Improved germline transmission in chicken chimeras produced by transplantation of gonadal primordial germ cells into recipient embryos.
In the avian species, germline chimera production could be possible by transfer of donor germ cells into the blood vessel of recipient embryos. This study was conducted to establish an efficient transfer system of chicken gonadal primordial germ cells (gPGCs) for producing the chimeras having a high capacity of germline transmission. Gonadal PGCs retrieved from 5.5-day-old embryos (stage 28) of Korean Ogol chicken (KOC with i/i gene) were transferred into the dorsal aorta of 2.5-day-old embryos (stage 17) of White Leghorn chicken (WL with I/I gene). Prospective evaluations of whether culture duration (0, 5, or 10 days) and subsequent Ficoll separation of gPGCs before transfer affected chimera production and germline transmission in the chimeras were made while retrospective analysis was conducted for examining the effect of chimera sexuality. A testcross analysis by artificial insemination of presumptive chimeras with adult KOC was performed for evaluating each treatment effect. First, comparison was made for evaluating whether experimental treatments could improve chimera production, but none of the treatments were significantly (P = 0.6831) influenced (5.1%-14.4%). Second, it was determined whether each treatment could enhance germline transmission in produced chimeras. More (P < 0.0001) progenies with black feathers (i/i) were produced in the germline chimeras derived from the transfer of 10-day-cultured gPGCs than from the transfer of 0- or 5-day-cultured gPGCs (0.6%-7.8% vs. 10.7%-49.7%). Ficoll separation was negatively affected (P < 0.0001), whereas there was no effect in chimera sexuality (P = 0.6011). In conclusion, improved germline transmission of more than a 45% transmission rate was found in chicken chimeras produced by transfer of 10-day-cultured gPGCs being separated without Ficoll treatment.


A study of residual lesions in horses that recovered from clinical signs of chronic equine dysautonomia.
Equine dysautonomia (ED) causes degeneration and loss of autonomic neurons. Approximately 50% of chronic cases recover, but it is unclear how they survive neuronal loss. To assess lesions, autonomic neuron numbers, interstitial cells of Cajal (ICC), and neurodegeneration in recovered cases. Thirteen cases (group ED), euthanized 10.3 ± 5.2 (1-16) years from diagnosis and 6 age-matched controls (group C). Prospective, case control; routine post mortem examination, neuron counts in peripheral and enteric ganglia and immunohistochemical assessment of neural networks (Protein gene product [PGP] 9.5), ICC (c-kit), and neurodegeneration (beta-amyloid precursor protein and ubiquitin) in intestine. Postmortem findings in group ED were small intestinal dilation (4/12, 33%) and muscular hypertrophy (4/12, 33%), and gastric mucosal hypertrophy (3/11, 27%) and ulceration (4/11, 36%). Neuron density was lower in group ED (mean 39% lower for cranial cervical ganglion [P < .001], median 44% lower in celiacomesenteric ganglion [P = .01]). In intestine, neuronal depletion was worst in ileum (median 100% lower in submucosal plexus [P < .001], 91% lower in myenteric plexus [P = .004]). Group ED had less PGP 9.5 staining in ileal myenteric plexus (mean 66% lower [P = .04]) and circular muscle (median 75% lower [P = .006]). In ileum, there was less c-kit staining in myenteric plexus (median 57% lower [P = .02]) but not muscularis externa. Beta-amyloid precursor protein and ubiquitin results were not indicitive of neurodegeneration. Intact ICC in muscularis externa might help maintain motility after neuronal loss. Treatment supporting ICC function warrants investigation.


Phthalate esters in main source water and drinking water of Zhejiang Province (China): Distribution and health risks.
To evaluate the distributions and health risks of phthalate esters in the main source water and corresponding drinking water of Zhejiang Province, the concentrations of 16 phthalate esters in water samples from 19 sites were measured from samples taken in the dry season and wet season. The concentration of the total phthalate ester congeners in source water ranged from 1.07 μg/L to 7.12 μg/L in the wet season, from 0.01 μg/L to 1.58 μg/L in the dry season, from 1.18 μg/L to 15.28 μg/L from drinking water in the wet season, and from 0.16 μg/L to 1.86 μg/L from drinking water in the dry season. Of the 16 phthalate esters, dimethyl phthalate, dibutyl phthalate, di-(2-ethyl-hexyl) phthalate, di-iso-butyl phthalate, bis-2-n-butoxyethyl phthalate, and dicyclohexyl phthalate were present in the samples analyzed, dominated by di-iso-butyl phthalate and di-(2-ethyl-hexyl) phthalate. The concentrations of phthalate esters in the wet season were all relatively higher than those in the dry season, and the drinking water had higher concentrations of phthalate esters than source water. The phthalate ester congeners studied pose little health risk to nearby citizens. Environ Toxicol Chem 2015;34:2205-2212. © 2015 SETAC.


Development of an educational intervention focused on sexuality for women with gynecological cancer.
The purpose of this article is to report on the development of an educational intervention that focuses on providing women with gynecological cancer information on sexuality. Intervention development was guided by the Medical Research Council framework for complex intervention development. A phased approach was taken to the design and evaluation of this complex intervention which included (1) an in-depth literature review, (2) selection of a theoretical framework, (3) a qualitative study, (4) development of intervention content and process, and (5) pilot testing of the intervention. The educational intervention consists of an information booklet combined with a verbal education session. Content of the intervention is guided by a conceptual framework of sexuality, whereas the intervention process is guided by andragogical principles and the PLISSIT model. Content validity was established by patient and expert review.


High Fluorescent Porphyrin-PAMAM-Fluorene Dendrimers.
Two new classes of dendrimers bearing 8 and 32 fluorene donor groups have been synthesized. The first and second generations of these porphyrin-PAMAM-fluorene dendrimers were characterized by 1H-NMR, 13C-NMR, FTIR, UV-vis spectroscopy, elemental analyses and MALDI-TOF mass spectrometry. The UV-vis spectra showed that the individual properties of donor and acceptor moieties were preserved, indicating that the new dendrimers could be used as photosynthetic antennae. Furthermore, for fluorescent spectroscopy, these dendrimers showed good energy transfer.


Crystallization and preliminary X-ray crystallographic studies on 4-alpha-glucanotransferase from Thermotoga maritima.
Thermotoga maritima 4-alpha-glucanotransferase (GTase), a 52 kDa molecular-weight amylolytic enzyme, has been crystallized by the hanging-drop vapour-diffusion method using PEG monomethylether 5000 as a precipitating agent. A complete data set has been collected to 2.6 A resolution using cryocooling conditions and synchrotron radiation. The crystals belong to space group I222 or I2(1)2(1)2(1), with unit-cell parameters a = 92.6, b = 180.3, c = 199.2 A.


Synthesis and analysis of the conformational preferences of 5-aminomethyloxazolidine-2,4-dione scaffolds: first examples of β(2)- and β(2, 2)-homo-Freidinger lactam analogues.
Constrained peptidomimetic scaffolds are of considerable interest for the design of therapeutically useful analogues of bioactive peptides. We present the single-step cyclization of (S)- or (R)-α-hydroxy-β(2)- or α-substituted-α-hydroxy-β(2, 2)-amino acids already incorporated within oligopeptides to 5-aminomethyl-oxazolidine-2,4-dione (Amo) rings. These scaffolds can be regarded as unprecedented β(2)- or β(2, 2)-homo-Freidinger lactam analogues, and can be equipped with a proteinogenic side chain at each residue. In a biomimetic environment, Amo rings act as inducers of extended, semi-bent or folded geometries, depending on the relative stereochemistry and the presence of α-substituents.


Harmonization of the Genetic Code Effectively Enhances the Recombinant Production of the Major Birch Pollen Allergen Bet v 1.
Enhancing the quality and yield of protein production in heterologous expression systems is an important issue for developing new biopharmaceuticals. It has been shown that the dynamics of protein folding is influenced by codon frequencies. As codon usage frequencies are species specific, this can affect heterologous protein expression. In this respect, "codon harmonization," that is, the usage of synonymous codons with usage frequencies in the host resembling the usage frequencies in the native organism, is a promising strategy. As recombinant proteins are important tools in the area of allergy research, we investigated in this study the influence of codon harmonization on the production of the major birch pollen allergen Bet v 1.0101. To accomplish this task, parallel production of several batches of rBet v 1, BWT, together with a harmonized variant, BH, was applied. The expression yield of soluble and insoluble protein was assayed via densitometric analysis of -SDS-PAGEs for every batch. The quality of purified proteins was assessed with a variety of physicochemical methods including mass spectrometry, circular dichroism, dynamic light scattering, Fourier transform infrared spectroscopy, in vitro degradation, and 1-anilino-8-naphthalene sulfonate-binding assays. Patients' IgE reactivity was tested in enzyme-linked immunosorbent assays and rat basophil mediator release experiments. No significant differences in the ligand-binding capacity and secondary structure elements, as well as, in immunological assays could be found; however, the production yield was drastically increased for BH. We could show that codon harmonization is a powerful method to enhance protein yields in heterologous expression systems and should be considered especially for difficult-to-express proteins.


Robots Learn to Recognize Individuals from Imitative Encounters with People and Avatars.
Prior to language, human infants are prolific imitators. Developmental science grounds infant imitation in the neural coding of actions, and highlights the use of imitation for learning from and about people. Here, we used computational modeling and a robot implementation to explore the functional value of action imitation. We report 3 experiments using a mutual imitation task between robots, adults, typically developing children, and children with Autism Spectrum Disorder. We show that a particular learning architecture--specifically one combining artificial neural nets for (i) extraction of visual features, (ii) the robot's motor internal state, (iii) posture recognition, and (iv) novelty detection--is able to learn from an interactive experience involving mutual imitation. This mutual imitation experience allowed the robot to recognize the interactive agent in a subsequent encounter. These experiments using robots as tools for modeling human cognitive development, based on developmental theory, confirm the promise of developmental robotics. Additionally, findings illustrate how person recognition may emerge through imitative experience, intercorporeal mapping, and statistical learning.


