Examining the Utility of a Telehealth Warm Handoff in Integrated Primary Care for Improving Patient Engagement in Mental Health Treatment: Randomized Video Vignette Study.
A warm handoff from a physician to a mental health provider is often patients' first contact with psychological services and provides a unique opportunity for improving treatment engagement in integrated primary care (IPC) settings. In light of the COVID-19 pandemic, this study sought to examine the impact of different types of telehealth mental health referrals on both the anticipated likelihood of accepting treatment services and anticipated likelihood of continued treatment engagement. A convenience sample of young adults (N=560) was randomized to view 1 of 3 video vignettes: warm handoff in IPC, referral as usual (RAU) in IPC, or RAU in standard primary care. Logistic associations between referral type and the likelihood of referral acceptance (χ21=10.9, P=.004) and the likelihood of continued engagement (χ21=32.6, P<.001) were significant. Participants who received a warm handoff were significantly more likely to anticipate both accepting the referral (b=0.35; P=.002; odds ratio 1.42, 95% CI 1.15-1.77) and engaging in continued treatment (b=0.62; P<.001; odds ratio 1.87, 95% CI 1.49-2.34) compared with those who received RAU in the standard primary care condition. Furthermore, 77.9% (436/560) of the sample indicated that they would be at least somewhat likely to access IPC mental health services for their own mental health concerns if they were readily available in their own primary care physician's office. A telehealth warm handoff resulted in the increased anticipated likelihood of both initial and continued engagement in mental health treatment. A telehealth warm handoff may have utility in fostering the uptake of mental health treatment. Nonetheless, a longitudinal assessment in a primary care clinic of the utility of a warm handoff for fostering referral acceptance and continued treatment engagement is needed to hone the adoptability of a warm handoff process and demonstrate practical evidence of effectiveness. The optimization of a warm handoff would also benefit from additional studies examining patient and provider perspectives about the factors affecting treatment engagement in IPC settings.


Lack of group X secreted phospholipase A₂ increases survival following pandemic H1N1 influenza infection.
The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX(-/-)) model and found that survival after infection was significantly greater in GX(-/-) mice than in GX(+/+) mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX(-/-) mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX(-/-) mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.


Binding affinity of hydroxamate inhibitors of matrix metalloproteinase-2.
Here we report molecular dynamics (MD) and free energy perturbation (FEP) simulations applied to hydroxamate-matrix metalloproteinase-2 (MMP-2) complex systems. We have developed some new force field parameters for the hydroxamate functional group that were not included in the AMBER94 force field but were necessary in our simulations. For the representation of the active zinc center, a bonded model was adopted in which restrained electrostatic potential fitting (RESP) charges were used as the electrostatic representation of this model. Using the resulted bonded model, FEP simulations predict the relative binding free energy in good agreement with the experimental value. By analyzing the molecular dynamics (MD) trajectories of the two complex systems, we can provide an explanation of why one of the two inhibitors is favored over the other. The results provide a chemical insight into the interactions between inhibitor and enzyme, and can indicate changes in the inhibitor that would enhance inhibitor-enzyme interactions.


Adaptation of Functioning After Pediatric Cochlear Implantation (FAPCI) into Hindi Language.
FAPCI is a parent/caregiver reporting questionnaire, which evaluates the communication performance of pre-school children with cochlear implants in the age range of 2-5 years, using behavioral examples of children's daily activities. Tools for the objective and effective measurement of communication for cochlear implanted Indian children in Hindi language are lacking. The primary aim of the study was to adapt American English version of FAPCI into the Hindi language. With a secondary aim to find out the communication functioning of Cochlear implanted children by administering FAPCI (HN) and comparing the findings with children with normal hearing. The FAPCI was translated to Hindi using the forward-backward procedure. The FAPCI (HN) was then administered to the parents of children with NH (n = 35) and CI (n = 44), 2-9 years of age. Internal consistency was checked using Cronbach's alpha. Other statistical analysis included Bartlett's test of sphericity, factor loading, Wilcoxon test and t test. During adaptation few items were modified and one item was removed which contained "inversion question" not used in Hindi language. The Hindi version of FAPCI showed excellent internal consistency (Cronbach's alpha > 0.90). The split-half coefficient for the first half of the data was equal to 0.96 and for the second half was equal to 0.95. The CI group had significantly lower FAPCI scores (61.14 ± 21.49) than the NH group (101.43 ± 9.24) (p < 0.05, Wilcoxon test). FAPCI-Hindi can be used to measure the communicative functioning of cochlear implanted children in Indian population and results may be used as a guideline to revise the speech and language therapy plans to maximize the cochlear implant benefits.


Subchronic effects of 2,3,7,8-TCDD or PCBs on thyroid hormone metabolism: use in risk assessment.
Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), or 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156) on thyroid hormone metabolism were studied in 13-week feeding studies in female Sprague-Dawley rats. The diets were supplemented with the compounds tested at concentrations ranging from 0.2 to 20 micrograms/kg diet for TCDD, 7 to 180 micrograms/kg diet for PCB 126, or 1.2 to 12 mg/kg diet for PCB 156, respectively. Significant correlations were found for all three compounds between reductions in plasma total thyroxine (TT4) levels and inductions of the microsomal phase II enzyme UDP-glucuronosyltransferase by using T4 as a substrate (T4UGT). Furthermore, the coinduction of certain phase I and II isozymes, i.c., cytochrome P450 1A1 (CYP1A1) and UGT1A1, by these compounds, clearly suggests the involvement of an Ah receptor-mediated mechanism in the disturbance of thyroid hormone metabolism by these polyhalogenated aromatic compounds. These results provide a mechanistic base for the use of certain effects on thyroid hormone metabolism by polyhalogenated aromatic compounds in risk assessment. By using these effects, potencies of PCB 126 and PCB 156 relative to TCDD ranged from 0.008 to 0.1 for PCB 126, and from 0.00007 to 0.004 for PCB 156, respectively. These values correspond very well with relative potencies of PCB 126 and PCB 156 by using some other well-known Ah receptor-mediated toxic and biochemical parameters.


Apolipoprotein E4 Suppresses Neuronal-Specific Gene Expression in Maturing Neuronal Progenitor Cells Exposed to HIV.
The apolipoprotein ε4 gene allele and the apolipoprotein E4 protein (ApoE4) are important host susceptibility factors linked to neurocognitive disorders associated with HIV infection or Alzheimer's disease. Our previous studies showed differential effects of the two most common human ApoE genotypes, APOE3/3 and APOE3/4, on gene expression by differentiating human neuroepithelial progenitor cells continuously exposed to HIV. To investigate the effects of ApoE3 versus ApoE4 isoforms specifically on maturing neurons, we adapted a human neuronal progenitor cell line, hNP1, with ApoE genotype APOE3/3. Differentiating hNP1 cells were exposed for 16 days to HIV- or mock-infected supernatants and to added recombinant ApoE isoforms rApoE3 or rApoE4 to modulate the ApoE phenotype of the cells. Gene expression was investigated using microarray and functional genomics analyses. Added rApoE3 differentially affected 36 genes. Added rApoE4 differentially affected 85 genes; 41 of which were differentially expressed only in HIV or mock-supernatant treated cells, and 80% of which were downregulated. Genes differentially downregulated only by rApoE4 represented multiple neuronal functions related to neurogenesis. Approximately five times more genes were differentially enriched by rApoE4 versus rApoE3 in the Gene Ontology (GO) cellular process analysis, with 4 orders of magnitude greater significance. Half of the top 10 GO processes affected by rApoE4 treatment were neurogenesis-related. The largest differences in gene expression between the two isoforms were observed within the HIV-exposed cultures, suggesting that HIV exposure magnifies ApoE4's suppressive effect on neuronal gene expression. This study provides evidence for neuronal-specific responses to ApoE4 that could affect neurogenesis and neuronal survival.


Deprivation level and choice in pigeons: a test of within-trial contrast.
Within-trial contrast has been proposed as a mechanism underlying preferences for stimuli that follow relatively more aversive events over stimuli that follow less aversive events. In this study, we manipulated deprivation level to test within-trial contrast predictions. In Experiment 1, pigeons encountered two discriminative stimuli, one presented when they were deprived and the other when they were prefed. When later given a choice between the two stimuli, pigeons strongly preferred the stimulus encountered when deprived, independently of their deprivation level at test. In Experiment 2, pigeons learned two simultaneous discriminations, one when deprived and the other when prefed. Here, subsequent tests between the two S+ or the two S- stimuli revealed no consistent preferences. These contrasting findings suggest that differential aversiveness is necessary but not sufficient to induce preferences via within-trial contrast.


Molecular design of "super" hydrogelators: understanding the gelation process of azobenzene-based sugar derivatives in water.
[structure: see text]. 1: R = beta-D-glucopyranoside. 2: R = alpha-D-glucopyranoside. 3: R = alpha-D-galactopyranoside. 4: R = alpha-D-mannopyranoside. As an attempt to rationally design aqueous organogelators, a bolaamphiphilic azobenzene derivative (1) bearing two sugar groups was synthesized. Compound 1 formed a gel in water even at concentrations as low as 0.05 wt % (0.65 mM). Spectroscopic studies and electron-micrographic observations have clarified the gel structure and the origin of the gelation ability for water.


An experimental procedure to perform mechanical characterization of small-sized bone specimens from thin femoral cortical wall.
The cortical shell of the femoral neck plays a role in determining the overall neck strength. However, there is a lack of knowledge about the mechanical properties of cortical tissue of the femoral neck due to challenges in implementing accurate testing protocols for the thin shell. Indeed, mechanical properties are commonly derived from mechanical testing performed on tissue samples extracted from the femoral diaphysis, i.e. assuming tissue homogeneity along the femur. The aim of this work was to set up a reliable methodology to determine mechanical properties of bone samples extracted from thin cortical shell of the femoral neck. A three-point bending test was used to determine elastic and post-elastic properties of cortical bone samples extracted from the inferior and superior femoral neck. An optical system was used to monitor the sample deflection. Accuracy was preliminarily evaluated by determining the elastic modulus of an aluminium alloy. A good intra- and inter-sample variability was found on determining aluminium elastic modulus: 1.6% and 3.6%, respectively. Additionally, aluminium elastic modulus value was underestimated by less than 1%. A pilot trial was performed on a human femoral neck to assess the procedure feasibility. A total of 22 samples were extracted from the inferior and superior femoral neck and successfully tested. Preliminary results suggest that mechanical properties of cortical bone tissue extracted from human femoral neck might be side dependent, the superior tissue seems to exhibit better mechanical properties than the inferior one, at least in terms of yield stress and maximum strain. This supposedly different mechanical competence must be further investigated. The proposed procedure makes it feasible to carry out such studies.


