Enhanced apoptotic propensity in diabetic cardiac mitochondria: influence of subcellular spatial location.
Cardiovascular complications, such as diabetic cardiomyopathy, account for the majority of deaths associated with diabetes mellitus. Mitochondria are particularly susceptible to the damaging effects of diabetes mellitus and have been implicated in the pathogenesis of diabetic cardiomyopathy. Cardiac mitochondria consist of two spatially distinct subpopulations, termed subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). The goal of this study was to determine whether subcellular spatial location is associated with apoptotic propensity of cardiac mitochondrial subpopulations during diabetic insult. Swiss Webster mice were subjected to intraperitoneal injection of streptozotocin or citrate saline vehicle. Ten weeks following injection, diabetic hearts displayed increased caspase-3 and caspase-9 activities, indicating enhanced apoptotic signaling (P < 0.05, for both). Mitochondrial size (forward scatter) and internal complexity (side scatter) were decreased in diabetic IFM (P < 0.05, for both) but not in diabetic SSM. Mitochondrial membrane potential (Delta(Psim)) was lower in diabetic IFM (P < 0.01) but not in diabetic SSM. Mitochondrial permeability transition pore (mPTP) opening was increased in diabetic compared with control IFM (P < 0.05), whereas no differences were observed in diabetic compared with control SSM. Examination of mPTP constituents revealed increases in cyclophilin D in diabetic IFM. Furthermore, diabetic IFM possessed lower cytochrome c and BcL-2 levels and increased Bax levels (P < 0.05, for all 3). No significant changes in these proteins were observed in diabetic SSM compared with control. These results indicate that diabetes mellitus is associated with an enhanced apoptotic propensity in IFM, suggesting a differential apoptotic susceptibility of distinct mitochondrial subpopulations based upon subcellular location.


[Immunologic disorders in mice reared by mothers with induced graft vs host reactions].
The mice fed by foster mothers with the induced graft-versus-host reaction showed high lethality at the age of 2-3 months and second year of life. During the second month of life the sick progeny exhibited lymphopenia, delayed skin allograft rejection, diminished number of T lymphocytes in the spleen and lymph nodes, depressed immune response to erythrocytic and abdominal typhi Vi-antigen. The immune response in old mice was elevated. Postmortem histological examination of 35 mice revealed tumours of lymphoid and reticular tissue in 6 and amyloidosis of the liver and spleen in 15 cases.


Bidirectional activity of the rat insulin II 5'-flanking region in transgenic mice.
We have identified a new transcription initiation site in the 5'-flanking regulatory region of the rat insulin II gene. This site is located on the opposite strand with respect to the insulin gene promoter, upstream of the insulin gene transcriptional enhancer. The cell-specific activity of this reverse promoter element is demonstrated in two lineages of transgenic mice, in which it directs expression of simian virus 40 T antigen specifically to the beta cells of the endocrine pancreas, resulting in development of pancreatic tumors. Analysis of RNA from the tumor cells demonstrates bidirectional transcription from the insulin regulatory region of the transgene. These data raise the possibility that bidirectional activity is a quality of the regulatory region of the insulin gene in its natural genomic context.


Hepatic artery stenosis after liver transplant: Donation after cardiac death donor vs donation after brain death donor grafts.
Hepatic artery stenosis (HAS) after liver transplant (LT) is a source of significant morbidity. Some reports have suggested higher arterial complications in patients who receive donation after cardiac death (DCD) livers. A total of 2860 consecutive LT were reviewed from a prospectively collected database. All angiograms performed in LT recipients were reviewed and primary patency rates determined by need for further intervention or graft loss due to HAT. Hepatic artery stenosis was seen in 4.6% of DCD and donation after brain death (DBD) recipients. Recipient male gender, age at transplant, complex donor hepatic artery anatomy, and prolonged operative time were all associated with HAS, but not DCD status. While HAS in recipients of DCD grafts required more stents (1.7% vs 0.6%, P = 0.04) and had worse primary patency rates (logrank, P = 0.02), outcomes as defined by HAT, patient and graft survival were not significantly different between the recipients of DCD or DBD grafts. We observed no significant difference in the incidence of hepatic artery complications, patient survival, or graft survival in recipients of DCD or DBD grafts. However, HAS in DCD recipients had worse primary patency and a higher need for stent placement.


Vitamin E succinate induces Fas-mediated apoptosis in estrogen receptor-negative human breast cancer cells.
Vitamin E succinate (VES), a derivative of the fat-soluble vitamin D-alpha-tocopherol (vitamin E), inhibited growth and induced apoptotic cell death of estrogen receptor-negative human breast cancer cells. VES-induced apoptosis in MDA-MB-231 and SKBR-3 cells occurred through a Fas pathway. Total protein levels of the Fas receptor (Fas; APO-1/CD-95) and the Fas ligand (Fas-L) were increased following VES treatment. In addition, VES increased cell surface Fas expression. Fas-neutralizing antibodies and Fas-L antisense oligonucleotides blocked VES-induced apoptosis. The presence of Fas-L antisense oligonucleotides also completely blocked the VES-mediated increase in Fas-L protein expression. These data indicate a role for Fas signaling in VES-mediated apoptotic cell death of human breast cancer cells. These findings also suggest that VES may be of clinical use in the treatment of aggressive human breast cancers, particularly those that are refractory to antiestrogen therapy.


Immunohistochemical study of fatty acid synthase in ovarian neoplasms.
In order to evaluate the prognostic significance of fatty acid synthase (FAS), the key enzyme in fatty acid biosynthesis, in ovarian benign and malignant tumors 98 patients with ovarian masses were immunohistochemically evaluated. Histologic features of the lesions and expression for FAS were statistically associated with clinical data and disease-free survival over a 5-year follow-up period. The mean age of patients was 65 years. TNM surgical stages were I in 31.8%, II in 28.2% and III in 40% of cases. The 5-year disease-free survival of the 85 malignant common epithelial ovarian tumors was 47.1% while 35.3 of patients died with active disease. Seventy-eight (79.6%) out of 98 cases expressed FAS in the neoplastic epithelial cells and 42 (42.9%) in the non-neoplastic stromal cells. Statistical analysis revealed FAS expression and stage of the disease to be significantly correlated to recurrence and survival rates only in the malignant common epithelial tumors. Moreover, multivariate analysis showed FAS expression (p=0.05) and tumor stage (p=0.03) to be independent prognostic predictors. FAS is a reliable predictor of recurrence and disease-free survival in common epithelial ovarian tumors along with neoplastic stage. Clinical data, other histologic subtypes and grading were not statistically significant.


Assessment of Interprofessional Team Collaboration Scale (AITCS): development and testing of the instrument.
Many health professionals believe they practice collaboratively. Providing insight into their actual level of collaboration requires a means to assess practice within health settings. This chapter reports on the development, testing, and refinement process for the Assessment of Interprofessional Team Collaboration Scale (AITCS). There is a paucity of literature and measurement tools addressing interprofessional collaborative team performance and the nature of effective teamwork processes and patient roles within collaborative teams. These gaps limit our knowledge about how health care teams form and function. Instruments are therefore needed to assess collaborative relationships. The AITCS, with its 47 items within 4 subscales (partnership, cooperation, coordination, and shared decision making) and assessed on a 5-point Likert scale, was administered to a total of 125 practitioners from 7 health care teams practicing within a variety of settings, in 2 provinces in Canada. Principal components and factor analysis of data resulted in 37 items loading onto 3 factors, explaining 61.02% of the variance. The internal consistency estimates for reliability of each subscale ranged from 0.80 to 0.97, with an overall reliability of 0.98. Thus, the AITCS is a reliable and valid instrument. The psychometric analysis of this instrument supports its value in measuring collaboration within teams and when patients are included as team members. The AITCS can be applied to continuing professional education interventions to determine change over time. It has limitations to the Canadian context and within the settings where participants practiced. Further test and retest reliability and longitudinal study application is needed.


An experience selecting quality features of apps for people with disabilities using abductive approach to explanatory theory generation.
This study determines one of the most relevant quality factors of apps for people with disabilities utilizing the abductive approach to the generation of an explanatory theory. First, the abductive approach was concerned with the results' description, established by the apps' quality assessment, using the Mobile App Rating Scale (MARS) tool. However, because of the restrictions of MARS outputs, the identification of critical quality factors could not be established, requiring the search for an answer for a new rule. Finally, the explanation of the case (the last component of the abductive approach) to test the rule's new hypothesis. This problem was solved by applying a new quantitative model, compounding data mining techniques, which identified MARS' most relevant quality items. Hence, this research defines a much-needed theoretical and practical tool for academics and also practitioners. Academics can experiment utilizing the abduction reasoning procedure as an alternative to achieve positivism in research. This study is a first attempt to improve the MARS tool, aiming to provide specialists relevant data, reducing noise effects, accomplishing better predictive results to enhance their investigations. Furthermore, it offers a concise quality assessment of disability-related apps.


Blood lipids in middle-aged British men.
The concentrations of serum total cholesterol, high density lipoprotein-cholesterol, and triglycerides have been measured in 7735 men aged 40 to 59 years who were drawn from general practices in 24 towns in England, Wales, and Scotland. The distribution of these blood lipids, their interrelations and their association with age, social class, body mass index, cigarette smoking, alcohol intake, and physical activity at work have been examined. Body mass index emerges as the factor most strongly associated with these three blood lipids. Serum total cholesterol increased with increasing body mass index until about 28 kg/m2 but thereafter showed no further rise. The relation between body mass index and high density lipoprotein-cholesterol was negative and linear; that between body mass index and triglycerides was positive and linear. The inverse relation between high density lipoprotein-cholesterol and triglycerides was independent of the fact that both were related to body mass index. Alcohol intake was associated with increased high density lipoprotein-cholesterol concentrations and cigarette smoking with lowered high density lipoprotein concentrations; the association with alcohol appeared to be dominant. No significant trends with age were observed for the three blood lipids. In this population, body mass index is closely associated with the concentration of blood lipids but its effects are probably indirect and mediated by a complex of dietary and other factors.