Canada First Nations Strengths in Community-Based Primary Healthcare.
First Nation (FN) peoples and communities in Canada are still grappling with the effects of colonization. Health and social inequities result in higher disease burden and significant disparities in healthcare access and responsiveness. For resilience, survival, and self-determination, FN are looking inwards for strengths. This paper reports on the cultural, community, and family strengths that have supported FN communities in developing community-based primary healthcare (CBPHC) strategies to support health and wellbeing. The study was a partnership between university-based researchers; The First Nations Health and Social Secretariat of Manitoba; and eight First Nation communities in Manitoba. Community-based participatory research methods were used to engage the participating communities. One hundred and eighty-three in-depth, semi-structured key informant interviews were completed between 2014 and 2016 with key members of the First Nation communities, i.e., community-based health providers and users of primary healthcare services, representing all age and genders. Data-collection and analysis were conducted following iterative grounded theory analysis. Community-based healthcare models based on local strengths support easier access and shorter wait times for care and compassionate care delivery. Resources such as homecare and medical transportation are helpful. Community cooperation, youth power, responsive leadership, and economic development as well as a strong cultural and spiritual base are key strengths supporting health and social wellbeing. Locally led, self-determined care adds strength in FN communities, and is poised to create long-lasting primary healthcare transformation.


Pharmacological actions and therapeutic uses of cannabis and cannabinoids.
This review highlights the pharmacology, pharmacokinetics, pharmacological actions, therapeutic uses and adverse effects of cannabinoids. The effect of cannabinoids on anaesthesia is mentioned briefly. Important advances have taken place in cannabinoid research over the last few years and have led to the discovery of novel ligands. The possible clinical applications of these ligands and the direction of future research are discussed.


Ataluren for the treatment of cystic fibrosis.
Alleles causing diseases that carry premature termination codons (PTCs) will cause premature cessation of translation, leading to loss of function and consequent disease. Recently, a novel agent, Ataluren, was developed through a high throughput screening program. Ataluren is orally bioavailable and was shown to be effective in Cystic Fibrosis (CF). Phase I and II studies established the safety and dosing regimens for Ataluren. The results of a short study showed modest improvements in pulmonary function and a reduction in quantitative cough assessment. There was improvement in nasal potential difference and nasal epithelial CFTR protein. In a phase III trial this effect was not observed in patients that were concomitantly treated with tobramycin inhalation. Following these positive findings, a multinational Phase III placebo-controlled efficacy trial is currently underway.


Expiratory and inspiratory forced vital capacity and one-second forced volume in asymptomatic never-smokers in Norway.
The objectives of this study were to examine within and between individual variation detected during forced expiratory (FE) and forced inspiratory (FI) manoeuvers in a general population and to investigate the dependence of these variables on age, body size, and gender. A random sample of asymptomatic never smokers who had never been exposed occupationally to quartz or asbestos and who were living on the south-western coast of Norway were examined by spirometry; 81% of the individuals invited to attend did so. Of the 488 subjects between 18 and 73 years of age, 98% contributed three acceptable recordings for forced expiratory vital capacity (FVC) and one-second forced expiratory volume (FEV1), 94% contributed three acceptable recordings for forced inspiratory vital capacity (FIVC) and 85% contributed three acceptable recordings for one-second forced inspiratory volume (FIV(1)). The within-subject variation increased with body height and was considerably larger for FIV(1) than for FVC, FEV(1) or FIVC. A four-parameter model of pulmonary function measurement divided by height squared, including a gender term and a linear and quadratic term of age, fit the median of the observed values well. The residuals had a close-to-normal distribution, and the fifth-percentile values were estimated as the lower limit of normal. The peak value of dynamic lung volumes was observed into the middle of the fourth decade of life, and the decline thereafter did not differ greatly between the genders or among the different indices. The forced inspiratory volumes are the first reported in any reference population.


Repeat radiosurgery for intracranial arteriovenous malformations.
Despite a high success rate in the stereotactic radiosurgical treatment of intracranial arteriovenous malformations (AVMs) that cannot be safely resected with microsurgery, some patients must be managed after treatment failure. To provide an update on the use of repeat linear accelerator radiosurgery as a treatment for failed AVM radiosurgery at the University of Florida. We reviewed 103 patients who underwent repeat radiosurgical treatment for residual AVM at the University of Florida between December 1991 and December 2007. Each of these patients had at least 2 radiosurgical treatments for the same AVM. Patient information, including AVM nidus volume, prescription dose, age, and sex, was collected at the time of initial treatment and again at the time of retreatment. Patients were followed up after treatment with magnetic resonance, computed tomography, and angiographic imaging at standard intervals to determine the status of their AVM. The median follow-up after retreatment was 31 months. Between the first and second treatments, the median AVM nidus volume was decreased by 69% (from a median volume of 12.7 to 4.0 cm), allowing the median prescribed dose to be increased from 1500 cGy on initial treatment to 1750 cGy on retreatment. The final obliteration rate on retreatment was 65.3%. After salvage retreatment, 5 patients (4.9%) experienced radiation-induced complications, and 6 patients (5.8%) experienced posttreatment hemorrhage. Repeat radiosurgery is a safe and effective salvage treatment for AVMs.


Calcification of the thoracic aorta by spiral computed tomography among hypertensive patients: associations and risk of ischemic cerebrovascular events.
Calcium is often deposited in the aorta, but the associations and clinical implications of calcification of the aorta have not yet been elucidated. In a prospective cohort of 455 hypertensive patients with at least 1 additional risk factor for atherosclerosis that underwent dual slice spiral computed tomography of the chest for assessment of arterial calcification (mean age 65.7+/-5.8, range 52-80 years, 48% female), we assessed for calcifications of the ascending and descending aorta and their association with the risk of subsequent ischemic cerebrovascular events during 3-year follow-up. Calcification of the ascending or descending aorta was present in 342 (75%) patients (60% calcification of the ascending aorta and 56% of the descending aorta). The main associations of calcification of the thoracic aorta were increasing age and the presence of coronary calcification, mitral annulus calcification, and aortic valve calcification. In a logistic regression model the main predictors of ischemic cerebrovascular events (n=27) during follow-up were the presence of severe calcification (thickness of > or = 5 mm) of the descending aorta (OR 4.9, 95%CI 1.8 to 13.5) and cigarette smoking (OR 2.8, 95%CI 1.1 to 6.7). Calcification of the thoracic aorta is highly prevalent among women and men with hypertension, is age-related, and correlates with calcification of the coronary arteries and heart valves. Only severe calcification of the descending aorta is associated with subsequent ischemic cerebrovascular events, suggesting that calcification of the thoracic aorta is a marker of the burden of vascular disease.


Risk of both intracranial hemorrhage and ischemic stroke in elderly individuals with nonvalvular atrial fibrillation taking direct oral anticoagulants compared with warfarin: Analysis of the ANAFIE registry.
Elderly patients with nonvalvular atrial fibrillation (NVAF) might have a higher risk of intracerebral hemorrhage. To investigate this, we compared the incidence of intracranial hemorrhage (ICH) and its subtypes, as well as ischemic stroke, in patients taking direct oral anticoagulants (DOACs) compared with warfarin in a real-world setting. We also determined the baseline characteristics associated with both ICH and ischemic stroke. Patients aged ⩾ 75 years with documented NVAF enrolled in the prospective, multicenter, observational All Nippon Atrial Fibrillation in the Elderly Registry between October 2016 and January 2018 were evaluated. The co-primary endpoints were the incidence of ischemic stroke and ICH. Secondary endpoints included subtypes of ICH. Of 32,275 patients (13,793 women; median age, 81.0 years) analyzed, 21,585 (66.9%) were taking DOACs and 8233 (25.5%) were taking warfarin. During the median 1.88-year follow-up, 743 patients (1.24/100 person-years) developed ischemic stroke and 453 (0.75/100 person-years) developed ICH (intracerebral hemorrhage, 189; subarachnoid hemorrhage, 72; subdural/epidural hemorrhage, 190; unknown subtype, 2). The incidence of ischemic stroke (adjusted hazard ratio (aHR) 0.82, 95% confidence interval (CI) 0.70-0.97), ICH (aHR 0.68, 95% CI 0.55-0.83), and subdural/epidural hemorrhage (aHR 0.53, 95% CI 0.39-0.72) was lower in DOAC users versus warfarin users. The incidence of fatal ICH and fatal subarachnoid hemorrhage was also lower in DOAC users versus warfarin users. Several baseline characteristics other than anticoagulants were also associated with the incidence of the endpoints. Of these, history of cerebrovascular disease (aHR 2.39, 95% CI 2.05-2.78), persistent NVAF, (aHR 1.90, 95% CI 1.53-2.36), and long-standing persistent/permanent NVAF (aHR 1.92, 95% CI 1.60-2.30) was strongly associated with ischemic stroke; severe hepatic disease (aHR 2.67, 95% CI 1.46-4.88) was strongly associated with overall ICH; and history of fall within 1 year was strongly associated with both overall ICH (aHR 2.29, 95% CI 1.76-2.97) and subdural/epidural hemorrhage (aHR 2.90, 95% CI 1.99-4.23). Patients aged ⩾ 75 years with NVAF taking DOACs had lower risks of ischemic stroke, ICH, and subdural/epidural hemorrhage than those taking warfarin. Fall was strongly associated with the risks of intracranial and subdural/epidural hemorrhage. The individual de-identified participant data and study protocol will be shared for up to 36 months after the publication of the article. Access criteria for data sharing (including requests) will be decided on by a committee led by Daiichi Sankyo. To gain access, those requesting data access will need to sign a data access agreement. Requests should be directed to email@example.com.


[Characteristic of metabolic syndrome in subjects with or without cardiovascular diseases].
Identification of risk factors of metabolic syndrome (MS) as a part of primary prophylaxis allows early diagnosis and appropriate treatment. Secondary prophylaxis may lead to decreased number of complications and deaths resulting from cardiovascular diseases in subjects with MS. To assess the risk factors of MS and incidence of MS in subjects with or without cardiovascular diseases. There were two groups of patients. I group--600 patients with primary prophylaxis, without cardiovascular diseases, aged 35-60 (49.57 +/- 8.5) and II group--231 patients with cardiovascular diseases (hypertension, ischaemic heart disease, type 2 diabetes), aged 27-69 (56.5 +/- 11.3). MS was diagnosed according to the IDF criteria from 2005. MS was diagnosed in 141 cases of 600 patients with primary prevention what gives 23.5% out of whole study group. In the I group the most common were: abdominal obesity (100%), hypertriglyceridemia (80.2%), hypertension (64.7%) and fasting hyperglycemia (55.2%). MS was diagnosed in 158 cases of 231 patients with cardiovascular disease what gives 68.4% out of whole study group. MS was the most frequent in patients with type 2 diabetes (90.32%), in patients with hypertension (71.58%) and the least common in patients with cardiovascular disease (59.05%). In the II group the most frequent were: abdominal obesity (100%), hypertension (89.24%), fasting hyperglycemia (75.32%). MS occurs more often in patients with cardiovascular diseases than in the total population. Cardiovascular diseases are connected with fasting hyperglycemia, systolic hypertension and high WHR.