Comparison of incremental and accelerating protocols of the rotarod test for the assessment of motor deficits in the 6-OHDA model.
The rotarod test, in which animals must balance on a rotating drum, is widely used to assess motor deficit in neurodegenerative disease models in rodents. Performance is measured by the duration that an animal stays on the rod as a function of drum speed. Two different protocols are widely used, incremental fixed speeds or an accelerating protocol, but there is little information on their equivalence or the relative power, reliability and sensitivity of the two protocols. The present study was undertaken to compare the incremental fixed-speed and accelerating rotarod protocols on two different lesions of the ascending forebrain dopamine pathways. Three groups of rats were used, controls, rats with 6-OHDA lesions of nigrostriatal bundle, and rats with terminal 6-OHDA lesions within the striatum. Rats were tested at different time points after the lesion. We report that whereas the incremental protocol is more sensitive to detect the presence of a lesion, the accelerating protocol provides a more discriminative test to correlate motor deficits against lesion size.


Chronic social stress in mice alters energy status including higher glucose need but lower brain utilization.
Chronic stress leads to changes in energy status and is a major risk factor for depression, with common symptoms of reductions in body weight and effortful motivation for reward. Indeed, stress-induced disturbed energy status could be a major aetio-pathogenic factor for depression. Improved understanding of these putative inter-relationships requires animal model studies of effects of stress on both peripheral and central energy-status measures and determinants. Here we conducted a study in mice fed on a standard low-fat diet and exposed to either 15-day chronic social stress (CSS) or control handling (CON). Relative to CON mice, CSS mice had attenuated body weight maintenance/gain despite consuming the same amount of food and expending the same amount of energy at any given body weight. The low weight of CSS mice was associated with less white and brown adipose tissues, and with a high respiratory exchange ratio consistent with increased dependence on glucose as energy substrate. Basal plasma insulin was low in CSS mice and exogenous glucose challenge resulted in a relatively prolonged elevation of blood glucose. With regard to hunger and satiety hormones, respectively, CSS mice had higher levels of acylated ghrelin in plasma and of ghrelin receptor gene expression in ventromedial hypothalamus and lower levels of plasma leptin, relative to CON mice. However, whilst CSS mice displayed this constellation of peripheral changes consistent with increases in energy need and glucose utilization relative to CON mice, they also displayed attenuated uptake of [18F]FDG in brain tissue specifically. Reduced brain glucose utilization in CSS mice could contribute to the reduced effortful motivation for reward in the form of sweet-tasting food that we have reported previously for CSS mice. It will now be important to utilize this model to further understanding of the mechanisms via which chronic stress can increase energy need but decrease brain glucose utilization and how this relates to regional and cellular changes in neural circuits for reward processing relevant to depression.


Post-harvest biological control by Pantoea agglomerans (CPA-2) on Golden Delicious apples.
To investigate the potential of Pantoea agglomerans to control the major post-harvest diseases on Golden Delicious apples. In laboratory trials, a high level of control of Penicillium expansum, Botrytis cinerea and Rhizopus stolonifer was obtained with P. agglomerans. In semi-commercial trials at 1degrees C in air and a low oxygen atmosphere, the reduction of blue mould was 81% and 100%, respectively, and control of grey mould was achieved equally with P. agglomerans and imazalil. In trials at 1degrees C and seven atmosphere conditions, maximum reduction in decay was 80% obtained at 3% O2-6% CO2. The population of P. agglomerans on apples followed the same pattern under all three atmosphere conditions studied. Pantoea agglomerans could be used effectively on apples under a wide range of temperature and atmosphere conditions. SIGNIFICANCE AND IMAPCT OF THE STUDY Pantoea agglomerans can be used as a biocontrol agent on apples at 8 x 10(7) cfu ml-1, the same concentration as in pears. This will facilitate the application of this biological control agent by the growers in packing houses.


Early increase of NOX2-derived oxidative stress in children: relationship with age.
Studies conducted in the prepubertal period showed that biomarkers of oxidative stress decreased with increasing age in normocholesterolemic children (NC), and, conversely, they are persistently high in hypercholesterolemic children (HC). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the most important cellular source of reactive oxygen species. No data have been reported concerning the behavior of age-related oxidative stress generated by NOX2, the catalytic subunit of NADPH oxidase, in children. We performed a cross-sectional study comparing oxidized low-density lipoprotein (ox-LDL), as a marker of oxidative stress, and NOX2 activity, as assessed by blood levels of soluble NOX2-derived peptide (sNOX2-dp), in a population of 250 children, including 125 NC and 125 HC. HC had higher sNOX2-dp (25.8 ± 16.1 pg/ml) and ox-LDL (23.6 ± 14.4 U/l) levels as compared with NC (15.4 ± 10.1 and 11.6 ± 6.4 pg/ml, respectively; P < 0.001). Multiple linear regression analysis showed that ox-LDL and total cholesterol were the only independent predictive variables associated with sNOX2-dp. In NC, ox-LDL and sNOX2-dp significantly decreased from the first to the second quintile of age. In HC, ox-LDL and sNOX2-dp levels did not show significant differences among quintiles of age. This study suggests that NOX2 contributes to generating ox-LDL during the early phase of life in NC and to the persistent high oxidative stress in the prepubertal period of HC.


Labeling of v-Src and BCR-ABL tyrosine kinases with [14C]herbimycin A and its use in the elucidation of the kinase inactivation mechanism.
The ansamycin antibiotic, herbimycin A, selectively inactivates cytoplasmic tyrosine kinases, most likely by binding irreversibly to the reactive SH group(s) of kinases. To further investigate the mechanism of herbimycin A action, we attempted to label tyrosine kinases with [14C]herbimycin A. p60v-src and p210BCR-ABL in immune complexes were labeled with [14C]herbimycin A, demonstrating that the antibiotic binds directly to tyrosine kinases. Digestion of [14C]herbimycin A-labeled p60v-src with Staphylococcus aureus V8 protease revealed that the herbimycin A binding site is within the C-terminal 26-kDa fragment of p60v-src, which contains the tyrosine kinase domain. Herbimycin A treatment inhibited labeling of p60v-src by [14C]fluorosulfonylbenzoyl adenosine, an affinity labeling reagent of nucleotide binding sites, indicating that herbimycin A-modified p60v-src cannot interact with ATP. The results suggest that herbimycin A inactivates tyrosine kinases by binding directly to the kinase domain, thereby inhibiting access to ATP.


Variability of chemical composition and antioxidant activity of essential oils between Myrtus communis var. Leucocarpa DC and var. Melanocarpa DC.
Essential oils (EOs) from several individuals of Myrtus communis L. (M. communis) growing in different habitats in Sardinia have been studied. The analyses were focused on four groups of samples, namely cultivated and wild M. communis var. melanocarpa DC, characterized by red/purple berries, and cultivated and wild M. communis var. leucocarpa DC, characterized by white berries. Qualitative and quantitative analyses demonstrated different EO fingerprints among the studied samples: cultivated and wild leucocarpa variety differs mainly from the melanocarpa variety by a high amount of myrtenyl acetate (>200 mg/mL and 0.4 mg/mL in leucocarpa and melanocarpa varieties respectively). Conversely, the wild group is characterized by a higher amount, compared with the cultivated species, of linalool (about 110 mg/mL and 20 mg/mL respectively), linalyl acetate (about 24 mg/mL and about 6 mg/mL respectively) whereas EOs of the cultivated plants were rich in pinocarveol-cis compared with wild plants (about 2 mg/mL and about 0.5 mg/mL respectively). Principal component analysis applied to the chromatographic data confirm a differentiation and classification of EOs from the four groups of M. communis plants. Finally, antioxidant activity of the studied EOs shows differences between the various categories of samples.


Can evidence change belief? Reported mobile phone sensitivity following individual feedback of an inability to discriminate active from sham signals.
In this study, we tested whether providing individuals, who described being sensitive to mobile phone signals, with accurate feedback about their ability to discriminate an active mobile phone signal from a sham signal had any impact on their subsequent symptom levels or their perceived sensitivity to mobile phones. Sixty-nine participants who reported sensitivity to mobile phones took part in a double-blind, placebo-controlled provocation study. Perceived sensitivity to mobile phones was assessed using a version of the Sensitive Soma Assessment Scale (SSAS) and the severity of any symptoms attributed to mobile phones was recorded. Both the overall ("negative") findings of the provocation study and the participant's own individual results ("correct" or "incorrect" at detecting a mobile phone signal) were then described to them. Six months later, perceived sensitivity and symptom severity were measured again. Fifty-eight participants (84%) received feedback and participated in the 6-month follow-up. No significant differences in SSAS scores or in symptom severity scores were found between individuals told that they were correct (n=31) or incorrect (n=27) in their ability to detect mobile phone signals in the provocation study. The provision of accurate feedback was insufficient to change attributions or reduce symptoms in this study. However, an overtly negative reaction to feedback was not observed among most participants, and some participants were willing to consider that factors other than electromagnetic field may be relevant in causing or exacerbating their symptoms. Discussing possible psychological factors with electromagnetic hypersensitivity patients may be beneficial for some.


Cell-free assembly of a polyoma-like particle from empty capsids and DNA.
A polyoma-like particle (PLP) is formed when polyoma DNA and purified empty capsids are incubated in a cell-free system. The DNA of this new particle is protected against the action of pancreatic DNase. The density of the purified PLP in CsCl is 1.32 g/cm3, which is intermediate between that of polyoma virions (1.34 g/cm3) and empty capsids (1.29 g/cm3). Purified PLP sediments at 190 S in sucrose and is stable in solutions of high ionic strength. When the DNA is extracted from PLP by the use of detergent and phenol, it is found to be doublestranded with a molecular weight of approximately 1.1 x 10(6). The particles are stable in CsCl at 4 degrees for at least 5 months. Electron micrographs indicate that highly purified PLPs stained with 2% PTA have the same appearance as polyoma capsids. Neither aggregates nor complexes bound by loose ionic bonds appear reasonable to explain these results. The evidence indicates that the DNA of this new polyoma-like particle, made under cell-free conditions, is protected by the capsid.


