Tumor bed radiotherapy in women following breast conserving surgery for breast cancer-safety margin with/without image guidance.
Image guided radiation therapy (IGRT) enables the achievement of higher precision in radiation delivery, a reduction in safety margins and a reduced risk of toxicity in healthy tissues. The present study investigated the magnitude of safety margins for the radiation boost setup on skin marks or metal clips implanted into the tumor bed during breast cancer surgery. One hundred eighty-four patients after breast conserving surgery with implanted metal clips into tumor bed were analyzed. The present study investigated the difference in safety margin required for the treatment setup on skin marks and metal clips. The skin marks were created using a positioning laser system in the treatment room. Metal clips implanted in the tumor bed were registered using IGRT with kilovoltage X-rays in orthogonal projection. Treatment setup was performed during free breathing. The safety margin corresponding to the planning target volume (PTV) was calculated from the recorded data. Calculated safety margins for the treatment setup on skin marks were 9.4, 11.1 and 11.1 mm in the anteroposterior, craniocaudal, and laterolateral directions, respectively. Corresponding safety margins with the use of IGRT and metal clips registration were 4.7, 5.1 and 5.9 mm, respectively. The safe PTV margin was 12 mm using setup on skin marks without IGRT, whereas a 6-mm margin was sufficient with the use of metal clip-based IGRT with daily online correction. IGRT has been adopted as the standard treatment method within the Oncology Centre of Multiscan and Pardubice Hospital (Pardubice, Czech Republic).


[Evaliating men's health survey results within the framework of "men's health school"].
Within the framework of "Men's Health School" 571 men were examined in 2014. The mean age of the surveyed men was 49.66+/-14.5 years. 86% (227) of the surveyed men had PSA levels from 0 to 4 ng/ml. Prostate ultrasound scan showed prostate enlargement in 37.2%+/-6.0 of men. The disturbances of libido or sexual life were registered in 45.5% (221) of the surveyed men. 58% of patients reported insufficient penile rigidity for sexual intercourse, 50% reported a sharp decrease in the amount of ejaculate, and 10% - pain during erection. Detailed medical history showed that in many patients the disease was provoked by family discord. The study findings revealed the poor condition of the male reproductive system in Kazakhstan. Resolving this problem requires considerable logistical costs, and an integrated approach to the early detection of diseases of the male reproductive system. The reproductive health of men was found to be affected by somatic, psychological and sexual health factors. At present we can say about the need for such "Men's Health School" in all regions on a regular basis, especially with the training of the primary care physicians.


Phylogenetic analysis and expression profiles of jasmonate ZIM-domain gene family provide insight into abiotic stress resistance in sunflower.
Jasmonate ZIM-domain (JAZ) proteins act as inhibitory factors of the jasmonic acid (JA) pathway, which is involved in regulating plant development and defense responses. However, there are no extensive studies available on JAZ genes in sunflower (Helianthus annuus L.). In this study, the phylogenetic analysis of 139 putative JAZ genes from eight plants demonstrated that these JAZs could be divided into five groups (Groups I-V), and the 27 sunflower JAZs (HaJAZs) were classified into these five groups. All groups contained genes from both monocotyledons and dicotyledons, indicating that the emergence of JAZ genes predates the differentiation of monocotyledons and dicotyledons. Both segmental and tandem duplications contributed greatly to this gene family's expansion in sunflower, especially in Group II. Moreover, the expression profiles of HaJAZ genes under normal conditions, hormone treatments or abiotic stresses were analyzed based on RNA-seq data. HaJAZ2 may be undergoing pseudogenization as a nonfunctional gene because it was not expressed in any tissue. Many HaJAZ genes in roots upregulated their expression when involved in responding to exogenous hormones, especially methyl-jasmonate. The abiotic stress treatments of sunflower showed that HaJAZ5, HaJAZ15, HaJAZ17, HaJAZ20, and HaJAZ21 tend to be sensitive to certain abiotic stresses. HaJAZs from different groups may share similar functions but also exercise their unique functions when responding to abiotic stresses. We speculated that this gene family was conserved in sequence but varied in its expression among duplicated HaJAZ genes, which implies that they may confer neofunctionalization in the adaptation to abiotic stresses; this work provides insight into the resistance of sunflowers and their adaptation to diverse environmental conditions.


Hospitalized child and teenager with chronic diseases: feelings about death.
Analyze the feelings of hospitalized children and adolescents with chronic diseases towards death. Qualitative research, with four children and one teenager with chronic diseases, aged between 11 and 13 years old, who were admitted at a teaching hospital in Brazil, in the period from January to March 2009. In-depth interviews were carried out using a ludic material for therapeutic purposes, named ''As a guest in the hospital". The empirical material was submitted to thematic analysis. Two mains meanings were obtained: Feelings of hospitalized children and adolescents with chronic diseases dealing with the death of the other; and children and adolescents with chronic diseases and the fear of their own deaths. Hospitalization makes children and adolescents come across the death of other sick people, arousing feelings of sadness, consternation, anxiety, making the fear of their own death become a threat. The health team needs to be attentive to the feelings of hospitalized children and adolescents facing death so that they can get the demands, minimizing fears and anguish.


MR imaging of brain maturation in normal and developmentally handicapped children.
White matter myelination was assessed in the frontal, temporal, and occipital lobes and in the internal capsule in 91 neurodevelopmentally handicapped infants on T2-weighted images (spin echo 3,000/120 ms) and compared with myelination scores from 53 normal control subjects. Clinical diagnosis was birth asphyxia (34), seizures with delays of various causes (33), congenital infections (15), and intracerebral hemorrhages (9). Myelination in the total group of patients was generally delayed. However, we found distinct differences in myelin deposition between groups. Myelination of handicapped children with seizures or with intrauterine infections was retarded most severely at all ages. Children with intracerebral hemorrhages were almost never significantly different from normals in any part of the brain, whereas children with birth asphyxia had myelination scores in between. We conclude that magnetic resonance staging of developmental processes, such as myelination, in the infants' brain helps to recognize delays at an early age.


[Nutritional support and parenteral nutrition in the oncological patient: an expert group consensus report].
Malnutrition is a frequent medical problem of cancer patients that negatively impacts their quality of life. To analyze and respond to different issues related to the nutritional management of cancer patients in the clinical setting. A multidisciplinary group of experts in Medical Oncology, Pharmacy, and Nutrition developed a list of topics related to the nutritional status of cancer patients, which were grouped into three blocks: Nutritional support; Parenteral nutrition (PN); and Home PN (HPN) in cancer patients. A literature search, which included articles published in Spanish, English, and French until February 2017, was carried out. The document was organized as a questionnaire with those questions that, according to the panel's criteria, could generate greater controversy or doubt. Of the 18 questions addressed, 9 focused on nutritional support: 5 were related to PN and 4 about HPN. Among the different recommendations, the panel emphasized that in the cancer patient, PN is indicated mainly when it is not possible to use the digestive tract and/or oral feeding and/or enteral nutrition is not sufficient or possible. Additionally, the objective of the HPN is to improve or maintain the nutritional status of a patient at home. This document seeks to lay down a set of recommendations and to identify key issues that may be useful for the nutritional management of cancer Patients.


Current status of genitourinary fistula.
From 1970-1985, 303 women with genitourinary fistulas were seen at the Mayo Clinic. The fistula formed after treatment for benign conditions in 74% of the patients and malignant conditions in 14%; in 12%, we were unable to establish the nature of the condition. Gynecologic surgery was responsible for 82% of the fistulas, obstetric procedures for 8%, various forms of irradiation for 6%, and trauma or fulguration for 4%. In the nonirradiated patient, the ideal time for operative repair was eight to 12 weeks after fistula formation or failed repair. With ureterovaginal fistulas, the patient's general condition and the degree of obstruction of the ureter influenced the time and method of repair. We used a vaginal approach for urethral fistulas and an abdominal one for ureteral repairs. Because of difficulty with adequate exposure and the proximity of the ureter, an abdominal approach was used in 20% of the patients with vesicovaginal fistulas; the remaining 80% were approached vaginally, regardless of size, number, or history of previous repairs. Ninety-two percent of the urethrovaginal fistulas were corrected on the first attempt; the four failures were managed successfully at the second attempt. Ninety-eight percent of the vesicovaginal fistulas were corrected on the first attempt when approached vaginally, and all were managed successfully when approached abdominally, regardless of the number, size, or previous operative attempts.


Focal venous hypertension as a pathophysiologic mechanism for tissue hypertrophy, port-wine stains, the Sturge-Weber syndrome, and related disorders: proof of concept with novel hypothesis for underlying etiological cause (an American Ophthalmological Society thesis).
To provide an in-depth re-examination of assumed causes of tissue hypertrophy, port-wine stains, and the Sturge-Weber, Cobb, Klippel-Trénaunay, and related syndromes to support an alternative unifying pathophysiologic mechanism of venous dysplasia producing focal venous hypertension with attendant tissue responses; to provide proof of concept with new patient data; to propose a novel etiological hypothesis for the venous dysplasia in these syndromes and find supportive evidence. Data from 20 patients with port-wine stains and corneal pachymetry readings was collected prospectively by the author in an institutional referral-based practice. The literature was searched using MEDLINE, and articles and textbooks were obtained from the bibliographies of these publications. Newly obtained dermatologic, corneal pachymetry, fundus ophthalmoscopic, ocular and orbital venous Doppler ultrasonography, and magnetic resonance imaging findings in patients with the Sturge-Weber syndrome or isolated port-wine stains, along with published data, reveal diffusely thickened tissues and neural atrophy in all areas associated with venous congestion. Contrary to traditional understanding, signs and symptoms in the Sturge-Weber and related syndromes, including both congenital and acquired port-wine stains, are shown to arise from effects of localized primary venous dysplasia or acquired venous obstruction rather than neural dysfunction, differentiating these syndromes from actual phacomatoses. Effects of focal venous hypertension are transmitted to nearby areas via compensatory collateral venous channels in the above conditions, as in the Parkes Weber syndrome. A novel underlying etiology-prenatal venous thrombo-occlusion-is proposed to be responsible for the absence of veins with persistence and enlargement of collateral circulatory pathways with data in the literature backing this offshoot hypothesis. The mechanism for isolated pathologic tissue hypertrophy in these syndromes clarifies physiologic mechanisms for exercise-induced muscle hypertrophy to occur via venous compression and increased capillary transudation.


