Baldness and Risk of Prostate Cancer in the Health Professionals Follow-up Study.
The association between male pattern baldness and prostate cancer has been inconsistent. We prospectively investigated the association between baldness at age 45 and prostate cancer risk in the Health Professionals Follow-up Study (HPFS), focusing on clinical and molecular markers. Baldness was self-reported on the 1992 questionnaire using the modified Norwood-Hamilton scale prior to diagnosis. We estimated HRs between baldness and prostate cancer risk among 36,760 men, with follow-up through 2014. We also investigated whether baldness was associated with prostate cancer defined by tumor protein expression of androgen receptor and the presence of the TMPRSS2:ERG fusion. During 22 years, 5,157 prostate cancer cases were identified. Fifty-six percent of the men had either frontal or vertex baldness. No significant associations were found between baldness and prostate cancer risk. Among men younger than 60 years, there was a statistically significant association between frontal and severe vertex baldness and overall prostate cancer (HR: 1.74; 95% confidence interval: 1.23-2.48). Baldness was not significantly associated with expression of molecular subtypes defined by AR and TMPRSS2:ERG IHC of prostate tumors. This study showed no association between baldness at age 45 and prostate cancer risk, overall or for clinical or molecular markers. The association between baldness and overall prostate cancer among younger men is intriguing, but caution is warranted when interpreting this finding. The null findings from this large cohort study, together with previous literature's inconclusive findings across baldness patterns, suggest that baldness is not a consistent biomarker for prostate cancer risk or progression.


[Combination of bacteriostatic and bactericidal drugs: lack of significant in vitro antagonism between penicillin, cephalothin, and rolitetracycline].
Although it is generally believed that bactericidal and bacteriostatic drugs should not be combined in vivo, in vitro experiments using the checkerboard dilution technique revealed no antagonism between penicillin/cephalothin and rolitetracycline but rather additive or synergistic activity of either drug combination in 40 to 50% of 20 Escherichia coli, and 14 Staphylococcus aureus strains. Slight antagonism occurred only between 3 and 8 h after combining penicillin/cephalothin and rolitetracycline in either bacteriostatic or bactericidal concentrations, but not after 24 h of incubation, nor was antagonism found with combinations of these drugs in bacteriostatic concentrations. Neither bacteriostatic nor bactericidal activity of penicillin/cephalothin and rolitetracycline was inhibited by pretreatment of one E. coli strain with bacteriostatic rolitetracycline or bacteriostatic penicillin/cephalothin concentrations. Penicillin and cephalothin could exert a bactericidal effect after 2-h exposure of the E. coli strain to bacteriostatic rolitetracycline concentrations. Combined action of subinhibitory penicillin and rolitetracycline concentrations resulted in more pronounced inhibition of growth than either drug alone. The higher activity of penicillin/cephalothin in combination with rolitetracycline on some E. coli and S. aureus strains might be due to a better access of rolitetracycline into bacterial cells whose cell walls have been weakened by cell wall-active, bactericidal drugs. Thus, growth of penicillin-induced spheroplasts of E. coli and stable staphylococcal L-forms was inhibited by much lower concentrations of rolitetracycline than were the corresponding parent cells with intact cell walls.


Low SpO2 With Normal SaO2 During General Anesthesia: A Case Report.
A 25-year-old Caucasian man with a history of spherocytosis, splenectomy, recurrent blood transfusion, and no cardiopulmonary disease presented for an emergent laparoscopic cholecystectomy with a baseline pulse oximetric saturation (SpO2) of 88% while breathing room air. The SpO2 increased to only 89% during preoxygenation with an FIO2 1.0. Multiple arterial blood samples revealed SaO2 as high as 100% with PaO2 averaging 390 mm Hg. He was subsequently diagnosed with a dyshemoglobin, hemoglobin Köln. The simultaneous presentation of a stable patient from a cardiopulmonary perspective with normal arterial oxygen tension and saturation in the blood gas analyses despite a low SpO2 measurement outlines the importance of integrating the history of present illness and both the importance and the limitation of the pulse oximetry.


Early analysis of the United States Army's telemedicine orthopaedic consultation program.
Telemedicine is a recent development, designed to assist patients with limited physical access to expert subspecialty medical care. The United States Army has established a telemedicine program, consisting of e-mail consultations from deployed health care providers to subspecialty consultants. Orthopaedic surgery became a participating consultant group in July 2007. The goal of this study is to describe the Army's telemedicine orthopaedic program and to review its progress and achievements. All consults initiated from July 2007 through April 2009 were reviewed. A total of 208 consults were received by the telemedicine orthopaedic consultation program. Predominant regions of origin were Iraq, Navy Afloat, and Afghanistan. The Army accounted for the majority of consults. Prevalent musculoskeletal complaints were fracture, sprain, neuropathy, and tendon injury. Of the 74 fracture consultations, hand and wrist fractures were most common. Symptomatic treatment or casting/splinting were the most common recommended treatments for all orthopaedic consults. Of the 170 consults requesting specific treatment recommendations for patients who likely otherwise would have been evacuated for further evaluation, surgical intervention or medical evacuation was only recommended in 25% and 16% of the consultations, respectively. The novel Army telemedicine orthopaedic consultation program developed for combat-deployed service members provides expert treatment recommendations for a variety of musculoskeletal injuries. Deployed health care providers located in austere combat environments can better determine both the necessity of medical evacuation and appropriate treatments for service members with musculoskeletal injuries when aided by orthopaedic surgery consultants, thereby limiting the number of unnecessary medical evacuations.


Interactive social media interventions to promote health equity: an overview of reviews.
Social media use has been increasing in public health and health promotion because it can remove geographic and physical access barriers. However, these interventions also have the potential to increase health inequities for people who do not have access to or do not use social media. In this paper, we aim to assess the effects of interactive social media interventions on health outcomes, behaviour change and health equity. We conducted a rapid response overview of systematic reviews. We used a sensitive search strategy to identify systematic reviews and included those that focussed on interventions allowing two-way interaction such as discussion forums, social networks (e.g. Facebook and Twitter), blogging, applications linked to online communities and media sharing. Eleven systematic reviews met our inclusion criteria. Most interventions addressed by the reviews included online discussion boards or similar strategies, either as stand-alone interventions or in combination with other interventions. Seven reviews reported mixed effects on health outcomes and healthy behaviours. We did not find disaggregated analyses across characteristics associated with disadvantage, such as lower socioeconomic status or age. However, some targeted studies reported that social media interventions were effective in specific populations in terms of age, socioeconomic status, ethnicities and place of residence. Four reviews reported qualitative benefits such as satisfaction, finding information and improved social support. Social media interventions were effective in certain populations at risk for disadvantage (youth, older adults, low socioeconomic status, rural), which indicates that these interventions may be effective for promoting health equity. However, confirmation of effectiveness would require further study. Several reviews raised the issue of acceptability of social media interventions. Only four studies reported on the level of intervention use and all of these reported low use. More research on established social media platforms with existing social networks is needed, particularly in populations at risk for disadvantage, to assess effects on health outcomes and health equity.


Phenotypic trait changes in laboratory--reared colonies of the maize herbivore, Diabrotica virgifera virgifera.
The North American and European maize pest Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae) was used to assess whether conditions of the natal field, subsequent laboratory rearing, or genetic population origin affect phenotypic traits of fitness, activity, or morphometrics. Standardized laboratory bioassays with large sample sizes revealed that none of the 16 tested traits, except crawling behaviours, appeared consistently stable across all seven tested colonies. Environmental conditions in the natal field of the F 0 generation affected trait averages of the subsequently reared F 1 generation in laboratory in ca. 47% of cases, and trait variability in 67% of cases. This was apparent for fitness and morphometrics, but less obvious for activity traits. Early generation laboratory rearing affected trait averages in ca. 56% of cases: morphometrics changed; fecundity and egg survival increased from F 1 to F 2. Trait variability increased or decreased in 38% of cases. Laboratory rearing for over more than 190 generations affected the trait averages in 60% of cases, reflected by decreases in flight activity and increases in body size, weight, and fecundity to some extent. It had little effect on trait variability, especially so for morphometric variability. The genetic population origin affected average levels of 55% and variability of 63% of phenotypic traits. A comparison among D. v. virgifera studies might be difficult if they use different populations or laboratory colonies. It is advised to consider possible effects of original field conditions, laboratory rearing, and population genetics when planning comparative studies targeting fitness, activity, or morphometric questions regarding Diabrotica species.


Structure-based Design of Pyridone-Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition.
Dysregulated translation of mRNA plays a major role in tumorigenesis. Mitogen-activated protein kinase interacting kinases (MNK)1/2 are key regulators of mRNA translation integrating signals from oncogenic and immune signaling pathways through phosphorylation of eIF4E and other mRNA binding proteins. Modulation of these key effector proteins regulates mRNA, which controls tumor/stromal cell signaling. Compound 23 (eFT508), an exquisitely selective, potent dual MNK1/2 inhibitor, was designed to assess the potential for control of oncogene signaling at the level of mRNA translation. The crystal structure-guided design leverages stereoelectronic interactions unique to MNK culminating in a novel pyridone-aminal structure described for the first time in the kinase literature. Compound 23 has potent in vivo antitumor activity in models of diffuse large cell B-cell lymphoma and solid tumors, suggesting that controlling dysregulated translation has real therapeutic potential. Compound 23 is currently being evaluated in Phase 2 clinical trials in solid tumors and lymphoma. Compound 23 is the first highly selective dual MNK inhibitor targeting dysregulated translation being assessed clinically.


Source apportionment of polychlorinated biphenyls in Chicago air from 1996 to 2007.
While the overall atmospheric polychlorinated biphenyl (PCB) levels in many urban areas are declining, it is not clear whether this decline is due to control strategies or merely due to natural attenuation. To investigate this issue, Positive Matrix Factorization (PMF) was used to identify the dominant sources of gas-phase PCBs in the atmosphere of Chicago, IL using a data set collected from 1996 to 2007 by the Integrated Atmospheric Deposition Network (IADN). Both the older PMF2 software and the newer EPA-sponsored PMF 3.0 software were employed. Both models resolved 5 factors, but they yielded somewhat different results in terms of the congener patterns of the factors and their temporal variation. The PMF2 software resolved factors that better resembled the original Aroclor formulations. While it is possible to apply an exponential decay model to this data set and derive statistically significant rate constants that indicate that ΣPCBs and some of the resolved factors are declining in Chicago air, examining plots of the 365-day moving average concentrations shows that they do not decrease in a fashion consistent with exponential decay. Instead, they display periods of decline as well as periods of increase. Thus an exponential decay model is not appropriate, and long-term time trends identified from this 12-year data set cannot be used to predict the future trends in PCB concentrations in the air of Chicago. Two of the five resolved factors resemble low MW Aroclors, and declined from 1996 to 2007. The other three factors, which represent the majority of the mass in the data set, are either not declining or actually increasing over time. Thus past efforts to eliminate PCBs from the Great Lakes ecosystem have been only marginally effective, if at all. Additional effort is needed to identify and eliminate atmospheric PCB sources in Chicago.


