Promoting Emotional and Psychological Well-Being During COVID-19 Pandemic: A Self-Help Virtual Reality Intervention for University Students.
Mental health problems are very common among university students, and the situation worsened during the COVID-19 pandemic. The closure of universities, the restrictions imposed, and the reduction of social activities led to considerable changes in students' lives, thus posing new mental health and emotional challenges. Within this context, promoting university students' general well-being, in particular emotional and psychological well-being, becomes essential. In addition to the possibility of online interventions aimed at overcoming distance limitations and reaching people at their home, other advanced technologies such as virtual reality (VR) have demonstrated the potential to improve people's well-being, quality of life, and positive experiences. The study reported in this article is aimed at exploring the feasibility and preliminary effectiveness of a self-help VR intervention lasting 3 weeks in promoting emotional well-being in university students. Forty-two university students voluntarily participated in a six-session intervention. In each session, a different virtual scenario was presented: two relaxing experiences and four transformative experiences based on metaphors or metaphoric ones aimed at encouraging students to be aware of their emotions and positive resources. Students were randomly allocated to an experimental group and to a waiting list group that started the intervention after 3 weeks. Before and after the six sessions, participants completed an assessment by completing online questionnaires. Results showed a significant increase in both emotional well-being and psychological well-being in the experimental group compared to the waiting list group. The majority of participants said that they would recommend the experience to other students.


The role of bioengineering in orthopedics.
Orthopedic bioengineering is an example of professionals in distinct disciplines applying their skills to problems that require an interdisciplinary approach. Two current research projects, the development of replacement ligaments and tendons and of an absorbable fracture fixation device, illustrate this integrated approach.


Surgical treatment of posttraumatic foreign bodies in the heart or great vessels.
Posttraumatic foreign bodies in the heart or great vessels is rare, which may cause cardiac tamponade, bleeding, shock, infection, embolism, arrhythmia, valve dysfunction, etc. The foreign bodies can be removed by surgery or percutaneous intervention. In this report we reviewed our experience in managing posttraumatic foreign bodies in 13 patients at our institution from 1992 to 2002.


Resistance training suppresses intra-abdominal fatty acid synthesis in ovariectomized rats.
Ovarian hormone loss is associated with a shift in fat distribution to intra-abdomin al adipose tissue (intra-AAT) depots and with lipid metabolism disorders, which predisposes individuals to developing insulin resistance. Resistance training (RT) prevents increases in intra-AAT after ovarian hormone loss. However, the molecular mechanisms underlying these changes remain unclear. We investigated the effects of ovariectomy and RT on gene expression related to lipogenesis and fat oxidation in the intra-AAT of ovariectomized rats. Sprague-Dawley rats (n=6/group) were divided into the groups: sham-sedentary, ovariectomized-sedentary, sham-RT and ovariectomized-RT. RT groups performed a 10-week climbing program on a ladder with progressive overload. Intra-AAT was subjected to morphometric and mRNA analysis. Ovariectomized-sedentary group had larger adipocytes and higher expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-CoA desaturase-1 (SCD-1), acetyl-CoA carboxylase (ACC), hormone-sensitive lipase (HSL) and lower expression of the oxidative carnitinepalmitoyltransferase-I (CPT-1). RT counteracted OVX-induced increases in PPAR-γ and SCD-1 and decreased SREBP-1c. ACC and HSL were downregulated in ovariectomized-RT compared with the ovariectomized-sedentary group. Ovariectomized-RT group had the highest CPT-1 gene expression. Adipocyte size decreased in ovariectomized-RT group. Results suggest that RT reduces intra-AAT adipocyte size in ovariectomized rats by suppressing intra-AAT fatty acid synthesis and enhancing fatty acid β-oxidation.


Functional roles of FgLaeA in controlling secondary metabolism, sexual development, and virulence in Fusarium graminearum.
Fusarium graminearum, the causal agent of Fusarium head blight in cereal crops, produces mycotoxins such as trichothecenes and zearalenone in infected plants. Here, we focused on the function of FgLaeA in F. graminearum, a homolog of Aspergillus nidulans LaeA encoding the global regulator for both secondary metabolism and sexual development. Prior to gene analysis, we constructed a novel luciferase reporter system consisting of a transgenic F. graminearum strain expressing a firefly luciferase gene under control of the promoter for either TRI6 or ZEB2 controlling the biosynthesis of these mycotoxins. Targeted deletion of FgLaeA led to a dramatic reduction of luminescence in reporter strains, indicating that FgLaeA controls the expression of these transcription factors in F. graminearum; reduced toxin accumulation was further confirmed by GC-MS analysis. Overexpression of FgLaeA caused the increased production of trichothecenes and additional metabolites. RNA seq-analysis revealed that gene member(s) belonging to ~70% of total tentative gene clusters, which were previously proposed, were differentially expressed in the ΔFgLaeA strain. In addition, ΔFgLaeA strains exhibited an earlier induction of sexual fruiting body (perithecia) formation and drastically reduced disease symptoms in wheat, indicating that FgLaeA seems to negatively control perithecial induction, but positively control virulence toward the host plant. FgLaeA was constitutively expressed under both mycotoxin production and sexual development conditions. Overexpression of a GFP-FgLaeA fusion construct in the ΔFgLaeA strain restored all phenotypic changes to wild-type levels and led to constitutive expression of GFP in both nuclei and cytoplasm at different developmental stages. A split luciferase assay demonstrated that FgLaeA was able to interact with FgVeA, a homolog of A. nidulans veA. Taken together, these results demonstrate that FgLaeA, a member of putative FgVeA complex, controls secondary metabolism, sexual development, and virulence in F. graminearum, although the specific regulation pattern differs from that of LaeA in A. nidulans.


Positive inotropic, positive chronotropic and coronary vasodilatory effects of rat amylin: mechanisms of amylin-induced positive inotropy.
Even though there are a few studies dealing with the cardiac effects of amylin, the mechanisms of amylin-induced positive inotropy are not known well. Therefore, we investigated the possible signaling pathways underlying the amylin-induced positive inotropy and compared the cardiac effects of rat amylin (rAmylin) and human amylin (hAmylin).Isolated rat hearts were perfused under constant flow condition and rAmylin or hAmylin was infused to the hearts. Coronary perfusion pressure, heart rate, left ventricular developed pressure and the maximum rate of increase of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease of left ventricle (-dP/dtmin) were measured.rAmylin at concentrations of 1, 10 or 100 nM markedly decreased coronary perfusion pressure, but increased heart rate, left ventricular developed pressure, +dP/dtmax and -dP/dtmin. The infusion of H-89 (50 μM), a protein kinase A (PKA) inhibitor did not change the rAmylin (100 nM)-induced positive inotropic effect. Both diltiazem (1 μM), an L-type Ca2+ channel blocker and ryanodine (10 nM), a sarcoplasmic reticulum (SR) Ca2+ release channel opener completely suppressed the rAmylin-induced positive inotropic effect, but staurosporine (100 nM), a potent protein kinase C (PKC) inhibitor suppressed it partially. hAmylin (1, 10 and 100 nM) had no significant effect on coronary perfusion pressure, heart rate and developed pressure, +dP/dtmax and -dP/dtmin.We concluded that rAmylin might have been produced vasodilatory, positive chronotropic and positive inotropic effects on rat hearts. Ca2+ entry via L-type Ca2+ channels, activation of PKC and Ca2+ release from SR through ryanodine-sensitive Ca2+ channels may be involved in this positive inotropic effect. hAmylin may not produce any significant effect on perfusion pressure, heart rate and contractility in isolated, perfused rat hearts.


Studentized maximum root procedures for coherent analyses of two-factor fixed-effects designs.
The authors provide generalizations of R. J. Boik's (1993) studentized maximum root (SMR) procedure that allow for simultaneous inference on families of product contrasts including simple effect contrasts and differences among simple effect contrasts in coherent analyses of data from 2-factor fixed-effects designs. Unlike the F-based simultaneous test procedures (STPs) proposed by M. A. Betz and K. R. Gabriel (1978) for coherent analyses allowing for inferences on all factorial contrasts, SMR STPs are designed for analyses where each contrast of interest is a product contrast, which is usually the case in analyses of data from factorial experiments. When both factors have more than 2 levels, SMR STPs always provide more power and precision than F STPs for inferences on product contrasts.


Daily profiles of plasma prolactin (PRL), growth hormone (GH), insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), testosterone, and melatonin, and of pituitary PRL mRNA and GH mRNA in male Long Evans rats in acute phase of adjuvant arthritis.
We studied the effects of adjuvant arthritis (AA) on the endocrine circadian rhythms of plasma prolactin (PRL), growth hormone (GH), insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), testosterone, and melatonin and of pituitary PRL and GH mRNA in male Long Evans rats. Groups of control and AA rats (studied 23 days after AA induction) that were housed under a 12/12 h light/dark cycle (light on at 06:00 h) were killed at 4 h intervals starting at 14:00 h. Cosinor analysis revealed a significant 12 h rhythm in PRL and PRL mRNA (p < 0.001) in controls with peaks at 14:00 h and 02:00 h, respectively. The peak at 02:00 h was abolished in the AA group resulting in a significant 24 h rhythm in parallel with that of PRL (p < 0.05) and PRL mRNA (p < 0.0001). Growth hormone showed no rhythm, but a significant rhythm of GH mRNA was present in both groups (p < 0.0001). Insulin-like growth factor-1 showed a 24 h rhythm in control but not in AA rats. The mean values of GH, GH mRNA, and IGF-1 were significantly reduced in AA. Luteinizing hormone displayed a significant 24 h rhythm (p < 0.01) peaking in the dark period in the control but not AA group. Testosterone showed in phase temporal changes of LH levels with AA abolishing the 02:00 h peak. Melatonin exhibited a significant 24 h rhythm in control (p < 0.001) and AA (p < 0.01) rats with maximum levels during the dark phase; the mesor value was higher in the AA males. These results demonstrate that AA interferes with the rhythms of all the studied hormones except the non-24 h (arrhythmic) GH secretion pattern and the rhythm in melatonin. The persistence of a distinct melatonin rhythm in AA suggests the observed disturbances of hormonal rhythms in this condition do not occur at the level of the pineal gland.