INDEPENDENT EVOLUTION OF TERRESTRIALITY IN ATLANTIC TRUNCATELLID GASTROPODS.
Phylogenetic analysis of truncatellid gastropods using comparative anatomy and ribosomal RNA sequences shows that terrestrial truncatellids likely evolved three times independently in the Caribbean. The terrestrial subfamily Geomelaniinae, characterized in part by pallial fertilization and uniquely derived features of radula and protoconch, occurs in the Greater Antilles and Cayman Islands. Truncatellinae, with renopericardial fertilization, has several widespread amphibious species and two terrestrial species restricted to Trinidad and Barbados. The species in Barbados may be the most recent animal species to evolve full terrestriality; Barbados emerged above sea level only about one million years ago. By the mid-Cenozoic, truncatellids had traits enabling them to colonize land in appropriate tectonic settings. Parallel trends in character evolution occurred in the terrestrial lineages. In older terrestrial radiations, transitional character states would likely be lost, potentially allowing parallelism to confound phylogenetic analysis of morphological characters.


Longitudinal alcohol consumption patterns and health-related quality of life: Results from the National Epidemiologic Survey on Alcohol and Related Conditions.
Given the limited nature of the evidence concerning longitudinal alcohol consumption patterns and health-related quality of life (HrQoL), this study examined these associations. Data were from the National Epidemiologic Survey on Alcohol and Related Conditions (waves 1 and 2). Multiple linear regression was used to assess the associations between longitudinal alcohol consumption patterns (abstainers, no consumption change, decreased consumption, increased consumption, ceased consumption and initiated consumption) and HrQoL (Short-Form 12-Item Health Survey). Increased consumption over follow up was related to non-significant reductions in mental HrQoL for moderate and heavy drinkers at wave 1, whereas decreased consumption coincided with improvements in mental HrQoL for heavy drinkers at wave 1 (β for Mental Health Summary Scale and Mental Health Subscale: 0.84 and 0.91; P-values significant for both scales). Similarly, initiation of consumption among lifetime abstainers at wave 1 was associated with reductions in mental HrQoL (β for Mental Health Summary Scale, Vitality Subscale, Social Functioning Subscale and Mental Health Subscale: -1.50, -1.89, -0.86 and -1.74; P-values significant for all scales). On the other hand, cessation of consumption was accompanied by reductions in physical HrQoL (β for Physical Health Summary Scale, Physical Functioning Subscale, Role Physical Subscale, Bodily Pain Subscale and General Health Subscale: -1.29, -1.11, -1.35, -0.87 and -0.88; P-values significant for all scales). Increased or decreased consumption were inversely associated with mental HrQoL, but decreased consumption was also associated with reductions in physical HrQoL. These findings were confirmed by the ceased consumption and initiated consumption patterns. [Imtiaz S, Loheswaran G, Le Foll B, Rehm J. Longitudinal alcohol consumption patterns and health-related quality of life: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Drug Alcohol Rev 2018;37:48-55].


Extraoral root lengthening with titanium screws.
The aim of the present study was to experimentally evaluate marginal and periapical healing in extracted and subsequently replanted teeth following extraoral cementing of apically exposed titanium root screws in the root canal. In 5 out of 6 replanted teeth, the periodontal tissues had healed with a normal periodontal membrane or healed surface resorptions indicating that only minor trauma had been inflicted during the extraoral procedure. In 3 out of 6 teeth, total or partial osseointegration of the titanium screws was seen, while a connective tissue capsule had formed around the remaining 3 screws. It was concluded that both of the healing results described in the present study, osseointegration and connective capsule formation, may be regarded as acceptable as long as inflammation is prevented, although it remains to be shown which one represents the end-point.


The Arabidopsis AtSTE24 is a CAAX protease with broad substrate specificity.
Following prenylation, the proteins are subject to two prenyl-dependent modifications at their C-terminal end, which are required for their subcellular targeting. First, the three C-terminal residues of the CAAX box prenylation signaling motif are removed, which is followed by methylation of the free carboxyl group of the prenyl cysteine moiety. An Arabidopsis homologue of the yeast CAAX protease STE24 (AFC1) was cloned and expressed in rce1 Delta ste24 Delta mutant yeast to demonstrate functional complementation. The petunia calmodulin CaM53 is a prenylated protein terminating in a CTIL CAAX box. Coupled methylation proteolysis assays demonstrated the processing of CaM53 by AtSTE24. In addition, AtSTE24 promoted plasma membrane association of the GFP-Rac fusion protein, which terminates with a CLLM CAAX box. Interestingly, a plant homologue of the second and major CAAX protease in yeast and animal cells, RCE1, was not identified despite the availability of vast amounts of sequence data. Taken together, these data suggest that AtSTE24 may process several prenylated proteins in plant cells, unlike its yeast homologue, which processes only a-mating factor, and its mammalian homologue, for which prenyl-CAAX substrates have not been established. Transient expression of GFPAtSTE24 in leaf epidermal cells of Nicotiana benthamiana showed that AtSTE24 is exclusively localized in the endoplasmic reticulum, suggesting that prenylated proteins in plants are first targeted to the endoplasmic reticulum following their prenylation.


Verification of a Many-Ion Simulator of the Dicke Model Through Slow Quenches across a Phase Transition.
We use a self-assembled two-dimensional Coulomb crystal of ∼70 ions in the presence of an external transverse field to engineer a simulator of the Dicke Hamiltonian, an iconic model in quantum optics which features a quantum phase transition between a superradiant (ferromagnetic) and a normal (paramagnetic) phase. We experimentally implement slow quenches across the quantum critical point and benchmark the dynamics and the performance of the simulator through extensive theory-experiment comparisons which show excellent agreement. The implementation of the Dicke model in fully controllable trapped ion arrays can open a path for the generation of highly entangled states useful for enhanced metrology and the observation of scrambling and quantum chaos in a many-body system.


Treatment of hydrocarbon contamination under flow through conditions by using magnetite catalyzed chemical oxidation.
Soil pollution by hydrocarbons (aromatic and aliphatic hydrocarbons) is a major environmental issue. Various treatments have been used to remove them from contaminated soils. In our previous studies, the ability of magnetite has been successfully explored to catalyze chemical oxidation for hydrocarbon remediation in batch slurry system. In the present laboratory study, column experiments were performed to evaluate the efficiency of magnetite catalyzed Fenton-like (FL) and activated persulfate (AP) oxidation for hydrocarbon degradation. Flow-through column experiments are intended to provide a better representation of field conditions. Organic extracts isolated from three different soils (an oil-contaminated soil from petrochemical industrial site and two soils polluted by polycyclic aromatic hydrocarbon (PAH) originating from coking plant sites) were spiked on sand. After solvent evaporation, spiked sand was packed in column and was subjected to oxidation using magnetite as catalyst. Oxidant solution was injected at a flow rate of 0.1 mL min(-1) under water-saturated conditions. Organic analyses were performed by GC-mass spectrometry, GC-flame ionization detector, and micro-Fourier transform infrared spectroscopy. Significant abatement of both types of hydrocarbons (60-70 %) was achieved after chemical oxidation (FL and AP) of organic extracts. No significant by-products were formed during oxidation experiment, underscoring the complete degradation of hydrocarbons. No selective degradation was observed for FL with almost similar efficiency towards all hydrocarbons. However, AP showed less reactivity towards higher molecular weight PAHs and aromatic oxygenated compounds. Results of this study demonstrated that magnetite-catalyzed chemical oxidation can effectively degrade both aromatic and aliphatic hydrocarbons (enhanced available contaminants) under flow-through conditions.


Nucleotide sequence of the Salmonella typhimurium metR gene and the metR-metE control region.
The nucleotide sequence of the Salmonella typhimurium metR gene and the metR-metE control region is presented. The metR gene codes for a polypeptide of 276 amino acids with a calculated Mr of 30,991. The metR gene product produced in a minicell system was found to migrate with an apparent Mr of 34,000. The transcription start sites for the metR and metE genes were determined by mung bean nuclease mapping. The metR and metE genes are divergently transcribed, with only 25 base pairs separating the transcription start sites. The overlapping nature of the metR and metE promoters suggests that there may be common regulatory signals for the two genes.


The canary in the coalmine; bee declines as an indicator of environmental health.
Bee declines have received much attention of late, but there is considerable debate and confusion as to the extent, significance and causes of declines. In part, this reflects conflation of data for domestic honeybees, numbers of which are largely driven by economic factors, with those for wild bees, many of which have undergone marked range contractions but for the majority of which we have no good data on population size. There is no doubt that bees are subject to numerous pressures in the modern world. The abundance and diversity of flowers has declined along with availability of suitable nest sites, bees are chronically exposed to cocktails of agrochemicals, and they are simultaneously exposed to novel parasites and pathogens accidentally spread by humans. Climate change is likely to exacerbate these problems in the future, particularly for cool- climate specialists such as bumblebees. Stressors do not act in isolation; for example pesticide exposure can impair both detoxification mechanisms and immune responses, rendering bees more susceptible to parasites. It seems certain that chronic exposure to multiple, interacting stressors is driving honeybee colony losses and declines of wild pollinators. Bees have a high profile and so their travails attract attention, but these same stressors undoubtedly bear upon other wild organisms, many of which are not monitored and have few champions. Those wild insects for which we do have population data (notably butterflies and moths) are overwhelmingly also in decline. We argue that bee declines are indicators of pervasive and ongoing environmental damage that is likely to impact broadly on biodiversity and the ecosystem services it provides.


Mucous glands in the middle ear - what is known and what is not.
A review of acquired and lacking knowledge on mucous glands in the human middle ear is presented. Investigations on whole-mount and section preparations from fetuses, prematures and infants, normal and slightly abnormal children and adults are reviewed in detail. It is concluded that mucous glands are not a normal, but a pathological component of the middle ear mucosa. Gland formation and degeneration are described. Theories on pathogenesis are discussed and new ideas for further research are indicated.


Regulation of the p53 protein by protein kinase C alpha and protein kinase C zeta.
The C-terminal of p53 (amino-acids 368-383) represses the DNA binding activity of p53. In vitro, phosphorylation of this region by Protein Kinase C (PKC) is associated with increased DNA binding activity. However, whether PKC can directly modulate p53 function in vivo is not known. Here, we demonstrate that cotransfection of p53 with either PKC alpha or PKC zeta increases p53's transcriptional activity. Mutagenesis of p53 indicates that serine 371 is the major site for phosphorylation by PKC alpha in vitro. Mutation of serine 371 caused a small decline in p53 activation by PKC alpha and PKC zeta. However, the alternatively spliced murine p53, which lacks the PKC phosphorylation sites, still demonstrated increased transcriptional activation when cotransfected with either PKC alpha or PKC zeta. The results indicate that phosphorylation of p53 by PKC in vitro does not correlate with the ability of PKC to upregulate p53's transcriptional activity in vivo.


