Musical expertise is related to altered functional connectivity during audiovisual integration.
The present study investigated the cortical large-scale functional network underpinning audiovisual integration via magnetoencephalographic recordings. The reorganization of this network related to long-term musical training was investigated by comparing musicians to nonmusicians. Connectivity was calculated on the basis of the estimated mutual information of the sources' activity, and the corresponding networks were statistically compared. Nonmusicians' results indicated that the cortical network associated with audiovisual integration supports visuospatial processing and attentional shifting, whereas a sparser network, related to spatial awareness supports the identification of audiovisual incongruences. In contrast, musicians' results showed enhanced connectivity in regions related to the identification of auditory pattern violations. Hence, nonmusicians rely on the processing of visual clues for the integration of audiovisual information, whereas musicians rely mostly on the corresponding auditory information. The large-scale cortical network underpinning multisensory integration is reorganized due to expertise in a cognitive domain that largely involves audiovisual integration, indicating long-term training-related neuroplasticity.


Down-regulation of neuronal nitric oxide synthase by nitric oxide after oxygen-glucose deprivation in rat forebrain slices.
The precise role that nitric oxide (NO) plays in the mechanisms of ischemic brain damage remains to be established. The expression of the inducible isoform (iNOS) of NO synthase (NOS) has been demonstrated not only in blood and glial cells using in vivo models of brain ischemia-reperfusion but also in neurons in rat forebrain slices exposed to oxygen-glucose deprivation (OGD). We have used this experimental model to study the effect of OGD on the neuronal isoform of NOS (nNOS) and iNOS. In OGD-exposed rat forebrain slices, a decrease in the calcium-dependent NOS activity was found 180 min after the OGD period, which was parallel to the increase during this period in calcium-independent NOS activity. Both dexamethasone and cycloheximide, which completely inhibited the induction of the calcium-independent NOS activity, caused a 40-70% recovery in calcium-dependent NOS activity when compared with slices collected immediately after OGD. The NO scavenger oxyhemoglobin produced complete recovery of calcium-dependent NOS activity, suggesting that NO formed after OGD is responsible for this down-regulation. Consistently, exposure to the NO donor (Z)-1-[(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-iu m-1,2-diolate (DETA-NONOate) for 180 min caused a decrease in the calcium-dependent NOS activity present in control rat forebrain slices. Furthermore, OGD and DETA-NONOate caused a decrease in level of both nNOS mRNA and protein. In summary, our results indicate that iNOS expression down-regulates nNOS activity in rat brain slices exposed to OGD. These studies suggest important and complex interactions between NOS isoforms, the elucidation of which may provide further insights into the physiological and pathophysiological events that occur during and after cerebral ischemia.


Iono-metabolomic guided elucidation of arsenic induced physiological and metabolic dynamics in wheat genotypes.
Despite the growing concerns about arsenic (As) toxicity, information on wheat adaptability in such an aggravating environment is limited. Thus, the present investigation based on an iono-metabolomic approach is aimed to decipher the response of wheat genotypes towards As toxicity. Wheat genotypes procured from natural conditions were characterized as high As-contaminated (Shri ram-303 and HD-2967) and low As-contaminated (Malviya-234 and DBW-17) based on ICP-MS As accumulation analysis. Reduced chlorophyll fluorescence attributes, grain yield and quality traits, and low grain nutrient status were accompanied by remarkable grain As accumulation in high As-contaminated genotypes, thus imposing a higher potential cancer risk and hazard quotient. Contrarily, in low As-contaminated genotypes, the richness of Zn, N, Fe, Mn, Na, K, Mg, and Ca could probably have supported less grain As accumulation, imparting better agronomic and grain quality traits. Additionally, from metabolomic analysis (LC-MS/MS and UHPLC), abundances of alanine, aspartate, glutamate, quercetin, isoliquiritigenin, trans-ferrulic, cinnamic, caffeic, and syringic bestow Malviya-234 as the best edible wheat genotype. Further, the multivariate statistical analysis (HCA, PCA, and PLS-DA) revealed certain other key metabolites (rutin, nobletin, myricetin, catechin, and naringenin) based genotypic discrimination that imparts strength to genotypes for better adaptation in harsh conditions. Out of the 5 metabolic pathways ascertained through topological analysis, the two main pathways vital for plant's metabolic adjustments in an As-induced environment were: 1. The alanine, aspartate and glutamate metabolism pathway, and 2. The flavonoid biosynthesis pathway. This is also evident from network analysis, which stipulates amino acid metabolism as a prominent As regulatory factor closely associated with flavonoids and phenolics. Therefore, the present findings are useful for wheat breeding programs to develop As adaptive genotypes that are beneficial for crop improvement and human health.


Salivary cortisol and explicit memory in postmenopausal women using hormone replacement therapy.
Circulating cortisol levels are known to influence explicit memory in humans and other primates. The present study investigated salivary cortisol and its association with explicit memory performance in 99 postmenopausal women (64 treated with conjugated equine estrogens or estradiol, and 35 matched controls not using any form of hormone therapy). Controls were compared with treated women taking estrogens alone (n=39), or taking estrogens in combination with a progestin (n=25). Mean time on hormone therapy was approximately 5 years, with initiation of treatment in close proximity to the onset of menopause. Explicit memory was assessed with the California Verbal Learning Test (CVLT). Saliva was collected before (basal or resting sample) and after (post-test sample) completing a set of cognitive tasks. Cortisol was measured using a high-sensitivity radioimmunoassay. Treated women were found to have higher resting cortisol concentrations than controls matched for time of day. Basal cortisol was a modest predictor of learning and memory on the CVLT. Higher cortisol was associated with better recall and fewer memory errors, which is consistent with experimental studies examining explicit memory under small increases in circulating cortisol load. Potential cumulative effects on the central nervous system of sustained exposure to mildly increased cortisol in conjunction with the long-term use of oral estrogens are discussed in the context of aging and dementia.


Potential disturbance of methylphenidate of gonadal hormones or pubescent development in patients with attention-deficit/hyperactivity disorder: A twelve-month follow-up study.
Several animal or case reports have demonstrated that methylphenidate (MPH) disrupts endogenous gonadal hormones and interferes with the pubescent development of children with attention-deficit/hyperactivity disorder (ADHD). Therefore, this prospective study examined the changes in gonadal hormones and pubescent development in children with ADHD undergoing 12-month MPH treatment. We recruited 146 patients with ADHD (mean age: 8.9 years, 76.7% males) and 70 healthy controls (mean age: 9.2 years, 65.7% males). Blood samples were obtained to measure the serum levels of sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, free testosterone, and prolactin in each child. The sex maturation of ADHD patients was evaluated using the Tanner Stage. Patients with ADHD (107 received MPH treatment and 39 were under natural observation) were followed up for 12 months, and we re-examined hormone levels and Tanner Stage at the endpoint. During a 12-month follow-up for all ADHD patients, the serum levels of SHBG and progesterone significantly decreased, while LH, FSH, and free-testosterone levels significantly increased. However, the duration, drug formulations, and doses of the MPH treatment did not significantly influence gonadal hormone trends or changes of Tanner Stage. This study provides evidence about gonadal hormone trends and pubescent development in children with ADHD who receive long-term MPH treatment in natural settings. We suggest that MPH treatment at usual doses does not significantly alter gonadal function trends in ADHD patients over the course of one year.


The hypertensive neonate.
Hypertension in neonates is increasingly recognized because of improvements in neonatal intensive care that have led to improved survival of premature infants. Although normative data on neonatal blood pressure remain limited, several factors appear to be important in determining blood pressure levels in neonates, especially gestational age, birth weight and maternal factors. Incidence is around 1% in most studies and identification depends on careful blood pressure measurement. Common causes of neonatal hypertension include umbilical catheter associated thrombosis, renal parenchymal disease, and chronic lung disease, and can usually be identified with careful diagnostic evaluation. Given limited data on long-term outcomes and use of antihypertensive medications in these infants, clinical expertise may need to be relied upon to decide the best approach to treatment. This review will discuss these concepts and identify evidence gaps that should be addressed.


Restrained expression of canine glucocorticoid receptor splice variants α and P prognosticates fatal disease outcome in SIRS.
Glucocorticoids play a central role in the inflammatory response and alleviate the symptoms in critically ill patients. The glucocorticoid action relies on the glucocorticoid receptor (GR) which translocates into the nucleus upon ligand-binding and regulates transcription of a battery of genes. Although the GR is encoded by a single gene, dozens of its splice variants have been described in diverse species. The GRα isoform encodes the full, functionally active protein that is composed of a transactivation, a DNA-binding, and a C-terminal ligand-binding domain. The second most highly expressed receptor variant, the GR-P, is formed by an intron retention that introduces an early stop codon and results in a probably dysfunctional protein with truncated ligand-binding domain. We described the canine ortholog of GR-P and showed that this splice variant is highly abundant in the peripheral blood of dogs. The level of cGRα and cGR-P transcripts are elevated in patients of SIRS and the survival rate is increased with elevated cGRα and cGR-P expression. The ratio of cGRα and cGR-P mRNA did not differ between the survivor and non-survivor patients; thus, the total GR expression is more pertinent than the relative expression of GR isoforms in assessment of the disease outcome.


Tools for quantitative form description; an evaluation of different software packages for semi-landmark analysis.
The challenging complexity of biological structures has led to the development of several methods for quantitative analyses of form. Bones are shaped by the interaction of historical (phylogenetic), structural, and functional constrains. Consequently, bone shape has been investigated intensively in an evolutionary context. Geometric morphometric approaches allow the description of the shape of an object in all of its biological complexity. However, when biological objects present only few anatomical landmarks, sliding semi-landmarks may provide good descriptors of shape. The sliding procedure, mandatory for sliding semi-landmarks, requires several steps that may be time-consuming. We here compare the time required by two different software packages ('Edgewarp' and 'Morpho') for the same sliding task, and investigate potential differences in the results and biological interpretation. 'Morpho' is much faster than 'Edgewarp,' notably as a result of the greater computational power of the 'Morpho' software routines and the complexity of the 'Edgewarp' workflow. Morphospaces obtained using both software packages are similar and provide a consistent description of the biological variability. The principal differences between the two software packages are observed in areas characterized by abrupt changes in the bone topography. In summary, both software packages perform equally well in terms of the description of biological structures, yet differ in the simplicity of the workflow and time needed to perform the analyses.