Pyrene-based dyad and triad leading to a reversible chemical and redox optical and magnetic switch.
Two new pyrene-polychlorotriphenylmethyl (PTM) dyads and triads have been synthesized and characterized by optical, magnetic, and electrochemical methods. The interplay between the different electronic states of the PTM moiety in the dyads and triads and the optical and magnetic properties of the molecules have been studied. The electronic spectra of the radicals 5(.) and 6(.) show the intramolecular charge-transfer transition at around 700 nm due to the acceptor character of the PTM radical. In the diamagnetic protonated derivatives 3 and 4 the fluorescence due to the pyrene is maintained, whereas in the radicals 5(.) and 6(.) and the corresponding anions 5(-) and 6(-) there is a clear quenching of the fluorescence, which is more efficient in the case of radicals. The redox activity of PTM radicals that are easily reduced to the corresponding carbanion has been exploited to fabricate electrochemical switches with optical and magnetic response.


Epignathus with fetiform features.
Epignathus is an extremely rare oropharyngeal teratoma that commonly arises from the palate, leading to a high mortality (80-100%) due to airway obstruction in the neonatal period. We present a case of epignathus immature teratoma with fetiform features, originating from basisphenoid in a 28-week preterm male baby, who succumbed to death immediately after birth. Since epignathus is a life-threatening condition at the time of delivery, a prenatal diagnosis is essential to coordinate the treatment and appropriate management by securing the airway, either by endotracheal intubation or tracheostomy followed by complete resection of the tumor.


Rational design of cationic lipids for siRNA delivery.
We adopted a rational approach to design cationic lipids for use in formulations to deliver small interfering RNA (siRNA). Starting with the ionizable cationic lipid 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA), a key lipid component of stable nucleic acid lipid particles (SNALP) as a benchmark, we used the proposed in vivo mechanism of action of ionizable cationic lipids to guide the design of DLinDMA-based lipids with superior delivery capacity. The best-performing lipid recovered after screening (DLin-KC2-DMA) was formulated and characterized in SNALP and demonstrated to have in vivo activity at siRNA doses as low as 0.01 mg/kg in rodents and 0.1 mg/kg in nonhuman primates. To our knowledge, this represents a substantial improvement over previous reports of in vivo endogenous hepatic gene silencing.


Association between multiple IV attempts and perceived pain levels in the emergency department.
Intravenous (IV) access is the most commonly performed procedure in the emergency department (ED). Patients with difficult venous access require multiple needlesticks (MNS) for successful IV cannulation and may experience increased pain with many attempts. To determine the association between number of IV attempts and overall pain experienced by the patient from IV placement. Cross-sectional observational study on consecutive patients undergoing IV placement with a 20-gauge IV in the upper extremity in an urban academic hospital. Exclusion criteria included refusal to participate or fully complete all survey questions. The total number of IV attempts and patient pain scores marked on a standardized visual analog scale was recorded. Mean pain scores of two groups, single needlestick (SNS) and MNS, were compared using Student's t-test. A total of 760 patients were approached, of whom 31 were excluded, leaving 729 patients in the analysis; 556 with SNS (76%) and 173 with MNS (24%). The mean pain score (95% CI) was 51 mm (46-55 mm) for the MNS group and 25 mm (23-28 mm) for the SNS group, p<0.001. Compared to patients who underwent one IV attempt, patients with two and three attempts had an average 19 mm and 33 mm increase in pain scores, respectively, with the highest average pain associated with five attempts. A total of 58% of MNS patients rated IV placement as the most painful experience while in the ED. Patients experience increased pain in association with multiple IV attempts.


MEK inhibition and immune responses in advanced melanoma.
phase II and III clinical trials demonstrated modest anti- tumor activity of Binimetinib (MEK162) - a potent allosteric inhibitor of MEK1 and MEK2- in patients with advanced NRAS mutant melanoma. The analysis of the NEMO study in NRAS mutated melanoma, has shown that pre-treatment with immunotherapy improved the outcome of binimetinib therapy. We discuss this finding in the context of in vitro and in vivo effects of MEK inhibition on immuno-critical pathways and interactions.


Urine Drug Testing in Cancer Pain Management.
Urine drug test (UDT) is an effective tool used in chronic opioid therapy to ensure patient adherence to treatment and detect nonmedical opioid use. The two main types of UDT used in routine clinical practice are the screening tests or immunoassays and the confirmatory tests or laboratory-based specific drug identification tests such as gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, or tandem mass spectrometry. UDT produces objective data on some nonmedical opioid use that may otherwise go undetected, such as the use of undisclosed medications, the nonuse of prescribed medications, and the use of illegal drugs. It allows clinicians to initiate an open and effective conversation about nonmedical opioid use with their patients. However, the test has certain limitations that sometimes compromise its use. Its interpretation can be challenging to clinicians because of the complexity of the opioid metabolic pathways. Clear guidelines or recommendations regarding the use of UDT in cancer pain is limited. As a result, UDT appears to be underused among patients with cancer pain receiving opioid therapy. More studies are needed to help standardize the integration and use of UDT in routine cancer pain management. IMPLICATIONS FOR PRACTICE: Despite its potential benefits, urine drug testing (UDT) appears to be underused among patients with cancer pain receiving opioid therapy. This is partly because its interpretation can be challenging owing to the complexity of the opioid metabolic pathways. Information regarding the use of UDT in opioid therapy among patients with cancer is limited. This review article will improve clinician proficiency in UDT interpretation and assist oncologists in developing appropriate treatment plans during chronic opioid therapy.


TMEPAI family: involvement in regulation of multiple signalling pathways.
The TMEPAI family, composed of TMEPAI and C18ORF1, is known to inhibit transforming growth factor-β (TGF-β) signalling via its competition for binding of receptor-regulated Smad with Smad anchor for receptor activation. However, TMEPAI has also been reported to be involved in androgen receptor signalling, phosphatase and tensin homologue deleted on chromosome 10 signalling, and formation of autophagosomes in addition to degradation of TβRI (TGF-β type I receptor) through lysosomes. Thus, TMEPAI seems to act as a regulator of multiple signalling pathways. A great deal of attention has already been paid to the relationship between the TMEPAI family and tumourigenicity. In this paper, therefore, we describe recent progresses in the understanding of how the TMEPAI family physiologically contributes to cellular functions and diseases.


[The effect of iron on peritoneal macrophage activity and sperm phagocytosis in rats].
Excessive activation of macrophages is considered to be the etiological factor of marital infertility. Peritoneal macrophages participate in the phagocytosis of menstrual detritus and sperm in the peritoneal cavity. Iron ingested by peritoneal macrophages could be responsible for their increased spermiophagy. This mechanism would operate in some gynecological diseases, particularly in endometriosis when the ectopic location of endometrial tissue in the pelvic cavity or oviduct becomes a source of cyclic menorrhagia into the peritoneal fluid. The aim of this study was to establish the effect of iron (Jectofer, Astra D, complex salt of Fe+3; 50 micrograms Fe+3/ml) on the morphology and phagocytic activity of LPS-activated peritoneal macrophages. Macrophages were cultured with iron in the presence or absence of iron chelator--Desferal (DFO) (Sigma; 500 micrograms/ml), using the method of Nechala and Hrudka [20]. The viability of cells was evaluated with the trypan blue exclusion test. Cells were washed twice, suspended in modified Dulbecco's medium, supplemented with 2% inactivated fetal calf serum and antibiotics, than transferred (1 x 10(6)) into a culture dish. Nonadherent cells were removed by repeated washing after 1 h incubation at 37 degrees C and 5% CO2. Macrophages were cultured in 1 ml medium with LPS (1 microgram/ml). After 2 or 24 h the macrophages were covered with the same number of rat epididymal sperm cells. Following 1.5 h of incubation, phagocytosis was assessed on the basis of the spermiophagic index (SPI). After 3.5 h of culture macrophages formed monolayers and groups of cells with intersecting sperm tails (Fig. 2). Increased sperm phagocytosis was observed in the macrophage culture exposed to iron for 3.5 h. SPI was significantly higher compared to control value (Fig. 1). The findings were confirmed with scanning and transmission electron microscopy. Macrophages cultured with iron for 3.5 h displayed features of activation, growing to considerable size and developing numerous elongated processes with which they surrounded spermatozoa. The cytoplasm was replete with endosomes containing spermatozoa (Fig. 3). Electron-dense structures could be seen in phagolysosomes. The presence of iron in these structures was confirmed by X-ray microanalysis (Fig. 6). In comparison, macrophages cultured in the presence of iron and iron chelator demonstrated diminished phagocytic activity (Fig. 1). After 24 h of culture macrophages formed cluster-like structures. Spermiophagy was still taking place outside such aggregates and macrophages had a normal appearance (Fig. 4). When iron was added to such culture very few macrophages and spermatozoa could be seen in the electron microscope (Fig. 5A). Iron-loaded macrophages underwent necrosis, their nucleus, plasma membrane and organelles displayed features of degeneration (Fig. 5B). SPI of macrophages exposed to iron for 24 h was significantly decreased as compared with control value (Fig. 1). The ultrastructure of macrophages exposed for 24 h to DFO only was not altered and the phagocytic activity was comparatively higher (Fig. 1). There was a great number of macrophages and spermatozoa forming giant aggregations. The present results suggest that iron enhances spermiophagy in 3.5 h culture. As phagocytic activity of macrophages was reduced by Desferal in 3.5 h culture, an iron chelator could be beneficial in endometriosis to reduce the iron content in the peritoneal cavity where a regular influx of new macrophages takes place.


