A test of maternal programming of offspring stress response to predation risk in threespine sticklebacks.
Non-genetic maternal effects are widespread across taxa and challenge our traditional understanding of inheritance. Maternal experience with predators, for example, can have lifelong consequences for offspring traits, including fitness. Previous work in threespine sticklebacks showed that females exposed to simulated predation risk produced eggs with higher cortisol content and offspring with altered anti-predator behavior. However, it is unknown whether this maternal effect is mediated via the offspring glucocorticoid stress response and if it is retained over the entire lifetime of offspring. Therefore, we tested the hypothesis that maternal exposure to simulated predation risk has long-lasting effects on the cortisol response to simulated predation risk in stickleback offspring. We measured circulating concentrations of cortisol before (baseline), 15 min after, and 60 min after exposure to a simulated predation risk. We compared adult offspring of predator-exposed mothers and control mothers in two different social environments (alone or in a group). Relative to baseline, offspring plasma cortisol was highest 15 min after exposure to simulated predation risk and decreased after 60 min. Offspring of predator-exposed mothers differed in the cortisol response to simulated predation risk compared to offspring of control mothers. In general, females had higher cortisol than males, and fish in a group had lower cortisol than fish that were by themselves. The buffering effect of the social environment did not differ between maternal treatments or between males and females. Altogether the results show that while a mother's experience with simulated predation risk might affect the physiological response of her adult offspring to a predator, sex and social isolation have much larger effects on the stress response to predation risk in sticklebacks.


Increased steroid production by the ovarian stromal tissue of postmenopausal women with endometrial cancer.
An increase in ovarian steroid secretion could play a role in the pathogenesis of endometrial cancer in postmenopausal women. The present study was undertaken to investigate steroid production by isolated ovarian stromal tissues of postmenopausal women with endometrial cancer and to study the effect of LH and insulin on ovarian steroidogenesis in postmenopausal women. Ovarian stromal tissue was obtained from 10 postmenopausal women with endometrial cancer and 8 women without cancer. The stroma was incubated in either the medium alone or the medium to which was added LH (50 ng/mL) or insulin (500 ng/mL). The ovarian stroma of postmenopausal women with cancer released significantly more androstenedione (A), testosterone, and dehydroepiandrosterone than that of women without cancer. Addition of LH resulted in a significant increase in A, testosterone, dehydroepiandrosterone, and progesterone release compared to that with vehicle alone. Addition of insulin stimulated the release of A from the ovarian stroma of women with cancer, but had no effect on the normal postmenopausal ovarian stroma. These results indicate that the ovarian stroma of postmenopausal women with endometrial cancer secrete significantly greater amounts of androgens than those of women without cancer and that both LH and insulin may be important factors contributing to this increase in ovarian steroidogenesis.


Epigenetic choreographers of neurogenesis in the adult mammalian brain.
Epigenetic mechanisms regulate cell differentiation during embryonic development and also serve as important interfaces between genes and the environment in adulthood. Neurogenesis in adults, which generates functional neural cell types from adult neural stem cells, is dynamically regulated by both intrinsic state-specific cell differentiation cues and extrinsic neural niche signals. Epigenetic regulation by DNA and histone modifiers, non-coding RNAs and other self-sustained mechanisms can lead to relatively long-lasting biological effects and maintain functional neurogenesis throughout life in discrete regions of the mammalian brain. Here, we review recent evidence that epigenetic mechanisms carry out diverse roles in regulating specific aspects of adult neurogenesis and highlight the implications of such epigenetic regulation for neural plasticity and disorders.


Characteristics and distribution research on extracellular polymer substance extracted from sewage sludge.
Extracellular polymer substance (EPS) is an important substance in sludge dewatering process and can be divided into slime, loosely bound EPS(LB-EPS) and tightly bound EPS(TB-EPS). The major components in different EPS layers in mechanical dewatered sludge (sample D) and sludge from thickening tank (sample U) were analyzed in the study. Results showed that, for all sludge samples, protein content in slime was much higher than that in LB-EPS and TB-EPS. In addition, from the results of total EPS content in four sludge samples (U: 98.68 mg gvss⁻¹, US (sample U+SDS): 135.27 mg gvss⁻¹, D:138.16 mg gvss⁻¹, DS:211.21 mg gvss⁻¹), it was found that sodium dodecyl sulfate (SDS) extracted more EPS content from sludge, which proved that SDS might cause substantial release of EPS, especially PN from sludge. Increase PS content in LB-EPS, and TB-EPS as addition of SDS, implied sensibility of cells in sludge to SDS. Differential Scanning Calorimetry found that bound water proportion in four different sludge samples ranged as follows: as D>DS>US>U. Results from other analytical techniques,such as FTIR and NMR, were also given the supported proof for the distribution changes of EPS and bound water.


Characteristics of normal stromal components and their correlation with cancer occurrence in human prostate.
Prostate cancer is one of the most common age-related malignancies. The occurrence frequency of prostate cancer is very different according to prostate zones. The prostate stroma is an important element in growth and differentiation of the normal prostate and also has a close relationship to the occurrence of benign prostatic hypertrophy and cancer. We examined 14 cases of normal prostate tissues obtained at autopsy and 11 cases of prostate cancer tissues at radical prostatectomy specimens with cancers for clarifying the characteristics of stromal components in the normal prostate and the correlation between the stroma and the occurrence of prostate cancers. Stromal cells, such as smooth muscle cells, myofibroblasts and fibroblasts were identified by immunohistochemistry (IHC). Connective tissue fibers were detected by Elastica van Gieson and also IHC stain. Quantitative analysis of the smooth muscle tissue and connective tissue fibers were performed using a computer image analyzer system. In the normal prostate, stromal components varied in each zone. Every zone of the prostate contained smooth muscle cells, myofibroblasts, fibroblasts and collagen fibers. Elastic fibers were clearly visible in the transition zone. Smooth muscle cells were the main stromal component but less numerous in the frequent occurrence zone (peripheral zone) of prostate cancer (p<0.05). Myofibroblasts and fibroblasts were found either in normal or cancer tissues, although a few in number. The increase of collagen fibers accompanied decrease of smooth muscle cells as prostate cancer grade increased (p<0.05). The characteristics of stromal components and their amounts in the normal prostate appear to correlate with a distinct predilection for cancer occurrence in the peripheral zone and a weak stromal reaction in prostate cancers.


Human albumin enhances expression of vascular endothelial growth factor in cultured human luteinizing granulosa cells: importance in ovarian hyperstimulation syndrome.
Ovarian hyperstimulation syndrome (OHSS) is a severe complication of ovarian stimulation for assisted reproductive techniques. Clinical manifestations are massive extravascular fluid accumulation and haemoconcentration. Vascular endothelial growth factor (VEGF) has been demonstrated to mediate the development of OHSS. Intravenous albumin at the time of oocyte aspiration has been suggested as an effective prophylactic treatment against the occurrence of severe OHSS. Here it is reported that in cultured human luteinizing granulosa cells, VEGF mRNA expression was enhanced by human albumin and maximum expression was observed in cultured granulosa cells obtained from patients with serum oestradiol concentrations >2000 pg/ml on the day of human chorionic gonadotrophin injection (P < 0. 05).


A Highly K(+)-Selective Two-Photon Fluorescent Probe.
A highly K(+)-selective two-photon fluorescent probe for the in vitro monitoring of physiological K(+) levels in the range of 1-100 mM is reported. The two-photon excited fluorescence (TPEF) probe shows a fluorescence enhancement (FE) by a factor of about three in the presence of 160 mM K(+), independently of one-photon (OP, 430 nm) or two-photon (TP, 860 nm) excitation and comparable K(+)-induced FEs in the presence of competitive Na(+) ions. The estimated dissociation constant (Kd ) values in Na(+)-free solutions (Kd (OP) =(28±5) mM and Kd (TP)=(36±6) mM) and in combined K(+)/Na(+) solutions (Kd (OP) =(38±8) mM and Kd (TP)=(46±25) mM) reflecting the high K(+)/Na(+) selectivity of the fluorescent probe. The TP absorption cross-section (σ2PA ) of the TPEF probe+160 mM K(+) is 26 GM at 860 nm. Therefore, the TPEF probe is a suitable tool for the in vitro determination of K(+).


A Retrospective Analysis of Full-face Dermal Filler Treatments: Product Choice, Volume Use, and Treatment Locations.
OBJECTIVE: The Vycross™ range of hyaluronic acid (HA) fillers supports a full-face approach to facial rejuvenation. It is important to understand how much filler can be safely injected and which products to use where, particularly for injectors who are new to this range. This study assessed whether Vycross fillers can be effectively and safely used in larger quantities and tracked real-world usage across facial zones. METHODS: This was a single-center, retrospective analysis set in normal clinical practice. The study included 66 consecutive adult female patients undergoing full-face rejuvenation with Vycross fillers within a single treatment plan guided by MD Codes. Filler usage and location were noted, and any adverse events were recorded. RESULTS: The mean age was 48.0 years, and median time from consultation to first filler usage was 18 days. Most patients (n=40; 60.6%) had only one filler session. Forty-seven patients (71.2%) also received botulinum toxin type A. In total, 309 filler syringes were used (mean: 4.7 per patient). Sixteen (5.2%), 181 (58.6%), and 112 (36.2%) syringes were used in the upper, mid and lower face, respectively. In the upper and midface, the majority was Voluma (15/16 and 120/181 syringes, respectively). In the lower face, filler use was split across Voluma, Volift and Volbella (41, 44 and 27 syringes, respectively). Five adverse events were reported at three weeks (swelling, n=2; asymmetry, n=2; lumps, n=1). All were easily resolved. No delayed events were reported. CONCLUSION: Substantial volumes of Vycross fillers can be effectively and safely used as part of a full-face approach to facial rejuvenation.


Intrathecal administration of cyclic AMP response element-binding protein-antisense oligonucleotide attenuates neuropathic pain after peripheral nerve injury and decreases the expression of N-methyl-D-aspartic receptors in mice.
The aim of the present study was to determine whether the cAMP response element binding protein (CREB) contributes to neuropathic pain during development stage. Adult (7-8 weeks old) male C57BL/6 mice weighing 20-25 g were used. Intrathecal catheter implantation and chronic constriction of the sciatic nerve of the animals were performed. Western blotting and reverse transcription PCR experiments were carried out. Our study demonstrated that the expression of spinal NMDAR after peripheral nerve injury was modulated by central CREB. Chronic constriction nerve injury (CCI) in mice induced thermal hyperalgesia and mechanical allodynia. The increase of NR1 and NR2B subunits of the NMDAR was significantly diminished by intrathecal administration of the CREB antisense oligonucleotide against CREB and pCREB. Additionally, nociceptive behavior induced by CCI was attenuated by intrathecal administration of the CREB antisense oligonucleotide during the period of injection, and the above effects of relieving pain lasted at least 12 days following the last injection. Our results suggested that central functional pCREB may contribute to the development of neuropathic pain and regulate the expression of the NR1 and NR2B subunits of the NMDAR in the process.