Comparison of pharmacological activity and safety of different stereochemical configurations of borneol: L-borneol, D-borneol, and synthetic borneol.
Chiral drugs generally exhibit differences in activity because they bind differently to their target receptor. The Chinese medicine borneol ('Bing Pian' in Chinese) is a bicyclic monoterpenoid with a wide range of biological activities. Three kinds of Chinese medicines comprising borneol are used clinically, namely, L-Borneolum ('Ai Pian' in Chinese), Borneolum ('Tian Ran Bing Pian' in Chinese), and synthetic borneol ('He Cheng Bing Pian' in Chinese). The three kinds of borneol have different stereochemical configurations, but their clinical uses are nearly identical, and their prices vary widely. However, there is no clear rational basis for the selection of these kinds of borneol in clinical applications. The purpose of this study was to clarify differences in the biological activity, safety, and structure-activity relationship of the three kinds of borneol. 'borneol', 'Bing Pian', 'Ai Pian', 'Tian Ran Bing Pian', and 'He Cheng Bing Pian' were selected as keywords to search for and extract relevant literature in the CNKI, PubMed, and Google Scholar databases up to November 2022. L-borneol has better potential in cerebrovascular diseases. The three kinds of borneol have stronger penetration-promoting effects on hydrophilic drugs. L-borneol and isoborneol promote intestinal mucosal absorption of drugs via bidirectional regulation of P-glycoprotein. D-borneol exhibits better antitumour sensitizing effects than L-borneol. L-borneol exhibits better inhibition of bacterial adhesion because of its C2 chiral centre. Synthetic borneol is less safe. L-borneol has excellent potential in many aspects, has various sources, and can effectively replace expensive D-borneol in some applications.


Frequency of tri- and multiradial configurations in fragile X chromosomes.
The appearance of tri- or multiradial configurations in fragile chromosomes is affected by the number of cell cycles in the folate antagonist system. In this study the lymphocytes were incubated for 96 h in a medium 199 without calf serum, and tri- or multiradial configurations were observed in 6 of 12 cases of fra(X) chromosome. The frequency ranged from 0.6% to 7.4% of fra(X) chromosomes.


"a" interfacial parameter in Nicolais-Narkis model for yield strength of polymer particulate nanocomposites as a function of material and interphase properties.
In this paper, "a" interfacial parameter in Nicolais-Narkis model is expressed by thickness "ri" and strength "σi" of interphase between polymer and nanoparticles as well as material properties. "a" parameter is connected to "B1" interfacial parameter in modified Pukanszky model and the effects of "ri" and "σi" on "a" are explained. The negligible difference between "a" values calculated by fitting the experimental results to Nicolais-Narkis model and also, by "B1" results confirms the accurateness of the suggested relation between "a" and "B1" parameters. Additionally, an inverse relation is found between "a" and "B1" parameters for nanocomposites containing spherical nanoparticles. The results demonstrate that the slight levels of "ri" and "σi" data give a large value of "a" which indicates the poor interfacial adhesion.


The regulation of medical computer software as a 'device' under the Food, Drug, and Cosmetic Act.
Recent developments in computer software have raised the possibility that federal regulators may claim to control medical computer software as a 'device' under the Food, Drug and Cosmetic Act (FDCA). The purpose of this paper is to analyze the FDCA to determine whether computer software is included in the statutory scheme, examine constitutional arguments relating to computer software, and discuss regulatory principles that should be taken into account when deciding appropriate regulation. This paper is limited to computer program output used by humans in deciding appropriate medical therapy for a patient.


A randomized controlled trial testing the effectiveness of a universal school-based depression prevention program 'Op Volle Kracht' in the Netherlands.
The incidence of depressive symptoms increases during adolescence, from 10.0% to 24.5% at age 11 to 15, respectively. Experiencing elevated levels of depressive symptoms increases the risk of a depressive disorder in adulthood. A universal school-based depression prevention program Op Volle Kracht (OVK) was developed, based on the Penn Resiliency Program, aimed at preventing the increase of depressive symptoms during adolescence and enhancing positive development. In this study the effectiveness of OVK will be tested and possible mediators of program effects will be focus of study as well. The effectiveness of OVK will be tested in a randomized controlled trial with two conditions, intervention (OVK) and control condition (care as usual). Schools are randomly assigned to research conditions. OVK will be incorporated in the school curriculum, maximizing program attendance. OVK consists of 16 lessons of 50 min, given by trained psychologists to groups of 11-15 students. OVK contains Cognitive Behavioral Therapy, social skills training, problem solving and decision making. Outcomes are measured at 6, 12, 18 and 24 months follow up, to monitor long term program effects. Primary outcome is level of depressive symptoms, secondary outcomes are: anxiety, hopelessness, cognitive bias, substance use, truancy, life satisfaction, coping, self-efficacy, optimism, happiness, friendship, school performance and school attitude. The questionnaires for students will be administered in the school setting. Parents will complete a questionnaire at baseline only. In this paper the study into the effectiveness of the depression prevention program OVK was described. It is expected that OVK will prevent the increase in depressive symptoms during adolescence and enhance positive development in the intervention condition, compared to the control condition. If OVK will be effective, it can be implemented in the school context by which numerous adolescents can be reached. Netherlands Trial Register (NTR): NTR2879.


Biologically Active Co(II) and Ni(II) Complexes of N-(2-Thienylmethylene)-2-Aminothiadiazole.
Co(II) and Ni(II) complexes Schiff base, N-(2-thienylmethylene)-2-aminothiadiazole have been prepared and characterized by their physical, spectral and analytical data. The title Schiff-base acts as NNS donor tridentate during the complexation reaction with these metal ions having a composition, [M(L)(2)]X(n) where M=Co(II) or Ni(II), L=, X=NO(3) (-), SO(4) (2-), C(2)O(4) (2-) or CH(3)CO(2) (-) and n=1 or 2 and show an octahedral geometry. In order to evaluate the effect anions upon chelation, the Schiff-base and its new complexes have been screened for their antibacterial activity against bacterial strains e.g., Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.


Face-to-Face Instruction and Personalized Regimens Improve the Quality of Inpatient Bowel Preparation for Colonoscopy.
Poor bowel preparation is commonly observed in inpatients undergoing colonoscopy, particularly those with higher risks for inadequate bowel preparation. The objective of this study was to determine whether personalized bowel preparation regimens combined with face-to-face instruction (FFI) could improve the quality of bowel preparation for inpatient. In this endoscopist-blinded, randomized controlled trial, 320 inpatients were enrolled and randomly allocated (1:1) to the control and intervention groups. The intervention group received FFI and personalized bowel preparation regimens, while the control group received the routine bowel preparation regimen and education. The primary outcome was adequate bowel preparation rate. Secondary outcomes included rates of procedure-related adverse events, incorrect diet restriction and laxative intake, etc. RESULTS: The adequate bowel preparation rate in the intervention group was significantly higher compared to control group [intention-to-treat (ITT) analysis: 70.0% vs 51.3%, P < 0.001; per-protocol (PP) analysis: 79.4% vs 58.6%, P < 0.001]. Bowel cleanliness was significantly improved in high-risk inpatients (ITT analysis: 65% vs 44.6%, P = 0.004; PP analysis: 73.0% vs 51.7%, P = 0.004) and in low-risk inpatients (ITT analysis: 80% vs 62.7%, P = 0.037; PP analysis: 92.3% vs 69.8%, P = 0.003). There were no significant differences between two groups regarding procedure-related adverse events. Personalized bowel preparation regimens combined with FFI improve the rate of adequate bowel preparation, especially for patients with high-risk factors. As such, inpatients could benefit from this novel approach for better bowel preparation to ultimately improve the quality of colonoscopies.


Rethinking the Inflammatory Balance in Psoriasis and Atherosclerosis.
Guénin S, Kazemi A, Cline A, et al. Rethinking the inflammatory balance in psoriasis and atherosclerosis. J Drugs Dermatol. 2023;22(8):832-833. doi:10.36849/JDD.7082.


In vivo phosphorylation and activation of ribosomal protein S6 kinases during Xenopus oocyte maturation.
Previous studies have shown that increased ribosomal protein S6 kinase activity in unfertilized Xenopus eggs can be resolved by DEAE-Sephacel chromatography into two peaks, designated S6 kinase I and S6 kinase II. We show here that antibody against bacterially expressed S6 kinase II cross-reacts with S6 kinase I. Both S6 kinases undergo marked phosphorylation when they are activated during oocyte maturation, and both become deactivated and dephosphorylated upon activation of eggs. Immunoblotting of extracts of oocytes reveals that all S6 kinase molecules undergo a decrease and increase in electrophoretic mobility upon activation and deactivation, respectively. The increase in electrophoretic mobility can be produced in vitro by incubation of activated S6 kinase with purified phosphatases. Phosphoamino acid analysis of S6 kinase II labeled in vivo during maturation reveals both phosphoserine and phosphothreonine, and phosphopeptide maps suggest that several kinases may phosphorylate and activate S6 kinase II in vivo. These results demonstrate that, during oocyte maturation and early development, S6 kinase activation and deactivation are regulated by phosphorylation and dephosphorylation, suggesting a probable mechanism for S6 kinase regulation in other mitogenically stimulated cells.


Torsional, Static, and Dynamic Cyclic Fatigue Resistance of Reciprocating and Continuous Rotating Nickel-Titanium Instruments.
The aim of this study was to evaluate torsional, dynamic, and static cyclic fatigue resistance of the reciprocating One RECI (OR; Micromega, Besançon, France), WaveOne Gold (WOG; Dentsply Maillefer, Ballaigues, Switzerland), rotary One Curve (OC, MicroMega), and ProTaper Next X2 (PTN X2; Dentsply Sirona, Charlotte, NC) instruments. A total of 120 OR (n = 30), WOG (n = 30), OC (n = 30), and PTN X2 (n = 30) nickel-titanium instruments were used. Torque and rotation angle until failure under static torsion loading were measured according to ISO 3630-1. Static and dynamic fatigue resistance was measured as the time to fracture in an artificial stainless steel canal with a 60° angle and 5-mm radius of curvature at intracanal temperature. The results were analyzed with 1-way analysis of variance and the post hoc Tukey test. The alpha-type error was set at 5%. Fracture instruments from torsion and fatigue tests were examined with a scanning electron microscope. OR showed higher static fatigue resistance and rotation angle at fracture than WOG, OC, and PTN X2 (P < .05). WOG exhibited higher torsional resistance than the others (P < .05). The cyclic fatigue tests in dynamic mode had higher TTF than static for the PTN X2 and WOG groups (P < .05). In the dynamic tests, OR and WOG showed higher TTF than OC and PTN X2 (P < .05). Under these experimental conditions, One RECI exhibited suitable mechanical properties with the highest cyclic fatigue resistance and angle of rotation among the tested instruments.