Comparison of mitostatic effect, cell uptake and tubulin-binding activity on colchicine and colcemid.
Mitostatic action, cellular uptake and the binding of colchicine and colcemid to tubulin were compared. It was shown that mitostatic action of low doses of colchicine developed only after 24 h incubation of the drug with mouse L fibroblasts, while the colcemid-induced block of mitosis was evident after 2 h incubation. The initial rate of uptake was about 10 times greater for colcemid than for colchicine. Cellular uptake of the drugs reached an equilibrium after 2 and 15-18 h incubation for colcemid and colchicine, respectively, and the plateau values were identical. The kinetics of colchicine and colcemid binding to bovine brain tubulin was studied by the DEAE-filter binding assay. Colcemid binds to tubulin much faster than does colchicine. The rate of colcemid efflux from L cells is much higher than that of colchicine. According to the efflux data, colcemid dissociates readily from a complex with tubulin (t1/2 = 10 min), while the colchicine-tubulin complex is stable for at least 1 h. These results are consistent with previously published data (Frankel, F.R. (1976) Proc. Natl. Acad. Sci. U.S.A. 72, 2798-2802), which showed that colcemid action on cells is more reversible than that of colchicine. We suggest that differences between colchicine and colcemid in the rate of mitostatic action and its reversibility are determined by the differences in parameters of tubulin binding.


The tunica propria in rhinoscleroma. An electron microscopic study.
The ultrastructure in 15 cases of scleroma was studied. The vacuoles of the Mikulicz cells had a definite limiting membrane containing two types of granular material, "A" considered to be antibody, and "B" considered antigenic. Inside the vacuoles infrequent beaded filamentous crystalloid structures were seen, probably of a proteinaceous nature. An enzymatic etiology causing disruption of the limiting vacuolar membrane was considered. New ultrastructural characteristics of the 'early' Mikulicz cell are described. The capillaries occasionally showed subendothelial amyloid deposition. The seromucinous glands were infrequent but of normal character.


Plasma nociceptin levels are reduced in migraine without aura.
It was demonstrated that both nociceptin, a novel opioid neuropeptide, and its receptor are present in trigeminovascular neurons. In an animal model nociceptin dose-dependently inhibited neurogenic dural vasodilatation. These results suggest that nociceptin may be involved in neurovascular headaches such as migraine. To test this hypothesis, we studied circulating nociceptin levels in 18 patients suffering from migraine without aura and in 24 controls. Headache-free migraineurs had significantly lower nociceptin levels than controls (5.79 +/- 1.82 vs. 9.74 +/- 2.43 pg/ml, P < 0.0001, Student's t-tests). Nociceptin levels were further reduced in six patients studied in the first 3 h of typical migraine attacks (1.04 +/- 0.17 pg/ml). Nociceptin levels correlated with the frequency of attacks in this group of migraineurs. Lower interictal nociceptin levels may contribute to a defective regulation of trigeminovascular neurons in migraineurs which might be important in the pain process of migraine.


Subcortical and cortical brain activity during the feeling of self-generated emotions.
In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organism's continuously changing internal state.


Bullous pemphigoid in younger adults: three case reports.
Bullous pemphigoid is an autoimmune subepidermal bullous dermatosis more commonly observed in the elderly (over 70 years old). Autoantibodies are produced for specific antigens of the epidermal basement membrane zone: BP 180 and BP 230 (hemidesmosome proteins). We report three cases of bullous pemphigoid in adults younger than 50 years old, discussing the clinical characteristics of the disease in younger patients.


Dehalogenation of α-hexachlorocyclohexane by iron sulfide nanoparticles: Study of reaction mechanism with stable carbon isotopes and pH variations.
The biodegradation of hexachlorocyclohexanes (HCHs) is known to be accompanied by isotope fractionation of carbon (13C/12C), but no systematic studies were performed on abiotic degradation of HCH isomers by iron (II) minerals. In this study, we explored the carbon isotope fractionation of α-HCH during dechlorination by FeS nanoparticles at different pH values. The results of three different experiments showed that the apparent rate constants during dehalogenation of α-HCH by FeS increased with pH. The lowest apparent rate constant value α-HCH during dehalogenation by FeS was 0.009 d-1 at pH value of 2.4, while the highest was 1.098 d-1 at pH 11.8. α-HCH was completely dechlorinated by FeS only at pH values 9.9 and 11.8, while the corresponding apparent rate constants were 0.253 d-1 and 1.098 d-1, respectively. Regardless of the pH used, the 1,2,4-trichlorobenzene (1,2,4-TCB), 1,2-dichlorobenzene (1,2-DCB), and benzene were the dominant degradation products of α-HCH. An enrichment factor (εC) of -4.7 ± 1.3‰ was obtained for α-HCH using Rayleigh model, which is equivalent to an apparent kinetic isotope effect (AKIEC) value of 1.029 ± 0.008 for dehydrohalogenation, and of 1.014 ± 0.004 for dihaloelimination, respectively. The magnitude of isotope fractionation from this study suggests that abiotic isotope fractionation by FeS must be taken into account in anoxic sediments and aquifers contaminated with HCH isomers, when high concentrations of FeS are present in the above-mentioned anoxic environments.


Cardiac and haemodynamic influence on carotid artery longitudinal wall motion.
What is the central question of this study? Carotid artery longitudinal wall motion (CALM) is a bidirectional forward and backward motion of the arterial wall; however, there is no evidence in humans for what controls CALM despite proposals for pulse pressure, left ventricular motion and shear rate. What is the main finding and its importance? Carotid artery longitudinal wall motion responses were heterogeneous when manipulating sympathetic activation and endothelium-independent vasodilatation, leading to non-significant group responses. However, individual CALM responses were associated with left ventricular rotation and shear rate. These findings are important when interpreting changes in CALM in humans with acute or chronic experimental designs. Carotid artery longitudinal wall motion (CALM) has recently attracted interest as an indicator of arterial health; however, the regulation of CALM is poorly understood. We conducted a series of studies aimed at manipulating pulse pressure (PP), left ventricular (LV) motion and carotid shear rate, which have been previously suggested to regulate various components of CALM pattern and magnitude. To determine the regulatory influences on CALM, 15 healthy men (22 ± 2 years old) were exposed to three acute interventions: the serial subtraction test (SST); the cold pressor test (CPT); and exposure to sublingual nitroglycerine (NTG). The SST elicited increases in PP (P < 0.01), apical LV rotation (P < 0.01) and carotid shear rate (P < 0.01), with no changes in CALM (P > 0.05). Likewise, the CPT elicited increases in PP (P = 0.01), basal LV rotation (P = 0.04) and carotid shear rate (P = 0.01), with no changes in CALM (P > 0.05). Conversely, exposure to NTG elicited no change in PP (P = 0.22), basal (P = 0.65) or apical LV rotation (P = 0.45), but did decrease carotid shear rate (P < 0.01), without altering CALM (P > 0.05). Considerable individual variability in CALM responses prompted further analyses where all three interventions were pooled for change scores. Changes in LV basal rotation were related to changes in systolic retrograde CALM (B = -0.025, P = 0.03), whereas changes in carotid shear rate were related to changes in diastolic CALM displacement (B = 0.0009, P = 0.01). The interventions were underpinned by relationships between CALM and both LV basal rotation and local shear rate at the individual level, indicating that cardiac and haemodynamic factors may influence CALM in humans.


Problematic Internet use and physical health.
Background and aims A considerable body of literature has emerged over the past two decades assessing the relationship between problematic or addictive use of the Internet and various indices of psychological well-being. Conversely, comparatively little research has assessed the relationship between problematic or addictive use of the Internet and one's physical health. Method The current study assesses this relationship using a sample of college students (N = 133) who responded online to two questionnaires: the Problematic Internet Use Questionnaire (PIUQ; Demetrovics, Szeredi&Rózsa, 2008) and the SF-36v2 Health Survey (Ware et al., 2008). Results The findings indicate that problematic Internet use is associated with poorer physical health. These results are consistent with other data that assessed the relationship between these two variables. Furthermore, this relationship supersedes the influence of the number of hours spent online per day. Conclusions The findings are discussed in terms of the limitations of the study design and conclusions that can be drawn from this preliminary empirical effort.


Transmit beamforming for optimal second-harmonic generation.
A simulation study of transmit ultrasound beams from several transducer configurations is conducted to compare second-harmonic imaging at 3.5 MHz and 11 MHz. Second- harmonic generation and the ability to suppress near field echoes are compared. Each transducer configuration is defined by a chosen f-number and focal depth, and the transmit pressure is estimated to not exceed a mechanical index of 1.2. The medium resembles homogeneous muscle tissue with nonlinear elasticity and power-law attenuation. To improve computational efficiency, the KZK equation is utilized, and all transducers are circular-symmetric. Previous literature shows that second-harmonic generation is proportional to the square of the transmit pressure, and that transducer configurations with different transmit frequencies, but equal aperture and focal depth in terms of wavelengths, generate identical second-harmonic fields in terms of shape. Results verify this for a medium with attenuation f1. For attenuation f1.1, deviations are found, and the high frequency subsequently performs worse than the low frequency. The results suggest that high frequencies are less able to suppress near-field echoes in the presence of a heterogeneous body wall than low frequencies.


