Nociceptin hyperpolarises neurones in the rat ventromedial hypothalamus.
Patch-clamp recording techniques were used to examine the effect of nociceptin upon neurones contained in slices from the rat ventromedial hypothalamus (VMH). Bath application of 50-300 nM nociceptin hyperpolarised neurones in a concentration-dependent manner that was not affected by either tetrodotoxin (TTX) or naloxone. In voltage-clamp studies nociceptin induced an outward current at -60mV that had a reversal potential of -100.2 +/- 4.6 mV and was abolished by bath application of 2 mM BaCl2.


A fibrous papule with abundant CD34-immunoreactive ganglion-like multinucleated giant cells: a case report and review of the literature.
Fibrous papules present clinically as benign, asymptomatic, dome-shaped, flesh colored papules on the face. Histologically, fibrous papules are characterized by fibrous stroma with fibroblasts and dilated blood vessels. Multiple variants of fibrous papules have been reported. Although scattered multinucleated cells in fibrous papules have been well described, we report a fibrous papule with abundant multinucleated ganglion-like giant cells that were immunoreactive with CD34. Recognition of such fibrous papule variants is important to avoid misdiagnosis as potentially more worrisome and/or aggressive melanocytic, soft tissue, or neural lesions that may require more aggressive treatment. Indeed, fibrous papules do not commonly appear on the differential diagnosis for lesions with multinucleated giant cells or ganglion-like cells and consideration should be given to their inclusion in the appropriate clinical setting.


A simple tandem mass spectrometry method for structural identification of pentose oligosaccharides.
Differentiation of stereoisomers that are only dissimilar in the orientation of chemical bonds in space by mass spectrometry remains challenging. Structural determination of carbohydrates by mass spectrometry is difficult, mainly due to the large number of stereoisomers in carbohydrates. Arabinose and xylose are pentose stereoisomers typically present in plant polysaccharides and exist in α- and β-anomeric configurations of furanose and pyranose forms. Conventional methods used to determine the structures of polysaccharides include hydrolysis of polysaccharides into oligosaccharides followed by identification of these oligosaccharides' structures individually through nuclear magnetic resonance spectroscopy (NMR). Although the sensitivity of mass spectrometry is much higher than that of NMR, conventional mass spectrometry provides only limited useful information on oligosaccharide structure determination, only the linkage positions of glycosidic bonds. In this study, we demonstrated a mass spectrometry method for the identification of linkage positions, anomeric configurations, and monosaccharide stereoisomers of intact oligosaccharides consisting of arabinose and xylose. We separated arabinose and xylose monosaccharides into α-furanose, β-furanose, α-pyranose, and β-pyranose forms through high-performance liquid chromatography and obtained the corresponding collision-induced dissociation mass spectra. Using these monosaccharide spectra and a flow chart consisting of the proper CID sequences derived from the dissociation mechanisms of pentose, a simple multi-stage tandem mass spectrometry method for structural identification of intact oligosaccharides consisting of arabinose and xylose was developed. The new mass spectrometry method provides a simple method for determining the structure of polysaccharides consisting of arabinose and xylose. The flow chart can be used in computer coding for automation, an ultimate goal for oligosaccharide structure determination.


Fracture mechanics parameters for failure prediction of composite resins.
This study contains the first part of a research project in which the applicability of fracture mechanics parameters to predict failure of a restored tooth was investigated. Fracture mechanics parameters have been used in dental research before, but were restricted to comparative studies between various brands of composites. The critical values of the opening mode stress intensity factor (KI), its equivalents, the strain energy release rate (GI), and the J integral (JI), were measured with single-edge notched-bend (SENB) specimens of dental composite in a three-point bend test. The measured values of KIc for Silux (KIc = 0.99 +/- 0.03 MNm-3/2) and P-30 (KIc = 1.88 +/- 0.12 MNm-3/2), compared with values from the literature, show quantitative agreement. The J integral was computed by means of finite element analysis (FEA) on a two-dimensional model of the SENB specimens. The critical value of the J integral (measured with SENB specimens, notch depth-to-width ratio (a/W) = 1/2) was used to predict failure of specimens having an arbitrary geometry. In this study, failure was predicted for SENB specimens with notch depth-to-width ratio (a/W) = 1/4 and 3/4. The predicted deflection and load at failure correspond well with the measured deflection and load.


Efficacy of Tylosin and Tilmicosin Against Experimental Mycoplasma gallisepticum Infection in Chickens.
Mycoplasma gallisepticum, the cause of chronic respiratory disease, remains one of the most important pathogens in the poultry industry. Controlling the impact of this disease is done by eradication of positive breeder flocks or by vaccination and medication. Tylosin and tilmicosin are often used in medication programs. However, recent data on the in vivo efficacy of these macrolide antibiotics are scarce. Therefore, two dose titration studies were conducted using a recently isolated M. gallisepticum strain belonging to the wild-type population with regard to its tilmicosin and tylosin minimal inhibitory concentration. In a first trial, broilers were infected with M. gallisepticum and treated with 10 or 20 mg tilmicosin/kg body weight (BW) in the drinking water for five successive days. In a second trial, broilers were infected with M. gallisepticum and treated with 35 or 100 mg tylosin/ kg BW in the drinking water for five successive days. Clinical scoring of respiratory signs, macroscopic scoring of respiratory tract lesions, M. gallisepticum isolation from the respiratory organs, weight gain, and mortality were monitored for efficacy evaluation. All tylosin and tilmicosin treatments significantly reduced the course of clinical respiratory disease, macroscopic lesions in the respiratory organs, and M. gallisepticum numbers in the respiratory tract and obtained higher weight gains compared with the Mycoplasma-infected untreated control group. A treatment of 100 mg tylosin/kg daily for 5 days was not more clinically efficacious than the dosage of 35 mg tylosin/kg daily for 5 days. At final necropsy, in animals treated with 20 mg/kg BW tilmicosin, significantly fewer respiratory tract lesions were present than in the animals treated with 10 mg/kg BW tilmicosin. Therefore, when tilmicosin is used to treat clinical outbreaks of M. gallisepticum in broilers, a dosing scheme of 20 mg tilmicosin/kg BW for five successive days seems to be the most recommended scheme.


Location and Causation of Residual Lymph Node Metastasis After Surgical Treatment of Regionally Advanced Differentiated Thyroid Cancer.
After initial surgical treatment of differentiated thyroid cancer (DTC) residual lymph node metastases are often found at the time of radioactive iodine (131I) therapy. Recurrence of DTC is due to persistent disease not removed at initial surgery which also did not respond to 131I treatment. This study aimed at determining locations of, and reasons for, residual nodal metastases detected by 131I scans with single-photon emission computed tomography (SPECT/CT) obtained prior to radioiodine therapy following surgical treatment of DTC. This is a retrospective study of 352 patients with intermediate and high-risk DTC treated with 131I therapy at the University of Michigan from 2007 to 2014. All patients underwent total thyroidectomy with or without lymph node dissection followed by radioiodine therapy. Pre-ablation diagnostic 131I scans with SPECT/CT were used postoperatively to localize nodal metastases, which were then compared with the cervical lymph node basins dissected at the time of surgery to determine the reason for residual nodal metastases: incomplete nodal dissection versus preoperative unrecognized nodal metastases. Of the 352 patients in the study, 146 (41.5%) had residual nodal metastases detected on 131I scans with SPECT/CT following initial surgery but prior to 131I therapy. Among the 146 patients with residual disease, there were a total of 218 distinct nodal metastases. Relative to the primary tumor, 71.6% (n = 156) of metastases were ipsilateral, 22.0% (n = 48) were contralateral, and 6.4% (n = 14) were non-sided in the central neck (level VI/VII). Cervical lymph node levels VI, III, and II had the greatest frequencies of residual metastases (33.9%, 22.9%, 18.8%, respectively). Residual metastases occurred because of incomplete nodal dissection (49.3%), lack of preoperative identification (37.7%), or a combination of both (13%). Residual nodal metastasis following initial surgical treatment for regionally advanced differentiated thyroid cancer is rather common on highly sensitive 131I scans with SPECT/CT and is due to both unrecognized nodal involvement preoperatively and incomplete removal of metastatic lymph nodes during compartment-orientated nodal dissection. The surgical management of high-risk DTC should include preoperative imaging to evaluate for nodal metastases in the central and lateral neck and compartment-orientated nodal dissection of involved compartments. Attention should be given to complete dissection in levels VI, III, and II, particularly when dissecting compartments ipsilateral to the primary tumor.


Epigenetic and neural correlates of selective social attention across adulthood.
Social isolation is one of the strongest predictors of increased risk of mortality in older adulthood. The ability to form and maintain the social relationships that mitigate this risk is partially regulated by the oxytocinergic system and one's ability to attend to and process social information. We have previously shown that an epigenetic change to the DNA of the oxytocin receptor gene ( OXTR methylation) affects the salience of social information in young adults. Little is known about how the oxytocinergic system ages and what effect this aging system has on social cognitive abilities throughout the lifespan. Here we explore age-related differences in the association between neural response during selective social attention and OXTR DNA methylation in young and older adults. We find that older adults activate diffuse areas of visual cortex and dorsolateral prefrontal cortex during selective social attention, consistent with the dedifferentiation and compensatory neural activation commonly reported in aging. We find a significant age-by- OXTR methylation interaction on neural response when attending to social stimuli in a complex display; young adults display a positive association between OXTR methylation and neural activation, replicating our prior finding that young adults with presumed diminished endogenous access to oxytocin recruit regions of the attentional cortex to a greater extent. This association does not hold for older adults. Instead, perceived social support interacts with OXTR methylation to influence neural response during selective social attention. These data suggest that environmental factors like social support moderate biological processes in aging and highlight the importance of a lifespan perspective for understanding associations between individual differences in the oxytocinergic system, neural function, and social behavior.