Taste of sugar at the membrane: thermodynamics and kinetics of the interaction of a disaccharide with lipid bilayers.
Sugar recognition at the membrane is critical in various physiological processes. Many aspects of sugar-membrane interaction are still unknown. We take an integrated approach by combining conventional molecular-dynamics simulations with enhanced sampling methods and analytical models to understand the thermodynamics and kinetics of a di-mannose molecule in a phospholipid bilayer system. We observe that di-mannose has a slight preference to localize at the water-phospholipid interface. Using umbrella sampling, we show the free energy bias for this preferred location to be just -0.42 kcal/mol, which explains the coexistence of attraction and exclusion mechanisms of sugar-membrane interaction. Accurate estimation of absolute entropy change of water molecules with a two-phase model indicates that the small energy bias is the result of a favorable entropy change of water molecules. Then, we incorporate results from molecular-dynamics simulation in two different ways to an analytical diffusion-reaction model to obtain association and dissociation constants for di-mannose interaction with membrane. Finally, we verify our approach by predicting concentration dependence of di-mannose recognition at the membrane that is consistent with experiment. In conclusion, we provide a combined approach for the thermodynamics and kinetics of a weak ligand-binding system, which has broad implications across many different fields.


Traditional and complementary medicine use among Ebola survivors in Sierra Leone: a qualitative exploratory study of the perspectives of healthcare workers providing care to Ebola survivors.
Considerable number of patients, including Ebola survivors, in Sierra Leone, are using traditional and complementary medicine (T&CM). Healthcare providers' (HCPs) views about T&CM is crucial in addressing the increased need for T&CM among patients. However, healthcare providers' views about T&CM in Sierra Leone is unknown. Our study explores healthcare providers' knowledge of and perception towards T&CM and how that influence their personal and professional T&CM use, communication with Ebola survivors about T&CM as well as its integration into the healthcare system in Sierra Leone. We employed a qualitative exploratory study design using semi-structured interviews to collect data from 15 conveniently sampled HCPs in all four geographical regions of Sierra Leone. We analysed our data using thematic network analysis framework. Healthcare providers perceived their knowledge about T&CM to be low and considered T&CM to be less effective and less safe than conventional medicine as well as not evidence-based. HCPs perception of T&CM as non-scientific and their lack of knowledge of T&CM were the key barriers to HCPs' self-use and recommendation as well as their lack of detailed discussion about T&CM with Ebola survivors. HCPs are open to T&CM integration into mainstream healthcare in Sierra Leone although at their terms. However, they believe that T&CM integration could be enhanced by effective professional regulation of T&CM practice, and by improving T&CM evidenced-based knowledge through education, training and research. Changing HCPs' negative perception of and increasing their knowledge about T&CM is critical to promoting effective communication with Ebola survivors regarding T&CM and its integration into the healthcare system in Sierra Leone. Strategies such as educational interventions for HCPs, conducting rigorous T&CM research, proper education and training of T&CM practitioners and effective professional regulation of T&CM practice could help in that direction.


Elevated peptides in lung lavage fluid associated with bronchiolitis obliterans syndrome.
The objective of this discovery-level investigation was to use mass spectrometry to identify low mass compounds in bronchoalveolar lavage fluid from lung transplant recipients that associate with bronchiolitis obliterans syndrome. Bronchoalveolar lavage fluid samples from lung transplant recipients were evaluated for small molecules using ESI-TOF mass spectrometry and correlated to the development of bronchiolitis obliterans syndrome. Peptides associated with samples from persons with bronchiolitis obliterans syndrome and controls were identified separately by MS/MS analysis. The average bronchoalveolar lavage fluid MS spectrum profile of individuals that developed bronchiolitis obliterans syndrome differed greatly compared to controls. Controls demonstrated close inter-sample correlation (R = 0.97+/-0.02, average+/-SD) while bronchiolitis obliterans syndrome showed greater heterogeneity (R = 0.86+/-0.09, average+/-SD). We identified 89 features that were predictive of developing BOS grade 1 and 66 features predictive of developing BOS grade 2 or higher. Fractions from MS analysis were pooled and evaluated for peptide content. Nearly 10-fold more peptides were found in bronchiolitis obliterans syndrome relative to controls. C-terminal residues suggested trypsin-like specificity among controls compared to elastase-type enzymes among those with bronchiolitis obliterans syndrome. Bronchoalveolar lavage fluid from individuals with bronchiolitis obliterans syndrome has an increase in low mass components detected by mass spectrometry. Many of these features were peptides that likely result from elevated neutrophil elastase activity.


Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence.
The yeast Sir2 protein mediates chromatin silencing through an intrinsic NAD-dependent histone deacetylase activity. Sir2 is a conserved protein and was recently shown to regulate lifespan extension both in budding yeast and worms. Here, we show that SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras (Ha-rasV12). SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation. Moreover, we show that SIRT1 and p53 co-localize in nuclear bodies upon PML upregulation. When overexpressed in primary mouse embryo fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence. Taken together, our data establish the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence.


Improvement of diagnostic criteria in growth hormone insensitivity syndrome: solutions and pitfalls. Pharmacia Study Group on Insulin-like Growth Factor I Treatment in Growth Hormone Insensitivity Syndromes.
A survey to identify children and adolescents with primary growth hormone insensitivity syndrome (GHIS) yielded 38 patients who were positively identified using a scoring system that included five criteria: height, basal growth hormone (GH), GH binding protein, basal insulin-like growth factor I (IGF-I) and the increase of IGF-I after 4 days of GH administration (IGF generation test). Because of an overlap of the accepted and excluded groups with respect to points scored, an attempt was made to improve the scoring system. The new criteria were: height below -3 SDS, basal GH 4 mU/l or above, GH binding below 10%, basal IGF-I and basal IGF binding protein-3 (IGFBP-3) below the 0.1 centile for age, an increase of IGF-I in the IGF generation test less than 15 micrograms/l, and the increase of IGFBP-3 less than 0.4 mg/l. With this scoring system, a clear separation between the accepted and the excluded groups was obtained. IGFBP-3 was included to give the GH-dependent parameters of the IGF system more weight and because the accuracy of IGFBP-3 in the IGF generation tests was greater than the accuracy of IGF-I, when the group of patients with GHIS was compared with a group of patients with GH deficiency. Unexpectedly, the IGF generation test was unable to segregate both cohorts completely. In the GHIS-positive group, a significant correlation was found between basal IGF-I or IGFBP-3 levels corrected for age (SDS) and height SDS (r = 0.49, p < 0.002 and r = 0.61, p < 0.0001, respectively). There was also a significant correlation between the changes of IGF-I or IGFBP-3 in the IGF generation test and height SDS. That is, the patients with a slight response to GH were those with the least growth retardation, suggesting the existence of partial GH insensitivity.


MR imaging of knee hyaline cartilage: evaluation of two- and three-dimensional sequences.
Magnetic resonance (MR) imaging of cadaveric knees was performed to determine optimal sequences for visualization of hyaline cartilage. Full-thickness cartilage lesions ranging in diameter from 1 to 5 mm and a partial-thickness cartilage lesion 15 mm in diameter were created in the femoral articular surfaces of three cadaveric knees. The knees were then imaged with a 1.5-T imager with various two-dimensional and high-resolution three-dimensional (3D) techniques. After imaging, the knee specimens were sectioned for evaluation. Measurements of cartilage thickness in fast spin-echo images correlated best with those in the gross specimen. Diffuse areas of cartilage thinning were also most accurately identified with fast spin-echo images. Small, focal cartilage defects were best delineated in 3D SPGR (spoiled GRASS [gradient-recalled acquisition in the steady state]) images.


Versican is crucial for the initiation of cardiovascular lumen development in medaka (Oryzias latipes).
Versican is an evolutionary conserved extracellular matrix proteoglycan, and versican expression loss in mice results in embryonic lethality owing to cardiovascular defects. However, the in utero development of mammals limits our understanding of the precise role of versican during cardiovascular development. Therefore, the use of evolutionarily distant species that develop ex utero is more suitable for studying the mechanistic basis of versican activity. We performed ENU mutagenesis screening to identify medaka mutants with defects in embryonic cardiovascular development. In this study, we described a recessive point mutation in the versican 3'UTR resulting in reduced versican protein expression. The fully penetrant homozygous mutant showed termination of cardiac development at the linear heart tube stage and exhibited absence of cardiac looping, a constricted outflow tract, and no cardiac jelly. Additionally, progenitor cells did not migrate from the secondary source towards the arterial pole of the linear heart tube, resulting in a constricted outflow tract. Furthermore, mutants lacked blood flow and vascular lumen despite continuous peristaltic heartbeats. These results enhance our understanding of the mechanistic basis of versican in cardiac development, and this mutant represents a novel genetic model to investigate the mechanisms of vascular tubulogenesis.


A hard hand-positioning device to decrease wrist and finger hypertonicity: a sensorimotor approach for the patient with nonprogressive brain damage.
To investigate whether a hand-positioning device placed in the palm of a patient with nonprogressive brain damage will decrease hypertonicity of the flexor muscles of the hand through proprioreceptive sensory input to the alpha-gamma coactivation loop, a hard cone was placed in the affected hand of 11 subjects who had sustained cerebrovascular accidents and had flexor hypertonicity of the upper extremity. Measurements of hypertonicity and functionality were made weekly for four weeks. All subjects experienced a significant decrease in flexor hypertonicity. Only slight changes were observed in functionality.


Psychrophilic prokaryote structural-functional relationships, biogeography and evolution within marine sediment.
Prokaryote diversity has been found to be surprisingly high in cold marine sediments with numerous clades detected spread throughout many phyla. Marine benthic sediment clades are largely ecotypically distinct and autochthonous. Since almost all marine sediment prokaryotic taxa have yet to be cultivated, functionality is currently overwhelmingly cryptic for most benthic prokaryotic taxa except those falling into specific lineages for which there is cultivation or detailed biogeochemical data. Multivariate statistical comparisons of 16S rRNA gene sequence and denaturing gradient gel electrophoresis (DGGE) data show distinct distribution patterns of prokaryotic communities in sediment layers. By comparison geographical differences and differences related to the physical texture and organic content seem to result in generally smaller differences.