The effect of variability in the powder/liquid ratio on the strength of zinc phosphate cement.
Aim. To investigate (a) variability in powder/liquid proportioning and (b) effect of variability on diametral tensile strength (DTS), in a zinc phosphate cement. Statistical analyses (α = 0.05) were by Student's t-test in the case of powder/liquid ratio and one-way ANOVA and Tukey HSD for pair-wise comparisons of mean DTS. The Null hypotheses were that (a) the powder-liquid mixing ratios would not differ from the manufacturer's recommended ratio (b) DTS of the set cement samples using the extreme powder/liquid ratios would not differ from those made using the recommended ratio. Methodology. 34 dental students dispensed the components according to the manufacturer's instructions. The maximum and minimum powder/liquid ratios, together with the manufacturer's recommended ratio, were used to prepare samples for DTS testing. Results. Powder/liquid ratios ranged from 2.386 to 1.018. The mean ratio (1.644) was not significantly different from the recommended value of 1.718 (P = 0.189). DTS values for the maximum and minimum ratios were both significantly different from each other (P < 0.001) and from the mean value obtained from the recommended ratio (P < 0.001). Conclusions. Variability exists in powder/liquid ratio for hand dispensed zinc phosphate cement. This variability can affect the DTS of the set material.


Physicochemical composition, phytochemical analysis and biological activity of ciricote (Cordia dodecandra A. D.C.) fruit from Yucatán.
The physicochemical properties, proximate composition, minerals, total polyphenols, carotenoids, phenolic compounds, antioxidant, and antibacterial activities of ciricote (Cordia dodecandra A. DC.) tropical fruit were investigated. Minerals were quantified by using micro-Energy Dispersive X-Ray Fluorescence. Lutein and β-carotene were identified in ciricote fruit by using UPLC-PDA analysis. The highest values of the total polyphenols content and antioxidant activity were presented in ethanolic crude extracts obtaining by the ultrasonic-assisted method with freeze-dried fruit. The phenolic acids profile was identified and quantified by UPLC-PDA-ESI-MS. The main phenolic acids were caffeoyl hexoside, rufescenolide, quercetin 3-O-rutinoside, and rosmarinic acid. The ciricote extracts presented antibacterial activity against Staphylococus aureus (Gram+) and Salmonella typhymurium (Gram-). In conclusion, the ciricote (Cordia dodecandra A. DC.) tropical fruits could be very useful source of biological macromolecules, micro-elements, and phytochemical compounds for the food and pharmaceutical industry.


Genotypic variation and antifungal susceptibilities of Candida pelliculosa clinical isolates.
At the Istituto Ricovero Cura Carattere Scientifico, Ospedale Maggiore di Milano, Italy, Candida pelliculosa accounted for 3.3 and 4.4 % of all Candida species other than Candida albicans collected during 1996 and 1998, respectively. Genetic variability was investigated by electrophoretic karyotyping and inter-repeat PCR, and the susceptibility to five antifungal agents of 46 strains isolated from 37 patients during these 2 years was determined. Combination of the two typing methods yielded 14 different DNA types. Although the majority of DNA types were randomly distributed among different units, one DNA type was significantly more common in patients hospitalized in a given unit compared with those from other wards (P=0.034), whereas another DNA type was more frequently isolated in patients hospitalized during 1996 than in those hospitalized during 1998 (P=0.002). Fluconazole, itraconazole and posaconazole MIC90 values were 16, 1 and 4 microg ml-1, respectively. All isolates but three were susceptible in vitro to flucytosine. All isolates were susceptible in vitro to amphotericin B. These data suggest that there are possible relationships among strains of C. pelliculosa, wards and time of isolation. Amphotericin B seems to be the optimal drug therapy in infections due to this yeast species.


Structure of a thiolate-bridged polymeric copper(I) compound, catena-(2,9-dimethyl-1,10-phenanthroline)-mu-(thiophenolato)-copper(I).
[Cu(C6H5S)(C14H12N2)], Mr = 380.97, monoclinic, P2(1), a = 10.047 (1), b = 15.797 (2), c = 10.581 (1) A, beta = 90.78 (1) degrees, V = 1679.2 A3, Z = 4, Dm (CCl4/C5H12) = 1.50, D chi = 1.51 g cm-3, lambda(Mo K alpha) = 0.7107 A, mu = 14.2 cm-1, F(000) = 784, T = 293 (1) K, R = 0.026, wR = 0.026 for 2709 observed reflections. The title compound, [Cu(Me2-phen)(C6H5S)]n, exists as chains of [Cu(Me1phen)]+ units linked by thiophenolate S atoms. Large bridging angles at thiolate S atoms [Cu(1)--S--Cu(2)(av.) = 134 (1) degrees] preclude any Cu--Cu bonding [Cu ... Cu = 4.246 (1), 4.284 (1) A] along the chain. The CuI atoms exhibit highly distorted tetrahedral coordination, with the largest deviations from tetrahedral stereochemistry involving the N--Cu--N and S--Cu--S angles [N--Cu--N(av.) = 78.0(2), S--Cu--S(av.) = 126 (3) degrees].


Altered white matter microstructure is related to cognition in adults with congenital heart disease.
Adults with congenital heart disease are at risk for persisting executive function deficits, which are known to affect academic achievement and quality of life. Alterations in white -matter microstructure are associated with cognitive impairments in adolescents with congenital heart disease. This study aimed to identify microstructural alterations potentially associated with executive function deficits in adults with congenital heart disease. Diffusion tensor imaging and tract-based spatial statistics were conducted in 45 patients (18 females) and 54 healthy controls (26 females) aged 18-32 years. Fractional anisotropy of white matter diffusion was compared between groups and correlated with an executive function score, derived from an extensive neuropsychological test battery. Patients showed widespread bilateral reduction in fractional anisotropy (P < 0.05, multiple comparison corrected) compared to controls. Lower fractional anisotropy was driven by patients with moderate and severe defect complexity (compared to controls: P < 0.001). Executive function scores were lower in patients (P < 0.05) and associated with lower fractional anisotropy in the left superior corona radiata and the corticospinal tract (corrected P < 0.05). Our findings confirm alterations of white matter microstructure in adults with congenital heart disease, mainly in those patients of moderate to severe complexity. These alterations are associated with impairments in executive functioning. A better understanding of the neurocognitive deficits may help counselling and care of patients with congenital heart disease across their lifespan and have the potential to improve their outcome and quality of life.


Inhibition of zymosan activation of human neutrophil oxidative metabolism by a mouse monoclonal antibody.
We have studied a neutrophil-specific murine monoclonal antibody, PMN7C3 (IgG3), which specifically alters PMN oxidative metabolism stimulated by serum-opsonized zymosan (STZ) or Candida albicans (STC). Polymorphonuclear cells (PMNs) exposed to PMN7C3 show a significant depression in O2- release (52.8% +/- 2.5% of control), H2O2 release (44.4% +/- 6.0% of control), and O2 consumption (73.9% +/- 2.6% of control) in response to STZ. O2 release in response to phorbol myristate acetate (PMA) was modestly reduced (78.4% +/- 3.7%) by PMN7C3 treatment, but not to the extent seen with STZ or STC. PMN7C3 did not affect O2 release by PMNs stimulated by zymosan opsonized with IgG or by S. aureus, A 23187, or FMLP. PMN7C3 was not cytotoxic, did not trigger oxidative metabolism when used as a stimulus, did not alter STZ-induced degranulation, and did not interfere with binding or uptake of STZ by PMNs. Exposure of PMNs to PMN7C3 decreased PMN rosette formation with erythrocytes coated with C3b (54% of control) or C3bi (63% of control), but had no affect on rosette formation with IgG-coated erythrocytes. PMN7C3 does not bind to monocytes and had no affect on rosette formation by this cell type. Binding of antibody PMN7C3 to the neutrophil surface inhibits the oxidative response to opsonized STZ or STC, possibly in part by altering the function or expression of C3b and C3bi receptors. Monoclonal antibodies such as PMN7C3 provide highly specific probes that may be used to define the molecular features of the stimulus-coupled response of PMN activation.


Automatic target selection for structural genomics on eukaryotes.
A central goal of structural genomics is to experimentally determine representative structures for all protein families. At least 14 structural genomics pilot projects are currently investigating the feasibility of high-throughput structure determination; the National Institutes of Health funded nine of these in the United States. Initiatives differ in the particular subset of "all families" on which they focus. At the NorthEast Structural Genomics consortium (NESG), we target eukaryotic protein domain families. The automatic target selection procedure has three aims: 1) identify all protein domain families from currently five entirely sequenced eukaryotic target organisms based on their sequence homology, 2) discard those families that can be modeled on the basis of structural information already present in the PDB, and 3) target representatives of the remaining families for structure determination. To guarantee that all members of one family share a common foldlike region, we had to begin by dissecting proteins into structural domain-like regions before clustering. Our hierarchical approach, CHOP, utilizing homology to PrISM, Pfam-A, and SWISS-PROT chopped the 103,796 eukaryotic proteins/ORFs into 247,222 fragments. Of these fragments, 122,999 appeared suitable targets that were grouped into >27,000 singletons and >18,000 multifragment clusters. Thus, our results suggested that it might be necessary to determine >40,000 structures to minimally cover the subset of five eukaryotic proteomes.


Characterization of the oxidation of amine metabolites of nitrotoluenes by rat hepatic microsomes. N- and C-hydroxylation.
The rat hepatic microsomal oxidation of amine metabolites of mono-and dinitrotoluene isomers has been investigated. Microsomes catalyzed the NADPH-dependent oxidation of 2-amino-6-nitrobenzyl alcohol, 2-amino-4-nitrobenzyl alcohol, and the isomeric aminobenzyl alcohols to ethyl acetate-extractable compounds capable of reducing ferric iron. The microsomal metabolism of 2-amino-6-nitrobenzyl alcohol, a metabolite of the hepatocarcinogen 2,6-dinitrotoluene, was characterized in detail. High pressure liquid chromatographic analysis indicated the formation of two metabolites, both of which were reducing agents. One metabolite was identified as 2-hydroxylamino-6-nitrobenzyl alcohol by comparison of its chromatographic properties and mass spectrum with those of the authentic compound. Mass spectral, proton NMR, and UV-visible spectroscopic studies suggested that the other metabolite was 2-amino-5-hydroxy-6-nitrobenzyl alcohol. The microsomal oxidation of 2-aminobenzyl alcohol also resulted in the formation of two reducing agents, one of which was the corresponding hydroxylamine. The formation of 2-hydroxylamino-6-nitrobenzyl alcohol from the microsomal oxidation of 2-amino-6-nitrobenzyl alcohol was linear with respect to time for at least 20 min, while aminophenol formation was only linear for 3 min. The rate of the microsomal oxidation of 2-amino-6-nitrobenzyl alcohol was decreased by known inhibitors of cytochrome P-450, while heat inactivation of microsomal flavin-containing monooxygenase had no effect. The rate of formation of both metabolites was increased 1.5-fold by phenobarbital pretreatment. Pretreatment with beta-naphthoflavone had no effect on the rate of N-hydroxylation, while a small but statistically significant increase in the rate of C-hydroxylation (117% of control) was observed. The rate of oxidation of 2-amino-6-nitrobenzyl alcohol was lower with microsomes from female rats than with those from males, yielding male/female ratios of 1.34 for aminophenol formation and 3.26 for hydroxylamine formation. These data indicate that 2-amino-6-nitrobenzyl alcohol, a metabolite of the hepatocarcinogen 2,6-dinitrotoluene, can be N-hydroxylated by hepatic microsomal cytochrome P-450. The results are consistent with the hypothesis that a hydroxylamine metabolite of 2,6-dinitrotoluene is sulfated in vivo to produce an electrophilic species.


