Mechanisms of dense core vesicle recapture following "kiss and run" ("cavicapture") exocytosis in insulin-secreting cells.
The molecular mechanisms underlying "kiss and run" or "cavicapture" exocytosis of dense core secretory vesicles are presently unclear. Although dynamin-1 has previously been implicated in the recapture process in neurons, the recruitment of this fission protein to a single exocytosing vesicle has not been examined in real time during peptide release from pancreatic beta-cells. Imaged simultaneously in clonal insulin-secreting cells by dual color total internal reflection fluorescence microscopy, monomeric red fluorescent protein (mRFP)-tagged neuropeptide Y and green fluorescent protein (GFP)-tagged synaptotagmin-1 or synaptobrevin-2 rapidly diffused from sites of exocytosis, whereas the vesicle membrane protein phogrin and tissue plasminogen activator (tPA) were retained, consistent with fusion pore closure. Vesicle recovery frequently involved the recruitment of enhanced GFP-tagged dynamin-1, and GTPase-defective dynamin-1(K44E) increased the dwell time of tPA-mRFP at the plasma membrane. By contrast, recruitment of GFP chimeras of clathrin, epsin, and amphiphysin was not observed. Expression of dynamin-1(K535A), mutated in the pleckstrin homology domain, caused the apparent full fusion of vesicles, as reported by the additional release of tPA-mRFP (15-nm diameter) and enhanced GFP-tagged phogrin. We conclude that re-uptake of vesicles after peptide release by cavicapture corresponds to a novel form of endocytosis in which dynamin-1 stabilizes and eventually closes the fusion pore, with no requirement for "classical" endocytosis for retreat from the plasma membrane.


The Potential Role of Nutrition in Overtraining Syndrome: A Narrative Review.
Competition between athletes and an increase in sporting knowledge have greatly influenced training methods while increasing the number of them more and more. As a result, the number of athletes who have increased the number and intensity of their workouts while decreasing recovery times is rising. Positive overtraining could be considered a natural and fundamental process when the result is adaptation and improved performance; however, in the absence of adequate recovery, negative overtraining could occur, causing fatigue, maladaptation, and inertia. One of the earliest forms of fatigue is overreaching. It is considered to be an accumulation of training that leads to reduced sports performance, requiring days or weeks to recover. Overreaching, if followed by adequate recovery, can lead to an increase in athletic performance. Nonetheless, if overreaching becomes extreme, combined with additional stressors, it could lead to overtraining syndrome (OTS). OTS, caused by systemic inflammation, leads to central nervous system (CNS) effects, including depressed mood, further inflammation, central fatigue, and ultimately neurohormonal changes. There are therefore not only physiological, biochemical, and immunological but also psychological symptoms or markers that must be considered, independently or together, being intrinsically linked with overtraining, to fully understand OTS. However, to date, there are very few published studies that have analyzed how nutrition in its specific food aspects, if compromised during OTS, can be both etiology and consequence of the syndrome. To date, OTS has not yet been fully studied, and the topic needs further research. The purpose of this narrative review is therefore to study how a correct diet and nutrition can influence OTS in all its aspects, from prevention to treatment.


Interaction of colicin E7 with the major coat protein (g8p) may confer limited protection on colicinogenic Escherichia coli against M13 bacteriophage infection.
Colicin release provides producer strains with a competitive advantage under certain circumstances. We found that propagation of M13 bacteriophage in cells producing colicin E7 is impaired, without alteration in the efficiency of bacteriophage adsorption, as compared with non-producing cells. In contrast to the protective effect of the colicin against M13 bacteriophage infection, the endogenously expressed colicin does not confer limited protection against transfection with M13 bacteriophage DNA. Furthermore, it was found that the translocation-receptor-binding domain and toxicity domain of the colicin are able to interact with the M13 major coat protein, g8p, during bacteriophage infection. Based on these observations, we propose that interaction between colicin E7 and g8p during infection interferes with g8p depolymerizing into the cytoplasmic membrane during bacteriophage DNA penetration, thus resulting in the limited protection against M13 bacteriophage infection.


Do coder characteristics influence validity of ICD-10 hospital discharge data?
Administrative data are widely used to study health systems and make important health policy decisions. Yet little is known about the influence of coder characteristics on administrative data validity in these studies. Our goal was to describe the relationship between several measures of validity in coded hospital discharge data and 1) coders' volume of coding (> or = 13,000 vs. <13,000 records), 2) coders' employment status (full- vs. part-time), and 3) hospital type. This descriptive study examined 6 indicators of face validity in ICD-10 coded discharge records from 4 hospitals in Calgary, Canada between April 2002 and March 2007. Specifically, mean number of coded diagnoses, procedures, complications, Z-codes, and codes ending in 8 or 9 were compared by coding volume and employment status, as well as hospital type. The mean number of diagnoses was also compared across coder characteristics for 6 major conditions of varying complexity. Next, kappa statistics were computed to assess agreement between discharge data and linked chart data reabstracted by nursing chart reviewers. Kappas were compared across coder characteristics. 422,618 discharge records were coded by 59 coders during the study period. The mean number of diagnoses per record decreased from 5.2 in 2002/2003 to 3.9 in 2006/2007, while the number of records coded annually increased from 69,613 to 102,842. Coders at the tertiary hospital coded the most diagnoses (5.0 compared with 3.9 and 3.8 at other sites). There was no variation by coder or site characteristics for any other face validity indicator. The mean number of diagnoses increased from 1.5 to 7.9 with increasing complexity of the major diagnosis, but did not vary with coder characteristics. Agreement (kappa) between coded data and chart review did not show any consistent pattern with respect to coder characteristics. This large study suggests that coder characteristics do not influence the validity of hospital discharge data. Other jurisdictions might benefit from implementing similar employment programs to ours, e.g.: a requirement for a 2-year college training program, a single management structure across sites, and rotation of coders between sites. Limitations include few coder characteristics available for study due to privacy concerns.


10 years' experience in fragile X testing among mentally retarded individuals in Greece: a molecular and epidemiological approach.
Fragile X syndrome, the second most common genetic cause of mental retardation, is due to the expansion of a trinucleotide repeat (CGG)n within the first exon of the FMR-1 gene. Molecular genetic analysis provides accurate diagnosis and facilitates genetic counselling and prenatal testing. Screening for the fragile X mutation in a sample of 3,888 individuals in Greece is reported: 1,755 children with non-specific mental retardation, 1,733 parents and other family members and 400 normal individuals. Molecular analysis allowed for the identification and characterization of 52 fragile X families confirming the clinical diagnosis in 57 males and 4 females. Sixty-six female carriers (6 mentally retarded) and 4 normal transmitting males were also identified. Four severely retarded males and their mothers carried unmethylated premutations, while a moderately retarded girl had a deletion of approximately equal to 150 bp. Overall sizing of the CGG repeat produced an allele distribution of 6-58 CGG repeats (mean 28-30), similar to that in other Caucasian populations.


Safety and antiviral activity of albinterferon alfa-2b dosed every four weeks in genotype 2/3 chronic hepatitis C patients.
A phase 2, randomized, multicenter, open-label study evaluated the safety and efficacy of albinterferon alfa-2b in interferon-alpha treatment-naïve patients with genotype 2/3, chronic hepatitis C virus infection. Forty-three patients were randomly assigned in a 1:1 ratio to receive subcutaneous albinterferon alfa-2b 1500 microg every 4 weeks (q4wk) or every 2 weeks (q2wk) with oral ribavirin 800 mg/day for 24 weeks. Primary efficacy end point was sustained virologic response (undetectable hepatitis C virus RNA 24 weeks after completion of treatment). Insulin resistance was also assessed. The safety of albinterferon alfa-2b was acceptable, with a similar adverse event profile in both treatment arms. Discontinuation as a result of adverse events occurred in 4.5% and 14.3% of patients in the q4wk and q2wk arms, respectively. No dose reductions caused by adverse events were reported in the q4wk arm versus 9.5% in the q2wk arm. Rapid viral response rates at week 4 were 68.2% and 76.2% for the q4wk and q2wk arms, respectively; the corresponding sustained virologic response rates were 77.3% and 61.9%. Insulin resistance at baseline was significantly associated with lower sustained virologic response rates independent of body mass index. Albinterferon alfa-2b administered at 4-week intervals was safe and well-tolerated and demonstrated significant antiviral activity in patients with genotype 2/3, chronic hepatitis C virus. Insulin resistance appeared to have an independent effect on treatment response.


The oncogenic protein kinase Tpl-2/Cot contributes to Epstein-Barr virus-encoded latent infection membrane protein 1-induced NF-kappaB signaling downstream of TRAF2.
The Epstein-Barr virus-encoded latent infection membrane protein 1 (LMP1) is a pleiotropic protein, the activities of which include effects on cell transformation and phenotype, growth, and survival. The ability of LMP1 to mediate at least some of these phenomena could be attributed to the activation of the transcription factor NF-kappaB. LMP1 promotes NF-kappaB activation through the recruitment of the adapter protein TRAF2 and the formation of a dynamic multiprotein complex that includes the NF-kappaB kinase, the IkappaB kinases, and their downstream targets, IkappaBs and p105. In this study, we have identified the oncogenic kinase Tpl-2/Cot as a novel component of LMP1-induced NF-kappaB signaling. We show that Tpl-2 is expressed in primary biopsies from patients with nasopharyngeal carcinoma and Hodgkin's disease, where LMP1 is also found. Inducible expression of LMP1 promotes the activation of Tpl-2, and a catalytically inactive Tpl-2 mutant suppresses LMP1-induced NF-kappaB signaling. In colocalization and coimmunoprecipitation experiments, Tpl-2 and TRAF2 were found to interact with Tpl-2 functioning downstream of TRAF2. Consistent with this observation, catalytically inactive Tpl-2 also blocked CD40-mediated NF-kappaB activation, which largely depends on TRAF2. The ability of Tpl-2 to influence LMP1-induced NF-kappaB occurs through modulation of both IkappaBalpha and p105 functions. Furthermore, Tpl-2 was found to influence the expression of angiogenic mediators, such as COX-2 in LMP1-transfected cells. These data identify Tpl-2 as a component of LMP1 signaling downstream of TRAF2 and as a modulator of LMP1-mediated effects.