Comparative study of microleakage of a pit and fissure sealant placed after preparation by Er:YAG laser in permanent molars.
The aim of this study was to assess the microleakage of a pit and fissure sealant on enamel treated with a laser, with and without etching. Sixty non-carious extracted molars were randomly assigned to 2 groups. For both groups, in the mesial halves, the fissures were widened mechanically with a bur and etched for 15 seconds. In group 1, the distal half was prepared with a laser alone; in group 2, a laser was followed by etching. Then the sealant was applied on all teeth. Laser alone showed the highest number of specimens with microleakage (63%) (P < .02) and the highest mean of microleakage (0.76 mm vs 0.12 mm, 0.17 mm, and 0.18 mm; P < .01). No significant difference was noted between the 2 types of enamel preparation when etching was performed. Laser irradiation did not eliminate the need for etching the enamel surface before applying the sealant.


Historical review of legislative and national initiatives for sickle cell disease.
The genes responsible for the transmission of sickle cell syndromes from one generation to the next were introduced into the new world during the 17th century. However, this disease was not recorded in the medical literature in the United States until 1910 by Herrick of Chicago. During the next 40 years, many additional cases were reported and a fairly large bibliography developed which dealt essentially with descriptive, clinical and pathological aspects of the disease. New interest in the syndrome occurred in 1949 when Pauling and his associates, employing chemical and electrophoretic techniques, showed that an abnormal hemoglobin was responsible for the sickling phenomenon. In the same year, Neel and Beet, working independently of each other, clarified the inheritance of the disease on the basis of the heterozygous-homozygous hypothesis. In 1958, Ingraham combined the techniques of electrophoresis, chromatography, and trypsin digestion ("fingerprinting") to show that the difference between hemoglobins A, C, and S was in the amino acid sequence of the polypeptide chains which make up the hemoglobin molecule. However, despite these notable advances, interest in the disease remained at a relatively low scientific and health care priority until February 1971, when President Nixon in his message to Congress indicated that greater attention and support for sickle cell disease should be made available at the national level. This paper will review some of the important legislative, political, and organizational initiatives which have had a significant impact on the development and implementation of the current national sickle cell disease program in the United States.


Influenza vaccination during pregnancy for prevention of influenza confirmed illness in the infants: A systematic review and meta-analysis.
Infants younger than 6 months of age are at particular risk for serious illness from influenza infection. Currently available influenza vaccines are, however, not licensed for use in infants <6 months old. Influenza vaccination during pregnancy elicits robust antibody responses in the women that will protect the infants against influenza infection during the first few months of life. We aimed to determine the impact of influenza vaccination during pregnancy to prevent laboratory-confirmed influenza infection and influenza-associated hospitalisations in infants <6 months old. An electronic search identified all studies assessing the proposed outcomes in infants after administration of influenza vaccine during pregnancy. Two meta-analyses were performed accordingly to studies restricting the evaluation to influenza-associated hospitalisations or not. Four randomized control trials and 3 observational studies reported on the prevention of laboratory-confirmed influenza infection in infants <6 months old. Maternal influenza vaccination was associated with a 48% [95% confidence interval (CI): 33 to 59] reduced risk of infants having laboratory-confirmed influenza infection. Four observational studies reported on the prevention of hospitalizations associated with laboratory-confirmed influenza infection and the pool estimate was 72% (95%CI: 39% to 87%). Receipt of influenza vaccine during pregnancy was associated with decreased risk of laboratory-confirmed influenza infection in the infants.


The Impact of the Philtrum on Facial Attractiveness, Perioral Proportions, and Perceptions of Facial Aging.
Lip enhancement continues to be one of the most popular facial procedures. State-of-the-art lip enhancement involves sculpting of perilabial soft tissue, in particular, the philtrum, but it is unclear how patients perceive their philtral contours. The aim of this study was to test the impact of the philtrum on attractiveness, and on the perception of facial proportions and age. Respondents (1100, including 50 aesthetic specialists) were presented with 2 sets of identical portraits, 1 set of a young Caucasian female and 1 set of an aged Caucasian female, with 1 portrait in each set having an upper lip lacking any philtral contours. The respondents were asked to choose which upper lip was more attractive, appeared longer, and looked older. Rankings were analyzed according to population demographics. Overall, most respondents considered the young face (84%) and the aged face (68%) with philtral contours to be more attractive. Moreover, the majority of respondents (81%) considered the upper lip of the young face without a philtrum to appear longer in a craniocaudal orientation (67% for the aged image), and 67% of respondents described the image of the young woman with no philtral definition as appearing older (55% for the aged face with no philtrum). This study confirms the authors' hypothesis that the existence of philtral contours exerts a significant impact on perioral attractiveness, and that its absence can be related to a longer appearance of the upper lip as well as an older facial appearance.


Nosocomial infections in intensive care units: an overview of their epidemiology, outcome, and prevention.
Among all hospitalized patients, ICU patients are at greatest risk for both endemic and epidemic nosocomial infections. The highest infection rates are seen in surgical, burn, trauma, and neonatal ICUs. Acquisition of infection is a major determinant of mortality in ICUs, and prolongs the length of ICU stay. Predominant pathogens include Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus aureus, enterococci, and Candida spp. They are more likely to be resistant to antimicrobial agents than are isolates from elsewhere in the hospital. Exposure to invasive medical devices is the predominant risk factor for infection, and strategies to prevent infection are aimed at reducing microbial colonization on and around devices. Improvements in technology, such as coating devices with antimicrobial agents, have been shown to be efficacious in preventing infection. Handwashing, particularly with antiseptic soaps, remains the cornerstone of infection control in the ICU.


Clinical phenotypes within nonconvulsive status epilepticus.
The study aimed to identify distinct phenotypes within nonconvulsive status epilepticus (NCSE). Consecutive episodes of NCSE in patients at least 14 years old were included. The level of consciousness was assessed through the Glasgow Coma Scale (GCS). Etiology of NCSE was defined as symptomatic (acute, remote, progressive) or unknown. Electroencephalographic (EEG) recordings were searched for lateralized periodic discharges (LPDs), generalized sharply and/or triphasic periodic potentials (GPDs), and spontaneous burst suppression (BS). According to treatment response, NCSE was classified as responsive, refractory, or superrefractory. Average linkage hierarchical cluster analysis was performed with Pearson correlation as similarity measure. Two hundred twenty-nine episodes of NCSE were included. Three clusters were identified. The first cluster linked GCS score 3-8, presence of spontaneous BS on EEG, acute symptomatic etiology, and treatment superrefractoriness. The second cluster gathered GCS score 9-12, presence of LPDs or GPDs on EEG, unknown etiology, and treatment refractoriness. The third cluster associated GCS score 13-15, absence of LPDs, GPDs, and spontaneous BS on EEG, and progressive and remote symptomatic etiology with treatment responsiveness. Phenotyping the heterogeneity of NCSE into electroclinical clusters can contribute to understanding correlations between pathologic and clinical domains, assessing the intrinsic severity of NCSE episodes, and estimating the likelihood of treatment responsiveness.


Can Computer Tomography Predict Compromise of Cardiac Structures After Percutaneous Closure of Interatrial Septal Defects?
Erosion of a cardiac structure after device closure of an interatrial septal communication (IASC-C), although rare, is a major and severe adverse event which may be underreported. On the other hand, unexplained episodes of transient chest pain occur more often and may be quite distressing. We sought to define the parameters relating the devices to the adjacent cardiac structures and to determine whether computer tomography (CT) could predict erosion of atrial or aortic wall or precordial pain symptoms occurring in the first months after device implantation. Retrospective observational study of 20 patients who underwent CT for de novo chest pain occurring after IASC-C or as a diagnostic test for suspected or proven coronary artery disease (CAD). Clinical follow up was for 20.5 ± 17.6 (6-84) months. CT was done 18 ± 10 (2-28) weeks after IASC-C. Indentation of the aortic root was found in 11 (55%) patients, the left atrial wall in 13 (65%) and the right atrial wall in eight (40%) of patients. Contact without indentation was found in nine (45%), 6 (30%) and 11 (55%) of patients respectively. Device indenting of the left and right atrial, as well as the aortic wall, occured in the majority of the patients examined after IASC-C. This finding may explain bouts of chest pain after the intervention in some patients, but does not predict clinically relevant erosion of a cardiac structure.


[Electrocution of foxes; an ethically acceptable method?].
The routine practice of electrocution of foxes by the Fox final apparatus was observed. The measured current was an average 0.31 (+/- 0.01 s.d.) A, the voltage 111.2 (+/- 18.7) V and the stunning time 3.0 (+/- 0.3) seconds (n = 40). The EEG (electroencephalogram) and the ECG (electrocardiogram) were recorded in 12 foxes. The current was initially applied for 1 sec. Ten foxes showed a general epileptiform insult (= unconscious) which was interrupted by a heart fibrillation, based on the EEG and ECG traces. Two foxes showed a general epileptiform insult while the heart fibrillation was incomplete. These two foxes recovered again. After the second stunning with a duration of about 3 seconds the heart fibrillation was complete in these animals. In the EEG and ECG experiments the voltage was on average 110.0 (+/- 7.9) V, the current 0.40 (+/- 0.11) A and the stunning time 1.1 (+/- 0.3) seconds (n = 12). The observations of the method in practice and the EEG and ECG measurements suggest that electrocution of foxes by the Fox final apparatus is a quick and effective method if the current delivery is at least 3 to 4 seconds.