[Corneal trephining for penetrating keratoplasty: study of the degree of precision and presentation of a new trephine].
The accuracy of corneal trephination with a Franceschetti trephine was investigated on Duragel contact lenses. A modified 7.3 mm Crock trephine (Brit. J. Ophthal. 62 [1978] 74-80) with a rotating diamond blade fitted was compared with the above-mentioned method. Trephination of Duragel lenses from the convex side yielded diameters either larger or smaller than 7 mm. With one exception trephination from the concave side produced disks smaller than 7 mm. All Duragel disks had an elliptical configuration after trephination with the Franceschetti trephine. Trephination with the modified Crock trephine yielded disks with diameters close to 7.3 mm in all meridians.


Coexistence of ankylosing spondylitis and Behcet's disease. Two cases with atypical presentation and course.
The prevelance of ankylosing spondylitis or sacroiliitis in Behcet's disease has been the subject of debate for some time. Two cases with atypical presentation and course are discussed. The first patient was a young woman with Behcet's disease whose primary complaint was neck pain. X-ray examination showed severe cervical involvement, characteristic of the type seen in women with ankylosing spondylitis. She subsequently developed anterior uveitis. The second patient was a man suffering from back pain and limited movement of his neck and back. When he was referred to our outpatient clinic, his severe anemia became the subject of the whole investigation. He was diagnosed with Behcet's disease with ankylosing spondylitis accompanied with amyloidosis and an end-stage renal failure.


Osthol and isopimpinellin from Fructus cnidii for the control of Dactylogyrus intermedius in Carassius auratus.
The efficacy of two active compounds, isolated from the fruit of Fructus cnidii, was determined against Dactylogyrus intermedius in goldfish (Carassius auratus). The chemical structure of the two compounds was identified by spectral analysis. Designated Compounds I and II, they were isolated by successive silica gel column chromatography and used, in combination, in an in vivo anthelmintic efficacy assay. At dose rates of 1.6 and 9.5 mg l(-1), respectively, the two compounds were 100% effective against D. intermedius compared to mebendazole (positive control), used at a concentration of 1.5 mg l(-1), which is 100% efficacious. Compounds I and II were shown to be safe for goldfish at dose rates of up to 6.4 and 12.5 mg l(-1), respectively. The median effective dose (ED(50)) of Compounds I and II for D. intermedius-infested goldfish after 48 h exposure was 0.807 and 8.050 mg l(-1), respectively. If the median lethal dose (LD(50)) values for goldfish of the two compounds are 6.749 and 12.759 mg l(-1), respectively, the ED(50) values for D. intermedius yielded a therapeutic index of 8.14 and 1.52 for Compounds I and II, respectively, at 48 h. Compounds I and II were identified as osthol and isopimpinellin by physico-chemical detection.


[A study on the characteristics of the occupational metal-fume fever].
Metal-fume fever is an occupational, acute poisoning disease of workers exposed to metallic oxides fume, especially zinc oxide fume is the most common cause. In order to recommend the diagnostic criteria, the authors of this paper mode hygienic investigations in the workplace, and clinical observations on to workers in the zinc metallurgic factories and copper processing factories. Scientific data for were collected this purpose.


Metabolic response to renal compensatory growth.
Forty-eight hours after unilateral nephrectomy in young male Sprague-Dawley rats the concentrations of free methionine, alanine and tyrosine in renal cortical tissue were increased by 15-65 percent while the corresponding plasma concentrations decreased by 23-35 percent. The renal cortical concentrations of valine and leucine increased by 41 percent and 26 percent while plasma concentrations remained unchanged. The cortical concentrations of ornithine, serine and threonine remained unchanged while the plasma concentration decreased by approximately one-third. The total free amino acid contained in the cortex was not changed, while total free amino acids in plasma decreased by 7 percent. These data are thought to reflect an increased uptake of methionine and tyrosine into renal cells during compensatory hypertrophy, and an increased incorporation into renal protein of serine, threonine and ornithine. All these changes as well as all other biochemical changes accompanying compensatory hypertrophy with the exception of an increase of the RNA/DNA ratio were prevented by starvation for 48 hours after unilateral nephrectomy.In young male Sprague-Dawley rats and adult male Charles River mice, the incorporation of (14)C-choline into acid-insoluble phospholipids (phosphatidylcholine, lysophosphatidylcholine and sphingomyelin) was already accelerated 5 minutes after contralateral nephrectomy and further rose to +68 ± 7 percent within 20 minutes to 3 hours. Incorporation of (14)C-choline into phospholipids remained accelerated for two to three days and reflected increased rates of phospholipid synthesis rather than increased choline uptake. Three hours after unilateral nephrectomy in mice, incorporation of i.p. injected (14)C-choline into phospholipids was accelerated 25 percent. The rate of turnover of free labelled renal phospholipids was not accelerated during compensatory renal growth. The very early increase of choline incorporation into phospholipids after contralateral nephrectomy, therefore, appears to reflect an increased rate of synthesis of membrane material.


On the antioxidant activity of melatonin.
Melatonin has been widely reported to be an effective antioxidant. Studies of its ability to inhibit the autoxidation of lipids in homogeneous solution and in model heterogeneous systems show that melatonin is not a peroxyl radical trapping antioxidant. In contrast, melatonin can inhibit metal ion-catalyzed oxidation processes.


Value of Islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of pancreatic origin.
Neuroendocrine tumors can present as liver metastases before discovery of the primary tumor. Islet 1 and PAX8 have recently been proposed as markers for neuroendocrine tumors of pancreatic origin. In this study, we compared the utility of Islet 1 and PAX8 in distinguishing pancreatic neuroendocrine tumors from neuroendocrine tumors of other sites and determined the usefulness of an immunohistochemical panel, including TTF1, CDX2, Islet 1 and/or PAX8, in identifying metastatic pancreatic neuroendocrine tumors. A total of 110 primary neuroendocrine tumors (33 pancreatic, 31 pulmonary, 23 ileal, 14 rectal, and 9 gastric) and 73 metastatic neuroendocrine tumors (28 pancreatic, 5 pulmonary, 37 ileal, 1 rectal, 1 colonic, and 1 duodenal) were studied. Islet 1 and PAX8 were positive in 27/33 (82%) and 29/33 (88%), respectively, of primary pancreatic neuroendocrine tumors, and in 19/28 (68%) and 15/28 (54%), respectively, of metastatic pancreatic neuroendocrine tumors. No cases of primary (0/23) or metastatic (0/37) ileal neuroendocrine tumors were positive with either Islet 1 or PAX8. There was Islet 1 positivity in 2/31 (6%) primary pulmonary, 12/14 (86%) primary rectal, and 1/1 metastatic rectal neuroendocrine tumors, and PAX8 positivity in 7/31 (23%) primary pulmonary, 11/14 (79%) primary rectal, and 2/9 (22%) primary gastric neuroendocrine tumors. ROC curve analysis incorporating sensitivity and specificity data of immunohistochemical panels for metastatic pancreatic neuroendocrine tumors showed that a four-stain panel, including Islet 1, PAX8, TTF1, and CDX2 significantly outperformed a three-stain panel composed of PAX8, TTF1, and CDX2 (P=0.019), and also showed a trend for better performance compared with a three-stain panel composed of Islet 1, TTF1, and CDX2 (P=0.072). Both Islet 1 and PAX8 are reliable immunohistochemical markers for pancreatic neuroendocrine tumors and would be useful adjuncts to other markers (TTF1, CDX2) currently used to work up a metastatic neuroendocrine tumor of unknown primary.


Three-dimensional structure model and predicted ATP interaction rewiring of a deviant RNA ligase 2.
RNA ligases 2 are scarce and scattered across the tree of life. Two members of this family are well studied: the mitochondrial RNA editing ligase from the parasitic trypanosomes (Kinetoplastea), a promising drug target, and bacteriophage T4 RNA ligase 2, a workhorse in molecular biology. Here we report the identification of a divergent RNA ligase 2 (DpRNL) from Diplonema papillatum (Diplonemea), a member of the kinetoplastids' sister group. We identified DpRNL with methods based on sensitive hidden Markov Model. Then, using homology modeling and molecular dynamics simulations, we established a three dimensional structure model of DpRNL complexed with ATP and Mg2+. The 3D model of Diplonema was compared with available crystal structures from Trypanosoma brucei, bacteriophage T4, and two archaeans. Interaction of DpRNL with ATP is predicted to involve double π-stacking, which has not been reported before in RNA ligases. This particular contact would shift the orientation of ATP and have considerable consequences on the interaction network of amino acids in the catalytic pocket. We postulate that certain canonical amino acids assume different functional roles in DpRNL compared to structurally homologous residues in other RNA ligases 2, a reassignment indicative of constructive neutral evolution. Finally, both structure comparison and phylogenetic analysis show that DpRNL is not specifically related to RNA ligases from trypanosomes, suggesting a unique adaptation of the latter for RNA editing, after the split of diplonemids and kinetoplastids. Homology modeling and molecular dynamics simulations strongly suggest that DpRNL is an RNA ligase 2. The predicted innovative reshaping of DpRNL's catalytic pocket is worthwhile to be tested experimentally.


Smoking, reward responsiveness, and response inhibition: tests of an incentive motivational model.
Incentive-motivation models of addiction suggest impairment of functional activity in mesocorticolimbic reward pathways during abstinence. This study tested implications for subjective and behavioral responses to nondrug incentives, cue-elicited craving, and prefrontal cognitive functions, particularly response inhibition. We tested 26 smokers after smoking and after overnight abstinence in counterbalanced order; 26 nonsmokers were also tested twice. Measures included a simple card-sorting test performed with and without financial incentive (the CARROT), the Snaith Hamilton Pleasure Scale as an index of subjective reward responsiveness, ratings of subjective craving and withdrawal before and after exposure to a cigarette, an index of oculomotor response inhibition (saccadic vs. antisaccadic eye movements), verbal fluency, and reversed digit span. Compared with the smoking condition, and independently of withdrawal severity, abstinence was associated with reduced cue reactivity, pleasure expectancies, responsiveness to financial incentive, and response inhibition (antisaccadic eye movements). Verbal fluency and reversed digit span were unaffected, contrary to findings elsewhere with heavier smokers. Nonsmokers' scores either fell between those of abstainers and recent smokers or approximated those of recent smokers. The data were in general consistent with behavioral predictions derived from the incentive-motivational model of addiction and suggest that abstinence may be associated with impairments of motivation and response inhibition, which are independent of other subjectively experienced withdrawal symptoms.


