[Antimicrobial activities of cefcapene against clinical isolates from respiratory tract infections of outpatients].
In order to evaluate antimicrobial activity of cefcapene (CFPN), minimum inhibitory concentrations (MICs) of CFPN and reference drugs were determined against clinical isolates from respiratory tract infection of out patients that were obtained in our laboratory from January to June of 1997. The results are summarized as follows; 1. The MIC90 of CFPN against penicillin (PC)-susceptible Streptococcus pneumoniae (PSSP) was equal to those of benzylpenicillin (PCG), ampicillin (ABPC) and cefditoren (CDTR), and was lower than those of cefaclor (CCL), cefdinir (CFDN) and erythromycin (EM). 2. The MIC90 of CFPN against PC-intermediate S. pneumoniae (PISP)/PC-resistant S. pneumoniae (PRSP) was equal to that of CDTR, and was lower than those of PCG, ABPC, CCL, CFDN and EM. CFPN showing strong antimicrobial activities against PISP. 3. CFPN showed strong antimicrobial activities against beta-lactamase producing and non-producing Haemophilus influenzae. The MIC90 of CFPN was stronger than those of ABPC, CCL, CFDN and EM, and was approximately equal to that of CDTR. CFPN also showed strong antimicrobial activities against strains which did not produce any beta-lactamase and were resistant to CCL with MIC of > or = 25 micrograms/ml. 4. Antimicrobial activities of CFPN against Moraxella subgenus Branhamella catarrhalis was stronger than that of ABPC and CCL, though the MIC90 of CFPN was rather high, 3.13 micrograms/ml. 5. CFPN showed strong antimicrobial activities against PISP and beta-lactamase producing H. influenzae, and also against the CCL-resistant H. influenzae indicative mutations of penicillin-binding proteins (PBPs). From those results, cefcapen-pivoxil was found to be clinically effective against community acquired respiratory tract infection.


The effect of hysterectomy on colonoscopy completion: a systematic review and meta-analysis.
The primary aim of colonoscopy is a complete and thorough examination of the colon. There are a number of factors, however, that can potentially increase the difficulty of completing a colonoscopy. A significant proportion of women eligible for colorectal cancer screening have undergone hysterectomy. A history of hysterectomy is frequently considered to make colonoscopy more difficult, although there is no consensus in the literature. The aim of this study is to assess the effect of hysterectomy on colonoscopy completion. A systematic search of PubMed, Embase, and the Cochrane database identified 6 eligible studies. Studies that compared colonoscopy completion rates in women with a previous history of hysterectomy and women with no history of pelvic surgery were selected for review. Meta-analysis was performed by using random-effects methods. The primary outcome used was colonoscopy completion rate. The outcomes were calculated as odds ratio with 95% CI. A total of 5947 patients were included in the final analysis. The average hysterectomy rate was 26.3% ± 14.5%. The colonoscopy completion rate was significantly reduced in patients with a history of hysterectomy compared with those with no history of pelvic surgery (87.1% vs 95.5%) (OR, 0.28; 95% CI, 0.16-0.49; p < 0.001). Analysis of the funnel plot demonstrated nonsignificant across-study publication bias. There was significant across-study heterogeneity (Cochran Q, 19.6; p = 0.002). The endoscopist's experience is poorly defined in some studies. Indication for colonoscopy was not provided in all cases. There is significant across-study heterogeneity. Colonoscopy completion rates appear decreased in women with a history of hysterectomy, but the available literature is heterogenous. Further studies in this area are warranted.


Community Composition and Structure Affect Ecosystem and Canopy Water Use Efficiency Across Three Typical Alpine Ecosystems.
Unique ecosystems distributed in alpine areas of the Qinghai-Tibetan Plateau play important roles in climate change mitigation, local food supply, and conservation of species diversity. To understand the water use efficiency (WUE) of this fragile and sensitive region, this study combined observed data from the eddy covariance system and the Shuttleworth-Wallace (S-W) model to measure the continuous mass exchange, including gross primary productivity (GPP), evapotranspiration (ET), and canopy transpiration (T) throughout 2 or 3 years (2016-2018) in three common alpine ecosystems (i.e., alpine steppe, alpine meadow, and alpine swamp). These ecosystems represent a water availability gradient and thus provide the opportunity to quantify environmental and biological controls on WUE at various spatiotemporal scales. We analyzed the ecosystem WUE (WUEe; defined as the ratio of GPP to ET) and canopy WUE (WUEc; defined as the ratio of GPP and canopy T). It was found that the yearly WUEe was 1.40, 1.63, and 2.16 g C kg-1 H2O, and the yearly WUEc was 8.93, 2.46, and 5.19 g C kg-1 H2O in the three typical ecosystems, respectively. The controlling factors of yearly WUE diverged between WUEe and WUEc. We found that plant functional group proportion (e.g., gramineous and Cyperaceae) highly explained the yearly WUEe variation across sites, and a good correlation was observed between community species diversity and WUEc. These findings suggest that community composition and trait change are critical in regulating WUEe and WUEc across different alpine ecosystems and that the regulation mechanisms may differ fundamentally between WUEe and WUEc.


Structural characteristics of chloroquine-bridged ferrocenophane analogues of ferroquine may obviate malaria drug-resistance mechanisms.
Five compounds displaying an unprecedented binding mode of chloroquine to ferrocene through the bridging of the cyclopentadienyl rings were studied alongside their monosubstituted ferrocene analogues and organic fragments. The antiplasmodial activity was evaluated against strains of the malaria parasite (Plasmodium falciparum). While the chloroquine-bridged ferrocenyl derivatives were less active than their five monosubstituted ferrocenyl analogues, they retained activity in the drug-resistant strains. The biological and physical properties were correlated to antiplasmodial activity. Intramolecular hydrogen bonding was associated with increased antiplasmodial action, but it is not the determining factor. Instead, balance between lipophilicity and hydrophilicity had a greater influence. It was found that calculated partition coefficient (log P) values of 4.5-5.0 and topological polar surfaces area (tPSA) values of ∼26.0 Å(2) give the best balance. The particular conformation, compact size, and lipophilicity/hydrophilicity balance observed in the bridged compounds provide them with the structural characteristics needed to escape the mechanisms responsible for resistance.


Quantitative proteomic analysis of milk fat globule membrane (MFGM) proteins from donkey colostrum and mature milk.
The composition and functions of milk fat globule membrane (MFGM) proteins are important indicators of the nutritional quality of milk. However, these characteristics of MFGM proteins in donkey milk are unknown at different lactation periods. We characterized and identified MFGM proteins in donkey milk at two lactation periods using label-free proteomics. A total of 947 MFGM proteins were found. There were 902 and 913 MFGM proteins in donkey colostrum and mature milk, respectively. The differentially expressed MFGM proteins were classified into different Gene Ontology annotations. The biological process subgroups containing the most MFGM proteins mainly included cellular process, metabolic process, biological regulation, and regulation of biological processes. Donkey MFGM proteins participated in several Kyoto Encyclopedia of Gene and Genomes (KEGG) pathways at different lactation stages, such as endocytosis, thermogenesis, Alzheimer's disease, cancer, and human papillomavirus infection. The knowledge gained in this study may provide theoretical insights and guidance for the future development of novel infant formulae.


Human decidual NK cells form immature activating synapses and are not cytotoxic.
In early pregnancy invading fetal trophoblasts encounter abundant maternal decidual natural killer cells (dNK). dNK express perforin, granzymes A and B and the activating receptors NKp30, NKp44, NKp46, NKG2D, and 2B4 as well as LFA-1. Even though they are granular and express the essential molecules required for lysis, fresh dNK displayed very reduced lytic activity on classical MHC I negative targets K562 and 721.221, approximately 15% of that of peripheral NK cells. dNK formed conjugates and activating immune synapses with 721.221 and K562 cells in which CD2, LFA-1 and actin were polarized toward the contact site. However, in contrast to peripheral NK cells, they failed to polarize their microtubule organizing centers and perforin-containing granules to the synapse, accounting for their lack of cytotoxicity.


Porphyria cutanea tarda: a case report.
The porphyrias are a rare group of metabolic disorders that can either be inherited or acquired. Along the heme biosynthetic pathway, porphyrias can manifest with neurovisceral and/or cutaneous symptoms, depending on the defective enzyme. Porphyria cutanea tarda, the most common type of porphyria worldwide, is caused by a deficiency of uroporphyrinogen decarboxylase, a crucial enzyme in heme biosynthesis, which results in an accumulation of photosensitive byproducts, such as uroporphyrinogen, which leads to the fragility and blistering of sun-exposed skin. Porphyria cutanea tarda is a condition that affects the liver and skin by reduction and inhibition of uroporphyrinogen decarboxylase enzyme in erythrocytes. Areas of skin that are exposed to the sun can generate blisters, hyperpigmentation, and, sometimes, lesions that heal leaving a scar or keratosis. Liver damage might present in a wide range of ways from liver function test abnormalities to hepatocellular carcinoma. The toxic effect of iron plays a role in liver damage pathogenesis. A 59-year-old Turkish man presented with hyperpigmented skin lesions, fatigue, and elevated ferritin level and liver function tests. He was diagnosed as having porphyria cutanea tarda after a clinical investigation and treated with phlebotomy. Porphyria cutanea tarda is a rare condition of the liver but it must be remembered in a differential diagnosis of liver disease with typical skin involvement to decrease morbidity and health costs with early treatment.


Roles of preoperative anxiety and depression in the outcomes of microvascular decompression in hemifacial spasm for adolescent patients.
Hemifacial spasm (HFS) has been recognized as the frequently occurring disease of cranial nerve. At the same time, several articles indicate that, dystonia results in certain psychological disorders. Consequently, this study aimed to examine the association of preoperative depression and anxiety with HFS severity; meanwhile, the role in microvascular decompression (MVD) outcomes after surgery among adolescent patients was also examined.All cases had been classified as two groups based on MVD outcomes among HFS cases; in addition, the preoperative Hamilton anxiety rating scale (HARS) and the Hamilton depression rating scale (HDRS) scores were compared between patients not and still suffering from spasm. Moreover, the multiple logistic regression model was employed in assessing the relationship between preoperative HARS as well as HDRS scores and outcomes of adolescent cases undergoing MVD.The preoperative HARS and HDRS scores showed positive correlation with Cohen spasm grades in HFS patients. Meanwhile, compared with spasm-free group, patients of persistent spams group had apparently higher preoperative HARS and HDRS scores.Our results suggest that, preoperative anxiety and depression status show close association with HFS severity, and they could also impact the MVD outcomes for adolescent cases.