Transfected Eimeria tenella could complete its endogenous development in vitro.
Live attenuated coccidiosis vaccines could be used as powerful carriers, expressing exogenous viral and bacterial antigens, to induce protective immunity against pathogenic organisms. We investigated the ability of Eimeria tenella to express an exogenous gene in vitro. Eimeria tenella sporozoites were transfected with the plasmid pH4-2EYFP-Actin3 containing the yellow fluorescent protein gene (yfp) and inoculated into primary chicken kidney cells (PCKCs), followed by incubation at 41 C in a 5% CO2 chamber. Fluorescent sporozoites were observed as early as 15-20 hr post-inoculation (PI). Fluorescence displayed by the expressed YFP protein was visible throughout the schizogony and gametogony stages of the tranfected E. tenella. Fluorescent oocysts were found between 200-327 hr PI. Higher fluorescence intensity was observed in the nucleus than in other compartments of the transfectants, while little or no fluorescence was seen in the refractile globule. The diversity of schizonts, particularly of the first generation, was presented by fluorescent nuclei arranged in different patterns. Our results demonstrated the ability of E. tenella to express an exogenous gene throughout the endogenous development in vitro. Completion of the endogenous development of transfected E. tenella in cell cultures will facilitate the study of foreign antigen expression in Eimeria spp., paving the way for the development of an Eimeria spp. vector vaccine that also carries and delivers other vaccines by oral administration.


Glomerular hemodynamics in moderate Goldblatt hypertension in the rat.
Glomerular hemodynamics were studied by micropuncture technique in the unclipped kidney in rats in which modest two kidney Goldblatt hypertension was maintained for 4 weeks and in normotensive controls. Both groups ingested less than 2 mEq Na+/day. In hypertensive rats at micropuncture, mean hydrostatic pressure was elevated both systematically (128 +/- 5 vs 113 +/- 3 mm Hg, p less than 0.05) and within glomerular capillaries (55 +/- 2 vs 48 +/- 1 mm Hg, p less than 0.05), resulting in an increase in the transglomerular hydrostatic pressure gradient (40 +/- 2 vs 33 +/- 1 mm Hg, p less than 0.05). The glomerular capillary permeability coefficient, however, was decreased in the hypertensive rats (0.063 +/- 0.017 vs 0.115 +/- 0.011 nl/s/g kw/mm Hg, p less than 0.05), resulting in no change in nephron filtration rate 38.9 +/- 2.3 vs 39.0 +/- 2.5 nl/min/g kw). Nephron plasma flow also remained unchanged (154 +/- 10 vs 140 +/- 7 ml/min/g kw). In separate studies in this model of hypertension, saralasin infusion demonstrated a peripheral effect of circulating angiotensin II which was increased over controls. Kidney mass and GFR were not different between clipped and unclipped kidneys. No consistent abnormalities were observed by light or electron microscopy either in glomeruli or in vessels in the unclipped kidney. This study demonstrates that glomerular hemodynamics may be altered early in the course of modest hypertension in this model without altering blood flow or filtration rate. The decrease in glomerular capillary area and/or permeability (LpA) in the hypertensive rats could be either a result of the increased effect of circulating angiotensin II or the direct effect of glomerular capillary hypertension.


Dispatches from the neighborhood watch: Using citizen science and field survey data to document color morph frequency in space and time.
Heritable color polymorphisms have a long history of study in evolutionary biology, though they are less frequently examined today than in the past. These systems, where multiple discrete, visually identifiable color phenotypes co-occur in the same population, are valuable for tracking evolutionary change and ascertaining the relative importance of different evolutionary mechanisms. Here, we use a combination of citizen science data and field surveys in the Great Lakes region of North America to identify patterns of color morph frequencies in the eastern gray squirrel (Sciurus carolinensis). Using over 68,000 individual squirrel records from both large and small spatial scales, we identify the following patterns: (a) the melanistic (black) phenotype is often localized but nonetheless widespread throughout the Great Lakes region, occurring in all states and provinces sampled. (b) In Ohio, where intensive surveys were performed, there is a weak but significantly positive association between color morph frequency and geographic proximity of populations. Nonetheless, even nearby populations often had radically different frequencies of the melanistic morph, which ranged from 0% to 96%. These patterns were mosaic rather than clinal. (c) In the Wooster, Ohio population, which had over eight years of continuous data on color morph frequency representing nearly 40,000 records, we found that the frequency of the melanistic morph increased gradually over time on some survey routes but decreased or did not change over time on others. These differences were statistically significant and occurred at very small spatial scales (on the order of hundreds of meters). Together, these patterns are suggestive of genetic drift as an important mechanism of evolutionary change in this system. We argue that studies of color polymorphism are still quite valuable in advancing our understanding of fundamental evolutionary processes, especially when coupled with the growing availability of data from citizen science efforts.


Functionalization of transition metal dichalcogenides with metallic nanoparticles: implications for doping and gas-sensing.
Transition metal dichalcogenides (TMDs), belonging to the class of two-dimensional (2D) layered materials, have instigated a lot of interest in diverse application fields due to their unique electrical, mechanical, magnetic, and optical properties. Tuning the electrical properties of TMDs through charge transfer or doping is necessary for various optoelectronic applications. This paper presents the experimental investigation of the doping effect on TMDs, mainly focusing on molybdenum disulfide (MoS2), by metallic nanoparticles (NPs), exploring noble metals such as silver (Ag), palladium (Pd), and platinum (Pt) as well as the low workfunction metals such as scandium (Sc) and yttrium (Y) for the first time. The dependence of the doping behavior of MoS2 on the metal workfunction is demonstrated and it is shown that Pt nanoparticles can lead to as large as 137 V shift in threshold voltage of a back-gated monolayered MoS2 FET. Variation of the MoS2 FET transfer curves with the increase in the dose of NPs as well as the effect of the number of MoS2 layers on the doping characteristics are also discussed for the first time. Moreover, the doping effect on WSe2 is studied with the first demonstration of p-type doping using Pt NPs. Apart from doping, the use of metallic NP functionalized TMDs for gas sensing application is also demonstrated.


Double kissing mini-culotte versus mini-culotte stenting: insights from micro-computed tomographic imaging of bench testing.
This study aimed to evaluate the morphologic characteristics of double kissing (DK) mini-culotte and mini-culotte stenting through imaging of bench testing. DK mini-culotte and mini-culotte stenting were performed in two silicone bifurcated phantoms with branch vessel diameter differences of 0.5 mm (Model 1) and 1.25 mm (Model 2), and their morphologic characteristics were evaluated by micro-computed tomography. In Model 1, metal carina length (0.25±0.13 mm vs 0.55±0.15 mm), area stenosis of the side branch ostium (SBO) (4.65±3.24% vs 12.5±3.93%), and maximum distance of malapposed struts for the wall facing the SBO (0.27±0.08 mm vs 0.49±0.15 mm) were lower in the DK mini-culotte group than in the mini-culotte group. In Model 2, metal carina length (0.21±0.47 mm vs 0.47±0.12 mm), SBO area stenosis (5.13±3.37% vs 15.00±6.18%), and maximum distance of malapposed struts (0.32±0.13 mm vs 0.68±0.10 mm) were also lower in the DK mini-culotte group. The results of factorial analysis showed that maximum distance of malapposed struts tended to be shorter in Model 1 (F=4.226, p=0.062). Compared with mini-culotte stenting, DK mini-culotte stenting was associated with shorter metal carina length, shorter maximum distance of malapposed struts, and smaller SBO area stenosis. Thus, DK mini-culotte stenting may obtain better morphologic characteristics.


Per capita alcohol consumption and liver cirrhosis mortality in 14 European countries.
To estimate the effects of changes in per capita alcohol consumption on liver cirrhosis mortality rates in various demographic groups across 14 western European countries. Yearly changes in gender- and age-specific mortality rates from 1950 to 1995 were analysed in relation to corresponding yearly changes in per capita alcohol consumption, employing the Box-Jenkins technique for time series analysis. Country-specific estimates were pooled into three regions: northern, central and southern Europe. Cirrhosis mortality data for 5-year age groups were converted into gender-specific mortality rates in the age groups 15+, 15-44, 45-64 and 65+ and expressed as the number of deaths per 100,000 inhabitants. Alcohol sales were used to measure aggregate consumption, which were calculated into consumption (litres 100% alcohol) per year per inhabitant over 14 years of age and weighted with a 10-year distributed lag model. The country-specific analyses demonstrated a positive and statistically significant effect of changes in per capita consumption on changes in cirrhosis mortality in 13 countries for males and in nine countries for females. The strongest alcohol effect was found in northern Europe, due mainly to a large effect in Sweden. Moreover, when different age groups were analysed significant estimates were obtained in 29 of 42 cases for males and in 20 of 42 cases for females. Most of the non-significant estimates were found in older age groups. The results suggest clearly that a change in the overall level of drinking as a general rule affect cirrhosis mortality in different drinking cultures as well as among different demographic groups. Moreover, the findings correspond with what is expected from the collectivity theory of drinking cultures.