Long-term viability and infectivity of intraradical forms of Glomus intraradices vesicles encapsulated in alginate beads.
Intraradical vesicles of Glomus intraradices were isolated, entrapped in alginate beads, and stored at 4 degrees C for periods from 2-74 months. The beads were used to inoculate leeks grown under standard conditions for 6 wk, then development of root colonization by G. intraradices was recorded. Colonization of leeks was high (mean > 50% in length) and did not vary markedly until five years of storage. After six years of storage, the inoculum proved infective and viable.


Pharmacokinetics and Bioavailability Enhancement of Baicalin: A Review.
Baicalin is one of the major bioactive components of Scutellaria radix, a Chinese herb that has been used since ancient times. Baicalin has various pharmacological activities, including antitumor, antimicrobial, and antioxidant, and has wide clinical applications. Baicalin displays a distinct pharmacokinetic profile including gastrointestinal hydrolysis, enterohepatic recycling, carrier-mediated transport, and complicated metabolism. The in vivo disposition of baicalin is affected by combinations of other herbs and baicalin can interact with other co-administered drugs due to competition between metabolic enzymes and protein binding. Furthermore, baicalin exhibits altered pharmacokinetic properties under different pathological conditions. Due to its low bioavailability, emerging novel baicalin preparations including nano/micro-scale baicalin delivery systems show better absorption and higher bioavailability in preclinical studies, and show promise for future clinical applications. Thus, this current review offers a comprehensive report on the pharmacokinetic behavior of baicalin and strategies to improve its bioavailability.


The assessment of stress, depression, and inflammation as a collective risk factor for periodontal diseases: a systematic review.
The purpose of this review was to provide a novel perspective utilizing an assessment of biomarkers to evaluate the impact of stress-related disorders on the progression of periodontal disease and evaluate the growing body of evidence of stress as a risk indicator for periodontal disease progression. Cross-sectional, case-control, and biomarker studies associating psychological disorders and periodontal disease were included in the literature search. Computational studies, animal studies, reviews, and studies lacking healthy controls were excluded. Electronic and manual literature searches were conducted by two independent reviewers in several databases as well as a manual search for relevant articles published up to January 2018. Twenty-six articles fulfilled the inclusion criteria and were included in the qualitative synthesis. Relationships between stress-related disorders and serum and salivary biomarkers such as cortisol, dehydroepiandrosterone (DHEA), chromogranin A (CgA), and pro-inflammatory cytokines were identified. The use of salivary pro-inflammatory cytokines alone is not sufficient for the identification of periodontal disease severity/progression with or without the presence of stress-associated diseases. Keeping in mind the limitations of this review, a positive qualitative correlation was observed in the literature among stress-related biomarkers and the severity of periodontal disease. This correlation may serve as an important reporter of patient susceptibility for periodontal breakdown in the future. Stress-related disorders should be included in the list of globally screened diseases because it can change the biochemistry of both the local periodontal microenvironment as well as the global systemic inflammatory burden.


The complete chloroplast genome of two Firmiana species and comparative analysis with other related species.
Firmiana is a small genus within the subfamily Sterculioideae of the Malvaceae. There are nine Firmiana species distributed in South and South-west China, most of which are endangered. Due to the shortage of plastid genomes data, the phylogenetic relationships and the evolutionary history of this genus remain unclear. Therefore, the complete chloroplast genomes of F. calcarean and F. hainanensis were sequenced using high-throughput sequencing and then compared with the chloroplast genomes of other reported Firmiana species. The genome size of F. calcarean and F. hainanensis is 161,263 and 160,031 bp long, respectively, containing a total of 131 genes (including 85 protein coding genes, 37 tRNAs, 8 rRNAs, and one pseudogene). Comparative analysis revealed that the genome structure, GC content, gene content and order, as well as the RNA editing sites within the chloroplast genomes of F. calcarean and F. hainanensis were similar to previously reported Firmiana species. ML phylogenetic analysis revealed that F. danxiaensis, F. hainanensis, F. calcarean, F. simplex, and F. major form a sister group to F. colorata, F. pulcherrima, and F. kwangsiensis. The SSRs, long repeats, and 21 highly divergent regions (Pi > 0.01) identified in this study might provide potential DNA markers for further population genetics and phylogenetic studies of Firmiana. Our findings can help design new species-specific molecular markers and the general framework to further explore the evolutionary history of Firmiana and to address their conservation challenges.


Five-years of a mandatory single-embryo transfer (mSET) policy dramatically reduces twinning rate without lowering pregnancy rates.
To report the outcomes of a program policy instituted in 2004 mandating single-embryo transfer (mSET) for all women aged <38 years, with at least seven zygotes, no prior failed fresh cycle at our center, and at least one good-quality blastocyst. Retrospective cohort study. Academic medical center. All women <38 years old undergoing a fresh cycle with autologous oocytes and all women undergoing a fresh cycle with donor oocytes from June 1, 1999, to May 31, 2004 (before mSET) and from June 1, 2004, to May 31, 2009 (after mSET). mSET policy implementation. Live-birth rate, multiple pregnancy rate, clinical volume, and outcomes of all mSET fresh IVF transfers were analyzed. Clinical volume was unchanged between the two time groups. After implementation of mSET, live-birth rates improved from 51.1% to 55.9% and multiple-birth rates dropped from 34.8% to 17.5%. A total of 364 mSET fresh transfers were performed with a live-birth rate of 64.6% and a multiple-birth rate of 3.4%. A mandatory SET policy based on prognostic factors can be instituted with no drop in clinical volume and no negative effect on delivery rates. Multiple gestation rates can be dramatically lowered.


Effect of graphene and graphene oxide on antibiotic resistance genes during copper-contained swine manure anaerobic digestion.
Copper is an important selectors for antibiotic resistance genes (ARGs) transfer because of metal-antibiotic cross-resistance and/or coresistance. Due to carbon-based materials' good adsorption capacity for heavy metals, graphene and graphene oxide have great potential to reduce ARGs abundance in the environment with copper pollution. To figure out the mechanics, this study investigated the effects of graphene and graphene oxide on the succession of ARGs, mobile genetic elements (MGEs), heavy metal resistance genes (HMRGs), and bacterial communities during copper-contained swine manure anaerobic digestion. Results showed that graphene and graphene oxide could reduce ARGs abundance in varying degrees with the anaerobic reactors that contained a higher concentration of copper. Nevertheless, graphene decreased the abundance of ARGs more effectively than graphene oxide. Phylum-level bacteria such as Firmicutes, Bacteroidetes, Spirochaetes, and Verrucomicrobiaat were significantly positively correlated with most ARGs. Network and redundancy analyses demonstrated that alterations in the bacterial community are one of the main factors leading to the changes in ARGs. Firmicutes, Bacteroidetes, and Spirochaetes were enriched lower in graphene reactor than graphene oxide in anaerobic digestion products, which may be the main reason that graphene is superior to graphene oxide in reduced ARGs abundance. Additionally, ARGs were close to HMRGs than MGEs in the treatments with graphene, the opposite in graphene oxide reactors. Therefore, we speculate that the reduction of HMRGs in graphene may contribute to the result that graphene is superior to graphene oxide in reduced ARGs abundance in anaerobic digestion.


A biometric authentication scheme for telecare medicine information systems with nonce.
In recent years, the increased availability of lower-cost telecommunications systems and customized patients monitoring devices made it possible to bring the advantages of telemedicine directly into the patient's home. These telecare medicine information systems enable health-care delivery services. These systems are moving towards an environment where automated patient medical records and electronically interconnected telecare facilities are prevalent. Authentication, security, patient's privacy protection and data confidentiality are important for patient or doctor accessing to Electronic Medical Records (EMR). A secure authentication scheme will be required to achieve these goals. Many schemes based on cryptography have been proposed to achieve the goals. However, many schemes are vulnerable to various attacks, and are neither efficient, nor user friendly. Specially, in terms of efficiency, some schemes are resulting in high time cost. In this paper we propose a new authentication scheme that is using the precomputing to avoid the time-consuming exponential computations. Finally, it is shown to be more secure and practical for telecare medicine environments.


Multiplex real-time PCR for the detection and quantification of latent and persistent viral genomes in cellular or plasma blood fractions.
In common with latent viruses such as herpesviruses, parvovirus B19, HBV and GBV-C are contained successfully by the immune response and persist in the host. When immune control breaks down, reactivation of both latent and persistent viruses occurs. Two multiplex assays were developed (B19, HBV, HHV-8), (EBV, CMV, VZV) for blood screening, and tested on blood donor samples from Ghana to determine baseline prevalence of viraemia in immunocompetent persons. Single-virus real-time quantitative PCR (qPCR) assays were optimised for viral load determination of positive initial screening. The qPCR method utilised was absolute quantification with external standards. Multiplex and single-virus qPCR assays had similar sensitivity, except for the B19 assay in which sensitivity was 100-fold lower. Assays were optimised for reproducibility and repeatability, with R(2) of 0.9 being obtained for most assays. With the exception of B19 and CMV, assays had 100% detection limit ranging between 10(1) and 10(2) copies, IU or arbitrary units under single-virus and multiplex assay conditions. The prevalence of viraemia was 1.6% HBV (0.8% DNA+/HBsAg-, 0.8% DNA+/HBsAg+), 0.8% parvovirus B19, and 3.3% GBV-C viraemia in the plasma fraction. The prevalence of four herpesviruses was 1.0% HHV-8, 0.85% CMV, and 8.3% EBV, and no detectable VZV viraemia.


