Long-Term Effect of Endoscopic Evacuation for Large Basal Ganglia Hemorrhage With GCS Scores ≦ 8.
Aims: The surgical evacuation, including stereotactic aspiration, endoscopic evacuation, and craniotomy, is the most effective way to reduce the volume of intracerebral hemorrhage. However, credible evidence for the effects of these techniques is still insufficient. The present study explored the long-term outcomes of these techniques in the treatment of basal ganglia hematoma with low Glasgow Coma Scale (GCS) scores (≤8) and large-volume (≥40 ml), which were predictors of high mortality. Methods: Two hundred and fifty-eight consecutive patients were reviewed retrospectively. The primary and secondary outcomes were 6-months mortality and 6-months modified Rankin Scale score, which were assessed by a multivariate logistic regression model. Results: Compared with the endoscopic evacuation group, the mortality was significantly higher in the stereotactic aspiration group (OR 6.858, 95% CI 3.146-14.953) and open craniotomy group (OR 3.315, 95% CI 1.497-7.341). Age (OR = 2.237, 95% CI 1.290-3.877) and herniation (OR = 2.257, 95% CI 1.172-4.348) were independent predictors for mortality. No significant difference in the neurological functional outcome was found in the stereotactic aspiration group (OR 0.501, 95% CI 0.192-1.308) and the craniotomy group (OR 0.774, 95% CI 0.257-2.335) compared with the endoscopic evacuation group. Conclusion: Endoscopic evacuation significantly decreased the 6-months mortality in patients with hemorrhage ≥40 ml and GCS ≤ 8.


Self-reported symptoms among Danish women following cosmetic breast implant surgery.
The aim of this study was to examine self-reported symptomatology and to identify distinctive characteristics among women with silicone breast implants (SBI). Using the Danish hospital and population registers we identified three groups of women with a hospital diagnosis of muscular rheumatism (a nonspecific soft-tissue diagnostic code) who had previously undergone SBI surgery (n = 28), breast reduction surgery (n = 29) or no breast surgery (n = 27); and three groups of women without a diagnosis of muscular rheumatism who had undergone SBI surgery (n = 21), breast reduction surgery (n = 27) or no breast surgery (n = 56). All study subjects completed a self-administered questionnaire focusing on sociodemographic factors, lifestyle habits, somatic symptoms and psychological symptoms. Women with SBI and women with breast reduction with no previous diagnosis of muscular rheumatism had similar patterns of reporting for most symptoms and characteristics. They reported significantly more somatic symptoms and psychological distress, including somatisation, obsessive-compulsiveness and depression, than women with no breast surgery. No significant differences in self-reported symptomatology and characteristics were observed among the three groups of women with a previous diagnosis of muscular rheumatism. Overall, women with prior muscular rheumatism reported more symptoms than those without. We concluded that self-reported somatic symptoms among women with SBI were similar to those of controls. Women with cosmetic breast surgery appear to have distinctive psychological characteristics. Our study emphasises the importance of taking the psychological profile and previous history of rheumatic diseases into account when examining women with SBI.


The effect of proboscis and corolla tube lengths on patterns and rates of flower visitation by bumblebees.
The rates at which bumblebees of different proboscis lengths forage on flowers of a series of corolla tube lengths were determined. The results indicate significant correlations between proboscis length and time spent by bees on flowers. Bumblebees of long proboscis length can forage significantly faster than bees of shorter proboscis length on flowers with long corolla tubes. There is also evidence which suggests that bumblebees of short proboscis length prefer and are more efficient on short corolla tubes. These results support the use of proboscis length as a morphological indicator of resource utilization in bumblebees.


The effectiveness of helmets in reducing all-terrain vehicle injuries and deaths.
This article examines the effectiveness of helmets in reducing all-terrain vehicle (ATV) related deaths and head injuries, conditional on the occurrence of injury producing accidents. A logit regression model is used to analyze cross-section data on ATV-related fatal and nonfatal injuries, and to determine the factors that are associated with deaths and head injuries. The results suggest that, given an accident resulting in injury or death, helmet use reduces the risk of death by about 42%, and could reduce the likelihood that a given nonfatal injury involves the head by about 64%. Other factors that are associated with the risk of fatality for injury accidents include the use of alcohol or drugs, driving on paved roads, the driver's age and sex, and the vehicle's engine size. A benefit-cost analysis of helmet use is conducted and policy implications are discussed.


Favorable response to analgesics does not predict a benign etiology of headache.
Distinguishing between primary and secondary headaches (HAs) is essential for the safe and effective management of patients with HA. A favorable response to analgesics may be observed with both classes of HAs and therefore is not a good predictor of who needs further evaluation. To systematically review the data that a favorable response to analgesics including triptans should not be used to exclude a serious secondary cause of HA. PubMed search of English-language articles between 1980 and 2007 and reference lists of these articles. Two authors independently reviewed articles for study results and quality. Inclusion was based on 100% agreement between authors. We included articles that described secondary HAs as (1) having a favorable response to analgesics and/or (2) having a favorable response to sumatriptan. Of the 548 studies identified by our search strategy, 18 were included in our final analysis. Seven of the 18 studies found that 46/103 patients (44%) described a significant or complete resolution of secondary HA from medications such as anti-emetics and nonsteroidal anti-inflammatory drugs (NSAIDs). Eleven of the 18 articles including 25/25 patients (100%) described a significant or complete resolution of secondary HA from sumatriptan, a serotonin 5HT agonist. A favorable response to analgesics including triptans should not be used to exclude a serious secondary cause of HA.


Costs of acute bacterial foodborne disease in Canada and the United States.
Bacterial foodborne disease is increasing in industrialized as well as developing countries. For Canada and the United States many millions of cases are believed to occur each year, based on extrapolations of survey data, human enteric isolations and reported foodborne disease cases. The economic impact of such a large number is probably in billions of dollars but the precise figure is difficult to calculate. Medical costs and lost income are easier to determine than losses to food companies, legal awards and settlements, value of lost leisure time, pain, grief, suffering and death. The evaluation of costs at the national level for Canada and the United States based on all available costs for 61 incidents showed that company losses and legal action are much higher than medical/hospitalization expenses, lost income or investigational costs. It was reckoned that on an annual basis an estimated 1 million cases of acute bacterial foodborne illness in Canada cost nearly $1.1 billion and 5.5 million cases in the United States cost nearly $7 billion. The value of deaths was a major contributor to the overall costs especially for diseases like listeriosis, salmonellosis, Vibrio infections, and haemorrhagic colitis. Salmonellosis is the economically most important disease because it affects all parts of the food system, unlike typhoid fever and botulism, which are largely controlled by public health authorities and the food industry.


Indications and limitations of third-generation aromatase inhibitors.
Use of aromatase inhibitors in postmenopausal breast cancer, initially in advanced disease but recently also for adjuvant therapy, represents a major advance. To summarize research leading to this success and to review clinical data from large Phase III trials revealing efficacy of novel third-generation aromatase inhibitors in metastatic and early breast cancer. Literature on PubMed and on ISI Web of Science for the last 10 years was searched using the word 'aromatase'. Recent key presentations and abstracts are also included. Third-generation aromatase inhibitors improve relapse-free survival compared to tamoxifen, and some trials reveal a survival advantage in early breast cancer. Although substantial data now confirm the safety of these potent compounds with respect to bone metabolism and cardiovascular risk, there is a need for continuous long-term follow-up, in particular into potential vascular effects. The mechanisms and optimal treatment of musculoskeletal and joint pain remain to be addressed. Ongoing studies evaluate sequential treatment versus monotherapy, potential differences between individual compounds and optimal duration of treatment, as well as combining aromatase inhibitors with novel targeting agents.


The compatibility of Xenopus antibody and homoiothermic complement.
Adult Xenopus laevis serum containing an anti-chicken erythrocyte antibody exhibits complement (C) activity by both the classical and the alternative pathways. Lytic activity is removed by heating serum to 50 degrees C for at least 20 min; it is also removed by polysaccharides and by 7.5 mM EDTA. The optimum temperature for Xenopus C activation is 25 degrees C. The ability of Xenopus antibody against chicken erythrocytes to co-operate with homoiothermic C in in vitro by lysis of chicken erythrocytes was tested. Removal of Xenopus C by heating resulted in apparent damage to the antibody, so C was removed by absorption with antibody/antigen complex. Xenopus antibody will apparently combine with guinea-pig and rat C to effect lysis of chicken erythrocytes; low levels of haemolysis were seen with human, rabbit and chicken sera, while horse and mouse sera were non-lytic. Xenopus C was able to restore the lytic activity of decomplemented rabbit anti-chicken erythrocyte serum.


The catch-22 of promotion: Is becoming department chair of surgery a threat to the triple threat?
Despite the "fourth threat" of administrative demands, department chairs of surgery are expected to continue being a "triple threat": productive in research, outstanding in teaching, and exemplary in practice. Increased demands despite limited time are the catch-22 of promotion. This study investigated the influence of becoming department chair on scholarly vigor. The surgeons listed in the Society of Surgical Chairs Membership Directory website (n = 118) were included in this study. Three measures were compared during the pre- and post-promotion phases: (1) research productivity (annual publications); (2) authorship position in publications (first-authorship, co-authorship, and senior-authorship); and (3) scholarly impact (m-index and National Institute of Health funding). The median [interquartile range] number of publications per year increased post-promotion versus pre-promotion (7.64 [3.81-14.15] vs 4.12 [2.08-7.03], P < .0005). The median [interquartile range] number of first-authorship publications per year decreased (0.50 [0.00-1.00] vs 0.64 [0.32-1.22], P < .05), whereas the median [interquartile range] number of co-authorship (4.23 [1.98-9.70] vs 2.02 [1.02-3.95], P < .0005) and senior-authorship (1.87 [0.99-4.03] vs 1.00 [0.36-2.24], P < .0005) publications per year increased post-promotion. The mean ± standard deviation m-index increased post-promotion (1.67 ± 1.19 vs 1.23 ± 0.83, P < .01). The mean ± standard deviation annual National Institute of Health grant funding amount of 48% (n = 57) of the department chairs increased post-promotion ($365,000 ± $899,000 vs $98,000 ± $143,000 pre-promotion, P < .05). The fourth threat of administrative demands is not a threat to the triple threat. This study showed the department chairs' continued scholarly vigor after promotion, providing insight into their tenacity, resilience, and dedication.