[Ichthyofauna associated to Thalassia testudinum at Lobos reef, Veracruz, Mexico: diversity and abundance].
The diversity and abundance of ichthyofauna associated with Thalassia testudinum in the Lobos coral reef, Veracruz, Mexico, were studied in September and October 2002. Thirty six visual censuses in four sample sites were made using a 50 x 2 m transect belt. On each census, fish species, abundance and size were recorded. Leaf size and cover of T. testudinum were estimated. The similarity of fish groups was calculated with the Gower coefficient. The most abundant coral reef fishes were: Scarus iseri, Halichoeres bivittatus, Sparisoma radians, Stegastes adustus and Stegastes leucostictus. The highest density (0.04078 ind/m2) and biomass (0.72408 g/m2) of fish species were recorded in site II, where leaf size was greater (30.8 cm). The analysis of variance showed significant differences between sites in leaf size (F = 18.30856; p = 0.00001) and cover (H = 33.8119; p = 0.00001). These differences suggest a relationship between fish diversity and abundance, and T. testudinum leaf size and cover. The Gower similarity index produced two groups of fishes; one of them (site II) showed the highest abundance. In this reef, the fishes associated to sea grasses seem to reflect the characteristics of T. testudinum.


Topological electronic structure and spin texture of quasi-one-dimensional higher-order topological insulator Bi4Br4.
The notion of topological insulators (TIs), characterized by an insulating bulk and conducting topological surface states, can be extended to higher-order topological insulators (HOTIs) hosting gapless modes localized at the boundaries of two or more dimensions lower than the insulating bulk. In this work, by performing high-resolution angle-resolved photoemission spectroscopy (ARPES) measurements with submicron spatial and spin resolution, we systematically investigate the electronic structure and spin texture of quasi-one-dimensional (1D) HOTI candidate Bi4Br4. In contrast to the bulk-state-dominant spectra on the (001) surface, we observe gapped surface states on the (100) surface, whose dispersion and spin-polarization agree well with our ab-initio calculations. Moreover, we reveal in-gap states connecting the surface valence and conduction bands, which is a signature of the hinge states inside the (100) surface gap. Our findings provide compelling evidence for the HOTI phase of Bi4Br4. The identification of the higher-order topological phase promises applications based on 1D spin-momentum locked current in electronic and spintronic devices.


Frictional resistance between orthodontic brackets and archwire: an in vitro study.
The purpose of this investigation was to determine the kinetic frictional resistance offered by stainless steel and Titanium bracket used in combination with rectangular stainless steel wire during in vitro translatory displacement of brackets. In this study. Brackets: (All brackets used had a torque of - 7° and an angulation of 0°): (1) Dynalock (Unitek) 0.018'' slot, 3.3 mm bracket width, (2) Mini Uni-Twin (Unitek) 0.018'' slot, 1.6 mm bracket width, (3) Ultra-Minitrim (Dentaurum) 0.022'' slot 3.3 mm bracket width, (4) Titanium (Dentaurum) 0.022'' slot, 3.3 mm bracket width. WIRES: (1) 0.016 x 0.022'' stainless steel (Dentaurum), (2) 0.017 x 0.025''stainless steel (Unitek), (3) 0.018 x 0.025'' stainless steel (Dentaurum), elastomeric modules (Ortho Organisers), 0. 009'' stainless steel ligature wires, hooks made of 0.021 x 0.025'' stainless steel wires, super glue to bond the hooks to the base of the bracket, acetone to condition the bracket and wires before testing and artificial saliva. Brackets were moved along the wire by means of an Instron universal testing machine (1101) and forces were measured by a load cell. All values were recorded in Newtons and then converted into gms (1N-102 gm). 200 gm was then subtracted from these values to find out the frictional force for each archwire/bracket combination. For each archwire/ bracket combination three readings were taken under wet and dry condition and also with stainless steel ligature and elastomeric modules separately. The results showed that narrow brackets generated more friction than wider brackets. Frictional force was directly proportional to wire dimension. Titanium brackets generated more friction than stainless steel brackets. Archwire and bracket ligated with elastomeric module generated more friction than when ligated with stainless steel ligature wire. Frictional forces in the wet condition were greater than in the dry condition for all archwire to bracket combinations. Frictional force was seen to be inversely proportional to bracket width, frictional force was inversely proportional to bracket width, and in the wet condition were greater than in the dry condition for all archwire to bracket combinations. This study of friction is its role in lessening the force actually received by a tooth from an active component such as a spring, loop or elastic. Hence greater applied force is needed to move a tooth with a bracket archwire combination demonstrating high magnitudes of friction compared with one with a low frictional value.


Ionic dependence of active Na-K transport: "clamping" of cellular Na+ with monensin.
The Na+ ionophore monensin was used to study the Na+- and K+-dependence of ouabain-inhibitable 86Rb+ uptake in ARL 15 cells, a rat liver cell line. Graded concentrations of monensin rapidly induced incremental elevations of cellular Na+ that were stable for up to 2 h. In experiments in which cellular Na+ was thus "clamped" at various levels, the activation curve for ouabain-inhibitable 86Rb+ uptake as a function of intracellular Na+ was found to be steepest near basal Na+ levels (Hill coefficient approximately equal to 2.4), indicating that these cells can respond to relatively large changes in passive Na+ entry by increasing the race of Na-K pump function with only minimal increases in cellular Na+. Exposure of cells to monensin also permitted examination of the extracellular-K+ dependence of ouabain-inhibitable 86Rb+ uptake in the presence of saturating intracellular Na+ and yielded a Hill coefficient of approximately 1.5. The rate of ATP hydrolysis calculated from measurements of the maximal rate of ouabain-inhibitable 86Rb+ uptake in intact cells was similar to the enzymatic Vmax of the Na+-K+-ATPase in cell lysates, suggesting that the Na+-K+-ATPase activity in these broken-cell preparations closely reflects the functional transport capacity of the Na-K pump.


Spinal-cord MRI in multiple sclerosis.
The potential of MRI of the spinal cord as a diagnostic tool in MS has recently gained much interest. Dual echo spin echo MRI is most sensitive for the detection of spinal-cord abnormalities, which range from multiple focal lesions to confluent areas of high signal intensity. In some patients, commonly those with primary progressive disease, diffuse areas of slightly increased signal intensity are found. Disappointingly, the relation between MRI findings and clinical disability is weak. Studies relating MRI findings with histopathology have revealed substantial axonal loss in the spinal cords of patients with MS, whether focal lesions are present of not. Further, diffuse cord atrophy is found in advanced MS, which may reflect axonal loss. In the diagnostic setting, spinal-cord imaging is valuable. First, asymptomatic spinal-cord lesions are very rare in disorders other than MS. For example, in a patient with equivocal brain findings such as an elderly patient with vascular-ischaemic lesions, a normal spinal-cord examination can help rule out MS. Second, presence of asymptomatic spinal lesions may help confirm a diagnosis of MS when few or no brain lesions are present.


Chip-to-chip optical interconnect using gold long-range surface plasmon polariton waveguides.
We demonstrate a novel on-board chip-to-chip optical interconnect using long-range surface plasmon polariton (LR-SPP) waveguides that feature 2.5-cm-long gold strips embedded in a low loss polymer cladding. A TM-mode vertical-cavity surface-emitting laser (VCSEL) operating at a wavelength of 1.3 microm was butt-coupled into the waveguides in order to excite a fundamental LR-SPP mode and then the transmitted light was received with a photo-diode (PD). The waveguide width is varied in the range of 1.5-5.0 microm in order to optimize the insertion loss where the 3-microm-wide waveguide provides a minimum insertion loss of -17 dB, consisting of 6 dB/cm propagation loss and 2 dB coupling loss. An interconnect system based on the optimized waveguide with a 4-channel array is assembled with the arrayed optoelectronic chips. It shows the feasibility of 10 Gbps (2.5 Gbps x 4 channels) signal transmission indicating that the LR-SPP waveguide is a potential transmission line for optical interconnection.


Coordination of synaptic adhesion with dendritic spine remodeling by AF-6 and kalirin-7.
Remodeling of central excitatory synapses is crucial for synapse maturation and plasticity, and contributes to neurodevelopmental and psychiatric disorders. Remodeling of dendritic spines and the associated synapses has been postulated to require the coordination of adhesion with spine morphology and stability; however, the molecular mechanisms that functionally link adhesion molecules with regulators of dendritic spine morphology are mostly unknown. Here, we report that spine size and N-cadherin content are tightly coordinated. In rat mature cortical pyramidal neurons, N-cadherin-dependent adhesion modulates the morphology of existing spines by recruiting the Rac1 guanine-nucleotide exchange factor kalirin-7 to synapses through the scaffolding protein AF-6/afadin. In pyramidal neurons, N-cadherin, AF-6, and kalirin-7 colocalize at synapses and participate in the same multiprotein complexes. N-cadherin clustering promotes the reciprocal interaction and recruitment of N-cadherin, AF-6, and kalirin-7, increasing the content of Rac1 and in spines and PAK (p21-activated kinase) phosphorylation. N-cadherin-dependent spine enlargement requires AF-6 and kalirin-7 function. Conversely, disruption of N-cadherin leads to thin, long spines, with reduced Rac1 contact, caused by uncoupling of N-cadherin, AF-6, and kalirin-7 from each other. By dynamically linking N-cadherin with a regulator of spine plasticity, this pathway allows synaptic adhesion molecules to rapidly coordinate spine remodeling associated with synapse maturation and plasticity. This study hence identifies a novel mechanism whereby cadherins, a major class of synaptic adhesion molecules, signal to the actin cytoskeleton to control the morphology of dendritic spines, and outlines a mechanism that underlies the coordination of synaptic adhesion with spine morphology.


Psychometric properties of Attitudes Towards Lesbians and Gay Men Scale with Chinese university students.
The 10-item Attitudes Towards Lesbian and Gay Men Scale was translated into traditional Chinese, with slight modification in item wordings (by replacing the words such as "lesbians" with "female homosexuals" and "gay men" with "male homosexuals"). Data were collected with a convenient sample of 462 Chinese undergraduate students in social work training programmes from three Hong Kong universities. Analysis of the data showed responses to the scale and its two subscales were internally consistent and a one-factor structure was found on the total scale and separately on each of its two subscales. Differences by religious belief and sex were observed using the total scale scores, as in previous studies using this scale. Researchers could consider using this scale with Hong Kong Chinese and in subsequent cross-cultural studies involving a wider range of Chinese respondents.