Pediatric In-Hospital Cardiac Arrest and Cardiopulmonary Resuscitation in the United States: A Review.
Pediatric in-hospital cardiac arrest (IHCA) occurs frequently and is associated with high morbidity and mortality. The objective of this narrative review is to summarize the current knowledge and recommendations regarding pediatric IHCA and cardiopulmonary resuscitation (CPR). Each year, more than 15 000 children receive CPR for cardiac arrest during hospitalization in the United States. As many as 80% to 90% survive the event, but most patients do not survive to hospital discharge. Most IHCAs occur in intensive care units and other monitored settings and are associated with respiratory failure or shock. Bradycardia with poor perfusion is the initial rhythm in half of CPR events, and only about 10% of events have an initial shockable rhythm. Pre-cardiac arrest systems focus on identifying at-risk patients and ensuring that they are in monitored settings. Important components of CPR include high-quality chest compressions, timely defibrillation when indicated, appropriate ventilation and airway management, administration of epinephrine to increase coronary perfusion pressure, and treatment of the underlying cause of cardiac arrest. Extracorporeal CPR and measurement of physiological parameters are evolving areas in improving outcomes. Structured post-cardiac arrest care focused on targeted temperature management, optimization of hemodynamics, and careful intensive care unit management is associated with improved survival and neurological outcomes. Pediatric IHCA occurs frequently and has a high mortality rate. Early identification of risk, prevention, delivery of high-quality CPR, and post-cardiac arrest care can maximize the chances of achieving favorable outcomes. More research in this field is warranted.


Effects of bilateral subthalamic stimulation on sleep in Parkinson's disease.
Sleep disturbances are frequently observed in Parkinson's disease (PD). Bilateral chronic subthalamic nucleus (STN) stimulation is an alternative treatment for advanced PD. Improvements in motor disturbances after STN stimulation are well documented and seem to be associated with better sleep quality, even though the objective effect on sleep structure remains unclear. We have therefore studied the sleep/wakefulness cycle before and after surgical treatment in 10 consecutive parkinsonian patients. Subjective sleep quality and sleep recordings were evaluated one month before and three months after initiation of STN stimulation. After surgery, the recordings were performed under two conditions: with stimulation (the "on" condition) and-if patients had given their consent-in the absence of stimulation (the "off" condition). With STN stimulation, subjective and objective sleep qualities were improved. Total sleep time, sleep efficiency and the durations of deep slow wave sleep and paradoxical sleep increased significantly. When stimulation was absent, sleep disturbances were similar to those observed before surgery. Chronic STN stimulation is associated with a sleep improvement, which can be explained in part by the concomitant decrease in motor disturbances but also by the reduction in dosages of antiparkinsonian medication. However, we can not exclude a direct effect of STN stimulation on sleep regulatory centres.


Stressful work characteristics, health indicators and work behavior: the case of machine operators.
This article shows the results of research on psychosocial risks for a group of machine and plant operators (n = 1014) from the construction, chemical, energy, mining, metal and food industries in Poland. The Psychosocial Risk Scale designed in Nofer Institute of Occupational Medicine (NIOM) by Moscicka-Teske and Potocka was used to indicate the occurrence of general and specific occupational stressors and the level of their stressfulness. The results revealed that the studied machine and plant operators experience job context stress - related to working environment features concerning work organization - more frequently than job content stressors - related to the type of tasks they perform. Moreover, a correlation analysis between work features and the health and occupational functioning of the respondents revealed significant but weak relationships between the variables (from -0.08 to -0.23). Comparative analysis revealed the differences between the studied sectors. Such a comparison makes it possible to set goals for each sector and to attempt to improve the distinctive areas.


Interferon-induced synthesis of 2-5A-dependent RNase in mouse JLS-V9R cells.
Interferon treatment of mouse JLS-V9R cells resulted in a 10- to 20-fold increase in the levels of the 2-5A (ppp(A2'p)nA)-dependent RNase. The nuclease was monitored in cell extracts by covalent and noncovalent binding of 32P-labeled 2-5A derivatives to the nuclease and by the appearance of 2-5A-mediated ribosomal RNA cleavage products. Untreated JLS-V9R cells contained very low levels of the nuclease (5-10% of that found in control Ehrlich ascites tumor cells). An increase in the nuclease was first detected between 3 and 6 hr after interferon treatment and was completely inhibited by actinomycin D. Control experiments indicated that the increase in the nuclease was not due to an intracellular redistribution of the enzyme. The results indicate that in JLS-V9R cells, interferon controls the activity of the 2-5A system at two levels: by inducing the synthesis of both the 2-5A-dependent RNase and the 2-5A-synthetase.


[IPA exercise at extreme ages of life, differences or similarities?]
Advanced practice nursing is intended for children, adolescents, adults and the elderly. In the field of mental health, this population-based approach allows advanced practice nurses to apply all of their skills for individualized and adapted care. Whether these professionals work in child and adolescent psychiatry or in psychiatry for the elderly, their practices have many similarities.


An update on potential biomarkers for diagnosing diabetic foot ulcer at early stage.
As one of major chronic complications of diabetes, diabetic foot ulcer (DFU) is the main cause of disability and death. The clinical diagnosis and prognosis of DFU is inadequate. For clinicians, if the risk stratification of DFU can be obtained earlier in diabetic patients, the hospitalization, disability and mortality rate will be reduced. In addition to the inflammatory biomarkers that have been widely concerned and used, e.g., procalcitonin, pentraxin-3, C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor-α (TNF-α), etc., a more comprehensive prediction of the risk and severity of DFU is needed to reflect new biomarkers for therapeutic intervention effects. Along with the development of systems biology technology, genomics, proteomics, metabolomics and microbiome have been used in the studies on DFU for better understanding of the disease. In this review, new biomarkers that are expected to assist in the accurate diagnosis and risk stratification of DFU will be discussed and summarized in detail.


The Korean Clinical Research Center for End-Stage Renal Disease Study Validates the Association of Hemoglobin and Erythropoiesis-Stimulating Agent Dose with Mortality in Hemodialysis Patients.
Anemia is an important risk factor for mortality in hemodialysis (HD) patients. However, higher hemoglobin (Hb) is not necessarily better, as seen in several studies. This study aimed to validate the clinical use of an Hb target of 10-11 g/dL in Korean HD patients. A total of 1,276 HD patients from the Clinical Research Center (CRC) for End-Stage Renal Disease (ESRD) were investigated in a prospective observational study. Cox proportional hazard analysis was conducted for each category of time-dependent Hb level and erythropoiesis-stimulating agent (ESA) dose, with subgroup analysis stratified by age and diabetes status. Using a reference Hb level of 10-11 g/dL, the hazard ratios (HRs) of death were 5.12 (95% confidence interval [CI], 2.62-10.02, P <0.05) for Hb level <9.0 g/dL, and 2.03 (CI, 1.16-3.69, P <0.05) for Hb level 9.0-10.0 g/dL, after adjustment for multiple clinical variables. However, an Hb level ≥11 g/dL was not associated with decreased mortality risk. In an adjusted model categorized by Hb and ESA dose, the risk of death at an Hb level <10 g/dL and a higher dose of ESA (≥126 U/kg/week) had an HR of 2.25 (CI, 1.03-4.92, P <0.05), as compared to Hb level 10-11 g/dL and a lower dose of ESA. In subgroup analysis, those older than 65 years or who were diabetic had greater risk for mortality only in Hb category <9.0 g/dL. However, there was no significant interaction between age or diabetes status and Hb. Using CRC-ESRD data, we validated the association between Hb and ESA dose and mortality in Korean HD patients. The clinical practice target of an Hb of 10-11 g/dL before the new KDIGO guideline era seems reasonable considering its survival benefit in HD patients.


Solid variant ABC of long tubular bones: A diagnostic conundrum for the radiologist.
Solid variant of aneurysmal bone cyst (sABC) is an extremely rare, reactive and non-neoplastic osseous lesion. On imaging it presents as a diaphyseal aggressive, eccentrically placed lytic and expansile lesion. However, differentiating this entity from the other possible malignant differentials is confounded by the histopathology mimicking several commoner lesions. We describe the distinctive MRI features of sABC of long bones from a series of four cases and briefly review the literature. We hope this review will educate all radiologists about this rare entity increasing their diagnostic confidence while formulating differentials for similar appearing lesions.


Willingness to pay for small-quantity lipid-based nutrient supplements for women and children: Evidence from Ghana and Malawi.
Small-quantity lipid-based nutrient supplements (SQ-LNS) are designed to enrich maternal and child diets with the objective of preventing undernutrition during the first 1,000 days. Scaling up the delivery of supplements such as SQ-LNS hinges on understanding private demand and creatively leveraging policy-relevant factors that might influence demand. We used longitudinal stated willingness-to-pay (WTP) data from contingent valuation studies that were integrated into randomized controlled nutrition trials in Ghana and Malawi to estimate private valuation of SQ-LNS during pregnancy, postpartum, and early childhood. We found that average stated WTP for a day's supply of SQ-LNS was more than twice as high in Ghana than Malawi, indicating that demand for SQ-LNS (and by extension, the options for effective delivery of SQ-LNS) may be very context specific. We also examined factors associated with WTP, including intervention group, household socioeconomic status, birth outcomes, child growth, and maternal and child morbidity. In both sites, WTP was consistently negatively associated with household food insecurity, indicating that subsidization might be needed to permit food insecure households to acquire SQ-LNS if it is made available for purchase. In Ghana, WTP was higher among heads of household than among mothers, which may be related to control over household resources. Personal experience using SQ-LNS was not associated with WTP in either site.


The philosophical foundations of 'health for all' and Universal Health Coverage.
The WHO constitution calls for 'health for all' and Universal Health Coverage has been called "the ultimate expression of fairness", however it is not always clear how health systems can move towards equity. Should we prioritise the needs of the worst off? And if so, should we direct resources to these marginalised groups or marginalised individuals? This article provides an overview of the philosophical underpinnings of health equity and proportionate universalism, highlighting the trade-offs involved in operationalising a core tenant of global health practice.


Müller Glia to Müller Glia Extracellular Vesicle-Dependent Signaling Induces Multipotency Genes Nestin and lin28 Expression in Response to N-methyl-D-aspartate (NMDA) Exposure.
Retinal Müller cells secrete extracellular vesicles that can be captured by other Müller cells. In response to a signal that may be deleterious for the retina, Müller glia-derived extracellular vesicles spread instructions to induce gene expression changes in other cells.


