Parent-Infant Interaction during the First Year of Life in Infants at High Risk for Cerebral Palsy: A Systematic Review of the Literature.
Perinatal adverse events put neonates at high risk for short and long-term disabilities, including cerebral palsy (CP). The most recent guidelines about early intervention in infants with brain damage have emphasized the importance of family involvement from the very first phases of development. Early parent-infant interactions are pivotal in promoting infant cognitive and social developmental trajectories. However, little is known about the extent to which severe adverse perinatal events can affect the quality of early parent-infant interactions. We systematically searched five databases (PubMed, PsycINFO, EMBASE, CINAHL, and Cochrane Library) for the publications assessing parent-infant interactions in infants at high neurological risk within 1 year of age. Articles were selected if they involved direct comparison between high-risk populations and healthy controls or low-risk populations, and if quantitative or semiquantitative tools were used to assess the parent-infant interaction. Measures of parent-infant interaction included infant interactive behaviors, parental interactive behaviors, and dyadic interactive patterns. The search yielded 18 publications that met the inclusion criteria. The articles represent a high level of heterogeneity in terms of infant neurological risk, infant age, and tools assessing interactive behaviors. Both infant and maternal behaviors within the investigated interactive exchanges were reported to be compromised, leading to subsequent overall impairment of the dyadic patterns. While the studies reviewed here provide general and important information, the review did not yield a clear picture of early dyadic interactions in high-risk infant populations. Further observational studies are warranted in order to provide a more accurate knowledge of the early dyadic exchanges between infants at high neurological risk and their parents, as they might provide a critical opportunity for early family centered habilitative interventions.


Stability of dried blood spots for HIV-1 drug resistance analysis.
The wide scale application of dried blood spots (DBS) as a collection tool for low-cost HIV drug resistance testing requires a greater understanding of the accuracy of DBS for genotype analysis and the stability of DBS under various environmental conditions. Analysis of a 50microl DBS via a single amplicon, nested PCR-based in-house assay (the Burnet genotyping assay) showed an average nucleotide concordance of 98.9% with plasma samples, although only 65% of nucleotide mixtures detected in plasma were also detected within DBS. The analysis of three DBS resulted in the detection of a greater number of nucleotide mixtures (72 and 109 mixtures detected within one and three DBS, respectively, n=10). Two DBS extraction protocols (silica particle; NucliSENS, bioMerieux and spin column extraction; High Pure, Roche) were assessed and found to be equivalent (79% and 84% recovery success respectively, n=19). FTA Elute paper (Whatman) was an inferior DBS collection medium compared to Whatman 903 paper. DBS appeared relatively tolerant to multiple freeze/thaw cycles, with 79% of DBS subjected to ten freeze/thaw cycles successfully amplified compared to 93% of DBS defrosted once (n=14). High temperature (37 degrees C) and high humidity (>90%) substantially impaired DBS recovery within two weeks of storage (38%, n=8), whilst storage at -20 degrees C or 4 degrees C adequately preserved DBS for this period (100% recovery, n=8). Therefore, whilst DBS are suitable for HIV drug resistance surveillance, the use of multiple DBS may be required to ensure accurate detection of minor HIV quasispecies and short-term storage of samples at either 4 degrees C or -20 degrees C is recommended.


Building bridges of excellence: a comprehensive competence framework for nurses in hospice and palliative care-a mixed method study.
Hospice and Palliative Care (HPC) is in high demand in China; however, the country is facing the shortage of qualified HPC nurses. A well-suited competence framework is needed to promote HPC human resource development. Nevertheless, existing unstandardized single-structured frameworks may not be sufficient to meet this need. This study aimed at constructing a comprehensive multi-structured HPC competence framework for nurses. This study employed a mixed-method approach, including a systematic review and qualitative interview for HPC competence profile extraction, a two-round Delphi survey to determine the competences for the framework, and a cross-sectional study for framework structure exploration. The competence profiles were extracted from publications from academic databases and interviews recruiting nurses working in the HPC field. The research team synthesized profiles and transferred them to competences utilizing existing competence dictionaries. These synthesized competences were then subjected to Delphi expert panels to determine the framework elements. The study analyzed theoretical structure of the framework through exploratory factor analysis (EFA) based on a cross-sectional study receiving 491 valid questionnaires. The systematic review involved 30 publications from 10 countries between 1995 and 2021, while 13 nurses from three hospitals were interviewed. In total, 87 and 48 competence profiles were respectively extracted from systematic review and interview and later synthesized into 32 competences. After the Delphi survey, 25 competences were incorporated into the HPC competence framework for nurses. The EFA found a two-factor structure, with factor 1 comprising 18 competences namely Basic Competences; factor 2 concluding 7 competences namely Developmental Competences. The two-factor HPC competence framework provided valuable insights into the need and directions of Chinese HPC nurses' development.


Critical time delay of the pineal melatonin rhythm in humans due to weak electromagnetic exposure.
Electromagnetic fields (EMFs) can increase free radicals, activate the stress response and alter enzyme reactions. Intracellular signalling is mediated by free radicals and enzyme kinetics is affected by radical pair recombination rates. The magnetic field component of an external EMF can delay the "recombination rate" of free radical pairs. Magnetic fields thus increase radical life-times in biological systems. Although measured in nanoseconds, this extra time increases the potential to do more damage. Melatonin regulates the body's sleep-wake cycle or circadian rhythm. The World Health Organization (WHO) has confirmed that prolonged alterations in sleep patterns suppress the body's ability to make melatonin. Considerable cancer rates have been attributed to the reduction of melatonin production as a result of jet lag and night shift work. In this study, changes in circadian rhythm and melatonin concentration are observed due to the external perturbation of chemical reaction rates. We further analyze the pineal melatonin rhythm and investigate the critical time delay or maturation time of radical pair recombination rates, exploring the impact of the mRNA degradation rate on the critical time delay. The results show that significant melatonin interruption and changes to the circadian rhythm occur due to the perturbation of chemical reaction rates, as also reported in previous studies. The results also show the influence of the mRNA degradation rate on the circadian rhythm's critical time delay or maturation time. The results support the hypothesis that exposure to weak EMFs via melatonin disruption can adversely affect human health.


Are N-of-1 trials an economically viable option to improve access to selected high cost medications? The Australian experience.
To explore the economic viability of N-of-1 trials for improving access to selected high cost medications in Australia. Cost and effectiveness estimates were derived from two N-of-1 trials conducted by The University of Queensland from 2003 to 2005-celecoxib versus sustained-release paracetamol for osteoarthritis in a general practice setting and gabapentin versus placebo for chronic neuropathic pain in a hospital setting. Effectiveness was determined by the proportion of responders to each medication. The costs of trials were offset against the savings generated by subsequent changes in prescribing. Decision analysis models with semi-Markov processes were used to compare different scenarios of N-of-1 trials versus usual care. The fixed cost of performing N-of-1 trials was approximately AUS$23,000 for each trial and the variable cost was approximately AUS$1300 per participant. Clinical outcomes favored celecoxib over paracetamol in 17% of participants and gabapentin over placebo in 24% of participants. Modeling these results showed that the cost-offsets from efficient use of medications were less than the cost of running a trial; however, the incremental costs per quality-adjusted life-year gained were AUS$6,896 and AUS$29,550 for the gabapentin/placebo and celecoxib/paracetamol trials, respectively, over a 5-year horizon. Key factors affecting the viability were the time horizon modeled, the variable cost per participant, the probability of response to the intervention medication, and rates of use in nonresponders and the usual care alternative. The N-of-1 strategy offers a realistic and viable option for increasing access to selected high cost medications where the medications are used for the symptomatic treatment of chronic disease, have rapid onset of action, and clinical response is unpredictable without a trial.


Starch films loaded with tannin: the study of rheological and physical properties.
Recently, the research on innovative food packaging has been oriented toward biodegradable materials to lower the environmental impact generated by conventional plastics. The films often carry functional additives interacting with the matrix and modifying its physical properties. In this work tannin, a scarcely exploited active additive, was used to obtain potato starch-based films, and its content was optimized on the basis of mechanical and microscopic tests. Rheological measurements were adopted to evaluate the tannin-starch interaction and the microstructure of the film forming solutions (FFSs). Their thickness, color, thermal conductivity, elastic modulus (Eel), elongation at break (EAB), surface wettability and water solubility were evaluated. Furthermore, microstructure was investigated through Fourier-transform infrared spectroscopy (FTIR), polarized light (POM) and scanning electron microscopy (SEM). It was observed that all FFSs behave as weak gels and tannin addition weakens the gel structure and decreases the gelatinization temperature from about 60 °C to 57 °C. Plastic and deformable films (Eel = 1.96 MPa and EAB = 189 %) were obtained at low tannin fractions, whereas, at a higher concentration, stiffer films (Eel = 12 MPa and EAB = 10 %), with hydrophobic behavior were produced. Among the tested tannin fractions, an intermediate value of 1.7 % (w/w) was found to be promising for industrial purposes.


Mitochondrial Involvement in Mental Disorders; Energy Metabolism, Genetic, and Environmental Factors.
Mental disorders such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) are generally characterized by a combination of abnormal thoughts, perceptions, emotions, behavior, and relationships with others. Multiple risk factors incorporating genetic and environmental susceptibility are associated with development of these disorders. Mitochondria have a central role in the energy metabolism, and the literature suggests energy metabolism abnormalities are widespread in the brains of subjects with MDD, BD, and SZ. Numerous studies have shown altered expressions of mitochondria-related genes in these mental disorders. In addition, environmental factors for these disorders, such as stresses, have been suggested to induce mitochondrial abnormalities. Moreover, animal studies have suggested that interactions of altered expression of mitochondria-related genes and environmental factors might be involved in mental disorders. Further investigations into interactions of mitochondrial abnormalities with environmental factors are required to elucidate of the pathogenesis of these mental disorders.


Conservative treatment of rotator cuff tears.
Among 124 shoulders in 114 patients with complete rotator cuff tears who had been treated conservatively from 1980 until 1989, 62 shoulders in 54 patients were observed to identify the findings on initial examinations and correlate them with the final results. The follow-up period averaged 3.4 years. According to modified criteria of Wolfgang, 51 shoulders in 45 patients (82%) rates satisfactory (excellent or good). The overall scores of pain, motion, and function improved significantly. The results were less satisfactory in patients observed more than six years. The patients with satisfactory results (Group 1) and unsatisfactory results (Group 2) among those observed more than five years were compared. In Group 1, the scores of pain, motion, and strength improved significantly at follow-up examinations, whereas those of function did not. In Group 2, no improvement was recognized in any categories. The only significant differences in the initial findings between the two groups were the active abduction angle and the abduction strength: the patients in Group 1 retained a good range of motion and strength, whereas those with unsatisfactory results had a limited range and muscle weakness on first examinations. Conservative treatment affords satisfactory results when it is given to the patients with well-preserved motion and strength, although in some cases function may deteriorate with time.


