frequently than their lobar counterparts should prompt more creative thinking regarding their management. A review of the endovascular, microsurgical, and radiosurgical literature for arteriovenous malformations of the basal ganglia and thalamus was performed, with close attention to surgical approaches, obliteration rates, and procedure-related complications. A complete resection rate of 91% and a mortality rate of 2.4% were found across surgical series of these lesions. These contrast with a 69% rate of complete obliteration and a 5.3% mortality rate (from latency-period hemorrhage) found when compiling results across the radiosurgical literature. Given an appropriate surgical corridor of access, often afforded by incident hemorrhage, arteriovenous malformations of the basal ganglia and thalamus should be considered for microsurgical extirpation with preoperative embolization. In experienced hands, this approach presents an expeditious and definitive opportunity to eliminate the risk of subsequent hemorrhage and resultant morbidity and mortality.


Loss of potyvirus transmissibility and helper-component activity correlate with non-retention of virions in aphid stylets.
The hypothesis that loss of aphid transmissibility of potyvirus mutants is due to non-retention of virions in the mouthparts was tested by feeding aphids through membranes on purified virions of aphid transmissible (AT or HAT) and non-aphid-transmissible (NAT) tobacco vein mottling virus (TVMV) or tobacco etch virus (TEV), in the presence of functional [potato virus Y (PVY) HC or TVMV HC] or non-functional (PVC HC) helper component (HC). TVMV virions were detected, by electron microscopic examination of immunogold-labelled thin sections, in the food canal or cibarium of 57% of 28 aphids fed on the transmissible combination of TVMV-AT and functional HC, while no virions were found in these structures in 25 aphids fed on the non-transmissible combinations: TVMV-NAT and PVY HC, or TVMV-AT and PVC HC. Autoradiography of intact stylets allowed the examination of much larger numbers of aphids, fed on 125I-labelled TEV; 48% of 523 aphids fed on the TEV-HAT and PVY HC combination retained label in the stylets: this correlated well with the percentage transmission in bioassays. In contrast, in non-transmissible combinations, label was found in the stylets of 0.77% of 389 aphids fed on TEV-NAT and PVY HC, and 1.35% of 223 aphids fed on TEV-HAT and PVC HC. No differences were found in the overall amount of label in the bodies of aphids fed on the transmissible and non-transmissible combinations. There was a strong tendency for virions to be retained in the distal third of the stylets; 56% of aphids positive for TVMV, and 82% of those positive for TEV, had label in this area. These data support the concept that virions retained within the stylets are those that are primarily involved in potyvirus transmission.


A Supramolecular Tetra-Keggin Polyoxometalate
Giant polyoxometalates with catalytic, magnetic, and antiviral properties, which are in part attributable to their structures, are currently of great interest. Herein is described the synthesis and characterization of 1, a structurally novel tetrameric complex from Keggin ions (see picture). This complex is stable under the physiological conditions of the stomach (pH 1-2), which is interesting since related keggin anions are among the least toxic and yet most potent antiviral agents of the more than 300 polyoxometalates investigated biologically and pharmacologically.


Community genetics in the time of next-generation molecular technologies.
Understanding the interactions of co-occurring species within and across trophic levels provides key information needed for understanding the ecological and evolutionary processes that underlie biological diversity. As genetics has only recently been integrated into the study of community-level interactions, the time is right for a critical evaluation of potential new, gene-based approaches to studying communities. Next-generation molecular techniques, used in parallel with field-based observations and manipulative experiments across spatio-temporal gradients, are key to expanding our understanding of community-level processes. Here, we introduce a variety of '-omics' tools, with recent studies of plant-insect herbivores and of ectomycorrhizal systems providing detailed examples of how next-generation approaches can revolutionize our understanding of interspecific interactions. We suggest ways that novel technologies may convert community genetics from a field that relies on correlative inference to one that reveals causal mechanisms of genetic co-variation and adaptations within communities.


Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones.
Rat hepatocytes rapidly incorporate [32P]Pi into phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]; their monoester phosphate groups approach isotopic equilibrium with the cellular precursor pools within 1 h. Upon stimulation of these prelabelled cells with Ca2+-mobilizing stimuli (V1-vasopressin, angiotensin, alpha 1-adrenergic, ATP) there is a rapid fall in the labelling of PtdIns4P and PtdIns(4,5)P2. Pharmacological studies suggest that each of the four stimuli acts at a different population of receptors. Insulin, glucagon and prolactin do not provoke disappearance of labelled PtdIns4P and PtdIns(4,5)P2. The labelling of PtdIns4P and PtdIns(4,5)P2 in cells stimulated with vasopressin or angiotensin initially declines at a rate of 0.5-1.0% per s, reaches a minimum after 1-2 min and then returns towards the initial value. The dose-response curves for the vasopressin- and angiotensin-stimulated responses lie close to the respective receptor occupation curves, rather than at the lower hormone concentrations needed to evoke activation of glycogen phosphorylase. Disappearance of labelled PtdIns4P and PtdIns(4,5)P2 is not observed when cells are incubated with the ionophore A23187. The hormone-stimulated polyphosphoinositide disappearance is reduced, but not abolished, in Ca2+-depleted cells. These hormonal effects are not modified by 8-bromo cyclic GMP, cycloheximide or delta-hexachlorocyclohexane. The absolute rate of polyphosphoinositide breakdown in stimulated cells is similar to the rate previously reported for the disappearance of phosphatidylinositol [Kirk, Michell & Hems (1981) Biochem. J. 194, 155-165]. It seems likely that these changes in polyphosphoinositide labelling are caused by hormonal activation of the breakdown of PtdIns(4,5)P2 (and may be also PtdIns4P) by the action of a polyphosphoinositide phosphodiesterase. We therefore suggest that the initial response to hormones is breakdown of PtdIns(4,5)P2 (and PtdIns4P?), and that the simultaneous disappearance of phosphatidylinositol might be a result of its consumption for the continuing synthesis of polyphosphoinositides.


Staphylococcus aureus carriage among GPs in The Netherlands.
The extent to which GPs serve as a reservoir for antibiotic-resistant Staphylococcus aureus is unknown and not well studied. To determine the prevalence of nasal S. aureus carriage among GPs in the Netherlands, as well as the antimicrobial resistance and the genotypes of isolated S. aureus. Observational, point-prevalence, and cross-sectional study. GPs attending the annual conference of the Dutch College of General Practitioners in 2006. Nasal swabs were randomly taken from 395 GPs and analysed for the presence of S. aureus. Antimicrobial susceptibility was determined by a microbroth dilution method and the genotypes by spa typing, which was associated with multilocus sequence typing. Of the GPs, 129/395 (33%; 95% confidence interval [CI] = 28 to 37%) were carriers of S. aureus. No meticillin-resistant S. aureus (MRSA) was found. Resistance was observed to penicillin (71%; 95% CI = 63 to 79%), fusidic acid (7%; 95% CI = 3 to 13%), and clarithromycin (6%; 95% CI = 3 to 12%). In 72% of the isolates, an MRSA-related genotype of S. aureus was found. The low antibiotic resistance found among S. aureus of GPs suggests that GPs are not a reservoir of antibiotic-resistant S. aureus strains. The relatively high resistance to fusidic acid, which has not previously been described in the Netherlands and is mostly because of antibiotic use, suggests that patients infect GPs and not the other way round. GPs may be at risk for nasal carriage of S. aureus with an MRSA-related genotype.


Stopping a Response When You Really Care about the Action: Considerations from a Clinical Perspective.
Response inhibition, whether reactive or proactive, is mostly investigated in a narrow cognitive framework. We argue that it be viewed within a broader frame than the action being inhibited, i.e., in the context of emotion and motivation of the individual at large. This is particularly important in the clinical domain, where the motivational strength of an action can be driven by threat avoidance or reward seeking. The cognitive response inhibition literature has focused on stopping reactively with responses in anticipation of clearly delineated external signals, or proactively in limited contexts, largely independent of clinical phenomena. Moreover, the focus has often been on stopping efficiency and its correlates rather than on inhibition failures. Currently, the cognitive and clinical perspectives are incommensurable. A broader context may explain the apparent paradox where individuals with disorders characterised by maladaptive action control have difficulty inhibiting their actions only in specific circumstances. Using Obsessive Compulsive Disorder as a case study, clinical theorising has focused largely on compulsions as failures of inhibition in relation to specific internal or external triggers. We propose that the concept of action tendencies may constitute a useful common denominator bridging research into motor, emotional, motivational, and contextual aspects of action control failure. The success of action control may depend on the interaction between the strength of action tendencies, the ability to withhold urges, and contextual factors.


Driven to tiers: socioeconomic and racial disparities in the quality of nursing home care.
Nursing home care is currently a two-tiered system. The lower tier consists of facilities housing mainly Medicaid residents and, as a result, has very limited resources. The nearly 15 percent of U.S. nonhospital-based nursing homes that serve predominantly Medicaid residents have fewer nurses, lower occupancy rates, and more health-related deficiencies. They are more likely to be terminated from the Medicaid/Medicare program, are disproportionately located in the poorest counties, and are more likely to serve African-American residents than are other facilities. The public reporting of quality indicators, intended to improve quality through market mechanisms, may result in driving poor homes out of business and will disproportionately affect nonwhite residents living in poor communities. This article recommends a proactive policy stance to mitigate these consequences of quality competition.


