Effects of two educational method of lecturing and role playing on knowledge and performance of high school students in first aid at emergency scene.
This study aimed to investigate the effects of two educational methods on students' knowledge and performance regarding first aid at emergency scenes. In this semi-experimental study, the sample was selected randomly among male and female public high school students of Isfahan. Each group included 60 students. At first the knowledge and performance of students in first aid at emergency scene was assessed using a researcher-made questionnaire. Then necessary education was provided to the students within 10 sessions of two hours by lecturing and role playing. The students' knowledge and performance was as-sessed again and the results were compared. It was no significant relationship between the frequency distribution of students' age, major and knowledge and performance before the educational course in the two groups. The score of knowledge in performing CPR, using proper way to bandage, immobilizing the injured area, and proper ways of carrying injured person after the education was significantly increased in both groups. Moreover, the performance in proper way to bandage, immobilizing injured area and proper ways of carrying injured person after educational course was significantly higher in playing role group compared to lecturing group after education. Iran is a developing country with a young generation and it is a country with high risk of natural disasters; so, providing necessary education with more effective methods can be effective in reducing mortality and morbidity due to lack of first aid care in crucial moments. Training with playing role is suggested for this purpose.


[Design of recombinant-stable plasmids of the pFH series].
By cloning synthetic oligonucleotides into pUC18 plasmid, pFH123--pFH127 plasmids have been constructed. Their polylinker area, along with sites of widely used restriction endonucleases, contains two pairs each of FokI and HgaI sites in the opposite orientation to provide subfragment with unique predetermined 5'-ends. Comparative stability of the new plasmids and their derivatives has been studied and compared with that of the earlier constructed pMB plasmids.


Glucocorticoid stimulation of Na-K-ATPase in superfused distal segments of kidney tubules in vitro.
The ability of glucocorticoids to regulate Na-K-ATPase activity directly was assessed in separated rat kidney tubules derived from the distal nephron. These tubules were superfused under sterile conditions and maintained in a viable condition for at least 24 h in a newly devised apparatus. Viability was assessed by measuring O2 consumption, protein/DNA ratios, and Na-K-ATPase and Mg-ATPase activities. At a concentration of 10(-8) M, dexamethasone elicited a 27% increase in tubular Na-K-ATPase activity in 6 h and a 32% increase in 24 h. In a separate series, assayed at 24 h, the maximal effect was obtained at a dexamethasone concentration of less than 10(-8) M, and by inspection half-maximal stimulation was obtained at approximately 10(-9) M. At a concentration of 10(-7) M, 17 beta-estradiol, testosterone, progesterone, and deoxycorticosterone acetate had no significant effect on tubular Na-K-ATPase activity. These results as well as the time-course and dose-response data imply that the response is mediated by the glucocorticoid receptor pathway. Since the magnitude of response in vitro was similar to the one obtained after injection of dexamethasone in vivo, much if not all of the action appears to be direct and independent of glucocorticoid-induced changes in the filtered Na+ load.


Patch-clamp recordings from cerebellar basket cell bodies and their presynaptic terminals reveal an asymmetric distribution of voltage-gated potassium channels.
Cerebellar basket cells form highly specialized inhibitory synaptic contacts with Purkinje cells, namely the pericellular basket and pinceau nerve terminal structures, wrapping around the Purkinje cell somatic and axon hillock regions. These inhibitory synaptic contacts are ideally located to control the ultimate output of the cerebellar cortex. Previous immunohistochemical studies have shown that these synaptic structures possess a very high density of the dendrotoxin (DTX)-sensitive potassium channel subunit, Kv1.2. We have taken advantage of this unique anatomical arrangement offering a high concentration of identified Kv channel subunits by combining whole-cell patch-clamp recording and fluorescence microscopy to establish a novel preparation and perform the first recordings from unambiguously identified mammalian CNS inhibitory presynaptic terminals. We report that DTX-sensitive potassium channels are present in basket cell terminals but not in the basket cell soma. This selective cellular distribution suggests that these channels play an important role in modulating cerebellar inhibitory synaptic transmission.


Do we need pharmacological therapy for atrial fibrillation in the ablation era?
Management of atrial fibrillation (AF) remains one of the most difficult problems of modern cardiology. Pharmacological antiarrhythmic therapy is used both for termination of episodes of AF and for prevention of AF recurrences. Recently, major trials have compared the strategy of maintenance of sinus rhythm, called rhythm control, with the strategy of heart rate control during AF and found that the rhythm control strategy was not superior to rate control in terms of mortality. Although subsequent analysis identified rhythm control as a factor of improved survival, these large trials have markedly influenced the management of AF. One of the hypotheses explaining the non-superiority of the rhythm control strategy was that the benefit of sinus rhythm was offset by the side effects of antiarrhythmic agents. As a consequence, attention was directed to non-pharmacological therapies, particularly to catheter ablation of the trigger or/and the atrial substrate using radiofrequency current or cryothermia. However, despite the reported good results of various types of interventions in the hands of highly qualified teams, catheter ablation cannot be applied to all patients with AF or to all types of AF. Furthermore, catheter ablation of AF requires sophisticated electrophysiologic laboratories equipped with expensive imaging techniques and a well-trained staff that cannot be available in sufficient number to cover the growing epidemic of AF with acceptable efficacy and safety even in rich countries. Therefore, there is still a need for pharmacological therapy aimed at the prevention of AF recurrences for the majority of AF patients. So far, attempts to provide the physician with efficient antiarrhythmic agents having a good safety profile have not been successful. However, recent research resulted in promising new approaches including prevention of AF using converting enzyme inhibitors or angiotensin 2 receptor blockers, new antiarrhythmic agents with multichannel effects such as dronedarone and tedisamil and atrial specific agents that theoretically should have no ventricular proarrhythmic effect as they target specific atrial channels such as I(KAch) and I(Kur) which are absent at the ventricular level. Other possible mechanisms of AF that represent potential targets, such as modification of stretch-activated ion channels, intervention of altered connexin expression and altered gap-junctional conductance, are currently investigated.


Potassium homeostasis in chronic experimental diabetes mellitus in rats.
To examine potassium homeostasis in diabetes mellitus, we observed the effect of dietary potassium loading on the renin-angiotensin-aldosterone system and potassium balance in streptozotocin-induced diabetic rats. In diabetic rats with 26.51 +/- 1.89 mmol/l of serum glucose, the plasma renin activity (PRA), plasma aldosterone (PA), immunoreactive insulin (IRI) and urinary excretion of prostaglandin E2 (PGE2) were all significantly lower than in control rats, but the plasma potassium and renal function were not significantly different. With potassium loading, both control and diabetic rats showed a similar increase in plasma potassium and urinary potassium excretion and a decrease in PRA, but the IRI, plasma corticosterone and urinary excretion of PGE2 exhibited no significant change. On the other hand, the PA was significantly increased only in the control rats, and not in the diabetic rats on potassium loading. Based up on these results, it is suggested that potassium homeostasis is well maintained in diabetic rats with normal renal function in spite of an attenuated response of aldosterone secretion to dietary potassium loading and insulin deficiency.


Low atmospheric pressure and humidity are related with more frequent pulmonary embolism episodes in male patients.
Pulmonary embolism is a frequent condition, related with high mortality. Frequency of pulmonary embolism episodes has been related with several meteorological factors. The aim of the study was to analyze the influence of meteorological factors on the occurrence of pulmonary embolism in male and female patients. Medical data of patients hospitalized at our institution in 2007-2008 was analyzed. Study group included 400 patients with pulmonary embolism, living in the region located at an average level of about 200 m above sea level, with climate of a transitional character between maritime and continental climates. No significant differences in seasonal distribution of pulmonary embolism episodes were observed. A significant inverse correlation of the number of pulmonary embolism cases and atmospheric pressure, as well as air humidity, was identified in male patients. No significant correlations of temperature, wind velocity, precipitation and number of PE cases were observed. The influence of meteorological factors on the occurrence of pulmonary embolism in males is a new finding. A prospective study is warranted to further analyze this result.


Bone but not Bone: Systemic Calcinosis Presenting as Lumbar Facet Pseudohypertrophy with Neurogenic Claudication.
Systemic sclerosis affects 14-21 per million persons annually and can present with calcinosis-deposition in the skin and subcutaneous tissues. In rare circumstances, paraspinal depositions are also seen, which can cause neural element compression requiring surgical intervention. Here we present the case of a 61-year-old woman with systemic sclerosis on goal-directed therapy who presented with neurogenic pseudoclaudication and imaging suggesting severe joint hypertrophy. The case illustrates that calcinosis in scleroderma can cause facet joint pseudohypertrophy that is difficult to distinguish from true hypertrophy on imaging. Such pseudohypertrophy is often refractory to medical therapy, necessitating surgical intervention. Last, owing to the fluid nature of the calcinotic fluid, decompression is often easier than would be expected based on preoperative imaging alone.


High prostate cancer mortality in Norway evaluated by automated classification of medical entities.
The new standard of cause of death classification is an automated selection of the underlying cause of death using the international software Automated Classification of Medical Entities (ACME). Norwegian mortality rates are, however, based on manual classification of deaths. The aim of this study was to investigate how the use of ACME would influence Norwegian prostate cancer mortality rates. A previously described cohort of Norwegian prostate cancer patients deceased during 1996 was applied. Multiple causes of death data based on information from death certificates, autopsies and queries was coded according to ACME specifications, thereby ACME selected the underlying cause of death. In addition, the underlying cause of death that originally was manually classified for the official mortality statistics was retrieved from Statistics Norway in all cases. Age-standardized prostate cancer mortality rates (world population) per 100,000 person-years were calculated. A total of 2012 cases were included. On the basis of ACME classification, the age-standardized prostate cancer mortality rate in Norway for 1996 would have been 24.4 (95% confidence interval: 22.9-26.0) as compared with the rate based on manual classification for the official mortality statistics of 24.9 (95% confidence interval: 23.4-26.5). Thus, automated classification by ACME does not significantly influence the age-adjusted Norwegian prostate cancer mortality rate for the year 1996. There is reason to assume that the use of manual classification of deaths is not a major explanation of the high prostate cancer mortality rates in Norway.


