Clinical selection criteria can predict futile intervention in patients referred for percutaneous endoscopic gastrostomy insertion.
Percutaneous endoscopic gastrostomy (PEG) placement is performed in a patient group with high mortality in the short and medium term. For a significant proportion of patients, the procedure provides no increase in survival. There are no standardised assessment tools available to determine the clinical appropriateness of PEG placement, nor any to predict clinical outcome. The study aims to determine whether clinical assessment, by a trained dietitian, of the appropriateness of PEG placement is predictive of mortality in the short and medium terms. A prospective audit was undertaken of all requests for PEG placement at a single large, publicly funded Australian tertiary hospital. The clinical appropriateness of each request was assessed by a trained dietitian, and data on age, sex, reason for referral, comorbidities and satisfaction of assessment criteria were collected, and patient outcome and survival were compared for all patients according to whether a PEG was inserted or not. Main outcome measures were mortality at 30 and 150 days after referral. During the period 2005-2008, 198 patients were referred for PEG; 94 were assessed as appropriate referrals, 104 as inappropriate. Eighty-four patients who underwent gastrostomy, after being assessed as appropriate, had significantly reduced mortality at 30 days (96.4% vs 74.6%, P < 0.0001) and 150 days (82.1% vs 57.9%, P = 0.0001) compared with all other patients. Patients who received PEG despite contrary advice had no significant survival advantage, at 30 days or 150 days, over patients who did not receive PEG. The application of selection criteria by trained assessors improves patient selection for PEG insertion and predicts mortality at early and later time points, by identifying patients unlikely to benefit from PEG. The group of patients who received a gastrostomy despite an adverse assessment had no mortality benefit - in these patients, the procedure may have been futile.


Transplantation of human tooth with proliferating periodontal tissue--long-term clinical follow-up study--.
A case report is presented on transplantation of a left third molar to replace a right second molar lost due to large furcation perforation. Two weeks after surgery, a reentry surgical procedure was performed on the furcation defect of the second molar to remove membrane and retrieve proliferating periodontal tissue. The left third molar and proliferating periodontal tissue were then transplanted into the bone defect of the right second molar. Radiographically, the transplanted tooth showed no root resorption over a 3-year period. The results indicate that teeth replanted with proliferating periodontal tissue have a favorable long-term prognosis.


[Interobserver agreement in the diagnosis of bladder outlet obstruction in women].
The diagnosis of bladder outlet obstruction (BOO) in women is a challenge for functional urology. In Mexico there are few data that report the prevalence of OTSV in women, being up to 24% in a group of patients. The aim of this study is to compare six different definitions of bladder outlet obstruction and evaluate the interobserver agreement in an educational setting. Urodynamic studies (UDS) of women with and without diagnosis of BOO were retrospectively assesed. Farrar, Chassagne, Lemack, Defreitas, Blavais and Groutz, Solomon-Greenwell definitions were evaluated. All UDS were independently reviewed by 5 observers. The easiest, the hardest and the fastest were chosen. Interobserver agreement to classify the patients as obstructed was assessed by kappa reliability statistical analysis. We classified the type of mistakes the participants made; error of interpretation and miscalculation. A total of 28 urodynamic studies were reviewed. All observers had a substantial agreement (0.64-0.78) to classify BOO using all but Lemack and Solomon-Greenwell definitions. A total 120 errors from 840 responses were found; 45.8% errors of interpretation of UDS and 54.1% miscalculation of the equation. Finally, all the participants chose the Solomon-Greenwell was the most difficult definition. Chassagne, Defreitas and Farrar definitions proved substantial interobserver agreement. Solomon-Greenwell and Lemack´s definitions had the highest number of pitfalls and the lowest level of agreement.


Beetle and plant arrow poisons of the Ju|'hoan and Hai||om San peoples of Namibia (Insecta, Coleoptera, Chrysomelidae; Plantae, Anacardiaceae, Apocynaceae, Burseraceae).
The use of archery to hunt appears relatively late in human history. It is poorly understood but the application of poisons to arrows to increase lethality must have occurred shortly after developing bow hunting methods; these early multi-stage transitions represent cognitive shifts in human evolution. This paper is a synthesis of widely-scattered literature in anthropology, entomology, and chemistry, dealing with San ("Bushmen") arrow poisons. The term San (or Khoisan) covers many indigenous groups using so-called 'click languages' in southern Africa. Beetles are used for arrow poison by at least eight San groups and one non-San group. Fieldwork and interviews with Ju|'hoan and Hai||om hunters in Namibia revealed major differences in the nature and preparation of arrow poisons, bow and arrow construction, and poison antidote. Ju|'hoan hunters use leaf-beetle larvae of Diamphidia Gerstaecker and Polyclada Chevrolat (Chrysomelidae: Galerucinae: Alticini) collected from soil around the host plants Commiphora africana (A. Rich.) Engl. and Commiphora angolensis Engl. (Burseracaeae). In the Nyae Nyae area of Namibia, Ju|'hoan hunters use larvae of Diamphidia nigroornata Ståhl. Larvae and adults live above-ground on the plants and eat leaves, but the San collect the underground cocoons to extract the mature larvae. Larval hemolymph is mixed with saliva and applied to arrows. Hai||om hunters boil the milky plant sap of Adenium bohemianum Schinz (Apocynaceae) to reduce it to a thick paste that is applied to their arrows. The socio-cultural, historical, and ecological contexts of the various San groups may determine differences in the sources and preparation of poisons, bow and arrow technology, hunting behaviors, poison potency, and perhaps antidotes.


Sebaceous carcinoma of the eyelid masquerading as superior limbic keratoconjunctivitis.
A 49-year-old woman had been treated for 18 months for superior limbic keratoconjunctivitis of the right eye. Pathologic examination of a biopsy specimen of the superior perilimbal conjunctiva disclosed intraepithelial carcinoma of sebaceous gland origin. Because of the extensive involvement of the conjunctival epithelium by tumor, a subtotal orbital exenteration was performed. To our knowledge, this is the first report of sebaceous carcinoma masquerading as superior limbic keratoconjunctivitis.


A comprehensive overview of computational protein disorder prediction methods.
Over the past decade there has been a growing acknowledgement that a large proportion of proteins within most proteomes contain disordered regions. Disordered regions are segments of the protein chain which do not adopt a stable structure. Recognition of disordered regions in a protein is of great importance for protein structure prediction, protein structure determination and function annotation as these regions have a close relationship with protein expression and functionality. As a result, a great many protein disorder prediction methods have been developed so far. Here, we present an overview of current protein disorder prediction methods including an analysis of their advantages and shortcomings. In order to help users to select alternative tools under different circumstances, we also evaluate 23 disorder predictors on the benchmark data of the most recent round of the Critical Assessment of protein Structure Prediction (CASP) and assess their accuracy using several complementary measures.


The excretion and degradation of chondroitin 4-sulphate administered to guinea pigs as free chondroitin sulphate and as proteoglycan.
The excretion and degradation was studied of (35)S-labelled 4-chondroitin sulphate injected into guinea pigs in the form of proteoglycan isolated from cartilage and in the form of free chondroitin 4-sulphate prepared from the same proteoglycan by proteolysis. When the proteoglycan was injected there was a delay of about 15-20min before significant amounts or radioactivity were excreted, whereas after injection of chondroitin 4-sulphate a considerable amount of radioactivity was excreted within 10min and a much higher proportion of the radioactive dose was excreted in 1h or 24h compared with the proteoglycan. In both cases, however, a major part of the radioactivity was not excreted even in 24h. Sterile conditions were used to collect the radioactive material directly from the bladder. When chondroitin 4-sulphate was injected, the molecular sizes of injected and excreted materials were similar, as assessed by gel chromatography on Sephadex G-200, whereas when proteoglycan was injected the molecular size of the excreted labelled material was similar to that of the chondroitin 4-sulphate chains in the original proteoglycan. In neither case did the size of the excreted labelled material change with time over 1h, and low-molecular-weight labelled material was virtually absent. In contrast, when urine was collected for 24h without preservative the labelled material in it was extensively degraded after either the proteoglycan or chondroitin 4-sulphate had been given. Chondroitin 4-sulphate became similarly degraded when incubated with non-sterile urine, but not when the urine was passed through a bacterial filter, suggesting that degradation was caused by contaminating micro-organisms in the experiments in which urine was collected for 24 h. It is concluded that chondroitin 4-sulphate chains of about 18000 molecular weight can be excreted readily as such, whereas intact proteoglycans must be degraded to free glycosaminoglycans first, although both are taken up by the tissues more rapidly than they are excreted.


Co-localization of cell surface receptors at high spatial resolution by single-particle fluorescence imaging.
Dual-wavelength single-particle fluorescence imaging has been used to quantify the co-localization of receptors and/or ligands on cells by widefield microscopy. Methods for correction of chromatic aberration and identification of submicroscopic artefacts are presented, with data for the lipopolysaccharide/CD14 and MHC class II/CD74 systems.


Effects of starvation and water quality on the purging process of farmed Murray cod (Maccullochella peelii peelii).
The aim of this study was to determine the effects of starvation and water quality during the purging process on the biometric parameters, fatty acids, and flavor volatiles of Murray cod farmed in a recirculation system. Market size Murray cod, at the end of the grow-out stage, were divided into eight treatments. The treatments were either fed/starved (F or S) and kept in clean water (CW: CWF2, CWS2, CWF4, and CWS4) or fed/starved and kept in recycled water (RW: RWF2, RWS2, RWF4, and RWS4) for either 2 or 4 weeks. Fish were sampled at 0, 2, and 4 week intervals. Food deprivation was responsible for a significant (P < 0.05) weight loss compared to that of fed treatments. The same was observed for the condition factor (K), hepatosomatic index (HSI), and dress-out percentage (DP). No significant changes were, however, observed in the visceral fat index (VFI). Saturated fatty acids (SFA) were highest in RWF4 and lowest in CWS4 (P < 0.05), while monounsaturated fatty acids (MUFA) were lowest in CWF4 (P < 0.05). Starvation did not affect the flavor volatile compounds, which were mainly affected by changes in water quality. Specifically, total aldehyde (% w/w) content was significantly (P < 0.05) affected by water quality, but the time of purging was not responsible for any noteworthy differences. This study was able to separate the effects of starvation and water quality, in the purging process, on the final eating quality of farmed market size Murray cod. It is concluded that because of the inevitable weight loss during starvation, Murray cod should be fed during the purging stage but kept in clean water and deprived of food only for the time necessary to empty the gastro-intestinal tract.