[Possibilities of primary prevention of stroke: elaboration of a population level strategy].
This review is devoted to principles of primary prevention of cerebral stroke. Prevalence of stroke and its contribution to development of complications and lethal outcomes is analyzed in detail. Main principles of prevention of stroke are delineated and contemporary international guidelines on correction risk factors (arterial hypertension, smoking, disorders of lipid metabolism, diabetes mellitus, atrial fibrillation) are reviewed. Special attention is given to the significance of asymptomatic stenoses of carotid arteries as predictors of stroke and to modern methods of diagnosis and treatment of such stenoses. Expediency of the use of hormonal replacement therapy with the aim of stroke prevention in postmenopausal women is considered. It is noted that antiaggregant therapy and specifically acetyl salicylic acid should be administered only in the presence of high risk of cardiovascular complications. The authors believe that overall success of stroke prevention depends on realization of complex long term national programs.


The role of orientation and position in shape perception.
This study investigates the contributions of position versus orientation information in shape perception by putting the two in conflict. Sampling the orientation of, e.g., a rounded pentagon and positioning the samples on a circle creates a stimulus in which element positions are consistent with a circle but element orientations with a pentagon. Whether orientation or position dominates the percept depends on a number of factors. First, perceived shape shows a band-pass relationship with respect to number of samples. Element orientation captures element position unless elements are widely separated or very closely spaced. This effect is scale invariant. Second, increasing element envelope size or decreasing carrier wavelength strengthens the influence of element orientation, while other parameters such as the phase and polarity of the carrier or the scale of the Gabor are irrelevant. Third, the overall shape of the contour modulates the effect. The strength of the positional signal rises as the orientation difference between adjacent elements increases. Consequently, the computation underlying contour shape relies on a weighted combination of element orientation and position with weights, not fixed, but dependent on stimulus details. When orientation is dominant, its signal is strong enough to alter positional information, giving rise to the illusion of, e.g., a pentagon despite elements being on a circle.


Metformin use and improved response to therapy in esophageal adenocarcinoma.
We investigated the radiographic and pathologic response rate of esophageal adenocarcinoma treated with neoadjuvant chemoradiation in patients taking metformin. Two hundred eighty-five patients with esophageal adenocarcinoma treated with concurrent chemoradiation (CRT) followed by esophagectomy from 1997 to 2012 were included in the study, including 29 diabetics taking metformin, 21 diabetics not taking metformin and 235 non-diabetics. Pre- and post-treatment positron emission tomography (PET) scans were available for 204 patients. Pathologic response was graded at the time of surgery. Response rates were compared using both the χ(2) statistic as well as ANOVA with post-hoc LSD analysis. Multivariate logistic regression analysis was performed to control for predictors of pathologic complete response (CR) after CRT. The overall rate of pathologic CR for the study population was 20%. The pathologic CR rate was higher in patients taking metformin (34.5%), compared to diabetic patients not taking metformin (4.8%, p = 0.01) and non-diabetic patients (19.6%, p = 0.05). Pathologic CR was related to metformin dose, with ≥ 1500 mg/d associated with a higher CR rate. No significant difference seen in pre-CRT maximum tumor SUV (p = 0.93), however post-CRT maximum SUV was significantly decreased in patients taking metformin (p = 0.05). On multivariate logistic regression, metformin use was independently associated with pathologic CR (p = 0.04). Metformin use was also associated with decreased in field loco-regional failure following radiation (p = 0.05). Metformin use is associated with a dose-dependent increased response to CRT in esophageal cancer and may be a sensitizer to this therapy.


The management of the oropharyngeal anterior wall cancer.
Anterior wall of the oropharynx or the base of the tongue is the site of different types of cancers, most of them usually diagnosed in advanced stages. The most common histological type of cancer diagnosed in these patients is squamous cell carcinoma (SCC). The treatment methods are multiple, but the optimal therapeutic option with best results on outcome and on the patients' quality life has not been established. The objectives of our study were to evaluate the tongue base SCCs treated by transhyoid approach and the oncological outcomes of the surgery combined with radiotherapy. The retrospective study was performed over a period of 10 years (2001-2010) on 37 previously untreated patients. All the tumors were biopsied and after histopathological (HP) diagnosis, the tumors were excised. All the specimens were fixed in 4% (v/v) buffered formalin and sent for the HP evaluation. In the study were included only the patient diagnosed on biopsy with different types of SCC. The mean age was 61 years old, most of the patients (94.59%) being males. We performed a tongue base transhyoid tumor resection in 23 (62.17%) cases followed by epiglottectomy in five (13.51%) cases or horizontal supraglottic laryngectomy in nine (24.32%) cases, respectively. Bilateral neck dissections and postoperative radiotherapy were performed in all cases. The postoperative and post-therapeutic evolution was favorable at three years (81.1%) and five years (75.67%). There were no signs of local or regional recurrences. The tumor specific three-year and five-year survival rates were: pT2 100%, pT3 87.5%, pT4a 71.42% and 57.14%, and pT4b 50% and 25%, respectively. The stage specific three-year and five-year survival rates were: stage II 100%, stage III 85.71%, stage IVA 83.33% and 79.16%, and stage IVB 50% and 25%, respectively. The prognosis for the SCC of the tongue base is poor. Cancer resection by transhyoid approach is a feasible procedure, which permits a good tumor control with limited postoperative morbidity, with an important benefit on the life quality of the patients.


The effect of magnitude in a simultaneous duration assessment task among children - a replication study.
The "magnitude effect" refers to the phenomenon where stimuli of greater magnitude appear to last longer in duration. Previous studies have explored this effect among children using various duration assessment tasks, but the findings have been inconsistent. Moreover, no replication studies have been conducted on this topic among children thus far. The simultaneous duration assessment task, which is one method for investigating time perception, has been used only twice in children and produced the magnitude effect. Thus, we aimed to replicate these findings and validate them through an additional replicated study. For these aims, we recruited 45 Arab-speaking children aged 7-12 to participate in two studies. In Study 1, they were asked to perform a simultaneous duration assessment task, where they had to assess the illumination durations of lightbulbs with strong and weak intensities simultaneously. In Study 2, they were asked to perform a duration reproduction task, where they had to reproduce the durations of illumination of the same stimuli. Both studies found a magnitude effect pattern, where the children tended to report that the lightbulb with the stronger intensity was illuminated for a longer duration or had a strong tendency to not choose the lightbulb with the weaker intensity. These results are discussed in terms of possible explanations for the conflicting results found in previous literature, as well as their consistency with the pacemaker model's explanation for the effect.


Non-operative management for high-grade isolated renal trauma in pediatric patients: a case series.
The kidney is the most commonly injured urinary tract organ in pediatric trauma with blunt mechanisms, causing around 80% of cases. Non-operative management (NOM) remained the first choice for minor blunt renal trauma; however, its value for major trauma is still under debate. We present three children with high-grade isolated renal trauma diagnosed using computed tomography scans and treated using NOM as the main strategy of treatment. The first patient (12-year-old) fully recovered without needing an auxiliary procedure. The second patient (6-year-old) developed urinoma and underwent percutaneous drainage of urinoma and double J stent (DJ) with an uneventful result. The third patient (14-year-old) developed urinoma and underwent percutaneous drainage and DJ stent. However, he experienced continuous hematuria that was treated via super-selective embolization. In conclusion, NOM for isolated high-grade renal trauma is feasible with good outcomes. If complications were developed during follow-up, minimally invasive procedures, such as super-selective angioembolization in continuing hemorrhage and initial drainage in urinoma, offered a comparable outcome without needing open surgery.


Confocal microscopy of the living eye.
Confocal microscopy is an imaging paradigm that allows optical sectioning of almost any material with increased axial and lateral spatial resolution and better image contrast. We have applied this technology to the study of the living eye of cats, albino rabbits, and humans. The technique allows in vivo, noninvasive, real time images of the eye at magnifications (630x) which allow resolution of anatomical detail at the cellular level. In this paper we report details of our current instrument techniques and some of our results. The past development, present state-of-the-art, and projected future advances and applications of this novel microscopy are discussed. Preliminary observations are reported for all layers of the cornea, the limbus, and wound-healing responses in single animals.


High performance workflow implementation for protein surface characterization using grid technology.
This study concerns the development of a high performance workflow that, using grid technology, correlates different kinds of Bioinformatics data, starting from the base pairs of the nucleotide sequence to the exposed residues of the protein surface. The implementation of this workflow is based on the Italian Grid.it project infrastructure, that is a network of several computational resources and storage facilities distributed at different grid sites. Workflows are very common in Bioinformatics because they allow to process large quantities of data by delegating the management of resources to the information streaming. Grid technology optimizes the computational load during the different workflow steps, dividing the more expensive tasks into a set of small jobs. Grid technology allows efficient database management, a crucial problem for obtaining good results in Bioinformatics applications. The proposed workflow is implemented to integrate huge amounts of data and the results themselves must be stored into a relational database, which results as the added value to the global knowledge. A web interface has been developed to make this technology accessible to grid users. Once the workflow has started, by means of the simplified interface, it is possible to follow all the different steps throughout the data processing. Eventually, when the workflow has been terminated, the different features of the protein, like the amino acids exposed on the protein surface, can be compared with the data present in the output database.


Neuro-Inspired Signal Processing in Ferromagnetic Nanofibers.
Computers nowadays have different components for data storage and data processing, making data transfer between these units a bottleneck for computing speed. Therefore, so-called cognitive (or neuromorphic) computing approaches try combining both these tasks, as is done in the human brain, to make computing faster and less energy-consuming. One possible method to prepare new hardware solutions for neuromorphic computing is given by nanofiber networks as they can be prepared by diverse methods, from lithography to electrospinning. Here, we show results of micromagnetic simulations of three coupled semicircle fibers in which domain walls are excited by rotating magnetic fields (inputs), leading to different output signals that can be used for stochastic data processing, mimicking biological synaptic activity and thus being suitable as artificial synapses in artificial neural networks.


Disseminated coccidioidomycosis in a heart transplant recipient.
A cardiac transplant patient developed disseminated coccidioidomycosis shortly after transplantation and institution of immunosuppressive therapy. The patient was maintained on intravenous and intrathecal amphotericin B for 19 months, but when therapy was discontinued, the disease relapsed and he died. At autopsy the cardiac allograft was without signs of rejection, but the patient had coccidioidomycotic lesions in multiple organs. There is an increasing number of reports of disseminated coccidioidomycosis in immunocompromised patients, especially those who receive steroids or immunosuppressive therapy. Coccidioidomycosis may represent a severe complication in the transplant patient.