Risk of Venous Thromboembolism Among Otolaryngology Patients vs General Surgery and Plastic Surgery Patients.
Venous thromboembolism (VTE), which includes deep venous thrombosis or pulmonary embolism, is the number 1 cause of preventable death in surgical patients. Current guidelines from the American College of Chest Physicians provide VTE prevention recommendations that are specific to individual surgical subspecialties; however, no guidelines exist for otolaryngology. To examine the rate of VTE for various otolaryngology procedures compared with an established average-risk field (general surgery) and low-risk field (plastic surgery). This cohort study compared the rate of VTE after different otolaryngology procedures with those of general and plastic surgery in the American College of Surgeons National Surgical Quality Improvement Program from January 1, 2005, through December 31, 2013. We used univariate and multivariable logistic regression analysis of clinical characteristics, cancer status, and Caprini score to compare different risk stratification of patients. Data analysis was performed from May 1, 2016, to April 1, 2017. Surgery. Thirty-day rate of VTE. A total of 1 295 291 patients, including 31 896 otolaryngology patients (mean [SD] age, 53.9 [16.7] years; 14 260 [44.7%] male; 21 603 [67.7%] white), 27 280 plastic surgery patients (mean [SD] age, 50.5 [13.9] years; 4835 [17.7%] male; 17 983 [65.9%] white), and 1 236 115 general surgery patients (mean [SD] age, 54.9 [17.2] years; 484 985 [39.2%] male; 867 913 [70.2%] white) were compared. The overall 30-day rate of VTE was 0.5% for otolaryngology compared with 0.7% for plastic surgery and 1.2% for general surgery. We identified a high-risk group for VTE in otolaryngology (n = 3625) that included free or regional tissue transfer, laryngectomy, composite resection, skull base surgery, and incision and drainage. High-risk otolaryngology patients experienced similar rates of VTE as general surgery patients across all Caprini risk levels. Low-risk otolaryngology patients (n = 28 271) experienced lower rates of VTE than plastic surgery patients across all Caprini risk levels. Malignant tumors were associated with VTE; however, the rates varied by cancer type and were 11-fold greater for cancers of the upper aerodigestive tract compared with thyroid cancers (odds ratio, 10.97; 95% CI, 7.38-16.31). Venous thromboembolism was associated with a 14-fold higher 30-day mortality among otolaryngology patients (5.1% mortality with VTE vs 0.4% mortality without VTE; difference, 4.7%; 95% CI of the difference, 2.2%-9.3%). Most patients undergoing otolaryngology procedures are at low risk of VTE, indicating that guidelines for a low-risk population could be adapted to otolaryngology. Patients undergoing high-risk otolaryngology procedures should be considered as candidates for more aggressive VTE prophylaxis.


Is there a latitudinal diversity gradient for symbiotic microbes? A case study with sensitive partridge peas.
Mutualism is thought to be more prevalent in the tropics than temperate zones and may therefore play an important role in generating and maintaining high species richness found at lower latitudes. However, results on the impact of mutualism on latitudinal diversity gradients are mixed, and few empirical studies sample both temperate and tropical regions. We investigated whether a latitudinal diversity gradient exists in the symbiotic microbial community associated with the legume Chamaecrista nictitans. We sampled bacteria DNA from nodules and the surrounding soil of plant roots across a latitudinal gradient (38.64-8.68 °N). Using 16S rRNA sequence data, we identified many non-rhizobial species within C. nictitans nodules that cannot form nodules or fix nitrogen. Species richness increased towards lower latitudes in the non-rhizobial portion of the nodule community but not in the rhizobial community. The microbe community in the soil did not effectively predict the non-rhizobia community inside nodules, indicating that host selection is important for structuring non-rhizobia communities in nodules. We next factorially manipulated the presence of three non-rhizobia strains in greenhouse experiments and found that co-inoculations of non-rhizobia strains with rhizobia had a marginal effect on nodule number and no effect on plant growth. Our results suggest that these non-rhizobia bacteria are likely commensals-species that benefit from associating with a host but are neutral for host fitness. Overall, our study suggests that temperate C. nictitans plants are more selective in their associations with the non-rhizobia community, potentially due to differences in soil nitrogen across latitude.


Relaxation to assist sleep medication withdrawal.
This study explores the usefulness of relaxation and gradual medication withdrawal in weaning insomniacs from sleep (hypnotic) medication. We recruited 40 volunteers from the community who had insomnia, half of whom were chronic users of hypnotics while the other half were nonmedicated. Half of all participants (10 medicated and 10 nonmedicated) received progressive relaxation. All medicated participants received a standard gradual drug withdrawal program. Medicated participants reduced sleep medication consumption by nearly 80%. Participants who received relaxation obtained additional benefits in sleep efficiency, rated quality of sleep, and reduced withdrawal symptoms. Medicated and nonmedicated participants attained comparable, improved sleep by posttreatment and follow-up. Hypnotic withdrawal was accompanied by serious worsening of insomnia, but this dissipated by the end of the withdrawal period. The psychological treatment of hypnotic-dependent insomnia has high potential for making an important clinical contribution.


Ultrastructural study of two cases of alpha-chain disease.
Intestinal biopsies of two patients with alpha heavy-chain disease were examined by electron microscopy. Except for a few differences, cells involved by the malignant neoplasia of the small intestine were similar and belonged to the plasma cell line and were, in fact, more like the cells observed in typical multiple myeloma. It is not surprising to find such cells in a disease which is characterized by the presence of alpha heavy chain in the serum since plasma cells are considered to be the main source of immunoglubulins. Moreover, the association of an intestinal plasmacytic neoplasia with the heavy chain of the immunoglobulin A in the serum agree with what is known of the normal synthesis by most of the plasma cells of the digestive tract of this immunoglobulin. Since lymphocytes can synthesize immunoglobulins and plasma cells probably originate from lymphocytes, too great an importance should not be attributed to morphological classification. Only an obvious, functional characteristic seems really useful for differentiation.


A possible mechanism of inotropic action of prolactin on rat heart.
Prolactin possesses positive inotropic actions in isolated heart preparations although the mechanism of this influence is not understood. Our study was designed to investigate the mechanism of this effect on the rat heart. Prolactin (50 ng/ml) produced a time-dependent increase (60%) in contractile force that reached maximum after 30 min and remained steady for a further 30 min. A similar time-dependent phenomenon was seen with 200 ng/ml prolactin although the maximum inotropic effect was reduced. Indomethacin (30 micrograms/ml) significantly reduced the inotropic effect of both prolactin concentrations although the effect of the hormone was not related to the release of 6-keto-PGF1 alpha, the prostacyclin metabolite. Propranolol (1-20 micrograms/ml) significantly reduced the positive inotropic effect of prolactin. Prolactin however had no influence on myocardial adenylate cyclase activity. Hearts that were removed from animals pretreated with 1.25 or 2.50 mg/kg reserpine did not respond to prolactin administration. It is suggested that the inotropic influence of prolactin is mediated by endogenous catecholamine liberation.


Regulation of lambda rex expression after infection of Escherichia coli K by lambda bacteriophage.
The ability of Escherichia coli K to support bacteriophage T4rII replication starts to decline at 3 to 6 min after infection by lambda. This inhibition appears to depend on expression of the lambdarex(+) gene, since little inhibition was observed following infection by a lambdarex mutant or by a hybrid bacteriophage lambdai(434) which lacks a functional rex gene. For promotion of the synthesis of rex product, cII(+) and N(+) genes are required and can act trans, whereas cY(+), also required, must be cis to a rex(+) gene. These genes presumably play a role in the transcription of the cI-rex operon because they are also known to be required for repressor (cI product) synthesis. Functional cIII, O, P genes are not necessary for ample rex product synthesis. We also observed full rex expression after infection by lambdasuscI mutants, suggesting that rex and repressor are separate gene products and that repressor is not required for inhibition of T4rII replication. We also report experiments with a rex mutant that is not leaky when in a lysogen but is sufficiently leaky shortly after infection to cause inhibition of T4rII replication.


A mock heart engineered with helical aramid fibers for in vitro cardiovascular device testing.
Mock heart circulation loops (MHCLs) serve as in-vitro platforms to investigate the physiological interaction between circulatory systems and cardiovascular devices. A mock heart (MH) engineered with silicone walls and helical aramid fibers, to mimic the complex contraction of a natural heart, has been developed to advance the MHCL previously developed in our group. A mock aorta with an anatomical shape enables the evaluation of a cannulation method for ventricular assist devices (VADs) and investigation of the usage of clinical measurement systems like pressure-volume catheters. Ventricle and aorta molds were produced based on MRI data and cast with silicone. Aramid fibers were layered in the silicone ventricle to reproduce ventricle torsion. A rotating hollow shaft was connected to the apex enabling the rotation of the MH and the connection of a VAD. Silicone wall thickness, aramid fiber angle and fiber pitch were varied to generate different MH models. All MH models were placed in a tank filled with variable amounts of water and air simulating the compliance. In this work, physiological ventricular torsion angles (15°-26°) and physiological pressure-volume loops were achieved. This MHCL can serve as a comprehensive testing platform for cardiovascular devices, such as artificial heart valves and cannulation of VADs.


Determination of haplotypes at structurally complex regions using emulsion haplotype fusion PCR.
Genotyping and massively-parallel sequencing projects result in a vast amount of diploid data that is only rarely resolved into its constituent haplotypes. It is nevertheless this phased information that is transmitted from one generation to the next and is most directly associated with biological function and the genetic causes of biological effects. Despite progress made in genome-wide sequencing and phasing algorithms and methods, problems assembling (and reconstructing linear haplotypes in) regions of repetitive DNA and structural variation remain. These dynamic and structurally complex regions are often poorly understood from a sequence point of view. Regions such as these that are highly similar in their sequence tend to be collapsed onto the genome assembly. This is turn means downstream determination of the true sequence haplotype in these regions poses a particular challenge. For structurally complex regions, a more focussed approach to assembling haplotypes may be required. In order to investigate reconstruction of spatial information at structurally complex regions, we have used an emulsion haplotype fusion PCR approach to reproducibly link sequences of up to 1kb in length to allow phasing of multiple variants from neighbouring loci, using allele-specific PCR and sequencing to detect the phase. By using emulsion systems linking flanking regions to amplicons within the CNV, this led to the reconstruction of a 59kb haplotype across the DEFA1A3 CNV in HapMap individuals. This study has demonstrated a novel use for emulsion haplotype fusion PCR in addressing the issue of reconstructing structural haplotypes at multiallelic copy variable regions, using the DEFA1A3 locus as an example.


