Cytology of the minor-vein phloem in 320 species from the subclass Asteridae suggests a high diversity of phloem-loading modes.
The discovery of abundant plasmodesmata at the bundle sheath/phloem interface in Oleaceae (Gamalei, 1974) and Cucurbitaceae (Turgeon et al., 1975) raised the questions as to whether these plasmodesmata are functional in phloem loading and how widespread symplasmic loading would be. Analysis of over 800 dicot species allowed the definition of "open" and "closed" types of the minor vein phloem depending on the abundance of plasmodesmata between companion cells and bundle sheath (Gamalei, 1989, 1990). These types corresponded to potential symplasmic and apoplasmic phloem loaders, respectively; however, this definition covered a spectrum of diverse structures of phloem endings. Here, a review of detailed cytological analyses of minor veins in 320 species from the subclass Asteridae is presented, including data on companion cell types and their combinations which have not been reported previously. The percentage of Asteridae species with "open" minor vein cytology which also contain sieve-element-companion cell complexes with "closed" cytology, i.e., that show specialization for both symplasmic and apoplasmic phloem loading, was determined. Along with recent data confirming the dissimilar functional specialization of structurally different parts of minor vein phloem in the stachyose-translocating species Alonsoa meridionalis (Voitsekhovskaja et al., 2009), these findings suggest that apoplasmic loading is indispensable in a large group of species previously classified as putative symplasmic loaders. Altogether, this study provides formal classifications of companion cells and of minor veins, respectively, in 24 families of the Asteridae based on their structural features, opening the way to a close investigation of the relationship between structure and function in phloem loading.


Microgravity induces overconfidence in perceptual decision-making.
Does gravity affect decision-making? This question comes into sharp focus as plans for interplanetary human space missions solidify. In the framework of Bayesian brain theories, gravity encapsulates a strong prior, anchoring agents to a reference frame via the vestibular system, informing their decisions and possibly their integration of uncertainty. What happens when such a strong prior is altered? We address this question using a self-motion estimation task in a space analog environment under conditions of altered gravity. Two participants were cast as remote drone operators orbiting Mars in a virtual reality environment on board a parabolic flight, where both hyper- and microgravity conditions were induced. From a first-person perspective, participants viewed a drone exiting a cave and had to first predict a collision and then provide a confidence estimate of their response. We evoked uncertainty in the task by manipulating the motion's trajectory angle. Post-decision subjective confidence reports were negatively predicted by stimulus uncertainty, as expected. Uncertainty alone did not impact overt behavioral responses (performance, choice) differentially across gravity conditions. However microgravity predicted higher subjective confidence, especially in interaction with stimulus uncertainty. These results suggest that variables relating to uncertainty affect decision-making distinctly in microgravity, highlighting the possible need for automatized, compensatory mechanisms when considering human factors in space research.


Effects of the COVID-19 pandemic on stroke response times: a systematic review and meta-analysis.
COVID-19 presents a risk for delays to stroke treatment. We examined how COVID-19 affected stroke response times. A literature search was conducted to identify articles covering stroke during COVID-19 that included time metrics data pre- and post-pandemic. For each outcome, pooled relative change from baseline and 95% CI were calculated using random-effects models. Heterogeneity was explored through subgroup analyses comparing comprehensive stroke centers (CSCs) to non-CSCs. 38 included studies reported on 6109 patients during COVID-19 and 14 637 patients during the pre-COVID period. Pooled increases of 20.9% (95% CI 5.8% to 36.1%) in last-known-well (LKW) to arrival times, 1.2% (-2.9% to 5.3%) in door-to-imaging (DTI), 0.8% (-2.9% to 4.5%) in door-to-needle (DTN), 2.8% (-5.0% to 10.6%) in door-to-groin (DTG), and 19.7% (11.1% to 28.2%) in door-to-reperfusion (DTR) times were observed during COVID-19. At CSCs, LKW increased by 24.0% (-0.3% to 48.2%), DTI increased by 1.6% (-3.0% to 6.1%), DTN increased by 3.6% (1.2% to 6.0%), DTG increased by 4.6% (-5.9% to 15.1%), and DTR increased by 21.2% (12.3% to 30.1%). At non-CSCs, LKW increased by 12.4% (-1.0% to 25.7%), DTI increased by 0.2% (-2.0% to 2.4%), DTN decreased by -4.6% (-11.9% to 2.7%), DTG decreased by -0.6% (-8.3% to 7.1%), and DTR increased by 0.5% (-31.0% to 32.0%). The increases during COVID-19 in LKW (p=0.01) and DTR (p=0.00) were statistically significant, as was the difference in DTN delays between CSCs and non-CSCs (p=0.04). Factors during COVID-19 resulted in significantly delayed LKW and DTR, and mild delays in DTI, DTN, and DTG. CSCs experience more pronounced delays than non-CSCs.