Endothelial TrkB receptor activation controls vascular tone of rat middle cerebral artery.
Little is known on the cerebrovascular BDNF (brain-derived neurotrophic factor)/TrkB (tropomyosin related kinase B) pathway. This study investigated the contribution of endogenous endothelial BDNF to the control of vascular tone of rat middle cerebral artery (MCA) and the capacity of exogenous agonist of TrkB receptors to induce their relaxation. Endothelial cells constitutively expressed both BDNF and activated TrkB receptors. Supporting endothelial BDNF as an autocrine regulator of basal myogenic tone, incubation of MCA with the TrkB antagonist cyclotraxin B induced contraction as observed with incubation in the presence of inhibitors of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) production. Exposure of MCA with the TrkB agonist LM22A-4 that increased expression of TrkB receptors phosphorylated at tyrosine 816 induced relaxation of preconstricted MCA (EC50 6.7 × 10-8 mol/L) as efficiently than acetylcholine (EC50 5.3 × 10-8 mol/L). Finally, endothelium removal, exposure to a TrkB antagonist or to inhibitors of NO and EDHF production prevented the relaxant effect of LM22A-4. In conclusion, our study identified endothelial BDNF as a new autocrine regulator of vascular tone of MCA, thus making the endothelial BDNF/TrkB pathway an attractive target for strategies aiming to improve blood supply to the brain.


Impact of estradiol, ER subtype specific agonists and genistein on energy homeostasis in a rat model of nutrition induced obesity.
Estrogens are known to be involved in the control of energy homeostasis. Here we investigated the role of ER alpha and ER beta in a model of nutrition induced obesity. Ovariectomized Wistar rats were fed a high fat diet and received either vehicle, E2, ER subtype selective agonists (Alpha and Beta) or genistein. After 10 weeks, body weight, visceral fat, serum leptin, blood lipids, and in the soleus muscle anabolic markers were determined. Treatment with E2 and Alpha decreased body weight, total cholesterol and VLDL. Visceral fat mass, adipocyte size, and serum leptin were reduced by E2, Alpha and Beta. In the soleus muscle, treatment with E2 and Beta modulated Igf1 and Pax7 gene expression and resulted in larger muscle fibers. Our data indicate that blood lipids are affected via ER alpha, whereas activation of ER beta results in an increase of soleus muscle mass. Adipose tissue homeostasis seems to be affected via both ERs.


Non-referral of unnatural deaths to coroners and non-reporting of unnatural deaths on death certificates in Taiwan: implications of using mortality data to monitor quality and safety in healthcare.
Mortality data has often been used to monitor the quality of cardiac care. To investigate the under-reporting of unnatural deaths in mortality data. All patients with a main discharge diagnosis of injury (ICD-9-CM code 800-999) who died in 2003 or 2004 were identified through record linkage between hospital discharge claims data and cause of death data in Taiwan. Percentages of unnatural deaths that had been referred to the coroner and in which injury-related information was reported on the death certificate were estimated. Of 4086 known or suspected unnatural deaths, only 57% (2346/4086) were referred to the coroner, and in 71% (2889/4086) injury-related information was reported on the death certificate. The percentages of referral and reporting were lowest for deaths related to complications in medical and surgical care. In deaths related to fracture of the femur and the effects of a foreign body, many doctors report injury-related information on the death certificate but do not refer the certification of cause of death to the coroner. The sensitivity of using mortality data alone to detect known or suspected unnatural deaths varied according to the types of injury and external causes. Monitoring cause of death data linked with hospital discharge record data could provide a better system for discovering these unnatural deaths.


Digital measurement of pelvic muscle strength in childbearing women.
Fourteen primigravidas were evaluated at 32 and 36 weeks antepartum (AP) and 6 weeks postpartum (PP) to test the reliability and validity of a digital measure of pelvic muscle strength using urine control as the criterion. Interrater reliabilities ranged from .67 to .77. Convergent validity was shown by negative correlations between clinical muscle scores and time required to interrupt urine flow at 32 weeks AP (r = -.41), 36 weeks AP (r = -.64) and 6 weeks PP (r = -.71). Validity was also demonstrated in a pattern of lower scores in women who had urine loss during coughing or reported incontinence as compared with those who did not. Women who had cesarean births had higher postpartum pelvic muscle scores with progressively lower scores demonstrated by those who gave birth vaginally without laceration, with episiotomy, and with laceration, F(3, 10) = 5.40, p = .02.


Nitrofurantoin-induced chronic liver disease. Clinical course and outcome of five cases.
Adverse liver reactions associated with nitrofurantoin treatment are rare but important complications. Both acute and chronic liver damage have been described. The present report describes five patients who developed chronic liver disease after 1 to 3 years of continued nitrofurantoin treatment. Liver histology was consistent with chronic active hepatitis in four patients, while postnecrotic cirrhosis was observed in one case. Follow-up examinations 2 to 3 years after withdrawal of the drug showed marked improvement clinically and in most cases also histologically.


STABILISE Technique for a Non-A Non-B Acute Aortic Dissection in Marfan Syndrome.
A 35-year-old man, with a deep pectus excavatum due to a Marfan syndrome treated 9 years before for an acute type A dissection involving only the aortic arch, by a Bentall surgery, was admitted for acute chest pain. Computed tomography (CT) scan showed an acute type non-A non-B dissection extending to the iliac. After 5 days with strict arterial blood pressure management, the patient had recurrent refractory chest pain and a hybrid technique associating full supra-aortic vessels debranching and STABILISE technique during the same procedure was performed. The patient had an uneventful recovery with CT scan showing complete aortic arch aneurysm exclusion.


[Recurrency in primary duodenal carcinoma (author's transl)].
18 months after the operation (duodenectomy and partial pancreatectomy) a tumor recurrency is observed in a 64 years old patient with primary adenocarcinoma of the duodenum. The roentgen diagnostic shows a partial destruction of the upper jejunal loops combined with a free passage.


Appearance of the cyst- or ductule-like structures and their role in the restoration of the rat pituitary autograft.
The anterior pituitary glands of 31-day-old male rats were autotransplanted under renal capsule. At the 3rd and 5th day after transplantation, the autografts were observed by electron microscopy and by immunohistochemistry using antiserum against S-100 protein, which serves as marker of folliculo-stellate (FS) cells. On the 3rd day, a large of the graft was replaced with loose connective tissue in which the FS cells were remarkable in number. The FS cells encircled a small number of granular cells and formed cyst- or ductule-like structures with neighboring FS cells. Together, FS cells and the encircled granular cells formed a basement membrane surrounding the entire ductule. Throughout the regenerating gland, many such ductules were found. On the 5th day, both granular cells and FS cells increased in number. The above observations suggest that FS cells may play an important role in the restoration of degenerated pituitary glandular tissues during the early stage of the transplantation.


Improving selectivity in gas chromatography by using chemically modified multi-walled carbon nanotubes as stationary phase.
Amino-terminated alkyl MWCNTs (MWCNTs-R-NH(2)), synthesized by chemical modification of the nanotube skeleton by nucleophilic substitution with 2,2'-(ethylenedioxy)diethylamine, were successfully used as stationary phases for gas chromatographic separation of esters and chloroaromatics. The presence of alkyl chains with polar embedded groups made the functionalized MWCNTs (f-MWCNTs) a mixed-mode GC separation material able to interact in different ways with the analytes. Compared with non-functionalized MWCNTs (nf-MWCNTs), MWCNTs-R-NH(2) had higher selectivity, enhanced resolution, and optimum retention behaviour, and they were proved to perform better than the commercial stationary phase Porapak QS (PQS), claimed to be suitable for similar applications. The so-prepared stationary phase was used for analysis of a synthetic mixture containing different classes of analytes, viz. esters, ketones, alcohols, alkanes, and aromatic hydrocarbons, and finally used for investigation of similar real matrices. In particular, the constituents of a commercial paint thinner were determined by direct injection of the sample, with good reproducibility (inter-day precision RSDs from 5 to 19%). Two unknown samples of commercial white spirit were also analysed for determination of the aromatic hydrocarbon content, and their composition was profiled on the basis of the different compounds identified.


Plate-Based Screening for DUB Inhibitors.
The evolutionally conserved and abundant post-translational modifier ubiquitin (Ub) is involved in a vast number of cellular processes. Imbalanced ubiquitination is associated with a range of diseases. Consequently, components of the ubiquitylation machinery, such as deubiquitinating enzymes (DUBs) that control the removal of Ub, are emerging as therapeutic targets. Here, we describe a robust assay suitable for small-molecule inhibitor screening. This assay has the potential to drive the development of small-molecule compounds that can selectively target DUBs.


Identification of cis- and trans-acting elements in pHW126, a representative of a novel group of rolling circle plasmids.
pHW126, pIGRK, pIGMS31 and pRAO1 are the only known members of a novel and as yet uncharacterised family of rolling circle plasmids. pHW126 contains only two open reading frames, of which one shows homology to pMV158-family mobilisation proteins. Here we provide evidence that the second open reading frame encodes a replication protein (Rep). Mutation or deletion of this gene resulted in replication deficient constructs, but providing functional Rep from a compatible vector rescued these constructs, indicating that Rep acts in trans. An approximately 300 bp cis-acting region representing the origin of replication was identified upstream of the rep gene. The origin was identified to be composed of three parts: an accessory region, a conserved stretch and four perfect tandem repeats. The two latter elements were essential for replication. Constructs with a deletion of the accessory region could still replicate, but their loss rate was high, indicating that the accessory region is necessary for plasmid maintenance under non-selective conditions. Interestingly, pHW126 could replicate in all Enterobacteriaceae tested while Agrobacterium tumefaciens and Pseudomonas syringae were inappropriate hosts. Thus, pHW126 seems to have a rather limited host range.


Anticipation or resilience in times of emergent crisis? COVID-19 responses in the United States, Taiwan, and South Korea.
This research employs Wildavsky's two -strategies-anticipation and resilience-as our conceptual framework to compare COVID-19 policies in the United States, South Korea, and Taiwan. Also, following Handmer and Dovers' three types of resilience, we develop theory-driven codes and then explain how governmental structures and cultural factors influenced governmental responses. We found that a key response to this pandemic is arguably correlated with how quick and flexible a government can adopt different types of resilient strategies. Our research provides a foundation for governmental emergency response discussions and management strategies to better cope with public health crises in the future.


[Identification of protein spots in silver-stained two-dimensional gels based on chemically assisted fragmentation by MALDI-TOF-PSD mass spectrometry].
Guanidination of the epsilon-amino group of lysine-terminated tryptic peptides,accomplished with O-methylisourea hydrogen sulfate, converted lysine into homoarginine residues, improving detection in MALDI-MS. Then tryptic peptides were labeled with sulfonic acid groups at the N-termini using 3-sulfopropionic acid NHS-ester chemistry. The derivatives enhanced post-source decay (PSD) fragmentation signals and produced a spectrum containing only y-ions. This facilitated de novo peptide sequencing, so it is an important contribution to unambiguous protein identification in proteome research. This method was successfully applied in nasopharyngeal carcinoma(NPC) proteome study.