Identification of tissue-specific and common methylation quantitative trait loci in healthy individuals using MAGAR.
Understanding the influence of genetic variants on DNA methylation is fundamental for the interpretation of epigenomic data in the context of disease. There is a need for systematic approaches not only for determining methylation quantitative trait loci (methQTL), but also for discriminating general from cell type-specific effects. Here, we present a two-step computational framework MAGAR ( https://bioconductor.org/packages/MAGAR ), which fully supports the identification of methQTLs from matched genotyping and DNA methylation data, and additionally allows for illuminating cell type-specific methQTL effects. In a pilot analysis, we apply MAGAR on data in four tissues (ileum, rectum, T cells, B cells) from healthy individuals and demonstrate the discrimination of common from cell type-specific methQTLs. We experimentally validate both types of methQTLs in an independent data set comprising additional cell types and tissues. Finally, we validate selected methQTLs located in the PON1, ZNF155, and NRG2 genes by ultra-deep local sequencing. In line with previous reports, we find cell type-specific methQTLs to be preferentially located in enhancer elements. Our analysis demonstrates that a systematic analysis of methQTLs provides important new insights on the influences of genetic variants to cell type-specific epigenomic variation.


Chlamydophila psittaci-negative ocular adnexal marginal zone lymphomas express self polyreactive B-cell receptors.
The pathogenesis of Chlamydophila psittaci-negative ocular adnexal extranodal marginal zone lymphomas (OAEMZLs) is poorly understood. OAEMZLs are monoclonal tumors expressing a biased repertoire of mutated surface immunoglobulins. Antigenic activation of the B-cell receptor (BCR) may have a role in the pathogenesis of these lymphomas. We have analyzed the reactivity of recombinant OAEMZL immunoglobulins. OAEMZL antibodies reacted with self-human antigens, as demonstrated by enzyme-linked immunosorbent assays, HEp-2 immunofluorescence and human protein microarrays. All the analyzed recombinant antibodies (rAbs) exhibited polyreactivity by comprehensive protein array antibody reactivity and some rAbs also demonstrated rheumatoid factor activity. The identity of several reactive antigens was confirmed by microcapillary reverse-phase high-performance liquid chromatography nano-electrospray tandem mass spectrometry. The tested rAbs frequently reacted with shared intracellular and extracellular self-antigens (for example, galectin-3). Furthermore, these self-antigens induced BCR signaling in B cells expressing cognate surface immunoglobulins derived from OAEMZLs. These findings indicate that interactions between self-antigens and cognate OAEMZL tumor-derived BCRs are functional, inducing intracellular signaling. Overall, our findings suggest that self-antigen-induced BCR stimulation may be implicated in the pathogenesis of C. psittaci-negative OAEMZLs.


Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens.
Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetically modified lactobacilli expressing myelin antigens. A panel of recombinant lactobacilli was constructed producing myelin proteins and peptides, including human and guinea pig myelin basic protein (MBP) and proteolipid protein peptide 139-151 (PLP(139-151)). In this study we examined whether these Lactobacillus recombinants are able to induce oral and intranasal tolerance in an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Lewis rats received soluble cell extracts of Lactobacillus transformants intranasally three times prior to induction of EAE. For the induction of oral tolerance, rats were fed live transformed lactobacilli for 20 days. Ten days after the first oral administration EAE was induced. Intranasal administration of extracts containing guinea pig MBP (gpMBP) or MBP(72-85) significantly inhibited EAE in Lewis rats. Extracts of control transformants did not reduce EAE. Live lactobacilli expressing guinea pig MBP(72-85) fused to the marker enzyme beta-glucuronidase (beta-gluc) were also able to significantly reduce disease when administered orally. In conclusion, these experiments provide proof of principle that lactobacilli expressing myelin antigens reduce EAE after mucosal (intranasal and oral) administration. This novel method of mucosal tolerance induction by mucosal administration of recombinant lactobacilli expressing relevant autoantigens could find applications in autoimmune disease in general, such as multiple sclerosis, rheumatoid arthritis and uveitis.


The lncRNA MEG3/miRNA-21/P38MAPK axis inhibits coxsackievirus 3 replication in acute viral myocarditis.
Evidence is emerging on the roles of long noncoding RNAs (lncRNAs) as regulatory factors in a variety of viral infection processes, but the mechanisms underlying their functions in coxsackievirus group B type3 (CVB3)-induced acute viral myocarditis have not been explicitly delineated. We previously demonstrated that CVB3 infection decreases miRNA-21 expression; however, lncRNAs that regulate the miRNA-21-dependent CVB3 disease process have yet to be identified. To evaluate lncRNAs upstream of miRNA-21, differentially expressed lncRNAs in CVB3-infected mouse hearts were identified by microarray analysis and lncRNA/miRNA-21 interactions were predicted bioinformatically. MEG3 was identified as a candidate miRNA-21-interacting lncRNA upregulated in CVB3-infected mouse hearts. MEG3 expression was verified to be upregulated in HeLa cells 48 h post CVB3 infection and to act as a competitive endogenous RNA of miRNA-21. MEG3 knockdown resulted in the upregulation of miRNA-21, which inhibited CVB3 replication by attenuating P38-MAPK signaling in vitro and in vivo. Knockdown of MEG3 expression before CVB3 infection inhibited viral replication in mouse hearts and alleviated cardiac injury, which improved survival. Furthermore, the knockdown of CREB5, which was predicted bioinformatically to function upstream of MEG3, was demonstrated to decrease MEG3 expression and CVB3 viral replication. This study identifies the function of the lncRNA MEG3/miRNA-21/P38 MAPK axis in the process of CVB3 replication, for which CREB5 could serve as an upstream modulator.


Oral Health Knowledge, Attitudes and Behaviors of Parents of Children with Diabetes Compared to Those of Parents of Children without Diabetes.
To compare the oral health knowledge, attitudes, and behaviors of parents of children, aged 6 to 13, who have type 1 (insulin-dependent) diabetes to those of parents of similarly aged children without diabetes. The study population consisted of 46 parents of children with diabetes and 46 parents of children without diabetes from outpatient clinics, providing medical care to children with and without diabetes, respectively. After gaining permission of clinic directors, the investigator approached parents, who were waiting in the clinics' reception areas, to complete the 33-item survey. The survey included questions on socio-demographic characteristics, their child's oral hygiene practices, dental visits, dietary habits, their own oral health knowledge and attitudes, and their child's diabetic condition, when relevant. A Chi-square test was used to determine significant differences between responses of the two groups of parents. All parents approached completed the survey. Children with diabetes had significantly less frequent sugary drink consumption and less untreated dental caries than children without diabetes. The majority of parents of children with diabetes selected "don't know" for statements related to diabetes and oral health, whereas most parents of children without diabetes agreed with the statements, resulting in significant differences between groups. Most parents of children with diabetes considered these same statements important to them, while the importance to parents of children without diabetes was variable. To maintain their children's oral health, parents of children with diabetes must receive more education regarding the prevention and control of the oral complications of diabetes.


A Case of Giant Petrous Apex Cholesteatoma With Pseudomonas Aeruginosa Infection.
Petrous apex cholesteatoma is a relatively rare and chronic aggressive disease that occurs in the petrous part of the temporal bone and can be classified as congenital or acquired. Due to the tendency of petrous cholesteatomas to cause bone destruction and invade important structures such as the facial nerve, cochlea, and semicircular canal, patients present mainly with severe hearing loss, progressive peripheral facial palsy, vertigo, etc. When the lesion invades the intracranial region or is infected, intracranial symptoms such as meningitis, lateral sinus thrombosis, and brain abscess may be present. We report a case of giant petrous cholesteatoma with Pseudomonas aeruginosa infection, with the aim of exploring the corresponding clinical treatment and surgical modalities to provide a reference for the clinical management of this type of disease.


Evaluation of an inter-professional workshop to develop a psychosocial assessment and child-centred communication training programme for paediatricians in training.
The quality of psychosocial assessment of children in consultations varies widely. One reason for this difference is the variability in effective mental health and communication training at undergraduate and post-qualification levels. In recognition of this problem, the Royal College of Paediatrics and Child Health in the United Kingdom have developed the Child in Mind Project that aims to meet this deficit in medical training. This paper describes the evaluation of a workshop that explored the experiences and expectations of health care professionals in the development of a training programme for doctors. The one-day inter-professional workshop was attended by 63 participants who were invited to complete evaluation forms before and immediately after the workshop. The results showed that the workshop was partially successful in providing an opportunity for an inter-professional group to exchange ideas and influence the development of a significant project. Exploring the content and process of the proposed training programme and the opportunity for participants to share experiences of effective practice were valued. Participants identified that the current culture within many health care settings would be an obstacle to successful implementation of a training programme. Working within existing training structures will be essential. Areas for improvement in the workshop included clearer statement of goals at the outset and a more suitable environment for the numbers of participants. The participants made a valuable contribution to the development of the training programme identifying specific challenges. Inter-professional collaborations are likely to result in more deliverable and relevant training programmes. Continued consultation with potential users of the programme - both trainers and trainees will be essential.


Exposure to Schistosoma mansoni infection in a rural area of Brazil. I: water contact.
The study of water contact patterns in rural Brazil presents unique challenges due to widely dispersed settlement patterns, the ubiquity of water contact sites, and the privatization of water resources. This study addresses these challenges by comparing the two most widely used methods of assessing water contact behaviour: direct observation and survey. The results of a 7-day direct observation of water contact were compared with water contact surveys administered 1 week after and then 1 year after the direct observation study. The direct observation study recorded a water contact rate higher than reported by other investigators (3.2 contacts per person per day); however, 75% of these contacts were for females and consisted mainly of domestic activities occurring around the household. A comparison of the frequency of water contact activities between the direct observation and the two surveys revealed several important points. First, no significant differences were found between methods for routine water contact activities (e.g. bathing), indicating that participants were able to accurately self-report some types of water contact activities. Second, significant differences were found in the recording of water contact activities that took place outside the observation area, indicating that direct observation may under-report water contact activities in areas where contact sites are dispersed widely. Third, significant differences between the direct observation and the survey method were more common for males than for females, indicating that the combination of widespread water contact sites and gender-specific division of labour may result in under-reporting of male contacts by direct observation methods. In short, despite the limitations in the recording of duration and body exposure, the survey method may more accurately record the frequency of water contact activities than direct observation methods in areas of widely dispersed water contact sites. Hence, surveys may be more suitable for the unique challenges of water contact in rural areas of Brazil.