Calorie restriction prevents hypertension and cardiac hypertrophy in the spontaneously hypertensive rat.
Because recent evidence demonstrated that calorie restriction (CR) has numerous beneficial cardiovascular effects, we investigated whether short-term CR could reduce hypertension and prevent cardiac hypertrophy inherent to the nonobese spontaneously hypertensive rat (SHR). After 5 weeks of either ad libitum feeding or short-term CR, SHRs subjected to short-term CR had lower systolic blood pressure (BP) and reduced left ventricular wall thickness as assessed by noninvasive tail-cuff BP measurements and echocardiography, respectively. In addition, ultrasound measurements of the femoral artery revealed that flow-mediated vasodilation was significantly improved in SHRs with CR compared to controls. Moreover, pressure myography of isolated mesenteric arteries and subsequent histological and biochemical analysis of these arteries demonstrated that short-term CR improved vascular compliance, increased endothelial nitric oxide synthase (eNOS) activity and nitric oxide bioavailability, and reduced vascular remodeling compared to ad libitum-fed SHRs. Although these effects are likely multifactorial, they were associated with elevated levels of the circulating adipokine, adiponectin, and enhanced AMP-activated protein kinase (AMPK) activity. To provide evidence that elevated adiponectin levels in the SHR is sufficient to prevent an increase in BP, adenoviral-mediated overexpression of adiponectin increased circulating levels of adiponectin, reduced BP, and activated the AMPK/eNOS pathway in the absence of CR. Overall, our findings provide compelling evidence that short-term CR exerts beneficial effects in the SHR via stimulation of an adiponectin/AMPK/eNOS signaling axis. As a result, CR may serve as an effective nonpharmacological treatment of hypertension, and targeting the adiponectin/AMPK/eNOS pathway may improve treatment of hypertension.


Plasmonic Scattering Imaging of Surface-Bonded Nanoparticles at the Solution-Solid Interface.
Imaging nanoscale objects at interfaces is essential for revealing surface-tuned mechanisms in chemistry, physics, and life science. Plasmonic-based imaging, a label-free and surface-sensitive technique, has been widely used for studying the chemical and biological behavior of nanoscale objects at interfaces. However, direct imaging of surface-bonded nanoscale objects remains challenging due to uneven image backgrounds. Here, we present a new surface-bonded nanoscale object detection microscopy that eliminates strong background interference by reconstructing accurate scattering patterns at different positions. Our method effectively functions at low signal-to-background ratios, allowing for optical scattering detection of surface-bonded polystyrene nanoparticles and severe acute respiratory syndrome coronavirus 2 pseudovirus. It is also compatible with other imaging configurations, such as bright-field imaging. This technique complements existing methods for dynamic scattering imaging and broadens the applications of plasmonic imaging techniques for high-throughput sensing of surface-bonded nanoscale objects, enhancing our understanding of the properties, composition, and morphology of nanoparticles and surfaces at the nanoscale.


Cognition or involvement? Explaining sexual-coercion in high-school dating.
The purpose of the present study was to examine a predictive model of perpetration of, and victimization by, sexual coercive practices. The theoretical perspective focused on the interactive nature of dating and sexual coercion within the dating context. The interactive nature of sexual coercion assumes that in each dating encounter, partners have expectations of developing some level of sexual and romantic relations. Thus, one of the partners may initiate a sexual advancement, while the other reacts to this initiation. The reaction may range from cooperation, through passive reaction to straight forward resistance. Any attempt to continue in the face of resistance should be defined as an attempt at sexual coercion. In order to asses perpetration and victimization risks, a planned behavior model was examined, including the relative importance of personal attitudes and subjective norms, operationalized as perceived peers' expectations. Further, the role of other factors related to social/cultural background (such as immigration status, religiosity, and gender) in contributing to either risk of victimization and perpetration was examined. Instruments and sample: A factorial survey design was carried out on a sample of 329 adolescents in eleventh grade, 157 males and 172 females. The findings indicate that males are more prone to both victimization and perpetration of sexual coercion. Overall, the current conceptualization of dating sexual coercion as an interactional process, based on socially constructed and personally interpreted scripts, has enabled the comparison of two major explanatory models--the TPB and the involvement model, and to show the primacy of involvement.


4-(4-Chloro-2-oxo-3(1H-phenanthro[9,10-d]imidazol-2-yl)-2H-chromen-6-yl) benzaldehyde as a fluorescent probe for medical imaging: linear and nonlinear optical properties.
This study presents the full theoretical optical and biological characteristics of a new fluorescent probe based on the phenanthroimidazole backbone (PB5). The aldehyde group was selected as the active group to bind to the protein during conjugation. The new fluorescent probe is based on the phenanthroimidazole backbone; however, unlike previously presented works, as the chromophore part, it contains the first introduction of the 4-chloro-2H-chromen-2-one part. In order to achieve the best cognitive aspect, the study included not only the dye itself but also the concanavalin A conjugate. The linear and non-linear optical properties and biological activities described in this study clearly indicate that the presented dye is a promising material as a fluorescent probe in medical imaging.


Nutritional clinical studies in dermatology.
Nutrition has long been associated with skin health, beauty, integrity and aging through multiple pathways and cofactors implicated in skin biology. The onset and clinical course of various common skin diseases, especially acne, psoriasis, atopic dermatitis, and hair loss, have been suggested to be critically affected by nutrition patterns and habits. The relationship between acne and diet, predominantly the role of high glycemic load diets and dairy consumption have recently gained increased interest. Abnormal nutritional conditions such as obesity or malnutrition often manifest themselves by specific cutaneous features and altered skin function. Skin photoprotection, rendered by various nutrients, is well documented and appropriate nutritional supplementation has been shown to exert beneficial effects upon impaired skin integrity, restore its appearance and promote skin health. It is our intention to provide a comprehensive review of the most recent information on the role of nutrition for common skin diseases and regulation of skin biology. Nutritional clinical studies in dermatology have been reviewed using the MedLine literature source and the terms "diet" or "nutrition" and "skin". The data on the relationship between nutrition and skin are until now controversial and much more work is needed to be done to clarify possible etiological correlations.


Chemiluminescence from alkoxy-substituted acridinium dimethylphenyl ester labels.
Chemiluminescent acridinium dimethylphenyl ester labels are used in automated immunoassays for clinical diagnostics. Light emission from these labels is triggered by alkaline peroxide in the presence of the cationic surfactant cetyltrimethylammonium chloride (CTAC). The surfactant plays a critical role in the chemiluminescence process of these labels by both accelerating their emission kinetics and increasing total light output enabling high throughout and improved assay sensitivity in automated immunoassays. Despite the surfactant's crucial role in the chemiluminescent reaction, no study has investigated how structural perturbations in the acridinium ring could impact the influence of the surfactant. We describe herein the synthesis and properties of three new alkoxy-substituted, acridinium dimethylphenyl esters where the nature of the alkoxy group in the acridinium ring was varied (hydrophobic or hydrophilic). Chemiluminescence measurements of these alkoxy-substituted labels indicate that hydrophilic functional groups in the acridinium ring, in particular sulfobetaine zwitterions, disrupt surfactant-mediated compression of emission times but not enhancement of light yield. These results support the hypothesis that surfactant-mediated effects require the binding of two different reaction intermediates to surfactant aggregates and, that surfactants influence light emission from acridinium esters by two separate mechanisms. Our studies also indicate that preservation of both surfactant effects on acridinium ester chemiluminescence and low non-specific binding of the label can be achieved with a relatively hydrophobic acridinium ring coupled to a hydrophilic phenolic ester leaving group.


Emotional and behavioral problems in adolescents and young adults with food allergy.
Adolescents with food allergy have poorer psychosocial outcomes compared with their nonallergic counterparts; however, few studies have prospectively examined the mental health of adolescents and young adults in this vulnerable population. Our objectives were to estimate the prevalence of emotional and behavioral problems in an epidemiological sample of adolescents and young adults with food allergy; determine whether food allergy is associated with adolescent and maternal reports of such problems; and examine the patterns of change in emotional and behavioral problems from adolescence to young adulthood among individuals with and without food allergy. Data came from 1303 participants at 14 and 21 years of age in the Mater University Study of Pregnancy. Emotional and behavioral problems were measured using self- and maternal-reported symptoms of depression, anxiety, attention/deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder. Maternal, but not self-reports suggested that emotional and behavioral problems were higher among adolescents with food allergy. Food allergy was associated with increased odds of elevated levels of maternal-reported symptoms of depression [OR = 4.50 (1.83, 11.07)], anxiety [OR = 2.68 (1.12, 6.44)], and ADHD [OR = 3.14 (1.07, 9.19)] in adolescence. Food allergy was also associated with depressive symptoms that persisted from adolescence to young adulthood [OR = 2.05 (1.04, 4.03)]. Emotional and behavioral problems, particularly symptoms of depression, anxiety, and ADHD, are common among adolescents with food allergy in the general population and, in the case of elevated levels of depressive symptoms, persist into young adulthood. Healthcare professionals should seek adolescent and parental perspectives when assessing emotional and behavioral problems and monitor mental health during the transition to adulthood.


Patient reported outcomes for patients who returned to sport compared with those who did not after hip arthroscopy: minimum 2-year follow-up.
Previous studies assessed elite athletes' return to sport (RTS) after hip arthroscopy, but few investigated a cohort including athletes from all levels of sport. This study compared athletes who returned to sport to those who did not, based on four patient-reported outcome (PRO) scores, including the Hip Outcome Score-Sports Specific Subscale (HOS-SSS). Between September 2008 and April 2012, hip arthroscopies were performed on 157 patients (168 hips) who reported playing a sport preoperatively and indicated their level of sports activity post-operatively. Two-year follow-up was available for 148 (94%) amateur and professional athletes with a total of 158 hips. Of these 60 cases (65 hips) did not return to sports (NRTS) and were in the NRTS group. The remaining 88 cases (93 hips) constituted the RTS group. The modified Harris Hip Score, Non-Arthric Hip Score, Hip Outcome-Activities of Daily Living (HOS-ADL), and HOS-SSS were used to assess outcomes. The HOS-SSS was used to assess specific sport-related movement. Both groups demonstrated significant improvement at 2 years post-operatively in visual analog score and four PRO scores (P < 0.001). There was no significant preoperative differences in HOS-SSS scores between groups; however, the RTS group had significantly higher HOS-SSS scores at 1 and 2 years post-surgery. Post-operatively, the RTS group had significantly better ability to jump, land from a jump, stop quickly and perform cutting/lateral movements (P < 0.05). In summary, patients who indicated RTSs demonstrated significantly higher PRO scores and abilities to perform several sport-related movements, compared with patients who did not.