Derived Arterial Stiffness is Increased in Patients with Obstructive Sleep Apnea and Periodic Limb Movements during Sleep.
Both periodic limb movements during sleep (PLMS) and obstructive sleep apnea (OSA) have been associated with increased risk of cardiovascular disease (CVD). OSA has also been linked to increased large arterial stiffness, which is considered an independent risk factor for CVD. We utilized a previously validated index of large artery stiffness (SIDVP) derived from the digital volume pulse (DVP) to seek comparison in patients with PLMS and OSA. Forty-nine adult male subjects, without known comorbidities that could affect arterial stiffness or on vasoactive medication, were retrospectively identified and categorized into controls (n = 8), PLMS (n = 13), OSA (n = 17), and OSA/PLMS (n = 11). The cutoff for PLMS was a periodic limb movement index (PLMI) > 15 events/h, and for OSA an apnea-hypopnea index (AHI) > 10 events/h. SIDVP was derived from the raw data of photoplethysmography of the nocturnal polysomnography, averaged for 2 min prior to sleep study initiation (baseline), after completion in the morning, and every half hour after sleep onset. The groups were age/body mass index-matched. Controls showed lower baseline, morning, and overall SIDVP compared to the other groups (p < 0.01). Patients with PLMS (PLMI: 50.69 ± 9.7 events/h) and the OSA group (AHI: 29.7 ± 2 events/h) demonstrated similar overall SIDVP (6.78 ± 0.08 versus 6.94 ± 0.04, respectively, p = 0.5), whereas the OSA/PLMS (AHI: 29.35 ± 8, PLMI: 50.63 ± 7.2) group demonstrated the highest (7.40 ± 0.06, p < 0.001). Based on an easily reproducible and applicable marker of large arterial stiffness, patients with significant PLMS had higher SIDVP when compared to controls and comparable to those with moderate/severe OSA. The OSA/PLMS group had the highest SIDVP, implying a possible additive effect of OSA and PLMS on arterial stiffness.


Donor CD8+ T cells mediate graft-versus-leukemia activity without clinical signs of graft-versus-host disease in recipients conditioned with anti-CD3 monoclonal antibody.
Donor CD8(+) T cells play a critical role in mediating graft-vs-leukemia (GVL) activity, but also induce graft-vs-host disease (GVHD) in recipients conditioned with total body irradiation (TBI). In this study, we report that injections of donor C57BL/6 (H-2(b)) or FVB/N (H-2(q)) CD8(+) T with bone marrow cells induced chimerism and eliminated BCL1 leukemia/lymphoma cells without clinical signs of GVHD in anti-CD3-conditioned BALB/c (H-2(d)) recipients, but induced lethal GVHD in TBI-conditioned recipients. Using in vivo and ex vivo bioluminescent imaging, we observed that donor CD8(+) T cells expanded rapidly and infiltrated GVHD target tissues in TBI-conditioned recipients, but donor CD8(+) T cell expansion in anti-CD3-conditioned recipients was confined to lymphohematological tissues. This confinement was associated with lack of up-regulated expression of alpha(4)beta(7) integrin and chemokine receptors (i.e., CXCR3) on donor CD8(+) T cells. In addition, donor CD8(+) T cells in anti-CD3-conditioned recipients were rendered unresponsive, anergic, Foxp3(+), or type II cytotoxic T phenotype. Those donor CD8(+) T cells showed strong suppressive activity in vitro and mediated GVL activity without clinical signs of GVHD in TBI-conditioned secondary recipients. These results indicate that anti-CD3 conditioning separates GVL activity from GVHD via confining donor CD8(+) T cell expansion to host lymphohemological tissues as well as tolerizing them in the host.


Metabotropic glutamate receptor, mGlu5, mediates enhancements of hippocampal long-term potentiation after environmental enrichment in young and old mice.
The metabotropic glutamate (mGlu) receptor, mGlu5, is of particular relevance for hippocampal function. It is critically required for the expression of long-term potentiation (LTP) and long-term depression (LTD), regulates neuronal oscillations, maintains the stability of place fields and is required for hippocampus-dependent memory. MGlu5-dysfunctions are associated with profound cognitive deficits in humans, and mGlu5 has been targeted as a putative cognitive enhancer. Cognitive enhancement, by means of environmental enrichment (EE) in rodents, results in improved hippocampal synaptic plasticity and memory. Here, we explored whether mGlu5 contributes to these enhancements. MGlu5-antagonism dose-dependently impaired the early phase of LTP (>4 h) in the CA1 region of young(3-4 month old) mice. Late-LTP (>24 h) was also impaired. LTP (>24 h) elicited in old (10-14 month old) mice displayed reduced sensitivity to mGlu5 antagonism. Short-term potentiation (STP, < 2 h) that was elicited by weaker afferent stimulation was unaffected by mGlu5-antagonism in both age-groups. EE significantly amplified STP (<2 h) in old and young animals, but did not increase the duration of synaptic potentiation, or promote induction of LTP. The improvement in STP was prevented by mGlu5-antagonism, in both young and old animals. These results indicate that modifications of the synapse that underlie improvements of LTP by EE require the contribution of mGlu5. Strikingly, although LTP in old mice does not critically depend on mGlu5, improvements in synaptic potentiation resulting from EE are mGlu5-dependent in old mice. Regarded in light of the known role for mGlu5 in hippocampal function and pathophysiology, these data suggest that mGlu5 regulation of synaptic information storage is pivotal to optimal hippocampal function. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'.


Care pathways for dementia: current perspectives.
Uncertainty appears to typify the experience of living with dementia. With an uncertain illness trajectory and unpredictable levels of deterioration and stability in symptoms, people with a diagnosis of dementia may live with uncertainty and anxiety and find it hard to make plans or decisions for their future. People with memory problems and caregivers seeking a diagnosis of dementia may also potentially find themselves navigating a labyrinth-like maze of services, practitioners, assessments, and memory tests, with limited understanding of test scores and little information about what support is available. In this context of uncertainty, the apparent clarity and certainty of a "dementia care pathway" may be attractive. However, the term "dementia care pathway" has multiple and overlapping meanings, which can potentially give rise to further confusion if these are ill-defined or a false consensus is presumed. This review distinguishes four meanings: 1) a mechanism for the management and containment of uncertainty and confusion, useful for the professional as well as the person with dementia; 2) a manual for sequencing care activities; 3) a guide to consumers, indicating eligibility for care activities, or a guide to self-management for dementia dyads, indicating the appropriateness of care activities; and 4) a manual for "walking with" the person. Examples of these approaches are presented from UK dementia services with illustrations of existing care pathways and associated time points, specifically focusing on: 1) early symptom identification and first service encounters, 2) assessment process, 3) diagnostic disclosure, 4) postdiagnostic support, and 5) appropriate interventions. We review the evidence around these themes, as well as discuss service pathways and referral routes used by some services in England and internationally. We conclude that the attraction of the term "care pathway" is seductive, but caution is needed in taking shared understandings for granted.


Relative efficacy of psychotherapy and combined therapy in the treatment of depression: a meta-analysis.
Reviews of the relative efficacy of psychotherapy and combined therapy (psychotherapy with pharmacotherapy) for depression have yielded contradicting conclusions. This may be explained by the clinical heterogeneity of the studies reviewed. To conduct a meta-analysis with an acceptable level of homogeneity in order to investigate the relative efficacy of psychotherapy and combined therapy in the acute treatment of depression. A systematic search was performed for RCTs published between 1980 and 2005 comparing psychotherapy and combined therapy in adult psychiatric outpatients with non-psychotic unipolar major depressive disorder. The studies were classified according to the chronicity and severity of the depression. Data were pooled by means of meta-analysis and statistical tests were conducted to measure heterogeneity. The meta-analysis included seven studies looking at a total of 903 patients. None of the heterogeneity tests established significance. This indicates a lack of evidence for the heterogeneity of the results. The dropout rates did not differ significantly between the two treatment modalities (25% in combined therapy and 24% in psychotherapy, p=0.77). At treatment termination, the intention-to-treat remission rate for combined therapy (46%) was better than for psychotherapy (34%) (p=0.0007); Relative Risk 1.32 (95% CI: 1.12-1.56), Odds Ratio 1.59 (95% CI: 1.22-2.09). In moderate depression, the difference between the remission rate for combined therapy and psychotherapy was statistically significant (47% compared to 34% respectively, p=0.001). This was not the case in mild major depression (42% compared to 37% respectively, p=0.29). The difference was also statistically significant in chronic major depression (48% compared to 32%, p<0.001), but not in non-chronic major depression (43% compared to 37%, p=0.22). On a more specific level, no differences were found in the remission rates for the treatment modalities in mild or moderate non-chronic depression. Combined therapy led to significantly better results than psychotherapy in moderate chronic depression only (48% compared to 32%, p<0.001). In the acute treatment of adult psychiatric outpatients with major depressive disorder, patient compliance with combined therapy matches compliance with psychotherapy alone. Combined therapy is more efficacious than psychotherapy alone. However, these results depend on severity and chronicity. Combined therapy outperformed psychotherapy in moderate chronic depression only. No differences were found in mild and moderate non-chronic depression. No data were found for mild chronic depression and for severe depression.


Roles of cyclooxygenase-2 and prostacyclin/IP receptors in mucosal defense against ischemia/reperfusion injury in mouse stomach.
We examined the roles of cyclooxygenase (COX) isozymes, prostaglandins (PGs), and their receptors in the mucosal defense against ischemia/reperfusion (I/R)-induced gastric lesions in mice. Male C57BL/6 mice, including wild-type animals and those lacking prostaglandin E(2) (EP)1, EP3, or prostaglandin I(2) (IP) receptors, were used after 18 h of fasting. Under urethane anesthesia, the celiac artery was clamped (ischemia) for 30 min, and then reperfusion was achieved for 60 min through the removal of the clamp, and the stomach was examined for lesions. I/R produced hemorrhagic gastric lesions in wild-type mice. The severity of lesions was significantly increased by pretreatment with indomethacin (a nonselective COX inhibitor) and rofecoxib (a selective COX-2 inhibitor) but not 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560; a selective COX-1 inhibitor). The expression of COX-2 mRNA was up-regulated in the stomach following I/R but not by sham operation or ischemia alone. The ulcerogenic response was markedly aggravated in IP receptor knockout mice but not those lacking EP1 or EP3 receptors. I/R increased the levels of 6-keto-PGF(1alpha) and PGE(2) in the stomach of wild-type mice, and this response was attenuated by indomethacin and rofecoxib but not SC-560. Pretreatment of wild-type mice with iloprost, a prostacyclin (PGI(2)) analog, significantly prevented the I/R-induced gastric lesions in the absence and presence of indomethacin or rofecoxib. PGE(2) also reduced the severity of I/R-induced gastric lesions, yet the effect was much less pronounced than that of iloprost. These results suggest that endogenous PGs derived from COX-2 play a crucial role in gastric mucosal defense during I/R, and this action is mainly mediated by PGI(2) through the activation of IP receptors.