Neurological diseases of ruminant livestock in Australia. IV: viral infections.
Most viral infections that affect the central nervous system of ruminants are exotic to Australia. As such, this review focuses on viruses of importance in Australian ruminants, including Akabane virus and the ruminant pestiviruses, bovine viral diarrhoea virus and border disease virus, as well as bluetongue virus. Each virus is discussed in terms of pathogenesis, clinical signs and diagnosis.


Sustaining Independent Careers in Vision Research: Demographics and Success in Second R01 Attainment Among Clinician-Scientists from 1985 to 2019.
To evaluate the success of ophthalmology and optometry clinician-scientists in obtaining a second R01 (renewal or new) and factors associated with this success, including gender, clinical specialty, degree, institution, and bench versus non-bench research. First-time National Eye Institute (NEI) R01 awardee data from 1985 to 2014 (N = 234) were analyzed to calculate second R01 success rates. Only R01 awards to ophthalmology or optometry clinician-scientists were included. Demographic data were obtained from clinicians with first-time NEI R01 funding spanning from 1962 to 2019 (N = 386). We obtained information regarding time span of the first R01, year of second R01, institution, and project title on the National Institutes of Health (NIH) Research Portfolio Online Reporting Tool, Expenditures and Results (RePORTER) database, and additional measures of gender, clinical specialty, and degree by performing Internet searches. Overall, from 1985 to 2014, 62.8% of ophthalmology or optometry clinician-scientists were awarded a second R01; at 5 years after receipt of the first R01 (the typical length of an R01), only 3.9% received their second R01. None of the factors examined (temporal cohort, gender, clinical specialty, degree, institution, or bench vs. non-bench research) was significantly associated with successful attainment of a second R01. We found an overall success rate of 62.8% for receiving a second R01, but 5 years after the first R01 an attainment rate for a second R01 of only ∼4%. Our study provides insight on significant leaks in the clinician-scientist pipeline and raises questions of how stakeholders should support this important group of individuals at the intersection of clinical medicine and biomedical research.


Relationship between the Induced Iron Overload Model and Hepatic Erythropoiesis in Xenopus laevis.
Iron is an essential element for hemoglobin synthesis during erythropoiesis. Iron overload, in contrast, adversely affects erythropoiesis and causes organ dysfunction. Research using various animal models may help to elucidate pathophysiological mechanisms induced by excess iron. In the present study, we evaluated the relationship between iron metabolism and erythropoietic activity in the African clawed frog, Xenopus laevis. In X. laevis, both erythropoiesis and iron metabolism occur in the liver. First, we developed a method to quantify iron levels in the liver and plasma using 2-nitroso-5-[N-n-propyl-N-(3-sulfopropyl) amino] phenol (Nitroso-PSAP). We then measured iron levels and analyzed hematopoietic parameters in frogs that were orally administered sodium ferrous citrate (SFC). The hepatic iron level increased in the SFC group, but the number of erythrocytes, hematocrit, and hemoglobin concentration did not change, suggesting that the regulation of the production and release of mature erythrocytes in the liver was not directly affected by dietary iron. At four days after administration of 2 mg/kg SFC, the number of immature erythrocytes decreased in the liver. Interestingly, atypical blood cells with hyper-segmented nuclei were observed, identified by acridine orange cell staining; these atypical blood cells were hardly detectable under the steady state. Compared with previously reported results in mice, the increase in the hepatic iron levels was small, but our results indicate that SFC affects hematopoietic activity. These results establish a novel model for iron metabolism and provide new insights into the relationship between iron metabolism and erythropoiesis in vertebrates.


Physical, hematological, and exercise response of collegiate female equestrian athletes.
Physiological testing is extensively used to assess current physical status, target strength/deficiencies, and determine predisposition to injury in athletes. No studies exist regarding these issues on equestrian athletes. The purpose of this study was to quantify the physical, hematological, and exercise response of female equestrian athletes in order to provided greater insight into the health fitness of this unique competitor, and to compare results to other better studied sport athletes. Following written informed consent, physiological assessments were performed on 24 collegiate female equestrian athletes (23.6+/-1.8 yrs; ht = 161.8+/-5.0 cm; wt = 64.9+/-9.3 kg) to quantify aerobic power (VO2max, VEmax, Timemax), anaerobic power (peak power, total work output, fatigue index), body composition (%BF, LBM), muscular strength (curl-ups, reverse sit-ups, pushups, handgrip strength), blood chemistries, and coronary risk profile. Data indicated that mean (+/-SD) LBM (49.0+/-4.5 kg) and BMI (24.8+/-1.7 wt/ht2) fell within reported athletic norms for females. Percent body fat (24.5+/-6.0%), however, was above average. Mean VO2max (33.9+/-4.5 ml/kg/min), treadmill time (10:06+/-:36 min:sec), and VEmax (90.3+/-16.0 l/min) were lower than predicted values. Observed peak power (5.3+/-0.9 w/kg), total work output (315.9+/-48.1 j/kg), fatigue index (66.9+/-7.9%), and handgrip strength (27.8+/-6.6 kg) were also lower than established norms for young females. Mean curl-up, reverse sit-up, and pushup responses (56.5+/-15.8, 36.6+/-13.2, 32.1+/-10.6, reps/min, respectively) were considered average to above average for this age group. Mean resting blood chemistry values were within normal ranges. When analyzing the blood pressure, body composition, and serum lipid data, results indicate an average to low risk for coronary heart disease in this population. Wide variation in lipid profiles in this group as compared to athletes in other sports is a concern. Although working with equine poses a constant danger, the lack of adequate physical conditioning of the equestrian may be a contributing factor in the growing number of injuries. When compared to female athletes in other sports, exercise performance was found to be lower. Equestrian athletes need to supplement conventional sport activity with traditional aerobic and anaerobic training regimens.


EOS 2D/3D X-ray imaging system: a systematic review and economic evaluation.
EOS is a biplane X-ray imaging system manufactured by EOS Imaging (formerly Biospace Med, Paris, France). It uses slot-scanning technology to produce a high-quality image with less irradiation than standard imaging techniques. To determine the clinical effectiveness and cost-effectiveness of EOS two-dimensional (2D)/three-dimensional (3D) X-ray imaging system for the evaluation and monitoring of scoliosis and other relevant orthopaedic conditions. For the systematic review of EOS, electronic databases (MEDLINE, Allied and Complementary Medicine Database, BIOSIS Previews, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, EMBASE, Health Management Information Consortium, Inspec, ISI Science Citation Index and PASCAL), clinical trials registries and the manufacturer's website were searched from 1993 to November 2010. A systematic review of studies comparing EOS with standard X-ray [film, computed radiography (CR) or digital radiography] in any orthopaedic condition was performed. A narrative synthesis was undertaken. A decision-analytic model was developed to assess the cost-effectiveness of EOS in the relevant indications compared with standard X-ray and incorporated the clinical effectiveness of EOS and the adverse effects of radiation. The model incorporated a lifetime horizon to estimate outcomes in terms of quality-adjusted life-years (QALYs) and costs from the perspective of the NHS. Three studies met the inclusion criteria for the review. Two studies compared EOS with film X-ray and one study compared EOS with CR. The three included studies were small and of limited quality. One study used an earlier version of the technology, the Charpak system. Both studies comparing EOS with film X-ray found image quality to be comparable or better with EOS overall. Radiation dose was considerably lower with EOS: ratio of means for posteroanterior spine was 5.2 (13.1 for the study using the Charpak system); ratio of means for the lateral spine was 6.2 (15.1 for the study using the Charpak system). The study comparing EOS with CR found image quality to be comparable or better with EOS. Radiation dose was considerably lower with EOS than CR; ratio of means for the centre of the back was 5.9 and for the proximal lateral point 8.8. The lowest ratio of means was at the nape of the neck, which was 2.9. No other outcomes were assessed in the included studies, such as implications for patient management from the nature and quality of the image. Patient throughput is the major determinant of the cost-effectiveness of EOS. The average cost per procedure of EOS decreases with utilisation. Using estimates of patient throughput at national level from Hospital Episode Statistics data suggests that EOS is not cost-effective for the indications considered. Throughput in the region of 15,100 to 26,500 (corresponding to a workload of 60 to 106 patient appointments per working day) for EOS compared with a throughput of only 7530 for CR (30 patient appointments per working day) is needed to achieve an incremental cost-effectiveness ratio of £30,000 per QALY. EOS can be shown to be cost-effective only when compared with CR if the utilisation for EOS is about double the utilisation of CR. The main limitation of the systematic review of the clinical effectiveness of EOS was the limited number and quality of the data available. In particular, there were no studies assessing the potential health benefits arising from the quality and nature of the image, over and above those associated with reduced radiation exposure. Uncertainty in the model inputs was not fully explored owing to a lack of reporting of standard deviations or confidence intervals in the published literature for most of the parameters. As a result, uncertainty in the cost-effectiveness results was not presented. Radiation dose is considerably lower with EOS than standard X-ray, whereas image quality remains comparable or better with EOS. However, the long-term health benefits from reduced radiation exposure with EOS are very small and there was a lack of data on other potential patient health benefits. The implications of any changes in the quality and nature of the EOS image compared with standard X-ray, for patient health outcomes, needs to be assessed. Given the higher cost of an EOS machine, utilisation is the major determinant of cost-effectiveness. Estimates of patient throughput at national level suggest that EOS is not cost-effective. The National Institute for Health Research Health Technology Assessment programme.