Tetrahydrobiopterin and antioxidants reverse the coronary endothelial dysfunction associated with left ventricular hypertrophy in a porcine model.
Endothelium-dependent G-protein mediated relaxations of epicardial coronary arteries is impaired with left ventricular hypertrophy. The objective of this study was to assess the effect of L-arginine, BH(4) and the combination of two antioxidants, superoxide dismutase and catalase, on endothelium-dependent relaxations in a swine left ventricular hypertrophy model. Aortic banding was performed 3 cm above the coronary ostia. Vascular reactivity studies were performed in standard organ chamber experiments to assess the NO pathway in the presence of methyltetrahydropterin (a BH(4) analogue), L-arginine, superoxide dismutase and catalase. There was a statistically significant increase in endothelium-dependent relaxation to serotonin and to bradykinin with methyltetrahydropterin and with superoxide dismutase plus catalase (P<0.05) but not with L-arginine compared to untreated coronary arteries from left ventricular hypertrophy animals. Plasma 3-nitrotyrosine level increased significantly from 918+/-122 to 1844+/-300 microM (P<0.05 vs. control) after 60 days of aortic banding. Endothelial dysfunction was not associated with a reduced expression of endothelial nitric oxide synthase 2 months after pressure overload left ventricular hypertrophy. Treatment with BH(4) and antioxidants constitutes an interesting approach for the prevention of endothelial dysfunction in epicardial coronary arteries associated with left ventricular hypertrophy.


Accuracy of Surgeon-Performed Ultrasound in Detecting Gallstones: A Validation Study.
Symptomatic gallstone disease is a common diagnosis in patients with abdominal pain. Ultrasound is considered the gold standard method to identify gallstones. Today the examination may be performed bedside by the treating clinician. Bedside ultrasound could provide a safe and time-saving diagnostic resource for surgeons evaluating patients with suspected symptomatic gallstones; however, large validation studies of the accuracy and reliability are lacking. The aim of this study was to prospectively investigate the accuracy of surgeon-performed ultrasound for the detection of gallstones. Between October 2011 and November 2012, 179 adult patients, with an acute or elective referral for an abdominal ultrasound examination, were examined with a right upper quadrant ultrasound scan by a radiologist as well as a surgeon. The surgeons had undergone a four-week-long ultrasound education before participating in the study. Ultrasound findings of the surgeon were compared to those of the radiologist, using radiologist-performed ultrasound as reference standard. Surgeon-performed ultrasound agreed with radiologist findings in 169 of 179 patients regarding the detection of gallstones, providing an accuracy of 94 %. The sensitivity was 88 % (67/76), specificity 99 % (102/103), positive predictive value 99 % (67/68), and negative predictive value 92 % (102/111). Agreement between the diagnosis set by the radiologists and the surgeons was high: Cohen's Kappa coefficient = 0.88. Ultrasound-trained surgeons may accurately diagnose gallstones using ultrasound and reach a high level of agreement with radiologists.


Predictiveness of antenatal umbilical artery Doppler for adverse pregnancy outcome in small-for-gestational-age babies according to customised birthweight centiles: population-based study.
To examine the relationship between smallness at birth and the predictive value of umbilical artery Doppler. Retrospective cohort. Tertiary referral university hospital, Barcelona. A total of 7645 singleton pregnancies delivered between January 2002 and June 2004. The associations with adverse outcome were assessed for small-for-gestational-age (SGA) babies according to customised standards who had normal and abnormal umbilical artery Doppler. Neonatal morbidity and perinatal mortality. Of the 369 SGA fetuses that had been identified antenatally, 70 (19%) had an abnormal umbilical artery Doppler and the babies from these pregnancies had a higher risk for neonatal morbidity when compared with babies with normal birthweight (OR 3.99, 95% CI 1.04-11.03). However, the remaining 299 (81%) fetuses with normal umbilical artery Doppler also had an elevated risk of neonatal morbidity (OR 2.26, 95% CI 1.04-4.39). Overall, many of the instances of adverse outcome associated with smallness for gestational age were attributable to the group with normal Doppler than to the group with abnormal Doppler. Normal antenatal umbilical artery Doppler cannot be taken as an indicator of low risk in pregnancies where the fetus is SGA according to customised percentiles.


