Selenium and asthma: a complex relationship.
Descriptive studies in humans investigating the relationship between selenium (Se) status and asthma have presented inconsistent results. The concept of low Se status as a potential risk factor for increased prevalence or severity of asthma is based on the role that Se, through its incorporation into selenoproteins, plays as a potent antioxidant capable of augmenting the oxidative stress that accompanies asthma. However, Se intake also exerts a significant influence over immune responses. Thus, the dual effects of Se status on controlling oxidative stress in the lungs and regulating T helper 2 responses that drive allergic asthma, as well as which selenoproteins are key to regulating these processes, must be considered when attempting to decipher the relationship between this essential nutrient and complex allergic diseases such as asthma.


Glycothermally Synthesized Carbon Dots with Narrow-Bandwidth and Color-Tunable Solvatochromic Fluorescence for Wide-Color-Gamut Displays.
Fluorescent carbon dots (CDs) represent a promising eco-friendly next-generation phosphor. However, most CDs exhibit broad photoluminescence (PL) spectra [full width at half-maximum (fwhm) over 60 nm]; few works on CDs with sharp PL spectra (fwhm less than 40 nm) have been reported. In addition, their syntheses and color tuning require harsh conditions of high temperatures, long reaction times, and high pressures with catalysts. Here, we successfully prepared narrow-bandwidth emissive CDs (fwhm of 27-40 nm) from phloroglucinol in a glycol solvent of 1,2-pentanediol at temperatures as low as 180 °C for a reaction duration of as short as 6 h under ambient conditions without any catalysts via an open reaction system in which dehydration and condensation reactions among phloroglucinol molecules were enhanced. We shifted the emission peak from 463 to 511 nm by selecting seven kinds of solvents with different polarities, that is, emission colors could be tuned from blue to green by taking advantage of fluorescence solvatochromism. The CD-dispersed polymer films showed a similar solvatochromic behavior and sharp PL spectra, verifying the feasibility of applying the CDs to displays with a wide color gamut.


Risk Factors, Length of Stay and In-Hospital Mortality of Methicillin-Resistant Staphylococcus aureus Infections: A Case-Control Study.
The emergence of strains of methicillin-resistant Staphylococcus aureus is a serious therapeutic challenge in healthcare provision. With this study, we aimed to investigate the risk factors and clinical outcomes (mortality and length of hospital stay) associated with methicillin-resistant Staphylococcus aureus infections in patients admitted to a district hospital in Portugal. A case-control study was performed in 96 cases and 122 controls, selected, respectively, as function of antibiotic resistance or sensitivity to methicillin. Data were obtained through consultation of clinical records and subjected to multivariate statistical analysis. We identified the following independent risk factors for the occurrence of methicillin-resistant Staphylococcus aureus infection: urinary catheter (aOR = 10.62, 95% CI 3.66 - 30.78), prior use of antibiotics in the last 30 days (aOR = 5.60, 95% CI 2.15 - 14.62), exposure to 5 - 7 days of hospitalization (aOR = 4.99, 95% CI 1.20 - 20.79) or to ≥ 8 days (aOR = 5.34, 95% CI 1.18 - 24.22), chronic obstructive pulmonary disease (aOR = 4.27, 95% CI 1.64 - 11.13) and recent hospitalization (aOR = 2.66, 95% CI 1.14 - 6.23). Compared to infections due to methicillin-susceptible Staphylococcus aureus, we found increased probability of having a longer hospital stay (aHR = 1.74, 95% CI 1.11 - 2.71) and in-hospital mortality was significantly higher (p = 0.001) between patients infected by methicillin-resistant Staphylococcus aureus. The results demonstrate that methicillin resistance is associated with an increased clinical risk to patients infected by Staphylococcus aureus, in particular, a raised mortality and prolonged hospitalization. Our study underlines the additional burden imposed by methicillin resistance in Staphylococcus aureus infections. This highlights an urgent need to reinforce and optimize prevention, control, timely detection and effective treatment strategies for multidrug--resistant Staphylococcus aureus strains.


Participation of ticks in the infectious cycle of canine visceral leishmaniasis, in Teresina, Piauí, Brazil.
In this study, we detected Leishmania spp. infection in R. sanguineus collected from dogs that were naturally infected with L. (L.) infantum. We examined 35 dogs of both sexes and unknown ages. The infected dogs were serologically positive by the immunofluorescence antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA), and Quick Test-DPP (Dual Path Platform), as well as parasitological examination of a positive skin biopsy or sternal bone marrow aspiration. Ten negative dogs were included as controls. The ticks that infested these dogs were collected in pools of 10 adult females per animal. The PCR was performed with specific primers for Leishmania spp., which amplified a 720-bp fragment. Of the 35 analyzed samples, a product was observed in eight samples (8/35; 22.9%). We conclude that the presence of parasite DNA suggests that ticks participate in the zoonotic cycle of canine visceral leishmaniasis, in the city of Teresina, Piauí.


Microarray analysis of equine endometrium at days 8 and 12 of pregnancy.
Establishment and maintenance of pregnancy in equids is only partially understood. To provide new insights into early events of this process, we performed a systematic analysis of transcriptome changes in the endometrium at Days 8 and 12 of pregnancy. Endometrial biopsy samples from pregnant and nonpregnant stages were taken from the same mares. Composition of the collected biopsy samples was analyzed using quantitative stereological techniques to determine proportions of surface and glandular epithelium and blood vessels. Microarray analysis did not reveal detectable changes in gene expression at Day 8, whereas at Day 12 of pregnancy 374 differentially expressed genes were identified, 332 with higher and 42 with lower transcript levels in pregnant endometrium. Expression of selected genes was validated by quantitative real-time RT-PCR. Gene set enrichment analysis, functional annotation clustering, and cocitation analysis were performed to characterize the genes differentially expressed in Day 12 pregnant endometrium. Many known estrogen-induced genes and genes involved in regulation of estrogen signaling were found, but also genes known to be regulated by progesterone and prostaglandin E2. Additionally, differential expression of a number of genes related to angiogenesis and vascular remodeling suggests an important role of this process. Furthermore, genes that probably have conserved functions across species, such as CRYAB, ERRFI1, FGF9, IGFBP2, NR2F2, STC1, and TNFSF10, were identified. This study revealed the potential target genes and pathways of conceptus-derived estrogens, progesterone, and prostaglandin E2 in the equine endometrium probably involved in the early events of establishment and maintenance of pregnancy in the mare.


Thermal annealment and nitric oxide effects on free radicals in x-irradiated cells.
Four kinds of radicals are identified in dry spores (Bacillus megaterium) after x-irradiation: those associated with singlet, doublet, triplet, and oxygen-complex types of spectra. The singlet, present only at low temperatures, gives rise irreversibly to the doublet at 25 degrees C. All hyperfine structure is depressed after annealment at 1000 degrees C and is lost when oxygen or nitric oxide is added. The physical results support the hypothesis that reactions of long-lived free radicals can account for the radiobiological phenomena of thermorestoration, nitric oxide protection, and latent oxygen effect.


[Evaluation of the contractile function of the right ventricle in patients with mitral-tricuspid valve defect].
A comparative analysis is presented of the Sonnenblick contractility index, end-diastolic and systolic pressure in the right ventricle, cardiac index in 76 patients with mitral-tricuspid disease and with a mitral disease alone. Higher figures of the contractility index of the right ventricle were obtained in patients with an organic tricuspid defect with a predominance of insufficiency, than in those with mitral insufficiency and relative tricuspid insufficiency. The contractility index of the right ventricle decreases along with an increasing stenosis of the right venous ostium. The study has demonstrated that the patients with mitral-tricuspid defects tend to display a less distinct inotropic reaction to Digoxin as compared with those having a mitral defect alone.


PDGF/VEGF signaling controls cell size in Drosophila.
In multicellular animals, cell size is controlled by a limited set of conserved intracellular signaling pathways, which when deregulated contribute to tumorigenesis by enabling cells to grow outside their usual niche. To delineate the pathways controlling this process, we screened a genome-scale, image-based Drosophila RNA interference dataset for double-stranded RNAs that reduce the average size of adherent S2R+ cells. Automated analysis of images from this RNA interference screen identified the receptor tyrosine kinase Pvr, Ras pathway components and several novel genes as regulators of cell size. Significantly, Pvr/Ras signaling also affected the size of other Drosophila cell lines and of larval hemocytes. A detailed genetic analysis of this growth signaling pathway revealed a role for redundant secreted ligands, Pvf2 and Pvf3, in the establishment of an autocrine growth signaling loop. Downstream of Ras1, growth signaling was found to depend on parallel mitogen-activated protein kinase (MAPK) and phospho-inositide-3-kinase (PI3K) signaling modules, as well as the Tor pathway. This automated genome-wide screen identifies autocrine Pvf/Pvr signaling, upstream of Ras, MAPK and PI3K, as rate-limiting for the growth of immortalized fly cells in culture. Since, Pvf2/3 and Pvr show mutually exclusive in vivo patterns of gene expression, these data suggest that co-expression of this receptor-ligand pair plays a key role in driving cell autonomous growth during the establishment of Drosophila cell lines, as has been suggested to occur during tumor development.


Relationship of infant mortality to the availability of obstetrical care in Indiana.
Projects that are currently under way in Indiana to improve access to obstetrical care have not addressed the availability of these services in nonmetropolitan areas. This study was designed to identify all physicians who were providing obstetrical services in every county throughout the state to determine if there is a correlation between the availability of these services and the infant mortality rate in nonmetropolitan counties. A state-wide physician profile maintained by the Indiana Academy of Family Physicians was cross-referenced with a telephone survey of all hospitals in the state to identify those physicians providing obstetrical services within each county in Indiana. The number of physicians in each county was then compared with the number of births per year by mothers from that county to determine whether nonmetropolitan counties had sufficient physicians to provide obstetrical services. Finally, these findings were compared with the most recent infant mortality rate for each nonmetropolitan county. A total of 610 family physicians, 311 obstetricians, and 75 general practitioners were providing obstetrical care in Indiana. There were 10 counties that did not have a physician who delivered babies practicing in that county. Thirty-two counties had more women who needed obstetrical care than the current number of physicians could serve. There was a negative correlation between physician availability and infant mortality in Indiana's nonmetropolitan counties (r = -.38; P less than .02). Access to care for pregnant patients is a major problem in rural Indiana and hampers Indiana's ability to reduce its current infant mortality rate.