[Lymphomatoid papulosis in an 8-month-old child. 9-year remission].
We report a case of lymphomatoid papulosis remarkable for its unusually early onset and spontaneous remission which has now lasted for 9 years.


Inability to walk due to scurvy: A forgotten disease.
Scurvy has become rare in modern societies, but should be considered in malnourished persons, alcoholics, and in infants on unsupplemented milk diets who present with musculoskeletal pain or a bleeding tendency. The diagnosis of scurvy can be challenging because of the rare incidence and vague and nonspecific early symptoms. We report here a case of scurvy in a young boy who presented with an inability to walk and severe musculoskeletal pain. The diagnosis was established based on his clinical picture, radiological appearance, and low serum level of vitamin C. The patient responded well to vitamin C supplementation with full resolution of his symptoms. He regained his ability to walk and his family was happy and satisfied with the outcome of treatment. Although the incidence of scurvy has become low in Saudi Arabia, it can still occur and early recognition is important because of the excellent prognosis.


Doctors as decision-makers: a computer-assisted study of diagnosis as a cognitive skill.
When viewed as a sequence of decisions clinical diagnosis becomes amenable to detailed investigation in terms of standard statistical concepts. A study of six clinicians diagnosing identical sets of cases of non-toxic goitre is used to illustrate an objective technique for studying the diagnostic process with the aid of a digital computer. Considerable variation in clinicians' routes to correct diagnosis is shown when these routes are compared in detail by five statistical measures related to the effective use of the information available to the clinicians. For rapid analysis of diagnostic skill two visual methods are presented. These can be developed for teaching undergraduates the interpretative skills involved in diagnosis and for studying such skills in experienced clinicians.


Lipoxin A4 and its analogue suppress the tumor growth of transplanted H22 in mice: the role of antiangiogenesis.
Tumor angiogenesis plays an essential role in carcinogenesis, cancer progression, and metastasis. Some studies indicate that lipoxins, endogenous anti-inflammatory lipid mediators, might be involved in tumor angiogenesis; however, the governing mechanisms are still unknown. In the present study, we examined the effects of exogenous lipoxin A(4) (LXA(4)) in mouse hepatocarcinoma cell line (H22) and H22-bearing mice model. It was found that in H22 cells, LXA(4) inhibited the production of vascular endothelial growth factor and reduced hypoxia-inducible factor-1 alpha level. In addition, its analogue, BML-111, blocked the expression of vascular endothelial growth factor in serum and tumor sections from H22-bearing mice. H&E staining and immunostaining with antibodies against CD34 revealed that BML-111 suppressed tumor-related angiogenesis in vivo, but LXA(4) could not influence the proliferation of primary cultured human umbilical vein endothelial cells. The tumor growth was also inhibited by BML-111. We also found that BML-111 enhanced the in situ apoptosis while inhibiting macrophage infiltration in tumor tissue. The results provide new evidence that LXA(4) suppresses the growth of transplanted H22 tumor in mice through inhibiting tumor-related angiogenesis.


Zn-Promoted C-H Reductive Elimination and H2 Activation via a Dual Unsaturated Heterobimetallic Ru-Zn Intermediate.
Reaction of [Ru(PPh3)3HCl] with LiCH2TMS, MgMe2, and ZnMe2 proceeds with chloride abstraction and alkane elimination to form the bis-cyclometalated derivatives [Ru(PPh3)(C6H4PPh2)2H][M'] where [M'] = [Li(THF)2]+ (1), [MgMe(THF)2]+ (3), and [ZnMe]+ (4), respectively. In the presence of 12-crown-4, the reaction with LiCH2TMS yields [Ru(PPh3)(C6H4PPh2)2H][Li(12-crown-4)2] (2). These four complexes demonstrate increasing interaction between M' and the hydride ligand in the [Ru(PPh3)(C6H4PPh2)2H]- anion following the trend 2 (no interaction) < 1 < 3 < 4 both in the solid-state and solution. Zn species 4 is present as three isomers in solution including square-pyramidal [Ru(PPh3)2(C6H4PPh2)(ZnMe)] (5), that is formed via C-H reductive elimination and features unsaturated Ru and Zn centers and an axial Z-type [ZnMe]+ ligand. A [ZnMe]+ adduct of 5, [Ru(PPh3)2(C6H4PPh2)(ZnMe)2][BArF4] (6) can be trapped and structurally characterized. 4 reacts with H2 at -40 °C to form [Ru(PPh3)3(H)3(ZnMe)], 8-Zn, and contrasts the analogous reactions of 1, 2, and 3 that all require heating to 60 °C. This marked difference in reactivity reflects the ability of Zn to promote a rate-limiting C-H reductive elimination step, and calculations attribute this to a significant stabilization of 5 via Ru → Zn donation. 4 therefore acts as a latent source of 5 and this operational "dual unsaturation" highlights the ability of Zn to promote reductive elimination in these heterobimetallic systems. Calculations also highlight the ability of the heterobimetallic systems to stabilize developing protic character of the transferring hydrogen in the rate-limiting C-H reductive elimination transition states.