Environmental dependency in the expression of costs of tolerance to deer herbivory.
Plant tolerance to natural enemy damage is a defense strategy that minimizes the effects of damage on fitness. Despite the apparent benefits of tolerance, many populations exhibit intermediate levels of tolerance, indicating that constraints on the evolution of tolerance are likely. In a field experiment with the ivyleaf morning glory, costs of tolerance to deer herbivory in the form of negative genetic correlations between deer tolerance and fitness in the absence of damage were detected. However, these costs were detected only in the presence of insect herbivores. Such environmental dependency in the expression of costs of tolerance may facilitate the maintenance of tolerance at intermediate levels.


Purification, crystallization and preliminary X-ray crystallographic analysis of MIL, a glycosylated jacalin-related lectin from mulberry (Morus indica) latex.
A quantitatively major protein has been purified from the latex of Morus indica. The purified previously uncharacterized protein, M. indica lectin (MIL), was further shown to be a glycosylated tetramer and belongs to the family of jacalin-related lectins. Crystallization of MIL was also accomplished and the tetragonal crystals diffracted synchrotron X-rays to a resolution of 2.8 Å.


[A comparative study of serum H-antibodies in typhoid patients and bacteria carriers].
A study was made of the dynamics of serum H-antibodies in typhoid patients depending on the period of the disease and the severity of its course; the blood sera of chronic carriers were examined as well. H-antibodies were determined in the indirect hemagglutination test with the use of erythrocyte H-dignoasticum. Antibodies of different physico-chemical nature (of IgG and IgM classes) were obtained by fractionation in columns with DEAE-cellulose. Results of the investigations showed that the titres of sum total serum H-antibodies failed to depend on the severity of the course of the disease. The maximum value of the mean geometrical titre of H-antibodies in the blood serum was determined on the 3rd-4th week from the onset of the disease. In chronic carriers the sum total H-antibody titres were greater than in typhoid patients. The serum H-antibody titres increased on account of IgG-globulins both in the typhoid patients and in carriers.


The tetraspanin superfamily member CD151 regulates outside-in integrin alphaIIbbeta3 signaling and platelet function.
The tetraspanin family member CD151 forms complexes with integrins and regulates cell adhesion and migration. While CD151 is highly expressed in megakaryocytes and to a lesser extent in platelets, its physiologic role in platelets is unclear. In this study, we investigate the physical and functional importance of CD151 in murine platelets. Immunoprecipitation/Western blot studies reveal a constitutive physical association of CD151 with integrin alpha(IIb)beta(3) complex under strong detergent conditions. Using CD151-deficient mice, we show that the platelets have impaired "outside-in" integrin alpha(IIb)beta(3) signaling with defective platelet aggregation responses to protease-activated receptor 4 (PAR-4) agonist peptide, collagen, and adenosine diphosphate (ADP); impaired platelet spreading on fibrinogen; and delayed kinetics of clot retraction in vitro. This functional integrin alpha(IIb)beta(3) defect could not be attributed to altered expression of integrin alpha(IIb)beta(3). CD151(-/-) platelets displayed normal platelet alpha granule secretion, dense granule secretion, and static platelet adhesion. In addition, CD151(-/-) platelets displayed normal "inside-out" integrin alpha(IIb)beta(3) signaling properties as demonstrated by normal agonist-induced binding of soluble fluorescein isothiocyanate (FITC)-fibrinogen, JON/A antibody binding, and increases in cytosolic-free calcium and inositol 1,4,5 triphosphate (IP(3)) levels. This study provides the first direct evidence that CD151 is essential for normal platelet function and that disruption of CD151 induced a moderate outside-in integrin alpha(IIb)beta(3) signaling defect.


[Targeting of MT-II gene in mouse ES cells].
A MT-II gene targeting vector--pMT-II6.7 with 6.7kb sequences homolog to mMT-II and its flanking region has been transfected into Mespu22 with electroporation. We have got 26 positive clones from 104 G418 and Ganc clones with PCR method. From the karyotype analysis, we found two clones with 84% and 88% normal karyotype. They are clone 5-2 and 8-4. Using Southern analysis, we confirm that the two clones are homologous recombinants. These cell lines still have the pluropotential ability to differentiate both in vitro and in vivo. Now we have got a chimera mouse with cells from clone 8-4.


Would I-123 di-iodotyrosine provide a harmless deiodination test? Concise communication.
Defective iodotyrosine deiodinase activity may benefit from a specific treatment, thus requiring an unequivocal diagnosis. In reported cases this diagnosis has been obtained from an in vivo deiodination test making use of di-iodotyrosine (DIT) labeled either with I-131 or I-125. Dosimetric calculation indicates that such tests may result in unacceptable irradiation of the thyroid of a child wrongly suspected of having defective iodotyrosine deiodinase activity; therefore other methods are needed. The use of I-123 DIT is shown to be feasible, but even a 1:30 reduction in the thyroid dose still remains too high. Suppression of thyroid I- uptake by ClO4-, together with I-125 DIT, eliminates almost all thyroid irradiation and provides a sensitive, harmless, and rapid test.


Anaphylactoid shock induced by oxytocin administration--a case report.
"Piton-S", a preparation of synthetic hormone of oxytocin, is the most common pharmacologic agent used for the induction and augmentation of labor, as well as preventing postpartum hemorrhage owing to its uterotonic properties. There are many adverse effects reported with oxytocin, including hypotension and tachycardia. Anaphylactoid reaction to oxytocin is extremely rare. Here we bring forth a case who sustained from anaphylactoid shock following oxytocin administration during the act of cesarean section. We would like to discuss the proper management of perioperative anaphylaxis after review of similar cases in the literature.


Fermentative production of chiral acetoin by wild-type Bacillus strains.
In recent years, there have been many studies on producing acetoin by microbial fermentation, while only a few studies have focused on chiral acetoin biosynthesis. The weight assignment method was first applied to balance the chiral purity (expressed as the enantiomeric excess value) and the titer of acetoin. Bacillus sp. H-18W, a thermophile, was selected from seven Bacillus strains for chiral acetoin production. To lower the cost of the fermentation medium, soybean meal was used as a feedstock. Four kinds of frequently used commercial proteinases with different active sites were tested for the hydrolyzation of the soybean meal, and the combination of the acidic proteinase and the neutral proteinase showed the best results. In a fermentation medium containing 100 g L-1 glucose and 200 g L-1 hydrolysate, Bacillus sp. H-18W produced 21.84 g L-1 acetoin with an ee value of 96.25% at 60 h. This is the first report of using a thermophilic strain to produce chiral acetoin by microbial fermentation. Thermophilic fermentation can reduce the risk of bacterial contamination and can save cooling water. Using soybean meal hydrolysate and glucose as feedstocks, this work provides an economical and alternative method for the production of chiral pure acetoin.


Characterization of the effect of TIMAP phosphorylation on its interaction with protein phosphatase 1.
TIMAP, TGF-β inhibited, membrane-associated protein, is highly abundant in endothelial cells (EC). We have shown earlier the involvement of TIMAP in PKA-mediated ERM (ezrin-radixin-moesin) dephosphorylation as part of EC barrier protection by TIMAP (Csortos et al., 2008). Emerging data demonstrate the regulatory role of TIMAP on protein phosphatase 1 (PP1) activity. We provide here evidence for specific interaction (K(a) = 1.80 × 10(6) M(-1)) between non-phosphorylated TIMAP and the catalytic subunit of PP1 (PP1c) by surface plasmon resonance based binding studies. Thiophosphorylation of TIMAP by PKA, or sequential thiophosphorylation by PKA and GSK3β slightly modifies the association constant for the interaction of TIMAP with PP1c and decreases the rate of dissociation. However, dephosphorylation of phospho-moesin substrate by PP1cβ is inhibited to different extent in the presence of non- (~60% inhibition), mono- (~50% inhibition) or double-thiophosphorylated (<10% inhibition) form of TIMAP. Our data suggest that double-thiophosphorylation of TIMAP has minor effect on its binding ability to PP1c, but considerably attenuates its inhibitory effect on the activity of PP1c. PKA activation by forskolin treatment of EC prevented thrombin evoked barrier dysfunction and ERM phosphorylation at the cell membrane (Csortos et al., 2008). With the employment of specific GSK3β inhibitor it is shown here that PKA activation is followed by GSK3β activation in bovine pulmonary EC and both of these activations are required for the rescuing effect of forskolin in thrombin treated EC. Our results suggest that the forskolin induced PKA/GSK3β activation protects the EC barrier via TIMAP-mediated decreasing of the ERM phosphorylation level.


Predictors of health-promoting behaviors among freshman dental students at Istanbul University.
The aim of this cross-sectional study was to determine the predictors of health-promoting behaviors among freshman dental students at Istanbul University. Data were collected from a convenience sample of 111 students using questionnaires including a sociodemographic section, the Health-Promoting Lifestyle Profile II, the Health Value Scale, the Generalized Self-Efficacy Scale, the Perceived Stress Scale, and the Multidimensional Scale of Perceived Social Support. Data were analyzed using descriptive statistics, t-test, Pearson's correlation, and stepwise multiple linear regression. The overall health-promoting lifestyle behaviors among these students were at a moderate level, indicating that they engaged in health-promoting behaviors sometimes to often. They scored highest on the spiritual growth but lower on the health responsibility subscales. Females reported having engaged more in health responsibility behaviors and lower in physical activity than did males. Students from high-income families reported more physical activity. Significant correlations were found between overall health-promoting lifestyle behaviors, self-efficacy, health value, stress, and social support. Among all the related factors, self-efficacy was the most strongly predictive factor: it explained 61 percent of the variance in overall health-promoting behaviors. Thus, self-efficacy as a cognitive-perceptual factor should be considered by dental educators when planning educational interventions to promote students' healthy lifestyle.


