Association of two DRD2 gene polymorphisms with acute and tardive antipsychotic-induced movement disorders in young Caucasian patients.
Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamine system. This study aimed to replicate previously reported associations in candidate genes for acute and tardive antipsychotic-induced MD in a young Caucasian sample. In 402 patients (median age 26 years), a total of 13 polymorphisms were genotyped in eight dopamine-related candidate genes selected a priori from the literature (regarding dopamine and serotonin receptors, dopamine degradation, and free radicals scavenging enzymes pathways). Patients with MD used on average a higher haloperidol dose equivalent when compared to those without MD. The prevalence of MD was high and did not differ between first- and second-generation antipsychotics. Significant associations were found between (a) the TaqI_D polymorphism and akathisia (OR = 2.3, p = 0.001 for each extra C-allele) and (b) the -141C polymorphism and tardive dyskinesia (OR = 0.20, p = 0.001 for each extra Del allele). The other polymorphisms were not significantly associated with an MD. Two associations were found between genetic variation TaqI_D and the -141C polymorphisms in the DRD2 gene and antipsychotic-induced MD; one with acute akathisia and one with tardive dyskinesia. These were previously reported to be associated with tardive dyskinesia and acute parkinsonism, respectively. These results suggest that the contribution of these DRD2 gene variants in the vulnerability of antipsychotic-induced MD takes place in a more general or pleiotropic way.


Molecular phylogenetic studies on filarial parasites based on 5S ribosomal spacer sequences.
This paper is the first large-scale molecular phylogenetic study on filarial parasites (family Onchocercidae) which includes 16 species of 6 genera: Brugia beaveri Ash et Little, 1962, B. buckleyi Dissanaike et Paramananthan, 1961; B. malayi (Brug, 1927) Buckley, 1960; B. pahangi (Buckley et Edeson, 1956) Buckley, 1960; B. patei (Buckley, Nelson et Heisch, 1958) Buckley, 1960; B. timori Partono et al, 1977; Wuchereria bancrofti (Cobbold, 1877) Seurat, 1921: W. kalimantani Palmieri. Purnomo, Dennis and Marwoto, 1980: Mansonella perstans (Manson, 1891) Eberhard et Orihel, 1984; loa loc, Stiles, 1905; Onchocerca volvulus (Leuckart, 1983) Railliet er Henry, 1910; O. ochengi Bwangamoi, 1969; O. gutturosa Neumann, 1910; Dirofilaria immitis (Leidy, 1856) Railliet e Henry, 1911; Acanthocheilonema viteae (Krepkogorskaya, 1933) Bain, Baker et Chabaud, 1982 and Litomosoides sigmodontis Chandler, 1931. 5S rRNA gene spacer region sequence data were collected by PCR, cloning and dideoxy sequencing. The 5S rRNA gene spacer region sequences were aligned and analyzed by maximum parsimony algorithms, distance methods and maximum likelihood methods to construct phylogenetic trees. Bootstrap analysis was used to test the robustness of the different phylogenetic reconstructions. The data indicated that 5S spacer region sequences are highly conserved within species yet differ significantly between species. Spliced leader sequences were observed in all of the 5S rDNA spacers with no sequence variation, although flanking region sequence and length heterogeneity was observed even within species. All of the various tree-building methods gave very similar results. This study identified four clades which are strongly supported by bootstrap analysis the Brugia clade; the Wuchereria clade; the Brugia-Wuchereria clade and the Onchocerca clade. The analyses indicated that L. sigmodontis and A. viteae may be the most primitive among the 16 species studied. The data did not show any close relationship between Loa loa and D. immitis presently classified in the same subfamily, and the constitution of the Dirofilariinae subfamily is questionable.


Molecular approaches to diagnosis and management of ovarian cancer.
The recent advances in the understanding of the pathogenesis of ovarian cancer have been helpful in addressing issues in diagnosis, prognosis and management. The study of ovarian tumours by novel techniques such as immunohistochemistry, fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase chain reaction and new tumour markers have aided the evaluation and application of new concepts into clinical practice. The correlation of novel surrogate tumour specific features with response to treatment and outcome in patients has defined prognostic factors which may allow the future design of tailored therapy based on a molecular profile of the tumour. These have also been used to design new approaches to therapy such as antibody targeting and gene therapy. The delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the pathogenesis of ovarian cancer has led initially to the development of anti-c-erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will have an impact in the diagnosis and the prevention of familial ovarian cancer. The important role played by recessive genes such as p53 in cancer has raised the possibility of restoration of gene function by gene therapy. Although the pathological diagnosis of ovarian cancer is still confirmed principally on morphological features, addition of newer investigations will increasingly be useful in addressing difficult diagnostic problems. The increasingly rapid pace of discovery of genes important in disease, makes it imperative that the evaluation of their contribution in the pathogenesis of ovarian cancer is undertaken swiftly, thus improving the overall management of patients and their outcome.


A principle-based approach to ethical issues in predictive genetic testing for breast cancer.
Genetic breast cancer susceptibility testing presents ethical challenges for healthcare providers and their patients. The familial aspects of genetic information, recognition of DNA as a shared history and present common thread for all people and widespread misunderstandings of genetic tests all contribute to these challenges. In this article an ethical framework internationally developed as a charter for medical professionalism is used to guide approaches to ethical dilemmas of breast cancer genetic testing. Specifically, three ethical principles are explored as they relate to testing: primacy of patient, patient autonomy, and social justice. Approaching breast cancer genetic testing from this framework could help to ensure thoughtful and ethical practices in this rapidly evolving field.


Black sky: Exposing electricity as the Achilles' heel of resilience.
The national power grid is the most critical and the most vulnerable life-support infrastructure in modern society. Electricity serves as the essential element in sustaining every other sector of critical infrastructure including water, fuel and communications. Collective experience with responding to and recovering from widespread, long-duration power outages - known as black sky events - is nearly non-existent. Understanding these risks and weaknesses requires a collaborative planning effort with the public and private sectors to identify and protect critical nodes within the interdependent infrastructure to ensure that recovery from a catastrophic event is possible. This also requires a 'whole community' approach to planning and execution to facilitate a response on an unprecedented level.


Molecular characterization of the effects of Y-27632.
Many key cellular functions, such as cell motility and cellular differentiation are mediated by Rho-associated protein kinases (ROCKs). Numerous studies have been conducted to examine the ROCK signal transduction pathways involved in these motile and contractile events with the aid of pharmacological inhibitors such as Y-27632. However the molecular mechanism of action of Y-27632 has not been fully defined. To assess the relative contribution of these Rho effectors to the effects of Y-27632, we compared the cytoskeletal phenotype, wound healing and neurite outgrowth in cells treated with Y-27632 or subjected to knockdown with ROCK-I, ROCK-II or PRK-2- specific siRNAs. Reduction of ROCK-I enhances the formation of thin actin-rich membrane extensions, a phenotype that closely resembles the effect of Y-27632. Knockdown of ROCK II or PRK-2, leads to the formation of disc-like extensions and thick actin bundles, respectively. The effect of ROCK-I knockdown also mimicked the effect of Y-27632 on wound closer rates. ROCK-I knockdown and Y-27632 enhanced wound closure rates, while ROCK-II and PRK-2 were not appreciably different from control cells. In neurite outgrowth assays, knockdown of ROCK-I, ROCK-II or PRK-2 enhances neurite lengths, however no individual knockdown stimulated neurite outgrowth as robustly as Y-27632. We conclude that several kinases contribute to the global effect of Y-27632 on cellular responses.


An analysis of the pediatric vaccine supply shortage problem.
In 2002, several factors resulted in pediatric vaccine manufacturers not being able to produce a sufficient number of vaccines to vaccinate all the children in the United States according to the Recommended Childhood Immunization Schedule. The resulting vaccine supply shortage resulted in thousands of children not being fully immunized according to this schedule, and hence, created an unnecessary risk for epidemic outbreaks of several childhood diseases. The Centers for Disease Control and Prevention responded to this crisis by using pediatric vaccine stockpiles to mitigate the impact of future shortages. This paper presents a stochastic model that captures the vaccine supply during production interruptions. This model is used to assess the impact of pediatric vaccine stockpile levels on vaccination coverage rates, by considering the probability that all children can be immunized according to the Recommended Childhood Immunization Schedule over a given time period and the expected minimum vaccine supply. The model is also used to assess the proposed pediatric vaccine stockpile levels recommended by the United States Department of Health and Human Services. The results of this analysis suggest that the proposed vaccine stockpile levels are adequate to meet future vaccine production interruptions, provided that such production interruptions do not last more than six months (which is not surprising, given that is the time period for which they were designed). However, given that recent vaccine production interruptions have lasted (on average) for over one year, the proposed vaccine stockpile levels are insufficient to meet the nation's pediatric immunization needs during such time periods, which in turn could lead to localized and/or widespread disease outbreaks. Moreover, a moderate investment in higher vaccine stockpile levels would lead to a significantly reduced risk of such events.


Magnesium: Nutrition and Homoeostasis.
The essential mineral magnesium is involved in numerous physiological processes. Recommended dietary intake is often not met and a low magnesium status increases the risk for various diseases. Magnesium status is regulated by several magnesium transport systems either in cellular or paracellular pathways. Numerous drugs either interfere with magnesium absorption in the intestines or the reabsorption from primary urine in the kidney. Low magnesium status has been identified as a significant risk factor for several diseases, including type-2 diabetes, cardiovascular diseases, arrhythmias, as well as general muscular and neurological problems. Therefore, an adequate magnesium supply would be of special benefit to our overall health.