Characterization of DNA sequences required for the CcrAB-mediated integration of staphylococcal cassette chromosome mec, a Staphylococcus aureus genomic island.
The mobile element staphylococcal cassette chromosome mec (SCCmec), which carries mecA, the gene responsible for methicillin resistance in staphylococci, inserts into the chromosome at a specific site, attB, mediated by serine recombinases, CcrAB and CcrC, encoded on the element. This study sought to determine the sequence specificity for CcrB DNA binding in vitro and for CcrAB-mediated SCCmec insertion in vivo. CcrB DNA binding, as assessed in vitro by electrophoretic mobility shift assay (EMSA), revealed that a 14-bp sequence (CGTATCATAAGTAA; the terminal sequence of the orfX gene) was the minimal requirement for binding, containing an invariant sequence (TATCATAA) found in all chromosomal (attB) and SCCmec (attS) integration sites. The sequences flanking the minimal attB and attS binding sites required for insertion in vivo were next determined. A plasmid containing only 37 bp of attS and flanking sequences was required for integration into the attB site at 92% efficiency. In contrast, at least 200 bp of sequence within orfX, 5' to the attB core, and 120 bp of specific sequence 3' to the orfX stop site and attB core were required for the highest insertion frequency. Finally, an attS-containing plasmid was inserted into wild-type Staphylococcus aureus strains without integrated SCCmec (methicillin susceptible) at various frequencies which were determined both by sequences flanking the att site and by the presence of more than one att site on either the chromosome or the integration plasmid. This sequence specificity may play a role in the epidemiology of SCCmec acquisition.


Enhanced Thermoelectric Performance in Black Phosphorene via Tunable Interlayer Twist.
Twist-angle two-dimensional (2D) systems are attractive in their exotic and tunable properties by the formation of the moiré superlattices, allowing easy access to manipulating intrinsic electrical and thermal properties. Here, the angle-dependent thermoelectric properties of twisted bilayer black phosphorene (tbBP) by first-principles calculations are reported. The simulations show that significantly enhanced Seebeck coefficient and power factor can be achieved in p-type tbBP due to merging of the multi-valley electronic states and flat moiré bands. Moreover, the twisted layers bring in a strong anharmonic phonon scattering and thus very low lattice thermal conductivity of 4.51 W m-1 K-1 at 300 K. Consequently, a maximal ZT value can be achieved in p-type 10.11° tbBP along the armchair direction up to 0.57 and 1.06 at 300 and 500 K, respectively. The room-temperature ZT value along the zigzag direction is also significantly increased by almost 40 times compared to pristine BP when the twist angle is close to 70.68°. This work demonstrates a platform to manipulate thermoelectric performance in 2D materials by creating moiré patterns, leading tbBP as a promising eco-friendly candidate for thermoelectric applications.


NR3E receptors in cnidarians: A new family of steroid receptor relatives extends the possible mechanisms for ligand binding.
Steroid hormone receptors are important regulators of development and physiology in bilaterian animals, but the role of steroid signaling in cnidarians has been contentious. Cnidarians produce steroids, including A-ring aromatic steroids with a side-chain, but these are probably made through pathways different than the one used by vertebrates to make their A-ring aromatic steroids. Here we present comparative genomic analyses indicating the presence of a previously undescribed nuclear receptor family within medusozoan cnidarians, that we propose to call NR3E. This family predates the diversification of ERR/ER/SR in bilaterians, indicating that the first NR3 evolved in the common ancestor of the placozoan and cnidarian-bilaterian with lineage-specific loss in the anthozoans, even though multiple species in this lineage have been shown to produce aromatic steroids, whose function remain unclear. We discovered serendipitously that a cytoplasmic factor within epidermal cells of transgenic Hydra vulgaris can trigger the nuclear translocation of heterologously expressed human ERα. This led us to hypothesize that aromatic steroids may also be present in the medusozoan cnidarian lineage, which includes Hydra, and may explain the translocation of human ERα. Docking experiments with paraestrol A, a cnidarian A-ring aromatic steroid, into the ligand-binding pocket of Hydra NR3E indicates that, if an aromatic steroid is indeed the true ligand, which remains to be demonstrated, it would bind to the pocket through a partially distinct mechanism from the manner in which estradiol binds to vertebrate ER.


Nevirapine nanosuspensions for HIV reservoir targeting.
In this paper we discuss, production, characterization and in-vivo evaluation of nevirapine nanosuspensions. Laser diffraction showed that the average particles size was 457 nm. Following single-dose administration, the plasma gamma concentration profiles showed fast release. Macrophage uptake studies confirmed enhanced cellular uptake for nanonized nevirapine with no added cytotoxicity. Gamma scintigraphy showed that the nanosuspension prepared can be used to target spleen, thymus and lungs, which represent anatomical viral reservoirs. Thus nevirapine nanosuspensions with targeting potential have been prepared successfully.


Expression of mismatch repair proteins in urothelial carcinoma of the urinary bladder.
Urothelial carcinoma of the urinary bladder (UCUB) is a frequently diagnosed malignancy. Mismatch repair (MMR), a proofreading machinery of the DNA, prevents tumorigenesis. The role of MMR deficiency in UCUB in eastern Indian population is not known. Immunohistochemistry panel for MLH1, PMS2, MSH2, and MSH6 (MMR proteins) was performed on the biopsy specimens of UCUB (N=100). MMR deficiency by immunohistochemistry was demonstrated in two cases (2%). One case showed deficiency of MSH2 and MSH6 and the other case showed the deficiency of all four mismatch proteins. Both cases showed high-grade invasive urothelial carcinoma by histomorphology. The prevalence of MMR deficiency by immunohistochemistry is 2% in eastern Indian population.


Involvement of LIMK1/2 in actin assembly during mouse embryo development.
LIMKs (LIMK1 and LIMK2) are serine/threonine protein kinases that involve in various cellular activities such as cell migration, morphogenesis and cytokinesis. However, its roles during mammalian early embryo development are still unclear. In the present study, we disrupted LIMK1/2 activity to explore the functions of LIMK1/2 during mouse early embryo development. We found that p-LIMK1/2 mainly located at the cortex of each blastomeres from 2-cell to 8-cell stage, and p-LIMK1/2 also expressed at morula and blastocyst stage in mouse embryos. Inhibition of LIMK1/2 activity by LIMKi 3 (BMS-5) at the zygote stage caused the failure of embryo early cleavage, and the disruption of LIMK1/2 activity at 8-cell stage caused the defects of embryo compaction and blastocyst formation. Fluorescence staining and intensity analysis results demonstrated that the inhibition of LIMK1/2 activity caused aberrant cortex actin expression and the decrease of phosphorylated cofilin in mouse embryos. Taken together, we identified LIMK1/2 as an important regulator for cofilin phosphorylation and actin assembly during mouse early embryo development.


[Demonstration of a specific androgen binding protein (ABP) in the seminal plasma of the ram].
A specific androgen binding protein has been demonstrated in the seminal plasma of adult Ram. This protein binds especially to 5 alpha-DHT and testosterone and much lower to oestradiol-17 beta. Its characteristics such as Ka (in order 10(9) M(-1) at 4 degrees C), relative mobility (Rf) and its specificity are similar to those of the androgen binding protein (ABP) of the Rete Testis Fluid and the epididymal plasma of the Ram. It is probable that this protein secreted from the testis, crosses the epididymis before being secreted in the seminal plasma at the moment of the ejaculation.


What support do caregivers of elderly want? Results from the Canadian Study of Health and Aging.
The aim of this paper is to document interest in support strategies among caregivers of elderly persons. We used data from the Canadian Study of Health and Aging caregiver questionnaire which included 43 informal caregivers of elderly persons living with dementia and 145 informal caregivers of elderly persons not living with dementia. While the study assessed interest in attending support groups (10.4%), receiving telephone support from either a professional (44.9%) or a fellow caregiver (41.0%), receiving a newsletter (40.5%), receiving volunteer support (24.2%), and interest in support via computer (14.8%), there were no significant differences between the two groups with regard to interest in any of the support services. Implications for program delivery are discussed. Planners may want to consider adding telephone support and newsletters to other supports already available for caregivers.


Reciprocal associations between smoking cessation and depression in older smokers: findings from the English Longitudinal Study of Ageing.
Depression is a particular problem in older people and it is important to know how it affects and is affected by smoking cessation. To identify reciprocal, longitudinal relationships between smoking cessation and depression among older smokers. Across four waves, covering six years (2002-2008), changes in smoking status and depression, measured using the 8-item Centre for Epidemiologic Studies Depression Scale, were assessed among recent ex-smokers and smokers (n = 2375) in the English Longitudinal Study of Ageing. In latent growth curve analysis, smoking at baseline predicted depression caseness longitudinally and vice versa. When both processes were modelled concurrently, depression predicted continued smoking longitudinally (B(β) = 0.21 (0.27); 95% CI = 0.08-0.35) but not the other way round. This was the case irrespective of mental health history and adjusting for a range of covariates. In older smokers, depression appears to act as an important barrier to quitting, although quitting has no long-term impact on depression.