Restoration of cellular ubiquitin reverses impairments in neuronal development caused by disruption of the polyubiquitin gene Ubb.
Disruption of the polyubiquitin gene Ubb leads to hypothalamic neurodegeneration and metabolic disorders, including obesity and sleep abnormalities, in mice. However, it has yet to be determined whether or not these neural phenotypes in Ubb(-/-) mice are directly caused by cell autonomous defects in maintaining proper levels of ubiquitin (Ub). To directly demonstrate that reduced levels of Ub are sufficient to cause neuronal abnormalities, we investigated the characteristics of cultured neurons isolated from Ubb(-/-) mouse embryonic brains. We found that neuronal morphology, neurite outgrowth, and synaptic development were significantly impaired in Ubb(-/-) neurons. Furthermore, we observed the growth of astrocytes in Ubb(-/-) cell cultures despite the fact that cells were cultured under conditions promoting neuronal growth. When the reduced levels of free Ub, but not Ub conjugates, in Ubb(-/-) cells were restored to those of wild-type cells by providing exogenous Ub via lentivirus-mediated delivery, the increased apoptosis observed in Ubb(-/-) cells was almost completely abolished. Ectopic expression of Ub also improved neuronal and glial phenotypes observed in Ubb(-/-) cells. Therefore, our study suggests that Ub homeostasis, or the maintenance of cellular free Ub above certain threshold levels, is essential for proper neuronal development and survival.


Clinicopathologic features and molecular subtypes of breast cancer in young women (age ≤35).
Breast cancer in young women is a relatively rare disease; however it tends to be more aggressive and is the leading cause of cancer death in this population. The aim of this study is to investigate the clinical and biological features of breast cancer arising in young Turkish breast cancer patients. Patients with breast cancer aged 35 or less (≤35 years) were selected for the study. In total 211 cases were included. Pathologic features; histologic subtypes, grade, lymphovascular invasion, axillary involvement, and stage were recorded for each. The most common subtype was luminal B (36.5%), followed by luminal A (30.8%), triple negative (23.2%) and HER2+(9.5%) subtypes. Twelve percent of the patients had stage 4, 32.7% had stage 3, 46.4% had stage 2, and 6.2% had stage 1 disease at the time of diagnosis. Mean tumour diameter was 3.87 cm (range 0.3-13 cm). The axillary lymph nodes were positive in 74.4% of the patients, while lympho-vascular invasion was seen in 56.4%. Some 9.5% of patients had grade 1, 51.2% had grade 2, and 31.8% had grade 3 tumors. Young women with breast cancer in Turkey are more likely to present with luminal B subtype. Tumors in young women are more likely to present with advanced disease, to be high grade and and to have more lymphovascular invasion. Further research should focus on whether we need new treatment strategies for young patients with breast carcinoma.


Surrogates' Perceptions of Service Quality While Making Decisions for ICU Patients.
A qualitative secondary analysis was undertaken to identify aspects of health care service quality in an intensive care unit from the perspective of surrogate decision makers (N = 19) who were making decisions for relatives at end of life. Directed content analysis was guided by the Donabedian model of health care quality. Nineteen participants averaged 59 years old and were over half female (53%) and patients' spouses (53%) and adult children (32%). Salient aspects of quality service included surrogate perceptions that clinicians conveyed honesty about the patient's condition and in an easily understandable way; staff were sensitive and responsive to emotions and practical needs; clinicians demonstrated a clear, confident understanding of the patient's condition; and support by clinicians was given for surrogates' choices. Surrogates also commented on the hospital and intensive care unit environment, including cleanliness, comfort, privacy, and noise level. Further research is needed to explore how decision-support strategies might include service quality concepts.


GPR68 Improves Nerve Damage and Myelination in an Immature Rat Model Induced by Sevoflurane Anesthesia by Activating cAMP/CREB to Mediate BDNF.
Ovarian cancer G-protein-coupled receptor 1 (OGR1, also known as GPR68) is a member of proton-sensing G-protein-coupled receptors, involved in cardiovascular physiology, tumor biology, and asthma, and exerts a neuroprotective effect against brain ischemia. The effects of GPR68 on anesthesia-induced nerve damage and myelination were investigated in this study. First, 2-day old postnatal rats were exposed to 4.9% sevoflurane for 2 h. Data from hematoxylin and eosin staining and Nissl staining showed that sevoflurane induced pathological changes in the hippocampus with a reduced number of neurons. GPR68 was downregulated in the hippocampus of sevoflurane-induced rats. Second, sevoflurane-induced rats were injected with adeno-associated virus (AAV)-mediated overexpression of GPR68, and overexpression of GPR68 ameliorated sevoflurane-induced pathological changes, enhanced the number of neurons, and improved the learning and memory function. Moreover, overexpression of GPR68 increased the number of BrdU-positive and Olig2-positive cells and enhanced protein expression of Olig2 in sevoflurane-induced rats. Third, the number of myelin basic protein (MBP) positive cells and protein expression of MBP in sevoflurane-induced rats were also enhanced by injection with AAV-GPR68. Overexpression of GPR68 attenuated sevoflurane-induced neuronal apoptosis and oxidative stress in rats. Lastly, overexpression of GPR68 upregulated protein expression of the brain-derived neurotrophic factor (BDNF) by increasing cAMP and phosphorylated cAMP response element-binding protein (CREB). In conclusion, GPR68 alleviated sevoflurane-induced nerve damage and myelination through BDNF-mediated activation of the cAMP/CREB pathway.


Immunogenicity of Split Inactivated Quadrivalent Influenza Vaccine in Adults with Obesity in the 2017/2018 Season.
BACKGROUND Obesity is associated with susceptibility to severe influenza infection and several disturbances of the immune response to the influenza vaccine. However, the effect of obesity on the immunogenicity of the influenza vaccine is not fully understood. Our objective here was to assess the immunogenicity of the split, inactivated quadrivalent influenza vaccine (QIV) in Polish adults with obesity. MATERIAL AND METHODS Fifty-three subjects with obesity aged 21-69 years were vaccinated with the QIV in 2017/2018 season. Antibody titers against the 4 vaccine strains were measured using the hemagglutination inhibition (HI) assay. The mean fold antibody increase (MFI), seroprotection rate (protection rate, PR), and seroconversion rate (response rate, RR) were calculated to assess vaccine immunogenicity. RESULTS The vaccine elicited a significant increase in the anti-HI titers against the QIV antigens. The MFI, PR, and RR for the QIV antigens also reached the required age-specific values, indicating the QIV meets current immunogenicity criteria. Individuals with class I and class II/III obesity had similar anti-HI titers, MFI, PR, and RR to each of the vaccine strains. Adults aged <60 years had similar anti-HI titers, MFI, PR, and RR to the QIV strains to those aged ≥60 years. CONCLUSIONS Our results indicate that the split virion, inactivated QIV is immunogenic in adults with obesity regardless of their degree of obesity and age (ie, <60 and ≥60 years).


Anti-inflammatory and antioxidant effects of muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus.
Recently we found that acute treatment with Oxotremorine (Oxo), a non-selective mAChRs agonist, up-regulates heat shock proteins and activates their transcription factor heat shock factor 1 in the rat hippocampus. Here we aimed to investigate: a) if acute treatment with Oxo may regulate pro-inflammatory or anti-inflammatory cytokines and oxidative stress in the rat hippocampus; b) if chronic restraint stress (CRS) induces inflammatory or oxidative alterations in the hippocampus and whether such alterations may be affected by chronic treatment with Oxo. In the acute experiment, rats were injected with single dose of Oxo (0.4 mg/kg) and sacrificed at 24 h, 48 h and 72 h. In the CRS experiment, the rats were exposed for 21 days to the CRS and then were treated with Oxo (0.2 mg/kg) for further 10 days. The acute Oxo treatment showed an ability to significantly reduce reactive oxygen species (ROS), singlet oxygen (1O2), pro-inflammatory cytokines levels (IL-1β and IL-6) and phosphorylated NF-κB-p65. Acute Oxo treatment also increased superoxide dismutase (SOD)-2 protein levels and stimulated SOD activity. No differences were detected in the anti-inflammatory cytokine levels, including IL-10 and TGF-β1. In the group of rats exposed to the CRS were found increased hippocampal IL-1β and IL-6 levels, together with a reduction of SOD activity level. These changes produced by CRS were counteracted by chronic Oxo treatment. In contrast, the upregulation of ROS and 1O2 levels in the CRS group was not counteracted by chronic Oxo treatment. The results revealed a hippocampal anti-inflammatory and antioxidant effect of Oxo treatment in both basal conditions and anti-inflammatory in the CRS rat model.


Interpretation of some organic photochemistry.
A general introduction to current organic photochemical research is presented. A limited survey of typical organic photochemical reactions, with an emphasis on recent studies, is given. Reactions of the n-pi* and pi-pi* type are included. Some new thoughts are included; among these is the relation of Möbius strip geometry to organic photochemistry.


Design and synthesis of vanadium hydrazide gels for Kubas-type hydrogen adsorption: a new class of hydrogen storage materials.
In this paper we demonstrate that the Kubas interaction, a nondissociative form of weak hydrogen chemisorption with binding enthalpies in the ideal 20-30 kJ/mol range for room-temperature hydrogen storage, can be exploited in the design of a new class of hydrogen storage materials which avoid the shortcomings of hydrides and physisorpion materials. This was accomplished through the synthesis of novel vanadium hydrazide gels that use low-coordinate V centers as the principal Kubas H(2) binding sites with only a negligible contribution from physisorption. Materials were synthesized at vanadium-to-hydrazine ratios of 4:3, 1:1, 1:1.5, and 1:2 and characterized by X-ray powder diffraction, X-ray photoelectron spectroscopy, nitrogen adsorption, elemental analysis, infrared spectroscopy, and electron paramagnetic resonance spectroscopy. The material with the highest capacity possesses an excess reversible storage of 4.04 wt % at 77 K and 85 bar, corresponding to a true volumetric adsorption of 80 kg H(2)/m(3) and an excess volumetric adsorption of 60.01 kg/m(3). These values are in the range of the ultimate U.S. Department of Energy goal for volumetric density (70 kg/m(3)) as well as the best physisorption material studied to date (49 kg H(2)/m(3) for MOF-177). This material also displays a surprisingly high volumetric density of 23.2 kg H(2)/m(3) at room temperature and 85 bar--roughly 3 times higher than that of compressed gas and approaching the DOE 2010 goal of 28 kg H(2)/m(3). These materials possess linear isotherms and enthalpies that rise on coverage and have little or no kinetic barrier to adsorption or desorption. In a practical system these materials would use pressure instead of temperature as a toggle and can thus be used in compressed gas tanks, currently employed in many hydrogen test vehicles, to dramatically increase the amount of hydrogen stored and therefore the range of any vehicle.