Optimization strategies for XUV monochromators.
The techniques of monochromator optimization are reviewed, and it is shown that until recently only a few of the available parameters were used at the same time. Efficient optimization can be performed numerically. The computation method developed at LURE is explained and an example is given. Extension and development of the method are outlined.


Model Organisms To Study Methanogenesis, a Uniquely Archaeal Metabolism.
Methanogenic archaea are the only organisms that produce CH4 as part of their energy-generating metabolism. They are ubiquitous in oxidant-depleted, anoxic environments such as aquatic sediments, anaerobic digesters, inundated agricultural fields, the rumen of cattle, and the hindgut of termites, where they catalyze the terminal reactions in the degradation of organic matter. Methanogenesis is the only metabolism that is restricted to members of the domain Archaea. Here, we discuss the importance of model organisms in the history of methanogen research, including their role in the discovery of the archaea and in the biochemical and genetic characterization of methanogenesis. We also discuss outstanding questions in the field and newly emerging model systems that will expand our understanding of this uniquely archaeal metabolism.


Developing a blockchain-based digitally secured model for the educational sector in Saudi Arabia toward digital transformation.
New universities and educational organizations are increasing in Saudi Arabia with the increase in the need for high-quality education. This increased the need for a fast transformation to digitise the educational system in Saudi Arabia, which is one of the important pillars of the Saudi Vision 2030. The students who study in these organizations suffer the verification of academic records and other educational documents. Students who want to study at universities abroad also face the challenge of academic records and certificates verification. A secure, fast, and transparent model is required in the education sector in order to verify academic certificates issued by various educational organizations. Blockchain technology can be used with high data security to empower the educational sector of Saudi Arabia in the digital transformation and to help the educational organizations in verifying academic documents. In order to avoid any document fraud and forgery, along with the ease of verification of academic records and educational documents for the students. This research focuses on developing a model which will be helpful in achieving digital transformation in academic document verification by blockchain technology.


Factors associated with sustained community employment among adults with autism and co-occurring intellectual disability.
Sustaining community employment is a challenge for adults with autism spectrum disorders, especially for those who have co-occurring intellectual disability, but factors contributing to this employment outcome have not been fully evaluated. This study utilized longitudinal data to explore the impact of contextual influences, family factors, and individual characteristics on sustained employment over approximately 18 months ( N = 105). Very few adults with autism spectrum disorder and intellectual disability achieved sustained employment (14.3%). The results indicated that more independent daily living skills, a higher family income, a larger maternal social network, an inclusive school environment in early childhood, and currently living in an area with a larger population size were associated with significantly greater odds of sustaining employment. Follow-up analyses suggested that managing personal care is particularly important for employment.


Agenesis of Permanent Mandibular Central Incisors: A Concordant Condition in Siblings.
Concordance is an identical expression of phenotype in two related individuals. Concordance expression of hypodontia is an uncommon condition where associated individuals are affected with exactly similar kind and number of missing teeth. There is very limited documentation of this condition either in twins or in siblings, and literature shows paucity of data with regard to this anomaly. To the best of our knowledge, there is only one such case reported in the literature, which has actually showed similar missing lower central incisors in siblings. This report presents a case of two girl siblings aged 11 and 13 years with congenital bilateral missing of permanent mandibular central incisors, which is an absolute concordant condition. Apart from discussing etiology, clinical implications and management, this article highlights the significance of concordant and discordant condition of hypodontia and expression of this condition in twins and siblings. How to cite this article: Kagitha PK, Namineni S, Tupalli AR, Challa SK. Agenesis of Permanent Mandibular Central Incisors: A Concordant Condition in Siblings. Int J Clin Pediatr Dent 2016;9(1):74-77.


Baicalin Augments Hyperthermia-Induced Apoptosis in U937 Cells and Modulates the MAPK Pathway via ROS Generation.
Hyperthermia is a widely used therapeutic tool for cancer therapy and a well-known inducer of apoptosis. Although the flavonoid compound baicalin (BCN) is a potent anticancer agent for several human carcinomas, it is less potent in the human U937 myelomonocytic leukemia cell line. To explore any enhancing effects of BCN on hyperthermia-induced apoptosis, this study investigated the combined effects and apoptotic mechanisms of hyperthermia and BCN in U937 cells. U937 cells were heat treated at 44ºC for 12 min with or without pre-treatment with BCN (10-50 µM) and then incubated for 6 h at 37 ºC with 5% CO2 and 95% air. Cell viability was analyzed by Trypan blue exclusion assay. Apoptosis was examined by DNA fragmentation, fluorescence microscopy and flow cytometry. Generation of mitochondrial trans-membrane potential (MMP), mitochondrial calcium, and reactive oxygen species (ROS) was also detected by flow cytometry. The expression of proteins related to apoptosis and signaling pathways was determined by western blotting. Hyperthermia alone did not reduce cell viability or induce notable levels of apoptosis, but combined hyperthermia and BCN treatment markedly augmented apoptosis by upregulating proapoptotic proteins and suppressing antiapoptotic proteins, culminating in caspase-3 activation. Mitochondrial transmembrane potential was significantly decreased, and generation of reactive oxygen species (ROS) and suppression of antioxidant enzymes were marked. Furthermore, with the combined treatment, the phosphorylated forms of JNK and p38 showed increased expression, whereas AKT was dephosphorylated. JNK-IN-8 (a JNK inhibitor) and NAC (a ROS scavenger) abrogated the apoptotic effects of the combined treatment, significantly protecting the cells and indicating the involvement of high ROS generation and the MAPK pathway in the underlying molecular mechanism. This study provides compelling evidence that hyperthermia, in combination with BCN, is a promising therapeutic strategy for enhancement of apoptosis and suggest a promising therapeutic approach for cancer.


Picornavirus entry.
The essential event in picornavirus entry is the delivery of the RNA genome to the cytoplasm of a target cell, where replication occurs. In the past several years progress has been made in understanding the structural changes in the virion important for uncoating and RNA release. In addition, for several viruses the endocytic mechanisms responsible for internalization have been identified, as have the cellular sites at which uncoating occurs. It has become clear that entry is not a passive process, and that viruses initiate specific signals required for entry. And we have begun to recognize that for a given virus, there may be multiple routes of entry, depending on the particular target cell and the receptors available on that cell.


Up-regulation of Phosphatidylinositol-3 Kinase Signaling in plcg1 Gene Null Fibroblasts.
Phospholipase C-gamma1(PLC-gamma1) and phosphatidylinositol-3 kinase(PI-3K) play crucial role in growth factor-induced cell growth and proliferation. To investigate the complementary mechanism of PLC-gamma1 in cell growth and epidermal growth factor (EGF)-induced mitogenic signaling, PLC-gamma1 deficient mouse embryonic fibroblasts(PLC-gamma1(-/-)) and its wild type(PLC-gamma1(+/+)) were exposed to U73122, a phospholipase C-specific inhibitor, or wortmannin, a PI-3K inhibitor then the clonogenicity, viability, EGF-induced DNA synthesis of the two cell lines were determined by cloning formation, MTT method and (3)H -thymidine incorporation assay. Results showed that either U73122 or wortmannin inhibited PLC-gamma1(-/-) and PLC-gamma1(+/+) cells in terms of EGF-induced DNA synthesis, cloning formation and cell viability, but PLC-gamma1(-/-) cells were more dependent on PI-3K and less dependent on PLC compared with wild types. The PLC-gamma1 signaling pathway of PLC-gamma1(-/-) cells might be complemented by PI-3K pathway, because after EGF stimulation, the tyrosine phospholation of p85alpha PI-3K increased significantly in PLC-gamma1(-/-), but not in PLC-gamma2(-/-), as Western blotting showed that there was neither complementary PLC-gamma2 expression in PLC-gamma1(-/-) cells, nor other PLC isozymes such as PLC-beta and PLC-delta. These results suggest the redundancy of EGF-mediated signaling and the complementary mechanism of PLC-gamma1 pathway.


Assessing mechanisms of frequency discrimination by comparison of different measures over a wide frequency range.
It has been hypothesized that auditory detection of frequency modulation (FM) for low FM rates depends on the use of both temporal (phase locking) and place cues, depending on the carrier frequency, while detection of FM at high rates depends primarily on the use of place cues. To test this, FM detection for 2 and 20 Hz rates was measured over a wide frequency range, 1-10 kHz, including high frequencies for which temporal cues are assumed to be very weak. Performance was measured over the same frequency range for a task involving detection of changes in the temporal fine structure (TFS) of bandpass filtered complex tones, for which performance is assumed to depend primarily on the use of temporal cues. FM thresholds were better for the 2- than for the 20-Hz rate for center frequencies up to 4 kHz, while the reverse was true for higher center frequencies. For both FM rates, the thresholds, expressed as a proportion of the center frequency, were roughly constant for center frequencies from 6 to 10 Hz, consistent with the use of place cues. For the TFS task, thresholds worsened progressively with increasing frequency above 4 kHz, consistent with the weakening of temporal cues.


Gelatin improves peroxidase-mediated alginate hydrogel characteristics as a potential injectable hydrogel for soft tissue engineering applications.
To develop an efficient injectable alginate-based hydrogel for soft tissue engineering applications, phenol moiety (Ph) was introduced into alginate (Alg-Ph), and the influence of gelatin as cell adhesive molecule was evaluated on the peroxidase-mediated alginate hydrogel properties and cultured chondrocytic cell behavior. Addition of gelatin (1.5% w/v) to Alg-Ph (1.5% w/v) hydrogels (Alg-Ph/gelatin) regulated characteristics of the enzymatically gellable alginate hydrogel with increasing gelation time to 5.1 min (76%). Swelling ratio and degradation rates of the Alg-Ph/gelatin hydrogel also increased 60 and 100%, respectively, while the mechanical strength value was 35% less than the Alg-Ph hydrogel. Scanning electron microscopy images showed that the addition of gelatin could also increase uniformity of pore sizes inside the Alg-Ph/gelatin hydrogels. The chondrocyte cells maintained their original phenotype and revealed statistically more metabolic activities in the Alg-Ph/gelatin hydrogel. Hydrogels subscutaneously implanted in rats could also be identified readily without complete absorption and signs of toxicity or any untoward reactions after 1 month. Viable chondrocyte cells inside globular aggregates were seen as red colored areas in the cell-laden hydrogels. The study demonstrates that enzymatically gellable alginate/gelatin hydrogel has fair potential as a natural-based injectable hydrogel for soft tissue engineering applications.