Identification and characterization of fluid milk consumer groups.
Consumption of fluid milk has steadily declined over the last few decades. Understanding the attributes of fluid milk products that are attractive to specific consumer groups may provide a sound basis for education and marketing to encourage increased dairy consumption and reverse the downward trend. The objective of this study was to identify the attributes of fluid milk that specific consumer groups find attractive and attributes that suggest a higher purchase likelihood. An adaptive choice-based conjoint (ACBC) survey was designed to assess attributes of fluid milk. The ACBC survey included Kano, importance, labeling identification, and beliefs questions to determine the key attributes that dictated consumer purchase and consumption. Self-reported purchase habits and attitudes for organic food products were also collected. Attributes in the ACBC exercise included fat content, package type, shelf life, and label claims. Maximum difference scaling was used to rank the importance of attributes in fluid milk that affected purchase. Maximum difference scaling was also used to rank qualities and issues associated with organic milk that were most motivating for those who identified as organic milk consumers. Results were analyzed by univariate and multivariate statistics. A total of 1,163 fluid milk consumers completed the survey, and of those, 434 were regular purchasers of organic milk. The ideal fluid milk from conjoint analysis was 2% milkfat, organic, packaged in a plastic jug, conventionally pasteurized, and contained no additives or label claims. The belief that "organic milk is healthier" was the most important motivator for purchases of organic milk, followed by the beliefs that "organic milk production encourages ethical treatment of animals" and "organic milk production supports local farms and farmers." Conjoint importance scores of all fluid milk consumers showed that milkfat content was the most important attribute, followed by flavor, package size, and price. For all milk consumers, designation as organic was ranked as the 8th most important of 14 attributes. Evaluation of these results on both aggregate and individual levels suggest that fluid milk consumers are not a homogeneous consumer group and that underlying consumer groups are led to purchase decisions by specific product features or expectations.


Beta-TrCP1-mediated degradation of PERIOD2 is essential for circadian dynamics.
Regulated degradation of circadian clock proteins is a crucial step for rhythm generation per se but also for establishing a normal circadian period. Here, the authors show that the F-box protein beta-transducin repeat containing protein 1 (beta-TrCP1) as part of the E3 ubiquitin ligase complex is an essential component of the mammalian circadian oscillator. Down-regulation of endogenous beta-TrCP1 as well as expression of a dominant-negative form both result in lengthening of the circadian period in oscillating fibroblasts. These phenotypes are due to an impaired degradation of PERIOD (PER) proteins, since expression of beta-TrCP interaction-deficient PER2 variants--but not wild-type PER2--results in a dramatic stabilization of PER2 protein as well as in the disruption of circadian rhythmicity. Mathematical modeling conceptualizes the authors' findings and suggests that loss of sustained rhythmicity in cells with eliminated beta-TrCP-mediated PER2 degradation is due to excessive nuclear repression, a prediction they verified experimentally.


Protective effects of sesamin on liver fibrosis through antioxidative and anti-inflammatory activities in rats.
Sesamin (Ses) from Sesamun indicum seeds has potent antioxidants and anti-inflammatory effects. This study focused on the antioxidant and anti-inflammatory effects of Ses on Carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats and the potential mechanism underlying the activation of NF-kB pathway. Hepatic fibrosis was induced by interaperitoneally (i.p.) administered with 20% CCl4 in corn oil (2 mL/kg for 8 weeks) in rats. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were checked. The levels of protein carbonyls and antioxidant enzymes such as superoxide dismutase (SOD) and GSH-Px were determined after Ses administration. H&E and Masson's trichrome staining for histopathological changes of liver tissues were observed. Western blotting was used to detect expression of IL-6, cyclooxygenase-2 (COX-2), and NF-kB activation. Finally, the levels of hydroxyproline in liver tissues were also determined. Ses decreased the release of liver enzymes - ALT, AST, and TBIL, reduced protein carbonyls, attenuated the reduction of SOD and GSH-Px activities induced by CCl4 in the liver tissue. It also significantly reduced the levels IL-6 and COX-2 in the liver caused by CCl4 by inhibition of NF-kB activation. Histological results indicated that Ses significantly improved the pathological lesions of liver fibrosis. Ses exerted hepatoprotective effects possibly due to the antioxidant effect and suppressing the NF-kB activation.


Orthopaedic manifestations in congenitally insensate patients.
The spectrum of orthopaedic problems in eight congenitally insensate patients was reviewed. The conditions included congenital insensitivity to pain, Riley-Day syndrome, and Lesch-Nyhan syndrome. In each of these conditions, the patient has an abnormality of interpretation of painful stimuli or lacks normal pain avoidance, leading to self-inflicted damage. The orthopaedic problems and complications included fracture, self-mutilation, autoamputation, osteomyelitis, septic arthritis, Charcot joints, scoliosis, and dislocation. Effective management consists of early diagnosis and patient/parent education to prevent as many complications as possible. Fractures may be treated conservatively, while progressive scoliosis requires operative intervention. Osteomyelitis, septic arthritis, and Charcot joints require appropriate operative treatment.


A case of duodenal involvement of multiple myeloma imaged by positron emission tomography with 18F-fluorodeoxyglucose.
A 61-year-old woman had been treated for multiple myeloma for 4 years when she developed abdominal pain. Ultrasonography and computed tomography revealed a tumor in the abdomen. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) showed increased FDG uptake in the tumor. In previous bone marrow lesions, which were in clinical remission after chemotherapy and radiotherapy, abnormal FDG uptake was not recognized. Pathological examination after surgery revealed the tumor to be a plasmacytoma of the duodenum. Plasmacytoma of the duodenum is rare but can be seen during the clinical course of multiple myeloma. A few reports have described FDG PET findings of plasmacytoma. Those previous reports and our present case suggest a potential value of FDG PET in the evaluation of multiple myeloma.


Prevalence and Causes of Hyperuricemia in Children.
Introduction There are various factors responsible for hyperuricemia in children, however, there is extremely limited local data available. In this study, we aim to determine the causes and risk factors associated with hyperuricemia. This study will assist pediatric consultants to identify children who might be at risk of hyperuricemia and manage them accordingly. Methods This study was conducted in pediatric outpatient departments of various tertiary care hospitals from January 2018 to December 2019. Five thousand (n = 5000) children of either gender between the age group of 1-14 years, were enrolled in the study after informed consent from their parents. Uric acid levels were assessed by using the UASure blood uric acid monitoring handheld device. Results In our study, n = 1301 (26.02%) children had hyperuricemia. Hyperuricemia was more common in male compared to females (65.49% vs. 34.51%; p-value <0.00001) and in older children (9 ± 2 years vs. 7 ± 3; p-value <0.00001). In hyperuricemia patients, the most common disorder was gastroenteritis (23.98%), followed by respiratory infection (23.14%) and asthma (15.45%). Conclusion Hyperuricemia in children is very prevalent in the local setting. Patients with pre-existing conditions like congenital heart disease, asthma, epilepsy, and cancers should routinely be screened for hyperuricemia and managed accordingly to avoid long-term complications associated with hyperuricemia.


Comparative phenotypic and genotypic discrimination of methicillin resistant and susceptible Staphylococcus aureus in Egypt.
The present study was designed to elucidate the phenotypic and genotypic characterization of S. aureus isolates in Egypt. The antibiotic susceptibility pattern of 133 identified S. aureus isolates revealed that over 70% of the isolates were multi-drug resistant (MDR). Fifty MDR isolates were characterized using antibiotyping and different molecular typing methods. Amplification of mecA gene confirmed 30 strains as methicillin-resistant S. aureus (MRSA) and 20 as methicillin-sensitive S. aureus (MSSA). Generally, 22 MRSA (73.33%) and ten MSSA (50%) harbored Panton-Valentine leukocidin (pvl) gene with no statistically significant difference (p=0.093). Staphylococcal cassette chromosome (SCC) mec typing revealed that 48% of the typeable MRSA isolates possessed SCCmec type IV. SCCmec and antimicrobial susceptibility typing signified the presence of community-acquired (CA)-MRSA in Egypt. Surprisingly, all isolates of SCCmec types I, II and III and 50% of both MRSA isolates of SCCmec types IV and V possessed pvl gene. It was clear that staphylococcal protein A (spa) and coagulase (coa) typing discriminated the isolates into eight different groups, whilst polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of coagulase gene yielded ten distinct RFLP banding patterns. This study presented the first baseline information on the characterization of MRSA and MSSA in Egypt.


Takayasu arteritis in children: preliminary experience with cyclophosphamide induction and corticosteroids followed by methotrexate.
To review the results of our treatment protocol in the last 7 years. Six patients (4 girls, 2 boys) with an age range of 12 to 17 years were diagnosed with Takayasu arteritis (TA) during this period. Patients were allocated to receive (1) oral steroids and methotrexate (MTX) (12.5 mg/m(2)/week) if they had disease limited to one side of the diaphragm only without pulmonary disease involvement (two patients); and (2) oral steroids and oral cyclophosphamide (CYC) (maximum total dose 150 mg/kg) followed by oral MTX for maintenance as above if the disease was more widespread (four patients). One patient died of pulmonary vasculitis during the first month of therapy. The remaining three patients with involvement of both the thoracic and abdominal aorta and branches received the second protocol for 12 to 18 months. All entered remission. Aortic bypass, aortorenal bypass, balloon dilatation, and unilateral nephrectomy were performed in these patients. The presented single-center experience suggests that CYC induction and corticosteroids followed by MTX is an effective and safe treatment for childhood TA.


Apoptotic signaling in bufalin- and cinobufagin-treated androgen-dependent and -independent human prostate cancer cells.
Prostate cancer has its highest incidence in the USA and is becoming a major concern in Asian countries. Bufadienolides are extracts of toxic glands from toads and are used as anticancer agents, mainly on leukemia cells. In the present study, the antiproliferative and apoptotic mechanisms of bufalin and cinobufagin on prostate cancer cells were investigated. Proliferation of LNCaP, DU145, and PC3 cells was measured by 3-(4,5-dimethylthiazol-2-yle)-2,5-diphenyltetrazolium bromide assay and the doubling time (tD) was calculated. Bufalin and cinobufagin caused changes in the tD of three prostate cancer cell lines, which were more significant than that of human mesangial cells. In addition, bufadienolides induced prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. After treatment, the caspase-3 activity and protein expression of caspase-3, -8, and -9 were elevated. The expression of other apoptotic modulators, including mitochondrial Bax and cytosolic cytochrome c, were also increased. However, expression of p53 was only enhanced in LNCaP cells. Downregulation of p53 by antisense TP53 restored the cell viability suppressed by bufalienolides. Furthermore, the increased expression of Fas was more significant in DU145 and PC3 cells with mutant p53 than in LNCaP cells. Transfection of Fas small interfering RNA restored cell viability in the bufadienolide-treated cells. These results suggest that bufalin and cinobufagin suppress cell proliferation and cause apoptosis in prostate cancer cells via a sequence of apoptotic modulators, including Bax, cytochrome c, and caspases. The upstream mediators might be p53 and Fas in androgen-dependent LNCaP cells and Fas in androgen-independent DU145 and PC3 cells.