Intergenerational Transmission of Depression during Adolescence: The Mediating Roles of Hostile Attribution Bias, Empathic Concern, and Social Self-Concept.
Few studies have empirically examined the role of peer microsystem in the intergenerational transmission of depression, and more importantly, little is known about the mechanisms underlying this potential pathway of intergenerational transmission. The purpose of the current study was to examine the sequential mediation effects of adolescent hostile attribution bias, empathic concern, and social self-concept on the association between maternal depression and adolescent depression. An urban Chinese sample of 761 mother-child dyads was investigated when the adolescents were in secondary school (M = 14.36 years, range =12.33-16.92 years, 52.3% female). The results provided evidence of cross-generational continuity in depression during adolescence, and the hypothesized sequential mediation model was supported. The findings highlight the importance of peer-related factors during the intergenerational transmission of depression and have important implications for interpersonal interventions that aim to prevent depression during adolescence. The limitations of the study and suggestions for future research are briefly discussed.


Application of Circulating Tumor DNA as a Biomarker for Non-Small Cell Lung Cancer.
Non-small cell lung cancer (NSCLC) is one of the most prevalent causes of cancer-related death worldwide. Recently, there are many important medical advancements on NSCLC, such as therapies based on tyrosine kinase inhibitors and immune checkpoint inhibitors. Most of these therapies require tumor molecular testing for selecting patients who would benefit most from them. As invasive biopsy is highly risky, NSCLC molecular testing based on liquid biopsy has received more and more attention recently. We aimed to introduce liquid biopsy and its potential clinical applications in NSCLC patients, including cancer diagnosis, treatment plan prioritization, minimal residual disease detection, and dynamic monitoring on the response to cancer treatment. We reviewed recent studies on circulating tumor DNA (ctDNA) testing, which is a minimally invasive approach to identify the presence of tumor-related mutations. In addition, we evaluated potential clinical applications of ctDNA as blood biomarkers for advanced NSCLC patients. Most studies have indicated that ctDNA testing is critical in diagnosing NSCLC, predicting clinical outcomes, monitoring response to targeted therapies and immunotherapies, and detecting cancer recurrence. Moreover, the changes of ctDNA levels are associated with tumor mutation burden and cancer progression. The ctDNA testing is promising in guiding the therapies on NSCLC patients.


Intraovarian regulation of folliculogenesis in the dog: A review.
Dog reproductive cycle is unique among other mammals in that females experience long and variable periods of ovarian inactivity. Neuroendocrine controls of the reproductive cycle have been thoroughly studied in the dog. However, there is little information regarding endocrine, paracrine and autocrine controls of dog ovarian folliculogenesis. Advancements in the understanding of mechanisms regulating dog ovarian follicle development will be helpful in the establishment of an approach to control cyclicity in this species. Furthermore, such information will likely be useful for the establishment of an in vitro follicle culture system to preserve fertility of genetically valuable disease models or endangered canids. This review highlights current knowledge on dog folliculogenesis with emphasis on endocrine, paracrine and autocrine controls of follicular development.


Towards 3D modelling and imaging of infection scenarios at the single cell level using holographic optical tweezers and digital holographic microscopy.
The analysis of dynamic interactions of microorganisms with a host cell is of utmost importance for understanding infection processes. We present a biophotonic holographic workstation that allows optical manipulation of bacteria by holographic optical tweezers and simultaneously monitoring of dynamic processes with quantitative multi-focus phase imaging based on self-interference digital holographic microscopy. Our results show that several bacterial cells, even with non-spherical shape, can be aligned precisely on the surface of living host cells and localized reproducibly in three dimensions. In this way a new label-free multipurpose device for modelling and quantitative analysis of infection scenarios at the single cell level is provided.


Pharmacological actions of leukotrienes C4, D4 and E4 on guinea pig isolated taenia caecum as a preparation to study leukotrienes.
The contractile effects of leukotrienes (LTs) C4, D4 and E4 were studied in guinea pigs isolated taenia caecum. LTs C4, D4 and E4 contracted taenia caecum at low concentrations in a concentration-dependent manner. The response to LTs was not influenced by a gamma-glutamyl transpeptidase inhibitor (L-serine borate), aminopeptidase inhibitor (L-cysteine) or cyclooxygenase inhibitor (flurbiprofen), suggesting that LTC4 and LTD4 were not metabolized or metabolized only slightly in the guinea pig isolated taenia caecum, and that each of the LTs showed the direct contractile action. Furthermore, FPL55712 antagonized the response to LTD4 and LTC4 competitively but not that to LTE4. These results suggested that the guinea pig isolated taenia caecum is useful preparation to study the pharmacological actions of LTs.


Regulation of the plant defence response in arbuscular mycorrhizal symbiosis.
The response of plants to arbuscular mycorrhizal fungi involves a temporal and spatial activation of different defence mechanisms. The activation and regulation of these defences have been proposed to play a role in the maintenance of the mutualistic status of the association, however, how these defences affect the functioning and development of arbuscular mycorrhiza remains unclear. A number of regulatory mechanisms of plant defence response have been described during the establishment of the arbuscular mycorrhizal symbiosis, including elicitor degradation, modulation of second messenger concentration, nutritional and hormonal plant defence regulation, and activation of regulatory symbiotic gene expression. The functional characterization of these regulatory mechanisms on arbuscular mycorrhiza, including cross-talk between them, will be the aim and objective of future work on this topic.


Acute Progressive Visual Loss in a Case of Acute Myeloid Leukemia: Challenges in the Utility of Molecular Tests in Early Diagnose of Cytomegalovirus Retinitis.
Cytomegalovirus (CMV) retinitis is one of the rare but debilitating presentations of the CMV infection in children with leukemia. Herein, we report a 12-year-old boy with acute myeloid leukemia complicated by rapid progressive visual loss during relapse of leukemia. The definite diagnosis of CMV retinitis was made after vitreous aspiration. Despite prompt treatment and ophthalmologic intervention, he died because of AML relapse. Viral infections, especially cytomegalovirus infection, may present with vague clinical pictures during any time of chemotherapy, which may not be easily distinguishable from bacterial or fungal retinitis and also chemotherapy-induced retinopathies. Clinician should consider CMV retinitis in seropositive patients especially those without detectable viremia.


Frameworking memory and serotonergic markers.
The evidence for neural markers and memory is continuously being revised, and as evidence continues to accumulate, herein, we frame earlier and new evidence. Hence, in this work, the aim is to provide an appropriate conceptual framework of serotonergic markers associated with neural activity and memory. Serotonin (5-hydroxytryptamine [5-HT]) has multiple pharmacological tools, well-characterized downstream signaling in mammals' species, and established 5-HT neural markers showing new insights about memory functions and dysfunctions, including receptors (5-HT1A/1B/1D, 5-HT2A/2B/2C, and 5-HT3-7), transporter (serotonin transporter [SERT]) and volume transmission present in brain areas involved in memory. Bidirectional influence occurs between 5-HT markers and memory/amnesia. A growing number of researchers report that memory, amnesia, or forgetting modifies neural markers. Diverse approaches support the translatability of using neural markers and cerebral functions/dysfunctions, including memory formation and amnesia. At least, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors and SERT seem to be useful neural markers and therapeutic targets. Hence, several mechanisms cooperate to achieve synaptic plasticity or memory, including changes in the expression of neurotransmitter receptors and transporters.


Childhood, adolescents, and young adults (≤25 y) colorectal cancer: study of Anatolian Society of Medical Oncology.
To evaluate the clinicopathologic characteristics and treatment outcomes of young patients with colorectal cancer (CRC). Between May 2003 and June 2010, 76 patients were found eligible for this retrospective study. Age, sex, presenting symptoms, patients with acute presentation, family history, presence of polyps, histologic features, localization and stage of the tumor, treatment outcomes, time and site of recurrence, sites of metastasis, and survival outcomes were recorded from the patient files. Seventy-six patients (55.3% male) with a median age of 23 years were evaluated. Patients were evaluated in 2 groups as follows: child-adolescent (0 to 19 y, n=20) and young adult (20 to 25 y, n=56). Sex and symptoms (abdominal pain and rectal bleeding) were significantly differed between the groups and acute presentation was close to statistical significance. Overall survival significantly increased in patients undergoing curative surgery (P<0.001). Other parameters affecting the survival was stage of disease (P=0.004). Response to palliative chemotherapy in metastatic patients (P=0.042) and postoperative adjuvant chemotherapy had a statistically significant survival advantage (P=0.028). Diagnosis of CRC should not be excluded solely on the basis of age. CRC features in young-adult patients are more similar to adults compared with that of child-adolescent patients according to the symptoms and presentation. In patients with CRC in this age group, curative surgery, adjuvant chemotherapy, and palliative chemotherapy provide survival advantage.


Intrahepatic Osler's disease: report of two cases and review of the literature.
Osler-Weber-Rendu disease is a hereditary vascular disease with multiple manifestations. The liver is involved rarely. Vascular abnormalities include telangiectasis and arteriovenous fistulas, sometimes associated with fibrosis and cirrhosis. Hepatic arteriovenous shunting may include secondary portal hypertension, reduced liver function and high cardiac output. Two cases of Osler-Weber-Rendu disease with extensive hepatic arteriovenous fistulation were described in detail and we report on their clinical features. In the first patient, treatment was symptomatic since liver transplantation is not indicated because the patient was asymptomatic. Embolization treatment of hepatic arteries was indicated in the second patient because he had biliary disease and recurrent cholangitis secondary to vasculo-biliary shunts. Therapy with arterial embolization, banding, or ligature of hepatic arteries is still limited and provides unsatisfactory long-term results. Liver transplantation offers now another therapeutic option for patients with intrahepatic high shunting and secondary pulmonary hypertension.


N-butanol extract of Capparis spinosa L. induces apoptosis primarily through a mitochondrial pathway involving mPTP open, cytochrome C release and caspase activation.
Capparis spinosa L., a Uygur medicine, had been shown to have anti-tumor activity in our early experiments with an N-butanol extract (CSBE) as its active fraction. However, the mechanisms responsible for its effects are not clearly understood. Here, we report that treatment of SGC-7901 cells with CSBE resulted in dose-dependent reduction of cell viability and induction of apoptosis. To observe the inhibitory and killing effects of CSBE on SGC-7901, the SRB method was adopted, apoptosis being observed by electron microscopy. To clarify the mechanisms of apoptosis, Western blot and enzyme-labeled methods were used to examine the release of cytochrome c (Cyt c) and the activation of the caspase cascade. By electron microscopy, apoptotic morphologic changes were detectable after CSBE administration. In this study, it was also demonstrated that CSBE induced apoptosis in SGC-7901 cells by inhibiting mPTP open, mitochondrial cytochrome c release, caspase-9 and caspase-3 activation. The findings indicated that CSBE induces apoptosis through mitochondrial pathway.