Silent changes of tuberculosis in Iran (2005-2015): A joinpoint regression analysis.
Tuberculosis (TB) poses a severe risk to public health through the world but excessively distresses low-income nations. The aim of this study is to analyze silent changes of TB in Iran (2005-2015): A joinpoint regression analysis. This is a trend study conducted on all patients (n = 70) that register in control disease center of Joibar (one of coastal cities and tourism destination in Northern Iran which was recognized as an independent town since 1998) during 2005-2015. The characteristics of patients imported to the SPSS 19 and variation in incidence rate of different forms of pulmonary TB (PTB) (PTB+ or PTB-) and extra-PTB (EPTB)/year was analyzed. Variation in incidence rate of TB for male and female groups and different age groups (0-14, 15-24, 25-34, 35-44, 45-54, 55-64, and above 65 years) was analyzed, variation in trend of this diseases for different groups was compared in intended years, and also, variation in incidence rate of TB was analyzed by Joinpoint Regression Software. The total number of TB was 70 cases during 2005-2015. The mean age of patients was 42.31 ± 21.26 years and median age was 40 years. About 71.4% of patients were PTB (55.7% for with PTB+ and 15.7% with PTB-) and rest of them (28.4%) were EPTB. In regard to classification of cases, 97.1% of them were new cases, 1.45% of them were relapsed cases, and 1.45% of them imported cases. In addition, history of hospitalization due to TB was observed in 44.3%. Despite recent developments of governmental health-care system in Iran and proper access to it and considering this fact that identification of TB cases with passive surveillance is possible. Hence, developing certain programs for sensitization of the covered population is essential.


Strategies to Reduce Mortality in Adult and Neonatal Candidemia in Developing Countries.
Candidemia, the commonest invasive fungal infection, is associated with high morbidity and mortality in developing countries, though the exact prevalence is not known due to lack of systematic epidemiological data from those countries. The limited studies report a very high incidence of candidemia and unique epidemiology with a different spectrum of Candida species. The recent global emergence of multi-drug resistant Candida auris is looming large as an important threat in hospitalized patients of developing countries. While managing candidemia cases in those countries several challenges are faced, which include poor infrastructure; compromised healthcare and infection control practices; misuse and overuse of antibiotics and steroids; lack of awareness in fungal infections; non-availability of advance diagnostic tests and antifungal drugs in many areas; poor compliance to antifungal therapy and stewardship program. Considering the above limitations, innovative strategies are required to reduce mortality due to candidemia in adults and neonates. In the present review, we have unraveled the challenges of candidemia faced by low resource countries and propose a ten part strategy to reduce mortality due candidemia.


Transfer RNA-mediated suppression of stop codons in protoplasts and transgenic plants.
We have developed a simple, rapid and sensitive assay for tRNA gene expression in plant cells. A plant tRNA(Leu) gene was site-specifically mutated to encode each of the three anticodon sequences (CUA, UUA and UCA) that recognize, respectively, the amber, ochre and opal stop codons. The suppression activity of these genes was detected by their ability to restore transient beta-glucuronidase (GUS) expression in tobacco protoplasts electroporated with GUS genes containing premature stop codons. Protoplasts co-electroporated with the amber suppressor tRNA gene and a GUS gene containing a premature amber stop codon showed up to 20-25% of the activity found in protoplasts transfected with the functional control GUS gene. Ochre and opal suppressors presented maximum efficiencies of less than 1%. This system could be adapted to examine transcription, processing or aminoacylation of tRNAs in plant cells. In addition, phenotypically normal, fertile tobacco plants expressing a stably incorporated amber suppressor tRNA gene have been obtained. This suppressor tRNA can be used to transactivate a target gene containing a premature amber stop codon by a factor of at least several hundred-fold.


The role of diminished beta cell reserve and insulin resistance in secondary sulfonylurea failure of type 2 diabetes mellitus.
The correction of hyperglycemia by insulin treatment has been shown to ameliorate beta cell function and insulin sensitivity in SU failure patients, and there also appears to have disparity between tests of beta cell function among these patients. The objectives of this study were to determine beta cell secretory reserve and insulin resistance of secondary SU failure type 2 diabetic patients who had fairly good glycemic control compared with those who were SU responsive and the disparity of beta cell responses to glucose and non-glucose stimuli were examined in these two groups. Eight secondary SU failure, insulin-treated and 11 SU responsive type 2 diabetic patients who were matched for age, degree of obesity, duration of diabetes as well as HbAlc were studied. Intravenous glucagon and oral glucose tolerance tests (OGTT) as well as short intravenous insulin tolerance test using arterialized venous blood were randomly performed on separate occasions to assess beta cell secretory reserve and insulin sensitivity, respectively. Basal (0.37+/-0.05 (SEM) vs 0.80+/-0.14 nmol/l; p=0.02) and stimulated c-peptide levels (0.66+0.08 vs 1.16+/-0.14 nmol/l; p=0.007) after glucagon as well as basal (0.46+/-0.06 vs 0.73+/-0.10 nmol/l; p=0.046) and maximal c-peptide responses (1.41+/-0.14 vs 1.97+/-0.14 nmol/l; p=0.021) to glucose stimulation were significantly lower in SU failure than SU responsive patients. However, the incremental changes of c-peptide over basal after glucagon (0.29+/-0.06 vs 0.37+/-0.09 nmol/l) and glucose (AUC: 36.9+/-7.6 vs 47.9+/-4.5 nmol/l/h) were not different between both groups. There were strong positive relationships between basal and stimulated c-peptide responses to glucagon (r=0.818; p=0.002) and glucose (r=0.85; p=0.001) in SU responsive patients but these relationships were not as strong in SU failure patients (r=0.682; p=0.062 and r=0.41; p=NS, respectively). Insulin sensitivity did not differ between the two groups. This study demonstrated that decreased basal, but not stimulated, insulin secretion was possibly a major factor associated with secondary SU failure in type 2 diabetic patients. With comparable glycemic control, there was no disparate beta cell responses to glucose and glucagon in patients with or without secondary SU failure.


Stimulatory cross-talk between NFAT3 and estrogen receptor in breast cancer cells.
Estrogen receptors (ERalpha and ERbeta) are ligand-regulated transcription factors that play critical roles in the development and progression of breast cancer by regulating target genes involved in cellular proliferation. The transcriptional activity of ERalpha and ERbeta is known to be modulated by cofactor proteins. We used a yeast two-hybrid system and identified NFAT3 as a novel ERbeta-binding protein. NFAT3 interacted with ERalpha and ERbeta both in vitro and in mammalian cells in a ligand-independent fashion. NFAT3 bound specifically to the ERbeta region containing the activation function-1 domain, a ligand-independent transactivation domain. Overexpression of NFAT3 enhanced both ERalpha and ERbeta transcriptional activities in a ligand-independent manner and up-regulated downstream estrogen-responsive genes including pS2 and cathepsin D. Reduction of endogenous NFAT3 with NFAT3 small interfering RNA or overexpression of NFAT3 deletion mutants that lack the ER-binding sites reduced the NFAT3 coactivation of ERalpha and ERbeta. NFAT3 increased binding of ERalpha to the estrogen-responsive element and was recruited to endogenous estrogen-responsive promoters. NFAT3 was expressed differentially in many breast cancer cell lines and overexpressed in a subset of breast cancer patients. Knockdown of endogenous NFAT3 reduced the growth of human breast cancer ZR75-1 cells in a ligand-independent manner. Taken together, these results suggest that NFAT3 may play important roles in ER signaling and represent a novel target for breast cancer therapy.


Rates of depression, anxiety, and stress in parents of children with congenital heart disease using the Depression Anxiety Stress Scale.
The Cardiac Neurodevelopmental Outcome Collaborative has recommended using the Depression Anxiety Stress Scale (DASS) to evaluate for depression, anxiety, and stress in parents of children with congenital heart disease (CHD). There has not been a longitudinal study investigating its utility in these parents. The aim of this study was to determine the trend of depression, anxiety, and stress in parents of patients with CHD. Our center uses this self-reported survey at every visit between 6 and 36 months of age. This was a single-centered, retrospective study from January 1, 2018, to June 1, 2020. Cox regression analysis was conducted using a composite end point of having an abnormal score in any of the three domains. Two hundred and seventy-three mothers and 139 fathers were included in the study. For mothers, scores in each domain were elevated at 12 and 24 months. For fathers, scores in each domain were elevated at 6 months, followed by a decrease before peaking again, with depression increasing at 36 months and anxiety and stress increasing at 30 months. Increased length of stay for the index surgery was associated with an abnormal score for mothers (B = 0.02, P < 0.01) and fathers (B = 0.01, P = 0.04). Being in a relationship with the father (B = -0.8, P < 0.01) was associated with freedom of an abnormal score for mothers. Scores concerning for depression, anxiety, and stress peak at different points for parents. Length of stay for the index surgery and being in a relationship are important factors in the mental health of parents.


Comparison of standard and modified enzyme immunoassay of phenytoin.
A modified method for the enzyme immunoassay (EMIT, Syva Company) of phenytoin is presented and compared with the standard method. Serum samples from 14 patients were analyzed for phenytoin content using both methods. All assays were performed by the same individual. Within-day and between-day variations of the modified method were determined. A carry-over study was done to determine if a sample with a high phenytoin concentration might contaminate subsequent samples with lower concentrations or whether samples with low concentrations could dilute subsequent samples with higher concentrations. Within-day and between-day variations of the modified method were 7.5% and 9.9%, respectively. These values are less than the 10% coefficient of variation limit claimed by the manufacturer of the standard method. The carry-over study revealed no significant carry-over with the modified method. An excellent correlation was observed between the values obtained from the two methods. The modified method can reduce assay costs by up to 40%. The modified method was found to provide accuracy and precision equivalent to the standard EMIT method at a substantial cost savings.


Hereditary benign intraepithelial dyskeratosis: a new case?
Hereditary benign intraepithelial dyskeratosis (HBID) is a rare disorder first described in 1960. To date, all but one published case trace their ancestry back to an Indian tribe in North Carolina. Affected patients usually develop asymptomatic ocular and oral lesions. The latter may resemble other dermatologic conditions that affect the oral mucosa, such as white sponge nevus. This report describes a case of a Brazilian patient who showed clinical and histological features of HBID, which appears to be the first reported case in South America. Although genetic analysis could not be carried out, the family history suggests a genetic etiology.