Probing the effect of an inhibitor of an ATPase domain of Hsc70 on clathrin-mediated endocytosis.
Hsc70 is known to be involved in clathrin-mediated endocytosis (CME) by which cells take up various extracellular materials. More specifically, this protein promotes the disassembly of clathrin-coated vesicles (CCVs) by directly binding to clathrin during CME. As the ATPase activity of Hsc70 is required for its association with clathrin, we have investigated the effect of an inhibitor (apoptozole, Az) of an ATPase domain of Hsc70 on CME. The results of biochemical studies show that Az binds to Hsc70 and Hsp70 without binding to other types of heat shock proteins. Structure-activity relationship studies provide information on the structural features responsible for the inhibition of the ATPase activity of Hsc70. The results obtained from cell experiments reveal that Az disrupts the interaction of Hsc70 with clathrin in cells, thereby leading to the accumulation of transferrin in CCVs and suppression of release of free Fe(3+) from CCVs during transferrin receptor-mediated endocytosis.


Quality of life and functional impairment in obsessive-compulsive disorder: a comparison of patients with and without comorbidity, patients in remission, and healthy controls.
Several studies have demonstrated that obsessive-compulsive disorder (OCD) is associated with interference in quality of life (QOL) and functional impairment. However, these studies did not compare individuals in remission to individuals who continue to have the disorder, predominantly used comparisons with norms and not with a matched normal sample, and did not always consider the impact of comorbidity. We administered multiple measures that assess QOL and functional impairment to 66 OCD patients who had previously consented for a clinical trial and to 36 age and sex matched individuals who denied any psychiatric history. Results confirm that OCD was associated with significantly lower QOL and functional impairment compared to healthy controls (HCs) in areas of work, social life, and family life. Individuals with OCD and other comorbid psychiatric diagnoses showed the poorest QOL and functioning, with comorbid depression accounting for much of the variance. The levels of QOL and functioning in individuals in remission tended to lie in between HCs and individuals with current OCD: their QOL or functioning did not differ significantly from HCs nor did they consistently differ significantly from those who had current OCD. These results suggest that individuals who are in remission have improved levels of QOL and functioning, whereas individuals with OCD are significantly impaired, and individuals with OCD and comorbid disorders are the most impaired. Treatment strategies should be focused on achieving remission of all symptoms to have the greatest impact on functioning and QOL.


Drug Delivery Innovations to Address Global Health Challenges for Pediatric and Geriatric Populations (Through Improvements in Patient Compliance).
Despite significant advances in pharmaceutical and biotechnological drug discovery, the global population is plagued with many challenging diseases. These are further compounded by anticipated explosion in an ageing population, which presents several problems such as polypharmacy, dysphagia, and neurologic conditions, resulting in noncompliance and disease complications. For antibiotics, poor compliance, can result in development of drug-resistant infections which can be fatal. Furthermore, children, especially, in developing countries die unnecessarily from easily treatable diseases (e.g., malaria), due to poor compliance arising from bitter taste and inability to swallow currently available medication. Although some of these challenges require the discovery of new drug compounds, a significant number can be resolved by employing pharmaceutics approaches to reduce the incidence of poor patient compliance. Such solutions are expected to make swallowing easier and reduce the need to swallow several solid medications, which is difficult for vulnerable pediatric and geriatric patients. This commentary will explore the current state of the art in the use of drug delivery innovations to overcome some of these challenges, taking cues from relevant regulatory agencies such as the Food and Drug Administration, the European Medicines Agency, World Health Organization, and the peer-reviewed scientific and clinical literature.


Simple Model of a Line Selected, Long Chain, Pulsed DF-CO(2) Chemical Transfer Laser.
A rate equation model of a pulsed DF-CO(2) chemical transfer laser is Simplified by investigating the relationship of kinetic mechanisms. The model reduces to one equation which when Solved permits calculation of all pulse characteristics as a function of time. At low levels of initiation, predictions of this laser simulation model are in excellent agreement with those of a more comprehensive model presented in an earlier paper. Model predictions are also found to be consistent with experiment. The simplicity of the present model lends itself to easy physical interpretation and permits efficient and accurate prediction of transfer laser performance characteristics in regimes of practical interest.


'Senescence-associated vacuoles' are involved in the degradation of chloroplast proteins in tobacco leaves.
Massive degradation of photosynthetic proteins is the hallmark of leaf senescence; however the mechanism involved in chloroplast protein breakdown is not completely understood. As small 'senescence-associated vacuoles' (SAVs) with intense proteolytic activity accumulate in senescing leaves of soybean and Arabidopsis, the main goal of this work was to determine whether SAVs are involved in the degradation of chloroplastic components. SAVs with protease activity were readily detected through confocal microscopy of naturally senescing leaves of tobacco (Nicotiana tabacum L.). In detached leaves incubated in darkness, acceleration of the chloroplast degradation rate by ethylene treatment correlated with a twofold increase in the number of SAVs per cell, compared to untreated leaves. In a tobacco line expressing GFP targeted to plastids, GFP was re-located to SAVs in senescing leaves. SAVs were isolated by sucrose density gradient centrifugation. Isolated SAVs contained chloroplast-targeted GFP and the chloroplast stromal proteins Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) and glutamine synthetase, but lacked the thylakoid proteins D1 and light-harvesting complex II of the photosystem II reaction center and photosystem II antenna, respectively. In SAVs incubated at 30 degrees C, there was a steady decrease in Rubisco levels, which was completely abolished by addition of protease inhibitors. These results indicate that SAVs are involved in degradation of the soluble photosynthetic proteins of the chloroplast stroma during senescence of leaves.


Thermal phenotypic plasticity of body size in Drosophila melanogaster: sexual dimorphism and genetic correlations.
Thirty isofemale lines collected in three different years from the same wild French population were grown at seven different temperatures (12-31 °C). Two linear measures, wing and thorax length, were taken on 10 females and 10 males of each line at each temperature, also enabling the calculation of the wing/thorax (W/T) ratio, a shape index related to wing loading. Genetic correlations were calculated using family means. The W-T correlation was independent of temperature and on average, 0.75. For each line, characteristic values of the temperature reaction norm were calculated, i.e. maximum value, temperature of maximum value and curvature. Significant negative correlations were found between curvature and maximum value or temperature of maximum value. Sexual dimorphism was analysed by considering either the correlation between sexes or the female/male ratio. Female-male correlation was on average 0.75 at the within line, within temperature level but increased up to 0.90 when all temperatures were averaged for each line. The female-male ratio was genetically variable among lines but without any temperature effect. For the female/male ratio, heritability (intraclass correlation) was about 0.20 and evolvability (genetic coefficient of variation) close to 1. Although significant, these values are much less than for the traits themselves. Phenotypic plasticity of sexual dimorphism revealed very similar reaction norms for wing and thorax length, i.e. a monotonically increasing sigmoid curve from about 1.11 up to 1.17. This shows that the males are more sensitive to a thermal increase than females. In contrast, the W/T ratio was almost identical in both sexes, with only a very slight temperature effect.


The effect of age on sildenafil biotransformation in rat and mouse liver microsomes.
Sildenafil [SIL (Viagra); Pfizer, New York, NY] is a widely prescribed agent for erectile dysfunction in men older than 65 years. The present study evaluated experimental models to assess age-dependent changes in SIL biotransformation using hepatic microsomes from male rats and mice ranging from 6 weeks to 26 months of age. The role of specific isoforms in the conversion of SIL to its primary circulating metabolite, UK-103,320 (piperazine N-desmethyl sildenafil) in the mouse was also investigated using immunoinhibitory antibodies. Although CYP2C11 largely mediated UK-103,320 formation in the rat, UK-103,320 formation was principally inhibited by a CYP3A antibody in the mouse. An age-related decrement in metabolite formation rate was observed for both species, although this effect was more pronounced in the old rats (reduced to 7% of young) than in the old mice (reduced to 51% of young). CYP2C expression was assessed by Western blot analysis in rat and mouse livers. Age-related differences in hepatic CYP3A expression in the mouse were also compared with metabolite formation rates in the mouse model. Decrements with age in CYP2C and -3A expression in the aging rodents paralleled the decrements in SIL biotransformation, suggesting that age-related differences in SIL metabolic rate may, in part, reflect differences in expression. Although the role of specific CYP enzymes and the clearance values for this reaction may differ among species, age-related changes in these rodent models are consistent with the reduced clearance of SIL observed in human studies.


Nitrogen-sparing effect of fat emulsion compared with glucose in the postoperative period.
The investigation was directed towards elucidating two questions of current interest in parenteral nutrition: (1) Is it at all possible to obtain positive nitrogen balance during the immediate postoperative course (the "catabolic phase")? (2) Is there any difference in the nitrogen balance if the main energy source consists of hypertonic carbohydrate solution or of fat emulsion? Nine patients were examined during the first six postoperative days after gastric resection with regard to nitrogen balance. All of them were given crystalline amino acids (Vamin) corresponding to 0.3 g N/kg body-weight and day together with fructose, electrolytes, and vitamins. Five of the patients were also given 50 kcal/kg body-weight and day mainly as fat emulsion (Intralipid) and the other four received the same amount of energy mainly as 54 percent glucose solution. The investigation showed that it was possible to obtain nitrogen equilibrium during the immediate postoperative course, whether the main non-protein supply consisted of hypertonic carbohydrate solution or of fat emulsion. There was no significant difference between the two energy sources in this respect. Fat emulsion as main energy source is preferable, however, for several reasons.