Status report on DOTS expansion and implementation during the 2nd quarter 2004 (April-June 2004).
DGHS, MoHFW gives a status report on DOTS expansion and implementation during the 2nd quarter 2004 inviting co-operation from all sectors to reach the target of covering the entire country under DOTS by 2005.


Ethanol extract of Cirsium japonicum attenuates hepatic lipid accumulation via AMPK activation in human HepG2 cells.
One of the most common causes of chronic liver disease, nonalcoholic fatty liver disease (NAFLD), is strongly associated with obesity and dysregulated insulin action in the liver. However, there are no pharmacological agents currently established for the treatment of NAFLD. A flowering plant in the Asteraceae family, Cirsium japonicum (CJ), exhibits a variety of pharmacological and antioxidative properties that promote hepatoprotection. In the present study, CJ ethanol extract was shown to reduce hepatic triglyceride (TG) and cholesterol accumulation. CJ significantly increased AMP-activated protein kinase (AMPK) phosphorylation in HepG2 hepatocytes and downregulated the level of the target genes, acetyl-CoA carboxylase and fatty acid synthase. In addition, CJ upregulated the expression of carnitine palmitoyltransferase-1, which is involved in fatty acid oxidation. The results of the present study indicated that the positive effects of CJ extract on high-fat diet-induced hepatic TG accumulation were mediated via the AMPK signaling pathway, indicating a potential target for the preventative treatment of NAFLD.


Prognostic Utility of the Glasgow Prognostic Score for the Long-Term Outcomes After Liver Resection for Intrahepatic Cholangiocarcinoma: A Multi-institutional Study.
The usefulness of the modified Glasgow prognostic score (GPS) as a prognostic tool remains unclear for patients undergoing curative surgery for intrahepatic cholangiocarcinoma (ICC). Therefore, this study investigated the prognostic usefulness of the GPS for patients who underwent ICC surgery. All ICC patients who had a curative-intent hepatectomy at 17 institutions between 2000 and 2016 were included. The correlation was assessed between the preoperative GPS and the baseline characteristics of the patients, histopathological parameters, surgical parameters, and the postresection overall survival (OS). There were 273 patients who met the eligibility criteria between the years 2000 and 2016. The postoperative OS rates at 1, 3, and 5 years were 83.8%, 56.3%, and 41.5%, respectively (median OS, 47.7 months). A multivariate analysis revealed the factors that were associated with a worse OS, which included an increased GPS (hazard ratio = 1.62; 95% confidence interval [CI]: 1.01-2.53; P = 0.03), an elevated carcinoembryonic antigen level (hazard ratio = 1.60; 95% CI: 1.06-2.41; P = 0.02), an elevated carbohydrate antigen 19-9 level (hazard ratio = 1.55; 95% CI: 1.05-2.30; P = 0.03), undifferentiated carcinoma (hazard ratio = 2.41; 95% CI: 1.56-3.67; P < 0.01), and positive metastasis to the lymph nodes (hazard ratio = 2.54; 95% CI: 1.76-3.67; P < 0.01). In ICC patients after a hepatectomy, an elevated GPS was associated with poorer OS, even if the tumour factors that affected GPS were eliminated by propensity-score matching. Preoperative GPS can be useful to predict the postoperative outcomes of ICC patients. Therefore, this relatively simple and inexpensive scoring system can be utilized to further refine patient stratification as well as to predict survival.


Treating Benign Paroxysmal Positional Vertigo in the Patient With Traumatic Brain Injury: Effectiveness of the Canalith Repositioning Procedure.
The aim of this study was to determine the effectiveness of the canalith repositioning procedure (CRP) in the treatment of benign paroxysmal positional vertigo (BPPV) among patients after mild-to-moderate traumatic brain injury. An unblinded, nonrandomized, case comparison interventional study with repeated measures (1, 5, 9, and 12 weeks postenrollment) of three groups of patients with traumatic brain injury (BPPV, n = 21; nonspecific dizziness, n = 23; no dizziness, n = 12) was conducted. Patients in the BPPV group received the CRP at baseline and repeatedly until a negative Dix-Hallpike Maneuver was observed. Participants in the other two groups did not receive the CRP. Symptom resolution at the 12-week follow-up was observed in 75% of patients in the BPPV group versus 8.3% in the nonspecific dizziness group (p = .0006). A significant Group × Time interaction was observed for the Dizziness Handicap Inventory (F = 4.2, p = .003) and 36-item Short Form Health Questionnaire physical component scores (F = 2.16, p = .035) with the BPPV group showing significantly improved scores by the 12-week follow-up. Although there were between-group differences on the 36-item Short Form Health Questionnaire mental health component scores (F = 4.06, p = .022), changes over time were not significant in the groups. Treatment with the CRP for posttraumatic BPPV resulted in significant symptom resolution and improvement in perceived physical health status.


