The use of information technologies for diagnosis in ophthalmology.
In 2003, a health IT programme for clinical decision support started in Lithuania. An initial goal was to create databases for ophthalmology images and to develop processing algorithms to extract diagnostically valuable information from images. We have investigated how vectors, consisting of the parameters derived from fundus images, are distributed and whether they form specific groups. When analysing the multidimensional patient data vectors, comprising all the 27 image parameters, it was impossible to separate the healthy eyes from the diseased ones. However, it was possible to simplify the system by eliminating redundant parameters and introducing new ones that represent a subset of parameters from the initial group. Thus it may prove possible to identify glaucoma using this system of parameters.


O2 consumption, aerobic glycolysis and tissue phosphagen content during activation of the Na+/K+ pump in rat portal vein.
Oxygen consumption, lactate production and tissue contents of ATP, phosphocreatine (PCr) and lactate were measured following readdition of K+ to K+-depleted rat portal veins, in order to study the energy turnover associated with Na+/K+ pumping. During incubation in K+-free medium at 37 degrees C spontaneous contractions disappeared in 10-20 min. Readdition of K+ (5.9 mM) after 40 min K+-free incubation caused hyperpolarization of the cell membrane for the first 5-10 min and then gradual depolarization with return of spontaneous action potentials and contractions by 10-20 min. During the first 4-6 min after K+ readdition aerobic lactate production was about doubled and then gradually returned to the original level (0.17 mumol/min g) at about 20 min. The increase in glycolytic rate was prevented by 1 mM ouabain. In contrast, O2 consumption (in K+-free medium, 0.38 mumol/min g) rose by about 10% when K+ was added and this increase lasted about 5 min. By 8 min after K+ addition the increased glycolysis and oxidative phosphorylation had accounted for each about the same amount of extra ATP generation over that extrapolated from the steady rate before K+ addition. The average total increase in ATP turnover in the first 8 min was 15%. During this period there was no change in the cellular content of ATP, PCr, or extractable ADP. The results indicate that Na+/K+ pumping utilizes a relatively small share of the total energy turnover in the vascular smooth muscle but is to a large extent dependent on aerobic glycolysis and therefore a major site of carbohydrate usage.


Impact of CD1d deficiency on metabolism.
Invariant natural killer T cells (iNKTs) are innate-like T cells that are highly concentrated in the liver and recognize lipids presented on the MHC-like molecule CD1d. Although capable of a myriad of responses, few essential functions have been described for iNKTs. Among the many cell types of the immune system implicated in metabolic control and disease, iNKTs seem ideally poised for such a role, yet little has been done to elucidate such a possible function. We hypothesized that lipid presentation by CD1d could report on metabolic status and engage iNKTs to regulate cellular lipid content through their various effector mechanisms. To test this hypothesis, we examined CD1d deficient mice in a variety of metabolically stressed paradigms including high fat feeding, choline-deficient feeding, fasting, and acute inflammation. CD1d deficiency led to a mild exacerbation of steatosis during high fat or choline-deficient feeding, accompanied by impaired hepatic glucose tolerance. Surprisingly, however, this phenotype was not observed in Jα18⁻/⁻ mice, which are deficient in iNKTs but express CD1d. Thus, CD1d appears to modulate some metabolic functions through an iNKT-independent mechanism.


[Characterization of the functional domain of STT3a of oligosaccharyltransferase from Dunaliella salina].
To investigate the function of STT3a gene in salt adaptation and flagellar regeneration of Dunaliella salina (D. salina), a pair of degenerate primers was designed according to conserved homologous amino acid sequences of VCVFTA and DVDYVL of STT3a from Chlamydomonas, Arabidopsis thaliana and other organisms. A cDNA sequence of 1 650 bp encoding a whole functional domain of STT3a was amplified from D. salina by RT-PCR and 3' Rapid Amplification of cDNA Ends (RACE), which shared homology with Chlamydomonas (48%), Arabidopsis thaliana (50%), Homo sapiens (46%), etc. Real-time fluorescence quantitative PCR (real-time Q-PCR) demonstrated that the STT3a mRNAs from D. salina were induced by increased concentration of NaCl, and increased to 11-fold higher by 3.5 mol/L NaCl than that by 1.5 mol/L NaCl (P < 0.01). Also, STT3a mRNA of D. salina maintained at a higher level in the process of flagellar regeneration with than without experiencing deflagellar treatment. In conclusion, the findings of this study demonstrate that the high expression of the STT3a gene enhances the capability of salt adaptation and flagellar regeneration in D. salina.


Combined modality treatment of Hodgkin's lymphoma.
Substantial clinical progress over the last decades has improved the first-line treatment and prognosis of patients with Hodgkin's lymphoma (HL). This success is mainly based on the introduction of combined modality treatment strategies including chemotherapy in all risk groups and important progress in radiation techniques. The knowledge emerging from numerous clinical trials as well as better staging and imaging techniques helped to develop more effective therapies. According to our current knowledge, a stage and risk factor-based allocation into early favorable, early unfavorable, and advanced stages remains a suitable instrument to tailor risk-adapted therapy. In most of the study groups, patients with early stage HL receive 2 to 4 cycles of chemotherapy followed by radiotherapy to the involved field. The treatment for advanced stages usually consists of 6 to 8 cycles, more intensive regimen, and radiotherapy for residual masses. Here, we review results from current clinical trials and discuss new therapeutic approaches in the combined modality treatment of HL.


Late-onset Becker muscular dystrophy: Refining the clinical features and electrophysiological findings.
The aim of this study was to characterize a unique distribution of muscle involvement in sporadic Becker muscle dystrophy (BMD). Retrospective chart review, clinical examination, electrophysiological studies, cardiac testing, and genetic testing were performed in 5 patients. Predominant weakness and atrophy of biceps brachii, hip adduction, and quadriceps muscles was noted along with calf and extensor forearm hypertrophy. Finger flexor muscles were severely weak in 3 of 5 patients, a feature that could lead to a misdiagnosis of inclusion body myositis. Creatinine kinase was only mildly elevated in most patients. Electromyography was abnormal in all patients. Muscle biopsy in 1 patient demonstrated normal immunostaining for dystrophin. We found a unique and uniform distribution of muscle involvement in 5 sporadic cases of BMD. Recognizing these features is important for differentiating it from other myopathies that may have similar features and avoids unnecessary invasive procedures such as muscle biopsy.


Cations in control: crystal engineering polyoxometalate clusters using cation directed self-assembly.
The synthetic engineering of anionic polyoxometalate (POM) clusters with predefined properties tailored to specific applications is a great challenge using routine "one-pot" POM syntheses. Under such conditions, difficulties often arise from the multitude of complex reaction pathways and self-assembly processes occurring in solution. In this respect the major role of the charge balancing cations cannot be ignored, in fact such cations are crucial, both in the assembly of the building blocks, linkage to the overall cluster, and then assembly into the bulk material. Further, the role of the cation facilitating the selective crystallization of a particular cluster type cannot be divorced from the reaction process since the crystallization process itself can help pull "virtual" building blocks into being. This perspective briefly outlines our efforts towards engineering novel POM based materials, highlighting the use of large organic cations as "Shrink-wrapping" agents to isolate new POM clusters, frameworks and cage compounds. Central to this perspective is the hypothesis that, in the case of POM cluster assembly, the mechanism and various equilibria which define the clusters can be controlled by the selective crystallisation using cation control. Consequently, this indicates that the process of crystallisation can have a profound effect on self-assembly at the molecular level. We therefore propose that the crystallization process itself may define the molecular structure of the cluster leading to the conundrum, which came first, the cluster or the crystal of the cluster?


The risk of arrhythmias following coronary artery bypass surgery: do smokers have a paradox effect?
Smoking is reported to increase the risk of arrhythmias. However, there are limited data on its effects on arrhythmias following coronary artery bypass graft (CABG). This is a retrospective review of a prospective database of all CABG patients over an eight-year period. Our cohort (n=2813) was subdivided into: current (n=1169), former (n=837), and non-smokers (n=807). Predictors of arrhythmias following CABG in relation to smoking status were analysed. Atrial arrhythmias occurred in 942 patients (33%). Ventricular arrhythmias occurred in 48 patients (2%) and high-grade atrioventricular block occurred in five patients (0.2%). Arrhythmias were lower in current smokers than former and non-smokers (29% vs. 40% vs. 39%, respectively P<0.001). Logistic regression analysis showed 30% arrhythmia risk reduction in smokers compared to non-smokers [odds ratio (OR) 0.7, 95% confidence intervals (CI) 0.5-0.8] and this effect persisted after accounting for potential confounders while former smokers had the same risk as non-smokers (OR 1.04, CI 0.9-1.3). There were no significant differences in mortality. Smokers are less prone to develop arrhythmias following CABG. This paradox effect is lost in former smokers. This effect is possibly due to a lower state of hyper adrenergic stimulation observed in smokers than non-smokers following the stress of surgery.


Isolated Vaginal Recurrence of Early-Stage Rectal Cancer Detected by 18F-FDG PET/CT.
The relapses of rectal cancer are most frequently localized in the pelvis, liver, and pelvic and para-aortic lymph nodes and lungs, whereas the vagina is an unusual site. We present here a 60-year-old woman presenting with lower abdominal discomfort 23 months after radical resection of rectal adenocarcinoma. An isolated, solitary, hypermetabolic mass in the right part of the vagina was detected by F-FDG PET/CT. Ultimately, the vaginal neoplasm was proved to be adenocarcinoma of rectal origin based on its shared histologic features and compatible immunostaining profile.