Mortality assessment attributed to long-term exposure to fine particles in ambient air of the megacity of Tehran, Iran.
Few studies regarding the health effects of long-term exposure to particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) have been carried out in Asia or the Middle East. The objective of our study was to assess total, lung cancer and chronic obstructive pulmonary disease (COPD) mortality attributed to long-term exposure to PM2.5 among adults aged over 30 years in Tehran from March 2013 to March 2016 using AirQ+ software. AirQ+ modeling software was used to estimate the number of deaths attributed to PM2.5 concentrations higher than 10 μg m-3. Air quality data were obtained from the Department of Environment (DOE) and Tehran Air Quality Control Company (TAQCC). Only valid stations with data completeness of 75% in all 3 years were selected for entry into the model. The 3-year average of the 24-h concentrations was 39.17 μg m-3. The results showed that the annual average concentration of PM2.5 in 2015-2016 was reduced by 13% compared to that in 2013-2014. The annual average number of all natural, COPD, and lung cancer deaths attributable to long-term exposure to PM2.5 in adults aged more than 30 years was 5073, 158, and 142 cases, respectively. The results of all three health endpoints indicate that the mortality attributable to PM2.5 decreased yearly from 2013 to 2016 and that the reduced mortality was related to a corresponding reduction in the PM2.5 concentration. Considering these first positive results, the steps that have been currently taken for reducing air pollution in Tehran should be continued to further improve the already positive effects of these measures on reducing health outcomes.


Growth patterns of height and weight among three groups of Samoan preadolescents.
The Samoan population affords an excellent opportunity to study the influences of modernization and migration on growth. Moreover, since Samoan adults in some settings have very high rates of obesity, the childhood precursors to obesity can be studied among Samoans. This study reports the results of a survey of 786 Samoan children between 5.5 and 11.5 years of age living in traditional, modern or migrant situations. It was found that the children from Western Samoa (traditional) were significantly shorter, lighter and lighter for height than their counterparts in American Samoa (modern) and Hawaii (migrant). The major influence on height and weight appears to be modernization (Western versus American Samoa), with migration (American Samoa versus Hawaii) playing only a small incremental role (significant only for weight among boys). The influences of modernization are likely to be exerted through changes in diet and activity among the children. Modernization and migration are associated with obesity among Samoan adults, and this pattern also seems to be established in preadolescents.


New antiepileptic medication linked to blue discoloration of the skin and eyes.
Ezogabine is an antiepileptic medication approved in June 2011 by the US Food and Drug Administration (FDA) as an adjunctive treatment for partial seizures. Minimal drug interactions and a novel mechanism of action made ezogabine an appealing new treatment option. However, adverse effects reported during clinical trials and following drug approval have been alarming. A Risk Evaluation Mitigation Strategy (REMS) program has been established for urinary retention. A safety alert was published in April 2013 warning ezogabine may cause retinal pigment abnormalities and/or blue-gray discoloration, most notably on or near the lips, nail beds, sclera and conjunctiva with long-term use. In October 2013, the FDA announced a formal label change to ezogabine to include a black boxed warning emphasizing the previously reported warnings of eye and skin discoloration and permanent vision changes. Given the unknown nature of the pathophysiology, consequences and potential for reversibility of these effects, GlaxoSmithKline and the FDA have published recommendations for patients currently receiving ezogabine. Further data from published case reports and long-term safety trials in the future may lend additional insight into these concerning effects.


Neuropeptides in hyperthermia.
Brain damage as a result of hyperthermia or heat-stress has been the focus of attention in many areas of neuroscience in recent years. Heat-induced alterations in structural components of the central nervous system (CNS) will obviously also influence the relevant transmitter systems, which may be involved in a variety of different behaviors. Indeed, many studies have indicated that excitatory amino acids, and monoaminergic and peptidergic systems are affected during hyperthermia. This chapter will address past and current research on various neuropeptides that have been implicated in the consequences of hyperthermia and various other heat disorders. However, considering the large and even increasing number of identified neuroactive peptides, it is necessary to limit this chapter to a few peptides or peptide systems, which have received particular attention in relation to hyperthermia. Among these are the opioid peptides, the tachykinins, calcitonin gene-related peptide (CGRP), and peptides belonging to the angiotensin system. Most of these neuropeptides are not only affected by hyperthermia and abnormal alterations in the body temperature but also are involved in the endogenous mechanisms of regulating body temperature. This review does not endeavor to fully cover the field but it does aim to give the reader an idea of how various neuropeptides may be involved in the control of body heat and how peptidergic systems are affected during various thermal changes, including both immediate and long-term consequences.


FOXP3 over-expression inhibits melanoma tumorigenesis via effects on proliferation and apoptosis.
The Forkhead box P3 (FOXP3) transcription factor is the key driver of regulatory T cell (Treg cells) differentiation and immunosuppressive function. In addition, FOXP3 has been reported to be expressed in many tumors, including melanoma. However, its role in tumorigenesis is conflicting, with both tumor suppressive and tumor promoting functions described. The aim of the current study was to characterize the expression and function of FOXP3 in melanoma. FOXP3 expression was detected by immunohistochemistry (IHC) in 12% (18/146) of stage III and IV melanomas. However expression was confined to fewer than 1% of cells in these tumors. Stable over-expression of FOXP3 in the SK-MEL-28 melanoma cell line reduced cell proliferation and clonogenicity in vitro, and reduced xenograft growth in vivo. FOXP3 over-expression also increased pigmentation and the rate of apoptosis of SK-MEL-28 cells. Based on its infrequent expression in human melanoma, and its growth inhibitory and pro-apoptotic effect in over-expressing melanoma cells, we conclude that FOXP3 is not likely to be a key tumor suppressor or promoter in melanoma.


Preventing dementia.
Primary prevention will become increasingly important as dementia prevalence increases and effective retardive therapies are developed. To date, only one randomized controlled trial (involving treatment of systolic hypertension) has demonstrated that the incidence of dementia can be reduced. Physicians should remain alert to possible secondary causes of dementia and correct these whenever possible. Primary and secondary prevention of stroke should reduce dementia related to cerebrovascular disease either directly or as a comorbid factor in Alzheimer's disease (AD). Epidemiological studies have revealed a number of risk factors for AD including genetic mutation, susceptibility genes, positive family history, Down's syndrome, age, sex, years of education, head trauma and neurotoxins. In case-control studies non-steroidal anti-inflammatory medication and estrogen replacement therapy appear to decrease the relative risk of developing AD. Further research to develop and test preventative therapies in AD and other dementias should be strongly encouraged.


Reduced angiogenesis and tumor progression in gelatinase A-deficient mice.
Matrix proteolysis is thought to play a crucial role in several stages of tumor progression, including angiogenesis, and the invasion and metastasis of tumor cells. We investigated the specific role of gelatinase A (matrix metalloproteinase 2) on these events using gelatinase A-deficient mice. In these mice, tumor-induced angiogenesis was suppressed according to dorsal air sac assay. When B16-BL6 melanoma cells or Lewis lung carcinoma cells were implanted intradermally, the tumor volumes at 3 weeks after implantation in the gelatinase A-deficient mice decreased by 39% for B16-BL6 melanoma and by 24% for Lewis lung carcinoma (P < 0.03 for each tumor). The number of lung colonies of i.v. injections fell by 54% for B16-BL6 melanoma and 77% for Lewis lung carcinoma (P < 0.014 and P < 0.0015, respectively). These results indicated that host-derived gelatinase A plays an important role in angiogenesis and tumor progression, suggesting the usefulness of gelatinase A inhibitors for anticancer chemotherapy.


Embryo donation for medical research: attitudes and concerns of potential donors.
The recent derivation of embryonic stem cell lines from human blastocysts and related implications for regenerative medicine has intensified a longstanding debate about the use of human embryos for research purposes. However, studies have shown that few couples with stored embryos opt to donate them for research. Herein, the attitudes and concerns of potential embryo donors to donation of surplus embryos for medical research were examined. From a total of 509 couples who had stored frozen embryos and who had received a questionnaire about embryo donations for medical research, 152 women (30%) and 123 male partners (24%) responded. Embryos had been stored for a mean of 2.25 years (range 3 months to 12 years). Some 10% of respondents indicated it probable, and 34% possible, that they would donate their surplus embryos for research in the future. Women respondents whose embryos had been stored longer, and those committed to the practice of a religion, were more worried about their embryos. Respondents positively disposed to donation commented on their desire not to waste embryos, a desire to help infertile couples, and/or to advance scientific knowledge. Those with negative views commented on the embryo as a potential child and expressed concerns about a perceived lack of control over the type of research to be carried out. Findings indicate a need for tailored education and counselling about embryo donation for medical research.


A MIQE-compliant real-time PCR assay for Aspergillus detection.
The polymerase chain reaction (PCR) is widely used as a diagnostic tool in clinical laboratories and is particularly effective for detecting and identifying infectious agents for which routine culture and microscopy methods are inadequate. Invasive fungal disease (IFD) is a major cause of morbidity and mortality in immunosuppressed patients, and optimal diagnostic criteria are contentious. Although PCR-based methods have long been used for the diagnosis of invasive aspergillosis (IA), variable performance in clinical practice has limited their value. This shortcoming is a consequence of differing sample selection, collection and preparation protocols coupled with a lack of standardisation of the PCR itself. Furthermore, it has become clear that the performance of PCR-based assays in general is compromised by the inadequacy of experimental controls, insufficient optimisation of assay performance as well as lack of transparency in reporting experimental details. The recently published "Minimum Information for the publication of real-time Quantitative PCR Experiments" (MIQE) guidelines provide a blueprint for good PCR assay design and unambiguous reporting of experimental detail and results. We report the first real-time quantitative PCR (qPCR) assay targeting Aspergillus species that has been designed, optimised and validated in strict compliance with the MIQE guidelines. The hydrolysis probe-based assay, designed to target the 18S rRNA DNA sequence of Aspergillus species, has an efficiency of 100% (range 95-107%), a dynamic range of at least six orders of magnitude and limits of quantification and detection of 6 and 0.6 Aspergillus fumigatus genomes, respectively. It does not amplify Candida, Scedosporium, Fusarium or Rhizopus species and its clinical sensitivity is demonstrated in histological material from proven IA cases, as well as concordant PCR and galactomannan data in matched broncho-alveolar lavage and blood samples. The robustness, specificity and sensitivity of this assay make it an ideal molecular diagnostic tool for clinical use.