Genetic and epigenetic study of an Alzheimer's disease family with monozygotic triplets.
Age at onset of Alzheimer's disease is highly variable, and its modifiers (genetic or environmental) could act through epigenetic changes, such as DNA methylation at CpG sites. DNA methylation is also linked to ageing-the strongest Alzheimer's disease risk factor. DNA methylation age can be calculated using age-related CpGs and might reflect biological ageing. We conducted a clinical, genetic and epigenetic investigation of a unique Ashkenazi Jewish family with monozygotic triplets, two of whom developed Alzheimer's disease at ages 73 and 76, while the third at age 85 has no cognitive complaints or deficits in daily activities. One of their offspring developed Alzheimer's disease at age 50. Targeted sequencing of 80 genes associated with neurodegeneration revealed that the triplets and the affected offspring are heterozygous carriers of the risk APOE ε4 allele, as well as rare substitutions in APP (p.S198P), NOTCH3 (p.H1235L) and SORL1 (p.W1563C). In addition, we catalogued 52 possibly damaging rare variants detected by NeuroX array in affected individuals. Analysis of family members on a genome-wide DNA methylation chip revealed that the DNA methylation age of the triplets was 6-10 years younger than chronological age, while it was 9 years older in the offspring with early-onset Alzheimer's disease, suggesting accelerated ageing.


Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large, international population.
To examine the scope and underpinnings of psychological insulin resistance (PIR) across eight Western nations, with special attention to the potential influence of beliefs about insulin and broader patient beliefs regarding medications and diabetes. A total of 1400 subjects with insulin-naïve, type 2 diabetes across eight nations completed an online survey. The survey assessed willingness to start insulin, beliefs about insulin and current medications, and diabetes-related emotional distress. The majority of respondents were male (59.3%), mean age was 51.6 years and mean diabetes duration was 6.1 years. A total of 17.2% reported they would be unwilling to start insulin (the PIR group), while 34.7% were ambivalent and 48.1% indicated they would be willing to do so. Marked differences by country were apparent, with PIR ranging from 5.9% (Spain) to 37.3% (Italy). Both unwilling and ambivalent patients reported significantly more negative (p < 0.001; p < 0.05) and fewer positive beliefs (p < 0.001; p < 0.01) about starting insulin, more negative feelings about their current medications (p < 0.01, p < 0.001), and more diabetes-related distress (p < 0.001; p < 0.05) than willing patients. Unwilling patients also reported significantly more negative (p < 0.05) and fewer positive beliefs (p < 0.001) about starting insulin than ambivalent patients. These are the first data demonstrating the prevalence of PIR across Western nations. PIR is strongly linked to positive and negative insulin beliefs, and may also reflect a broader discomfort with medications and with diabetes in general. Of note, however, PIR is a marker of behavioral intent only; it is not known whether this predicts actual behavior at the time when insulin is prescribed. When addressing patients who are reluctant to initiate insulin therapy, clinicians may find it valuable to inquire about their beliefs about insulin and their current medications.


Synthesis, Characterization, and Computational Studies on Gallium(III) and Iron(III) Complexes with a Pentadentate Macrocyclic bis-Phosphinate Chelator and Their Investigation As Molecular Scaffolds for 18F Binding.
With the aim of obtaining improved molecular scaffolds for 18F binding to use in PET imaging, gallium(III) and iron(III) complexes with a macrocyclic bis-phosphinate chelator have been synthesized and their properties, including their fluoride binding ability, investigated. Reaction of Bn-tacn (1-benzyl-1,4,7-triazacyclononane) with paraformaldehyde and PhP(OR)2 (R = Me or Et) in refluxing THF, followed by acid hydrolysis, yields the macrocyclic bis(phosphinic acid) derivative, H2(Bn-NODP) (1-benzyl-4,7-phenylphosphinic acid-1,4,7-triazacyclononane), which is isolated as its protonated form, H2(Bn-NODP)·2HCl·4H2O, at low pH (HClaq), its disodium salt, Na2(Bn-NODP)·5H2O at pH 12 (NaOHaq), or the neutral H2(Bn-NODP) under mildly basic conditions (Et3N). A crystal structure of H2(Bn-NODP)·2HCl·H2O confirmed the ligand's identity. The mononuclear [GaCl(Bn-NODP)] complex was prepared by treatment of either the HCl or sodium salt with Ga(NO3)3·9H2O or GaCl3, while treatment of H2(Bn-NODP)·2HCl·4H2O with FeCl3 in aqueous HCl gives [FeCl(Bn-NODP)]. The addition of 1 mol. equiv of aqueous KF to these chloro complexes readily forms the [MF(Bn-NODP)] analogues. Spectroscopic analysis on these complexes confirms pentadentate coordination of the doubly deprotonated (bis-phosphinate) macrocycle via its N3O2 donor set, with the halide ligand completing a distorted octahedral geometry; this is further confirmed through a crystal structure analysis on [GaF(Bn-NODP)]·4H2O. The complex adopts the geometric isomer in which the phosphinate arms are coordinated unsymmetrically (isomer 1) and with the stereochemistry of the three N atoms of the tacn ring in the RRS configuration, denoted (N)RRS, and the phosphinate groups in the RR stereochemistry, denoted (P)RR, (isomer 1/RR), together with its (N)SSR (P)SS enantiomer. The greater thermodynamic stability of isomer 1/RR over the other possible isomers is also indicated by density functional theory (DFT) calculations. Radiofluorination experiments on the [MCl(Bn-NODP)] complexes in partially aqueous MeCN/NaOAcaq (Ga) or EtOH (Ga or Fe; i.e. without buffer) with 18F- target water at 80 °C/10 min lead to high radiochemical incorporation (radiochemical yields 60-80% at 1 mg/mL, or ∼1.5 μM, concentration of the precursor). While the [Fe18F(n-NODP)] is unstable (loss of 18F-) in both H2O/EtOH and PBS/EtOH (PBS = phosphate buffered saline), the [Ga18F(Bn-NODP)] radioproduct shows excellent stability, RCP = 99% at t = 4 h (RCP = radiochemical purity) when formulated in 90%:10% H2O/EtOH and ca. 95% RCP over 4 h when formulated in 90%:10% PBS/EtOH. This indicates that the new "GaIII(Bn-NODP)" moiety is a considerably superior fluoride binding scaffold than the previously reported [Ga18F(Bn-NODA)] (Bn-NODA = 1-benzyl-4,7-dicarboxylate-1,4,7-triazacyclononane), which undergoes rapid and complete hydrolysis in PBS/EtOH (refer to Chem. Eur. J. 2015, 21, 4688-4694).


Quantification of functional abilities in Rett syndrome: a comparison between stages III and IV.
We aimed to evaluate the functional abilities of persons with Rett syndrome (RTT) in stages III and IV. The group consisted of 60 females who had been diagnosed with RTT: 38 in stage III, mean age (years) of 9.14, with a standard deviation of 5.84 (minimum 2.2/maximum 26.4); and 22 in stage IV, mean age of 12.45, with a standard deviation of 6.17 (minimum 5.3/maximum 26.9). The evaluation was made using the Pediatric Evaluation of Disability Inventory, which has 197 items in the areas of self-care, mobility, and social function. The results showed that in the area of self-care, stage III and stage IV RTT persons had a level of 24.12 and 18.36 (P=0.002), respectively. In the area of mobility, stage III had 37.22 and stage IV had 14.64 (P<0.001), while in the area of social function, stage III had 17.72 and stage IV had 12.14 (P=0.016). In conclusion, although persons with stage III RTT have better functional abilities when compared with stage IV, the areas of mobility, self-care, and social function are quite affected, which shows a great functional dependency and need for help in basic activities of daily life.


Home care and the ADA: do limitations on coverage violate the law?
To avoid liability, home care agencies must have a firm grasp of the basic requirements of the Americans with Disabilities Act (ADA) and Section 504 of the Rehabilitation Act of 1973 ("Section 504"). Agency leaders must understand the legal issues that arise whenever care is limited or denied to persons with disabilities.


Involvement of wiskott-aldrich syndrome protein in B-cell cytoplasmic tyrosine kinase pathway.
Bruton's tyrosine kinase (Btk) has been shown to play a role in normal B-lymphocyte development. Defective expression of Btk leads to human and murine immunodeficiencies. However, the exact role of Btk in the cytoplasmic signal transduction in B cells is still unclear. This study represents a search for the substrate for Btk in vivo. We identified one of the major phosphoproteins associated with Btk in the preB cell line NALM6 as the Wiskott-Aldrich syndrome protein (WASP), the gene product responsible for Wiskott-Aldrich syndrome, which is another hereditary immunodeficiency with distinct abnormalities in hematopoietic cells. We demonstrated that WASP was transiently tyrosine-phosphorylated after B-cell antigen receptor cross-linking on B cells, suggesting that WASP is located downstream of cytoplasmic tyrosine kinases. An in vivo reconstitution system demonstrated that WASP is physically associated with Btk and can serve as the substrate for Btk. A protein binding assay suggested that the tyrosine-phosphorylation of WASP alters the association between WASP and a cellular protein. Furthermore, identification of the phosphorylation site of WASP in reconstituted cells allowed us to evaluate the catalytic specificity of Btk, the exact nature of which is still unknown.


New treatment of acute hypoxemic respiratory failure: noninvasive pressure support ventilation delivered by helmet--a pilot controlled trial.
To assess the efficacy of noninvasive pressure support ventilation (NPSV) using a new special helmet as first-line intervention to treat patients with hypoxemic acute respiratory failure (ARF), in comparison to NPSV using standard facial mask. Prospective clinical pilot investigation with matched control group in three intensive care units of university hospitals. Thirty-three consecutive patients without chronic obstructive pulmonary disease and with hypoxemic ARF (defined as severe dyspnea at rest, respiratory rate >30 breaths/min, PaO2:FiO2 < 200, and active contraction of the accessory muscles of respiration) were enrolled. Each patient treated with NPSV by helmet was matched with two controls with ARF treated with NPSV via a facial mask, selected by simplified acute physiologic score II, age, PaO2/FiO2, and arterial pH at admission. Primary end points were the improvement of gas exchanges, the need for endotracheal intubation, and the complications related to NPSV. The 33 patients and the 66 controls had similar characteristics at baseline. Both groups improved oxygenation after NPSV. Eight patients (24%) in the helmet group and 21 patients (32%) in the facial mask group (p = .3) failed NPSV and were intubated. No patients failed NPSV because of intolerance of the technique in the helmet group in comparison with 8 patients (38%) in the mask group (p = .047). Complications related to the technique (skin necrosis, gastric distension, and eye irritation) were fewer in the helmet group compared with the mask group (no patients vs. 14 patients (21%), p = .002). The helmet allowed the continuous application of NPSV for a longer period of time (p = .05). Length of stay in the intensive care unit, intensive care, and hospital mortality were not different. NPSV by helmet successfully treated hypoxemic ARF, with better tolerance and fewer complications than facial mask NPSV.