A case of asymptomatic giant aneurysm of the common hepatic artery.
The authors are presenting a case of asymptomatic giant aneurysm of the common hepatic artery in a 72 year-old woman. The patient came under our observation with a complete, recent diagnosis. However, two years earlier in another clinic, a para-hilar hepatic mass with partially calcified walls was incidentally found during an abdominal ultrasound. An abdominal TC without contrast medium showed the mass to be hepatic hydatid cysts. TC images after 2 years showed a growth in diameter from 7 to 12 cm. Having undergone an hysterectomy and a rectal prosthesis, technical difficulties occurred because of the aneurysm's characteristics. The authors would like to emphasize that the rarity of the lesion must not exclude it from the diagnostic protocol of abdominal masses: ultrasound must be accompanied by a Doppler and the TC must be made using a contrast medium. Furthermore, revascularization surgery may create difficulties that cannot be previously prevented.


Recent progress of nanomedicine in the treatment of Alzheimer's disease.
Alzheimer's disease (AD) is the most common cause of memory disruption in elderly subjects, with the prevalence continuing to rise mainly because of the aging world population. Unfortunately, no efficient therapy is currently available for the AD treatment, due to low drug potency and several challenges to delivery, including low bioavailability and the impediments of the blood-brain barrier. Recently, nanomedicine has gained considerable attention among researchers all over the world and shown promising developments in AD treatment. A wide range of nano-carriers, such as polymer nanoparticles, liposomes, solid lipid nanoparticles, dendritic nanoparticles, biomimetic nanoparticles, magnetic nanoparticles, etc., have been adapted to develop successful new treatment strategies. This review comprehensively summarizes the recent advances of different nanomedicine for their efficacy in pre-clinical studies. Finally, some insights and future research directions are proposed. This review can provide useful information to guide the future design and evaluation of nanomedicine in AD treatment.


The effect of exogenous testosterone on ectoparasite loads in free-ranging western fence lizards.
Numerous factors impact the dynamics of host-parasite relationships, such as host sex, hormonal state, reproductive condition, host health, and behavior. In particular, males from a variety of taxa frequently carry heavier parasite burdens than females, particularly during breeding season when testosterone concentrations are elevated. Using western fence lizards (Sceloporus occidentalis), we tested the hypothesis that high circulating testosterone concentrations in male lizards induce high tick and mite loads. We implanted male lizards with either testosterone or control implants in the field during the spring, when tick and mite loads are highest. One month later, testosterone-implanted males had significantly higher tick loads, but lower mite loads, than control males. These results suggest that testosterone differentially impacts ectoparasitic acarine burdens. Testosterone may modulate aspects of lizard physiology and behavior that enhance or diminish parasitism by certain acarines during periods of peak reproductive effort.


Optimal decision support rules improve personalize warfarin treatment outcomes.
We tested optimization-based approaches to generate decision support rules used to improve personalized warfarin treatment based on clinical and genetic characteristics. Our approach simulated warfarin treatment outcomes using five existing treatment plans for clinical avatars (virtual patients). We used individual clinical avatar Time-in-Therapeutic-Range to represent the two-sided adverse risk to bleeding (over dosed - above therapeutic range) and thrombosis (under dosed - below therapeutic range) and as the objective function in the optimization to minimize overall risk. A series of optimization approaches demonstrate that correctly selected decision rules matched to particularly characterized patients produce treatment plans that minimize risk. Finally, a decision tree algorithm was used to produce decision rules, each of which indicated a specific treatment plan that optimally reduce risks for a patient subgroup. The optimization approach minimizes entropy/impurity property thus producing rules that identify treatment plans that minimize overall adverse risks for the largest possible patient subgroups.


Micturition by functional magnetic stimulation.
Effectiveness of functional magnetic stimulation (FMS) technology on bladder contraction and bladder emptying was evaluated in twenty-two spinal cord injured subjects. FMS of the bladder was performed by stimulating the sacral nerves or the suprapubic region using a commercially available magnetic stimulator with a round coli. With sacral stimulation, the mean change in bladder pressure (Pves) was 24.4 +/- 4.88 cm H2O; with suprapubic stimulation, the mean change in Pves was 16.5 +/- 4.44 cm H2O. The change in Pves with sacral stimulation was higher than with suprapubic stimulation (p < .01). Seventeen subjects demonstrated voiding, either with sacral or suprapubic stimulation. Using a water-cooled coli, one subject demonstrated complete bladder emptying. FMS of the bladder has the potential to be a useful non-invasive technology for bladder emptying and bladder training in patients with neurogenic bladders.


Her2 activation mechanism reflects evolutionary preservation of asymmetric ectodomain dimers in the human EGFR family.
The receptor tyrosine kinase Her2, an intensely pursued drug target, differs from other members of the EGFR family in that it does not bind EGF-like ligands, relying instead on heterodimerization with other (ligand-bound) EGFR-family receptors for activation. The structural basis for Her2 heterodimerization, however, remains poorly understood. The unexpected recent finding of asymmetric ectodomain dimer structures of Drosophila EGFR (dEGFR) suggests a possible structural basis for Her2 heterodimerization, but all available structures for dimers of human EGFR family ectodomains are symmetric. Here, we report results from long-timescale molecular dynamics simulations indicating that a single ligand is necessary and sufficient to stabilize the ectodomain interface of Her2 heterodimers, which assume an asymmetric conformation similar to that of dEGFR dimers. This structural parallelism suggests a dimerization mechanism that has been conserved in the evolution of the EGFR family from Drosophila to human. DOI:http://dx.doi.org/10.7554/eLife.00708.001.


Acute responsiveness to calcitonin in chronic renal failure.
The acute effect of porcine calcitonin was tested in 17 patients undergoing chronic haemodialysis. In normal adults calcitonin has no effect on plasma calcium or phosphate levels, but in nine patients both concentrations were substantially reduced after calcitonin. This hypocalcaemic and hypophosphataemic effect was a function of the initial plasma phosphate level but was unrelated to the initial plasma calcium level. Plasma hydroxyproline levels were not significantly different in the two groups an were unaffected by calcitonin. In 11 patients fasting plasma calcitonin levels were undetectable with an assay sensitive to 0-1 mug/1. Calcitonin seems to have an acute effect in chronic renal failure which may not operate by arresting bone resorption but is dependent on the plasma phosphate concentration.


Patterns of carriage of group B streptococci in genitourinary medicine clinic patients.
Anogenital carriage of group B streptococci was found in 46% (57/125) of men and 38% (68/179) of women attending a genitourinary medicine clinic. Colonisation with group B streptococci was more common in patients who had a history of more than one sexual partner in the preceding three months, but was not related to any previous sexually transmitted infection. Group B streptococci were isolated from either one or both partners of 28 couples, in 12 of which both partners yielded isolates that were indistinguishable by serotyping and phage typing. Colonisation with matching isolates of group B streptococci was more common in couples who had relatively stable relationships.


Evaluation of a loop-mediated isothermal amplification method for rapid detection of channel catfish Ictalurus punctatus important bacterial pathogen Edwardsiella ictaluri.
Channel catfish Ictalurus punctatus infected with Edwardsiella ictaluri results in 40--50 million dollars annual losses in profits to catfish producers. Early detection of this pathogen is necessary for disease control and reduction of economic loss. In this communication, the loop-mediated isothermal amplification method (LAMP) that amplifies DNA with high specificity and rapidity at an isothermal condition was evaluated for rapid detection of E. ictaluri. A set of four primers, two outer and two inner, was designed specifically to recognize the eip 18 gene of this pathogen. The LAMP reaction mix was optimized. Reaction temperature and time of the LAMP assay for the eip 18 gene were also optimized at 65 degrees C for 60 min, respectively. Our results show that the ladder-like pattern of bands sizes from 234 bp specifically to the E. ictaluri gene was amplified. The detection limit of this LAMP assay was about 20 colony forming units. In addition, this optimized LAMP assay was used to detect the E. ictaluri eip 18 gene in brains of experimentally challenged channel catfish. Thus, we concluded that the LAMP assay can potentially be used for rapid diagnosis in hatcheries and ponds.


Whole-Genome Sequence of Marine Bacterium Phaeodactylibacter xiamenensis Strain KD52, Isolated from the Phycosphere of Microalga Phacodactylum tricornutum.
Phaeodactylibacter xiamenensis KD52 is a novel bacterium isolated from a culture of the alga Phaeodactylum tricornutum in Xiamen, Fujian Province, China. Here, we present the first draft genome sequence of this strain, which will provide an opportunity to further understand the functional genes related to signing for nutrition from the host algae and the molecular mechanisms underlying its beneficial properties.


Employment-related anxiety and depression in senior college students in China.
To examine the association of employment-related events with depression and anxiety in senior college students in China. Altogether 1321 senior college students were recruited from Central South University and the survey was administered anonymously. Anxiety and depression were assessed with the Self-rating Anxiety Scale (SAS) and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Employment-related events were reflected by the employment-related options when students were surveyed. Logistic regression was used to estimate the effect of employment-related events on anxiety and depression. We collected 1178 valid questionnaires. Taking 50 and 16 as the cutting-point of SAS and CES-D, we found 18.9% and 55.4% of the participants showed symptoms of anxiety and depression, respectively. After controlling confounding factors, those students who had taken the entrance exam of graduate schools and were optimistic for the result, those who had taken the entrance exam of graduate schools but were pessimistic for the result, and those who neither took the entrance exam of graduate schools nor received a job offer, had a higher risk of anxiety than those who would attend a graduate school without exam, and the odds ratios were 2.5, 2.3, and 3.5, respectively. For students' depression, the odds ratios of the three categories mentioned above were 2.0, 1.5, and 2.6, respectively. Senior college students who face bad employment-related events are at a higher risk of anxiety and depression.