Characterization and expression of the beta-N-acetylhexosaminidase gene family of Tribolium castaneum.
Enzymes belonging to the beta-N-acetylhexosaminidase family cleave chitin oligosaccharides produced by the action of chitinases on chitin into the constituent N-acetylglucosamine monomer. Four genes encoding putative chitooligosaccharidolytic beta-N-acetylhexosaminidases (hereafter referred to as N-acetylglucosaminidases (NAGs)) in the red flour beetle, Tribolium castaneum, namely TcNAG1, TcFDL, TcNAG2, and TcNAG3, and three other related hexosaminidases were identified by searching the recently completed genome [Tribolium Genome Sequencing Consortium, 2007. The first genome sequence of a beetle, Tribolium castaneum, a model for insect development and pest biology. Nature, submitted for publication]. Full-length cDNAs for all four NAGs were cloned and sequenced, and the exon-intron organization of the corresponding genes was determined. Analyses of their developmental expression patterns indicated that, although all four of the NAGs are transcribed during most developmental stages, each gene had a distinct spatial and temporal expression pattern. TcNAG1 transcripts are the most abundant, particularly at the late pupal stage, while TcNAG3 transcripts are the least abundant, even at their peak levels in the late larval stages. The function of each NAG during different developmental stages was assessed by observations of lethal phenotypes after gene-specific double-stranded RNA (dsRNA)-mediated transcript depletion as verified by real-time PCR. TcNAG1 dsRNA was most effective in interrupting all three types of molts: larval-larval, larval-pupal, and pupal-adult. Treated insects died after failing to completely shed their old cuticles. Knockdown of transcripts for the other three NAG genes resulted in phenotypes similar to those of TcNAG1 dsRNA-treated insects, but the effects were somewhat variable and less severe. Sequence comparisons with other enzymatically characterized insect homologs suggested that TcFDL, unlike the other NAGs, may have a role in N-glycan processing in addition to its apparent role in cuticular chitin turnover. These results support the hypothesis that TcNAGs participate in chitin turnover and/or N-glycan processing during insect development and that each NAG fulfills an essential and distinct function.


Specification of neural crest cell formation and migration in mouse embryos.
Of all the model organisms used to study human development, rodents such as mice most accurately reflect human craniofacial development. Collective advances in mouse embryology and mouse genetics continue to shape our understanding of neural crest cell development and by extrapolation the etiology of human congenital head and facial birth defects. The aim of this review is to highlight the considerable progress being made in our understanding of cranial neural crest cell patterning in mouse embryos.


Brief imaginal exposure exercises for social anxiety disorder: A randomized controlled trial of a self-help momentary intervention app.
Emerging technological interventions for psychological disorders are being developed continually. Offering imaginal exposure exercises as a self-help intervention presents the opportunity to acquire foundational skills to address social anxiety. The current study evaluates the feasibility and effectiveness of a novel smartphone application for social interaction anxiety. Participants (n = 82) were adults meeting criteria for social anxiety disorder. They were randomly assigned to imaginal exposure (IE; n = 39) or self-monitoring (n = 43) delivered multiple times daily via a smartphone application for a one-week trial. It was expected that participants using the IE exercises would demonstrate significantly greater declines in social anxiety in addition to increases in self-efficacy and that compliance would serve as a predictor of outcome. Mixed-effects models were utilized. Participants using IE (vs. self-monitoring) evidenced significantly greater reductions in social anxiety from pre- to post-treatment and at 1-month follow-up. Similarly, IE (vs. self-monitoring) led to significantly greater increases in self-efficacy from pre- to post-treatment and 1-month follow-up. Further, more completed IE exercises predicted significantly greater changes in social anxiety and self-efficacy at subsequent timepoints compared with self-monitoring. Findings suggest that a brief IE self-help intervention was effective in targeting social interaction anxiety.


Expression site associated genes of Trypanosoma brucei rhodesiense.
Upstream of at least some telomere-linked genes for the variant surface glycoproteins (VSGs) of African trypanosomes are expression site associated genes (ESAGs) whose transcription is co-ordinated with the transcription of the adjacent VSG gene [Cully et al. (1985) Cell 42, 173-182]. The function of the corresponding ESAG proteins is not known. Here we show the sequences of two members of the ESAG-I family that are upstream of the VSG genes expressed in metacyclic variant antigen types 4 and 7 of Trypanosoma brucei rhodesiense. The corresponding metacyclic ESAG-I proteins of about 330 amino acids display extensive positional identity both with each other and with two other ESAG-I proteins of Trypanosoma brucei brucei. Only about 7% of the positions are occupied by a different amino acid in each of the four putative ESAG proteins while 40% of the positions are identical. Thus, the ESAG-I proteins are much more highly conserved than are the VSGs studied to date.


Erratum.
Stent fracture and occlusion after treatment of symptomatic vertebral artery ostium stenosis with a self-expanding device: A case report by Jun Lu, Jiachun Liu, Daming Wang and Shuo Wang, Interventional Neuroradiology 2014 20: 755-760, DOI: 10.15274/INR-2014-10068. In the above article the author affiliations were listed incorrectly, the correct version is listed below: Jun Lu(1), Jiachun Liu(2), Daming Wang(2) and Shuo Wang(1) (1)Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (2)Department of Neurosurgery, Beijing Hospital, Beijing, China.


Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate.
Among a sample of 43 women with epilepsy treated for at least 2 years with valproate (n=22) or other antiepileptic drugs (AEDs) (n=21), polycystic ovary syndrome (PCOS) was diagnosed in three women, two of them were treated with valproate. Although the rate of PCOS and of menstrual disturbances, weight body mass index (BMI) and waist to hip ratio as well as fasting blood glucose levels, fasting insulin, proinsulin and C-peptide values was similar in this small sample of women treated with valproate and other AEDs, valproate exposure was associated with higher androgen levels, higher postprandial (pp) insulin and proinsulin levels, as well as lower cholesterol and low density lipoprotein (LDL) cholesterol levels. The pronounced increase in pp insulin levels during VPA treatment may indicate an effect of the fatty acid derivate VPA on pancreatic islet cells.


Titanium dioxide nanoparticles as multifunctional surface-active materials for smart/active nanocomposite packaging films.
Environmental issues such as plastic packaging and high demand for fresh and safe food has increased the interest for developing smart/active food packaging films with colloidal nanoparticles (NPs). Titanium dioxide nanoparticles (TNPs) are cost effective and stable metal oxide NPs which could be used as a functional nano-filler for biodegradable food packaging due to their excellent biocompatibility, photo catalyzing, and antimicrobial properties. This article has comprehensively reviewed the functional properties and advantages of TNPs-containing smart/active films. The advantage of adding TNPs for ameliorating food packaging materials such as their physical, mechanical, moisture/light barrier, optical, thermal resistance, microstructure and chemical properties as well as, antibacterial, and photocatalytic properties are discussed. Also, the practical and migration properties of administrating TNPs in food packaging material are investigated. The ethylene decomposition activity of TNPs containing active films, could be used for increasing the shelf life of fruits/vegetables after harvesting. TNPs are safe with negligible migration rates which could be used for fabrication of multifunctional smart/active packaging films due to their antimicrobial properties and ethylene gas scavenging activities.


Effect of chloramphenicol on colony formation from erythrocytic precursors.
In the present experiments, we compare the behavior of erythropoietic precursors and granulocytic precurosors exposed to chloramphenicol. Subcutaneous injection of 20 mg of chloramphenicol sodium succinate on five successive days induced a reduction in the number of erythrocytic colony-forming units (CFU-E) and erythropoietic burst-forming units (BFU-E) in murine marrow and spleen, while no change in number of granulocytic precursors (CFU-C) in murine hemopoietic organs was observed. In vitro studies demonstrated concentration-dependent inhibition of chloramphenicol or chloramphenicol sodium succinate in the colony formatin of all these precursors from murine and human bone marrow. However, erythropoietic burst formation of murine and human BFU-E was completely suppressed by the addition of chloramphenicol or chloramphenicol sodium succinate to the culture medium at therapeutic concentrations (20--40 microgram/ml). From the present results, it can be concluded that the reduced number of BFU-E in mice after injection of chloramphenicol sodium succinate resulted from the selective toxicity of chloramphenicol to BFU-E at therapeutic concentrations.


Graphene matrix for signal enhancement in ambient plasma assisted laser desorption ionization mass spectrometry.
In this work, the signal intensity of ambient plasma assisted laser desorption ionization mass spectrometry (PALDI-MS) was significantly increased with graphene as matrix. The graphene functions as a substrate to trap analytes, absorb energy from the visible laser irradiation and transfer energy to the analytes to facilitate the laser desorption process. The desorbed analytes are further ionized by helium plasma and analyzed by MS. Compared with a traditional organic matrix, α-cyano-4-hydroxycinnamic acid (CHCA), graphene exhibited much higher desorption efficiency for most of the compounds benefitting from the strong optical absorption at 532nm. The performance has been confirmed by the facile analysis of more than forty compounds with various structures. Additionally, this method was successfully applied to distinguish three kinds of Chinese tea leaves by detecting the endogenous caffeine and theanine, which proved the utility, facility and convenience of this method for rapid screening of main components in real samples.


Comparing the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in type 2 diabetes mellitus patients after coronary stents implantation: a systematic review and meta-analysis of randomized controlled trials.
Since antiplatelet therapy in type 2 diabetes mellitus (T2DM) patients is very important after intracoronary stenting, and because the most commonly used therapies have been the dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel and the triple antiplatelet therapy (TAPT) consisting of aspirin, clopidogrel and cilostazol, we aim to compare the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in T2DM patients. Systematic literature search was done from the databases of PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI) and WanFang. Randomized controlled trials (RCTs) comparing the effectiveness and safety between triple therapy and dual therapy in T2DM patients after coronary stents placement were included. Endpoints included major adverse cardiac effects (MACEs), target lesion revascularization (TLR), target vessel revascularization (TVR), death, stent thrombosis, bleeding and adverse drug reactions during a 9-12 months period, as well as platelet activities. Four studies including 1005 patients reporting the adverse clinical outcomes and six studies including 519 patients reporting the platelet activities, with a total of 1524 patients have been analyzed in this meta-analysis. The pooling analysis shows that TAPT has significantly decreased the occurrence of MACEs (RR: 0.55; 95 % CI: 0.36-0.86, P = 0.009), TLR (RR 0.41; 95 % CI: 0.21-0.80, P = 0.008), TVR (RR 0.55; 95 % CI: 0.34-0.88, P = 0.01) and the overall incidence of Death/ Myocardial Infarction (MI)/TVR (RR 0.54; 95 % CI: 0.31-0.94, P = 0.03) during this 9 to 12 months follow up period after stents implantation. Stent thrombosis was almost similar in both groups. Bleeding seemed to favor DAPT but the result was not statistically significant. Platelet aggregation, platelet reactivity index (PRI) and platelet reactivity unit (PRU) were also reduced with Weight Mean Difference (WMD) of (-13.80; 95 % CI: -17.03 to -10.56, P < 0.00001), (-22.87; 95 % CI: -23.66 to -22.07, P < 0.00001) and (-44.17; 95 % CI: -58.56 to -29.77, P < 0.00001) respectively. Since MACEs have been significantly decreased in the triple group, TAPT appears to be more effective than DAPT in T2DM patients after intracoronary stenting. No significant difference in stent thrombosis and bleeding risks between these 2 groups shows TAPT to be almost as safe as DAPT in these diabetic patients.