Atomistically informed hierarchical modeling for revisiting the constituent structures from heredity and nano-micro mechanics of sheath-core carbon fiber.
To better understand the heterogeneous anisotropic nanocomposite features and provide reliable underlying constitutive parameters of carbon fiber for continuum-level simulations, hierarchical modeling approaches combining quantum chemistry, molecular dynamics, numerical and analytical micromechanics are employed for studying the structure-performance relationships of the precursor-inherited sheath-core carbon fiber layers. A robust debonding force field is derived from energy matching protocols, including bond dissociation enthalpy calculations and rigid-constraint potential energy surface scan. Logistic long range bond stretching curves with exponential parameters and shifted force vdW curves are designed to diminish energy perturbations. The pseudo-crystalline microstructure is proposed and validated using virtual wide angle X-ray diffraction patterns and bond-orientational order parameters. The distribution or alignment features of the nanocomposite microstructures are collected from quantum chemical topology analysis and normal vector extractions. Non-equilibrium tensile loading simulation predicts the decomposed strain energy contributions, principal-axis modulus, strength limit, localized stress, and fracture morphologies of the model. Finally, an atomistically-informed stiffness prediction model combining numerical homogenization and analytical self-consistent Eshelby-Mori-Tanaka-type effective mean field micromechanics theory is proposed, giving a successful estimation of the overall stiffness matrix of the sheath-core carbon fiber system. The hierarchical models in combination with the carbonization reaction template will help in providing efficient and feasible schemes for the synergistic process-performance control of distinct types of carbon fiber.


Initial multicenter technical experience with the Apollo device for minimally invasive intracerebral hematoma evacuation.
No conventional surgical intervention has been shown to improve outcomes for patients with spontaneous intracerebral hemorrhage (ICH) compared with medical management. We report the initial multicenter experience with a novel technique for the minimally invasive evacuation of ICH using the Penumbra Apollo system (Penumbra Inc, Alameda, California). Institutional databases were queried to perform a retrospective analysis of all patients who underwent ICH evacuation with the Apollo system from May 2014 to September 2014 at 4 centers (Medical University of South Carolina, Stony Brook University, University of California at San Diego, and Semmes-Murphy Clinic). Cases were performed either in the neurointerventional suite, operating room, or in a hybrid operating room/angiography suite. Twenty-nine patients (15 female; mean age, 62 ± 12.6 years) underwent the minimally invasive evacuation of ICH. Six of these parenchymal hemorrhages had an additional intraventricular hemorrhage component. The mean volume of ICH was 45.4 ± 30.8 mL, which decreased to 21.8 ± 23.6 mL after evacuation (mean, 54.1 ± 39.1% reduction; P < .001). Two complications directly attributed to the evacuation attempt were encountered (6.9%). The mortality rate was 13.8% (n = 4). Minimally invasive evacuation of ICH and intraventricular hemorrhage can be achieved with the Apollo system. Future work will be required to determine which subset of patients are most likely to benefit from this promising technology.


Old Pathogen, New Challenges: A Narrative Review of the Multilevel Drivers of Syphilis Increasing in American Men Who Have Sex With Men.
Since the turn of the current century, syphilis incidence and prevalence have been increasing more rapidly among men who have sex with men (MSM) than any other US subpopulation, exceeding their previously high rates in the 1970s and 1980s, before the AIDS epidemic. The reasons for these trends are multifactorial and complex, involving individual behavioral, sociocultural, structural, and biological factors, which will be reviewed in this article. Men who have sex with men tend to have more sexual partners than heterosexuals, and engage in practices (e.g., anal sex) that are highly efficient for syphilis transmission and nondetection of primary chancres. In the era of highly active antiretroviral therapy rendering adherent patients noninfectious and the use of preexposure prophylaxis, there is substantially less concern about HIV transmission and acquisition among MSM, resulting in higher levels of condomless sex. The increased concentration of syphilis among black MSM is partially related to assortative mixing, that is, black MSM being more likely to have other black sex partners, as well as decreased access to preventive services and treatment due to economic marginalization, Societal rejection and discrimination may also potentiate factors that may increase sexual risks resulting in syphilis, for example, depression and substance use. The anticipation of experiencing homophobic discrimination in health care settings may lead many sexually active MSM to delay needed screening and treatment, thus being infectious to partners for longer periods than other populations. To effectively control the syphilis epidemic among MSM, scaling up a combination of programs, ranging from enhanced community education to training clinicians and health care systems to provide culturally competent care, will be necessary.


Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence.
We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A.


Butting in vs. being a friend: cultural differences and similarities in the evaluation of imposed social support.
Imposed social support can be more harmful than helpful due to its potential to threaten the recipient's autonomy. These findings may reflect cultural contexts that foster autonomy (e.g., European American [EA]). Imposed social support may be interpreted more positively in cultural contexts that place emphasis on mutual responsibility for solving problems (e.g., Russian [RU]). We compared EA (n = 128) and RU (n = 125) young adults' reports of recent episodes of support. EAs were more likely than RUs to be satisfied with these interactions, a difference mediated by levels of nondirective support. Cultural differences emerged in interpretations of support. Unsolicited support from family was interpreted more positively by RUs than by EAs. Thus, although nondirective support contributed to support satisfaction across cultural groups, cultural context influenced young adults' interpretations of imposed support.


A simple Na(2)SO(3) feeding method for K(L)a measurement in large-scale fermentors.
A simple and convenient method for measuring K(L)a in large-scale fermentors was proposed. This method was based on the measurement of the dissolved oxygen concentration under steady state conditions established by an equivalency of the sulfite ion feed and chemical oxidation rates. This method had the following advantages: It was a steady state method, and so it was not necessary to consider the response lag of a dissolved oxygen probe and the response lag due to gas phase mixing in fermentors. The oxygen content of the effluent gas in this measuring system was nearly the same as that of the sparged air. Therefore, it was possible to use the oxygen partial pressure of the sparged air for the calculation of the driving force of oxygen transfer. The detailed information on the kinetics of sulfite oxidation was not necessary, because the dissolved oxygen concentration in steady state was not influenced by sulfite oxidation rates. The K(L)a measurement was finished in as short a period as 150 s, even in a fermentor with a volume of 10 m(3). Since the amount of Na(2)SO(4) accumulation in the test fermentors was very small because of the quick measurement, the K(L)a values obtained by this method were applicable to the electrolyte-free system. Furthermore, we could discharge the used liquid from the fermentors into a drain without any pretreatment due to the low salt concentration.


Scalable DNA-Based Magnetic Nanoparticle Agglutination Assay for Bacterial Detection in Patient Samples.
We demonstrate a nanoparticle-based assay for the detection of bacteria causing urinary tract infections in patient samples with a total assay time of 4 h. This time is significantly shorter than the current gold standard, plate culture, which can take several days depending on the pathogen. The assay is based on padlock probe recognition followed by two cycles of rolling circle amplification (RCA) to form DNA coils corresponding to the target bacterial DNA. The readout of the RCA products is based on optomagnetic measurements of the specific agglutination of DNA-bound magnetic nanoparticles (MNPs) using low-cost optoelectronic components from Blu-ray drives. We implement a detection approach, which relies on the monomerization of the RCA products, the use of the monomers to link and agglutinate two populations of MNPs functionalized with universal nontarget specific detection probes and on the introduction of a magnetic incubation scheme. This enables multiplex detection of Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa at clinically relevant concentrations, demonstrating a factor of 30 improvement in sensitivity compared to previous MNP-based detection schemes. Thanks to the universal probes, the same set of functionalized MNPs can be used to read out products from a multitude of RCA targets, making the approach truly scalable for parallel detection of multiple bacteria in a future integrated point of care molecular diagnostics system.


Current state of cartilage tissue engineering.
Damage to cartilage is of great clinical consequence given the tissue's limited intrinsic potential for healing. Current treatments for cartilage repair are less than satisfactory, and rarely restore full function or return the tissue to its native normal state. The rapidly emerging field of tissue engineering holds great promise for the generation of functional cartilage tissue substitutes. The general approach involves a biocompatible, structurally and mechanically sound scaffold, with an appropriate cell source, which is loaded with bioactive molecules that promote cellular differentiation and/or maturation. This review highlights aspects of current progress in cartilage tissue engineering.


Glutamine kinetics during intravenous glutamine supplementation in ICU patients on continuous renal replacement therapy.
To investigate glutamine kinetics during continuous renal replacement therapy (CRRT) in multiple organ failure (MOF) patients with and without exogenous intravenous glutamine supplementation. In a pragmatic clinical study 12 patients without urine production receiving CRRT were prospectively randomized in a cross-over design to receive glutamine intravenously for 20 h before placebo or placebo before glutamine on two consecutive days. Alanyl-glutamine or placebo (saline) was infused. Plasma glutamine concentration was measured in artery, femoral vein, and filtration fluid. Blood flow across the leg was measured and the efflux of glutamine calculated. The rate of appearance of glutamine was calculated from the plasma decay curve of glutamine concentration on the day of treatment. Glutamine supplementation increased plasma concentrations from 570+/-252 to 831+/-367 micromol l(-1). Glutamine losses into the filtration fluids were similar during treatment and control days: 25+/-13 vs. 24+/-11 mmol 24 h(-1), corresponding to 3.6+/-1.9 and 3.5+/-1.6 g 24 h(-1), respectively. Net glutamine balance across the leg was also similar on treatment and control days: 150+/-138 and 188+/-205 nmol min(-1) 100 ml(-1), respectively. The rate of appearance of glutamine was 54+/-17 g 24 h(-1). The loss of glutamine into the ultrafiltrate during CRRT in MOF patients suggests a greater need for exogenous glutamine than in patients without renal failure. The leg efflux and the filtration losses of glutamine were not affected in response to intravenous glutamine supplementation.