What Kurt Schneider Really Said and What the DSM Has Made of it in Its Different Editions: A Plea to Redefine Hallucinations in Schizophrenia.
Kurt Schneider has played a leading role in shaping our current view of schizophrenia, placing certain manifestations of delusions and hallucinations at the center of the disorder, especially ideas of persecution and voice-hearing. The first part of this review summarizes Schneider's original ideas and then traces how the different editions of the DSM merged aspects of Kraepelin's, Bleuler's, and Schneider's historical concepts. Special attention is given to the transition from the DSM-IV to the DSM-5, which eliminated much of Schneider's original concept. In the second part of the article, we contrast the current definition of hallucination in the DSM-5 with that of Schneider. We present empirically derived arguments that favor a redefinition of hallucinations, much in accordance with Schneider's original ideas. We plea for a two-dimensional model of hallucinations that represents the degree of insight and perceptuality, ranging from thoughts with full "mineness" via perception-laden thoughts and intrusions (including "as if" experiences") to hallucinations. While we concur with the DSM-5 that cognitions that are indistinguishable from perceptions should be labeled as hallucinations, we suggest expanding the definition to internally generated sensory phenomena, including those with only partial resemblance to external perceptions, that the individual considers real and that may lie at the heart of a subsequent delusional superstructure.


External Validity: The Next Step for Systematic Reviews?
Systematic reviews-which identify, assess, and summarize existing research-are usually designed to determine whether research shows that an intervention has evidence of effectiveness, rather than whether an intervention will work under different circumstances. The reviews typically focus on the internal validity of the research and do not consistently incorporate information on external validity into their conclusions. In this article, we focus on how systematic reviews address external validity. We conducted a brief scan of 19 systematic reviews and a more in-depth examination of information presented in a systematic review of home visiting research. We found that many reviews do not provide information on generalizability, such as statistical representativeness, but focus on factors likely to increase heterogeneity (e.g., numbers of studies or settings) and report on context. The latter may help users decide whether the research characteristics-such as sample demographics or settings-are similar to their own. However, we found that differences in reporting, such as which variables are included and how they are measured, make it difficult to summarize across studies or make basic determinations of sample characteristics, such as whether the majority of a sample was unemployed or married. Evaluation research and systematic reviews would benefit from reporting guidelines for external validity to ensure that key information is reported across studies.


Comparison of internal process control viruses for detection of food and waterborne viruses.
Enteric viruses are pathogens associated with food- and waterborne outbreaks. The recovery of viruses from food or water samples is affected by the procedures applied to detect and concentrate them. The incorporation of an internal process control virus to the analyses allows monitoring the performance of the methodology. The aim of this study was to produce a recombinant adenovirus (rAdV) and apply it together with bacteriophage PP7 as process controls. The rAdV carries a DNA construction in its genome to differentiate it from wild-type adenovirus by qPCR. The stability of both control viruses was evaluated at different pH conditions. The rAdV was stable at pH 3, 7, and 10 for 18 h. PP7 infectious particles were stable at pH 7 and showed a 2.14 log reduction at pH 10 and total decay at pH 3 after 18 h. Three virus concentration methods were evaluated: hollow-fiber tap water ultrafiltration, wastewater ultracentrifugation, and elution-PEG precipitation from lettuce. Total and infectious viruses were quantified and their recoveries were calculated. Virus recovery for rAdV and PP7 by ultrafiltration showed a wide range (2.10-84.42 and 13.54-84.62%, respectively), whereas that by ultracentrifugation was 5.05-13.71 and 6.98-13.27%, respectively. The performance of ultracentrifugation to concentrate norovirus and enteroviruses present in sewage was not significantly different to the recovery of control viruses. For detection of viruses from lettuce, genomic copies of PP7 were significantly more highly recovered than adenovirus (14.74-18.82 and 0.00-3.44%, respectively). The recovery of infectious virus particles was significantly affected during sewage ultracentrifugation and concentration from lettuce. The simultaneous use of virus controls with dissimilar characteristics and behaviors might resemble different enteric viruses.


High-throughput 3D cell invasion chip enables accurate cancer metastatic assays.
Chemotaxis is the phenomenon by which the migration and invasion of cells is directed in response to an extracellular chemical gradient. Chemotaxis of tumor cells and tumor-associated inflammatory and stromal cells is mediated by chemokines, chemokine receptors, growth factors, and growth factor receptors. Current techniques used to study chemotactic driven cell invasion and metastasis utilize two-dimensional migration assays involving imaging and analyzing tumor cells on glass slides or plastic surfaces, which requires large numbers of cells and often lacks real-time monitoring of vertical cell movement and systematically controlled chemotactic gradients, leading to contradictory results compared to those from clinical investigations and animal models. We addressed such challenges by developing a high-throughput microdevice with 4000 ultraminiaturized wells to monitor real-time, three-dimensional cell invasion over a wide range of cell densities and also screen drugs that inhibit cell invasion and potentially prevent metastatic malignancy. Additionally, this microdevice generates opposing gradients for two types of cells on the same chip, which builds a controlled system with sequentially changing components to study environmental effects from basal and immune cells.


Considerations for emotion-aware consumer products.
Emotion-aware consumer products require reliable, short-term emotion assessment (i.e., unobtrusive, robust, and lacking calibration). To explore the feasibility of this, an experiment was conducted where the galvanic skin response (GSR) and three electromyography (EMG) signals (frontalis, corrugator supercilii, and zygomaticus major) were recorded on 24 participants who watched eight 2-min emotion inducing film fragments. The unfiltered psychophysiological signals were processed and six statistical parameters (i.e., mean, absolute deviation, standard deviation, variance, skewness, and kurtosis) were derived for each 10-s interval of the film fragment. For each physiological signal, skewness and kurtosis discriminated among affective states, accompanied by other parameters, depending on the signal. The skewness parameter also showed to indicate mixed emotions. Moreover, a mapping of events in the fragments on the signals showed the importance of short-term emotion assessment. Hence, this research identified generic features, denoted important considerations, and illustrated the feasibility of emotion-aware consumer products.


Nicotine restores monoamine neurotransmitter changes in the cortex and hippocampus of reserpinized rats as a model of depression.
A number of studies have shown that nicotine has an antidepressant-like effect. The prevalence of smoking is much higher in people suffering from depression. In addition, the administration of nicotine from transdermal nicotine patch can exert antidepressant activity in nonsmokers and the continuous infusion of nicotine to rats attenuates learned helplessness, a putative behavioral model of depression. The aim of the present study is to elucidate the neurochemical effect of nicotine on monoamine levels in the cerebral cortex and hippocampus of reserpinized rats as a model of depression. In the present study, rats were divided into control animals treated with saline and reserpinized group which received a daily i.p injection of reserpine for 15 days to establish the animal model of depression. Starting from the 16th day, the reserpinized rats were divided into reserpinized rats, and reserpinized rats treated daily with nicotine (0.4 mg/kg) for 15 and 30 days. After decapitation, the cerebral cortex and hippocampus of each rat were dissected out. The levels of monoamine neurotransmitters (serotonin, norepinephrine and dopamine) were measured in each area using a spectrofluorimeter. The daily i.p injection of reserpine induced a significant decrease in monoamine levels in the cortex and hippocampus. Nicotine administration restored the changes in monoamine neurotransmitters induced by reserpine in both areas after 30 days. The data of the present study suggest that the antidepressant-like effect of nicotine could be mediated by the effect of nicotine on monoamine neurotransmitters in the cortex and hippocampus of rat brain.


Task-Independent Cognitive State Transition Detection From Cortical Neurons During 3-D Reach-to-Grasp Movements.
Complex reach, grasp, and object manipulation tasks require sequential, temporal coordination of movements by neurons in the brain. Detecting cognitive state transitions associated with motor tasks from sequential neural data is pivotal in rehabilitation engineering. The cognitive state detectors proposed thus far rely on task-dependent (TD) models, i.e., the detection strategy exploits a priori knowledge of the movement tasks to determine the actual cognitive states, regardless of whether these cognitive states actually depend on the movement tasks or not. This approach, however, is not viable when the tasks are not known a priori (e.g., the subject performs many different tasks) or there is paucity of neural data for each task. Moreover, some cognitive states (e.g., holding) may be invariant to the movement tasks performed. Here we propose a real-time (online) task-independent (TI) framework to detect cognitive state transitions from spike trains and kinematic measurements. We constructed this detection framework using 452 single-unit neural spike recordings collected via multielectrode arrays in the premotor dorsal and ventral (PMd and PMv) cortical regions of two nonhuman primates performing 3-D multiobject reach-to-grasp tasks. We used the detection latency and accuracy of state transitions to measure the performance. We find that, in both online and offline detection modes: 1) TI models have significantly better performance than corresponding TD models when using neuronal data alone and 2) during movements, the addition of the kinematics history to the TI models further improves detection performance. These findings suggest that TI models may accurately detect cognitive state transitions. Our framework could pave the way for a TI control of neural prosthesis from cortical neurons.


[Is physical inactivity associated with musculoskeletal disorders?].
The aim of our study was to determine the relationship between musculoskeletal disorders (MD) and physical activity levels (PAL) in individuals. 125 individuals (74 female, 51 male) aged between 20-65 participated in the study. Extended Nordic Musculoskeletal Questionnaire was used to examine MD, International Physical Activity Questionnaire was used to determine PAL. The mean age of the cases was 31.56 ± 7.09 years. It was found that individuals were 33.6% sufficiently active, 39.2% minimally active, 27.2% inactive. Body regions which were most commonly reported for experiencing pain, low back (51.2%), upper back (51.2%), neck (48.8%) at some point in their lifetime, neck (38.4%), upper back (35.2%), low back (35.2%) during the past 12 months, upper back (29.6%), neck (28.8%), low back (23.2%) in the past month, upper back (16.8%), shoulders (12.8%), neck and low back (11.2%) on the day of study. When MD during the past 12 months, in the past month, on the day of study were compared with PAL, statistically significant relation was found between knee pain and PAL (p=0.002, p=0.001, p=0.023, respectively). The results showed that musculoskeletal pain was more frequent in spine (low back, upper back, neck). When the presence of MD compared with PAL, statistically significant relation was found between knee pain and PAL. In our study, patients with knee pain had high PAL, this can be explained by, those who are physically active tend to experience sport related injuries than inactive individuals and anatomic feature of knee joint.