Coronapp: A web application to annotate and monitor SARS-CoV-2 mutations.
The avalanche of genomic data generated from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus requires the development of tools to detect and monitor its mutations across the world. Here, we present a webtool, coronapp, dedicated to easily processing user-provided SARS-CoV-2 genomic sequences and visualizing the current worldwide status of SARS-CoV-2 mutations. The webtool allows users to highlight mutations and categorize them by frequency, country, genomic location and effect on protein sequences, and to monitor their presence in the population over time. The tool is available at http://giorgilab.unibo.it/coronannotator/ for the annotation of user-provided sequences. The full code is freely shared at https://github.com/federicogiorgi/giorgilab/tree/master/coronannotator.


Association of body mass index with cause specific deaths in Chinese elderly hypertensive patients: Minhang community study.
Most studies have suggested that elevated body mass index (BMI) was associated with the risk of death from all cause and from specific causes. However, there was little evidence illustrating the effect of BMI on the mortality in elderly hypertensive patients in Chinese population. The information of 10,957 hypertensive patients at baseline not less than 60 years were from Xinzhuang, a town in Minhang district of Shanghai, was extracted from the Electronic Health Record (EHR) system. All study participants were divided into eight categories of baseline BMI (with cut-points at 18, 20, 22, 24, 26, 28 and 30 kg/m(2)). Relative hazard ratio of death from all cause, cardiovascular and non-cardiovascular cause by baseline BMI groups were calculated, standardized for sex, age, smoking, drinking, physical activity, systolic blood pressure, history of cardiovascular disorders, serum lipid disturbance, diabetes mellitus and antihypertensive drug treatment. DURING FOLLOW UP (MEDIAN: 3.7 years), 561 deaths occurred. Underweight (BMI<18 kg/m(2)) was associated with significantly increased mortality from all cause mortality (OR: 2.00; 95% CI: 1.43-2.79) and non cardiovascular mortality (OR: 2.76; 95% CI: 1.87-4.07), but not with cardiovascular mortality. For the cause specific analysis, the underweight was associated significantly with neoplasms (OR: 2.15; 95% CI: 1.16-4.00) and respiratory disorders (OR: 3.41; 95% CI: 1.64-7.06). The results for total mortality and specific cause mortality were not influenced by sex, age and smoking status. Our study revealed an association between underweight and increased mortality from non-cardiovascular disorders in elderly hypertensive patients in Chinese community. Overweight and obesity were not associated with all cause or cause specific death.


Expression and Characterization of Mammalian Carotenoid Cleavage Dioxygenases.
Carotenoid cleavage dioxygenases (CCDs) are nonheme iron enzymes that catalyze double bond processing of carotenoids and their apocarotenoid metabolites. Mammalian genomes encode three members of this protein family, namely BCO1, BCO2, and RPE65. Mutations and genetic polymorphism in the corresponding genes are associated with inherited blinding diseases, vitamin A deficiency, and high carotenoid plasma levels. Here we describe a method for the heterologous expression of mammalian BCO1 and BCO2 in E. coli and the biochemical characterization of these recombinant enzymes. Dissecting the enzymatic properties of CCDs will advance our knowledge of the biochemical processes that are govern by these disease-associated enzymes and may assist the design of interventions directed against these disease states.


Evaluation of Myocardial Stiffness in Cardiac Amyloidosis Using Acoustic Radiation Force Impulse and Natural Shear Wave Imaging.
Increased myocardial stiffness (MS) is an important hallmark of cardiac amyloidosis (CA) caused by myocardial amyloid deposition. Standard echocardiography metrics assess MS indirectly via downstream effects of cardiac stiffening. The ultrasound elastography methods acoustic radiation force impulse (ARFI) and natural shear wave (NSW) imaging assess MS more directly. This study compared MS in 12 healthy volunteers and 13 patients with confirmed CA using ARFI and NSW imaging. Parasternal long-axis acquisitions of the interventricular septum were obtained using a modified Acuson Sequoia scanner and a 5V1 transducer. ARFI-induced displacements were measured through the cardiac cycle, and ratios of diastolic-over-systolic displacement were calculated. NSW speeds from aortic valve closure were extracted from echocardiography-tracked displacement data. ARFI stiffness ratios were significantly lower in CA patients than controls (mean ± standard deviation: 1.47 ± 0.27 vs. 2.10 ± 0.47, p < 0.001), and NSW speeds were significantly higher in CA patients than controls (5.58 ± 1.10 m/s vs. 3.79 ± 1.10 m/s, p < 0.001). A linear combination of the two metrics exhibited greater diagnostic potential than either metric alone (area under the curve = 0.97 vs. 0.89 and 0.88). MS was measured to be significantly higher in CA patients using both ARFI and NSW imaging. Together, these methods have potential utility to aid in clinical diagnosis of diastolic dysfunction and infiltrative cardiomyopathies.


Exogenous aluminum accumulates in the lysosomes of cultured rat cortical neurons.
In order to study the intracellular localization of aluminum, 0.01% AlCl3 was added to rat cerebral organotypic cultures following 14 days incubation in a standard medium. The cultures were maintained in the aluminum (Al)-containing medium for 1 or 3 days. Subsequently, electron probe X-ray micro-analysis (EPXMA), was used to localize aluminum in the neurons. The Al was found in the cells as early as after 1 day of AlCl3 exposure. The Al was detected exclusively in the neuronal lysosomes, in 66% (1 day exposure) and 97% (3 days) of the measured lysosomes. This localization was confirmed by laser microprobe mass analysis (LAMMA) measurements. Our results demonstrate an Al localization in the neurons, exposed to exogenous Al, different from that in the brains of patients with Alzheimer's disease.


Actin cytoskeleton of resting bovine platelets.
Actin filaments in resting discoid bovine platelets were examined by fluorescence and electron microscopy. Rhodamine-phalloidin staining patterns showed a characteristic wheel-like structure which consisted of a central small circle connected by several radial spokes to a large peripheral circle. This wheel-like structure was composed of actin filaments forming a characteristic arrowhead structure with heavy meromyosin from muscle. Actin filaments were densely arrayed in parallel with a marginal microtubule band and radiated out from the center to the periphery. Platelets treated with colchicine lost their marginal microtubule band but retained their wheel-like structure and normal discoid form. Cytochalasin B disrupted the wheel-like structure but not the marginal microtubule band or the normal discoid form. After simultaneous treatment with both cytochalasin B and colchicine, platelets lost their discoid shape. These results suggest that actin filaments and microtubules both play important roles in the maintenance of the discoid shape of resting bovine platelets.


Impact of anodal high-definition transcranial direct current stimulation of medial prefrontal cortex on stroop task performance and its electrophysiological correlates. A pilot study.
Medial prefrontal cortex (MPC) has been associated with a wide range of cognitive functions; however, its specific role in interference control is not fully understood. The current study investigates the role of MPC in interference control by externally stimulating it with an electric current and studying associated behavioral and neurophysiological markers. Participants randomly assigned to experimental and sham groups were administered with a high-definition transcranial direct current stimulation (HD-tDCS) of 2 mA for 15 min. They performed a classic color-word Stroop task before, during, and immediately after the stimulation, while electroencephalography (EEG) was acquired throughout the experiment. A decrease in reaction time (RT) for incongruent and neutral trials of the Stroop task was observed in the experimental group compared to the sham group with a significant reduction in the Stroop Effect after stimulation; however, no significant change was observed in the amplitude and latency of N200, P200, and N450 event related potentials. Furthermore, the resting state complexity of the neural signals in the medial frontal region was decreased in the experimental group with a decrease in theta frequency band during the Stroop task. We conclude that the stimulation of MPC increases its efficiency in resolving the conflict by reducing theta power during the Stroop task, which is also reflected in the reduced complexity in the resting state EEG. (ClinicalTrials.gov Identifier: NCT04318522).


Induction of experimental autoimmune arthritis by a public epitope of the T cell receptor variable alpha domain of an arthritogenic T cell clone.
T cell receptor (TCR) peptide immunizations have been demonstrated to protect against experimental autoimmune diseases. These findings have led to clinical trials employing TCR peptides in multiple sclerosis and rheumatoid arthritis patients. Previously, we identified a strongly immunogenic region of the TCR alpha chain of an arthritogenic T cell clone (AV11 66-80). In this report, we show that rats immunized with AV11 66-80 developed arthritis with clinical symptoms and histology similar to adjuvant arthritis (AA). Transfer of this disease into naive rats using AV11 66-80-specific T cells proved the T cell-mediated character of the disease. The AV11 66-80 arthritic rats developed resistance to Mycobacterium tuberculosis-induced AA, indicating that both forms of arthritis depended on similar regulatory mechanisms. This first demonstration of TCR peptide-induced arthritis, together with an earlier report on a polymorphism in this very same AV11 66-80 region involved in arthritis resistance in mice, suggests a central role of the public epitope AV11 66-80 in the control of autoimmune arthritis. Although TCR peptide immunizations can be exploited to prevent experimental autoimmunity, caution should be taken in the induction of TCR peptide-specific T cells for immunotherapy to avoid adverse effects as shown here.


The promise of human organoids in the digestive system.
The advent of organoid technology has enabled scientists and clinicians to utilize cells from primary tissues or pluripotent stem cells (PSCs) to grow self-organizing tissue systems, thus attaining cellular diversity, spatial organization, and functionality as found within digestive tracts. The development of human gastrointestinal (GI) and hepato-biliary-pancreatic organoids as an in-a-dish model present novel opportunities to study humanistic mechanisms of organogenesis, regeneration and pathogenesis. Herein, we review the recent portfolios of primary tissue-derived and PSC-derived organoids in the digestive systems. We also discuss the promise and challenges in disease modeling and drug development applications for digestive disorders.