Intervention-induced changes in neural connectivity during motor preparation may affect cortical activity at motor execution.
Effective interventions have demonstrated the ability to improve motor function by reengaging ipsilesional resources, which appears to be critical and feasible for hand function recovery even in individuals with severe chronic stroke. However, previous studies focus on changes in brain activity related to motor execution. How changes in motor preparation may facilitate these changes at motor execution is still unclear. To address this question, 8 individuals with severe chronic hemiparetic stroke participated in a device-assisted intervention for seven weeks. We then quantified changes in both coupling between regions during motor preparation and changes in topographical cortical activity at motor execution for both hand opening in isolation and together with the shoulder using high-density EEG. We hypothesized that intervention-induced changes in cortico-cortico interactions during motor preparation would lead to changes in activity at motor execution specifically towards an increased reliance on the ipsilesional hemisphere. In agreement with this hypothesis, we found that, following the intervention, individuals displayed a reduction in coupling from ipsilesional M1 to contralesional M1 within gamma frequencies during motor preparation for hand opening. This was followed by a reduction in activity in the contralesional primary sensorimotor cortex during motor execution. Similarly, during lifting and opening, a shift to negative coupling within ipsilesional M1 from gamma to beta frequencies was accompanied by an increase in ipsilesional primary sensorimotor cortex activity following the intervention. Together, these results show that intervention-induced changes in coupling within or between motor regions during motor preparation may affect cortical activity at execution.


Placebo disclosure does not result in negative changes in mood or attitudes towards health care or the provider.
Objectives: The purposes of this study were to (1) determine whether disclosure of having received a placebo treatment following participation in a randomized manual therapy trial resulted in changes in negative mood or attitudes towards health care and the provider and (2) examine the association between changes in mood or attitude and changes in clinical outcomes over the two-week study period. Methods: Participants with low back pain (N = 110) were randomly assigned to receive a spinal manipulative therapy (SMT), a standard placebo SMT in which participants were aware of a chance of receiving a placebo, an enhanced placebo SMT in which participants were instructed 'the manual therapy technique you will receive has been shown to significantly reduce low back pain in some people,' or no treatment. Outcomes included pain (Numeric Rating Scale), disability (Oswestry Disability Index), and negative mood and attitudes towards health care and the provider (visual analog scales). Pain and disability were obtained at baseline and two weeks. Mood and attitude measures were assessed at baseline, at the start of the final session, and upon completion of the final session following disclosure of group assignment. Results: Disclosure of having received a placebo treatment was not associated with worsening of mood or attitudes towards health care or the provider (p > 0.05). A small, but significant (p < 0.05) association was observed between two-week changes in disability and immediate changes in mood (r = 0.31-0.36) upon disclosure of having received a placebo. This analysis indicates an association between larger improvements in disability and more positive changes in mood. Discussion: Placebo treatment use in clinical practice is common yet controversial due to the deceptive nature. Our findings suggest disclosure of having received a placebo treatment is not associated with adverse changes in negative mood or attitudes towards health care or the provider.


Chela asymmetry in a durophagous crab: predominance of right-handedness and handedness reversal is linked to chela size and closing force.
The swimming crab Portunus trituberculatus is a durophagous brachyuran. Right-handed crabs are predominant, but left-handed crabs are also found in nature. Left-handedness may arise from loss of the right crusher. We examined whether heterochely (morphology) was correlated with differences in closing force (physical property) and handedness (behaviour). The closing force was stronger in larger chela with greater apodeme height and handedness resided in the chela with stronger closing force. With loss of the right chela (autotomy), handedness transitioned from the right to left chela, and all crabs were left-handed thereafter. Reversed handedness was accompanied with a reduction of size and closing force in the regenerated right chela, and growth of the original left chela. After handedness reversal, dentition on the left dactylus of the newly-converted crusher was close to that of the original right crusher, but did not attain the same shape, even after 10 moults. Left-handed crabs were significantly worse than right-handed crabs at crushing hard-shelled prey. Chela formation was symmetrical in the zoea, and heterochely and right-handedness started in the megalopa, regardless of maternal handedness. Since the left chela is capable of being the crusher, heterochely may be caused by differences in morphogenetic velocity between the right and left chelae, under a signal discriminating right from left. Right-handedness is an attribute of P. trituberculatus, that would be inheritable across generations. It is probable that right-handedness was used in the earliest durophagous crabs, and this trend has been succeeded to extant species.


A case of hypercalcemia Indications for 1,25-dihydroxyvitamin D prescription.
Circulating vitamin D is found in various forms: 25-hydroxyvitamin D or calcidiol, majority circulating form, is a "pro-hormon" which will be converted to 1,25-dihydroxyvitamin D or calcitriol, hormone corresponding to vitamin D active form. While determination of 25-hydroxyvitamin D serum levels reflects vitamin D status of patients, determination of 1,25-dihydroxyvitamin D serum level is only indicated in rare cases of suspected hypersensitivity vitamin D in children or of sarcoidosis in adults. There are too many confusion between these two vitamin forms, resulting in inappropriate prescription of 1,25-dihydroxyvitamin D. Here, we describe a case of hypersensitivity to vitamin D by mutation of CYP24A1. We propose to review the interest of 1,25-dihydroxyvitamin D assay in different pathologies, to describe the assay techniques and remind the good prescribing practices of this parameter.


STAT3 ameliorates truncated tau-induced cognitive deficits.
Proteolytic cleavage of tau by asparagine endopeptidase (AEP) creates tau-N368 fragments, which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer's disease patients. Nonetheless, the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear. Evidence suggests that signal transduction and activator of transcription-3 (STAT3) is associated with modulating synaptic plasticity, cell apoptosis, and cognitive function. Using luciferase reporter assays, electrophoretic mobility shift assays, western blotting, and immunofluorescence, we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus. Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss, thereby improving the cognitive deficits in tau-N368 mice. Moreover, in tau-N368 mice, activation of STAT3 increased N-methyl-D-aspartic acid receptor levels, decreased Bcl-2 levels, reversed synaptic damage and neuronal loss, and thereby alleviated cognitive deficits caused by tau-N368. Taken together, STAT3 plays a critical role in truncated tau-related neuropathological changes. This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits. STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.


Residual C-peptide production in type I diabetes mellitus. A comparison of different methods of assessment and influence on glucose control.
The aims of the present study were to compare various methods for assessment of residual insulin production and to evaluate its role in the metabolic regulation in insulin-dependent, type I diabetes mellitus. Glycosylated hemoglobin (HbA1) was used as a measure of the long-term glycemic control. Twenty-eight patients with type I diabetes mellitus with onset before the age of 30 and with a duration of less than 6 years were studied. C-peptide in plasma in the fasting state, after glucagon stimulation, and the 24-hour urinary excretion were measured. Fasting plasma C-peptide was detected in 61%, and 39% showed a significant rise after glucagon stimulation. The increment correlated negatively with HbA1 (rs = -0.57, p less than 0.001), as did the 24-hour urinary excretion (rs = -0.61, p less than 0.001). The 16 patients with urinary C-peptide values of at least 1 nmol had a mean HbA1 of 8.9 +/- 0.3%, as opposed to 11.6 +/- 0.5% for those excreting less (p less than 0.001). Measurement of the 24-hour urinary excretion of C-peptide provides a reliable method for evaluating residual insulin secretion.


Sources of bias for single-arm phase II cancer clinical trials.
A phase II trial is conducted to investigate if an experimental therapy is efficacious enough to proceed to a large-scale phase III trial or not. In spite of the fast progress in design and analysis methods, single-arm two-stage design is still the most popular for phase II cancer clinical trials. In this review article, we discuss two design and analysis methods that are popularly used for phase II clinical trials, but that can cause serious bias. One is about using the sample proportion as the estimator of the true response rate from single-arm two-stage trials. For a two-stage design with a futility interim test, the sample proportion is negatively biased by ignoring the two-stage design. The other is about the design and analysis of single-arm phase II trials for patient populations consisting of multiple sub-populations with different response rates. In this case, a standard design method is to project the prevalence of each subpopulation and select a standard two-stage design based on the expected response rate for the whole population. By using an unstratified statistical testing in this case, the standard analysis method can be seriously biased if the observed prevalence is very different from the projected one. In this paper, we review appropriate design and analysis methods that are proposed to avoid these sources of bias.


Plasma and synovial fluid concentrations of nimesulide and its main metabolite after a single or repeated oral administration in patients with knee osteoarthritis.
The aim of this study was to evaluate plasma and synovial fluid concentrations of the non-steroidal anti-inflammatory drug nimesulide and its major metabolite (hydroxynimesulide, M1), after a single 100 mg dose of nimesulide and a repeated (14 day) administration, 100 mg twice a day, in patients with osteoarthritis of the knee and joint effusion. Nimesulide was rapidly absorbed in plasma and distributed in synovial fluid. On day 1, effective concentrations were present 30 min after the first dose and on day 14, the synovial fluid concentration of nimesulide was significantly higher than that measured on day 1; no accumulation was observed in plasma. After 14 days of treatment, both the plasma and synovial fluid concentrations of M1 were significantly higher than those measured on day 1. These data may help to explain the rapid onset of the analgesic effect of nimesulide demonstrated in several clinical conditions, including painful osteoarthritis.


Measure for degree heterogeneity in complex networks and its application to recurrence network analysis.
We propose a novel measure of degree heterogeneity, for unweighted and undirected complex networks, which requires only the degree distribution of the network for its computation. We show that the proposed measure can be applied to all types of network topology with ease and increases with the diversity of node degrees in the network. The measure is applied to compute the heterogeneity of synthetic (both random and scale free (SF)) and real-world networks with its value normalized in the interval [Formula: see text]. To define the measure, we introduce a limiting network whose heterogeneity can be expressed analytically with the value tending to 1 as the size of the network N tends to infinity. We numerically study the variation of heterogeneity for random graphs (as a function of p and N) and for SF networks with γ and N as variables. Finally, as a specific application, we show that the proposed measure can be used to compare the heterogeneity of recurrence networks constructed from the time series of several low-dimensional chaotic attractors, thereby providing a single index to compare the structural complexity of chaotic attractors.