Post-transplantation HTLV-1 myelopathy in three recipients from a single donor.
This paper reports for the first time three cases of infection by HTLV-I via organ transplantation; all the organs coming from the same asymptomatic infected donor. The need is considered for the implementation of compulsory screenings for HTLV antibodies on organ donors and on blood banks. The determination of antibodies for HTLV-I/II on samples of serum and cerebral spinal fluid from the patients and the donor was performed by enzyme immunoassay and western blot. Analysis of proviral DNA was performed by polymerase chain reaction. To detect changes in the sequence of amino acids, the tax gene was sequentiated, amplified, and compared with ATK prototype stocks. Spinal cord magnetic resonance imaging, cerebral spinal fluid, and somatosensory evoked potential studies were carried out in all patients. All three transplanted patients developed a myelopathy within a very short period of time. In all three patients and donor the virus belonged to the Cosmopolitan A subtype. The homology of HTLV-I sequences recovered from the patients and donor was 100% in all four cases. Proviral load was high in all three patients. The factors that certainly contributed to the infection in the first place, and the development of the disease later, were on the one hand the high proviral load and their immunosuppressed condition, and on the other the virus genotype, which proved to be an aggressive variant. However, the analysis of the histocompatibility antigen showed that two of the patients carried an haplotype that has been associated with a lower risk of developing this disease. It is argued that, although in Spain and other European countries there is not compulsory screening for HTLV antibodies because of the studies that show a low seroprevalence, in view of the cases here reported, and to avoid the serious consequences that such infection has on transplanted patients, compulsory screenings, both on organ donors and on blood banks, should be implemented.


Transplanted hESC-Derived Retina Organoid Sheets Differentiate, Integrate, and Improve Visual Function in Retinal Degenerate Rats.
To investigate whether sheets of retina organoids derived from human embryonic stem cells (hESCs) can differentiate, integrate, and improve visual function in an immunodeficient rat model of severe retinal degeneration (RD). 3D hESC-derived retina organoids were analyzed by quantitative PCR and immunofluorescence. Sheets dissected from retina organoids (30-65 days of differentiation) were transplanted into the subretinal space of immunodeficient rho S334ter-3 rats. Visual function was tested by optokinetic testing and electrophysiologic recording in the superior colliculus. Transplants were analyzed at 54 to 300 days postsurgery by immunohistochemistry for donor and retinal markers. Retina organoids contained multiple retinal cell types, including progenitor populations capable of developing new cones and rods. After transplantation into an immunodeficient rat model of severe RD, the transplanted sheets differentiated, integrated, and produced functional photoreceptors and other retinal cells, according to the longer human developmental timetable. Maturation of the transplanted retinal cells created visual improvements that were measured by optokinetic testing and electrophysiologic recording in the superior colliculus. Immunohistochemistry analysis indicated that the donor cells were synaptically active. Extensive transplant projections could be seen within the host RD retina. Optical coherence tomography imaging monitored long-term transplant growth and survival up to 10 months postsurgery. These data demonstrate that the transplantation of sheets dissected from hESC-derived retina organoids is a potential therapeutic method for restoring vision in advanced stages of RD.


A sentence is to speech as what is to action?
This article offers a conceptual framework for integrated analysis of subprocesses in action and language, based on goal-directed action. Anatomical substrates are discussed in the companion paper (Arbib and Bota, 2003) which approaches "Integrative Models of Broca's Area and the Ventral Premotor Cortex" within the context of explaining why the evolution of the human brain yielded mechanisms which support language in a multi-modal vocal-manual-facial system rather than privileging the vocal mode. Arbib and Bota (2003) examine homologies between different cortical areas in macaque and human to revisit the Mirror System Hypothesis (MSH) of Rizzolatti and Arbib (1998)--the notion that the mirror system for grasping (which has its frontal outpost in premotor area F5 of the macaque) provides the substrate for the evolution of the language-ready brain which supports parity of communication. They also offer a critique and extension based on the work of Aboitiz and García (1997; Aboitiz et al., 2006). Arbib and Bota (2003) also discussed the utility of neuroinformatics in relating information across diverse cortical atlases and evaluating degrees of homology for brain regions of interest in different species (for discussion, see Deacon, 2004; Arbib and Bota, 2004).


A preliminary predictive model for selenium nutritional status in residents based on three selenium biomarkers.
Selenium (Se) is an essential nutrient and an important component of many selenoproteins that possess fundamental importance to human health. Selenium deficiency and excess will cause corresponding diseases in the human body. The nutritional health of Se in the human body mainly depends on the daily dietary Se intake of the human body, which in turn depends to a certain extent on the content of Se transmitted along the food chain. This study aims to research the transport of Se through the soil-crop-human chain in regions with different Se levels, and to establish the model between the residents' dietary Se intake and the three Se biomarkers (hair, nails, and plasma), to predict the nutritional health status of Se in residents through Se biomarkers. Carry out field and cross-sectional surveys of populations in Loujiaba Village and Longshui Village. Samples were collected from soil, crops, drinking water, residents' hair, nails, plasma, and diet. The concentration of available Se fractions was extracted from soil samples using 0.1 mol/L K2HPO4. The concentration of total Se for all samples was determined by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS), and the relative standard deviation was less than 5%. In this study, hair, nails, and blood samples were collected from volunteers according to the Declaration of Helsinki and the Ethics Committee of Soochow University. The dietary nutritional structure and dietary Se intake of the population were randomly selected by 12 volunteers using the duplicate portion method. Data were described using mean ± standard deviation. We performed saliency analysis and correlation analysis (with Pearson correlation coefficient), and fitted a regression to evaluate the associations between these variables. The soil total Se (5201 ± 609.2 μg/kg) and available Se (307.7 ± 83.5 μg/kg) in Luojiaba Village (LJB) were significantly higher than the soil total Se (229.2 ± 32.5 μg/kg) and available Se (21.9 ± 4.0 μg/kg) in Longshui Village (LS). The residents' dietary Se intake of LJB (150.3 ± 2.2 μg/d) was within the World Health Organization (WHO) recommended intake range, while LS (16.0 ± 0.4 μg/d) was close to the range of Keshan disease occurrence, and there was a risk of insufficient Se intake. The correlation analysis found significant positive correlations between residents' dietary Se intake and the three Se biomarkers. According to the preliminary model established in this study, if the daily dietary Se intake of residents reaches the WHO recommended value of 55-400 μg, the hair, nails, and plasma of Se concentration will be 522.1-2850.5 μg/kg, 1069.0-6147.4 μg/kg, and 128.3-661.36 μg/L, respectively. Selenium is transmitted through the soil-crop-human chain, and the Se concentration that enters the human body through the food chain in high-Se areas is significantly higher than that in low-Se areas. The nutritional health status of Se in the human body depends on the daily dietary intake of the human body, and there is a significant correlation between the daily dietary Se intake of the human body and the three biomarkers of Se levels in the human body, so the three biomarkers can be used to evaluate the Se nutritional health of the human.


Evaluation of the Protective Effect of Deoxyribonucleic Acid Vaccines Encoding Granule Antigen 2 and 5 Against Acute Toxoplasmosis in BALB/c Mice.
AbstractToxoplasma gondii infects a broad range of warm-blooded hosts, including humans. Important clinical manifestations include encephalitis in immunocompromised patients as well as miscarriage and fetal damage during early pregnancy. Toxoplasma gondii dense granule antigen 2 and 5 (GRA2 and GRA5) are essential for parasitophorous vacuole development of the parasite. To evaluate the potential of GRA2 and GRA5 as recombinant DNA vaccine candidates, these antigens were cloned into eukaryotic expression vector (pcDNA 3.1C) and evaluated in vaccination experiments. Recombinant DNA vaccines constructed with genes encoding GRAs were validated in Chinese hamster ovary cells before evaluation using lethal challenge of the virulent T. gondii RH strain in BALB/c mice. The DNA vaccines of pcGRA2 and pcGRA5 elicited cellular-mediated immune response with significantly higher levels of interferon-gamma, interleukin-2 (IL-2), IL-4, and IL-10 (P < 0.05) compared with controls. A mixed T-helper cell 1 (Th1)/Th2 response was associated with slightly prolonged survival. These findings provide evidence that DNA vaccination with GRA2 and GRA5 is associated with Th1-like cell-mediated immune responses. It will be worthwhile to construct recombinant multiantigen combining full-length GRA2 or/and GRA5 with various antigenic proteins such as the surface antigens and rhoptry antigens to improve vaccination efficacy.


Characterization of esophageal motility and esophagogastric junction in preterm infants with bronchopulmonary dysplasia.
To characterize esophageal motility and function of the esophagogastric junction (EGJ) in preterm infants with bronchopulmonary dysplasia (BPD). High-resolution manometry with impedance was used to investigate esophageal motility and EGJ function in 28 tube-fed preterm infants with BPD. Patients with BPD were studied at term age during oral feeding. Thirteen healthy term-aged infants were included as controls. Esophageal analysis derived objective measures to evaluate esophageal contractile vigor, bolus distension pressure, EGJ relaxation, and EGJ barrier function (in rest and during respiration). In addition, we investigated the effect of BPD severity on these measures. A total of 140 nutritive swallows were analyzed (BPD, n = 92; controls, n = 48). Normal esophageal peristaltic wave patterns were observed in all infants. BPD patients had higher distal contractile esophageal strength compared with controls (Kruskal-Wallis (KW) P = .048), and their deglutitive EGJ relaxation was comparable to controls. Severe BPD patients showed higher bolus distension pressures, higher EGJ resting pressures, and increased EGJ contractile integrals compared with mild BPD patients (Mann-Whitney U P = .009, KW P = .012 and KW P = .028, respectively). Preterm infants with BPD consistently present with normal peristaltic esophageal patterns following nutritive liquid swallows. The EGJ barrier tone and relaxation pressure appeared normal. In general, infants with BPD do not have altered esophageal motor function. There is however evidence for increased flow resistance at the EGJ in severe BPD patients possibly related to an increased contractility of the diaphragm.


[Modification of the Hungate vessel for cultivation of facultative and obligate anaerobic bacteria].
Modified Hungate vessel made of native penicillinum bottles and chemical vessels has been created and experimentally studied. The vessels can be used for cultivation of facultative and obligate anaerobe microorganisms on liquid and solid nutrient media. Locking devices of the vessel are described.