Assessment of cancellous bone structure: comparison of strut analysis, trabecular bone pattern factor, and marrow space star volume.
Cancellous bone architecture is an important determinant of bone strength. Recently, several approaches to the assessment of bone structure in histological sections have been described; however, no comparative studies of these different methods have been reported. We have developed computerized methods for the simultaneous assessment of several indices of bone structure, including trabecular bone pattern factor, marrow space star volume, node-to-terminus ratio, trabecular number, and trabecular separation. The relationships between these variables has been examined in iliac crest cancellous bone obtained from 41 healthy subjects, 17 male and 24 female, aged 20-80 years (mean 47.9 years). All structural indices assessed showed significant correlations with cancellous bone area (p < 0.0001). Values for trabecular bone pattern factor and marrow space volume were highly correlated (r = 0.789; p < 0.0001). A comparison of indices obtained by strut analysis with trabecular bone pattern factor and marrow space star volume also revealed significant relationships, especially for the terminus-to-terminus strut length (r = 0.704 and r = 0.634, respectively; p < 0.0001) and node to terminus ratio (r = -0.947 and r = -0.788, respectively; p < 0.0001). The node-to-terminus ratio and trabecular bone pattern factor showed significant relationships with age which were independent of sex, cancellous bone area and trabecular width (p < 0.01 and p < 0.005, respectively). Our results demonstrate strong correlations between the different two-dimensional indices of bone structure in cancellous bone from healthy subjects. Trabecular penetration is likely to be an important determinant of all these variables, which may therefore reflect connectivity; however, direct comparison of these methods with three-dimensional techniques is required to establish their true relationship to bone structure.


Selective rod degeneration and partial cone inactivation characterize an iodoacetic acid model of Swine retinal degeneration.
PURPOSE. Transgenic pigs carrying a mutant human rhodopsin transgene have been developed as a large animal model of retinitis pigmentosa (RP). This model displays some key features of human RP, but the time course of disease progression makes this model costly, time consuming, and difficult to study because of the size of the animals at end-stage disease. Here, the authors evaluate an iodoacetic acid (IAA) model of photoreceptor degeneration in the pig as an alternative model that shares features of the transgenic pig and human RP. METHODS. IAA blocks glycolysis, thereby inhibiting photoreceptor function. The effect of the intravenous injection of IAA on swine rod and cone photoreceptor viability and morphology was followed by histologic evaluation of different regions of the retina using hematoxylin and eosin and immunostaining. Rod and cone function was analyzed by full-field electroretinography and multifocal electroretinography. RESULTS. IAA led to specific loss of rods in a central-to-peripheral retinal gradient. Although cones were resistant, they showed shortened outer segments, loss of bipolar cell synaptic connections, and a diminished flicker ERG, hallmarks of transition to cone dysfunction in RP patients. CONCLUSIONS. IAA provides an alternative rod-dominant model of retinal damage that shares a surprising number of features with the pig transgenic model of RP and with human RP. This IAA model is cost-effective and rapid, ensuring that the size of the animals does not become prohibitive for end-stage evaluation or therapeutic intervention.


A new beta-thalassaemia frameshift mutation detected by PCR after selective hybridization to immobilized oligonucleotides.
A previously undescribed mutation (-1, +3, codon 24) causing beta-thalassaemia was identified in an Egyptian patient. It consists in the concomitant deletion of a G in codon 24 and its replacement with the new trinucleotide CAC, thus resulting in the shift of the beta-globin reading frame. The sequence of the chromosome of interest was isolated from the homologous one by means of selective hybridization to an immobilized oligonucleotide. The presence of this mutation in the proband's family was confirmed by dot blot hybridization with an oligonucleotide probe.


Surface-enhanced Raman spectroscopy study on the structure changes of 4-mercaptopyridine adsorbed on silver substrates and silver colloids.
Surface-enhanced Raman scattering (SERS) of 4-mercaptopyridine (4-mpy) adsorbed on HNO3 etched silver foil, chemically deposited silver films (silver mirror) and silver colloids were measured. The SERS study has revealed that 4-mpy was adsorbed onto the three kinds of silver surfaces by a sulfur-silver bond with the plane of pyridine ring being normal to the silver substrates. The structure of 4-mpy adsorbed on the silver surfaces depends largely on the pH values of environment. When the pH values of the environment are changed, the structure of 4-mpy adsorbed on silver surfaces can easily be altered through a protonation or deprotonation reaction occurring on the N atom of the pyridine ring, and the modified structure shows unique characters on the SERS spectrum. Owing to the remarkable enhancement ability of SERS technique and characteristic spectrum of different species, a monolayer of 4-mpy assembled on a silver mirror holds potential as a H+ sensor for highly sensitive detection of the proton concentration in an aqueous solution.


Developmental and age-related changes in proteins in the female reproductive tract of Heligmosomoides polygyrus (Nematoda).
Proteins in the female reproductive tract of Heligmosomoides polygyrus at days 8, 16, 35, 90, and 140 postinfection (PI) were examined using polyacrylamide gel electrophoresis. Sixteen-day-old and 140-day-old worms also were examined histochemically. Egg production of these worms was assessed for each age group. In analyzing proteins using electrophoresis, the reproductive tracts were separated into 3 sections: the tip, or anteriormost part of tract, containing oogonia; the middle region, containing developing oocytes; and the posterior region, containing the uterus with fertilized eggs. Three major reproductive tract proteins were identified as having molecular weights of greater than 140 kDa, 115 kDa, and 82 kDa. These were found in all parts of the reproductive tract from worms of all ages except those at 8 days PI (which are too young to produce eggs) and are believed to be yolk proteins. Four low molecular weight proteins (L1-4) are believed to be nucleoproteins. L4 was absent from the posterior section of the reproductive tracts and L3 was limited to the posterior sections and may be associated with sperm stored in the uterus. Of 5 high molecular weight proteins the second heaviest, designated H2, appeared to be relatively more concentrated in the posterior sections of the reproductive tract. An 85-kDa protein was limited to the tip and middle sections of reproductive tracts. Histochemical tests on sectioned H. polygyrus showed strong positive reactions for protein in cytoplasmic granules in developing oocytes and in eggs of younger worms (16 days) but a reduced reaction in older worms (140 days). Strains for collagen showed a slight positive reaction in and between developing oocytes and a strong reaction in the egg shells. Stains for nucleoproteins particularly reacted with sperm stored in the uterus, and slightly reacted with fertilized eggs and the nucleoli of the intestinal and ovarian epithelium. Egg production by H. polygyrus increased to 123 eggs/female/day by 16 days PI but declined from 121 eggs/female/day at 35 days PI to 64 eggs/female/day in worms 140 days old. Electrophoresis indicated no loss in the different types of proteins in the reproductive tract of older worms, but histochemistry and protein content assays suggest that older worms that produce fewer eggs contain a relatively smaller amount of protein in the female reproductive tract.


Sustained expression of vascular endothelial growth factor and angiopoietin-1 improves blood-spinal cord barrier integrity and functional recovery after spinal cord injury.
Spinal cord injury (SCI) results in immediate disruption of the spinal vascular network, triggering an ischemic environment and initiating secondary degeneration. Promoting angiogenesis and vascular stability through the induction of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1), respectively, provides a possible therapeutic approach in treating SCI. We examined whether supplementing the injured environment with these two factors, which are significantly reduced following injury, has an effect on lesion size and functional outcome. Sustained delivery of both VEGF(165) and Ang-1 was realized using viral vectors based on the adeno-associated virus (AAV), which were injected directly into the lesion epicenter immediately after injury. Our results indicate that the combined treatment with VEGF and Ang-1 resulted in both reduced hyperintense lesion volume and vascular stabilization, as determined by magnetic resonance imaging (MRI). Western blot analysis indicated that the viral vector expression was maintained into the chronic phase of injury, and that the use of the AAV vectors did not exacerbate infiltration of microglia into the lesion epicenter. The combined treatment with AAV-VEGF and AAV-Ang-1 improved locomotor recovery in the chronic phase of injury. These results indicate that combining angiogenesis with vascular stabilization may have potential therapeutic applications following SCI.


Estimation of trends of mortality rates in selected industrialized countries.
"The first part of the...paper [compares]....mortality trends of various age groups in twelve selected industrialized countries..., covering the period from the beginning of the 50s until 1980/81.... Essential changes regarding the age-group specific mortality trends will be [outlined]....An estimation of trends of age-group specific mortality rates in the selected countries will be presented in the second part of this paper.... The trend and the levels of the estimated mortality rates as well as the comparison between the selected countries will be described." Rates are presented separately for males and females.


Analytical performance characteristics and clinical utility of a novel assay for total hepatitis C virus core antigen quantification.
The detection and quantification of hepatitis C virus (HCV) core antigen in serum or plasma by the use of different assay formats have previously been shown to represent useful markers of viral replication. In the present study, the intrinsic performance characteristics and the potential clinical utility of a novel assay for the quantification of total HCV core antigen were comprehensively assessed by using clinical serum samples and specimens contained in various evaluation panels. The Architect HCV Ag assay showed a specificity of 100%. The intra- and interassay coefficients of variation ranged from 3.6 to 8.0% and from 4.7 to 9.5%, respectively. Except for HCV genotype 2 isolates, the analytical sensitivity was always less than 10 fmol core antigen/liter, corresponding to approximately 500 to 3,000 IU of HCV RNA/ml. Linearity was guaranteed throughout the dynamic range (10 to 20,000 fmol/liter). When seroconversion panels were tested, the assay was not inferior to HCV RNA detection and reduced the preseroconversion period by 4 to 16 days. The results obtained by core antigen and HCV RNA quantification for 385 clinical specimens were correlated by regression analysis (r = 0.857), but the calculated conversion equation differed significantly from the line of identity. Monitoring of viral kinetics by use of either core antigen or RNA concentrations in 38 HCV-infected patients undergoing antiviral combination therapy resulted in very similarly shaped curves in all cases. Finally, the Architect HCV Ag assay was also shown to enable high-throughput screening of in vitro HCV RNA replication. With these results taken together, the Architect HCV Ag assay proved to be a specific, reproducible, highly sensitive, and clinically applicable test format which will find its future place in the context of virological HCV diagnostics.