Noncontiguous finished genome sequence and description of Paenibacillus antibioticophila sp. nov. GD11(T), the type strain of Paenibacillus antibioticophila.
Paenibacillus antibioticophila strain GD11(T) sp. nov. is the type strain of a new species within the genus Paenibacillus. This strain, whose genome is described here, was isolated from human faeces of a 63-year-old woman with multidrug-resistant tuberculosis who was receiving numerous antibiotics at the time of stool collection. P. antibioticophila is a Gram-positive aerobic bacterium. We describe here the features of this bacterium, together with the complete genome sequence and annotation. The 5 562 631 bp long genome contains 5084 protein-coding and 71 RNA genes.


A role for methanogens and methane in the regulation of GLP-1.
The gastrointestinal (GI) microbiome has emerged as a potential regulator of metabolism. However, the precise mechanisms of how microorganisms may influence physiology remain largely unknown. Interestingly, GI microorganisms, including methanogens, are localized within the same regions as the glucagon-like peptide-1 (GLP-1) secreting L cells. GLP-1 plays key roles appetite and glucose regulation. Furthermore, both methane and GLP-1 levels are altered in obese humans with metabolic disease. We predict that high-fat diet-induced obesity alters the abundance of GI methanogens and that methane may play a role in the GLP-1 secretory response from the L cell. To demonstrate this, GLP-1 secretion response and faecal methanogens were examined in mice given a high-fat diet for 14 weeks. In addition, the direct effect of methane on GLP-1 secretion was assessed in two L-cell models (NCI-H716 and GLUTag). High-fat diet caused a significant increase in both GLP-1 secretion and faecal methanogen content. There was a direct correlation between GLP-1 secretion response and faecal methanogen levels. In L cells, methane stimulated GLP-1 secretion and enhanced intracellular cAMP content. These results indicate that alterations in the methanogen communities occurring in obesity may play a vital role in directly enhancing GLP-1 secretion, and that methane can directly stimulate the secretion of GLP-1.


[Scintigraphically detected "hot" thyroid nodules in the specimens from patients of the Thyroid Disease Clinic in Gda'nsk--clinico- histopathological analysis].
A group of 153 patients with scintigraphically detected autonomic "hot" nodules of the thyroid has been subjected to clinical and histopathological analysis. Substantial part of these patients (30.1%) had hyperthyroidism, partly (in 19.9% of cases) in the form of the thyrocardiac syndrome. A most frequent histopathological lesion found within "hot" nodules was follicular adenoma. The occurrence of malignancy in the form of highly differentiated thyroid carcinoma was observed in 2.6% of cases. The incidence of thyroid carcinoma within "hot" nodules was in our material only two and half times smaller than in a previously analyzed group of patients with "cold" nodules of the thyroid.


[Insurance system. Prevention from viewpoint of the insurer].
The purpose of an insurance must not be restricted to the payment of claims to those insured persons who suffered a loss, for loss prevention is much preferable to claim settlement. A whole range of different institutions and measures has been established by the Swiss insurers, in which many insurance branches participate. The loss preventing activities can be listed as follows:--Activities of the fire insurers to prevent and fight fires. This is the prevailing duty of the Consulting Agency for Fire Prevention (BfB) as well as the Fire Prevention Service for Industry and Trade (BVD).--Activities of the accident insurers to prevent accidents. The fight against accidents, mostly traffic accidents, in sports and at home is the foremost task of the Swiss Council for the Prevention of Accidents (BfU), an institution created by the Conference of Accident Insurance Managers (UDK) and the Swiss National Accident Insurance Fund (SUVA).--The Health Service in life insurance, after all the periodical medical examinations and consultations granted by many insurers to their insured persons, as well as the pamphlets aiming at health education published by several Companies and finally institutions and measures to promote fitness, e.g. VITA-Parcours.


Family Planning and Fertility Counseling Perspectives of Gender Diverse Adults and Youth Pursuing or Receiving Gender Affirming Hormone Therapy.
To describe family planning and fertility counseling perspectives of reproductive-age gender diverse adults and youth pursuing gender affirming hormone therapy. This was a cross sectional survey study of gender diverse adults and youth pursuing or receiving gender affirming hormone therapy. The primary outcomes of interest were parental desire and priorities for fertility preservation. Fifty-seven individuals (46 adults and 11 youths) completed the survey; 51% were transgender women, 35% were transgender men, and 14% identified as non-binary. 32 participants expressed interest in (n = 15, 26%) or uncertainty about (n = 18, 32%) future parenthood. 48% of participants had considered gamete cryopreservation, but only 7% each previously completed or planned to pursue this fertility option; 67% cited cost as a barrier. Participants with interest in or uncertainty about future parenthood were more likely to consider cryopreservation (P <.001) or stopping hormones for fertility preservation (P <.001). 58% of respondents reported discussing fertility preservation with a health care provider with lower rates among youth participants (P = .017). From a family planning perspective, 58% of respondents described counseling as adequate; 23% described it as inadequate and 19% reported not receiving any counseling. Participants who endorsed strong or uncertain parental desire were more likely to report inadequate counseling (P = .016). Gender diverse individuals interested in or undecided about future parenthood were more likely to consider cryopreservation and report inadequate family planning counseling. Therefore, current counseling practices may be insufficient and referral to a fertility specialist should be considered.


A new miniature, open-loop, extracorporeal insulin infusion pump.
This extracorporeal insulin infuser has been designed to be compact, simple to operate, and suitable either for clinical investigations of insulin-dependent diabetes mellitus or for long term treatment of the condition. A syringe driver of unconventional design is used, and the syringe will be available prefilled with insulin, specially formulated at standard strength for long term infusion. The device is electronically controlled to give variable rates of basal infusion, preset by switch and supplemented by bolus infusions demanded by pushbutton prior to meals. Sufficient insulin is carried in the syringe to meet the needs of most diabetics for at least a week without refilling, and the battery life is commensurately long. Signalling of the mealtime dose regime, and of alarm and failure conditions is by audible means. Insulin will most commonly be delivered subcutaneously, though other routes are possible.


Influence of the "hammock effect" in wheelchair cushion cover on mechanical loading over the ischial tuberosity in an artificial buttocks model.
The purpose of this study is to quantify hammock effects over artificial bony prominence using a newly developed buttocks model similar to human buttocks, and examine differences between various cushions and covers. A repeated measures design was used where immersions were measured with diverse weights on each type of cushion with or without covers. Polyurethane foam and air-cell cushions were used. Elastic original covers (cover 1) were evaluated for each cushion, and another less elastic cover (cover 2) was also used for the foam cushion. "Immersion" was defined as the difference in gauge readings between no load and each loading phase. Hammock effect was estimated by calculating the difference in load with and without a cover at any immersion from the approximate regression equation on immersion. All intraclass correlations were more than 0.99. The absolute hammock effect for each cover for each cushion increased as the immersion deepened. For the air-cell cushion, the relative hammock effect also increased and was higher than that for foam cushion at deeper immersion. For the foam cushion, the relative hammock effect on the cushion with cover 2 (160.5-188.6%) was higher than that with cover 1 (107.3-123.7%) at any immersion. The hammock effect could be quantified by the validated and reliable model. The mechanical property of the covers, the pressure redistributing property of the cushions and the length of bony prominence all influenced the intensity of the hammock effect.


The Pyk2 FERM regulates Pyk2 complex formation and phosphorylation.
The focal adhesion kinase Pyk2 integrates signals from cell adhesion receptors, growth factor receptors, and G-protein-coupled receptors leading to the activation of intracellular signaling pathways that regulate cellular phenotypes. The intrinsic mechanism for the activation of Pyk2 activity remains to be fully defined. Previously, we reported that mutations in the N-terminal FERM domain result in loss of Pyk2 activity and expression of the FERM domain as an autonomous fragment inhibits Pyk2 activity. In the present study, we sought to determine the mechanism that underlies these effects. Utilizing differentially epitope-tagged Pyk2 constructs, we observed that Pyk2 forms oligomeric complexes in cells and that complex formation correlates positively with tyrosine phosphorylation. Similarly, when expressed as an autonomous fragment, the Pyk2 FERM domain formed a complex with other Pyk2 FERM domains but not the FAK FERM domain. When co-expressed with full-length Pyk2, the autonomously expressed Pyk2 FERM domain formed a complex with full-length Pyk2 preventing the formation of Pyk2 oligomers and resulting in reduced Pyk2 phosphorylation. Deletion of the FERM domain from Pyk2 enhanced Pyk2 complex formation and phosphorylation. Together, these data indicate that the Pyk2 FERM domain is involved in the regulation of Pyk2 activity by acting to regulate the formation of Pyk2 oligomers that are critical for Pyk2 activity.


Constriction/dilatation of the cerebral microvessels by intravascular endothelin-1 in cats.
The effects of intracarotidly injected endothelin (ET)-1 (0.01-3 nmol) on the local cerebral blood volume (CBV) in the parietotemporal cortex were examined by the photoelectric method in 17 anesthetized cats. CBV reflects the cumulative dimensions of the cerebral microvessels. Low doses of ET-1 (0.01 and 0.1 nmol) elicited mild but significant reductions in CBV without changes in the systemic arterial blood pressure (SABP). High doses of ET-1 (3 nmol) initially induced marked declines of CBV, which were attributable to the significant falls in SABP. CBV subsequently exhibited significant increases. The CBV increases were not secondary to the accompanying elevations of SABP, since they were unaffected by inhibition of the SABP changes after preinjection of BQ-123 (1 mg/kg), an ET antagonist specific to the ETA receptors. The CBV increases, however, were prevented by continuous administration of NG-mono-methyl-L-arginine (0.35 mg/kg/min), an inhibitor of nitric oxide synthesis, plus BQ-123. We conclude that while low doses of intravascular ET-1 constrict the cerebral microvessels, high doses of ET-1 dilate the cerebral microvessels through the induction of nitric oxide probably in the cerebrovascular endothelium.


Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions.
Persistent high risk type human papillomavirus (HR-HPVs) infections induce dysplasia or cancer of the anogenital tract, most notably of the uterine cervix. The viral genome usually persists and replicates as an episomal molecule in early dysplasia, whereas in advanced dysplasia or cervical cancer HPV genomes are frequently integrated into the chromosomal DNA of the host cell. Previous studies suggested that modification of critical cellular sequences by integration of HPV genomes might significantly contribute to the neoplastic transformation of anogenital epithelia (insertional mutagenesis). This prompted us to characterize the integration loci of high risk HPV genomes in a large set of genital lesions. We amplified E6/E7 oncogene transcripts derived from integrated HPV16 and HPV18 genomes and characterized in detail the co-transcribed cellular sequences of 64 primary genital lesions and five cervical cancer cell lines. Database analyses of the cellular parts of these fusion transcripts revealed 51 different integration loci, including 26 transcribed genes (14 known genes, 12 EST sequences with unknown gene function). Seventeen sequences showed similarity to repetitive elements, and 26 sequences did not show any database match other than genomic sequence. Chromosomal integration loci were distributed over almost all human chromosomes. Although we found HPV sequences integrated into cancer related genes and close to fragile sites, no preferential site or integration motif could be identified. These data demonstrate that target directed insertional mutagenesis might occur in few HPV-induced anogenital lesions, however, it is rather the exception than the rule.


Mumps outbreaks in a highly vaccinated population: Investigation of a neutralization titre against the current circulating wildtype genotype G5 mumps virus.
Mumps outbreaks continue to occur globally, despite high levels of uptake of the mumps vaccine. In order to address immunity to the current circulating wildtype virus, we sought to determine a mumps G5 specific IgG quantitative value which correlates with genotype G5 specific neutralization ability in vitro. Sera from 199 individuals including controls and acute mumps cases were assessed for mumps specific IgG titres using five different enzyme immunoassays coated with antigen from different mumps virus strains. A subset of 66 sera was also assessed for in vitro neutralizing antibody against a contemporary circulating genotype G5 mumps virus. For all the different antigenic targets, mumps specific IgG titres were higher in patients following acute mumps infection compared to controls. In acute mumps infected patients, females showed significantly higher serum titres of anti-G5 IgG compared to males (p<0.05). Furthermore, control males did not show any change in G5 specific IgG with increasing age whereas females show a progressive rise in titre. Linear regression analysis revealed a significant association between the mumps G5 specific IgG levels in the EIA and the in vitro neutralization titres (r(2)=0.59). Specific IgG to the current circulating genotype G5 mumps strain showed significantly lower titres in males which supports our previous observation that there is a male gender bias in cases of acute mumps infection. Furthermore, in this preliminary study, the data indicate that genotype G5 specific IgG levels of >40 RU/ml are required for neutralization capability to be observed in vitro.


Acidic glycosaminoglycans, isolation and structural analysis of a proteodermatan sulfate from dermatosparactic calf skin.
Dermatan sulfate and hyaluronic acid are the major glycosaminoglycan components of dermatosparactic and normal calf skin but the ratio of hyaluronic acid to dermatan sulfate is 50-70% higher in dermatosparactic calf skin than that in normal calf skin. Hyaluronic acid in normal calf skin could be extracted to 93% of the total by NaCl and guanidine hydrochloride, while in dermatosparactic calf skin 57% of hyaluronic acid remained in the insoluble material after NaCl and guanidine hydrochloride extraction. The recovery of proteodermatan sulfate in NaCl extracts was similar in normal and dermatosparactic skin. The amount of proteodermatan sulfate extracted in guanidine hydrochloride form normal calf skin was 2-4 fold higher than that from dermatosparactic calf skin. No significant difference between dermatosparactic and normal calf skin proteodermatan sulfate could be detected in terms of size of the core protein (Mr = 55,000) by sodium dodecyl sulfate polyacrylamide gel electrophoresis, amino acid analysis, immunological cross-reactivity using polyclonal antibodies against either dermatosparactic or normal calf skin core protein, tryptic peptides or size of dermatan sulfate chains (Mr = 17,000-18,000) on gel chromatography.


1-Methyl-5-nitro-imidazolium chloride.
The title salt, C4H6N3O2 +·Cl-, exhibits multiple hydrogen-bonding inter-actions involving the nitro-imidazolium cation and the chloride anion. Strong hydrogen bonds between the amine hydrogen atom and the chloride anion link the ionic moieties. Of note, with respect to H⋯Cl inter-actions, the central aromatic hydrogen atom displays a shorter inter-action than the other aromatic hydrogen atom. Finally, inter-actions are observed between the nitro moiety and methyl H atoms. While no π-π stacking is observed, anion-π inter-actions are present. The crystal was refined as a two-component twin.


[Cerebral venous thrombosis].
Although more rare than arterial thrombosis, cerebral venous thrombosis are a non-negligible cause of stroke. Characterised by the large diversity of clinical presentations and etiologies, they have a much better prognosis than arterial stroke. The evolution remains unforeseeable, with a non-negligible proportion of worsening at the acute phase and diagnosis must be early to begin as soon as possible the treatment, which is at present based on heparin therapeutics. Neuroimaging examinations are essential for diagnosis of CVT. MR Imaging with MR venography is the key procedure. New sequences are on evaluation in CVT bringing some physiopathogical arguments (Diffusion weighted imaging) or help for diagnosis (with T2* MRI sequence). If D-dimers dosage is helpful for diagnosis of deep venous thrombosis, its interest remains to be determined during CVT. CVT diagnosis is a challenge for the clinician. Because of the multiple causes and favorising factors, CVT are at the convergence of many specialties and could thus benefit of each one contribution for better understanding the physiopathology, improving earlier diagnosis or identifying the severe forms that could require right away more aggressive treatments than heparin. The interest of local thrombolysis or thrombectomy remains to be determined in an international randomised study.


Blunted ACTH response to dexamethasone suppression-CRH stimulation in posttraumatic stress disorder.
Previous studies have suggested that patients with posttraumatic stress disorder (PTSD) have an enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) system and a blunted ACTH response to corticotropin releasing hormone (CRH). The effects of two dexamethasone dosages (0.75 and 1.5 mg) on the ACTH and cortisol concentrations after CRH stimulation (100 microg) were studied in eight patients with PTSD and matched healthy control subjects. Compared to healthy subjects, patients with PTSD have a blunted ACTH response to CRH. Cortisol concentrations were only significantly influenced by dexamethasone dosage. Our results give further evidence for a central role of the pituitary in reflecting changes of the negative feedback sensitivity of the HPA system in patients with PTSD.


Changes in resting-state cerebral blood flow and its connectivity in patients with focal to bilateral tonic-clonic seizures.
Arterial spin labeling (ASL) is an important tool for understanding cerebral perfusion in epilepsy patients. The aim of this study was to explore patterns of change in cerebral blood flow (CBF) and CBF connectivity in patients with focal to bilateral tonic-clonic seizures (FBTCS). High-resolution three-dimensional (3-D) T1-weighted and 3-D pseudo-continuous ASL magnetic resonance imaging (MRI) was collected from 32 patients with FBTCS and 16 healthy volunteers using a 3.0 T MRI scanner. Cerebral blood flow and its connectivity were compared between the FBTCS and control group. Correlation analysis was used to explore relationships of CBF and its connectivity changes with clinical parameters. Cerebral blood flow data of spatial standardization and normalization were used to improve statistical power. Patients with FBTCS exhibited increased CBF in the bilateral thalamus, caudate nucleus, olfactory cortex, and gyrus rectus, but decreased CBF in the bilateral supplementary motor areas (SMA) and middle cingulate cortex (MCC). Patients with FBTCS showed significant positive correlation between CBF and gray matter volume (GMV) in bilateral SMA and MCC. No significant correlations between CBF and clinical parameters were found among FBTCS patients. The anterior cingulate cortex (ACC) showed positive CBF connectivity with the bilateral SMA and MCC, and these CBF connectivity measures differed significantly between groups (cluster-level, FWE-corrected, P < 0.001). These findings suggest that patients with FBTCS have changes in cerebral CBF and CBF connectivity, which may relate to the underlying neuropathology of FBTCS.


Injuries in the adolescent porcine spine exposed to mechanical compression.
An experimental porcine study in which functional lumbar spinal units were tested in compression to failure. Biomechanical, radiographic, magnetic resonance imaging, and histological characteristics are described. To explain the different patterns of injury seen in adults and adolescents resulting from traumatic injury to the vertebrae and to explain the mechanism behind traumatic displacement of the ring apophysis seen in athletes. Recent investigations of the spine in adolescent who have sustained trauma have shown injuries to the growth zone, whereas studies of adults have shown injuries to the vertebral body. A higher frequency of abnormalities in the discs, the vertebral bodies, the endplates, and the ring apophyses has been demonstrated in athletes with high loads on the spine. There is controversy over the etiology of these changes. Twelve functional lumbar spinal units (vertebra-disc-vertebra) obtained from six young male pigs were tested in compression to failure. All units were examined with plain radiography and magnetic resonance imaging before and after compression. After the compression, histologic samples were taken from the injury site. Identical traumatic changes were seen in all functional lumbar spinal units, i.e., fracture in the endplate through the growth zone posteriorly and displacement of the anulus fibrosus with a bony fragment at the point of insertion of the vertebra. The nucleus pulposus was ruptured and displaced through the fracture line in all cases. The injuries were not seen on radiographs but were detected on magnetic resonance images, as confirmed on microscopic and histologic examination. This study shows that the weakest part of the lumbar spine of the juvenile pig, when compressed, is the growth zone and the junction between the point of insertion of the anulus fibrosus and the vertebra. This location of weakness may explain the high frequency of disc degeneration and "persisting apophysis" seen in the spine of athletes.


Trichinella spiralis: acceleration and inhibition of cyst calcification in rats.
Daily administration of vitamin D3 (75,000 IU/kg b. wt) for 7 days accelerated Trichinella spiralis cyst calcification in rats with a 14-week-old infection. When disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered (50 mg/kg b. wt) from 2 days before until 2 days after vitamin D3 treatment, cyst calcification was inhibited. Thus, the ability to inhibit E. spiralis calcification has demonstrated for the first time.