Canine factor VII deficiency: lessons learned in applying methods-based laboratory proficiency testing.
Canine inherited factor VII deficiency is a mild-to-moderate, inherited coagulopathy that affects several breeds of dog. We identified 2 polymorphisms near the disease-causing F7 gene mutation, one of which interfered with testing in several Beagles by causing allele dropout of the normal, wild-type allele. In the absence of an external proficiency program among veterinary genetic testing laboratories, implementation of an internal proficiency program, which requires 2 independent methods for genotyping dogs at any given locus, was further enhanced by ensuring minimally non-overlapping primer pairs between the 2 assays. After redesign of our clinical tests, all dogs were re-examined, and the correct genotypes were identified. These changes ensure higher accuracy in future testing of the F7 mutation.


The SPOCC (Selective Procedures, Operative Cases, and Consults) program as an advance in orthopaedic resident record keeping.
This paper outlines the development and use of a software package developed at the University of New Mexico that allows residents to use a simple menu driven program for record keeping. Selective Procedures, Operative Cases, and Consults (SPOCC) was developed for recording data in individually arranged formats and searching on a number of input parameters. As Residency Review Committees become more stringent in their demand for documentation of activities, this program will give residents the ability to quickly recall any number of selective procedures, consults or operative cases, along with case specific data to enable them to review cases, study results in relation to future follow-up, generate statistics, and stimulate research ideas. SPOCC can be run on any dual floppy or hard disk personal computer that uses MS-DOS or PC-DOS 2.0 or greater. It requires 256 kilobytes of free memory, and a color or monochrome monitor. A printer is optional.


Adsorption of pneumocins and aerocins on bacterial cells.
Adsorption of aerocins 1a-E26, 1b-E47, 1b-E43, 2-E26, 2-E47 and pneumocins A-114 and A-902 was found to be dependent on the presence of specific receptors on the surface of sensitive bacteria. Resistant mutants, selected by these bacteriocins, were incapable of adsorption owing to loss or altered structure of receptors. Maximal numbers of Killing Units of pneumocins and aerocins adsorbed by one bacterial cell of sensitive strains were determined. Kinetics of adsorption and degree of killing of bacteria in relation to concentration of bacteriocins were studied. The lethal effect on bacteria was of the "single hit" type, i. e. one particle of aerocin respectively pneumocin killed one bacterial cell.


Molecular characterization of Sarcocystis spp. as a cause of protozoal encephalitis in a free-ranging black bear.
A free-ranging juvenile male black bear (Ursus americanus), found dead in Alberta, Canada, had severe nonsuppurative encephalitis. Lesions in the brain were most severe in the gray matter of the cerebral cortex, and included perivascular cuffs of lymphocytes and plasma cells, areas of gliosis that disrupted the neuropil, and intralesional protozoan schizonts. The left hindlimb had suppurative myositis associated with Streptococcus halichoeri. Immunohistochemistry and molecular analyses (PCR and sequencing of 4 discriminatory loci: 18S rDNA, ITS-1 rDNA, cox1, rpoB) identified Sarcocystis canis or a very closely related Sarcocystis sp. in the affected muscle and brain tissues. The main lesion described in previously reported cases of fatal sarcocystosis in bears was necrotizing hepatitis. Fatal encephalitis associated with this parasite represents a novel presentation of sarcocystosis in bears. Sarcocystosis should be considered a differential diagnosis for nonsuppurative encephalitis in bears.


Autonomic Measures in Differentiating Depressive Disorders: A Potential AID.
The present study aimed at exploring the potential utility of autonomic regulation as a useful marker in the diagnostic differentiation between unipolar and bipolar depression. Respiratory sinus arrhythmia (RSA), low-frequency (LF) of heart rate variability, and systolic blood pressure (SBP) were assessed in patients with bipolar depression (31) and major depressive disorder (MDD=32), and in healthy controls (HCs=32). Since bipolar depressed subjects were maintained on specific medications to manage manic/hypomanic symptoms, we explored whether mood stabilizers (atypical antipsychotics and anticonvulsants or their combinations) could independently affect the physiological parameters. When the autonomic measures were analyzed by a multivariate analysis of variance (MANCOVA), after controlling for BMI, the combination of variables (RSA, LF, SBP) discriminated patients with bipolar depression and MDD from HC (F(6, 178)=3.036, p=0.007, Λ=0.823, partial η2=0.093). In any case, we cannot exclude that mood stabilizers might have affected SBP values in the bipolar group. To deconstruct this multivariate effect, pairwise ANOVAs and discriminant analyses contrasted groups and documented that RSA was the primary variable distinguishing the groups. Discriminant function analyses showed that RSA had a significant discriminating weight between bipolar depressed patients and HC subjects (p<0.0005). By contrast, RSA showed a trend towards the statistical significance in discriminating between bipolar depression and MDD patients (p=0.06). The assessment of RSA and SBP in outpatient settings might be helpful in the differential diagnosis of affective disorders.


Complications in Percutaneous Dialysis Interventions: How to Avoid Them, and How to Treat Them When They do Occur.
Because of the increasing prevalence of end-stage renal disease, more percutaneous interventions are being performed. They serve an important role, allowing for restoration of access function, which is achieved with high level of technical success. However, complications are inevitable during any types of procedure, and percutaneous dialysis interventions are no exception. To provide safe and effective care these patients need, anyone performing endovascular dialysis interventions needs to understand the possible complications, how they can be avoided, and how they can be addressed if they are to occur. Topics in this article include complications seen while intervening on the thrombosed access, complications of angioplasty, potentially devastating complications of central venous interventions, and complications of dialysis catheter placement. Further, patients with end-stage renal disease are generally sicker than the average patient, usually afflicted by multiple comorbidities and are therefore more complicated from a medical perspective. This places them at higher risk for acute cardiopulmonary decompensation or arrest than any other interventional radiology patient subset. As result, we also briefly review general medical complications in this population.


High-strength, thermosensitive double network hydrogels with antibacterial functionality.
Herein, we report a method of fabricating strong and thermosensitive double network (T-DN) poly(N-isopropyl acrylamide) (PNIPAM)-based hydrogels, i.e. rigid and brittle poly(2-acrylamido-2-methylpropanesulfonic acid sodium salt) (PNaAMPS) as the first and soft and ductile poly(N-isopropyl acrylamide-co-acrylamide) (P(NIPAM-co-AAm)) as the second interpenetrating each other. In particular, NIPAM was deliberately integrated into the double network as an adjustor of elastic modulus and hydrophilicity, besides thermosensitivity. Such double network construction strategy resulted in PNaAMPS/P(NIPAM-co-AAm) T-DN hydrogels of excellent mechanical properties (0.83-1.37 MPa) and desirable temperature-dependent swellabilities. Besides, T-DN hydrogels with various NIPAM contents exhibited good biocompatibility with high cell survival rates around normal body temperatures. Furthermore, crystal violet (CV) could be readily loaded to impart antibacterial functionality to the T-DN hydrogels against E. coli. The double network construction strategy could be adapted to fabricating high-strength antibacterial hydrogels for a broad range of biomedical applications.


Serum neutrophil gelatinase-associated lipocalin the estimation of hospital prognosis in patients with ST-elevated myocardial infarction.
We aimed to assess the clinical significance of serum levels of neutrophil gelatinase-associated lipocalin (sNGAL) for predicting in-hospital outcomes in patients with ST-elevated myocardial infarction (STEMI). Patients admitted within 24 hours of developing STEMI clinical symptoms were evaluated for sNGAL on hospitalization days 1 and 12. Recurrent myocardial infarction, early post-infarction angina, acute cerebrovascular accident, and death were assessed as adverse outcomes during hospitalization. The actors associated with adverse outcome were evaluated using univariate and multivariate regression analysis. Among the 260 STEMI patients included, 32% had ≥1 adverse in-hospital outcome, and significantly higher sNGAL on day 12, (but not on day 1) compared to sNGAL in patients with favorable outcome (p = 0.033). Type-2 diabetes mellitus, age > 60 years, reduced glomerular filtration rate during hospitalization, and high sNGAL on day 12 were identified as risk factors for adverse in-hospital outcome, associated with a 14% increase for each 1-year increment in age after 60 years, and a dramatic increase (3.2 times) for high sNGAL on day 12, with sNGAL ≥ 1.046 ng/ml indicating complicated hospitalization course. sNGAL concentration on the 12th day was associated with the existing adverse outcomes, acting as a marker of MI severity.


Evaluation of the apical sealing ability of bioceramic sealer, AH plus & epiphany: An in vitro study.
This in vitro study evaluated and compared the microleakage of three sealers; Endosequence bioceramic (BC) sealer, AH Plus and Epiphany. Study was done on 75 extracted human single rooted permanent teeth, which were decoronated and the root canals were instrumented. The specimens were randomly divided into three groups (n = 25) and obturated by continuous wave condensation technique. Group A: using Endosequence BC, Group B: using AH Plus sealer, Group C: using Resilon Epiphany system. Microleakage was evaluated using dye penetration method. Teeth were split longitudinally and then horizontally markings were made at 2, 4 and 6 mm from the apex. Dye penetration evaluation was done under stereomicroscope (30X magnification). The dye penetration in Group B was more than in Group A and C in both vertical and horizontal directions, suggesting that newly introduced BC sealer and Epiphany sealer sealed the root canal better compared to AH Plus Sealer. Newer root canal sealers seal the root canal better but cannot totally eliminate leakage.


[Mechanism of action and mode of administration of high-dose inhaled corticotherapy in the treatment of asthma].
The commercial availability of high-dose inhaled corticosteroid preparations for the treatment of asthma offers an occasion for reviewing the different mechanisms of action of glucocorticoids notably glucocorticoids, notably their interference with lipocortin protein synthesis and arachidonic acid metabolism. A favourable effect on bronchial hyper-reactivity and on delayed hypersensitivity reactions has also been observed. The problems raised by the various preparations responsible for varying degrees of systemic activity, the difficulties inherent in the use of inhalers and the side-effects of these products are discussed. The effectiveness and safety of the current high-dose inhaled preparations are emphasized.