Crystallization and preliminary X-ray crystallographic analysis of the small subunit of the heterodimeric laccase POXA3b from Pleurotus ostreatus.
Laccases are multicopper oxidases of great biotechnological potential. While laccases are generally monomeric glycoproteins, the white-rot fungus Pleurotus ostreatus produces two closely related heterodimeric isoenzymes composed of a large subunit, homologous to the other fungal laccases, and a small subunit. The sequence of the small subunit does not show significant homology to any other protein or domain of known function and consequently its function is unknown. The highest similarity to proteins of known structure is to a putative enoyl-CoA hydratase/isomerase from Acinetobacter baumannii, which shows an identity of 27.8%. Diffraction-quality crystals of the small subunit of the heterodimeric laccase POXA3b (sPOXA3b) from P. ostreatus were obtained using the sitting-drop vapour-diffusion method at 294 K from a solution consisting of 1.8 M sodium formate, 0.1 M Tris-HCl pH 8.5. The crystals belonged to the tetragonal space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = 126.6, c = 53.9 Å. The asymmetric unit contains two molecules related by a noncrystallographic twofold axis. A complete data set extending to a maximum resolution of 2.5 Å was collected at 100 K using a wavelength of 1.140 Å.


True complete left bundle branch block morphology strongly predicts good response to cardiac resynchronization therapy.
To determine whether patients with congestive heart failure and true left bundle branch block (LBBB) morphology have better response to cardiac resynchronization therapy (CRT) than do patients without true LBBB. We defined true LBBB as conventional LBBB plus QRS duration ≥ 130 ms and mid-QRS notching/slurring in at least two of the leads I, aVL, V1, V2, V5, or V6. We prospectively enrolled 58 patients with heart failure and allocated them to three groups: true LBBB (t-LBBB, n = 22); non-true LBBB (nt-LBBB, LBBB with no notch or notches in fewer than two of the leads, n = 17); and non-specific intraventricular conduction delay (IVCD, n = 19). At 6 month follow-up, mean absolute increases in left ventricular ejection fraction were 16.0% ± 11.6% in t-LBBB, 8.1% ± 11.2% in nt-LBBB (P = 0.02), and 3.3% ± 7.8% in IVCD (P < 0.001, t-LBBB vs. IVCD) and changes in mean New York Heart Association class were -1.2 ± 0.6 in t-LBBB, -0.8 ± 0.6 in nt-LBBB (P = 0.071), and -0.5 ± 0.6 in IVCD (P = 0.01, t-LBBB vs. IVCD). All patients with t-LBBB were responders, some were super-responders. Multivariate analysis showed that t-LBBB (odds ratio, OR, 11.680; 95% confidence interval, CI, 1.966-69.390; P = 0.007) and left ventricular end-diastolic dimension (OR, 0.891; 95% CI, 0.797-0.996; P = 0.043) are independent predictors of super-response to CRT. In patients with conventional wider LBBB morphology, the presence of mid-QRS notching or slurring is a strong predictor of better response to CRT.


Pressor factors and cardiovascular pressor reponsiveness in essential hypertension.
The sympathetic system, the body sodium-fluid volume state, the reninangiotensin system, functional and structural characteristics of the heart and blood vessels, and some other components are important complementary factors in blood pressure regulation. A deviation from the normal equilibrium among these components, with a persisting non-physiologic increase in pressor factor(s) or in the basal vascular tone and/or cardiovascular reactivity to pressor factors, leads to hypertension. This review discusses recent observations and concepts regarding the roles of various pressor factors as well as cardiovascular pressor responsiveness in the pathogenesis of essential hypertension and in the anti-hypertensive mechanism of diuretic treatment.


Inverse modulation of plant immune and brassinosteroid signaling pathways by the receptor-like cytoplasmic kinase BIK1.
Maintaining active growth and effective immune responses is often costly for a living organism to survive. Fine-tuning the shared cross-regulators is crucial for metazoans and plants to make a trade-off between growth and immunity. The Arabidopsis regulatory receptor-like kinase BAK1 complexes with the receptor kinases FLS2 in bacterial flagellin-triggered immunity and BRI1 in brassinosteroid (BR)-mediated growth. BR homeostasis and signaling unidirectionally modulate FLS2-mediated immune responses at multiple levels. We have shown previously that BIK1, a receptor-like cytoplasmic kinase, is directly phosphorylated by BAK1 and associates with FLS2/BAK1 complex in transducing flagellin signaling. In contrast to its positive role in plant immunity, we report here that BIK1 acts as a negative regulator in BR signaling. The bik1 mutant displays various BR hypersensitive phenotypes accompanied with increased accumulation of de-phosphorylated BES1 proteins and transcriptional regulation of BZR1 and BES1 target genes. BIK1 associates with BRI1, and is released from BRI1 receptor upon BR treatment, which is reminiscent of FLS2-BIK1 complex dynamics in flagellin signaling. The ligand-induced release of BIK1 from receptor complexes is associated with BIK1 phosphorylation. However, in contrast to BAK1-dependent FLS2-BIK1 dissociation, BAK1 is dispensable for BRI1-BIK1 dissociation. Unlike FLS2 signaling which depends on BAK1 to phosphorylate BIK1, BRI1 directly phosphorylates BIK1 to transduce BR signaling. Thus, BIK1 relays the signaling in plant immunity and BR-mediated growth via distinct phosphorylation by BAK1 and BRI1, respectively. Our studies indicate that BIK1 mediates inverse functions in plant immunity and development via dynamic association with specific receptor complexes and differential phosphorylation events.


[Current problems of immunoprophylaxis of infectious and non-infectious diseases].
Progress in immunology greatly contributed to the understanding of mechanisms of infectious immunity and vaccine action. Moreover, it facilitated the development of new vaccines and vaccination not only of healthy children but also of subjects with health problems and chronic diseases including the use of several vaccines. The number of contraindications could be decreased without a rise in the frequency of post-vaccination complications. Immunoprophylaxis allowed the incidence of controllable infections to be reduced; the level of epidemiologic well-being achieved in the course of this work provided a basis for eradication of some diseases. At the same time, successes of vaccination made mankind dependent on the use of vaccines. As a result, discontinuation of mass vaccination and even temporal decrease of its scale in the absence of certain infections or in the situation of their sporadic occurrence (i.e. the lack of natural immunization) lead to their reappearance. Specific features of modern immunoprophylaxis of infectious and non-infectious pathology and its timetable are described.


Unusually high numbers of ribosomal RNA genes in copepods (Arthropoda: Crustacea) and their relationship to genome size.
We report on copy numbers of 18S ribosomal RNA genes in three species of copepods (Crustacea: Copepoda), two of which possess an unusual arrangement in which 5S genes are included within the 18S-5.8S-28S repeat unit. Slot blots of genomic and standard DNA were hybridized with an 18S rRNA gene probe constructed from one of the marine species and hybridization was quantified using chemiluminescence. Diploid 18S rRNA gene copy numbers are estimated as ca. 15 300 and 33 500 in the marine species Calanus finmarchicus (13.0 pg DNA in 2C adult nuclei) and C. glacialis (24.2 pg DNA), respectively, and ca. 840 and 730 in two freshwater populations of Mesocyclops edax (both ca. 3 pg DNA) from Virginia and Nova Scotia, respectively. The roughly proportional relationship between 2C somatic nuclear DNA contents and rRNA gene copy number in the sibling species C. finmarchicus and C. glacialis may reflect polytenic replication of entire genomes during abrupt speciation events. Copy numbers may also reflect differential losses during embryonic chromatin diminution.


Long-term prognosis of acute kidney injury after acute myocardial infarction.
Acute kidney injury (AKI) is a common complication during hospitalization and is an accepted risk factor for in-hospital mortality. However, the association of severity of AKI with the long-term risk of death is not well defined. To examine the independent effect of the severity of AKI on long-term risk of death following acute myocardial infarction (AMI), we performed an observational study of 147007 elderly Medicare patients admitted for AMI from January 1994 through February 1996 as a part of the Cooperative Cardiovascular Project. We evaluated the association between AKI and all-cause mortality. We defined AKI as absolute changes in serum creatinine level, categorized as none (creatinine level increase, < or =0.2 mg/dL), mild (0.3-0.4 mg/dL increase), moderate (0.5-0.9 mg/dL increase), and severe (> or =1.0 mg/dL increase). Overall, 19.4% of the patients had AKI, including 7.1% with mild AKI, 7.1% with moderate AKI, and 5.2% with severe AKI. Less than 10% of patients who had severe AKI were alive at 10 years compared with 12.2%, 21.1%, and 31.7% patients with moderate, mild, and no AKI, respectively. The adjusted hazard ratio for death for in-hospital survivors at 10 years was 1.15 (95% confidence interval [CI], 1.12-1.18) for mild AKI, 1.23 (95% CI, 1.20-1.26) for moderate AKI, and 1.33 (95% CI, 1.28-1.38) for severe AKI. Similar results were obtained in several secondary analyses that included inpatient mortality, excluded mortality in the first 3 years, and stratified by some specified high-risk groups. Moderate or severe AKI were comparable in strength with other known correlates of cardiovascular mortality. Acute kidney injury has an independent and graded association with long-term mortality. These results should stimulate additional mechanistic and interventional studies and plans for follow-up of patients with AKI after discharge.