Anomalous origin of the right coronary artery from the main pulmonary artery treated surgically in a 6-week-old infant. A case report and review of the literature.
In the present paper, the authors describe a case of a rare congenital defect - anomalous origin of the right coronary artery from the main pulmonary artery diagnosed in a 5-week-old infant who was deemed eligible for surgical treatment based solely on echocardiography. Such anatomical abnormalities of the coronary arteries are subtle and thus extremely difficult to visualize, especially in patients in whom permanent extensive damage of the cardiac muscle has not yet occurred. For this reason, the diagnosis is usually established when the disease is highly advanced, oftentimes only postmortem. In this paper, the authors present early echocardiographic evaluation, successful surgical treatment and post-operative echocardiographic examination. Fetal echocardiographic examinations demonstrated single vascular anomalies. The suspicion was verified after birth. Other congenital defects, including genetic defects, were also investigated. In the 5th week of life, cardiac ECHO showed abnormal origin of the right coronary artery from the trunk of the pulmonary artery. The child was deemed eligible for surgical treatment of the defect. The surgical translocation of the ostium of the right coronary artery to the aorta was done with success, and the child was discharged on the 14th day of hospitalization. The present case report demonstrates that careful examination of the child with precise echocardiographic examination makes it possible to establish an early diagnosis of this rare defect. This discrete defect can be treated early, before the symptoms, often connected with irreversible changes in the myocardium, appear.


Extended subendocardial resection. A surgical approach to ventricular tachyarrhythmias that cannot be mapped intraoperatively.
The optimal surgical management of patients with sustained, uniform-morphology ventricular tachycardia is endocardial activation sequence mapping during ventricular tachycardia and directed resection and/or cryoablation of the involved endocardium. The results of these procedures are superior to those obtained with nondirected aneurysmectomy. The optimal operative procedure when stable uniform ventricular tachycardia cannot be induced intraoperatively is uncertain. Between April, 1982, and April, 1984, intraoperative endocardial mapping was attempted on 33 patients with prior ventricular tachycardia. There were six perioperative deaths. Completely satisfactory intraoperative electrophysiologic maps were obtained in only 17 of the remaining 27 patients (63%). In 10 of these 27 patients, stable ventricular tachycardia could not be induced in the operating room, and satisfactory mapping thus could not be performed. In the first three of these 10 patients, limited subendocardial resection was performed either in regions with fractionated activity during sinus rhythm (two patients) or in regions suggested by preoperative catheter mapping (one patient). Ventricular tachycardia recurred postoperatively in two of these three patients. In the next seven patients, all visible endocardial scar around the border of the aneurysm was resected. Clinical ventricular tachycardia could not be induced at postoperative electrophysiologic study and has not recurred in these seven patients. These results suggest that complete endocardial resection provides an acceptable operative approach when intraoperative electrophysiologic mapping is not satisfactory.


Current Tolerance-Associated Peripheral Blood Gene Expression Profiles After Liver Transplantation Are Influenced by Immunosuppressive Drugs and Prior Cytomegalovirus Infection.
Spontaneous operational tolerance to the allograft develops in a proportion of liver transplant (LTx) recipients weaned off immunosuppressive drugs (IS). Several previous studies have investigated whether peripheral blood gene expression profiles could identify operational tolerance in LTx recipients. However, the reported gene expression profiles differed greatly amongst studies, which could be caused by inadequate matching of clinical parameters of study groups. Therefore, the purpose of this study was to validate differentially expressed immune system related genes described in previous studies that identified tolerant LTx recipients after IS weaning. Blood was collected of tolerant LTx recipients (TOL), a control group of LTx recipients with regular IS regimen (CTRL), a group of LTx recipients with minimal IS regimen (MIN) and healthy controls (HC), and groups were matched on age, sex, primary disease, time after LTx, and cytomegalovirus serostatus after LTx. Quantitative Polymerase Chain Reaction was used to determine expression of twenty selected genes and transcript variants in PBMCs. Several genes were differentially expressed between TOL and CTRL groups, but none of the selected genes were differentially expressed between HC and TOL. Principal component analysis revealed an IS drug dosage effect on the expression profile of these genes. These data suggest that use of IS profoundly affects gene expression in peripheral blood, and that these genes are not associated with operational tolerance. In addition, expression levels of SLAMF7 and NKG7 were affected by prior cytomegalovirus infection in LTx recipients. In conclusion, we found confounding effects of IS regimen and prior cytomegalovirus infection, on peripheral blood expression of several selected genes that were described as tolerance-associated genes by previous studies.


Localization of simian immunodeficiency virus nucleic acid and antigen in brains of fetal macaques inoculated in utero.
Neurological dysfunction has been shown to be associated with human immunodeficiency virus (HIV) infection. The incidence of these abnormalities is greater in HIV-infected children when compared with adults, and the patterns of neurological disease are also known to differ from those observed in the adult population. The reasons for these differences are unclear but are most likely related to the immaturity of the host's immune and central nervous systems at the time of infection. This is thought to be particularly true for infants infected with HIV prenatally. To examine these questions, the brains of fetal rhesus macaques that were infected with SIVmac251 at various time points in utero were examined. Direct fetal inoculations were performed on gestational day (GD) 65 (n = 8; early second trimester), GD 110 (n = 4; early third trimester) and GD 130 (n = 2; mid third trimester), with harvest of fetal tissues on GD 80, 100, 130, or 145. Eleven sham controls were included with harvest at correlative time points. Specimens were examined by routine histology, immunohistochemistry, and in situ hybridization to localize viral antigens and SIV nucleic acid. Histologically, scattered glial nodules, spongiosis, and mineralization were found in the basal ganglia and deep white matter in 4 of the 14 fetuses (3 inoculated on GD 65 and one on GD 110). These fetuses and those without histological lesions had viral nucleic acid and SIV antigen in the stroma of the choroid plexus, meninges, and external granular layer of the cerebellum and in columns of cells in the cortical plate. In contrast to juvenile and adult macaques, very few SIV-positive perivascular mononuclear cells were present. These findings suggest that SIV has a different distribution in the brain of fetal macaques after direct infection when compared with adult or juvenile animals. Furthermore, the results of these studies suggest that differences in neurological disease between pediatric and adult patients with acquired immune deficiency syndrome are most likely related to the time of infection.


The effect of phenobarbitone on protein synthesis by liver polyribosomes in fed and starved rats.
1. The effect of phenobarbitone on the rate of protein synthesis and on the sedimentation patterns of various liver subcellular fractions containing ribosomes was studied in rats. 2. Phenobarbitone treatment increased the incorporation of [114C]leucine into protein by all preparations, provided they had not been subjected to preliminary treatment with Sephadex G-25. The phenobarbitone-induced effect on incorporation was associated with a gain in liver weight and a higher degree of polyribosomal aggregation. 3. Preparations that were treated with Sephadex G-25 incorporated more radioactivity into protein, but did not show the response to phenobarbitone treatment. 4. When the influence of starvation and phenobarbitone was studied separately on membrane-bound and membrane-free polyribosomes, it was shown that whereas both classes of polyribosomes were affected by starvation, apparently only the former class was susceptible to phenobarbitone stimulation of protein synthesis. 5. The decreased capacity for protein synthesis of polyribosomes from starved rats was independent of their association with the membranes of the endoplasmic reticulum, but resulted from polyribosomal disaggregation, from an intrinsic defect of the polyribosomes themselves and from changes in composition of the cell cap. 6. The results are discussed in relation to the problem of the control of protein biosynthesis and of the functional separation of membrane-bound and membrane-free polyribosomes.


Recurrence of biliary disease following non-operative management in elderly patients.
The purpose of this study was to determine the proportion of symptomatic recurrence following initial non-operative management of gallstone disease in the elderly and to test possible predictors. This is a single institution retrospective chart review of patients 65 years and older with an initial hospital visit (V1) for symptomatic gallstone disease, over a 4-year period. Patients with initial "non-operative" management were defined as those without surgery at V1 and without elective surgery at visit 2 (V2). Baseline characteristics included age, sex, Charlson comorbidity index (CCI), diagnosis, and interventions (ERCP or cholecystostomy) at V1. Outcomes assessed over 1 year were as follows: recurrence (any ER/admission visit following V1), surgery, complications, and mortality. A survival analysis using a Cox proportional hazards model was performed to assess predictors of recurrence. There were 195 patients initially treated non-operatively at V1. Mean age was 78.3 ± 7.8 years, 45.6% were male, and the mean CCI was 2.1 ± 1.9. At V1, 54.4% had a diagnosis of biliary colic or cholecystitis, while 45.6% had a diagnosis of cholangitis, pancreatitis, or choledocholithiasis. 39.5% underwent ERCP or cholecystostomy. Excluding 10 patients who died at V1, 31.3% of patients had a recurrence over the study period. Among these, 43.5% had emergency surgery, 34.8% had complications, and 4.3% died. Median time to first recurrence was 2 months (range 6 days-4.8 months). Intervention at V1 was associated with a lower probability of recurrence (HR 0.3, CI [0.14-0.65]). One-third of elderly patients will develop a recurrence following non-operative management of symptomatic biliary disease. These recurrences are associated with significant rates of emergency surgery and morbidity. Percutaneous or endoscopic therapies may decrease the risk of recurrence.


Primary Healthcare Policy Research: Including Variables Associated With the Social Determinants of Health Matters Comment on "Universal Health Coverage for Non-communicable Diseases and Health Equity: Lessons From Australian Primary Healthcare".
Fisher et al have provided a solid addition to health policy literature in their finding that universal health coverage supports equitable access to Australian primary healthcare (PHC), despite factors such as episodic care and poor distribution of services. Their definition of PHC was comprehensive, extending beyond medical care to include social determinants of health and public policy. However, they limited their operational definition for purposes of the study to general practice, community health and allied health. Applying a narrower definition risks lost opportunities to identify policy implications for equity beyond financial accessibility. The populations most at risk of non-communicable diseases also face significant language, culture, and individual and systemic discrimination barriers to access. Future policy research should consider using a comprehensive PHC definition in determining variables of interest and designing research methodologies, to avoid missing important knowledge that allows existing biases within primary care to continue.