Three-dimensional solutions of the Boltzmann equation: heat transport at long mean free paths.
A kinetic transport model for arbitrary meshes is presented and the method is applied to heat transfer in a rare gas between parallel plates at different temperatures. The method uses "propagating" rays for tracking the transport of particles throughout the phase space in three-dimensional spatial meshes. Two collision operators are tested with the model, a simple monoenergetic operator and the Bhatnagar-Gross-Krook (BGK) model. Results are generated for several Knudsen numbers in the transition regime. The results of the kinetic simulation, which employ the BGK operator, compare favorably with those of a finite-difference solution of the Boltzmann equation using the BGK collision operator [T. Ohwada, Phys. Fluids 8, 2153 (1996)]. In addition, the results for both collision models exhibit fair agreement with experimental data of Teagan and Springer [Phys. Fluids. 11, 497 (1968)].


Phthalate metabolites in obese individuals undergoing weight loss: Urinary levels and estimation of the phthalates daily intake.
Human exposure to chemicals commonly encountered in our environment, like phthalates, is routinely assessed through urinary measurement of their metabolites. A particular attention is given to the specific population groups, such as obese, for which the dietary intake of environmental chemicals is higher. To evaluate the exposure to phthalates, nine phthalate metabolites (PMs) were analyzed in urine collected from obese individuals and a control population. Obese individuals lost weight through either bariatric surgery or a conservative weight loss program with dietary and lifestyle counseling. Urine samples were also collected from the obese individuals after 3, 6 and 12months of weight loss. Individual daily intakes of the corresponding phthalate diesters were estimated based on the urinary PM concentrations. A high variability was recorded for the levels of each PM in both obese and control urine samples showing the exposure to high levels of PMs in specific subgroups. The most important PM metabolite as percentage contribution to the total PM levels was mono-ethyl phthalate followed by the metabolites of di-butyl phthalate and di 2-ethyl-hexyl phthalate (DEHP). No differences in the PM levels and profiles between obese entering the program and controls were observed. Although paralleled by a significant decrease of their weight, an increase in the urinary PM levels after 3 to 6months loss was seen. Constant figures for the estimated phthalates daily intake were observed over the studied period, suggesting that besides food consumption, other human exposure sources to phthalates (e.g. air, dust) might be also important. The weight loss treatment method followed by obese individuals influenced the correlations between PM levels, suggesting a change of the intake sources with time. Except for few gender differences recorded between the urinary DEHP metabolites correlations, no other differences were observed for the urinary PM levels as a function of age, body mass index or waist circumference. Linear regression analysis showed almost no significance of the relationship between measured urinary PMs and serum free thyroxine, thyroid-stimulating hormone (TSH) for all obese individuals participating to the study, while for the control samples, several PMs were significantly associated with the serum TSH levels.


cis-Resveratrol produces anti-inflammatory effects by inhibiting canonical and non-canonical inflammasomes in macrophages.
Resveratrol, a natural phenolic compound found in red grapes and wine, exists as cis and trans isomers. Recent studies have shown that trans-resveratrol possesses anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-tumor and immunomodulatory properties. However, it remains unclear whether cis-resveratrol may exhibit similar activities. The objective of the present study was to examine the effects of cis- and trans-resveratrol on the production of pro-inflammatory cytokines and mediators in human macrophages. We examined the possibility that cis- and trans-resveratrol may affect cytokine secretion by modulating inflammasomes, intracellular multi-protein complexes, the assembly of which leads to caspase-1 activation and secretion of active IL-1β by macrophages. Our results show that pre-treatment of macrophages with cis-resveratrol not only reduces pro-IL-1β production and IL-1β secretion, but also suppresses ATP-induced transcription and activation of caspase-1 and caspase-4. Notably, cis-resveratrol inhibits the expression of the purinergic receptor, P2X(7)R, and the endoplasmic reticulum stress marker, Glc-regulated protein 78, but also reduces reactive oxygen species production. Moreover, cis-resveratrol attenuates cyclooxygenase-2 expression and prostaglandin E2 production. cis-Resveratrol also decreases the phosphorylation of p38 MAPK and expression of the c-Jun protein. These results indicate that cis-resveratrol produces anti-inflammatory effects by inhibiting both the canonical and non-canonical inflammasomes, and associated pathways in human macrophages.


Studies of the reactions of tripodal pyridine-containing ligands with Re(CO)5Br leading to rheniumtricarbonyl complexes with potential biomedical applications.
The complexes formed from the reaction of N-acylated tris-(pyridin-2-yl)methylamine (LH) with [Re(CO)(5)Br] depend on the structure of the ligand and the reaction conditions. Thus, while N-[1,1,1-tris-(pyridin-2-yl)methyl]acetamide coordinates through the three pyridine nitrogens to give a stable cationic complex [LHRe(CO)(3)Br], the analogous N-benzoyl ligand reacts under similar conditions to give a neutral complex [LRe(CO)(3)] with coordination through two pyridine nitrogens and a deprotonated amide. To try to explain these different outcomes, the reactions of some structurally related N-acylated [1,1-bis(pyridin-2-yl)]methylamines (L'H) with [Re(CO)(5)Br] have been studied and the reaction pathways identified. These studies indicate that a neutral complex [L'HRe(CO)(3)Br] is initially formed in which the amide portion of the ligand is uncoordinated, but that this complex under appropriate conditions then rearranges to give a cationic complex [L'HRe(CO)(3)]Br in which the coordinated amide nitrogen either remains protonated or is present in its imidic acid tautomeric form. Elimination of HBr from these complexes either thermally or in the presence of base then gives stable neutral complexes [L'Re(CO)(3)]. The impact of the N-acyl group and any substituent at the apex of the tripodal ligands (L''H) on the relative stabilities of intermediate complexes on the reaction pathway helps provide an explanation for the observed difference in behaviour of the N-acylated tris(pyridin-2-yl)methylamines (LH).


Background field removal technique using regularization enabled sophisticated harmonic artifact reduction for phase data with varying kernel sizes.
An effective background field removal technique is desired for more accurate quantitative susceptibility mapping (QSM) prior to dipole inversion. The aim of this study was to evaluate the accuracy of regularization enabled sophisticated harmonic artifact reduction for phase data with varying spherical kernel sizes (REV-SHARP) method using a three-dimensional head phantom and human brain data. The proposed REV-SHARP method used the spherical mean value operation and Tikhonov regularization in the deconvolution process, with varying 2-14mm kernel sizes. The kernel sizes were gradually reduced, similar to the SHARP with varying spherical kernel (VSHARP) method. We determined the relative errors and relationships between the true local field and estimated local field in REV-SHARP, VSHARP, projection onto dipole fields (PDF), and regularization enabled SHARP (RESHARP). Human experiment was also conducted using REV-SHARP, VSHARP, PDF, and RESHARP. The relative errors in the numerical phantom study were 0.386, 0.448, 0.838, and 0.452 for REV-SHARP, VSHARP, PDF, and RESHARP. REV-SHARP result exhibited the highest correlation between the true local field and estimated local field. The linear regression slopes were 1.005, 1.124, 0.988, and 0.536 for REV-SHARP, VSHARP, PDF, and RESHARP in regions of interest on the three-dimensional head phantom. In human experiments, no obvious errors due to artifacts were present in REV-SHARP. The proposed REV-SHARP is a new method combined with variable spherical kernel size and Tikhonov regularization. This technique might make it possible to be more accurate backgroud field removal and help to achive better accuracy of QSM.


Lower GDNF Serum Level Is a Possible Risk Factor for Constipation in Patients With Parkinson Disease: A Case-Control Study.
Background: Constipation is a significant symptom of Parkinson's disease (PD). Glial-derived neurotrophic factor (GDNF) is important for the morphogenesis of the enteric nervous system and plays a critical role in the preservation of mucosal integrity under enteric glia surveillance. The aim of this work was to evaluate the serum levels of GDNF in patients with PD with and without constipation. Methods: This work included 128 patients with PD. The patients were classified into three groups: those with PD but no constipation (nCons-PD) (n = 49), those with prodromal stage constipation (Cons-Pro-PD) (n = 48), and those with clinical stage constipation (Cons-Clinic-PD) (n = 31). The association between serum GDNF concentration and constipation was explored using logical regression. Results: The nCons-PD group's mean GDNF levels were 528.44 pg/ml, which was higher than the Cons-Pro-PD group's 360.72 pg/ml and the Cons-Clinic-PD group's 331.36 pg/ml. The results of binary logistic regression indicated that GDNF was a protective factor in the prevention of constipation. Cons-Clinic-PD group had a higher score of MDS-UPDRS-II, MDS-UPDRS-III, MDS-UPDRS-IV, and a higher H-Y staging as compared with nCons-PD group. Relative to the nCons-PD group, Cons-Clinic-PD had higher NMSS scores, lower MoCA and PDSS scores, and were more likely to have RBD. Conclusions: GDNF serum levels are lower in patients with PD who are constipated. A low GDNF level is a potential risk factor for constipation in patients with PD.


Dry eye in 2008.
Although researchers continue to investigate the multifarious etiologic, anatomical, physiological, and pathological factors of dry eye, successful treatment remains a challenge. Dry eye prevalence is substantial across populations and the term 'dry eye' is used to describe numerous causes and varied pathophysiologies. Advanced study of the physiological aspects of the ocular anatomy (e.g. cornea and conjunctiva, tear film, eyelids) allows improved understanding of the mechanisms involved in dry eye and the impact of different causes on these entities. Sophisticated diagnostics are being developed to efficiently identify dry eye. Management options include a variety of novel agents in the pipeline. The development of improved etiological understanding and diagnostics for dry eye, as well as emerging therapeutics, will likely allow targeted therapy in the future.


Clinical Response to a PARP Inhibitor and Chemotherapy in a Child with BARD1-Mutated Refractory Neuroblastoma: A Case Report.
Despite advances in the treatment of high-risk neuroblastoma, approximately half of these patients die from the disease. Targeted therapy based on synthetic lethality associated with homologous recombination deficiency (HRD) caused by germline mutations in homologous recombination repair genes has shown great efficacy in several adult solid tumors. Here we report the first successful treatment of a pediatric patient with refractory neuroblastoma and a germline pathogenic mutation in BARD1 using a PARP inhibitor, talazoparib, in combination with cytotoxic chemotherapy and radiation therapy. Allele-specific expression in RNA-seq indicates bi-allelic loss of BARD1 in tumor; however, the HRD score was below the threshold currently used for HRD classification in adult cancers. Our study demonstrates that the use of PARP inhibition in combination with DNA-damaging agents should be considered in children with BARD1-mutated neuroblastoma and cautions against the use of HRD score alone as a biomarker for this pediatric population.