Enhancing learning approaches: practical tips for students and teachers.
In an integrated curriculum such as problem-based learning (PBL), students need to develop a number of learning skills and competencies. These cannot be achieved through memorization of factual knowledge but rather through the development of a wide range of cognitive and noncognitive skills that enhance deep learning. The aim of this article is to provide students and teachers with learning approaches and learning strategies that enhance deep learning. We reviewed current literature in this area, explored current theories of learning, and used our experience with medical students in a number of universities to develop these tips. Incorporating the methods described, we have developed 12 tips and organized them under three themes. These tips are (1) learn how to ask good questions, (2) use analogy, (3) construct mechanisms and concept maps, (4) join a peer-tutoring group, (5) develop critical thinking skills, (6) use self-reflection, (7) use appropriate range of learning resources, (8) ask for feedback, (9) apply knowledge learnt to new problems, (10) practice learning by using simulation, (11) learn by doing and service learning, and (12) learn from patients. Practicing each of these approaches by students and teachers and applying them in day-to-day learning/teaching activities are recommended for optimum performance.


Analysis of latent tuberculosis infection treatment adherence among refugees and other patient groups referred to the Baltimore City Health Department TB clinic, February 2009-March 2011.
We sought to determine the proportion of refugee patients at the Baltimore City Health Department Tuberculosis program (BCHD-TB) successfully completing latent tuberculosis infection (LTBI) treatment, as compared to other referral groups, and to identify factors associated with treatment completion. We completed a retrospective cohort analysis of individuals referred to BCHD-TB program for LTBI care between February 1, 2009 and March 31, 2011. Among 841 patients evaluated by BCHD-TB and diagnosed with LTBI, 81% of refugees, 50% of non-refugee foreign-born, and 35% of US-born patients completed LTBI treatment. In multivariate analysis, refugees had greater odds of LTBI treatment completion (Adjusted Odds Ratio 7.2; 95% CI 4.2-12.4, p < 0.001) compared to US-born individuals adjusting for age, gender, and treatment regimen. Overall, LTBI treatment completion remains suboptimal. At BCHD-TB, LTBI treatment completion was significantly higher among refugees than other referral groups. Additional efforts are needed to optimize LTBI care, and future efforts may need to be tailored for different risk groups.


DNA Genotyping of Suspected Partial Hydatidiform Moles Detects Clinically Significant Aneuploidy.
The diagnosis of partial hydatidiform mole (PM) is especially difficult early in gestation as the morphology of nonmolar abortus (NMA) may mimic PM. Molecular genotyping analysis can definitively identify diandric triploidy, the genetic basis for PM, whereas NMA cases show a biparental inheritance. This 4-year retrospective study sought to determine what proportion of NMA cases which were initially suspected as being PM was aneuploid, and whether this knowledge of aneuploidy status is clinically useful. Cases with atypical villous morphology on histopathology suggestive of PM were subjected to molecular genotyping. The genotyping testing panel contained 19 highly polymorphic short-tandem repeat markers on chromosomes 13, 18, 21, X, and Y and 2 nonpolymorphic markers for sex determination. Informative molecular genotyping analysis was available in 127 cases (56 PMs and 71 NMAs). Aneuploidy was detected in 15/71 of NMAs (21.1%): 7 cases of trisomy 18, 3 of trisomy 13, 1 of trisomy 21, and 4 of monosomy X. It is concluded that most cases of aneuploid NMAs (11/15) detected by molecular genotyping analysis of atypical villous morphology cases are sporadic in type with a low or age-related recurrence risk. Nevertheless, this information may be useful in subsequent counseling and in women undergoing in vitro fertilization by directing preimplantation genetic diagnosis in subsequent cycles. In about a quarter of aneuploid NMAs (4/15) specific aneuploidy types which may be caused by unbalanced familial chromosome rearrangement are identified and are clinically important to patient management. Detection of clinically relevant aneuploidy in NMAs represents an important secondary benefit to the adoption of molecular genotyping analysis in suspected PM.


RPE65 is highly uveitogenic in rats.
To examine the hypothesis that RPE65, a protein specific to the retinal pigment epithelium, is uveitogenic in rats. Rats of four inbred strains (Lewis, Brown Norway, Fischer, and SHR) were immunized with native or recombinant bovine RPE65, or with S-antigen (S-Ag), emulsified with complete Freund adjuvant, and treated simultaneously with killed Bordetella pertussis bacteria, as indicated. Development of ocular changes was examined and scored both clinically and histologically. Lewis rats immunized with RPE65 showed development of acute and severe inflammatory eye disease that affected most ocular tissues. The minimum uveitogenic dose of RPE65 was similar to that of S-Ag (1 microg per rat), but the changes induced by RPE65 at higher dose ranges were less severe than those induced by S-Ag. Concurrent treatment of the RPE65-immunized rats with B. pertussis bacteria was not critical for disease induction, but enhanced dramatically the pathogenic reaction. Unlike the results with several other retinal proteins, no pinealitis was detected in rats immunized with RPE65. Fischer (F344) rats resembled Lewis rats in being similarly affected by RPE65 or S-Ag. In contrast, Brown Norway (BN) rats developed severe disease when immunized with RPE65, but showed minimal changes in response to S-Ag. SHR rats responded poorly to disease induced by RPE65, and S-Ag-induced disease failed to develop. RPE65 is highly uveitogenic in rats, thus suggesting that this molecule could be involved in pathogenic autoimmunity in the human eye.


[Acetylcholinesterase activity in visual cortex structures during early visual deprivation].
By means of quantitative histochemical methods it has been shown that an early photic deprivation (animals kept in a dark chamber for two months after their birth) leads to a decrease in the activity level of acetylcholinesterase (AChE) in the visual area of the cerebral cortex. With the recovery of the visual function (animals kept in normal photic conditions for two weeks) the AChE activity becomes markedly normalized. The obtained data allow to suggest that the decrease in AChE activity due to deprivation is functionally determined.


Molecular basis of sulfolactate synthesis by sulfolactaldehyde dehydrogenase from Rhizobium leguminosarum.
Sulfolactate (SL) is a short-chain organosulfonate that is an important reservoir of sulfur in the biosphere. SL is produced by oxidation of sulfolactaldehyde (SLA), which in turn derives from sulfoglycolysis of the sulfosugar sulfoquinovose, or through oxidation of 2,3-dihydroxypropanesulfonate. Oxidation of SLA is catalyzed by SLA dehydrogenases belonging to the aldehyde dehydrogenase superfamily. We report that SLA dehydrogenase RlGabD from the sulfoglycolytic bacterium Rhizobium leguminsarum SRDI565 can use both NAD+ and NADP+ as cofactor to oxidize SLA, and indicatively operates through a rapid equilibrium ordered mechanism. We report the cryo-EM structure of RlGabD bound to NADH, revealing a tetrameric quaternary structure and supporting proposal of organosulfonate binding residues in the active site, and a catalytic mechanism. Sequence based homology searches identified SLA dehydrogenase homologs in a range of putative sulfoglycolytic gene clusters in bacteria predominantly from the phyla Actinobacteria, Firmicutes, and Proteobacteria. This work provides a structural and biochemical view of SLA dehydrogenases to complement our knowledge of SLA reductases, and provide detailed insights into a critical step in the organosulfur cycle.


Identification of Methylated Transcripts Using the TRIBE Approach.
m6A is the most abundant internal modification on mRNA. Recent improvements of high-throughput sequencing techniques enables its detection at the transcriptome level, even at the nucleotide resolution. However most current techniques require large amounts of starting material to detect the modification. Here, we describe a complementary technique of standard meRIP-seq/miCLIP-seq approaches to identify methylated RNA using a low amount of material. We believe this approach can be applied in vivo to identify methylated targets in specific tissues or subpopulations of cells.


Lifetime exposure to ultraviolet radiation and the risk of multiple sclerosis in the US radiologic technologists cohort study.
Low exposure to ultraviolet radiation (UVR) from sunlight may be a risk factor for developing multiple sclerosis (MS). Possible pathways may be related to effects on immune system function or vitamin D insufficiency, as UVR plays a role in the production of the active form of vitamin D in the body. This study examined whether lower levels of residential UVR exposure from sunlight were associated with increased MS risk in a cohort of radiologic technologists. Participants in the third and fourth surveys of the US Radiologic Technologists (USRT) Cohort Study eligible (N = 39,801) for analysis provided complete residential histories and reported MS diagnoses. MS-specialized neurologists conducted medical record reviews and confirmed 148 cases. Residential locations throughout life were matched to satellite data from NASA's Total Ozone Mapping Spectrometer (TOMS) project to estimate UVR dose. Findings indicate that MS risk increased as average lifetime levels of UVR exposures in winter decreased. The effects were consistent across age groups <40 years. There was little indication that low exposures during summer or at older ages were related to MS risk. Our findings are consistent with the hypothesis that UVR exposure reduces MS risk and may ultimately suggest prevention strategies.


Efficacy of Lactobacillus paracasei sub. paracasei F19 on abdominal symptoms in patients with symptomatic uncomplicated diverticular disease: a pilot study.
The standard therapeutic approach for symptomatic uncomplicated diverticular disease (DD) remains to be defined, and only a few studies have tested the efficacy of probiotics in these patients. Patients with symptomatic uncomplicated DD were randomized to a control arm, i.e., (group A, [N.=16], high-fibre diet alone), or to Group B ([n=18], twice daily 1 sachet of probiotic + high-fibre diet), or group C ([N.=16], twice daily 2 sachets of probiotic + high-fibre diet). The probiotic Genefilus F19© containing Lactobacillus paracasei sub. paracasei F19 was administered for 14 days/month for 6 months. The primary endpoint under consideration was a decrease in abdominal pain and bloating intensity after treatment. Bloating decreased significantly in Groups B and C VAS score group B: 4.6 ± 2.6 vs. 2.3 ± 2.0, P<0.05, group C: 3.9 ± 2.9 vs. 1.8 ± 2.1, P<0.05). The decrease in abdominal pain within 24 hours in these groups did not reach statistical significance. During treatment, none of the group B (N.=4) or group C patients (N=3) with abdominal pain >24 hours reported the recurrence of this symptom, while the 3 group A patients reported at least one episode (P=0.016). No significant difference regarding abdominal pain <24 hours and bloating was observed between the two groups of patients treated with a low or high probiotic dose. Lactobacillus paracasei F19, in association with a high-fibre diet, is effective in reducing abdominal bloating and prolonged abdominal pain in symptomatic uncomplicated diverticular disease, and could thus be a promising option in the treatment of these patients.