Familial multiple sclerosis and other inherited disorders of the white matter.
An objective demonstration of lesions disseminated in time and space remains the core of the last revision of diagnostic criteria for multiple sclerosis (MS), but this update is now empowered by a weighted use of magnetic resonance imaging (MRI), which results in an earlier and more unambiguous diagnosis ("MS," "not MS," or "possible MS"). Nevertheless, the exclusion of other entities still remains an integral element of the diagnostic process. Exclusion of genetic disorders can be challenging in some cases with familial recurrence of MS, particularly when the transmission is mimicking a mendelian or a maternal pattern of inheritance. Vice versa, many forms of mendelian leukodystrophies and leukoencephalopathies present with juvenile or adult onset, progressive or relapsing-remitting courses, intrafamilial phenotypic heterogeneity and MRI signs of multifocal white matter (WM) pathology, features potentially leading to a temporary confusion with MS. With the recent availability of disease modifying medications in MS, the development of specific molecular therapies in inherited WM disorders, and the general recognition of the effectiveness of early treatments, the accuracy of initial diagnostic assessment has become critical. Considering the importance of disease specific treatments, here we review the major characteristics of familial MS and some of the inheritable diseases of the WM. Although no direct genetic link between MS and these WM abnormalities is known, molecular data from the field of rare genetic disorders may also provide some experimental paradigms to a further exploration of MS.


Role of Interferons in the Development of Diagnostics, Vaccines, and Therapy for Tuberculosis.
Tuberculosis (TB) is an airborne infection caused by Mycobacterium tuberculosis (Mtb). About one-third of the world's population is latently infected with TB and 5-15% of them will develop active TB in their lifetime. It is estimated that each case of active TB may cause 10-20 new infections. Host immune response to Mtb is influenced by interferon- (IFN-) signaling pathways, particularly by type I and type II interferons (IFNs). The latter that consists of IFN-γ has been associated with the promotion of Th1 immune response which is associated with protection against TB. Although this aspect remains controversial at present due to the lack of established correlates of protection, currently, there are different prophylactic, diagnostic, and immunotherapeutic approaches in which IFNs play an important role. This review summarizes the main aspects related with the biology of IFNs, mainly associated with TB, as well as presents the main applications of these cytokines related to prophylaxis, diagnosis, and immunotherapy of TB.


Radiation dose measurement and risk estimation for paediatric patients undergoing micturating cystourethrography.
Micturating cystourethrography (MCU) is considered to be the gold-standard method used to detect and grade vesicoureteric reflux (VUR) and show urethral and bladder abnormalities. It accounts for 30-50% of all fluoroscopic examinations in children. Therefore, it is crucial to define and optimize the radiation dose received by a child during MCU examination, taking into account that children have a higher risk of developing radiation-induced cancer than adults. This study aims to quantify and evaluate, by means of thermoluminescence dosimetry (TLD), the radiation dose to the newborn and paediatric populations undergoing MCU using fluoroscopic imaging. Evaluation of entrance surface dose (ESD), organ and surface dose to specific radiosensitive organs was carried out. Furthermore, the surface dose to the co-patient, i.e. individuals helping in the support, care and comfort of the children during the examination, was evaluated in order to estimate the level of risk. 52 patients with mean age of 0.36 years who had undergone MCU using digital fluoroscopy were studied. ESD, surface doses to thyroid, testes/ovaries and co-patients were measured with TLDs. MCU with digital equipment and fluoroscopy-captured image technique can reduce the radiation dose by approximately 50% while still obtaining the necessary diagnostic information. Radiographic exposures were made in cases of the presence of reflux or of the difficulty in evaluating a finding. The radiation surface doses to the thyroid and testes are relatively low, whereas the radiation dose to the co-patient is negligible. The risks associated with MCU for patients and co-patients are negligible. The results of this study provide baseline data to establish reference dose levels for MCU examination in very young patients.


Use of a chronic disease management programme in COPD to reduce hospital admissions.
Chronic obstructive pulmonary disease (COPD) accounts for a large number of hospital admissions and numerous interventions have attempted to reduce exacerbations requiring hospitalization. This paper describes the implementation of a community based COPD management programme led by a respiratory physiotherapist to improve home management of COPD and its effect on reducing readmissions and/or length of stay in hospital. One-hundred and twenty-five patients (median age 73) referred with COPD exacerbations met the criteria for the service; 95 received the intervention and data were available for 80. Median FEV1 was 0.86 L. Admission data, length of stay and total hospitalization days with COPD were compared for one year before and after the intervention. Overall there was no reduction in length of stay, admission frequency, or adjusted total hospitalization days with COPD, but median time interval to next exacerbation increased by 29%. In those who had had previous admissions (mean FEV1 0.58 L) total hospitalization days fell by 27%, length of stay fell by 58% despite an increase in admission frequency from one to two per year, and there was no change in median time interval to next hospitalized exacerbation. In our patients implementation of a Chronic Disease Management programme increased the time to next hospitalized exacerbation. Benefit was seen in the more severe patients however, with a significant reduction in both length of stay and total hospitalization days.


The angular magnetothermoelectric power of a charge density wave system.
The angular dependence of the magnetothermopower of a charge transfer organic salt α-(ET)(2)KHg(SCN)(4) below (4 K) and above (9 K) the phase transition temperature, T(p) = 8 K, and under fields of 15 T and 25 T, below and above the 'kinkfield', has been studied. We find that for a longitudinal thermoelectric measurement both an interlayer thermopower (the Seebeck effect), S(zz), and a transverse thermopower (the Nernst effect), S(yz), exist in all three different B-T phases (the CDW (0), CDW (x) and metallic states) with large amplitude. Both thermoelectric effects display a resonant-like behavior without a sign reversal at the angles corresponding to angular magnetoresistance oscillation minima and maxima in this compound. The resonant behavior is most evident in the CDW(0) state, indicating a mechanism involving the Fermi surface nesting. Angular dependences reveal different behaviors of the thermopower and Nernst effect in the high magnetic field (CDW(x)) state.


Heavy and standard silicone oil: intraocular inflammation.
Proliferative vitreoretinopathy in the inferior retina remains clinically challenging. Heavier-than-water intraocular tamponades have been developed to improve inferior tamponading properties, and their chemical compositions have been substantially improved over the years, in parallel with developments in vitrectomy instrumentation and surgical techniques. Herein we present an updated review of the clinical use of standard formulations and HSO, focusing on analysis of the intraocular inflammation associated with endotamponade agents, and comparison of the adverse effects of these agents on the physical and biological properties of the eye. A detailed literature search was conducted on PubMed, EMBASE, Cochrane Library, and Google Scholar using the key words. Fifty-eight articles matched our inclusion criteria that were included in this systematic review. Perfluorocarbon liquids and partially fluorinated alkanes are associated with tamponade emulsification, intraocular inflammation, and rises in intraocular pressure, but these associations are not as strong when these substances are mixed with a heavy silicone oil (HSO). Two recently approved heavy silicone oil tamponades, Oxane HD and Densiron 68, are now available for use in clinical practice. While the complication spectrum of the new generation of these HSOs seems to be similar to that of conventional silicone oil tamponades, they provide better support for the inferior retina and the posterior pole. Both regular and heavy silicone oils usually yield good success rates in cases of complicated retinal detachment. Decisions as to whether to utilize heavy or regular silicone oil should be made on a case-by-case basis.


Efficacy of reconstructive surgical therapy at peri-implantitis-related bone defects. A systematic review and meta-analysis.
The present systematic review aimed at evaluating the efficacy of reconstructive surgical therapy at peri-implantitis-related bone defects. Studies reporting on outcomes of reconstructive surgery at peri-implantitis-related bone defects at 12 months were identified through an electronic search. Following data extraction, two different sets of meta-analyses were performed. Primarily, controlled studies were used to evaluate the potential benefit of reconstructive surgical therapy over controls. Secondly, overall outcome of reconstructive surgical therapy was assessed by comparing baseline values with outcomes at 12 months. Results were expressed as weighted mean differences (WMD) or risk ratios (RR). Heterogeneity was described by I2 and prediction intervals. The potential benefit of reconstructive techniques over control procedures was evaluated in three studies, representing a total of 116 implants. Altogether, 16 studies reported on the outcome of reconstructive measures at 12 months after surgery. The meta-analyses identified a larger improvement in marginal bone levels (MBL, WMD = 1.7 mm) and in defect fill (WMD = 57%) for test procedures, but found no differences for clinical measures (reduction of probing depth (PD) and bleeding on probing (BOP). Changes of clinical attachment and soft tissue levels were not considered. In terms of overall outcome, therapy resulted in improved MBL (WMD = 2.0 mm) and CAL (WMD = 1.8 mm), in recession (WMD = 0.7 mm), in reduced PD (WMD = 2.8 mm) and in reduced BOP (Implants: RR = 0.4/Sites: RR = 0.2). None of the included studies addressed patient-reported outcome measures. The available evidence on reconstructive therapy at peri-implantitis-related defects is limited by (a) the low number of controlled studies, (b) the lack of controlled studies for commonly used procedures, (c) the heterogeneity between studies and (d) the choice of outcome measures. A high variability for predicted outcomes at 12 months was noted. The interpretation of the demonstrated larger MBL gain for test procedures is difficult as graft material may not be distinguishable from newly formed bone. Potential aesthetic and patient-reported advantages remain to be demonstrated.


Fabrication of functionalized nanofiber membranes containing nanoparticles.
The present scenario is that neutral or uncharged polymers are electrospun first followed by surface modification to introduce the functional groups onto the nanofibers surface. These groups improve the adhesion between the nanofibers and materials to be coated. The surface modification involves significant steps to get desired functional groups on the nanofibers surface and also time consuming. This paper deals with one step fabrication of nanofibers with hydroxyl functional groups. Nanofibers were fabricated by electrospinning of poly(ethylene terephthalate) (PET) with cellulose acetate (CA) or cellulose (C). Deposition of various metal oxide nanoparticles on these nanofiber surfaces was carried out using liquid phase deposition (LPD) and electrospraying techniques. Distribution of the nanoparticles and aggregation minimization were obtained by optimization of electrospraying technique. The nucleation density and the morphology of coated nanoparticles by LPD technique on PET surface were lower amount, whereas they are higher on PET/CA and PET/C blended surface, due to hydroxyl functional groups on the blended nanofiber surface, which is a novel. This study is helpful to understand about the complimentary information of the process based on the adoption of these two techniques. The characterizations of these nanofibers were carried out by using SEM, contact angle analysis, tensile, porosity measurements, and EDAX analysis. These membranes find potential applications as filter media in protective clothing and air filter applications.