The exploration of pharmacokinetic and pharmacodynamic data using interactive three-dimensional graphs, a tool borrowed from particle physics.
Computerized interactive 3-dimensional graphical displays were originally developed to aid in the exploration of multidimensional data from particle physics experiments. This technique can be equally well applied to speed the analysis of multivariate pharmaco-kinetic and pharmacodynamic data. The application of this technique to the results of a drug study demonstrated its effectiveness in providing a rapid overview of the data and in displaying new perspectives on the multivariate data, helping to identify sources of variability within the study. Multiple concentration-time curves from a given administration period can be distinguished within a single plot, using visual cues provided by rotating the display. Simultaneous comparison of large numbers of curves allows rapid evaluation of intersubject variability. Comparing the concentration-time curves from a single subject, each in succession, quickly identifies sources of intra-subject variability. Manipulating the display by a fourth dimensional parameter shows the degree of relationship between the concentration-time curves and associated dynamic variables. Exploratory analysis using such kinematic display software, provides a rapid, visually concrete impression of the relationships present in kinetic and dynamic data before the application of standard statistical routines.


Reconstructing a health system and a profession: priorities of Iraqi nurses in the Kurdish region.
To evaluate nurses' priorities for health system reconstruction and professional development in Iraq, a survey of 744 Iraqi nurses was conducted, with the research process managed via the Internet. Seven definite priorities emerged along with significant differences in priorities related to years of experience, age, speciality area of nursing practice, gender, level of education, and geographic location of practice. Results indicate that nurses should be included in health system reconstruction processes and that support for the development of the nursing profession should be included in the plan for overall reconstruction.


Identified neurones isolated from leech CNS make selective connections in culture.
Neurones cultured in vitro offer distinct advantages for studying how processes grow towards their targets and form synaptic connections. In contrast to the complex events occurring during the development of the nervous system, synapse formation in culture can be analysed in a few neurones at a time and under controlled conditions. We have now dissected out and cultured single identified neurones from the central nervous system (CNS) of the adult leech. Various types of sensory cells, motor cells, and interneurones can be identified in leech ganglia--each with a stereotyped set of properties, including: (1) the electrical characteristics of its membrane, (2) the arborisation of its branches and the morphology of its terminals and (3) the pattern of connections it makes with other identified neurones, skin or muscle. Thus, cultured cells can be compared in detail with their counterparts in situ. We have found that isolated cells survive for several weeks, maintain their membrane properties, sprout and form selective connections.


Archaeal hyperthermostable mannitol dehydrogenases: A promising industrial enzymes for d-mannitol synthesis.
Recently, the term healthy lifestyle connected to low-calorie diets, although it is not possible to get rid of added sugars as a source of energy, despite the close relation of added sugars to some diseases such as obesity, diabetes, etc. As a result, the sweetener market has flourished, which has led to increased demand for natural sweeteners such as polyols, including d-mannitol. Various methods have been developed to produce d-mannitol to achieve high productivity and low cost. In particular, metabolic engineering for d-mannitol considers one of the most promising approaches for d-mannitol production on the industrial scale. To date, the chemical process is not ideal for large-scale production because of its multistep mechanism involving hydrogenation and high cost. In this review, we highlight and present a comparative evaluation of the biochemical parameters that affecting d-mannitol synthesis from Thermotoga neapolitana and Thermotoga maritima mannitol dehydrogenase (MtDH) as a potential contribution for d-mannitol bio-synthesis. These species were selected because purified mannitol dehydrogenases from both strains have been reported to produce d-mannitol with no sorbitol formation under temperatures (90-120 °C).


Nitrite-specific active transport system of the cyanobacterium Synechococcus sp. strain PCC 7942.
Studies on the nitrite uptake capability of a mutant of Synechococcus sp. strain PCC 7942 lacking the ATP-binding cassette-type nitrate-nitrite-bispecific transporter revealed the occurrence of a nitrite-specific active transport system with an apparent Km (NO2-) of about 20 microM. Similar to the nitrate-nitrite-bispecific transporter, the nitrite-specific transporter was reversibly inhibited by ammonium in the medium.


Probing soft fibrous materials by indentation.
Indentation is often used to measure the stiffness of soft materials whose main structural component is a network of filaments, such as the cellular cytoskeleton, connective tissue, gels, and the extracellular matrix. For elastic materials, the typical procedure requires fitting the experimental force-displacement curve with the Hertz model, which predicts that f=kδ1.5 and k is proportional to the reduced modulus of the indented material, E/(1-ν2). Here we show using explicit models of fiber networks that the Hertz model applies to indentation in network materials provided the indenter radius is larger than approximately 12lc, where lc is the mean segment length of the network. Using smaller indenters leads to a relation between force and indentation displacement of the form f=kδq, where q is observed to increase with decreasing indenter radius. Using the Hertz model to interpret results of indentations in network materials using small indenters leads to an inferred modulus smaller than the real modulus of the material. The origin of this departure from the classical Hertz model is investigated. A compacted, stiff network region develops under the indenter, effectively increasing the indenter size and modifying its shape. This modification is marginal when large indenters are used. However, when the indenter radius is small, the effect of the compacted layer is pronounced as it changes the indenter profile from spherical towards conical. This entails an increase of exponent q above the value of 1.5 corresponding to spherical indenters. STATEMENT OF SIGNIFICANCE: The article presents a study of indentation in network biomaterials and demonstrates a size effect which precludes the use of the Hertz model to infer the elastic constants of the material. The size effect occurs once the indenter radius is smaller than approximately 12 times the mean segment length of the network. This result provides guidelines for the selection of indentation conditions that guarantee the applicability of the Hertz model. At the same time, the finding may be used to infer the mean segment length of the network based on indentations with indenters of various sizes. Hence, the method can be used to evaluate this structural parameter which is not easily accessible in experiments.


Reasons for improper simple hysterectomy in patients with invasive cervical cancer in the northern region of Thailand.
To determine the reasons for improper simple hysterectomy in the presence of invasive cervical cancer. The medical records of 70 patients who had undergone simple hysterectomy in the presence of invasive cervical cancer and were referred to Chiang Mai University Hospital between January 1991 and December 1998 were reviewed. Approximately half of the patients presented with abnormal vaginal bleeding. Failure to perform a Papanicolaou smear before the operation accounted for 35.4%. Normal pelvic examination in which no gross invasive tumor was observed accounted for 59%. The most common indications for inappropriate operation was cervical dysplasia. The reasons for inappropriate simple hysterectomy included lack of preoperative cervical cytology (22.8%), incomplete evaluation of cervical dysplasia or microinvasion on biopsy (21.4%), false-negative cervical cytology (18.6%), failure to perform an endocervical curettage following conization (8.6%), emergency hysterectomy (8.6%), failure to perform indicated conization (5.6%), errors in colposcopic examination (4.3%), incomplete evaluation of an abnormal cervical cytology (1.4%), failure to perform endocervical currettage following loop conization (1.4%), failure to review slide (1.4%), failure to check the pathology report (1.4%), failure to biopsy a gross cervical lesion, and skipped lesion in upper part of the endocervix (1.4%). One case of invasive disease was missed for unknown reason. Most cases of inappropriate hysterectomy resulted from deviation from guideline for cervical cancer detection. Preoperative Papanicolaou smear and strict adherence to the well-established diagnostic protocol for patients with an abnormal smear are advised to prevent such occurrence.


The dentition of European Speleomantes spp. (Urodela, Plethodontidae) with special regard to sexual dimorphism.
Dentigerous bones and dentition of juveniles and adults of several European Speleomantes-species were investigated using scanning electron microscopy. In the juveniles examined, all dentigerous bones bore bicuspid teeth. The adult males showed the well-known dentitional sexual dimorphism, i.e. monocuspid largely conical, elongated and strongly curved premaxillary teeth. However, teeth of the anterior portion of the maxillae and some teeth of the dentary were also clearly monocuspid; the remaining teeth had differently shaped apices considered to be different grades of bicuspidity. Vomerine teeth were exclusively bicuspid. Monocuspid, but smaller teeth were also found on the premaxilla of an adult female. The conical monocuspid tooth in adults is a modified metamorphosed tooth. Monocuspids, at least on the premaxillae, may be constantly present in males and development of monocuspids probably depends on differential sensitivities of the tooth producing tissue for androgen stimuli.


Promotion of ambulation of patients with spinal muscular atrophy by early fitting of knee-ankle-foot orthoses.
Seven children with spinal muscular atrophy aged between 20 months and four years, none of whom had ever walked, were fitted with knee-ankle-foot orthoses. All the children could sit unsupported and therefore were at point 9 on the Vignos functional scale. Two children achieved autonomous walking, three assisted walking and the remaining two could stand without aid. During the follow-up period there was no progression of weakness and neither scoliosis nor contractures developed.


Carcinoma of the esophagus.
Carcinoma of the esophagus continues to have a low 5-year cure rate despite advances in radical surgery and super-voltage radiation. Neither patient education nor newer diagnostic techniques have improved survival. The reported operative mortality is 4 to 30% for esophagogastrostomy and 10 to 44% for colon interposition. Average survival time with surgery is 11 to 28 months and 5 to 11 months with irradiation. Local recurrence is high (33 to 76%) with irradiation. The reported 5-year survival rate with preoperative irradiation followed by surgery is higher (14 to 25%). Recent reports have concentrated on improving functional rehabilitation rather than improving cure rates. Palliative surgery is more acceptable because of lowered operative morbidity and mortality and the high complication rate with radiation therapy for far advanced disease. New approaches of interest include fundoplication added to esophagogastrostomy, substernal gastric bypass with anastomosis in the neck, reversed gastric tube (Heimlich operation), the addition of postoperative rather than preoperative irradiation in patients with potentially curable lesions, the use of preoperative hyperalimentation, and the potential application of immunotherapy.


Structural basis of a fungal galectin from Agrocybe cylindracea for recognizing sialoconjugate.
Galectin from an edible fungus Agrocybe cylindracea (ACG) has a strong preference for N-acetylneuraminyl lactose (NeuAcalpha2-3lactose). The sugar recognition mechanism of ACG was explored by the X-ray crystallographic analyses of ligand-free ACG, and its complex with lactose, 3'-sulfonyl lactose and NeuAcalpha2-3lactose. The refined structure shows that ACG is a "proto"-type galectin composed of a beta-sandwich of two antiparallel sheets, each with six strands, in contrast to the five and six strands in animal galectins. ACG dimer in solution was classified as being among the "layer"-type. The carbohydrate recognition domain (CRD) of this galectin is common to those of animal galectins, except for substitution of one residue, Ala64, which corresponds to Asn46 in human galectin 1. A five-residue insertion in ACG at positions 42-46 involving Ser44 and Asn46 modified the architecture of the sugar binding site that contributes sialic acid specificity. Furthermore, it was found that the binding of a sulfate ion near the CRD in the ligand-free form led to a change in the conformation of the loop region caused by main-chain cis/trans transition between Ser44 and Pro45.