Repeated toluene and cyclohexane inhalation produces differential effects on HPA and HPT axes in adolescent male rats.
Misused volatile solvents typically contain toluene (TOL) as the main psychoactive ingredient. Cyclohexane (CHX) can also be present and is considered a safer alternative. Solvent misuse often occurs at early stages of life, leading to permanent neurobehavioral impairment and growth retardation. However, a comprehensive examination of the effects of TOL and CHX on stress regulation and energy balance is lacking. Here, we compared the effect of a binge-pattern exposure to TOL or CHX (4,000 or 8,000 ppm) on body weight, food intake, the hypothalamus-pituitary-adrenal (HPA) and hypothalamus-pituitary-thyroid (HPT) axes in male adolescent Wistar rats. At 8,000 ppm, TOL decreased body weight gain without affecting food intake. In addition, TOL and CHX altered the HPA and HPT axes' function in a solvent- and concentration-dependent manner. The highest TOL concentration produced HPA axis hyperactivation in animals not subjected to stress, which was evidenced by increased corticotropin-releasing-factor (CRF) release from the median eminence (ME), elevated adrenocorticotropin hormone (ACTH) and corticosterone serum levels, and decreased CRF mRNA levels in the hypothalamic paraventricular nucleus (PVN). TOL (8,000 ppm) also increased triiodothyronine (T3) serum levels, decreased pro-thyrotropin-releasing-hormone (pro-TRH) mRNA transcription in the PVN, pro-TRH content in the ME, and serum thyroid stimulating hormone (TSH) levels. CHX did not affect the HPA axis. We propose that the increased HPT axis activity induced by TOL can be related to the impaired body weight gain associated with inhalant misuse. These findings may contribute to a better understanding of the effects of the misused solvents TOL and CHX.


Catalytic C-H Arylation of Aliphatic Aldehydes Enabled by a Transient Ligand.
The direct arylation of aliphatic aldehydes has been established via Pd-catalyzed sp3 C-H bond functionalization in the presence of 3-aminopropanoic acids as transient directing groups. The reaction showed excellent functional group compatibility and chemoselectivity in which a predominant preference for functionalizing unactivated β-C-H bonds of methyl groups over others was achieved. In addition, C-H bonds of unactivated secondary sp3 carbons can also be functionalized. The extreme popularity and importance of aliphatic aldehydes would result in broad applications of this novel method in organic chemistry and medicinal sciences.


Coaggregation of Two Anionic Azo Dyestuffs: A Combined Static Light Scattering and Small-Angle X-ray Scattering Study.
The formation of azo dyestuff aggregates in dilute aqueous solution induced by the addition of Mg2+, Ca2+, Sr2+, or Ba2+ ions is followed by time-resolved static light scattering (SLS) and time-resolved small-angle X-ray scattering (SAXS). Time-dependent molar mass data of the growing aggregates is interpreted by means of a kinetic model introduced by Lomakin et al. ( Proc. Natl. Acad. Sci. U.S.A. 1996 , 93 , 1125 ) for the description of β-amyloid aggregation. This interpretation reveals significant trends within the homologous series of alkaline earth cations. The trends refer to the nucleation and the growth rate of the dyestuff fibers. Time-resolved SAXS experiments indicate that these first two stages are followed by a third one during which a network forms by partial lateral alignment of fibers. At high enough dyestuff concentrations, this network formation even leads to a gel-like phase. Anomalous SAXS (ASAXS) on such a gel phase formed upon the addition of Sr2+ revealed the extent of neutralization of the dyestuff molecules within the gel by the specifically interacting alkaline earth cations.


Performance of Broilers Supplemented With Peppermint ( Mentha piperita L.) Powder.
This study was conducted to determine the effects of dietary supplementation of peppermint ( Mentha piperita L.) on the performance of broiler chicks. 500 Ross broiler chicks were divided into 5 treatment groups of 4 replications in a completely randomized design format. The diets were ISO-caloric and ISO-nitrogenous ones and contained 1.5, 3, 4.5, and 6 g/kg of peppermint powder. At start, growing, and end periods, the effects of peppermint powder on average daily weight gain, feed conversation ratio, and mortality rate were studied. The results of the present study showed that over a production period of 42 days peppermint had a significant effect on average daily weight gain and feed conversation ratio when compared with the control group ( P < .05). The level of 4.5 g/kg had the highest average daily weight gain (52.78 g), and control treatment with 46.98 g had the least average daily weight gain among different levels of peppermint. The level of 4.5 g/kg and 6 g/kg of peppermint had the least mortality compared to control treatment during training period ( P < .05). From this experiment, we can conclude that treatment with 4.5 g/kg peppermint powder has better performance and carcass characteristics in broilers.


[Comparative study of the mutagenic activity of dicurin on five test-objects].
Mutagenic activity of dicourol belonging to coumarol derivatives has been studied on 5 test-objects (mice, cultivated lymphocytes of human blood, yeast-saccharomycetes, Tradescantia, Crepis). Results of investigations allowed attributing dicourol to highly hazardous mutagens. In this connection it is admitted unadvisable to enforce it into agricultural practice. The tested objects differ in their dicourol mutagenic sensibility as follows: cultivated lymphocytes of human blood - Tradescantia - yeast - Crepis - mice.


Dartmouth's next generation EIS system: preliminary hardware considerations.
Our previous system covered the frequency range of 0 to 1 MHz. In this new design we propose to cover the range from 0 to 10 MHz. The higher frequencies have forced us to reconsider several design decisions in view of both the physics of the problem and the performance of available electronic components. In this presentation we examine in detail the constraints faced by the designer, starting from wiring consideration to measurement techniques. We will also present the solutions we selected to overcome the limitations we discovered. The problems include phase detection, amplitude measurements, system organization and layout and finally system calibration.


[Treatment of ascites in cirrhotic patients].
Ascites is the most frequent complication of hepatic cirrhosis and its appearance brings a reduction of survival. The treatment aims to mobilise the intraperitoneal liquid and to prevent its reaccumulation. The first step of treatment includes rest in bed, a hyposodic and spironolactone diet, alone or in combination with furosemide or torasemide. However, 10-20% of patients do not respond to treatment or develop adverse effects that limit its use, which is termed refractory ascites. These patients must be considered as possible candidates for a liver transplant and, when this is not possible, the chosen treatment is total paracentesis with an intravenous infusion of albumin. In patients who do not tolerate paracentesis, or who require its realisation with great frequency, other therapeutic options can be evaluated, such as surgical anastomoses, intrahepatic portosystemic percutaneous derivation and, in the final instance, peritoneo-venous shunt.


The need for drug and poison information--the Singapore physicians' perspective.
There appears to be a significant prevalence of poisoning and adverse drug reactions in Singapore. However, the resources needed by physicians to assist them in the management of such cases are limited. This study examines the information resources currently utilised by medical professionals in assisting them in the management of poisonings and adverse drug reactions. The preferred features of an ideal Drug and Poison Information Centre in the local setting were also explored. A questionnaire survey involving all practicing physicians in Singapore to find out the current information resources utilised for Drug and Poison Information and the need for enhanced resources and its preferred form was looked at. A total of 1,071 practicing physicians responded forming 24% of all physicians in Singapore as of December 1997. Of these, 636 (61.3%) were general practitioners and the rest specialists. The main sources of poison information were Drug Index of Malaysia and Singapore or DIMS (73.7%), standard textbooks (70.1%), fellow colleagues (44.6%) and pharmacists (41.0%). In the opinion of most (82.4%), one well run and efficient Drug and Poison Information Centre was adequate for the whole island. The majority (58.9%) preferred that experienced individuals who could be consulted upon in times of need man such a service. The study shows the need for enhanced drug and poison information resources. The local physician community also expects guidance and expert advice from a specialist. With this in mind, it is worthwhile examining in depth the issues surrounding poison and adverse drug reaction management and the need for readily accessible Drug and Poison Information resources in Singapore.


Liver-Targeting Composite Nanocarrier Delivery System Based on Chitosan Nanoparticles and Phospholipid Complexes.
Liver fibrosis is mainly caused by excessive accumulation of extracellular matrix and structural changes in the liver, ultimately leading to cirrhosis if left untreated. Reducing hyaluronan synthesis by inhibiting hyaluronic acid deposition or regulating the expression of hyaluronic synthase can ameliorate liver fibrosis symptoms. In this study, we aimed to improve the bioavailability and liver-targeting capacity of hydroxymethyl coumarin (4-MU) using a newly developed phospholipid complex chitosan nanoparticle (4-MU PC/CNP) optimized using the Box-Behnken design. The composite nanocarrier delivery system was formulated using solvent evaporation technology, and formulation and process parameters were evaluated. Furthermore, 4-MU PC/CNPs and their pharmacokinetics were characterized. The established 4-MU PC/CNPs had an average particle size of 153.07 ± 0.29 nm, a polydispersity index value of 0.383, and a positive zeta potential of ∼35.4 mV. Compared with 4-MUs, 4-MU PC/CNPs exhibited significantly improved water solubility, faster plasma clearance and tissue distribution, and better liver targeting. Pharmacokinetic analysis showed that the oral bioavailability of 4-MU in 4-MU PC/CNPs was significantly higher than that of simple 4-MU. In conclusion, 4-MU PC improved drug lipid (oil-water distribution coefficient of 1.31 ± 0.03) and water solubilities (2.05 times the drug substance). 4-MU PC/CNPs significantly improved 4-MU oral bioavailability, representing a promising approach for enhancing drug solubility. This study demonstrates that the targeting parameters of 4-MU PC/CNPs in the liver were all greater than 1, indicating that they specifically targeted the liver, thereby potentially alleviating liver fibrosis.


Factors responsible for target site selection in Tn10 transposition: a role for the DDE motif in target DNA capture.
Tn10, like several other transposons, exhibits a marked preference for integration into particular target sequences. Such sequences are referred to as integration hotspots and have been used to define a consensus target site in Tn10 transposition. We demonstrate that a Tn10 hotspot called HisG1, which was identified originally in vivo, also functions as an integration hotspot in vitro in a reaction where the HisG1 sequence is present on a short DNA oligomer. We use this in vitro system to define factors which are important for the capture of the HisG1 target site. We demonstrate that although divalent metal ions are not essential for HisG1 target capture, they greatly facilitate capture of a mutated HisG1 site. Analysis of catalytic transposase mutants further demonstrates that the DDE motif plays a critical role in 'divalent metal ion-dependent' target capture. Analysis of two other classes of transposase mutants, Exc+ Int- (which carry out transposon excision but not integration) and ATS (altered target specificity), demonstrates that while a particular ATS transposase binds HisG1 mutants better than wild-type transposase, Exc+ Int- mutants are defective in HisG1 capture, further defining the properties of these classes of mutants. Possible mechanisms for the above observations are considered.