Self-marked preparation of site-specific transmission electron microscope lamellae of nanodevices using focusing ion beam technique.
The precise extraction of a thin slice (lamellae) from nano electronic devices using a focused ion beam (FIB) is crucial for transmission electron microscopy analysis, but it remains a challenge for 100 nm and beyond scale device components. In this study, we introduce a new method that utilises the device's own features as markers during FIB thinning process by continuously monitoring the intermediate structures with secondary electron scanning electron microscopy (SE-SEM) imaging. This allows for the targeted extraction of the desired device component with high precision. We successfully demonstrate the effectiveness of this approach by extracting lamellae from 100 nm length channel in arrayed carbon nanotube film field-effect transistors using FIB lift-out.


Breast cancer in West Africa: molecular analysis of BRCA genes in early-onset breast cancer patients in Burkina Faso.
Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths among women in Africa after cervical cancer. Even if the epidemiological data are now aligned with those relating to industrialized countries, the knowledge concerning breast cancer in Africa, particularly in Western Africa, still lack clinical data, medical treatments, and the evaluation of genetic and non-genetic factors implicated in the etiology of the disease. The early onset and the aggressiveness of diagnosed breast cancers in patients of African ancestry strongly suggest that the genetic risk factor may be a key component, but so far, very few studies on the impact of germ line mutations in breast cancer in Africa have been conducted, with negative consequences on prevention, awareness and patient management. Through Next Generation sequencing (NGS), we analyzed all of the coding regions and the exon-intron junctions of BRCA1 and BRCA2 genes-the two most important genes in hereditary breast cancer-in fifty-one women from Burkina Faso with early onset of breast cancer with or without a family history. We identified six different pathogenic mutations (three in BRCA1, three in BRCA2), two of which were recurrent in eight unrelated women. Furthermore, we identified, in four other patients, two variants of uncertain clinical significance (VUS) and two variants never previously described in literature, although one of them is present in the dbSNP database. This is the first study in which the entire coding sequence of BRCA genes has been analyzed through Next Generation Sequencing in Burkinabe young women with breast cancer. Our data support the importance of genetic risk factors in the etiology of breast cancer in this population and suggest the necessity to improve the genetic cancer risk assessment. Furthermore, the identification of the most frequent mutations of BRCA1 and BRCA2 in the population of Burkina Faso will allow the development of an inexpensive genetic test for the identification of subjects at high genetic cancer risk, which could be used to design personalized therapeutic protocols.


Chasing language through the brain: Successive parallel networks.
To describe the spatio-temporal dynamics and interactions during linguistic and memory tasks. Event-related electrocorticographic (ECoG) spectral patterns obtained during cognitive tasks from 26 epilepsy patients (aged: 9-60 y) were analyzed in order to examine the spatio-temporal patterns of activation of cortical language areas. ECoGs (1024 Hz/channel) were recorded from 1567 subdural electrodes and 510 depth electrodes chronically implanted over or within the frontal, parietal, occipital and/or temporal lobes as part of their surgical work-up for intractable seizures. Six language/memory tasks were performed, which required responding verbally to auditory or visual word stimuli. Detailed analysis of electrode locations allowed combining results across patients. Transient increases in induced ECoG gamma power (70-100 Hz) were observed in response to hearing words (central superior temporal gyrus), reading text and naming pictures (occipital and fusiform cortex) and speaking (pre-central, post-central and sub-central cortex). Between these activations there was widespread spatial divergence followed by convergence of gamma activity that reliably identified cortical areas associated with task-specific processes. The combined dataset supports the concept of functionally-specific locally parallel language networks that are widely distributed, partially interacting in succession to serve the cognitive and behavioral demands of the tasks.


Expression optimization and biochemical properties of two glycosyl hydrolase family 3 beta-glucosidases.
The β-glucosidases from Saccharomycopsis fibuligera (SfBGL1) and Trichoderma reesei (TrBGL1) were cloned and expressed in Pichia pastoris. Methanol concentration and pH significantly affected the production. The combined effects of the two factors were optimized by using the response surface method, resulting in a 137% and 84% increase in rTrBGL1 and rSfBGL1 yield compared to single-factor experiment. Structure and biochemical properties of the two enzyme were investigated and compared. They belong to glycosyl hydrolase family 3 and exhibit significant hydrolysis activity and low-level transglycosylation activity. The two enzymes show similar substrate affinity and ion-tolerance, and both of them can be activated by Cr(6+), Mn(2+) and Fe(2+). The rSfBGL1 has greater catalytic speed, higher specific activity and acid-tolerance than rTrBGL1, but rTrBGL1 is more thermostable and has higher optimal temperature than rSfBGL1. This study provides a useful and quick optimal method for recombinant enzyme production and makes a valuable comparison of biochemical properties, which opens important avenues of exploration for relationship between structure and function and further practical applications.


Floating Tophi in a Baker Cyst Secondary to Gout: Ultrasound Features and Differential Diagnosis.
We report the case of a 36-year-old man with a recent diagnosis of gout, who presents with a fullness behind his right knee that fluctuates in size with time. An ultrasound revealed a Baker cyst that contained both large and punctate internal hyperechoic foci. Cyst aspiration revealed negatively birefringent crystals, which were consistent with gout.


Serum cholesterol and squalene in hepatocellular carcinoma.
In 15 patients with hepatocellular carcinoma, the serum squalene level is raised significantly in parallel with the serum cholesterol level, though significantly decreased in patients with cholestatic hepatobiliary disease. Serum levels of cholesterol and/or squalene, therefore, could be regarded as a laboratory index reflecting a peculiar sterol metabolism in hepatocellular carcinoma.


A new EAE model of brain demyelination induced by intracerebroventricular pertussis toxin.
Experimental autoimmune encephalomyelitis (EAE) is a primary animal model of multiple sclerosis (MS). MS predominantly presents with evidence of lesions in the subcortical periventricular white matter regions of the brain. Research into the pathogenesis of the demyelinating lesions in the brain has been hampered by the fact that conventional models of EAE present with progressive ascending paralysis which recapitulates mainly the spinal cord lesions of multiple sclerosis. There is little evidence of brain involvement. Systemic administration of pertussis toxin (PTx) has been shown to induce the proinflammatory cascade of TGF-beta, IL-6, and Th17 in the central nervous system, which recently has been identified as essential in the development of EAE. To determine whether intracerebroventricular (icv) administration of PTx would result in subcortical periventricular demyelinating lesions in the brain, we examined the effect in a MOG induced EAE model. We found that icv PTx induced subcortical periventricular brain lesions that resemble the pathologic demyelinating lesions of MS. Moreover, icv PTx induced Th17 infiltration and increased expression of cytokines IL-6 and TGF-beta. We thus generated a highly reproducible model with remarkable histological similarities to the predominant demyelinating brain lesions seen in MS.


Dynamic changes occur in patterns of endometrial EFNB2/EPHB4 expression during the period of spiral arterial modification in mice.
Transient, human and murine decidua-associated, Natural Killer lymphocytes (uNK cells) have special, localized roles in early gestational endometrial remodeling and angiogenesis. To determine if uNK cells promote a specific vessel subtype, a histological time-course study of implantation site endothelia was undertaken using normal C57BL/6J (B6) and uNK-deficient B6.129-Rag2 tm1Fwa Il2rg tm2Cgn (alymphoid) mice, a strain lacking pregnancy-induced structural modifications of spiral arteries. Antibodies to EFNB2, EPHB4, and LYVE1, respectively, identified arterial, venous, and lymphatic endothelia. Unexpectedly, many uNK cells in B6 endometrium showed strong EFNB2 expression early in gestation, then became EPHB4+. This molecular transition coincided with structural modifications of spiral arteries that shifted from EFNB2+/EPHB4(-) to EFNB2+/EPHB4+. NK cells from B6 spleen and liver did not express EFNB2. LYVE1 expression was similar in endometrium from B6 and alymphoid mice, but EFNB2 and EPHB4 expression in alymphoid mice was dramatically different. Strong stromal expression of both molecules developed mesometrially, and this was reduced by B6 lymphocyte transfer. Trophoblasts reacted with each marker in both strains. Expression of EFNB2 by uNK cells and trophoblasts may be the key regulatory mechanism that drives their positional association with EFNB2+ arteries and prevents association of both cell types with EPHB4+ veins. Gain of EPHB4 by midgestation spiral arteries may signal completion of pregnancy-induced arterial modification and provide a repulsion mechanism that limits subsequent interactions of the modified vessel with uNK cells and trophoblasts.


Thinness expectations and weight cycling in a sample of middle-aged adults.
The False Hope Syndrome suggests that unrealistic expectations of dieting and weight loss are key constructs in the prediction of behavioral failure and may exacerbate weight cycling. The objective of this study was to determine cross-sectional associations among dieting and thinness expectations and weight cycling history within the framework of the False Hope Syndrome. Participants were middle-aged (45±12 years) women (n=116) and men (n=98) recruited via worksite intranet distributions. Information on dieting and thinness expectations, weight loss attempts, and weight cycling history was gathered using standard questionnaires. More women than men reported currently dieting (43% vs. 26%; p<0.01). Moderate [OR=2.54; 95%CI: 1.01-6.45] and higher [OR=2.70; 95%CI: 1.07-6.80] levels of the thinness expectation score were significantly associated with the greater odds of weight cycling, independent of age, sex, BMI, and weight loss attempts. These data are the first to extend the pervasive and potent influence of thinness expectancy to middle-aged persons and in particular, to men.