The promotion effect of π-π interactions in Pd NPs catalysed selective hydrogenation.
The utilization of weak interactions to improve the catalytic performance of supported metal catalysts is an important strategy for catalysts design, but still remains a big challenge. In this work, the weak interactions nearby the Pd nanoparticles (NPs) are finely tuned by using a series of imine-linked covalent organic frameworks (COFs) with different conjugation skeletons. The Pd NPs embedded in pyrene-COF are ca. 3 to 10-fold more active than those in COFs without pyrene in the hydrogenation of aromatic ketones/aldehydes, quinolines and nitrobenzene, though Pd have similar size and surface structure. With acetophenone (AP) hydrogenation as a model reaction, systematic studies imply that the π-π interaction of AP and pyrene rings in the vicinity of Pd NPs could significantly reduce the activation barrier in the rate-determining step. This work highlights the important role of non-covalent interactions beyond the active sites in modulating the catalytic performance of supported metal NPs.


Interleukin 12 induction of interferon gamma-dependent protection against malaria.
Intraperitoneal injection of recombinant Interleukin 12 (rIL-12) at 30 ng/day for 5 days beginning 1 to 2 days before sporozoite challenge or administration of a single dose of 150 ng of rIL-122 days before challenge protected 100% of BALB/c mice against challenge with 10(2) Plasmodium yoelii sporozoites. rIL-12-induced protection was eliminated in all mice by administration of a monoclonal antibody against interferon gamma and in 50% of mice by administration of NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthase. rIL-12 protected BALB/c mice treated with cytotoxic anti-CD4 and anti-CD8 monoclonal antibodies, as well as T-cell- and B-cell-deficient severe combined immunodeficiency mice. These data suggest that rIL-12 stimulates non-B, non-T cells to produce interferon gamma that kills intrahepatic parasites by stimulating nitric oxide production. If rIL-12 proves to be well tolerated by humans, our findings support consideration of rIL-12 as an immunoprophylactic against malaria.


Evaluation of Phenamacril and Ipconazole for Control of Rice Bakanae Disease Caused by Fusarium fujikuroi.
This study evaluated the use of phenamacril and ipconazole, alone and in mixtures, for the control of rice bakanae disease caused by Fusarium fujikuroi. Mixtures were studied with the goal of reducing the selection of fungicide-resistant field isolates of the fungus. When tested alone, both phenamacril and ipconazole exhibited high antifungal activity against F. fujikuroi mycelial growth; the average EC50 value for 19 field isolates was 0.1544 μg/ml for phenamacril and 0.0472 μg/ml for ipconazole. A 2:1 mixture of phenamacril and ipconazole caused a slightly synergistic (greater than additive) inhibition of mycelial growth. Inhibition of F. fujikuroi sporulation was highest for ipconazole alone, intermediate with the 2:1 mixture, and lowest for phenamacril alone. Inhibition by phenamacril and ipconazole alone or by the 2:1 mixture was substantially lower for spore germination than for mycelial growth or sporulation. When the total fungicide concentration was <24 g of a.i./100 kg of treated rice seeds, the fungicides, whether alone or in the 2:1 mixture, were not phytotoxic to seeds or seedlings of two rice cultivars. In a greenhouse experiment, the 2:1 mixture of phenamacril and ipconazole at 6 g of a.i./100 kg of treated seeds provided 100% control of rice bakanae disease on two cultivars. Overall, the results indicate that the use of a 2:1 mixture of phenamacril and ipconazole should control rice bakanae disease while reducing the occurrence of fungicide resistance in F. fujikuroi.


Polygenic Risk Scores and the Risk of Childhood Overweight/Obesity in Association With the Consumption of Sweetened Beverages: A Population-Based Cohort Study.
Background: Sugar-sweetened beverage (SSB) and non-nutritive sweetened beverage (NNSB) consumption is associated with obesity and are targets for population-level dietary interventions. In children (<16 years), we evaluate whether SSB or NNSB consumption is associated with subsequent (2 years later) overweight and/or obesity, and the effect of consumption on subsequent overweight/obesity differs by BMI polygenic risk score (BMI-PRS). Methods: The nationally representative Longitudinal-Study-of-Australian-Children had biennial data collection from birth (n = 5107) until age 14/15 years (n = 3127). At age 11/12 years, a comprehensive biomedical assessment, including PRS assessment, was undertaken (n = 1422). Parent- or self-reported beverage consumption (SSBs: soft drinks, energy drinks, and/or juice; NNSBs: diet drinks) was measured as any/none over previous 24 hours. BMI-PRS was derived using published results (high PRS ≥75th percentile). At ages 4/5-14/15 children were classified as having obesity, overweight/obesity, or not having overweight/obesity using BMI z-score (CDC cut points). Results: SSB consumption had limited association with subsequent overweight/obesity. NNSB consumption was associated with ∼8% more children with subsequent overweight/obesity at most ages. In older children with high BMI-PRS, associations between NNSB consumption and subsequent overweight/obesity strengthened with age [at age 14-15 for high BMI-PRS, difference in proportion with overweight/obesity among NNSB consumers vs. nonconsumers = 0.38 (95% confidence interval: 0.22 to 0.55, p ≤ 0.001)]. There was limited association between SSB consumption and BMI-PRS. Conclusion: NNSB consumption was associated with increased risk of overweight/obesity for children with greater genetic risk at older ages (12-15 years). Focused intervention among children with high genetic risk could target NNSB consumption; however, reverse causality (children with genetic risk and/or high BMI consume more NNSBs) cannot be excluded.


High performance liquid chromatography of hemoglobins: factors affecting resolution.
We have investigated the effect of various factors on resolution of hemoglobin mixtures by ion exchange HPLC. Small changes in the pH of start buffer had a considerable effect on the ability to separate HBs A2 and S. Complete separation of Hbs A2, S, A, Hb A1 fraction and Hb F required 30 min. gradient elution programs. Aging of the hemolysate obscured the presence of small amounts of Hb F. Deterioration in column performance was attributed to dissolution of some of the column packing material as well as irreversible binding of hemoglobin component(s) to the ion exchanger. Substantial differences in elution time were observed between different columns requiring modifications in the gradient programs with some columns. The resolution achieved makes the HPLC technique a powerful new tool for hemoglobin analysis.


Changes in the population of immunoreactive S-100-positive folliculo-stellate cells in hens during induced molting.
The goal of this study was to determine whether the population of folliculo-stellate (FS) cells in the hen's pituitary change during induced molting. White Leghorn laying hens were subjected to induced molting by feed withdrawal; feeding was resumed on the fourth day after egg laying ceased. The anterior pituitaries were collected from hens at pretreatment, at 3 and 5 d after feed withdrawal and at 3 d after cessation of egg laying, 10 d after cessation of egg laying (6 d after resumption of feeding), on the day of and 1 wk after resumption of egg laying (RL and 1WRL, respectively). Pituitaries were processed to detect FS cells by immunocytochemistry for the S-100 protein. Sections were then examined under a light microscope with an image analysis computer system. S-100 immunoreactive cells were found in the cephalic and caudal lobes of the anterior pituitary in all groups of hens. The majority of S-100 immunoreactive cells formed clusters of cells that faced into the follicle and surrounded the glandular cells with long cytoplasmic processes. The S-100 immunoreactive area in the cephalic lobe was significantly increased in the RL group (P < 0.05), but decreased thereafter in 1WRL group. The S-100-positive cell area in the caudal lobe did not show significant changes during induced molting. These results suggest that FS cell population is likely to increase at the final stage of induced molting and may be involved in control of pituitary functions for the resumption of ovulation.


Detection of urinary tract infections in 3- to 5-year-old girls by mothers using a nitrite indicator strip.
A program to detect urinary tract infections among 3- to 5-year-old girls was conducted in Madison-Dane County, Wisconsin using local pharmacies as the distribution site for test kits. Screening was conducted at home by mothers with a nitrite dip-strip on three consecutive first morning specimens. Twenty-one percent of the target population participated during a one-month study period. Eighteen cases were found among 1,573 participants (1.1%). In addition, 243 girls other than those in the target area or age group participated and yielded eight additional cases, for a total of 26 cases among 1,816 total participants. The rate of false-positive nitrite tests was 0.3%. Newspapers were the most effective means of alerting the public to the program. The only factors which were associated with less awareness or participation were low socioeconomic and rural residence. Past history of infection, minor urinary symptoms, and pyuria were common among the bacteriuric girls. Immunoglobulin-coated bacteria suggestive of tissue invasion were present in one third of the cases. Vesico-ureteral reflux was present in five and caliectasis in two of 23 girls studied. Despite the likelihood that some bacteriuric girls, particularly those infected with gram-positive organisms were not detected, screening at home appears to be a highly efficient method of detecting urinary tract infections in large populations of preschool children.


[Final declaration of the Japanese Society of Psychiatry and Neurology concerning the participation of psychiatrists in executions].
To begin with, this author has reviewed papers addressing the issue around the participation of psychiatrists in legal executions. The questions of reasoning for the exclusion of the mentally incompetent from execution, what exactly constitutes "competency to be executed," and whether to assess a criminal's competency for execution or to offer treatment to death row inmates who have been found incompetent are under debate. Then, making known the temporary declaration of the Japanese Society of Psychiatry and Neurology, the author has told that it should insist in the final declaration as follows: First, the secretiveness with which the Ministry of Justice and the correctional facilities in Japan handle the death penalty cases should be abolished. Second, in the present situation of the medical care in Japanese penal facilities, the employed psychiatrists should not be involved in the examination or the treatment of the death row inmates. Third, nevertheless the psychiatrist should not examine whether the inmate is competent to be executed in principle, this indifference may bring on the execution of the incompetent in present situation of Japan. Forth, it is not permitted ethically to offer the medical treatment to restore the inmate's competency. Fifth, because the Japanese death penalty confronts the false charges, if the capital punishment case requesting for retrial or preparing it reveal mentally abnormal and the condition is so severe that the inmate cannot assist legal counsel appropriately, the inmate should be transferred to hospital to be provided treatment. And finally the inmate whose competency is doubted should automatically be commuted to life imprisonment.