[Evaluation of selected parameters of specific immunity in children with osteosarcoma at various stages of antitumour treatment].
Typical cells of specific immunity are lymphocytes. T cells may specifically recognize antigens using T Cell Receptors (TCRs). Antigen presentation by specialized cells is a necessary element of specific immunity. It leads to initiating an immune response. After antigen dependent activation T cells transform to memory and effector lymphocytes. Cells engaged directly in destruction of the tumour are CD8+cytotoxic T lymphocytes, CD4+ lymphocytes, Tγδ lymphocytes, NK, NKT cells and indirectly B lymphocytes. One of the main methods of osteosarcoma treatment in children is chemotherapy. The goal is to destroy the cancer cells by putting them in a state of apoptosis. All of the medications used as chemotherapy carry the risk of short-term and long-term problems including leukopenia, immune disorders such as immunodeficiency. was evaluation by flow cytometry selected elements of specific cellular immunity in children with osteosarcoma at various stages of antitumour treatment. The study was performed on the group of 44 children with osteosarcoma, aged from 6 to 20 years (average 14.9 years; median 15.0 years). T and B lymphocytes and subpopulations: CD4+, CD8+, CD3+?HLA-DR+, CD3+γδ; NK, NKT cells were analyzed in peripheral blood with use of flow cytometry method with monoclonal antibodies. Examinations were performed before the therapy - in diagnostic period (examination I), after the neoadjuvant chemotherapy (examination II), 10-14 days after the surgery (examination III), 5 months after the surgery (after adjuvant chemotherapy, examination IV). The number of T and B lymphocytes was decreasing after each stage of cytostatic therapy, with the biggest differences for CD19+ cells (medians: I examination - 205.0; II exam. - 62.0; IV exam. - 24.0 cells/mL); in single cases the number of cells decreased even under 10/mL (norm 200-500 cells/mL). 1. In children and youth with osteosarcoma antineoplastic treatment contributes to the suppression of the immune system, decreasing definitely the number and percentage of B lymphocytes, T helper lymphocytes and NK cells. 2. Decreased number of CD3+, CD4+, CD19+ and NK lymphocytes during chemotherapy may contribute to the progression of neoplastic disease in the future, after treatment. 3. Evaluation of immunologic status in patients with osteosarcoma may be helpful in monitoring of antineoplastic therapy effectiveness, may prevent the formation of unfavourable clinical changes and may be the basis for correction of the cytostatic agents' administration.


Phylogenetic Analysis of Wild Species and the Maternal Origin of Cultivars in the Genus Lilium Using 114 Plastid Genomes.
Lilies are one of the most important ornamental flowers worldwide with approximately 100 wild species and numerous cultivars, but the phylogenetic relationships among wild species and their contributions to these cultivars are poorly resolved. We collected the major Lilium species and cultivars and assembled their plastome sequences. Our phylogenetic reconstruction using 114 plastid genomes, including 70 wild species representing all sections and 42 cultivars representing six hybrid divisions and two outgroups, uncovered well-supported genetic relationships within Lilium. The wild species were separated into two distinct groups (groups A and B) associated with geographical distribution, which further diversified into eight different clades that were phylogenetically well supported. Additional support was provided by the distributions of indels and single-nucleotide variants, which were consistent with the topology. The species of sections Archelirion, Sinomartagon III, and Leucolirion 6a and 6b were the maternal donors for Oriental hybrids, Asiatic hybrids, Trumpet hybrids, and Longiflorum hybrids, respectively. The maternal donors of the OT hybrids originated from the two sections Archelirion and Leucolirion 6a, and LA hybrids were derived from the two sections Leucolirion 6b and Sinomartagon. Our study provides an important basis for clarifying the infrageneric classification and the maternal origin of cultivars in Lilium.


Excellent Electrocatalytic Hydrogen Evolution Reaction Performances of Partially Graphitized Activated-Carbon Nanobundles Derived from Biomass Human Hair Wastes.
Carbonaceous materials play a vital role as an appropriate catalyst for electrocatalytic hydrogen production. Aiming at realizing the highly efficient hydrogen evolution reaction (HER), the partially graphitized activated-carbon nanobundles were synthesized as a high-performance HER electrocatalyst by using biomass human hair ashes through the high-temperature KOH activation at two different temperatures of 600 and 700 °C. Due to the partial graphitization, the 700 °C KOH-activated partially graphitized activated-carbon nanobundles exhibited higher electrical conductivity as well as higher textural porosity than those of the amorphous activated-carbon nanobundles that had been prepared by the KOH activation at 600 °C. As a consequence, the 700 °C-activated partially graphitized activated-carbon nanobundles showed the extraordinarily high HER activity with the very low overpotential (≈16 mV at 10 mA/cm2 in 0.5 M H2SO4) and the small Tafel slope (≈51 mV/dec). These results suggest that the human hair-derived partially graphitized activated-carbon nanobundles can be effectively utilized as a high-performance HER electrocatalyst in future hydrogen-energy technology.


Caries removal with Er:YAG laser followed by dentin biomodification with carbodiimide and chitosan: Wettability and surface morphology analysis.
This study aimed to investigate dentin wettability and surface morphology after selective removal of carious lesion by erbium-doped yttrium aluminum garnet (Er:YAG) laser, followed by dentin biomodification with carbodiimide (EDC) and chitosan (CHI). Seventy-eight bovine dentin specimens were submitted to caries induction. Specimens were distributed according to methods of carious removal (n = 39): bur at low-speed (40,000 rpm) or Er:YAG laser (noncontact mode, 250 mJ/pulse and 4Hz). All specimens were etched with 35% phosphoric acid, and subdivided according to dentin biomodification (n = 13): Control (no biomodification), EDC or CHI. The contact angle (n = 10) between adhesive system (3M ESPE) and dentin surface was measured by a goniometer. Eighteen specimens (n = 3) were analyzed by scanning electron microscopy. Data were analyzed by two-way ANOVA and Tukey's test (α = .05). The method used to remove carious lesion did not influence the wettability of dentinal surface (p = .748). The angles produced on the remaining dentin after biomodification were influenced (p = .007). CHI promoted higher contact angles (p = .007) and EDC did not differ from the control group (p = .586). In the bur-treated group, most tubules were open, regardless of which biomodifier was used. Laser modified the organic matrix layer. CHI promoted partially closed tubules in some areas while EDC exposed dentinal tubules. Regardless of which method was used for selective removal of carious lesion, biomodification with EDC did not affect the dentin wettability, whereas CHI changed the wettability of remaining dentin. Both biomodifiers promoted a slight change on dentin morphology.


Amantadine treatment of psychotropic-induced weight gain in children and adolescents: case series.
The purpose of this study was to explore whether amantadine would slow or reverse significant weight gain in children and adolescents treated with antipsychotics and/or mood stabilizers that may promote increases in weight. Eight boys and one girl ages 9-16 years and their parents consented to an open trial of amantadine 100 mg po bid or tid for weight gain in children. Side effects and body mass index were determined at baseline and during amantadine treatment. A mean weight gain of 10.5 kg (19.9% mean increase in body weight) occurred from baseline to the beginning of amantadine treatment. Amantadine trial length averaged 14.5 weeks (range 4-33 weeks). A planned comparison using repeated measures analysis of variance demonstrated strong support for a "slowing weight gain" mechanism (p = 0.001) for weight gain and body mass. Weight loss was strongly correlated with length of amantadine treatment (p = < 0.05). One child experienced orthostatic hypotension with concomitant stimulant medication. No other side effects or exacerbation of psychiatric symptoms was reported. Amantadine appears to stabilize weight gain related to psychotropic medications. Decreased weight and body mass index may occur with continued amantadine usage. Controlled trials of amantadine in children and adolescents taking weight-gain-inducing psychotropics are warranted.


Molecular Characterization of Chitin Synthase Gene in Tetranychus cinnabarinus (Boisduval) and Its Response to Sublethal Concentrations of an Insecticide.
The carmine spider mite, Tetranychus cinnabarinus (Boisduval), is one of the most important acarine pest species. At present, its control remains primarily dependent on using various chemical insecticides/acaricides in agricultural crops worldwide. To clarify the mechanism whereby T. cinnabarinus responds to insecticide exposure, we identified the chitin synthase 1 gene (TcCHS1) and then explored the gene expression levels of TcCHS1 at different developmental stages of T. cinnabarinus. We also investigated the effects of sublethal concentrations of diflubenzuron on the toxicities and survivals of T. cinnabarinus eggs and larvae as well as TcCHS1 expression levels. The full-length cDNA sequence contains an open reading frame (ORF) of 4881 nucleotides that encoded for a 1474 amino acid residues protein. The predicted TcCHS1 protein had a molecular mass of 168.35 kDa and an isoelectric point of 6.26, and its amino acid sequence contained all the signature motifs (EDR, QRRRW and TWGTR) of chitin synthases. The results of phylogenetic analyses demonstrated that the putative CHS1 amino acid sequence of T. cinnabarinus revealed high similarities with chitin synthases in other insects and mites. Additionally, at the molecular level, transcriptional analysis by real-time quantitative PCR in different developmental stages of T. cinnabarinus revealed that TcCHS1 mRNA was expressed in all stages, and highest in eggs and female adults, but lowest in deutonymphs. Furthermore, the results of toxicity bioassays indicated that diflubenzuron treatment resulted in high mortality rates in eggs and larvae of T. cinnabarinus. The mRNA expression levels of TcCHS1 from the eggs and larvae of T. cinnabarinus were up-regulated in response to sublethal concentrations of diflubenzuron exposures. Together, all these results demonstrate that diflubenzuron has ovicidal and larvicidal effects and TcCHS1 may play an important role in the growth and development of T. cinnabarinus and may disrupt the chitin biosynthesis, thereby controlling T. cinnabarinus populations.


Magnetic structure of CeRhIn(5) under magnetic field.
The magnetically ordered ground state of CeRhIn(5) at ambient pressure and zero magnetic field is an incommensurate helicoidal phase with the propagation vector k = (1/2,1/2,0.298) and the magnetic moment in the basal plane of the tetragonal structure. We determined by neutron diffraction the two different magnetically ordered phases of CeRhIn(5) evidenced by bulk measurements under applied magnetic field in the basal plane. The low temperature high magnetic phase corresponds to a commensurate sine-wave structure of the magnetization with k = (1/2,1/2,1/4). At high temperature, the phase is incommensurate with k = (1/2,1/2,0.298) and a possible small ellipticity. The propagation vector of this phase is the same as that of the zero-field structure.


[Rehabilitation of the olfactory sense after laryngectomy -- the larynx bypass].
Patients after laryngectomy lose their previous sense of smell, since air normally circulates via the tracheostoma and active air intake through the nose is no longer possible. The larynx bypass with a throat mask is an aid here. Nasal air circulation is made possible by this connecting piece between the mouth and tracheostoma. Twenty patients (17 men and 3 women, mean age 60 years) who underwent laryngectomy between November 2003 and February 2004 were examined using Sniffin' Sticks with and without the larynx bypass. Moreover, patients were asked about the practicability of the larynx bypass using a visual analog scale (VAS). In addition to larynx bypass function, we were also interested in the handling for the laryngectomized patients. Overall, patients were able to correctly identify more items with the larynx bypass. The results were significantly better with than without the larynx bypass (p < 0.001). However, the first application of the larynx bypass was considered cumbersome. The median VAS was 5. Patients had a better sense of smell with the larynx bypass. However, due to its rather moderate practicability, the larynx bypass does not seem to be suited for daily use in its present form.