[Indications for a favourable effect of intensive insulin therapy for newly-diagnosed type 2 diabetes].
In a recent Chinese trial, patients with newly-diagnosed type 2 diabetes mellitus received a short-term, intensive therapy with insulin during 2-4 weeks, or oral medication. Euglycaemia was achieved in nearly all patients. After one year, about half of the patients who had received insulin were in complete remission, as opposed to 27% of those on oral medication. The favourable pathophysiological mechanisms in the insulin group may be related to the biological effects of insulin, such as reducing the toxic influence of glucose on beta-cells and so-called beta-cell rest. These interesting findings need confirmation, notably in caucasoid populations, before guidelines for treatment of patients with type 2 diabetes can be changed.


Aptamer-PROTAC Conjugates (APCs) for Tumor-Specific Targeting in Breast Cancer.
Development of proteolysis targeting chimeras (PROTACs) is emerging as a promising strategy for targeted protein degradation. However, the drug development using the heterobifunctional PROTAC molecules is generally limited by poor membrane permeability, low in vivo efficacy and indiscriminate distribution. Herein an aptamer-PROTAC conjugation approach was developed as a novel strategy to improve the tumor-specific targeting ability and in vivo antitumor potency of conventional PROTACs. As proof of concept, the first aptamer-PROTAC conjugate (APC) was designed by conjugating a BET-targeting PROTAC to the nucleic acid aptamer AS1411 (AS) via a cleavable linker. Compared with the unmodified BET PROTAC, the designed molecule (APR) showed improved tumor targeting ability in a MCF-7 xenograft model, leading to enhanced in vivo BET degradation and antitumor potency and decreased toxicity. Thus, the APC strategy may pave the way for the design of tumor-specific targeting PROTACs and have broad applications in the development of PROTAC-based drugs.


Factors in academia and service that influence baccalaureate graduates' membership in the American Nurses' Association.
The intent of this study was to explore relationships among models of influence, association experiences, attitudes toward the American Nurses' Association (ANA), attitudes toward professionalism, and first-year baccalaureate nurse graduates joining the American Nurses' Association. One hundred sixty-three baccalaureate nurses from programs in three northeastern states returned a mailed questionnaire. Analysis of the data showed that graduates identified deans and faculty as more favorably disposed toward the ANA as compared to supervisors, head nurses, and peers. Faculty were identified more often as influencing subjects to join the ANA. Respondents saw the ANA as valuable for the profession, representing nursing, and promoting standards but they generally did not hold membership. Professionalism content in the curriculum had no relationship to scores on either of the two scales or to ANA membership. Having had ANA content was positively related to seeing the ANA as promoter of human rights and as a voice for nursing. There were significant differences between ANA members and non-members and use of the professional organization as a major referent and seeing the ANA as an accreditor. It was concluded that faculty and deans were positive models of influence for new graduates regarding the Association but did not affect membership for those graduates. Further study of curriculum content and professional role model behavior in the work setting is urgently needed.


Determinants of coping responses among Mexican American adolescents.
This study examined relationships among perceived stress, self-esteem, acculturation, and gender with the coping response of 472 Mexican American adolescents aged 14 to 16 years. Subjects were drawn from a predominantly Mexican American population located in the Lower Rio Grande Valley region of Texas. Data were collected through a self-report instrument consisting of perceived stress, acculturative status, self-esteem, and coping strategy scales. Subjects reported relatively high perceived stress levels, low acculturation, and moderate self-esteem scores with no significant gender differences. Analysis revealed self-esteem as most predictive of a more effective overall coping response. Results suggest Mexican American adolescents possessing high self-esteem are less likely to encounter damage to their sense of self when confronted with stressors, thus allowing for productive coping.


Intravenous leiomyomatosis with caval involvement: report of a case with radical resection and venous replacement.
Intravenous leiomyomatosis is a rare, histologically benign neoplasm that may be malignant in its specific tendency to intravascular extension. A case of intravenous leiomyomatosis with extension into the entire inferior vena cava in a 41-year-old woman is described. The patient was diagnosed with syncope 3 years after hysterectomy and was treated with a 1-stage procedure including venous replacement.


Analysis of the peripheral blood T-cell receptor (TCR) repertoire in monozygotic twins discordant for Crohn's disease.
T cell involvement in the inflammatory process of Crohn's Disease (CD) is evident by an increase in activated T cells and their cytokines in actively inflamed CD tissue. It has been suggested that CD may involve a superantigen based on the observation that a significant proportion of CD patients express elevated levels of V beta 8+ T cells in their peripheral blood compared to normal controls. In order to determine whether a superantigen might play a role in the pathogenesis of CD we have compared the TCR repertoires of four pairs of monozygotic twins discordant for CD. By using monozygotic twins, we could rule out the effects of HLA and other genes on the TCR repertoire. The TCR repertoires were analyzed by using a panel of V-segment-specific mAb and by quantitative polymerase chain reaction (qPCR) using V beta-specific oligonucleotide primers. In all cases the TCR repertoires of the affected and unaffected sibs were strikingly similar. We did not observe any TCR segment that was consistently altered in frequency or expression levels in all of the affected sibs compared to their identical twin. Furthermore, we did not see an increase in V beta 8+T cells in the peripheral blood of the CD sibs relative to their normal counterpart. These studies suggest that the presence of CD does not alter the TCR repertoire of peripheral blood in any obvious way and argue against the role of a superantigen in the etiology of pathogenesis of CD.


Debye series for light scattering by a spheroid.
The Debye series is developed for electromagnetic scattering by a spheroid in order to decompose the far-zone fields into various physical processes. The geometrical rainbow angle and supernumerary spacing parameter are determined from the Debye intensity by fitting the results to an Airy function and comparing them to their assumed values in ray optics and Airy theory, respectively. Eccentricity-related scattering phenomena including the rainbow's angular shift, the disappearance of the rainbow, and the rainbow-enhanced glory are quantitatively demonstrated and analyzed.


Experiences against HIV/AIDS/STDS of Somalis in exile in Gothenburg, Sweden.
Since 1989, the City of Göteborg Immigrant Services Administration has been making efforts to inform about HIV/AIDS. The purpose has been to ensure that even immigrant residents of the City of Göteborg (Gothenburg) have access to relevant information about HIV/AIDS. The administration's efforts have been a part of the collected efforts of Gothenburg to prevent the spreading of HIV. This paper attempts to discover and describe experiences against HIV/AIDS/STDs of Somalis in Exile in Gothenburg, Sweden. A qualitative sociological in-depth interviews with 13 individuals (6 women and 7 men) and with semi-structured and themetized emerging design was carried on. A follow up focus group interviews with 10 individuals (2 women and 8 men) was also performed. The paper reveals that the general understanding of subjects on the issues under discussion is almost the same though details may vary from one research participant to the other. They have described this through narratives. STDs and specially HIV/AIDS was perceived as something dishonourable by the subjects. The HIV/AIDS is perceived as a sin which Allah sends to punish those who have fornication or sex without marriage (Zinna). Of course, this tendency of shying off the problem leads to ignorance of how to behave, which in turn decreases the risk of perceptions and as a result may also increase the risk of being infected. As concerns protection as a preventive measure, attitudes vary. The traditionalists have argued that condom increased the possibility of promiscuity or fonication, while young and more modern people saw condom as something good. We may conclude that Somalis who have arrived in Western world and in Sweden as adults did never have a modern sexual education for themselves due to socio-cultural reasons and this has important implication for giving proper information to their children about sex organs, human sexual development and preventive measures against HIV/AIDS/STDs. These immigrant parents should be offered culturally sensitive communication and educational programmes aimed at raising their awareness about teenagers sexuality and the preventive measures against HIV/AIDS/STDs.


Ex utero Intrapartum Treatment to Ventricular Pacing: A Novel Delivery Strategy for Complete Atrioventricular Block with Severe Bradycardia.
Fetuses with anti-SSA-mediated complete atrioventricular block (CAVB) are at high risk for perinatal death if they present at <20 weeks of gestation and develop ventricular rates of <55 beats per minute (bpm), cardiac dysfunction, or hydrops [Izmirly et al.: Circulation 2011;124:1927-1935; Jaeggi et al.: J Am Coll Cardiol 2002;39:130-137; Eliasson et al.: Circulation 2011;124:1919-1926]. After our experience with two such fetuses who died with pulseless electrical activity despite being paced within 30 min of birth, we performed an ex utero intrapartum treatment procedure to ventricular pacing on a 36-week CAVB fetus with cardiac dysfunction, mild hydrops, and a ventricular rate of 46 bpm. While still on placental bypass, temporary epicardial ventricular pacing leads were successfully placed; the infant was delivered and made a successful transition to postnatal life. This approach can improve the 11-fold increase in mortality for the preterm fetus with long-standing CAVB, severe bradycardia, and heart failure.


Lateral differences in visual inspection time? The role of apparent motion cues.
There are a number of reports of a left hemisphere advantage for visual inspection time, but some investigators employing slightly different methodologies have failed to replicate the effect. The present experiment was an attempt to identify one of the factors that could have lead to these discrepant findings: The role of apparent motion cues. In Experiment 1, a lateralized version of the inspection time task was administered via a computer monitor wherein the pi stimulus was masked with a figure vulnerable to apparent motion cues. With this mask, a strong left hemisphere advantage was observed. In Experiments 2 and 3, the test was administered on a tachistoscope or computer monitor, but in both cases the stimulus was masked with a pattern "forest" mask. Under these conditions, there was no lateral difference. This result implies that the left hemisphere advantage for inspection time relies on apparent motion cues.


Transitions curriculum impact on students and care.
Transitions of patient care from the inpatient to outpatient setting is a high-risk time often resulting in medical errors and adverse events. Transitions of care programmes have been demonstrated to reduce negative outcomes. Several professional societies have highlighted care transitions as a central pillar of patient care and therefore a crucial aspect of health professional education; however, little data exist on medical student education in this area. The Transitions of Care Curriculum was developed and delivered to all Harvard Medical School Core I Internal Medicine Clerkship students at Beth Israel Deaconess Medical Center, Boston, MA between January 2017 and March 2019, where 12-14 students participated each quarter and included didactic teaching followed by experiential learning. Student data were collected via postclerkship survey. Patient data were collected via chart review. Student self-reported comfort level with transitions in care skills and medical errors were analysed. All student measures related to comfort with transitions in care skills demonstrated statistically significant improvement after curriculum participation(p < 0.001). Of the patients with a completed postdischarge note, students identified ≥1 postdischarge related issue in 33 of 70 patients, with multiple issues identified in many of these patients. Seventy-six total issues were identified. The Transitions of Care Curriculum demonstrated promising student and patient outcomes, suggesting that students can successfully learn and advance clinical skills while having a positive impact on a highly needed and important aspect of patient care by reducing postdischarge errors and adverse events.