Associations between brominated flame retardants in house dust and hormone levels in men.
Brominated flame retardants (BFRs) are used in the manufacture of a variety of materials and consumer products in order to meet fire safety standards. BFRs may persist in the environment and have been detected in wildlife, humans and indoor dust and air. Some BFRs have demonstrated endocrine and reproductive effects in animals, but human studies are limited. In this exploratory study, we measured serum hormone levels and flame retardant concentrations [31 polybrominated diphenyl ether (PBDE) congeners and 6 alternate flame retardants] in house dust from men recruited through a US infertility clinic. PBDE congeners in dust were grouped by commercial mixtures (i.e. penta-, octa- and deca-BDE). In multivariable linear regression models adjusted by age and body mass index (BMI), significant positive associations were found between house dust concentrations of pentaBDEs and serum levels of free T4, total T3, estradiol, and sex hormone binding globulin (SHBG), along with an inverse association with follicle stimulating hormone (FSH). There were also positive associations of octaBDE concentrations with serum free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH) and testosterone and an inverse association of decaBDE concentrations with testosterone. Hexabromocyclododecane (HBCD) was associated with decreased SHBG and increased free androgen index. Dust concentrations of bis-tribromophenoxyethane (BTBPE) and tetrabromo-diethylhexylphthalate (TBPH) were positively associated with total T3. These findings are consistent with our previous report of associations between PBDEs (BDE 47, 99 and 100) in house dust and hormone levels in men, and further suggest that exposure to contaminants in indoor dust may be leading to endocrine disruption in men.


The role of the MHC on resistance to group a streptococci in mice.
The severity of infection with Streptococcus pyogenes is strongly influenced by the host's genetics. This observation extends to the murine model of streptococcal infection, where the background of the mouse strain determines the infection outcome (BALB/c are resistant, whereas C3H/HeN are susceptible). To determine the extent to which the MHC complex (H2) contributed to diseases susceptibility, the response to S. pyogenes of congenic BALB mice from a resistant background (BALB/c), but carrying the H2(k) region of susceptible C3H/HeN mice (BALB/k), was examined. BALB/k were as susceptible as the H2 donor strain (C3H/HeN). Linkage analysis performed in F(2) backcross ([BALB/c x C3H/HeN] x BALB/c) mice confirmed the presence of a susceptibility locus within the H2 region on proximal chromosome 17. The possibility that modulation of T cell responses to streptococcal superantigens (GAS-SAgs) by different H2 haplotypes may influence disease severity was examined. BALB/k exhibited a significantly stronger response at the level of cell proliferation and cytokine production to GAS-SAgs than did BALB/c mice. However, the fact that T cell-deficient SCID-C3H/HeN mice also exhibited a susceptible phenotype suggests a more important contribution of innate effector cells to disease susceptibility. Lower transcriptional levels of certain inflammation-related regulatory genes located on chromosome 17 were detected in macrophages from susceptible than in those from resistant mice in response to infection. These results suggest that susceptibility to S. pyogenes may be associated with an altered transcription of specific genes that may compromise the endogenous regulatory processes controlling the inflammatory cascade and favor the progression to sepsis.


The Impact of Autonomy-Framed and Control-Framed Implementation Intentions on Snacking Behaviour: The Moderating Effect of Eating Self-Efficacy.
Autonomy-supportive implementation intention exercises have been shown to facilitate goal-directed behaviour (Koestner et al., ). The current study explored whether eating self-efficacy moderated the impact of autonomy-framed versus control-framed implementation intentions to reduce high-calorie snack intake. The study employed a randomised prospective design, involving two waves of data collection conducted in 2016. At Time 1, UK participants (N = 300) completed an online questionnaire which asked them to report their snacking behaviour over the previous 7 days. Participants were subsequently asked to form either an autonomy-framed implementation intention or a control-framed implementation intention. Seven days later, participants reported their consumption of high-calorie snacks and completed a measure of eating self-efficacy. Hierarchical multiple regression analysis revealed that eating self-efficacy moderated the effects of implementation intention framing. Autonomy-framed implementation intentions had a greater impact on the avoidance of snacking for high eating self-efficacy participants than did control-framed implementation intentions. In contrast, for low eating self-efficacy participants, control-framed implementation intentions had more impact than did autonomy-framed implementation intentions. The results suggest that if implementation intentions to promote healthy diet are to be effective, the role of eating self-efficacy should be considered, and the design of interventions adapted accordingly.


An important role of interleukin-10 in counteracting excessive immune response in HT-29 cells exposed to Clostridium butyricum.
Clostridium butyricum has become increasingly important in preventing and treating intestinal inflammation. In the intestine it may increase the resistance of the gut to pathogen invasion via inducing the secretion of anti-inflammatory cytokines. Interleukin 10 (IL-10) plays a central role in preventing certain inflammatory diseases by down-regulating inflammatory cascades. In a previous study, we observed that the level of IL-10 mRNA was modulated by C. butyricum. The aim of this study was to investigate whether C. butyricum achieves its beneficial effects through IL-10. We treated HT-29 cells with anti-IL-10 (IL-10 antibody) or siIL-10 (IL-10 small interfering RNA) to disrupt IL-10. In both cases, the effects of C. butyricum-induced NF-κB activation and IL-8 expression were enhanced. We also found that neutralization or knockdown of IL-10 could induce apoptosis and necrosis of HT-29 cells treated with C. butyricum compared with control cells. These findings show that IL-10 serves an important role in C. butyricum-mediated immune protection, and in host recognition of C. butyricum.


Binding of 92 kDa and 72 kDa progelatinases to insoluble elastin modulates their proteolytic activation.
92 kDa and 72 kDa gelatinases, two neutral proteinases exhibiting elastinolytic activity and secreted as zymogens by aortic smooth muscle cells, were shown to bind to insoluble elastin. The active form of each enzyme interacted with substrate more avidly than latent form. Once bound to insoluble elastin, 92 kDa progelatinase was totally unaffected by any potential activators tested (tissue kallikrein, neutrophil elastase, plasmin, and stromelysin-1), except aminophenylmercuric acetate (APMA). Binding of 72 kDa progelatinase to insoluble elastin induced a fast autoactivation of the proenzyme followed by its inactivation. This process can be partly inhibited by tissue inhibitor of matrix metalloproteinases-2 (TIMP-2), EDTA and a synthetic inhibitor of matrix metalloproteinases (BB-94). Such an autoactivation process was also partially observed following adsorption of 72 kDa gelatinase to elastin-derived peptides but not to gelatin. Therefore, elastin can act as a template to direct its own proteolysis by 72 kDa gelatinase; such a mechanism could be relevant to the focal elastolysis in the arterial wall during arteriosclerosis.


Glutamatergic receptor dysfunction in spinal cord contributes to the exaggerated exercise pressor reflex in heart failure.
Excitatory amino acids (e.g., glutamate) released by contraction-activated skeletal muscle afferents into the dorsal horn of the spinal cord initiate the central component of the exercise pressor reflex (EPR) in physiological conditions. However, the role of glutamate and glutamate receptors in mediating the exaggerated EPR in the chronic heart failure (CHF) state remains to be determined. In the present study, we performed microinjection of glutamate receptor antagonists into ipisilateral L4/L5 dorsal horns to investigate their effects on the pressor response to static contraction induced by stimulation of the peripheral end of L4/L5 ventral roots in decerebrate sham-operated (sham) and CHF rats. Microinjection of glutamate (10 mM, 100 nl) into the L4 or L5 dorsal horn caused a greater pressor response in CHF rats compared with sham rats. Furthermore, microinjection of either the broad-spectrum glutamate receptor antagonist kynurenate (10 mM, 100 nl) or the N-methyl-d-aspartate (NMDA) receptor antagonist dl-2-amino-5-phosphonovalerate (50 mM, 100 nl) or the non-NMDA-sensitive receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (5 mM, 100 nl) into L4/5 dorsal horns decreased the pressor response to static contraction in CHF rats to a greater extent than in sham rats. Molecular evidence showed that the protein expression of glutamate receptors (both non-NMDA and NMDA) was elevated in the dorsal horn of the lumbar spinal cord in CHF rats. In addition, data from microdialysis experiments demonstrated that although basal glutamate release at the dorsal horn at rest was similar between sham and CHF rats (225 ± 50 vs. 260 ± 63 nM in sham vs. CHF rats, n = 4, P > 0.05), CHF rats exhibit greater glutamate release into the dorsal horn during muscle contraction compared with sham rats (549 ± 60 vs. 980 ± 65 nM in sham vs. CHF rats, n = 4, P < 0.01). These data indicate that the spinal glutamate system contributes to the exaggerated EPR in the CHF state.


Five-year change in morphological and functional alterations of the thyroid gland: the Study of Health in Pomerania.
While cross-sectional data on thyroid epidemiology are common, few longitudinal data on the incidence and progression of thyroid disorders exist. The aim of this study was to analyze the 5-year change and the incidence of morphological and functional alterations of the thyroid gland in a previously iodine-deficient area. We used 5-year follow-up data based on 2941 participants (20-79 years) of the population-based Study of Health in Pomerania. The thyroid structure and size were measured by ultrasonography. Thyroid function and serum autoantibodies to thyroperoxidase (anti-TPO-Ab) were evaluated. During follow-up, the median iodine/creatinine ratio decreased slightly from 134.2 to 130.4 μg/g. The mean thyroid volume was nonsignificantly increased by 0.73 mL [confidence interval (CI) -1.68-3.41 mL]. The incidence rate of goiter was 34.0 [CI 30.7-37.7] per 1000 person-years (py), the incident rate of nodules was 16.6 [CI 14.5-19.1] per 1000 py. Median serum thyrotropin levels increased slightly (0.10 [CI -0.10-0.34 mIU/L]). The incidence of positive anti-TPO-Ab was 3.4 [CI 2.6-4.7] per 1000 py. For all thyroid parameters, the regression rates were higher than the incidence rates. After iodine fortification became effective in this previously iodine-deficient region, there is a negative net balance between occurring and reverting goiter and nodules. Along with balanced incidences of hyper- and hypothyroid dysfunction and the low incidence of autoimmune-related findings, these findings indicate that the current iodine status is sufficient to prevent iodine deficiency-related disorders in the adult population of the study region.