N-Glycosylation engineering of lepidopteran insect cells by the introduction of the beta1,4-N-acetylglucosaminyltransferase III gene.
The baculovirus-insect cell expression system is in widespread use for expressing post-translationally modified proteins. As a result, it is potentially applicable for the production of glycoproteins for therapeutic and diagnostic purposes. For practical use, however, remodeling of the biosynthetic pathway of host-cell N-glycosylation is required because insect cells produce paucimannosidic glycoforms, which are different from the typical mammalian glycoform, due to trimming of the non-reducing terminal beta1,2-GlcNAc residue of the core structure by a specific beta-N-acetylglucosaminidase. In order to establish a cell line which could be used as a host for the baculovirus-based production of glycoproteins with mammalian-type N-glycosylation, we prepared and characterized Spodoptera frugiperda Sf21 cells that had been transfected with the rat cDNA for beta1,4-N-acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of a bisecting GlcNAc. As evidenced by structural analyses of N-glycans prepared from whole cells and the expressed recombinant glycoproteins, the introduction of GnT-III led to the production of bisected hybrid-type N-glycans in which the beta1,2-GlcNAc residue at the alpha1,3-mannosyl branch is completely retained and which has the potential to be present in mammalian cells. These results and other related findings suggest that bisected oligosaccharides are highly resistant to beta-N-acetylglucosaminidase activity of the S. frugiperda fused lobes gene product, or other related enzymes, which was confirmed in Sf21 cells. Our present study demonstrates that GnT-III transfection has the potential to be an effective approach in humanizing the N-glycosylation of lepidopteran insect cells, thereby providing a possible preliminary step for the generation of complex-type glycoforms if the presence of a bisecting GlcNAc can be tolerated.


Impassable YscP substrates and their impact on the Yersinia enterocolitica type III secretion pathway.
Yersinia type III machines secrete protein substrates across the bacterial envelope and, following assembly of their secretion needles, transport effector Yops into host cells. According to their destination during type III secretion, early, middle, and late secretion substrates can be distinguished; however, the signals and mechanisms whereby these proteins are recognized and transported by the secretion machine are not understood. Here, we examine several hybrids between secretion substrates and the impassable reporter protein glutathione S-transferase (GST). YscP-GST and YopR-GST blocked type III secretion; however, YscF-, YopD-, YopN-, and LcrV-GST did not. Unlike YopR-GST, which can block type III machines only during their assembly, expression of YscP-GST led to an immediate and complete block of all secretion. The secretion signal of YscP was mapped to its first 10 codons or amino acids; however, YscP(Delta 2-15)-GST, lacking this secretion signal, imposed a partial blockade. YscP-GST copurified with the type III ATPase complex (YscN, YscL, and YscQ) and with YscO, suggesting that the association of specific machine components with the impassable substrate may cause the block in type III secretion.


Physical activity: A primary health quality determinant among community-dwelling geriatric women in Taiwan.
To investigate the associations between frailty, physical activity and depression in community-dwelling geriatric women. A cross-sectional research design. Community geriatric women in Illan County, Taiwan. Of note 216 participants, 65 years and older with full mobility, independent and able to communicate in Mandarin or Taiwanese Hokkien. An average weekly physical activity score International Physical Activity Questionnaire-Short Form (IPAQ-SF) and Taiwan Geriatric Depression Scale. Classification and regression tree (CART) analysis was used to perform decision analysis. The average IPAQ-SF score for the 216 participants was 9109.52. When an IPAQ-SF score of 4452 or below was obtained by participants, 38% of them encountered depression-like syndromes, regardless of their frailty status. Diabetes, high risk of metabolic syndrome and lower education were the risk factors found to cause depression among participants with low physical activity levels. As women have a longer life expectancy and experience twice the rates of depression of men particularly after menopause, healthcare providers should emphasize exercise and lifestyle changes in order to improve the quality of health in geriatric women.


Effect of glucagon on hepatic taurocholate uptake: relationship to membrane potential.
Since glucagon can hyperpolarize hepatic plasma membrane and stimulate biliary bile acid secretion in vitro, we studied the effect of glucagon on taurocholate uptake and its relationship to plasma membrane potential in isolated rat hepatocytes. [14C]taurocholate uptake was linear through 1 min and contained a saturable sodium-dependent and a nonsaturable sodium-independent component. Km of taurocholate uptake by the sodium-dependent system was 18.4 microM. Hill coefficient for Na+ was 2.59 and for taurocholate was 1.1, suggesting that the stoichiometry is 2 Na+:1 bile acid. Stimulation of taurocholate uptake by glucagon was limited to the sodium-dependent component, detected within 5 min of hormone exposure, and was maximum at 30 min. Glucagon, from 10(-8) to 10(-5) M, stimulated taurocholate uptake and hyperpolarized concurrently the plasma membrane potential. Because valinomycin produced a dose-related depolarization of plasma membrane potential, this agent was used to counteract the effects of glucagon. With 10(-6) M glucagon, valinomycin (10(-10) M) depolarized membrane potential from -35.50 to -28.00 mV and inhibited taurocholate uptake from 60% above the control rate to 5% below. These data strongly suggest that taurocholate uptake by isolated hepatocytes is an electrogenic process, and its stimulation by glucagon may be mediated by changes in plasma membrane potential.


Prenatal glucocorticoid overexposure causes permanent increases in renal erythropoietin expression and red blood cell mass in the rat offspring.
Glucocorticoids promote maturation of fetal systems, including erythropoiesis, in preparation for extrauterine life. However, recent studies have shown that prenatal glucocorticoid excess can cause long-term deleterious cardiometabolic and other consequences to the offspring. Here, we examined the effect of prenatal treatment with the synthetic glucocorticoid dexamethasone (DEX) during the last week of gestation on red blood cell (RBC) mass in the rat offspring. DEX-treated offspring at 9 months of age had significantly higher RBC count (9.4 ± 0.1 vs. 8.8 ± 0.2 × 10(12) liter; P = 0.02), hematocrit (50.0 ± 0.5 vs. 46.7 ± 0.7%; P=0.004), hemoglobin (17.3 ± 0.2 vs. 16.2 ± 0.2 g/dl; P = 0.02) and number of reticulocytes (258.2 ± 8.8 vs. 235.7 ± 5.6 × 10(9) liter; P = 0.04), compared with offspring of vehicle-treated control pregnancies. White blood cells and platelets were unaltered. Renal mRNA expression and plasma concentrations of erythropoietin, the main regulator of erythropoiesis, were increased by nearly 100% in both newborn and adult DEX-treated rats (P < 0.01). This increase was accompanied by marked elevation in renal expression of hepatocyte nuclear factor 4α mRNA, whereas other erythropoietin-regulating transcription factors, such as hypoxia-inducible factor 1, hypoxia-inducible factor 2, and GATA2 were unchanged. These data indicate that RBC mass can be programmed by prenatal glucocorticoid excess, and if extrapolatable to humans, provide a novel mechanism for fetal origins of polycythemia and its associated complications.


[Incompetence of duodenal stump sutures after stomach resection in ulcer disease].
Among 356 gastric resections of the Billroth 11 type performed for ulcerous disease there were 11 cases of suture incompetency of the duodenal stump (3.1%). This complication was mainly caused by technical difficulties arising in operations under complicated anatomical conditions and tactical errors of a surgeon in selection of the technic of the stump suturing. The treatment of the duodenal stump suture incompetency consisted in urgent relaparotomy with a tramponade and drainage at the site of incompetency and application of a complex of conservative measures. During the first days after relaparotomy a drainage is connected into a pump-aspirator. In case of complicated duodenal ulcers resection with the aim of "ulcer exclusion" seems to be rational.


Long-lasting decreased pain threshold negatively affects functional recovery after arthroscopic rotator cuff repair.
The relationship between sensitization and postoperative function in patients undergoing arthroscopic rotator cuff repair (ARCR). The purpose of this study was to evaluate the effect of pre-and postoperative reductions in the pressure pain threshold (PPT) on postoperative clinical outcomes in patients with ARCR and investigate changes in PPT and clinical outcomes resulting from postoperative administration of weak opioids activating the central inhibitory system. This retrospective study included patients who underwent primary ARCR, categorized into Group A (excellent/good Constant scores) and B (fair/poor Constant scores). In a complementary study, patients were randomized to the Control or Tramadol groups. Both studies evaluated the PPT, visual analog scale, active range of motion (ROM), Constant score, and retear rates pre-and postoperatively. In the primary study with 158 patients, those with poor clinical outcomes exhibited significantly lower PPT at the affected shoulder preoperatively at 3 months postoperatively compared to those with good outcomes. The PPT of the affected side was lower than that of the uninvolved side not only at 1 and 3 months but also preoperatively and at 6 months in the poor outcome group. In the secondary study involving 96 patients, weak opioid administration was associated with increased PPT for 3 months, improved ROM at 3 months postoperatively, and reduced postoperative pain 1 year postoperatively. Patients experiencing poor postoperative clinical outcomes exhibited prolonged lowered PPT. Lowered PPT due to sensitization may adversely affect functional recovery and pain perception. Elevating PPT using weak opioids improved clinical outcomes during the acute perioperative period after ARCR. III.


Three viologen-derived Zn-organic materials: photochromism, photomodulated fluorescence, and inkless and erasable prints.
Three zinc-viologen compounds, namely, {[Zn(Mebpy)(Hbtc)Cl]·2H2O}n (1), {[Zn3(Cebpy)2(Hbtc) (H2btc)2 (OH)2]·4H2O}n (2), and {[Zn4(Cebpy)2(IPA)3(OH)2]·2H2O}n (3) (Mebpy = N-methyl-4,4'-bipyridinium, Cebpy = N-carboxyethyl-4,4'-bipyridinium, H3btc = 1,3,5-benzenetricarboxylic acid, and H2IPA = isophthalic acid) have been constructed from aromatic carboxylic acid and viologen-derived ligands. In compound 1, the Hbtc2- ligands bridge Zn2+ cations to form a 1D fence-like chain with the Mebpy+ ligand suspended on the chains. Compound 2 possesses a 2D (4, 4) double-layered grid structure based on linear trinuclear Zn3O2 cluster units. The structure of compound 3 can be described as a 3D open-framework based on tetranuclear Zn4O2 cluster units and helical chains with helical channels. All three compounds display photochromic properties from pale yellow to dark blue after being irradiated by a xenon lamp with different photoresponsive rates. Compounds 2 and 3 can be deposited in paper simply by coating them with a solution of ethanol. The papers can be used as inkless and erasable print media. In addition, the photo-modulated luminescence of these compounds was also investigated.