Factors affecting breastfeeding adherence among Chinese mothers: A multicenter study.
Breastfeeding is beneficial for both infant and mother, but discontinuation of breastfeeding is very common.To investigate maternal breastfeeding intention and the rate of breastfeeding based on the theory of reasoned action, and analyze the predominant factors associated with breastfeeding and breastfeeding problems.This observational study was conducted in 3 hospitals. Three researchers recruited women at 3 time points in the hospitals: initial documentation of pregnancy at the outpatient department, prenatal admission, and postpartum discharge. SPSS version 21 was used for statistical analyses. Significance was set at P < .05. In the multivariate analysis, binary logistic regression was used and odds ratios (ORs) with 95% confidence intervals (CI) were calculated.We recruited 1260 women, with 420 pregnant women at each time point. 55.1% of the infants were exclusively breastfed, 40.6% were mixed fed, and 4.3% were formula fed when discharged from hospital. A total of 53.8% of the mothers declared having breastfeeding problems. The multivariate analysis showed that nonsuccessful breastfeeding was associated with neonatal birth length, food intake before breastfeeding, infrequent sucking, the intention of breastfeeding, understanding level of the benefits of breastfeeding and that breastfeeding problems were related with the understanding level of the benefits of breastfeeding, neonatal birth length, normal vaginal delivery, breast size, the experience of breastfeeding, use of pacifier and the needs of family member's support in breastfeeding.Most mothers who intended to practice exclusive breastfeeding initially chose to add formula and had breastfeeding problems when discharged from hospital. Successful breastfeeding depends on antenatal and postnatal breastfeeding education and on support provided by healthcare professionals.


Fruits and vegetables consumption and esophageal squamous cell carcinoma: a case-control study.
The authors examined the association of food group intakes and the risk of esophageal squamous cell carcinoma (SCC) in a hospital-based case-control study in Iran. In total, 47 patients with esophageal SCC and 96 controls underwent face-to-face private interviews. Usual dietary intake was assessed using a semiquantitative food frequency questionnaire. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals. Cases had higher tobacco consumption and symptomatic gastresophageal reflux, whereas controls had higher mean body mass index (25.3 vs. 20.4) and years of education. A protective independent effect was observed for the highest tertile of total fruit consumption (OR: 0.13, CI: 0.04-0.45, P value = 0.001). Within the group of fruits, a significant inverse association was observed for bananas and kiwis (P for trends: 0.03 and 0.02, respectively). The risk of SCC decreased monotonically with increasing intake frequency of oranges (P value for trend = 0.01). The effect of total vegetable consumption on esophageal SCC was not significant, although a reduction in risk was observed in the highest tertile of intake (OR: 0.66, CI: 0.23-1.87, P value = 0.43). The results of the present study suggest a reasonable association between fruit consumption and esophageal SCC in a Middle Eastern high-risk population.


Ultraviolet-induced alterations of beat rate and electrical properties of embryonic chick heart cell aggregates.
Embryonic heart cell aggregates were irradiated with ultraviolet light at wavelengths between 260 and 310 nm. Spontaneous beat rate was monitored with the aid of a closed-circuit TV camera and, in separate experiments, electrophysiological changes were assayed by intracellular recording. The characteristic response of 7-day aggregates was an increase in spontaneous beat rate to a maximum plateau level, followed by a rather abrupt cessation of beating. Intracellular recordings during irradiation showed a marked decline in the maximum rate of rise, overshoot, and repolarization phase of the action potential, and a significant change in threshold toward zero. The action spectrum for the termination of beating peaked between 290 and 295 nm; it fell off sharply at longer wavelengths and more slowly at shorter wavelengths. The maximum increase in beat rate was increasingly greater for shorter wavelengths and exhibited no peak in the wavelength range investigated. The sensitivity of aggregates to 295-nm light, as measured by the inverse of irradiation time required to terminate beating, decreased with increasing aggregate size and external potassium concentration, was relatively independent of temperature, and increased with embryonic age. The ultraviolet-induced increase in beat rate and termination of beating are attributed to separate complementary processes, a depolarization of the membrane, and a decline in "fast" sodium conductance.


Characterization of an HLA-C-restricted CTL response in chronic HIV infection.
HIV-specific CTL play an important role in the host control of HIV infection. HIV-nef may facilitate escape of HIV-infected cells from CTL recognition by selectively downregulating the expression of HLA-A and HLA-B molecules, while surface expression of HLA-C is unaffected. The HLA-C-restricted CTL responses have previously been largely ignored and poorly characterized. We examined the frequency, function, and phenotype of HLA-C-restricted CTL in ten antiretroviral therapy-naïve Caucasian and African individuals with chronic HIV-1 infection (for at least 8 years; CD4 cell counts in the range of 50-350) who carried the HLA-Cw04 allele. HLA-Cw04-restricted CTL that recognize a conserved epitope within HIV-1 envelope (aa 375-383 SF9) were analyzed using IFN-gamma ELISPOT assays and phenotypic analysis was carried out by flow cytometry. HLA-C-restricted CTL play an important role in the HIV-specific response, and can account for as much as 54% of the total response. HLA-C-restricted CTL are functionally and phenotypically identical to HLA-A- and HLA-B-restricted CTL. HLA-C-restricted CTL in chronic HIV infection are memory cells of an intermediate phenotype, characterized by high CD27 and low CD28 expression and lack of perforin production.


Glucocorticoid regulation of surfactant components in immature lambs.
To assess effects of dose and duration of glucocorticoid exposure on maturation of the fetal lung, we administered single or multiple doses of betamethasone (0.5 mg/kg im) to pregnant sheep for 2 or 21 days before preterm delivery at 125 days of gestation. Lung function (compliance, lung volume at 40 cmH2O pressure, and ventilatory efficiency index) was increased after two to four weekly doses of glucocorticoid (2.5- to 4-fold increase) and after 48 h of exposure (1.4- to 2.3-fold). Total protein of lavage fluid decreased similarly with three doses, four doses, and 48 h of treatment. In lambs with long-term exposure to betamethasone, there was a similar, dose-dependent increase in concentrations of saturated phosphatidylcholine and surfactant proteins A (SP-A) and B (SP-B) (maximal 2- to 3-fold in tissue and 10- to 15-fold in lavage fluid). Levels of SP-A and SP-B were closely correlated in lavage fluid. In animals treated for 48 h, only tissue SP-B was increased (2.7-fold). We conclude that 48 h of glucocorticoid treatment improves lung function in the premature lamb without a detectable increase in lavage surfactant components and that longer exposure to antenatal glucocorticoid increases surfactant lipid and proteins in a coordinated fashion. The enhanced response with repetitive dosing indicates that the process of glucocorticoid-induced lung maturation is either reversible and/or gestational age dependent.


Epidemiology of Dance-Related Injuries Presenting to Emergency Departments in the United States, 2000-2013.
Dance is a popular activity associated with many physical and mental health benefits, but injuries are a concern for all skill levels. Previous studies have focused on professional dancers or particular genres, meaning the population-wide characteristics of injuries is unknown. This study's objective was to identify the incidence and types of dance-related injuries evaluated in emergency departments in the United States over the 14-year period 2000-2013. Data were obtained from the nationally representative National Electronic Injury Surveillance System from 2000-2013. National estimates of injuries were determined using complex sample design. Trends using 2-year intervals were calculated using linear regression and injury proportion ratios using Pearson's X2. The average annual incidence of dance-related injuries requiring emergency medical attention was 17,145 per year. The number of injuries grew from 14,204 in 2000/1 to 21,356 in 2012/3, a change of 33.4% after accounting for population growth. Lower limb injuries were most common, particularly ankle and knee sprains. Females presented with a greater proportion of ankle (injury proportion ratio [IPR]=1.34, p=0.029) and foot sprains (IPR=2.11, p<0.001) but a lower proportion of shoulder sprains (IPR=0.41, p<0.001) and face lacerations (IPR=0.13, p<0.001). Younger dancers presented with a lower proportion of knee (IPR=0.79, p=0.006) and low back sprains (IPR=0.68, p=0.019). The average annual incidence of dance-related injuries of a serious enough nature to require presentation to the emergency department in the United States was 17,145 per year, with ankle and knee sprains being the most common. Injury numbers have increased in recent years.


Direct binding of Copine3 with Jab1 activates downstream ErbB2 signaling and motility in SKBr3 breast cancer cells.
Copine3, a known calcium-dependent membrane binding protein, contains two tandem C2 domains and an A domain. This protein has been shown to interact with receptor tyrosine kinase 2 (ErbB2), but little is known concerning the physiological function of Copine3. To better understand its cellular function, we carried out a yeast two-hybrid screen to find Copine3 binding partners. Among the identified proteins, Jun activation domain-binding protein 1 (Jab1) appears to directly interact with Copine3. This physical interaction between Copine3 and Jab1 as well as the specific binding regions of both proteins were confirmed in vitro and in vivo. Our results also demonstrate that binding of Copine3 to ErbB2 is increased when Jab1 is overexpressed in SKBr3 breast cancer cells. Furthermore, two ErbB2 downstream signaling proteins [phosphatidylinositol 3 (PI3) kinase and protein kinase B (AKT)] were also activated by Jab1 overexpression in these cells. These data suggest that binding of Copine3 and Jab1 regulates, at least to some extent, the ErbB2 signaling pathway. Moreover, overexpression of both Copine3 and Jab1 in SKBr3 cells effectively increased cellular migration. Collectively, our findings indicating that Jab1 enhances the ErbB2 binding ability of Copine3, further activating the ErbB2 signaling pathways involved in breast cancer cell pathogenesis.


Eye movement differences between dyslexics, normal, and retarded readers while sequentially fixating digits.
The eye movements of 13 dyslexics, 10 normal, and 16 retarded readers were recorded while they sequentially fixated 7 equidistantly spaced digits from left to right (L----R) and right to left (R----L). This nonreading task simulated the sequential motor components of the reading process. Dyslexics and their controls were selected on the basis of comprehensive and quantifiable criteria. All three groups were of the same chronological age. The dyslexics and retarded readers had also the same reading difficulties, but the causes of their problems were different. Dyslexics made significantly more regressions than the normal or the retarded readers in both directions (L----R and R----L). These results were in line with the ones reported in similar studies and suggest that the dyslexics' erratic eye movements and their excessive number of regressions are present even in nonreading, nonverbal sequential tasks. It may, therefore, be possible to use the eye movement records from nonreading sequential tasks for the objective diagnosis of dyslexia. As such tasks do not depend on reading, they may even be used before reading age.


Creating a Learning Culture for Medical Consortia in China.
In China's recent health care reforms, both individuals and organizations have shown an ever-growing desire and demand for new knowledge and skills. A health care delivery system (HCDS) should explore new ways for creating a learning organization (LO) and should organically combine HCDS culture construction with the LO construction to build a cultural atmosphere that is conducive to the development of the LO. This article describes the implementation phase, characteristics, and realization strategy of an HCDS construction for the ultimate purpose of enhancing HCDS cohesion, solidarity, and sustainable development.