An adaptive multi-stage phase I dose-finding design incorporating continuous efficacy and toxicity data from multiple treatment cycles.
Phase I designs traditionally use the dose-limiting toxicity (DLT), a binary endpoint from the first treatment cycle, to identify the maximum-tolerated dose (MTD) assuming a monotonically increasing relationship between dose and efficacy. In this article, we establish a general framework for a multi-stage adaptive design where we jointly model a continuous efficacy outcome and continuous/quasi-continuous toxicity endpoints from multiple treatment cycles. The normalized Total Toxicity Profile (nTTP) is used as an illustration for quasi-continuous toxicity endpoints, and we replace DLT with nTTP to take into account multiple grades and types of toxicities. In addition, the proposed design accommodates non-monotone dose-efficacy relationships, and longitudinal toxicity data in effort to capture the adverse events from multiple cycles. Stage 1 of our design uses toxicity data to perform dose-escalation and identify a set of initially allowable (safe) doses; stage 2 of our design incorporates an efficacy outcome to update the set of allowable doses for each new cohort and randomizes the new cohort of patients to the allowable doses with emphasis towards those with higher predicted efficacy. Stage 3 uses all data from all treated patients at the end of the trial to make final recommendations. Simulations showed that the design had a high probability of making the correct dose selection and good overdose control across various dose-efficacy and dose-toxicity scenarios. In addition, the proposed design allows for early termination when all doses are too toxic. To our best knowledge, the proposed dual-endpoint dose-finding design is the first such study to incorporate multiple cycles of toxicities and a continuous efficacy outcome.


Increased coagulation factor levels leading to allograft renal vein thrombosis.
A patient with end-stage kidney disease is described, who lost his renal allograft in the early post-transplant period due to allograft renal vein thrombosis. Prior to transplantation, he had been treated by hemodialysis and lost several vascular accesses because of thrombosis. A search for potential thrombophilic factors disclosed a unique combination of increased clotting factor levels, i.e. FVIII, FIX, FXI and homocysteine. More common hereditary and acquired hypercoagulability factors have been excluded in this patient. While clotting factor deficiencies are well known causes of hemophilia, their levels should also be measured in the workup of transplant candidates with a history of multiple vascular access thrombosis.


The steady-state kinetics of yeast phosphoglycerate kinase. Anomalous kinetic plots and the effects of salts on activity.
1. A re-investigation of the kinetics of yeast phosphoglycerate kinase in the direction of 1,3-bisphosphoglycerate formation has been carried out, covering a 1000-fold range in substrate concentrations. A variety of improved spectrophotometric and fluorimetric assay procedures have been used. 2. Kinetic plots proved to be non-linear for each variable substrate. A variety of checks have been carried out to show that this is not due to artifacts in the assay procedures or heterogeneity of the enzyme preparation. 3. The effects of a variety of salts on the activity of the enzyme have been examined. Most salts, especially those with multivalent anions, can cause activation of the enzyme, but inhibit at high concentration. 4. The salt effect is shown to be principally due to anions rather than cations, and not to ionic strength changes. Sulphate, as one of the most effective anions has been used in most comparisons. 5. Salt activation is steepest when the substrate concentrations are low; maximum activation has been about 5-fold with 0.2 mM MgATP and 0.2 mM 3-phosphoglycerate. Inhibition at the higher salt concentrations is strongest at the same substrate concentrations as when activation is steepest, indicating a link between the two effects. 6. The presence of 20 mM or more Na2SO4 converted non-linear kinetic plots to linear ones. A study of the kinetics in the presence of 40 mM Na2SO4 was interpreted in terms of a random sequential binding mechanism, with sulphate acting as a competitive inhibitor. 7. Possible explanations for these anomalous results are discussed in terms of several mechanisms which have been shown to apply in other systems.


[Comparison of 2 techniques for inhaled anesthetic induction with sevoflurane in coronary artery revascularization].
Our objective was to evaluate efficacy, side effects, and hemodynamic alterations during anesthetic induction with sevoflurane in patients undergoing coronary artery bypass surgery, comparing the techniques of administration with tidal volume breathing and with vital capacity breaths. This was a randomized controlled trial enrolling 30 patients scheduled for myocardial revascularization. Anesthetic induction with inhaled sevoflurane was performed with 2 techniques: sevoflurane administered with tidal volume breathing (n=15) and with vital capacity breaths (n=15). We assessed time until a bispectral index (BIS) of 50 or less was reached. We also recorded adverse effects and alterations in hemodynamic variables during induction. The time to induction was significantly shorter in the tidal volume group. The time until reaching a BIS of 50 or less was significantly shorter in the vital capacity group. Hemodynamics were similar in both groups (no significant differences). In both groups mean arterial pressure decreased significantly from baseline (P<0.05) and systolic and diastolic blood pressures both decreased slightly, with no significant heart rate or ST segment changes. Adverse effects were few and not serious. Mean arterial pressure decreased in both groups, with no significant differences. The results indicate that hemodynamic stability seems to be similar with both techniques for providing inhaled anesthetic induction with sevoflurane.