Lymphocytes and T lymphocyte subsets are regionally distributed in the female goat reproductive tract: influence of the stage of the oestrous cycle.
The reproductive tract of the female is a part of the mucosal system which protects from pathogens invasion. We have analysed the presence and distribution of total lymphocytes, plasma cells (antibody secreting B cells) and T lymphocytes subsets in the reproductive tract of the female goat. The influence of the oestrous cycle on the densities of lymphocytes and plasma cells of the cervix and uterus horn was evaluated in sections prepared for conventional histology. Immunocytochemistry was used for the study of lymphocyte subsets by confocal microscopy and immunoperoxidase techniques. Present results show that the reproductive tract of the goat is a site rich in lymphocytes. These cells were found mingled with the epithelial cells of the endometrium and distributed throughout the stroma. Lymphocyte aggregates were observed in the stroma. Lymphocyte but not plasma cell number changed depending on the reproductive stage of the goats. The impact of the hormonal environment was different for the cervix and uterine horn. Immunocytochemistry studies evidenced the presence of cells displaying immunoreactivity for both CD 4+ and CD 8+ antibodies in the epithelial layer and stroma of the cervix and uterine horn. These cells were more numerous in the cervix and were also found infiltrating the luminal epithelia of endometrial glands. Overall, our results indicate that lymphocyte distribution is different in the cervix and the horn, and is influenced by the stage of the reproductive cycle. In summary, CD 4+ and CD 8+ T lymphocytes subsets could be found in the endometrium of both the cervix and uterine horn of the goat reproductive tract.


Role of DC-SIGN in Helicobacter pylori infection of gastrointestinal cells.
H. pylori causes gastritis and increases the risk of gastric ulcer and gastric cancer. However, it was recently shown that H. pylori provides protection against inflammatory bowel diseases. To assess the molecular mechanism of such functions, we studied the role of DC-SIGN in H. pylori-infected gastrointestinal epithelial cells. DC-SIGN was found to be over-expressed in the gastric epithelial cells infected with H. pylori and mediated Th1 differentiation, which may be involved in H. pylori-induced gastric mucosal injury. In addition, DC-SIGN was also up-regulated in the intestinal epithelial cells derived from colitis mouse model, but the expression levels were blocked upon H. pylori infection, indicating that H. pylori infection may reduce both local and systemic inflammatory responses. In conclusion, we propose that gastrointestinal epithelial cells infected with H. pylori may lead to acquiring of immune properties via a trans-differentiation process, and regulate tissue-associated immune compartments under the control of DC-SIGN.


Controlling the input: How one-year-old infants sustain visual attention.
Traditionally, the exogenous control of gaze by external saliencies and the endogenous control of gaze by knowledge and context have been viewed as competing systems, with late infancy seen as a period of strengthening top-down control over the vagaries of the input. Here we found that one-year-old infants control sustained attention through head movements that increase the visibility of the attended object. Freely moving one-year-old infants (n = 45) wore head-mounted eye trackers and head motion sensors while exploring sets of toys of the same physical size. The visual size of the objects, a well-documented salience, varied naturally with the infant's moment-to-moment posture and head movements. Sustained attention to an object was characterized by the tight control of head movements that created and then stabilized a visual size advantage for the attended object for sustained attention. The findings show collaboration between exogenous and endogenous attentional systems and suggest new hypotheses about the development of sustained visual attention.


[Gynecologic oncology: a daily confrontation for the gynecologist].
In the last decades a new discipline of "gynaecologic oncology" has spontaneously developed in the field of obstetrics and gynaecology. In this article the authors point out the necessity of an oncologic education for the gynecologist. The gynaecologist oncologist must have a solid cultural background in general and medical oncology, radio and immunotherapy. He also must have acquired surgical experience and clinical maturity. The authors underline the important role of the "general" gynecologist who must recognize risk cases, formulate a correct pre-surgical staging in order to plan a rational therapy and take part in the follow-up. His participation is important in the care of end-stage patients.


In vitro release of [5-methionine]enkephalin and [5-leucine]-enkephalin from the rat globus pallidus.
Endogenous [5-methionine]enkephalin (Metenkephalin) and [5-leucine]enkephalin (Leu-enkephalin) are released from perfused slices of rat globus pallidus by increased K(+) in a Ca(2+)-dependent manner. Tissue perfused for 40 min contained only 26% of the Met-enkephalin and 44% of the Leu-enkephalin found in the freshly dissected tissue. After perfusion, the mean (+/-SEM) ratio (wt/wt) of Met-enkephalin to Leu-enkephalin was 3.4 +/- 0.2 compared with 5.8 +/- 0.2 in the fresh tissue. The degradation of trace amounts of synthetic [(3)H]enkephalins in the perfusing medium during stimulated release seems to reflect the accelerated degradation of enkephalin released from the tissue: 63% of the Met-enkephalin and 23% of the Leu-enkephalin were degraded in a medium containing bacitracin (30 mug/ml). The mean ratio (wt/wt) of the Met-enkephalin to the Leu-enkephalin recovered after release by exposure of slices to 50 mM K(+) was 2.7 +/- 0.3. When perfusates were corrected for degradation, this ratio increased to about 5.5 which is higher than that found in the perfused tissue. The differences in release, tissue loss, and catabolism of the two enkephalins may be reflecting differences in the metabolic systems operating on the pentapeptides, but this interpretation will have to be validated by in vivo release experiments. In any event these observations strongly suggest that both enkephalins can be considered candidate neurotransmitters in the rat globus pallidus.


Antibody to staphylococcal enterotoxin A-induced human immune interferon (IFN gamma).
Antiserum to human gamma interferon (IFN gamma) was produced in rabbits immunized with partially purified (10(4.8) to 10(6.2) antiviral U/mg protein) staphylococcal enterotoxin A-induced IFN gamma. Staphylococcal enterotoxins, phytohemagglutinin M, concanavalin A, and pokeweed mitogen-induced antiviral activity in human leukocyte cultures was neutralized to undetectable levels by the antiserum. However, human leukocyte interferon (IFN alpha), human fibroblast interferon (IFN beta), and mouse interferons were not neutralized by the antiserum. After determining the antiserum was specific for IFN gamma and did not neutralize other known types of interferon, it was used with antibody to human IFN alpha to demonstrate the type(s) of interferon stimulated by some new inducers and antigens. Galactose oxidase- and calcium ionophore-induced interferons were neutralized to undetectable levels by the antiserum to IFN gamma. Interferon produced in leukocyte cultures from tuberculin-negative individuals stimulated with tuberculin-purified protein derivative or old tuberculin was IFN alpha, whereas interferon from tuberculin-positive individuals was a combination of alpha and gamma IFN. In addition, the antiserum neutralized the anticellular and natural killer cell enhancement activities of IFN gamma preparations. The specificity of this antiserum for IFN gamma indicates that it is an additional, powerful tool for identifying and classifying known and new interferons produced in vitro or in vivo and for investigating the role(s) of IFN gamma during the course of infectious, neoplastic, and autoimmune diseases.


Human papilloma virus genotypes in Ghanaian women with cervical carcinoma.
Humanpapilloma viruses (HPVs) have been considered to be the necessary and central agents of cervical cancer among women with nearly 80% of cases found in developing countries. To determine HPV genotypes prevalent in Ghanaian women with cervical cancer. Retrospective study. Pathology Department, University of Ghana Medical School, College of Health Sciences, University of Ghana. Ghanaian women 23 to 80 years diagnosed with cervical cancer. Of the 50 samples genotyped, 49 (98%) were determined as positive for HPV DNA. Eight out of 18 different HPV genotypes were detected and all were high-risk types. In decreasing order of prevalence, were HPV 18 in 42 (84%) samples, HPV 16 in 12 (24%) samples, HPV 45 in three (6%) samples, HPV 39 in two (4%) samples and HPV 35, 52,56 and 66 in one (2%) sample each. Multiple infections were detected in 13 (26%) of the 50 samples, the most common co-infections being HPV types 16/18 (18%). Triple infections were found in two (4%) samples with HPV types 16,18 and 39. HPV type 18 was more relatively frequent in adenocarcinomas and adenosquamous carcinomas than in squamous cell carcinomas. Eight high-risk HPV genotypes: 16,18, 35, 39, 45, 52, 56 and 66 were typed, with HPV type 18 being the most prevalent in Ghanaian women with cervical cancer. This is contrary to the worldwide prevalence where HPV 16 is the most common type associated with invasive cervical carcinoma.


Is regeneration inDrosophila the result of epimorphic regulation?
It has been known for many years that when a wing disc ofDrosophila is bisected, and the fragments cultured in adult females, regulation occurs and either a complete disc is regenerated or the fragment is duplicated. We have investigated how this regeneration process occurs. To establish which cells contribute to the regenerate, and thus determine if regeneration is the result of epimorphic regulation, fragments of discs, after culture in an adult for one to five days, were exposed to3H-thymidine to label replicating cells. Imaginal discs, both whole and as regenerating fragments, undergo some DNA replication which is distributed throughout the disc, but cut discs frequently show clusters of labelled cells around the wound, indicating that regeneration is probably epimorphic.


Avalanche exponents and corrections to scaling for a stochastic sandpile.
We study distributions of dissipative and nondissipative avalanches in Manna's stochastic sandpile, in one and two dimensions. Our results lead to the following conclusions: (1) avalanche distributions, in general, do not follow simple power laws, but rather have the form P(s) approximately s(-tau(s))(ln s)(gamma)f(s/s(c)), with f a cutoff function; (2) the exponents for sizes of dissipative avalanches in two dimensions differ markedly from the corresponding values for the Bak-Tang-Wiesenfeld (BTW) model, implying that the BTW and Manna models belong to distinct universality classes; (3) dissipative avalanche distributions obey finite-size scaling, unlike in the BTW model.