Influence of 5-HT1A receptor agonists on sympathetic and parasympathetic nerve activity.
Activity in central sympathetic pathways can be modified by stimulating central alpha 2-adrenoceptors, e.g., with clonidine, or, more recently, by stimulating central 5-hydroxytryptamine (5-HT1A) receptors. Stimulation of 5-HT1A receptors causes central sympathoinhibition and an increase in cardiac vagal drive, which results in a profound fall in blood pressure. However, the central sympathoinhibition observed with 5-HT1A agonists such as 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] is not uniform for all regional sympathetic outflows, renal outflow being the most sensitive. The classical centrally acting antihypertensive drugs, the alpha 2-adrenoceptor agonists, also cause differential sympathoinhibition, but cardiac rather than renal nerve activity is the most sensitive. Now, if a 5-HT1A agonist is combined with an alpha 1-adrenoceptor antagonist, e.g., urapidil, then uniform central sympathoinhibition is observed. 5-HT1A agonists also differ from alpha 2-adrenoceptor agonists in that they increase central vagal drive. Further, 5-HT-containing boutons have been shown to make synaptic contact with cardiac vagal motoneurons (CVMs), and there is also a high density of 5-HT1A binding in the brain nuclei containing these CVMs. This suggests that there is an excitatory 5-HT-containing pathway that innervates CVMs and involves the activation of 5-HT1A receptors. In this respect, cardiopulmonary afferent fiber activation of CVMs is blocked by central administration of 5-HT1A receptor antagonists. In conclusion, 5-HT1A receptors are important in the patterning of sympathetic outflow by central cardiovascular pathways and are involved in the central control of parasympathetic outflow, at least to the heart.


Rhodium-Catalyzed Alkene Difunctionalization with Nitrenes.
The Rh(II) -catalyzed oxyamination and diamination of alkenes generate 1,2-amino alcohols and 1,2-diamines, respectively, in good to excellent yields and with complete regiocontrol. In the case of diamination, the intramolecular reaction provides an efficient method for the preparation of pyrrolidines, and the intermolecular reaction produces vicinal amines with orthogonal protecting groups. These alkene difunctionalizations proceed by aziridination followed by nucleophilic ring opening induced by an Rh-bound nitrene generated in situ, details of which were uncovered by both experimental and theoretical studies. In particular, DFT calculations show that the nitrogen atom of the putative [Rh]2 =NR metallanitrene intermediate is electrophilic and support an aziridine activation pathway by N⋅⋅⋅N=[Rh]2 bond formation, in addition to the N⋅⋅⋅[Rh]2 =NR coordination mode.


Predictive risk factors for distant metastasis in pediatric differentiated thyroid cancer from Saudi Arabia.
Despite their excellent prognosis, children and young adults (CAYA) with differentiated thyroid cancer (DTC) tend to have more frequent occurrence of distant metastasis (DM) compared to adult DTC. Data about DM in CAYA from Middle Eastern ethnicity is limited. Medical records of 170 patients with DTC ≤18 years were retrospectively reviewed. Clinico-pathological factors associated with lung metastasis in CAYA, their clinical presentation and outcome were analyzed. Rick factors related to distant metastasis-free survival (DMFS) for the whole cohort were evaluated. DM was observed in 27 patients and all were lung metastasis. Lung metastasis was significantly associated with younger age (≤15 years), extrathyroidal extension (ETE), multifocal tumors, bilaterality, presence of lymph node (LN) disease and high post-operative stimulated thyroglobulin (sTg). Highest negative predictive values were seen with low post-operative sTg (97.9%), absence of LN disease (93.8%), absence of ETE (92.2%) and age older than 15 years (92.9%). Post-therapy whole body scan (WBS) identified most of the lung metastasis (21 of 27; 77.8%). Upon evaluating patients response according to ATA guidelines, excellent response was seen in only one patient, while biochemical persistence and structural persistence were seen in 11.1% (3/27) and 77.8% (21/27), respectively. Elevated post-operative sTg (>10ng/ml) was the only risk factor found to be significantly associated with both biochemical persistence (with or without structural persistence (p = 0.0143)) and structural persistence (p = 0.0433). Cox regression analysis identified age and post-operative sTg as independent risk factors related to DMFS. Based on these two risk factors for DMFS, patients were divided into 3 groups: low risk (no risk factors), intermediate risk (1 risk factor) and high risk (both risk factors). 20-year DMFS rates in the low-, intermediate- and high-risk groups were 100.0%, 81.3% and 23.7% respectively (p < 0.0001). Higher suspicion for metastatic pediatric DTC should be considered in patients who are young, have LN disease, extrathyroidal extension and elevated post-operative sTg. Persistent disease, despite therapy, is very common and it appears to be related to post-operative sTg level. Hence, risk adaptive management is desirable in CAYA with DTC.


Phenethyl isothiocyanate, by virtue of its antioxidant activity, inhibits invasiveness and metastatic potential of breast cancer cells: HIF-1α as a putative target.
Hypoxia-inducible factor 1α (HIF-1α) plays a crucial role in facilitating tumor progression and metastasis. Reducing the levels of HIF-1α might therefore be an important anticancer strategy. This could be achieved by understanding the key cellular events involved in HIF-1α activation. Present study explored the effect of phenethyl isothiocyanate (PEITC), a natural isothiocyanate, found in cruciferous vegetables on the expression of HIF-1α and HSP90 in breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231) under both normoxia and hypoxia. This study established the possible role of ROS in the up-regulation of these markers in breast cancer cells. PEITC-induced nuclear accumulation of Nrf2, increased the activities of several antioxidant enzymes, and thus reduced the ROS burden of the tumor cells by acting as an indirect antioxidant. This resulted in the down-regulation of HSP90 and thereby HIF-1α expression. HSP90 was also found to be involved in the regulation of HIF-1α. A probable link between down-regulation of HIF-1α with reduction of ROS by PEITC through induction of Nrf2 was determined. Finally, our study demonstrated that modulation of HIF-1α by PEITC retarded adhesion, aggregation, migration and invasion of the breast cancer cells, thereby showing anti-metastatic effect. Activities of MMPs (2 & 9) and expression of VEGF were also altered by PEITC.


Sequence of the structural gene for xanthine dehydrogenase (rosy locus) in Drosophila melanogaster.
We determined the nucleotide sequence of a 4.6-kb EcoRI fragment containing 70% of the rosy locus. In combination with information on the 5' sequence, the gene has been sequenced in entirety. rosy cDNAs have been isolated and intron/exon boundaries have been determined. We find an open reading frame which spans four exons and would encode a protein of 1335 amino acids. The molecular weight of the encoded protein (xanthine dehydrogenase), based on the amino acid translation, is 146,898 daltons which agrees well with earlier biophysical estimates. Characteristics of the protein are discussed.


Blue petrels recognize the odor of their egg.
Most studies on avian olfactory communication have focused on mate choice, and the importance of olfaction in subsequent nesting stages has been poorly explored. In particular, the role of olfactory cues in egg recognition has received little attention, despite eggs potentially being spread with parental odorous secretions known to elicit individual discrimination. Here, we used behavioral choice tests to determine whether female blue petrels (Halobaena caerulea) can discriminate the odor of their own egg from the odor of a conspecific egg. Females preferentially approached the odor of their own egg, suggesting that blue petrels can recognize their own egg using odor cues. This finding raises the question of the adaptive value of this mechanism, and may inspire further research on odor-based egg discrimination in species suffering brood parasitism.


Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine-refractory differentiated thyroid cancer.
Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. This subanalysis evaluated the efficacy and safety of lenvatinib in Japanese patients who participated in SELECT. Outcomes for Japanese patients (lenvatinib, n = 30; placebo, n = 10) were assessed in relationship to the SELECT population (lenvatinib, n = 261; placebo, n = 131). The primary endpoint was PFS; secondary endpoints included overall survival, overall response rate, and safety. Lenvatinib PFS benefit was shown in Japanese patients (median PFS: lenvatinib, 16.5 months; placebo, 3.7 months), although significance was not reached, presumably due to sample size (hazard ratio, 0.39; 95% confidence interval, 0.10-1.57; P = 0.067). Overall response rates were 63.3% and 0% for lenvatinib and placebo, respectively. No significant difference was found in overall survival. The lenvatinib safety profile was similar between the Japanese and overall SELECT population, except for higher incidences of hypertension (any grade: Japanese, 87%; overall, 68%; grade ≥3: Japanese, 80%; overall, 42%), palmar-plantar erythrodysesthesia syndrome (any grade: Japanese, 70%; overall, 32%; grade ≥3: Japanese, 3%; overall, 3%), and proteinuria (any grade: Japanese, 63%; overall, 31%; grade ≥3: Japanese, 20%; overall, 10%). Japanese patients had more dose reductions (Japanese, 90%; overall, 67.8%), but fewer discontinuations due to adverse events (Japanese, 3.3%; overall, 14.2%). There was no difference in lenvatinib exposure between the Japanese and overall SELECT populations after adjusting for body weight. In Japanese patients with radioiodine-refractory differentiated thyroid cancer, lenvatinib showed similar clinical outcomes to the overall SELECT population. Some differences in adverse event frequencies and dose modifications were observed. Clinical trial registration no.: NCT01321554.