Promoting reverse cholesterol transport contributes to the amelioration of atherosclerosis by paeoniflorin.
Reverse cholesterol transport (RCT) offers a practical approach to mitigating atherosclerosis. Paeoniflorin, a monoterpenoid glycoside found in plants of the Paeoniaceae family, has shown various effects on cardiovascular and liver diseases. Nevertheless, its impact on atherosclerosis in vivo remains poorly understood. The objective of this study is to examine the effect of paeoniflorin on atherosclerosis using apolipoprotein E-deficient (ApoE-/-) mice and explore the underlying mechanisms, with a specific focus on its modulation of RCT. ApoE-/- mice were continuously administered paeoniflorin by gavage for three months. We assessed lipid parameters in serum and examined pathological changes and gene expressions related to RCT pathways in the aorta, liver, and intestine. In an in vitro study, we utilized RAW264.7 macrophages to investigate the inhibitory effect of paeoniflorin on foam cell formation and its potential to promote RCT. The results revealed that paeoniflorin reduced atherosclerosis, alleviated hyperlipidemia, and mitigated hepatic steatosis. Paeoniflorin may promote RCT by stimulating cholesterol efflux from macrophages via the liver X receptor alpha pathway, enhancing serum high-density lipoprotein cholesterol and apolipoprotein A-I levels, and regulating key genes in hepatic and intestinal RCT. Additionally, treatment ApoE-/- mice with paeoniflorin suppressed the expression of inflammation-related genes, including CD68, tumor necrosis factor alpha, and monocyte chemoattractant protein-1, and mitigated oxidative stress in both the aorta and liver. Our results indicated that paeoniflorin has the potential to be a more effective and safer treatment for atherosclerosis, thanks to its promotion of RCT and its anti-inflammatory and anti-oxidative effects.


Distorted copper homeostasis with decreased sensitivity to cisplatin upon chaperone Atox1 deletion in Drosophila.
Copper is an integral part of a number of proteins and thus an essential trace metal. However, free copper ions can be highly toxic and every organism has to carefully control its bioavailability. Eukaryotes contain three copper chaperones; Atx1p/Atox1 which delivers copper to ATP7 transporters located in the trans-Golgi network, Cox17 which provides copper to the mitochondrial cytochrome c oxidase, and CCS which is a copper chaperone for superoxide dismutase 1. Here we describe the knockout phenotype of the Drosophila homolog of mammalian Atox1 (ATX1 in yeast). Atox1-/- flies develop normally, though at reduced numbers, and the eclosing flies are fertile. However, the mutants are unable to develop on low-copper food. Furthermore, the intestinal copper importer Ctr1B, which is regulated by copper demand, fails to be induced upon copper starvation in Atox1-/- larvae. At the same time, intestinal metallothionein is upregulated. This phenotype, which resembles the one of the ATP7 mutant, is best explained by intestinal copper accumulation, combined with insufficient delivery to the rest of the body. In addition, compared to controls, Drosophila Atox1 mutants are relatively insensitive to the anticancer drug cisplatin, a compound which is also imported via Ctr1 copper transporters and was recently found to bind mammalian Atox1.


A network module-based method for identifying cancer prognostic signatures.
Discovering robust prognostic gene signatures as biomarkers using genomics data can be challenging. We have developed a simple but efficient method for discovering prognostic biomarkers in cancer gene expression data sets using modules derived from a highly reliable gene functional interaction network. When applied to breast cancer, we discover a novel 31-gene signature associated with patient survival. The signature replicates across 5 independent gene expression studies, and outperforms 48 published gene signatures. When applied to ovarian cancer, the algorithm identifies a 75-gene signature associated with patient survival. A Cytoscape plugin implementation of the signature discovery method is available at http://wiki.reactome.org/index.php/Reactome_FI_Cytoscape_Plugin.


Evaluating the use of paralogous protein domains to increase data availability for missense variant classification.
Classification of rare missense variants remains an ongoing challenge in genomic medicine. Evidence of pathogenicity is often sparse, and decisions about how to weigh different evidence classes may be subjective. We used a Bayesian variant classification framework to investigate the performance of variant co-localisation, missense constraint, and aggregating data across paralogous protein domains ("meta-domains"). We constructed a database of all possible coding single nucleotide variants in the human genome and used PFam predictions to annotate structurally-equivalent positions across protein domains. We counted the number of pathogenic and benign missense variants at these equivalent positions in the ClinVar database, calculated a regional constraint score for each meta-domain, and assessed this approach versus existing missense constraint metrics for classifying variant pathogenicity and benignity. Alternative pathogenic missense variants at the same amino acid position in the same protein provide strong evidence of pathogenicity (positive likelihood ratio, LR+ = 85). Additionally, clinically annotated pathogenic or benign missense variants at equivalent positions in different proteins can provide moderate evidence of pathogenicity (LR+ = 7) or benignity (LR+ = 5), respectively. Applying these approaches sequentially (through PM5) increases sensitivity for classifying pathogenic missense variants from 27 to 41%. Missense constraint can also provide strong evidence of pathogenicity for some variants, but its absence provides no evidence of benignity. We propose using structurally equivalent positions across related protein domains from different genes to augment evidence for variant co-localisation when classifying novel missense variants. Additionally, we advocate adopting a numerical evidence-based approach to integrating diverse data in variant interpretation.


Association study of the dystrobrevin-binding gene with schizophrenia in Australian and Indian samples.
Numerous studies have reported association between variants in the dystrobrevin binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. However, the pattern of results is complex and to date, no specific risk marker or haplotype has been consistently identified. The number of single nucleotide polymorphisms (SNPs) tested in these studies has ranged from 5 to 20. We attempted to replicate previous findings by testing 16 SNPs in samples of 41 Australian pedigrees, 194 Australian cases and 180 controls, and 197 Indian pedigrees. No globally significant evidence for association was observed in any sample, despite power calculations indicating sufficient power to replicate several previous findings. Possible explanations for our results include sample differences in background linkage disequilibrium and/or risk allele effect size, the presence of multiple risk alleles upon different haplotypes, or the presence of a single risk allele upon multiple haplotypes. Some previous associations may also represent false positives. Examination of Caucasian HapMap phase II genotype data spanning the DTNBP1 region indicates upwards of 40 SNPs are required to satisfactorily assess all nonredundant variation within DTNBP1 and its potential regulatory regions for association with schizophrenia. More comprehensive studies in multiple samples will be required to determine whether specific DTNBP1 variants function as risk factors for schizophrenia.


Assessment of an improved stack sample collection system for 3H and 14C.
Lawrence Berkeley National Laboratory developed a simple, efficient, and cost-effective replacement for the traditional glass column system used to monitor H and C emissions from rooftop stacks. The primary goals in developing a replacement (the modified jar system) were to 1) maintain or improve collection efficiency while keeping leakage to less than 5%, 2) simplify the set-up process, and 3) reduce costs. Both the traditional glass column assembly and the modified jar system were operated in tandem for a 13-mo period. Results showed that the modified sample jar system provided equivalent or improved collection efficiency for both H and C. Additional advantages included reduced leak-test errors, quicker and simpler set-up, and material costs that were reduced by nearly an order of magnitude.


Serum YKL-40 levels in acute appendicitis.
Acute appendicitis is one of the most common abdominal emergencies. The clinical diagnosis is often difficult even for experienced surgeons, however, as evidenced by the high rate of negative explorations. A delay in diagnosis of acute appendicitis is associated with increased risk of perforation and further complications. The aim of the present study was to assess the preoperative YKL-40 levels on for a clinical suspicion of acute appendicitis. Between August 2008 and December 2008, a total of 34 patients who underwent appendectomy with a clinical diagnosis of acute appendicitis were studied. Patients underwent appendectomy with the preoperative diagnosis of acute appendicitis. The appendix specimens were classified as normal appendix (group 1; 10 patients), acute appendicitis (group 2; 24 patients). Serum YKL-40 levels were determined by a commercial ELISA. The levels of serum YKL-40 were significantly higher in the group 2 compared with the group 1 (66.4 +/- 13.2 vs 41.6 +/- 11.6 ng/mL, p < 0.001). Receiver operating characteristic curves of YKL-40 levels counts was on a statistically significant level (area under the curve [AUC] = 0.926, p < 0.001). YKL-40 may be a useful marker for diagnosis of acute appendicitis but the number of subjects was limited in this study, future studies are required to confirm the results presented here (Fig. 1, Ref. 13).


Interleukin promoter polymorphisms and prognosis in colorectal cancer.
There is strong evidence that cancer-associated inflammation promotes tumor growth and progression. This is especially true for colorectal cancer (CRC). Interleukins (ILs) are important modulators for inflammation. We examined whether promoter polymorphisms in key IL genes (IL4, IL4R, IL6, IL8 and IL10) are associated with the risk or clinical outcome of CRC. Five single-nucleotide polymorphisms (SNPs) were analyzed in genomic DNA from a cohort including 308 Swedish incident cases of CRC with data on Dukes' stage and up to 16 years of follow-up and 585 healthy controls. The selected SNPs have previously been shown to be functional and/or associated with cancer. None of the analyzed SNPs associated with the risk of CRC. When stratifying by tumor stage, significantly more patients carrying at least one G allele of IL10-1082 had tumors with Dukes' stages A + B than with stages C + D (P(trend) = 0.035 for genotype distribution). Analyzing associations with overall survival time, we found the rare T allele of IL4-590 to be related to a longer survival [CT versus CC Cox proportional hazard ratio 0.69, 95% confidence intervals 0.46-1.03, TT versus CC 0.32 (0.10-1.03)]. For IL6-174, the CG genotype was associated with a longer survival when compared with the CC genotype [0.64 (0.40-1.01)]. The present study was particularly suitable for survival analysis because all patients were sampled before the diagnosis of CRC. Our results suggest that the SNPs IL4-590 and IL6-174 may be useful markers for CRC prognosis. The predicted biological effect of these SNPs in relation to promotion of cancer progression is consistent with the observed increased survival time.


A case of adams-oliver syndrome.
Adams-Oliver syndrome (AOS) is a congenital condition characterized by aplasia cutis congenita, transverse limb defects, and cutis marmorata telangiectatica. AOS can also be associated with extensive lethal anomalies of internal organs, including the central nervous, cardiopulmonary, gastrourointestinal, and genitourinary systems. Generally, the more severe these interrelated anomalies are, the poorer the prognosis becomes. In the relevant literature on this topic, it is somewhat unclear as to whether the prognosis of AOS without lethal anomalies alters the lifespan. We report a case of AOS with typical skin defects only, and no internal organ anomalies.