Do healthcare tax credits help poor-health individuals on low incomes?
In several countries, personal income tax permits tax credits for out-of-pocket healthcare expenditure. Tax credits benefit taxpayers at all income levels by reducing their net tax liability and modify the price of out-of-pocket expenditure. To the extent that consumer demand is price elastic, they may influence the amount of eligible healthcare expenditure for which taxpayers may claim a credit. These effects influence, in turn, income distributions and taxpayers' health status and therefore income-related inequality in health. Redistributive consequences of tax credits have been widely investigated. However, little is known about the ability of tax credits to alleviate health inequality. In this paper, we study the potential effects that tax credits for health expenses may have on income-related inequality in health status with reference to the Italian institutional setting. The analysis is performed using a tax-benefit microsimulation model that reproduces the personal income tax and incorporates taxpayers' behavioral responses to changes in tax credit rate. Our results suggest that the current healthcare tax credit design tends to favor the richest part of the population.


Transcriptomic analysis reveals importance of ROS and phytohormones in response to short-term salinity stress in Populus tomentosa.
Populus tomentosa (Chinese white poplar) is well adapted to various extreme environments, and is considered an important species to study the effects of salinity stress on poplar trees. To decipher the mechanism of poplar's rapid response to short-term salinity stress, we firstly detected the changes in H2O2 and hormone, and then profiled the gene expression pattern of 10-week-old seedling roots treated with 200 mM NaCl for 0, 6, 12, and 24 h (h) by RNA-seq on the Illumina-Solexa platform. Physiological determination showed that the significant increase in H2O2 began at 6 h, while that in hormone ABA was at 24 h, under salt stress. Compared with controls (0 h), 3991, 4603, and 4903 genes were up regulated, and 1408, 2206, and 3461 genes were down regulated (adjusted P ≤ 0.05 and |log2Ratio|≥1) at 6, 12, and 24 h time points, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation revealed that the differentially expressed genes (DEGs) were highly enriched in hormone- and reactive oxygen species-related biological processes, including "response to oxidative stress or abiotic stimulus," "peroxidase activity," "regulation of transcription," "hormone synthetic and metabolic process," "hormone signal transduction," "antioxidant activity," and "transcription factor activity." Moreover, K-means clustering demonstrated that DEGs (total RPKM value>12 from four time points) could be categorized into four kinds of expression trends: quick up/down over 6 or 12 h, and slow up/down over 24 h. Of these, DEGs involved in H2O2- and hormone- producing and signal-related genes were further enriched in this analysis, which indicated that the two kinds of small molecules, hormones and H2O2, play pivotal roles in the short-term salt stress response in poplar. This study provides a basis for future studies of the molecular adaptation of poplar and other tree species to salinity stress.


Upstaging of non-Hodgkin's lymphoma in a child based on 67Gallium scintigraphy.
To describe a patient whose non-Hodgkin's lymphoma (NHL) appeared to be localized by standard modalities but who was upstaged after Gallium scintigraphy suggested disseminated disease. A patient with biopsy proven NHL in the maxillary sinus was staged as having localized disease based on computed tomography (CT) scans, bone scintigraphy, and evaluation of bone marrow and spinal fluid. Open biopsy of a bony lesion, standard modalities for lymphoma staging, and Gallium scintigraphy were obtained. Gallium scanning showed bony lesions not previously seen with the standard modalities. Open biopsy of one of these lesions confirmed disseminated disease. Gallium scanning aids in the early identification of metastases in some patients with NHL and should be included in a standard evaluation of apparently localized disease.


Cystojejunostomy for non-parasitic hepatic cyst with biliary communication.
Non-parasitic hepatic cysts containing bile are rare entities and pose a challenge in surgical management as they cannot be managed by simple de-roofing. The biliary communication to the cyst cavity should either be closed meticulously, or these cysts should be managed by an internal drainage procedure such as cystoenterostomy. We report a 17-year-old Indian girl, in which such a cyst was treated by cystojejunostomy.


Antimicrobial behavior of semifluorinated-quaternized triblock copolymers against airborne and marine microorganisms.
Semifluorinated-quaternized triblock copolymers (SQTCs) were synthesized by chemical modification of polystyrene-block-poly(ethylene-ran-butylene)-block-polyisoprene ABC triblock copolymers. Surface characterization of the polymers was performed by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) analysis. The surface of the SQTC showed very high antibacterial activity against the airborne bacterium Staphylococcus aureus with >99 % inhibition of growth. In contrast in marine fouling assays, zoospores of the green alga Ulva settled on the SQTC, which can be attributed to the positively charged surface. The adhesion strength of sporelings (young plants) of Ulva and Navicula diatoms (a unicellular alga) was high. The SQTC did not show marked algicidal activity.


One small step for rhinos, one giant leap for wildlife management--imaging diagnosis of bone pathology in distal limb.
Chronic foot disease poses a threat to the general health, represents a tremendous clinical challenge, and often is a reason for euthanasia in captive megaherbivores, among them the elephant and rhinoceros. Nevertheless, apart from the elephant, foot pathology is handled as being confined only to soft tissues whereas bone pathology is often overlooked. As a case in point, the authors selected the second largest mammal on land, the rhinoceros. We performed a computed tomographic (CT) study using the highest resolution available in veterinary world, followed by digital radiography of eight distal limbs from two white and one Indian rhinoceroses. Our study demonstrated that bone pathology in rhinoceroses' foot is present and in large numbers, yet none of these were diagnosed ante mortem. Even when the animals were euthanized due to foot problems, the decision was based on soft tissue pathology rather than orthopedic reasons. Even more worrying is the fact that the largest number of osteopathologies was present in one of the white rhinoceroses that showed no discernable related clinical signs. This study describes for the first time the existence of bone pathology in white rhinoceros foot, in addition to the two previously described rhinoceros species--Indian and black rhinoceroses. Furthermore, the chronic foot disease reported for the Indian rhinoceros in our study was not restricted to soft tissue structures as was presumed ante mortem but included severe bone pathology. New evidence suggesting that osteopathology in rhinoceroses' distal limb is more widespread than it was thought before could force us to rethink of radiographic diagnosis in captive megaherbivores as routine examination incorporated into their health management. The anticipated improvements in radiologic examinations in megaherbivores will increase the effectiveness of their management and husbandry and open the way for improved animal welfare and better wildlife conservation.


Management of hypercholesterolemia in children.
Cardiovascular disease (CVD) remains the leading cause of death and morbidity in our society. One of the major risk factors for CVD is hypercholesterolemia. Hypercholesterolemia in children can be caused by a hereditary disorder or can be secondary to other diseases or drugs. In order to prevent CVD later in life, children with hypercholesterolemia should be identified and treated as early as possible. Currently, several different screening strategies have been developed, using either universal screening or case finding to search for children at risk. Once those children are identified, the first step in treatment is lifestyle adjustment. If cholesterol levels remain elevated, the drugs of first choice are statins. Other pharmacological options are ezetimibe or bile acid sequestrants. These agents have all proven to be safe and effective in lowering low-density lipoprotein cholesterol levels and improving surrogate markers of CVD. However, there is a need for long-term follow-up studies to answer the question as to whether it is safe to initiate treatment at a young age to prevent CVD later in life.


Macroscopic detection of the strong stochasticity threshold in Fermi-Pasta-Ulam chains of oscillators.
The largest Lyapunov exponent of a system composed by a heavy impurity embedded in a chain of anharmonic nearest-neighbor Fermi-Pasta-Ulam oscillators is numerically computed for various values of the impurity mass M. A crossover between weak and strong chaos is obtained at the same value epsilon(T) of the energy density epsilon (energy per degree of freedom) for all the considered values of the impurity mass M. The threshold epsilon(T) coincides with the value of the energy density epsilon at which a change of scaling of the relaxation time of the momentum autocorrelation function of the impurity occurs and that was obtained in a previous work [Phys. Rev. E 65, 036228 (2002)]]. The complete Lyapunov spectrum does not depend significantly on the impurity mass M. These results suggest that the impurity does not contribute significantly to the dynamical instability (chaos) of the chain and can be considered as a probe for the dynamics of the system to which the impurity is coupled. Finally, it is shown that the Kolmogorov-Sinai entropy of the chain has a crossover from weak to strong chaos at the same value of the energy density as the crossover value epsilon(T) of largest Lyapunov exponent. Implications of this result are discussed.


Association of donor age, body mass index, hemoglobin, and smoking status with in-hospital mortality and length of stay among red blood cell-transfused recipients.
Recent publications have reported conflicting findings regarding associations of blood donor demographics and mortality of transfused patients. We hypothesized that the analysis of additional donor characteristics and consideration of alternative outcomes might provide insight into these disparate results. We analyzed data from a retrospective cohort of transfused patients from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). We used stratified Cox regression models to estimate associations between blood donor characteristics and hospital mortality and posttransfusion length of stay among patients transfused red blood cell (RBC) units. Donor characteristics evaluated included age, body mass index, hemoglobin levels, and smoking status. The statistical analyses were adjusted for recipient factors, including total number of transfusions. We studied 93,726 patients in 130,381 hospitalizations during which 428,461 RBC units were transfused. There were no associations between blood donor characteristics and hospital mortality. Receipt of RBC units from donors less than 20 years of age was associated with a shorter hospital length of stay (hazard ratio for discharge per transfused unit, 1.03; 95% confidence interval, 1.02-1.04; p < 0.001) but not for other donor characteristics. We found no evidence of associations between blood donor factors and in-hospital mortality. Our finding of shorter hospital length of stay in patients transfused RBCs from younger donors is intriguing but requires confirmation. Future collaborations are needed to develop a framework of appropriate methodologic approaches to be used in linked analyses across large cohorts.


Determination of normal ranges for serum C3 and C4 levels in an adult Zimbabwean population.
To determine reference levels of serum complement proteins (C3 and C4) by analyzing the concentrations of this serum component in blood samples drawn from otherwise healthy adult Zimbabweans. This was a cross sectional study carried out at the University of Zimbabwe College of Medicine and National Blood Transfusion Services, Harare, Zimbabwe. Ninety five ethnically heterogenous apparently healthy blood donors aged between 18 and 60 years were enrolled in the study. These included 50 males and 45 females. Serum C3 and C4 levels were determined using an immuno-turbidimetric method. Serum levels of complement (C3) ranged from 66 to 185 mg/dl. The respective levels of C4 were 15 to 52 mg/dl. These values varied significantly with age. Serum levels of C3 in patients aged 18 to 50 years were 63 to 192 mg/dl; they were lower (80 to 124 mg/dl) in patients in the 51 to 60 year old age bracket. C4 levels were lower (12 to 49 mg/dl) in the younger adults (18 to 40 years) than in those aged 41 to 60 years (24 to 53 mg/dl). The levels of both C3 and C4 did not vary with gender. This study is probably the first to establish local reference ranges for C3 and C4 in Zimbabwe. These results should find useful clinical and research application.