Attention, gaze shifting, and dual-task interference from phonological encoding in spoken word planning.
Controversy exists about whether dual-task interference from word planning reflects structural bottleneck or attentional control factors. Here, participants named pictures whose names could or could not be phonologically prepared, and they manually responded to arrows presented away from (Experiment 1), or superimposed onto, the pictures (Experiments 2 and 3); or they responded to tones (Experiment 4). Pictures and arrows/tones were presented at stimulus onset asynchronies of 0, 300, and 1,000 ms. Earlier research showed that vocal responding hampers auditory perception, which predicts earlier shifts of attention to the tones than to the arrows. Word planning yielded dual-task interference. Phonological preparation reduced the latencies of picture naming and gaze shifting. The preparation benefit was propagated into the latencies of the manual responses to the arrows but not to the tones. The malleability of the interference supports the attentional control account. This conclusion was corroborated by computer simulations showing that an extension of WEAVER++ (A. Roelofs, 2003) with assumptions about the attentional control of tasks quantitatively accounts for the latencies of vocal responding, gaze shifting, and manual responding.


In vivo optogenetic activation of Nav1.8+ cutaneous nociceptors and their responses to natural stimuli.
Optogenetic methods that utilize expression of the light-sensitive protein channelrhodopsin-2 (ChR2) in neurons have enabled selective activation of specific subtypes or groups of neurons to determine their functions. Using a transgenic mouse model in which neurons natively expressing Nav1.8 (a tetrodotoxin-resistant voltage-gated sodium channel) also express the light-gated channel ChR2, we have been able to determine the functional properties of Nav1.8-expressing cutaneous nociceptors of the glabrous skin in vivo. Most (44 of 53) of the C-fiber nociceptors isolated from Nav1.8-ChR2+ mice were found to be responsive to blue (470 nm) light. Response characteristics, including conduction velocity and responses to mechanical stimuli, were comparable between nociceptors isolated from Nav1.8-ChR2+ and control mice. Interestingly, while none of the non-light-responsive C-fibers were sensitive to heat or cold, nearly all (77%) light-sensitive fibers were excited by mechanical and thermal stimuli, suggesting that Nav1.8 is predominantly expressed by C-fiber nociceptors that are responsive to multiple stimulus modalities. The ability to activate peripheral nociceptors with light provides a method of stimulation that is noninvasive, does not require mechanical interruption of the skin, and accesses receptive fields that might be difficult or impossible to stimulate with standard stimuli while allowing repeated stimulation without injuring the skin.NEW & NOTEWORTHY Transgenic mice that express the blue light-sensitive protein channelrhodopsin2 (ChR2) in nociceptive nerve fibers that contain voltage-gated sodium channel Nav1.8 were used to determine functional properties of these afferent fibers. Electrophysiological recordings in vivo revealed that most nociceptive fibers that possess Nav1.8 are C-fiber nociceptors that respond to multiple stimulus modalities. Furthermore, responses evoked by blue light stimulation were comparable to those elicited by noxious mechanical, heat, and cold stimuli.


Requirement of the Preservation of Mental Nerve During the Transfer of Depressor Anguli Oris Composite Flap.
Reconstruction of wide lower lip defects is still a challenging subject in terms of obtaining functional and aesthetically acceptable results. Lower lip reconstruction with depressor anguli oris muscle was first described by Tobin in 1983. Since the sensory innervation of this composite muscle flap is provided by the mental nerve, it has been advocated that the mental nerve should be preserve during flap elevation. However, no further study has been conducted about this subject since then. Sixteen patients with lower lip mass have undergone excisional biopsy. The resultant defects were higher than 30% of the total lower lip. All the defects were reconstructed with Depressor anguli oris composite flaps. In 9 of the patients, the mental nerve was preserved and included to the flap, while in remaining patients it was sacrificed. The results were evaluated in terms of sensation, function, and aesthetic appearance. In unilaterally reconstructed cases, the results regarding sensation and general complications were similar. However, in bilaterally reconstructed cases, especially where the mental nerve was preserved, the limited arc of rotation has resulted in functional complications, such as whistle deformity in the midline and drooling. The mental nerve does not just limit the arc of rotation of the Depressör anguli oris composite flap but also remains as a potential route for metastasis via perineural invasion. Preservation and inclusion of the mental nerve during reconstruction with Depressor anguli oris flap do not provide any superior outcome; on the contrary, these results in various unfavorable events make this flap a poor option. The skin and mucosa of the DAO flap are innervated by the buccal branch of the trigeminal nerve; thus, the mental nerve should not be preserved during surgery.


Potential urban threat after a radiological fire event.
An accident involving both fire and radioactive material might eventually deteriorate into a dual-threat situation. Such scenario connects two important consequences: (a) fire damage and (b) radiation health threat. Computational simulations considering hypothetic fire scenarios in hospitals using radioactive material can provide valuable information about such an event. The initial decision in regards to an emergency response should consider the fire consequences and radiation doses distribution in the environment with consequences appearing at different times. While the fire presents an immediate threat, radiation exposure also creates immediate and future concerns. The purpose of this study is to evaluate leukemia risk from a hypothetical radiological fire event in a hospital operating Cs-137 gamma blood irradiator. The simulation in this study used the Hotspot Health Physics software to generate output data such as total effective dose (TED). The data from HotSpot was then used as an input to the leukemia risk equations from Biological Effects of Ionizing Radiation Committee V and VII (BEIR V and VII) models accordingly. Results suggest that the risks are dependent of wind speed and height of release; however, when age and sex are taken into account different outputs are shown. Also, the risk model can be changed from BEIR VII (low doses) to BEIR V (high doses) as radiation doses rise due to its time-dependent behavior. Such change would bring potential impacts on logistics and risk communication.


A silencer element in the first intron of the glutamine synthetase gene represses induction by glucocorticoids.
The enzyme glutamine synthetase (GS) ranks as one of the most remarkable glucocorticoid-inducible mammalian genes. In many tissues and cell lines, the synthetic glucocorticoid dexamethasone alone increases GS expression several fold. The direct response is mainly mediated by a cellular glucocorticoid receptor that, upon binding of the hormone, interacts with glucocorticoid responsive elements (GREs) of the gene. In cells of hepatocellular origin the response is mediated by a GRE located in the first intron of the gene. Surprisingly, hepatocytes do not respond to glucocorticoids with enhanced GS expression, despite the presence of an intact glucocorticoid receptor, which, in the same cells, stimulates expression of other genes such as tyrosine amino transferase. Reporter gene assays identified a sequence element downstream from the intronic GRE that inhibits the enhancement of expression by glucocorticoids. This silencer was designated GS silencer element of the rat. Gel mobility shift assays demonstrate the binding of a factor in hepatocyte nuclear extract. This yet unknown factor was designated GS silencer-binding protein. It is absent in FAO cells that respond to glucocorticoids with enhanced expression of GS and present in HepG2 cells that do not respond.


[The voice evaluation protocol of the European Laryngological Society (ELS) -- first results of a multicenter study].
A multidimensional protocol has been established by the ELS in order to reach better agreement and standardisation for functional assessment of pathologic voices. In order to evaluate the validity, practicability and applicability of this protocol the experiences of 6 european voice centres have been analysed in a retrospective study. The ELS protocol comprises 5 dimensions: perceptual voice evaluation, videostroboscopy, acoustics, aerodynamics and subjective rating by the patient. Results obtained in 94 patients with benign voice disorders were evaluated retrospectively in a multicenter study. According to our results, the validity, practicability and applicability of the ELS protocol was largely satisfactory. This was true for all "common" voice disorders, but not for extreme voice alterations (e. g. spasmodic dysphonia, aphonia, substitution voices). The 5 dimension proofed to be not redundant and were able to selectively differentiate pre- post changes among various etiologies of voice disorders, various types of treatment and genders.


Nitrate signaling and early responses in Arabidopsis roots.
Nitrogen (N) is an essential macronutrient that impacts many aspects of plant physiology, growth, and development. Besides its nutritional role, N nutrient and metabolites act as signaling molecules that regulate the expression of a wide range of genes and biological processes. In this review, we describe recent advances in the understanding of components of the nitrate signaling pathway. Recent evidence posits that in one nitrate signaling pathway, nitrate sensed by NRT1.1 activates a phospholipase C activity that is necessary for increased cytosolic calcium levels. The nitrate-elicited calcium increase presumably activates calcium sensors, kinases, or phosphatases, resulting in changes in expression of primary nitrate response genes. Consistent with this model, nitrate treatments elicit proteome-wide changes in phosphorylation patterns in a wide range of proteins, including transporters, metabolic enzymes, kinases, phosphatases, and other regulatory proteins. Identifying and characterizing the function of the different players involved in this and other nitrate signaling pathways and their functional relationships is the next step to understand N responses in plants.


[Acute miliary tuberculosis].
The clinical picture of acute miliary tuberculosis is characterized in 120 patients followed up by the author in 1975-1996. The patients' age varied from 17 to 62 years. Variants of clinical forms of miliary tuberculosis, specific features of the course tuberculous meningoencephalitis in miliary tuberculosis are given. In the past 3 years, the clinical picture of the disease has aggravated and its extremely severe malignant forms appeared.


Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.
The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose.


[Correlative study on the level of serum type IV collagen, laminin and the diameters of portal veins in patients with viral hepatitis].
The contents of serum Type IV collagen and laminin were detected by radioimmunoassay and the diameters of portal veins were measured by B-mode ultrasound in 102 patients with different type of viral hepatitis. The results show that an increase of levels of Type IV collagen and laminin was found in patients with chronic severe hepatitis and fulminant hepatitis. The levels of Type IV collagen and laminin were obviously increased in the patients who have the diameter of portal vein > or = 12 mm compared with the patients who have the diameter of protal < 12 mm. There was a positive correlation between the levels of Type IV collagen, laminin and the diameters of portal vein.


Preoperative Noninvasive Mapping Allowed Targeted Concomitant Surgical Ablation and Revealed COVID-19 Infection.
In March 2020, a 64-year-old female with mitral valve insufficiency and persistent atrial fibrillation underwent preoperative noninvasive mapping for developing an ablation strategy. In the computed tomography (CT) scan, typical signs of COVID-19 were described. Since the consecutive polymerase chain reaction (PCR) test was negative, the severely symptomatic patient was planned for urgent surgery. Noninvasive mapping showed that atrial fibrillation was maintained by left atrial structures and pulmonary veins only. On admission day, the preoperative routine COVID-19 PCR test was positive, and after recovery, uneventful mitral valve repair with cryoablation of the left atrium and pulmonary veins was performed. Our case describes the potential benefit of preoperative noninvasive mapping for the development of a surgical ablation strategy, as well as the challenges in managing urgent surgical patients during the COVID-19 pandemic and the corresponding diagnostic relevance of CT.