Neuroanatomical and pharmacological evidence for a functional interaction between GABAergic and NPY-Y1 transmission in the amygdala of Y1R/LacZ transgenic mice.
Several lines of evidence indicate that GABA and neuropeptide Y (NPY) are functionally coupled and may interact in the regulation of fear- and anxiety-induced behavior. Neuroanatomical studies demonstrated that GABA and NPY coexist in neurons of the amygdaloid complex and that NPY may directly modulate the activity of GABAergic neurons by stimulating Y1 receptors. By using a transgenic mouse model harboring a construct comprising the murine Y1 receptor gene promoter fused to a lacZ reporter gene (Y1R/LacZ mice), we showed that long-term treatment with positive (diazepam or abecarnil) or negative (FG7142) modulators of GABAA receptor function induced a marked increase or decrease, respectively, in Y1 receptor gene expression in the amygdala. Furthermore, we demonstrated that a sustained increase in the brain concentrations of neuroactive steroids, induced by pharmacological treatment or by physiological conditions such as pregnancy, increases Y1 receptor gene expression in the amygdala of Y1R/LacZ transgenic mice, an effect similar to that induced by diazepam or abecarnil. These data provide evidence of a functional interaction between GABAergic and NPY-Y1 mediated transmission and suggest that neuroactive steroids may play an important role in the regulation of the NPY transmission. Finally, our data support a role of Y1 receptors in the behavioral and neuroendocrine responses to stress that, however, appears to be independent on the activation of the GABAergic system.


Ribonuclease L mediates the cell-lethal phenotype of double-stranded RNA editing enzyme ADAR1 deficiency in a human cell line.
ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. Mutation of ADAR1 leads to a severe neurodevelopmental and inflammatory disease of children, Aicardi-Goutiéres syndrome. In mice, Adar1 mutations are embryonic lethal but are rescued by mutation of the Mda5 or Mavs genes, which function in IFN induction. However, the specific IFN regulated proteins responsible for the pathogenic effects of ADAR1 mutation are unknown. We show that the cell-lethal phenotype of ADAR1 deletion in human lung adenocarcinoma A549 cells is rescued by CRISPR/Cas9 mutagenesis of the RNASEL gene or by expression of the RNase L antagonist, murine coronavirus NS2 accessory protein. Our result demonstrate that ablation of RNase L activity promotes survival of ADAR1 deficient cells even in the presence of MDA5 and MAVS, suggesting that the RNase L system is the primary sensor pathway for endogenous dsRNA that leads to cell death.


Derivation and basic characterization of colorectal carcinoma primary cell lines.
Colorectal carcinoma is one of the most common malignancies in western countries. Among different approaches to its research, primary cancer cell lines can play an important role. The main purposes of this study were: 1) to establish an effective and reproducible method of colorectal cancer cell isolation and cultivation from primary tumours and lymph node metastases and 2) to elucidate the biological features of the tumours favouring successful cell cultivation. The tumour cells were obtained from colectomy specimens. Primary tumour and lymph node metastasis tissue was used for establishing the tissue cultures. Colectomy samples were further processed for routine histopathological assessment: tumour grade, stage, angioinvasion and perineural spread were evaluated. Features of tissue culture cells were assessed using phase contrast microscopy and immune-histochemical techniques. WST-1 assay and X-CELLigence real time analysis were carried out for viability and proliferation testing before and after treatment with irinotecan and oxaliplatin. Molecular features of the tumour including K-RAS/B-RAF/N-RAS mutations were tested using allele-specific PCR. Results of the cultivation process were compared to the histopathological and molecular features of the tumours. In total, we obtained 33 samples from the primary site of tumours and 20 samples from lymph node metastases; in total, 27 cell lines were successfully isolated. Morphologic features characteristic of tumour cells in primary cell lines and epithelial differentiation (positive for AE1/AE3 cytokeratin) were evaluated. Higher tumour stage, angioinvasion and presence of perineural spread in primary tumour correlated positively with successful cell isolation from lymph node metastasis. All samples tested were NRAS wild-type. No correlation was found between molecular phenotype and the cell culture features. A higher proliferation potential was observed in the primary tumour cells, whereas higher sensitivity to irinotecan was found in the lymph node metastatic cells. Using mechanical dissociation, we successfully derived and cultivated CRC cells from primary tumours and lymph node metastases with success rate 3 % and 70% respectively. Primary tumour features favouring successful establishment of cell cultures were identified.


Novel Use of Biphasic Cuirass Ventilation During Definitive Radiation Therapy: A Technical Report.
The use of biphasic cuirass ventilator supported radiation therapy has never been documented. We present the first technical report here. A 57-year-old man with obstructive sleep apnea presented with a T0N1M0 right sided, human papillomavirus related head and neck cancer diagnosed on excisional lymph node biopsy. On further workup, the cancer was found to have originated in the right tonsil and was staged as T1N1. The patient started definitive treatment with concurrent chemo-radiation therapy, but after 5 treatments was no longer able to lay in a supine position for treatment. Diagnostic imaging workup eventually revealed an idiopathic right sided hemi-diaphragm eventration. After consultation with cardiology, pulmonology, and head and neck surgery, recommendation was made for tracheostomy to tolerate supine radiotherapy position, but the patient refused. Instead, computed tomography simulation for radiotherapy replanning was performed using a combination of biphasic cuirass ventilation, home continuous positive airway pressure and oxygen. The patient then tolerated definitive treatment to a dose of 69.96 Gray in 33 fractions with concurrent chemotherapy and experienced no unexpected side effects. Although complex, daily treatment setup was consistent. Daily onboard imaging was precise and accurate. The patient continues to follow up with radiation oncology, medical oncology, and pulmonology. This is the first use of biphasic cuirass ventilator supported radiotherapy reported in the scientific literature. Although daily treatment setup is complex, its use could be considered in patients unable to tolerate radiation therapy treatment positioning as an alternative to tracheostomy.


A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial.
Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge. To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting. A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up. An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography; and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control. Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days. Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18-3.13; P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation. Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required. anzctr.org.au Identifier: ACTRN12610000766011.


Quantitative laser scanning confocal autofluorescence microscopy of normal, premalignant, and malignant colonic tissues.
Laser scanning confocal autofluorescence microscopy (LSCAM) using 351- to 364-nm excitation light was used to quantitatively compare fluorescent spectral emission of unstained, frozen histological sections of normal, premalignant, and malignant colonic tissues. To identify the spatial origins of fluorescent signals accurately, the same frozen section slides used for microscopy were fixed and histochemically stained immediately following LSCAM imaging. Tissue fluorescence emission was quantified in terms of the intrinsic fluorescence coefficient beta (lambda), defined as the fluorescence power per unit tissue volume per unit wavelength (centered at lambda) divided by the incident light irradiance. Over all emission wavelengths, colonic tissues emitted autofluorescence ranging from beta (lambda) approximately 10(-1.5) to 10(-3.0) cm-1. In the 530- to 610-nm spectral region, markedly increased autofluorescence (beta up to 10(-2.5)) was observed in the dysplastic cells of adenomatous polyps, as compared to normal epithelial cells. Compared to adenomatous polyps, decreased dysplastic cell autofluorescence was observed in adenocarcinoma. The brightest fluorescence in the lamina propria, which was attributed to eosinophils (beta approximately 10(-2.5)) in previous studies, was also observed in other granular structures (beta up to 10(-1.4)). LSCAM reveals quantitative significant differences in fluorescence emission between normal and diseased colonic tissues.


Multigeneration reproduction ratios and the effects of clustered unvaccinated individuals on epidemic outbreak.
An SIR epidemiological community-structured model is constructed to investigate the effects of clustered distributions of unvaccinated individuals and the distribution of the primary case relative to vaccination levels. The communities here represent groups such as neighborhoods within a city or cities within a region. The model contains two levels of mixing, where individuals make more intra-group than inter-group contacts. Stochastic simulations and analytical results are utilized to explore the model. An extension of the effective reproduction ratio that incorporates more spatial information by predicting the average number of tertiary infections caused by a single infected individual is introduced to characterize the system. Using these methods, we show that both the vaccination coverage and the variation in vaccination levels among communities affect the likelihood and severity of epidemics. The location of the primary infectious case and the degree of mixing between communities are also important factors in determining the dynamics of outbreaks. In some cases, increasing the efficacy of a vaccine can in fact increase the effective reproduction ratio in early generations, due to the effects of population structure on the likely initial location of an infection.


Sensitivity of glaciers and small ice caps to greenhouse warming.
Recent field programs on glaciers have supplied information that makes simulation of glacier mass balance with meteorological models meaningful. An estimate of world-wide glacier sensitivity based on a modeling study of 12 selected glaciers situated in widely differing climatic regimes shows that for a uniform 1 K warming the area-weighted glacier mass balance will decrease by 0.40 meter per year. This corresponds to a sea-level rise of 0.58 millimeter per year, a value significantly less than earlier estimates.