[Regional infection control network in limited resource hospitals].
There are many hospitals and clinics in Japan. However, a large number comprise small-scale facilities that do not have a specialist in the management of contagious diseases or bacteriological testing facilities. Although foundation hospitals such as university hospitals have the materials and human resources to provide measures to prevent infection from communicable diseases, taking such preventative measures is a huge burden on smaller institutions. Treatment in large hospitals differs from that in small and medium-sized institutions, and, in some cases, the two may not require the same measures. In the future it will be necessary to devise and implement measures to prevent the transmission of disease in various types of medical treatment facility according to their individual circumstances. This will require pre and post-graduate education concerning communicable diseases and measures for the prevention of their transmission, as well as utilizing a regional network for transmission prevention involving government and the private sector.


Mechanisms for enhanced feeding in the cold in rats.
The effect of environmental cold upon feeding, food-motivated behavior, and gastric clearance of food was studied in rats. Rats ate liquid diet in either a 5 degrees C or 22 degrees C ambient temperature (TA) following (a) 24-hr food deprivation at TA of either 5 or 22 degrees C, or (b) 0- or 48-hr food deprivation at TA 22 degrees C. Rats ate more at 5 degrees C than at 22 degrees C regardless of the ambient temperature during deprivation. Rats increased feeding in the cold by increasing meal frequency but not meal size. Cold (5 degrees C) TA also enhanced the urge to eat. Rats bar pressed for food more often in the cold TA on a variable interval 30-sec schedule when gastric clearance of food was prevented by a pyloric noose and when food cleared from the stomach normally. Also, quinine adulteration of food suppressed food intake only in the 22 degrees C TA. Cold (5 degrees C) TA enhanced gastric clearance of liquid food within 20 min of ingestion. These results support the view that the peripheral sensation of cold is an adequate stimulus for feeding and that cold TA can stimulate feeding directly by increasing the urge to eat and indirectly, secondary to increased gastric clearance.


Affective disorders and aggression disorders: evidence for a common biological mechanism.
Ever since the discovery that the classical antidepressants--tricyclics and MA oxidase inhibitors--exert an influence on central 5-HT, this neurotransmitter has been studied in depression, particularly in those forms responsive to this type of treatment. This chapter reviews the evidence in favor of a relationship between depression and central 5-HT dysfunctions. Most of the findings have been derived from patients with depression as the principal diagnosis. Some data have originated from patients suffering from a somatic illness and from depression as well. Both peripheral and central data are discussed. Although no single 5-HT-related finding in depression has so far been unequivocally established, the available evidence, in balance, justifies the tentative conclusion that disturbances in 5-HT metabolism can occur in depression. Lowered CSF 5-HIAA, the major indicator of disturbed central 5-HT metabolism in depression, has also been reported in aggression disorders, both in patients who had committed suicidal acts and in those with outward-directed aggression. The finding can not be explained by a concomitant state of depression. Rather than to discard the classical 5-HT-depression hypothesis, in favor of a 5-HT-aggression hypothesis, the hypothesis is launched that disturbances in serotonergic regulation can give rise to both mood and aggression disorders. This would provide a biological explanation for the clinical observation that those disorders frequently go hand in hand.


Use of the enzyme-linked immunosorbent assay to detect serum antibody responses of volunteers who received attenuated influenza A virus vaccines.
Sera from volunteers who received live influenza A wild-type or ts recombinant virus were tested by hemagglutination inhibition (HI) assay, neuraminidase inhibition (NI) assay, and the enzyme-linked immunosorbent assay (ELISA) to determine which assay system was the most sensitive in detecting an immunological response to infection. The ELISA was performed with inactivated whole virus antigen, and the optical density at each of five serial twofold dilutions of pre- and postimmunization sera was measured. The difference in the amount of ELISA antibody in pre- and postinoculation serum specimens was taken to be proportional to the area between the respective titration curves. The ELISA was more sensitive than the HI or NI test in detecting a seroresponse in volunteers infected with A/Hong Kong/123/77 (H1N1), A/New Jersey/8/76 (Hswine N1), or A/Alaska/6/77 (H3N2) ts recombinant virus. These results suggest that the ELISA should be used to determine the frequency of infection with attenuated viruses as well as the 50% human infectious dose of candidate live influenza A vaccine viruses.