Microdialysis measurement of monoamine and amino acid release from the medial preoptic region of the sheep in response to heat exposure.
Concentrations of monoamines and metabolites and amino acids were measured in microdialysis samples taken from the medial preoptic area of 5 conscious sheep before, during and after exposure to an ambient temperature of 45 degrees C. Concentrations of dopamine, noradrenaline and aspartate significantly increased, and those of the serotonin metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), significantly decreased during heat exposure and although panting was induced, body temperature did not change. Concentrations of noradrenaline and aspartate declined and 5-HIAA increased to preheat exposure levels during the 60 min after the ambient temperature was reduced but levels of dopamine and its metabolite, homovanillic acid, remained elevated. Dopamine, noradrenaline, 5-HIAA and aspartate concentrations were not significantly altered by isolation stress and did not show significant changes in the cortex following heat exposure. These experiments provide further support for the proposed roles of dopamine, noradrenaline, serotonin and aspartate in the neural control of autonomic thermoregulatory responses.


Enhanced Light Emission due to Formation of Semi-polar InGaN/GaN Multi-quantum Wells.
InGaN/GaN multi-quantum wells (MQWs) are grown on (0001) sapphire substrates by metal organic chemical vapor deposition (MOCVD) with special growth parameters to form V-shaped pits simultaneously. Measurements by atomic force microscopy (AFM) and transmission electron microscopy (TEM) demonstrate the formation of MQWs on both (0001) and ([Formula: see text]) side surface of the V-shaped pits. The latter is known to be a semi-polar surface. Optical characterizations together with theoretical calculation enable us to identify the optical transitions from these MQWs. The layer thickness on ([Formula: see text]) surface is smaller than that on (0001) surface, and the energy level in the ([Formula: see text]) semi-polar quantum well (QW) is higher than in the (0001) QW. As the sample temperature is increased from 15 K, the integrated cathodoluminescence (CL) intensity of (0001) MQWs increases first and then decreases while that of the ([Formula: see text]) MQWs decreases monotonically. The integrated photoluminescence (PL) intensity of (0001) MQWs increases significantly from 15 to 70 K. These results are explained by carrier injection from ([Formula: see text]) to (0001) MQWs due to thermal excitation. It is therefore concluded that the emission efficiency of (0001) MQWs at high temperatures can be greatly improved due to the formation of semi-polar MQWs.


Honduras: Caribbean Coast.
The coast of Honduras, Central America, represents the southern end of the Mesoamerican Barrier Reef System, although its marine resources are less extensive and studied than nearby Belize and Mexico. However, the coastal zone contains mainland reef formations, mangroves, wetlands, seagrass beds and extensive fringing reefs around its offshore islands, and has a key role in the economy of the country. Like most tropical areas, this complex of benthic habitats experiences limited annual variation in climatic and oceanographic conditions but seasonal and occasional conditions, particularly coral bleaching and hurricanes, are important influences. The effects of stochastic factors on the country's coral reefs were clearly demonstrated during 1998 when Honduras experienced a major hurricane and bleaching event. Any natural or anthropogenic impacts on reef health will inevitably affect other countries in Latin America, and vice versa, since the marine resources are linked via currents and the functioning of the system transcends political boundaries. Much further work on, for example, movement of larvae and transfer of pollutants is required to delineate the full extent of these links. Anthropogenic impacts, largely driven by the increasing population and proportion of people living in coastal areas, are numerous and include key factors such as agricultural run-off, over-fishing, urban and industrial pollution (particularly sewage) and infrastructure development. Many of these threats act synergistically and, for example, poor watershed management via shifting cultivation, increases sedimentation and pesticide run-off onto coral reefs, which increases stress to corals already affected by decreasing water quality and coral bleaching. Threats from agriculture and fishing are particularly significant because of the size of both industries. The desire to generate urgently required revenue within Honduras has also led to increased tourism which provides an overarching stress to marine resources since most tourists spend time in the coastal zone. Hence the last decade has seen a dramatic increase in coastal development, a greater requirement for sewage treatment and more demand for freshwater, particularly in the Bay Islands. Although coastal zone management is relatively recent in Honduras, it is gaining momentum from both large-scale initiatives, such as the Ministry of Tourism's 'Bay Islands Environmental Management Project', and national and international NGO projects. For example, a series of marine protected areas and legislative regulations have been established, but management capacity, enforcement and monitoring are limited by funding, expertise and training. Existing and future initiatives, supported by increased political will and environmental awareness of stakeholders, are vital for the long-term economic development of the country.


Synthesis and evaluation of a conformationally constrained pyridazinone PNA-monomer for recognition of thymine in triple-helix structures.
A novel conformationally constrained pyridazinone E(ag)-base PNA-monomer 2 capable of binding thymine in a triplex motif was designed and synthesised. A bis-PNA with the E(ag)-base incorporated in the Hoogsteen strand was hybridised with a complementary DNA. Thermal stability studies revealed an increase in T(m) (4.3 degrees C per mod.) compared to a no-base unit, but showed no improvement over a previously described unconstrained analogue (E, 1). Surprisingly, no significant difference was found in the thermodynamic parameters (DeltaH degrees, DeltaS degrees and DeltaG degrees ) for PNA-DNA triplex formation involving 2 or the unconstrained analogue 1.


Modulation of red cell band 4.1 function by cAMP-dependent kinase and protein kinase C phosphorylation.
Human erythrocyte protein 4.1 is phosphorylated in vivo by several protein kinases including protein kinase C and cAMP-dependent kinase. We have used cAMP-dependent kinase purified from red cells and protein kinase C purified from brain to test the effects of phosphorylation on band 4.1 function. In solution, each kinase catalyzed the incorporation of 1-4 mol of PO4/mol of band 4.1. Phosphorylation of band 4.1 by each kinase resulted in a significant (50-80%) reduction in the ability of band 4.1 to promote spectrin binding to F-actin. Direct measurement of spectrin-band 4.1 binding showed that phosphorylation by each kinase also caused dramatic reduction in this association. Phosphorylation of band 4.1 by each kinase for increasing time periods enabled us to demonstrate an approximately linear inverse relationship between PO4 incorporation into band 4.1 and spectrin binding. These results show that phosphorylation of band 4.1 by cAMP-dependent kinase and protein kinase C may be central to the regulation of red cell cytoskeletal organization and membrane mechanical properties.


Preliminary studies on phospholipase A2-induced mouse paw edema as a model to evaluate antiinflammatory agents.
Phospholipase A2 (PLA2) is a key component of the inflammatory process because of its role in the generation of eicosanoids and platelet-activating factor (PAF). Manipulation of PLA2 activity offers a novel therapeutic approach for the development of antiinflammatory agents; however, there is a need for a suitable in vivo model. Injection of 1 microgram of snake venom PLA2 (A. piscivorus piscivorus, D-49) into the mouse hind footpad produced a significant three- to four-fold rise in paw edema within 10 min, compared to the saline control. Edema formation depended on enzyme concentration and appeared specific for PLA2 since edema was negated by enzyme pretreatment with p-bromophenacyl bromide, a nonspecific PLA2 inhibitor. Moreover, injection of a protein such as bovine serum albumin did not result in significant edema. Coinjection of phenidone (lipoxygenase inhibitor, 50 micrograms), indomethacin (cyclooxygenase inhibitor, 50 micrograms), cyproheptadine (antihistamine/antiserotonin, 50 micrograms), aristolochic acid (putative PLA2 inhibitor, 100 micrograms), or kadsurenone (PAF antagonist, 50 micrograms) with PLA2 (1 microgram/paw) resulted in partial reduction (44.5, 34.2, 54.7, 64, and 50% inhibition, respectively) of edema formation. Oral administration of cyproheptadine (10 mg/kg), indomethacin (10 mg/kg), BW 755c (100 mg/kg), or dexamethasone (1 mg/kg) 1-3 h before challenge also decreased PLA2-induced edema (63.0, 30.1, 47.8, or 62.5% inhibition, respectively). The data suggest that mouse paw edema resulting from PLA2 injection is a multicomponent event, influenced by both autacoids and lipid mediators of inflammation.


Stereotactic Body Radiotherapy for the Treatment of Renal Tumors.
The purpose of this study was to evaluate the response of actively growing renal masses to stereotactic body radiation therapy (SBRT). We retrospectively reviewed our institutional review board-approved kidney database and identified 4 patients who underwent SBRT, 15 Gy dose, for their rapidly growing renal masses. Three patients had a decreased tumor size after radiation treatment by 20.8%, 38.1%, and 20%. The other patient had a size gain of 5.6%. This patient maintained a similar tumor growth rate before and after SBRT. Mean follow-up time was 13.8 months. SBRT represents an effective management option in select patients with larger rapidly growing kidney masses.


Metabolic and regulatory roles of leucine in neural cells.
Dietary leucine transported into the brain parenchyma serves several functions. Most prominent is the role of leucine as a metabolic precursor of fuel molecules, alpha-ketoisocaproate and ketone bodies. As alternatives to glucose, these compounds are forwarded by the producing astrocytes to the adjacent neural cells. Leucine furthermore participates in the maintenance of the nitrogen balance in the glutamate/glutamine cycle pertinent to the neurotransmitter glutamate. Leucine also serves as a regulator of the activity of some enzymes important for brain energy metabolism. Another role of leucine as an informational molecule is in mTOR signaling that participates in the regulation of food ingestion. The importance of leucine for brain function is stressed by the fact that inborn errors in its metabolism cause metabolic diseases often associated with neuropathological symptoms. In this overview, the current knowledge on the metabolic and regulatory roles of this essential amino acid in neural cells are briefly summarized.


Generalized eruptive histiocytoma. A case report with a review of the literature.
A case of generalized eruptive histiocytoma in a 52-year-old Indian male is described. This is probably the tenth case in the world and the first from this country. Histopathological features are discussed in detail and the literature is reviewed.