Evaluation of treatment and posttreatment changes of protraction facemask treatment using the PAR index.
The purpose of this study was to use the Peer Assesment Rating (PAR) index score to evaluate the treatment and posttreatment changes of Class III patients treated by protraction facemask. The sample consisted of 20 Chinese children, 6 to 11 years old, with Class III skeletal malocclusion who had been treated with maxillary expansion and a protraction facemask. The average treatment time was 8.2 months, followed by 1 year of retention with a Class III functional appliance. Study casts were taken pretreatment (T1), posttreatment (T2), 1 year follow-up (T3), and 2 years follow-up (T4). After treatment, PAR scores were calculated for each time period. Differences among the 4 time periods were analyzed with the Wilcoxin matched-pairs test. Significant reductions in PAR scores were found at T2 (56%), T3 (70%), and T4 (63%) compared with T1. Immediately posttreatment (T2), 17 (85%) of 20 patients had improved PAR scores by a reduction of at least 30%. Reductions were caused primarily by correction of the anterior crossbite. One year after treatment (T3), further reductions in PAR score were noted (P <.01) as a result of better alignment of the anterior segment, improvement of the buccal occlusion, and overbite and midline corrections. Two years after treatment (T4), PAR scores were higher than at the previous time period. The increases were due to relapses in overjet (4 of 20 patients), overbite, and centerline corrections. These results indicate that significant reductions in the severity of Class III malocclusion can be achieved with early orthopedic facemask treatment. In most cases, further improvement in the PAR score can be expected 1 and 2 years after treatment. In a few patients, the benefits of early treatment are negated by relapses in overjet, overbite, and centerline corrections during the follow-up period.


Clinicopathologic analysis of mullerian adenosarcoma: the M.D. Anderson Cancer Center experience.
The records of 41 patients diagnosed with adenosarcoma of the female genital tract between 1982 and 1996 were reviewed. The median age at diagnosis is 51 years (range, 14-84). The most common symptom is vaginal bleeding (71%). Clinical signs at presentation include pelvic mass (37%), uterine polyps (29%), and enlarged uterus (22%). In 71% of patients, the tumor originates from the uterus. Other sites include ovary (15%), pelvis (12%), cervix (2%). A history of thyroid cancer, benign ovarian cyst, and polycystic ovarian disease is found more frequently than expected in this patient population, whereas no relationship to endometriosis is observed. Surgery is the mainstay of treatment, but platin-based chemotherapy given upfront in inoperable patient has definite efficacy. An overall response rate of 92.5% was observed after primary therapy (surgery with or without radiotherapy, and/or chemotherapy), with a median survival of 48 months (range, 1-174). Thirty-eight percent of patients had recurrent disease. The median time to recurrence is 12 months (range, 5-132). Although 60% of patients with recurrence achieved a complete remission after treatment, only 1 (8%) is alive without disease, and 3 (22%), with disease at the time of this analysis. In our series, histologic sarcomatous overgrowth is a predictor of poor prognosis (p<0.03), however myometrial invasion and stage of disease seem to be of less prognostic significance. Adenosarcoma is a tumor with a fair prognosis. Most tumor can be cured with surgery, but recurrence carries a bad prognosis.


Human homologue of murine T200 glycoprotein.
We report the identification of the human homologue of murine T200 glycoprotein. Peptide-mapping experiments suggest that the structure of the glycoprotein is highly conserved between the two species. Many of the properties of human T200 homologue are similar to those of murine T200 glycoprotein: it is broadly distributed within the hematopoietic system but is not detectable on nonhematopoietic cells; there are also structural differences between the forms of the glycoprotein found on T and B lymphoblastoid cell lines. These results suggest the homologous glycoproteins may play similar functional roles in both species.


[Angioedema of the mucous membranes of the upper aerodigestive tract after administration of ACE inhibitors].
Inhibitors of angiotensin converting enzyme may rarely cause an angioneurotic oedema of the upper aerodigestive tract. The pathomechanism of this side effect depends on an interaction of the drug with hormones regulating the vascular resistance such as the kallikrein kinin system and the prostaglandin system. Anglo-oedema is characterised by subcutaneous or submucosal swelling, which preferably affects the lips, the soft palate, the tongue and the larynx. Pathomechanisms, differential diagnosis and treatment of ACE-inhibitor induced oedema of the upper aerodigestive tract are described by means of 3 case reports.


[Genetic aspects of hyperpepsinogenetic duodenal ulcer].
The authors provide the data of examination of 93 children aged 2 to 15 years and their 67 parents with regard to familial predisposition to the hyperpepsinogenemic form of duodenal ulcer. It has been established that the content of uropepsinogen was appreciably heightened only in those children in whom one of the parents of the opposite sex as regards the child's sex had hyperpepsinogenemic duodenal ulcer. The problems of hyperpepsinogenuria inheritance couple with sex are discussed.


Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism. Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n = 871) or suspected (n = 15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n = 1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain. The ASD (p = 6.1e-13), sibling (p = 4.9e-3) and unrelated (p = 3.0e-3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height-a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r = 0.24, p = 2.1e-3) and parents (r = 0.17, p = 8.0e-7; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r = 0.13, p = 1.9e-3; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants. This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered. We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair).


Distinct genetic regions are associated with differential population susceptibility to chemical exposures.
Interactions between environmental factors and genetics underlie the majority of chronic human diseases. Chemical exposures are likely an underestimated contributor, yet gene-environment (GxE) interaction studies rarely assess their modifying effects. Here, we describe a novel method to profile the human genome and identify regions associated with differential population susceptibility to chemical exposures. Single nucleotide polymorphisms (SNPs) implicated in enriched chemical-disease intersections were identified and validated for three chemical classes with expected GxE interaction potential (neuroactive, hepatoactive, and cardioactive compounds). The same approach was then used to characterize consumer product classes with unknown risk for GxE interactions (washing products, cosmetics, and adhesives). Additionally, high-risk variant sets that may confer differential population susceptibility were identified for these consumer product groups through frequent itemset mining and pathway analysis. A dataset of 2454 consumer product chemical-disease linkages, with risk values, SNPs, and pathways for each association was developed, describing the interplay between environmental factors and genetics in human disease progression. We found that genetic hotspots implicated in GxE interactions differ across chemical classes (e.g., washing products had high-risk SNPs implicated in nervous system disease) and illustrate how this approach can discover new associations (e.g., washing product n-butoxyethanol implicated SNPs in the PI3K-Akt signaling pathway for Alzheimer's disease). Hence, our approach can predict high-risk genetic regions for differential population susceptibility to chemical exposures and characterize chemical modifying factors in specific diseases. These methods show promise for describing how chemical exposures can lead to varied health outcomes in a population and for incorporating inter-individual variability into chemical risk assessment.


The approach to melancholy on 30.1 Aristotelian problem.
Τhe 30.1 Aristotelian problem is the most comprehensive and organized analysis of the phenomenon of melancholy in Aristotelian Corpus. Although, there are serious doubts if this text, as it was survived today, was written by Aristotle (384-322 B.C.) or by one of his followers -perhaps Theophrastus (372-287 B.C.)- nevertheless it is widely accepted that reflects the authentic ideas of Aristotle. The two counterbalancing sentiments, this of mirthfulness and this of moroseness, which are attributed in the text to the "melancholic" persons, introduce the primary difficulty, in order to be understood the unclear notion of melancholy in this work. All the previous approaches understood these sentiments, as diversity in the symptomatology of melancholy that is the ancient mental disorder which is similar to modern depression. But according to our point of view, this text is a study of pathological physiology, underling the significant role of black bile as the causative factor of the above two emotions in humans under the specific influence of temperature. Humor's overheat had as result the mirthfulness and its overcooling the moroseness. The reference to the healthy people and the graduation of the quantity of black bile in human body, as little, middle and massive, which is associated to the mentally ill persons, indicate that these two emotions were not only recognized as pathological manifestations of patients, but also as temperamental characteristics of healthy people, which arise from the same alteration of this humor, when its quantity is limited. Examining deeper the psychopathological aspect of this content, we may assume that, due to the fact mirthfulness was presented in the form of excessive enthusiasm, passion and courage and on the other hand moroseness by the distinctive elements of irrational fear, indolence and absurdity, the first one referred to mania and the second to melancholy, since their descriptions correspond to the basic features of each disease. Therefore, under the new reading, black bile should be perceived as the common source of the above two mental disorders, expressing the Aristotelian version of their correlation, which preoccupied many of the ancient Greek physicians as Themison (1st century B.C.) and his followers, Rufus of Ephesus (1st century A.D.), Galen (130-201 A.D.) and Aretaeus of Cappadocia (2nd century A.D.). This one probably derived from the difficulty to be fixed the limits between these two diseases, because anger and fear could be present in both situations provoking the confusion. Finally, we should reject the hypothesis of bipolar disorder's presentation, because text's generality does not allow the limitation to only one pathological phenomenon, while the absence of particular data on the duration and sequence of the two different emotional states acts as a deterrent for such a conclusion.