Emergency surgery admissions and the COVID-19 pandemic: did the first wave really change our practice? Results of an ACOI/WSES international retrospective cohort audit on 6263 patients.
The COVID-19 pandemic is having a deep impact on emergency surgical services, with a significant reduction of patients admitted into emergency surgical units world widely. Reliable figures of this reduction have not been produced yet. Our international audit aimed at giving a precise snapshot of the absolute and relative changes of emergency surgical admissions at the outbreak of the pandemic. Datasets of patients admitted as general surgical emergencies into 45 internationally distributed emergency surgical units during the months of March and April 2020 (Covid-19 pandemic outbreak) were collected and compared with those of patients admitted into the same units during the months of March and April 2019 (pre-Covid-19). Primary endpoint was to evaluate the relative variation of the presentation symptoms and discharge diagnoses between the two study periods. Secondary endpoint was to identify the possible change of therapeutic strategy during the same two periods. Forty-five centres participated sent their anonymised data to the study hub, for a total of 6263 patients. Of these, 3810 were admitted in the pre-Covid period and 2453 in the Covid period, for a 35.6% absolute reduction. The most common presentation was abdominal pain, whose incidence did not change between the two periods, but in the Covid period patients presented less frequently with anal pain, hernias, anaemia and weight loss. ASA 1 and low frailty patients were admitted less frequently, while ASA>1 and frail patients showed a relative increase. The type of surgical access did not change significantly, but lap-to-open conversion rate halved between the two study periods. Discharge diagnoses of appendicitis and diverticulitis reduced significantly, while bowel ischaemia and perianal ailments had a significant relative increase. Our audit demonstrates a significant overall reduction of emergency surgery admissions at the outbreak of the Covid-19 pandemic with a minimal change of the proportions of single presentations, diagnoses and treatments. These findings may open the door to new ways of managing surgical emergencies without engulfing the already busy hospitals.


[Clinical and X-ray diagnosis of initial degenerative changes in the lumbar section of the spine in flight personnel].
The paper demonstrates the diagnostic validity of X-ray computerized and magnetic/resonance tomographies in detecting early degenerative/dystrophic processes in the lumbar compartment of vertebrae in flying personnel. Examination of 215 aviators with varying degrees of impairment of the vertebrae-pelvis-lower extremity biokinematic system allowed to relate protrusions of the intervertebral disks. Correlation between the neurologic pattern of disease and different forms of protrusions was studied. Pathogenesis of the radiculopathy syndrome was made more clear. Potentials of the X-ray computerized and magnetic/resonance tomographies were given a comparative analysis. As was established, the two methods are not mutually exclusive. MRI is more advantageous in the diagnosis of degenerative/dystrophic changes in soft a tissue structures. On the other hand, the X-ray computerized tomography is preferable for visualization of changes in highly dense tissues. Semiotics of processes articularis arthrosis was studied. Discovered were X-ray detectable morphological signs of arthrosis which had never been discussed in literature. Main strategies of medical treatment of patients with various forms of protrusions are proposed.


A novel VARS2 gene variant in a patient with epileptic encephalopathy.
Background: Mitochondrial disorders are heterogeneous clinical syndromes caused by defective activity in the mitochondrial respiratory chain, resulting in a faulty oxidative phosphorylation system. These inherited disorders are individually rare, and furthermore they are phenotypic variables. The genetically characterized mitochondrial disorders are rarely associated with epileptic encephalopathies.Case presentation: We present the clinical phenotype, biochemical analysis, and electrographic and neuro-radiological features of a 5-month-old girl with epileptic encephalopathy, microcephaly, severe psychomotor delay, hypertrophic cardiomyopathy, and abnormal MRI scan. Using whole-genome sequencing technique, compound heterozygous mutations of the VARS2 gene were revealed, with one previously unreported frameshift mutation.Conclusion: Our report extends the phenotypic spectrum of VARS2-related disorders with an initial presentation of epileptic encephalopathy and early death due to malignant arrhythmia.