[Investigation on nutritional intakes for hospitalized children with blood disease].
To investigate the diet and nutritional status of hospitalized children with blood disease in order to provide nutritional guidelines. The patients' daily dietary intakes, including breakfast, lunch, dinner and additional meals, were recorded in detail for seven consecutive days. The intake amount of various nutrients was calculated using the dietary database. The majority of children with blood disease showed inadequate intakes of calories [mean 1825.81 kCal/d, 73.62% of the recommended intake (RNI)] and protein (mean 67.68 g/d, 81.34% of RNI). Intakes of vitamin E and riboflavin were adequate, but intakes of vitamin A, thiamine and vitamin C (66.67%, 77.78% and 69.89% of RNI, respectively) were inadequate. Iron and selenium intakes were adequate, but calcium and zinc intakes (41.11% and 56.21% of RNI, respectively) were grossly inadequate. Hospitalized children with blood disease had decreased dietary intakes of calories, protein, vitamin A, vitamin C, thiamin, calcium and zinc. The dietary pattern and nutritional intake need to be improved.


Chinese herbal medicine Yougui Pill reduces exogenous glucocorticoid-induced apoptosis in anterior pituitary cells.
Long-term glucocorticoid use may result in sustained suppression of one or more secreted components from the hypothalamo-pituitary-adrenal axis, and often results in apoptosis. Yougui Pill (YGP), a 10-component traditional Chinese herbal medicine, has been shown to be clinically effective for glucocorticoid-induced suppression of the hypothalamo-pituitary-adrenal axis. However, the pharmacological and molecular mechanisms remain unclear. We hypothesized that YGP would exert an anti-apoptosis effect on dexamethasone-treated anterior pituitary cells. In vivo experiments showed that YGP significantly reduced the number of apoptotic cells, down-regulated mRNA expression of cytochrome c, caspase-3, and caspase-9, and up-regulated mRNA expression of Bcl-2. These findings suggest that YGP reduced glucocorticoid-induced apoptosis in rat anterior pituitary cells by regulating the mitochondria-mediated apoptosis pathway.


Teaching Professionalism in Postgraduate Medical Education: A Systematic Review.
This systematic review sought to summarize published professionalism curricula in postgraduate medical education (PGME) and identify best practices for teaching professionalism. Three databases (MEDLINE, Embase, ERIC) were searched for articles published from 1980 through September 7, 2017. English-language articles were included if they (1) described an educational intervention addressing professionalism, (2) included postgraduate medical trainees, and (3) evaluated professionalism outcomes. Of 3,383 articles identified, 50 were included in the review. The majority evaluated pre- and posttests for a single group (24, 48%). Three (6%) were randomized controlled trials. The most common teaching modality was small-group discussions (28, 56%); other methods included didactics, reflection, and simulations. Half (25, 50%) used multiple modalities. The professionalism topics most commonly addressed were professional values/behavior (42, 84%) and physician well-being (23, 46%). Most studies measured self-reported outcomes (attitude and behavior change) (27, 54%). Eight (16%) evaluated observed behavior and 3 (6%) evaluated patient outcomes. Of 35 studies that evaluated statistical significance, 20 (57%) reported statistically significant positive effects. Interventions targeting improvements in knowledge were most often effective (8/12, 67%). Curriculum duration was not associated with effectiveness. The 45 quantitative studies were of moderate quality (Medical Education Research Study Quality Instrument mean score = 10.3). Many published curricula addressing professionalism in PGME are effective. Significant heterogeneity in curricular design and outcomes assessed made it difficult to synthesize results to identify best practices. Future work should build upon these curricula to improve the quality and validity of professionalism teaching tools.


Mycoplasma gallisepticum strain S6 genome contains three regions hybridizing with 16 S rRNA and two regions hybridizing with 23 S and 5 S rRNA.
Southern hybridization and cloning experiments revealed existence of 3 regions hybridizing with 16 S rRNA and 2 regions hybridizing with 23 S and 5 S rRNA in Mycoplasma Gallisepticum strain S6 genome thus forming 4 separate contiguous regions. One set of a putative rRNA genes is organized classically for eubacteria order 16 S-23 S-5 S. The other two 16 S rRNA and the other one 23 S-5 S rRNA hybridizing regions are separated from each other and from the complete rRNA operon for a distance of more than 6 kb.


Clinical, histopathological and therapeutic considerations in non-neoplastic abnormal uterine bleeding in menopause transition.
With the decline of ovarian hormonal function, from the fifth decade of life, women enter the menopause transition, during which bleeding becomes irregular in duration and time of occurrence. Secondary to ovarian dysfunction, developmental and maturation endometrial anomalies occur, which are clinically translated by abnormal uterine bleeding, which in many cases at this age can be caused by organic lesions (fibroma, polyps, endometritis, endometrial hyperplasia, adenomyosis, etc.). The retrospective study included a total of 256 patients with abnormal uterine bleeding in menopause transition. Statistics showed that the incidence of these types of bleeding increases with age (64.5%) and parity (30.5%), with symptoms consisting mostly in different clinical forms of abnormal uterine bleeding (62.1%), and leiomyomas prevailing at histopathological examination (49.6%). Progesterone replacement therapy was the first therapeutic choice for correcting these types of bleeding. Progesterone therapy is useful not only for therapeutic purposes to amend the bleeding, but also as a precaution against the development of endometrial carcinoma. Progestogens cancel the proliferative and mitogenic effect of estrogens, even when administered in sequential regimen 10-12 days per month.


[The significance of blood vessels on both sides of the growth plate].
A new 3-D presentation of the whole vasculature of the epiphyseal growth plate clearly allows for a distinction between arterial and venous sections of the blood circulation. Histological investigations using these processing methods could neither prove the connection between epiphyseal and metaphyseal vessels through the growth plate in newborns nor the concept of an arterial epiphyseal blood supply of the growth plate presented by Trueta. It is rather a question of an arterial metaphyseal perfusion and an epiphyseal venous drainage system.


Advances in modelling X-ray absorption spectroscopy data using reverse Monte Carlo.
Modern extended X-ray absorption fine structure (EXAFS) analysis is based on multiple-scattering calculations. Those calculations are carried out for fixed atomic configurations and proper account of the thermal and static disorder, corresponding to well-defined pair and higher-order distribution functions, can be obtained using different methods. The application of the Reverse Monte Carlo (RMC) method is able to provide tridimensional models of the atomic structure compatible with a given set of experimental data, producing useful and consistent structural models. This method has been proposed and applied also to EXAFS data by several authors in the last 25 years and has been fully implemented in the framework of the RMC-GnXAS method for EXAFS data-analysis. Here we present the extension and application of this method to multiple-edge studies of molecules, crystalline solids and liquids, including the long-range constraints provided by other techniques (e.g. diffraction). The potential and possible weaknesses of the RMC method are discussed, as well as the importance of accounting for the effect of noise levels in XAFS data. Results of RMC refinements are reported for several exemplary cases including Br2 and GeI4 molecular gases, crystalline Ge and AgBr, amorphous Ge and liquid AgBr. Those applications show the general interest for this method, and the importance of combining multiple set of data for improving the accuracy of the structural refinement both at short and long range.


Human papillomavirus 16 E6/E7-immortalized human gingival keratinocytes with epithelial mesenchymal transition acquire increased expression of cIAP-1, Bclx and p27(Kip1).
Epithelial mesenchymal transition (EMT) has been implicated in neoplastic invasion and metastasis. We have previously generated six cell lines from human gingival mucosal keratinocytes immortalized by E6/E7 of human papillomavirus type 16. Ldk and NuB1 lines represented EMT phenotype and other four lines represented cobblestone non-EMT phenotype. These cell lines were utilized as model cells to determine whether inhibitors of apoptosis proteins and cell-cycle regulators were molecular players during EMT. EMT cells exhibited increased expression of vimentin, vascular endothelial growth factor (VEGF) receptor1 and the ability to form tubules on Matrigel as well as to grow anchorage independently. We found that EMT cells expressed significantly elevated levels of cIAP-1, Bclx and p27(kip) higher than non-EMT cells. These proteins could therefore be used as intrinsic indicators of EMT of human gingival keratinocytes.


bilbo, a non-LTR retrotransposon of Drosophila subobscura: a clue to the evolution of LINE-like elements in Drosophila.
We used the repetitive character of transposable elements to isolate a non-LTR retrotransposon in Drosophila subobscura. bilbo, as we have called it, has homology to TRIM and LOA elements. Sequence analysis showed a 5' untranslated region (UTR), an open reading frame (ORF) with no RNA-binding domains, a downstream ORF that had structural homology to that of the I factor, and, finally, a 3' UTR which ended in several 5-nt repeats. The results of our phylogenetic and structural analyses shed light on the evolution of Drosophila non-LTR retrotransposons and support the hypothesis that an ancestor of these elements was structurally complex.


[Maintenance of the relation between the pulsed secretion of hormones and the internal sleep structure in human African trypanosomiasis].
In order to determine whether sleep disturbances would affect the hormonal patterns and the normal relationships between hormone pulses and sleep stages, the 24-hour profiles of cortisol, prolactin and plasma renin activity (PRA) were analysed in 6 sleeping sickness patients studied at Brazzaville and in 5 healthy African controls studied in Abidjan. Polysomnographic recordings were done continuously and blood was taken every 10 minutes throughout the 24-hour period. Plasma was analyzed for cortisol, prolactin and PRA. The circadian rhythm of cortisol, considered as an example of an endogenous rhythm was attenuated in all the patients but one, but as in normal subjects, slow wave sleep (SWS) remained associated with the declining phases of the secretory episodes. Prolactin and PRA profiles, which are strongly influenced by the sleep-wake cycle did not show the increase normally associated with long sleep periods and reflected the spreading of sleep and wakefulness throughout the 24-hour period. However, rapid-eye movement (REM) sleep began in sleeping sickness patients, as in normal subjects, during the descending phases of prolactin pulses. In both groups, PRA reflected the sleep stage distribution with non rapid-eye movement (NREM) sleep occurring during the ascending phases and REM sleep during the descending phases of the oscillations. However, in sleeping sickness patients, the marked sleep fragmentation often did not allow sufficient time for PRA to increase significantly, as observed with regular NREM-REM sleep cycles. These results demonstrate that, together with the disruption of the sleep-wake cycle, there are profound differences in the temporal organization of the 24 hour hormone profiles in human African trypanosomiasis.(ABSTRACT TRUNCATED AT 250 WORDS)


[A Japanese case of human herpes virus-8-associated multicentric castleman disease complicated by hemophagocytic syndrome].
We report a Japanese case of human herpes virus-8 (HHV-8)-associated multicentric Castleman disease(MCD) complicated by hemophagocytic syndrome(HPS). A 60-year-old man presented with persistent fever and progressive pancytopenia in June 2004. On physical examination, anemia, icterus, hepatosplenomegaly, and generalized lymphadenopathy were detected. Laboratory findings showed elevated levels of serum ferritin and soluble interleukin-2 receptor. Anti-human immunodeficiency virus (HIV) antibody was negative. Bone marrow aspiration revealed a normocellular marrow with an increased number of hemophagocytic histiocytes. Biopsy of cervical lymph node disclosed pathological features compatible with the plasmablastic variant of Castleman disease. HHV-8 DNA was detected in the specimen from lymph node by polymerase chain reaction. Thus, the diagnosis of HHV-8-associated MCD complicated by HPS was made. The patient was treated with immunotherapy and subsequent chemotherapy. However, he died of bacterial sepsis after one-month therapy. This case report provides some evidence that HHV-8 may be a causative agent of MCD even in HIV-seronegative Japanese patients.