Efficacy of a Disease-Specific Nutritional Support for Pressure Ulcer Healing: A Systematic Review and Meta-Analysis.
The aim of this systematic review was to summarize the evidence on the efficacy of high-calorie, high-protein nutritional formula enriched with arginine, zinc, and antioxidants (disease-specific support) in patients with pressure ulcers (PUs). Randomized controlled trials in English published from January 1997 until October 2015 were searched for in electronic databases (EMBASE, Medline, PubMed, and CINAHL). Studies comparing a disease-specific nutritional support (oral supplements or tube feeding) to a control nutritional intervention enabling the satisfaction of energy requirements regardless of the use of high-calorie formula or placebo or no support for at least 4 weeks were considered eligible. Study outcomes were the percentage of change in PU area, complete healing and reduction in the PU area ≥40% at 8 weeks, and the percentage of change in area at 4 weeks. A total of 3 studies could be included in the meta-analysis. Compared with control interventions, formulas enriched with arginine, zinc and antioxidants resulted in significantly higher reduction in ulcer area (-15.7% [95%CI, -29.9, -1.5]; P=0.030; I2=58.6%) and a higher proportion of participants having a 40% or greater reduction in PU size (OR=1.72 [95%CI, 1.04, 2.84]; P=0.033; I2=0.0%) at 8 weeks. A nearly significant difference in complete healing at 8 weeks (OR=1.72 [95%CI, 0.86, 3.45]; P=0.127; I2=0.0%) and the percentage of change in the area at 4 weeks (-7.1% [95%CI, -17.4, 3.3]; P=0.180; I2=0.0%) was also observed. This systematic review shows that the use of formulas enriched with arginine, zinc and antioxidants as oral supplements and tube feeds for at least 8 weeks are associated with improved PU healing compared with standard formulas.


Testing for meningitis in children with bronchiolitis.
Viral bronchiolitis accounts for almost 20% of all-cause hospitalizations of infants (ie, children younger than age 1 year). The annual incidence of fever in viral bronchiolitis has been documented at 23% to 31%. However the incidence of concurrent serious bacterial infections is low (1%-7%), with meningitis occurring in less than 1% to 2% of cases, but lumbar puncture is performed in up to 9% of viral bronchiolitis cases. To our knowledge, no study has examined clinical factors that influence a physician's decision to perform a lumbar puncture in the setting of viral bronchiolitis. We present a retrospective, case-control study of hospitalized infants younger than one year diagnosed with viral bronchiolitis who underwent lumbar puncture as part of an evaluation for meningitis. The objective of the study was to determine clinical factors that influence a physician's decision to perform a lumbar puncture in the setting of viral bronchiolitis. Although the presence of apnea, cyanosis, meningeal signs, positive urine culture results, and young age were factors found to be preliminarily associated with the performance of a lumbar puncture in the setting of bronchiolitis, young age was the only significant clinical factor found after multivariable regression; no other demographic, clinical, laboratory, or radiologic variables were found to be significant.


The Use of Smart Speakers in Care Home Residents: Implementation Study.
The use of smart speakers to improve well-being had been trialed in social care by others; however, we were not aware of their implementation in most care homes across a region in the Southwest of the United Kingdom. For the widespread adoption of new technology, it must be locally demonstrable and become normalized. The aim of this study was to install smart speakers in care homes in a rural and coastal region and to explore if and how the devices were being used, the barriers to their implementation, and their potential benefits. Email, workshops, drop-in sessions, phone, and cold calling was used to contact all 230 care homes, offering a free smart speaker and some advisory support. Care homes accepting the devices were asked to complete a feedback diary. Nonresponse rate for diary completion was high and was thus supplemented with a telephone survey. Over the course of 7 months, we installed 156 devices in 92 care homes for older people, 50 devices for people with physical or mental health needs, and 8 for others. The devices were used mainly for music but also for poetry, recipes, light controls, jokes, and video calls. Care home managers reported the benefits for the residents, including enhanced engagement with home activities, enjoyment, calming effects, and the acquisition of new skills. Implementation problems included internet connectivity, staff capacity, and skills. Affordable consumer devices such as smart speakers should be installed in all care homes to benefit residents. Voice-activated technologies are easy to use and promote interaction. This study indicates that implementation in care homes was possible and that smart speakers had multifaceted benefits for residents and staff. Most care homes in this region now use smart speakers for their residents, thereby normalizing this practice.


POLG1 mutations cause a syndromic epilepsy with occipital lobe predilection.
The epileptic semiology of 19 patients (from 15 families) with mitochondrial disease due to mutations in the POLG1 gene is presented. The patients were either homozygous for the 1399G > A (p.A467T) or 2243G > C (p.W748S) mutations or compound heterozygotes for these two mutations. While the clinical features have been reviewed, detailed analysis of their epilepsy is presented for the first time. Irrespective of genotype, patients developed an epileptic syndrome with initial features of occipital lobe epilepsy. Occipital seizure phenomena included flickering coloured light, sometimes persisting for weeks, months or even years, ictal visual loss, horizontal/vertical nystagmus or oculoclonus, dysmorphopsia, micro-/macropsia and palinopsia. Most patients developed simple partial seizure phenomena with motor symptoms suggesting frontal lobe seizure initiation or spread. Simple and complex partial seizures, clonic- and/or myoclonic seizures with epilepsia partialis continua and frequent convulsive status epilepticus were observed in this syndrome that appears to be a symptomatic and secondary generalized or multifocal epilepsy with focal occipital predilection. The mean age of seizure presentation was 18.4 years (6-58 years). All patients developed status epilepticus and 11 patient deaths were, all related to prolonged convulsive status epilepticus, including two with liver failure apparently precipitated by treatment with sodium valproate.


Multipage storage in a LiNbO(3):Fe crystal sheet using the photorefractive light-climbing effect.
The storage application of the light-climbing effect in a LiNbO(3):Fe crystal has been studied experimentally. A new type of photorefractive storage in LiNbO(3):Fe crystals, in which one could write the multipage simultaneously and at a later time read out the multistored pages, using only one readout beam simultaneously, has been demonstrated successfully. Furthermore the signal-to-noise ratio of the output images was high because the climbing lights suppressed the fanning noise scattering lights.


[Change in prevalence of physical and sports activities in a cohort of students].
Sedentary lifestyle is one of the worldwide problems of Public Health. Given that, physical activity has both direct and indirect effects on the mortality and morbidity on non-communicable chronic diseases. The aim was to determine the change in prevalence of sedentary lifestyle in a cohort of students. The Universidad Nacional Autónoma de México makes an Automated Medical Examination to students. In this evaluation, the sport, physical activity and other risk factors were analyzed in students admitted in 2010 to the Faculty of Medicine that were previously analyzed in 2007. A total of 593 students were studied. The mean age was 15.1 ± 1.4 years. The prevalence of physical inactivity increased from 38.3 to 39.9 %. When stratified by gender, women were more sedentary (p < 0.05). Sports activities decreased significantly in frequency and time. In the sedentary population, the prevalence of overweight increased in men and the obesity in women. Smoking increased 4.9 % and alcohol consumption in 36.7 % in both sexes. The prevalence of physical inactivity was higher compared to other countries. Smoking and alcohol consumption increased so it is necessary to follow up and implement programs of health promotion.


Modulation by adenosine of GABA-activated current in rat dorsal root ganglion neurons.
1. The modulation by adenosine of GABA-activated current (IGADA) was studied in freshly isolated rat dorsal root ganglion (DRG) neurons using the whole-cell patch-clamp technique. 2. In most of the DRG neurons examined (68/90, 75.5%) adenosine (1-10 microM) suppressed IGABA, while in some neurons examined, it potentiated (16/90, 17.8%) IGABA. It exerted no effects on IGABA in a few cells (6/90, 6.7%). 3. Adenosine shifted the GABA concentration-response curve downward with no significant change of the EC50. The maximal response to GABA was suppressed by 29.6 +/- 2.6%. The adenosine-induced inhibition of IGABA showed no voltage dependence. 4. 8-Cyclopentyl-1,3-dimethylxanthine (DPCPX; 1 microM), a selective A1 adenosine receptor antagonist, partially reversed adenosine inhibition of IGABA and completely blocked N6-cyclo-hexyladenosine (CHA; an A1 adenosine receptor agonist) inhibition of IGABA. DPCPX (1 microM) also blocked the suppression of IGABA by 2-chloroadenosine (CADO). CGS21680, a selective A2A adenosine receptor agonist, did not inhibit IGABA and DMPX, a selective A2A adenosine receptor antagonist, did not prevent adenosine inhibition of IGABA. 5. Intracellular application of H-7 (20 microM; a protein kinase C inhibitor) reversed adenosine inhibition of IGABA while inclusion of cAMP (1 mM), H-9 (20 microM; a protein kinase A inhibitor) and BAPTA (10 mM; a chelator of calcium ions) in the recording pipette did not affect the depression of IGABA by adenosine. IGABA was also suppressed by internal perfusion of PMA, a protein kinase C activator. 6. The results suggest that adenosine, as a neuromodulator, exerts a modulatory effect on the GABA-induced presynaptic inhibition in primary sensory transmission.


[Intestinal fatty acid binding protein: marker of enterocyte damage in acute and chronic gastroenterological diseases].
Intestinal fatty acid binding protein, a small cytosolic protein abundantly present in mature enterocytes of small and large intestine, has proven to be a sensitive marker for damage to the intestinal epithelium. Upon cellular damage of the enterocyte, intestinal fatty acid binding protein is readily released into the systemic circulation, passes through the glomerular filter and can be detected in the urine. In this review, the authors review studies on the application of this protein as a biomarker in acute and chronic gastrointestinal diseases.