The CO2 laser in infertility surgery.
The CO2 laser has been receiving increasing publicity recently regarding its use intraabdominally for infertility surgery. The concept of using the CO2 laser for reconstructive pelvic surgery is relatively new and considered controversial by many. A brief review of the biophysics of the CO2 laser, points of laser safety and the action of the CO2 laser beam on tissues enhances a discussion of the different methods of using the CO2 laser intraabdominally for reconstructive pelvic surgery.


[The diagnosis and surgical procedure in penetrating neck wounds].
In 53.6% of people with wounds of the neck there are injuries of the large vessels. Wounds of the neck often involve the trachea, pharynx, esophagus, mediastinum, pleural cavity. Active surgical management, careful revision of the wound canal, use of instrumental methods of examination allow the timely diagnosing of the penetrating character of the wound and performing rational operative interventions preventing fatal complications.


Cloning of herpes simplex virus type 1 sequences representing the whole genome.
Sequences representative of the whole genome of herpes simplex virus type 1 (HSV-1) strain KOS were cloned in the plasmid vector pBR325 in the form of EcoRI-generated DNA fragments. The cloned fragments were identified by digestion of the chimeric plasmid DNA with restriction enzymes EcoRI or EcoRI and BglII followed by comparison of their electrophoretic mobilities in agarose gels with that of similarly digested HSV-1 virion DNA. The cloned fragments showed the same migration patterns as the corresponding fragments from restricted virion DNA, indicating that no major insertions or deletions were present. The presence of HSV-1 sequences in the chimeric plasmids was confirmed by hybridization of plasmid DNA to HSV-1 virion DNA. Additionally, some of the cloned fragments were shown to be biologicaly active in that they efficiently rescued three HSV-1 temperature-sensitive mutants in cotransfection marker rescue experiments.


Identification, capture, and biotelemetry of socially living monkeys.
Remote monitoring of physiologic function using socially living monkeys differs from that using individually housed animals in that access to subjects may be limited. Some logistic aspects of working with socially housed monkeys are reviewed, including identification of individuals and capturing subjects. Methods of remote sampling include hormonal assays of urine and fecal samples, measurement of physical indices as estimates of reproductive status, and the use of telemetry devices to record activity and biopotentials. Key factors in the selection of a telemetry system are discussed. In many cases, remote monitoring may permit assessment of physiologic function without the stress of handling or restraint.


Neuronal cell adhesion genes and antidepressant response in three independent samples.
Drug-effect phenotypes in human lymphoblastoid cell lines recently allowed to identify CHL1 (cell adhesion molecule with homology to L1CAM), GAP43 (growth-associated protein 43) and ITGB3 (integrin beta 3) as new candidates for involvement in the antidepressant effect. CHL1 and ITGB3 code for adhesion molecules, while GAP43 codes for a neuron-specific cytosolic protein expressed in neuronal growth cones; all the three gene products are involved in synaptic plasticity. Sixteen polymorphisms in these genes were genotyped in two samples (n=369 and 90) with diagnosis of major depressive episode who were treated with antidepressants in a naturalistic setting. Phenotypes were response, remission and treatment-resistant depression. Logistic regression including appropriate covariates was performed. Genes associated with outcomes were investigated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) genome-wide study (n=1861) as both individual genes and through a pathway analysis (Reactome and String databases). Gene-based analysis suggested CHL1 rs4003413, GAP43 rs283393 and rs9860828, ITGB3 rs3809865 as the top candidates due to their replication across the largest original sample and the STAR*D cohort. GAP43 molecular pathway was associated with both response and remission in the STAR*D, with ELAVL4 representing the gene with the highest percentage of single nucleotide polymorphisms (SNPs) associated with outcomes. Other promising genes emerging from the pathway analysis were ITGB1 and NRP1. The present study was the first to analyze cell adhesion genes and their molecular pathways in antidepressant response. Genes and biomarkers involved in neuronal adhesion should be considered by further studies aimed to identify predictors of antidepressant response.


Effectiveness of complete versus partial androgen withdrawal therapy for the treatment of prostatic cancer as studied in the Dunning R-3327 system of rat prostatic adenocarcinomas.
Standard initial therapy for metastatic prostatic cancer involves surgical or chemically induced castration. Castration lowers the serum testosterone level by over 90% but does not completely eliminate all potential serum androgens (i.e., it induces a partial androgen withdrawal). This has led some investigators to suggest that a more complete form of androgen withdrawal in which the very low levels of serum androgens remaining after castration are neutralized by the simultaneous treatment with a direct acting antiandrogen (i.e., complete androgen withdrawal) might be more effective than simply castration alone. To determine whether complete androgen withdrawal is any more effective than partial androgen withdrawal therapy, the slow growing, well differentiated H and the fast growing, poorly differentiated G sublines of the serially transplantable Dunning R-3327 system of rat prostatic adenocarcinomas were used as a test system since both of these cancers are androgen responsive. These studies demonstrated that: (a) complete androgen withdrawal consisting of surgical castration in combination with daily treatment with the potent antiandrogen, cyproterone acetate, was no more effective in terms of tumor growth retardation or overall host survival than was partial androgen withdrawal induced by castration alone; (b) serum testosterone levels must be maintained below 0.5 ng/ml but do not have to be completely eliminated to produce the maximum therapeutic response; and (c) prostatic cancers are more sensitive than is the normal prostate to growth stimulation by serum testosterone.


Systematic review of the effectiveness of continuing dental professional development on learning, behavior, or patient outcomes.
This study is based on a systematic review of studies using a randomized controlled trial or quasi-experimental design in order to synthesize existing evidence evaluating the effectiveness of continuing professional development (CPD) interventions in dentistry on learning gains, behavior change, or patient outcomes. The authors searched a range of electronic databases from 1986 to the present and screened all potentially relevant studies for inclusion, using pre-established inclusion/exclusion criteria. Following data extraction and quality appraisal of all included studies, a narrative synthesis of the studies was undertaken. Ten studies (in fourteen articles) were included. All were evaluation studies of CPD interventions targeted exclusively at dentists. The ten included studies evaluated a range of interventions: courses/workshops, written information, CAL, audit/self-reflection, face-to-face support, and black box combinations of these interventions. Two high- and moderately high-quality studies evaluated CAL CPD for dentists and found equivocal impact of CAL for dentists. A black box combination of interventions was rigorously evaluated and showed moderate impact on patient care. This finding suggests that multimethod and multiphased CPD has potential for the greatest impact. There is a need for more high-quality randomized controlled trials evaluating CPD interventions in dentistry. It is important that future evaluations of CPD interventions clarify the nature of the interventions such that they are explicit and replicable and that appropriate outcomes are selected (health of patients and change in practice or behavior as well as knowledge and understanding) in order to move the evidence base of effective practice forward in this area of dental education.


Narrative Review of New Methods for Assessing Food and Energy Intake.
Dietary self-report instruments are essential to nutritional analysis in dietetics practice and their use in research settings has facilitated numerous important discoveries related to nutrition, health and chronic diseases. An important example is obesity, for which measuring changes in energy intake is critical for assessing efficacy of dietary interventions. However, current methods, including counting calories, estimating portion size and using food labels to estimate human energy intake have considerable constraints; consequently, research on new methodologies/technologies has been encouraged to mitigate the present weaknesses. The use of technologies has prompted innovation in dietary analysis. In this review, the strengths and limitations of new approaches have been analyzed based on ease of use, practical limitations, and statistical evaluation of reliability and validity. Their utility is discussed through the lens of the 4Ms of Obesity Assessment and Management, which has been used to evaluate root causes of obesity and help select treatment options.


Assessing the impact of transplant site on ovarian tissue transplantation: a single-arm meta-analysis.
Survival rates of young women undergoing cancer treatment have substantially improved, with a focus on post-treatment quality of life. Ovarian tissue transplantation (OTT) is a viable option to preserve fertility; however, there is no consensus on the optimal transplantation site. Most studies on OTT are nonrandomized controlled trials with limited sample sizes and uncontrolled statistical analyses, leaving the question of which transplant site yields the highest chance of achieving a live birth unanswered. This meta-analysis aimed to assess the effect of different ovarian transplant sites on postoperative reproductive outcomes. We adhered to the PRISMA Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Systematic searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library from inception to September 17, 2023. The inclusion criteria were as follows: (1) women who underwent OTT with a desire for future childbirth, and (2) reports of specific transplant sites and corresponding pregnancy outcomes. The exclusion criteria included the inability to isolate or extract relevant outcome data, case reports, non-original or duplicate data, and articles not written in English. Twelve studies (201 women) were included in the meta-analysis of cumulative live birth rates (CLBR) after OTT. The CLBR, which encompasses both spontaneous pregnancies and those achieved through assisted reproductive technology (ART) following OTT to the ovarian site, was 21% (95% CI: 6-40, I2: 52.81%, random effect). For transplantation to the pelvic site, the live birth rate was 30% (95% CI: 20-40, I2: 0.00%, fixed effect). Combining transplantation to both the pelvic and ovarian sites resulted in a live birth rate of 23% (95% CI: 11-36, I2: 0.00%, fixed effect). Notably, heterotopic OTT yielded a live birth rate of 3% (95% CI: 0-17, I2: 0.00%, fixed effect). Pregnancy outcomes were not significantly different after orthotopic ovarian transplantation, and pregnancy and live birth rates after orthotopic OTT were significantly higher than those after ectopic transplantation. INPLASY202390008.


The Role of Glycation on the Aggregation Properties of IAPP.
Epidemiological evidence shows an increased risk for developing Alzheimer's disease in people affected by diabetes, a pathology associated with increased hyperglycemia. A potential factor that could explain this link could be the role that sugars may play in both diseases under the form of glycation. Contrary to glycosylation, glycation is an enzyme-free reaction that leads to formation of toxic advanced glycation end-products (AGEs). In diabetes, the islet amyloid polypeptide (IAPP or amylin) is found to be heavily glycated and to form toxic amyloid-like aggregates, similar to those observed for the Aβ peptides, often also heavily glycated, observed in Alzheimer patients. Here, we studied the effects of glycation on the structure and aggregation properties of IAPP with several biophysical techniques ranging from fluorescence to circular dichroism, mass spectrometry and atomic force microscopy. We demonstrate that glycation occurs exclusively on the N-terminal lysine leaving the only arginine (Arg11) unmodified. At variance with recent studies, we show that the dynamical interplay between glycation and aggregation affects the structure of the peptide, slows down the aggregation process and influences the aggregate morphology.