Percutaneous pinning with interphalangeal joint locked in phalanx fractures: The surgical technique and the results.
The purpose of the study was to compare the operation time, the fracture healed time, the postoperative function recovery between the techniques that temporary locking of the interphalangeal joint and traditional manual reduction in the treatment of percutaneous pinning of the phalanx fractures. Patients with phalanx fractures from January 2015 to January 2018 who were admitted to our hospital were retrospectively reviewed. Patients received surgery with traditional manual or temporary locking of the interphalangeal joint reduction. The information of patients, including age, gender, the length of the operation, the fracture healed time, the postoperative function recovery, complication, and length of postoperative hospital stay, was collected. All of the information were evaluated and compared between the 2 groups. All of the surgery were performed by 2 experienced hand surgeons of our department. The patients in the 2 groups were followed up for an average of 6 months after surgery. All patients completed the operation and were followed up completely. There was no significant difference in baseline data between the 2 groups (P > .05). The observation group who received surgery with the interphalangeal joint locked technique had significantly shorter in operative time than the control group (P < .05). And postoperative complications in the observation group were significantly less than those in the control group (P < .05). However, the postoperative functional recovery in both groups was no significant difference between the 2 groups (P > .05). And there were no significant differences in the fracture healed time and length of postoperative hospital stay between the 2 groups (P > .05). Both surgical techniques can enable patients to achieve good function, but the technique of interphalangeal joint locked is effective in the treatment of the phalanx fractures, as it is characterized by short operations and a quick recovery. However, this technique is only suitable for extra-articular phalanx fractures that the AO/ASIF classification of type A2.3 and less than 2 weeks, not for other phalanx fractures.


Relation of electrocardiographic criteria for left atrial enlargement to two-dimensional echocardiographic left atrial volume measurements.
Left atrial (LA) enlargement by 2-dimensional (2-D) echocardiography predicts adverse cardiovascular outcomes. Electrocardiographic (ECG) criteria for LA enlargement are based on M-mode echocardiographic LA diameter, which is inferior to 2-D-derived LA volumes. This study compared established ECG criteria for LA enlargement with atrial volume obtained by 2-D echocardiography to determine if traditional ECG criteria accurately represent LA chamber enlargement, therefore offering a low-cost screening tool. A total of 261 randomly selected patients who underwent electrocardiography and 2-D echocardiography were enrolled. ECG parameters and electronically derived P-wave medians were analyzed with electronic calipers for maximal accuracy. LA volumes by 2-D echocardiography were measured with Simpson's method of discs, with enlargement defined as 32 ml/m(2). Sensitivity and specificity tables and receiver-operating characteristic curves were constructed for each criterion. Univariate and multivariate analyses were performed for predictors of 2-D echocardiographic LA enlargement. LA enlargement was present in 43% of patients. ECG P-wave duration was the most sensitive for the detection of LA enlargement (69%) but had low specificity (49%). Conversely, a biphasic P wave was the most specific (92%) but had low sensitivity (12%). The maximum area under the receiver-operating characteristic curve for any criterion was 0.64, too low to be of clinical utility. In conclusion, established ECG criteria for LA enlargement do not reliably reflect LA enlargement and lack sufficient predictive value to be useful clinically. These results suggest that P-wave abnormalities should be noted as nonspecific LA abnormalities, with the term "LA enlargement" no longer used.


Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy.
Monotopic proteins exert their function when attached to a membrane surface, and such interactions depend on the specific lipid composition and on the availability of enough area to perform the function. Nanodiscs are used to provide a membrane surface of controlled size and lipid content. In the absence of bound extrinsic proteins, sodium phosphotungstate-stained nanodiscs appear as stacks of coins when viewed from the side by transmission electron microscopy (TEM). This protocol is therefore designed to intentionally promote stacking; consequently, the prevention of stacking can be interpreted as the binding of the membrane-binding protein to the nanodisc. In a further step, the TEM images of the protein-nanodisc complexes can be processed with standard single-particle methods to yield low-resolution structures as a basis for higher resolution cryoEM work. Furthermore, the nanodiscs provide samples suitable for either TEM or non-denaturing gel electrophoresis. To illustrate the method, Ca2+-induced binding of 5-lipoxygenase on nanodiscs is presented.


Occurrence of infectious diseases in dialysed patients.
Chronic kidneys' failure as well as hemodialysis operations lead to disorders of many organs' and system's functions. We can observe a decrease in the immunulogical system's efficiency, which consequently causes the decrease in a human body's defence abilities. The dialysed patients are subject to a frequent contact with medical equipment and they require numerous examinations. All these factors, including the dialysis itself, increase the risk of occurrence of various types of infections, both bacterial and viral ones. The aim of the work was to try to define the kind and frequency of infectious diseases occurring among the dialysed patients. In order to conduct the research, the questionnaire among 50 patients in the centre of dialysis of the hospital in Chełm was made. Among the examined group, the most frequently occurring infectious diseases were infections of the ureter, bronchitis, flu and ear infection. Among 30% of the examined, inflammatory and thrombotic changes within a dialysis drainage tube occurred. 22% of the examined are the carriers of HBV. Among 36%, however, the antibodies of HCV were detected. 1. The hemodialysed patients make up a group that is at increased risk of infectious diseases. 2. The infection of B and C type is the exceptional problem among the hemodialysed patients. 3. The frequency of infectious diseases occurrence increases along with age and length of dialysotherapy. 4. Education of the patients about how to prevent infections brings measurable effects in the form of the decreasing number of morbidity cases.


A novel triplex real-time PCR assay for the differentiation of lumpy skin disease virus, goatpox virus, and sheeppox virus.
Three members of Capripoxvirus (CaPV) genus, including lumpy skin disease virus (LSDV), goatpox virus (GTPV), and sheeppox virus (SPPV), are mentioned as notifiable forms by World Organization for Animal Health. These viruses have negatively impacted ruminant farming industry worldwide, causing great economic losses. Although SPPV and GTPV cause more severe clinical disease in only one animal species, they can transfer between sheep and goats. Both homologous and heterologous immunization strategies are used to protect animals against CaPVs. However, development of accurate and rapid methods to distinguish these three viruses is helpful for the early detection, disease surveillance, and control of CaPV infection. Therefore, we developed a novel triplex real-time PCR (qPCR) for the differentiation of LSDV, GTPV, and SPPV. Universal primers were designed to detect pan-CaPV sequences. Species-specific minor groove binder (MGB)-based probes were designed, which were labeled with FAM for LSDV, HEX for GTPV, and ROX for SPPV. The sensitivity, specificity, reproducibility, and ability of detecting mixed infections were evaluated for the triplex qPCR. Further, 226 clinical samples of the infection and negative controls were subjected to the triplex qPCR, and the results were verified using PCR-restriction fragment length polymorphism (PCR-RFLP) and sequencing methods for PRO30 gene. The triplex qPCR could successfully distinguish LSDV, GTPV, and SPPV in one reaction, and the assay sensitivity was 5.41, 27.70, and 17.28 copies/μL, respectively. No cross-reactivity was observed with other viruses causing common ruminant diseases, including des petits ruminants virus, foot-and-mouth disease virus, bluetongue virus, ovine contagious pustular dermatitis virus, infectious bovine rhinotracheitis virus, and bovine viral diarrhea-mucosal disease virus. Inter-and intra-assay variabilities were < 2.5%. The results indicated that the triplex qPCR was highly specific, sensitive, and reproducible. Simulation experiments revealed that this assay could successfully distinguish two or three viruses in case of mixed infections without any cross-reaction. For clinical samples, the results were completely consistent with the results of PCR-RFLP and sequencing. This demonstrated that the assay was reliable for clinical application. The triplex qPCR is a robust, rapid, and simple tool for identifying various types of CaPV as it can successfully distinguish LSDV, GTPV, and SPPV in one reaction. Furthermore, the assay can facilitate more accurate disease diagnosis and surveillance for better control of CaPV infection.


3-Bromo-5-meth-oxy-4-(4-methyl-piperidin-1-yl)furan-2(5H)-one.
There are two molecules in the asymmetric unit of title compound, C(11)H(16)BrNO(3), which was obtained via the tandem Michael addition-elimination reaction of 3,4-dibromo-5-meth-oxy-furan-2(5H)-one and 4-methyl-piperidine in the presence of potassium fluoride. The furan-one rings are approximately planar [maximum atomic deviations of 0.026 (2) and 0.015 (2) Å, respectively]. The packing is stabilized by weak inter-molecular C-H⋯O and C-H⋯Br inter-actions.


alpha 1-Microglobulin.
A new low-molecular weight plasma protein was discovered and isolated from human urine by Ingemar Beggård. He named it alpha 1-microglobulin. The protein has a molecular weight of 26,000, contains about 20% carbohydrate, is electrophoretically heterogenous, carries a brown-coloured, unidentified substance, and is present in serum in free, as well as in high molecular weight complexes. alpha 1-Microglobulin seems to interfere with the in vitro response of lymphocytes to some antigens. The site of synthesis of alpha 1-microglobulin is unclear.


In vitro studies on the hypoglycemic potential of Ficus racemosa stem bark.
Medicinal plants have been reported to play an important role in modulating glycemic responses and have preventive and therapeutic implications. Several mechanisms have been proposed for the antidiabetic effect of medicinal plants such as inhibition of carbohydrate-metabolizing enzymes, manipulation of glucose transporters, beta-cell regeneration and enhancing insulin-releasing activity. The present investigation evaluated the possible mechanism of action through which Ficus racemosa stem bark (Moraceae) exerts its hypoglycemic effect using suitable in vitro techniques. Ficus racemosa bark (FRB) exhibited significantly higher (P < or = 0.01) glucose-binding capacity than wheat bran (WB) and acarbose (ACB) consequently showed significantly higher (P < or = 0.01) retardation of glucose diffusion compared to WB and ACB. In case of amylolysis kinetics the liberation of glucose was greatly inhibited by FRB, as reflected by a significantly lower (P < or = 0.01) glucose diffusion rate in the system containing FRB compared to the control and acarbose. Furthermore, FRB significantly increased (P < or = 0.01) the rate of glucose transport across the yeast cell membrane and also in isolated rat hemi-diaphragm. The findings indicate F. racemosa bark to possess strong hypoglycemic effect and hence can be utilized as an adjunct in the management of diabetes mellitus.