Growth arrest and suppression of tumorigenicity of bladder-carcinoma cell lines induced by the P16/CDKN2 (p16INK4A, MTS1) gene and other loci on human chromosome 9.
Wild-type P16/CDKN2 (p16INK4A, MTS1) cDNA, directed by the cytomegalovirus (CMV) immediate early promoter, was transfected into RT4 and RT112 bladder-carcinoma cell lines bearing a mutated endogenous P16/CDKN2 gene and lacking endogenous P16/CDKN2 respectively. In both cases, only transfected clones with rearranged exogenous P16/CDKN2 cDNA could be grown and propagated in cell culture. This result is reminiscent of transfection of wild-type p53 into cells with a deleted or mutated endogenous gene and suggests that P16/CDKN2, over-expressed under control of the strong CMV promoter, induces growth arrest in RT4 and RT112 cells. Transfer of human chromosome 9 to RT4 cells produced RT4/H9 hybrid clones retaining the P16/CDKN2 gene, since in RT4/H9 cell clones P16/CDKN2-gene expression is modulated by the physiological control of chromosomal regulatory sequence. All the RT4/H9 clones lost the entire chromosome 9, except clone 4 and clone 5, which maintained a deleted and an intact chromosome 9 respectively. Loss of several loci in 9p21, including P16/CDKN2, in tumors induced in nude mice by clone 4 and clone 5 suggests that P16/CDKN2 or other genes in 9p21 suppress tumorigenicity in bladder-carcinoma cells. Tumors induced by clone 4 and clone 5 show loss of markers in 9q. The regions 9q22.3, 9q32-33 and 9q34.2, which were maintained in the 2 clones and lost in their derived tumors, may contain tumor-suppressor genes relevant in bladder carcinoma. The results of this study suggest that the P16/CDKN2 gene controls growth of bladder-carcinoma cells when it is over-expressed, and may be involved in the development of bladder carcinoma, but other genes in 9p21 and 9q may participate in bladder-cancer progression.


Biventricular repair of double outlet right ventricle with non-committed ventricular septal defect (VSD) by VSD rerouting to the pulmonary artery and arterial switch.
Biventricular repair of double outlet right ventricle non-committed ventricular septal defect (DORVncVSD) is usually achieved by a VSD rerouting to the aorta. This technique can be limited by the presence of tricuspid chordae and by the pulmonary artery to tricuspid valve distance. Furthermore, there is an important risk of late subaortic obstruction related to the long patch required that creates a potential akinetic septal area. Presented here is another technique; by VSD rerouting to the pulmonary infundibulum and arterial switch. Ten patients, with DORVncVSD, underwent a VSD rerouting to the pulmonary infundibulum followed by arterial switch. Seven had a previous pulmonary artery banding and one a moderate infundibular stenosis. The median age at surgery was 16 months (range 3 weeks to 4.5 years). All patients had a bilateral infundibulum, with a large persistent subaortic conus, D malposition of the aorta, side-by-side vessels and double loop coronary patterns. The VSD was perimembranous with inlet or trabecular extension. Subaortic obstruction was constant. The VSD was severely distant from both the aortic and the pulmonary annulus. The operation was conducted through a combined approach. The VSD was constantly enlarged superiorly. The almost permanent subaortic obstruction was released. The VSD was always found quite close to the pulmonary infundibular ostium. The arterial switch technique was adapted to the complex coronary anatomy. There was one non-cardiac death. At a mean follow-up of 20 months, all nine survivors are in NYHA class I, in sinus rhythm, and have no subaortic gradient greater than 15 mm. This technique of VSD rerouting to the pulmonary artery and arterial switch limits greatly the size of the rerouting patch, respects the tricuspid chordae and is independent of the pulmonary artery-tricuspid valve distance. In this early series of biventricular repair of DORVncVSD, the VSDs were always found close to the pulmonary artery, allowing this new type of repair.


Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma.
Altered deposition of extracellular matrix (ECM) in the airway smooth muscle (ASM) layer as observed in asthma may influence ASM mechanical properties. We hypothesized that ECM in ASM is associated with airway function in asthma. First, we investigated the difference in ECM expression in ASM between asthma and controls. Second, we examined whether ECM expression is associated with bronchoconstriction and bronchodilation in vivo. Our cross-sectional study comprised 19 atopic mild asthma patients, 15 atopic and 12 nonatopic healthy subjects. Spirometry, methacholine responsiveness, deep-breath-induced bronchodilation (ΔR(rs) ) and bronchoscopy with endobronchial biopsies were performed. Positive staining of elastin, collagen I, III and IV, decorin, versican, fibronectin, laminin and tenascin in ASM was quantified as fractional area and mean density. Data were analysed using Pearson's or Spearman's correlation coefficient. Extracellular matrix expression in ASM was not different between asthma and controls. In asthmatics, fractional area and mean density of collagen I and III were correlated with methacholine dose-response slope and ΔR(rs) , respectively (r = 0.71, P < 0.01; r = 0.60, P = 0.02). Furthermore, ASM collagen III and laminin in asthma were correlated with FEV(1) reversibility (r = -0.65, P = 0.01; r = -0.54, P = 0.04). In asthma, ECM in ASM is related to the dynamics of airway function in the absence of differences in ECM expression between asthma and controls. This indicates that the ASM layer in its full composition is a major structural component in determining variable airways obstruction in asthma.


Oral fungi in HIV: challenges in antifungal therapies.
Oral candidiasis (OC) caused by Candida species is a common fungal infection among HIV-infected individuals. Despite the wide use of antiretroviral therapy (ART) resulting in a declined prevalence, OC remains the most common oral lesions seen in those living with HIV/AIDS. Various topical and systemic antifungal drugs are available to treat OC. However, due to the patients' immunodeficiency and the nature of OC as biofilm-associated infection, relapse is frequently observed after cessation of antifungal therapy. In addition, long-term antifungal therapy may lead to drug resistance. This review article addressed three major challenges in the treatment of OC in HIV infection including antifungal drug resistance, biofilm-associated infection of OC, and the host underlying immunodeficiency. To reduce the risks of antifungal drug resistance, the author recommends that future studies should focus on herbal plant-derived compounds with antifungal activity that may be used in combination with the drugs. Also, it is recommended that more research should be carried out to explore how to enhance the host innate immunity against oral Candida.


Research on Early Warning Mechanism and Model of Liver Cancer Rehabilitation Based on CS-SVM.
Since the 20th century, cancer has become one of the main diseases threatening human health. Liver cancer is a malignant tumor with extremely high clinical morbidity and fatality rate and easy recurrence after surgery. Research on the postoperative recurrence time and recurrence location of patients with liver cancer has a crucial influence on the postoperative intervention of patients. Evaluation of the clinical manifestations of patients after liver cancer surgery is conducted according to medical knowledge or national standards to determine the main factors affecting liver cancer rehabilitation. In order to better study the mechanism of liver cancer recurrence, this paper uses CS-SVM to predict the recurrence time of liver cancer patients, so as to timely intervene the patients. There are five evaluation indicators which are basic indicators, immune indicators, microenvironment indicators, psychological indicators, and nutritional indicators, respectively. This paper collects the clinical evaluation data of postoperative follow-up visits for patients with liver cancer in a hospital, improves the parameter selection process of the support vector machine by using the search ability of the cuckoo algorithm, and establishes an algorithm-optimized prediction model of support vector machine for the prognosis of liver cancer to predict the location and approximate time of recurrence. According to the clinical evaluation data of patients with liver cancer after surgery, logistics regression, BP neural network, and other related methods are used to predict the prognosis of liver cancer patients after surgery. The prediction effects of several methods are compared, and the superiority of the model is discussed. At the end of this article, we conducted an empirical analysis on the clinical evaluation data of patients with liver cancer after surgery. For the collected samples of 776 liver cancer recurrences after surgery, the established liver cancer prognosis outcome prediction model was used to predict the recurrence time and recurrence location, respectively. The mean square error of recurrence time prediction is 9.2101, which is much smaller than the prediction mean square error of BP neural network of 177.9451; the prediction accuracy of recurrence location is 95.7%, which is much higher than the 63.14% of logistic regression. The empirical analysis results show that the improved support vector machine model based on cuckoo established in this paper can effectively predict the time and location of cancer recurrence.


The Elementary Particles of Quantum Fields.
The elementary particles of relativistic quantum field theory are not simple field quanta, as has long been assumed. Rather, they supplement quantum fields, on which they depend on but to which they are not reducible, as shown here with particles defined instead as a unified collection of properties that appear in both physical symmetry group representations and field propagators. This notion of particle provides consistency between the practice of particle physics and its basis in quantum field theory.


Concentrations of Water-Soluble Vitamins in Blood and Urinary Excretion in Patients with Diabetes Mellitus.
We examined the concentrations of water-soluble vitamins in blood and urinary excretion of 22 patients with type 2 diabetes mellitus (type 2DM) and 20 healthy control participants. Macronutrient and vitamin intakes of type 2DM subjects were measured using a weighed food record method. Control participants consumed a semipurified diet for eight days. Multiple linear regression models were used to determine whether significant differences existed in vitamin concentrations in blood independent of age, sex, and other confounding factors. Concentrations of vitamins B2, B6, C, niacin, and folate in blood were significantly lower in type 2DM subjects than in controls, independent of confounding factors. Renal clearances of vitamins B6, C, niacin, and folate were significantly higher in type 2DM subjects than in controls. In conclusion, concentrations of vitamins B2, B6, C, niacin, and folate in blood were significantly lower in type 2DM subjects than in controls, independent of confounding factors; based on the evidence of increased urinary clearance of these vitamins, the lower levels were likely due to impaired reabsorption processes.


Living and working conditions of the professionals of the a Mobile Emergency Service.
The assistance provided by the Mobile Emergency Service (SAMU) may result in changes in the health of the workers. This is a cross-sectional epidemiological study which aimed to evaluate the sociodemographic, health and lifestyle characteristics and the working conditions among professionals of the SAMU in Campinas, SP, Brazil. A questionnaire was used to collect sociodemographic, lifestyle, health and work data. The sample consisted of 197 workers - nurses, physicians, nursing technicians, auxiliary nurses, drivers and administrative personnel. There was a prevalence of males (61.4%), mean age 39.1 years (SD=8.3); married (63.5%), with children (76.7%); of the category of drivers (30.5%), monitored by physicians (18.3%) and auxiliary nurses (16.8%); 42.1% had additional employment, 48% performed overtime and 25.3% worked more than 70 hours per week. The majority practiced physical (56.5%) and leisure (96.5%) activities. New facets of the life of these workers were revealed and may contribute to programs aimed at health promotion.