Injectable multifunctional chitosan/dextran-based hydrogel accelerates wound healing in combined radiation and burn injury.
Clinical wound management of combined radiation and burn injury (CRBI) remains a huge challenge due to serious injuries induced by redundant reactive oxygen species (ROS), the accompanying hematopoietic, immunologic suppression and stem cell reduction. Herein, the injectable multifunctional Schiff base cross-linked with gallic acid modified chitosan (CSGA)/oxidized dextran (ODex) hydrogels were rationally designed to accelerate wound healing through elimination of ROS in CRBI. CSGA/ODex hydrogels, fabricated by mixing solutions of CSGA and Odex, displayed good self-healing ability, excellent injectability, strong antioxidant activity, and favorable biocompatibility. More importantly, CSGA/ODex hydrogels exhibited excellent antibacterial properties, which is facilitated for wound healing. Furthermore, CSGA/ODex hydrogels significantly suppressed the oxidative damage of L929 cells in an H2O2-induced ROS microenvironment. The recovery of mice with CRBI in mice demonstrated that CSGA/ODex hydrogels significantly reduced the hyperplasia of epithelial cells and the expression of proinflammatory cytokine, and accelerated wound healing which was superior to the treatment with commercial triethanolamine ointment. In conclusion, the CSGA/ODex hydrogels as a wound dressing could accelerate the wound healing and tissue regeneration of CRBI, which provides great potential in clinical treatment of CRBI.


Low-Density Lipoprotein Cholesterol Corrected for Lipoprotein(a) Cholesterol, Risk Thresholds, and Cardiovascular Events.
Background Conventional "low-density lipoprotein cholesterol (LDL-C)" assays measure cholesterol content in both low-density lipoprotein and lipoprotein(a) particles. To clarify the consequences of this methodological limitation for clinical care, our study aimed to compare associations of "LDL-C" and corrected LDL-C with risk of cardiovascular disease and to assess the impact of this correction on the classification of patients into guideline-recommended LDL-C categories. Methods and Results Lipoprotein(a) cholesterol content was estimated as 30% of lipoprotein(a) mass and subtracted from "LDL-C" to obtain corrected LDL-C values (LDL-Ccorr30). Hazard ratios for cardiovascular disease (defined as coronary heart disease, stroke, or coronary revascularization) were quantified by individual-patient-data meta-analysis of 5 statin landmark trials from the Lipoprotein(a) Studies Collaboration (18 043 patients; 5390 events; 4.7 years median follow-up). When comparing top versus bottom quartiles, the multivariable-adjusted hazard ratio for cardiovascular disease was significant for "LDL-C" (1.17; 95% CI, 1.05-1.31; P=0.005) but not for LDL-Ccorr30 (1.07; 95% CI, 0.93-1.22; P=0.362). In a routine laboratory database involving 531 144 patients, reclassification of patients across guideline-recommended LDL-C categories when using LDL-Ccorr30 was assessed. In "LDL-C" categories of 70 to <100, 100 to <130, 130 to <190, and ≥190 mg/dL, significant proportions (95% CI) of participants were reassigned to lower LDL-C categories when LDL-Ccorr30 was used: 30.2% (30.0%-30.4%), 35.1% (34.9%-35.4%), 32.9% (32.6%-33.1%), and 41.1% (40.0%-42.2%), respectively. Conclusions "LDL-C" was associated with incident cardiovascular disease only when lipoprotein(a) cholesterol content was included in its measurement. Refinement in techniques to accurately measure LDL-C, particularly in patients with elevated lipoprotein(a) levels, is warranted to assign risk to the responsible lipoproteins.


An easy approach to the Robins-Breslow-Greenland variance estimator.
The Mantel-Haenszel estimate for the odds ratio (and its logarithm) in stratified case control studies lacked a generally acceptable variance estimate for many years. The Robins-Breslow-Greenland estimate has met this need, but standard textbooks still do not provide an explanation of how it is derived. This article provides an accessible derivation which demonstrates the link between the Robins-Breslow-Greenland estimate and the familiar Woolf estimate for the variance of the log odds ratio, and which could easily be included in Masters level courses in epidemiology. The relationships to the unconditional and conditional maximum likelihood estimates are also reviewed.


Kappa opioid receptor in nucleus accumbens regulates depressive-like behaviors following prolonged morphine withdrawal in mice.
Prolonged withdrawal from opioids leads to negative emotions. Kappa opioid receptor (KOR) plays an important role in opioid addiction and affective disorders. However, the underlying mechanism of KOR in withdrawal-related depression is still lacking. We found that escitalopram treatment had a limited effect in improving depression symptoms in heroin-dependent patients. In mice, we demonstrated prolonged (4 weeks) but not acute (24 h) withdrawal from morphine induced depressive-like behaviors. The number of c-Fos positive cells and the expression of KOR in the nucleus accumbens (NAc), were significantly increased in the prolonged morphine withdrawal mice. Conditional KOR knockdown in NAc significantly improved depressive-like behaviors. Repeated but not acute treatment with the KOR antagonist norBNI improved depressive-like behaviors and reversed PSD95, synaptophysin, p-ERK, p-CREB, and BDNF in NAc. This study demonstrated the important role of striatal KOR in morphine withdrawal-related depressive-like behaviors and offered therapeutic potential for the treatment of withdrawal-related depression.


Clinical Guidance on the Monitoring and Management of Trastuzumab Deruxtecan (T-DXd)-Related Adverse Events: Insights from an Asia-Pacific Multidisciplinary Panel.
Trastuzumab deruxtecan (T-DXd)-an antibody-drug conjugate targeting the human epidermal growth factor receptor 2 (HER2)-improved outcomes of patients with HER2-positive and HER2-low metastatic breast cancer. Guidance on monitoring and managing T-DXd-related adverse events (AEs) is an emerging unmet need as translating clinical trial experience into real-world practice may be difficult due to practical and cultural considerations and differences in health care infrastructure. Thus, 13 experts including oncologists, pulmonologists and a radiologist from the Asia-Pacific region gathered to provide recommendations for T-DXd-related AE monitoring and management by using the latest evidence from the DESTINY-Breast trials, our own clinical trial experience and loco-regional health care considerations. While subgroup analysis of Asian (excluding Japanese) versus overall population in the DESTINY-Breast03 uncovered no major differences in the AE profile, we concluded that proactive monitoring and management are essential in maximising the benefits with T-DXd. As interstitial lung disease (ILD)/pneumonitis is a serious AE, patients should undergo regular computed tomography scans, but the frequency may have to account for the median time of ILD/pneumonitis onset and access. Trastuzumab deruxtecan appears to be a highly emetic regimen, and prophylaxis with serotonin receptor antagonists and dexamethasone (with or without neurokinin-1 receptor antagonist) should be considered. Health care professionals should be vigilant for treatable causes of fatigue, and patients should be encouraged to use support groups and practice low-intensity exercises. To increase treatment acceptance, patients should be made aware of alopecia risk prior to starting T-DXd. Detailed monitoring and management recommendations for T-DXd-related AEs are discussed further.


In vivo immunomodulatory effects of adipose-derived mesenchymal stem cells conditioned medium in experimental autoimmune encephalomyelitis.
Mesenchymal stem cells (MSCs) are well known to possess neuroprotective and immunomodulatory effects, due to cell-to-cell interaction and their soluble factors. We conducted a comparative analysis of the immunomodulatory properties of adipose tissue mesenchymal stem cells (AT-MSCs) and their conditioned media (CM), derived from C57/BL6 mice, for mitigating the adverse clinical course of experimental autoimmune encephalomyelitis (EAE). We measure IL4, IL17 and IFNɣ production of supernatant from spleen cells. We analyzed brain cell infiltration, splenocyte proliferation and evaluated the percentage of CD4+CD25+FOXP3+splenic cell population in all EAE C57/BL6 mice. AT-MSCs and its conditioned medium induced CD4+CD25+FOXP3+regulatory T cells after in vitro co-culture with naïve T cells. There is no significant difference in the clinical scores and body weight of EAE mice treated with AT-MSCs and CM. The reduction in proliferative responses and brain cell infiltration was more pronounced in mice injected with CM than other groups. It is found that the percentage of splenic CD4+CD25+FOXP3+ population as well as the level of IL4 production in mice administrated with AT-MSCs is increased compared to other animals. Our results suggest that AT-MSCs-derived CM is promising in stem cell therapy, due to their neuroprotective and immunomudulatory properties.


Gene-activated titanium implants for gene delivery to enhance osseointegration.
Osseointegration is the direct and intimate contact between mineralized tissue and titanium implant at the bone-implant interface. Early establishment and stable maintenance of osseointegration is the key to long-term implant success. However, in patients with compromised conditions such as osteoporosis and patients beginning early load-bearing activities such as walking, lower osseointegration around titanium implants is often observed, which might result in implant early failure. Gene-activated implants show an exciting prospect of combining gene delivery and biomedical implants to solve the problems of poor osseointegration formation, overcoming the shortcomings of protein therapy, including rapid degradation and overdose adverse effects. The conception of gene-activated titanium implants is based on "gene-activated matrix" (GAM), which means scaffolds using non-viral vectors for in situ gene delivery to achieve a long-term and efficient transfection of target cells. Current preclinical studies in animal models have shown that plasmid DNA (pDNA), microRNA (miRNA), and small interference RNA (siRNA) functionalized titanium implants can enhance osseointegration with safety and efficiency, leading to the expectation of applying this technique in dental and orthopedic clinical scenarios. This review aims to comprehensively summarize fabrication strategies, current applications, and futural outlooks of gene-activated implants, emphasizing nucleic acid targets, non-viral vectors, implant surface modification techniques, nucleic acid/vector complexes loading strategies.


Validity of the 24-hr. dietary recall and seven-day record for group comparisons.
The internal validity of a 24-hr. dietary recall and a seven-day dietary record was investigated among a group of non-institutionalized elderly subjects who were participating in a congregate meals program. Internal validity was assessed by comparing reported intake with unobtrusively obtained data on actual intake. Validity results suggest that the recall is prone to over-reporting low intakes and under-reporting high intakes. This pattern has been referred to as the "flat-slope syndrome." Records collected during the first few dyas were less prone to this syndrome; however, validity declined by the fifth, sixth, and seventh record days. Also, as the record progressed to the seventh day, the demographic nature of the sample became biased due to drop-outs and decreased usability of the records.