The dynamics of life stressors and depressive symptoms in early adolescence: a test of six theoretical models.
Structural equation modeling was used to compare 6 competing theoretically based psychosocial models of the longitudinal association between life stressors and depressive symptoms in a sample of early adolescents (N= 907; 40% Hispanic, 32% Black, and 19% White; mean age at Time 1 = 11.4 years). Only two models fit the data, both of which included paths modeling the effect of depressive symptoms on stressors recall: The mood-congruent cognitive bias model included only depressive symptoms to life stressors paths (DS-->S), whereas the fully transactional model included paths representing both the DS-->S and stressors to depressive symptoms (S-->DS) effects. Social causation models and the stress generation model did not fit the data. Findings demonstrate the importance of accounting for mood-congruent cognitive bias in stressors-depressive symptoms investigations.


s-Allyl cysteine, s-ethyl cysteine, and s-propyl cysteine alleviate β-amyloid, glycative, and oxidative injury in brain of mice treated by D-galactose.
The neuroprotective effects of s-allyl cysteine, s-ethyl cysteine, and s-propyl cysteine in D-galactose (DG)-treated mice were examined. DG treatment increased the formation of Aβ(1-40) and Aβ(1-42), enhanced mRNA expression of β-amyloid precursor protein (APP) and β-site APP cleavage enzyme 1 (BACE1), and reduced neprilysin expression in brain (P < 0.05); however, the intake of three test compounds significantly decreased the production of Aβ(1-40) and Aβ(1-42) and suppressed the expression of APP and BACE1 (P < 0.05). DG treatments declined brain protein kinase C (PKC) activity and mRNA expression (P < 0.05). Intake of test compounds significantly retained PKC activity, and the expression of PKC-α and PKC-γ (P < 0.05). DG treatments elevated brain activity and mRNA expression of aldose reductase (AR) and sorbitol dehydrogenase as well as increased brain levels of carboxymethyllysine (CML), pentosidine, sorbitol, and fructose (P < 0.05). Test compounds significantly lowered AR activity, AR expression, and CML and pentosidine levels (P < 0.05). DG treatments also significantly increased the formation of reactive oxygen species (ROS) and protein carbonyl and decreased the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (P < 0.05); however, the intake of test compounds in DG-treated mice significantly decreased ROS and protein carbonyl levels and restored brain GPX, SOD, and catalase activities (P < 0.05). These findings support that these compounds via their anti-Aβ, antiglycative, and antioxidative effects were potent agents against the progression of neurodegenerative disorders such as Alzheimer's disease.


Effects of tributyltin exposure in hermit crabs: Clibanarius vittatus as a model.
Tributyltin (TBT) contamination affects the reproductive system of many species of invertebrates worldwide. The present study was designed to evaluate the effects of exposure to TBT pollution on the reproduction of the hermit crab Clibanarius vittatus. An orthogonal experiment was designed with two treatments: contamination (with or without TBT in the food) and crab sex (males and females). The animals were reared in the laboratory for nine months, and macroscopic and histological analyses of reproductive organs were carried out after the end of the experiment. Tributyltin was recorded in exposed crabs, but no morphological alterations were detected in the gonads of males, regardless of whether they were exposed to TBT. In contrast, females exposed to TBT displayed disorganization and atrophy of their ovaries, thus directly affecting reproduction in this hermit crab species. This effect observed in female hermit crabs may harm populations located in harbor regions, where TBT concentration is high, even after the worldwide TBT ban.


Assessment of Computed Tomography-Defined Muscle and Adipose Tissue Features in Relation to Length of Hospital Stay and Recurrence of Hypertriglyceridemic Pancreatitis.
Analytic morphometric assessment has recently been proposed to be applied to the study of acute pancreatitis (AP). However, the relationship between body composition and the outcomes of hypertriglyceridemic pancreatitis (HTGP) is still unclear. The aim of this study was to evaluate body composition in relation to the length of hospital stay (LOS) and recurrence of HTGP. Patient characteristics, admission examination data, body composition parameters, LOS, and recurrence within 1 year were collected from the institutional pancreatitis database and follow-up records. Logistic regression analysis was used to identify risk factors for LOS and recurrence of HTGP. Of the 196 included patients, 158 (80.6%) were men and 53 (27.0%) were sarcopenic. The average LOS was 15.83±10.02 days. The recurrence rate of HTGP was 36.7%. Multivariate analysis with multiple linear regression suggested that subcutaneous adipose tissue (SAT) area (p=0.019) and high-density lipoprotein-cholesterol (HDL-C) (p=0.001) were independently associated with the LOS for HTGP after adjusting for age and sex. The multivariate adjusted hazard ratios for SAT area and HDL-C, with respect to the relationship between body parameters and LOS, were 1.008 (95% confidence interval [CI], 1.001-1.015) and 0.090 (95% CI, 0.022-0.361), respectively. No significant differences were observed between the AP and recurrent AP (RAP) groups in terms of characteristics, admission examination data, and body composition parameters. SAT area and HDL-C are associated with LOS in patients with HTGP. The body composition of patients at the first symptom onset of HTGP cannot predict recurrence.


[Absorption of anti-tuberculous drugs after gastric surgery (author's transl)].
Although partial gastrectomy does not, as a rule, greatly impair the absorption of ethambutol by tuberculous patients, subtotal or total gastrectomy may reduce it by 40--60 per cent. Rifampicin and isoniazid are almost completely absorbed; but postprandial administration of rifampicin may be preferable in these cases. In the presence of anacidity absorption of isoniazid is slowed down but not reduced quantitatively. To estimate the degree to which absorption is impaired the drug levels in the blood after oral and intravenous administration should be determined over two consecutive days.


Enhancement by clofazimine and inhibition by dapsone of production of prostaglandin E2 by human polymorphonuclear leukocytes in vitro.
The effects of the antileprosy agents clofazimine and dapsone (1 to 10 micrograms/ml) on the spontaneous and stimulated release of prostaglandin E2 (PG E2) by human polymorphonuclear leukocytes (PMNL) in vitro have been investigated. PMNL were obtained from normal adult volunteers and three patients with leprosy (two borderline lepromatous and one subpolar lepromatous leprosy). The synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) at a concentration of 10(-7) M was used as the stimulant of PG E2 synthesis. None of the test agents at the concentrations used inhibited the binding of radiolabeled FMLP to PMNL. However, dapsone at 5 and 10 micrograms/ml inhibited the spontaneous and FMLP-induced release of PG E2 by PMNL. Clofazimine, on the other hand, significantly increased both the spontaneous and the FMLP-induced synthesis of PG E2 by PMNL. The enhancing effects of clofazimine on FMLP-mediated synthesis of PG E2 were particularly striking and were observed at concentrations of 1 to 10 micrograms of the drug per ml. Measurements of PMNL spontaneous and FMLP-induced synthesis of PG E2 in the presence of both clofazimine and dapsone (5 micrograms/ml) indicated that the two drugs are mutually antagonistic. PMNL from both normal control subjects and patients with leprosy were equally sensitive to these effects of clofazimine and dapsone. The immunostimulatory and immunosuppressive properties of dapsone and clofazimine, respectively, may be related to the opposite effects of these agents on PG E2 synthesis in human leukocytes.


Periprocedural management of oral anticoagulation in patients with atrial fibrillation: approach in the era of new oral anticoagulants.
A growing number of patients with atrial fibrillation are treated with oral anticoagulation (OAC), and a large proportion of them will require surgical or other invasive procedures. These procedures typically involve interruption of OAC with or without the use of heparin bridging; however; there has been a dramatic change in this practice during the past 3 years. The introduction of short-acting, new oral anticoagulants and the growing popularity of some low-risk procedures with continued OAC have transformed our practice. Physicians and surgeons who treat patients with atrial fibrillation must be aware of these changes and understand how to deal with the new challenges they may encounter.


Hierarchical Optimization of High-Performance Biomimetic and Bioinspired Membranes.
Biomimetic and bioinspired membranes have emerged as an innovative platform for water purification and aqueous separations. They are inspired by the exceptional water permeability (∼109 water molecules per second per channel) and perfect selectivity of biological water channels, aquaporins. However, only few successes have been reported for channel-based membrane fabrication due to inherent challenges of realizing coherence between channel design at the angstrom level and development of scalable membranes that maintain these molecular properties at practice-relevant scales. In this article, we feature recent progress toward practical biomimetic membranes, with the review organized along a hierarchical structural perspective that biomimetic membranes commonly share. These structures range from unitary pore shapes and tubular hydrophobic channel geometries to self-assembled bilayer structures and finally to macroscale membranes covering a size range from the angstrom, to the micrometer scale, and finally to the centimeter and larger scales. To maximize the advantage of water channel implementation into membranes, each feature needs to be optimized in an appropriate manner that provides a path to successful scale-up to achieve high performance in practical biomimetic and bioinspired membranes.


Impaired Ca2+-dependent activation of large-conductance Ca2+-activated K+ channels in the coronary artery smooth muscle cells of Zucker Diabetic Fatty rats.
The large-conductance Ca(2+)-activated K(+) (BK) channels play an important role in the regulation of cellular excitability in response to changes in intracellular metabolic state and Ca(2+) homeostasis. In vascular smooth muscle, BK channels are key determinants of vasoreactivity and vital-organ perfusion. Vascular BK channel functions are impaired in diabetes mellitus, but the mechanisms underlying such changes have not been examined in detail. We examined and compared the activities and kinetics of BK channels in coronary arterial smooth muscle cells from Lean control and Zucker Diabetic Fatty (ZDF) rats, using single-channel recording techniques. We found that BK channels in ZDF rats have impaired Ca(2+) sensitivity, including an increased free Ca(2+) concentration at half-maximal effect on channel activation, a reduced steepness of Ca(2+) dose-dependent curve, altered Ca(2+)-dependent gating properties with decreased maximal open probability, and a shortened mean open-time and prolonged mean closed-time durations. In addition, the BK channel beta-subunit-mediated activation by dehydrosoyasaponin-1 (DHS-1) was lost in cells from ZDF rats. Immunoblotting analysis confirmed a 2.1-fold decrease in BK channel beta(1)-subunit expression in ZDF rats, compared with that of Lean rats. These abnormalities in BK channel gating lead to an increase in the energy barrier for channel activation, and may contribute to the development of vascular dysfunction and complications in type 2 diabetes mellitus.