Modelling mood states in athletic performance.
Because moods are transitory emotional states that can be influenced by a range of personality and environmental factors, the notion that elite athletes will always tend to produce a so-called iceberg profile of mood, and that less successful performers will not, is open to question. Evidence for such a claim is based principally upon descriptive studies. The present experiment used the POMS inventory as a predictor of cross-country running performance among a group of experienced male athletes. Race times from two competitive events were plotted against each of six mood factors. Using data from race 1, a multiple-regression model--incorporating the interdependence of tension, anger and depression--was able to predict rank order of finishing positions for race 2 with acceptable accuracy (rs = 0.74, P less than 0.01). The present approach differs from the traditional model of mood research in sport in that it provides a prescriptive, rather than a descriptive, focus. Although the model that has been developed appears promising, it is likely that in sports where demands on athletes are very different from those made upon cross-country runners, an alternative model may be required.


A comparison of the short- and long-term effects of corticosterone exposure on extinction in adolescence versus adulthood.
Human and nonhuman adolescents have impaired retention of extinction of learned fear, relative to juveniles and adults. It is unknown whether exposure to stress affects extinction differently in adolescents versus adults. These experiments compared the short- and long-term effects of exposure to the stress-related hormone corticosterone (CORT) on the extinction of learned fear in adolescent and adult rats. Across all experiments, adolescent and adult rats were trained to exhibit good extinction retention by giving extinction training across 2 consecutive days. Despite this extra training, adolescents exposed to 1 week of CORT (200 μg/ml) in their drinking water showed impaired extinction retention when trained shortly after the CORT was removed (Experiment 1a). In contrast, adult rats exposed to CORT (200 μg/ml) for the same duration did not exhibit deficits in extinction retention (Experiment 1b). Exposing adolescents to half the amount of CORT (100 μg/ml; Experiment 1c) for 1 week similarly disrupted extinction retention. Extinction impairments in adult rats were only observed after 3 weeks, rather than 1 week, of CORT (200 μg/ml; Experiment 1d). Remarkably, however, adult rats showed impaired extinction retention if they had been exposed to 1 week of CORT (200 μg/ml) during adolescence (Experiment 2). Finally, exposure to 3 weeks of CORT (200 μg/ml) in adulthood led to long-lasting extinction deficits after a 6-week drug-free period (Experiment 3). These findings suggest that although CORT disrupts both short- and long-term extinction retention in adolescents and adults, adolescents may be more vulnerable to these effects because of the maturation of stress-sensitive brain regions. (PsycINFO Database Record (c) 2014 APA, all rights reserved).


A randomized controlled comparison of seclusion and mechanical restraint in inpatient settings.
No evidence is available on the relative restrictiveness of seclusion and mechanical restraint, although guidelines recommend use of the least restrictive intervention. This study compared the restrictiveness of these interventions from patients' point of view. Data were collected from three general psychiatric admission units in South Germany. A total of 102 patients with schizophrenia, an affective disorder, or a personality disorder were included in a comprehensive cohort study with optional randomization. Restrictions of human rights as measured by the Coercion Experience Scale (CES) were the primary outcome variable. Possible total scores range from 1 to 5, with higher scores indicating a higher level of restriction. Twenty-six patients were randomly assigned to seclusion (N=12) or mechanical restraint (N=14). A total of 76 were excluded from randomization and included in the cohort arms (48 experienced seclusion, and 28 experienced mechanical restraint). No difference in mean CES total scores was found between the randomly assigned patients after they experienced seclusion or mechanical restraint (seclusion median score=1.88 [range 1.24-4.24]; restraint median score=2.14 [range 1.28-4.00]). When randomly assigned patients and patients in the cohort arms were considered as a group, no significant difference in CES scores was found (seclusion median score=.40, [range 1.1-4.2]; restraint median score=2.59 [range 1.1-4.0]). The results do not provide evidence for using one intervention rather than the other. Clinical decisions should take into account patients' preferences. Randomized controlled trials of coercive interventions are feasible. Such studies contribute to the development of ethical and evidence-based guidelines.


Role of diets in modifying gastrointestinal neurotransmitter enzyme activity.
Manipulation of diet, by altering the composition or quantity, can produce alterations in the central nervous system as evidenced by changes in memory or behavior. The present study was designed to examine the effects of fasting/starvation or a choline deficient diet on the enzymes that synthesize and degrade acetylcholine and norepinephrine, both neurotransmitters in the gastrointestinal tract. This study was conducted on three groups of male rats: control nontreated, choline deficient diet for 14 days, and fasting/starvation (water only) for 3 days. Enzyme activities were determined throughout the length of the gut. The lack of dietary choline produced a decrease in adrenergic enzyme activity but had little effect on cholinergic enzyme activities. Starvation decreased adrenergic enzyme activities and increased activity of the acetylcholine synthesizing enzyme in most segments of the gastrointestinal tract. Starvation was also a stressor, as evidenced by elevated levels of plasma and adrenal corticosterone. The implication from these experiments is that dietary manipulation may produce functional changes (i.e., motility and secretion) in the gastrointestinal tract as a result of altering neurotransmitter enzyme activities.


Hypoxia-mediated in vivo release of dopamine in nucleus tractus solitarii of rabbits.
A wide variety of neuroactive substances have been suggested to be involved in the respiratory depression observed in response to severe hypoxia. By use of the technique of microdialysis, the release of dopamine (DA) was measured in the nucleus tractus solitarii during severe hypoxic provocations (6% O2 in N2) in the adult pentobarbital-anesthetized rabbit. DA release was analyzed by high-performance liquid chromatography with electrochemical detection. Such hypoxic provocations caused pronounced phase of depression in the phrenic nerve activity and enhanced release of DA. After bilateral carotid sinus nerve denervation, acute severe hypoxia did not give rise to enhanced release of DA or to phrenic nerve depression. Mild hypoxic (9% or 12% O2 in N2) or hypercapnic (6% CO2) stimuli resulted in an increased phrenic nerve activity without any concomitant changes in DA release. Decerebration at the midcollicular level in rabbits prevented an enhanced release of DA in the nucleus tractus solitarii during severe hypoxia. The results suggest that 1) DA is involved in the central ventilatory response to severe hypoxia, 2) not only the initial excitatory but also the second depressive phase in response to severe hypoxia is mediated partially by the peripheral chemoreceptors, and 3) the depressive phase is dependent on intact connections from suprapontine structures.


Strong Enantiomeric Preference on the Macroion-Counterion Interaction Induced by Weakly Associated Chiral Counterions.
The role of chiral counterions on the attraction and self-assembly of chiral Pd12L24 metal organic cages (MOCs) with NO3- being the original counterion is studied by laser light scattering and isothermal titration calorimetry. Nitrates can trigger the self-assembly of macrocationic Pd12L24 into hollow spherical blackberry-type supramolecular structures via counterion-mediated attraction. Although chiral counteranions, such as N-(tert-butoxycarbonyl)-alanine (Boc-Ala), have weaker interaction with the MOCs compared to NO3-, they can induce different assembly behaviors between two enantiomeric MOCs by inhibiting the MOC-nitrate binding and weakening the interaction between them. The d-counterions are capable of selectively suppressing and slowing down the assembly of l-MOCs and also considerably decreasing their assembly size due to the much weaker MOC-nitrate interaction. The same scenario is observed for l-counterions when interacting with the d-MOCs. This study unveils the role of weakly associated chiral counterions on the central chiral macroions, especially their supramolecular structure formation, and provides additional evidence on the mechanism of the homochirality phenomenon.


Plasma fibronectin and complement in surgical patients.
Plasma fibronectin and a fragment of the third component of complement (C3b) are both opsonins of the reticulo-endothelial system. Twenty patients undergoing uncomplicated gastro-intestinal surgery were studied. There was a significant reduction in plasma fibronectin and total haemolytic complement, but not C3, in the early postoperative period (days 1 to 3). In six surgical patients critically ill with severe sepsis both plasma fibronectin concentrations and C3 concentration were reduced significantly when compared with the early postoperative period of uncomplicated surgery. In addition, in the critically ill patients, direct evidence of complement activation was demonstrated. These studies show a transient reduction of humoral host defence mechanisms following surgery which may be permissive to bacteraemia and complement activation.


A high throughput method for identifying personalized tumor-associated antigens.
Circulating autoantibodies against tumor-associated antigens (TAAs) and their pattern of glycosylation can be used as diagnostic indicators of cancer. Using random peptide library screening, we identified patient-specific sets of peptides recognized by colon cancer patients' serum IgG and IgM antibodies. We demonstrate a strategy for analyzing BLAST search results for identifying tumor-associated antigens represented by peptides that mimic sequential epitopes. Statistical analysis of the frequency with which the proteins are retrieved by BLAST homology searching and an estimation of the probability of a match by chance can identify the proteins that are the real targets of the immune response against tumors. In addition, we observed an over-expression of the mRNA for the match-producing protein only in the corresponding tumor sample, out of fourteen tumor and normal samples analyzed. This observation confirms that personalized tumor-associated antigens can be identified by BLAST homology search following random peptide library screening on cancer patient's serum antibodies.


Relationships between cellobiose catabolism, enzyme levels, and metabolic intermediates in Clostridium cellulolyticum grown in a synthetic medium.
Continuous cultures, under cellobiose sufficient concentrations (14. 62 mM) using a chemically defined medium, were examined to determine the carbon regulation selected by Clostridium cellulolyticum. Using a synthetic medium, a q(cellobiose) of 2.57 mmol g cells(-1) h(-1) was attained whereas the highest value obtained on complex media was 0.68 mmol g cells(-1) h(-1) (Payot et al. 1998. Microbiology 144:375-384). On a synthetic medium at D = 0.035 h(-1) under cellobiose excess, lactate and ethanol biosynthesis were able to use the reducing equivalents supplied by acetic acid formation and the H(2)/CO(2) ratio was found equal to 1. At a higher dilution rate (D = 0.115 h(-1)), there was no lactate production and the pathways toward ethanol and NADH-ferredoxin-hydrogenase contributed to balance the reducing equivalents; in this case a H(2)/CO(2) ratio of 1.54 was found. With increasing D, there was a progressive increase (i) in the steady-state concentration of NADH and NAD(+) pools from 11.8 to 22.1 micromol (g cells) (-1), (ii) in the intracellular NADH/NAD(+) ratios from 0.43 to 1.51. On synthetic media, under cellobiose excess the carbon flow was also equilibrated by three overflows: exopolysaccharide, extracellular protein, and amino acid excretions. At D = 0.115 h(-1), 34% of the cellobiose consumed was converted into exopolysaccharides; this deviation of the carbon flow and the increase of the phosphoroclastic activity decreased dramatically the pyruvate excretion and explained the break in lactate production. Whatever the dilution rate, C. cellulolyticum, using ammonium and cellobiose excess, always spilled usual amino acids accompanied by other amino compounds. In vitro, GAPDH, phosphoroclastic reaction, alcohol dehydrogenase, and acetate kinase activities were high under conditions giving high in vivo specific production rates. There were also correlations between the in vitro lactate dehydrogenase activity and in vivo lactate production, but in contrast with the preceding activities, these two parameters decreased with D. All the results demonstrate that C. cellulolyticum was able to optimize carbon catabolism from cellulosic substrates in a synthetic medium.