Within-subject comparisons of implant-supported mandibular prostheses: evaluation of masticatory function.
In the past, fixed prostheses were believed to be more efficient implant-supported devices than removable types for edentulous patients. However, this hypothesis was never properly tested. Therefore, a within-subject crossover clinical trial was designed in which 145 completely edentulous subjects were tested wearing implant-supported mandibular fixed prostheses and long-bar overdentures. Eight subjects received the fixed appliance first and seven the removable type. The patients' perceptions of various characteristics of the implant-supported prostheses were measured after a minimum of two months' adaptation. Mandibular movements and jaw muscle electromyographic activity were recorded while the patients chewed five standard-sized test foods: bread, apple, hard cheese, sausage, and raw carrot. The prostheses were then changed, worn for the same period of adaptation, and the procedures repeated. There were three test sessions per prosthesis, and each included five trials per food. The measurements were repeated three times at one-week intervals. Mastication time was found to be shorter for three foods (bread, cheese, and sausage) when subjects wore the long-bar overdenture. The vertical amplitude of the masticatory strokes was significantly less with the overdenture for all foods except carrot. Cycle duration was significantly longer with the overdenture for sausage and carrot. Contrary to what might be expected, the long-bar overdenture appears to be no less efficient than the fixed prosthesis. Furthermore, these data suggest that patients are capable of adapting their masticatory movements to the characteristics of the two prostheses.


Immune checkpoint inhibitors modulate the cytotoxic effect of chemotherapy in lung adenocarcinoma cells.
Immunotherapy using immune checkpoint inhibitors (ICIs) has significantly improved survival in patients with non-small cell lung cancer (NSCLC), and ICIs are increasingly used in combination with cytotoxic treatments, such as chemotherapy. Although combined treatments are more effective, not all patients respond to the therapy; therefore, a detailed understanding of the effect of treatment combinations at the tumour level is needed. The present study aimed to explore whether ICIs could affect the cytotoxic effects of chemotherapy on lung adenocarcinoma cell lines with different PD-L1 expression levels (high, HCC-44; low, A-549). Using the resazurin-based assay, the efficacy of seven chemotherapeutic agents (cisplatin, etoposide, gemcitabine, pemetrexed, vinorelbine, docetaxel and paclitaxel) was compared in the presence or absence of the individually chosen single doses of four ICIs (nivolumab, pembrolizumab, atezolizumab and durvalumab). The results revealed that different ICIs can exhibit either potentiating or depotentiating effects, depending on the chemotherapy agent or lung adenocarcinoma cell line used. Durvalumab was the most promising ICI, which potentiated most chemotherapy agents in both cell lines, especially in the case of high PD-L1 expression. By contrast, nivolumab, exhibited depotentiating trends in several combinations. The immunostaining of γH2AX in treated cells confirmed that the potentiation of the chemotherapeutic cytotoxicity by durvalumab was at least partially mediated via increased DNA damage; however, this effect was strongly dependent on the chemotherapy agent and cell line used. Our future studies aim to address the specific mechanisms underlying the observed ICI-induced potentiation or depotentiation.


Medical Emergency Team Event Characteristics from an Australian Pediatric Hospital: A Single-Center, Retrospective Study.
To describe the characteristics of medical emergency team (MET) events at an Australian pediatric, tertiary-care center in a way that would allow for comparison with other MET systems. A retrospective, single-center, observational study. Consecutive MET events that occurred between January 2013 and July 2014 at Princess Margaret Hospital for Children in Perth, Western Australia, were included. There were 46 445 hospital admissions during the study period and 197 MET events in children. This gives a rate of 4.2 MET events per 1000 admissions. Out of 197 pediatric MET events analyzed, there were 2 deaths (1.0%) that occurred during the MET events. All 197 patients were actively treated, with none receiving "do not attempt resuscitation" orders. Of pediatric MET events, 24% (48 of 197) were admitted to the PICU, and 75% (149 of 197) stayed in the ward where the call was made. In this tertiary-care, pediatric hospital in Australia, the MET event rate and the rate of admission to the PICU because of MET events are lower than those reported for US pediatric hospitals. Despite these differences, Australian data suggest that outcomes are similar to US pediatric hospitals.


Soluble tag-assisted peptide head-to-tail cyclization: total synthesis of mahafacyclin B.
A soluble tag-assisted liquid-phase method was successfully applied to peptide head-to-tail cyclization, leading to the total synthesis of antimalarial cyclic heptapeptide, mahafacyclin B (1). The cyclization was carried out in the liquid phase with the tag remaining, which allowed rapid reaction workup and product isolation.


Evaluation of The Pathogenic Potential of Insecticidal Serratia marcescens Strains to Humans.
We observed the death of insect caterpillars of Spodoptera exigua in the laboratory culture line and identified Serratia marcescens as the bacterial causative agent of the insect death. We confirmed that S. marcescens had insecticidal activity against S. exigua and caused high mortality of larvae. The LC50 values of S. marcescens CFU per 1 cm2 of insect diet surface were similar for all isolates. Our research reports novel strains with high pesticidal activity as candidates for future research on a new bioinsecticide. As bioinsecticides cannot be harmful to non-target organisms, we determined the pathogenic properties of S. marcescens to humans. We proved the ability of S. marcescens to damage mammalian epithelial cells. All strains had cytopathic effects to Vero cells with a cytotoxic index ranging from 51.2% ± 3.8% to 79.2% ± 4.1%. We found that all of the strains excreted catecholate siderophore - enterobactin. All isolates were resistant to sulfamethoxazole, tobramycin, gentamicin, cefepime, and aztreonam. We did not observe the ESBL phenotype and the integrons' integrase genes. Resistance to sulfamethoxazole was due to the presence of the sul1 or sul2 gene. The use of resistant S. marcescens strains that are pathogenic to humans in plant protection may cause infections difficult to cure and lead to the spread of resistance genes. The results of our study emphasize the necessity of determination of the safety to vertebrates of the bacteria that are proposed to serve as biocontrol agents. The novelty of our study lies in the demonstration of the indispensability of the bacteria verification towards the lack of hazardous properties to humans. We observed the death of insect caterpillars of Spodoptera exigua in the laboratory culture line and identified Serratia marcescens as the bacterial causative agent of the insect death. We confirmed that S. marcescens had insecticidal activity against S. exigua and caused high mortality of larvae. The LC50 values of S. marcescens CFU per 1 cm2 of insect diet surface were similar for all isolates. Our research reports novel strains with high pesticidal activity as candidates for future research on a new bioinsecticide. As bioinsecticides cannot be harmful to non-target organisms, we determined the pathogenic properties of S. marcescens to humans. We proved the ability of S. marcescens to damage mammalian epithelial cells. All strains had cytopathic effects to Vero cells with a cytotoxic index ranging from 51.2% ± 3.8% to 79.2% ± 4.1%. We found that all of the strains excreted catecholate siderophore – enterobactin. All isolates were resistant to sulfamethoxazole, tobramycin, gentamicin, cefepime, and aztreonam. We did not observe the ESBL phenotype and the integrons' integrase genes. Resistance to sulfamethoxazole was due to the presence of the sul1 or sul2 gene. The use of resistant S. marcescens strains that are pathogenic to humans in plant protection may cause infections difficult to cure and lead to the spread of resistance genes. The results of our study emphasize the necessity of determination of the safety to vertebrates of the bacteria that are proposed to serve as biocontrol agents. The novelty of our study lies in the demonstration of the indispensability of the bacteria verification towards the lack of hazardous properties to humans.


Interaction of Plasmodium falciparum casein kinase 1 with components of host cell protein trafficking machinery.
A pool of Plasmodium falciparum casein kinase 1 (PfCK1) has been shown to localize to the host red blood cell (RBC) membrane and be secreted to the extracellular medium during trophozoite stage of development. We attempted to identify mechanisms for secretion of PfCK1 and its appearance on the RBC membrane. We found that two host proteins with established functions in membrane trafficking in higher eukaryotes, GTPase-activating protein and Vps9 domain-containing protein 1 (GAPVD1), and Sorting nexin 22, consistently co-purify with PfCK1, suggesting that the parasite utilizes trafficking pathways previously thought to be inactive in RBCs. Furthermore, reciprocal immunoprecipitation experiments with GAPVD1 identified parasite proteins suggestive of a protein recycling pathway hitherto only described in higher eukaryotes. Thus, we have identified components of a trafficking pathway involving parasite proteins that act in concert with host proteins, and which we hypothesize mediates trafficking of PfCK1 to the RBC during infection.


A comprehensive study of risk factors for post-operative pneumonia following resection of meningioma.
Post-operative pneumonia (Pop) following meningioma surgery is the dominant systemic complication which could cause serious threats to patients. It is unclear whether hematological biochemical markers are independently associated with the Pop. This study attempted to perform a more comprehensive study of taking both clinical factors and hematological biomarkers into account to promote the management of patients after meningioma surgery. We collected clinical and hematological parameters of 1156 patients undergoing meningioma resection from January 2009 to January 2013. According to whether the symptoms of pneumonia had manifested,patients were divided into the Pop group and the Non-Pop group. We analyzed the distinctions of clinical factors between the two groups. We successively performed univariate and multivariate regression analysis to identify risk factors independently associated with the Pop. 4.4% patients infected with the Pop (51 of 1156). The median age at diagnosis of the Pop patients was significantly older than the Non-Pop group (p = 0.002). There were strike distinctions of post-operative hospital stays between two groups, with 21 days and 7 days each (p < 0.001). On multivariate analysis, tumor relapse (p < 0.001), skull base lesions (p = 0.001), intra-operative blood transfusion (p = 0.018) and cardiovascular diseases (p = 0.001) were linked with increased risk of the Pop following meningioma resection. For hematological biochemical markers, it was the factor of Red blood cell distribution width-standard deviation (RDW-SD) (OR 5.267, 95%CI 1.316, 21.078; p = 0.019) and Neutrophils lymphocytes ratio (NLR) (OR 2.081, 95%CI 1.063, 4.067; p = 0.033) that could appreciably predict the Pop. Apart from tumor recurrence, localizations, intra-operative blood transfusion and cardiovascular diseases are independent risk factors for the Pop. We initially found hematological RDW-SD and NLR are also important predictors.