Promotion of Flowering in Brassica campestris L. cv Ceres by Sucrose.
Flower initiation of the quantitative long-day plant Brassica campestris cv Ceres was earlier and at a lower final leaf number when sucrose was added to the medium in which plants were grown in sterile culture. The optimal concentration of sucrose was 40 to 80 millimolar. This flower-promoting effect of sucrose was not osmotic, as mannitol, sodium chloride, and polyethylene glycol were not effective at equal osmotic potentials.Seedlings grown heterotrophically after treatment with 4-chloro-5-(dimethylamino)-2-phenyl-3-(2H)-pyridazinone to prevent chlorophyll accumulation were also induced to form flower primordia earlier as the sucrose concentration in the medium was increased up to 80 millimolar. Inclusion of 4 millimolar sodium nitrate in the culture medium of green plants did not reduce the flower-promoting effects of sucrose but delayed initiation in plants grown without added sucrose.Removal of CO(2) during a single main or supplementary light period, or both, greatly reduced flower initiation. It is concluded that sucrose may be an important controlling factor determining floral initiation in Brassica.


Approximate Optimization Study of Light Curing Waterborne Polyurethane Materials for the Construction of 3D Printed Cytocompatible Cartilage Scaffolds.
Articular cartilage, which is a white transparent tissue with 1-2 mm thickness, is located in the interface between the two hard bones. The main functions of articular cartilage are stress transmission, absorption, and friction reduction. The cartilage cannot be repaired and regenerated once it has been damaged, and it needs to be replaced by artificial joints. Many approaches, such as artificial joint replacement, hyaluronic acid injection, microfracture surgery and cartilage tissue engineering have been applied in clinical treatment. Basically, some of these approaches are foreign material implantation for joint replacement to reach the goal of pain reduction and mechanism support. This study demonstrated another frontier in the research of cartilage reconstruction by applying regeneration medicine additive manufacturing (3D Printing) and stem cell technology. Light curing materials have been modified and tested to be printable and cytocompatible for stem cells in this research. Design of experiments (DOE) is adapted in this investigation to search for the optimal manufacturing parameter for biocompatible scaffold fabrication and stem cell attachment and growth. Based on the results, an optimal working process of biocompatible and printable scaffolds for cartilage regeneration is reported. We expect this study will facilitate the development of cartilage tissue engineering.


[Impact of inherited thrombophilia on the development of some pregnancy complications].
To assess the clinical significance of inherited thrombophilia [IT] for the development of some pregnancy complications. The incidence of the following factors was studied in 97 pregnant women with pregnancy complications and in 103 controls: R506Q mutation encoding Factor V Leiden [FVL] synthesis, Prothrombin G20210A mutation, T677 methylenetetrahydropholate reductase mutation [MTHFR], 4G/4G polymorphism of the plasminogen activator inhibitor [PAI 4G/4G]. Among 97 patients in the group studied 39 had early onset severe preeclampsia [PE], 14--placental abruption [AP] without PE, 18--intrauterine growth restriction [IUGR] without PE, 12--stillbirth [SB] without PE, 14--habitual spontaneous abortions [HSA]. The control group included 103 clinically healthy pregnant women with at least one previous uneventful pregnancy, without history of thromboembolic disorders. In addition, patients with severe PE with and without IT were compared regarding g. a. and birthweight at delivery and intrauterine fetal loss rate. DNA analysis was performed according to internationally accepted standards. Pregnancy outcomes were ascertained from hospital records. Statistical significance (p < 0.05) was assessed by means of Student's t-test. FVL mutation was found in 23.7% (23/97) of the patients from the studied group and in 5.8% (6/103) of the controls. Prothrombin G20210A carriers were 11% (11/97) of the studied and 3.8% (4/103) of the controls, while with PAI 4G/4G polymorphism they were 30.9% (30/97) and 14.5% (15/103) respectively. MTHFR T677 was not more frequent in the studied group (8.2%) compared to the control one (29%). Eight of the patients (9.6%) were carriers of more than one mutation. In 22 cases with early onset severe PE and IT gestational age and birthweight at delivery were lower than in the cases with severe PE without IT while intrauterine fetal loss rate did not differ significantly between the two groups. Inherited thrombophilia is found more frequently in women with pregnancy complications like PE, IUGR, AP, SB, HSA. The incidence of homozygous MTHFR T677 is not higher in these cases. IT worsens the prognosis of severe PE. The diagnosis of IT is important since anithrombotic therapy has to be considered to protect the mother and the fetus.


State Tobacco Policies as Predictors of Evidence-Based Cessation Method Usage: Results From a Large, Nationally Representative Dataset.
Evidence-based cessation methods including nicotine replacement therapy (NRT), non-NRT medications, quitlines, and behavioral treatments are underutilized by smokers attempting to quit. Although a number of studies have demonstrated a relationship between state-level tobacco policies (eg, taxation, appropriations) and cessation, whether such state-level factors influence likelihood of using an evidence-based treatment is unclear. Accordingly, the aims of the present study were: (1) to describe evidence-based cessation method utilization by state and (2) to examine the effect of state-level factors on cessation method utilization above and beyond individual-level predictors. Data were utilized from the 2010-2011 Tobacco Use Supplement to the Current Population Survey (TUS-CPS). Participants included 9232 smokers who reported a past-year quit attempt. Data on 11 state-level predictors were collated from national datasets. Analyses were based on: (1) descriptive characterization of quit method usage, (2) logistic regression models to determine state-level factors as predictors of quit method utilization, controlling for individual-level predictors, (3) cluster analyses grouping states with similar state-level factors, and (4) examination of cluster as a predictor of cessation method. Tobacco control appropriations significantly predicted NRT, quitline, and behavioral treatment utilization. Additional state-level factors that demonstrated significant relationships included Medicaid coverage of non-NRT medications and behavioral treatment, tobacco tax rate, smoking prevalence, and percentage of population uninsured. State clustering significantly predicted quit method across all four methods. State-level factors influence the likelihood of residents utilizing evidence-based quit methods. Results are discussed in terms of implications for tobacco policy at the state level. Results from the present study highlight state tobacco control appropriations as a robust predictor of evidence-based cessation method utilization. Other significant state-level predictors of evidence-based cessation method utilization included Medicaid coverage of non-NRT medications and behavioral treatment, tobacco tax rate, smoking prevalence, and percentage of population uninsured. Moreover, state-level predictors clustered together to significantly predict evidence-based cessation method utilization. Thus, increasing tobacco control appropriations, extending health insurance coverage, maximizing revenue from tobacco taxation and tobacco settlements, and ultimately decreasing smoking prevalence are important targets for individual states to promote utilization of evidence-based cessation methods.


[The prognosis following surgical resection of small-cell nonanaplastic bronchogenic carcinoma according to the new staging guideline: an analysis of 1433 patients].
To validate current guidelines for staging bronchogenic lung carcinoma. Between 1969 and 1996, small-cell non-anaplastic tumors of bronchogenic carcinoma classified by the recently proposed TNM guidelines of the Spanish Society of Pneumology and Chest Surgery (SEPAR) were resected from 1,433 patients. We used the Kaplan-Meier method to calculate survival and compared the curves using a log-rank test. A stage IA classification was given to 142 patients and IB to 575. Thirty-seven cases were classified IIA and 336 were IIB. Of the latter, 177 were T2N1M0 and 159 were T3N0M0. Two hundred forty-eight patients were in stage IIIA, 54 T3N1M0, 23 T1N2M0, 120 T2N2M0 and 51 T3N2M0. Ninety-five stage IIIB patients were classified as follows: 37 T4N0M0, 35 T4N1M0, and 23 T4N2M0. Five-year survival for IA patients, at 75% was significantly better than the 60% rate for IB patients (p = 0.0021). Likewise, the prognosis for stage IIA, where five-year survival was 57%, was significantly better than for IIB at 39% (p = 0.0434). The prognosis for patients classified as T1NM0 was better than for those classified as T2N1M0, which was 38% (p = 0.0320). The survival of those classified as T3N0M0 (42%) was not significantly different from that of T1N1M0 (p = 0.1754) or T2N1M0 (p = 0.5360) patients. We found no significant difference between T1N1M0 and stage IB (p = 0.3847) patients. Among stage III patients, we observed no difference in survival between stage IIIA and IIIB (p = 0.1914). In stage IIIA, patients classified as T3N2M0 had a significantly lower rate of survival (p = 0.0399). The presence of mediastinal ganglia in stage IIIB was associated with a lower survival rate (p = 0.0328). The new guidelines for staging non-small cell anaplastic lung carcinoma do not provide consistent prognoses for homogeneous groups of patients, at least not in certain categories.