Positron emission tomography in Alzheimer's disease.
Twenty-one patients with a clinical diagnosis of dementia of the Alzheimer's type (DAT) and 29 healthy, age-matched controls were studied using positron emission tomography (PET) and [18F]2-fluoro-2-deoxy-D-glucose to measure regional cerebral glucose consumption in the resting state. Reductions in ratio measures of relative metabolism in some parietal, temporal, and frontal regions were found in mild, moderate, and severe DAT groups. A significant increase in right/left metabolic asymmetry, particularly in parietal regions, also was seen in mild and moderate groups. Only in the severely demented patients was the absolute cerebral metabolic rate reduced significantly from control values. Fourteen patients had repeated PET studies, but only those patients with moderate to severe dementia showed a decline in IQ over 6 to 15 months. There were no significant changes in metabolic measures over time. PET is useful in quantifying regional cerebral dysfunction in DAT, even in the early stages of the disease.


Organization of the variant domains of alpha satellite DNA on human chromosome 21.
The de novo creation of long, homogeneous, satellite DNA domains was postulated previously to occur by saltatory amplification. In this paper, pulsed field gel electrophoresis analysis of the alpha satellite DNA block organization of the human chromosome 21 supports this hypothesis. Double-dimension electrophoresis indicated that the variant copies of the basic alpha satellite repeat of chromosome 21 are organized in a single 3,150 Kb-long domain. It was also established that the other satellite DNAs found in man (beta, II, and III) are organized independently of the alpha satellite DNA block of the same chromosome.


Isolation and Identification of Lactic Acid Bacteria from Traditional Dairy Products in Baotou and Bayannur of Midwestern Inner Mongolia and q-PCR Analysis of Predominant Species.
In this study, traditional culture method and 16S rRNA gene analysis were applied to reveal the composition and diversity of lactic acid bacteria (LAB) of fermented cow milk, huruud and urum from Baotou and Bayannur of midwestern Inner Mongolia. Also, the quantitative results of dominant LAB species in three different types of dairy products from Baotou and Bayannur were gained by quantitative polymerase chain reaction (q-PCR) technology. Two hundred and two LAB strains isolated from sixty-six samples were identified and classified into four genera, namely Enterococcus, Lactococcus, Lactobacillus, Leuconostoc, and twenty-one species and subspecies. From these isolates, Lactococcus lactis subsp. lactis (32.18%), Lactobacillus plantarum (12.38%) and Leuconosto mesenteroides (11.39%) were considered as the dominated LAB species under the condition of cultivating in MRS and M17 medium. And the q-PCR results revealed that the number of dominant species varied from samples to samples and from region to region. This study clearly shows the composition and diversity of LAB existing in fermented cow milk, huruud and urum, which could be considered as valuable resources for LAB isolation and further probiotic selection.


Developmental potential of aged oocyte rescued by nuclear transfer following parthenogenetic activation and in vitro fertilization.
Mouse oocyte aged in vitro cannot develop normally following activation. To investigate the roles of nucleus or cytoplasm elements in oocyte aged in vitro process and their subsequent development capability following activation, we reconstructed oocytes with MII chromosome spindle and cytoplasm from aged and fresh oocytes by nuclear transfer. The subsequent developmental potential after parthenogenetic activation (PA) or in vitro fertilization (IVF) was evaluated. After nuclear transfer, more than 75.6% of karyoplast and cytoplast pairs can be fused and reconstructed oocytes have a normal haploid karyotype. Following PA, aged oocytes cannot develop beyond four-cell stage, reconstructed oocytes from fresh nucleus and aged cytoplasm developed to blastocyst with a low percentage (9.1%). Instead, blastocyst formation rate of reconstructed oocyte from aged nucleus and fresh cytoplasm was higher (60.0%). Following IVF, zygote with diploid karyotype can be formed from zona pellucida (ZP)-free oocyte. After cultured in vitro, aged oocytes cannot develop beyond two-cell; reconstructed oocytes from fresh nucleus and aged cytoplasm developed to blastocyst with low percentage (15.0%). However, high blastocyst formation rate (86.2%) can be obtained from reconstructed oocytes from aged nucleus and fresh cytoplasm. Furthermore, after embryo transfer, three viable pups have been obtained, although the efficiency is very low. These observation demonstrated that cytoplasm is more crucial than nucleus to aging process. Fresh cytoplasm could partly rescue nucleus susceptibility to apoptosis from aging in vitro.


Psychological and Aesthetic Outcomes in Breast Cancer Patients.
Patients who undergo breast cancer treatment require psychosocial and aesthetic rehabilitation. Advantages of breast reconstruction in-patient rehabilitation are well known. Oncoplastic organ-preserving surgery offers aesthetically better results, yet is often considered less safe than more radical procedures. We compared the aesthetic and psychological outcomes in patients undergoing breast reconstruction and oncoplastic breast cancer treatment. In total, 1130 patients who received either breast reconstruction or oncoplastic breast cancer surgery were included in the study. Patients were classified into two groups. Group 1 included 510 patients who received breast reconstruction surgery. Group 2 included 620 patients who received oncoplastic surgery. The following aspects were compared between the two groups: demographics, tumor progression, and immunohistochemical aspects, complications, hospitalization stay, and psychological and aesthetic outcomes. Patients in the oncoplastic group showed statistically significant higher psychosocial and aesthetic outcomes, as well as lower incidence of complications, revision rate, disease progression, and recurrence. The majority of oncoplastic patients were treated in early stages of breast cancer. Offering superior treatment results, oncoplastic organ-preserving surgery should be favored in patients with earlier stages of cancer progression.


Small bowel perforations due to deliberate ingestion of injurious foreign bodies--a personal experience.
Ingestion of foreign bodies is not an uncommon problem in our society. The patients usually ingest different types of foreign bodies either accidentally or deliberately. Rare in children but adults are not uncommonly affected and are either psychiatric patients or ingest foreign bodies accidentally. Life threatening complications may occur at times due to ingestion of sharp and pointed objects. An interesting case of ingestion of multiple injurious foreign bodies presenting with multiple small intestinal perforations is presented with review of literature.


Investigation of sorption behavior between pyrene and colloidal organic carbon from activated sludge processes.
The sorption behavior of pyrene for different size fractions of colloidal organic carbon (COC) originating from two biological wastewater treatment facilities (a full-scale activated sludge system (FSAS) and a membrane bioreactor (MBR)) was investigated by fluorescence quenching. Fluorescence lifetime measurements demonstrated a dynamic quenching component in all samples, including the colloidal-free filtrates. COC sorption coefficients (Kcoc) for pyrene ranged from <1 x 10(3) L/kgcoc to 80 x 10(3) L/kgcoc and were comparable to values obtained in the literature for natural organic matter. Both linear and nonlinear behaviors were observed in the Freundlich-described converted isotherms (n = 0.89-2.1). The aromatic content of COC was quantified by the molar extinction coefficient at 280 nm (e280). Good correlations were observed between COC-pyrene sorption coefficients and e280 coefficients, suggesting that e280 may be a useful tool for predicting colloidal transport of hydrophobic organic compounds (HOCs) from activated sludge systems. The removal of COC from treated effluents may appreciably reduce the concentrations of HOCs discharged to receiving streams.


Deep lamellar keratoplasty in the treatment of keratoconus.
To present our experience with a series of patients treated with deep lamellar keratoplasty (DLK) for keratoconus (KC). A single surgeon, prospective, consecutive series. The study included all patients with KC who underwent DLK between March 1999 and November 2003 at the Royal Adelaide Hospital. The parameters evaluated included patients' demographics, pre- and post-operative best corrected visual acuities, post-operative keratometry, and intra- and post-operative complications. There were 22 patients (23 eyes); 10 females and 12 males, with a mean age of 35 +/- 13 years (median, 33.5; range, 17-73). The median follow-up period was 13 months (range 7-38). In 89% (16/18) of eyes which underwent DLK, and in which a visual acuity could be obtained, a best corrected visual acuity of at least 6/12 was recorded. There were two episodes of Descemet's membrane perforation (8.7%), in which the procedure was converted to penetrating keratoplasty without complications. One patient developed a double anterior chamber, which resolved spontaneously without consequences. The visual outcomes and complication rates seen in our series are comparable to the recent published literature. Hence DLK can be considered as a suitable alternative to penetrating keratoplasty for the surgical treatment of KC.


Abandoned babies in the UK - a review utilizing media reports.
In the absence of national policy or comprehensive data, the phenomenon of abandoned babies is poorly understood in the UK. This study aims to use media reports as a resource to collate existing information on abandoned babies and to draw conclusions to inform future response. An exhaustive media search using electronic searches and media monitoring was undertaken to glean systematic information on all abandoned babies in the UK from 1998-2005. These were matched onto two databases - the UK Crime Statistics and the UK Abandoned Children Register in an attempt to align information on infant abandonment. Media reports were coded to list gender, survival, age, parental finding and circumstantial data. Our figures suggest an average of 16 babies abandoned yearly, while official sources give conflicting indications because of incomplete data gathering and child over-inclusion. Through systematic coding of media reports, 124 babies were identified over a 7-year period. Of these, 96 (77.4%) were newborns (<1 week old) and 28 (22.6%) were older babies (>1 week old). Adjusted logistic regression analysis found the strongest predictors of survival were age at abandonment and 'findability'. Newborn babies were less likely to survive than older babies (33.7% newborns died vs. 0% older babies, P < 0.0001). Babies left in a non-findable location (34%) had a 5.19 (2.06, 13.11) higher odds of death compared with those to be found. Most babies (74%) were abandoned outdoors and only 9.7% were left with a memento. Few mothers, almost exclusively those of older babies, were found (37.1%). Of those found, 92% were located within 3 days of abandoning their baby. Media interest is transient - 44.8% cases have a single report - and are typified by negative headlines (81.5%). This database currently represents the most accurate and comprehensive picture of the newborn abandonment phenomenon in the UK, a phenomenon that is rare but with high media and social interest. If the future well-being of mother and baby are to be catered for, clearer evidence-based policy and provision is vital.