[Floating-Harbor syndrome: first case in Italy associated with growth hormone deficiency].
The Floating-Harbor Syndrome (FHS) is a rare entity characterised by a clinical triad: facial dysmorphism, retarded speech development and short stature with delayed bone age. The case of a 9-year and 8/12 months old boy showing the typical features of this syndrome associated to a severe GH deficiency is reported. At diagnosis of FHS, the weight was 16 kg (< 3 degrees percentile), height 112 cm (< 3 degrees percentile), cranial circumference 53.8 cm (> 90 degrees percentile). The evaluation of growth hormone secretion by two Insulin Tolerance Tests confirmed an insufficient GH peaks response (2.7 ng/ml and 4.6 ng/ml). He had a slight mental delay (IQ: 60) involving language skills. After 1 year of treatment with r-hGH (0.6 IU/kg/week), an increase in growth velocity (11 cm/year) in the length (123 cm), and in body weight (20.5) has been observed. This case is the 22nd report with this syndrome and the first in Italy. The association between GH deficiency and FHS, and the beneficial effects of a substitutive treatment are described.


Positive youth development: a pathway to healthy teens.
As part of its continuing mission to serve trustees and staff of health foundations and corporate giving programs, Grantmakers In Health (GIH) convened a group of experts from the fields of philanthropy, research, government, and health care to examine recent research on youth development and effective approaches for promoting healthy decision making by adolescents. This Issue Dialogue, Positive Youth Development: A Pathway to Healthy Teens-held June 13, 2002 in Washington, DC-provided an opportunity for grantmakers to explore how they can apply youth development principles and asset-based strategies to their grantmaking to promote healthy development and healthy decision making by the adolescents in their communities. This Issue Brief incorporates the information and ideas shared during the meeting into a background paper prepared for participants at the Issue Dialogue. It provides an introduction to positive youth development; describes the characteristics of effective services and programs; reviews the research in this area; and provides examples of programs sponsored by the government, national organizations, and foundations that are intended to support and promote positive youth development.


Parallel Interconnected Kinetic Asymmetric Transformation (PIKAT) with an Immobilized ω-Transaminase in Neat Organic Solvent.
Comprising approximately 40% of the commercially available optically active drugs, α-chiral amines are pivotal for pharmaceutical manufacture. In this context, the enzymatic asymmetric amination of ketones represents a more sustainable alternative than traditional chemical procedures for chiral amine synthesis. Notable advantages are higher atom-economy and selectivity, shorter synthesis routes, milder reaction conditions and the elimination of toxic catalysts. A parallel interconnected kinetic asymmetric transformation (PIKAT) is a cascade in which one or two enzymes use the same cofactor to convert two reagents into more useful products. Herein, we describe a PIKAT catalyzed by an immobilized ω-transaminase (ωTA) in neat toluene, which concurrently combines an asymmetric transamination of a ketone with an anti-parallel kinetic resolution of an amine racemate. The applicability of the PIKAT was tested on a set of prochiral ketones and racemic α-chiral amines in a 1:2 molar ratio, which yielded elevated conversions (up to >99%) and enantiomeric excess (ee, up to >99%) for the desired products. The progress of the conversion and ee was also monitored in a selected case. This is the first report of a PIKAT using an immobilized ωTA in a non-aqueous environment.


Honey bees, neonicotinoids and bee incident reports: the Canadian situation.
Neonicotinoid insecticides have been the target of much scrutiny as possible causes of recent declines observed in pollinator populations. Although neonicotinoids have been implicated in honey bee pesticide incidents, there has been little examination of incident report data. Here we summarize honey bee incident report data obtained from the Canadian Pest Management Regulatory Agency (PMRA). In Canada, there were very few honey bee incidents reported in 2007-2011 and data were not collected prior to 2007. In 2012, a significant number of incidents were reported in the province of Ontario, where exposure to neonicotinoid dust during planting of corn was suspected to have caused the incident in up to 70% of cases. Most of these incidents were classified as 'minor' by the PMRA, and only six cases were considered 'moderate' or 'major'. In that same year, there were over three times as many moderate or major incidents due to older non-neonicotinoid pesticides, involving numbers of hives or bees far greater than the number of moderate or major incidents suspected to be due to neonicotinoid poisoning. These data emphasize that, while exposure of honey bees to neonicotinoid-contaminated dust during corn planting needs to be mitigated, other pesticides also pose a risk.


Integration of thermal and osmotic regulation of water homeostasis: the role of TRPV channels.
Maintenance of body water homeostasis is critical for preventing hyperthermia, because evaporative cooling is the most efficient means of dissipating excess body heat. Water homeostasis is achieved by regulation of water intake and water loss by the kidneys. The former is achieved by sensations of thirst that motivate water acquisition, whereas the latter is regulated by the antidiuretic action of vasopressin. Vasopressin secretion and thirst are stimulated by increases in the osmolality of the extracellular fluid as well as decreases in blood pressure and/or blood volume, signals that are precipitated by water depletion associated with the excess evaporative water loss required to prevent hyperthermia. In addition, they are stimulated by increases in body temperature. The sites and molecular mechanisms involved in integrating thermal and osmotic regulation of thirst and vasopressin secretion are reviewed here with a focus on the role of the thermal and mechanosensitive transient receptor potential-vanilloid (TRPV) family of ion channels.


Nucleoprotein cytochemistry during oogenesis in a unisexual fish, Poecilia formosa.
Cytochemical methods and electron microscopy were used to study changes in the chemical composition of nuclear, nucleolar and perinuclear bodies during the early stages of oocyte development in Poecilia formosa, an apomictic species of fish that produces only female offspring. Prominent accumulations of ribonucleoprotein (RNP) occur in nucleoli and appear on either side of the nuclear envelope during diplotene. In certain planes of section, RNP material seems to be in transit across this interface. En bloc acid extractions or RNAase treatment abolished basophilia and markedly reduced the electron density of both nucleoli and cytoplasmic nucleolar-like bodies. DNA-specific fluorescent probes such as mithramycin failed to reveal nucleolar cores in poeciliid oocytes, although the same procedures showed unequivocal localization of GC-rich DNA cores within multiple nucleoli of diplotene oocytes from Xenopus laevis or the rainbow trout, Salmo gairdneri. Also, cytological hybridization studies, utilizing [3H]rRNA as a probe for nucleolar DNA, failed to show localizations of silver grains above nucleoli in autoradiograms of poeciliid oocytes. Feulgen-stained pachytene oocytes of P. formosa have twice the number of chromosome strands seen in similar stages of oocytes from two, related bisexual species, P. mexicana and P. latipinna. Although the bivalent nature of these chromosomes could not be resolved with the light microscope, configurations resembling, but not identical to, synaptonemal complexes were identified by electron microscopy.


Total Body Irradiation in the "Hematopoietic" Dose Range Induces Substantial Intestinal Injury in Non-Human Primates.
The non-human primate has been a useful model for studies of human acute radiation syndrome (ARS). However, to date structural changes in various parts of the intestine after total body irradiation (TBI) have not been systematically studied in this model. Here we report on our current study of TBI-induced intestinal structural injury in the non-human primate after doses typically associated with hematopoietic ARS. Twenty-four non-human primates were divided into three groups: sham-irradiated control group; and total body cobalt-60 (60Co) 6.7 Gy gamma-irradiated group; and total body 60Co 7.4 Gy gamma-irradiated group. After animals were euthanized at day 4, 7 and 12 postirradiation, sections of small intestine (duodenum, proximal jejunum, distal jejunum and ileum) were collected and fixed in 10% formalin. The intestinal mucosal surface length, villus height and crypt depths were assessed by computer-assisted image analysis. Plasma citrulline levels were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total bone marrow cells were counted and hematopoietic stem/progenitor cells in bone marrow were analyzed by flow cytometer. Histopathologically, all segments exhibited conspicuous disappearance of plicae circulares and prominent atrophy of crypts and villi. Intestinal mucosal surface length was significantly decreased in all intestinal segments on day 4, 7 and 12 after irradiation (P < 0.02-P < 0.001). Villus height was significantly reduced in all segments on day 4 and 7 (P = 0.02-0.005), whereas it had recovered by day 12 (P > 0.05). Crypt depth was also significantly reduced in all segments on day 4, 7 and 12 after irradiation (P < 0.04-P < 0.001). Plasma citrulline levels were dramatically reduced after irradiation, consistent with intestinal mucosal injury. Both 6.7 and 7.4 Gy TBI reduced total number of bone marrow cells. And further analysis showed that the number and function of CD45(+)CD34(+) hematopoietic stem/progenitors in bone marrow decreased significantly. In summary, TBI in the hematopoietic ARS dose range induces substantial intestinal injury in all segments of the small bowel. These findings underscore the importance of maintaining the mucosal barrier that separates the gut microbiome from the body's interior after TBI.


Failure analysis in the identification of synergies between cleaning monitoring methods.
The 4 monitoring methods used to manage the quality assurance of cleaning outcomes within health care settings are visual inspection, microbial recovery, fluorescent marker assessment, and rapid ATP bioluminometry. These methods each generate different types of information, presenting a challenge to the successful integration of monitoring results. A systematic approach to safety and quality control can be used to interrogate the known qualities of cleaning monitoring methods and provide a prospective management tool for infection control professionals. We investigated the use of failure mode and effects analysis (FMEA) for measuring failure risk arising through each cleaning monitoring method. FMEA uses existing data in a structured risk assessment tool that identifies weaknesses in products or processes. Our FMEA approach used the literature and a small experienced team to construct a series of analyses to investigate the cleaning monitoring methods in a way that minimized identified failure risks. FMEA applied to each of the cleaning monitoring methods revealed failure modes for each. The combined use of cleaning monitoring methods in sequence is preferable to their use in isolation. When these 4 cleaning monitoring methods are used in combination in a logical sequence, the failure modes noted for any 1 can be complemented by the strengths of the alternatives, thereby circumventing the risk of failure of any individual cleaning monitoring method.