A single auditory tone alters the perception of multiple visual events.
We aimed to show that a single auditory tone crossmodally affects multiple visual events using a multiple stream/bounce display (SBD), consisting of two disk pairs moving toward each other at equal speeds, coinciding, and then moving apart in a two-dimensional (2-D) display. The temporal offsets were manipulated between the coincidences of the disk pairs (0 to ±240 ms) by staggering motion onset between the pairs. A tone was presented at the coincidence timing of one of the disk pairs on half of the trials. Participants judged whether the disks in each of two pairs appeared to stream through or bounce off each other. Results show that a tone presented at either of the disk pairs' coincidence points promoted bouncing percepts in both disk pairs compared to no-tone trials. Perceived bouncing persisted in the disk-pair whose coincidence was offset 60 ms before and up to more than 120 ms after the audiovisual coincidence timing of the other disk-pair. The temporal window of bounce promotion was comparable to that obtained with a conventional SBD. The interaction of a single auditory event and multiple visual events was also modulated by the kind of experimental task (the stream/bounce or simultaneity judgments). These findings suggest that, using a single auditory cue, the perceptual system resolves the ambiguity of the motion of multiple disk pairs presented within the conventional temporal window of crossmodal interaction.


Reduction in the number of repeated operations for the treatment of subacute and chronic subdural hematomas by placement of subdural drains.
The aim of this study was to determine the influence of closed-system subdural drainage on repeated operation rates after burr hole evacuation of subacute and chronic subdural hematomas (SDHs). Five hundred consecutive operations for the treatment of SDH via burr holes were performed between January 1, 1996, and April 15, 2002, at the Auckland Hospital. Hospital records were used to ascertain demographic data, operation, and repeated operation details. Rates of repeated surgeries were compared in patients with and without subdural drains. Repeated operations were performed less frequently in patients with subdural drains, occurring in 31 (10%) of 310 cases involving drains and in 35 (19%) of 188 cases without drains (p < 0.01). Demographics between the two groups were not significantly different except for mean patient age, which was higher among patients with a subdural drain. A lower rate of repeated operation was observed in patients who had undergone drain placement, regardless of whether there was visible evidence of brain reexpansion. Patients have lower rates of repeated surgeries if subdural drains are placed following evacuation of an SDH via a burr hole. To reach high clinical significance, 12 patients must undergo this simple intervention. If technically feasible, subdural drains should be inserted regardless of any occurrence of brain expansion during surgery.


Therapeutic DNA vaccination of vertically HIV-infected children: report of the first pediatric randomised trial (PEDVAC).
Twenty vertically HIV-infected children, 6-16 years of age, with stable viral load control and CD4+ values above 400 cells/mm(3). Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. clinicaltrialsregister.eu _2007-002359-18IT.


Evidence that regulation of intramembrane proteolysis is mediated by substrate gating during sporulation in Bacillus subtilis.
During the morphological process of sporulation in Bacillus subtilis two adjacent daughter cells (called the mother cell and forespore) follow different programs of gene expression that are linked to each other by signal transduction pathways. At a late stage in development, a signaling pathway emanating from the forespore triggers the proteolytic activation of the mother cell transcription factor σK. Cleavage of pro-σK to its mature and active form is catalyzed by the intramembrane cleaving metalloprotease SpoIVFB (B), a Site-2 Protease (S2P) family member. B is held inactive by two mother-cell membrane proteins SpoIVFA (A) and BofA. Activation of pro-σK processing requires a site-1 signaling protease SpoIVB (IVB) that is secreted from the forespore into the space between the two cells. IVB cleaves the extracellular domain of A but how this cleavage activates intramembrane proteolysis has remained unclear. Structural studies of the Methanocaldococcus jannaschii S2P homolog identified closed (substrate-occluded) and open (substrate-accessible) conformations of the protease, but the biological relevance of these conformations has not been established. Here, using co-immunoprecipitation and fluorescence microscopy, we show that stable association between the membrane-embedded protease and its substrate requires IVB signaling. We further show that the cytoplasmic cystathionine-β-synthase (CBS) domain of the B protease is not critical for this interaction or for pro-σK processing, suggesting the IVB-dependent interaction site is in the membrane protease domain. Finally, we provide evidence that the B protease domain adopts both open and closed conformations in vivo. Collectively, our data support a substrate-gating model in which IVB-dependent cleavage of A on one side of the membrane triggers a conformational change in the membrane-embedded protease from a closed to an open state allowing pro-σK access to the caged interior of the protease.


Scapular and rotator cuff muscle activity during arm elevation: A review of normal function and alterations with shoulder impingement.
OBJECTIVE: The purpose of this manuscript is to review current knowledge of how muscle activation and force production contribute to shoulder kinematics in healthy subjects and persons with shoulder impingement. RESULTS: The middle and lower serratus anterior muscles produce scapular upward rotation, posterior tilting, and external rotation. Upper trapezius produces clavicular elevation and retraction. The middle trapezius is primarily a medial stabilizer of the scapula. The lower trapezius assists in medial stabilization and upward rotation of the scapula. The pectoralis minor is aligned to resist normal rotations of the scapula during arm elevation. The rotator cuff is critical to stabilization and prevention of excess superior translation of the humeral head, as well as production of glenohumeral external rotation during arm elevation. Alterations in activation amplitude or timing have been identified across various investigations of subjects with shoulder impingement as compared to healthy controls. These include decreased activation of the middle or lower serratus anterior and rotator cuff, delayed activation of middle and lower trapezius, and increased activation of the upper trapezius and middle deltoid in impingement subjects. In addition, subjects with a short resting length of the pectoralis minor exhibit altered scapular kinematic patterns similar to those found in persons with shoulder impingement. CONCLUSION: These normal muscle functional capabilities and alterations in patient populations should be considered when planning exercise approaches for the rehabilitation of these patients.


Phylogenetic characterization of marine bacterium strain 2-40, a degrader of complex polysaccharides.
The marine bacterium strain 2-40 was isolated from the salt marsh cord grass, Spartina alterniflora, in the Chesapeake Bay watershed, VA, USA. It is Gram-negative, requires sea salts and is a strict aerobe. It degrades numerous complex polysaccharides and synthesizes eumelanin. By 16S rDNA analysis, the isolate was shown to be a member of the gamma-subclass of the Proteobacteria, related to Microbulbifer hydrolyticus and to a cellulolytic nitrogen-fixing bacterium.


The dermal suspension sling: shaping the inferior pedicle during breast reduction.
Complaints following reduction mammaplasty using the inferior pedicle include the migration of the deep tissue, a lack of medial fullness, poor projection, and bottoming-out. These are attributed to the lack of deep tissue suspension and skin envelope relaxation. We address these issues through horizontal dermal suspension and plication of the inferior pedicle. The inferior pedicle is designed with medial and lateral triangular flaps in the areas, which would normally be excised. These triangular flaps are deepithelialized and defatted. The flaps are attached to the chest wall above the inferior pedicle to create a dermal sling. The breast mound is further contoured by horizontally plicating the dermis below the nipple-areola complex (NAC), which creates projection and rotates the NAC into the desired position in relation to the chest wall. Sixty-six women have undergone breast reduction using the horizontal dermal suspension sling modification to the inferior pedicle breast reduction technique. Breast projection and shape were sustained during follow-up, of which the median interval was 16 months. Dermal suspension and horizontal dermal plication provides a structural foundation to the inferior pedicle. The sling-like effect from the dermal suspension maintains a defined inframammary fold and maintains medial and lateral borders of the breast. Horizontal dermal plication shortens the length of the inferior pedicle while generating improved breast projection by rotating the NAC anteriorly. The firmly shaped inferior pedicle breast mound allows the skin flap to drape over the breast mound with minimal tension.


Long-Lasting Sparks: Multi-Metastability and Release Competition in the Calcium Release Unit Network.
Calcium (Ca) sparks are elementary events of biological Ca signaling. A normal Ca spark has a brief duration in the range of 10 to 100 ms, but long-lasting sparks with durations of several hundred milliseconds to seconds are also widely observed. Experiments have shown that the transition from normal to long-lasting sparks can occur when ryanodine receptor (RyR) open probability is either increased or decreased. Here, we demonstrate theoretically and computationally that long-lasting sparks emerge as a collective dynamical behavior of the network of diffusively coupled Ca release units (CRUs). We show that normal sparks occur when the CRU network is monostable and excitable, while long-lasting sparks occur when the network dynamics possesses multiple metastable attractors, each attractor corresponding to a different spatial firing pattern of sparks. We further highlight the mechanisms and conditions that produce long-lasting sparks, demonstrating the existence of an optimal range of RyR open probability favoring long-lasting sparks. We find that when CRU firings are sparse and sarcoplasmic reticulum (SR) Ca load is high, increasing RyR open probability promotes long-lasting sparks by potentiating Ca-induced Ca release (CICR). In contrast, when CICR is already strong enough to produce frequent firings, decreasing RyR open probability counter-intuitively promotes long-lasting sparks by decreasing spark frequency. The decrease in spark frequency promotes intra-SR Ca diffusion from neighboring non-firing CRUs to the firing CRUs, which helps to maintain the local SR Ca concentration of the firing CRUs above a critical level to sustain firing. In this setting, decreasing RyR open probability further suppresses long-lasting sparks by weakening CICR. Since a long-lasting spark terminates via the Kramers' escape process over a potential barrier, its duration exhibits an exponential distribution determined by the barrier height and noise strength, which is modulated differently by different ways of altering the Ca release flux strength.


Vertical transmission of HTLV-I/II: a review.
The vertical transmission of the human T-cell lymphotropic virus type I (HTLV-I) occurs predominantly through breast-feeding. Since some bottle-fed children born to carrier mothers still remain seropositive with a frequency that varies from 3.3% to 12.8%, an alternative pathway of vertical transmission must be considered. The prevalence rate of vertical transmission observed in Japan varied from 15% to 25% in different surveys. In Brazil there is no evaluation of this form of transmission until now. However, it is known that in Salvador, Bahia, 0.7% to 0.88% of pregnant women of low socio-economic class are HTLV-I carriers. Furthermore the occurrence of many cases of adult T-cell leukemia/lymphoma and of four cases of infective dermatitis in Salvador, diseases directly linked to the vertical transmission of HTLV-I, indicates the importance of this route of infection among us. Through prenatal screening for HTLV-I and the refraining from breast-feeding a reduction of approximately 80% of vertical transmission has been observed in Japan. We suggest that in Brazil serologic screening for HTLV-I infection must be done for selected groups in the prenatal care: pregnant women from endemic areas, Japanese immigrants or Japanese descendents, intravenous drug users (IDU) or women whose partners are IDU, Human immunodeficiency virus carriers, pregnant women with promiscuous sexual behavior and pregnant women that have received blood transfusions in areas where blood donors screening is not performed. There are in the literature few reports demonstrating the vertical transmission of HTLV-II.