Effect of kinesio-taping on the acute phase of the post-operative reconstruction of the anterior cruciate ligament: A randomized controlled trial.
Evaluate the Kinesio taping (KT) effects on reducing pain and edema on postoperative (PO) after anterior cruciate ligament (ACL) reconstruction. Controlled and randomized clinical study. Individuals of both sexes, aged 18-45, underwent ACL reconstruction were randomized into intervention (IG; n = 19) and control (CG; n = 19) groups. Intervention consisted of KT bandage applications at hospital discharge for seven days, and on the 7th PO day, which was removed on the 14th PO. CG received specific instructions from the physiotherapy service. All volunteers were evaluations before and immediately after surgery, on the 7th and 14th PO day. Pain threshold (KgF), evaluated by algometer; edema (cm), evaluated by the perimetry measurements and volume of the lower limbs and the truncated cone test (ml) were the evaluated variables. The Student's t-test and Mann-Whitney U test were used to evaluate intergroup, analysis of variance (ANOVA) and Dunnett's test to evaluate intragroup. Edema reduction and increased nociceptive threshold were significant in the 7th (p < 0.001; p = 0.003) and 14th (p < 0.001; p = 0.006) PO day in IG when compared to CG patients. IG perimetry levels, on the 7th and 14th PO were similar to preoperative period (p = 0.229; p = 1.000). IG nociceptive threshold value was similar on the 14th PO to before the surgery (p = 0.987). The same pattern did not occur in CG. KT treatment reduced edema and increased nociceptive threshold in the 7th and 14th PO ACL reconstruction.


Perceived Barriers and Potential Strategies to Improve Self-Management Among Adults with Type 2 Diabetes: A Community-Engaged Research Approach.
Type 2 diabetes (T2D) is a leading cause of morbidity and mortality that disproportionately affects adults living in urban areas in the USA. Our goal was to actively engage community members in research to identify strategies to improve T2D self-management in an urban community in Baltimore, MD. We partnered with the Johns Hopkins Community Research Advisory Council to establish our stakeholder advisory board-the Diabetes Action Board (DAB). In response to input from DAB members regarding the best approaches for conducting community-centered T2D research, we conducted three 90-min focus groups of local adults living with T2D to identify ways to improve self-management. DAB members were involved in each stage of the research, including development of the protocol and materials, participant recruitment, and interpretation and dissemination of findings. In total, 24 adults with self-reported T2D (75 % participation rate; 79 % female) residing in the local area participated in focus groups. Participants reported that barriers within their daily home and work environments, inadequate neighborhood resources, and suboptimal healthcare quality hindered their self-management. Reported strategies that may help to improve self-management included social support from family members, providers, and community members; improved access to healthy food; and wide availability of free or low-cost T2D educational materials and classes within the local area. Our study demonstrates a successful mechanism for engaging community members in the design, implementation, and dissemination of T2D research. This research approach was beneficial for building a sustainable partnership to support future work in the local community.