Diabetes and impaired glucose tolerance in Aboriginal Australians: prevalence and risk.
The prevalence and risk of having impaired glucose tolerance (IGT) and diabetes was estimated relative to body mass index (BMI) among Australian Aboriginal people. A stratified analysis was undertaken of community screening data. Measures included fasting and 2-h glucose concentrations, and BMI (five strata: <22, 22-24.9, 25-29.9, 30-34.9 and >/=35 kg/m(2)). Age was stratified into three groups: 15-34.9, 35-44.9, and >/=45 years. Participants were men and women, ages 15-94 years (n=2626). The prevalence of IGT and diabetes, respectively, adjusted for age and BMI, was 139 and 142 cases/1000 persons among men, and 157 and 152 cases/1000 persons among women. Odds ratios (95% CI) for IGT and diabetes for increasing BMI strata >/=22 kg/m(2) ranged from 1.7 (1.0 to 2.9) to 5.1 (2.4-10.5) for IGT, and from 2.0 (1.2-3.5) to 6.1 (3.3-11.1) for diabetes. For IGT and diabetes, across genders, the population attributable risk percentages (95% CI) for BMI >/=22 kg/m(2) were 34.1% (26.2-41.9%) for IGT, and 46.4% (38.5-54.5%) for diabetes. Diabetes and IGT have reached epidemic proportions among Australian Aboriginal people. An urgent need exists for programmes to reduce the prevalence of diabetes risk factors, especially BMI of 22 kg/m(2) or more, a limit lower than advocated for Euro-American populations.


Peripheral Pruning: A Safe Approach to Thinning Extra-Large Anterolateral Thigh Flaps.
Thinning of anterolateral thigh (ALT) flaps has been described to achieve optimal contouring. Previous studies caution against thinning large flaps owing to the risk of vascular compromise leading to partial or total flap necrosis. This study aims to demonstrate a reliably safe method for thinning extra-large (>240 cm) flaps. A retrospective review of 53 consecutive ALT flaps performed at a single institution was completed. Of these flaps, 18 (34%) were thinned primarily by sharp excision of sub-Scarpa's fat along the periphery of the flap using loupe magnification. A central cuff of fat is left to surround and protect the perforator. There were 53 total flaps in our series. Eighteen of the flaps were thinned by peripheral pruning. Eleven (61%) of the flaps reconstructed defects of the lower extremity, whereas 4 (22%) reconstructed upper extremity defects and 3 (17%) reconstructed scalp defects (Table 1). The mean size of the thinned flap group was 35% larger than the nonthinned group (n = 18, 261 cm ± 109 cm vs n = 35, 192 cm ± 146 cm). Ten thinned flaps (55%) were extra large, with flap areas over 240 cm. The average amount of excised fat weighed 41 g ± 18 g. The average body mass index in the thinned flap group was 28.8 kg/m, which is classified as overweight. The average body mass index in the nonthinned flap group was 24.6 kg/m, which is classified as normal weight (Table 2). There were no cases of partial flap necrosis in the thinned flap group. A single case of total flap loss occurred in the thinned flap group secondary to hematoma formation during administration of therapeutic heparin for a mechanical heart valve. There were no other complications in the thinned flap group. This is the first study to demonstrate a reliable technique for primary thinning of extra-large ALT flaps in the Western population. No complications related to thinning were observed. Peripheral pruning of sub-Scarpa's fat is a safe and reliable method of thinning extra-large ALT flaps without increasing the risk of flap necrosis.


The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America.
Guidelines for the diagnosis and treatment of patients with encephalitis were prepared by an Expert Panel of the Infectious Diseases Society of America. The guidelines are intended for use by health care providers who care for patients with encephalitis. The guideline includes data on the epidemiology, clinical features, diagnosis, and treatment of many viral, bacterial, fungal, protozoal, and helminthic etiologies of encephalitis and provides information on when specific etiologic agents should be considered in individual patients with encephalitis.


Assessment of the efficacy of an indigeniously developed pulse oximeter dental sensor holder for pulp vitality testing.
Current routine methods of assessment of pulp vitality rely on stimulation of nerve fibres and give no direct indication of blood flow within the pulp. Pulse oximeter is a proven, atraumatic method of measuring vascular status, by evaluating oxygen saturation. This study explores the use of customized dental pulse oximeter sensor holder to assess pulpal vascular oxygen saturation in permanent teeth. Pulse oximeter readily differentiated between known vital and nonvital teeth. Vital teeth consistently provided oxygen saturation values that were lower than the values recorded on the patient's fingers. Pulse oximeter is an accurate, atraumatic clinical alternative to the present electrical and thermal methods of assessing pulp vitality in teeth.


On hating to hate.
Hate may be the most dangerous of all emotions for the survival of the planet. The author addresses two questions: What obscures hate when it is actually present? and What masquerades as hate but isn't? Using illustrations from a wide range of fields, the author contends that discerning hate is both essential and far trickier than we think. She concludes by asserting that overcoming hate requires imagination. We must learn to imagine a world without hate and unimagine a world with hate.


Methods for biological data integration: perspectives and challenges.
Rapid technological advances have led to the production of different types of biological data and enabled construction of complex networks with various types of interactions between diverse biological entities. Standard network data analysis methods were shown to be limited in dealing with such heterogeneous networked data and consequently, new methods for integrative data analyses have been proposed. The integrative methods can collectively mine multiple types of biological data and produce more holistic, systems-level biological insights. We survey recent methods for collective mining (integration) of various types of networked biological data. We compare different state-of-the-art methods for data integration and highlight their advantages and disadvantages in addressing important biological problems. We identify the important computational challenges of these methods and provide a general guideline for which methods are suited for specific biological problems, or specific data types. Moreover, we propose that recent non-negative matrix factorization-based approaches may become the integration methodology of choice, as they are well suited and accurate in dealing with heterogeneous data and have many opportunities for further development.


[Serotonin metabolism in normal pregnant women and fetus].
To evaluate serotonin (5-HT) metabolism in normal pregnant women and their fetuses, plasma free 5-HT, 5-hydroxyindoleacetic acid (5-HIAA). Tryptophan (TRP) and platelet free 5-HT content were determined by HPLC with electrochemical detection. Plasma free 5-HT and TRP concentrations and platelet 5-HT content in pregnant women did not change during pregnancy. In contrast, plasma free 5-HIAA increased after 30 weeks of gestation and reached its peak at 37 weeks. 5-HT, 5-HIAA and TRP concentrations in umbilical cord plasma were significantly higher than in maternal plasma. However, platelet 5-HT content in the fetus was significantly lower than in the mother. No significant correlation was found between 5-HT concentrations in maternal and cord plasma. However, a significant correlation was found between 5-HIAA, concentrations in maternal and cord plasma. The total 5-HT/TRP ratio in cord blood was significantly lower than in the maternal vein. The 5-HIAA/5-HT ratio in cord plasma was markedly higher than in maternal plasma. In conclusion, we demonstrated the patterns of plasma free 5-HT, 5-HIAA, TRP and platelet 5-HT concentrations in normal pregnant women and their fetuses. Furthermore, rapid 5-HT metabolism in the fetus was suggested.


Impact of Revised Broad-Spectrum Cephalosporin Clinical and Laboratory Standards Institute Breakpoints on Susceptibility in Enterobacteriaceae Producing AmpC β-Lactamase.
We evaluated the impact of revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for broad-spectrum cephalosporins (BSCs) on the susceptibilities of 1,742 isolates of Enterobacter species, Serratia marcescens, Citrobacter freundii, and Morganella morganii. The 2011 CLSI criteria for cefotaxime and ceftazidime reduced the rates of susceptibility by 2.9% and 5.9%, respectively. The 2014 CLSI criteria for cefepime reduced the rate of susceptibility by 13.9%, and categorized 11.8% isolates as susceptible-dose dependent (SDD) for cefepime. Among 183 isolates with extended-spectrum β-lactamase (ESBL) phenotype, implementation of the new criteria reduced the rates of susceptibility to cefotaxime, ceftazidime, and cefepime by 2.8%, 14.8%, and 53.6%, respectively. The proportion of ESBL phenotype among BSC-susceptible isolates was low (0.9% for cefotaxime, 3.0% for ceftazidime, and 3.3% for cefepime). In summary, implementation of new CLSI criteria led to little change in susceptibility to cefotaxime and ceftazidime but a substantial change in susceptibility to cefepime. The recognition of revised CLSI criteria for BSC and SDD will help clinicians to select the optimal antibiotic and dosing regimen.


Nurses' intention to remain employed in hospitals: Understanding the shortage in the context of Myanmar.
This study aims to ascertain the rate and identify the factors associated with nurses' intention to remain employed at hospitals in the Yangon Region. A cross-sectional descriptive study was conducted among 300 nurses aged between 20 and 60 years working at both private and public hospitals in the Yangon Region during May to June 2015. Chi-square tests were used to identify factor associations, and multiple logistic regression was examined to determine predictive factors. The study revealed that 63.6% of nurses intended to remain employed. Marital status (adjusted odd ratio: 2.22; 95% confidence interval [CI]: 1.05-4.32), work characteristics (adjusted odd ratio: 2.42; 95% CI: 1.33-4.41), job stress and burnout (adjusted odd ratio: 1.77; 95% CI: 1.01-3.11), and recognition (adjusted odd ratio: 1.96; 95% CI: 1.07-3.59) were found to be significant predictors of nurses' intention to remain employed at the hospitals. Recognition and other nonmonetary incentive support systems should be provided to enhance the retention of nurses at the hospitals.