Clinical presentation of familial exudative vitreoretinopathy.
To describe the clinical characteristics, staging and presentation of patients with familial exudative vitreoretinopathy (FEVR) in our clinical practice over the last 25 years. Case series, retrospective review. We included 273 eyes of 145 patients. Data collected from charts included gender, gestational age at birth, birthweight, age at presentation, referring diagnosis, family history, prior ocular surgery, and clinical presentation in each eye. Eyes with invasive posterior segment procedures before initial presentation were excluded. Demographics on presentation and clinical staging. Patients were slightly male predominant (57%) with a mean birthweight of 2.80 kg (range, 740 g-4.76 kg), mean gestational age of 37.8 weeks (range, 25-42), and mean age at presentation of almost 6 years (range, <1 month-49 years). A positive family history of FEVR was obtained in 18% of patients. A positive family history for ocular disease consistent with but not diagnosed as FEVR was obtained in an additional 19%. Stage 1 FEVR was identified in 45 eyes, stage 2 in 33 eyes, stage 3 in 42 eyes, stage 4 in 89 eyes, and stage 5 in 44 eyes. Radial retinal folds were seen in 77 eyes, 64 of which were temporal or inferotemporal in location. The FEVR patient population is remarkable for the wide range of age at presentation, gestational age, and birthweight. Although a positive family history on presentation may support the diagnosis of FEVR, a negative family history is of little help. The majority of retinal folds extended radially in the temporal quadrants, but radial folds were seen in almost all quadrants. Fellow eyes demonstrated a wide variation in symmetry. The presentation of FEVR may mimic the presentation of other pediatric and adult vitreoretinal disorders, and careful examination is often crucial in making the diagnosis of FEVR. The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Investigating the synergistic interaction of diabetes, tobacco smoking, alcohol consumption, and hypercholesterolemia on the risk of pancreatic cancer: a case-control study in Italy.
The aims of the present research are to investigate the possible predictors of pancreatic cancer, in particular smoking status, alcohol consumption, hypercholesterolemia, and diabetes mellitus, in patients with histologically confirmed pancreatic carcinoma and to examine the synergism between risk factors. A case-control study (80 patients and 392 controls) was conducted at the Teaching Hospital "Agostino Gemelli" in Rome. A conditional logistic regression was used for the statistical analysis and results were presented as odds ratio (OR) and 95% confidence intervals (95% CI). We also investigated the possible interactions between risk factors and calculated the synergism index (SI). The multivariate analysis revealed that hypercholesterolemia and alcohol consumption resulted in important risk factors for pancreatic cancer even after the adjustment for all variables (OR: 5.05, 95% CI: 2.94-8.66; OR: 2.25, 95% CI: 1.30-3.89, resp.). Interestingly, important synergistic interactions between risk factors were found, especially between ever smoking status and alcohol consumptions (SI = 17.61) as well as alcohol consumption and diabetes (SI = 17.77). In conclusion, the study confirms that hypercholesterolemia and alcohol consumption represent significant and independent risk factors for pancreatic cancer. Moreover, there is evidence of synergistic interaction between diabetes and lifestyle factors (drinking alcohol and eating fatty foods).


A prospective study of risk factors for the development of depression and disordered eating in adolescents.
There is evidence that females display higher levels of depressive symptoms and disordered eating than males from adolescence onward. This study examined whether different risk factors and their interaction with sex (moderator effect) prospectively predicted depressive symptoms and disordered eating in adolescents. A total of 415 female adolescents and 413 male adolescents were evaluated at 2 different times: In the first evaluation (T1) the mean age of the participants was 12.8 years, and in the second evaluation (T2) it was 14.9 years. Differences between sexes were observed in relation to depressive symptoms at T2 and in disordered eating at T1 and T2. Body dissatisfaction was a significant predictor of both depressive symptoms and disordered eating. In addition, moderation tests indicated that the interaction between self-esteem and sex and the interaction between body mass index and sex significantly predicted depressive symptoms and disordered eating, respectively.


The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121).
When overexpressed, the membrane glycoprotein PC-1 may play a role in human insulin resistance through the inhibition of insulin receptor (IR) autophosphorylation. A PC-1 variant (K121Q, with lysine 121 replaced by glutamine) is also associated with whole-body insulin resistance when not overexpressed. To better understand the effects of the Q allele on IR function and downstream signaling, we transfected cultured cells with cDNAs for either the Q or the K alleles. In human MCF-7 cells, the Q allele was severalfold more effective (P < 0.05-0.01) than the K allele in reducing insulin stimulation of IR autophosphorylation, insulin receptor substrate-1 phosphorylation, phosphatidylinositol 3-kinase activity, glycogen synthesis, and cell proliferation. Similar data on IR autophosphorylation inhibition were also obtained in mouse R-/hIR and human HEK 293 cell lines. In transfected MCF-7 cells, 125I-labeled insulin binding and IR content were unchanged, and PC-1 overexpression did not influence IGF-1 stimulation of IGF-1 receptor autophosphorylation. Both the Q and K alleles directly interacted with the IR, as documented by coimmunoprecipitation assays. This interaction was greater for the Q allele than for the K allele (P < 0.01), suggesting that direct PC-1-IR interactions are important for the PC-1 inhibitory effect on insulin signaling. In conclusion, the Q allele has stronger inhibitory activity on IR function and insulin action than the more common K allele, and this is likely a consequence of the intrinsic characteristics of the molecule, which more strongly interacts with the IR.


Colorimetric Sensor Array for Monitoring CO and Ethylene.
Developing miniaturized and inexpensive detectors remains an important and practical goal for field-deployable monitoring of toxic gases and other bioactive volatiles. CO (a common toxic pollutant) and ethylene (the phytohormone primarily responsible for fruit ripening) share the capability of strong back-π-bonding to low-oxidation-state metal ions, which has proved important in the development of metal-ion-based sensors for these gases. We report herein cumulative colorimetric sensor arrays based on Pd(II)-silica porous microsphere sensors and their application as an optoelectronic nose for rapid colorimetric quantification of airborne CO and ethylene. Quantitative analysis of two gases was obtained in the range of 0.5 to 50 ppm with detection limits at the sub-parts-per-million level (∼0.4 ppm) after 2 min of exposure and ∼0.2 ppm after 20 min (i.e., <0.5% of the permissible exposure limit for CO and <10% of the ethylene concentration needed for fruit ripening). We further validate that common potential interfering agents (e.g., changes in humidity or other similar air pollutants such as NO x, SO2, H2S, or acetylene) are not misidentified with CO or ethylene. Finally, the sensor is successfully used for the quantification of ethylene emitted from ripening bananas, demonstrating its potential applications in the monitoring of fruit ripening during storage.


Associations between DSM-IV mental disorders and subsequent non-fatal, self-reported stroke.
To examine the associations between a wide range of mental disorders and subsequent onset of stroke. Lifecourse timing of stroke was examined using retrospectively reconstructed data from cross-sectional surveys. Data from the World Mental Health Surveys were accessed. This data was collected from general population surveys over 17 countries of 87,250 adults. The Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of DSM-IV mental disorders. A weighted subsample (n=45,288), was used for analysis in the present study. Survival analyses estimated associations between first onset of mental disorders and subsequent stroke onset. Bivariate models showed that 12/16 mental disorders were associated with subsequent stroke onset (ORs ranging from 1.6 to 3.8). However, after adjustment for mental disorder comorbidity and smoking, only significant relationships between depression and stroke (OR 1.3) and alcohol abuse and stroke (OR 1.5) remained. Among females, having a bipolar disorder was also associated with increased stroke incidence (OR 2.1). Increasing number of mental disorders was associated with stroke onset in a dose-response fashion (OR 3.3 for 5+ disorders). Depression and alcohol abuse may have specific associations with incidence of non-fatal stroke. General severity of psychopathology may be a more important predictor of non-fatal stroke onset. Mental health treatment should be considered as part of stroke risk prevention. Limitations of retrospectively gathered cross sectional surveys design mean further research on the links between mental health and stroke incidence is warranted.


[Influence of age on quality of life of patients with intestinal stoma].
The work presents the research data on quality of life of 63 patients with temporary intestinal stoma. The basic group was made of 35 patients aged 60+ years, 38 patients younger than 60 years were included in the control group. Researches were carried out by means of a scale of an estimation of quality of life MOS-SF-36 in 3 and 6 months after the colostomy. In 3 months after colostomy, the indicators estimating physical well-being were above in the control group, the indicators estimating mental well-being were comparable. In 6 months the positive dynamics of indicators of physical health was marked in the group of 60+ patients but it was less than in the control group. Indicators of mental health in elderly patients did not vary considerably in this period, unlike the indicators of younger patients where authentic improvement was marked. The conclusion is drawn that age is the independent factor influencing quality of life of stomas patients, thus quality of life suffered more in older patients.


Multiplicity of hypoxia-inducible transcription factors and their connection to the circadian clock in the zebrafish.
In zebrafish, as in most vertebrates, three different isoforms of the hypoxia-inducible transcription factor, Hif-1α, Hif-2α, and Hif-3α, have been identified. The expression data of genes encoding these three proteins, as analyzed so far, show distinct expression patterns for all three isoforms during early development, under hypoxic conditions, and during exercise, suggesting differential roles for all three proteins under these different conditions. While isoform-specific functions for Hif-1α and Hif-2α have been identified in recent years, the role of Hif-3α remains somewhat elusive. Several studies mostly using mammalian cells or tissues discussed Hif-3α as a competitive inhibitor of Hif-1α and Hif-2α. In zebrafish, the expression changes for Hif-1α and Hif-3α observed during development and under environmental stress conditions do not support this hypothesis, and recent studies indicate that Hif-3α is also able to directly control transcriptional activity of certain genes. The Hif signaling pathway is tightly connected to cell circuitries such as glucose and lipid metabolism, and only very recently a further linkage to the circadian clock has been described. In this context a detailed analysis of the mRNA concentrations of hif-1α, hif-2α, and hif-3α also revealed a circadian expression pattern for hif-3α mRNA under normoxic conditions in zebrafish larvae. In addition, accumulation of Hif-1α protein during short-term hypoxia was found to depend on the time within the daily light and dark cycle at which hypoxia was encountered, suggesting that the hypoxia signaling pathway may be regulated by the circadian clock. This is supported by the fact that some of the downstream genes of the Hif signaling pathway, namely, erythropoietin and vascular endothelial growth factor, are known to be clock controlled as well. Furthermore, in developing zebrafish, the disruption of the circadian rhythm was shown to result in a diminished hypoxic response with a modified life cycle of erythrocytes and an altered patterning of the vascular bed, leading to even higher mortality rates of chronodisrupted animals. Hif protein, in turn, is known to affect the circadian clock pathway in zebrafish. Previously, we demonstrated that Hif-1α directly binds to defined E-boxes of the period 1 gene, leading to a sustained dampening of its oscillation amplitude. Here we show that Hif-1α also binds to the promoter of the period 2 gene, indicating that multiple connections between the Hif signaling pathway and the circadian clock exist. The redundancy of the coupling between both pathways might be evidence for the coevolution of both circuits after the great oxygenation event about 2.5 billion years ago. Coupling the circadian clock and the hypoxic signaling pathway may have conferred selective advantages by facilitating a coordinated response of cells and organisms to alternating day-night cycles and concomitant variable food availabilities in the face of varying oxygen supply.