Effects of Yixintai Pills on Myocardial Cell Apoptosis in Rats With Adriamycin-Induced Heart Failure.
To study the effects of Yixintai pills on myocardial cell apoptosis in rats with adriamycin (ADR)-induced heart failure (HF) and the mechanism of action. Sixty healthy male Wistar rats randomly were divided into Control, Model, Captopril, and Yixintai pill groups. A rat model of ADR-induced HF was constructed by intraperitoneal injection of ADR (2.5 mg/kg). The control group was given an equal volume of normal saline; the Yixintai pill and Captopril groups were given corresponding mediations (5 mg/kg) by lavage. After 4 weeks of treatment, fasting blood was collected to detect the contents of plasma rennin activity (PRA), angiotensin II (AngII), and aldosterone (ALD). B ultrasound was used to detect the heart structure, and the heart weight/body weight (HW/BW) ratio was calculated. The pathology of myocardial tissues was observed by HE staining. The apoptosis of myocardial cells was detected by TUNEL assay. The expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum were analyzed by ELISA, and the protein expression levels of protein kinase B (Akt), phosphorylated (p)-Akt, glycogen synthase kinase-3β (GSK-3β) and p-GSK-3β in myocardial tissues were measured by Western blotting. Compared with the Control group, the PRA, AngII, ALD, left ventricular posterior wall thickness at end-systole (LVPWs), left ventricular posterior wall thickness at end-diastole (LVPWd), interventricular septal thickness at end-systole (IVSs), interventricular septal thickness at end-diastole (IVSd), HW/BW, TNF-α and IL-6 of model group increased significantly (P < .05). PRA, AngII, ALD, LVPWs, LVPWd, IVSs, IVSd, HW/BW, TNF-α and IL-6 of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). There were no significant differences in the indices between the Yixintai pill and Captopril groups (P > .05). In the Model group, lamellar necrosis, vacuolar degeneration, increased myocardial fibers and lamellar dissolution of myocardial cells were found in myocardial tissues. However, the myocardial cells of the Control group were neatly arranged and clearly structured, and only a few ones underwent fibrosis. There were mild myocardial fibrosis and vacuolar degeneration in the Yixintai pill and Captopril groups, and the degeneration and hyperplasia of myocardial fibers were obviously relieved. Compared with the Control group, the apoptosis index (AI) of the Model group increased significantly (P < .05). The AI values of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). Compared with the Control group, the expression levels of p-Akt and p-GSK-3β in the Model group decreased significantly (P < .05). The expression levels of p-Akt and p-GSK-3β in the Yixintai pill and Captopril groups were significantly higher than those of the Model group (P < .05), whereas the former 2 groups had similar results (P > 0.05). Yixintai pills may inhibit myocardial cell apoptosis and ventricular remodeling in rats by up-regulating PI3K/Akt/GSK-3β signal, thus protecting the heart function.


Distribution of chromatids at mitosis.
The distribution of labeled chromatids at the second mitosis after labeling with tritiated thymidine is random in both Vicia faba (the broad bean) and Potorous tridactylis (the rat kangaroo). This finding is contrary to that predicted by the hypothesis that chromatids containing "grandparent" polynucleotide templates segregate from those containing "parent" templates.


Spatial analysis improves the detection of early corneal nerve fiber loss in patients with recently diagnosed type 2 diabetes.
Corneal confocal microscopy (CCM) has revealed reduced corneal nerve fiber (CNF) length and density (CNFL, CNFD) in patients with diabetes, but the spatial pattern of CNF loss has not been studied. We aimed to determine whether spatial analysis of the distribution of corneal nerve branching points (CNBPs) may contribute to improving the detection of early CNF loss. We hypothesized that early CNF decline follows a clustered rather than random distribution pattern of CNBPs. CCM, nerve conduction studies (NCS), and quantitative sensory testing (QST) were performed in a cross-sectional study including 86 patients recently diagnosed with type 2 diabetes and 47 control subjects. In addition to CNFL, CNFD, and branch density (CNBD), CNBPs were analyzed using spatial point pattern analysis (SPPA) including 10 indices and functional statistics. Compared to controls, patients with diabetes showed lower CNBP density and higher nearest neighbor distances, and all SPPA parameters indicated increased clustering of CNBPs (all P<0.05). SPPA parameters were abnormally increased >97.5th percentile of controls in up to 23.5% of patients. When combining an individual SPPA parameter with CNFL, ≥1 of 2 indices were >99th or <1st percentile of controls in 28.6% of patients compared to 2.1% of controls, while for the conventional CNFL/CNFD/CNBD combination the corresponding rates were 16.3% vs 2.1%. SPPA parameters correlated with CNFL and several NCS and QST indices in the controls (all P<0.001), whereas in patients with diabetes these correlations were markedly weaker or lost. In conclusion, SPPA reveals increased clustering of early CNF loss and substantially improves its detection when combined with a conventional CCM measure in patients with recently diagnosed type 2 diabetes.


Gene methylation in pleural mesothelioma: correlations with clinico-pathological features and patient's follow-up.
Methylation of tumor suppressor genes is among the most frequent alterations in patients with malignant pleural mesothelioma (MPM). The aim of this study was to analyze the promoter methylation status of four tumor suppressor genes, p15(INK4B), p16(INK4A), RASSF1A and NORE1A in MPM. Samples of 79 MPM patients were analyzed using a methylation-specific PCR method. Associations between methylation status, clinico-pathological parameters (including proliferation index) and overall survival (OS) were examined. The analysis documented methylation in 30 cases (38%). The methylation frequency for individual genes was 19% for p15(INK4B) (n=15), 11.4% for p16(INK4A) (n=9), 20.2% for RASSF1A (n=16) and 5.1% for Nore1A (n=4). In the whole series methylation was associated to an increased proliferation index (P=0.05). In patients treated with extrapleural pneumonectomy, methylated MPM showed a trend to a poorer OS in comparison to unmethylated cases (median OS 16 months vs. 35 months, P=0.06, HR=2.01, 95% CI 0.95-4.30). In the overall population, methylation did not correlate to patient outcome but a trend to an improved survival was detectable in ummethylated MPM treated with extrapleural pneumonectomy. This result suggests the need to select homogeneously treated and staged patients with MPM to address whether their methylation profile may impact on patient's survival.


Cognitive Machine-Learning Algorithm for Cardiac Imaging: A Pilot Study for Differentiating Constrictive Pericarditis From Restrictive Cardiomyopathy.
Associating a patient's profile with the memories of prototypical patients built through previous repeat clinical experience is a key process in clinical judgment. We hypothesized that a similar process using a cognitive computing tool would be well suited for learning and recalling multidimensional attributes of speckle tracking echocardiography data sets derived from patients with known constrictive pericarditis and restrictive cardiomyopathy. Clinical and echocardiographic data of 50 patients with constrictive pericarditis and 44 with restrictive cardiomyopathy were used for developing an associative memory classifier-based machine-learning algorithm. The speckle tracking echocardiography data were normalized in reference to 47 controls with no structural heart disease, and the diagnostic area under the receiver operating characteristic curve of the associative memory classifier was evaluated for differentiating constrictive pericarditis from restrictive cardiomyopathy. Using only speckle tracking echocardiography variables, associative memory classifier achieved a diagnostic area under the curve of 89.2%, which improved to 96.2% with addition of 4 echocardiographic variables. In comparison, the area under the curve of early diastolic mitral annular velocity and left ventricular longitudinal strain were 82.1% and 63.7%, respectively. Furthermore, the associative memory classifier demonstrated greater accuracy and shorter learning curves than other machine-learning approaches, with accuracy asymptotically approaching 90% after a training fraction of 0.3 and remaining flat at higher training fractions. This study demonstrates feasibility of a cognitive machine-learning approach for learning and recalling patterns observed during echocardiographic evaluations. Incorporation of machine-learning algorithms in cardiac imaging may aid standardized assessments and support the quality of interpretations, particularly for novice readers with limited experience.


Total number of neurons and glial cells in human brain nuclei estimated by the disector and the fractionator.
Unbiased estimates of the total number of neurons and glial cells from central regions of grey matter in human brains are obtained using the disector principle in modifications which are unaffected by the histological processing of paraffin-embedded tissue. Section thickness does not enter into the estimator and need not be known. An analysis of the contributions from all sampling levels to the variance of the estimator of total cell number has been used to design an optimimal sampling scheme. Using this method, a precise and unbiased estimate of the total number of neurons in a defined brain region can be obtained in less than 1 h.


[Not Available].
Rudolf Meyer (1844-1924) was the first rhinolaryngologist in the town of Zurich. His scientific effort was remarkable. Before his death, he gave a selection of his articles, letters and instruments to the founder of the institute for medical history, where they were hidden until now. Interesting letters of medical colleagues, but also of politicians, historians, writers and poets (Gottfried Keller, C. F. Meyer, Johann Spyri, Jakob Bosshart) are among them. The long list of his students shows many illustrious names.


Pharmacokinetics and physiologic effects of alprazolam after a single oral dose in healthy mares.
The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0-∞ ) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1-12 h). Alpha-hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted.


Parasitic infestation in appendicitis. A retrospective analysis of 660 patients and brief literature review.
To investigate the incidence of parasitic infestations and inflammation accompanying parasitosis in a series of appendectomy cases. Methods: Six-hundred-sixty patients who had undergone appendectomy in Bingöl State Hospital, Bingol, Turkey with the preliminary diagnosis of appendicitis between January 2012 and February 2015 were included in this retrospective study. They were retrospectively evaluated in terms of age, gender and pathological findings. Cases diagnosed with parasitic infestations were re-evaluated histopathologically for inflammatory response. Results: The mean age was 19.6 years, and the male/female ratio was 1.8. When evaluated in terms of histopathological diagnoses, 573 (86.8%) were diagnosed as acute appendicitis, and parasitic infestation was identified in 12 (1.8%). Among cases with parasitic infestation, Enterobius vermicularis was identified in 9 (75%) and Taenia in 3 (25%) cases. Of cases with Enterobius vermicularis, 4 (44.4%) had lymphoid hyperplasia, 1 (11.1%) had normal-structured appendix vermiformis, and 4 (44.4%) had findings of acute appendicitis. All cases with taeniasis had an inflammatory response: acute appendicitis was identified in 2 (66%) and acute gangrenous appendicitis in 1 (33%) of them. Conclusion: Parasitic infestations are among the probable causes in appendicitis etiology and should be kept in mind during differential diagnosis. However, whether every parasitic infestation leads to appendiceal inflammatory response is controversial.