Vape shop retailers' perceptions of their customers, products and services: A content analysis.
The popularity of electronic cigarettes (e-cigarettes) has spurred the growth of vape shops, but little is known about the retailers who may play an important role in the introduction and dissemination of vape products. In this paper we examine how retailers profile their customers and their perceptions of vaping, and the services their shops provide. Semi-structured interviews were conducted with a convenience sample of retailers (n=77) located across southern California. Open-ended questions were coded and analyzed using a content analysis approach. Three themes emerged from the content analysis: who vapes, why people vape, and the vape shop environment. Retailers profiled customers as friendly, health conscious, and interested in tobacco cessation or cessation maintenance. Retailers believed e-cigarettes were used recreationally or as products that help curb other addictive behaviors. While most retailers reported positive experiences with vaping, some reported potentially negative experiences including failed cessation attempts, dual use of e-cigarettes and combustible cigarettes, and increased nicotine dependence. Retailers reported that they regularly answer questions about vaping and believe their shops function as social lounges that are tied to other recreational activities. Retailers attach certain characteristics to their clientele, perceive certain health benefits associated with vaping, and seek to establish their shops as places that provide guidance on vape products as well as shops with a recreational aesthetic. As vape shops grow in popularity, additional research on, and regulation of, these retailers will be necessary. Education campaigns are needed to inform retailers of the benefits and consequences of vaping.


A prospective comparative study of narrow-band imaging, chromoendoscopy, and conventional colonoscopy in the diagnosis of colorectal neoplasia.
Discrimination between neoplastic and non-neoplastic lesions is crucial in colorectal cancer screening. Application of narrow-band imaging (NBI) in colonoscopy visualises mucosal vascular networks in neoplastic lesions and may improve diagnostic accuracy. To compare the diagnostic efficacy of NBI in differentiating neoplastic from non-neoplastic colorectal lesions with diagnostic efficacies of standard modalities, conventional colonoscopy, and chromoendoscopy. In this prospective study, 180 colorectal lesions from 133 patients were observed with conventional colonoscopy, and under low-magnification and high-magnification NBI and chromoendoscopy. Lesions were resected for histopathological analysis. Endoscopic images were stored electronically and randomly allocated to two readers for evaluation. Sensitivity, specificity and diagnostic accuracy of each endoscopic modality were assessed by reference to histopathology. NBI and chromoendoscopy scored better under high magnification than under low magnification in comparison with conventional colonoscopy. The diagnostic accuracy of NBI with low or high magnification was significantly higher than that of conventional colonoscopy (low magnification: p = 0.0434 for reader 1 and p = 0.004 for reader 2; high magnification: p<0.001 for both readers) and was comparable to that of chromoendoscopy. Both low-magnification and high-magnification NBI were capable of distinguishing neoplastic from non-neoplastic colorectal lesions; the diagnostic accuracy of NBI was better than that of conventional colonoscopy and equivalent to that of chromoendoscopy. The role of NBI in screening colonoscopy needs further evaluation.


2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease.
We describe three patients, from two Spanish families, with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency, a recently described X-linked neurodegenerative inborn error of isoleucine metabolism. Two of them are males with severe lactic acidosis suggestive of a mitochondrial encephalopathy, and the third is a female who was less severely affected, suggesting skewed X-inactivation. Molecular studies revealed a new missense mutation, 740A-->G, in one family and a previously described mutation, 388C-->T, in the other, causing the amino acid substitutions N247S and R130C, respectively. Both male patients died, one of them despite treatment with an isoleucine-restricted diet, but the disease has remained stable in the female patient after 1 y of treatment.


Increased adipose tissue secretion of interleukin-6, but not of leptin, plasminogen activator inhibitor-1 or tumour necrosis factor alpha, in Graves' hyperthyroidism.
This study was designed to investigate adipose tissue secretion of interleukin-6 (IL-6), leptin, tumour necrosis factor alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) in Graves' hyperthyroidism. We studied 10 patients before and during (after 8 weeks) anti-thyroid treatment for Graves' hyperthyroidism and 16 healthy, euthyroid control subjects. Plasma levels of thyroid hormones and serum/plasma levels of IL-6, leptin, TNF-alpha and PAI-1 were analysed. Subcutaneous fat biopsies were taken for subsequent measurement of IL-6, leptin, TNF-alpha and PAI-1 protein secretion. In patients with Graves' disease, the anti-thyroid treatment resulted in significant reductions of plasma thyroxine and triiodothyronine levels. No differences in serum concentration or adipose tissue secretion of leptin or TNF-alpha were observed either before, as compared with during, anti-thyroid treatment, or in comparison with euthyroid controls. In contrast, plasma PAI-1 activity, but not adipose tissue secretion of PAI-1, was increased both in Graves' disease before as compared with during anti-thyroid treatment (P=0.01) and in thyrotoxic patients compared with euthyroid controls (P=0.0001). Finally, adipose secretion of IL-6 was increased both before (8-fold, P=0.001) and during (6-fold, P<0.0001) treatment as compared with control subjects. Accordingly, serum concentration of IL-6 was also increased by about 50% in thyrotoxic patients as compared with healthy controls (P=0.03). In Graves' hyperthyroidism regardless of thyroid status, adipose tissue secretion of IL-6, but not of leptin, TNF-alpha or PAI-1, is markedly increased in comparison with euthyroid controls. This suggests that autoimmune thyroidal disorder may regulate adipose tissue release of IL-6.


Long-term follow-up in osteogenesis imperfecta type VI.
This retrospective study on long-term outcomes in osteogenesis imperfecta type VI found that patients who received intravenous bisphosphonate treatment had an increase in lumbar spine areal bone mineral density, a higher final height z-score, and some reshaping of vertebral bodies. Osteogenesis imperfecta (OI) type VI is an ultra-rare bone fragility disorder caused by recessive mutations in SERPINF1. Here, we describe long-term outcomes in OI type VI and compare the clinical phenotypes caused by different types of SERPINF1 mutations. This study includes a retrospective chart review of 13 individuals with OI type VI. In the absence of therapy, lumbar spine areal bone mineral density (BMD) did not increase during childhood and longitudinal growth seemed to stall after the age of 6 to 8 years. The phenotype was similar between individuals with different types of SERPINF1 mutations. Intravenous bisphosphonate treatment was associated with an increase in lumbar spine areal BMD and some reshaping of compressed vertebral bodies. Patients who had started bisphosphonate treatment early (before the age of 6 years) were taller than patients who had received bisphosphonate treatment later during their growing years. Lower extremity fractures were frequent despite bisphosphonate treatment and scoliosis was present in all patients who had reached the final height. Most patients had restricted mobility. In four patients, intravenous bisphosphonate treatment was eventually substituted by subcutaneous injections of denosumab, without clear changes in the clinical picture. Patients with OI type VI who received intravenous bisphosphonate treatment during growth had an increase in lumbar spine areal BMD, a higher final height z-score, and presented some reshaping of vertebral bodies. More effective treatment modalities are clearly required in OI type VI.


Combined cytosine arabinoside and prednisone therapy for meningoencephalitis of unknown aetiology in 10 dogs.
The differential diagnosis for young to middle-aged dogs with progressive neurological signs, focal or multifocal computed tomography/magnetic resonance imaging lesions, mononuclear cerebrospinal fluid pleocytosis and negative infectious titres includes granulomatous meningoencephalomyelitis, breed-specific meningoencephalitis, infectious meningoencephalitis of unknown origin and central nervous system neoplasia. The terminology meningoencephalitis of unknown aetiology may be preferable for cases that lack histopathological diagnoses. The safety and efficacy of a combination of cytosine arabinoside and prednisone protocol is evaluated, in this study, for the treatment of meningoencephalitis of unknown aetiology in 10 dogs. Cases were selected based on neuroanatomical localisation, negative regional infectious disease titres, cerebrospinal fluid pleocytosis and brain imaging. Clinical response was gauged through follow-up examinations, owner and referring veterinarian surveys and review of medical records. Partial or complete remission was achieved in all dogs; the median survival time for the 10 dogs was 531 days (range 46 to 1025 days), with five of the 10 dogs alive at the time of writing. Prednisone/cytosine arabinoside is a safe empirical therapy for dogs with meningoencephalitis of unknown aetiology; this drug combination may prolong survival time.


E-Cadherin Immunostaining in Equine Melanocytic Tumors.
Melanocytic tumors are an important neoplastic disease in human and veterinary medicine, presenting large differences regarding tumor behavior between species. In horses, these tumors present a prolonged benign behavior, with rare invasiveness and metastases. In humans and small animals, invasion and metastasis have been associated with an Epithelial-Mesenchymal Transition, where the loss of E-cadherin expression plays a key role in tumor progression. This process and the role of E-cadherin have not yet been evaluated in equine melanocytic tumors. This study aimed to assess the immunolabeling of E-cadherin in equine melanocytic tumors and relate this with clinicopathological variables. A total of 72 equine melanocytic tumors were classified as benign and malignant and evaluated by immunohistochemistry for E-cadherin expression. A different pattern of immunostaining was found, contrasting with other species. A total of 69.4% of tumors presented raised immunolabeling of E-cadherin, with 70.7% of melanomas remaining with high expression. The typical loss of immunostaining was not seen in malignant melanomas and no differences were found between benign and malignant melanomas regarding E-cadherin immunostaining. The high immunolabeling of E-cadherin may contribute to the low invasiveness of these tumors, and it is in accordance with the benign behavior of equine melanoma and with the genetic factors associated with its development.


Preimplantation genetic diagnosis of haemophilia.
Preimplantation genetic diagnosis (PGD) aims to increase the number of options available to couples who could have a child affected with haemophilia and reduce the anxiety these couples often associate with reproduction. The female partner must undergo an in vitro fertilization cycle, and the eggs or embryos are then biopsied. Embryos which are unaffected by haemophilia can then be transferred to the uterus. The clear advantage of this technique is that the woman knows from the very beginning that the pregnancy is unaffected by haemophilia, and she can avoid conventional invasive prenatal diagnosis and the difficult decision on whether or not to terminate an affected pregnancy. Several strategies for this single cell genetic diagnosis have been described. These include embryonic sexing using polymerase chain reaction, embryonic sexing using fluorescent in situ hybridization, specific diagnosis using restriction enzymes, sequencing and haplotype analysis. Over the years, PGD has attracted much ethical commentary, both supportive and critical, regarding the fundamental principles of embryo selection and destruction. New scientific advances and their potential applications are considered.