Guide for the practical application of the ICRP Human Respiratory Tract Model. A report of ICRP supporting guidance 3: approved by ICRP committee 2 in October 2000.
The ICRP Publication 66 Human Respiratory Tract Model for Radiological Protection (HRTM) has been applied to calculate dose coefficients (doses per unit intake) and bioassay functions in ICRP Publications 68, 71, 72 and 78. For these purposes, ICRP assigned numerical values to a range of model parameters, such as the size of the inhaled particles and the breathing rate of the subjects. These are known as 'default' or 'reference' values, and were chosen to be typical, representative values. In any particular situation the actual values of many parameters can be considerably different from the reference values. Usually, doses from intakes of radionuclides are low compared with the relevant limit or constraint, and the resulting difference is unimportant. There are, however, circumstances where more reliable assessments of intake and dose are desirable. This Guidance Document therefore gives advice on applying specific information within the framework of the HRTM for assessing occupational and environmental exposures and for interpreting bioassay data. Chapters on each aspect of the model (morphometry, physiology, deposition, clearance, gases and vapours, dosimetry) provide: A summary of how the HRTM treats that topic;Information on the reference values of relevant parameters;Guidance on choosing between default values;Information on how doses and bioassay quantities (lung retention, urine, and faecal excretion) vary with the values of selected parameters, giving guidance on the importance of obtaining specific information;Simple examples of the use of specific information relating to the topic.Annexes give additional information for those directly involved in applying the HRTM to specific situations, including guidance on obtaining parameter values. A brief overview is given of the deposition, characterisation, and sampling of aerosols, with references to further information, as there are relevant text books already available. Issues specific to radioactive aerosols, such as low particle number concentrations for high specific activity materials are, however, addressed. Guidance on obtaining information about absorption of inhaled radionuclides into blood is given in greater detail, because this is a topic on which ICRP has traditionally given guidance, and because a compilation of such information is not readily available elsewhere. Several detailed examples are also provided. One involves assessment of an individual's intake and committed dose from comprehensive bioassay monitoring data. The others deal with the derivation of HRTM absorption parameter values from experimental data, and their application, with additional information on e.g. size distribution, to calculate dose coefficients and interpret bioassay data.


MELD and other factors associated with survival after liver transplantation.
Allocation of cadaveric livers for transplantation in the United States is now based on the severity of illness as determined by the model for end-stage liver disease (MELD) score, a function of bilirubin, creatinine and international normalized ratio (INR). The aim of our study was to determine the association of various pre-transplant risk factors, including the MELD score, on patient survival after orthotopic liver transplantation (OLT). The medical records of 499 consecutive patients (233 female, 266 males, mean age 50.9 +/- 10.6 years) undergoing cadaveric OLT at our institution between June 1990 and February 1998 were reviewed. In the 407 patients alive at the latest contact, follow-up was 4.7 years, with a minimum of 20 months (maximum of 9.4 years). Variables considered for analysis included MELD score, age, pre-transplant renal dysfunction requiring dialysis, Child-Pugh classification, underlying liver disease, diabetes mellitus, and heart disease (ischemic/valvular/other). There were 92 deaths during follow-up. In univariate analysis, the MELD score, renal failure requiring hemodialysis pre-OLT, age > 42 years, and underlying etiology of liver disease were significantly associated with death during long-term follow-up. In multivariate models, age, underlying etiology of liver disease and renal failure requiring hemodialysis were independent predictors of death after OLT.


Is There a Clinically Meaningful Change in the Blood Pressure of Osteoarthritis Patients with Comorbid Hypertension During the Course of Balneotherapy?
Balneotherapy (BT) is a treatment modality that uses the physical and chemical effects of water, including thermomineral, acratothermal, and acratopegal waters. It has many effects on cardiovascular system. The aim of the study is to investigate the effects of 3-week BT on blood pressure of osteoarthritis (OA) patients with no hypertension (HT), and controlled or uncontrolled HT. The OA patients (n = 270) were divided into three groups: No HT, controlled HT, and uncontrolled HT. All the groups received BT in the facilities of our university hospital at the same time every day (10:00-11:30 AM) for 10 min per day, 5 days per week, for a total duration of 15 days in a 3-week period. Systolic and diastolic blood pressures and pulse rates were measured before and after BT on daily basis. Overall, (1) the pulse rates of study groups measured after BT were significantly increased compared to before BT; (2) the systolic blood pressures of study groups measured before and after BT were found as comparable; and (3) the diastolic blood pressures of no HT and controlled HT groups measured before and after BT were not statistically significant (P > 0.05); however, in the uncontrolled HT group, the diastolic blood pressure showed a decreasing trend after BT (P < 0.05). In patients with OA, BT can be safely used without resulting in any meaningful changes in systolic and diastolic blood pressures in patients with normal and controlled HT but a decrease in diastolic blood pressure of patients with uncontrolled HT. This may be an advantage in OA patients having HT as comorbid disease.


RAT ELECTRORETINOGRAM: EVIDENCE FOR SEPARATE PROCESSES GOVERNING B-WAVE LATENCY AND AMPLITUDE.
Studies of the simultaneous changes in the latency and amplitude of the b-wave of the rat electroretinogram (ERG) under three different conditions of adaptation show that the latency is primarily a function of the absolute stimulus intensity, being only slightly affected by conditions that strongly reduce the amplitude. This implies that the latency and the amplitude are determined by two independent processes, with the latency-process more closely linked to the initial photochemical events. Furthermore, the different adaptation conditions have surprisingly similar effects on the shape and amplitude of the electroretinogram, which suggests that they all produce only one type of variation in the amplitudedetermining process.