Potential benefit of retrospective use of neutron monitors in improving ionising radiation exposure assessment on international flights: issues raised by neutron passive dosimeter measurements and EPCARD simulations during sudden changes in solar activity.
Since air transport became more accessible, more and more people have been exposed to ionising radiation of cosmic origin. Measuring the neutron dose equivalent is a good approximation of total ambient dose equivalent, as neutrons carry about 50 % of the dose at flight altitudes. The aim of our study was to compare our measurements of the neutron component of secondary cosmic radiation dose, taken with passive dosimeters, with the data obtained from a simulation generated by EPCARD software, which is common in assessing flight crew exposure to ionising radiation. We observed deviations (both above and below) from the expected proportion of the neutron component (between 40 and 80 %), which pointed to certain issues with actual passive dosimeter measurement and the EPCARD simulation. The main limitation of the dosimeter are large uncertainties in high energy neutron response, which may result in underestimation of neutron dose equivalent. The main drawback of the software simulation is monthly averaging of solar potential in calculations, which can neglect sporadic high energy events. Since airlines worldwide almost exclusively use software (due to costs and convenience) to estimate the dose received by their crew, it is advisable to retrospectively recalculate the dose taking into account neutron monitor readings when solar activity changes.


Prerequisites for providing effective support to family caregivers within the primary care setting - results of a study series in Germany.
General Practitioners are considered to be well placed to monitor home-care settings and to respond specifically to family caregivers. To do this, they must be sensitive to the needs and expectations of caregivers. In order to determine the current status of GP care in terms of the support given to family caregivers, a series of studies were conducted to gather the perspectives of both caregivers and GPs. The results are used to derive starting points as to which measures would be sensible and useful to strengthen support offered to family caregivers in the primary care setting. Between 2020 and 2021, three sub-studies were conducted: a) an online survey of 612 family caregivers; b) qualitative interviews with 37 family caregivers; c) an online survey of 3556 GPs. Family caregivers see GPs as a highly skilled and trustworthy central point of contact; there are many different reasons for consulting them on the subject of care. In the perception of caregivers, particular weaknesses in GP support are the absence of signposting to advisory and assistance services and, in many cases, the failure to involve family caregivers in good time. At the same time, GPs do not always have sufficient attention to the physical and psychological needs of family caregivers. The doctors interviewed consider the GP practice to be well suited to being a primary point of contact for caregivers, but recognise that various challenges exist. These relate, among other things, to the timely organisation of appropriate respite services, targeted referral to support services or the early identification of informal caregivers. GP practices can play a central role in supporting family caregivers. Caregivers should be approached by the practice team at an early stage and consistently signposted to help and support services. In order to support care settings successfully, it is important to consider the triadic constellation of needs, wishes and stresses of both the caregiver and the care recipient. More training and greater involvement of practice staff in the support and identification of caregivers seems advisable.


Hereditary methemoglobinemia due to cytochrome b5 reductase deficiency in blood cells without associated neurologic and mental disorders.
Following the observation of two fraternal patients without neurologic symptoms, but with hereditary methemoglobinemia due to cytochrome b5 reductase deficiency in erythrocytic and nonerythrocytic cells, a familial study of their paternal and maternal relatives was undertaken. Ferrihemoglobin reductase activities in erythrocytes from the two patients were found to be impaired, and cytochrome b5 reductase activities in platelets and leukocytes were essentially absent. Any deficiencies of the enzyme activities seemed not to be found in nonhematopoietic cells. The enzyme activities in blood cells derived from the parents and some of their paternal and maternal family members showed levels intermediate between those of the patients and those of the normal control, which seemed to be heterozygous. The present cases did not belong to either the classic erythrocytic or the generalized type, and their enzyme deficiency was found rather to be restricted to their blood cells and not associated with neurologic and mental disorders. A necessity of diagnosis by tissues other than blood cells is discussed for a severe form of generalized-type hereditary methemoglobinemia with associated neurologic and mental disorders.


Supportive follow-up in patients treated with radical intent for high-grade glioma.
Ongoing supportive follow-up for patients with malignant glioma lacks good evidence to define and guide practice, and certain approaches have previously been criticized. In the UK, it commonly involves routine hospital visits with imaging to monitor treatment effects and detect disease progression. Through use of an observational study evaluate and compare oncologist-led follow-up with a multidisciplinary group follow-up method from the perspective of patients and caregivers. A total of 40 patients, and 32 of their caregivers, were recruited 3 months after completing radical radiotherapy treatment. Face-to-face interviews conducted at home with patients gathered information about access to and experiences of follow-up services. Standardized questionnaires measured patients' quality of life and unmet care needs, and caregivers' psychological wellbeing. Assessment was repeated three times over a 6-month period. Inevitable attrition left 26/40 patients and 19/32 caregivers with complete data. Most (65%) patients' quality of life improved or was maintained over the study period. However, psychological support for patients and caregivers was suboptimal, notably 56% of caregivers had probable psychiatric morbidity. Though few significant differences were found between the two follow-up methods, multidisciplinary follow-up provided better continuity of care and more efficient test result provision. Innovative interventions are required to ameliorate psychological distress in patients and caregivers.


Rapid differential diagnosis of cerebral toxoplasmosis and primary central nervous system lymphoma by thallium-201 SPECT.
This study sought to assess whether 201Tl brain SPECT can significantly reduce the time required for the differential diagnosis of primary central nervous system (CNS) lymphoma and cerebral toxoplasmosis in patients with AIDS. Eighteen patients who presented with focal lesions on CT or MRI, or both, underwent 201Tl brain SPECT shortly after admission and before a CT-guided stereotactic brain biopsy. Early and delayed 201Tl uptake ratios were obtained for patients with positive 201Tl study results, and the retention index of 201Tl was calculated. Ten patients had 11 foci of significantly increased 201Tl uptake in regions of corresponding CT/MRI lesions. Five of these patients had biopsy-proven lymphomas, one of them in two separate foci. Another patient was found to have metastatic adenocarcinoma. Three patients had a clinical course and response to radiation therapy consistent with lymphoma, and study results in another patient were considered falsely positive. Of nine patients with no 201Tl uptake in regions of CT/MRI lesions, two had biopsy findings consistent with a benign etiology, and the other seven improved clinically on antitoxoplasmosis medications alone. The overall sensitivity of 201Tl brain SPECT was 100%, and specificity was 90%. The 201Tl retention index in patients with lymphomas was significantly higher than that in patients with adenocarcinomas and nonmalignant lesions (1.35 +/- 0.16 versus 0.24 and 0.56, respectively). Thallium-201 brain SPECT is a sensitive and specific method for rapid differential diagnosis of CNS lymphoma and toxoplasmosis in patients with AIDS. The 201Tl retention index is useful in differentiating CNS lymphomas from other malignant and nonmalignant pathologies.


Predictors of Mortality in Dementia: The PRIME Study.
Dementia is a terminal illness. While various baseline characteristics of patients, such as age, sex, and dementia severity, are known to predict mortality, little research has examined how changes in patients' symptoms over time predict survival. There are also limited data on patients seen in memory clinics, as opposed to other health care settings, and whether antipsychotic medications are associated with mortality in dementia once patients' demographic and clinical features are controlled for. To identify predictors of mortality in patients with dementia. Of 970 patients recruited from nine memory clinics around Australia, 779 patients had dementia at baseline. Patients completed measures of dementia severity, cognition, functional ability, neuropsychiatric symptoms, caregiver burden, and medication use at baseline and at regular intervals over a three-year period. Mortality data were obtained from state registries eight years after baseline. Overall, 447 (57.4%) of the patients with dementia died within the eight years. Older age, male sex, more severe dementia and functional impairment at baseline, greater decline in dementia severity and functional impairment over six months, taking a larger number of medications, and use of atypical antipsychotic medication predicted earlier mortality. The findings confirm that demographic and diagnostic features predict the survival of patients with dementia. Importantly, the findings indicate that changes in dementia severity and functional impairment over time predict mortality independently of baseline levels, and provide further evidence for the higher mortality risk of patients taking antipsychotic medications.


Increase in body size is correlated to warmer winters in a passerine bird as inferred from time series data.
Climate change is expected to affect natural populations in many ways. One way of getting an understanding of the effects of a changing climate is to analyze time series of natural populations. Therefore, we analyzed time series of 25 and 20 years, respectively, in two populations of the citril finch (Carduelis citrinella) to understand the background of a dramatic increase in wing length in this species over this period, ranging between 1.3 and 2.9 phenotypic standard deviations. We found that the increase in wing length is closely correlated to warmer winters and in one case to rain in relation to temperature in the summer. In order to understand the process of change, we implemented seven simulation models, ranging from two nonadaptive models (drift and sampling), and five adaptive models with selection and/or phenotypic plasticity involved and tested these models against the time series of males and females from the two population separately. The nonadaptive models were rejected in each case, but the results were mixed when it comes to the adaptive models. The difference in fit of the models was sometimes not significant indicating that the models were not different enough. In conclusion, the dramatic change in mean wing length can best be explained as an adaptive response to a changing climate.


Impact of endolymphatic mastoid shunt surgery on saccule and lateral semicircular canal function.
Endolymphatic mastoid shunt surgery (EMSS) is widely performed in patients with medically intractable Meniere's disease. Although many patients report an improvement of symptoms after surgery, the mechanisms which are responsible for the relief of complaints are not known. To date, only few studies exist which studied the influence of EMSS on vestibular function. The present study examines the effect of EMSS on saccule function by measuring vestibular evoked myogenic potentials and the effect on lateral semicircular canal function by sinusoidal harmonic acceleration (SHA) testing. No changes in vestibulo-collic reflexes were found after surgery compared to before surgery. SHA testing resulted in comparable phase lag and gain pre- and postoperatively. Although central compensation is clinically evident no effect in specific vestibular diagnostic testing is seen. Modulations of canal-otolith interaction might suggest a change of symptoms. The only method so far to evaluate the success of EMSS is the patient's subjective assessment.