Enhancing docosahexaenoic acid production in Aurantiochytrium species using atmospheric and room temperature plasma mutagenesis and comprehensive multi-omics analysis.
Aurantiochytrium sp. belongs to marine heterotrophic single-cell protist, which is an important decomposer in marine ecosystem. Aurantiochytrium sp. has gained notoriety because of its ability to accumulate high-value docosahexaenoic acid (DHA), but the key factors of DHA synthesis were unclear at present. In this study, Atmospheric and Room Temperature Plasma technology was applied to the mutagenic breeding of Aurantiochytrium sp., and transcriptomics and proteomics were adopted to analyze the DHA-biosynthesis mechanism. According to the growth and DHA accumulation profiles, the mutant strain Aurantiochytrium sp. R2A35 was selected. The DHA content in total lipids was greatly improved from 49.39 % of the wild strain R2 to 63.69 % of the mutant strain. Moreover, the DHA content in the biomass of Aurantiochytrium sp. R2A35 as 39.72 % was the highest DHA productivity reported so far. The differentially expressed genes distinguished from transcriptome and the TMT-identified differential proteins distinguished from proteome confirmed that the expression of acetyl-CoA carboxylase and ketoacyl reductase was up-regulated by 4.78-fold and 6.95-fold, respectively and the fatty acid synthase was concurrently down-regulated by 2.79-fold, so that more precursor was transported to the polyketide synthase pathway, thereby increasing the DHA yield in Aurantiochytrium sp. R2A35. This research would provide reference for the DHA metabolism process and contribute to the understanding of the decomposer - Aurantiochytrium sp. in marine ecosystems.


Bone modeling patterns and morphometric craniofacial variation in individuals from two prehistoric human populations from Argentina.
Native human populations from South America display high levels of craniofacial variation encompassing gracile and robust skulls. Nevertheless, the processes of bone modeling by which morphological variation among populations were attained, remain poorly understood. Here we analyze the relationship between patterns of bone formation and resorption and morphometric variation in the upper face of adults belonging to farmers and hunter-gatherers from northwestern and south Argentina. Our analyses reveal a common pattern of bone modeling of the malar bone characterized by the presence of formation areas. Thus, the larger size and greater development of malar bone exhibited by hunter-gatherers would be linked to a greater magnitude of bone formation activity. Conversely, the glabella and the superciliary arch presented both formation and resorption areas with a variable distribution among individuals. In the extreme corresponding to more robust morphologies, the great development of the glabella is related to the presence of large formation fields, both in the upper region and toward the frontonasal suture. The less robust morphologies show resorption fields at the upper margin of the glabella, which would contribute to the weaker development of this region. The superciliary arch showed a complex relationship between its morphometric and histological variation; the individuals located at both extremes of the shape space presented large resorption areas located on its upper margin. Overall, our results show the existence of intraspecific variation in the patterns of bone modeling in the human upper face.


Caution needed in altering the 'optimum' fluoride concentration in drinking water.
The US Public Health Service has finalized its recommendation relating to community water fluoridation (Federal Panel on Community Water Fluoridation, US Department of Health and Human Services, 2015). It recommends an optimal concentration of 0.7 mg/l F based on their argument that this concentration provides the best balance of protection from dental caries while limiting the risk of dental fluorosis. The rationale for this recommendation can be questioned, particularly given the contrasting etiologies and impact on the community. Uncertainty surrounds the key evidence considered by the panel. This study argues that the panel should have exercised more caution and called for further research before reducing the 'optimal' concentration of fluoride in water supplies. Up-to-date data on caries and fluorosis trend by age group or birth cohort, analyses on attributable risk for fluorosis, data on individual and population impact of caries and fluorosis, water intake over an extended period across the seasons, and the curvilinear relationship of fluoride concentration in water supplies and caries protection would have all been desirable to inform the panel, given the foreshadowing of the recommendation in late 2011. Further, a wider range of policy directions to achieve the best balance of protection from dental caries while limiting the risk of dental fluorosis are available from the international literature. Assessment of these should have been more evident. There is a public health policy responsibility to monitor water fluoridation programs so as to achieve a near maximum reduction in dental caries without unacceptable levels of dental fluorosis. However, recommendations to alter existing policy need to be cognizant of the balancing of risk and protective exposures across the entire population and potentially all ages and to be based on recent data that are purposefully collected, critically analyzed and carefully interpreted.


Common gastroenterological problems. II.--Sliding hiatus hernia.
A sliding hiatus hernia is a common radiological finding and is not always relevant to the patient's symptoms. The possibility of an alternative explantation for the complaint of retrosternal pain or dyspepsia should always be considered, and when anaemia is present the site of occult blood loss is often lower in the gastrointestinal tract. The majority of patient's with symptomatic gastro-oesophageal reflux can be controlled with medical measures. Surgical intervention in cases of uncomplicated hiatus hernia should be recommended only after careful preoperative assessment and even then a satisfactory result cannot be absolutely guaranteed.


Antimicrobial Multidrug Resistance: Clinical Implications for Infection Management in Critically Ill Patients.
The increasing incidence of antimicrobial resistance (AMR) worldwide represents a serious threat in the management of sepsis. Due to resistance to the most common antimicrobials prescribed, multidrug-resistant (MDR) pathogens have been associated with delays in adequate antimicrobial therapy leading to significant increases in mortality, along with prolonged hospital length of stay (LOS) and increases in healthcare costs. In response to MDR infections and the delay of microbiological results, broad-spectrum antibiotics are frequently used in empirical antimicrobial therapy. This can contribute to the overuse and misuse of antibiotics, further promoting the development of resistance. Multiple measures have been suggested to combat AMR. This review will focus on describing the epidemiology and trends concerning MDR pathogens. Additionally, it will explore the crucial aspects of identifying patients susceptible to MDR infections and optimizing antimicrobial drug dosing, which are both pivotal considerations in the fight against AMR. Expert commentary: The increasing AMR in ICUs worldwide makes the empirical antibiotic therapy challenging in septic patients. An AMR surveillance program together with improvements in MDR identification based on patient risk stratification and molecular rapid diagnostic tools may further help tailoring antimicrobial therapies and avoid unnecessary broad-spectrum antibiotics. Continuous infusions of antibiotics, therapeutic drug monitoring (TDM)-based dosing regimens and combination therapy may contribute to optimizing antimicrobial therapy and limiting the emergence of resistance.


Bullous pemphigoid: serum antibody titre and antigen specificity.
2 antigens have been identified as possible targets for autoantibody depositions in bullous pemphigoid: a 230-kD protein (BP230) and a 180-kD protein (BP180). We studied the relationship of these 2 antigens with the immunofluorescence determined serum antibody titre: 2 groups of bullous pemphigoid patients were selected on the basis of immunoblot-determined antibody specificity. One group (13 patients) had antibody specificity for BP230 and not for BP180, while the other group (9 patients) had antibody specificity for BP180 and not for BP230. The immunofluorescence titres of the circulating antibodies determined on monkey oesophagus substrate displayed, for the BP230-specific group, a mean of 1:1102. The maximal observed titre was 1:5120. The mean titre in the BP180-specific group was only 1:29, with a highest titre of only 1:160. This result suggests that in routine indirect immunofluorescence of bullous pemphigoid sera, the contribution of the BP180-specific antibodies to the total anti-epidermal basement membrane zone antibody titre is relatively much lower than that of the BP230-specific antibodies. Thus, at high dilutions, only the BP230-specific antibodies contribute to the overall indirect immunfluorescence titre.


The effect of participating in the labor preparation classes on maternal vitality and positive affect during the pregnancy and after the labor.
Pregnant women predispose to physical and emotional diseases. Vitality and positive affect are against the depression and low energetic mood Exercise and physical activities in pregnancy have short and long term consequences for mothers and their growing fetus and affected in mood regulation. Respiratory and relaxation skills could decrease stress, pain and use of analgesics during labor. In this study, 117 primigravida and multigravida women (59 women in case and 58 in control groups) were enrolled. Women in case group participated in delivery preparation classes since 20 weeks of pregnancy for 8 sessions. The control group was just received routine pregnancy care. The education was about pregnancy and delivery, physical exercises and relaxation skills. Questionnaires of vitality and positive affect toward the labor were completed three times: before intervention, after the 8(th) session and after delivery to 2 weeks later by an interview. Data analyzed using SPSS16 software and repeated measurement. There was a significant difference in vitality and positive affect regarding type of delivery before and after intervention and after delivery in case group(p < 0.0001).There was no significant difference in vitality and positive affect scores after delivery and after intervention (p < 0.083, p < 0.545). There was significant difference in vitality and positive affect scores regarding between case and control groups after the intervention and after the delivery (p < 0.001, p < 0.0001). Considering the results of this study, it could be recommended that all pregnant women should contribute in delivery preparation classes to improve their mood, confidence, vitality toward labor.


Synthesis of a biotinylated heptose 1,7-bisphosphate analogue, a probe to study immunity and inflammation.
d-glycero-d-manno-Heptose-1β,7-bisphosphate (HBP) is a bacterial metabolite that can induce a TIFA-dependent innate immune response in mammals. It was recently discovered that after HBP enters into the cytoplasm of the host cell, it is transformed into ADP-heptose-7-phosphate, which then leads to ALPK1-TIFA-dependent inflammatory response. In order to provide a molecular tool allowing the discovery of the proteins involved in this novel inflammatory pathway, we designed and synthesized a biotinylated analogue of HBP. This chemical probe displays an anomeric β-phosphate and a phosphonate at the 7-position, and a d-configured 6-position to which is attached the biotin moiety. To do so, different synthetic strategies were explored and described in this report. Moreover, we demonstrated that the biotinylated version of HBP is still biologically active and can activate the NF-κB pathway in HEK293T cells.


Hyper-polyploid embryos survive after implantation in mice.
Polyploids generated by natural whole genome duplication have served as a dynamic force in vertebrate evolution. As evidence for evolution, polyploid organisms exist generally, however there have been no reports of polyploid organisms in mammals. In mice, polyploid embryos under normal culture conditions normally develop to the blastocyst stage. Nevertheless, most tetraploid embryos degenerate after implantation, indicating that whole genome duplication produces harmful effects on normal development in mice. Most previous research on polyploidy has mainly focused on tetraploid embryos. Analysis of various ploidy outcomes is important to comprehend the effects of polyploidization on embryo development. The purpose of this present study was to discover the extent of the polyploidization effect on implantation and development in post-implantation embryos. This paper describes for the first time an octaploid embryo implanted in mice despite hyper-polyploidization, and indicates that these mammalian embryos have the ability to implant, and even develop, despite the harmfulness of extreme whole genome duplication.