TEMPORAL VARIATION IN POPULATIONS OF THE MARINE ISOPOD EXCIROLANA: HOW STABLE ARE GENE FREQUENCIES AND MORPHOLOGY?
Excirolana braziliensis is a dioecious marine isopod that lives in the high intertidal zone on both sides of tropical America. It lacks a dispersal phase and displays a remarkable degree of genetic divergence even between localities less than 1 km apart. Nine populations of this nominal species from both sides of the Isthmus of Panama and one population of the closely allied species, Excirolana chamensis, from the eastern Pacific were studied for 2 yr for allozymic temporal variation in 13 loci and for 3 to 4 yr for morphological variation in nine characters. The genetic and morphological constitution of 9 out of 10 populations remained stable. Allele frequencies at two loci and overall morphology in a tenth beach occupied by E. braziliensis changed drastically and significantly between 1986 and 1988. The change in gene frequency is too great to explain by genetic drift occurring during a maximum of 14 generations regardless of assumed effective population size; drift is also unlikely to have caused observed changes in morphology. Selective survival of a previously rare genotype is more plausible but still not probable. The most credible explanation is that the resident population at this locality became extinct and that the beach was recolonized by immigrants from another locality. Such infrequent episodes of extinction and recolonization from a single source may account for the large amount of genetic divergence between local populations of E. braziliensis. However, the low probability of large temporal genetic change even in a species such as this, in which gene flow between local demes is limited and generation time is short, suggests that a single sample through time is usually adequate for reconstructing the genetic history of populations.


Three-dimensional sonography of the endometrium and adjacent myometrium: preliminary observations.
By evaluating a series of patients undergoing pelvic sonography with routine 2-dimensional (2D) as well as 3-dimensional (3D) reconstructed images in the coronal plane, we attempted to characterize the types of additional information that can be obtained. Ninety randomly selected patients undergoing transvaginal pelvic sonography were imaged according to a standard 2D protocol. A 3D uterine volume was then acquired in the sagittal plane and reconstructed in the coronal plane. The endometrium and surrounding myometrium were evaluated for architecture, masses, the relationship of masses to the endometrial cavity, and the anatomic configuration of the cavity. Ninety-one studies were obtained. Additional findings were obtained on the coronal view in 28 studies (30.8%). No additional findings were obtained in 63 studies (69.2%). Normal endometrial and myometrial findings were obtained by conventional 2D imaging in 42 of 91 patients. Of this group, additional findings were shown in 2 (5%) patients. Forty-nine of the 91 patients had abnormal findings by 2D imaging. Additional information was obtained in 26 (53%) of these patients. Added information included uterine anomalies, better definition of the endometrium, more accurate delineation and location of endometrial polyps, location of leiomyomas, visualization of cystic areas within the myometrium, and confirmation of the location of intrauterine devices. The 3D reconstructed view of the endometrium and adjacent myometrium appears to be most helpful after a conventional transvaginal study, showing abnormalities within the endometrium and myometrium but being of little added benefit if the conventional findings are normal.


Time-Resolved Laser-Induced Fluorescence Spectroscopy as a Guidance Tool for Laser Lithotripsy of Gallbladder Stones.
Although laser lithotripsy for fragmentation of gallbladder stones has been applied successfully in many clinical situations, this approach has two major limitations: (1) the potential to damage or perforate the bile duct and (2) the efficiency can be affected by the chemical composition of the gallstones. The present study evaluated the use of time-resolved laser-induced fluorescence spectroscopy to classify stone types and distinguish stone from tissue. Ex vivo time-resolved laser-induced fluorescence analysis (excitation wavelength λex = 400 nm and emission wavelength = 450-700 nm) of 54 gallbladder stones and seven gallbladder tissue samples was conducted. The spectral and temporal parameters were analyzed using linear discrimination analysis (LDA) to differentiate stone from tissue and to classify different stone types using two wavelength regions (λ1 = 510-530 nm and λ2 = 550-570 nm). Examination of 54 gallbladder stones and seven gallbladder tissue samples showed a significant difference in spectral- and temporal-derived parameters. The data were classified using LDA, and the overall accuracy was 94.88%, 84.39%, and 85.79% for both spectral and temporal parameters, only spectral parameters, and only temporal parameters, respectively. Our findings establish the feasibility of using time-resolved laser-induced fluorescence spectroscopy as a tool to identify gallbladder stone types and as a stone-tissue detection system to improve the effectiveness of laser lithotripsy procedures and reduce the risk of damaging biliary tract tissues.


Population genetic structure and genetic diversity of Chinese pomfret at the coast of the East China Sea and the South China Sea.
The Chinese pomfret Pampus chinensis is one of the most economic and ecological important marine fish species in China. In the present study, the population genetic structure and genetic diversity of P. chinensis were evaluated from a total sample size of 180 individuals representing six populations from the East China Sea and the South China Sea using mitochondrial cytochrome c oxidase subunit I (COI) gene. A total of 24 variable sites (including 3 singleton sites and 21 parsimony information sites) were observed, and 18 haplotypes were defined. The haplotype diversity (Hd) of the populations ranged from 0.559 to 0.775, and the nucleotide diversity (π) ranged from 0.330 to 1.090%. Analysis of molecular variance (AMOVA) reveals that the main variation (66.02%) was among individuals within populations. The average pairwise differences and ϕST values indicated significant genetic differentiation between Dongxing population and the other populations. The results of the present study are helpful for the sustainable management and utilization of this species.


Identification of weight-control behaviors practiced by diverse groups of college students.
THIS STUDY INVESTIGATED: 1) what weight-related behaviors college students practiced; 2) if the behaviors were performed for weight-related reasons; and 3) whether the behavioral practices differed by gender, race, and body weight status. This cross-sectional study used a questionnaire to collect information from a non-probability sample of undergraduate students (n=379; 48% men) recruited from large introductory psychology classes. Chi-square tests were conducted to examine simple comparisons, and multiple logistic regression analyses assessed differences. Male students reported adopting significantly fewer weight-related behaviors than females. Most frequently males increased exercise (69.2%), increased fruit and vegetable consumption (50%), skipped meals (46%), cut out sweets and junk foods (40%), and cut out between-meal snacks (35%). Female students most frequently increased exercise (67.4%), skipped meals (63%), increased fruit and vegetable consumption (62%), reduced the amount of food eaten (60%), and cut out between-meal snacks (51%). Negative behaviors were engaged in by only a few participants. Weight-related reasons were a significant factor for weight-related behavior adoption. Multiple logistic regression analyses showed that gender was consistently and significantly associated with the adoption of weight-related behaviors, while race and weight status were less consistently associated. Findings of this study will be helpful to dietitians who counsel college students. Results of this study may support efforts to bring more comprehensive behaviorally-focused health and nutrition interventions to college campuses.


Competitive inhibitor binding assay (CIBA) of ACE inhibitors.
We describe a new principle for measuring concentrations of pharmacologically active captopril or other angiotensin-converting enzyme (ACE) inhibitors in blood. Serum is incubated with 125-I-labeled ACE inhibitor (substance 351A, a lisinopril analogue, Merck Sharp & Dohme) in a nonequilibrated system, in which label and ACE inhibitor compete for binding to added serum ACE. Free label is separated by adsorption to coated charcoal. Concentration of captopril or other ACE inhibitor is calculated from a standard curve. Results in healthy volunteers showed rapid absorption of captopril with maximal concentration of active drug within 1 h, and fast disappearance within 2.5 h. Stability of captopril was improved by immediate 1:100 dilution of blood samples with assay buffer. In spite of this precaution, analysis should be performed within two days to avoid loss of active drug due to polymerization and protein binding. Samples of other tested ACE inhibitors can be frozen and later analyzed at convenience. The new principle is simple, sensitive, and specific.


Apoptotic cells are present in ischemic zones of deep partial-thickness burns.
Deep partial-thickness burns exhibit ambiguous behavior, either spontaneously healing or evolving into full-thickness burns. The aim of this study was to investigate these lesions for the presence of apoptotic cells and to compare their rate with that of superficial and full-thickness burns. We used colocalization of DNA fragments (ie, terminal deoxynucleotidyl transferase Biotin-dUTP nick end labeling) and Fas ligand CD95 antibodies to calculate the apoptotic rate of superficial, deep partial-thickness and full-thickness burns in 45 patients after the thermal injury. Biopsies were collected mainly during the acute postburn phase (first week of hospitalization). Deep partial-thickness burns presented apoptotic cells, both in the dermis and in cutaneous adnexa, and showed a higher apoptotic rate than superficial and full-thickness burns (44.5% in deep partial thickness, interquartile range 6.3-90.5%; 5.6% in superficial partial thickness, interquartile range: 0-13%; 0% for full-thickness burn; P = .000243). A significant greater apoptotic rate was present in cells of deep partial-thickness burns when compared with superficial and full thickness. These data would suggest that deep burns sustain an ischemic damage that forces cells to undergo apoptosis and could represent the biologic basis for their clinical evolution into full-thickness burns. Further correlation studies are now required to confirm this hypothesis.


The Ca2+ antagonists binding cytosolic protein has properties of the Ca2+ channel.
In our previous work (Krizanová et al. 1989) we have described a protein from rabbit skeletal muscle cytosolic fraction, which is able to bind dihydropyridines and phenothiazines. In the present work conclusive evidence is provided for the ability of the phospholipid-reconstituted cytosolic protein to transport calcium. The calcium transport was stimulated by BAY K 8644 and inhibited in the presence of PN 200-110. Our observations were confirmed also by electrophysiological measurements on planar lipid bilayers. The possibility that the cytosolic fraction was contaminated with membranes could be definitely ruled out. Nevertheless, the nature of the protein under study is still in the frame of guess.


Orbiting orbitals: visualization of vibronic motion at a conical intersection.
The Jahn-Teller (JT) active unpaired electron of single metalloporphyrin radical anions is imaged through scanning tunneling microscopy. It is demonstrated that the electron is delocalized over the porphyrin macrocycle and its topographic image is determined by vibronic motion: the orbital of the electron adiabatically follows the zero-point pseudorotation of skeletal deformations. Transformation of the polar graphs of the observed images allows visualization of the adiabatic vibrational density to which the electron is coupled. The vibronic potential at the conical intersection is visualized and the half-integer angular momentum characteristic of the Berry phase is revealed in the radial function of the electron. The measurements underscore the economy of Jahn-Teller dynamics: small atomic displacements (∼10(-1) Å) determined by weak interactions (∼10 meV) control the motion of the electron on a 10 Å scale and determine the molecular shape and function.