Superoxide differentially controls pulmonary and systemic vascular tone through multiple signalling pathways.
the aim of this study was to determine the relative importance of Ca(2+) sensitization, ion channels, and intracellular Ca(2+) ([Ca(2+)](i)) in the mixed constrictor/relaxation actions of superoxide anion on systemic and pulmonary arteries. pulmonary and mesenteric arteries were obtained from rat. Superoxide was generated in arteries and cells with 6-anilino-5,8-quinolinequinone (LY83583). Following pre-constriction with U46619, 10 μmol/L LY83583 caused constriction in pulmonary and relaxation in mesenteric arteries. Both constrictor and relaxant actions of LY83583 were inhibited by superoxide dismutase and catalase. LY83583 caused Rho-kinase-dependent constriction in α-toxin-permeabilized pulmonary but not mesenteric arteries. Phosphorylation of myosin phosphatase-targeting subunit-1 (MYPT-1; as determined by western blot), was enhanced by LY83583 in pulmonary artery only. However, in both artery types, changes in tension were closely correlated with changes in phosphorylation of the 20 kDa myosin light chain as well as changes in [Ca(2+)](i) (as measured with Fura PE-3), with LY83583 causing increases in pulmonary and decreases in mesenteric arteries. When U46619 was replaced by 30 mmol/L K(+), all changes in [Ca(2+)](i) were abolished and LY83583 constricted both artery types. The K(V) channel inhibitor 4-aminopyridine abolished the LY83583-induced relaxation in mesenteric artery without affecting constriction in pulmonary artery. However, LY83583 caused a similar hyperpolarizing shift in the steady-state activation of K(V) current in isolated smooth muscle cells of both artery types. superoxide only causes Rho-kinase-dependent Ca(2+) sensitization in pulmonary artery, resulting in constriction, and whilst it opens K(V) channels in both artery types, this only results in relaxation in mesenteric.


Rapid tumor vaccine using Toll-like receptor-activated ovarian cancer ascites monocytes.
Novel therapeutic strategies in ovarian cancer (OC) are needed as the survival rate remains dismally low. Although dendritic cell-based cancer vaccines are effective in eliciting therapeutic responses, their complex and costly manufacturing process hampers their full clinical utility outside specialized clinics. Here, we describe a novel approach of generating a rapid and effective cancer vaccine using ascites-derived monocytes for treating OC. Using the ID8 mouse ovarian tumor model and OC patient samples, we isolated ascites monocytes and evaluated them with flow cytometry, Luminex cytokine and chemokine array analysis, ex vivo cocultures with T cells, in vivo tumor challenge and T cell transfer experiments, RNA-sequencing and mass spectrometry. We demonstrated the feasibility of isolating ascites monocytes and restoring their ability to function as bona fide antigen-presenting cells (APCs) with Toll-like receptor (TLR) 4 lipopolysaccharide and TLR9 CpG-oligonucleotides, and a blocking antibody to interleukin-10 receptor (IL-10R Ab) in the ID8 model. The ascites monocytes were laden with tumor antigens at a steady state in vivo. After a short 48 hours activation, they upregulated maturation markers (CD80, CD86 and MHC class I) and demonstrated strong ex vivo T cell stimulatory potential and effectively suppressed tumor and malignant ascites in vivo. They also induced protective long-term T cell memory responses. To evaluate the translational potential of this approach, we isolated ascites monocytes from stage III/IV chemotherapy-naïve OC patients. Similarly, the human ascites monocytes presented tumor-associated antigens (TAAs), including MUC1, ERBB2, mesothelin, MAGE, PRAME, GPC3, PMEL and TP53 at a steady state. After a 48-hour treatment with TLR4 and IL-10R Ab, they efficiently stimulated oligoclonal tumor-associated lymphocytes (TALs) with strong reactivity against TAAs. Importantly, the activated ascites monocytes retained their ability to activate TALs in the presence of ascitic fluid. Ascites monocytes are naturally loaded with tumor antigen and can perform as potent APCs following short ex vivo activation. This novel ascites APC vaccine can be rapidly prepared in 48 hours with a straightforward and affordable manufacturing process, and would be an attractive therapeutic vaccine for OC.


Characterization of photodegradation of meta-tetra(hydroxyphenyl)chlorin (mTHPC) in solution: biological consequences in human tumor cells.
The photobleaching of meta-tetra(hydroxyphenyl)chlorin (mTHPC) (irradiation wavelength 413 nm) in protein-containing solution was evaluated by decay in absorbance in Soret band and in fluorescence (lambda exc = 423 nm, lambda em = 655 nm). Light exposure resulted in a decrease in absorption throughout the spectrum and simultaneous appearance of new absorption bands in the spectral region 325-450 nm. The rate of mTHPC photodegradation, followed by decay in absorbance, was 15-fold lower than that observed in fluorescence. This fact reflects the photobleaching of presumably monomeric, fluorescing species of mTHPC. In order to determine the consequences of photobleaching of fluorescing mTHPC material on cellular uptake and photocytotoxicity, human HT29 colon adenocarcinoma cells were incubated with photobleached mTHPC during 5 h with or without following irradiation with the fixed fluence. Surprisingly, but up to the time when the fluorescence decreased by 50%, only a slight decrease in photocytotoxicity was detected. Either aggregated forms that have been taken up undergo intracellular monomerization (but we did not observe increase in fluorescence in living cells) or the photodynamic activity is mostly due to aggregates. The discrepancy of mTHPC-photodynamic therapy (PDT) effect and fluorescence measurements may suggest that aggregated mTHPC plays an important role in mTHPC-PDT.


Bacteriophage WO-B and Wolbachia in natural mosquito hosts: infection incidence, transmission mode and relative density.
Bacteriophages of Wolbachia bacteria have been proposed as a potential transformation tool for genetically modifying mosquito vectors. In this study, we report the presence of the WO-B class of Wolbachia-associated phages among natural populations of several mosquito hosts. Eighty-eight percent (22/25) of Wolbachia-infected mosquito species surveyed were found to contain WO-B phages. WO-B phage orf7 sequence analysis suggested that a single strain of WO-B phage was found in most singly (23/24) or doubly (1/1) Wolbachia-infected mosquitoes. However, the single Wolbachia strain infecting Aedes perplexus was found to harbour at least two different WO-B phages. Phylogenetic analysis suggested that horizontal transmission of WO-B phages has occurred on an evolutionary scale between the Wolbachia residing in mosquitoes. On an ecological scale, a low trend of co-transmission occurred among specific WO-B phages within Wolbachia of each mosquito species. Assessment of the density of WO-B phage by real-time quantitative polymerase chain reaction (RTQ-PCR) revealed an average relative density of 7.76 x 10(5)+/- 1.61 x 10(5) orf7 copies per individual mosquito for a single Wolbachia strain infecting mosquitoes, but a threefold higher density in the doubly Wolbachia-infected Aedes albopictus. However, the average combined density of WO-B phage(s) did not correlate with that of their Wolbachia hosts, which varied in different mosquito species. We also confirmed the presence of WO-B-like virus particles in the laboratory colony of Ae. albopictus (KLPP) morphologically, by transmission electron microscopy (TEM). The viral-like particles were detected after purification and filtration of Ae. albopictus ovary extract, suggesting that at least one WO-B-like phage is active (temperate) within the Wolbachia of this mosquito vector. Nevertheless, the idea of utilizing these bacteriophages as transformation vectors still needs more investigation and is likely to be unfeasible.


Atypical structural connectome asymmetry and associations with network communication in autism spectrum disorder.
Autism spectrum disorder is a common neurodevelopmental condition showing connectome disorganization in sensory and transmodal cortices. However, alterations in the inter-hemispheric asymmetry of structural connectome are remained to be investigated. Here, we studied structural connectome asymmetry in individuals with autism using dimensionality reduction techniques and assessed its topological underpinnings by associating with network communication measures. We found that the sensory and heteromodal association regions showed significant between-group differences in inter-hemispheric asymmetry between individuals with autism and neurotypical controls. In addition, the network communication ability was particularly altered between visual and limbic areas. Our findings provide insights for understanding structural connectome alteration in autism and its topological underpinnings.Clinical Relevance- This study provides insights into the understanding of atypical macroscale structural connectome organization in individuals with autism.


Teaching Health Law.
This column will be the first in a series exploring innovative ways to teach concepts and ideas in health law across a wide variety of classrooms, schools, and curriculums.


Modelling of hydrogen sulfide dispersion from the geothermal power plants of Tuscany (Italy).
We applied the Eulerian code DISGAS (DISpersion of GAS) to investigate the dispersion of the hydrogen sulfide (H2S) from 32 geothermal power plants (out of 35 active) belonging to the geothermal districts of Larderello, Travale-Radicondoli and Monte Amiata, in Tuscany (Italy). An updated geographic database, for use in a GIS environment, was realized in order to process input data required by the code and to handle the outputs. The results suggest that H2S plumes emitted from geothermal power plants are mainly concentrated around the stacks of emission (H2S concentration up to 1100μg/m3) and rapidly dilute along the dominant local wind direction. Although estimated values of air H2S concentrations are orders of magnitude higher than in unpolluted areas, they do not indicate an immediate health risk for nearby communities, under the more frequent local atmospheric conditions. Starting from the estimated values, validated by measurements in the field, we make some considerations about the environmental impact of the H2S emission in all the geothermal areas of the Tuscany region.