Environmental and individual determinants of core and non-core food and drink intake in preschool-aged children in the United Kingdom.
Strategies to achieve healthier diets for children are likely to benefit from an understanding of the determinants. We examined environmental and individual predictors of children's intake of 'core' foods (fruit and vegetables) and 'non-core' foods (snacks and sweetened beverages). Predictors included parental intake, home availability, parental feeding styles (Encouragement and Monitoring) and children's food preferences. Based on research with older children, we expected intake of both food types to be associated with maternal intake, core foods to be more associated with children's preferences and non-core food intake more with the home environment. Primary caregivers (n=434) of children (2-5 years) from preschools and Children's Centres in London, UK, completed a self-report survey in 2008. Multiple regression analyses indicated children's fruit intake was associated with maternal fruit intake (B=0.29; P=0.000), children's liking for fruit (B=0.81; P=0.000) and a Monitoring style of parental feeding (B=0.13; P=0.021). Children's vegetable intake was similarly associated with maternal intake (B=0.39; P=0.000), children's liking for vegetables (B=0.77; P=0.000), Encouragement (B=0.19; P=0.021) and Monitoring (B=0.11; P=0.029). Non-core snack intake was associated with maternal intake (B=0.25; P=0.029), Monitoring (B=-0.16; P=0.010), home availability (B=0.10; P=0.022) and television viewing (TV) (B=0.28; P=0.012). Non-core drink intake was associated with maternal intake (B=0.32; P=0.000) and TV (B=0.20; P=0.019). Results indicate commonalities and differences in the predictors of core and non-core food intake, with only maternal intake being important across all types. Effective interventions to improve young children's diets may need to call on different strategies for different foods.


Enhancing bioavailability through thermal processing.
Formulation intervention, through the application of processing technologies, is a requirement for enabling therapy for the vast majority of drugs. Without these enabling technologies, poorly soluble drugs may not achieve therapeutic concentrations in the blood or tissue of interest. Conversely, freely soluble and/or rapidly cleared drugs may require frequent dosing resulting in highly cyclic tissue concentrations. During the last several years, thermal processing techniques, such as melt mixing, spray congealing, sintering, and hot-melt extrusion, have evolved rapidly and several new technologies, specifically dry powder coating, injection molding, and KinetiSol(®) dispersing, have been adapted to the pharmaceutical arena. An examination of the contemporary literature is reported in this review to summarize the variety and utility of thermal processing technologies employed for solubility enhancement and controlled release. In particular, the impact of these processing technologies on bioavailability, considered in terms of both rate and extent, has been reviewed.


An efficient and reproducible Agrobacterium-mediated transformation method for hexaploid wheat (Triticum aestivum L.).
Despite wheat being a worldwide staple, it is still considered the most difficult to transform out of the main cereal crops. Therefore, for the wheat research community, a freely available and effective wheat transformation system is still greatly needed. We have developed and optimised a reproducible Agrobacterium-mediated transformation system for the spring wheat cv 'Fielder' that yields transformation efficiencies of up to 25%. We report on some of the important factors that influence transformation efficiencies. In particular, these include donor plant health, stage of the donor material, pre-treatment by centrifugation, vector type and selection cassette. Transgene copy number data for independent plants regenerated from the same original immature embryo suggests that multiple transgenic events arise from single immature embryos, therefore, actual efficiencies might be even higher than those reported. We reported here a high-throughput, highly efficient and repeatable transformation system for wheat and this system has been used successfully to introduce genes of interest, for RNAi, over-expression and for CRISPR-Cas9 based genome editing.


Comparative analysis in cereals of a key proline catabolism gene.
Proline accumulation and catabolism play significant roles in adaptation to a variety of plant stresses including osmotic stress, drought, temperature, freezing, UV irradiation, heavy metals and pathogen infection. In this study, the gene Delta1 -pyrroline-5-carboxylate dehydrogenase (P5CDH), which catalyzes the second step in the conversion of proline to glutamate, is characterized in a number of cereal species. P5CDH genes from hexaploid wheat, Triticum turgidum (durum wheat), Aegilops tauschii, Triticum monococcum, barley, maize and rice were shown to be conserved in terms of gene structure and sequence, present as a single copy per haploid, non-polyploid genome and located in evolutionarily conserved linkage groups. A wheat cDNA sequence was shown by yeast complementation to encode a functional P5CDH activity. A divergently-transcribed rab7 gene was identified immediately 5' of P5CDH in all grasses examined, except rice. The rab7/P5CDH intergenic region in these species, which presumably encompasses 5' regulatory elements of both genes, showed a distinct pattern of sequence evolution with sequences in juxtaposition to each ORF conserved between barley, wheat, A. tauschii and T. monococcum. More distal 5' sequence in this intergenic region showed a higher rate of divergence, with no homology observed between these regions in the wheat and barley genomes. Maize and rice showed no similarity in regions 5' of P5CDH when compared with wheat, barley, and each other, apart from a 22 bp region of conserved non-coding sequence (CNS) that is similar to a proline response element identified in the promoter of the Arabidopsis proline dehydrogenase gene. A palindromic motif similar to this cereal CNS was also identified 5' of the Arabidopsis AtP5CDH gene showing conservation of this sequence in monocot and dicot lineages.