Glycemia and cardiovascular risk: challenging evidence based medicine.
Optimal glycemic control is well known to reduce effectively the risk of micro vascular complications both in type 1 and type 2 diabetes mellitus. However the role of glycemic control in decreasing the risk of myocardial infarction and ischemic stroke, the leading causes of death in patients with diabetes, has been so far controversial. In this review, based on data recently reported from large interventional studies, we discuss the possible causal relationship between glycemia and cardiovascular outcomes in type 1 and type 2 diabetes. Strict glycemic control right from the diagnosis of the disease may be effective in reducing long term incidence of cardiovascular (CV) disease in both T1 and T2 diabetics. Nevertheless such a strategy could be potentially harmful for T2 diabetics with long duration of sub optimal glycemic control and already established CV complications. Treatment targets in these patients should be individualized taking into account other aspects of glycemic control and diabetes complications such as hypoglycemia and autonomic neuropathy.


De novo discovery of metabolic heterogeneity with immunophenotype-guided imaging mass spectrometry.
Imaging mass spectrometry enables in situ label-free detection of thousands of metabolites from intact tissue samples. However, automated steps for multi-omics analyses and interpretation of histological images have not yet been implemented in mass spectrometry data analysis workflows. The characterization of molecular properties within cellular and histological features is done via time-consuming, non-objective, and irreproducible definitions of regions of interest, which are often accompanied by a loss of spatial resolution due to mass spectra averaging. We developed a new imaging pipeline called Spatial Correlation Image Analysis (SPACiAL), which is a computational multimodal workflow designed to combine molecular imaging data with multiplex immunohistochemistry (IHC). SPACiAL allows comprehensive and spatially resolved in situ correlation analyses on a cellular resolution. To demonstrate the method, matrix-assisted laser desorption-ionization (MALDI) Fourier-transform ion cyclotron resonance (FTICR) imaging mass spectrometry of metabolites and multiplex IHC staining were performed on the very same tissue section of mouse pancreatic islets and on human gastric cancer tissue specimens. The SPACiAL pipeline was used to perform an automatic, semantic-based, functional tissue annotation of histological and cellular features to identify metabolic profiles. Spatial correlation networks were generated to analyze metabolic heterogeneity associated with cellular features. To demonstrate the new method, the SPACiAL pipeline was used to identify metabolic signatures of alpha and beta cells within islets of Langerhans, which are cell types that are not distinguishable via morphology alone. The semantic-based, functional tissue annotation allows an unprecedented analysis of metabolic heterogeneity via the generation of spatial correlation networks. Additionally, we demonstrated intra- and intertumoral metabolic heterogeneity within HER2/neu-positive and -negative gastric tumor cells. We developed the SPACiAL workflow to provide IHC-guided in situ metabolomics on intact tissue sections. Diminishing the workload by automated recognition of histological and functional features, the pipeline allows comprehensive analyses of metabolic heterogeneity. The multimodality of immunohistochemical staining and extensive molecular information from imaging mass spectrometry has the advantage of increasing both the efficiency and precision for spatially resolved analyses of specific cell types. The SPACiAL method is a stepping stone for the objective analysis of high-throughput, multi-omics data from clinical research and practice that is required for diagnostics, biomarker discovery, or therapy response prediction.


Shaddock peels (Citrus maxima) phenolic extracts inhibit α-amylase, α-glucosidase and angiotensin I-converting enzyme activities: a nutraceutical approach to diabetes management.
In this study, the interactions of free and bound phenolic-rich extracts from shaddock peels (popular in folklore for the management of diabetes and hypertension) with α-amylase and α-glucosidase (key enzymes linked to type-2 diabetes) and angiotensin I-converting enzyme (ACE) (key enzyme linked to hypertension) were assessed. The free phenolics of shaddock (Citrus maxima) peels were extracted with 80% acetone, while the bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate; and their interaction with the enzymes were assessed. The phenolic extracts inhibited α-amylase, α-glucosidase and ACE enzyme activities in a dose-dependent manner; however, bound phenolics had significantly higher (P<0.05) α-amylase inhibitory activities, than free phenolics, which had significantly higher (P<0.05) ACE inhibitory activities. There was no significant difference (P>0.05) in their α-glucosidase inhibitory activities. The stronger inhibition of α-glucosidase when compared to α-amylase is of great pharmaceutical importance. The phenolic inhibited sodium nitroprusside induced lipid peroxidation in pancreas in a dose dependent manner. Therefore, free and bound phenolic extracts from shaddock peels could be used as nutraceutical for the management of hypertension and type-2 diabetes.


Motivations for and barriers to engaging in continuing veterinary medical education.
To identify reasons for engagement in continuing veterinary medical education (CVME) activities, obstacles to participation, ways to provide more effective programs, and ideas to improve participation in CVME. Focus group interviews. Selected practicing veterinarians from a state that did mandate continuing education for relicensure. 12 focus group interviews were held throughout the state of California between May and September 1998. Practitioners were asked to respond to questions about where they obtain information to improve their practice, what value they see in CVME, what motivates them to participate, what obstacles to CVME participation exist, and ways CVME providers and practitioners could overcome those obstacles. 84 practitioners participated in the focus group interviews. In addition to the educational value of CVME, participation was used to rejuvenate practice life and prevent feelings of isolation. Continuing education activities ranged from problem-oriented chats with colleagues to formal educational programs. Timing of events, distance, money, solo practice, stage of career, and family demands were identified as barriers to participation. Designing and marketing CVME with specific learning objectives and for specific career stages and using new educational delivery technologies were suggested to overcome some of these barriers. If CVME is to improve practice and patient care, it should be integrated into a practice's strategic planning and considered a legitimate business expense. Decisions about CVME participation are made easier if program objectives are clearly outlined.


Role of superoxide anions in changes of endothelial vasoactive response during acute hyperglycemia.
The effects of acute hyperglycemia on endothelial Ca2+ signaling, formation of endothelium-derived relaxing factor (EDRF) and bioactivity of EDRF were investigated. Hyperglycemia increased 2,5-tert-butyl-1,4-hydrochinone (BHQ)-initiated Ca2+ signaling and EDRF formation in a concentration-dependent manner. The effect of elevated D-glucose on Ca2+/EDRF response could be diminished by co-incubation with the antioxidants vitamin E, probucol, GSH, vitamin C and superoxide dismutase. Convincingly, hyperglycemic conditions yielded an increase in superoxide anion release from endothelial cells and the superoxide anion-generating mixture xanthine oxidase/hypoxanthine mimicked the effect of hyperglycemia on Ca2+/EDRF signaling. Besides an enhanced formation of the vasodilatatory NO compound EDRF, hyperglycemia enhanced NO degradation by endothelial cells and, thus, reduced bioactivity of EDRF. We suggest that vasoactivity during acute hyperglycemia depends on the superoxide anion scavenging properties of the vascular wall. In acute hyperglycemia and early stages of diabetes, radical scavenging capacity may be suitable to protect NO degradation, resulting in an enhanced vasodilation. In contrast, decreased free radical scavenging properties of the vasculature in prolonged hyperglycemia and in later stages of diabetes might promote NO degradation by an overshoot of superoxide anions, resulting in an attenuation of endothelium-dependent vasodilation.


Nebivolol: a third-generation beta-blocker that augments vascular nitric oxide release: endothelial beta(2)-adrenergic receptor-mediated nitric oxide production.
Nebivolol is a beta(1)-selective adrenergic receptor antagonist with proposed nitric oxide (NO)-mediated vasodilating properties in humans. In this study, we explored whether nebivolol indeed induces NO production and, if so, by what mechanism. We hypothesized that not nebivolol itself but rather its metabolites augment NO production. Mouse thoracic aorta segments were bathed in an organ chamber. Administration of nebivolol did not affect NO production. When nebivolol was allowed to metabolize in vivo in mice, addition of plasma of these mice caused a sustained 2-fold increase in NO release. Interestingly, coadministration of a selective beta(2)-adrenergic receptor antagonist (butoxamine) prevented the response. Immunohistochemistry and Western blot analysis demonstrated the presence of beta(2)- but not beta(1)-adrenergic receptors on endothelial cells. In the absence of calcium, metabolized nebivolol failed to increase NO production, suggesting a role for calcium-dependent NO synthase. With digital fluorescence imaging, a rapid and sustained rise in endothelial cytosolic free Ca(2+) concentration was observed after administration of metabolized nebivolol, which also was abrogated by butoxamine pretreatment. In vivo metabolized nebivolol increases vascular NO production. This phenomenon involves endothelial beta(2)-adrenergic receptor ligation, with a subsequent rise in endothelial free [Ca(2+)](i) and endothelial NO synthase-dependent NO production. This may be an important mechanism underlying the nebivolol-induced, NO-mediated arterial dilation in humans.


Molecular biology of human serum cholinesterase.
More than 90% of the amino acid sequence of purified human serum cholinesterase has been determined in our laboratory. Purified enzyme was digested with several proteolytic enzymes; the resulting polypeptides were then separated, purified, and sequenced. Optimal sequence regions were identified and used as the basis for the synthesis of three 17-mer oligonucleotide probes. In addition, one long peptide of 58 amino acid residues was selected for construction of two unique sequence oligonucleotide probes of 39-mer and 53-mer; the peptide regions corresponding to the latter are six amino acids apart. The probes have been used to screen a human liver cDNA library and a human genomic library. Several positive clones to both types of probes have been identified. These are being characterized, and some of them have been or are now being sequenced. A high degree of homology in the amino acid sequence of the active center of human serum cholinesterase and that of acetylcholinesterase from the Torpedo fish has been noted. It appears that this region of cholinesterases has been conserved during evolution, and there may be an important, still unrecognized role for serum nonspecific cholinesterase in mammalian metabolism.


Exosomal linc-FAM138B from cancer cells alleviates hepatocellular carcinoma progression via regulating miR-765.
Exosomes are small vesicles with a diameter of 30-150 nm secreted by cells, which can be used as signal carriers to transfer nucleic acids, proteins, lipids and other functional substances to the recipient cells and play a role in cell communication. Hepatocellular carcinoma is the fourth most common cause of cancer-related death worldwide. Studies have shown that long non-coding RNAs (lncRNAs) are involved in the development and progression of many types of tumors. Our present study found that linc-FAM138B was reduced in HCC tissues and cell lines, low expression of linc-FAM138B indicated a poor prognosis in HCC patients. Interestingly, linc-FAM138B could be packaged into cancer cells. And exo-FAM138B inhibited the proliferation, migration and invasion of HCC cells. Furthermore, linc-FAM138B sponged miR-765 levels. And exo-si-FAM138B promoted HCC progression, while deletion of miR-765 reversed the role of exo-si-FAM138B. In vivo tumorigenesis experiments showed that exo-FAM138B suppressed HCC growth via modulating miR-765. In conclusion, exo-linc-FAM138B secreted by cancer cells inhibited HCC development via targeting miR-765, which provided a new idea and perspective for in-depth understanding of the complex signal regulation in HCC process.