[Intramedullary nail placement with percutaneous Kirschner wires. Illustration of method and clinical examples].
Unreamed nailing is an established method for internal fixation of femoral und tibial shaft fractures. The interlocking technique allows the stabilization of metaphyseal fractures, too, but the risk of malalignment increases. The "palisade method" presented here allows the precise positioning of the nail in the marrow cavity and works as a tool for successful minimally invasive nailing in the meta/epiphyseal region. The method is easy to use and suited particularly in combination with the UFN and UTN, but is in principal applicable to other nails, too. In contrast to the "Poller Screw" method developed by Krettek et al., no biomechanical augmentation of the osteosynthesis remains.


Gender-related differences in outcome after BMS or DES implantation in patients with ST-segment elevation myocardial infarction treated by primary angioplasty: insights from the DESERT cooperation.
Several studies have found that among patients with ST-segment elevation myocardial infarction (STEMI) treated by thrombolysis, female sex is associated with a worse outcome. However, still controversial is the prognostic impact of gender in primary angioplasty, especially in the era of drug-eluting stents (DES). Therefore, the aim of this study was to investigate sex-related differences in clinical outcome in patients with STEMI treated with primary angioplasty with Bare-Metal Stent (BMS) or DES. Our population is represented by 6298 STEMI patients undergoing primary angioplasty and stent implantation included in the DESERT database. Follow-up data were collected from 3 to 6 years after primary angioplasty. Female gender was observed in 1466 (23.2%) out of 6298 STEMI patients. Women were older (65.3 ± 12.4 vs 59.3 ± 11.4 years, p < 0.001), with higher prevalence of diabetes (18.6% vs 14.5%, p < 0.001), hypertension (52.4% vs 41.4%, p < 0.001), slightly longer ischemia time (272 ± 247 vs 258 ± 220 min, p = 0.06). No difference was observed in terms of angiographic and procedural characteristics. Follow-up data were available at a mean of 1201 ± 441 days. At long-term follow-up female gender was associated with a significantly higher rate of death (11.7% vs 8.5%, HR [95% CI] = 1.45 [1.18-1.78], p < 0.001), while no difference was observed in terms of reinfarction (HR [95% CI] = 1.14 [0.89-1.45], p = 0.3), ST (HR [95% CI] = 1.12 [0.85-1.48], p = 0.4), with similar temporal distribution (acute, subacute, late and very late) between male and female patients, and no difference in TVR (HR [95% CI] = 1.11 [0.95-1.3], p = 0.2, p = 0.2). These results were confirmed in both patients receiving BMS or DES. The impact of female gender on mortality disappeared after correction for baseline confounding factors (HR [95% CI] = 0.88 [0.71-1.09], p = 0.25). This study shows that in patients with STEMI treated by primary angioplasty, female gender is associated with higher mortality rate in comparison with men, and this is mainly due to their higher clinical and angiographic risk profiles. In fact, female sex did not emerge as an independent predictor of mortality.


Acute effects of alcohol on larval zebrafish: a genetic system for large-scale screening.
Larval zebrafish are used extensively for developmental genetic studies due to their salient features, such as small size, external development, optical transparency, and accessibility in large numbers. However, their use for the study of drug and alcohol abuse has not been explored. Here we investigated the response of larval zebrafish to acute treatment of alcohol. Our analyses showed that like adults, the larval zebrafish exhibited a dose-dependent locomotor response to ethanol: intermediate doses led to hyperactivity, whereas high doses have a neurodepressive effect resulting in hypoactivity and sedation. Alcohol also induced morphological changes of melanocytes, providing a visible cellular measure of the biological effects of alcohol in vivo. In addition, alcohol induced thigmotaxis behavior (preference for the edge of a compartment). In the behaviors we analyzed, genetic background influenced the locomotor responses to alcohol. The present study demonstrates that larval zebrafish exert a response to the acute treatment of alcohol, which is genetically modifiable. Therefore, the larval zebrafish represent a tractable vertebrate model system for a large-scale genetic analysis of the biological effects of alcohol.


Health risk assessment of heavy metal concentration in muscle of Chelon auratus and Chelon saliens from the southern Caspian Sea.
Heavy metals are one of the most serious pollutants in aquatic ecosystems, and their accumulation in fish products causes harmful effects on human health. In this context, we set out to determine the concentrations of heavy metals in the muscle of two fish species of commercial interest, Chelon auratus and Chelon saliens on the south coast of the Caspian Sea. We aimed to assess the degree of environment contamination in this area and to estimate the potential risk to human health derived from the consumption of fish. The mean concentrations of the different metals analysed were very varied in both species. In fact, some concentrations exceeded the permissible limits for the protection of human health for Cd and Pb, and some values of As were above those referenced by other authors in same species in the Caspian Sea. None of the estimated daily intake values exceeded the tolerable intake based on the consumption under consideration. Nonetheless, the accumulative hazard values evidenced a potential risk to human health, Pb and Hg being those giving a higher target hazard quotient. The cancer risk from exposure to As from fish consumption in children was above the "acceptable" risk to life. Thus, in view of the accumulative nature of heavy metals, a moderate and non-abusive fish consumption in this area, particularly in children, would be recommendable.


Non-typhoidal Salmonella group D bacteremia and urosepsis in a patient diagnosed with HIV Infection.
Urinary tract infections caused by non-typhoid Salmonella are rare and usually develops in patients with predisposing factors such as immune deficiency or occult urologic problems. This report describes a case where Salmonella Group D was isolated from the blood and urine of a patient with documented human acquired immunodeficiency syndrome who developed urosepsis and was successfully treated with antibiotics.


Assessing the aneurysm occlusion efficacy of a shear-thinning biomaterial in a 3D-printed model.
Metallic coil embolization is a common method for the endovascular treatment of visceral artery aneurysms (VAA) and visceral artery pseudoaneurysms (VAPA); however, this treatment is suboptimal due to the high cost of coils, incomplete volume occlusion, poor reendothelialization, aneurysm puncture, and coil migration. Several alternative treatment strategies are available, including stent flow diverters, glue embolics, gelfoam slurries, and vascular mesh plugs-each of which have their own disadvantages. Here, we investigated the in vitro capability of a shear-thinning biomaterial (STB), a nanocomposite hydrogel composed of gelatin and silicate nanoplatelets, for the minimally-invasive occlusion of simple necked aneurysm models. We demonstrated the injectability of STB through various clinical catheters, engineered an in vitro testing apparatus to independently manipulate aneurysm neck diameter, fluid flow rate, and flow waveform, and tested the stability of STB within the models under various conditions. Our experiments show that STB is able to withstand at least 1.89 Pa of wall shear stress, as estimated by computational fluid dynamics. STB is also able to withstand up to 10 mL s-1 pulsatile flow with a waveform mimicking blood flow in the human femoral artery and tolerate greater pressure changes than those in the human aorta. We ultimately found that our in vitro system was limited by supraphysiologic pressure changes caused by aneurysm models with low compliance.


CITED1 as a marker of favourable outcome in anti-endocrine treated, estrogen-receptor positive, lymph-node negative breast cancer.
To investigate CITED1 as a potential biomarker of anti-endocrine response and breast cancer recurrence, given its previously determined role in mediating estrogen-dependant transcription. The study is a continuation of earlier work establishing the role of CITED1 in mammary gland development. CITED1 mRNA is associated with estrogen-receptor positivity and selectively expressed in the GOBO dataset of cell lines and tumours representing the luminal-molecular subtype. In patients treated with tamoxifen, higher CITED1 correlated with better outcome, suggesting a role in anti-estrogen response. The effect was particularly evident in the subset of estrogen-receptor positive, lymph-node negative (ER+/LN-) patients although noticeable divergence of the groups was apparent only after five years. Tissue microarray (TMA) analysis further validated the association of CITED1 protein, by immunohistochemistry, with favourable outcome in ER+, tamoxifen-treated patients. Although we also found a favourable response to anti-endocrine treatment in a larger TCGA dataset, the tamoxifen-specific effect was not replicated. Finally, MCF7 cells overexpressing CITED1 showed selective amplification of AREG but not TGFα suggesting that maintenance of specific ERα-CITED1 mediated transcription is important for the long-term response to anti-endocrine therapy. These findings together confirm the proposed mechanism of action of CITED1 and support its potential use as a prognostic biomarker.


Radiation oncologists' perspectives on reducing radiation-induced heart disease in early breast cancer.
Radiotherapy (RT) as an adjuvant treatment for breast cancer (BC), has caused a reduction of recurrences and BC-related deaths. But it has also induced cardiovascular mortality. Oxidative stress is the principle mediator of RT-induced heart disease, similar to many conventional cardiovascular risk factors. The aggregate effect of cardiovascular conditions, RT of heart substructures, implied techniques, and population cardiac mortality rates is not well understood. Due to uncertainties in this field, this article aims to briefly review the recommended strategies for risk assessment, plan optimization, and screening for prevention of RT-induced heart disease in BC patients.


A recurrent missense mutation of keratin 1 gene in a Chinese family with epidermolytic hyperkeratosis (severe palmoplantar hyperkeratosis, type 1).
Epidermolytic hyperkeratosis (EHK) is an autosomal dominantly inherited genodermatosis manifesting with blistering and erythroderma in infancy and widespread hyperkeratosis of the skin, particularly over flexural areas, in adulthood. It can be classified into six clinical phenotypes. We report the case of a 25-year-old man who presented with severe palmoplantar thickening and hyperkeratosis over the flexures for nearly 24 years. Histopathological findings showed characteristic features of EHK, and EHK type PS-1 (severe palmoplantar hyperkeratosis, type 1) was suspected. Further investigation revealed that his father, sister, and nephew (the son of his sister) were similarly affected. A heterozygous missense mutation in exon 7 of KRT1 (c.1436T>C), resulting in an isoleucine to threonine substitution at codon 479 (designated p.I479T), was detected in all affected individuals within the pedigree. Up to now, there has been one sporadic case and one family (including 14 affected individuals) with EHK type PS-1 reported since DiGiovanna and Bale described 25 patients (from two families) with EHK type PS-1 out of 51 patients (from 21 families) with EHK. Although the mutation (c.1436T>C) in KRT1 reported here is a recurrent one, it has not been reported in Chinese patients with EHK. It is interesting to note that the same mutation in KRT1 can cause different phenotypes of EHK. We expand the clinical heterogeneity of EHK due to the same mutation (c.1436T>C) in KRT1 and enrich the database of the KRT1 gene mutations underlying EHK in the Chinese population.