The pst operon of enteropathogenic Escherichia coli enhances bacterial adherence to epithelial cells.
Enteropathogenic Escherichia coli (EPEC) adheres in vivo and in vitro to epithelial cells. Two main adhesins, the bundle-forming pilus and intimin, encoded by the bfp operon and eae, respectively, are responsible for the localized and the intimate adherence phenotypes. Deletion of the pst operon of EPEC abolishes the transport of inorganic phosphate through the phosphate-specific transport system and causes the constitutive expression of the PHO regulon genes. In the absence of pst there is a decrease in the expression of the main EPEC adhesins and a reduction in bacterial adherence to epithelial cells in vitro. This effect is not related to PHO constitutivity, because a Deltapst phoB double mutant that is defective in the transcription of the PHO genes also displayed low levels of adherence and expression of adhesins. Likewise, a PHO-constitutive phoR mutation did not affect bacterial adherence. The expression of the per operon, which encodes the bfp and ler regulators PerA and PerC, is also negatively affected by the pst deletion. Overall, the data presented here demonstrate that the pst operon of EPEC plays a positive role in the bacterial adherence mechanism by increasing the expression of perA and perC and consequently the transcription of bfp and eae.


Correlating Abdominal Wall Thickness and Body Mass Index to Predict Usefulness of Right Lower Quadrant Ultrasound for Evaluation of Pediatric Appendicitis.
To inform selective and efficient use of appendix ultrasound (US) beyond adult parameters of body mass index (BMI) of less than 25 kg/m, we correlate abdominal wall thickness (AWT) with age and BMI to generate parameters for male and female children. Information presented in chart format can aid in the decision to utilize US for the evaluation of appendicitis. In this observational study, 1600 pediatric computed tomography scans of the abdomen and pelvis were analyzed to obtain measurements of AWT in the right lower quadrant. Measurements were correlated by patient age, BMI, and sex. Results and consensus-based recommendations were presented in chart format with color-coded groupings to allow for convenient referencing in the clinical setting. One thousand four hundred eighty-eight computed tomography scans and AWT measurements were included. All age groups with BMI of less than 25 kg/m and all male and female groups younger than 6 years regardless of BMI had median AWT of less than 4 cm resulting in strong recommendation for US. Males older than 6 years and all female age groups with BMI of greater than 30 kg/m and female older than 15 years and BMI of greater than 25 kg/m had AWT of more than 5 cm resulting in low recommendation for US. While the BMI cutoff standard of less than 25 kg/m for usefulness of appendix US holds in the adult population, our data expand the acceptable range in children younger than 9 years regardless of BMI and male children with BMI up to 30 kg/m. Female children younger than 15 years with a BMI up to 30 kg/m may also be amenable to right lower quadrant US based on AWT. These parameters inform selective and efficient use of US for appendix evaluation.


Retrograde labeling in peripheral nerve research: it is not all black and white.
Retrograde labeling has become an important method of evaluation for peripheral nerve regeneration after injury. We review the features of the commonly used retrograde tracers Fast Blue, Fluoro-Gold, and Fluoro Ruby in addition to the various application methods (conduit reservoir, intramuscular injection, and crystal powder application) and the techniques used to count stained neurons. Upon application of the staining techniques and dyes in a rat and mouse nerve injury model, Fluoro-Gold was found to stain the greatest number of neurons with all application methods. However, due to variability of staining intensity, neuron size, and background staining, it is difficult to count the stained neurons accurately. Fast Blue stains consistently using intramuscular injection in the mouse but fails to provide adequate staining using the muscle injection method in the rat model and shows high failure rates using the conduit reservoir technique. However, crystal dye application with Fast Blue to the cut nerve end provides excellent results. We believe that it is imperative to use the various tracers and application methods prior to their experimental use to develop a consistent standardized approach to retrograde labeling.


[The conformation of apoB-100 in phylogenetically and functionally different lipoproteins of low and very low density: algorithm of formation of phenotypes of hyper lipoproteinimia (a lecture)].
The cells' malabsorption of three classes of lipoproteins--chylomicrons and lipoproteins of low and very low density,--form under electrophoresis six phenotypes of hyperlipoproteinemia. In phylogenesis, cells absorb lipoproteins in a consecutive way by apoE/B-48, apoB-100 and apoE/B-100 receptor endocytosis. The domain-ligand in lipoproteins of very low density is forming when apoB-100 takes active conformation "deformed bilayer apoprotein-lipid" in association with domain apoE apoE/B-100 ligand is formed. Another active conformation apoB-100 in domain is globule with lipids in "pocket" forming apoB-100 ligand In blood 9 subclasses are formed: pre-ligand and post-ligand chylomicrons, lipoproteins with low density and lipoproteins with very low density. The ligand lipoproteins bind receptors of membrane and absorb cells. Both pre-chylomicrons, pre-lipoproteins with low density, pre-lipoproteins with very low density and post-chylomicrons, post-lipoproteins with low density, post-lipoproteins with very low density remain in blood. The sub-classes of lipoproteins form at electrophoregram 6 phenotypes of hyperlipoproteinemia: phenotype I-pre-chylomicrons + pre-lipoproteins with very low density; phenotype IIa--post-lipoproteins with low density; phenotype IIb--pre-lipoproteins with very low density; phenotype III--post-chylomicrons + pre-lipoproteins with very low density; phenotype IV--pre-lipoproteins with very low density; phenotype V--pre-chylomicrons + post-chylomicrons + pre-lipoproteins with very low density + post-lipoproteins with very low density. The formation under electrophoresis of primary phenotypes and secondary types of hyperlipoproteinemia occurs according single algorithm. In aphysiological sense, the major mass of palmitic and oleic lipoproteins with very low density absorb cells without transformation into lipoproteins with low density. Only linoleic and linolenic lipoproteins with very low density which are formed after binding of apoB-100 of triglycerides the same name and which are not much in blood acquire density of lipoproteins with low density physiologically. Under high content of triglycerides in blood main mass of lipoproteins with low density consists of aphysiologic palmitic lipoproteins with very low density with hydrated density lipoproteins with low density, the cause of hyperlipoproteinemia of phenotype III is genotype e21e2 apoE; hyperlipoproteinemia of phenotype V--genotype e4/e4 and probably toxic inhibition of activity (synthesis) phylogenetically late stearil-KoA-desaturase-2.


Radioactive waste disposal implications of extending Part IIA of the Environmental Protection Act to cover radioactively contaminated land.
A short study has been carried out of the potential radioactive waste disposal issues associated with the proposed extension of Part IIA of the Environmental Protection Act 1990 to include radioactively contaminated land, where there is no other suitable existing legislation. It was found that there is likely to be an availability problem with respect to disposal at landfills of the radioactive wastes arising from remediation. This is expected to be principally wastes of high volume and low activity (categorised as low level waste (LLW) and very low level waste (VLLW)). The availability problem results from a lack of applications by landfill operators for authorisation to accept LLW wastes for disposal. This is apparently due to perceived adverse publicity associated with the consultation process for authorisation coupled with uncertainty over future liabilities. Disposal of waste as VLLW is limited both by questions over volumes that may be acceptable and, more fundamentally, by the likely alpha activity of wastes (originating from radium and thorium operations). Authorised on-site disposal has had little attention in policy and guidance in recent years, but may have a part to play, especially if considered commercially attractive. Disposal at BNFL's near surface disposal facility for LLW at Drigg is limited to wastes for which there are no practical alternative disposal options (and preference has been given to operational type wastes). Therefore, wastes from the radioactively contaminated land (RCL) regime are not obviously attractive for disposal to Drigg. Illustrative calculations have been performed based on possible volumes and activities of RCL arisings (and assuming Drigg's future volumetric disposal capacity is 950,000 m3). These suggest that wastes arising from implementing the RCL regime, if all disposed to Drigg, would not represent a significant fraction of the volumetric capacity of Drigg, but could have a significant impact on the radiological capacity with respect to 226Ra plus 232Th. The government's decision-making programme for managing solid radioactive wastes in the UK may possibly achieve a general consensus that the use of landfill for LLW from the RCL regime has a fundamental role to play. However, this is unlikely to change the situation within the next few years. No new national facility arising from this programme is likely to be available during the first decade of the operation of a new RCL regime. Hence it appears that Drigg will need to play an important role for some years to come.


Multiplexed protein measurement: technologies and applications of protein and antibody arrays.
The ability to measure the abundance of many proteins precisely and simultaneously in experimental samples is an important, recent advance for static and dynamic, as well as descriptive and predictive, biological research. The value of multiplexed protein measurement is being established in applications such as comprehensive proteomic surveys, studies of protein networks and pathways, validation of genomic discoveries and clinical biomarker development. As standards do not yet exist that bridge all of these applications, the current recommended best practice for validation of results is to approach study design in an iterative process and to integrate data from several measurement technologies. This review describes current and emerging multiplexed protein measurement technologies and their applications, and discusses the remaining challenges in this field.