Echocardiographic Patterns of Left Ventricular Diastolic Function in Cardiac Amyloidosis: An Updated Evaluation.
Multimodal imaging has allowed cardiac amyloidosis (CA) to be increasingly recognised as a treatable cause of heart failure with preserved ejection fraction, but its prognosis remains poor due to late diagnosis. To assess the left ventricular diastolic function (LVDF) patterns in a large contemporary CA cohort according to the current recommendations and to identify their determinants. We conducted a monocentric, observational study on a cohort of CA patients from a tertiary CA referral centre. Diastolic function was analysed using standard echocardiography and clinical, laboratory and survival parameters were collected. Four hundred and sixty-four patients with one of the three main type of CA were included: 41% had grade III diastolic dysfunction (restrictive mitral pattern), 25% had grade II diastolic dysfunction, and 25% had grade I diastolic dysfunction; 9% were unclassified. No difference was found between the main CA types. After multivariate analyses, grades II and III were independently associated with dyspnoea, elevated NT-proBNP, cardiac infiltration and systolic dysfunction (global longitudinal strain). Grade I patients had a better prognosis. All LVDF patterns can be observed in CA. One quarter of CA patients have grade I LVDF, reflecting the emergence of earlier stage-related phenotypes with a better prognosis.


BBSome function is required for both the morphogenesis and maintenance of the photoreceptor outer segment.
Genetic mutations disrupting the structure and function of primary cilia cause various inherited retinal diseases in humans. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic ciliopathy characterized by retinal degeneration, obesity, postaxial polydactyly, intellectual disability, and genital and renal abnormalities. To gain insight into the mechanisms of retinal degeneration in BBS, we developed a congenital knockout mouse of Bbs8, as well as conditional mouse models in which function of the BBSome (a protein complex that mediates ciliary trafficking) can be temporally inactivated or restored. We demonstrate that BBS mutant mice have defects in retinal outer segment morphogenesis. We further demonstrate that removal of Bbs8 in adult mice affects photoreceptor function and disrupts the structural integrity of the outer segment. Notably, using a mouse model in which a gene trap inhibiting Bbs8 gene expression can be removed by an inducible FLP recombinase, we show that when BBS8 is restored in immature retinas with malformed outer segments, outer segment extension can resume normally and malformed outer segment discs are displaced distally by normal outer segment structures. Over time, the retinas of the rescued mice become morphologically and functionally normal, indicating that there is a window of plasticity when initial retinal outer segment morphogenesis defects can be ameliorated.


Supplying sows energy on the expected day of farrowing improves farrowing kinetics and newborn piglet performance in the first 24 h after birth.
The farrowing process is one of the most energy-demanding activities for the modern hyperprolific sow. This study evaluated the effects of supply of energy on the expected date of farrowing on the farrowing kinetics and piglets' performance during the first 24 h after birth. A total of 80 sows were used. The sows and their respective litters were considered as the experimental unit. On the expected day of farrowing, the sows were allocated to one of the following groups: sows that did not have access to feed from farrowing induction until the end of the farrowing process (CON, n = 40); sows fed 500 g of energetic supplement, which consisted of 250 g of the basal lactation diet plus 250 g of cane sugar, 18 h after farrowing induction (SUP, n = 40). The farrowing duration, farrowing assistance, birth interval, number of total born, stillborn and mummified piglets were recorded for each sow. Piglets were weighed individually at birth and 24 h later. The interval from birth to first suckle was evaluated individually for each piglet in 16 randomly selected litters (eight litters per treatment group). Blood glucose concentrations of six sows were measured shortly after expulsion of the first piglet. Farrowing duration, farrowing assistance and stillborn rate tended to be greater (P = 0.06, P = 0.09 and P = 0.07, respectively) in sows from the CON group compared to sows from the SUP group. However, there was no difference (P > 0.05) between the groups for birth interval. Colostrum intake was greater (P < 0.05) for piglets from the SUP group compared to piglets from the CON group. Additionally, BW gain of the piglets suckling the SUP group was greater (P < 0.05) than those suckling the CON group at 24 h after birth. The blood glucose concentrations during the expulsive stage of farrowing were greater (P < 0.05) in the SUP group than for sows from the CON group. In conclusion, supplying modern hyperprolific sows energy on the expected day of farrowing is a valuable nutritional intervention to improve the farrowing kinetics and piglets' performance in early life.


The Store and Treat process for sludge liquor management.
Process sewage from sludge dewatering is particularly suitable for separate partial-flow treatment owing to its highly concentrated components and mostly elevated temperature. The procedures normally foreseen are those offering an effective treatment plant discharge based on a simple operating method and at low cost. With the Store and Treat process developed by Hamburger Stadtentwässerung existing sludge liquor basins can be used for an additional biological partial-flow treatment at reasonable cost without abandoning the advantage of quantity management.


Three-week bright-light intervention has dose-related effects on threat-related corticolimbic reactivity and functional coupling.
Bright-light intervention is reported to successfully treat depression, in particular seasonal affective disorder, but the neural pathways and molecular mechanisms mediating its effects are unclear. An amygdala-prefrontal cortex corticolimbic circuit regulates responses to salient environmental stimuli (e.g., threat) and may underlie these effects. Serotonin signaling modulates this circuit and is implicated in the pathophysiology of seasonal and other affective disorders. We evaluated the effects of a bright-light intervention protocol on threat-related corticolimbic reactivity and functional coupling, assessed with an emotional faces functional magnetic resonance imaging paradigm at preintervention and postintervention. In a double-blind study conducted in the winter, 30 healthy male subjects received bright-light intervention (dose range between participants: .1-11.0 kilolux) for 30 minutes daily over a period of 3 weeks. Additionally, we considered serotonin transporter-linked polymorphic region (5-HTTLPR) genotype status as a model for differences in serotonin signaling and moderator of intervention effects. Bright-light dose significantly negatively affected threat-related amygdala and prefrontal reactivity in a dose-dependent manner. Conversely, amygdala-prefrontal and intraprefrontal functional coupling increased significantly in a dose-dependent manner. Genotype status significantly moderated bright-light intervention effects on intraprefrontal functional coupling. This is the first study to evaluate the effects of clinically relevant bright-light intervention on threat-related brain function. We show that amygdala-prefrontal reactivity and communication are significantly affected by bright-light intervention, an effect partly moderated by genotype. These novel findings support that this threat-related corticolimbic circuit is sensitive to light intervention and may mediate the therapeutic effects of bright-light intervention.


The Burden and Visit Prevalence of Pediatric Chronic Rhinosinusitis.
Objectives Pediatric chronic rhinosinusitis has a substantial impact, but its epidemiology has yet to be elucidated. Our objectives were (1) to determine the associated national visit burden and (2) to assess its frequency relative to other frequent childhood otolaryngological illnesses. Study Design Analysis of national survey databases. Setting Ambulatory care settings in the United States, 2005 to 2012. Subjects and Methods Cases with a diagnosis of chronic rhinosinusitis were assessed in total and as a proportion of all visits reported in National Ambulatory Medical Care Surveys. To place these data into context, results for acute rhinosinusitis, allergic rhinitis, upper respiratory tract infection, and otitis media were also extracted and compared. Data specific to individual age group and calendar year were assessed. Results Chronic rhinosinusitis accounted for 5.6 million visits per annum (range, 3.7-7.5 million) among patients 0 to 20 years of age. Children in the >5- to 10-year-old and >10- to 15-year-old age groups were more likely to be affected ( P < .001). Among all visits, chronic rhinosinusitis was diagnosed in 2.1% (95% confidence interval [CI], 1.9%-2.4%), acute rhinosinusitis in 0.6% (95% CI, 0.5%-0.7%), allergic rhinitis in 2.6% (95% CI, 2.3%-2.8%), upper respiratory tract infection in 8.0% (95% CI, 7.5%-8.4%), and otitis media in 6.7% (95% CI, 6.5%-7.1%). Chronic rhinosinusitis visits were significantly more prevalent than for acute rhinosinusitis (relative risk, 3.40; 95% CI, 2.70-4.10; P < .0001). Among those >15 to 20 years of age, chronic rhinosinusitis was 2.18-fold (95% CI, 1.65-2.70) more frequently diagnosed than otitis media. Conclusions The visit burden from pediatric chronic rhinosinusitis exceeds that of acute rhinosinusitis and equals the burden from allergic rhinitis.


Differential characteristics of primary infection and re-infection can cause backward bifurcation in HCV transmission dynamics.
Backward bifurcation, a phenomenon typically characterized by the co-existence of multiple stable equilibria when the associated reproduction number of the model is less than unity, has been observed in numerous disease transmission models. This study establishes, for the first time, the presence of this phenomenon in the transmission dynamics of hepatitis C virus (HCV) within an IDU population. It is shown that the phenomenon does not exist under four scenarios, namely (i) in the absence of re-infection, (ii) in the absence of differential characteristics of HCV infection (with respect to infectivity, progression, treatment and recovery) between re-infected individuals and primary-infected individuals, (iii) when re-infected and treated individuals do not transmit HCV infection and (iv) when the average infectivity-adjusted duration of re-infection is less than that of primary infection. This study identifies, using sensitivity analysis, five parameters of the model that have the most influence on the disease transmission dynamics, namely: effective contact rate, progression rate from acute to chronic infection, recovery rate from acute infection, natural death rate and the relative infectiousness of chronically-infected individuals. Numerical simulations of the model show that the re-infection of recovered individuals has marginal effect on the HCV burden (as measured in terms of the cumulative incidence and the prevalence of the disease) in the IDU community. Furthermore, treatment of infected IDUs, even for small rate (such as 4%), offers significant impact on curtailing HCV spread in the community.


Adjuvant Chemotherapy Is Associated With Improved Survival in Locally Invasive Node Negative Non-Small Cell Lung Cancer.
The objectives of this study are to explore factors that are associated with use of adjuvant chemotherapy and to evaluate its impact on overall survival in node-negative patients who undergo lung and chest wall resection for non-small cell lung cancer (NSCLC). Patients who underwent concomitant lung and chest wall resection for NSCLC were abstracted from the National Cancer Database. Clinical, pathologic, treatment, and follow-up data were obtained. Patients with pathologic nodal metastases or patients who received any radiation treatment were excluded, and the cohort was dichotomized based on administration of adjuvant postoperative chemotherapy. Between 1998 and 2010, 824 patients met the inclusion criteria. This cohort exclusively consisted of pT3 N0 patients who did not receive any induction treatment or adjuvant radiation treatment. Adjuvant chemotherapy was administered to 255 patients (31%). Patients in the chemotherapy group were younger and had shorter inpatient length of stay. Both groups had similar comorbidities, tumor size, unplanned readmission rate, and incomplete resection rate. In multivariable analysis, younger age and shorter length of stay were associated with a greater likelihood of receiving adjuvant chemotherapy. Adjuvant chemotherapy was associated with improved survival (hazard ratio 0.74, 95% CI: 0.6 to 0.9), whereas increasing age, white race, length of inpatient stay, tumor size, and residual tumor were independently associated with greater risk of death. Patients who undergo lobectomy with chest wall resection for locally advanced NSCLC should be strongly considered for postoperative adjuvant chemotherapy even in the absence of nodal disease. Actual selection of patients for adjuvant chemotherapy is affected by perioperative factors.


Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice.
Mutations in SPG4, encoding the microtubule-severing protein spastin, are responsible for the most frequent form of hereditary spastic paraplegia (HSP), a heterogeneous group of genetic diseases characterized by degeneration of the corticospinal tracts. We previously reported that mice harboring a deletion in Spg4, generating a premature stop codon, develop progressive axonal degeneration characterized by focal axonal swellings associated with impaired axonal transport. To further characterize the molecular and cellular mechanisms underlying this mutant phenotype, we have assessed microtubule dynamics and axonal transport in primary cultures of cortical neurons from spastin-mutant mice. We show an early and marked impairment of microtubule dynamics all along the axons of spastin-deficient cortical neurons, which is likely to be responsible for the occurrence of axonal swellings and cargo stalling. Our analysis also reveals that a modulation of microtubule dynamics by microtubule-targeting drugs rescues the mutant phenotype of cortical neurons. Together, these results contribute to a better understanding of the pathogenesis of SPG4-linked HSP and ascertain the influence of microtubule-targeted drugs on the early axonal phenotype in a mouse model of the disease.


Management of symptomatic sacral perineural cysts with microsurgery and a vascularized fasciocutaneous flap.
The optimal treatment of symptomatic perineural (Tarlov) cysts is controversial. Numerous surgical techniques have been proposed with conflicting results. A series of Tarlov cysts treated with a novel surgical approach is presented. Patients with surgically treated symptomatic perineural cysts during 2013-2016 were included. The main indications for surgery were persistent radicular symptoms, pelvic pain, urinary and/ or bowel disturbances. At surgery, the cyst was opened and fenestrated. The cyst wall was then closed with packing, fibrin glue and a pedicled vascularized fasciocutaneous flap rotated into the area for obliteration of the dead space. Patients were followed-up with clinical visits and repeat magnetic resonance imaging (MRI) scans. Seven consecutive patients were included. The mean age was 50.3 years (range, 25-80 years) and the mean duration of symptoms was 49.3 months (range, 3-130 months). With one exception, all patients had urine and/or bowel problems (incontinence) preoperatively. A lumbar drain was inserted in five patients. The mean follow-up period was 15.4 months. Symptoms improved in 4/7 patients, in two cases no clinical difference was noted while one patient deteriorated. In two cases, a spinal cord stimulator was eventually implanted. In all seven cases, a significantly decreased cyst size was noted on MRI. Cyst fenestration and the use of a vascularized fasciocutaneous flap successfully obliterated all cysts, with satisfactory clinical efficacy. Larger and comparative studies are warranted to clarify the long-term effects of this surgical technique in patients with symptomatic Tarlov cysts.


High risk and little knowledge: overdose experiences and knowledge among young adult nonmedical prescription opioid users.
Opioid-involved overdoses in the United States have dramatically increased in the last 15 years, largely due to a rise in prescription opioid (PO) use. Yet few studies have examined the overdose knowledge and experience of nonmedical PO users. In depth, semi-structured, audio-recorded interviews were conducted with 46 New York City young adults (ages 18-32) who reported using POs nonmedically within the past 30 days. Verbatim interview transcripts were coded for key themes in an analytic process informed by grounded theory. Despite significant experience with overdose (including overdose deaths), either personally or within opioid-using networks, participants were relatively uninformed about overdose awareness, avoidance and response strategies, in particular the use of naloxone. Overdose experiences typically occurred when multiple pharmaceuticals were used (often in combination with alcohol) or after participants had transitioned to heroin injection. Participants tended to see themselves as distinct from traditional heroin users, and were often outside of the networks reached by traditional opioid safety/overdose prevention services. Consequently, they were unlikely to utilize harm reduction services, such as syringe exchange programs (SEPs), that address drug users' health and safety. These findings suggest that many young adult nonmedical PO users are at high risk of both fatal and non-fatal overdose. There is a pressing need to develop innovative outreach strategies and overdose prevention programs to better reach and serve young PO users and their network contacts. Prevention efforts addressing risk for accidental overdose, including opioid safety/overdose reversal education and naloxone distribution, should be tailored for and targeted to this vulnerable group.


Risk of single and combined exposure of birds to non-steroidal anti-inflammatory drugs and lead.
Pharmaceuticals and heavy metals such as diclofenac and lead, respectively, have been identified as environmental contaminants toxic to birds and posing serious threats to declining populations of raptors worldwide. The aim of the present study was to test the hypothesis that a sublethal combination of non-steroidal anti-inflammatory drugs and lead induces more pronounced effects than single exposures in birds. A total of 40 Japanese quails (Coturnix coturnix japonica) at the age of 2 months and average weight of 180g were on a random basis divided into four experimental groups of 10 specimens (i.e., control, diclofenac, lead, and lead+diclofenac exposures). Six lead shots in the total weight of 1.5 grams were inserted into the crop on day 0 of the experiment, while a total of 5 mg/kg of diclofenac administered intramuscularly were divided into treatments on days 0 and 5. Group responses were compared using haematology and biochemistry after 10 days. There was no mortality in control and both single and combined diclofenac and lead exposure groups, nor did the birds show any clinical signs of intoxication. Univariate analyses of blood parameters yielded a decrease in haematocrit in birds exposed to both substances when compared with the control, a lower haemoglobin level of the lead-exposed group, increased activity of aspartate aminotransferase in the NSAIDs-exposed group, increased activity of alkaline phosphatase in birds exposed to a combination of diclofenac and lead, and a higher phosphorus level in the lead-exposed group. The principal component analysis revealed no multivariate pattern of responses of blood parameters and did not allow separation of exposure groups from controls when the variables and samples were projected onto a two dimensional space. Results of the present study can enhance understanding of combination toxicity of veterinary drugs and heavy metals in birds, i.e. a scenario that has become environmentally relevant in recent decades. Fortunately, individual blood parameter effects prevailed and no joint mortal effects were recognised in Japanese quails exposed to a combination of sublethal doses of diclofenac and lead.


Etiology, clinical presentation, and outcome of children with fulminant hepatic failure: Experience from a tertiary center in Pakistan.
To determine etiologies, clinical presentations and outcomes of children with fulminant hepatic failure in the first liver transplant center of Pakistan. It was a retrospective, observational study, conducted in Paediatric Gastroenterology Department of Shifa International Hospital. Patients between one month to 16 years were included who fulfilled the Pediatric Acute Liver Failure study group (PALFSG) definition of acute liver failure as biochemical evidence of liver injury with no known co-existing chronic liver disease, coagulopathy not corrected by vitamin K, an International Normalized Ratio (INR) greater than 1.5 if the patient has encephalopathy, or greater than 2.0 if the patient does not have encephalopathy. The data collected was recorded on a self-constructed proforma after IRB approval. There were 28 patients in the study which ncluded 17 males and 11 females with a mean age of 72.86±52.50 months. The most common etiologies were Hepatitis A (29%) in isolation or co-infection with Wilson Disease, typhoid fever. It was followed by seronegative hepatitis (29%). Majority (64%) had acute presentation (7 to 28 days), jaundice (82%) being the most common symptom. Severity of encephalopathy was significantly associated with outcome (p=0.02). There were 6 (21%) patients who succumbed to death. The study highlights infective diseases as the predominant etiology causing fulminant liver failure in children. Our study highlights lower mortality in children.


Physiologically based pharmacokinetic model for cefazolin in rabbits and its preliminary extrapolation to man.
In the present study, the physiologically based pharmacokinetic model, which succeeded previously in predicting the pharmacokinetics of beta-lactam antibiotics in rats [A. Tsuji, T. Yoshikawa, K. Nishide, H. Minami, M. Kimura, E. Nakashima, T. Terasaki, E. Miyamoto, C.H. Nightingale, and T. Yamana: Physiologically based pharmacokinetic model for beta-lactam antibiotics. I: tissue distribution and elimination in rats. J. Pharm. Sci. 72, 1239-1252 (1983)], was applied to cefazolin pharmacokinetics in rabbits and man. After iv bolus dosing in normal rabbits, the time courses of cefazolin concentration in plasma and various tissues (lung, heart, muscle, skin, bone, gut, liver, and kidney) were found to be very similar to those in rats. The values of physiological parameters (tissue plasma flows, tissue volumes, tissue/plasma albumin ratio) and biochemical parameters determined in this study (for nonlinear plasma protein binding, intrinsic renal clearance of active secretion and reabsorption) were incorporated into mass balance equations derived from the model. There was reasonable agreement between the model predictions and the observed data for cefazolin and inulin in rabbits. The model was also successful in the prediction of cefazolin disposition in rabbits with renal failure. Using available information reported for cefazolin in man, a preliminary extrapolation from the present model was attempted, and the overall predicted results after iv administration of 1 g cefazolin in man were compared with the serum and bone tissue data. The length of the effective antibacterial period for the drug is also discussed in terms of its predicted concentration unbound with proteins in various tissue interstitial fluids in man.