Staging performance of whole-body DWI, PET/CT and PET/MRI in invasive ductal carcinoma of the breast.
The aim of the present study was to evaluate the performance of whole-body diffusion-weighted imaging (WB-DWI), whole-body positron emission tomography with computed tomography (WB-PET/CT), and whole-body positron emission tomography with magnetic resonance imaging (WB-PET/MRI) in staging patients with untreated invasive ductal carcinoma of the breast. Fifty-one women with newly diagnosed invasive ductal carcinoma of the breast underwent WB-DWI, WB-PET/CT and WB-PET/MRI before treatment. A radiologist and a nuclear medicine physician reviewed in consensus the images from the three modalities and searched for occurrence, number and location of metastases. Final staging, according to each technique, was compared. Pathology and imaging follow-up were used as the reference. WB-DWI, WB-PET/CT and WB-PET/MRI correctly and concordantly staged 33/51 patients: stage IIA in 7 patients, stage IIB in 8 patients, stage IIIC in 4 patients and stage IV in 14 patients. WB-DWI, WB-PET/CT and WB-PET/MRI incorrectly and concordantly staged 1/51 patient as stage IV instead of IIIA. Discordant staging was reported in 17/51 patients. WB-PET/MRI resulted in improved staging when compared to WB-PET/CT (50 correctly staged on WB-PET/MRI vs. 38 correctly staged on WB-PET/CT; McNemar's test; p<0.01). Comparing the performance of WB-PET/MRI and WB-DWI (43 correct) did not reveal a statistically significant difference (McNemar test, p=0.14). WB-PET/MRI is more accurate in the initial staging of breast cancer than WB-DWI and WB-PET/CT, however, the discrepancies between WB-PET/MRI and WB-DWI were not statistically significant. When available, WB-PET/MRI should be considered for staging patient with invasive ductal breast carcinoma.


Biological and molecular characterization of a U.S. isolate of Hosta virus X.
Hosta virus X (HVX) is rapidly becoming a serious pathogen of commercially important hosta plants worldwide. We report here biological and molecular characterization of a U.S. isolate of HVX, HVX-37. HVX-37 infectivity was tested in 21 hosta cultivars over three growth seasons, and three types of responses were defined based upon the ability of the virus to cause local and/or systemic infections. Four cultivars resistant to systemic HVX infection were identified. The full-length sequence of the HVX-37 genome was determined, the first complete sequence of a U.S. HVX isolate. Comparison with the previously sequenced HVX-Korea (Kr) genome revealed a high level of sequence similarity, as well as some differences. Notably, a 105-nucleotide long, near-perfect direct repeat in the Kr isolate is absent in HVX-37. The accuracy of the HVX-37 genome sequence was confirmed by infectivity of in vitro transcripts synthesized from a full-length HVX-37 cDNA on Nicotiana benthamiana and hosta plants.


The influence of electrochemical cycling protocols on capacity loss in nickel-rich lithium-ion batteries.
The transition towards electric vehicles and more sustainable transportation is dependent on lithium-ion battery (LIB) performance. Ni-rich layered transition metal oxides, such as NMC811 (LiNi0.8Mn0.1Co0.1O2), are promising cathode candidates for LIBs due to their higher specific capacity and lower cost compared with lower Ni content materials. However, complex degradation mechanisms inhibit their use. In this work, tailored aging protocols are employed to decouple the effect of electrochemical stimuli on the degradation mechanisms in graphite/NMC811 full cells. Using these protocols, impedance measurements, and differential voltage analysis, the primary drivers for capacity fade and impedance rise are shown to be large state of charge changes combined with high upper cut-off voltage. Focused ion beam-scanning electron microscopy highlights that extensive microscale NMC particle cracking, caused by electrode manufacturing and calendering, is present prior to aging and not immediately detrimental to the gravimetric capacity and impedance. Scanning transmission electron microscopy electron energy loss spectroscopy reveals a correlation between impedance rise and the level of transition metal reduction at the surfaces of aged NMC811. The present study provides insight into the leading causes for LIB performance fading, and highlights the defining role played by the evolving properties of the cathode particle surface layer.


Health-related quality of life among haemodialysis patients--relationship with clinical indicators, morbidity and mortality.
To verify the association between quality of life and morbidity, mortality and clinical indicators in haemodialysis patients. While a number of therapies have been reported to increase quality of life in end-stage renal disease, patients report that they remain substantially burdened by limited physical functioning and by dialysis-related symptoms. Indeed, quality of life may be the most critical outcome for those undergoing haemodialysis. Furthermore, quality of life has been associated with clinical indicators, morbidity and survival in haemodialysis patients. Descriptive cohort study of patients undergoing haemodialysis at the Nephrology Hemodialysis Unit of the Hospital de Clínicas in Porto Alegre, Brazil. Forty haemodialysis patients were followed for 12 months and evaluated for demographics, time on dialysis, diabetes mellitus, clinical indicators (dose of dialysis--Kt/V, haematocrit and serum albumin) and comorbidities. The comorbidities were evaluated with the end-stage renal disease severity index and health-related quality of life with The Medical Outcomes Study 36 (SF-36). Men present higher health-related quality of life scores in the energy and fatigue component (P = 0.04). Patients treated for over one year at the beginning of follow up and patients with less schooling had better results in General Health Perception (P < 0.05). The health-related quality of life evaluation of patients who later died showed that they already had a worse perception of physical functioning as compared to the survivors (P = 0.05). Patients with diagnosed diabetes perceived their physical functioning more negatively compared with those with other etiologies of end-stage renal disease (P = 0.045). We found a correlation between physical functioning and serum albumin (r = 0.341, P < 0.05) and between physical functioning and haematocrit (r = 0.317, P < 0.05). The end-stage renal disease severity index was more strongly related to physical functioning (r = -0.538, P < 0.001). Comparing the patients' results to the indicators above and below the established targets, we observed a trend to worse health-related quality of life in patients with Kt/V above target. However, in the case of albumin, patients with results above target tended to have better results. A close relationship was observed between quality of life and morbidity and mortality. Among the clinical indicators, albumin and haematocrit have the greatest influence on quality of life. Haemodialysis patients experience various problems that may adversely influence their quality of life. Special care must be given to those who have diabetes mellitus, high morbidity scores, low serum albumin and low haematocrits.


Characterization of benzodiazepine and gamma-aminobutyric recognition sites and their endogenous modulators.
The solubilization and partial purification from rat brain cortex homogenates of [3H]gamma-aminobutyric acid (GABA) and [3H]diazepam recognition sites and of their endogenous modulators (GABA-modulin and an endogenous compound which specifically bound [3H]diazepam) are reported. A high percentage of GABA binding sites (virtually free of benzodiazepine binding sites) was solubilized from homogenates of rat brain cortex incubated at 0 degree C with 1% Triton X-100 and a mixture of protease inhibitors. A large proportion of benzodiazepine binding sites was solubilized in the absence of apparent GABA binding capacity by incubating crude synaptic membrane preparations at 37 degree C with 0.05% Triton X-100. The characteristics of these two solubilized binding sites resemble those of the membrane-bound binding sites. However, unlike the membrane-bound sites, solubilized GABA and benzodiazepine binding sites are insensitive to GABA stimulation, while solubilized GABA binding sites are no longer protected by the benzodiazepines against heat inactivation. These results indicate that GABA and benzodiazepine recognition sites reside in two different molecules which, when bound to membranes, can interact reciprocally and modulate their binding affinity for specific ligands.


[Interrelation of the toxicity and capacity of pertussis vaccines to alter the body immune response to heterogenetic antigens].
The influence of immunization with pertussis vaccines differing in toxicity on the intensity of the formation of antibodies to heterologous antigens (S. typhi Vi-antigen) and on the resistance of the body to natural infection (S. typhimurium) was studied in mice. The toxicity of pertussis vaccines was found to be related to their capacity for changing immune response to heterologous antigen. In mice showing pronounced toxicosis the injection of pertussis vaccine resulted in a decrease in their capacity for Vi-hemagglutinin formation. The appearance of a definite degree of resistance ot S. typhimurium was observed in mice previously immunized with pertussis vaccine possessing pronounced toxic properties. Nevertheless, the appearance of enhanced resistance to infection was observed only in the animals previously immunized with a nontoxic preparation.


Circulating endothelin-3 and prolactin concentrations in healthy lactating women during the early puerperium.
To study the association between the circulating concentrations of endothelin-3 and prolactin in the early puerperium. Prospective clinical study, including twenty-five healthy puerperal women breast-feeding their healthy full-term infants. Venous blood was drawn on day 1 and 4 post partum, and plasma endothelin-3 and serum prolactin were determined. Circulating endothelin-3 and prolactin levels on day 4 did not differ significantly from the corresponding levels on day 1. However, a significant negative correlation was found on day 4 between endothelin-3 and prolactin values (r = -0.688, P < 0.001) and an even stronger negative association existed between the net change in endothelin-3 from days 1 to 4 and the corresponding change in prolactin values (r = -0.732, P < 0.001). On the fourth day post partum, lactating healthy women show negative correlation between circulating endothelin-3 and prolactin levels. Whether this indicates a role for endothelin-3 in the control of prolactin secretion in the post partum period remains to be clarified.


Crosslinked hydrogel loaded with chitosan-supported iron oxide and silver nanoparticles as burn wound dressing.
Burns can result in infection, disability, psychosocial and economic issues. Advanced wound dressings like hydrogel absorb exudate and maintain moisture. Considering the antimicrobial properties of silver nanoparticles and iron oxide nanoparticles, the efficiency of cross-linked hydrogel loaded with chitosan-supported iron oxide and silver nanoparticles for burn wounds repair was investigated in animal model. Cellulose hydrogel dressing made from carboxymethylcellulose and hydroxyethylcellulose crosslinked with different concentrations of citric acid (10, 15, 20, and 30%) was produced. The physicochemical characteristics of the synthetized hydrogels including Fourier-Transform Infrared spectroscopy, Thermal behavior, Swelling properties, and Scanning Electron Microscope (SEM) were evaluated. The silver nanoparticles and iron nanoparticles were produced and the characteristics, cytotoxicity, antimicrobial activities and their synergistic effect were investigated. After adding nanoparticles to hydrogels, the effects of the prepared wound dressings were investigated in a 14-day animal model of burn wound. The results showed that the mixture comprising 12.5 ppm AgNps, and IONPs at a concentration ≤100 ppm was non-cytotoxic. Moreover, the formulations with 20% CA had a swelling ratio of almost 250, 340, and 500 g/g at pHs of 5, 6.2, and 7.4 after one hour, which are lower than those of formulations with 5 and 10% CA. The total mass loss (59.31%) and the exothermic degradation happened in the range of 273-335 °C and its Tm was observed at 318.52 °C for hydrogels with 20% CA. Thus, the dressing comprising 20% CA which was loaded with 12.5 ppm silver nanoparticles (AgNPs) and 100 ppm iron oxide nanoparticles (IONPs) indicated better physicochemical, microbial and non-cytotoxic characteristics, and accelerated the process of wound healing after 14 days. It was concluded that the crosslinked hydrogel loaded with 12.5 ppm AgNPs and 100 ppm IONPs possesses great wound healing activity and could be regarded as an effective topical burn wound healing treatment.