Preliminary patient-reported outcomes analysis of 3-dimensional radiation therapy versus intensity-modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial.
The authors analyzed a preliminary report of patient-reported outcomes (PROs) among men who received high-dose radiation therapy (RT) on Radiation Therapy Oncology Group study 0126 (a phase 3 dose-escalation trial) with either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT). Patients in the 3D-CRT group received 55.8 gray (Gy) to the prostate and proximal seminal vesicles and were allowed an optional field reduction; then, they received 23.4 Gy to the prostate only. Patients in the IMRT group received 79.2 Gy to the prostate and proximal seminal vesicles. PROs were assessed at 0 months (baseline), 3 months, 6 months, 12 months, and 24 months and included bladder and bowel function assessed with the Functional Alterations due to Changes in Elimination (FACE) instrument and erectile function assessed with the International Index of Erectile Function (IIEF). Analyses included the patients who completed all data at baseline and for at least 1 follow-up assessment, and the results were compared with an imputed data set. Of 763 patients who were randomized to the 79.2-Gy arm, 551 patients and 595 patients who responded to the FACE instrument and 505 patients and 577 patients who responded to the IIEF were included in the completed and imputed analyses, respectively. There were no significant differences between modalities for any of the FACE or IIEF subscale scores or total scores at any time point for either the completed data set or the imputed data set. Despite significant reductions in dose and volume to normal structures using IMRT, this robust analysis of 3D-CRT and IMRT demonstrated no difference in patient-reported bowel, bladder, or sexual functions for similar doses delivered to the prostate and proximal seminal vesicles with IMRT compared with 3D-CRT delivered either to the prostate and proximal seminal vesicles or to the prostate alone.


Isolation and characterisation of a sucrose: sucrose 1-fructosyltransferase gene from perennial ryegrass (Lolium perenne).
A sucrose: sucrose 1-fructosyltransferase (1-SST) gene and cDNA (Lp 1-SST) from perennial ryegrass (Lolium perenne) were isolated. The Lp 1-SST gene was fully sequenced and shown to contain three exons and two introns. Nucleotide sequence analysis of the 4824 bp Lp 1-SST genomic sequence revealed 1618 bp of 5' UTR and an open reading frame of 1962 bp encoding a protein of 653 amino acids. Lp 1-SST is 95% identical to the tall fescue 1-SST and contains plant fructosyltransferase functional domains. Lp 1-SST corresponds to a single copy gene in perennial ryegrass, and is expressed in young leaf bases and mature leaf sheaths. The recombinant Lp 1-SST protein from corresponding cDNA expression in Pichia pastoris showed 1-SST activity.


[The odontogenic keratocyst--odontogenic cyst or benign tumor?].
The odontogenic keratocyst is the third most common cyst of the jaws, after the follicular and radicular cyst. Keratocysts most commonly occur as single lesions in the jaw of otherwise healthy persons. Multiple odontogenic keratocysts are a well-recognized feature of the nevoid basal cell carcinoma syndrome. The mandible, especially the third molar region, the angle of the mandible and the ascending ramus are involved far more frequently than the maxilla. Clinically, the cysts often remain asymptomatic and there are two specific histological entities: the orthokeratinized and the parakeratinized odontogenic keratocyst. Different surgical treatment options like marsupialization, enucleation with curettage or peripheral ostectomy, and osseous resection (marginal or segmental) have been discussed in the literature with variable rates of recurrence. Besides a predilection for recurrence, the keratocysts, in contrast to other odontogenic cysts, show a more aggressive clinical behavior and demonstrate a high mitotic count and higher turnover rate of the epithelium. This led to the tentative suggestion that the keratocyst might be a benign cystic neoplasm rather than simply an odontogenic cyst.


Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force.
Recombinant activated factor VII (rFVIIa) has been approved by the U.S. Food and Drug Administration (FDA) for almost a decade for hemophilic patients with inhibitors. Its off-label use as a hemostatic agent in massive bleeding caused by a wide array of clinical scenarios is rapidly expanding. While evidence-based guidelines exist for rFVIIa treatment in hemophilia, none are available for its off-label use. The aim of this study is to develop expert recommendations for the use of rFVIIa in patients suffering from uncontrolled bleeding (with special emphasis on trauma) until randomized, controlled trials allow for the introduction of more established evidence-based guidelines. A multidisciplinary task force comprising representatives of the relevant National Medical Associations, experts from the Medical Corps of the Army, Ministry of Health and the Israel National Trauma Advisory Board was established in Israel. Recommendations were construed based on the analysis of the first 36 multi-trauma patients accumulated in the prospective national registry of the use of rFVIIa in trauma, and an extensive literature search consisting of published and prepublished controlled animal trials, case reports and series. The final consensus guidelines, together with the data of the first 36 trauma patients treated in Israel, are presented in this article. Results of the first 36 trauma patients: The prolonged clotting assays [prothrombin time (PT) and partial thromboplastin time (PTT)] shortened significantly within minutes following administration of rFVIIa. Cessation of bleeding was achieved in 26 of 36 (72%) patients. Acidosis diminished the hemostatic effect of the drug, while hypothermia did not affect it. The survival rate of 61% (22/36) seems to be favorable compared with published series of similar, or less severe, trauma patients (range 30%-57%). As a result of the lack of controlled trials, our guidelines should be considered as suggestive rather than conclusive. However, they provide a valuable tool for physicians using rFVIIa for the expanding off-label clinical uses.


Deadly competition and life-saving predation: the potential for alternative stable states in a stage-structured predator-prey system.
Predators often undergo complete ontogenetic diet shifts, engaging in resource competition with species that become their prey during later developmental stages. Theory posits that this mix of stage-specific competition and predation, termed life-history intraguild predation (LHIGP), can lead to alternative stable states. In one state, prey exclude predators through competition (i.e. juvenile competitive bottleneck), while in the alternative, adult predators control prey density to limit competition and foster coexistence. Nevertheless, the interactions leading to these states have not been demonstrated in an empirical LHIGP system. To address this gap, we manipulated densities of cannibalistic adult cyclopoid copepods (Mesocyclops edax) and their cladoceran prey (Daphnia pulex) in a response-surface design and measured the maturation and survival of juvenile copepods (nauplii). We found that Daphnia reduced and even precluded both nauplii maturation and survival through depletion of a shared food resource. As predicted, adult copepods enhanced nauplii maturation and survival through Daphnia consumption, yet this positive effect was dependent on the relative abundance of Daphnia as well as the absolute density of adult copepods. Adult copepods reduced nauplii survival through cannibalism at low Daphnia densities and at the highest copepod density. This work demonstrates that predation can relax a strong juvenile competitive bottleneck in freshwater zooplankton, though cannibalism can reduce predator recruitment. Thus, our results highlight a key role for cannibalism in LHIGP dynamics and provide evidence for the interactions that drive alternative stable states in such systems.


In which patients should sheathless IABP be used? An analysis of vascular complications in 1211 cases.
The purpose of our study is to compare the results of the sheathed and sheathless techniques for intraaortic balloon pump (IABP) insertion and to determine the rate of vascular complications in both conditions. A total of 1211 patients were examined representing a period of 19 years. Three hundred five sheathless (Group I) and 906 sheathed (Group II) IABP catheters were evaluated retrospectively. Data were analyzed with univariate analysis and logistic regression. Relative risk (RR) values were calculated in order to examine the effect of sheath. Limb ischemia was seen in 129 patients (10.9%). Although the incidence of peripheral arterial disease (PAD) was relatively higher in Group I (11.1% vs. 3.6%), the ischemic complication rate was lower in Group I (5.2% vs. 12.4%; p = 0.001). Presence of PAD (p = 0.001) and diabetes mellitus (DM) (p = 0.007) was found to be the risk factors of ischemia related to IABP use in all cases. In logistic regression analysis, presence of PAD, DM, and sheathed method was found to be the risk factors of ischemia. The patients who had all of these risk factors suffered from limb ischemia (RR value: 35.17). PAD, DM, and sheathed insertion technique are the major risk factors of ischemia during IABP use. Among all these risk factors, the only modifiable risk factor is the use of introducer sheath. With the presence of PAD and DM, the choice of sheathed method would increase the probability of ischemia almost 35 times. Sheathless method of insertion should be preferred in patients with DM and PAD.


Synaptic and subcellular localization of A-kinase anchoring protein 150 in rat hippocampal CA1 pyramidal cells: Co-localization with excitatory synaptic markers.
Excitatory and inhibitory ionotropic receptors are regulated by protein kinases and phosphatases, which are localized to specific subcellular locations by one of several anchoring proteins. One of these is the A-kinase anchoring protein (AKAP150), which confers spatial specificity to protein kinase A and protein phosphatase 2B in the rat brain. The distribution of AKAP150 was examined at rat hippocampal CA1 pyramidal cell asymmetric and symmetric post-synaptic densities and with respect to the distribution of markers of excitatory (vesicular glutamate transporter 1, glutamate receptor subunit 1) and inhibitory receptors (vesicular GABA transporter, GABA receptor type A beta2/3 subunits, gephyrin) and the Golgi marker, trans-Golgi network glycoprotein 38. AKAP150 was close to asymmetric synapses, consistent with numerous molecular and biochemical studies suggesting its interaction with components of the excitatory postsynaptic density. In contrast, we did not find AKAP150-immunoreactivity associated with inhibitory synapses in rat CA1 neurons, despite reports demonstrating an in vitro interaction between AKAP150 and GABA receptor type A receptor beta subunits, and the reported co-localization of these proteins in rat hippocampal cultures. There was some overlap between AKAP150 and GABA receptor type A receptor beta2/3-immunoreactivity intracellularly in perinuclear clusters. These findings support previous work indicating the integration of kinase and phosphatase activity at excitatory synapses by AKAP150, but do not support a role for selective targeting of AKAP150 and its accompanying proteins to inhibitory synapses.