Universal SARS-CoV-2 polymerase chain reaction screening and assisted reproductive technology in a coronavirus disease 2019 pandemic epicenter: screening and cycle outcomes from a New York City fertility center.
To evaluate the prevalence of coronavirus disease 2019 (COVID-19) and efficacy of a universal screening program in patients undergoing controlled ovarian stimulation (COS). Single-center retrospective cohort study. Academic fertility center in an epicenter of the COVID-19 pandemic. All patients undergoing COS from June 17, 2019, to February 28, 2021. Universal COVID-19 screening starting June 17, 2020, with SARS-CoV-2 polymerase chain reaction testing within 5 days of oocyte retrieval, patient-reported symptom screening, and temperature monitoring. The primary outcome was the number of positive COVID-19 cases in patients undergoing COS cycles. The secondary outcomes were cycle outcomes compared with before COVID-19 COS cycles, adverse outcomes in COVID-canceled cycles, and center-specific COVID-19 detection rates compared with New York City cases. From June 17, 2020, to February 28, 2021, 1,696 COS cycles were initiated with only seven positive COVID-19 cases for an overall positivity rate of 0.4%. When compared with before COVID cycles from June 17, 2019, to February 28, 2020, the volume of COS cycles were higher, while the overall cycle cancelation rate was lower during COVID-19. Cycle outcomes including oocyte yield and blast utilization rates were unchanged from pre-COVID cycles. Cases of COVID-19, while very low, occurred more frequently during surges in New York City rates. Assisted reproductive technology can be performed during the COVID-19 pandemic utilizing frequent universal screening and safe practices with low SARS-CoV-2 positivity, low cycle cancelation rates, and positive patient outcomes.


Clinical studies with In-111 BLEDTA, a tumor-imaging conjugate of bleomycin with a bifunctional chelating agent.
Indium-111 BLEDTA, a bleomycin analog containing an EDTA group, was used for tumor imaging in 110 patients with cancer. Scans with In-111 BLEDTA agreed with biopsy results in 75 of 95 patients (79% accuracy). A positive scan was obtained in 71 of 88 patients with a positive biopsy (81% sensitivity). In 21 of 95 patients (22%), the scan revealed tumor sites that had not been detected. The main limitation of visualization was the size of the tumor (1.5--2.0 cm diameter was the smallest size seen). Background radioactivity in the liver, spleen, and bone marrow also made tumor detection in these areas more difficult. The cause of this background, and of false-positive uptake in sites of inflammation, is correlated with specific radiolabeling of polymorphonuclear leukocytes by In-111 BLEDTA. Means of eliminating this background are discussed.


The prescription talk - an approach to teach patient-physician conversation about drug prescription to medical students.
Background: Medication communication from physicians to patients often is poor, by this among others enhancing the risk of non-adherence. In this context, a neglect regarding the prescription talk has been complained. Aim of the project: In a newly developed elective medical students work on physician-patient conversations dealing with drug prescription. Essential aspects related to an effective and safe drug treatment are combined with steps of shared decision-making. Together with a tutor, students develop a (model) conversation guide that might be tailored according to individual needs and views. Description/Methods: In a one-week course 3rd-5th year medical students treat a paper case according to problem-based learning. This is accompanied by a one-hour lecture and literature provided on an online learning platform (ILIAS). During a workshop, aspects of drug treatment and patient participation are integrated into a guide for a prescription talk. At the end of the week the students are invited to apply the (if need be individualized) guide in a simulated physician-patient communication with an actor. The conversation is evaluated using a checklist based upon the (model) conversation guide. Results: Informal and formalized feedback indicate high acceptance and satisfaction of participants with this elective. The checklist turned out to be of acceptable to good reliability with mostly selective items. Portfolio entries and written evaluation suggest that participants' positions and attitudes are influenced.


Fungal biotransformation of organophosphines.
1. The biotransformations of triphenyl phosphite and of triphenyl-, tri-n.-butyl-, diethylphenyl-, and ethylmethylphenyl-phosphines by the fungi Mortierella isabellina ATCC 42613, Helminthosporium species NRRL 4671, and Aspergillus foetidus ATCC 10254, have been examined. 2. The triaryl and tri-n.-butyl substrates underwent oxidation at phosphorus in low yield, a process attributed largely to auto-oxidation under the experimental conditions used. 3. The alkyl aryl phosphines were enzymically oxidized at phosphorus, but concurrent auto-oxidation also occurred. 4. Incubation of ethylmethylphenyl phosphine with M. isabellina gave the corresponding S(-) phosphine oxide in a 92% yield with an enantiomeric purity of 13%.


Epidemiology and clinical characteristics of sarcoidosis: an update from a population-based cohort study from Olmsted County, Minnesota.
Information about the epidemiology, clinical manifestations and comorbidities of sarcoidosis among Caucasians is relatively scarce. This review focuses primarily on the data from a recently published Caucasianpredominant population-based cohort from Olmsted County, Minnesota. Overall, the incidence rate was 10.0 per 100,000 population, which suggested that sarcoidosis is less common in Caucasians than in Blacks, but is more common in Caucasians than in Asians. Intrathoracic involvement was seen in the vast majority of patients, but less than half have respiratory symptoms. The most common extra-thoracic manifestations were skin rash followed by arthralgia, ophthalmologic involvement, hepatic involvement, splenomegaly, renal involvement, neurological involvement, extra-thoracic lymphadenopathy, exocrine gland involvement, upper respiratory tract involvement and cardiac involvement. Compared to sex and age-matched subjects, patients with sarcoidosis suffer from increased rates of cardiovascular disease, venous thromboembolism and hospitalized infection.


Autonomous Movement System Induced by Synergy between pH Oscillation and a pH-Responsive Oil Droplet.
A sustainable droplet motion that is driven by pH oscillation was obtained. The pH oscillation is only of a single pulse in a batch reactor. However, it shows continuous oscillation around the moving droplet, as the motion itself controls the diffusion flux in an asymmetric manner. Various types of motions that are spontaneous in nature may be obtained by a single-pulse oscillation coupled with mass transport.


Stress degrades working memory-related frontostriatal circuit function.
Goal-directed behavior is dependent on neuronal activity in the prefrontal cortex (PFC) and extended frontostriatal circuitry. Stress and stress-related disorders are associated with impaired frontostriatal-dependent cognition. Our understanding of the neural mechanisms that underlie stress-related cognitive impairment is limited, with the majority of prior research focused on the PFC. To date, the actions of stress across cognition-related frontostriatal circuitry are unknown. To address this gap, the current studies examined the effects of acute noise-stress on the spiking activity of neurons and local field potential oscillatory activity within the dorsomedial PFC (dmPFC) and dorsomedial striatum (dmSTR) in rats engaged in a test of spatial working memory. Stress robustly suppressed responses of both dmPFC and dmSTR neurons strongly tuned to key task events (delay, reward). Additionally, stress strongly suppressed delay-related, but not reward-related, theta and alpha spectral power within, and synchrony between, the dmPFC and dmSTR. These observations provide the first demonstration that stress disrupts the neural coding and functional connectivity of key task events, particularly delay, within cognition-supporting dorsomedial frontostriatal circuitry. These results suggest that stress-related degradation of neural coding within both the PFC and striatum likely contributes to the cognition-impairing effects of stress.


An overview of the effect of sodium glucose cotransporter 2 inhibitor monotherapy on glycemic and other clinical laboratory parameters in type 2 diabetes patients.
We aimed to determine the effect of sodium glucose cotransporter 2 (SGLT2) inhibitor monotherapy on glycemic and other clinical laboratory parameters versus other antidiabetic medications or placebo therapy in patients with type 2 diabetes mellitus. In addition, we aimed to investigate the risk of diabetic ketoacidosis associated with SGLT2 inhibitor therapy and evaluate its weight-sparing ability. Meta-analysis. PubMed and MEDLINE were searched to identify eligible studies up to December 2015. Randomized controlled trials that assessed the efficacy and safety of SGLT2 inhibitor monotherapy versus placebo therapy or active control were considered. The Cochrane Collaboration Risk of Bias Tool was used to evaluate quality and bias. The mean difference was used to evaluate the glycemic and other clinical laboratory parameters for SGLT2 inhibitor intervention versus control by drugs or placebo. Similarly, the risk ratio was used to assess adverse events, and the I (2) was used to evaluate heterogeneity. SGLT2 inhibitors significantly decreased glycated hemoglobin (HbA1c) (P<0.001), weight (P<0.001), and the low-density lipoprotein/high-density lipoprotein ratio (P=0.03) compared with placebo therapy. No statistically significant changes were found in fasting plasma glucose, 2-hour postprandial glucose, or lipid parameters. Significant changes in the uric acid level were found for SGLT2 inhibitors versus placebo therapy (P=0.005) or active control (P<0.001). Although no significant change in levels of ketones occurred (P=0.93), patients receiving SGLT2 inhibitors were at greater risk of increased ketone bodies. Events suggestive of urinary tract infection and pollakiuria presented the greatest risk for patients receiving SGLT2 inhibitors versus active control or placebo therapy. SGLT2 inhibitors significantly decreased HbA1c, body weight, and the low-density lipoprotein/high-density lipoprotein ratio and were found to be safe and well tolerated in type 2 diabetes mellitus patients. Further randomized control trials are required to establish their risk for ketoacidosis.


A mathematical model for fibroblast growth factor competition based on enzyme kinetics.
In this paper, we develop a mathematical model for the competition of two species of fibroblast growth factor, FGF-1 and FGF-2, for the same cell surface receptor. We provide pathways for this interaction using experimental data obtained by Neufeld and Gospodarowicz reported in 1986 [9]. These pathways demonstrate how the interaction of two fibroblast growth factors affects cell proliferation. Upon development of these pathways, we use simulations in MATLAB and optimization to extrapolate the values of a variety of biochemical parameters imbedded within the model. Furthermore, it should be possible to use the model as the basis for a testable hypothesis. We explore this predictive ability with further simulations in MATLAB.