A systematic review and meta-analysis: the therapeutic and preventive effect of Lactobacillus reuteri DSM 17,938 addition in children with diarrhea.
To summarize the effect of adding Lactobacillus reuteri in the treatment plan for diarrheal disease in children, and analyze the potential of probiotics in preventing the occurrence of diarrheal disease. Search for randomized controlled trials of Lactobacillus reuteri for the treatment and prevention of diarrhea in the Pubmed, Web of science, Medline, and Cochrane databases. Data such as the number of diarrhea patients, time, length of stay, clinical symptoms and effect of diarrhea prevention were extracted for meta-analysis. Relative risk and confidence interval (RR and 95% CI) were used as outcome indicators. 963 participants in the 9 RCTs came from multiple countries/regions. Compared with placebo/no intervention, the number of diarrhea patients in the Lactobacillus reuteri group was significantly reduced on the day 1 (RR = 0.87, 95%CI: 0.78-0.97) and day 2 (RR = 0.61, 95%CI: 0.44-0.83). Cumulative statistics analysis showed that the effect was stable and significant starting on the 4th day after treatment. A few studies have shown that Lactobacillus reuteri can reduce the time of diarrhea, the number of days with watery stools, and days of hospital stay. However, it has no effect on the occurrence of nosocomial diarrhea (RR = 1.11, 95%CI: 0.68-1.83), rotavirus diarrhea (RR = 1.46, 95%CI: 0.78-2.72), antibiotic-related diarrhea (RR = 1.76, 95%CI: 0.77-4.05), and diarrhea (RR = 1.35, 95%CI: 0.95-1.92). Addition of Lactobacillus reuteri in the treatment plan has a significant effect on reducing the number of diarrhea and reducing the symptoms of diarrhea, but has no obvious effect on the prevention of diarrhea. Combining probiotics and improving the ability of probiotics to respond is the focus of attention.


Psychological Safety in Intensive Care Unit Rounding Teams.
Rationale: Psychological safety is the condition by which members of an organization feel safe to voice concerns and take risks. Although psychological safety is an important determinant of team performance, little is known about its role in the intensive care unit (ICU). Objectives: To identify the factors associated with psychological safety and the potential influence of psychological safety on team performance in critical care. Methods: We performed daily surveys of healthcare providers in 12 ICUs within an integrated health system over a 2-week period. Survey domains included psychological safety, leader familiarity, leader inclusiveness, role clarity, job strain, and teamwork. These data were linked to daily performance on lung-protective ventilation and spontaneous breathing trials. We used regression models to examine the antecedents of psychological safety as well as the influence of psychological safety on both perceived teamwork and actual performance. Results: We received 553 responses from 270 unique providers. At the individual provider level, higher leader inclusiveness (adjusted β = 0.32; 95% confidence interval [CI], 0.24 to 0.41) and lower job strain (adjusted β = -0.07, 95% CI, -0.13 to -0.02) were independently associated with greater psychological safety. Higher psychological safety was independently associated with greater perception of teamwork (adjusted β = 0.30; 95% CI, 0.25 to 0.36). There was no association between team psychological safety and performance on either spontaneous breathing trials (incident rate ratio for each 1-unit change in team psychological safety, 0.85; 95% CI, 0.81 to 1.10) or lung-protective ventilation (incident rate ratio, 0.77; 95% CI, 0.57 to 1.04). Conclusions: Psychological safety is associated with several modifiable factors in the ICU but is not associated with actual use of evidence-based practices.


A portable device for single point strain analysis in sheet metal forming processes.
Strain measurement is one of the basic techniques in sheet metal forming for quantifying the deformation of a material under the effects of various loading conditions. The main components in the automatic strain measurement system are the image acquisition hardware and image processing software. This paper presents an automatic single point strain analysis system for sheet metal forming applications. The proposed system is very portable and consists of a USB microscope with different end caps for image acquisition. The software system was developed using Python - OpenCV library and provided with a graphical user interface (GUI).