The roles of epigenetic regulation in cholangiocarcinogenesis.
Cholangiocarcinoma (CCA), a heterogeneous malignancy of bile duct epithelial cells, is characterized by aggressiveness, difficult diagnosis, and poor prognosis due to limited understanding and lack of effective therapeutic strategies. Genetic and epigenetic alterations accumulated in CCA cells can cause the aberrant regulation of oncogenes and tumor suppressors. Epigenetic alterations with histone modification, DNA methylation, and noncoding RNA modulation are associated with the carcinogenesis of CCA. Mutation or silencing of genes by various mechanisms can be a frequent event during CCA development. Alterations in histone acetylation/deacetylation at the posttranslational level, DNA methylation at promoters, and noncoding RNA regulation contribute to the heterogeneity of CCA and drive tumor development. In this review article, we mainly focus on the roles of epigenetic regulation in cholangiocarcinogenesis. Alterations in epigenetic modification can be potential targets for the therapeutic management of CCA, and epigenetic targets may become diagnostic biomarkers of CCA.


Left-sided predominance of hypodontia irrespective of cleft sidedness in a French population.
Individuals with oral clefts exhibit considerably more dental anomalies than do individuals without clefts. Our aim was to evaluate the prevalence of tooth agenesis in a sample composed of 124 children (81 boys and 43 girls, mean age 12.5 years) with clefts registered with the Cleft Palate Center in Strasbourg (France). Cleft types and dental agenesis were assessed by clinical and radiographic examination. Cleft types were divided into four groups according to the clinical extent of the cleft (cleft lip only [CL, 12.9%], cleft lip and alveolus [CLA, 4%], cleft lip and palate [CLP, 49.2%], and cleft palate only [CP, 33.9%]). Of the subjects 63% had evidence of hypodontia: maxillary lateral incisors (54%) and upper and lower premolars (32%) were the most common missing teeth. The number of dental ageneses associated with CP (54%) and CLP (79%) was significantly higher than that with CL (33%). All these anomalies were found in proportionately higher frequencies as the severity of the cleft increased, and we found left side predominance for hypodontia (p < .01) irrespective of cleft sidedness. Both right-sided and left-sided clefts were more frequently correlated with left-sided dental agenesis. This left-sided prevalence suggests that common signaling malfunctions might be involved, both in dental development anomalies and cleft genesis.


The determination of Al, Cr, Co, Fe, and Ni in whole blood by electrothermal atomic absorption spectrophotometry.
Procedures for the determination of aluminum, chromium, cobalt, nickel, and iron in whole blood are presented and discussed. Chromium, cobalt, nickel, and iron were determined from one sample after decomposition of the blood with a mixture of nitric and perchloric acids. A graphite furnace was used for the determination of chromium, cobalt and nickel, and flame AAS was used for iron. The determination of Al was done from separate samples by GFAAS after dilution with 1% Triton TX-100. The normal concentration of these elements was measured in rabbit and dog blood.


[Orthopedic shoes: Still in touch with the times?].
Deformities of the foot due to rheumatic disease, particularly rheumatoid arthritis, occur in 85-95% of patients during the course of their disease. This study investigates whether treatment with orthopedic shoes still has a place in modern therapies. Foot orthotics and technical orthopedic shoes can play an important role in purely conservative treatment as well as postoperative therapy. Due to a lack of knowledge concerning modern orthopedic shoe techniques, this treatment option has slipped out of focus--in part because of its association with the old-fashioned unshapely black orthopedic shoes. Nevertheless, these shoes can contribute significantly to maintenance of patient mobility; a factor of extreme importance to the individuals who already suffer considerably from the disease per se.


Lead Tolerance and Enrichment Characteristics of Several Ornamentals Under Hydroponic Culture.
The growth response, tolerance, and enrichment characteristics of six ornamental species, Chlorophytum comosum, Calendula officinalis, Iris lacteal, Belamcanda chinensis, Saponaria officinalis, and Polygonum lapathifolium were studied under hydroponic culture with lead (Pb) concentrations ranging from 0 to 1000 mg/L. The results showed that the growth of the tested ornamental species under Pb stress was inhibited. Belamcanda chinensis presented the largest tolerance index (0.75), and Calendula officinalis had the highest toxicity threshold (500 mg/L) under Pb stress. The highest Pb contents in the shoots were detected in Iris lacteal and Belamcanda chinensis. The enrichment coefficients in the shoots of Iris lacteal and Belamcanda chinensis were significantly higher than those in the other ornamental species. In conclusion, Iris lacteal and Belamcanda chinensis are the most tolerant and have the greatest Pb enrichment and translocation abilities under Pb stress, and thus, they have a strong potential to restore Pb-contaminated water bodies and soils.


Distribution of adrenergic receptors in the enteric nervous system of the guinea pig, mouse, and rat.
Adrenergic receptors in the enteric nervous system (ENS) are important in control of the gastrointestinal tract. Here we describe the distribution of adrenergic receptors in the ENS of the ileum and colon of the guinea pig, rat, and mouse by using single- and double-labelling immunohistochemistry. In the myenteric plexus (MP) of the rat and mouse, alpha2a-adrenergic receptors (alpha2a-AR) were widely distributed on neurons and enteric glial cells. alpha2a-AR mainly colocalized with calretinin in the MP, whereas submucosal alpha2a-AR neurons colocalized with vasoactive intestinal polypeptide (VIP), neuropeptide Y, and calretinin in both species. In the guinea pig ileum, we observed widespread alpha2a-AR immunoreactivity on nerve fibers in the MP and on VIP neurons in the submucosal plexus (SMP). We observed extensive beta1-adrenergic receptor (beta1-AR) expression on neurons and nerve fibers in both the MP and the SMP of all species. Similarly, the beta2-adrenergic receptor (beta2-AR) was expressed on neurons and nerve fibers in the SMP of all species, as well as in the MP of the mouse. In the MP, beta1- and beta2-AR immunoreactivity was localized to several neuronal populations, including calretinin and nitrergic neurons. In the SMP of the guinea pig, beta1- and beta2-AR mainly colocalized with VIP, whereas, in the rat and mouse, beta1- and beta2-AR were distributed among the VIP and calretinin populations. Adrenergic receptors were widely localized on specific neuronal populations in all species studied. The role of glial alpha2a-AR is unknown. These results suggest that sympathetic innervation of the ENS is directed toward both enteric neurons and enteric glia.


Immunoprophylactic anti-Rho(D) treatment after mismatched transfusions.
80 cases of anti-Rho(D) treatment after mismatched transfusions are reviewed to compare the intramuscular (i.m.) and intravenous (i.v.) route of treatment. No severe reactions such as renal failure occurred with either method of anti-D treatment. If the Rh-immune globulin is injected i.m., 20 micrograms anti-D per ml red cells are used. For i.v. anti-D administration, 10-12 micrograms anti-D are suggested. The i.v. method of anti-D treatment is recommended for the future. Furthermore, a scheme of treatment for after mismatched transfusions is described.


Invasive spindle cell carcinoma of the conjunctiva managed by full-thickness eye wall resection.
To describe an invasive spindle cell carcinoma of the conjunctiva managed by full-thickness eye wall resection. A 51-year-old man developed a conjunctival mass that was excised and proved to be a spindle cell carcinoma. A tumor recurrence 20 months later was evaluated by ultrasound biomicroscopy (UBM) and managed by full-thickness eye wall resection and scleral graft. UBM depicted an epibulbar mass with deep invasion through the limbus to Descemet membrane. The tumor was removed by full-thickness eye wall resection and scleral graft. Deep scleral invasion of conjunctival spindle cell carcinoma can sometimes be managed by local resection rather than irradiation or enucleation.


The relevance of AMP-activated protein kinase in insulin-secreting β cells: a potential target for improving β cell function?
AMP-activated protein kinase (AMPK) is present in different kinds of metabolically active cells. AMPK is an important intracellular energy sensor and plays a relevant role in whole-body energy homeostasis. AMPK is activated, among others, in response to glucose deprivation, caloric restriction and increased physical activity. Upon activation, AMPK affects metabolic pathways leading to increased formation of ATP and simultaneously reducing ATP-consuming processes. AMPK is also expressed in pancreatic β cells and is largely regulated by glucose, which is the main physiological stimulator of insulin secretion. Results of in vitro studies clearly show that glucose-induced insulin release is associated with a concomitant inhibition of AMPK in β cells. However, pharmacological activation of AMPK significantly potentiates the insulin-secretory response of β cells to glucose and to some other stimuli. This effect is primarily due to increased intracellular calcium concentrations. AMPK is also involved in the regulation of gene expression and may protect β cells against glucolipotoxic conditions. It was shown that in pancreatic islets of humans with type 2 diabetes, AMPK is downregulated. Moreover, studies with animal models demonstrated impaired link between glucose and AMPK activity in pancreatic islet cells. These data suggest that AMPK may be a target for compounds improving the functionality of β cells. However, more studies are required to better elucidate the relevance of AMPK in the (patho)physiology of the insulin-secreting cells.


Maternal closeness, kinship ties, and future orientation among rural African American youth: The mediating role of ethnic identity.
Few studies have considered the importance of kin or extended family relationships on future orientation. Additionally, some of the underlying processes linking social bonds to future orientation remain poorly understood. Based on theoretical work focused on attachment and identity, this study tested the potential mediating effects of ethnic identity on the links between close relationships (maternal closeness and kinship ties) and future orientation over time. Specifically, the study tested the extent to which ethnic identity mediated the relationship between maternal closeness and future orientation, and the relationship between kinship ties and future orientation. In addition, it tested whether sex moderated the relationships between maternal closeness/kinship ties and future orientation measures (education and career) as well as between ethnic identity and future orientation measures. Self-report data were collected twice, approximately 6 months apart, during a school year from a sample of rural African American adolescents (n = 274, Mage = 14.81, SD = 1.48). Findings provided evidence of mediation effects by ethnic identity on the relationships between maternal closeness and future orientation measures, and the link between kinship ties and future orientation measures. In addition, sex moderated the associations between ethnic identity and future education orientation as well as between maternal closeness and future education orientation; no moderation effects were found for the links with future career orientation measures. Maternal closeness and kinship ties appear to be critical for supporting ethnic identity and for developing educational and career future orientation among rural African American youth.