The impact of hypodontia: a qualitative study on the experiences of patients.
Congenital absence of teeth affects 2-6 per cent of the population, but its impact on quality of life (QoL) is not fully understood. The symptoms of hypodontia can vary and therefore also the treatment and management of this condition. Determining and understanding the possible impact of hypodontia on patients could inform and improve the management of such patients. A purposive sample of 10 participants aged 16-25 years (five males and five females) with mild, moderate, or severe hypodontia at various stages of treatment was recruited. The participants had previously completed a 49-item Oral Health Impact Profile (OHIP) questionnaire with summary scores ranging from 24 to 143. All subjects participated in semi-structured interviews, and these were transcribed and analysed using NVivo software. The results show that the role of hypodontia patients in the treatment decision-making process changes significantly as they move from childhood to adulthood. Participants indicated dissatisfaction with the lack of communication with dental services throughout early adolescence as they became more cognizant of their condition which in turn led to concerns with regard to appearance which impacted on their psychosocial well-being. Hypodontia patients expect improved communication with dental practitioners and services as they become more cognizant of their condition and wish to become more actively involved in the decision-making process regarding their current and future treatment.


HIV: new drugs, new guidelines.
This review discusses recent changes in HIV treatment guidelines, focussing on the optimal time for starting antiretroviral therapy (ART) in chronic asymptomatic infection, and treatment options for ART-naïve patients. Understanding of HIV pathogenesis has progressed significantly, with a growing appreciation of the role of HIV replication in causing inflammation and promoting both AIDS and non-AIDS diseases. Early suppression of HIV replication with ART benefits the individual, and by reducing transmission and promoting engagement with care also brings public health benefits. For years, efavirenz-based ART was favoured by treatment guidelines, reflecting unsurpassed performance in clinical trials. New treatment options show high efficacy and safety and include single-tablet coformulations for once-daily dosing to improve convenience. Recent data have demonstrated superiority over efavirenz of regimens based on rilpivirine in patients with low pre-ART HIV-1 RNA load and raltegravir or dolutegravir regardless of the viral load. Some guidelines now recommend starting ART regardless of CD4 cell counts, whereas others take a more cautious approach pending results from studies that are testing the clinical benefit of early therapy. New treatment options allow therapy to be tailored to the patient's circumstances and are suitable for early ART initiation.


Multiple adenomas of the human pituitary. A retrospective autopsy study with clinical implications.
In a review of autopsy material from two centers, 20 pituitary glands were found containing multiple adenomas. In total, 44 adenomas were identified histologically; 16 glands contained double tumors and in four glands triple adenomas were found. Size was measured in 30 tumors, all of which were microadenomas. Thirty-four adenomas were located in the lateral wings and 10 lay in the median wedge. Forty-one tumors were chromophobic and three were basophilic. Immunocytochemical analysis of the 44 tumors demonstrated the presence of prolactin in 11, adrenocorticotropic hormone in three, growth hormone in one, and alpha-subunit as well as follicle-stimulating hormone and luteinizing hormone in one. Of the 20 patients studied, there were 11 men and nine women, with an average age of 69 years. All patients died from various nonendocrine causes. With the exception of one patient who appeared mildly acromegalic, no correlation was observed between pituitary morphology and clinical data. This study found a 10.4% frequency of adenomas in pituitaries studied randomly at autopsy. Multiple tumors were encountered in 0.9% of cases. Despite its low frequency, adenoma multiplicity may underlie surgical failure in cases in which one adenoma is removed and the other is left behind.


[Passive immunotherapy with Venimmun for the prevention of habitual abortion--early pregnancy factor, placenta protein 12, placenta protein 14, tumor necrosis factor alpha--parameters for monitoring immunotherapy].
In a study it was investigated to what extent the early pregnancy factor, the placental proteins 12 and 14 and tumor necrosis factor alpha are suited to control and select patients with habitual abortions for immunotherapy. Immunotherapy shows good clinical results. Placental protein 12 ist not suited for selecting patients. Placental protein 14 shows typical changes after the application of polyvalent immunoglobulin and could be an important prognostic factor. Tumor necrosis factor alpha seems to be useful for selecting patients for immunotherapy, because in cases of habitual abortions this factor can be a sign for immunological causes. In the late phase of pregnancy, early pregnancy factor is also an indicator for disturbances of pregnancy.


Effect of a triaxial nuclear shape on proton tunneling: the decay and structure of 145Tm.
Gamma rays deexciting states in the proton emitter 145Tm were observed using the recoil-decay tagging method. The 145Tm ground-state rotational band was found to exhibit the properties expected for an h{11/2} proton decoupled band. In addition, coincidences between protons feeding the 2{+} state in 144Er and the 2{+}-->0{+} gamma-ray transition were detected, the first measurement of this kind, leading to a more precise value for the 2{+} excitation energy of 329(1) keV. Calculations with the particle-rotor model and the core quasiparticle coupling model indicate that the properties of the pi{11/2} band and the proton-decay rates in 145Tm are consistent with the presence of triaxiality with an asymmetry parameter gamma approximately 20 degrees .


Glycosylation and cell surface expression of Kv1.2 potassium channel are regulated by determinants in the pore region.
Voltage-gated K(+) channels contain six membrane spanning segments and a pore-forming domain. We used site-directed mutation to examine the role of specific amino acids in the extracellular region of the pore in Kv1.2. When expressed in CHO cells, a K(+) current was not observed for mutants S356A, S360A, T383A and T384A. However, coexpression of the Kvbeta2 subunit and the S360A mutant resulted in a robust peak current. Immunocytochemistry for Kv1.2 showed staining throughout the cytoplasm in cells coexpressing the beta2 and S360A, whereas only the perinuclear region was stained in cells expressing the S360A mutant. Western blotting revealed that the major immunoreactive protein in wild-type- and mutant-expressing cells is 60-kDa, but 87-kDa bands were also detected in cells expressing wild-type Kv1.2 and cells coexpressing beta2and S360A. These results suggest that amino acids in the pore region help regulate ion permeability or cellular trafficking by affecting glycosylation of Kv1.2.


Genome Editing for Sustainable Crop Improvement and Mitigation of Biotic and Abiotic Stresses.
Climate change poses a serious threat to global agricultural activity and food production. Plant genome editing technologies have been widely used to develop crop varieties with superior qualities or can tolerate adverse environmental conditions. Unlike conventional breeding techniques (e.g., selective breeding and mutation breeding), modern genome editing tools offer more targeted and specific alterations of the plant genome and could significantly speed up the progress of developing crops with desired traits, such as higher yield and/or stronger resilience to the changing environment. In this review, we discuss the current development and future applications of genome editing technologies in mitigating the impacts of biotic and abiotic stresses on agriculture. We focus specifically on the CRISPR/Cas system, which has been the center of attention in the last few years as a revolutionary genome-editing tool in various species. We also conducted a bibliographic analysis on CRISPR-related papers published from 2012 to 2021 (10 years) to identify trends and potential in the CRISPR/Cas-related plant research. In addition, this review article outlines the current shortcomings and challenges of employing genome editing technologies in agriculture with notes on future prospective. We believe combining conventional and more innovative technologies in agriculture would be the key to optimizing crop improvement beyond the limitations of traditional agricultural practices.


"Your Health Care--Be Involved": the evaluation of a provincial patient afety tips initiative.
When patients take an active role in their healthcare, the results may be better, safer care. That is the premise behind the Ontario Hospital Association's (OHA) "Your Health Care--Be Involved" campaign. Launched in September 2005 by the OHA's Patient Safety Support Service, the campaign encourages active two-way communication between patients and providers and highlights the important role of patient involvement in the form of five patient safety tips. This article discusses the development, implementation and evaluation of Ontario's first-ever patient safety tips program, and what its future might hold.


[Drug monitoring of antipsychotics and antidepressants during acute admission in a psychiatric state hospital in Germany].
In the treatment of affective and schizophrenic psychosis, modern atypical antipsychotic agents and newer antidepressive agents recently have increasingly been used. In this prospective naturalistic study, patients were examined who had previously been treated psychopharmaceutically for a schizophrenic (n = 52) or depressive (n = 38) disorder and were readmitted in a psychiatric emergency clinic. While Serum levels were examined major interest was to find out similarities or differences in the drug compliance of schizophrenic and depressive patients before rehospitalization.


Development and validation of a clinical instrument to predict risk of an adverse drug reactions in hospitalized patients.
Development and internal validation of a clinical tool for assessment of the risk of adverse drug reactions (ADR) in hospitalized patients. Nested case-control study in an open cohort of all patients admitted to a general hospital. Cases of ADR were matched to two controls. Eighty four patient variables collected at the time of the ADR were analyzed by conditional logistic regression. Multivariate logistic regression with clustering of cases in a random sample of 2/3 of the cases and respective controls, with baseline odds-ratio corrected with an estimate of ADR incidence, was used to obtain regression coefficients for each risk factor and to develop a risk score. The clinical tool was validated in the remaining 1/3 observations. The study was approved by the institution's research ethics committee. In the 8060 hospitalized patients, ADR occurred in 343 (5.31%), who were matched to 686 controls. Fourteen variables were identified as independent risk factors of ADR: female, past history of ADR, heart rate ≥72 bpm, systolic blood pressure≥148 mmHg, diastolic blood pressure <79 mmHg, diabetes mellitus, serum urea ≥ 67 mg/dL, serum sodium ≥141 mmol/L, serum potassium ≥4.9 mmol/L, main diagnosis of neoplasia, prescription of ≥3 ATC class B drugs, prescription of ATC class R drugs, prescription of intravenous drugs and ≥ 6 oral drugs. In the validation sample, the ADR risk tool based on those variables showed sensitivity 61%, specificity 73% and area under the ROC curve 0.73. We report a clinical tool for ADR risk stratification in patients hospitalized in general wards based on 14 variables.