Accuracy of Community Informant Led Detection of Maternal Depression in Rural Pakistan.
Maternal depression is a global mental health and a public health priority. Despite the priority its active detection is still a challenge. We tested the accuracy of an adapted version of Community Informant Detection Tool for Maternal Depression (CIDT-MD) in rural settings of Pakistan. Using a single stage design, trained community informants (lady health workers and lay peers) identified women (pregnant and/or with children) with symptoms of probable depression using CIDT-MD. This was immediately followed by diagnostic interviews of all the women using the Structured Clinical Interview for the Diagnostic and Statistical Manual (SCID-V) for current major depressive episode by trained assessors, blinded to the outcome of CIDT-MD. Data were analyzed using Statistical Package for Social Sciences (Version 25.0, IBM Corp., Armonk, NY, USA) and FACTOR software (Version. 10.3.01, Virgili University, Tarragona, Spain). Descriptive statistics, factor analysis, validity, reliability and known group validity was conducted to evaluate the psychometric properties of the adapted CIDT-MD. In all, 425 women, with mean age of 28 years (SD = 4.7), participated. Nearly 10% were illiterate, while the rest (90%) had an education ranging from eight to 15 years of schooling. The majority (73.2%) of the participants had 1-3 children while only 17.4% had >3 children. The sensitivity and specificity of CIDT-MD in detecting depressive symptoms was 97.5% (95% CI: 94.2-99.1) and 82.4% (95% CI: 77.8-86.4) respectively. It's positive predictive value (PPV), 77.3% (95% CI: 72.9-81.2) and the negative predictive value (NPV) was 98.17% (95% CI: 95.7-99.2). While factor analysis revealed high inter-item correlation for most items (0.62-0.77) with an adequately fair Kaiser-Meyer-Olkin (KMO) sampling adequacy (0.73), significant Bartlett's test of sphericity (p < 0.001). Uni-dimensionality for the CIDT-MD based on one-dimensional congruence (0.97), explained common variance (0.85), excellent internal consistency (0.90), good criterion validity (Area Under Curve = 81%), tester-test reliability (0.87-0.89) and statistically significant known group analysis (p < 0.001). The adapted version of the Community Informant Detection Tool for Maternal Depression is a valid and a reliable tool for active case detection of maternal depression in rural settings of Pakistan.


Kinetically Enhanced Electrochemical Redox of Polysulfides on Polymeric Carbon Nitrides for Improved Lithium-Sulfur Batteries.
The kinetics and stability of the redox of lithium polysulfides (LiPSs) fundamentally determine the overall performance of lithium-sulfur (Li-S) batteries. Inspired by theoretical predictions, we herein validated the existence of a strong electrostatic affinity between polymeric carbon nitride (p-C3N4) and LiPSs, that can not only stabilize the redox cycling of LiPSs, but also enhance their redox kinetics. As a result, utilization of p-C3N4 in a Li-S battery has brought much improved performance in the aspects of high capacity and low capacity fading over prolonged cycling. Especially upon the application of p-C3N4, the kinetic barrier of the LiPS redox reactions has been significantly reduced, which has thus resulted in a better rate performance. Further density functional theory simulations have revealed that the origin of such kinetic enhancement was from the distortion of molecular configurations of the LiPSs anchored on p-C3N4. Therefore, this proof-of-concept study opens up a promising avenue to improve the performance of Li-S batteries by accelerating their fundamental electrochemical redox processes, which also has the potential to be applied in other electrochemical energy storage/conversion systems.


The transcription factor MIST1 is a novel human gastric chief cell marker whose expression is lost in metaplasia, dysplasia, and carcinoma.
The lack of reliable molecular markers for normal differentiated epithelial cells limits understanding of human gastric carcinogenesis. Recognized precursor lesions for gastric adenocarcinoma are intestinal metaplasia and spasmolytic polypeptide expressing metaplasia (SPEM), defined here by ectopic CDX2 and TFF2 expression, respectively. In mice, expression of the bHLH transcription factor MIST1, normally restricted to mature chief cells, is down-regulated as chief cells undergo experimentally induced metaplasia. Here, we show MIST1 expression is also a specific marker of human chief cells. SPEM, with and without MIST1, is present in human lesions and, akin to murine data, likely represents transitional (TFF2(+)/MIST1(+) = "hybrid"-SPEM) and established (TFF2(+)/MIST1(-) = SPEM) stages. Co-visualization of MIST1 and CDX2 shows similar progressive loss of MIST1 with a transitional, CDX2(+)/MIST1(-) hybrid-intestinal metaplasia stage. Interinstitutional analysis and comparison of findings in tissue microarrays, resection specimens, and biopsies (n > 400 samples), comprising the entire spectrum of recognized stages of gastric carcinogenesis, confirm MIST1 expression is restricted to the chief cell compartment in normal oxyntic mucosa, rare in established metaplastic lesions, and lost in intraepithelial neoplasia/dysplasia and carcinoma of various types with the exception of rare chief cell carcinoma ( approximately 1%). Our findings implicate MIST1 as a reliable marker of mature, healthy chief cells, and we provide the first evidence that metaplasia in humans arises at least in part from the chief cell lineage.


Erythema induratum of Bazin in an infant after Bacille Calmette-Guerin vaccination.
We report the first case of erythema induratum of Bazin (EIB) after Bacille Calmette-Guerin (BCG) vaccination in an infant. The patient developed recurrent multiple erythematous and subcutaneous nodules on his legs 2 months after a BCG vaccination. He had no other symptoms or family history of tuberculosis (TB). Histopathological findings revealed a granulomatous lobular panniculitis. EIB often appears as a chronic, nodular eruptions that frequently occur on the lower legs of females with tuberculin hypersensitivity. To date, only a few cases of infants with EIB have been reported. There have been no clinical reports of EIB after BCG vaccination. Our case suggests that Mycobacterium bovis in the BCG vaccination may have caused EIB.


Effect of endothelin-1 on actomyosin ATPase activity. Implications for the efficiency of contraction.
Endothelin is a powerful inotropic peptide that increases isometric force in isolated papillary muscle and the extent of shortening in isolated single cardiac myocytes. Its mechanism of action has been variously attributed to increased Ca2+ activation, increased Ca2+ sensitivity of the contractile proteins, and increased intracellular pH, but the physiological function of the changes in cardiac performance remains obscure. In this study, the effects of endothelin-1 on both force development and the kinetics of contraction have been examined. Isometric force, actomyosin ATPase activity, and unloaded shortening velocity were measured. The effects were dose dependent. From 1 to 50 pmol/L endothelin-1 did not alter force development in isolated trabeculae with intact endothelial cells, but actomyosin ATPase activity was increased. Between 100 pmol/L and 10 nmol/L endothelin-1 raised isometric force, decreased actomyosin ATPase activity, and decreased unloaded shortening velocity. The reduction in ATPase activity was progressively enhanced as sarcomere length was increased from 1.9 t0 2.4 microns. These results indicate that the effects of endothelin-1 on the force of contraction and the rate of ATP hydrolysis are not tightly coupled and are changed in the opposite directions by endothelin-1 over most of its effective dose-range. This raises the possibility that endothelin-1 may increase the economy of contraction. A novel function of endothelin may be the modulation of the efficiency of contraction, particularly when increased preload raises the contractile work of the heart.


RNA interference-mediated knockdown of p21(WAF1) enhances anti-tumor cell activity of oncolytic adenoviruses.
The ability of oncolytic adenoviruses to replicate in and lyse cancer cells offers a potential therapeutic approach. However, selectivity and efficacy of adenovirus replication need to be improved. In this study, we present that loss of p21(WAF1) promotes adenovirus replication and more effective cell killing. To test our hypothesis, we took HCT116 colon cancer cell lines carrying deletions of either p21(WAF1) or p53, and infected these cell lines with wild-type adenovirus (WtD) or the oncolytic adenoviruses, ONYX-015 and Delta-24. We found that WtD, ONYX-015 and Delta-24 induced stronger cytopathic effects in HCT116 p21-/- cells compared with HCT116-WT cells. This was accompanied by increased virus production. siRNA-mediated knockdown of p21(WAF1), and similarly of p27(KIP1), in HCT116-WT cells also enhanced replication of and cell killing by these viruses. Furthermore, we found that TE7, an esophageal carcinoma cell line, also showed a strong cell-killing effect and virus production when p21(WAF1) expression was suppressed by RNA interference before adenoviruses infection. Also, H1299 and DU-145 cells transfected with p21(WAF1) siRNA showed higher virus production after ONYX-015 and Delta-24 infections. These observations suggest that p21(WAF1) plays a role in mediating replication of oncolytic viruses with potential implications for adenoviral therapy of cancer.


Iodine status and cognitive function of women and their five year-old children in rural Sidama, southern Ethiopia.
Iodine deficiency is one of the most common micronutrient deficiencies worldwide and is a major cause of preventable mental retardation. The purpose of this study was to assess the iodine status and cognitive function of women of childbearing age and their five-year-old children. A cross-sectional study was conducted in a rural village in southern Ethiopia. A convenience sample of one hundred women and their five year-old children participated in the study. Goiter grade, urinary iodine excretion, Raven's CPM and cognitive tests from the Kaufman ABC-II, were administered to the women and their children. The use of iodized salt was only 2%. The mean iodine content of water in and around the study area was 4.46 microg/l. Occurrence of goiter was 85% in the women and 33% in children. Urinary iodine excretion for all participants was <49 microg/L, the top of the range for moderate iodine deficiency. The median urinary iodine excretion (UIE) was 1 microg/L for both mothers and children. For children, measures of short term memory (Sequential index) were correlated with the visual processing (Simultaneous index) (r = 0.49, p < 0.0001). Goiter and urinary iodine excretion were correlated to Sequential index (r = 0.39, p = 0.0011 and r = 0.2, p = 0.05) respectively, but not to the Simultaneous index for children. Sequential (r = 0.21, p = 0.03) and Simultaneous (r = 0.29, p = 0.004) indices of mothers and children were correlated. The high prevalence of goiter and the low urinary iodine excretion demonstrate serious long- and short-term iodine deficiency in the study area. Relations between measures of iodine status and short term memory in children raise concern about potential functional effects of iodine deficiency.


Right Atrial Myxoma.
A 54 yr old man, non-smoker, non-alcoholic, and non-diabetic, non-hypertensive, non-obese, with moderate daily activity and no significant past medical history, presented with chief complaints of dyspnoea NYHA Class III, which was associated with diaphoresis and restlessness. On examination, a long systolic murmur of grade III-IV, increasing on inspiration, was audible in the tricuspid area. The murmur did not have any postural relation. An abnormal thud-like sound was audible in left parasternal region. There was no evidence of any pleuro-pericardial rub. Transthoracic echocardiography showed a large (7×4 cm), mobile mass arising in the right atrium superiorly, prolapsing through tricuspid valve, into the right ventricle, resulting in moderate tricuspid regurgitation. 2D echo (Figure 1) and cardiac MRI (Figure 2) of the heart showed a isointense to mildly hypointense mass from the right atrium prolapsing through the tricuspid valves into the right ventricle on T2 weighted images. There was abscence of any enhancement of the mass after administration of IV gadolinium. The patient underwent excision of the myxoma. Histopathological examination showed a tumour with extensive myxomatous matrix with dispersed cellular components. The tumour cells were arranged in single or multiple layers surrounding vascular channels, which were lined by endothelium. The tumour cells had spindle-shaped nuclei with occasionaly vacuolated eosinophilic cytoplasm. There was no increase in mitosis. In addition there was background of lympho-plasmacytic infiltrate (Figure 3). The patient remained asymptomatic for the period of one and a half years of follow up post-operatively.