Estimates of Future New Particle Formation under Different Emission Scenarios in Beijing.
New particle formation (NPF) is a leading source of particulate matter by number and a contributor to particle mass during haze events. Reductions in emissions of air pollutants, many of which are NPF precursors, are expected in the move toward carbon neutrality or net-zero. Expected changes to pollutant emissions are used to investigate future changes to NPF processes, in comparison to a simulation of current conditions. The projected changes to SO2 emissions are key in changing future NPF number, with different scenarios producing either a doubling or near total reduction in sulfuric acid-amine particle formation rates. Particle growth rates are projected to change little in all but the strictest emission control scenarios. These changes will reduce the particle mass arising by NPF substantially, thus showing a further cobenefit of net-zero policies. Major uncertainties remain in future NPF including the volatility of oxygenated organic molecules resulting from changes to NOx and amine emissions.


Hospital-acquired meningitis in patients undergoing craniotomy: incidence, evolution, and risk factors.
To establish the incidence of postcraniotomy meningitis, identify etiologic agents, assess patients' medical progress in relation to both length of hospitalization and mortality, and analyze risk factors. This study was developed at Hospital São Paulo, a tertiary university hospital, between August 1995 and January 1998. We conducted a case-control trial, in which 50 pairs of patients were matched. An 8.9%-postcraniotomy meningitis incidence was found. Gram-negative bacilli were the most common etiologic agents isolated. Mortality among the patients was 30%. Mean hospital stay for the patients was 42.9 +/- 22.1 days; for the controls, mean hospital stay was 19.0 +/- 11.4 days (P =.00001). Although several risk factors were identified by univariate analysis, including postoperative external ventricular shunt (OR = 2.92, CI 95% = 1.245-6.865, P =.014), remote site infection (OR = 2.85, CI 95% = 0.995-8.173, P =.051), and repeat operation (OR = 5.02, CI 95% = 1.569-16.066, P =.007), only repeat operation remained in the multivariate analysis model (OR = 3.68, CI 95% = 1.158-11.700, P =.027). Postcraniotomy meningitis resulted in a high mortality rate and a longer hospital stay, with repeat operation identified among the risk factors.


A Human Chondrocyte-Derived In Vitro Model of Alcohol-Induced and Steroid-Induced Femoral Head Necrosis.
BACKGROUND Worldwide, femoral head necrosis (FHN), which is also known as avascular necrosis of the femoral head or osteonecrosis of the femoral head, affects millions of people. Excess alcohol intake and steroid use are two common associations with FHN, but their pathogenesis remains unknown. The aim of this study was to develop an in vitro model using human chondrocytes to study alcohol-induced and steroid-induced FHN. MATERIAL AND METHODS In this study, the in vitro model used a monolayer culture of articular chondrocytes derived from patients with non-traumatic FHN (Ficat and Arlet, Stage III). Normal chondrocytes were obtained from patients with femoral neck fracture resulting from road traffic accident (Garden, Stage IV). Alcohol-stimulated and steroid-stimulated articular chondrocytes were evaluated by a cell proliferation assay, measurement of calcium levels (alizarin red), measurement of alkaline phosphatase (ALP) levels, detection of glycosaminoglycan (GAG) secretion using safranin O histochemical staining, and analysis of cartilage-specific genes, ACAN, SOX9, OPG, TGF-β, RANKL, and RUNX2, using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS Both alcohol and steroids, but especially steroids, accelerated the degradation of cartilage by suppression of chondrogenesis while promoting chondrocyte hypertrophy and activating osteogenic differentiation, as assessed by cell proliferation assay, detection of glycosaminoglycan (GAG) secretion, and analysis of cartilage-specific genes. CONCLUSIONS A human chondrocyte-derived in vitro model of alcohol-induced and steroid-induced FHN demonstrated chondrocyte hypertrophy and activated osteogenic differentiation.


Adolescent girls speak about violence in their community.
Adolescent girls growing up in urban environments have been placed at increased risk for being exposed to violence in their communities. Yet few studies have examined their perceptions of the risk factors, violence, and the pressures they face on a daily basis. The present research describes two adolescent girls' perspectives concerning the challenges, fears, hopes, risks, and pressures they have experienced growing up in their community. The results have implications for violence intervention and prevention programs with adolescent girls living in urban environments.


Comparison of commercial ELISA test kits from Australia and the USA with the serum neutralization test in cell cultures for the detection of antibodies to the infectious laryngotracheitis virus of chickens.
The objective of this work was the evaluation under our conditions of two commercial ELISA kits for the detection of antibodies to avian infectious laryngotracheitis (ILT) virus, one from Australia (Trop-ELISA, TropBio) and one from the USA (ProFLOK-ELISA, KPL), and to compare their performance with the conventional serum neutralization test (SNT) in chick embryo liver cells. Repeatability varied considerably, particularly when using the Trop-ELISA. Therefore, if individual results are important, at least two parallel measurements per serum sample are recommended. In 89.3% of the sera tested by SNT, results of two parallel measurements did not vary by more than one 2-fold dilution step. There was good linear correlation between both ELISAs and the SNT, the correlation coefficient for the Trop-ELISA being r = 0.758 and for the ProFLOK-ELISA r = 0.867. The negative/positive cut-off was redefined to suit our conditions. Sera with a SN titre of > or = 1:4 were considered positive. Sera with < or = 15% absorption in the ProFLOK-ELISA were considered clearly negative. For the Trop-ELISA, extinctions of > or = 0.477 were considered positive, < or = 0.168 clearly negative. Values in between were regarded as doubtful for young chickens and as possibly due to non-specific reactions in older chickens. The sensitivity and specificity of the ELISAs relative to the SNT were 87 and 77% for the Trop-ELISA, and 95 and 60%, respectively, for the ProFLOK-ELISA. However, the results indicate that the sensitivity of the ELISA is higher than that of the SNT, because most sera showed similar deviations from SNT results with both ELISAs. Generally, both ELISAs were a suitable alternative to the SNT under our conditions, as long as only negative/positive results are required.


Impacted upper-ureteral calculi >1 cm: blind access and totally tubeless percutaneous antegrade removal or retrograde approach?
To compare blind access and totally tubeless percutaneous antegrade removal and pneumatic transurethral ureterolithotripsy for the management of impacted upper-ureteral calculi >1 cm. Seventy patients (41 male, 29 female) with impacted upper-ureteral calculi >1 cm were selected in randomized order for pneumatic transurethral ureterolithotripsy (35 patients) or blind access and totally tubeless percutaneous nephrolithotomy (PCNL) (35 patients). Ultrasonography and intravenous urography were performed for all patients before surgery. After operation, plain films and ultrasonography were done. In the PCNL group, blind access was achieved from the lumbar notch area in all 35 patients, but in 3 patients, the exposure was not optimal for approaching the ureteropelvic junction (UPJ). So we injected contrast material into the collecting system, and, under fluoroscopic control, another access was achieved. In 33 patients (94.3%), intact removal of the stones was performed. In the other two patients, we fragmented the stones with the Swiss Lithoclast by an antegrade approach. The success rate thus was 100%. The mean operative time was 38 minutes (range 25-48 minutes). In the transurethral lithotripsy group, 12 stones (34.2%) migrated upward to the pelvis of kidney, and 5 stones (14.2%) fragmented incompletely. In these cases, a double- J stent was inserted, and SWL was performed. In follow-up, plain films and ultrasonography showed complete clearance in these patients. Eighteen calculi (51.4%) fragmented completely with the Lithoclast. The mean operative time in this group was 34 minutes (range 20-58 minutes). In the presence of moderate to severe hydronephrosis, blind access and totally tubeless PCNL is an effective option for large, impacted upper-ureteral calculi. Flexible ureteroscopy with laser lithotripsy is expensive and not readily available. Pneumatic transurethral ureterolithotripsy has a back-pressure effect and pushes back the calculi to the kidney. Thus, this procedure does not have satisfactory results in the management of these calculi.


Functional interaction between local anaesthetics and calcium antagonists in guineapig myocardium: 2. Electrophysiological studies with bupivacaine and nifedipine.
The negative inotropic effect of local anaesthetics is potentiated by several calcium antagonists in guineapig myocardium [1]. Therefore, we studied which effects on cardiac ionic currents could be responsible for this interaction. Concentration-response curves for bupivacaine were studied in isolated guineapig atria and papillary muscles (slow action potentials). Effects on action potentials were assessed in the absence (n = 7 atria, n = 8 papillary muscles) or presence of nifedipine (8 x 10(-8) mol litre-1 in n = 8 atria, 10(-8) mol litre-1 in n = 8 papillary muscles). The effect on the Ca2+ current was assessed directly using the patch-clamp technique in guineapig ventricular myocytes. Bupivacaine reduced contractile force and upstroke velocity of atrial action potentials. Only the negative inotropic effect was potentiated in the presence of nifedipine. Force and upstroke velocity of slow action potentials were diminished by bupivacaine. Both variables were affected at significantly smaller concentrations of bupivacaine when given in combination with nifedipine. The Ca2+ current was reduced significantly by bupivacaine 5 x 10(-5) mol litre-1 (mean -18 (SD 7)%, n = 9). Its effect was accentuated in the presence of nifedipine 10(-9) mol litre-1 (-47 (4)%, n = 7). Bupivacaine 3 x 10(-4) mol litre-1 given alone exerted a comparable effect (-53 (4)%, n = 4). Variables indicative of Ca2+ channel function (contractile force, upstroke of slow but not normal action potentials, Ca2+ inward current) revealed potentiation of the effects of bupivacaine by nifedipine.


[Dynamics of the human respiratory system parameters at different rates of +Gz load rise].
Studies of the dynamics of human respiratory system parameters during 15-s runs with +Gz loads from 6 to 9 units and rates of rise equal to 1, 2, 3 and 5 units/s showed that increase in the rate of rise produced specific shifts in the breathing cycle structure which characterize the voluntary adaptation of humans to g-loads. Results also make it evident that despite absence of difference in the respiratory reactions during +Gz runs, in the period following exposure the distinct increases in the parameters of external breathing and gas-energy exchange correlated with the rate of g-rise. This allows the conclusion that because of the reasons discussed in the paper the physiological cost of Gz-tolerance grows as the rate of g-rise gets high.