Peroxisomal beta-oxidation and steatohepatitis.
Fatty acid beta-oxidation occurs in both mitochondria and peroxisomes. Mitochondria catalyze the beta-oxidation of the bulk of short-, medium-, and long-chain fatty acids derived from diet, and this pathway constitutes the major process by which fatty acids are oxidized to generate energy. Peroxisomes are involved, preferentially, in the beta-oxidation chain shortening of very long chain fatty acids (VLCFAs) and in the process produce H2O2. Long-chain fatty acids and VLCFAs are also metabolized by the cytochrome P450 CYP4A omega-oxidation system to toxic dicarboxylic acids (DCAs) that serve as substrates for peroxisomal beta-oxidation, and this process also leads to the production of superoxide and H2O2. The genes encoding peroxisomal, microsomal, and certain mitochondrial fatty acid metabolizing enzymes in liver are transcriptionally regulated by peroxisome proliferator-activated receptor alpha (PPAR alpha). Deficiencies of the enzymes of peroxisomal beta-oxidation have been recognized as important causes of disease. Evidence from mice deficient in PPAR alpha (PPAR alpha-/-), deficient in peroxisomal fatty acyl-CoA oxidase (AOX-/-), the first enzyme of the classical beta-oxidation system, and deficient in both PPAR alpha and AOX (PPAR alpha-/-AOX-/-) points to the critical importance of PPAR alpha-inducible peroxisomal and microsomal oxidation systems that metabolize LCFAs and VLCFAs in the pathogenesis of nonalcoholic microvesicular hepatic steatosis and steatohepatitis. These and other mouse models should provide greater understanding of the molecular mechanism responsible for hepatic steatosis and steatohepatitis. Deficiency of AOX disrupts the oxidation of VLCFAs, DCAs, and other substrates leading to extensive microvesicular steatosis and steatohepatitis. Loss of this enzyme also causes sustained hyperactivation of PPAR alpha, leading to transcriptional up-regulation of PPAR alpha-regulated genes, indicating that unmetabolized substrates of AOX function as ligands of PPAR alpha. beta-Oxidation is the major process by which fatty acids are oxidized to generate energy, especially when glucose availability is low during periods of starvation. Mice deficient in PPAR alpha and those nullizygous for both PPAR alpha and AOX show a minimal steatotic phenotype under fed conditions but manifest an exaggerated steatotic response to fasting, indicating that defects in PPAR alpha-inducible fatty acid oxidation determine the severity of fatty liver phenotype to conditions reflecting energy-related stress.


Reliability and validity of the Korean version of the community balance and mobility scale in patients with hemiplegia after stroke.
[Purpose] The aim of this study was to translate and adapt the Community Balance and Mobility Scale (CB&M) into Korean (K-CB&M) and to verify the reliability and validity of scores obtained with Korean patients. [Subjects and Methods] A total of 16 subjects were recruited from St. Vincent's Hospital in South Korea. At each testing session, subjects completed the K-CB&M, Berg balance scale (BBS), timed up and go test (TUG), and functional reaching test. All tests were administered by a physical therapist, and subjects completed the tests in an identical standardized order during all testing sessions. [Results] The inter- and intra-rater reliability coefficients were high for most subscores, while moderate inter-rater reliability was observed for the items "walking and looking" and "walk, look, and carry", and moderate intra-rater reliability was observed for "forward to backward walking". There was a positive correlation between the K-CB&M and BBS and a negative correlation between the K-CB&M and TUG in the convergent validity assessments. [Conclusion] The reliability and validity of the K-CB&M was high, suggesting that clinical practitioners treating Korean patients with hemiplegia can use this material for assessing static and dynamic balance.


Reconstruction and Validation of Arterial Geometries for Computational Fluid Dynamics Using Multiple Temporal Frames of 4D Flow-MRI Magnitude Images.
Segmentation and reconstruction of arterial blood vessels is a fundamental step in the translation of computational fluid dynamics (CFD) to the clinical practice. Four-dimensional flow magnetic resonance imaging (4D Flow-MRI) can provide detailed information of blood flow but processing this information to elucidate the underlying anatomical structures is challenging. In this study, we present a novel approach to create high-contrast anatomical images from retrospective 4D Flow-MRI data. For healthy and clinical cases, the 3D instantaneous velocities at multiple cardiac time steps were superimposed directly onto the 4D Flow-MRI magnitude images and combined into a single composite frame. This new Composite Phase-Contrast Magnetic Resonance Angiogram (CPC-MRA) resulted in enhanced and uniform contrast within the lumen. These images were subsequently segmented and reconstructed to generate 3D arterial models for CFD. Using the time-dependent, 3D incompressible Reynolds-averaged Navier-Stokes equations, the transient aortic haemodynamics was computed within a rigid wall model of patient geometries. Validation of these models against the gold standard CT-based approach showed no statistically significant inter-modality difference regarding vessel radius or curvature (p > 0.05), and a similar Dice Similarity Coefficient and Hausdorff Distance. CFD-derived near-wall hemodynamics indicated a significant inter-modality difference (p > 0.05), though these absolute errors were small. When compared to the in vivo data, CFD-derived velocities were qualitatively similar. This proof-of-concept study demonstrated that functional 4D Flow-MRI information can be utilized to retrospectively generate anatomical information for CFD models in the absence of standard imaging datasets and intravenous contrast.


Costs and Benefits of Household Fuel Policies and Alternative Strategies in the Jing-Jin-Ji Region.
Air pollution is still one of the most severe problems in northern China, especially in the Jing-Jin-Ji region around Beijing. In recent years, China has implemented many stringent policies to address the air quality issue, including promoting energy transition toward cleaner fuels in residential sectors. But until 2020, even in the Jing-Jin-Ji region, nearly half of the rural households still use solid fuels for heating. For residents who are not covered by the clean heating campaign, we analyze five potential mitigation strategies and evaluate their environmental effects as well as the associated health benefits and costs. We estimate that substitution with electricity or gas would reduce air pollution and premature mortality more strongly, while the relatively low investment costs of implementing clean coal or biomass pellet lead to a larger benefit-cost ratio, indicating higher cost efficiency. Hence, clean coal or biomass pellet could be transitional substitution options for the less developed or remote areas which cannot afford a total transition toward electricity or natural gas in the short term.


Nosocomial outbreak of Crimean-Congo hemorrhagic fever, Sudan.
To confirm the presence of Crimean-Congo hemorrhagic fever in Sudan, we tested serum of 8 patients with hemorrhagic fever in a rural hospital in 2008. Reverse transcription-PCR identified Crimean-Congo hemorrhagic fever virus. Its identification as group III lineage indicated links to virus strains from South Africa, Mauritania, and Nigeria.


Toponome imaging system: in situ protein network mapping in normal and cancerous colon from the same patient reveals more than five-thousand cancer specific protein clusters and their subcellular annotation by using a three symbol code.
In a proof of principle study, we have applied an automated fluorescence toponome imaging system (TIS) to examine whether TIS can find protein network structures, distinguishing cancerous from normal colon tissue present in a surgical sample from the same patient. By using a three symbol code and a power of combinatorial molecular discrimination (PCMD) of 2(21) per subcellular data point in one single tissue section, we demonstrate an in situ protein network structure, visualized as a mosaic of 6813 protein clusters (combinatorial molecular phenotype or CMPs), in the cancerous part of the colon. By contrast, in the histologically normal colon, TIS identifies nearly 5 times the number of protein clusters as compared to the cancerous part (32 009). By subcellular visualization procedures, we found that many cell surface membrane molecules were closely associated with the cell cytoskeleton as unique CMPs in the normal part of the colon, while the same molecules were disassembled in the cancerous part, suggesting the presence of dysfunctional cytoskeleton-membrane complexes. As expected, glandular and stromal cell signatures were found, but interestingly also found were potentially TIS signatures identifying a very restricted subset of cells expressing several putative stem cell markers, all restricted to the cancerous tissue. The detection of these signatures is based on the extreme searching depth, high degree of dimensionality, and subcellular resolution capacity of TIS. These findings provide the technological rationale for the feasibility of a complete colon cancer toponome to be established by massive parallel high throughput/high content TIS mapping.


An optimal transition time to extracorporeal cardiopulmonary resuscitation for predicting good neurological outcome in patients with out-of-hospital cardiac arrest: a propensity-matched study.
Prolonged conventional cardiopulmonary resuscitation (CCPR) is associated with a poor prognosis in out-of-hospital cardiac arrest (OHCA) patients. Alternative methods can be needed to improve the outcome in patients with prolonged CCPR and extracorporeal cardiopulmonary resuscitation (ECPR) can be considered as an alternative method. The objectives of this study were to estimate the optimal duration of CPR to consider ECPR as an alternative resuscitation method in patients with CCPR, and to find the indications for predicting good neurologic outcome in OHCA patients who received ECPR. This study is a retrospective analysis based on a prospective cohort. We included patients ≥ 18 years of age without suspected or confirmed trauma and who experienced an OHCA from May 2006 to December 2013. First, we determined the appropriate cut-off duration for CPR based on the discrimination of good and poor neurological outcomes in the patients who received only CCPR, and then we compared the outcome between the CCPR group and ECPR group by using propensity score matching. Second, we compared CPR related data according to the neurologic outcome in matched ECPR group. Of 499 patients suitable for inclusion, 444 and 55 patients were enrolled in the CCPR and ECPR group, respectively. The predicted duration for a favorable neurologic outcome (CPC1, 2) is < 21 minutes of CPR in only CCPR patients. The matched ECPR group with ≥ 21 minutes of CPR duration had a more favorable neurological outcome than the matched CCPR group at 3 months post-arrest. In matched ECPR group, younger age, witnessed arrest without initial asystole rhythm, early achievement of mean arterial pressure ≥ 60 mmHg, low rate of ECPR-related complications, and therapeutic hypothermia were significant factors for expecting good neurologic outcome. ECPR should be considered as an alternative method for attaining good neurological outcomes in OHCA patients who required prolonged CPR, especially of ≥ 21 minutes. Younger or witnessed arrest patients without initial asystole were good candidates for ECPR. After implantation of ECPR, early hemodynamic stabilization, prevention of ECPR-related complications, and application of therapeutic hypothermia may improve the neurological outcome.