Knee and hip agonist-antagonist relationship in male under-19 soccer players.
The purpose of this study was to evaluate the strength of the knee flexors and extensors and hip abductor and adductor muscles in young soccer players. Twenty-three male under-19 soccer players participated in this study (age: 17.7 ± 0.2 years; height: 173.0 ± 1.1 cm; body mass: 66.1 ± 1.3 kg). Body composition was measured using a bioelectrical impedance (InBody770), and the dynamometry was performed by an isokinetic dynamometer (Biodex System 3) for knee flexion and extension, and by an isometric dynamometer (Smart Groin Trainer), for hip adduction and abduction. Comparisons were made between dominant members (D) vs. non-dominant members (ND) and adductors vs. abductors (ADD:ABD) using the Wilcoxon test. There were statistically significant differences in the peak torques between the dominant and non-dominant members in the flexion function (Z = -4.198, p < 0.01) and in the extension function (Z = -4.197, p < 0.01) of the knee in concentric muscular action, and the flexion (Z = -4.198, p < 0.01) and in the extension (Z = -4.198, p < 0.01) of the knee in eccentric muscular action. No statistically significant differences were obtained in the conventional ratio (Z = -0.456, p = 0.648) nor the functional ratio (Z = -0.335, p = 0.738) between D and ND members. There were no statistically significant differences between adductors and abductors at the moment of strength for absolute values (N). The reference absolute and normalized to the weight values and the ADD:ABD can be used as a guideline for classifying players in screening and comparison in return tests to sports practice after an injury.


Integrated Multiorgan Bedside Ultrasound for the Diagnosis and Management of Sepsis and Septic Shock.
Despite decades of research, the mortality rate of sepsis and septic shock remains unacceptably high. Delays in diagnosis, identification of an infectious source, and the challenge of providing patient-tailored resuscitation measures routinely result in suboptimal patient outcomes. Bedside ultrasound improves a clinician's ability to both diagnose and manage the patient with sepsis. Indeed, multiple point-of-care ultrasound (POCUS) protocols have been developed to evaluate and treat various subsets of critically ill patients. These protocols mostly target patients with undifferentiated shock and have been shown to improve clinical outcomes. Other studies have shown that POCUS can improve a clinician's ability to identify a source of infection. Once a diagnosis of septic shock has been made, serial POCUS exams can be used to continuously guide resuscitative efforts. In this review, we advocate that the patient with suspected sepsis or septic shock undergo a comprehensive POCUS exam in which sonographic information across organ systems is synthesized and used in conjunction with traditional data gleaned from the patient's history, physical exam, and laboratory studies. This harmonization of information will hasten an accurate diagnosis and assist with hemodynamic management.


A theoretical study on the reaction pathways and the mechanism of 1,3- dipolar cycloaddition of vinyl acetylene and methyl azide.
1,3-dipolar cycloaddition procedure is one of the most widely practiced methods in order to synthesize heterocyclic compounds. Although, it seems very simple, but, there are numerous precursors of heterocyclic molecules who have more than one positions to react with a 1,3-dipole species. As a result, while using a precursor with more than one position for reaction, it is probable to synthesize several products with different structures. This paper studies all possible interactions of vinyl acetylene, which has two positions for reaction, with methyl azide. This reaction could lead to the emergence of any 1,3-dipolar cycloaddition products. Our ultimate goal is to help researchers to find out how precursors containing both carbon-carbon double, and the triple bonds interact with 1,3- dipolar species. The present study used the DFT calculations at B3LYP/6-311++G(3df,pd) level to check all probable interactions between vinyl acetylene and methyl azide, and determined Potential Energy Surface, and optimized all species.


Impact of spatial clustering on disease transmission and optimal control.
Spatial heterogeneities and spatial separation of hosts are often seen as key factors when developing accurate predictive models of the spread of pathogens. The question we address in this paper is how coarse the resolution of the spatial data can be for a model to be a useful tool for informing control policies. We examine this problem using the specific case of foot-and-mouth disease spreading between farms using the formulation developed during the 2001 epidemic in the United Kingdom. We show that, if our model is carefully parameterized to match epidemic behavior, then using aggregate county-scale data from the United States is sufficient to closely determine optimal control measures (specifically ring culling). This result also holds when the approach is extended to theoretical distributions of farms where the spatial clustering can be manipulated to extremes. We have therefore shown that, although spatial structure can be critically important in allowing us to predict the emergent population-scale behavior from a knowledge of the individual-level dynamics, for this specific applied question, such structure is mostly subsumed in the parameterization allowing us to make policy predictions in the absence of high-quality spatial information. We believe that this approach will be of considerable benefit across a range of disciplines where data are only available at intermediate spatial scales.


Hydrolysis of prostaglandin glycerol esters by the endocannabinoid-hydrolyzing enzymes, monoacylglycerol lipase and fatty acid amide hydrolase.
Cyclooxygenase-2 (COX-2) can oxygenate the endocannabinoids, arachidonyl ethanolamide (AEA) and 2-arachidonylglycerol (2-AG), to prostaglandin-H2-ethanolamide (PGH2-EA) and -glycerol ester (PGH2-G), respectively. Further metabolism of PGH2-EA and PGH2-G by prostaglandin synthases produces a variety of prostaglandin-EA's and prostaglandin-G's nearly as diverse as those derived from arachidonic acid. Thus, COX-2 may regulate endocannabinoid levels in neurons during retrograde signaling or produce novel endocannabinoid metabolites for receptor activation. Endocannabinoid-metabolizing enzymes are important regulators of their action, so we tested whether PG-G levels may be regulated by monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH). We found that PG-Gs are poor substrates for purified MGL and FAAH compared to 2-AG and/or AEA. Determination of substrate specificity demonstrates a 30-100- and 150-200-fold preference of MGL and FAAH for 2-AG over PG-Gs, respectively. The substrate specificity of AEA compared to those of PG-Gs was approximately 200-300 fold higher for FAAH. Thus, PG-Gs are poor substrates for the major endocannabinoid-degrading enzymes, MGL and FAAH.


Risk factors for bronchial hyperresponsiveness in workers exposed to acid anhydrides.
Risk factors for bronchial hyperresponsiveness have previously been established in the general community. In settings where occupational asthma is a risk, it has not been established whether occupational sensitization or measures of exposure are important. Bronchial responsiveness to histamine was measured in a cohort of 506 workers exposed to acid anhydrides. Skin-prick tests were performed with conjugates of phthalic, maleic and trimellitic anhydride with human serum albumin and with common inhalant allergens. Employment and smoking histories were recorded. Occupational exposure was measured using personal air samplers and estimates of past exposure made by retrospective exposure assessment. Three hundred and seventy workers (73%) had bronchial responsiveness measured (median age 39 yrs, range 18-77) and 46 (12%) of these were hyperresponsive (provocative dose causing a 20% fall in forced expiratory volume in one second (FEV1; PD20) < or = 8 micromol). Twelve (3%) of these responsive workers had a skin-prick test reaction to an acid anhydride conjugate, 124 (34%) to a common inhalant allergen, and 148 (40%) were current smokers. Multivariate analysis showed that occupational sensitization, sensitization to a common inhalant allergen, age, and pack-years of smoking were independent risk factors for bronchial hyperresponsiveness. Of these only occupational sensitization was completely independent of baseline FEV1. It is concluded that sensitization to acid anhydrides is a significant risk factor for bronchial hyperresponsiveness. However, measures of personal acid anhydride exposure were not associated with bronchial hyperresponsiveness.


Hormonal approach to breast cancer prevention.
Breast cancer is more frequent in nulliparous women, while its incidence is significantly reduced by full-term pregnancy. The fact that the protection conferred by pregnancy is observed in women from different countries and ethnic groups, regardless of the endogenous incidence of this malignancy, indicates that this protection does not result from extrinsic factors specific to a particular environmental, genetic, or socioeconomic setting, but rather from an intrinsic effect of parity on the biology of the breast. Using an experimental system we have shown that treatment of young virgin rats with human chorionic gonadotropin (hCG), like full-term pregnancy, efficiently inhibits the initiation and progression of chemically induced mammary carcinomas. Treatment of young virgin rats with hCG induced a profuse lobular development of the mammary gland, reduced the proliferative activity of the mammary epithelium, and induced the synthesis of inhibin, a secreted protein with tumor-suppressor activity. HCG treatment also increased the expression of the programmed cell death (PCD) genes testosterone repressed prostate message 2 (TRPM2), interleukin 1-beta-converting enzyme (ICE), p53, c-myc, and bcl-XS, induced apoptosis, and downregulated cyclins. PCD genes were activated through a p53-dependent process, modulated by c-myc, and with partial dependence on the bcl-2 family-related genes. The possibility that this hormonal treatment activates known or new genes was tested by differential display technique. We have identified a series of new genes, hormone-induced-1 (HI-1) among them. The characterization of their functional role will contribute to clarify the mechanisms through which hCG inhibits the initiation and progression of mammary cancer. Of great significance was the observation that PCD genes remained activated even after lobular formations had regressed due to the cessation of hormone administration. We postulate that this mechanism plays a major role in the long-lasting protection exerted by hCG from chemically induced carcinogenesis, and might be also involved in the lifetime reduction in breast cancer risk induced in women by full-term pregnancy. The implications of these observations are two-fold: on one hand, they indicate that hCG, as pregnancy, may induce early genomic changes that control the progression of the differentiation pathway, and on the other, that these changes are permanently imprinted in the genome, regulating the long-lasting refractoriness to carcinogenesis. The permanence of these changes, in turn, makes them ideal surrogate markers of hCG effect in the evaluation of this hormone as a breast cancer preventive agent.