Cation selectivity of and cation binding to the cGMP-dependent channel in bovine rod outer segment membranes.
The properties of the cGMP-dependent channel present in membrane vesicles prepared from intact isolated bovine rod outer segments (ROS) were investigated with the optical probe neutral red. The binding of neutral red is sensitive to transport of cations across vesicular membranes by the effect of the translocated cations on the surface potential at the intravesicular membrane/water interface (Schnetkamp, P. P. M. J. Membr. Biol. 88: 249-262). Only 20-25% of ROS membrane vesicles exhibited cGMP-dependent cation fluxes. The cGMP-dependent channel in bovine ROS carried currents of alkali and earth alkali cations, but not of organic cations such as choline and tetramethylammonium; little discrimination among alkali cations (K greater than Na = Li greater than Cs) or among earth alkali cations (Ca greater than Mn greater than Sr greater than Ba = Mg) was observed. The cation dependence of cGMP-induced cation fluxes could be reasonably well described by a Michaelis-Menten equation with a dissociation constant for alkali cations of about 100 mM, and a dissociation constant for Ca2+ of 2 mM. cGMP-induced Na+ fluxes were blocked by Mg2+, but not by Ca2+, when the cations were applied to the cytoplasmic side of the channel. cGMP-dependent cation fluxes showed a sigmoidal dependence on the cGMP concentration with a Hill coefficient of 2.1 and a dissociation constant for cGMP of 92 microM. cGMP-induced cation fluxes showed two pharmacologically distinct components; one component was blocked by both tetracaine and L-cis diltiazem, whereas the other component was only blocked by tetracaine.


Correlation between p53 gene mutations and circulating antibodies in betel- and tobacco-consuming North Indian population.
Alterations in p53 tumour suppressor gene and its expression may be implicated in the pathogenesis of betel- and tobacco-related oral cancer. There is wide regional variation in betel- and tobacco-consuming habits in different parts of the Indian subcontinent. The purpose of this study was to determine the correlations between p53 gene mutations, protein accumulation and serum antibodies in oral precancer and cancer. We analysed 30 potentially malignant oral lesions (leukoplakia) and 30 oral squamous cell carcinomas (SCCs) from northern India because the betel quid-consuming habits are different from those prevalent in other regions of India. p53 mutations were analysed by polymerase chain reaction amplification of genomic DNA and direct sequencing, p53 protein accumulation by immunohistochemical analysis and circulating p53 antibodies by ELISA. p53 gene mutations, analysed within exons 5-9, were observed in five out of 30 (17%) potentially malignant oral lesions and seven out of 30 (23%) oral SCCs. All the mutations were base substitution mutations. Three missense and two nonsense mutations were observed in potentially malignant oral lesions, while six missense and one nonsense mutations were identified in oral SCCs. The probable hot spots for the mutations were identified at codons 126, 136 and 174, which have not been observed thus far. A good correlation was observed between p53 missense mutation, p53 antibodies and p53 protein accumulation in matched potentially malignant and malignant oral lesions. All the potentially malignant and cancerous lesions harbouring missense mutations showed accumulation of p53 protein and the majority of these patients showed circulating p53 antibodies suggesting that serological detection of p53 antibodies may serve as a surrogate marker for p53 alterations in oral lesions.


Sex and Urbanicity Contribute to Variation in Lymphocyte Distribution across Ugandan Populations.
Management of patient care and interpretation of research data require evaluation of laboratory results in the context of reference data from populations with known health status to adequately diagnose disease or make a physiological assessment. Few studies have addressed the diversity of lymphocyte subsets in rural and urban Ugandan populations. Here, 663 healthy blood bank donors from semi-urban centers of Kampala consented to participate in a study to define lymphocyte reference ranges. Whole blood immunophenotyping was performed to determine the frequency and absolute counts of T, B, and NK cells using clinical flow cytometry. Results from blood bank donors were compared to a rural cohort from the district of Kayunga and more urban clinical trial participants from the capital city, Kampala. Relationships between hematological and lymphocyte parameters were also explored. In the semi-urban blood donors, females were significantly different from males in all parameters except the frequency of CD8 T and B cells. Females had higher absolute counts of CD4 T, CD8 T and B cells, whereas males had higher NK cell counts. NK cell frequency and counts were significantly higher in semi-urban blood donors, regardless of sex, compared to more urban study participants. CD8 T cell frequency and counts were significantly higher in the blood donors compared to the rural participants, irrespective of sex. Interestingly, basophil counts were positively associated with overall T cell counts. These findings suggest that both sex and level of cohort urbanicity may influence lymphocyte subset distributions in Ugandans.


Top-down modulation of gaze capture: Feature similarity, optimal tuning, or tuning to relative features?
It is well-known that we can tune attention to specific features (e.g., colors). Originally, it was believed that attention would always be tuned to the exact feature value of the sought-after target (e.g., orange). However, subsequent studies showed that selection is often geared towards target-dissimilar items, which was variably attributed to (1) tuning attention to the relative target feature that distinguishes the target from other items in the surround (e.g., reddest item; relational tuning), (2) tuning attention to a shifted target feature that allows more optimal target selection (e.g., reddish orange; optimal tuning), or (3) broad attentional tuning and selection of the most salient item that is still similar to the target (combined similarity/saliency). The present study used a color search task and assessed gaze capture by differently coloured distractors to distinguish between the three accounts. The results of the first experiment showed that a very target-dissimilar distractor that matched the relative color of the target but was outside of the area of optimal tuning still captured very strongly. As shown by a control condition and a control experiment, bottom-up saliency modulated capture only weakly, ruling out a combined similarity-saliency account. With this, the results support the relational account that attention is tuned to the relative target feature (e.g., reddest), not an optimal feature value or the target feature.


Mechanism of destruxin a inhibits juvenile hormone binding protein transporting juvenile hormone to affect insect growth.
Destruxin A, a non-ribosomal peptide toxin produced by Metarhizium, exhibits potent insecticidal activity by targeting various tissues, organs, and cells of insects. Our previous research has revealed that DA possesses the ability to bind to multiple proteins. In this study, we aimed to identify the most sensitive binding proteins of DA and investigate the physiological processes in which DA regulated. Through RNAi technology, we screened 22 binding proteins of DA in silkworm hemolymph. Among them, the juvenile hormone binding protein (JHBP), a hormone transport protein crucial for growth and development regulation, exhibited the highest sensitivity to DA. Subsequent experiments demonstrated that DA could inhibit the body weight gain of silkworm larvae, accelerate the pupation occurrence, and modulate the content of free juvenile hormone (JH) in the hemolymph. We also observed that DA could induce conformational changes in both the JHBP and the JHBP-JH binding complex. Notably, at low dosage, DA influenced the binding of JHBP to JH, while at high dosage, it irreversibly affected the binding of JHBP to JH. Molecular docking and point-mutant experiments suggested that DA might affect the N-arm of JHBP, which is responsible for JH binding. Additionally, we discovered that JHBP is widely distributed in various tissues of the silkworm, including the epidermis, gut, fat body, Malpighian tubule, gonad, muscle, trachea, and hemocyte. This study provides novel insights into the insecticidal mechanism of DA and enhances our understanding of the pathogenic process of Metarhizium.


Ellagic acid inhibits oxidized low-density lipoprotein (OxLDL)-induced metalloproteinase (MMP) expression by modulating the protein kinase C-α/extracellular signal-regulated kinase/peroxisome proliferator-activated receptor γ/nuclear factor-κB (PKC-α/ERK/PPAR-γ/NF-κB) signaling pathway in endothelial cells.
Previous studies have shown that vascular endothelium-derived matrix metalloproteinases (MMPs) contribute to the destabilization of atherosclerotic plaques, a key event triggering acute myocardial infarction. In addition, studies have reported that the PKC-MEK-PPARγ signaling pathway is involved in oxidized low-density lipoprotein (oxLDL)-induced expression of MMPs. Ellagic acid, a phenolic compound found in fruits and nuts, has potent antioxidant, anti-inflammatory, and anticancerous properties. However, the molecular mechanisms underlying its antiatherogenic effects remain to be clarified. This study aimed to assess whether the effects of ellagic acid on the fibrotic markers MMP-1 and MMP-3 are modulated by the PKC-ERK-PPAR-γ signaling pathway in human umbilical vein endothelial cells (HUVECs) that have been exposed to oxLDL. It was found that ellagic acid significantly inhibited oxLDL-induced expressions of MMP-1 and MMP-3. Pretreatment with ellagic acid and DPI, a well-known ROS inhibitor, attenuated the oxLDL-induced expression and activity of PKC-α. In addition, ellagic acid as well as pharmacological inhibitors of ROS, calcium, and PKC strongly suppressed the oxLDL-induced phosphorylation of extracellular signal-regulated kinase (ERK) and NF-κB activation. Moreover, ellagic acid ameliorated the oxLDL-induced suppression of PPAR-γ expression. In conclusion, the data suggest that ellagic acid elicits its protective effects by modulating the PKC-α/ERK/PPAR-γ/NF-κB pathway, resulting in the suppression of ROS generation and, ultimately, inhibition of MMP-1 and MMP-3 expression in HUVECs exposed to oxLDL.


Backbone-controlled LUMO energy induces intramolecular C-H activation in ortho-bis-9-borafluorene-substituted phenyl and o-carboranyl compounds leading to novel 9,10-diboraanthracene derivatives.
The choice of backbone linker for two ortho-bis-(9-borafluorene)s has a great influence on the LUMO located at the boron centers and, therefore, the reactivity of the respective compounds. Herein, we report the room temperature rearrangement of 1,2-bis-(9-borafluorenyl)-ortho-carborane, C2B10H10-1,2-[B(C12H8)]2 ([2a]) featuring o-carborane as the inorganic three-dimensional backbone and the synthesis of 1,2-bis-(9-borafluorenyl)benzene, C6H4-1,2-[B(C12H8)]2 (2b), its phenylene analog. DFT calculations on the transition state for the rearrangement support an intramolecular C-H bond activation process via an SEAr-like mechanism in [2a], and predicted that the same rearrangement would take place in 2b, but at elevated temperatures, which indeed proved to be the case. The rearrangement gives access to 3a and 3b as dibora-benzo[a]fluoroanthene isomers, a form of diboron polycyclic aromatic hydrocarbon (PAH) that had yet to be explored. The isolated compounds 2b, 3a, and 3b were fully characterized by NMR, HRMS, cyclic voltammetry (CV), single-crystal X-ray diffraction analysis, and photophysical measurements, supported by DFT and TD-DFT calculations.