A post-hoc analysis of reduction in diabetic foot ulcer size at 4 weeks as a predictor of healing by 12 weeks.
Percent area reduction (PAR) after 4 weeks of diabetic foot ulcer (DFU) treatment has been suggested as a clinical monitoring parameter to distinguish DFUs that will heal within 12 weeks from those that will not despite standard wound care. The purpose of this post-hoc analysis of control DFU treatment outcomes from two published, randomized, controlled studies was to assess the relationship between PAR during early standard wound care and ulcer closure by week 12. The proportion of DFUs healed after 12 weeks was 57% (39 out of 69; 95% confidence interval [CI], 44% to 68%) in study A and 52% (38 out of 73; 95% CI, 40% to 64%) in study B for wounds with > or = 50% PAR by week 4 and 5% (three out of 64; 95% CI, 1% to 13%) and 2% (one out of 44; 95% CI, 0.1% to 12%), respectively, for DFUs with < 50% PAR at week 4. Regardless of baseline size category, DFUs with < 50% PAR at 4 weeks were less likely to heal by 12 weeks than DFUs with > or = 50% PAR (P < or = 0.001). Using pooled data, PAR at weeks 1 to 3 also varied between ulcers that did and did not heal after 12 weeks but sensitivity and specificity was highest on week 4. These findings confirm that percent reduction in wound size is an early predictor of treatment outcome and that protocols of care should be re-evaluated if > or = 50% PAR is not achieved. Studies to assess DFU healing before and after 4 weeks of standard wound care are needed to further refine these guidelines of care.


Non-aneurysmal subarachnoid hemorrhage as presentation of moyamoya disease in an adult.
The presentation of moyamoya disease (MMD) as an aneurysmal subarachnoid hemorrhage (SAH) is relatively frequent and in the absence of aneurysms is extremely rare. A 53-year-old male patient suddenly developed severe headache associated with dysarthria and an altered state of consciousness. At the time of admission, he was found drowsy with global aphasia, stiff neck, right hemiparesis and right Babinski's sign. A non-contrast brain computed tomography was performed and a small bleeding in the subarachnoid space over the left frontal and parietal cortex was observed. Four-vessel cerebral angiography showed bilateral stenosis of the internal carotid arteries, with multiple tortuous vessels branching from the anterior and middle cerebral arteries. These abnormal vessels were anastomosing with branches from the posterior cerebral and middle meningeal arteries. With this information, a diagnosis of MMD was made. A three-dimensional reconstruction from digital angiography ruled out aneurysms or vascular malformations. After 4 weeks, another angiography was performed and remained the same as previous one. Clinical and radiological characteristics of this case are consistent with previous reports, supporting the theory that non-aneurysmal SAH in MMD is caused by rupture of fragile moyamoya vessels.


Fatal poisoning among patients with drug addiction.
Fatal poisonings among drug addicts in Denmark in 2012 were examined. Cause of death, abuse pattern and geographic differences are discussed and data are compared with previous studies. All fatal poisonings examined at the three institutes of forensic medicine in Denmark in 2012 were included in the study. A total of 188 fatal intoxications were recorded. The median age increased from 37.5 in 2007 to 41.5 in 2012. The majority were men (77%). Methadone (59%) was the main intoxicant. The decrease in the frequency of heroin/morphine deaths since 1997 (71%) continued, declining to 44% in 2002, 33% in 2007 and finally to 27% in 2012. Few deaths from central stimulants (amphetamine and cocaine) occurred. Multiple drug use was common and consisted mainly of opioids, cocaine, amphetamine, cannabis, benzodiazepines and alcohol. Heroin/morphine use was most frequent on Funen and in South Jutland. Cocaine was most frequently detected in East Denmark, while amphetamine was more frequent in West Denmark. The number of fatal poisonings among drug addicts has stabilised around 200. The increase in methadone deaths continued and, as in 2007, methadone was the main intoxicant. The increase in methadone deaths seems to be associated with use of methadone in substitution treatment. Nevertheless, methadone treatment also seems to save lives, as indicated by the increasing median age. Use of antidepressants and antipsychotics increased to a high level compared with 2007, indicating that a considerable number of drug addicts also have psychiatric illness. none. not relevant.


The temporal dynamics of waiting when reward is increasing.
The temporal dynamics of waiting are complex. The present study used a video game involving contingencies that produced differential reinforcement of wait times by arranging for the magnitude of the reward to be related to the duration of each inter-response time. In previous research, when outcomes were gradually increasing in value from a minimum to a maximum, two modes of behavior are observed: waiting as little as possible before cashing in (i.e., responding rapidly) or waiting until the maximum is available (i.e., responding slowly). When outcomes were either a smaller sooner or larger later reward, two modes of behavior were again observed which corresponded to choosing either reward immediately after it was available. In the present study, outcome values increased linearly for a period of time, leveled off, increased abruptly, and then increased linearly. This configuration produced three modes of wait times in people - responding immediately, responding immediately after the abrupt increase, and responding when the maximum possible reward was achieved on each trial. Three factors were evaluated as possible causes of each behavioral mode, a desire for immediacy or action, the trade-off between molecular and molar maximization, and ease of responding.


The Association between Human Leukocyte Antigen Class II DR3-DQ2 Haplotype and Type 1 Diabetes in Children of the East Azerbaijan State of Iran.
Type 1 diabetes mellitus (T1D) is an autoimmune disease. Several associations between human leukocyte antigen (HLA) complex and T1D were found in various populations. Associations with various HLA types depend on the investigated populations. However, such associations have not yet been investigated in the East Azerbaijan state of Iran with Turkish ethnicity. The aims of the current study was to describe T1D genetic susceptibility conferred by HLA class II alleles (DRB1*0301, DQA1*0501 and DQB1*0201) and to determine haplotype frequencies among T1D patients. This study was a case-control study. The number of samples was determined using the Cochran formula. Eighty unrelated T1D patients, including 42 (52.5%) females and 38 (47.5%) males, were randomly recruited from the East Azerbaijan state of Iran. Typing of HLA was performed by polymerase chain reaction-sequence-specific priming (PCR-SSP) on DNA extracted from peripheral blood mononuclear cells of 80 unrelated patients and 80 unrelated healthy control donors, who were selected randomly. For haplotype analysis, the logistic regression model was performed that allows joint estimation of Single-nucleotide polymorphisms (SNPs) via haplotypes. The frequency of drb1*0301 (82.5% vs. 11.3%), dqa1*0501 (82.5% vs. 36.3%) and dqb1*0201 (81.3% vs. 35%) were significantly higher among patients compared with that of healthy subjects. Our investigation demonstrated that there is a highly significant association between the studied alleles and T1D. It can be construed that haplotype HLA-DR3-DQ2 has a very modest effect with respect to the risk of T1D.


Hyperphagic effect of B-HT 920 in a modified X-maze test.
The influence on rat-feeding behavior of B-HT 920 (a selective agonist of D2DA receptors at low doses, but also a potent stimulant of alpha 2-adrenoceptors at high doses) was examined using a new experimental model. The apparatus adopted was an X-maze with alternate open and covered arms, each baited with two food-pellets. Individual rats were placed in the apparatus and observed for 5 min. Two essential aspects of rat behavior in the presence of food were considered: tasting and feeding. A number of parameters were recorded: latency to tasting and feeding; interval between tasting and feeding; total feeding time. We also took into account the type of arm in which the rats indulged in their first bout of tasting and feeding. In the first series of experiments, B-HT 920 was injected intraperitoneally (0.1, 1, 2 and 3 mg/kg) into fed and fasted rats; in the second series, the drug was injected intracerebroventricularly (10, 20 and 80 micrograms/rat) into fasted rats. In both experimental conditions, the drug significantly modified the animals' feeding behavior and affected their natural preference for the closed arms as places of choice in which to feed. Comparison of the results with those obtained using norepinephrine (20 micrograms/rat, intracerebroventricularly), a well-known hyperphagic agent, shows that B-HT 920 strongly stimulates feeding. Also, the results of the intracerebroventricular experiments confirm that the effect on feeding appears at doses that are active both on alpha 2-adrenoceptors and on D2DA receptors, as can be deduced from penile erection and stretching and yawning elicited in rats by the same D2DA stimulant doses. The involvement of the latter receptors in feeding has been investigated by means of a new series of experiments with rats treated with the D2DA antagonist sulpiride, before B-HT 920 at 100 micrograms/kg. The possible mechanisms underlying B-HT 920-hyperphagic effects and the value of the X-maze feeding test as a simple procedure indicative of changes in rat feeding and emotionality are discussed in the light of these latest findings.


Myogenic tone in coronary arteries from spontaneously hypertensive rats.
The aims of this study were to investigate myogenic tone in cannulated coronary arteries from SHR (spontaneously hypertensive rats) and WKY (Wistar-Kyoto rats) at 5 and 20 weeks of age under pressurised no-flow conditions. Pressure-diameter relationships (20-200 mm Hg) were determined in the presence (active) and absence (passive) of calcium and myogenic tone at each pressure was calculated. Active, but not passive diameter-pressure relationships were significantly different between strains at both ages. Active diameters were similar between strains at pressures up to 140 mm Hg at 5 and 20 weeks. At higher pressures SHR arteries generated more tone. Maximum myogenic tone was similar between strains in spite of increased wall thickness in the SHR at both ages. Endothelium denudation increased myogenic tone to a greater extent in the SHR at both ages. Active diameters of endothelium-denuded SHR arteries were smaller than those of WKY in the range 20-120 mm Hg at 5 week and 20-80 and 160-180 mm Hg at 20 weeks. These results demonstrate that during both the developmental and established phases of hypertension, myogenic tone is not enhanced in intact SHR coronary arteries, except at the highest pressures. Following endothelium removal SHR arteries generated greater myogenic tone also at lower pressures. These data demonstrate a greater endothelium-mediated antagonism of myogenic tone in SHR coronary arteries.


Gastroduodenal mucosal protection induced by dehydroleucodine: mucus secretion and role of monoamines.
In previous work we have demonstrated that dehydroleucodine (DhL) prevents gastric damage induced by necrosis-inducing agents such as absolute ethanol (EtOH). In this study we examine the effects of DhL on gastroduodenal morphology and monoamine levels by histological and biochemical methods, respectively, as an approach to elucidating the cytoprotective mechanism of the drug. Histological evidence shows that DhL prevents formation of gastroduodenal mucosal lesions induced by EtOH and that this protective effect is related to the ability of the drug to stimulate mucus production. DhL itself does not affect the tissue concentration of NE, DA and 5-HT. However, it prevents the depletion of DA and 5-HT provoked by EtOH. We propose that the abundant mucoid blanket secreted after treatment with DhL acts as a diffusion barrier against EtOH. It is also possible that DhL could act as a "cell stabilizer," by inhibiting the degranulation of cells containing monoamines.