Skin necrosis after total knee arthroplasty.
Nine patients were treated for skin necrosis after total knee arthroplasty. Eight patients had predisposing factors, which may have increased their risk of developing wound complications. Seven patients developed necrosis over the patellar tendon or tibial tubercle, of whom 6 were treated with muscle flap coverage. Two patients developed necrosis over the patella, both of whom were treated with local wound care and skin grafting. Successful wound healing and salvage of the total knee arthroplasty was achieved in all cases. Treatment of necrosis over the patellar tendon or tibial tubercle usually requires muscle flap coverage, whereas necrosis over the patella may be treated with local wound care and skin grafting.


Role of matrix metalloproteinases in asthma.
Airway inflammation and remodeling are key features of asthma. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) are thought to contribute to the pathogenesis of asthma via their influence on the function and migration of inflammatory cells as well as matrix deposition and degradation. TIMPs bind MMPs in a 1:1 fashion. Thus, an increase in the molar ratio of MMP/TIMP may favor tissue injury, while the reverse could be associated with increased fibrosis. MMP-9 is the predominant MMP in asthma, and its expression is enhanced when patients have spontaneous exacerbations or in response to local instillation of allergen in the airway. As acute inflammation resolves, MMP-9 levels return toward normal. Interestingly, corticosteroids downregulate MMP and enhance TIMPs. Even though it is clear that enhanced airway inflammation in asthma is associated with increased expression of MMPs, whether specific inhibitors of MMP could reduce airway injury and facilitate orderly healing in asthma is still unknown.


The study of in vivo quantification of aluminum (Al) in human bone with a compact DD generator-based neutron activation analysis (NAA) system.
The feasibility and methodology of using a compact DD generator-based neutron activation analysis system to measure aluminum in hand bone has been investigated. Monte Carlo simulations were used to simulate the moderator, reflector, and shielding assembly and to estimate the radiation dose. A high purity germanium (HPGe) detector was used to detect the Al gamma ray signals. The minimum detectable limit (MDL) was found to be 11.13 μg g(-1) dry bone (ppm). An additional HPGe detector would improve the MDL by a factor of 1.4, to 7.9 ppm. The equivalent dose delivered to the irradiated hand was calculated by Monte Carlo to be 11.9 mSv. In vivo bone aluminum measurement with the DD generator was found to be feasible among general population with an acceptable dose to the subject.


Hgcl2-induced acute renal failure in the rat. Effect of water diuresis, saline loading, and diuretic drugs.
A variety of pretreatment-treatment protocols were applied to rats with ARF induced by the subcutaneous injection of 6 mg of HgCl2 per kilogram body weight. Renin depletion induced by DOCA-saline pretreatment was associated with protection against HgCl2-induced ARF only when the saline diuresis was maintained by drinking 1% NaCl after injury. Twenty-four dehydration followed by free access to tap water annihilated the protective effect of DOCA-saline pretreatment despite maintained depletion of renal renin. Continuous intravenous loading with saline and furosemide, although increasing renal renin levels, afforded as much protection as saline loading alone. Ethacrynic acid, which did not increase salt excretion in our rats, as well as water diuresis, failed to be protective. A loose correlation was found between he amount of histological damage to the convoluted parts of the proximal tubules and the degree of renal functional impairment. Thus protection against HgCl2-induced ARF was independent of the renal renin level but closely related to urinary NaCl excretion after the injury. Saline diuresis could act by relieving or preventing tubular obstruction.


Combinations of resveratrol, cisplatin and oxaliplatin applied to human ovarian cancer cells.
In this study, combinations of resveratrol with platinum drugs cisplatin and oxaliplatin were administered to human ovarian A2780, A2780(cisR) and A2780(ZD0473R) cell lines with the aim of offering a means of overcoming drug resistance. Cell viability was quantified using the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Combination indices and dose response curves were used as measures of the combined drug action. Greatest synergism was observed when resveratrol was administered first followed by the platinum drug (cisplatin or oxaliplatin) 2 h later, and the least synergism was achieved when the two types of compounds were administered as a bolus. The results can be explained by assuming that the administration of resveratrol 2 h before the platinum drug may sensitize the ovarian cancer cells to platinum-induced apoptosis, thus providing a means of overcoming drug resistance. If the results are confirmed in vivo, they may be significant clinically.


Incidence and management of percutaneous transluminal angioplasty-induced venous rupture in the "fistula first" era.
Percutaneous transluminal angioplasty (PTA)-induced venous rupture is a common complication of hemodialysis access interventions. The authors sought to determine if venous rupture rates and management differed between grafts and fistulas, and in the fistula subset, between transposed and nontransposed fistulas. Patients experiencing venous rupture during hemodialysis PTA over a 5-year period were identified. Of 1,985 hemodialysis interventions, 75 ruptures occurred in 69 patients (46 women) with a mean age of 63 years (range, 31-88 y). Rupture rates, proportion of successful treatments, and treatment type and number (ie, balloon tamponade, stent, covered stent) were determined. Rupture was more common in fistulas overall (5.6%, 39 of 693) compared with grafts (2.8%, 36 of 1,292; P = .002), in transposed (10.7%, 20 of 187) compared with nontransposed fistulas (3.8%, 19 of 506; P = .001), and in transposed fistulas compared with grafts (P = .0001). There was no significant difference between nontransposed fistulas and grafts. Treatment success (ie, resolution of extravasation) was the same among groups: 69% (27 of 39) in fistulas overall, 70% (14 of 20) in transposed fistulas, 68% (13 of 19) in nontransposed fistulas, and 72% (26 of 36) in grafts. There was a greater need for stents in grafts (38.9%, 14 of 36) compared with fistulas (12.8%, five of 39; P = .003). PTA-induced rupture is more common in fistulas than grafts, and this effect seems nearly entirely driven by transposed fistulas. Although rupture treatment in fistulas of all types yielded similar success to grafts, and graft ruptures were more difficult to treat than fistula ruptures, the high rupture rates in transposed fistulas attest to the increased difficulty of treating this subset of fistulas.


Cut throat zone II neck injury and advantage of a feeding jejunostomy.
Penetrating neck injuries account for 5-10% of trauma cases and are potentially life threatening. We report a case of cut- throat zone II neck injury in a 45-year-old male extending up to posterior pharyngeal wall and exposing the underlying cervical vertebra. Tracheostomy was done and wound repair was started from the posterior aspect in layers using 3-0 Vicryl. Intraoperatively, a conscious decision was taken for a feeding jejunostomy for postoperative feeding, which was likely to be prolonged, in view of sensory-nerve damage along the transected pharynx. Prolonged use of Nasogastric tube for postoperative feeding was thus avoided and the discomfort, risk of aspiration and foreign body at injury site eliminated. One week postoperative, the patient experienced severe bouts of coughing and restlessness on oral intake; during this period enteral nutrition was maintained through feeding jejunostomy. At the time of discharge at 1 month, the patient was accepting normal diet orally and was detubated and vocalizing normally. We conclude that postoperative nutrition is an important area to be considered for deep neck wound with nerve injuries due to delayed tolerance to oral feeding till the regeneration of sensory nerves. A feeding jejunostomy or feeding gastrostomy performed simultaneously in such patients with nerve injuries is far superior over nasogastric-tube feeding when prolonged postoperative feeding is expected.


Effects of recombinant human cytokines on precursor-B acute lymphoblastic leukemia cells.
An in vitro colony assay was used to examine the growth stimulatory effects of a variety of recombinant human lymphohemopoietic cytokines on human precursor-B acute lymphoblastic leukemia (ALL) cells. Of 23 cases evaluated, 16 formed significant numbers of colonies (mean 280, range 36-939) when cultured in 10% fetal calf serum in 0.8% methylcellulose containing 10% partially purified B-cell growth factor (BCGF). Immunoperoxidase staining of cells from cultures confirmed a precursor-B phenotype (HLA-DR+, CD-10+, CD-19+, CD-34+, Ig-, CD-3-, CD-11C-). When these cases were cultured with recombinant human cytokines (but without BCGF) only a minority showed colony formation, in all instances less than seen with BCGF. Three cases were stimulated both by interleukin 3 (IL-3) and the putative pre-B growth factor interleukin 7 (IL-7). One case was stimulated both by tumor necrosis factor alpha and by interleukin 6 (IL-6); these results were confirmed on highly purified CD-10+, CD-19+ cells prepared by fluorescence-activated cell sorting. A further case was stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF), including CD-10+, CD-19+ purified cells. All cases responding to recombinant cytokines were heavily pretreated patients at relapse, whereas none of the newly diagnosed untreated cases showed any response. These results confirm that activities present in BCGF are the major stimulant for precursor-B ALL proliferation in vitro. None of the recombinant cytokines examined, including IL-7, appeared to have consistent activity under these culture conditions. The molecules regulating growth of ALL remain to be more precisely defined.


Early mammalian erythropoiesis requires the Dot1L methyltransferase.
Histone methylation is an important regulator of gene expression; its coordinated activity is critical in complex developmental processes such as hematopoiesis. Disruptor of telomere silencing 1-like (DOT1L) is a unique histone methyltransferase that specifically methylates histone H3 at lysine 79. We analyzed Dot1L-mutant mice to determine influence of this enzyme on embryonic hematopoiesis. Mutant mice developed more slowly than wild-type embryos and died between embryonic days 10.5 and 13.5, displaying a striking anemia, especially apparent in small vessels of the yolk sac. Further, a severe, selective defect in erythroid, but not myeloid, differentiation was observed. Erythroid progenitors failed to develop normally, showing retarded progression through the cell cycle, accumulation during G₀/G₁ stage, and marked increase in apoptosis in response to erythroid growth factors. GATA2, a factor essential for early erythropoiesis, was significantly reduced in Dot1L-deficient cells, whereas expression of PU.1, a transcription factor that inhibits erythropoiesis and promotes myelopoiesis, was increased. These data suggest a model whereby DOT1L-dependent lysine 79 of histone H3 methylation serves as a critical regulator of a differentiation switch during early hematopoiesis, regulating steady-state levels of GATA2 and PU.1 transcription, thus controlling numbers of circulating erythroid and myeloid cells.


Advances in Plasmonics and Nanophotonics.
Recent developments in subwavelength localization of light have paved the way of novel research directions in the field of optics, plasmonics, and nanophotonics [...].