Peritoneal dissemination is inhibited by treatment with antibodies against CD44H, beta(1) integrin, and carcinostatic agents in NUGC-4 human gastric cancer cells.
Peritoneal dissemination frequently occurs after surgery in patients with gastric cancer. The presence of peritoneal metastasis after surgery affects the prognosis, therefore, a way must be found to effectively prevent the development of peritoneal dissemination. Very little is known about the biochemical processes involved in the initial attachment of gastric cancer cells to peritoneal mesothelial cells. We conducted in vitro and in vivo studies to assess the role of adhesion molecules and TGF-beta 1 in this process, using 4 gastric cancer cell lines. NUGC-4 cells, which disseminate early after inoculation into the abdominal cavity of nude mice, predominantly expressed CD44H and beta(1) integrin. We found that NUGC-4 cells adhered to monolayers of mesothelial cells more firmly than other cell lines. Adhesion of NUGC-4 cells to mesothelial cells was partially inhibited by antibodies against CD44H or the beta(1) subunit of integrin, and was completely blocked by a combination of these 2 antibodies. Treatment with ligands for CD44H and beta(1) integrin also inhibited this adhesion. In the NUGC-4 cell culture medium, larger amounts of transforming growth factor beta 1(TGF-beta 1) was detected in proportion to the increase in cancer cells than in the other cell lines. TGF-beta 1 increased the expression of CD44H in NUGC-4 cells and in mesothelial cells, and augmented the adhesion and implantation of NUGC-4 cells to mesothelial cells accompanied by accumulation of extracellular matrix (ECM) components. Carcinostatic agents decreased the expression of CD44H but increased the expression of E-cadherin in NUGC-4 cells. Treatment with carcinostatic agents and antibodies against CD44H and beta(1) integrin inhibited the dissemination of NUGC-4 cells in the peritoneal cavity of nude mice, and prolonged their survival time. These findings suggest that CD44H and integrins mediate in the initial attachment of gastric cancer cells to mesothelial cells, and TGF-beta 1 participates in the promotion of the disease. It is possible that a treatment strategy that interferes with CD44H or integrins function and increases the functions of E-cadherin immediately after surgery may result in the decreased intra-abdominal spread of gastric cancer.


Preparing Cities for Future Pandemics: Unraveling the Influence of Urban and Housing Variables on COVID-19 Incidence in Santiago de Chile.
In this study, we analyzed how urban, housing, and socioeconomic variables are related to COVID-19 incidence. As such, we have analyzed these variables along with demographic, education, employment, and COVID-19 data from 32 communes in Santiago de Chile between March and August of 2020, before the release of the vaccines. The results of our Principal Component Analysis (PCA) confirmed that those communes with more economic, social, organizational, and infrastructural resources were overall less affected by COVID-19. As the dimensions affecting COVID-19 are based on structural variables, this study discusses to what extent our cities can be prepared for the next pandemic. Recommendations for local decision-makers in controlling illegal immigration and investing in housing and urban parks are drawn.


Neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the substantia nigra and the locus coeruleus in BALB/c mice.
The purpose of the present study was to determine whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), administered systemically or as a local infusion, has a direct neurotoxic action upon dopamine (DA) neurons in the substantia nigra (SN) and norepinephrine (NE) neurons in the locus coeruleus (LC) in BALB/c mice. Results indicated that both acute and repeated MPTP infusions (2 micrograms/0.3 microliter per side) significantly impaired locomotor activity, decreased stereotyped behavior and caused a disturbed pattern of locomotion in mice. The biochemical changes parallel the behavioral changes. Repeated MPTP infusions to the SN decreased DA levels markedly in the SN and the striatum; chronic MPTP infusions to the LC reduced NE levels markedly in the LC and the hippocampus. Furthermore, repeated MPTP injections for 7 days (30 mg/kg, one injection per day) have resulted in a long-lasting effect on both the nigral-striatal and the coeruleus-hippocampal systems. DA levels in the SN and the striatum were decreased at 1, 3, 7 and 28 days after the last MPTP injection. Similarly, NE levels in the LC and the hippocampus were also reduced markedly at the same time intervals examined. Behaviorally, repeated MPTP treatment also produced long-lasting motor deficits in mice at all time intervals studied. Moreover, the LC appeared to be more sensitive than the SN to the neurotoxic effects of MPTP. Immunohistochemical results have similarly revealed that repeated MPTP treatment markedly decreased tyrosine hydroxylase-positive cells and fibers in the SN and the LC. It also markedly decreased DA-beta-hydroxylase-positive cells and fibers in the LC.(ABSTRACT TRUNCATED AT 250 WORDS)


Accuracy of femoral templating in reproducing anatomical femoral offset in total hip replacement.
Restoration of hip biomechanics is a crucial component of successful total hip replacement. Preoperative templating is recommended to ensure that the size and orientation of implants is optimised. We studied how closely natural femoral offset could be reproduced using the manufacturers' templates for 10 femoral stems in common use in the UK. A series of 23 consecutive preoperative radiographs from patients who had undergone unilateral total hip replacement for unilateral osteoarthritis of the hip was employed. The change in offset between the templated position of the best-fitting template and the anatomical centre of the hip was measured. The templates were then ranked according to their ability to reproduce the normal anatomical offset. The most accurate was the CPS-Plus (Root Mean Square Error 2.0 mm) followed in rank order by: C stem (2.16), CPT (2.40), Exeter (3.23), Stanmore (3.28), Charnley (3.65), Corail (3.72), ABG II (4.30), Furlong HAC (5.08) and Furlong modular (7.14). A similar pattern of results was achieved when the standard error of variability of offset was analysed. We observed a wide variation in the ability of the femoral prosthesis templates to reproduce normal femoral offset. This variation was independent of the seniority of the observer. The templates of modern polished tapered stems with high modularity were best able to reproduce femoral offset. The current move towards digitisation of X-rays may offer manufacturers an opportunity to improve template designs in certain instances, and to develop appropriate computer software.


Comparative evaluation of cyclosporine A/HPβCD-incorporated PLGA nanoparticles for development of effective ocular preparations.
To improve poor water solubility of cyclosporine A (CsA), hydroxypropyl-beta-cyclodextrin (HPβCD) was incorporated into the nanoparticle formulation. Solid complexes of CsA with HPβCD in different ratios were prepared by the kneading method. CsA containing alone or in combination with HPβCD in poly-lactide-co-glycolide (P-CsA or P-CsA-HPβCD) nanoparticles were prepared by the emulsification solvent evaporation method. The mean size of CsA-loaded NPs was found to be approximately 220 nm. The solubility of CsA was significantly improved and the phase solubility diagram of CsA-HPβCD systems showed an A(L) type phase. Nanoparticles showed high CsA encapsulation efficiency (88%) and production yield (89%). Release rate was increased by the presence of HPβCD and total cumulative release ranged from 75% to 96% in 24 h. In vitro cytotoxicity study assay resulted in a low toxicity for all types of nanoparticles. After 6 h incubation period, the cellular uptake was found at 33% and 32% for P-CsA and P-HPβCD-CsA nanoparticles, respectively.


Acute injection and chronic perfusion of kisspeptin elicit gonadotropins release but fail to trigger ovulation in the mare.
Kisspeptin has emerged as the most potent gonadotropin-releasing hormone (GnRH) secretagogue and appears to represent the penultimate step in the central control of reproduction. In the sheep, we showed that kisspeptin could be used to manipulate gonadotropin secretion and control ovulation. Prompted by these results, we decided to investigate whether kisspeptin could be used as an ovulation-inducing agent in another photoperiodic domestic mammal, the horse. Equine kisspeptin-10 (eKp10) was administered intravenously as bolus injections or short- to long-term perfusions to Welsh pony mares, either during the anestrus season or at various stages of the cycle during the breeding season. In all the experimental conditions, eKp10 reliably increased peripheral concentrations of both luteinizing hormone and follicle-stimulating hormone. The nature of the response to eKp10 was consistent across experimental conditions and physiological states: the increase in gonadotropins was always rapid and essentially transient even when eKp10 was perfused for prolonged periods. Furthermore, eKp10 consistently failed to induce ovulation in the mare. To gain insights into the underlying mechanisms, we used acute injections or perfusions of GnRH. We also cloned the equine orthologues of the kisspeptin precursor and Kiss1r; this was justified by the facts that the current equine genome assembly predicted an amino acid difference between eKp10 and Kp10 in other species while an equine orthologue for Kiss1r was missing altogether. In light of these findings, potential reasons for the divergence in the response to kisspeptin between ewe and mare are discussed. Our data highlight that kisspeptin is not a universal ovulation-inducing agent.


Bisulfite sequencing and dinucleotide content analysis of 15 imprinted mouse differentially methylated regions (DMRs): paternally methylated DMRs contain less CpGs than maternally methylated DMRs.
Imprinted genes in mammals show monoallelic expression dependent on parental origin and are often associated with differentially methylated regions (DMRs). There are two classes of DMR: primary DMRs acquire gamete-specific methylation in either spermatogenesis or oogenesis and maintain the allelic methylation differences throughout development; secondary DMRs establish differential methylation patterns after fertilization. Targeted disruption of some primary DMRs showed that they dictate the allelic expression of nearby imprinted genes and the establishment of the allelic methylation of secondary DMRs. However, how primary DMRs are recognized by the imprinting machinery is unknown. As a step toward elucidating the sequence features of the primary DMRs, we have determined the extents and boundaries of 15 primary mouse DMRs (including 12 maternally methylated and three paternally methylated DMRs) in 12.5-dpc embryos by bisulfite sequencing. We found that the average size of the DMRs was 3.2 kb and that their average G+C content was 54%. Dinucleotide content analysis of the DMR sequences revealed that, although they are generally CpG rich, the paternally methylated DMRs contain less CpGs than the maternally methylated DMRs. Our findings provide a basis for the further characterization of DMRs.


Dispersal patterns and population genetic structure of Aedes albopictus (Diptera: Culicidae) in three different climatic regions of China.
Aedes albopictus is an indigenous primary vector for dengue and Zika viruses in China. Compared with its insecticide resistance, biology and vector competence, little is known about its genetic variation, which corresponds to environmental variations. Thus, the present study examines how Ae. albopictus varies among different climatic regions in China and deciphers its potential dispersal patterns. The genetic variation and population structure of 17 Ae. albopictus populations collected from three climatic regions of China were investigated with 11 microsatellite loci and the mitochondrial coxI gene. Of 44 isolated microsatellite markers, 11 pairs were chosen for genotyping analysis and had an average PIC value of 0.713, representing high polymorphism. The number of alleles was high in each population, with the ne value increasing from the temperate region (3.876) to the tropical region (4.144). Twenty-five coxI haplotypes were detected, and the highest diversity was observed in the tropical region. The mean Ho value (ca. 0.557) of all the regions was significantly lower than the mean He value (ca. 0.684), with nearly all populations significantly departing from HWE and displaying significant population expansion (p value < 0.05). Two genetically isolated groups and three haplotype clades were evaluated via STRUCTURE and haplotype phylogenetic analyses, and the tropical populations were significantly isolated from those in the other regions. Most genetic variation in Ae. albopictus was detected within populations and individuals at 31.40 and 63.04%, respectively, via the AMOVA test, and a relatively significant positive correlation was observed among only the temperate populations via IBD analysis (R2 = 0.6614, p = 0.048). Recent dispersions were observed among different Ae. albopictus populations, and four major migration trends with high gene flow (Nm > 0.4) were reconstructed between the tropical region and the other two regions. Environmental factors, especially temperature and rainfall, may be the leading causes of genetic diversity in different climatic regions. Continuous dispersion contributes to the genetic communication of Ae. albopictus populations across different climatic regions, and environmental factors, especially temperature and rainfall, may be the leading causes of genetic variation.