Effects of regulation on methadone and buprenorphine provision in the wake of Hurricane Sandy.
Hurricane Sandy led to the closing of many major New York City public hospitals including their substance abuse clinics and methadone programs, and the displacement or relocation of thousands of opioid-dependent patients from treatment. The disaster provided a natural experiment that revealed the relative strengths and weaknesses of methadone treatment in comparison to physician office-based buprenorphine treatment for opioid dependence, two modalities of opioid maintenance with markedly different regulatory requirements and institutional procedures. To assess these two modalities of treatment under emergency conditions, semi-structured interviews about barriers to and facilitators of continuity of care for methadone and buprenorphine patients were conducted with 50 providers of opioid maintenance treatment. Major findings included that methadone programs presented more regulatory barriers for providers, difficulty with dose verification due to impaired communication, and an over reliance on emergency room dosing leading to unsafe or suboptimal dosing. Buprenorphine treatment presented fewer regulatory barriers, but buprenorphine providers had little to no cross-coverage options compared to methadone providers, who could refer to alternate methadone programs. The findings point to the need for well-defined emergency procedures with flexibility around regulations, the need for a central registry with patient dose information, as well as stronger professional networks and cross-coverage procedures. These interventions would improve day-to-day services for opioid-maintained patients as well as services under emergency conditions.


The effect of talker- and listener-related factors on intelligibility for a real-word, open-set perception test.
The aims of this study were to evaluate whether talker intelligibility is consistent across listeners differing in age and gender and to investigate the process of attunement to talker characteristics in children and adults. Word intelligibility rates were obtained from 135 listeners (adults, 11-12-year-olds, and 7-8-year-olds) for 45 talkers from a homogeneous accent group. There were 2 test conditions, each containing multiple talkers. Both test conditions contained multiple talkers. In the single-word condition, key words were presented in isolation, whereas in the triplet condition, triplets of key words were preceded by a precursor sentence by the same talker. For identical word materials, word intelligibility at a signal-to-noise ratio of +6 dB varied significantly across talkers from 81.2% to 96.4%. Overall, younger listeners made significantly more errors than older children or adults, and women talkers were more intelligible than other classes of talkers. The relative intelligibility of the 45 talkers was highly consistent across listener groups, suggesting that talker intelligibility is primarily determined by talker-related factors rather than by the interrelation of talker- and listener-related factors. The presence of a precursor sentence providing indexical information did improve word intelligibility for the bottom quartile of listeners in each of the listener groups.


Review: In vivo models for defining molecular subtypes of the primitive neuroectodermal tumor genome: current challenges and solutions.
Primitive neuroectodermal tumors (PNET) of the brain include medulloblastoma (MB) and central nervous system primitive neuroectodermal tumor (CNS PNET) subtypes, which share histological features yet differ at the genomic level and in clinical outcome. Delineation of the genetic anomalies between PNET subtypes is a current challenge for establishing effective targeted therapeutic strategies against these aggressive tumors. Current efforts have demonstrated that specific molecular pathways drive a subset of MB and CNS PNET, but the genetic basis for the deadliest forms of these tumors remains poorly understood and anecdotal. This is in part due to an overall lack of biologically relevant in vivo and in vitro model systems capable of direct comparison and identification of the genetic origins among PNET subtypes. Forward genetic, random mutagenesis in mice is an effective phenotype-driven method to model the genetic origins of human disease including cancer. We have applied this method to PNET by developing a single Sleeping Beauty transposon insertional mutagenesis mouse model that recapitulates the morphological similarities and genetic heterogeneity of MB and CNS PNET capable of identifying genetic drivers important for genesis of PNET. Importantly, this model has allowed new PNET phenotypes to be observed and is designed to reveal biologically relevant candidate oncogenes and tumor suppressor genes for MB and CNS PNET molecular subgroups in mice and humans. The ultimate goal of the approach we have taken is to uncover new understanding of the genetic basis for MB and CNS PNET development, how they are distinguished from each other, and offer potential targets for therapeutic testing to improve patient clinical outcome.


Analysis of cephalometrics for orthognathic surgery: Determination of norms applicable to Rajasthani population.
To determine the hard tissue surgical cephalometric norms statistically and geometrically in well-balanced faces having clinically acceptable facial profile in the Rajasthan population. To compare the cephalometric analyses of Rajasthanis males and females and to compare the craniofacial pattern of Rajasthani population with Caucasian norms. Lateral cephalograms of 200 subjects (100 males and 100 females) in the age group of 18-25 years, class I malocclusion and acceptable facial profile were obtained. Cephalometric analysis was performed and studied. The study revealed that parameters, such as all horizontal skeletal parameters, PNS-N, PNS-ANS, Ar-Go, Go-Pg and upper OP to HP angle show no statistical significant difference between Rajasthani males and females. When comparing Rajasthani males and Caucasian males, the study suggested statistically significant difference in the mean values of parameters, such as PTM-N, L1-MP, 6-MP, Go-Pog, B-Pog, Ar-Go-Gn, U1 to NF and L1 to MP. When comparing Rajasthani females and Caucasian females, the study revealed no statistically significant difference between the mean values of parameters, such as N-A-Pg, N-A, N-B, L1-MP, Ar-Go-Gn, upper OP to HP angle and AB-OP and rest of the parameters showed highly significant difference between Caucasian females and Rajasthani females. This study indicates that Rajasthani population has a bimaxillary protrusion with predominant tendency toward horizontal growth pattern of the mandible and this tendency is further exaggerated in females. Rajasthani females also showed an increased length of the anterior cranial base, maxilla and mandible and in dental parameters they showed increased maxillary dental height and both Males and females showed decreased mandibular dental height.


What threshold for adjuvant therapy in older breast cancer patients?
To consider the question of when to prescribe adjuvant treatment for elderly breast cancer patients, particularly when comorbidities are present. Knowledge of the threshold relapse risks above which adjuvant treatment is worth prescribing would enhance decision making. A Markov analysis of data from the medical literature was conducted. Patients aged 65 to 85 years were considered, along with three levels of comorbidity. The threshold risk of relapse at 10 years (RR10), at which time treatment provides absolute reduction or reduction of an absolute 1% in relapse or mortality, was evaluated. The threshold RR10 for an absolute reduction in mortality risk by adjuvant treatment was low through the age of 85 years. However, for an absolute 1% reduction, the effect of treatment on relapse and the effect of treatment on mortality increasingly diverged. The threshold RR10 for an absolute 1% reduction in relapse risk remained fairly low (5% to 6% for tamoxifen, 12% to 19% for chemotherapy). The threshold RR10 for an absolute 1% reduction in mortality risk, although starting close to the RR10 for an absolute 1% reduction in relapse risk, rose sharply. For tamoxifen, the difference between the two was 4% for an average 65-year-old, 6% at the age of 75 years, and 15% at the age of 85 years. For chemotherapy, the differences were 6%, 12%, and 30%, respectively. Similarly, thresholds increased with increasing comorbidity. In older and sicker patients, the maximum benefit was reached after 5 years rather than 10 years. Older breast cancer patients can expect a reduction in relapse that is fairly similar to that of younger patients. However, the effect on mortality diverges markedly, and attention should be paid to this difference in clinical decision making. Comorbidity should be considered in recommendations for adjuvant treatment, including clinical practice guidelines.


Substance P-immunoreactive nerves in the rat kidney.
An indirect immunohistochemical method in which an avidin-biotinylated horseradish peroxidase complex is bound to the secondary antibody was used to visualize substance P-immunoreactive (SPI) nerves in the rat kidney. Rats were perfused with 2% paraformaldehyde + 0.15% picric acid in 0.1 M phosphate buffer, then transferred to the buffer. After 24-48 h, the kidneys were sectioned with a Vibratome at 200 or 300 micron and incubated in the primary antiserum for 18 h at room temperature. A dense plexus of SPI nerves innervates the rat renal calyx. A small proportion of intrarenal SPI axons innervates interlobular arteries and afferent arterioles, but most perivascular SPI axons terminate on interlobar and arcuate arteries. The densest plexuses are located on segments of interlobar arteries near the hilus of the kidney. Some of these axons probably are nociceptive; others may be chemo- or baroreceptive.


Analysis of differentially methylated regions in great apes and extinct hominids provides support for the evolutionary hypothesis of schizophrenia.
The persistence of schizophrenia in human populations separated by geography and time led to the evolutionary hypothesis that proposes schizophrenia as a by-product of the higher cognitive abilities of modern humans. To explore this hypothesis, we used here an evolutionary epigenetics approach building on differentially methylated regions (DMRs) of the genome. We implemented a polygenic enrichment testing pipeline using the summary statistics of genome-wide association studies (GWAS) of schizophrenia and 12 other phenotypes. We investigated the enrichment of association of these traits across genomic regions with variable methylation between modern humans and great apes (orangutans, chimpanzees and gorillas; great ape DMRs) and between modern humans and recently extinct hominids (Neanderthals and Denisovans; hominid DMRs). Regions that are hypo-methylated in humans compared to great apes show enrichment of association with schizophrenia only if the major histocompatibility complex (MHC) region is included. With the MHC region removed from the analysis, only a modest enrichment for SNPs of low effect persists. The INRICH pipeline confirms this finding after rigorous permutation and bootstrapping procedures. The analyses of regions with differential methylation changes in humans and great apes do not provide compelling evidence of enrichment of association with schizophrenia, in contrast to our previous findings on more recent methylation differences between modern humans, Neanderthals and Denisovans. Our results further support the evolutionary hypothesis of schizophrenia and indicate that the origin of some of the genetic susceptibility factors of schizophrenia may lie in recent human evolution.


Construction of Versatile and Functional Nanostructures Derived from CO2 -based Polycarbonates.
The construction of amphiphilic polycarbonates through epoxides/CO2 coupling is a challenging aim to provide more diverse CO2 -based functional materials. In this report, we demonstrate the facile preparation of diverse and functional nanoparticles derived from a CO2 -based triblock polycarbonate system. By the judicious use of water as chain-transfer reagent in the propylene oxide/CO2 polymerization, poly(propylene carbonate (PPC) diols are successfully produced and serve as macroinitiators in the subsequent allyl glycidyl ether/CO2 coupling reaction. The resulting ABA triblock polycarbonate can be further functionalized with various thiols by radical mediated thiol-ene click chemistry, followed by self-assembly in deionized water to construct a versatile and functional nanostructure system. This class of amphiphilic polycarbonates could embody a powerful platform for biomedical applications.