Tubeless tracheal resection and reconstruction for management of benign stenosis.
We reported a tubeless tracheal resection and reconstruction for the management of benign posttracheostomy tracheal stenosis. A 34-year-old man with stridor, severe respiratory distress, and recurrent pneumonia was referred to our attention for treatment of benign posttracheostomy tracheal stenosis. As he refused general anesthesia, the procedure was performed while he was under local anesthesia and spontaneous ventilation. Sedation was started with infusion of dexmedetomidine 0.7 mg/kg/min and of remifentanil 0.5 mg/kg/h; also, 40%-50% oxygen was delivered using a laryngeal mask at a rate of 3.5 mL/min. An additional dose of 2% lidocaine was injected into the surgical site during the operation to achieve an adequate level of anesthesia. A standard resection and reconstruction of trachea was carried out and no recurrence was found in the follow-up of 41 months. Tubeless tracheal surgery seems to be a feasible and safe procedure. Larger prospective series should validate our results.


Survival of Helicobacter pylori in milk and tap water.
The survival capacity of Helicobacter pylori in artificially contaminated milk and tap water was investigated in the study. Helicobacter pylori could survive for up to 10 days in milk at 4 degrees C storage but only 4 days in tap water with a steady decrease of colony forming units. However, electron microscopy clearly showed that the non-culturable coccoid form was present in tap water which had been kept at 4 degrees C for 7 days. It is concluded that H. pylori may survive in tap water as well as in milk, with the implication that they may, thereby, act as a vehicle of transmission.


3D structural analysis of flagella/cilia by cryo-electron tomography.
Three dimensional arrangement of proteins inside the axoneme is essential information to elucidate the flagellar/ciliary bending mechanism. Cryo-electron tomography provides structural information in situ at ~30 Å resolution and thus is a suitable method for flagella/cilia research. The biggest challenge in cryo-electron tomography is the low signal-to-noise ratio. Therefore, subtomogram averaging, an in silico processing step to detect identical structural units based on 3D image analysis, aligns them three dimensionally and average is required to improve the signal-to-noise ratio. When structural units are not exactly identical, they must be classified. In this chapter, we describe our strategy to extract, align, classify, and average molecular structures from cryo-electron tomograms of flagella/cilia, utilizing longitudinal periodicity and pseudo-ninefold symmetry in the axoneme.


Clinical features of late cytomegalovirus infection after hematopoietic stem cell transplantation.
Late cytomegalovirus (CMV) disease beyond day 100 after hematopoietic stem cell transplantation (HSCT) has become an increasing problem after the introduction of preemptive ganciclovir (GCV) administration. To clarify the risk factors and outcome for late CMV reactivation and disease, we retrospectively analyzed the records of 101 Japanese adult patients who underwent allogeneic HSCT between 1998 and 2005 at our hospital. Fifty-one developed late positive CMV antigenemia, with a cumulative incidence of 53%. Recipient CMV seropositivity, the use of alemtuzumab, chronic GVHD, and high-dose steroids were significantly associated with late positive antigenemia. Eight patients developed late CMV disease, with a cumulative incidence of 8%, including retinitis and gastrointestinal disease. None progressed to a fatal disease. The use of alemtuzumab was identified as an independent significant risk factor for late CMV disease, although it was not associated with increased non-relapse mortality. Among the 51 patients with late positive antigenemia, 28 had consistently less than three positive cells, 25 of whom showed negative conversion without antiviral agents. In conclusion, late CMV antigenemia appeared to develop frequently, especially in patients with profound immune suppression; however, a fatal outcome could be prevented by optimal preemptive therapy. Low-level antigenemia may not require antiviral treatments.


Characterization of the CT-based risk factors for concomitant patellofemoral instability in patients with anterior cruciate ligament injury.
Underestimation of concomitant patellofemoral instability in patients with anterior cruciate ligament (ACL) injury has aroused extensive attention. However, the characteristics of the combined injury is not well recognized. Hence, we aimed to characterize the features of the combined injury, and determine the radiographic risk factors. Fifteen radiological parameters were identified after discussion and pilot-tested. Radiographic measurements were compared using the analysis of variance model with Tukey post hoc analysis. A stepwise binomial logistic regression was performed and a nomogram model combining the significant risk factors was created. The model performance was validated by C-index, calibration plot, and decision curve. A total of 204 patients (mean [SD] age, 25.1 [6.7] years; 108 [52.9%] male) were included. The final model was updated through regression analysis using 4 parameters as significant risk factors: lateral femoral condyle ratio (OR (95% CI), 1.194 (1.023 to 1.409)), medial anterior tibial subluxation (mATS) (OR (95% CI), 1.234 (1.065 to 1.446)), medial posterior plateau tibial angle (mPPTA) (OR (95% CI), 1.266 (1.088 to 1.500)), and trochlear depth (OR (95% CI), 0.569 (0.397 to 0.784)). C-index for the nomogram was 0.802 (95% CI, 0.731 to 0.873) and was confirmed to be 0.784 through bootstrapping validation. Calibration plot established a good agreement between prediction and observation. Decision curve analysis showed that if threshold probability was over 10%, using the nomogram adds more benefit than either all or none scheme. Lateral femoral condyle ratio, mATS, mPPTA, and trochlear depth are strong adverse predictors of patellofemoral instability in patients with ACL injury. This study characterizes the radiological features of the combined injury. Patellofemoral instability should be noted when treating ACL injuries. • The radiological characteristics of the combined ACL injury and patellofemoral instability is not well recognized. • Lateral femoral condyle ratio, mATS, mPPTA, and trochlear depth are predominant risk factors for patellofemoral instability in patients with ACL injury. • Patellofemoral instability should be noted when treating ACL injuries.


Anterior fixation of unstable pelvic ring fractures using the modified Stoppa approach: mid-term results are independent on patients' age.
Open surgical management of unstable pelvic ring injuries has been discussed controversially compared to percutaneous techniques in terms of surgical site morbidity especially in older patients. Thus, we assessed the impact of age on the outcome following fixation of unstable pelvic ring injuries through the modified Stoppa approach. Out of a consecutive series of 92 patients eligible for the study, 63 patients (mean age 50 years, range 19-78) were evaluated [accuracy of reduction, complications, failures, Majeed-Score, Oswestry Disability Questionnaire (ODI), Mainz Pain Staging System (MPSS)] at a mean follow-up of 3.3 years (range 1.0-7.9). Logistic multivariate regression analysis was performed to assess the outcome in relation to increasing patient age and/or Injury Severity Score (ISS). Out of 63 patients, in 36 an "anatomic" reduction was achieved. Ten postoperative complications occurred in eight patients. In five patients, failure of fixation was noted at the anterior and/or posterior pelvic ring. In 49 patients, an "excellent" or "good" Majeed-Score was obtained; the mean ODI was 14 % (range 0-76 %); 50 patients reported either no or only minor chronic pelvic pain (MPSS). Only an increasing ISS conferred an increased likelihood of the occurrence of a non-anatomical reduction, a "poor" or "fair" Majeed-Score, or an ODI >20 %. Increasing age did not impact the analysed parameters. Open reduction and internal fixation of the anterior pelvic ring through a modified Stoppa approach in unstable pelvic ring injuries did not result in an unfavourable outcome with increasing age of patients.


Synthesis and anti-HIV activity of novel phenyl branched cyclopropyl nucleosides.
Novel phenyl branched cyclopropyl nucleoside analogues were designed and synthesized as potential antiviral agents. Cyclopropanation was performed via classical Simmons-Smith reaction using Zn(Et)2 and CH2I2. Coupling of the mesylates 11 and 12 with natural bases (A,C,T,U) and desilylation afforded a series of novel cyclopropyl nucleosides 21-28. The synthesized compounds were evaluated for their antiviral and antitumor activity against various viruses such as HIV, HSV-1, HSV-2 and HCMV.


Local Failure After Accelerated Partial Breast Irradiation with Intraoperative Radiotherapy with Electrons: An Insight into Management and Outcome from an Italian Multicentric Study.
The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6-6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.


Immune-modulating effects of melatonin, N-acetylserotonin, and N-acetyldopamine.
Melatonin and N-acetylserotonin (NAS) have antioxidant properties. In the present study, we examined whether melatonin, NAS, and N-acetyldopamine (NAD) have a modulatory effect on tumor necrosis factor-alpha (TNF-alpha) synthesis and superoxide production. Differentiated THP-1-derived human monocytes were coincubated with Escherichia coli lipopolysaccharide (LPS) and rising concentrations of melatonin, NAS, or NAD. After 24 h, TNF-alpha was measured in cell supernatants. In addition, the production of superoxide by HL-60-derived human neutrophils upon stimulation with 4-beta-phorbol 12-beta-myristate 13-alpha-acetate (PMA) or N-formyl methionyl-leucyl-phenylalanine (fMLP) and increasing concentrations of melatonin, NAS, or NAD was determined. Incubation of THP-1-derived monocytes with increasing concentrations of melatonin, NAS, or NAD resulted in a marked decrease in LPS-stimulated TNF-alpha production, which was dose-dependent and on the order of 96-98%. Incubation of HL-60-derived neutrophils with increasing concentrations of melatonin, NAS, or NAD resulted in a modest decrease in PMA-stimulated superoxide production, which was dose-dependent. At the 100 microM dose, melatonin, NAS, or NAD resulted in a 14 +/- 4%, 30 +/- 1%, and 29 +/- 1% decrease in PMA-stimulated superoxide production, respectively. Coincubation of HL-60 cells with melatonin, NAS, or NAD also resulted in a modest dose-dependent decrease in fMLP-stimulated superoxide production. At the 100 microM dose, melatonin, NAS, or NAD resulted in a 13 +/- 1%, 14 +/- 1%, and 14 +/- 1% decrease in superoxide production, respectively. Our results indicate that the inhibitory effect of melatonin, NAS, or NAD on LPS-induced TNF-alpha production is robust and dose-dependent. These compounds are equally effective in attenuating the generation of oxidant radicals, although to a lesser degree.