Use of handgrip strength in the assessment of the muscle function of chronic kidney disease patients on dialysis: a systematic review.
Even though handgrip strength (HGS) is considered a simple and reliable method to evaluate muscle function and, indirectly, the nutritional status in clinical settings, there is still no consensus concerning its use in patients with chronic kidney disease (CKD) undergoing dialysis. This study presents a systematic review of the literature on the use of HGS as a parameter for nutritional assessment and a prognostic marker in patients on dialysis. The MEDLINE database (1966 to October 2009) was consulted for this systematic review by using the search terms hand strength or muscle strength dynamometer and dialysis. Eighteen articles were identified and included in the analysis. Similar to the general population, HGS values were associated with age and gender. The analysed studies showed correlation between muscle function estimated by HGS and variables used in the assessment of muscle mass and nutritional status, as well as the prediction of clinical complications. The analysis indicates that HGS is a useful tool for continuous and systematic assessment of muscle mass related to nutritional status in patients on dialysis. However, it is still necessary to standardize the techniques used for HGS, especially with respect to the position of measurement, the evaluation period, the choice of arm side and the diagnostic criterion.


From What to Why, the Growing Need for a Focus Shift Toward Explainability of AI in Digital Pathology.
While it is impossible to deny the performance gains achieved through the incorporation of deep learning (DL) and other artificial intelligence (AI)-based techniques in pathology, minimal work has been done to answer the crucial question of why these algorithms predict what they predict. Tracing back classification decisions to specific input features allows for the quick identification of model bias as well as providing additional information toward understanding underlying biological mechanisms. In digital pathology, increasing the explainability of AI models would have the largest and most immediate impact for the image classification task. In this review, we detail some considerations that should be made in order to develop models with a focus on explainability.


The development and testing of Thai facial soft tissue thickness data in three-dimensional computerized forensic facial reconstruction.
Forensic facial reconstruction is a useful tool to assist the public in recognizing human remains, leading to positive forensic investigation outcomes. To reproduce a virtual face, facial soft tissue thickness is one of the major guidelines to reach the accuracy and reliability for three-dimensional computerized facial reconstruction, a method that is making a significant contribution to improving forensic investigation and identification. This study aimed to develop a facial soft tissue thickness dataset for a Thai population, and test its reliability in the context of facial reconstruction. Three-dimensional facial reconstruction was conducted on four skulls (2 males and 2 females, with ages ranging between 51 to 60 years). Two main tools of three-dimensional computer animation and modeling software-Blender and Autodesk Maya-were used to rebuild the three-dimensional virtual face. The three-dimensional coordinate (x, y, z) cutaneous landmarks on the mesh templates were aligned homologous to the facial soft tissue thickness markers on the three-dimensional skull model. The final three-dimensional virtual face was compared to the target frontal photograph using face pool comparison. Four three-dimensional virtual faces were matched at low to moderate levels, ranging from 30% to 70% accuracy. These results demonstrate that the facial soft tissue thickness database of a Thai population applied in this study could be useful for three-dimensional computerized facial reconstruction purposes.


Customized 3D printed multi-drug systems: an effective and efficient approach to polypharmacy.
Combination therapies continue to improve therapeutic outcomes as currently achieved by polypharmacy. Since the introduction of the polypill, there has been a significant improvement in adherence and patient outcomes. However, the mass production of polypills presents a number of technical, formulation, and clinical challenges. The current one-size-fits-all approach ignores the unique clinical demands of patients, necessitating the adoption of a more versatile tool. That will be the novel, but not so novel, 3D printing. The present review investigates this promising paradigm shift from one medication for all, to customized medicines, providing an overview of the current state of 3D-printed multi-active pharmaceutical forms, techniques applied and printing materials. Details on cost implications, as well as potential limitations and challenges are also elaborated. 3D printing of multi-active systems, is not only beneficial but also essential. With growing interest in this field, a shift in manufacturing, prescribing, and administration patterns is, at this point, unavoidable. Addressing limitations and challenges, as well as data presentation on clinical trial results, will aid in the acceleration of this technology's implementation. However, it is clear that 3D printing is not the end of it, as evidenced by the emerging 4D printing technology.


Nitric Oxide in Arthritis
Although arthritis occurs in many different forms, loss of articular cartilage and joint inflammation are the predominant pathophysiological processes consistently present in this group of diseases. Depending upon the particular arthritide, these two pathologies may take place together or separately. Evidence is accumulating to suggest that NO is produced locally within human osteoarthritic and rheumatoid joints. The articular chondrocytes and, perhaps, infiltrating leukocytes appear to be the major intraarticular sources of NO. All published data agree that biosynthesis of NO increases in animal models of rheumatoid arthritis, and inhibitors of NO synthases show strong prophylactic, anti-inflammatory activity. However, one study suggests that therapeutic activity may be weak. Chondrocytes produce large amounts of NO after exposure to interleukin-1 (IL-1). In rabbit, human and rat, but not bovine, articular cartilage endogenously produced NO inhibits the biosynthesis of matrix proteoglycans. However, studies with bovine articular cartilage further indicate that NO partially protects proteoglycans from degradation in response to IL-1. These data encourage the notion that NO is involved in the pathophysiology of arthritis, but caution that this involvement may be complex.


Antibacterial and Antitubercular Activities of Cinnamylideneacetophenones.
Cinnamaldehyde is a natural product with broad spectrum of antibacterial activity. In this work, it was used as a template for design and synthesis of a series of 17 cinnamylideneacetophenones. Phenolic compounds 3 and 4 exhibited MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) values of 77.9 to 312 µM against Staphylococcus aureus, Streptococcus mutans, and Streptococcus sanguinis. Compounds 2, 7, 10, and 18 presented potent effects against Mycobacterium tuberculosis (57.2 µM ≤ MIC ≤ 70.9 µM). Hydrophilic effects caused by substituents on ring B increased antibacterial activity against Gram-positive species. Thus, log Po/w were calculated by using high-performance liquid chromatography-photodiode array detection (HPLC-PDA) analyses, and cinnamylideneacetophenones presented values ranging from 2.5 to 4.1. In addition, the effects of 3 and 4 were evaluated on pulmonary cells, indicating their moderate toxicity (46.3 µM ≤ IC50 ≤ 96.7 µM) when compared with doxorubicin. Bioactive compounds were subjected to in silico prediction of pharmacokinetic properties, and did not violate Lipinski's and Veber's rules, corroborating their potential bioavailability by an oral route.


Genetic contributions to rare childhood lung diseases.
Epidemiological studies have suggested that many rare diseases with respiratory involvement have a genetic component. Molecular advances have increased the understanding of the pathophysiology of these diseases which has led to better diagnostic and prognostic methods. There may be many genes responsible for diseases such as primary ciliary dyskinesia and systemic lupus erythematosus in addition to the effect of modifier genes. The genotype:phenotype correlation in these diseases remains to be elucidated. In some diseases, such as familial dysautonomia and sickle cell, the gene has been identified which allows for accurate pre-natal testing. Further, in diseases where the genetic abnormality is known, such as chronic granulomatous disease, gene therapy remains a realistic prospect and phase I studies are about to commence or currently underway. This article reviews those rare diseases in which there is or is likely to be a significant genetic contribution.


Site-Specific Differences in PD-1 Blockade Success and Biomarkers in Urothelial Carcinoma Treated with Pembrolizumab.
Since tumors in different human organs may have different tumor microenvironments, we evaluate time-course changes in all tumor locations after pembrolizumab treatment in urothelial carcinoma (UC) to examine the differences in efficacy of pembrolizumab per organ. Further, we uncover the usefulness of inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), CRP, and kinetics of these markers to predict pembrolizumab success and relation to overall survival (OS) in UC. A total of 115 cancerous lesions from 44 UC patients were measurable based on RECIST 1.1 criteria. The serum CRP and NLR levels were measured at baseline prior to pembrolizumab treatment and at least every 3 weeks just prior to pembrolizumab administration. Site-specific success (ie, patients with CR/PR/SD by RESIST 1.1) rates for pembrolizumab treatments were as follows: primary tumors: 67%, lymph node: 70%, lung: 44%, liver: 40%, and peritoneal metastasis: 56%. Focusing on the major metastasis sites, lymph nodes and lungs, we examined the relationships between NLR, CRP, or that kinetics and pembrolizumab success. In lymph nodes, both early NLR kinetics (P = .005) and CRP kinetics (P = .035) was a predictor for pembrolizumab success. On the other hand, none of 4 was not in lung metastases. Regarding to the mortality, the multivariate analysis revealed that early NLR kinetics was a prognostic biomarker for OS among the 4, independent of performance status and liver metastasis. We revealed that site-specific pembrolizumab success in UC. Early NLR kinetics was a predictor for lymph node pembrolizumab success and OS in our cohorts.


Neuronal differentiation modulates the dystrophin Dp71d binding to the nuclear matrix.
The function of dystrophin Dp71 in neuronal cells remains unknown. To approach this issue, we have selected the PC12 neuronal cell line. These cells express both a Dp71f cytoplasmic variant and a Dp71d nuclear isoform. In this study, we demonstrated by electron and confocal microscopy analyses of in situ nuclear matrices and Western blotting evaluation of cell extracts that Dp71d associates with the nuclear matrix. Interestingly, this binding is modulated during NGF-induced neuronal differentiation of PC12 cells with a twofold increment in the differentiated cells, compared to control cells. Also, distribution of Dp71d along the periphery of the nuclear matrix observed in the undifferentiated cells is replaced by intense fluorescent foci localized in the center of the nucleoskeletal structure. In summary, we revealed that Dp71d is a dynamic component of nuclear matrix that might participate in the nuclear modeling occurring during neuronal differentiation.