Learning Object Names at Different Hierarchical Levels Using Cross-Situational Statistics.
Objects in the world usually have names at different hierarchical levels (e.g., beagle, dog, animal). This research investigates adults' ability to use cross-situational statistics to simultaneously learn object labels at individual and category levels. The results revealed that adults were able to use co-occurrence information to learn hierarchical labels in contexts where the labels for individual objects and labels for categories were presented in completely separated blocks, in interleaved blocks, or mixed in the same trial. Temporal presentation schedules significantly affected the learning of individual object labels, but not the learning of category labels. Learners' subsequent generalization of category labels indicated sensitivity to the structure of statistical input.


Insights on inhibition of Plasmodium falciparum plasmepsin I by novel epoxyazadiradione derivatives - molecular docking and comparative molecular field analysis.
In the present study, we have explored the anti-malarial potential of epoxyazadiradione, the natural entity extracted from the neem seed oil and its chemical derivatives, against Plasmodium falciparum. The Surflex dock analysis of 41 compounds against an indispensable target, plasmepsin I (PM-I) revealed that around 70% of the compounds are found to have good binding capacity with the consensus score (C-score) of 5 to 4 with few hydrogen bonds. To elucidate the major structural requirements, vital for binding with the plasmepsin enzyme and to develop the predictive models, three-dimentional quantitative structural activity relationship (3D-QSAR) - comparative molecular field analysis (CoMFA) was carried out using Sybyl X.0. Robust and predictive models were obtained with cross-validated correlation coefficient (q2) value of 0.967 and the non-cross-validated correlation coefficient (r2) value of 0.825, which were validated by an external test set with the predictive correlation coefficient r2(pred) values of 0.773. Three zones were identified for substitution with bulky groups and one zone for substitution with non-bulky groups. Three positions favouring the electronegative group substitution and one for the electropositive group substitution were identified. The physicochemical properties of ligands with the highest C-score were studied. Communicated by Ramaswamy H. Sarma.


Prevalence and Genetic Analysis of β-Thalassemia in the Dali Bai Autonomous Prefecture of the Yunnan Province, China.
Background: β-Thalassemia is the most common monogenetic hemolytic hemoglobin-associated disease in the south of China; the distribution of genetic mutations associated with this condition varies according to geographic regions. This study investigated the prevalence and distribution of β-thalassemia-associated mutations across different ethnic groups in the Dali Bai Autonomous Prefecture of the Yunnan Province, China. Methods: This cross-sectional study included 4723 participants (15-45 years old) who volunteered for thalassaemia screening from the Dali Bai Autonomous Prefecture from May 2017 to October 2020. Cellulose acetate membrane electrophoresis was used to screen for β-thalassemia carriers. Genotypic analyses was performed using polymerase chain reaction-based reverse dot blotting and DNA sequencing. Results: The overall prevalence of β-thalassemia in the study population was 2.01%. The genotypic analyses showed the presence of four types of mutations in the β-globin gene: CD26 (GAG→AAG), CD56 (GGC→GAC), IVS-II-81 (C→T), and CD121 (GAA→CAA). In contrast to previous studies from other regions of Yunnan Province, our results showed that the prevalence of CD26 mutations was significantly higher than that of the other mutations. Conclusion: Our data suggests that the Dali Autonomous Prefecture is an area with a high prevalence of β-thalassemia. Moreover, CD26 was the only β-thalassemia mutation that we have detected. Moreover, the vast majority of the β-thalassemia mutations observed were CD26.


Minimally functional rat adrenal medullary pheochromocytomas.
In this study of 29-month-old male Fischer and Sprague-Dawley rats, the tumor pheochromocytoma occurred in seven of 20 Fischer rats (35%) and ten of 22 Sprague-Dawley rats (45%). Mean blood pressures and mean urinary vanillylmandelic acid levels of rats with pheochromocytomas did not vary significantly from rats with no tumors. Pheochromocytoma in our rats generally was non-functional or of minimal clinical significance. The content of chromaffin granules in tumor cells varied from abundant to not detectable, thus it was apparent that the absence of detectable chromaffin granules does not eliminate the diagnosis of pheochromocytoma.


Disparities in vaccinations and cancer screening among U.S.- and foreign-born Arab and European American non-Hispanic White women.
Disparities in vaccinations and cancer screening exist when comparing foreign-born and U.S.-born women collectively and disaggregated by race and ethnicity. The purpose of this study was to estimate and compare the age-adjusted prevalence of not receiving a flu or pneumonia vaccine, clinical breast examination, mammogram or Pap smear among U.S.- and foreign-born White women by region of birth and examine associations while controlling for potential confounders. We pooled 12 years of National Health Interview Survey data (n = 117,893). To approximate an "Arab-American" ethnicity, we identified 15 "Arab" countries from the Middle East region that comprise the Arab Nations. Data was requested from the National Center for Health Statistics Research Data Center. We used the χ(2) statistic to compare descriptive statistics and odds ratios (ORs) with 95% CIs were used for inferential statistics. Compared to U.S.-born, foreign-born Whites from the Arab Nations had higher estimates of not receiving recommended vaccinations and cancer screenings. In crude and adjusted analyses, foreign-born Arab-American women were less likely to report receiving a flu vaccine (OR, 0.34; 95% CI, 0.21-0.58), pneumonia vaccine (OR, 0.14; 95% CI, 0.06-0.32), Pap smear (OR, 0.13; 95% CI, 0.05-0.31), or clinical breast examination (OR, 0.16; 95% CI, 0.07-0.37) compared with U.S.-born White women. There were no differences for mammography. This national study examining uptake of flu and pneumonia vaccines and preventive cancer screenings suggests that estimates are lower for foreign-born Arab-American women compared with U.S.-born White women. Future studies should collect qualitative data that assess the cultural context surrounding prevention and screening behaviors among Arab-American women.


Antenatal corticosteroid treatment: factors other than lung maturation.
Antenatal corticosteroid (CS) therapy improves both fetal lung mechanism and gas exchange due to accelerated morphologic development of type one and two pneumocytes. This therapy also enhances the production of surfactant binding proteins and fetal lung antioxidant enzymes. In women with threatening preterm delivery, a single course is advocated between 24 and 34 weeks' gestation with either betamethasone (two doses of 12 mg 24 h apart) or dexamethasone (four doses of 6 mg at 12-h intervals). Such treatment reduces the rate of respiratory distress syndrome, comorbidity, and mortality in neonates in the first 48 h of life. The optimal time interval between CS administration and delivery is reported to be 1-7 days. Weekly repeat courses reduce the occurrences and severity of respiratory diseases but are associated with reduce fetal growth. Multiple courses should be avoided. However, a repeat course should be considered in women at risk of preterm birth 7 or more days after an initial course in women who remain at risk of preterm birth <34 weeks' gestation. CS may be harmful in growth restricted fetuses associated with an absent or reversed end-diastolic UA flow since they are at increased risk of acidosis and perinatal death. The purpose of this publication is to update and highlight antenatal CS therapy.


[Effects of duration of early organ dysfunction and therapeutic strategy on outcomes in patients with severe acute pancreatitis].
To investigate the characteristics of early organ dysfunction in patients with severe acute pancreatitis (SAP) and therapeutic regimens. A total of consecutive 74 patients with a confirmed diagnosis of SAP admitted between January 2000 and June 2005 were divided into two groups, transient group (<or=72 h, n = 20) and persistent group (>72 h, n = 54). The differences in local complications and mortality were compared between the two groups. Among the seventy-four SAP patients, the incidence rate of cardiovascular dysfunction was 80%, respiratory dysfunction 47%, hepatic dysfunction 37% and renal dysfunction 20%. The incidence of multiple organ dysfunction in transient group was much lower than that in persistent group (P < 0.01). The local complications and death in transient group patients were less than that in persistent group (P = 0.038, P = 0.054, respectively), irrespective of onset of organ dysfunction on admission or later during the first week. The important determinant of risk of death from SAP is the persistence of early organ dysfunction for more than 72 h. Consequently, aggressively ameliorating the blood perfusion and the oxygenation in tissue is the priority in reducing organ dysfunction or shortening the duration of organ dysfunction.


A Single Central Pattern Generator for the Control of a Locomotor Rolling Wave in Mollusc Aplysia.
Locomotion in mollusc Aplysia is implemented by a pedal rolling wave, a type of axial locomotion. Well-studied examples of axial locomotion (pedal waves in Drosophila larvae and body waves in leech, lamprey, and fish) are generated in a segmented nervous system via activation of multiple coupled central pattern generators (CPGs). Pedal waves in molluscs, however, are generated by a single pedal ganglion, and it is unknown whether there are single or multiple CPGs that generate rhythmic activity and phase shifts between different body parts. During locomotion in intact Aplysia, bursting activity in the parapedal commissural nerve (PPCN) was found to occur during tail contraction. A cluster of 20 to 30 P1 root neurons (P1Ns) on the ventral surface of the pedal ganglion, active during the pedal wave, were identified. Computational cluster analysis revealed that there are 2 phases to the motor program: phase I (centered around 168°) and phase II (centered around 357°). PPCN activity occurs during phase II. The majority of P1Ns are motoneurons. Coactive P1Ns tend to be electrically coupled. Two classes of pedal interneurons (PIs) were characterized. Class 1 (PI1 and PI2) is active during phase I. Their axons make a loop within the pedal ganglion and contribute to locomotor pattern generation. They are electrically coupled to P1Ns that fire during phase I. Class 2 (PI3) is active during phase II and innervates the contralateral pedal ganglion. PI3 may contribute to bilateral coordination. Overall, our findings support the idea that Aplysia pedal waves are generated by a single CPG.


Adaptive Heat Engine.
A major limitation of many heat engines is that their functioning demands on-line control and/or an external fitting between the environmental parameters (e.g., temperatures of thermal baths) and internal parameters of the engine. We study a model for an adaptive heat engine, where-due to feedback from the functional part-the engine's structure adapts to given thermal baths. Hence, no on-line control and no external fitting are needed. The engine can employ unknown resources; it can also adapt to results of its own functioning that make the bath temperatures closer. We determine resources of adaptation and relate them to the prior information available about the environment.