[An interferon inhibitor in regulating the activity of human natural killer cells].
The action of mouse serum interferon--alpha/beta (IFN) at the dose of 100 U/ml, of its inhibitor (I) at the dose of 8 U/ml as well as of their combination with the above doses on sensitivities of mouse target cells (TC) of sensitive to IFN line L 929 and resistant to the one line MCB in natural cytotoxic reaction was studied. Cytotoxic activity of human natural killer cells was detected in 14 hrs cytotoxic test using 3H-uridine for labelling of TC. IFN, I, and IFN+I were added to cell cultures for 24 hrs at 37 degrees C with following removing of preparations. It has been shown that I abolished protective effect of IFN on TC L 929 whereas the one possessed the protective action on TC MCB in natural cytotoxic reaction. These data confirmed a suggestion about immunoregulatory properties of I which displayed in abolition or realization of protective effect on TC in natural cytotoxic reaction in dependence on initial sensitivity of TC to antiviral IFN action.


Host Resistance to Uromyces appendiculatus in Common Bean Genotypes.
Rust, induced by the fungus Uromyces appendiculatus, is one of the most serious bean diseases. The involved mechanisms in rust resistance were evaluated in 10 common bean genotypes during the 2019/2020 and 2020/2021 growing seasons. The disease parameters such as final rust severity (FRS%), area under the disease progress curve (AUDPC) and disease increase rate (r-value) were lower in the resistant genotypes than in highly susceptible genotypes. Biochemical compounds such as total phenols and the activity of antioxidant enzymes such as catalase, peroxidase and polyphenol oxidase were increased in the resistant genotypes compared to susceptible genotypes. In the resistance genotypes, the levels of oxidative stress markers such as hydrogen peroxide (H2O2) and superoxide (O2•-) increased dramatically after infection. The electrolyte leakage percentage (EL%), was found to be much greater in susceptible genotypes than resistant genotypes. The resistant gene SA14, which was found in genotypes Nebraska and Calypso at 800 bp, had an adequate level of resistance to bean rust with high grain yield potential. After infection, the transcriptions levels of 1,3-D-glucanases and phenylalanine ammonia lyase) were higher in the resistant genotypes than susceptible genotypes. In conclusion, the resistant genotypes successfully displayed desirable agronomic traits and promising expectations in breeding programs for improving management strategies of common bean rust disease. The resistance was mediated by antioxidant enzymes, phenolic compounds, and defense gene expressions, as well as the resistant gene SA14.


The influence of small field sizes, penumbra, spot size and measurement depth on perturbation factors for microionization chambers.
The purpose of this study was the investigation of perturbation factors for microionization chambers in small field dosimetry and the influence of penumbra for different spot sizes. To this purpose, correlated sampling was implemented in the EGSnrc Monte Carlo (MC) user code cavity: CScavity. CScavity was first benchmarked against results in the literature for an NE2571 chamber. An efficiency increase of 17 was attained for the calculation of a realistic chamber perturbation factor in a water phantom. Calculations have been performed for microionization chambers of type PinPoint 31006 and PinPoint 31016 in full BEAMnrc linac simulations. Investigating the physical backgrounds of the differences for these small field settings, perturbation factors have been split up into (1) central electrode perturbation, (2) wall perturbation, (3) air-to-water perturbation (chamber volume air-to-water) and (4) water volume perturbation (water chamber volume to 1 mm(3) voxel). The influence of different spot sizes, position in penumbra, measuring depth and detector geometry on these perturbation factors has been investigated, in a 0.8 x 0.8 cm(2) field setting. p(cel) for the PP31006 steel electrode shows a variation of up to 1% in the lateral position, but only 0.4% for the PP31016 with an Al electrode. The air-to-water perturbation in the optimal scanning direction for both profiles and depth is most influenced by the radiation field, and only to a small extent the chamber geometry. The PP31016 geometry (shorter, larger radius) requires less total perturbation within the central axis of the field, but results in slightly larger variations off axis in the optimal scanning direction. Smaller spot sizes (0.6 mm FWHM) and sharper penumbras, compared to larger spot sizes (2 mm FWHM), result in larger perturbation starting in the penumbra. The longer geometries of the PP31006/14/15 exhibit in the non-optimal scanning direction large variations in total perturbation (p(tot) 1.201(4) (0.6 mm spot, 3 mm off axis, type A MC uncertainty) to 0.803(4) (5 mm off axis)) mainly due to volume perturbation. Therefore in IMRT settings, when the detector is not always in the optimal scanning direction, the PP31016 geometry requires less extreme perturbation (max p(tot) 1.130(3)) and shows less variation. However, these results suggest that small variations in positioning, spot size or MLC result in large differences in perturbation factors. Therefore even these 0.016 cm(3) ionization chambers are limited in their use for a field setting of 0.8 x 0.8 cm(2), as used in this investigation.


Vitamin E-Coated Dialyzer Inhibits Oxidative Stress.
To examine the effects of vitamin E-coated dialyzer on oxidative stress in vitro. A dialyzer with a synthetic polymer membrane (APS-11SA) and vitamin E-coated dialyzer (VPS-11SA) were connected to a blood tubing line, and U937 cells were circulated in the device. The circulating fluid was collected at 1, 2, 5, 10, 25, and 50 cycles, which are estimated numbers of passes through the dialyzer. Intracellular reactive oxygen species (ROS) production, malondialdehyde (MDA), and Cu/Zn-superoxide dismutase (SOD) were quantified. Intracellular ROS production was increased in the first cycle by APS-11SA and was decreased throughout the experiment by VPS-11SA. Intracellular ROS production in the VPS-11SA device was lower, and MDA levels were decreased. MDA levels were lower during VPS-11SA processing than during APS-11SA processing. Cu/Zn-SOD levels remained unchanged. Our results highlight anti-oxidative-stress effects of a vitamin E-coated dialyzer.


Effect of iron supplementation on platelet count in adult patients with iron deficiency anemia.
Iron deficiency anemia (IDA) affects more than 1.2 billion individuals globally. In addition to anemia, reactive thrombocytosis is also a common clinical hematological condition in patients with IDA. However, some case reports have described the thrombotic complications in association with IDA-induced thrombocytosis. Patients with a high risk of thrombosis need prompt identification and effective treatment to prevent thrombotic complications. While iron replacement treatment has been shown to decrease platelet count in this context, there is limited published evidence on how iron supplementation affects the thrombocytosis caused by IDA. We retrospectively examined the clinical records of 440 patients with IDA from an RCT completed from 1 January 2016, to 30 December 2017, and data obtained from this study was used for post hoc analysis to examine the effect of iron on platelet count in IDA-induced thrombocytosis.The mean ± standard deviation (SD) platelet counts of the 440 patients with IDA was 310.23 ± 98.72 × 109/L. With baseline platelet counts>450 × 109 /L as the cutoff for thrombocytosis, patients were divided into 2 groups: 36 (8.1%) in the IDA with thrombocytosis group (mean ± SD platelet count, 521.67 ± 73.85 × 109/L) and the remaining 404 in the IDA without thrombocytosis group (mean ± SD platelet count, 291.39 ± 76.11 × 109/L).Differences were found in baseline characteristics including white blood cell (WBC) count, hemoglobin (Hb) level, mean corpuscular volume (MCV), transferrin saturation (TSAT), serum iron (SI) level, and total iron-binding capacity (TIBC) between the two groups (P < .05). From baseline to 8 weeks of continuous iron supplementation treatment, the mean platelet counts in both groups were decreased at 2-week treatment intervals. And in the IDA with thrombocytosis group, half of the patients resolved thrombocytosis after 2 weeks of iron supplementation, and the counts of all patients with thrombocytosis decreased below 450 × 109 /L within 6 weeks.In conclusion, the rate of reactive thrombocytosis in patients with IDA was 8.1%. IDA patients with thrombocytosis showed more severe anemia, lower ferritin, and more advanced iron deficiency than those without thrombocytosis. Platelet counts of half of the patients with thrombocytosis reduced below cut off of 450 × 109/L for thrombocytosis after 2 weeks of treatment, and all patients resolved thrombocytosis after 6 weeks. Our study provided clinical evidence for more effective and individualized iron management in the future. IDA patients with thrombocytosis should take active iron treatment and increase follow-up frequency to prevent thrombotic events. For patients with persistent thrombocytosis, a concomitant clonal process should be considered.


The influence of warm-up duration on simulated rugby league interchange match performance.
The study was conducted to understand the effects of a short (10 min) and a long (30 min) duration warm-up on subsequent readiness to exercise and movement during simulated rugby league match play. Methods: Using a randomised cross-over design, 13 male rugby players (age: 23.6 ± 4.1 y) completed 10- or 30-min warm-up immediately before 2 × 23 min rugby league movement simulation protocol. Results: Total distance, high- and low speed running and tympanic temperature (ES = 0.56 to 20.8) were all higher in the 30 min warm-up, with differences in relative distance and heart rate unclear (ES = -0.36 to 0.06). Differences in participants' readiness to exercise after the warm-ups were unclear (ES = 0.25). Differences between trials for movement characteristics (ES = -0.13 to -0.32), RPE (ES = -0.13 to 0.04) and B[La] after the simulation were mostly unclear, with only trivial changes in high-speed running (ES = 0.08) and a lower heart rate (ES = -0.26) between the two playing bouts after the 30 min warm-up trial. Conclusion: Practitioners can use warm-ups between 10 or 30 minutes for rugby league interchange players without any implications for subsequent match running performance.


Constitutive activation of the opioid receptor-like (ORL1) receptor by mutation of Asn133 to tryptophan in the third transmembrane region.
We have introduced a series of point mutations into the human opioid receptor-like (ORL1) receptor and characterized them for their ability to constitutively activate G protein-coupled receptor signalling pathways. Among the 12 mutants generated, mutation at Asn133 (N133W) gave increased basal signalling through three separate pathways. N133W increased the basal activity of G14- and G16-dependent pathways by two- to three-fold. The constitutive activity of the mutant was confirmed by the finding that the enhanced activity is dependent on the level of receptor expression. In HEK-293 cells stably expressing N133W, signalling through Gi/o-dependent pathways was also observed. Radioligand binding studies revealed that the affinity for nociceptin of the wild-type ORL1 receptor and the N133W mutant do not differ significantly, suggesting that the ligand binding and signalling functions of constitutively active mutants of G protein-coupled receptors are not necessarily intrinsically linked. In conclusion, our results demonstrate that a mutation in the third transmembrane domain is able to increase the basal signalling activity of the human ORL1 receptor.


Hydrogen bonding in ortho-substituted arylamides: the influence of protic solvents.
We combine molecular modeling and NMR methods to better understand intramolecular hydrogen bonding (H-bonding) in a frequently used arylamide foldamer building block, ortho-methoxy-N-methylbenzamide. Our results show that solvents have a profound influence on the cumulative number and stabilizing effects of intramolecular H-bonds, and thus conformational preferences, of foldamers based on this compound. While intramolecular H-bonds are conserved in aprotic environments, they are significantly disrupted in protic solvents. Furthermore, these solvent effects can be accurately quantified using the computational approach presented here. The results could have significant implications in foldamer design, particularly for applications in aqueous environments.