Cancer of appendix as a presenting feature of Crohn's disease.
Appendiceal neoplasms are rare. Colonic malignancies, including appendiceal carcinomas, have been rarely reported in Crohn's disease patients. The involvement of the appendix in Crohn's disease is not often seen. We report an interesting case in which a caecal Crohn's disease patient presented for the first time with an appendiceal adenocarcinoma.


Alcon LADARWave customcornea retreatments.
To present our experience performing wavefront-guided ablations for the treatment of residual refractive error following previous refractive surgery. Four different cases are presented-1) primary wavefront-guided LASIK; 2) wavefront-guided lift-flap LASIK retreatment; 3) wavefront-guided photorefractive keratectomy (PRK) retreatment; and 4) wavefront-guided PRK over radial keratotomy retreatment. All procedures were performed with the Alcon CustomCornea laser platform. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, and wavefront analysis (6.5-mm pupil) were performed preoperatively and 3 months after CustomCornea retreatment. The Alcon LADARWave device was used for wavefront measurements. Total lower order and higher order aberrations were decreased following wavefront-guided retreatment, resulting in improved quality of vision. The maximum target offset (+ 0.75 diopters) can be used to prevent an overcorrection of defocus (myopia) when treating a significant amount of spherical aberration. Wavefront-guided ablation was an effective treatment for residual lower and higher order aberrations following previous refractive surgery. Custom ablation treatment algorithms need to be developed specifically for retreatment procedures.


The segetal flora of Italy: an occurrence dataset from relevés in winter cereals and allied crop types.
The segetal flora of winter crops includes mostly native or archaeophyte annual species that are often strong specialists of their habitats. Threatened by the intensification of agriculture, segetal flora is particularly valuable from a perspective of biodiversity conservation and evolution. Moreover, it contributes to maintain biodiversity in agroecosystems and provides several ecosystem services. The dataset here described was set up to provide the first inventory of the segetal flora of Italian winter cereal crops and allied crop types, the latter including flax and autumn-sown legumes. It includes 24,676 georeferenced occurrence data deriving from 1,240 floristic and phytosociological relevés. The data were collected from the greater part of Italian territory, in a temporal range spanning from 1946 to 2018.


Is there a role for pneumonectomy in pulmonary metastases? International Registry of Lung Metastases.
Although sublobar and lobar resections are accepted operations for pulmonary metastases, pneumonectomy is viewed as a major incursion on Stage IV patients. We considered it important to ascertain the current results of pneumonectomy for pulmonary metastases since little information is available. Of the 5,206 patients with pulmonary metastasectomy reported by the International Registry of Lung Metastases, 133 (3%) underwent primary, and 38 (1%) completion pneumonectomy between 1962 and 1994. Data were analyzed to determine the operative mortality rates, survival rates, and determinants of survival. Primary pneumonectomy was performed for metastatic disease mainly from epithelial (49%, 65 of 133) and sarcomatous (33%, 43 of 133) tumors. Indications were central lesion, eg, proximal endobronchial or hilar nodal metastases. Operative mortality was 4% (4 of 112) and a 5-year survival rate of 20% was achieved following complete resection (R0) in 112 patients. In contrast, the 21 incompletely resected patients had an operative mortality rate of 19% (4 of 21), and the majority did not survive beyond 2 years (p = 0.02). Survival was determined by the completeness of resection and not histology of the primary tumor, number of metastases, nodal status, and disease-free interval. In the 38 completion pneumonectomy patients, 35 were operated for recurrent disease and 3 for residual disease. Sarcomatous secondaries predominated in 28 patients. Complete resection was achieved in 31 patients (82%). The operative mortality rate was 3% (1 of 38 patients) and the 5-year survival rate was 30%. Pneumonectomies for pulmonary metastases, albeit infrequently performed, were associated with acceptable operative mortality and long-term survival when performed in selected patients amenable to complete resection.


These may not be the courses you are seeking: a systematic review of open online courses in health professions education.
Open Online Courses (OOCs) are increasingly presented as a possible solution to the many challenges of higher education. However, there is currently little evidence available to support decisions around the use of OOCs in health professions education. The aim of this systematic review was to summarise the available evidence describing the features of OOCs in health professions education and to analyse their utility for decision-making using a self-developed framework consisting of point scores around effectiveness, learner experiences, feasibility, pedagogy and economics. Electronic searches of PubMed, Medline, Embase, PsychInfo and CINAHL were made up to April 2019 using keywords related to OOC variants and health professions. We accepted any type of full text English publication with no exclusions made on the basis of study quality. Data were extracted using a custom-developed, a priori critical analysis framework comprising themes relating to effectiveness, economics, pedagogy, acceptability and learner experience. 54 articles were included in the review and 46 were of the lowest levels of evidence, and most were offered by institutions based in the United States (n = 11) and United Kingdom (n = 6). Most studies provided insufficient course detail to make any confident claims about participant learning, although studies published from 2016 were more likely to include information around course aims and participant evaluation. In terms of the five categories identified for analysis, few studies provided sufficiently robust evidence to be used in formal decision making in undergraduate or postgraduate curricula. This review highlights a poor state of evidence to support or refute claims regarding the effectiveness of OOCs in health professions education. Health professions educators interested in developing courses of this nature should adopt a critical and cautious position regarding their adoption.


A pseudo-outbreak due to Acinetobacter species (GIM-1) contamination of the pneumatic transport system of a Large University Hospital.
To establish the source and contamination routes resulting in positive clinical and surveillance microbiological cultures with carbapenem-resistant, GIM-1 metallo-β-lactamase-positive Acinetobacter pitii and Acinetobacter radioresistens from 21 patients in 8 departments. Retrospective, descriptive study. A 1,300-bed tertiary care academic medical facility consisting of 90 buildings linked by a pneumatic transport system (PTS). Microbiological workup of the cluster strains included matrix-assisted laser desorption/ionization time-of-flight species identification, phenotypic carbapenemase tests, polymerase chain reaction-based genotyping of carbapenemase, and pulsed-field gel electrophoresis. Outbreak management procedures were employed according to institutional regulations. The rarity of GIM-1 Acinetobacter species in the hospital and region, the lack of epidemiological links between patients, and the fact that in some patients the apparent colonization was clearly nonnosocomial prompted the suspicion of a pseudo-outbreak. Numerous environmental cultures were positive for GIM-1-positive Acinetobacter (including archived sample requisition forms, PTS capsules, cultures from line-diverter and dispenser stations, and sterilized transport capsules following PTS delivery). Moreover, it was observed that condensation fluid from subterranean PTS tubing resulted in water entry in PTS capsules, possibly conferring specimen contamination. After extensive system disinfection, environmental surveys of the PTS were negative, and no further positive patient specimens were encountered. This is the first report of a PTS-associated pseudo-outbreak. The large number of falsely positive patient-related specimens in conjunction with the potential hazard of airborne and contact spread of multidrug-resistant microorganisms (in this case, GIM-1 carbapenem-resistant Acinetobacter species) underscores the need for implementation of infection control-based monitoring and operating procedures in a hospital PTS.


A Case of a Survivor of a Suicide Bomb Attack and Winnicott's "Survival of Destruction".
The author discusses Winnicott's concept of the use of an object, illustrating how it was used in the case of a woman who survived a suicide bomb attack that killed four people. The author as analyst extends Winnicott's and Ogden's ideas by demonstrating in his clinical work that the therapist must survive the patient's unconscious omnipotent belief that her love kills and must maintain his capacity for reverie. The therapist not only has to recover from the pain inflicted by the patient's demand for love, he must also change in response to the feeling of having been destroyed. In the case presented, in order for the process of survival to become real for the patient, the therapist had to discover about himself that he unconsciously shared a common reality with the patient-he, too, was experiencing features of a silenced survivor and experienced an identification with the oppressor.


Completely regioselective direct C-H functionalization of benzo[b]thiophenes using a simple heterogeneous catalyst.
The first completely selective C3 C-H arylation of benzo[b]thiophenes is reported, demonstrating previously unexploited reactivity of palladium. Benzo[b]thiophenes are coupled with readily available aryl chlorides using a ligand-free, dual catalytic system of heterogeneous Pd/C and CuCl. The reaction is operationally simple and insensitive to air and moisture, and it provides valuable products with complete selectivity. Significant investigations into the nature of the active catalytic species and mechanistic considerations are discussed.


Evaluation of bovine beta casein polymorphism in two dairy farms located in northern Italy.
Bovine beta casein A1 is one of the most common variants in dairy cattle breeds; it is considered a risk factor in milk intolerance and in other important human diseases, because of the bioactive peptide beta casomorphin-7 (BCM7) produced by raw or processed A1-milk, but not by A2-milk, during digestion. The aim of this study was to perform a cheap and rapid method to investigate beta casein polymorphism in copious animals. The study included 2 dairy farms with a totally of 1230 cows. Beta casein genotypes were estimated evaluating Exon 7 region of bovine beta casein gene (CSN2) by sequences analysis. In the population included in the study 5 variants (A1, A2, B, F, I) and 13 genotypes (A1A1, A1A2, A1B, A1F, A1I, A2A2, A2B, A2F, A2I, BB, BF, BI, FI) were detected. The method showed high sensibility and specificity, resulted low-cost and few time consuming.


Effect of Incubation Temperature on Antibiotic Resistance and Virulence Factors of Acinetobacter baumannii ATCC 17978.
Acinetobacter baumannii is a notorious opportunistic pathogen that is prevalent mainly in hospital settings. The ability of A. baumannii to adapt and to survive in a range of environments has been a key factor for its persistence and success as an opportunistic pathogen. In this study, we investigated the effect of temperature on the clinically relevant phenotypes displayed by A. baumannii at 37°C and 28°C. Surface-associated motility was significantly reduced at 28°C, while biofilm formation on plastic surfaces was increased at 28°C. Decreased susceptibility to aztreonam and increased susceptibility to trimethoprim-sulfamethoxazole were observed at 28°C. No differences in virulence, as assayed in a Galleria mellonella model, were observed. Proteomic analysis showed differential expression of 629 proteins, of which 366 were upregulated and 263 were downregulated at 28°C. Upregulation of the Csu and iron uptake proteins at 28°C was a key finding for understanding some of the phenotypes displayed by A. baumannii at 28°C.


Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans.
The family of small leucine-rich repeat proteins and proteoglycans (SLRPs) contains several extracellular matrix molecules that are structurally related by a protein core composed of leucine-rich repeats (LRRs) flanked by two conserved cysteine-rich regions. The small proteoglycan decorin is the archetypal SLRP. Decorin is present in a variety of connective tissues, typically "decorating" collagen fibrils, and is involved in important biological functions, including the regulation of the assembly of fibrillar collagens and modulation of cell adhesion. Several SLRPs are known to regulate collagen fibrillogenesis and there is evidence that they may share other biological functions. We have recently determined the crystal structure of the protein core of decorin, the first such determination of a member of the SLRP family. This structure has highlighted several correlations: (1) SLRPs have similar internal repeat structures; (2) SLRP molecules are far less curved than an early model of decorin based on the three-dimensional structure of ribonuclease inhibitor; (3) the N-terminal and C-terminal cysteine-rich regions are conserved capping motifs. Furthermore, the structure shows that decorin dimerizes through the concave surface of its LRR domain, which has been implicated previously in its interaction with collagen. We have established that both decorin and opticin, another SLRP, form stable dimers in solution. Conservation of residues involved in decorin dimerization suggests that the mode of dimerization for other SLRPs will be similar. Taken together these results suggest the need for reevaluation of currently accepted models of SLRP interaction with their ligands.


Design and analysis of annular antenna arrays with different reflectors.
The design and performance of annular antenna arrays with reflectors is presented. Arrays with three shapes of reflectors are analysed and simulated. These include the corner reflector, the circular reflector and the elliptical reflector. Power-density distributions within the annular arrays with and without reflectors are obtained by using the FDTD method. Also, the image theory method is used to verify the FDTD results in one case. By comparing the power-density distribution pattern of all four of the array designs (three with different reflectors, one without reflector), it is readily seen in each case that the array with reflectors yields better power-efficiency than the array without reflectors and the elliptical reflector yields the best performance. Comparisons of each array are made using 4, 6 and 8 antennae in the annular array. By using the optimized results of the elliptical reflector, the requirement for the input-power level to each antenna is greatly reduced.


Factuality levels of diagnoses in Swedish clinical text.
Different levels of knowledge certainty, or factuality levels, are expressed in clinical health record documentation. This information is currently not fully exploited, as the subtleties expressed in natural language cannot easily be machine analyzed. Extracting relevant information from knowledge-intensive resources such as electronic health records can be used for improving health care in general by e.g. building automated information access systems. We present an annotation model of six factuality levels linked to diagnoses in Swedish clinical assessments from an emergency ward. Our main findings are that overall agreement is fairly high (0.7/0.58 F-measure, 0.73/0.6 Cohen's κ, Intra/Inter). These distinctions are important for knowledge models, since only approx. 50% of the diagnoses are affirmed with certainty. Moreover, our results indicate that there are patterns inherent in the diagnosis expressions themselves conveying factuality levels, showing that certainty is not only dependent on context cues.


Thermal treatment of the minority game.
We study a cost function for the aggregate behavior of all the agents involved in the minority game (MG) or the bar attendance model (BAM). The cost function allows us to define a deterministic, synchronous dynamic that yields results that have the main relevant features than those of the probabilistic, sequential dynamics used for the MG or the BAM. We define a temperature through a Langevin approach in terms of the fluctuations of the average attendance. We prove that the cost function is an extensive quantity that can play the role of an internal energy of the many-agent system while the temperature so defined is an intensive parameter. We compare the results of the thermal perturbation to the deterministic dynamics and prove that they agree with those obtained with the MG or BAM in the limit of very low temperature.


'Priming' the brain to generate rapid upper-limb reactions.
Evoked autonomic nervous system (ANS) activity may be an important modulator of rapid reactions, generated in the face of urgency and may serve to augment the parallel somatosensory processing to adjust speed of processing. The primary objective of the current study was to temporally pair auditory stimuli with whole body perturbations to determine if conditioning could 'prime' the central nervous system (CNS) to respond faster and with greater ANS reactivity to the auditory stimulus alone. Healthy young participants (n = 19) were seated in a custom chair, which tilted backwards upon the release of an electromagnet and were instructed to reach to grasp a handle located in front of their arm as fast as possible following an auditory cue. Three conditions were completed in the following order: (1) baseline-auditory cue alone (5 trials); (2) paired-auditory cue, followed by a chair tilt 110 ms later (20 trials); and (3) post-pairing-auditory cue alone (5 trials). Participants were not informed of the switch from paired to auditory-only stimuli in the first trial of the post-pairing task condition. Reaction time was measured using electromyography, and autonomic nervous system activity was monitored via the electrodermal response (EDR). The first trial post-pairing had significantly faster reaction time (Δ = 21 ms) and significantly greater EDR amplitude compared to the last trial prior to pairing (baseline). The amplitude of contraction and overall time to handle contact were not significantly different between the first trial post-pairing and the last trial prior to pairing. This study demonstrates that the CNS can be 'primed' to generate rapid reactions and an elevated autonomic response in the absence of whole body instability. This indicates that afferent volume generated following whole body instability is not the only determinant of rapid reactions and emphasizes the importance of physiologic measures of autonomic activity with respect to stimulus-evoked reaction time.


Identification of Ser(1275) and Ser(1309) as autophosphorylation sites of the human insulin receptor in intact cells.
In a previous report we described Ser(1275) and Ser(1309) as autophosphorylation sites of the human insulin receptor (IR) tyrosine kinase (TK) in vitro. The question remained whether the observed phosphorylation was exclusive for the in vitro activated receptor or a more general, mechanism of the activated receptor in situ. In this study, we determined the intrinsic activity of the IR to phosphorylate both serine residues in intact cells. For this purpose CHO-09 and NIH-3T3 derived cell-lines expressing the human IR were metabolically labelled with [(32)P]orthophosphate, followed by hormone stimulation of the receptor. The IR was isolated by immunoprecipitation and SDS-PAGE and subsequently analysed for serine phosphorylation by phosphopeptide mapping of HPLC-purified tryptic phosphopeptides. Activation of the IR in the intact cell appeared to result in phosphate incorporation into Ser(1275) and Ser(1309), providing strong evidence that both serine residues are phosphorylation sites of the activated receptor in intact cells.


Parental coronavirus disease vaccine hesitancy for children in Bangladesh: a cross-sectional study.
Background: Coronavirus disease 2019 (COVID-19) requires mass immunization to control the severity of symptoms and global spread. Data from developed countries have shown a high prevalence of parental COVID-19 vaccine hesitancy. However, parental vaccine hesitancy data in low- and middle-income countries are scarce. This study aimed to assess the prevalence of parental vaccine hesitancy and identify subgroups with higher odds of vaccine hesitancy in parents in Bangladesh. Methods: A cross-sectional study was conducted on the parents of children aged <18 years from October 10, 2021 to October 31, 2021. Parents participated in face-to-face interviews in randomly selected locations in Bangladesh using a vaccine hesitancy questionnaire. Factors associated with COVID-19 vaccine hesitancy were identified using binary logistic regression analysis. Results: Data from 2,633 eligible parents were analyzed. Overall, 42.8% reported COVID-19 vaccine hesitancy for their youngest child. The final model suggested the following factors were associated with hesitancy: children's age; parent's age, religion, occupation, monthly household income, permanent address, living location, status of tobacco use, adherence with regular government vaccination programs (other than COVID-19), perceptions of COVID-19 vaccine efficacy among Bangladeshi children, self-vaccination intentions, reported family members' illness or death from COVID-19, and perceived threat of COVID-19 were the independent predictors of parental COVID-19 vaccine hesitancy. Conversely, participants who were not tobacco users, parents who were very likely to believe that their children or family members could be infected with COVID-19 in the following year and who were very concerned about their children or a family member contracting COVID-19 in the next year had significantly lower odds of COVID-19 vaccine hesitancy. Conclusions: Our study suggested that vaccine hesitation varied based on sociodemographic characteristics, religion, behavior, and perceived COVID-19 threat. Therefore, interventions focused on addressing vaccine hesitancy among specific subgroups are warranted.


Acute effect of physical exercise on serum insulin-like growth factor-binding protein 2 and 3 in healthy men: role of exercise-linked growth hormone secretion.
The purpose of this study was to delineate the role of GH on serum IGF-I, IGFBP-2 and -3 responses to exercise. Hormones were evaluated in six trained male subjects before (-30, -15, 0), during (+15) and after (+30, +45, + 60, +90 min) a thirty-minutes treadmill exercise (60% VO2max), both after a single administration of a somatostatin analog (i.e., octreotide, 0.1 mg sc) and after saline. The same evaluations were performed without exercise with similar treatments. The results showed that: 1) octreotide significantly inhibited the GH response to exercise, 2) exercise increased IGFBP-3 concentration (+37.4% at +90, p < 0.05), whereas no modification of IGFBP-2 and of IGF-I/ IGFBP-2 and IGFBP-3/IGFBP-2 ratios were observed, 3) octreotide amplified the IGFBP-3 increase after exercise (p < 0.01 vs. exercise, from + 30 to + 60, or octreotide alone) and, without exercise, slightly increased IGFBP-3 (+15% at +75, p < 0.05) and decreased IGF-I (-14.8% at +75, p < 0.01). We concluded that GH has a reduced role, as a stimulating factor, in the serum acute IGFBP-3 increase after exercise and that octreotide is probably able to directly amplify this response. Unfortunately, we can only speculate on the physiological pathways involved.


Formaldehyde (FA) interacts with biological molecules such as DNA and it induces DNA-protein cross-links (DPCs), oxidative stress, reactive oxygen species (ROS), methylation, chromosomal damage, fragmentation, and adducts of DNA, which are considered the most important genotoxic effects caused by exposure to FA. The purpose of this study was to evaluate the percentage of DNA fragmentation on lymphocytes and spermatozoa from Wistar rats exposed to different doses of FA. The results about the percentage of fragmentation of DNA in lymphocytes and spermatozoa, were statistical different from controlled group versus treated groups respectively to (p < 0.05). Pathological changes were observed in the seminiferous tubules, especially in rats exposed to 30 mg/kg of FA. This study provided additional evidence supporting that FA induces DNA strand breaks in both cells and therefore genotoxic damage in Wistar rats.