[Methods of preoperative and operative prevention of thromboembolic complications of intra-atrial thrombosis].
Methods of preoperative and operative prophylactics of thromboembolic complications in patients with mitral stenosis complicated by intraatrial thrombosis are described. In a group of patients given anticoagulants during a month as preoperative preparation there was a six times decreased amount of thromboembolic complications in the nearest postoperative period. The anticoagulant treatment is thought to be effective when applied continuously (no less than 3-4 weeks); no complications due to anticoagulant therapy were noted.


The effects of amino acids on albumin synthesis by the isolated perfused rat liver.
Albumin synthesis was measured in the isolated perfused rat liver by using the livers of both well-fed and starved rats. Starvation markedly decreased albumin synthesis. The livers from starved rats were unable to increase synthesis rates after the addition to the perfusates of single amino acids or the addition of both glucagon and tryptophan. Arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine, added together to ten times their normal peripheral blood concentrations, restored synthesis rates to normal. The plasma aminogram (i.e. the relative concentrations, of amino acids) was altered by depriving rats of protein for 48h. The use of blood from the deprived rats as perfusate, instead of normal blood, decreased albumin synthesis rates significantly by livers obtained from well-fed rats. The addition of single amino acids, including the non-metabolizable amino acid, alpha-aminoisobutyric acid, to the above mixture increased albumin synthesis rates to normal values. It is concluded that amino acids play an important role in the control of albumin synthesis and that more than one mechanism is probably involved.


68Ga-PSMA-PET: added value and future applications in comparison to the current use of choline-PET and mpMRI in the workup of prostate cancer.
Positron emission tomography (PET) has been commonly and successfully used, in combination with computed tomography (CT) and more recently magnetic resonance (MRI), in the workup of intermediate or high-risk prostate cancer (PCa). Nowadays, new specific receptor targeted PET tracers in prostate cancer imaging have been introduced; one of the most used is 68Ga-PSMA, that evaluates the expression of prostate-specific membrane antigen (PSMA). This tracer has been rapidly taken into account for its better sensitivity and specificity compared to lipid metabolism tracers, such as 11C/18F labelled fluorocholine. Besides, in the era of theranostics, this tracer is having a useful application not only for imaging but also for therapeutic purposes. The aim of this review article is, in the first part, to give an overview of the main indications and future development of 68Ga-PSMA imaging, using PET/CT or PET/MRI, according to the clinical course of the disease and in view of the current use of multiparametric MRI (mpMRI) and choline PET in the management of PCa. In the second part, a brief overview of the promising 18F-labelled PSMA tracers and the current use of PSMA radionuclide therapy will be provided.


Current practice and factors influencing the provision of periodontal healthcare in primary dental care in Scotland: an explorative study.
To understand current practice and the beliefs of dentists and hygienists towards factors which may influence the management of patients with periodontal diseases in primary dental care in Scotland. To inform the scope of a guidance publication and the future development of diagnostic analyses tools. A qualitative approach of semi-structured telephone interviews with a randomly selected sample of dentists and hygienists was used. Interviews continued until saturation was reached and were audio-recorded and transcribed verbatim. The data were analysed using the method of framework analysis. To increase the participation of hygienists the topic guide was adapted into a self-reporting questionnaire and posted to all hygienists in Scotland. Eighteen dentists and three hygienists were interviewed. Key themes identified were extent of control over working environment, capabilities to treat appropriately and changing patients' oral hygiene behaviour. Factors which facilitated the management of patients with periodontal diseases were 'access to a hygienist' and 'beliefs about capabilities', while 'routine and habit', 'motivation of patients' and 'time and money' were perceived as barriers. Some evidence of variation in treatment provision and of varying levels of confidence among practitioners about treating more advanced periodontal conditions was identified. Two hundred and thirty-seven hygienists returned the postal questionnaire. Agreement was found with the views of the interviewed hygienists on beliefs about capabilities and routine record-keeping. To improve the periodontal health of patients requires consideration of both extrinsic and intrinsic factors present in primary dental care. Practitioners would find having guidance on managing patients with basic periodontal examinations of three and four, referral criteria to secondary care, record-keeping and techniques to change patients' oral hygiene behaviour particularly useful. Applying the evaluative framework pre-publication indicated where knowledge translation interventions may be required in the future.


Clinical use of growth hormone-releasing factor for induction of superovulation.
A consistent body of in vivo and in vitro evidence suggests that insulin-like growth factor-I (IGF-I) and possibly growth hormone (GH) play a stimulatory role in the regulation of the ovarian follicular cycle. Administration of GH in protocols of induction of superovulation gave promising results. In the present study, 10 patients with a previously normal response to gonadotrophins were administered s.c. GH-releasing factor (GRF) combined with gonadotrophins for superovulation induction in an in-vitro fertilization/embryo transfer-gamete intra-Fallopian transfer (IVF/ET-GIFT) programme. Administration of GRF was followed by shortening of the stimulatory cycle and reduction of the total number of gonadotrophin ampoules utilized per patient relative to a previous stimulatory cycle with gonadotrophins alone. A significant increase of both follicular fluid IGF-I levels (compared to the previous cycle) and plasma GH levels immediately following GRF administration throughout the GRF cycle suggest that GRF supported the ovarian response to gonadotrophins through stimulation of the GH-IGF-I axis. A possible direct effect of GRF is discussed. Before employing GRF for superovulation in infertile patients, the pituitary GH response to provocative stimuli should be evaluated on an individual basis.


Analyses of transplanted murine tumors for HSV DNA sequences.
Meignier et al. (1986) report the results of exposure of C57BL/6NCr mice to vaginal plugs containing live or inactivated herpes simplex virus 1 or 2 (HSV-1 or HSV-2) or recombinant viruses 5 times a week for up to 114 weeks. Genital organs showing abnormalities were transplanted into nude mice. Of 33 transplants, 13 produced subcutaneous tumors in nude mice and 12 were subsequently transplanted into C57BL/6NCr mice. We report that the DNA extracted from coded tumor tissues of nude mice and from normal viscera of the same rodents did not hybridize with HSV-1 and HSV-2 DNA probes representing the viral genomic regions shown previously to be capable of morphologically transforming cells in culture. The sensitivity of the assays was such that we could detect 0.5 copies of the HSV sequences of complexity equal to or greater than 1 Kbp per cell DNA equivalent. To control for the sensitivity of the assays in the actual hybridizations, the tumor-cell DNA was also hybridized with a beta-globin mouse DNA probe. A striking feature of these control hybridizations was the detection of beta-globin polymorphism in some nude mouse tumors. The beta-globin polymorphism allowed us to conclude that the analyzed tissues contained significant amounts of the tumor cells occurring in the C57BL/6NCr mice.


[Communication during injections in children. Interactions between mothers-and-children and nurses' aides].
In this qualitative study, we have analysed the communication established between mother-child and the nursing auxiliary personal in situations of injection medication in children. Data were classified according to the FORREST Theoretical Model. The non participative observation method was used with field note in twelve situations. The prevalence of blocking categories was confirmed as Disapproval, Depreciation and Tranquilizing the mother with stereotyped comments. The facilitating categories show subcategories such as recognizing feelings and presence of child clarifying and orientating mother or the responsible person. Authors concluded that there was prevalence of blocking categories when verbal communication resources were not used to interact with mother and child, without establishing a relationship of friendship and confidence and making the relation ineffective.


[Treatment of patients with acute head injury in Vestfold 1987-96].
In Norway, patients with severe head injuries are transported to a regional, neurosurgical department for surgery, but some are operated on by surgeons without neurosurgical training in local hospitals. Data were retrospectively collected from the records of all patients (n = 161) hospitalised alive with a severe head injury occurring within Vestfold County (1987-96). Overall lethality was 27%. 54 patients (34%) underwent decompressive surgery. 31 patients were operated in the local hospital, by 13 different surgeons. 30 of these patients had extracerebral haematomas. These patients had a significantly worse outcome than the 23 patients operated in a regional neurosurgical department. Patients with an epidural haematoma had a better outcome than patients with an acute subdural haematoma. We retrospectively classified ten operations in the local hospital as inadequate. In Norway and countries with a similar hospital system, local hospitals should establish guidelines for safe and swift transport of head injury patients to the nearest neurosurgical department, and should not try to perform neurosurgical decompression in such patients.


Patient-specific hepatocyte-like cells derived from induced pluripotent stem cells model pazopanib-mediated hepatotoxicity.
Idiosyncratic drug-induced hepatotoxicity is a major cause of liver damage and drug pipeline failure, and is difficult to study as patient-specific features are not readily incorporated in traditional hepatotoxicity testing approaches using population pooled cell sources. Here we demonstrate the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis. In vitro cytotoxicity assays confirmed that HLCs from patients with clinically identified hepatotoxicity were more sensitive to PZ-induced toxicity than other individuals, while a prototype hepatotoxin acetaminophen was similarly toxic to all HLCs studied. Transcriptional analyses showed that PZ induces oxidative stress (OS) in HLCs in general, but in HLCs from susceptible individuals, PZ causes relative disruption of iron metabolism and higher burden of OS. Our study establishes the first patient-specific HLC-based platform for idiosyncratic hepatotoxicity testing, incorporating multiple potential causative factors and permitting the correlation of transcriptomic and cellular responses to clinical phenotypes. Establishment of patient-specific HLCs with clinical phenotypes representing population variations will be valuable for pharmaceutical drug testing.