Tail feather strength in tail-assisted climbing birds is achieved through geometric, not material change.
Birds encompass vast ecomorphological diversity and practise numerous distinct locomotor modes. One oft-cited feature seen in climbing birds is an increase in tail 'stiffness', yet it remains unclear to what extent these feathers are altered, and the specific mechanism by which differences in functional performance are attained. We collected a broad taxonomic sample of tail feathers (6525 total, from 774 species representing 21 avian orders and ranging in size from approximately 3 g to greater than 11 kg) and present data on their material properties, cross-sectional geometry and morphometrics. Ordinary and phylogenetic least-squares regressions of each variable versus body mass were conducted to assess scaling relationships and demonstrate that tail-supported climbers exhibit longer tail feathers with a wider rachis base and tip, and a greater second moment of area and maximum bending moment. However, no differences were observed in the material properties of the keratin itself. This suggests that tail-supported arboreal climbing birds of multiple orders have independently adopted similar morphologies. Moreover, these geometric relationships follow the same allometric scaling relationships as seen in the long bones of mammalian limbs, suggesting that the morphology of these developmentally and evolutionarily distinct structures are governed by similar functional constraints of weight support.


Ototoxic destruction by co-administration of kanamycin and ethacrynic acid in rats.
It is well known that ethacrynic acid (EA) can potentiate the ototoxicity of aminoglycoside antibiotics (AmAn) such as kanamycin (KM), if they were applied at the same time. Currently, to create the model of EA-KM-induced cochlear lesion in rats, adult rats received a single injection of EA (75 mg/kg, intravenous injection), or followed immediately by KM (500 mg/kg, intramuscular injection). The hearing function was assessed by auditory brainstem response (ABR) measurement in response to click and/or tone bursts at 4, 8, 12, 16, 20, 24, and 32 kHz. The static microcirculation status in the stria vascularis after a single EA injection was evaluated with eosin staining. The pathological changes in cochlear and vestibular hair cells were also quantified after co-administration of EA and KM. After a single EA injection, blood flow in vessels supplying the stria vascularis rapidly diminished. However, the blood supply to the cochlear lateral wall partially recovered 5 h after EA treatment. Threshold changes in ABR were basically parallel to the microcirculation changes in stria vascularis after single EA treatment. Importantly, disposable co-administration of EA and KM resulted in a permanent hearing loss and severe damage to the cochlear hair cells, but spared the vestibular hair cells. Since the cochlear lateral wall is the important part of the blood-cochlea barrier, EA-induced anoxic damage to the epithelium of stria vascularis may enhance the entry of KM to the cochlea. Thus, experimental animal model of selective cochlear damage with normal vestibular systems can be reliably created through co-administration of EA and KM.


Paraplegia due to recurrent multiple hydatid cyst of the spine: a case report.
Recurrence after surgical treatment of hydatid cyst of the spine is extremely common. Preexisting fibrosis, fragility of the cyst wall, confluent cysts and proximity to vital structures makes radical excision difficult and repeated recurrences are inevitable. This case report describes a recurrent hydatid cyst presenting as three separate cysts in the dorsal spine in a middle-aged male. The extradural cyst caused paraplegia. The extraspinal cyst presented as an extrapleural mass in relation with the eighth, ninth and the tenth ribs near the costo-vertebral junction. The three cysts were resected en masse. Complete neurological recovery occurred with no recurrence at four years follow-up. Resection of the hydatid cyst en masse offers the best chance of cure and must be attempted in all cases. A prolonged chemotherapy should be administered in all cases.


Flower development.
Flowers are the most complex structures of plants. Studies of Arabidopsis thaliana, which has typical eudicot flowers, have been fundamental in advancing the structural and molecular understanding of flower development. The main processes and stages of Arabidopsis flower development are summarized to provide a framework in which to interpret the detailed molecular genetic studies of genes assigned functions during flower development and is extended to recent genomics studies uncovering the key regulatory modules involved. Computational models have been used to study the concerted action and dynamics of the gene regulatory module that underlies patterning of the Arabidopsis inflorescence meristem and specification of the primordial cell types during early stages of flower development. This includes the gene combinations that specify sepal, petal, stamen and carpel identity, and genes that interact with them. As a dynamic gene regulatory network this module has been shown to converge to stable multigenic profiles that depend upon the overall network topology and are thus robust, which can explain the canalization of flower organ determination and the overall conservation of the basic flower plan among eudicots. Comparative and evolutionary approaches derived from Arabidopsis studies pave the way to studying the molecular basis of diverse floral morphologies.


Development of self-recognition, personal pronoun use, and pretend play during the 2nd year.
This study examined the relation of visual self-recognition to personal pronoun use and pretend play. For a longitudinal sample (N=66) at the ages when self-recognition was emerging (15, 18, and 21 months), self-recognition was related to personal pronoun use and pretend play such that children showing self-recognition used more personal pronouns and demonstrated more advanced pretend play than did children not showing self-recognition. The finding of a relation among these measures provides additional evidence that in the middle of the 2nd year of life a metarepresentation of self emerges in the human child.


Safety and efficacy of erythropoietin in traumatic brain injury patients: a pilot randomized trial.
Background. Erythropoietin (EPO) is a neuroprotective agent utilized in stroke patients. This pilot study represents the first randomized trial of EPO in traumatic brain injury (TBI) patients. Methods. Adult, blunt trauma patients with evidence of TBI were randomized to EPO or placebo within 6 hours of injury. Baseline and daily serum S-100B and Neuron Specific Enolase (NSE) levels were measured. Results. TBI was worse in the EPO (n = 11) group compared to placebo patients (n = 5). The use of EPO did not impact NSE (P = .89) or S100 B (P = .53) levels compared to placebo. Conclusions. At the dose used, EPO did not reduce neuronal cell death compared to placebo; however, TBI severity was worse in the EPO group while levels of NSE and S100-B were similar to the less injured placebo group making it difficult to rule out a treatment effect. A larger, balanced study is necessary to confirm a potential treatment effect.


Low Frequency Of Regulatory B-Cells And Increased CD4+ and CD8+ Interferon-γ-producing cells in patients with tropical spastic paraparesis associated with human T-cell lymphotropic virus type.
Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown. The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects. Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in healthy control subjects. The low percentage of Breg cells in patients and the increase in the frequency of Th1 cells suggest an imbalance in the control of the inflammatory response that contributes to the immunopathogenesis of TSP/HAM.


Reporter mice for the study of long-term effects of drugs and toxic compounds.
Noninvasive, imaging-based methodologies provide for the first time the possibility to spatio-temporally investigate physiopathological events and long-term effects of drug administration of exposure to environmental and alimentary toxic compounds. Hence, this novel methodology could enable us to measure the dynamics of specific molecular pathways in live animals. In the last few years, animals, particularly mice, were genetically modified to respond to a specific stimulus with the production of proteins, named "reporters," that are easily detected and quantitated by in vivo and ex vivo imaging. These "reporter mice" are gradually being applied to the pharmaco-toxicological research. In the generation of a reporter mouse useful for pharmaco-toxicological studies several elements need to be considered in the selection of the reporter system: the half-life of proteins should be compatible with the necessities of the study to assess the onset and the termination of the stimulus of interest, in all tissues the response should be proportional to the given stimulus, and the imaging modalities requested for reporter measurements should be applicable to high-throughput screening. Bioluminescence-based imaging (BLI) in small animals has the advantage over other modalities that does not require too sophisticated equipment or specifically and highly trained personnel, and furthermore may be carried out at a relative rapidity and low cost; for these reasons several luciferases have been developed for in vivo imaging applications and used in the generation of reporter mice. We here describe a BLI-based reporter mouse created to respond to estrogenic stimuli, which has been applied to the study of female physiopathology as well as for the identification of the effects of selective drugs or toxic compounds present in the environment and in the alimentary chain.


Neuroprotection against 1-Methyl-4-phenylpyridinium-induced cytotoxicity by naturally occurring polydatin through activation of transcription factor MEF2D.
Polydatin is the major active ingredient of Polygonum cuspidatum Sieb. Et Zucc. A recent study indicated that polydatin could protect against substantia nigra dopaminergic degeneration in rodent models associated with Parkinson's disease. However, mechanisms that underlie the neuroprotection of polydatin have not been fully elucidated. In the current study, the neuroprotective effects and detailed mechanisms of action of polydatin were investigated in Parkinson's disease-related cellular models. Polydatin dose- and time-dependently prevented neurotoxicity caused by 1-methyl-4-phenylpyridinium ion (MPP+) in primary cerebellar granule neurons. Moreover, we found that polydatin enhanced the activity of the transcription factor myocyte enhancer factor 2D (MEF2D) at both basal and pathological conditions using luciferase reporter gene assay. Additionally, western blot analysis revealed that polydatin could downregulate glycogen synthase kinase 3β (GSK3β), which is a negative regulator of MEF2D. Molecular docking simulations finally suggested an interaction between polydatin and a hydrophobic pocket within GSK3β. All these results suggest that polydatin prevents MPP+-induced neurotoxicity via enhancing MEF2D through the inhibition of GSK3β and that treatment with polydatin is worthy of further anti-Parkinson's disease study in future.


Gender differences in empathy and clinical symptoms in chronic schizophrenia patients: a large sample study based on a Chinese Han population.
Empathy is social cognition and reduced empathy in schizophrenia (SCZ) has been noted; however, whether there are gender differences in empathy remains unclear. Therefore, the purpose of this study was to explore this issue by examining a large sample of the population with SCZ. We recruited 987 SCZ patients (M/F = 638/349). The empathy was assessed by The Interpersonal Reactivity Index (IRI). The Positive and Negative Syndrome Scale (PANSS) was adopted to assess their clinical psychiatric symptoms and their ability to recognise the facial emotions of others was assessed by the Pictures Of Facial Affect (POFA). Female SCZ patients had higher IRI total score than male patients. In male patients, Pearson correlation analysis showed that empathy was negatively correlated with PANSS total score and negative symptom subscale scores, but positively correlated with anger identification. In female patients, IRI total score was negatively correlated with PANSS total score as well as its positive and negative symptom subscale scores (all p < 0.05). There are gender differences in the empathy of SCZ patients, with female patients having greater empathy and a correlation with their clinical symptoms. This gender difference may provide potential clinical value for the treatment of SCZ.KEY POINTSFemale SCZ were more likely to empathise than males;Female patients had more severe clinical symptoms than males;There were gender differences in the association between certain specific clinical presentations and empathy.In future studies, it may be useful to investigate gender differences in schizophrenia empathy for the diagnosis and treatment of the disorder.