End-of-life nursing education: Enhancing nurse knowledge and attitudes.
To evaluate the effectiveness of a palliative and end-of-life care nursing education program on nurses' knowledge and attitudes toward caring for patients with advanced serious illness or nearing death. It is projected that 9 million Americans will be over 85 years old, in the year 2030; many will be living with disabilities and serious medical conditions. Expanding access to palliative care resources and knowledgeable providers is essential for meeting the future demands required by the aging population. A quasi-experimental research design with pre-test and post-test measures was utilized. Potential sample included 134 nurses who participated in a 6-week, 12-hour End-of-Life Nursing Education Consortium (ELNEC) Core Curriculum© educational program. Changes in knowledge were measured using The Palliative Care Quiz for Nursing (PCQN) (n = 61), while changes in attitudes in caring for dying patients were measured using the Thanatophobia Scale (TS) (n = 57). Results suggest that while post-test PCQN knowledge scores increased significantly (t = -7.498; p = .000), practicing nurses were somewhat lacking in EOL care knowledge answering 13/20 questions correctly before, and 15/20 questions correctly after the educational intervention. Results also indicated that the sample had positive attitudes in caring for this patient population initially, but that attitudes improved significantly post-intervention (t = 3.944; p = .000). Results support the use of the ELNEC© curriculum for EOL education among this sample, suggesting that educating practicing nurses about EOL is an effective mechanism for both increasing knowledge and improving attitudes. Results also suggest that more education is warranted.


Lifetime evidence for a weak lowest electronic transition in adenosine.
The fluorescence decay of adenosine in 1:1 glycol/water glass has been determined at 77K using narrow pulse (700 ps) laser excitation at 290 nm and fluorescence detection with a scanned narrow-gate (100 ps) fast sampler together with digital averaging. Data analysis by re-iterative non-linear least squares convolution shows the decay is best represented by the bi-exponential form I(t) = 0.59exp - t/1.2ns + 0.41 exp - t/7.0ns. This leads to intrinsic radiative lifetimes of 150 ns and 220 ns respectively and a combined oscillator strength of 1.5 x 10(-2). Compared with the overall oscillator strength of 0.29 for the entire first absorption band of adenosine this indicates that transitions to and from the lowest-lying state in this band are quite forbidden. This is not accounted for by current theoretical considerations.


Stop-flow comprehensive two-dimensional liquid chromatography combined with mass spectrometric detection for phospholipid analysis.
A novel comprehensive two-dimensional liquid chromatographic (LC × LC) system for characterization of phospholipid (PL) molecular species belonging to six phospholipid classes was developed. To tackle such a task, a silica hydrophilic interaction liquid chromatography (HILIC) column was used as the first dimension ((1)D), and reversed-phase liquid chromatography (RP-LC) with a C18 column was used as the second dimension ((2)D) in combination with mass spectrometric detection. Fraction transfer from the (1)D to the (2)D was performed by means of a two-position ten-port switching valve, operated under stop-flow conditions. The capability of the investigated LC × LC approach was demonstrated in the separation of phospholipid molecular species contained in two Folch-extracted cow's milk and plasma samples. Within the phosphatidylcholine class, up to 16 and 14 different species were identified, respectively, by means of the HILIC×RP-LC-MS system employed under both positive and negative ionization mode.


The lipoma-like hibernoma: A case report of a rare entity.
Hibernoma is a rare tumor developing from fat cells. It is a slowly evolving, benign tumor that is rarely pain-inducing. The most frequently encountered histological form is the typical hibernoma. The main differential diagnosis is liposarcoma. Here we present a case of a lipoma-like tumor of the arm: a rare variant of hibernoma. A 45-year-old man presents with a swelling of the left arm evolving for one year. Physical examination revealed a mobile, firm, and well-defined mass of the lateral left upper arm measuring 5 cm in length with no cutaneous lesions overlying. MRI and ultrasound confirmed the presence of a highly vascularized mass suggestive of a liposarcoma. A biopsy of the mass was performed concluding to a lipoma with no evident signs of malignancy. The patient underwent a surgical resection of the mass. Histopathological examination showed a well-differentiated adipose proliferation arranged in diffuse patterns of mature adipocytes. Large hibernoma-like foci were also noted. The diagnosis of a lipoma-like hibernoma was confirmed. Hibernoma represents is an uncommon benign tumor. It usually occurs in areas where the brown fat persists, including the thighs, shoulders, back, and neck in decreasing frequency. Commonly, this tumor occurs between the second and third decades of life. Clinically, it presents as a slow growing, painless mass. It may occasionally be painful due to compression of the surrounding structures. MRI shows T1w and T2w hyperintensity, with contrast enhancement after gadolinium injection. On histopathological examination, the structure is distinguished by an association of mature cells, round cells with central nuclei and eosinophilic cytoplasm, and multivacuolated cells. Surgical excision is the optimal treatment. The differential diagnosis concerns lipomas and well-differentiated liposarcomas. Lipoma-like hibernoma is an uncommon benign tumor which might imitate a liposarcoma clinically and radiologically. Histopathological examination is necessary to establish the diagnosis.