Quantitative proteome analysis of overexpressed Cripto-1 tumor cell reveals 14-3-3γ as a novel biomarker in nasopharyngeal carcinoma.
We previously found that Cripto-1 is involved in the tumorigenesis of nasopharyngeal carcinoma (NPC). Here, to identify new NPC related proteins and to investigate the clinicopathological correlations of it in NPC, Cripto-1 over-expressed cell (CNE1/CR1(+)) was established. Two-dimensional difference in gel electrophoresis (2D-DIGE) analysis and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify 23 differential proteins in CNE1/CR1(+) and parental cells. Among them, 14-3-3γ showed the potential to be a NPC related protein. 14-3-3γ expression was found in 58.3% (60/103) tumor tissues as detected by IHC, and 69.6% (16/23) NPC fresh tumors expressed higher 14-3-3γ than paired non-cancerous tissues as detected by Western blot. Moreover, 14-3-3γ expression was positively correlated with N classification (p=0.031), distant metastasis (M classification, p=0.018) and clinical stage (p=0.046) of NPC patients. As determined by the Kaplan-Meier method, 14-3-3γ expression in NPC was significantly associated with overall survival (p=0.015). Multivariate analysis also showed that the expression of 14-3-3γ protein was an independent prognostic factor for outcome of NPC. In this study, we identified upregulated 14-3-3γ by 2D-DIGE in CNE1/CR-1(+). We also demonstrated that 14-3-3γ might be a potential biomarker for the prognosis of patients with NPC. We believe that three aspects of this manuscript will make it interesting to general readers of Journal of Proteomics. Firstly, based on our previous report, we further validated that Cripto-1 can promote the proliferation and invasion of nasopharyngeal carcinoma (NPC). In this context, we used 2D-DIGE to identify new NPC related proteins. As a result, 14-3-3γ showed the potential to be a candidate. Secondly, we reported for the first time that the expression level of 14-3-3γ was significantly increased in human NPC patient tissues, and 14-3-3γ overexpression correlated statistically with N classification, distant metastasis, and clinical stage. Our results highlight the clinical significance of 14-3-3γ in NPC. Finally, we found that high 14-3-3γ expression is associated with poor survival in NPC patients. Thus, this study has identified that the 14-3-3γ involves in the carcinogenesis of NPC. Our findings may also provide new insights into understanding the molecular mechanism involved in NPC carcinogenesis and progression, and may lead to the development of new approaches for effective diagnosis and therapy.


Ambrisentan therapy for pulmonary arterial hypertension.
The purpose of this study was to examine the efficacy and safety of four doses of ambrisentan, an oral endothelin type A receptor-selective antagonist, in patients with pulmonary arterial hypertension (PAH). Pulmonary arterial hypertension is a life-threatening and progressive disease with limited treatment options. Endothelin is a vasoconstrictor and smooth muscle cell mitogen that plays a critical role in the pathogenesis and progression of PAH. In this double-blind, dose-ranging study, 64 patients with idiopathic PAH or PAH associated with collagen vascular disease, anorexigen use, or human immunodeficiency virus infection were randomized to receive 1, 2.5, 5, or 10 mg of ambrisentan once daily for 12 weeks followed by 12 weeks of open-label ambrisentan. The primary end point was an improvement from baseline in 6-min walk distance (6MWD); secondary end points included Borg dyspnea index, World Health Organization (WHO) functional class, a subject global assessment, and cardiopulmonary hemodynamics. At 12 weeks, ambrisentan increased 6MWD (+36.1 m, p < 0.0001) with similar and statistically significant increases for each dose group (range, +33.9 to +38.1 m). Improvements were also observed in Borg dyspnea index, WHO functional class, subject global assessment, mean pulmonary arterial pressure (-5.2 mm Hg, p < 0.0001), and cardiac index (+0.33 l/min/m2, p < 0.0008). Adverse events were mild and unrelated to dose, including the incidence of elevated serum aminotransferase concentrations >3 times the upper limit of normal (3.1%). Ambrisentan appears to improve exercise capacity, symptoms, and hemodynamics in patients with PAH. The incidence and severity of liver enzyme abnormalities appear to be low.


[Effect of water on the thermostability of free radicals in tendon collagen].
Recombination-kinetic method was applied for studying collagen of rat tail tendons. Annealing of UV-induced free radicals in tendons of various humidity was investigated.


Prevalence and characteristics of postpartum thyroid dysfunction in São Paulo, Brazil.
Postpartum thyroid dysfunction (PPTD) is an autoimmune disorder characterized by the development of transient hyperthyroidism and, more frequently, hypothyroidism (or both) during the first six months of the puerperal period. A variable incidence has been reported in part because of differences in the number of women studied, the frequency of thyroid assessment postpartum, diagnostic criteria and methodology. The aim of this study was to evaluate thyroid function, ultrasound images and titre of autoantibodies against thyroid antigens in a cohort of pregnant women who met the criteria of 'normal' thyroid gland structure on clinical examination and imaging and normal thyroid function tests without a significantly positive anti-thyroid peroxidase (TPO) antibody titre (i.e. < 100 U/ml) in the first trimester. Eight hundred nulliparous or multiparous (one to seven previous pregnancies) pregnant women (age 26.1 +/- 4.8 years, mean +/- SD), were submitted to clinical, laboratory and ultrasonographic examination in the first trimester of pregnancy. Among these forty-six patients were excluded because of thyroid dysfunction, ultrasound structural abnormalities or a positive anti-TPO antibody titre (> 100 U/ml). A total number of 754 women were available for further studies in the postpartum period. A relatively large number of these patients (386) were lost for follow-up either before or after delivery. A cohort of 368 puerperal women was followed up regularly at 3, 6, 12 and 24 months after delivery, with periodic thyroid function tests, random urine iodine measurements, assays for serum autoantibodies against thyroid antigens and imaging by ultrasound. The provisional diagnosis of PPTD was established in 78 out of 368 who had positive anti-TPO levels and ultrasonographic thyroid structural changes. Twenty-nine of these patients had a transient rise of anti-TPO autoantibodies characterizing an autoimmune reaction. These autoantibodies levels progressively declined or became negative. Moreover none of these patients had evidence for altered thyroid function during the 18-24 months of follow-up. The remaining 49 patients (13.3%) progressively developed thyroid function abnormalities (mainly hypothyroidism) indicating the presence of thyroid gland changes due to PPTD. Further follow-up studies indicated that at 18-24 months, 42 patients had serum levels of anti-TPO-Ab that were more elevated, as compared with the first year values. Predictive factors found during pregnancy for developing PPTD were: (1) relatively low levels of anti-TPO, between 60 and 100 U/ml (odds ratio 3.1 : 1), and (2) ultrasonographic thyroid structural changes in the first trimester (odds ratio 6.4 : 1). We conclude that the prevalence of postpartum thyroid dysfunction in our geographical area ranges from 6.7% to 13.3%, considering, respectively, all pregnant women that were examined (n = 754) or only the number of puerperal women actually followed-up (n = 368). A transient form of thyroid autoimmune reaction characterized by elevated serum levels of anti-TPO that progressively declined or disappeared was observed in 29 puerperal women. Sonographic structural and echogenicity changes in the thyroid gland and borderline positive anti-TPO levels (between 60 and 100 U/ml) during pregnancy were considered to be of predictive value for development of postpartum thyroid dysfunction.


Treg-driven tumour control by PI3Kδ inhibition limits myeloid-derived suppressor cell expansion.
Recent studies have demonstrated that blocking the PI3Kδ signalling enzyme (by administering a small molecule inhibitor, PI-3065) can potently improve the anti-tumour T-cell response through direct inhibition of Tregs. This treatment also has a negative impact on MDSC numbers but the primary mechanism driving this effect has remained unclear. The 4T1 breast cancer mouse model was used in combination with PI-3065 to gain insights into the effect of PI3Kδ inhibition on MDSCs. PI-3065 treatment resulted in a concomitant reduction in MDSC expansion and tumour size. However, targeting Tregs independent of PI-3065 was also associated with reduced tumour volume and MDSC numbers. Surgical removal of tumours resulted in a rapid and significant decline in MDSC numbers, whilst ex vivo studies using cells from PI-3065-treated mice demonstrated no direct effect of the inhibitor on MDSC activity. Our data suggest that MDSCs are not inhibited directly by PI-3065 treatment but that their reduced recruitment and immunosuppression within the tumour microenvironment is an indirect consequence of PI3Kδ-inhibition-driven tumour control. This indicates that PI3Kδ inhibition drives tumour immunity by breaking down multiple immunosuppressive pathways through both direct mechanisms (on Treg) and indirect mechanisms, secondary to tumour control (on MDSCs).


Citrus essential oil: would it be feasible as antimicrobial in the bioethanol industry?
Essential oils (EOs) extracted from Citrus peels contain 85%-99% volatile components (a mixture of monoterpenes, sesquiterpenes, and their oxygenated derivatives) and 1%-15% non-volatile compounds. Citrus EOs have been long known for their antimicrobial properties, owing to which these EOs have a diverse range of applications. However, no studies have reported the applicability of Citrus EOs for the control of bacterial and yeast contaminants in the bioethanol industry. In this regard, the present review aimed to explore the feasibility of Citrus EOs in this industry. The Web of Science database was searched for reports that described the association of Citrus EOs with the most common microorganisms in the bioethanol industry to evaluate the efficacy of these EOs as antimicrobial agents in this context. The objective of the review was to suggest a novel antimicrobial that could replace sulfuric acid and antibiotics as the commonly used antimicrobial agents in the bioethanol industry. Citrus EOs exhibit antibacterial activity against Lactobacillus, which is the main bacterial genus that contaminates this fermentation process. The present report also confirms the selective action of these EOs on the contaminating yeasts and not/less on ethanol-producing yeast Saccharomyces cerevisiae, however further studies should be conducted to investigate the effects of Citrus EOs in yeast-bacterium co-culture.


Vasopressor effects of intracerebroventricular injections of PEC-60, a novel porcine 60-residue intestinal peptide, in the awake unrestrained male rat.
Intracerebroventricular injections (140-4300 pmol) of a 60-residue polypeptide (now designated PEC-60) isolated from pig intestine produced a dose-dependent increase (peak action 21% +/- 2; ED50 value of 1.7 nmol for the peak effect) in mean arterial blood pressure (MAP) in the awake, unrestrained male rat. The heart rate (HR) was significantly reduced with the highest doses used (1400 and 4300 pmol). The pancreatic secretory trypsin inhibitor (PSTI), with a high degree of sequence similarity to PEC-60, did not significantly change MAP and HR (4300 pmol). These results may indicate a biological role for the putative PEC-60-like peptide demonstrated within central catecholamine cardiovascular neurons.


Patient-centered communication and diagnostic testing.
Although patient-centered communication is associated with improved health and patient trust, information about the impact of patient-centered communication on health care costs is limited. We studied the relationship between patient-centered communication and diagnostic testing expenditures. We undertook an observational cross-sectional study using covert standardized patient visits to study physician interaction style and its relationship to diagnostic testing costs. Participants were 100 primary care physicians in the Rochester, NY, area participating in a large managed care organization (MCO). Audio recordings of 2 standardized patient encounters for each physician were rated using the Measure of Patient-Centered Communication (MPCC). Standardized diagnostic testing and other expenditures, adjusted for patient demographics and case-mix, were derived from the MCO claims database. Analyses were adjusted for demographics and standardized patient detection. Compared with other physicians, those who had MPCC scores in the lowest tercile had greater standardized diagnostic testing expenditures (11.0% higher, 95% confidence interval [CI], 4.5%-17.8%) and greater total standardized expenditures (3.5% higher, 95% CI, 1.0%-6.1%). Whereas lower MPCC scores were associated with shorter visits, adjustment for visit length and standardized patient detection did not affect the relationship with expenditures. Total (testing, ambulatory and hospital care) expenditures were also greater for physicians who had lower MPCC scores, an effect primarily associated with the effect on testing expenditures. Patient-centered communication is associated with fewer diagnostic testing expenditures but also with increased visit length. Because costs and visit length may affect physicians' and health systems' willingness to endorse and practice a patient-centered approach, these results should be confirmed in future randomized trials.