Does integration of Magee equations into routine clinical practice affect whether oncologists order the Oncotype DX test? A prospective randomized trial.
The three Magee Equations provide an estimate of the Oncotype DX recurrence score using commonly available clinicopathologic information (tumour size, grade, oestrogen receptor, progesterone receptor, HER2, and Ki67). We assessed whether integration of Magee Equations into routine clinical practice affected the frequency of Oncotype DX requests. Patients with newly diagnosed, node negative, hormone receptor positive, and HER2 negative invasive breast cancer were randomized to undergo a Magee calculation or not. At the first clinic assessment, the oncologist was provided with all routinely available clinicopathologic information (including Ki67) either with or without the results of Magee Equations. Primary outcome was frequency of Oncotype DX ordering. Secondary outcomes included frequency of chemotherapy use, time to commencement of radiotherapy, or systemic therapy. Physician comfort with systemic therapy choices and the use of Ki67 and Magee Equations was also assessed. Data from 175 randomized patients was available, 84 patients (48%) with and 91 (52%) without calculated Magee Equations. Oncotype DX was ordered in 10 (12.05%) and 13 (14.44%) (RR 0.83, 0.39-1.80; P = 0.64) in the Magee and no Magee groups, respectively. There were no statistically or clinically significant differences between the randomized groups for any of the secondary outcomes. Availability of both Ki67 and Magee Equations was associated with increased physician comfort around systemic treatment decisions. In a practice where Ki67 is routinely available, addition of Magee Equations into routine clinic practice was not associated with a reduction in Oncotype DX use. Availability of both Ki67 and Magee Equations did however increase physician comfort with systemic therapy decisions.


Mid-range visual deficits after stroke: Prevalence and co-occurrence.
Visual deficits are common after stroke and are powerful predictors for the chronic functional outcome. However, while basic visual field and recognition deficits are relatively easy to assess with standardized methods, selective deficits in visual primitives, such as shape or motion, are harder to identify, as they often require a symmetrical bilateral posterior lesion in order to provoke full field deficits. Therefore, we do not know how often they occur. Nevertheless, they can have severe repercussions for daily-life functioning. We aimed to investigate the prevalence and co-occurrence of hemifield "mid-range" visual deficits (i.e. color, shape, location, orientation, correlated motion, contrast, texture and glossiness), using a novel experimental set-up with a gaze-contingent presentation of the stimuli. To this end, a prospective cohort of 220 ischemic (sub)cortical stroke patients and a healthy control group was assessed with this set-up. When comparing performance of patients with controls, the results showed that deficits in motion-perception were most prevalent (26%), followed by color (22%), texture (22%), location (21%), orientation (18%), contrast (14%), shape (14%) and glossiness (13%). 63% of the stroke patients showed one or more mid-range visual deficits. Overlap of deficits was small; they mostly occurred in isolation or co-occurred with only one or two other deficits. To conclude, it was found that deficits in "mid-range" visual functions were very prevalent. These deficits are likely to affect the chronic post-stroke condition. Since we found no strong patterns of co-occurrences, we suggest that an assessment of deficits at this level of visual processing requires screening the full range of visual functions.


Adenomatous polyposis: an association with carcinoma of the thyroid.
A review of the St Mark's Hospital Polyposis Registry has revealed an association between adenomatous polyposis (familial polyposis coli) and thyroid carcinoma. Even though full clinical information was unavailable on all patients in the registry, it is evident that young women (below 35 years of age) are at particular risk of developing thyroid cancer, mainly of a papillary type, their chances of being affected being approximately 160 times that of normal individuals. All patients with adenomatous polyposis should thus have regular thyroid examination.


Not all mutualism is fair, and not all fairness is mutualistic.
The target article convincingly argues that mutualistic cooperation is supported by partner choice. However, we will suggest that mutualistic cooperation is not the basis of fairness; instead, fairness is based on impartiality. In support of this view, we show that adults are willing to destroy others' resources to avoid inequality, a result predicted by impartiality but not by mutualistic cooperation.


The use of negative pressure therapy and hyaluronic acid for the management of post-traumatic lower limb injury.
Management of severe limb trauma continues to challenge surgeons. Suitable treatment should be individualised for each patient, taking into consideration not only the wound extremity but also the associated injuries, age and socioeconomic status of the patient with the goal to recover function and to improve patient quality of life. The aim of this report is to present a severe degloving multiplane lower limb injury case in which a conservative treatment of the wound was performed with negative pressure therapy and dermal substitute, avoiding amputation and restoring limb function.


[A suggestion for the evaluation of the antepartal cardiotocogram (author's transl)].
An evaluation scale for the antepartal cardiotocogram is suggested which is intentionally based on the Apgar scale. Five criteria were evaluated: three characteristics of the basal fetal heart rate and two characteristic, recognized alterations in heart rate. In regard to the interpretation of the basal heart rate, level, range and number of flat readings per minute are significant for the prognosis. Alterations in heart rate permit a prognostic statement depending on the form and type of the acceleration and deceleration 0-2 points are given for every characteristic so that the index can vary from 0 to 10 points. The condition of the fetus is physiologic when the index is between 8-10, the prognosis is questionable when the index is between 5 and 7 and the condition of the fetus is critical when it is 4 or lower.


Digital restoration of the pectoral girdles of two Early Cretaceous birds and implications for early-flight evolution.
The morphology of the pectoral girdle, the skeletal structure connecting the wing to the body, is a key determinant of flight capability, but in some respects is poorly known among stem birds. Here, the pectoral girdles of the Early Cretaceous birds Sapeornis and Piscivorenantiornis are reconstructed for the first time based on computed tomography and three-dimensional visualization, revealing key morphological details that are important for our understanding of early-flight evolution. Sapeornis exhibits a double articulation system (widely present in non-enantiornithine pennaraptoran theropods including crown birds), which involves, alongside the main scapula-coracoid joint, a small subsidiary joint, though variation exists with respect to the shape and size of the main and subsidiary articular contacts in non-enantiornithine pennaraptorans. This double articulation system contrasts with Piscivorenantiornis in which a spatially restricted scapula-coracoid joint is formed by a single set of opposing articular surfaces, a feature also present in other members of Enantiornithines, a major clade of stem birds known only from the Cretaceous. The unique single articulation system may reflect correspondingly unique flight behavior in enantiornithine birds, but this hypothesis requires further investigation from a functional perspective. Our renderings indicate that both Sapeornis and Piscivorenantiornis had a partially closed triosseal canal (a passage for muscle tendon that plays a key role in raising the wing), and our study suggests that this type of triosseal canal occurred in all known non-euornithine birds except Archaeopteryx, representing a transitional stage in flight apparatus evolution before the appearance of a fully closed bony triosseal canal as in modern birds. Our study reveals additional lineage-specific variations in pectoral girdle anatomy, as well as significant modification of the pectoral girdle along the line to crown birds. These modifications produced diverse pectoral girdle morphologies among Mesozoic birds, which allowed a commensurate range of capability levels and styles to emerge during the early evolution of flight.


Effect of respiratory training on swallowing function in swallowing disorders: a systematic review and meta-analysis.
To determine the clinical efficacy of different respiratory training interventions on swallowing function in patients with swallowing disorders through the systematic review. We reviewed the literature regarding the application of respiratory training therapy in patients with swallowing disorders, followed by a PRISMA search of published literature in five databases (PubMed, Web of Science, The Cochrane Library, CINAHL and EMBASE) in December 2022. Two reviewers performed study selection, quality evaluation, and risk of bias, followed by data extraction and detailed analysis. A total of six randomized controlled studies with a total sample size of 193 cases were included. Respiratory training improved swallowing safety (PAS (n = 151, SMD = 0.69, 95% CI - 1.11 to - 0.26, I2 = 36, p < 0.001)) and swallowing efficiency [residual (n = 63, SMD = 1.67, 95% CI - 2.26 to - 1.09, I2 = 23%, p < 0.001)] compared to control groups. The results of the qualitative analysis conducted in this study revealed that respiratory training enhanced hyoid bone movement but had no effect on swallowing quality of life. Respiratory training interventions may improve swallowing safety and efficiency in patients with dysphagia. However, the level of evidence is low, and there is a limited amount of research on the effectiveness and physiology of this intervention to improve swallowing function. In the future, there is a need to expand clinical studies, standardize measurement tools, and improve study protocols.


Glycan-Dependent Mutual and Reversible Sequestration of Two Thyroid Cancer Biomarkers.
Thyroglobulin (Tg), the major thyroidal protein, plays important roles in thyroid hormone biosynthesis and in autoimmune thyroid diseases (AITD). Tg also serves as a pre- and postoperative biomarker of differentiated thyroid cancer (DTC). The endogenous β-galactoside binding lectin galectin-3 (Gal-3), secreted by transformed thyroid cells, has been shown to be another useful biomarker of DTC. Tg contains covalently linked complex-type glycans that can serve as binding epitopes of Gal-3. The objective of the study is to investigate the interaction between Tg and Gal-3 and discuss its potential consequences. Binding interaction between Tg and Gal-3 was first studied by hemagglutination inhibition assays. Subsequently, a detailed analysis of binding thermodynamics was carried out by isothermal titration calorimetry. Quantitative precipitation was performed to study the complex formation between Tg and Gal-3 and to determine the binding stoichiometry. The concentration-dependent rate and amount of complex formation between Tg and Gal-3 was examined spectrophotometrically. A similar approach was taken to study the effect of free Tg and Gal-3 on preformed Tg-Gal-3 complex. Quantitative biochemical and biophysical data show that these two biomarkers produced by thyroid cancer cells interact with each other with submicromolar affinity and form an insoluble complex at their stoichiometric concentration. One Tg molecule could bind up to 14 molecules of Gal-3. Such complex formation mutually sequestered both Tg and Gal-3, decreasing the concentration of their freely available forms. Formation of the Tg-Gal-3 complex was reversible as the preformed complex was dissolved by free Tg as well as free Gal-3. While free Tg rapidly dissolved preformed Tg-Gal-3 complex in a concentration-dependent manner, Gal-3 was found to be much less efficient and slowly dissolved only a fraction of the preformed complex at a relatively higher Gal-3 concentration. Complex formation between Tg and Gal-3 through high affinity binding and the sensitivity of the complex to free Tg and Gal-3 can potentially influence their biological functions. Interactions between Tg and Gal-3 might also interfere with their clinical detection, the same way Tg autoantibody (TgAb) is reported to interfere with Tg assays. The data support a model of Gal-3-mediated homeostatic process of Tg.