Effect of multiple freezing and thawing of serum on TT virus and hepatitis B virus DNA positivity.
This study was done to determine the effect of freezing and thawing of serum on the stability of TTV and HBV DNA levels. Seven TTV DNA positive samples were randomly selected among the sera having HBV DNA with concentrations ranging from 12 pg/ml to 4162 pg/ml and they were frozen and thawed up to eight times and then analyzed for changes on TTV- and HBV DNA levels. TTV DNA positivity and HBV DNA concentrations were tested by using semi-nested PCR and Digene hybrid capture system, respectively. Seven cycles of freezing and thawing did not significantly change HBV DNA concentrations and TTV DNA positivity in any of the samples tested. After eight cycles, only three samples were tested, and all were positive for HBV DNA, but negative for TTV DNA. Our results show that both TTV- and HBV DNA positives continued until the seventh cycle of freezing and thawing in all samples tested.


Biofeedback control of skin potential level.
This study explored the possibility of using biofeedback to arrest spontaneous declines in tonic electrodermal levels. For 3 days, 10 subjects (S) received 20 minutes of training in increasing skin potential level (SPL) negativity (arrested declines), followed by 20 minutes of training in decreasing SPL negativity (facilitating declines), with reverse order for half of the Ss. Simultaneous analogue and binary feedback of SPL were used. Training in the direction of SPL increases resulted in arrest of spontaneous declines in SPL negativity but did not result in large-magnitude increases above baseline. Training in the direction of SPL decreases facilitated declines in SPL. The absolute mean difference between the increase condition and the decrease condition on the 3rd day was 8.28 mV. Correlations suggested that considerable intraindividual variability may have been independently related to the Locus of Control personality dimension and to a Law of Initial Values limitation on SPL change. It was concluded that SPL was controllable to the extent of facilitating or arresting spontaneous declines.


Combined association of central obesity and depressive symptoms with risk of heart disease: A prospective cohort study.
To examine the combined association of central obesity and depressive symptoms with risk of heart disease in a national prospective cohort study of the Chinese population. Data came from 10,722 community-dwelling adults aged over 45 years, from the China Health and Retirement Longitudinal Study during 2011-2018. Central obesity was assessed with waist circumference (WC) in physical examinations (men with a WC of ≥ 90 cm and women with a WC of ≥ 80 cm). Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (score ≥ 10). Participants were assigned to four groups according to central obesity (yes/no) and depressive symptoms (yes/no). Cox proportional hazard regression was used after adjusting for covariates. During 7 years of follow-up, we identified 1080 heart disease cases. Compared with people without central obesity and depressive symptoms, the multivariable-adjusted hazard ratios (95% confidence intervals) were 1.39 (1.18, 1.64) for those who had central obesity alone, 1.44 (1.18, 1.77) for those who had depressive symptoms alone, and 1.88 (1.55, 2.30) for those who had both central obesity and depressive symptoms. The combined association in men was more evident than that in women. Our study provided evidence that the coexistence of central obesity and depressive symptoms were associated with a substantially increased risk of heart disease compared to those without these two conditions.