Validity of record ratings of the Global Assessment Scale.
The Global Assessment Scale (GAS) is a comprehensive rating of psychiatric status that is usually based on face-to-face interviews. Validity has not been established for the use of the GAS when it is based on secondary sources of information about the patient, source of patient information, although secondary sources have been used for this purpose. The current study examined agreement between GAS ratings based on medical records and ratings based on face-to-face interviews. Results showed moderate agreement between the two sets of ratings, with the intraclass correlation-coefficient (ICC) equaling .62. Record-based (R)-GAS ratings were upwardly biased and were restricted in range when compared with interview-based (I)-GAS ratings. A case-by-case analysis showed that the disagreement could be accounted for by inconsistent documentation of the degree of functional impairment in the most severely disturbed patients. We conclude the following: If R-GAS ratings are used, designs should be modified to adjust for probable overestimated functioning of the most severely disturbed patients.


The Impact of Alcoholic Beverages on Human Health.
As summarized in the World Health Organization's latest Global Status Report on Alcohol, the pleasure of alcohol is indicated by the fact that, worldwide, just over two-fifths of the population aged 15+ years drink alcohol; 2 [...].


In Their Own Words: Clinician Experiences and Challenges in Administering Evidence-Based Treatments for PTSD in the Veterans Health Administration.
The aim of the present study was to increase the understanding of clinician experiences with administering two evidence-based psychotherapies (EBPs) for PTSD (Cognitive Processing Therapy and Prolonged Exposure therapy) in the Veterans Affairs Healthcare System (VA). The study assessed clinician perceptions through the use of two, one-hour focus groups and employed a rigorous data analysis approach, Consensual Qualitative Research. Clinicians who work in an outpatient PTSD clinic at a New England VA, and who routinely administer EPBs for PTSD, participated in the study. Results were categorized into seven domains by the coding team, including 1) EBP Strengths, 2) EBP Weaknesses, 3) Challenges Specific to the Veteran Population, 4) Perceived EBP Effectiveness, 5) Active Ingredients for Treating PTSD, 6) Treatment Structure and Process, and 7) Suggested Changes/Improvements to EBPs. These domains are discussed in detail, with several core ideas falling under each domain. Operational definitions and representative quotes are provided. Overall, clinicians provided a balanced perspective and identified both strengths and weaknesses of the EBPs for PTSD. They identified several challenges in applying these treatments to veteran populations, and shared their beliefs about treatment effectiveness, how they use these treatments in their clinical practice, and how they would change the treatments if given an opportunity to do so. In this way, the study offers a small but important step in attempting to address the science-practice gap related to EBP for PTSD implementation efforts in the VA.


Nuclear magnetic resonance-based metabolomic analysis in the assessment of preclinical atherosclerosis in type 1 diabetes and preeclampsia.
Evaluate the role of plasma metabolomics in atherosclerosis according to the presence of type 1 diabetes (T1D) or previous preeclampsia. We recruited 105 women without cardiovascular disease and last pregnancy ≥5 years previously, divided according to the presence of T1D or previous preeclampsia. Preclinical atherosclerosis was defined as the presence of carotid plaque (intima-media thickness ≥1.5 mm) assessed by ultrasonography. Metabolomics were evaluated by nuclear magnetic resonance (NMR). Bivariate and multivariate-adjusted differences in NMR-metabolomics were evaluated. The participants were 44.9 ± 8.1 years-old; 20% harbored plaques. There were significant differences in lipidic-, energetic- and nitrogen-related metabolites according to the presence of T1D/preeclampsia (p < 0.05). In multivariate-adjusted models (by age, statins, blood pressure and T1D/preeclampsia), only lipidomic-related metabolites were associated with atherosclerosis in the whole sample. However, stronger associations were observed in women with previous preeclampsia (vs. without; per 0.5 mmol/L increments); phosphatidylcholine, OR 4.08 (1.32-27.22); free cholesterol, 5.18 (1.22-21.97); saturated fatty acids, OR 2.99 (1.37-6.48); w-7, OR 2.29 (1.15-4.56); and w-9 fatty acids, OR 1.49 (1.00-2.23). NMR-metabolomics showed a differential pattern according to the presence of T1D/preeclampsia in relation to preclinical atherosclerosis. Since most of these metabolites mirror lifestyle factors, they could help tailor dietetic advice in high-risk women.


Alanine administration does not stimulate gluconeogenesis in preterm infants.
Gluconeogenesis partially depends on sufficient precursor supply, and plasma alanine concentrations are generally low in preterm infants. Stimulation of gluconeogenesis may contribute to the prevention of hypoglycemia, an important clinical problem in these infants. In this study we evaluated the effect of extra precursor supply on gluconeogenesis in preterm infants. In 11 infants, gestational age < or = 32 weeks, glucose production rate (GPR) and gluconeogenesis were measured using the [6,6-(2)H(2)]glucose dilution technique and mass isotopomer distribution analysis with [2-(13)C]glycerol, respectively. Unlabeled glucose was administered throughout the study period at a rate of 22 micromol. kg(-1). min(-1). Five infants received alanine (1.5 mg. kg(-1). min(-1)) during the last 3 hours of the study protocol, and 6 infants served as controls. In the control group the rate of gluconeogenesis and GPR remained constant at 4.0 +/- 0.3 micromol. kg(-1). min(-1) and 8.3 +/- 0.6 micromol. kg(-1). min(-1), respectively. In the alanine group plasma alanine concentrations increased from 45 +/- 23 to 829 +/- 115 micromol/L (P =.001); gluconeogenesis and GPR did not differ from control: 3.8 +/- 0.2 micromol. kg(-1). min(-1) and 6.4 +/- 2.0 micromol. kg(-1). min(-1), respectively. We conclude that administration of the gluconeogenic precursor alanine does not stimulate gluconeogenesis in preterm infants, despite a sharp increase in plasma alanine concentrations. We speculate either a restricted capacity of the enzymes involved in the gluconeogenic pathway or a low secretion rate of glucoregulatory hormones as causative mechanisms involved in the gluconeogenic pathway in the preterm neonate.


Hybrid synapse formation between spinal motoneurons and superior cervical ganglion neurons in vitro: a study of the functional reconstruction of visceral organs.
Spinal motoneurons (SMNs) were co-cultured with labeled superior cervical ganglion neurons (SCGNs) in complete medium on coverslips prepared by the microisland technique. "Hybrid" synapses formation between SMNs and SCGNs was examined by double immunostaining, reverse transcription-polymerase chain reaction (RT-PCR), and electrophysiological assays. The number of synaptic puncta was significantly higher in co-cultured cells compared to controls (P<0.01). Spontaneous synaptic currents (SSCs) were also significantly increased in SCGNs within the co-cultured population of cells (P<0.01). These SSCs could be blocked by a specific nicotinic receptor blocker, but not by a glutamate receptor antagonist. These observations clearly demonstrate the functional synapses formation increased in our co-culture system, suggesting that the "hybrid" synapse formation occurred between somatic and automatic neurons. Our data also indicate that acetylcholine and nicotinic receptors may be involved in mediating these processes.


Cerebellar nuclear afferents from the lateral reticular nucleus in the cat.
Cerebellar afferent fibers were anterogradely stained throughout their length after injections of horseradish peroxidase labeled wheat germ agglutinin in the lateral reticular nucleus in cats. Most fibers ascended through the ipsilateral restiform body, but a few fibers ran on the contralateral side. Some anterogradely stained fibers crossed the midline in cerebellum. Terminal fibers were present in the granular layer and in the cerebellar nuclei. Plexuses of nuclear terminal fibers were found in the ipsilateral interposed and dentate nuclei and were dense in the former. A smaller number of presumably terminal fibers were observed in the ipsilateral fastigial nucleus and in the contralateral cerebellar nuclei. The findings give further evidence for the lateral reticular nucleus being an important source of cerebellar nuclear afferents.


Determinants of induced abortion among women received maternal health care services in public hospitals of Arba Minch and Wolayita Sodo town, southern Ethiopia: unmatched case-control study.
About 210 million women become pregnant per year, with one out of every ten pregnancies terminating unsafely worldwide. In developing countries, unsafe induced abortion is a leading cause of maternal mortality and morbidity. In addition, the burden of public health is also greatest in developing regions. In Ethiopia, abortion was responsible for 8.6% of maternal deaths. Despite the problem's significance, little is known about the factors that lead to women terminating their pregnancies. Therefore, this study aims to identify the factors associated with having induced abortion in public hospitals of Arba Minch and Wolayita Sodo town, Southern Ethiopia. An institutional-based unmatched case-control study was conducted among 413 women from 15th April to 15th June 2021 in selected public hospitals of Arba Minch and Wolayita Sodo town, Southern Ethiopia. Cases were women who received induced abortion care services or who received post-abortion care services after being presented to the selected public hospital with an attempt of induced abortion whereas controls were women who came for maternal health care (antenatal or postnatal care) services in selected public hospitals and never had history of induced abortion. The data were collected by pretested and structured questionnaires with face-to-face interviews via Kobo Collect v3.1 mobile tools and analyzed by STATA version14. Logistic regression model was used to identify factors associated with induced abortion. In this study P-value less than 0.05 with 95% CI was declared a result as statistically significant. In this study, 103 cases and 309 controls were participated. Urban residence (AOR = 2.33, 95%CI:1.26, 4.32), encountered first sex at age of 20-24 years (AOR = 0.51, 95%CI:0.27,0.97), multiple sexual partner (AOR = 5.47, 95%CI: 2.98,10.03), women who had one child (AOR = 0.32, 95%CI: 0.10, 0.99), and good knowledge of contraceptives (AOR = 0.12, 95%CI: 0.03, 0.46) were identified as determinants of induced abortion. Interventions focusing on those identified factors could probably reduce the burden and consequences of induced abortion. Sexual and reproductive health education and family planning programs would target urban dwellers, women who start sexual intercourse between the ages of 15 and 19, women with more than one sexual partner, women with a desire to limit childbearing, and women with poor contraceptive knowledge in order to reduce induced abortion.