Development of one novel multiple-target plasmid for duplex quantitative PCR analysis of roundup ready soybean.
To enforce the labeling regulations of genetically modified organisms (GMOs), the application of reference molecules as calibrators is becoming essential for practical quantification of GMOs. However, the reported reference molecules with tandem marker multiple targets have been proved not suitable for duplex PCR analysis. In this study, we developed one unique plasmid molecule based on one pMD-18T vector with three exogenous target DNA fragments of Roundup Ready soybean GTS 40-3-2 (RRS), that is, CaMV35S, NOS, and RRS event fragments, plus one fragment of soybean endogenous Lectin gene. This Lectin gene fragment was separated from the three exogenous target DNA fragments of RRS by inserting one 2.6 kb DNA fragment with no relatedness to RRS detection targets in this resultant plasmid. Then, we proved that this design allows the quantification of RRS using the three duplex real-time PCR assays targeting CaMV35S, NOS, and RRS events employing this reference molecule as the calibrator. In these duplex PCR assays, the limits of detection (LOD) and quantification (LOQ) were 10 and 50 copies, respectively. For the quantitative analysis of practical RRS samples, the results of accuracy and precision were similar to those of simplex PCR assays, for instance, the quantitative results were at the 1% level, the mean bias of the simplex and duplex PCR were 4.0% and 4.6%, respectively, and the statistic analysis ( t-test) showed that the quantitative data from duplex and simplex PCR had no significant discrepancy for each soybean sample. Obviously, duplex PCR analysis has the advantages of saving the costs of PCR reaction and reducing the experimental errors in simplex PCR testing. The strategy reported in the present study will be helpful for the development of new reference molecules suitable for duplex PCR quantitative assays of GMOs.


Nanothorn electrodes for ionic polymer-metal composite artificial muscles.
Ionic polymer-metal composites (IPMCs) have recently received tremendous interest as soft biomimetic actuators and sensors in various bioengineering and human affinity applications, such as artificial muscles and actuators, aquatic propulsors, robotic end-effectors, and active catheters. Main challenges in developing biomimetic actuators are the attainment of high strain and actuation force at low operating voltage. Here we first report a nanostructured electrode surface design for IPMC comprising platinum nanothorn assemblies with multiple sharp tips. The newly developed actuator with the nanostructured electrodes shows a new way to achieve highly enhanced electromechanical performance over existing flat-surfaced electrodes. We demonstrate that the formation and growth of the nanothorn assemblies at the electrode interface lead to a dramatic improvement (3- to 5-fold increase) in both actuation range and blocking force at low driving voltage (1-3 V). These advances are related to the highly capacitive properties of nanothorn assemblies, increasing significantly the charge transport during the actuation process.


Frequency-doubling technology perimetry and multifocal visual evoked potential in glaucoma, suspected glaucoma, and control patients.
The gold standard in functional glaucoma evaluation is standard automated perimetry (SAP). However, SAP depends on the reliability of the patients' responses and other external factors; therefore, other technologies have been developed for earlier detection of visual field changes in glaucoma patients. The frequency-doubling perimetry (FDT) is believed to detect glaucoma earlier than SAP. The multifocal visual evoked potential (mfVEP) is an objective test for functional evaluation. To evaluate the sensitivity and specificity of FDT and mfVEP tests in normal, suspect, and glaucomatous eyes and compare the monocular and interocular mfVEP. Ninety-five eyes from 95 individuals (23 controls, 33 glaucoma suspects, 39 glaucomatous) were enrolled. All participants underwent a full ophthalmic examination, followed by SAP, FDT, and mfVEP tests. The area under the curve for mean deviation and pattern standard deviation were 0.756 and 0.761, respectively, for FDT, 0.564 and 0.512 for signal and alpha for interocular mfVEP, and 0.568 and 0.538 for signal and alpha for monocular mfVEP. This difference between monocular and interocular mfVEP was not significant. The FDT Matrix was superior to mfVEP in glaucoma detection. The difference between monocular and interocular mfVEP in the diagnosis of glaucoma was not significant.


Exuberated numbers of tumor-specific T cells result in tumor escape.
Cytotoxic T cells (CTL) play a major role in tumor rejection. Expansion of CTLs, either by immunization or adoptive transfer, is a prominent goal in current immunotherapy. The antigen-specific nature of these expansion processes inevitably initiates a clonotypic attack on the tumor. By injecting an Ovalbumin-expressing melanoma into OT-I mice, in which >90% of CTLs recognize an Ovalbumin peptide, we show that an increased number of tumor-specific CTLs causes emergence of escape variants. We show that these escape variants are a result of antigen silencing via a yet undetermined epigenetic mechanism, which occurs frequently and is spontaneously reversible. We further show that an increase in the time of tumor onset in OT-I compared with C57BL/6J is a result of immune selection.


Production performance, haematological parameters, serum biochemistry, and expression of HSP-70 in broiler chickens fed dietary ascorbic acid during heat stress.
An experiment was carried out to assess the efficacy of supplemental ascorbic acid (AA) on broiler chicken production performance, blood haematological profile, biochemical profile, and carcass traits under heat stress conditions. A total of 192-day-old broiler chicks were divided into four groups, each with six replicates of eight each (4 × 6 × 8). Four corn-based dietary treatments were formulated: T1 (control diet), T2 (T1 + AA at 200 mg/kg), T3 (T1 + AA at 400 mg/kg), and T4 (T1 + AA at 600 mg/kg) for a period of 42 days. Despite the high temperature and humidity, the 600 mg AA supplemental groups (T4) gained significantly (P ≤ 0.05) more body weight and had a higher feed intake and better feed conversion ratio (FCR) than the control group (T1). After 28 days of feeding the three AA-supplemented diets, antibody titres (humoral immune response) were significantly higher (P ≤ 0.05). The response to intradermally injected phyto-haemagglutinin (PHA-P), an index of the in vivo cell-mediated immune response, was found to be increased (P ≤ 0.05) in the 400 and 600 mg AA-supplemented groups after 35 days. Higher levels of AA (T4) supplementation significantly (P ≤ 0.05) improved haematological values such as haemoglobin (Hb), total erythrocyte count (TEC), total leukocyte count (TLC), and differential leukocyte count (DLC), heterophil:lymphocyte (H:L) in comparison to the control group (T1). The supplemented group improved the serum biochemical profile of the birds, with an increase (P ≤ 0.05) in total serum protein, albumin, and globulin and a decrease in serum cholesterol and corticosterone levels in the T4 group compared to the control group. Heat shock protein-70 (HSP-70) was gradually elevated after increasing the ascorbic acid concentration (P ≤ 0.05) at 14 and 21 days. As a result, it can be concluded that supplementing ascorbic acid at 600 mg/kg is beneficial for improving the performance, immunity, and blood haematological biochemical profile and upregulating the HSP-70 gene of broiler chickens under heat stress conditions.


Differential stability of Drosophila embryonic mRNAs during subsequent larval development.
The relative stabilities of specific embryonic mRNAs that persist in Drosophila melanogaster larvae were determined using an approach that combined RNA density labeling with cell-free translation. Unlike the other methods commonly used to measure the decay of individual mRNAs, the density labeling approach does not depend on the use of transcriptional inhibitors or on the measurement of precursor pool specific activities. Using this approach, we have determined that different embryonic mRNA species persist for varying periods during subsequent development, with half-lives ranging from approximately 2 to approximately 30 h. The embryonic histone mRNAs are relatively unstable; they are no longer detectable by 9 h of larval development. By 41 h of larval development, 90% of the nonhistone mRNAs assayed have decayed considerably; computerized scanning densitometry of translation products indicates that these transcripts are not decaying as members of discrete half-life classes. The persisting mRNAs that remain are very long-lived; their in vitro translation products can still be detected after 91 h of larval development. We have tentatively identified the mRNAs that encode actin, tropomyosin, and tubulin as members of this stable mRNA population. Although embryonic mRNAs do fall into these three broad classes of stability, they appear to decay with a continuum of half-lives. Because the range of half-lives is so great, mRNA stability is probably an important factor controlling mRNA abundance during Drosophila development.


Mechanism of action of a T suppressor factor (TsF) in contact sensitivity: the T cell target for TsF activity in adoptive transfer of immunity is not effector cell.
The passive transfer of contact sensitivity (CS) by immune cells into normal animals requires the interaction of two distinct Ly-1+ T cells, one which is Vicia villosa lectin (VV)-nonadherent, the other which adheres to VV. Functional deletion of either cell type abrogates the adoptive transfer of CS into normal animals, whereas VV-nonadherent cells alone can transfer CS into animals pretreated with cyclophosphamide (Cy). An antigen-specific T suppressor factor, designated TNP-TsF, inhibits the transfer of CS into normal adoptive recipients. TNP-TsF mediates its suppressive activity by inducing an I-J+ subfactor (designated I-J2) from the assay population by the interaction of PC1-F (a TNP-binding subfactor of TNP-TsF) with antigen-primed Ly-2+ T cells. This I-J+ subfactor then complements TNBS-F (an antigen-nonbinding subfactor of TNP-TsF) to form an antigen-nonspecific effector molecule which suppresses DTH responses in an antigen-nonspecific fashion. We report here that TNP-TsF suppresses the adoptive transfer of CS into normal animals but not into animals pretreated with Cy. TNBS-F + I-J2, the effector complex of TNP-TsF, also suppresses the transfer of CS into normal but not Cy-treated animals. When the Ly-1 immune cells were separated into VV-adherent and -nonadherent populations, the TNBS-F + I-J2 suppressor complex suppressed the functional activity of the VV-adherent cell population, but not the VV-nonadherent cells. This suppressive activity correlates with the need for VV-adherent cells in the transfer of CS into normal but not Cy-treated recipients. When an I-J+ molecule (I-J1) from an SRBC-specific TsF was used in place of I-J2 to form a suppressor complex with TNBS-F, this TNBS-F + I-J1 TsF suppressed the transfer of CS into both normal and Cy-treated recipients. This difference in functional suppressive activity correlated with a difference in target cell specificity: TNBS-F + I-J1 suppressed the VV-nonadherent TDTH cell, whereas TNBS-F + I-J2 suppressed the VV-adherent T cell of CS. Immune cells which are transferred under conditions which do not require the VV-adherent cell for transfer are not suppressed by TNBS-F + I-J2 or TNP-TsF, but are suppressed by the TNBS-F + I-J1.(ABSTRACT TRUNCATED AT 250 WORDS)


Percoll semen preparation enhances human oocyte fertilization in male-factor infertility as shown by a randomized cross-over study.
The aim of this study was to compare two methods of semen preparation: multiple tube swim-up and Percoll separation, using a randomized cross-over clinical study, in which sperm parameters, oocyte fertilization rates, embryo quality and cell stage were analysed. Overall, there was no difference between the two preparation methods in the normozoospermic cycles. In the male-factor cycles, Percoll extracted a higher total number of spermatozoa (P = 0.02), increased the concentration of motile spermatozoa (P = 0.02), increased the total number of motile spermatozoa per sample (P = 0.02), and enhanced the recovery rate of motile spermatozoa (P = 0.04) compared to swim-up. There was a significant improvement in fertilization rates (P = 0.0006), in the percentage of embryos over 2-cell stage on day of transfer (P = 0.004), and in the number of replaced embryos per transfer (P = 0.01) in the Percoll as compared to swim-up cycles. There was no significant difference in embryo quality. We conclude, therefore, that in advanced reproductive procedures where sperm dysfunction exists, semen preparation with Percoll should replace the swim-up technique.