Patellar and hamstring autografts are associated with different jump task loading asymmetries after ACL reconstruction.
After anterior cruciate ligament reconstruction (ACLR), there is a higher re-injury rate to the contralateral limb in athletes who undergo surgery using a bone-patellar-tendon-bone (BPTB) autograft than using a semitendinosus and gracilis hamstring tendon (HT) autograft. This may be influenced by differing lower-limb loading asymmetries present when athletes of each graft type return to play (RTP). The aim of this study was to compare bilateral countermovement jump (CMJ) phase-specific impulse asymmetries between athletes with BPTB and HT autografts 9 months post-ACLR, and to identify the relationship between impulse and isokinetic strength asymmetries. Male field sport athletes with a BPTB (n = 22) or HT (n = 22) autograft were tested approximately 9 months post-ACLR. An uninjured control group (n = 22) was also tested on a single occasion. Phase-specific bilateral absolute impulse asymmetries were calculated during the CMJ and compared between groups using Kruskal-Wallis and post-hoc testing. A linear regression model was used to assess the relationship between impulse asymmetries and isokinetic concentric knee extensor strength asymmetries. BPTB athletes demonstrated greater impulse asymmetries than HT athletes during the eccentric (P = 0.01) and concentric (P = 0.008) phases of the jump. Isokinetic strength asymmetry was a significant predictor of CMJ concentric impulse asymmetry in both BPTB (r2 = 0.39) and HT athletes (r2 = 0.18) but not eccentric impulse asymmetry in any group. The greater loading asymmetries demonstrated by BPTB than HT athletes 9 months after ACLR may contribute to the differing incidence rates of contralateral ACL injury. The findings suggest that graft-specific loading asymmetries should be targeted during rehabilitation prior to RTP.


Relationship Between Age at Menopause, Obesity, and Incident Heart Failure: The Atherosclerosis Risk in Communities Study.
Background The mechanisms linking menopausal age and heart failure (HF) incidence are controversial. We investigated for heterogeneity by obesity on the relationship between menopausal age and HF incidence. Methods and Results Using postmenopausal women who attended the Atherosclerosis Risk in Communities Study Visit 4, we estimated hazard ratios of incident HF associated with menopausal age using Cox proportional hazards models, testing for effect modification by obesity and adjusting for HF risk factors. Women were categorized by menopausal age: <45 years, 45 to 49 years, 50 to 54 years, and ≥55 years. Among 4441 postmenopausal women, aged 63.5±5.5 years, there were 903 incident HF events over a mean follow-up of 16.5 years. The attributable risk of generalized and central obesity for HF incidence was greatest among women who experienced menopause at age ≥55 years: 11.09/1000 person-years and 7.38/1000 person-years, respectively. There were significant interactions of menopausal age with body mass index and waist circumference for HF incidence, Pinteraction 0.02 and 0.001, respectively. The hazard ratios of incident HF for a SD increase in body mass index was elevated in women with menopausal age <45 years [1.39 (1.05-1.84)]; 45-49 years [1.33, (1.06-1.67)]; and ≥55 years [2.02, (1.41-2.89)]. The hazard ratio of incident HF for a SD increase in waist circumference was elevated only in women with menopausal age ≥55 years [2.93, (1.85-4.65)]. Conclusions As obesity worsened, the risk of developing HF became significantly greater when compared with women with lower body mass index and waist circumference, particularly among those who had experienced menopause at age ≥55 years.


Autoregulation of a bacterial sigma factor explored by using segmental isotopic labeling and NMR.
Bacterial sigma factors combine with the catalytic core RNA polymerase to direct the process of transcription initiation through sequence-specific interactions with the -10 and -35 elements of promoter DNA. In the absence of core RNA polymerase, the DNA-binding function of sigma is autoinhibited by its own N-terminal 90 amino acids (region 1.1), putatively by a direct interaction with conserved region 4.2, which binds the -35 promoter element. In the present work, this mechanism of autoinhibition was studied by using a combination of NMR spectroscopy and segmental isotopic labeling of a sigma70-like subunit from Thermotoga maritima. Our data argue strongly against a high-affinity interaction between these two domains. Instead we suggest that autoinhibition of DNA binding occurs through an indirect steric and/or electrostatic mechanism. More generally, the present work illustrates the power of segmental isotopic labeling for probing molecular interactions in large proteins by NMR.


Relationship of symptoms, perceived health, and stigma with quality of life among urban HIV-infected African American men.
To explore the relationship of symptom prevalence and intensity, perceptions of health, and stigma on quality of life (QOL) among HIV-infected African American men. Cross-sectional correlational descriptive study. The sample consisted of HIV-infected African American men (N=55), all urban, age range 23-66 years (M=48.84, SD=7.67), average length of time since HIV diagnosis 10.79 years (SD=6.4). A questionnaire consisting of 5 instruments was used: (a) sociodemographic characteristics, (b) Holzemer Signs and Symptom Checklist for HIV, (c) perceptions of health, (d) Berger HIV Stigma Scale, and (e) Holmes HIV/AIDS-Targeted Quality of Life Scale. Prevalent symptoms were fatigue (98%), fear (92.7%), shortness of breath (92.7%), gastrointestinal upset (85.5%), numbness (80.0%), and headache (76.4%). Symptoms with the highest intensity were gastrointestinal upset, body changes, fear, and fatigue. Symptom intensity was significantly associated with the measures of stigma and QOL. The results underscore the importance of incorporating a holistic view of the relationship of symptoms with QOL for HIV-infected African American men. Without efforts to ameliorate stigmatizing effects, however, nurses may be falling short in helping individual African American men with HIV infection achieve a better QOL.


Phenolic content and antioxidant activity of raspberry and blackberry cultivars.
Raspberry (Aksu Kirmizisi, Rubin, Newburgh, Hollanda Boduru, Heritage) and blackberry (Bursa 1, Bursa 2, Jumbo, Chester) cultivars were assayed for antioxidant activity (determined as 2,2-azino-di-[3-ethylbenzothialozine-sulphonic acid][ABTS], 2,2-diphenyl-1-picrylhydrazyl radical [DPPH], and cupric ion reducing antioxidant capacity [CUPRAC]), total phenol, total flavonoid, and total anthocyanin contents. In addition, 10 anthocyanins and anthocyanidins were determined in raspberry and blackberry by liquid chromatography-mass spectrometry (LC-MS/MS). Raspberry and blackberry had the highest ABTS, DPPH, CUPRAC, total phenol, and total flavonoid contents in methanol extracts, whereas total anthocyanin contents were the highest in water extracts. The antioxidant activity of the raspberry and blackberry was directly related to the total amount of phenolic compounds detected in the raspberry and blackberry. All antioxidant activity values were highly correlated with anthocyanin content in blackberry (0.93 < or = r < or = 0.99, P = 0.05). On the other hand, high correlation between total flavonoid content and antioxidant activity was recorded in water extract of blackberry (0.91 < or = r < or = 0.93, P = 0.05). ABTS value was highly correlated with total flavonoid content in methanol extract (r = 0.90), whereas total flavonoid content was relatively less correlated with DPPH (r = 0.85) and CUPRAC (r = 0.89).


Identification of native and hybrid elms in Spain using isozyme gene markers.
Two elm taxa occur naturally in the Iberian Peninsula: the Field elm (Ulmus minor) and the Wych elm (U. glabra). In addition, a third taxon, the foreign Siberian elm (U. pumila), was probably introduced in the 16th century as an ornamental tree and has spread spontaneously throughout the Peninsula. The natural hybridization between U. minor and U. pumila produced new individuals whose morphological traits appear to be mixed. Ulmus pumila, as well as its hybrids, has a high resistance to Dutch elm disease (DED). For this reason, it is commonly used in breeding programmes. Extensive hybridization and the high mortality produced by the last DED epidemic have endangered the conservation of the native elm. In this study, isozyme analyses are used to characterize the taxa U. minor and U. pumila. Siberian elms from Spain and China are compared with the native U. minor. Siberian elm produces isozyme patterns that completely differentiate it from U. minor. Three loci are completely different between the species: 6Pgd2, Mdh1 and Prx2. Isozyme markers can also be used to distinguish native elms from the hybrids that have evolved for generations.


The European perspective on nitrogen emission and deposition.
Europe has been successful in reducing the emissions of several nitrogenous pollutants over recent decades. This is reflected in concentrations and deposition rates that have decreased for several components. Emissions of nitrogen containing gases are estimated to have decreased in Europe by 10%, 21% and 14% for N(2)O, NO(x) and NH(3), respectively, between 1990 and 1998. The main reductions are the result of a decrease in industrial and agricultural activities in the east of Europe. The reductions are a result of the economic situation, measures in the transport sector, industry, and the agricultural sector, with only a small part of the reduction due to specific measures designed to reduce emissions. The reduction is significant but far from the end goal for large areas in Europe, in relation to different environmental problems. The Gothenburg Protocol will lead to reductions of 50% and 12% in 2010 relative to 1990 for NO(x) and NH(3), respectively. The N(2)O emissions are expected to grow by 9% between 1998 and 2010. Further reductions are necessary to reach critical limits for ecosystem protection, air quality standards, and climate change. Emissions of nitrogen compounds result from an overload of reactive nitrogen that is produced by combustion processes, by synthesis of ammonia, or by import from other areas as concentrated animal feeds. Some improvements can be made in the efficiency of combustion processes and agricultural systems. However, measures to reduce emissions substantially need to focus on decreasing the production or import of reactive N. Reactive N ceilings for regions, based on critical limits for all N-related effects, can help to focus such measures. An integrated approach might have advantages over the pollutant-specific approach, to combat nitrogen pollution. This could provide the future direction for European policy to reduce the impacts of excess nitrogen.