Coupled Active Systems Encode an Emergent Hunting Behavior in the Unicellular Predator Lacrymaria olor.
Many single-celled protists use rapid morphology changes to perform fast animal-like behaviors. To understand how such behaviors are encoded, we analyzed the hunting dynamics of the predatory ciliate Lacrymaria olor, which locates and captures prey using the tip of a slender "neck" that can rapidly extend more than seven times its body length (500 μm from its body) and retract in seconds. By tracking single cells in real-time over hours and analyzing millions of sub-cellular postures, we find that these fast extension-contraction cycles underlie an emergent hunting behavior that comprehensively samples a broad area within the cell's reach. Although this behavior appears complex, we show that it arises naturally as alternating sub-cellular ciliary and contractile activities rearrange the cell's underlying helical cytoskeleton to extend or retract the neck. At short timescales, a retracting neck behaves like an elastic filament under load, such that compression activates a series of buckling modes that reorient the head and scramble its extensile trajectory. At longer timescales, the fundamental length of this filament can change, altering the location in space where these transitions occur. Coupling these fast and slow dynamics together, we present a simple model for how Lacrymaria samples the range of geometries and orientations needed to ensure dense stochastic sampling of the immediate environment when hunting to locate and strike at prey. More generally, coupling active mechanical and chemical signaling systems across different timescales may provide a general strategy by which mechanically encoded emergent cell behaviors can be understood or engineered.


Arrested Foveal Development in Preterm Eyes: Thickening of the Outer Nuclear Layer and Structural Redistribution Within the Fovea.
The aim of this study was to define landmarks to better characterize foveal microstructure in normal subjects and in preterms with or without signs of immaturity, and to report on thickness changes of outer foveal layers following analysis of optical coherence tomography (OCT) B-scan images. Selected eyes from eight young adults with a history of prematurity (24-33 weeks of gestation) and five controls were imaged using conventional and directional OCT. Retinal layer thickness analysis was performed at selected temporal eccentricities defined by the individual distance between two landmarks for each case, the foveal center and the foveal rim. The use of a foveal center and foveal rim landmark transformation enabled comparisons of interindividual B-scans at corresponding landmark positions in both controls and preterms. We found a 20% shorter foveal center to foveal rim distance in preterms with an immature fovea than in controls. Reflectometric and manual segmentation measurements showed increased thickness of inner retinal layers and photoreceptor cell body and outer plexiform layers centrally, but no observable change of photoreceptor inner and outer segment thickness. Our landmark-based analysis of OCT images using reflectometry and manual segmentation provides complementary findings in comparisons of normal and immature foveal structures. We show a central thickness increase in the outer nuclear layer, outer plexiform layer, and postreceptor layers in preterms with signs of arrested foveal development. We found no indication of abnormal photoreceptor inner or outer segment development in preterms.


Evaluation of postmortem urea nitrogen, creatinine and uric acid levels in pericardial fluid in forensic autopsy.
In postmortem biochemistry, there is insufficient data available for the practical analysis of factors in the pericardial fluid. The aim of the present study was to examine postmortem pericardial fluid for urea nitrogen (UN), creatinine (Cr) and uric acid (UA) levels to investigate the pathophysiology of death in forensic autopsy cases (total, n = 409; within 48 h postmortem), which included blunt, sharp instrument injury, asphyxiation, drowning, fire fatalities, hyperthermia, hypothermia, methamphetamine-related fatalities, other poisoning, delayed death from trauma and natural diseases. There was a significant elevation in the three markers for chronic renal failure, gastrointestinal bleeding, hyperthermia, hypothermia, methamphetamine fatalities and delayed traumatic death, which was comparable with the clinical criteria for their serum levels. These postmortem findings showed azotemia due to renal failure, elevated protein catabolism and rhabdomyolysis. Although the pericardial levels were otherwise similar to the clinical serum reference ranges, only the drowning fatalities showed significantly lower levels for each marker. These observations suggested the stability of UN, Cr and UA in the pericardial fluid within 48 h postmortem and their usefulness for the pathophysiological investigation of death involving azotemia.


Validation and cost-effectiveness of a home-based screening system for amblyopia.
To investigate the cost-effectiveness of a novel home-based screening system for amblyopia and amblyogenic risk factors. Evaluation of diagnostic test or technology. Two thousand four hundred forty-two preschoolers 3 to 6 years of age from 10 kindergartens randomly selected from Guangzhou participated in the study in 2009. Preschoolers were assessed for amblyopia and amblyogenic risk factors by their parents using the home-based screening system and were re-evaluated by professionals who conducted a comprehensive eye examination. Sensitivity, specificity, positive predictive value, negative predictive value, and the cost-benefit of the home-based screening system were calculated by comparing the results from the home-assessed model and those from the professional evaluation. Three thousand three hundred children were invited to participate in the study, and 2308 (1216 boys and 1092 girls) completed all of the procedures. Twenty-four amblyopes were found by professional examinations. Fifteen of these amblyopes had not been diagnosed previously, and 12 of them were detected by the home-assessment model. The sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 94.1%, 8.2%, and 99.9%, respectively. Professional examinations cost an average of US $1131.00 per case of amblyopia detected, whereas the cost was only US $266.00 per case for the home-based method. For amblyogenic factors, 50, 87, and 96 children were classified into grade I, II, or III according to the professional examinations. The corresponding numbers in the home-based system were 23, 29, and 15, respectively. Accordingly, the true positive rates were 46.0%, 33.3%, and 15.6% for each grade. The home-based amblyopia screening system was found to be a simple, effective, and cost-beneficial method for amblyopia screening and amblyogenic risk factors. The approach offers a practical option for developing areas with large populations. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Fetal tissue biopsy: techniques and indications.
A considerable variety of invasive intrauterine procedures has been developed in the last 15 years. This article describes techniques for obtaining fetal blood, skin, liver, tumour specimens and chorionic villi, and discusses their indications and risks.


Expression of RPE65, a putative receptor for plasma retinol-binding protein, in nonmelanocytic skin tumours.
In a recent report we described RPE65, a protein originally characterized in retinal pigment epithelium, to be expressed in normal human epidermis. RPE65 is suspected to be involved in cellular uptake of retinol which is transported in the bloodstream complexed with plasma retinol-binding protein. To evaluate protein and mRNA expression of RPE65 in actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) compared with normal skin. RPE65 mRNA expression in skin tumours relative to normal skin of the respective donor was studied by real-time polymerase chain reaction in AK (n = 15), invasive SCC (n = 30) and BCC (n = 18). A peptide-specific anti-RPE65 antibody was used for immunohistochemical staining of formalin-fixed and paraffin-embedded tissue sections of the respective tumours. RPE65 mRNA expression was reduced in AK. A highly significant reduction of RPE65 mRNA was observed in invasive SCC relative to normal skin of the respective donors. Immunohistochemistry revealed a continuous staining of basal and suprabasal keratinocytes in normal human epidermis. RPE65 in AK shown by immunohistochemical staining was reduced and quite irregular, whereas invasive SCC revealed no staining of tumour cells with the anti-RPE65 antibody. RPE65 mRNA values were elevated, whereas immunohistochemical staining for RPE65 protein was heterogeneous in BCC. These results suggest progressive downregulation of RPE65 from AK to invasive SCC.


Remission of orbital sarcoma in a dog, using doxorubicin therapy.
A 7-year-old female mixed-breed dog with an undifferentiated sarcoma of the orbit was treated for 7 months with doxorubicin hydrochloride. Though remission was achieved, the dog died of acute heart failure.


γ-Enolase C-terminal peptide promotes cell survival and neurite outgrowth by activation of the PI3K/Akt and MAPK/ERK signalling pathways.
γ-Enolase, a glycolytic enzyme, is expressed specifically in neurons. It exerts neurotrophic activity and has been suggested to regulate growth, differentiation, survival and regeneration of neurons. In the present study, we investigated the involvement of γ-enolase in PI3K (phosphoinositide 3-kinase)/Akt and MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) signalling, the two pathways triggered predominantly by neurotrophic factors. Whereas the PI3K/Akt pathway, rather than the MAPK/ERK pathway, is involved in γ-enolase-enhanced cell survival, γ-enolase-stimulated neurite outgrowth requires both pathways, i.e. the activation of both PI3K and ERK1/2, leading to subsequent expression of the growth-cone-specific protein GAP-43 (growth-associated protein of 43 kDa). MEK (MAPK/ERK kinase) and PI3K inhibition blocked or attenuated the neurite outgrowth associated with dynamic remodelling of the actin-based cytoskeleton. We show that γ-enolase-mediated PI3K activation regulates RhoA kinase, a key regulator of actin cytoskeleton organization. Moreover, the inhibition of RhoA downstream effector ROCK (Rho-associated kinase) results in enhanced γ-enolase-induced neurite outgrowth, accompanied by actin polymerization and its redistribution to growth cones. Our results show that γ-enolase controls neuronal survival, differentiation and neurite regeneration by activating the PI3K/Akt and MAPK/ERK signalling pathways, resulting in downstream regulation of the molecular and cellular processes of cytoskeleton reorganization and cell remodelling, activation of transcriptional factors and regulation of the cell cycle.


Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures-the OPENTHYRO register cohort.
The relationship between thyrotoxicosis and osteoporotic fractures remains controversial, particularly in men. Register-based cohort study including all patients with a serum thyrotropin (TSH) measurement in the region of Funen 1996-2010. All TSH determinations were done in the same lab, which served all hospitals and General Practice (GP) practices in the region. Persons with raised TSH or a history of thyroid/pituitary disease or use of thyroid medications were excluded. The study population consisted of 222,138 (96%) persons with normal and 9217 (4%) with low TSH (<0.3 mIU/L). A single low TSH at baseline was associated with increased risk of hip fractures (adj HR 1.16, 95% CI 1.07-1.26, p < 0.001) but not major osteoporotic fractures (MOF, adj HR 1.06, 95% CI 0.99-1.12, p = 0.058) over a median follow-up of 7.5 years. When men were analyzed separately, results did not reach statistical significance. We found a significant association between duration of thyrotoxicosis and fracture. For each 6 months in which the mean TSH value was decreased (<0.3 mIU/L), hip fracture risk increased by a factor 1.07 (adj HR, 95% CI 1.04-1.10, p < 0.001) and MOF by 1.05 (adj HR, 95% CI 1.03-1.07, p < 0.001). Overt thyrotoxicosis was associated with an increased risk of hip fractures but not MOF. In euthyroid patients, the risk of fractures increased significantly with each SD unit of TSH decrease: Hip fracture (HR 1.45, 95% CI 1.22-1.71, p < 0.001) and MOF (HR 1.32, 95% CI 1.19-1.46, p < 0.001). In a population-based cohort, a single, first measurement of decreased TSH in patients without known thyroid disease was associated with an increased long-term risk of hip fracture, which remained significant in women but not in men after adjusting for confounders. Moreover, the risk of both hip fracture and MOF increased exponentially by the length of time during which TSH had remained low.