Rectal cancer diagnosed after resection of isolated brain metastasis.
Brain metastasis of colorectal cancer is infrequent, and isolated brain metastases are more infrequent. Thus, when neurological symptoms, such as paralysis or disturbance of consciousness appear, there is a high probability that the cancer has spread to other organs. Here, we present a 64-year-old man with a progressive headache, decreased motivation, and aphasia who was diagnosed with a brain tumor in the left frontal region. He underwent a craniotomy, and the brain tumor was diagnosed as adenocarcinoma. We performed a colonoscopy and diagnosed rectal cancer without other distant metastases. After whole-brain radiotherapy (WBRT), low anterior resection for primary rectal tumor was performed using a robotic system. The patient was discharged in good condition and received postoperative adjuvant therapy for rectal cancer. He showed no signs of recurrence after 1 year of follow-up. We described a rare case of rectal cancer that was diagnosed after resection of isolated brain metastasis. A good prognosis was achieved with surgery and WBRT.


Setting control limits for Escherichia coli counts in samples collected routinely from pig or beef carcasses.
Records of Escherichia coli counts in samples routinely collected from carcasses were obtained from one pork and three beef packing plants. The data obtained from each plant were divided into sets from consecutive 6-month periods. For each set of counts, log total counts were calculated for subsets of various sizes. For each set of log total counts, the mean (x), the standard deviation (SD), and an action limit of x + 3 SD were calculated, and the set was tested for a normal distribution. With the data from samples collected at the pork packing plant during 6 years, the proportion of samples with counts of zero in the 12 sets ranged from 15 to 45%. For that plant, appropriate action limits could be derived from log total counts for subsets of nine unit values. With the data from samples collected during 8 years at one beef packing plant, the proportion of samples with counts of zero in the 16 sets ranged from 88 to 99%. For that plant, appropriate action limits could be derived from log total counts for subsets of 15 unit values. With the data from samples collected during 2 or 2.5 years at each of the other beef packing plants, the proportion of samples with counts of zero in all sets was > 99%. For those data, action limits could not be derived from values for subsets of log total counts.


Study of gaseous substrate fermentations: carbon monoxide conversion to acetate. 2. Continuous culture.
The fermentation of gaseous substrates such as CO, H(2), and CO(2) may be performed in a continuous stirred tank reactor, as well as the traditional batch reactor. In this article, the conversion of carbon monoxide by Peptostreptococcus productus is demonstrated in a stirred tank reactor under both mass transfer-controlled and nonmass transfer-controlled conditions. Utilizing a non-steady-state procedure, intrinsic rates are evaluated under non-mass transfer-controlled conditions in a time period of only 5-6 hours. A steady-state procedure was used to evaluate CSTR performance under mass transfer-controlled conditions. The mass transfer coefficient was calculated, followed by the development of a model to predict CSTR behavior for this gas phase substrate.


An Economic Analysis of Intensive Multidisciplinary Interventions for Treating Medicaid-Insured Children with Pediatric Feeding Disorders.
Background. Intensive multidisciplinary intervention (IMI) represents a well-established treatment for pediatric feeding disorders (PFDs), but program availability represents an access care barrier. We develop an economic analysis of IMI for weaning from gastronomy tube (G-tube) treatment for children diagnosed with PFDs from the Medicaid programs' perspective, where Medicaid programs refer to both fee-for-service and managed care programs. Methods. The 2010-2012 Medicaid Analytic eXtract claims provided health care data for children aged 13 to 72 months. An IMI program provided data on average admission costs. We employed a finite-horizon Markov model to simulate PFD treatment progression assuming 2 treatment arms: G-tube only v. IMI targeting G-tube weaning. We compared the expenditure differential between the 2 arms under varying time horizons and treatment effectiveness. Results. Overall Medicaid expenditure per member per month was $6814, $2846, and $1550 for the study population of children with PFDs and G-tube treatment, the control population with PFDs without G-tube treatment, and the no-PFD control population, respectively. The PFD-diagnosed children with G-tube treatment only had the highest overall expenditures across all health care settings except psychological services. The expenditure at the end of the 8-year time horizon was $405,525 and $208,218 per child for the G-tube treatment only and IMI arms, respectively. Median Medicaid expenditure was between 1.7 and 2.2 times higher for the G-tube treatment arm than for the IMI treatment arm. Limitations. Data quality issues could cause overestimates or underestimates of Medicaid expenditure. Conclusions. This study demonstrated the economic benefits of IMI to treat complex PFDs from the perspective of Medicaid programs, indicating this model of care not only holds benefit in terms of improving overall quality of life but also brings significant expenditure savings in the short and long term.


Clinical significance of fractional flow reserve for evaluation of functional lesion severity in stent restenosis and native coronary arteries.
Fractional flow reserve (FFR) is a valid surrogate for hemodynamic significance in stenotic native coronary arteries, but its validity in patients with coronary stent restenosis is unknown. Prospective. University hospital. We studied 42 patients (mean age +/- 1 SD, 62 +/- 10 years) with stent restenosis and 57 patients (mean age, 61 +/- 12 years) with a native coronary lesion. All patients demonstrated a single coronary lesion of intermediate severity (stenosis diameter, 40 to 70%). Determination of FFR and quantitative angiography of the stenosis were performed. Stenosis diameter was comparable in both groups (native, 52 +/- 11%; stent, 52 +/- 9%; not significant [NS]). FFR was lower in stent restenosis (0.77 +/- 0.15 vs 0.82 +/- 0.12, p < 0.05) and more often pathologic with an FFR < 0.75 (48% vs 26%, p < 0.05) compared to native coronary stenosis. However, the area under the receiver operating characteristic curve for native stenosis was 0.82 (95% confidence interval [CI], 0.71 to 0.94) and for stent restenosis was 0.84 (95% CI, 0.71 to 0.97; NS). In patients with an FFR > 0.75, there was no adverse coronary event that was related to the stented lesion in the subsequent 6 months. The threshold of stenosis diameter of coronary lesions for pathologic FFR measurement (FFR < 0.75) is similar for stent restenosis and native coronary stenosis. Thus, FFR measurement seems to be applicable for decision making in patients with stent restenosis.


Generalized emissivity inverse problem.
Inverse problems have recently drawn considerable attention from the physics community due to of potential widespread applications [K. Chadan and P. C. Sabatier, Inverse Problems in Quantum Scattering Theory, 2nd ed. (Springer Verlag, Berlin, 1989)]. An inverse emissivity problem that determines the emissivity g(nu) from measurements of only the total radiated power J(T) has recently been studied [Tao Wen, DengMing Ming, Xianxi Dai, Jixin Dai, and William E. Evenson, Phys. Rev. E 63, 045601(R) (2001)]. In this paper, a new type of generalized emissivity and transmissivity inverse (GETI) problem is proposed. The present problem differs from our previous work on inverse problems by allowing the unknown (emissivity) function g(nu) to be temperature dependent as well as frequency dependent. Based on published experimental information, we have developed an exact solution formula for this GETI problem. A universal function set suggested for numerical calculation is shown to be robust, making this inversion method practical and convenient for realistic calculations.


[A case of carcinoma originating from accessory breast tissue of the axilla].
We report a case of carcinoma originating from accessory breast tissue of axilla and review 33 reported cases of carcinoma in heterotopic breast tissue. Although the incidence of accessory breast cancer is not high, early diagnosis and treatment are necessary, keeping in mind the possibility of this carcinoma when subcutaneous nodules of uncertain origin are found around the breast. Surgical treatment which must at least include wide local extirpation including the surrounding tissues and dissection of the axillary lymph nodes is necessary and adjunctive chemotherapy and irradiation appear to be useful.


[Autism spectrum symptoms in children with congenital blindness].
Autism spectrum symptoms in children with congenital blindness Abstract. Objective: Previous studies reported increased rates of autistic symptoms in children with impaired visual abilities (IV). However, the application of existing screening questionnaires for autism spectrum disorders (ASD) proved problematic, as intact visual abilities are typically required. The current study examines the general applicability of three autism-screening questionnaires in children with congenital blindness. Methods: Autistic symptoms were assessed in 15 children with congenital blindness, 15 children with ASD (without IV), and 20 typically developing controls (aged from 8 to 14 years), using the Social Communication Questionnaire, the Marburg Rating Scale for Asperger's Syndrome, and the Social Responsiveness Scale. Results: Items assessing motor, mimic/gesture-related, or joint attention deficits were identified as highly prevalent in children with congenital blindness. These children scored, in general, higher on ASD-screening questionnaires than typically developing controls but lower than sighted children with ASD. Depending on the screening questionnaire used, between 23 % and 67 % of the sample with congenital blindness reached clinical cutoff scores for ASD. SRS total score was negatively correlated to cognitive empathy and verbal IQ in those children. Conclusions: Mothers of children with congenital blindness reported increased autistic symptoms in ASD-screening questionnaires. ASD and IV might share a broad range of symptoms. Future development and validation of screening instruments specifically adapted to the needs of persons with impaired visual abilities seem necessary.


Glandular odontogenic cyst: a case report and clinicopathologic analysis of the relationship to central mucoepidermoid carcinoma.
Glandular odontogenic cyst (GOC), an unusual multilocular cystic lesion of jaws exhibiting the features of both botryoid odontogenic cyst and mucoepidermoid tumor has been reported recently as a new entity with uncertain histogenesis. The World Health Organization named GOC as an independent pathologic entity and classified it as a developmental odontogenic epithelial cyst. We report an additional case, describe its clinicopathologic features, and discuss the similarity to the central mucoepidermoid carcinoma.


Plasma Metabolites Associated with OCT Features of Age-Related Macular Degeneration.
The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD. Prospectively designed, cross-sectional study. Subjects with a diagnosis of AMD and a control group (> 50 years old) from Boston, United States, and Coimbra, Portugal. All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons. Plasma metabolite levels associated with OCT features. We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR < 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed. To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature. Proprietary or commercial disclosure may be found after the references.