Noninvasive detection of patients with ischemic and nonischemic heart disease prone to ventricular fibrillation.
Abnormalities in the fast Fourier transforms of signal-averaged electrocardiograms (ECGs) obtained during sinus rhythm appear to distinguish patients with ischemic heart disease and sustained monomorphic ventricular tachycardia from those without ventricular tachycardia. This study was performed to determine the power of frequency analysis to detect patients with a history of ventricular fibrillation, to determine the extent to which spectra of signal-averaged ECGs from patients with ischemic and nonischemic heart disease are comparable and to compare results of signal-averaged ECG analysis in patients with ventricular fibrillation with results of programmed ventricular stimulation. Signal-averaged ECGs were obtained during sinus rhythm from 60 patients with sustained ventricular tachycardia (Group I) and 34 patients with ventricular fibrillation (Group II). Results of signal-averaged ECG analysis were abnormal in 92% of patients with ventricular tachycardia and 85% of patients with ventricular fibrillation (p = NS). Abnormal spectra were detected in the signal-averaged ECGs from 90% of patients with ischemic and from 86% of patients with nonischemic heart disease (p = NS). In contrast, the results of programmed stimulation differed markedly between the two patient groups. Sustained ventricular arrhythmias were induced in 91% of the patients with ventricular tachycardia compared with only 46% of those with ventricular fibrillation (p less than 0.0001). Moreover, ventricular tachycardia was inducible in 81% of patients with ischemic heart disease compared with only 50% of those with nonischemic heart disease (p less than 0.02). Thus, abnormalities in the spectra of signal-averaged ECGs were found in the majority of patients with ventricular fibrillation and were detectable even in those whose arrhythmia was not inducible by programmed stimulation. These results broaden the potential clinical application of noninvasive interrogation of signal-averaged ECGs to include the prospective identification of patients with ischemic or nonischemic heart disease prone to ventricular tachycardia or ventricular fibrillation.


Coma and vegetative states: state of the art and proposal of a novel approach combining existing coma scales.
Brain damage of various aetiologies can lead to different disorders of consciousness (DOC), varying from coma to vegetative, to minimally conscious states. Each state is characterised by a different degree of wakefulness, awareness, pain sensitivity and is differentially handled with respect to treatment, ethical considerations and end-oflife decisions. Thus, its correct identification is crucial while devising or modulating appropriate treatment strategies. Actually, the main coma scales cannot always accurately determine the state of consciousness of an individual, while other tools (e.g. imaging techniques) present a certain degree of uncertainty. A complementary approach may be constituted by a 24-hour observation of patients, for a sufficient period of days, using an ad hoc behavioural scale, further correlated with physiological and pharmacological parameters measured on patients. The method herein described might help recognising the presence of consciousness of the different DOC patients, and thus discerning a vegetative from a minimally conscious state.


Structure and dynamic properties of stretched water in graphene nanochannels by molecular dynamics simulation: effects of stretching extent.
Water confined in nanochannels can be stretched with variation of the external pressure, leading to unusual properties compared with bulk water. In order to unravel the impacts of stretching extent on the structural and dynamic properties of water confined in hydrophobic graphene nanochannels with various channel widths (L = 1 nm, 2 nm and 3 nm), molecular dynamics (MD) simulations were performed in this work. It was found that an ultrahigh negative pressure was present in the confined space with the increase of stretching extent before cavitation. The interfacial density peak and tetrahedral arrangement were reduced with the increasing hydrogen bond length, indicating the more disordered structural organization, especially in channels with small channel widths. On the other hand, the hydrogen bond lifetime was increased due to the prolonged stability of the hydrogen bond under stretching. The remarkably increased diffusion coefficients of confined water with the increasing stretching coefficient result from the faster diffusion of interfacial water along the channel surface regardless of channel width. At last, the oscillating tangential pressure profile inside the nanochannels demonstrated that the confined water under stretching consists of multiple layers exhibiting alternate positive and negative pressures, which is reduced with the increase of stretching coefficient, corresponding to the enhanced diffusion.


Surgical Treatment of Bilateral Tibia Deformity in a 9-Year-Old Child Suffering from Osteogenesis Imperfecta Type III: A Case Report.
BACKGROUND Osteogenesis imperfecta is a rare inherited connective tissue disorder that is mainly characterized by long bone deformities and increased susceptibility to bone fractures. The aim of this study was to present a surgical technique in a child suffering from osteogenesis imperfecta and progressive, severe bowing deformity of both tibias, as an alternative method to advanced, innovative surgical systems. CASE REPORT A 9-year-old child (male) was referred to our orthopedic clinic for inability to walk independently due to extreme anterior bowing of both tibias. After the diagnosis of osteogenesis imperfecta type III was established, bilateral surgical treatment with multiple osteotomies and intramedullary, flexible Titanium Elastic Nail System (TENS) nails was decided. Six months post-operatively callus formation was obvious in x-rays and at the latest follow-up (1 year post-operatively) the patient regained the ability to walk independently. CONCLUSIONS In types of osteogenesis imperfecta which are characterized by extreme deformities (type III) surgical intervention seems to be the only solution for these patients to walk again. We present a relatively simple technique of correcting such deformities, indicating that no matter which technique will be used (simple or more complicated) the final goal should be to restore the walking ability with as little complications as possible.


Where one hand meets the other: limb-specific and action-dependent movement plans decoded from preparatory signals in single human frontoparietal brain areas.
Planning object-directed hand actions requires successful integration of the movement goal with the acting limb. Exactly where and how this sensorimotor integration occurs in the brain has been studied extensively with neurophysiological recordings in nonhuman primates, yet to date, because of limitations of non-invasive methodologies, the ability to examine the same types of planning-related signals in humans has been challenging. Here we show, using a multivoxel pattern analysis of functional MRI (fMRI) data, that the preparatory activity patterns in several frontoparietal brain regions can be used to predict both the limb used and hand action performed in an upcoming movement. Participants performed an event-related delayed movement task whereby they planned and executed grasp or reach actions with either their left or right hand toward a single target object. We found that, although the majority of frontoparietal areas represented hand actions (grasping vs reaching) for the contralateral limb, several areas additionally coded hand actions for the ipsilateral limb. Notable among these were subregions within the posterior parietal cortex (PPC), dorsal premotor cortex (PMd), ventral premotor cortex, dorsolateral prefrontal cortex, presupplementary motor area, and motor cortex, a region more traditionally implicated in contralateral movement generation. Additional analyses suggest that hand actions are represented independently of the intended limb in PPC and PMd. In addition to providing a unique mapping of limb-specific and action-dependent intention-related signals across the human cortical motor system, these findings uncover a much stronger representation of the ipsilateral limb than expected from previous fMRI findings.


Facial nerve motor-evoked potential monitoring during skull base surgery predicts facial nerve outcome.
To determine whether monitoring facial nerve motor-evoked potentials (FNMEPs) elicited by transcranial electrical stimulation during skull base tumour surgery is useful for predicting facial nerve outcome. This study analysed FNMEP findings in 26 patients with skull base tumours. Corkscrew electrodes positioned at C3 or C4 and Cz were used to deliver supramaximal stimuli (180-550 V). FNMEPs were recorded from the orbicularis oculi and oris muscles. The correlation between the final-to-baseline FNMEP ratio and postoperative facial nerve function was examined. Postoperative facial nerve function correlated significantly with the FNMEP ratios in the orbicularis oculi (p = 0.004) and orbicularis oris (p<0.001) muscles. An FNMEP ratio of <50% consistently predicted immediate postoperative facial palsy, although the degree of palsy differed among patients. All patients had satisfactory facial nerve function (House and Brackmann grades I and II) postoperatively if the FNMEP ratio remained at >50%. Intraoperative FNMEP monitoring can be useful for predicting facial nerve function after skull base surgery. This new method is a valuable adjunct to conventional facial nerve monitoring.


A type II cannabis extract and a 1:1 blend of Δ(9)-tetrahydrocannabinol and cannabidiol display distinct antinociceptive profiles and engage different endocannabinoid targets when administered into the subarachnoid space.
Introduction: Cannabis extracts are being increasingly used to mitigate chronic pain. Current guidelines for their prescription rely on Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content as well as the ratio of these major cannabinoids present in the blend. Here we assessed whether these descriptors were representative of product effectiveness to produce a desired outcome such as analgesia. Methods: In this study, we used a rat model of diabetic neuropathy and assessed the reduction in mechanical allodynia following intrathecal injection of pure THC, pure CBD, a 1:1 mix of these compounds and a "balanced" chemotype II cannabis extract. Engagement of endocannabinoid targets by different treatments was investigated using CB1 (AM251) and CB2 (AM630) receptor antagonists as well as a TRPV1 channel blocker (capsazepine). Results: Antinociceptive responses induced by an equivalent amount of THC administered in its pure form, as a THC:CBD mix or as a "balanced" extract were distinct. Furthermore, the 1:1 THC:CBD mix and the balanced extract had not only different response profiles but their relative engagement of CB1, CB2 receptors and TRPV1 channels was distinct. Discussion: These findings indicate that antinociceptive responses and targets engaged by blended cannabinoids are composition-specific, and cannot be simply inferred from THC and CBD contents. This information may have implications in relation to the way medicinal cannabis products are prescribed.


Effect of Institutional Kidney Transplantation Case-Volume on Post-Transplant Graft Failure: a Retrospective Cohort Study.
The impact of institutional case volume to graft failure rate after adult kidney transplantation is relatively unclear compared to other solid organ transplantations. A retrospective cohort study of 13,872 adult kidney transplantations in Korea was performed. Institutions were divided into low- (< 24 cases/year), medium- (24-60 cases/year), and high- (> 60 cases/year) volume centers depending on the annual case volume. One-year graft failure rate was defined as the proportion of patients who required dialysis or re-transplantation at one year after transplantation. Postoperative in-hospital mortality and long-term graft survival were also measured. After adjustment, one year graft failure was higher in low-volume centers significantly (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.26-1.78; P < 0.001) and medium-volume centers (aOR, 1.87; 95% CI, 1.57-2.23; P < 0.001) compared to high-volume centers. Low-volume centers had significantly higher mortality (aOR, 1.75; 95% CI, 1.15-2.66; P = 0.01) than that of high-volume centers after adjustment. Long-term graft survival of up to 9 years was superior in high-volume centers compared to low- and medium-volume centers (P < 0.001). Higher-case volume centers were associated with lower one-year graft failure rate, lower in-hospital mortality, and higher long-term graft survival after kidney transplantation.