The role of an objective function in the mathematical modelling of wide-angle X-ray diffraction curves of semi-crystalline polymers.
To decompose a wide-angle X-ray diffraction (WAXD) curve of a semi-crystalline polymer into crystalline peaks and amorphous halos, a theoretical best-fitted curve, i.e. a mathematical model, is constructed. In fitting the theoretical curve to the experimental one, various functions can be used to quantify and minimize the deviations between the curves. The analyses and calculations performed in this work have proved that the quality of the model, its parameters and consequently the information on the structure of the investigated polymer are considerably dependent on the shape of an objective function. It is shown that the best models are obtained employing the least-squares method in which the sum of squared absolute errors is minimized. On the other hand, the methods in which the objective functions are based on the relative errors do not give a good fit and should not be used. The comparison and evaluation were performed using WAXD curves of seven polymers: isotactic polypropylene, polyvinylidene fluoride, cellulose I, cellulose II, polyethylene, polyethylene terephthalate and polyamide 6. The methods were compared and evaluated using statistical tests and measures of the quality of fitting.


A guideline-based approach to asthma management.
The management of asthma has dramatically improved in recent years because of a better understanding of the disease and an organized approach to therapy. All of the various components and tools for evaluating individuals with asthma may be found in the Expert Panel Report Guidelines by the National Heart, Lung, and Blood Institute, initially published in 2007. These comprehensive guidelines help health care professionals care for individuals with asthma throughout their lifespan. This article will assist the health care provider to use these evidence-based guidelines.


Heterogeneity of nuclear glucocorticoid receptor interactions.
When thymocytes are incubated with glucocorticoids at 37 degrees, 60--70% of the receptor bound steroid is associated with the nucleus. Under conditions where the rate of steroid-receptor formation is not limiting the transfer of steroid-receptors from the cytoplasm to the nucleus occurs rapidly with a T 1/2 of 30 seconds. These observations have led us to investigate whether or not all glucocorticoid receptor complexes are associated with the nucleus in the same manner. To this end, nuclear glucocorticoid-receptor complexes have been extracted by differential salt extraction and DNase I and DNase II digeston. Of the nuclear dexamethasone receptor complex initially bound, 70--75% is resistant to 0.2 M KCl extraction (designated N2) and 25--30% is resistant to 0.4 extraction (designated N4). N2 can be further extracted with 0.4 M KCl whereas N4 is resistant to reextraction with either 0.2 M KCl, suggesting that N2-N4 (N2-4) and N4 represent distinct physical forms of nuclear dexamethasone receptor. In intact cells, N2 and N4 differ under the following physiological condition. (1) N4 binding occurs prior to N2-4; (2) a cold chase of unlabeled dexamethasone decreases N2-4 by 70% but N4 binding by only 10%; (3) N4 binding decreases more rapidly than N2-4 following a decrease in hormone concentration by dilution; (4) a cold chase of either cortexolone or progesterone preferentially decreases N2-4 and has little effect on N4. In addition, the nuclear N2-4 and N4 distribution differ for cortisol, dexamethasone and triamcinolone acetonide, three steroids having different in vitro biological potencies. DNase I treatment of nuclei solubilizes approximately 60% of nuclear DNA yet releases only 20--30% of nuclear receptor, whereas DNase II solubilizes only 10% of nuclear DNA and releases 76--80% of nuclear receptor. As seen with salt extraction, the resistance of nuclear glucocorticoid-receptor complexes to a DNase I and II is dependent on the steroid molecule which is associated with the receptor. Of the steroids we have tested, nuclear triamcinolone acetonide and dexamethasone receptor complexes are most resistant to nuclease attack. Nuclear cortisol receptor complexes are readily solubilized by either DNase I or II under conditions where little dissociation of steroid from receptor occurs. These data represent evidence for physiologically distinct forms of nuclear glucocorticoid receptor interaction. In addition, they demonstrate the importance of the steroid portion of the steroid receptor in directing the nature and/or location of steroid receptors within or on the nucleus.


The effects of carbodiimides on functions associated with the energy-conservation mechanism in beef heart sub-mitochondrial particles.
N,N'-di-n-propyl-, N,N'di-n-butyl-, N,N'-di-n-pentyl-, N,N'di-n-hexyl-, N,N'di-n-octoyl, N,N'-dibenzhydryl-, and N,N'-dibenzhydrylcarbodiimides were synthesized. They were all effective inhibitors (2 nmoles carbodiimide per milligram protein) of the ATP-driven reduction of NAD by succinate and the ATP-driven transhydrogenase activities catalyzed by beef heart submitochondrial particles (SMP). They had no effect on the nonenergy-linked transhydrogenase and stimulated the succinate-driven aerobic transhydrogenase activity of beef heart SMP. It was concluded that they exert their effects by reacting with the N,N'-dicyclohexylcarbodiimide-binding protein. Water-soluble carbodiimides were not effective inhibitors.


The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats.
Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35 ± 9.8 mm(2)); increased levels of TNF-α, IL-1β, and MDA (2311 ± 302.3 pg/mL, 901.9 ± 106.2 pg/mL, 121.1 ± 4.3 nmol/g, respectively); increased MPO activity (26.1 ± 3.8 U/mg); and reduced GSH levels (180.3 ± 21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77 ± 5.3 mm(2)); reduced TNF-α, IL-1β, and MDA formation (1502 ± 150.2 pg/mL, 632.3 ± 43.4 pg/mL, 78.4 ± 7.6 nmol/g, respectively); lowered MPO activity (11.7 ± 2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9 ± 40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.


Roles of platelets and proteinase-activated receptors in gastric ulcer healing.
Proteinase-activated receptors (PARs) are expressed on the surface of many cells, but those on the platelet have been among the most thoroughly characterized. PARs act as key receptors mediating the proaggregatory and pro-secretory effects of thrombin. In addition to contributing to hemostasis, platelets are increasingly being viewed as important contributors to healing and to tumor growth. This is attributable to the many pro- and anti-angiogenic factors that are stored within platelets, which can be released at the sites of injury and new vessel growth. In this paper, we review the importance of the platelet in gastric ulcer healing, the contribution of platelet-contained angiogenic factors to the healing of gastric ulcers, and the role of PARs in regulating the release of angiogenic factors from platelets. Taken together, our results suggest that PARs, including those expressed on platelets, are a rational therapeutic target for modulating healing processes and tumor growth.


Short Report on Effectiveness of an Autistic-Delivered Peer Support Program: Preliminary Results.
There is little research on the effectiveness of autistic peer-delivered services. This study examines early outcomes associated with the Community Autism Peer Specialist program (CAPS), which was created in partnership with autistic individuals and is delivered by autistic adults who have received training in the delivery of peer support services to enhance the community functioning of autistic youth and adults. A single group pre-test/post-test design was used to examine early outcomes in the areas of independent living needs, social functioning, service engagement, and quality of life. A total of 23 individuals with autism aged 14-41 years were included in the study. Reductions were found in social functioning impairments and unmet needs after three months in the program. Participants also reported greater engagement in mental health services and activities that promote wellness compared with before the program. This study suggests that peer support services delivered by autistic peers may be an effective intervention approach for autistic youth and adults. Future studies with a more rigorous study design (e.g., randomized controlled trials), a larger sample size, and longer-term outcome measurements are needed to further investigate the effectiveness of CAPS and similar autistic-delivered services.


Pseudoaneurysm of external iliac artery after extracorporeal shock wave lithotripsy revealing Behçet disease.
Extracorporeal shock wave lithotripsy (ESWL) can lead to rare but severe arterial complications. The causal relationship of ESWL with arterial pseudoaneurysm formation in a patient with Behçet disease is discussed. A 35-year-old man presented with acute recrudescence of right flank pain caused by ureteral lithiasis immediately after having undergone a last session of ESWL. Abdominal examination revealed a painful pulsatile mass in the right iliac region. Contrast-enhanced computed tomography identified a pseudoaneurysm of the right external iliac artery in a patient with a medical history of Behçet disease. The pseudoaneurysm was treated endovascularly, including the use of a covered stent with intensive immunosuppressive therapy. We obtained successful exclusion of the pseudoaneurysm. This case highlights that arterial pseudoaneurysm may occur after ESWL in patients with Behçet disease. Strict follow-up after ESWL sessions is necessary.


Enhancement of glioma radiotherapy and chemotherapy response with targeted antibody therapy against death receptor 5.
TRA-8 is an agonistic mouse monoclonal antibody that binds to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor 5, which induces apoptosis in cancer cells through a caspase-8-dependent mechanism. We investigated the ability of TRA-8 to augment the radiotherapy (RT) and chemotherapy response of human glioma cells in vitro and in vivo. The in vitro cytotoxicity of TRA-8 and temozolomide (Tmz) or RT was examined using adenosine triphosphate-dependent viability and clonogenic survival assays with five glioma cell lines. Death receptor 5 expression was determined by flow cytometry. In vivo studies included subcutaneous and intracranial xenograft models testing various combination treatments, including RT, Tmz, and TRA-8. TRA-8, combined with Tmz or RT, produced enhanced cytotoxicity against five glioma cell lines compared with the use of the individual agents alone. Death receptor 5 upregulation occurred in response to RT. Complete tumor regression in the subcutaneous experiments was the most common in animals that received combination therapy with TRA-8/Tmz/RT. TRA-8 enhanced tumor growth delay in combination with RT or Tmz. TRA-8 alone had limited activity against intracranial tumors. In contrast, the median survival of mice treated with TRA-8/Tmz/RT was significantly greater than the control or TRA-8-alone-treated mice. The median survival of the mice treated with TRA-8/Tmz/RT or chemoradiotherapy only was significantly greater than the control or TRA-8-treated mice. A trend toward improved survival was observed between TRA-8/Tmz/RT-treated and Tmz/RT-treated mice. These preliminary findings support the hypothesis that TRA-8 will augment the RT and chemotherapy response in gliomas. A humanized version of TRA-8 is being evaluated in a Phase II clinical trial.