Drug dealing on Facebook, Snapchat and Instagram: A qualitative analysis of novel drug markets in the Nordic countries.
Internet use has changed drug dealing over the past decade owing to the emergence of darknet services. Yet, little is known about drug dealing in public online services. This study reports findings from a Nordic comparative study on social media drug dealing. It is the first in-depth study on the increase of digitally mediated drug dealing outside the cryptomarkets. A qualitative study using online ethnography and semi-structured interviews. One hundred and seven participants aged 16-45 years (mean age 23.1 years), with 83.2% being male, were interviewed. Data was coded in NVivo using general themes: modus operandi, trust and risk. Ethnographical data shows a high degree of drug-dealing activity on Facebook, Instagram, Snapchat and Facebook Messenger. Buyers and sellers also use encrypted platforms, such as darknet forums and the Wickr app on their smartphones. The medium used varies across the countries, as well as motivations for usage in connection with risk perceptions. Despite national differences, social media is a common tool used in selling and buying illegal drugs. Availability affects the prevalence of use of various social media; however, prevalence is also crucial for which media is used. Many of the participants report easily drifting in and out of social media dealing and buying, without being aware of the seriousness of the offence. Based on the differences in attachment to the seller career, we advise that policing strategies should be supplemented with-and even stand in the back of-prevention campaigns.


The value of tissue polypeptide specific antigen TPS determination in serum of women with breast cancer comparison to mucin-like associated antigen MCA and CA 15-3 antigen.
The aim of the study was TPS diagnostic value determination in the serum of women with breast cancer as compared with MCA and CA 15-3. The relationship between the serum concentration of these antigens and patient age, clinical stage, histological grade, presence of metastases to lymph nodes and histological type of neoplasm was evaluated. Studies were conducted on the sera of 139 women before surgical procedure aged 28-81, treated in the Clinic of Oncology, at Karol Marcinkowski University of Medical Sciences in Poznań. The TPS concentration was determined using the "BEKI Diagnostics" immunoenzymatic method, MCA - by the "Roche" test and CA 15-3 concentration was determined by the "Abbott" immunofluorescent test. The study showed significantly higher levels of TPS, CA 15-3 and MCA in women with cancer, compared with values in healthy women and women with mastopathy. The highest median of concentration and frequency of occurrence was obtained for TPS. A correlation between enhancement of TPS and CA 15-3 concentration with clinical stage was observed. A similar connection was noted in women with metastases to the lymph nodes. Serum MCA concentration results did not demonstrate the above effects. The study suggests, that in estimating the clinical condition of women with breast cancer, the simultaneous determination of TPS with CA 15-3 seems to be a more useful prognostic factor than TPS or CA 15-3 with MCA.


[Right para-tracheal triangle lymphadenectomy for esophageal carcinoma].
To investigate the incidence of lymph node metastasis (LNM) in the right para-tracheal triangle (RPT) of esophageal carcinoma patients and the technique of dissection. On the top of double mediastinal and abdominal lymphadenectomy, 333 esophageal carcinoma patients received RPT lymphadenectomy through the right pleural apical approach from 1990 to 2001. In these 333 patients, the lymph node metastasis (LNM) rate in the RPT was 36.40%. A total of 457 nodes among 2 159 nodes removed gave a metastasis degree of 24.96%. The LNM rates in RPT for cervical, upper third, middle third, and lower third segments of esophagus were 66.67%, 45.45%, 34.19% and 15.79% (P < 0.05), while their respective metastasis degrees were 44.44%, 27.04%, 24.32% and 18.92% (P > 0.05). The frequency of positive nodes in the RPT for PTI, PT1, PT2, PT3 and PT4 was 0, 17.24%, 28.7%, 45.16% and 53.57%, while those of metastasis degree were 0, 8.77%, 17.62%, 33% and 41.17% (P < 0.01). The frequency of LNM in the RPT in papillary, erosive, patch-like and covert type of early tumor was 40%, 3.85%, 0 and 0 (P < 0.05), while those of the metastasis degree were 29.41%, 1.82%, 0 and 0 (P < 0.01). Higher rate of LNM in progressive stenotic esophageal carcinoma was observed compared with those of the other gross types (56.52%, P < 0.05), so was the degree (P < 0.01). The frequency of LNM in the RPT for mono-focal and multi-focal tumor was 34.98% and 70% without significant difference (P > 0.05), while the degree was 24.29% and 53.33% (P < 0.05). Postoperative complications were: leak (0.6%), and recurrent laryngeal nerve injury (1.2%). No injury of vein or infra-clavicular artery, tracheal damage or mortality occurred. 1. The lymph node metastasis from esophageal carcinoma has a tendency of wide spread and right para-tracheal triangle is an important region to be doomed. 2. With location, depth of tumor invasion and differentiation of tumor as major factors affecting LNM of esophageal carcinoma, dissection of this region should be paid more emphasis. 3. In early lesions, higher frequency of LNM in the RPT is found in papillary and erosive lesions than in the other macroscopic types. 4. Exposing the RPT, lymph node by dissection through a right pleural apical approach is very important and significant.


Osteochondrosis of the articular-epiphyseal cartilage complex in young horses: evidence for a defect in cartilage canal blood supply.
The objectives of this study were to determine in horses 1) the ages at which viable cartilage canal vessels are present in the articular-epiphyseal cartilage complex of three predilection sites and one nonpredilection site of osteochondrosis (OC), 2) the prevalence of lesions of OC in these sites, and 3) whether there was an association of lesions of OC with necrotic cartilage canal blood vessels. The medial femoral condyle, lateral femoral trochlear ridge, and distal ends of the tibia and proximal phalanx were examined grossly, microradiographically, and histologically in 35 horses 18 months old or younger. Cartilage canals containing patent blood vessels were present in all sites examined in foals less than 3 weeks old and were absent from all sites by 7 months of age. The overall prevalence of lesions of OC at one or more of the sites examined was 12/35 (34%). Prevalence increased to 11/22 (50%) in horses 2 months old and older. These lesions occurred primarily in the medial condyle of the femur (n = 5) and the intermediate ridge of the distal tibia (n = 5). All lesions seen in horses between 3 weeks and 5 months of age were associated with necrotic cartilage canal blood vessels. In horses 7 months of age and older, lesions of OC were considered chronic because of extensive involvement of the subchondral bone and bone marrow. These results suggest that OC lesions develop prior to 7 months of age and that ischemic necrosis of cartilage secondary to a defect in vascular supply is an important factor in the pathogenesis of this disease in horses.


Noise in the postanaesthesia care unit.
Although the postanaesthesia care unit (PACU) can be noisy, the effect of noise on patients recovering from anaesthesia is unknown. We studied the sources and intensity of noise in the PACU and assessed its effect on patients' comfort. We measured noise in a five-bed PACU with a sound level meter. Noise levels were obtained using an A-weighted setting (dBA) and peak sound using a linear scale (dBL). Leq (average noise level at 5-s intervals), maximum Leq (LeqMax), minimum Leq (LeqMin) and noise peaks (Lpc) were calculated. During recording, an independent observer noted the origin of sounds from alarms and noise above 65 dB intensity (P65dB). Two hours after leaving the PACU, patients were asked about their experience and to rank their complaints on a visual analogue scale (VAS) using unstructured and structured questionnaires. We made 20,187 measurements over 1678 min. The mean Leq, LeqMax and LeqMin were 67.1 (SD 5.0), 75.7 (4.8) and 48.6 (4.1) dBA respectively. The mean Lpc was 126.2 (4.3) dBL. Five per cent of the noise was at a level above 65 dBA. Staff conversation caused 56% of sounds greater than 65 dB and other noise sources (alarm, telephone, nursing care) were each less than 10% of these sounds. Five patients reported disturbance from noise. There was no significant difference in Leq measured for patients who found the PACU noisy and those who did not [59.5 (3.1) and 59.4 (2.4) dBA respectively]. Stepwise multiple logistic regression indicated that only pain was associated with discomfort. Even though sound in the PACU exceeded the internationally recommended intensity (40 dBA), it did not cause discomfort. Conversation was the most common cause of excess noise.


Compulsive exercise and eating disorders.
The aim of this review was to develop an empirically supported cognitive behavioural model of compulsive exercise within the context of the eating disorders. A systematic review of the correlates and predictors of compulsive exercise among eating disordered patients identified four key correlates. These were subsequently validated by a second review, incorporating both the clinical and non-clinical as well as the exercise science literatures. A proposed model is presented which is both evidence-based and testable.


The calmodulin-like protein CML43 functions as a salicylic-acid-inducible root-specific Ca(2+) sensor in Arabidopsis.
Many signalling pathways in plants are regulated by the second messenger calcium (Ca(2+)). In the standard model, Ca(2+)-sensor proteins, such as CaM (calmodulin), detect Ca(2+) signals and subsequently regulate downstream targets to advance the signal transduction cascade. In addition to CaM, plants possess many CMLs (CaM-like proteins) that are predicted to function as Ca(2+) sensors, but which remain largely uncharacterized. In the present study, we examined the biochemical properties, subcellular localization and tissue-specific distribution of Arabidopsis CML43. Our data indicate that CML43 displays characteristics typical of Ca(2+) sensors, including high-affinity Ca(2+) binding, conformational changes upon Ca(2+) binding that expose hydrophobic regions and stabilization of structure in the presence of Mg(2+) or Ca(2+). In vivo localization analysis demonstrates that CML43 resides in cytosolic and nuclear compartments. Transgenic plants expressing a CML43:GUS (β-glucoronidase) promoter reporter gene revealed that CML43 promoter activity is restricted almost exclusively to root tips under normal growth conditions. GUS reporter activity in these transgenic plants was strongly increased when exposed to the defence compound SA (salicylic acid). Furthermore, immunoblot analysis revealed that the CML43 protein accumulates following treatment with SA. Collectively, our findings suggest that CML43 functions as a Ca(2+) sensor in root tips during both normal growth and plant immune response.