High pressures are generated at the tip of laparoscopic graspers.
Despite its importance the interface between tissue and instrument is poorly understood. A thin film pressure transducer was deployed between the jaws of eight different laparoscopic instruments and a simulated tissue to study the forces generated at the tip of laparoscopic graspers and the effect of a change in angle of tissue tension at the interface between tissue and laparoscopic grasper. Pressure was concentrated at the tip of the instrument. Localized pressures increased on average from 210 kPa to 650 kPa as the angle of grasp was increased from 0 to 135 degrees. There was a wide variation between instruments with some exhibiting increases in tip pressure of a factor of eight as the angle was increased. High pressures are generated at the tip of laparoscopic graspers. Pressures increase as the angle of incidence of the grasper in relation to the tissue increases. The changes in pressure with change in angle are independent of load and handle pressure.


A melanocortin-4 receptor (MC4R) polymorphism is associated with performance traits in divergently selected Large White pig populations.
The melanocortin-4 receptor (MC4R) has a vital role in the control of energy balance and the genetic basis of obesity. A polymorphism, which results in the replacement of aspartic acid with asparagine at position 298 of the porcine MC4R gene, within the seventh transmembrane domain, has previously been described. In the current study, allele frequencies for this Asp298Asn polymorphism were investigated in lines of Large White pigs which had been divergently selected for seven generations based on lean food conversion (LFC), lean growth with ad libitum feeding (LGA), lean growth with restricted feeding (LGS) and daily feed intake (DFI). The association of the Asp298Asn polymorphism with performance traits in these lines was assessed. The frequency of Asp298 was higher (P < 0.001) in the LFC high line (0.48) than the low line (0.00), while the frequency of Asn298 was higher (P < 0.01) in the LGA high line (0.22) than the low line (0.04). When analysed across all lines, the Asp298Asn polymorphism was significantly associated with ultrasonic backfat depth, average daily gain and daily feed intake (P < 0.05). Asp298 homozygous animals had mean values of 13.3 mm, 733 g and 1933 g for backfat, average daily gain and daily feed intake respectively, compared with 14.7 mm, 805 g and 2098 g for Asn298 homozygotes. Therefore, the data support a role for the MC4R Asp298Asn polymorphism in the genetic basis of economically important traits in Large White pigs.


Intermediate CAG repeat lengths (53,54) for MJD/SCA3 are associated with an abnormal phenotype.
We report on a Dutch family in which 4 members in 2 generations have intermediate repeat lengths (53 and 54) for Machado-Joseph Disease/Spinocerebellar Ataxia (MJD/SCA3). All but the youngest have a restless legs syndrome with fasciculations and a sensorimotor axonal polyneuropathy. Central neurological abnormalities are only present in 2. This family shows that intermediate repeat lengths can be pathogenic and may predispose for restless legs and peripheral nerve disorder.


Occupational stress, social support, and quality of life among Jordanian mental health nurses.
Occupational stress affects physical and mental health of mental health nurses. This study measured levels of occupational stress and identified the variables that are associated with occupational stress among Jordanian mental health nurses. A descriptive design was conducted, using self-report questionnaires and demographic characteristics. Data were collected from 181 mental health nurses who were recruited from all mental health settings in Jordan. Jordanian mental health nurses showed high levels of occupational stress regarding "client-related difficulties," "lack of resources," and "workload." The highest level of social support as indicated by these Jordanian mental health nurses was from a spouse/partner followed by colleagues. Regarding quality of life (QOL), physical health scores were higher than mental health scores. Occupational stress correlated significantly and negatively with QOL-physical scores, QOL-mental scores, and social support scores, and correlated positively with being physically assaulted, verbally assaulted, and the respondent having the intention to leave his or her current job. Social support, QOL-mental scores, verbal assault, ward type, and intention to leave the current job were the best predictors of occupational stress among Jordanian mental health nurses. Mental health nurses are under significant occupational stress levels; therefore, comprehensive interventions aimed at minimizing the risk of occupational stress and improving social support and quality of life among mental health nurses are needed.


Role of cytochrome P450-dependent transient receptor potential V4 activation in flow-induced vasodilatation.
Fluid shear stress elicits endothelium-dependent vasodilatation via nitric oxide and prostacyclin-dependent and -independent mechanisms. The latter includes the opening of Ca(2+)-operated potassium channels by cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) leading to endothelial hyperpolarization. We previously reported that EETs activate the transient receptor potential (TRP) V4 channel in vascular endothelial cells and that Ca(2+) influx in these cells in response to mechanical stimuli is dependent on the activation of CYP epoxygenases. We therefore hypothesized that the TRPV4 channel is involved in the flow-induced vasodilatation attributed to the endothelium-derived hyperpolarizing factor (EDHF). In the presence of N(omega)-nitro-l-arginine methyl ester and diclofenac, precontracted mouse carotid arteries displayed a considerable vasodilatation in response to step-wise increases in luminal flow. The EDHF-mediated, flow-induced vasodilatation could be inhibited by the epoxygenase inhibitor MS-PPOH, was abolished after down-regulation of CYP epoxygenases in tissue culture, and could be restored by viral expression of CYP2C9 in the endothelium. The TRPV4-channel inhibitor ruthenium red (RuR) inhibited the EDHF-mediated flow response, but the combination of MS-PPOH and RuR had no further effect. RuR also inhibited the response in CYP2C9-overexpressing vessels. Moreover, TRPV4-deficient mice demonstrated a blunted EDHF-mediated response to increases in luminal flow in comparison to their wild-type littermates, and the addition of MS-PPOH was without effect in these mice (up to 38 +/- 3% in TRPV4(-/-) vs. 57 +/- 6% in TRPV4(+/+), P < 0.01). In cultured human endothelial cells, exposure to fluid shear stress induced the translocation of the TRPV4 channel from a perinuclear localization to the cell membrane. We conclude that the TRPV4 channel is involved in flow-induced, endothelium-dependent vasodilatation of murine carotid arteries. Moreover, the activation of the TRPV4 channel by flow requires an active CYP epoxygenase and the translocation of the channel to the cell membrane.


Electrochemical synthesis of magnetic iron oxide nanoparticles with controlled size.
We present a novel and facile method enabling synthesis of iron oxide nanoparticles, which are composed mainly of maghemite according to X-ray diffraction (XRD) and Mössbauer spectroscopy studies. The proposed process is realized by anodic iron polarization in deaerated LiCl solutions containing both water and ethanol. Water seems to play an important role in the synthesis. Morphology of the product was studied by means of transmission electron microscopy and XRD. In the solution containing almost 100% of water a black suspension of round shaped maghemite nanoparticles of 20-40 nm size is obtained. Regulating water concentration allows to control nanoparticle size, which is reduced to 4-6 nm for 5% of water with a possibility to reach intermediate sizes. For 3% or lower water concentration nanoparticles are of a needle-like shape and form a reddish suspension. In this case phase determination is problematic due to a small particle size with the thickness of roughly 3 nm. However, XRD studies indicate the presence of ferrihydrite. Coercivities of the materials are similar to those reported for nanoparticle magnetite powders, whereas the saturation magnetization values are considerably smaller.


Selectivity of alkali cation influx across the plasma membrane of oat roots: cation specificity of the plasma membrane ATPase.
Influx of alkali cations (Li(+), Na(+), K(+), Rb(+), Cs(+)) across plasma membranes of cells of excised roots of Avena sativa cv. Goodfield was selective, but different, in the absence and in the presence of 1 mm CaSO(4). Ca(2+) reduced the influx rates of all of the alkali cations-especially Na(+) and Li(+). Transport selectivity changed as the external concentrations of the alkali cations increased.Plasma membrane ATPase, purified from Avena sativa roots, was differentially stimulated by alkali cations. This specificity, however, was not altered by Ca(2+) or the external cation concentrations. A close correspondence existed between the relative influx rates of K(+), Rb(+), and Cs(+) and the relative stimulation of the ATPase by these cations. A similar correspondence did not occur for Na(+) and Li(+).Selective cation transport in oat roots could result, in part, from the specificity of the plasma membrane ATPase, but other factors such as specific carriers or porters or differential diffusion rates must also be involved.


Long-term outcome of centrally located low-grade glioma in children.
Optimal management of children with centrally located low-grade glioma (LGG) is unclear. Initial interventions in most children are chemotherapy in younger and radiation therapy (RT) in older children. A better understanding of the inherent risk factors along with the effects of interventions on long-term outcome can lead to reassessment of the current approaches to minimize long-term morbidity. To reassess the current treatment strategies of centrally located LGG, we compared the long-term survival and morbidity of different treatment regimens. Medical records of patients primarily treated at Texas Children's Cancer and Hematology Centers between 1987 and 2008 were reviewed. Forty-seven patients with a median follow-up of 79 months were included in the analysis. The 5-year overall survival and progression-free survival (PFS) for all patients were 96% and 53%, respectively. The 5-year PFS for those treated initially with RT (12 patients; median age, 11 years [range, 3-15 years]) and with chemotherapy (28 patients; median age, 2 years [range 0-8 years]) were 76% and 37%, respectively (log-rank test P = .02). Among children who progressed after chemotherapy, the 5-year PFS after salvage RT was 55%. Patients diagnosed at a younger age (<5 years) were more likely to experience endocrine abnormalities (Fisher exact test; P<.00001). Effective and durable tumor control was obtained with RT as initial treatment. In younger patients, chemotherapy can delay the use of RT; however, frequent progression and long-term morbidity are common. More effective and less toxic therapies are required in these patients, the majority of whom are long-term survivors.


Carbon monoxide inhalation decreased lung injury via anti-inflammatory and anti-apoptotic effects in brain death rats.
Brain death (BD) induces acute lung injury and makes donor lungs unfit for transplantation. Carbon monoxide (CO) inhalation at 50-500 ppm exerts anti-inflammatory and anti-apoptosis effects in several lung injury models. We examined whether CO inhalation would show favorable effects on lung injury in BD rats. BD rats inhaled 250 ppm CO for two hours. Inhalation decreased the severity of lung injury, as checked by histological examination. CO treatment reversed aggravation in PaO(2)/FiO(2), base excess and pH of BD rats. CO inhalation downregulated the pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6), and inhibited activity of myeloperoxidase in lung tissue. Inhalation significantly decreased cell apoptosis of lungs, and inhibited mRNA expression of intercellular adhesion molecule-1 and caspase-3 in the lungs. Further, the inhalation activated phosphorylation of p38 expression and inhibited phosphorylation of extracellular signal-regulated kinase expression in the lungs. In conclusion, CO exerts potent protective effects on lungs from BD rats, exhibiting anti-inflammatory and anti-apoptosis functions by modulating the mitogen-activated protein kinase signal transduction.