13C-urea breath test in Helicobacter pylori diagnosis and eradication. Correlation to histology, origin of 'false' results, and influence of food intake.
Which protocol is optimal for the 13C-urea breath test (UBT) for Helicobacter pylori detection is controversial. This study aimed to characterize a very simple UBT protocol for the clinical routine (two-point-analysis performed with 75 mg 13C-urea and citric acid) with special consideration of 'false' UBT results. RESULTS; UBT was evaluated in reference to histology (Warthin-Starry). In mismatching results re-gastroscopy was performed. By UBT, 74 of 77 patients with H. pylori-positive histology were detected (sensitivity, 96%). The false-negative UBTs were due to low colonization densities during spontaneous H. pylori elimination or pyloric obstruction. Seven of 49 patients with negative histology had a positive UBT, but re-gastroscopy showed that all of them had a positive histology when multiple antral biopsy specimens were taken (UBT specificity, 100%). UBT correlated only weakly with H. pylori colonization density. No correlation was found between UBT and gastric neutrophil and lymphocyte infiltration. UBT reproducibility was excellent (93 of 94 in a 6-month period). Non-fasting conditions induced a shift to lower UBT results in H. pylori-positive and to higher UBT results in negative patients, resulting in 2 of 10 false-positive and 1 of 10 false-negative UBTs. This simple version of the urea breath test combines the highest sensitivity with excellent reproducibility. It is superior to histologic detection of H. pylori in the clinical routine and an optimal tool for monitoring H. pylori eradication. Fasting conditions are required for the test.


Change and persistence of personal identities after the transition to retirement.
This study addresses the question of how retired people's self-image differs from that of working people, and what factors predict people's self-definition as professionals or retirees. Seven hundred ninety-two Swiss persons aged 58-70 (386 men, 406 women; 349 not retired, 443 retired) were asked to rate the importance of different self-description domains (such as profession, family-roles, personal values, etc.). Results indicated that the profession domain remains important for self-description even after retirement, to the extent that retirement status does not predict the importance of the professional identity at all. Rather, consistent with social identity theory, the importance of the profession for self-description is best predicted by the status of the (former or current) job. The importance of the retirement status for self-definition is predicted best by a positive attitude toward aging. In general, retired respondents rated more domains of self-description as important than did not-yet-retired respondents, and no domain was less important after retirement. In other words, identity diversity was higher for the retired than for the not-yet-retired persons. In addition, high identity diversity correlated with a high satisfaction across different life domains.


Giant vesicles "colonies": a model for primitive cell communities.
Current research on the origin of life typically focuses on the self-organisation of molecular components in individual cell-like compartments, thereby bringing about the emergence of self-sustaining minimal cells. This is justified by the fact that single cells are the minimal forms of life. No attempts have been made to investigate the cooperative mechanisms that could derive from the assembly of individual compartments. Here we present a novel experimental approach based on vesicles "colonies" as a model of primitive cell communities. Experiments show that several advantages could have favoured primitive cell colonies when compared with isolated primitive cells. In fact there are two novel unexpected features typical of vesicle colonies, namely solute capture and vesicle fusion, which can be seen as the basic physicochemical mechanisms at the origin of life.


Disseminating a smokeless tobacco cessation intervention model to dental hygienists: a randomized comparison of personalized instruction and self-study methods.
This study evaluated 2 methods of disseminating an empirically validated smokeless tobacco intervention delivered during routine dental care. Twenty cities within 12 states were stratified and then randomized to 1 of 3 groups: personalized instruction (PI), self-study (SS), or delayed training (DT) control. Dental hygienists in the SS condition were sent a manual and video. Those in the PI condition were recruited to attend a workshop. Thirty-seven percent of eligible hygienists agreed to participate. At 12 months postenrollment, hygienists in the SS and PI conditions significantly increased their "Assist" behaviors (discuss cessation techniques, help patient set a quit date, and provide cessation materials) and reported fewer perceived barriers to delivering the intervention as compared with hygienists in DT. An economic analysis suggests that SS is more cost-effective than PI.


Decreased homotopic functional connectivity in traumatic brain injury.
Homotopic functional connectivity (HoFC), the synchrony in activity patterns between homologous brain regions, is a fundamental characteristic of resting-state functional connectivity (RsFC). We examined the difference in HoFC, computed as the correlation between atlas-based regions and their counterpart on the opposite hemisphere, in 16 moderate-severe traumatic brain injury patients (msTBI) and 36 healthy controls. Regions of decreased HoFC in msTBI patients were further used as seeds for examining differences between groups in correlations with other brain regions. Finally, we computed logistic regression models of regional HoFC and fractional anisotropy (FA) of the corpus callosum (CC). TBI patients exhibited decreased HoFC in the middle and posterior cingulate cortex, thalamus, superior temporal pole, and cerebellum III. Furthermore, decreased RsFC was found between left cerebellum III and right parahippocampal cortex and vermis, between superior temporal pole and left caudate and medial left and right frontal orbital gyri. Thalamic HoFC and FA of the CC discriminate patients as msTBI with a high accuracy of 96%. TBI is associated with regionally decreased HoFC. Moreover, a multimodality model of interhemispheric connectivity allowed for a high degree of accuracy in disease discrimination and enabled a deeper understanding of TBI effects on brain interhemispheric reorganization post-TBI.


Shape Transformations of Vesicles Self-Assembled from Amphiphilic Hyperbranched Multiarm Copolymers via Simulation.
The understanding of shape transformations of vesicles is of fundamental importance in biological and clinical sciences. Hyperbranched polymer vesicles (branched polymersomes) are newly emerging polymer vesicles with special structure and property. They have also been regarded as a good model for biomembranes. However, the shape transformations of hyperbranched polymer vesicles have not been studied from either an experimental or theoretical level. Herein, the shape transformations of vesicles self-assembled from amphiphilic hyperbranched multiarm copolymers (HMCs) in response to the interaction parameters between the hydrophobic core and hydrophilic arms and the polymer concentrations are investigated carefully through dissipative particle dynamics (DPD) simulations. In the morphological phase diagram, two types of vesicles are obtained: one type corresponds to vesicles without holes formed at low concentrations including unilamellar vesicles, double-lamellar vesicles, discocyte-shaped vesicles, and tubular vesicles, and the other type corresponds to vesicles with holes formed at high concentrations including stomatocyte-shaped vesicles, toroidal vesicles, genus-3 (G-3) toroidal vesicles with three holes, and genus-4 (G-4) toroidal vesicles with four holes. In addition, both the self-assembly mechanisms and the dynamics for the formation of these vesicles have been systematically studied. The current work will offer theoretical support for fabricating novel vesicles with various shapes from hyperbranched polymers.


The origins of oncomice: a history of the first transgenic mice genetically engineered to develop cancer.
This perspective describes the concurrent development in the 1980s of the first transgenic mice genetically engineered to express dominant oncogenes, involving independent researchers who were largely unaware of each other's strategies and progress. We relate the experimental designs, the pitfalls and challenges encountered, and the eventual success in developing distinctive mouse models of cancer, wherein tumors arose heritably in various organs. These early oncomice have produced a wealth of new knowledge, become topics of intellectual property, and spawned a vibrant field of cancer research that is revealing mechanisms of tumorigenesis and suggesting new therapeutic strategies for treating the human disease.


[Interpretation of consensuses on treatment of female patients with periodontal disease].
Periodontal tissue is the target tissue of sex hormone, physiological change of sex hormones affects the response of periodontal tissue to bacterial plague. The treatment of periodontal disease of female patients in special periods such as adolescence, menstruation, prepregnancy, pregnancy, puerperium, and menopause should be chosen carefully and correctly. This article attempts to expound these issues.


Amyotrophic lateral sclerosis: effect of serum on anterior horn cells in tissue culture.
A high proportion of diluted serums of patients with amyotrophic lateral sclerosis were toxic to the anterior horn cells of the mouse in tissue culture. This is not a general cytotoxicity, since apparently only the neurons were killed. Serums from other degenerative neurological diseases were inactive.


A self-management program for low vision: program overview and pilot evaluation.
This article describes a new low vision-specific self-management (SM) program for older adults with vision impairment, and provides preliminary data on program evaluation from two small pilot groups. The SM program was an 8-week, structured group program aiming to enhance participants' skills to manage the practical and emotional consequences of vision impairment. The pilot evaluation was a single group post-test design. Participants took part in a structured interview to obtain their views on the content, format and delivery of the program. The program was perceived as useful and the duration and level of information provided were deemed appropriate. Participants reported the program to have a positive impact on their mood, understanding of low vision and services available and their ability to manage the challenges of low vision. The content and delivery of the program is appropriate for older individuals with vision impairment. Further work is required to provide a methodologically sound evaluation of this program and contribute to the evidence-base regarding the effectiveness of approaches to vision rehabilitation.


3D domain swapping, protein oligomerization, and amyloid formation.
In 3D domain swapping, first described by Eisenberg, a structural element of a monomeric protein is replaced by the same element from another subunit. This process requires partial unfolding of the closed monomers that is then followed by adhesion and reconstruction of the original fold but from elements contributed by different subunits. If the interactions are reciprocal, a closed-ended dimer will be formed, but the same phenomenon has been suggested as a mechanism for the formation of open-ended polymers as well, such as those believed to exist in amyloid fibrils. There has been a rapid progress in the study of 3D domain swapping. Oligomers higher than dimers have been found, the monomer-dimer equilibrium could be controlled by mutations in the hinge element of the chain, a single protein has been shown to form more than one domain-swapped structure, and recently, the possibility of simultaneous exchange of two structural domains by a single molecule has been demonstrated. This last discovery has an important bearing on the possibility that 3D domain swapping might be indeed an amyloidogenic mechanism. Along the same lines is the discovery that a protein of proven amyloidogenic properties, human cystatin C, is capable of 3D domain swapping that leads to oligomerization. The structure of domain-swapped human cystatin C dimers explains why a naturally occurring mutant of this protein has a much higher propensity for aggregation, and also suggests how this same mechanism of 3D domain swapping could lead to an open-ended polymer that would be consistent with the cross-beta structure, which is believed to be at the heart of the molecular architecture of amyloid fibrils.