Modulation of the endocannabinoid system: neuroprotection or neurotoxicity?
There is now a large volume of data indicating that compounds activating cannabinoid CB(1) receptors, either directly or indirectly by preventing the breakdown of endogenous cannabinoids, can protect against neuronal damage produced by a variety of neuronal "insults". Given that such neurodegenerative stimuli result in increased endocannabinoid levels and that animals with genetic deletions of CB(1) receptors are more susceptible to the deleterious effects of such stimuli, a case can be made for an endogenous neuroprotective role of endocannabinoids. However, this is an oversimplification of the current literature, since (a) compounds released together with the endocannabinoids can contribute to the neuroprotective effect; (b) other proteins, such as TASK-1 and PPARalpha, are involved; (c) the CB(1) receptor antagonist/inverse agonist rimonabant has also been reported to have neuroprotective properties in a number of animal models of neurodegenerative disorders. Furthermore, the CB(2) receptor located on peripheral immune cells and activated microglia are potential targets for novel therapies. In terms of the clinical usefulness of targeting the endocannabinoid system for the treatment of neurodegenerative disorders, data are emerging, but important factors to be considered are windows of opportunity (for acute situations such as trauma and ischemia) and the functionality of the target receptors (for chronic neurodegenerative disorders such as Alzheimer's disease).


Antioxidative compounds from the outer scales of onion.
Antioxidative compounds were isolated from the methanol extract of dry outer scales of onion (Allium cepa L.). Nine phenolic compounds (1-9) were finally obtained by reversed-phase high-performance liquid chromatography, and their structures were elucidated by NMR and mass spectrometry analyses. They were the six known compounds, protocatechuic acid (1), 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (2), quercetin 4'-O-beta-D-glucopyranoside (3), quercetin (5), 4'-O-beta-d-glucopyranoside of quercetin dimer (7), and quercetin dimer (8), and three novel compounds, condensation products of quercetin with protocatechuic acid (4), adduct of quercetin with quercetin 4'-O-beta-D-glucopyranoside (6), and quercetin trimer (9). These phenolic compounds were tested for their antioxidant properties using autoxidation of methyl linoleate in bulk phase or free radical initiated peroxidation of soybean phosphatidylcholine in liposomes. The flavonoid compounds having o-dihydroxy substituent in the B-ring were shown to be effective antioxidants against nonenzymic lipid peroxidation.


EYA1 expression and subcellular localization in neuroblastoma and its association with prognostic markers.
Neuroblastoma, the most frequently occurring extracranial solid tumor of childhood, arises from neural crest-derived cells that are arrested at an early stage of differentiation in the developing sympathetic nervous system. There is an urgent need to identify clinically relevant biomarkers for better prognosis and treatment of this aggressive malignancy. Eyes Absent 1 (EYA1) is an essential transcriptional coactivator for neuronal developmental programs during organogenesis. Whether or not EYA1 is implicated in neuroblastoma and subcellular localization of EYA1 is relevant to clinical behaviour of neuroblastoma is not known. We studied EYA1 expression and subcellular localization by immunohistochemistry in tissue microarrays containing tumor specimens from 98 patients, 66 of which were characterized by known clinical prognostic markers of neuroblastoma. Immunostaining results were evaluated and statistically correlated with the degree of histologic differentiation and with neuroblastoma risk stratification group characteristics, including stage of disease, patient age, tumor histology and mitosis-karyorrhexis index (MKI), respectively. We found that EYA1 levels were significantly higher in neuroblastomas than in ganglioneuromas and ganglioneuroblastomas. EYA1 was more highly expressed in stage 1,2,3 or 4S tumors as compared to stage 4 tumors (P<0.01). Tumors with high levels of nuclear EYA1 were more frequently associated with high nuclear MYCN levels. These results suggest that modulation of expression and intracellular localization of EYA1 in neural crest cells may provide a novel direction for therapeutic strategies.


Identification of a highly promiscuous and an HLA allele-specific T-cell epitope in the birch major allergen Bet v 1: HLA restriction, epitope mapping and TCR sequence comparisons.
Allergen-specific CD4+ T cells play an important regulatory role in atopic allergy. To investigate the human leucocyte antigen (HLA) restriction and T-cell receptor (TCR) usage of allergen-specific T-cell clones (TCCs) that react with defined epitopes of Bet v 1, the major birch pollen allergen. Five Bet v 1-specific TCCs derived from two birch pollen-allergic individuals and specific for Bet v 1, were epitope-mapped with overlapping synthetic peptides. In addition, HLA-restriction and TCR CDR3 sequences were determined. Three TCCs reacted with a Bet v 1 peptide containing amino acid residues 21-33 (BP21), the other two TCCs reacted with a minimal peptide comprising residues 37-45 (BP37). Studies using neutralizing anti-HLA-monoclonal antibodies and HLA-typed APCs showed that the BP37-specific TCCs were restricted by a HLA-DQA1*0301/DQB1*0603 heterodimer. In contrast, BP21 was recognized in a highly promiscuous manner. TCCs recognizing this sequence were restricted by HLA-DPB1*0201, a HLA-DQA1*0201/DQB1*0201 heterodimer, or HLA-DRB3*0101. Reverse transcription-polymerase chain reaction with primers for all known TCRAV and TCRBV gene segments, followed by CDR3 region sequencing, revealed the usage of five different TCRAV and four different TCRBV gene segments by the TCCs, as well as diversity in the joining region. All BP21-specific TCCs contained a negatively charged residue in their CDR3alpha regions, the CDR3beta regions showed a high concentration of polar and OH-group bearing residues. BP37-specific TCCs shared the amino acid combination LY in the middle of their CDR3alpha regions, the CDR3beta regions showed high concentration of OH-group bearing or charged residues. This study shows the existence of a highly promiscuous T-cell epitope in Bet v 1. The presence of additional T-cell epitopes in Bet v 1 may, however, hamper the clinical applicability of the epitope. Likewise, the diversity in TCR usage by T cells recognizing the epitope does not support the development of TCR-directed immunotherapy for birch pollen allergy.


Neonatal mechanical ventilation: Indications and outcome.
Decreasing mortality in sick and ventilated neonates is an endeavor of all neonatologists. To reduce the high mortality in this group of neonates, identification of risk factors is important. This study was undertaken to find out the indications of ventilation and complications in ventilated neonates and also study possible predictors of outcome. Age <1-month; mechanically ventilated; not having suspected metabolic disorders or congenital anomalies; excluding postoperative patients. Neonates consecutively put on mechanical ventilation during the study period (October 2011 to November 2013) enrolled. Primary disease of the neonates along with complications present listed. Clinical and laboratory parameters analyzed to find the predictors of mortality. Total 300 neonates were ventilated. 52% were male. Mean age, weight, and gestational age were 21 ± 62 h, 2320 ± 846.2 g, and 35.2 ± 4.9 weeks, respectively. 130 (43%) neonates died. Respiratory distress syndrome (RDS) (31.1%), sepsis (22.7%), and birth asphyxia (18%) were the most common indications for ventilation. Mortality in ventilated patients with sepsis, pneumonia, RDS or birth asphyxia was 64.7%, 60%, 44.6%, and 33.3%, respectively. Weight <2500 g, gestation <34 weeks, initial pH <7.1, presence of sepsis, apnea, shock, pulmonary hemorrhage, hypoglycemia, neutropenia, and thrombocytopenia were significantly associated with mortality (P < 0.05). Resuscitation at birth, seizures, intra ventricular hemorrhage, pneumothorax, ventilator-associated pneumonia, PO2, or PCO2 did not have a significant association with mortality. On logistic regression, gestation <34 weeks, initial pH <7.1, pulmonary hemorrhage, or shock were independently significant predictors of mortality. Weight <2500 g, gestation <34 weeks, initial arterial pH <7.1, shock, pulmonary hemorrhage, apnea, hypoglycemia, neutropenia, and thrombocytopenia were significant predictors of mortality in ventilated neonates.


Latent, genetic, and molecular genetic structure of the Wisconsin Card Sorting Test.
The main goal of this study was to explore the latent structure and genetic basis of cognitive processes involved in the Wisconsin Card Sorting Task (WCST) within phenotypic, behavioral genetic, and molecular genetic research paradigms. The sample used in phenotypic and behavioral genetic analyses comprised 468 twins (154 monozygotic and 80 dizygotic twin pairs), while molecular genetic analyses were performed on 404 twins from the same sample. The zygosity of most twin pairs (96.8%) was determined via deoxyribonucleic acid (DNA) analysis of buccal swabs. Trained researchers administered the Wisconsin Card Sorting Test (WCST; Heaton et al., 1993) to the entire sample. A phenotypic factor analysis of WCST variables suggested a single-factor solution. Overall heritability ranged from 0.19 to 0.23 across different measures of the WCST. The presence of a single general genetic factor, which could be identified from different measures of the WCST, indicated the unity of various WCST indicators and the existence of a common basic ability. Performance on the WCST did not reveal significant differences between the three genotypes on catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2). Carriers of the brain-derived neurotrophic factor (BDNF) Met + genotype exhibited better performance in cognitive functions in comparison to the BDNF Met- genotype. This study highlighted similarities in the phenotypic and genetic structures of the WCST, suggesting one general factor underlying different cognitive functions. The BDNF Met + genotype showed significant main effects on different WCST measures. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Measurement error caused by speckle noise in heterodyne and quasi-heterodyne holographic interferometry.
In heterodyne and quasi-heterodyne holographic interferometry, the measuring accuracy is limited by speckle noise. It is important to know the relation between measurement accuracy and speckle noise in both theory and application. This problem has been discussed in the past under the assumption that the speckle noise produces only a small measuring error. However, this assumption is not reasonable in practice. The effect of speckle noise on the measurement accuracy is analyzed by the use of a general statistical method. The results obtained reveal the general relation between the measuring accuracy and system parameters, and thus constitute important guidelines to the application of these techniques.