Obscurin is a semi-flexible molecule in solution.
Obscurin, a giant modular cytoskeletal protein, is comprised mostly of tandem immunoglobulin-like (Ig-like) domains. This architecture allows obscurin to connect distal targets within the cell. The linkers connecting the Ig domains are usually short (3-4 residues). The physical effect arising from these short linkers is not known; such linkers may lead to a stiff elongated molecule or, conversely, may lead to a more compact and dynamic structure. In an effort to better understand how linkers affect obscurin flexibility, and to better understand the physical underpinnings of this flexibility, here we study the structure and dynamics of four representative sets of dual obscurin Ig domains using experimental and computational techniques. We find in all cases tested that tandem obscurin Ig domains interact at the poles of each domain and tend to stay relatively extended in solution. NMR, SAXS, and MD simulations reveal that while tandem domains are elongated, they also bend and flex significantly. By applying this behavior to a simplified model, it becomes apparent obscurin can link targets more than 200 nm away. However, as targets get further apart, obscurin begins acting as a spring and requires progressively more energy to further elongate.


Yersinia enterocolitica induces apoptosis and inhibits surface molecule expression and cytokine production in murine dendritic cells.
Yersinia enterocolitica evades innate immunity by expression of a variety of pathogenicity factors. Therefore, adaptive immunity including CD4(+) T cells plays an important role in defense against Y. enterocolitica. We investigated whether Y. enterocolitica might target dendritic cells (DC) involved in adaptive T-cell responses. For this purpose, murine DC were infected with Y. enterocolitica wild-type and mutant strains prior to incubation with ovalbumin (OVA) as antigen and 5-(6)-carboxyfluorescein diacetate N-succinimidyl ester-labeled OVA-specific T cells from DO11.10 mice. While T-cell proliferation was partially affected by infection of DC with plasmid-cured and YopP-deficient Yersinia mutant strains, no T-cell proliferation occurred after infection of DC with wild-type Y. enterocolitica. Infection of DC with Y. enterocolitica wild type resulted in decreased up-regulation of major histocompatibility complex class II, CD54 (intercellular adhesion molecule 1), CD 80, and CD86 expression. Experiments with plasmid-cured Y. enterocolitica or a YopP-deficient mutant strain revealed that YopP accounts for inhibition of surface molecule expression. Wild-type Y. enterocolitica suppressed the release of KC, tumor necrosis factor alpha, interleukin-10 (IL-10), and IL-12 by DC, while infection of DC with plasmid-cured Y. enterocolitica or with the YopP-deficient mutant resulted in the production of these cytokines. Moreover, infection with wild-type Y. enterocolitica induced apoptosis in DC mediated by YopP. Apoptosis occurred despite translocation of NF-kappaB to the nucleus, as demonstrated by electromobility shift assays. Together, these data demonstrate that Y. enterocolitica targets functions of murine DC that are required for T-cell activation. This might contribute to evasion of adaptive immune responses by Y. enterocolitica.


Negative feedback effects of gonadal steroids are preserved with aging in postmenopausal women.
There is now evidence for alterations in the neuroendocrine control of the reproductive axis with aging, but its sensitivity to gonadal steroid negative feedback remains controversial. To examine the independent effect of age and gonadal steroid negative feedback, younger (45-55 yr; n = 7) and older (70-80 yr; n = 6) postmenopausal women (PMW) were studied at baseline on no HRT, after 1 month of transdermal estrogen (50 microg/d; E) and again after a further month of E and 7 d of transvaginal progesterone (P) (100 mg bid; E + P). At each admission, blood was sampled every 5 min for 8 h for measurement of gonadotropin free alpha-subunit (FAS), which was used as a marker of GnRH pulse frequency. LH and FSH were measured in pooled samples. Midfollicular and midluteal phase levels of E2 and P were achieved during the E and E + P treatments and were not different between younger and older PMW. There was a negative feedback effect of E and E + P on mean LH (P < 0.0001) and an additional effect of age (P < 0.003), with older women having lower values throughout. Mean FSH was also decreased with E and E + P (P < 0.0001) and was consistently lower in the older women (P < 0.05). Mean FAS levels decreased with hormonal treatment (P < 0.0001) and age (P < 0.001), but the effect of hormonal treatment was attenuated in the older group (P < 0.005). FAS pulse frequency was unchanged with addition of E, but dramatically decreased with E + P (P < 0.002). Both hormonal replacement (P < 0.05) and age (P < 0.005) decreased FAS pulse amplitude, an effect that was attributable entirely to E as there was no additional change with E + P. These studies indicate that: 1) both age and gonadal steroids independently decrease mean LH, FSH, and FAS in PMW; 2) responsiveness to steroid negative feedback on FAS is attenuated with aging in absolute but not relative terms, whereas the effect on mean levels of LH and FSH is clearly preserved; and 3) FAS pulse frequency is unchanged with E2 administration but decreases dramatically with addition of P in both old and young PMW.


Uveitis as a Predictor of Predisposition to Autoimmunity.
The right environmental trigger can lead to immune system activation, which, in turn, can create an autoimmune reaction. Although each autoimmune disease is characterized by specific symptoms, many nonspecific symptoms can make these conditions difficult to diagnose. In this literature review, we seek an association between immunization-induced uveitis and an autoimmune diagnosis and/or autoimmune flare-up in patients. Our goal is to consider adverse reactions to vaccines as a possible warning sign of current or future autoimmune disease. If an immunization-induced adverse reaction is known to be a predictor of an autoimmune disease, the clinician could raise suspicion for autoimmune disease when a patient presents with vaccine-associated uveitis. While no direct correlations can be made yet, our review supports closer scrutiny of the association of immunizations and autoimmune disorders. The occurrence of uveitis across several autoimmune diseases could mean a possible link between vaccine-induced uveitis and undiagnosed autoimmune disease. Researchers can, therefore, perform retrospective studies on vaccinated patients and investigate the occurrence of uveitis, along with the timeframe of resolution and presenting symptoms at the time of the diagnosis of autoimmune disease.


Bioavailability of oral methylnaltrexone increases with a phosphatidylcholine-based formulation.
Methylnaltrexone (MNTX), a peripherally restricted opioid antagonist with mu-opioid receptor selectivity, can reduce opioid activity in the gastrointestinal tract while sparing the pain relief afforded by opioids. Since the bioavailability of oral MNTX is low, it is necessary to explore the oral formulations of MNTX that increase its bioavailability. An MNTX-phosphatidylcholine complex (MNTX-PC) formulation was prepared. The physicochemical properties of MNTX-PC were analyzed, and its bioavailability was evaluated in rats. After 250 mg/kg of oral MNTX-PC, plasma samples were collected up to 9 h. The concentrations of the compound in rat plasma were quantified using LC/MS/MS. Two MNTX plasma concentration peaks were observed at 120 and 180 min for the MNTX-PC group and control (MNTX in a water solution). Tmax was 180 min, C(max) was 1083.7 ± 293.9 ng/mL, and T(½) was 496 min for the MNTX-PC group. For control, T(max) was 180 min, C(max) was 448.4 ± 126.0 ng/mL, and T(½) was 259 min. The AUC₀₋₅₄₀ min for the MNTX-PC group was 5758.2 ± 1474.2 ngh/mL; for control, 1405.9 ± 447.8 ngh/mL. Thus, the relative bioavailability after the oral administration of MNTX-PC was 410% compared to that of control. MNTX-PC formulation significantly enhanced the oral bioavailability of MNTX.


Pinacidil stimulates osteoblast function in osteoblastic MC3T3-E1 cells.
This study examined the effect of pinacidil, a nonselective adenosine triphosphate-sensitive potassium channel opener, on the function of osteoblastic MC3T3-E1 cells. Pinacidil caused a significant elevation of collagen synthesis, alkaline phosphatase activity, osteocalcin synthesis and mineralization in the cells (p < 0.05). Pinacidil significantly decreased the production of osteoclast differentiation inducing factors such as TNF-α, IL-6 and receptor activator of nuclear factor-κB ligand in the presence of antimycin A, which inhibits mitochondrial electron transport. Moreover, pinacidil prevented antimycin A-induced reactive oxygen species and nitrotyrosine production. These results demonstrate that pinacidil may have positive effects on skeletal structure.


[Reduction of spondylolisthesis by temporary adjacent segment distraction].
Multiple instrument systems are currently available for the reduction of spondylolisthesis, where posteriorly oriented tensile forces are directly acting on the slipped vertebra. The aim of this clinical study was to evaluate the clinical efficacy of a new indirect reduction manoeuvre applied to the lumbar spine. A total number of 32 patients (14 female, 18 male) suffering of spondylolisthesis were reduced by transpedicular instrumentation during June 2001 until October 2003. The cranial adjacent vertebra was temporarily instrumented and the reduction of the slipped vertebra was facilitated by the application of traction on the instrumentation leading to tension of the longitudinal ligaments. Posterior transforaminal lumbar interbody fusion (TLIF) or anterior lumbar interbody fusion (ALIF) was then carried out according to the degree of degenerative shortening of the anterior long. spinal ligament. On the last follow up (average 32 month postoperatively; min.: 22 month) both the reduction of the spondylolisthesis and the ossification of the interbody fusion was evaluated radiologically. Physical function and patients satisfaction was measured by means of the SF 36 questionnaire. The dislocation was reduced in all cases (81% on average). At the time of the last follow up bony fusion was depicted on the radiographs in all 32 patients. A distinct improvement in all categories of the SF 36 (in 5 out of 8 categories statistic significant) could be demonstrated. Temporary intraoperative instrumentation of the cranial adjacent segment proofs to be a simple an effective method for the sufficient reduction of spondylolisthesis.


Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure.
Chimeric antigen receptor (CAR) T cell therapies have resulted in profound clinical responses in the treatment of CD19-positive hematological malignancies, but a significant proportion of patients do not respond or relapse eventually. As an alternative to CAR T cells, T cells can be engineered to express a tumor-targeting T cell receptor (TCR). Due to HLA restriction of TCRs, CARs have emerged as a preferred treatment moiety when targeting surface antigens, despite the fact that functional differences between engineered TCR (eTCR) T and CAR T cells remain ill-defined. Here, we compared the activity of CAR T cells versus engineered TCR T cells in targeting the B cell malignancy-associated antigen CD20 as a function of antigen exposure. We found CAR T cells to be more potent effector cells, producing higher levels of cytokines and killing more efficiently than eTCR T cells in a short time frame. However, we revealed that the increase of antigen exposure significantly impaired CAR T cell expansion, a phenotype defined by high expression of coinhibitory molecules and effector differentiation. In contrast, eTCR T cells expanded better than CAR T cells under high antigenic pressure, with lower expression of coinhibitory molecules and maintenance of an early differentiation phenotype, and comparable clearance of tumor cells.