Cross-cultural validation and psychometric properties of the Arabic Brief COPE in Saudi population.
Coping strategies for stress tend to vary in different cultural. The Brief COPE (BC) is the most commonly used self-report instrument to identify the types of coping strategies used which has a total of 14 strategies with 28 items. The aim of this study was to translate into Arabic and validate the Brief COPE scale in the Saudi Arabian population. A cross-sectional method was used to assess the reliability, validity, and cultural appropriateness of the Arabic version of the Brief COPE (A-BC) among 302 males and females (33.8% females). The test-retest reliability was strong at 0.8, and the principal component factor analysis yielded a 3-factor structure, namely 'active coping', 'passive coping', and 'support-seeking', with Composite Reliability scores of 0.84, 0.75, and 0.81 respectively. Confirmatory factor analysis indicated an acceptable factors structure. The 3-factor structure of the A-BC was found to be a valid and reliable instrument among the Saudi population. This makes the scale useful in both clinical practice and clinical research.


A 6-Day-Old Male Infant with Severe Hyperbilirubinemia Diagnosed with Hereditary Spherocytosis at a Tertiary Hospital in East Java, Indonesia: A Diagnostic and Management Challenge in a Developing Country.
BACKGROUND Hereditary spherocytosis (HS) is an autosomal dominant inherited disorder that causes severe hyperbilirubinemia in neonates. There is no factual data about the prevalence in Indonesia. It is common that neonates with suspected hereditary spherocytosis are not diagnosed or treated adequately in developing countries such as Indonesia. CASE REPORT A 6-day-old baby was referred from a secondary public hospital to our tertiary hospital in Malang, East Java with severe hyperbilirubinemia unresponsive to the 2 days of conventional phototherapy. Initial laboratory examination showed total serum bilirubin level 28.83 mg/dL and indirect bilirubin level 25 mg/dL. Complete blood count showed hemoglobin level of 10.3 g/dL with high MCHC 36.9 g/dL and increased RDW 18.7%. The HS ratio (MCHC per MCV) was 0.41. The blood smear showed spherocytes with positive family history from the mother and grandmother. There were no specific tests such as EMA binding, cryohemolysis, or analysis of erythrocyte membrane protein available in our hospital. The patient was then treated with 2 sessions of intensive phototherapy with phototherapy unit bilisphere 360 LED. The total serum bilirubin level dropped to 12.19 mg/dL. In this case, we decided to perform intensive phototherapy first, not only because of facility-based constraints to do timely exchange transfusion, but also due to the low socio-economic and educational background of the parents. CONCLUSIONS There are some challenges in diagnosing and treating HS adequately in Indonesia. Limitations of specific tests, inadequacy of conventional phototherapy, lack of awareness of and adherence to guidelines, and facility-based inability to perform timely exchange transfusion all can contribute to severe hyperbilirubinemia and its sequelae.


Shortness of breath: pulmonary embolism, ischemic heart failure, or both? The role of concomitant surgery.
We present a case of a patient who underwent successful concomitant surgical management of his massive pulmonary embolism and severe multivessel coronary disease. His presentation with shortness of breath prompted a comprehensive evaluation, which revealed both problems. This experience emphasizes the importance of considering both problems, because treating one but not the other could be catastrophic.


Bcl-2 oncoprotein expression and apoptosis in neuroblastoma.
Bcl-2 protooncogene, originally discovered at the chromosomal breakpoint of the t(14;18) in follicular lymphoma, is known to regulate the process of programmed cell death or apoptosis. The inhibition of apoptosis is thought to be one of the mechanisms involved in the development of tumors. To investigate the possible association of bcl-2 protooncogene with the tumorigenesis of neuroblastomas, the authors examined bcl-2 expression by immunohistochemistry in 49 neuroblastomas and 7 ganglioneuromas. The distribution of apoptotic cells was also examined by the TUNEL method (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Bcl-2 oncoprotein was detected in the cytoplasm in 40 of 49 neuroblastomas (81.6%). There was no correlation between bcl-2 oncoprotein expression and the clinical features of neuroblastoma. The incidence of bcl-2-positive tumors in ganglioneuroma was significantly lower than that in neuroblastoma (28.6%) (P < .01). TUNEL stained the nuclei of tumor cells in 11 of 34 (32.4%) neuroblastomas. TUNEL-positive cells tended to be located around calcifications in neuroblastomas in patients less than 1 year old. Examination of serial sections showed that apoptotic cells were distributed in the area where bcl-2 oncoprotein was not expressed. What we have observed indicates that apoptosis of neuroblastoma cells may be regulated by bcl-2 expression. Our observations suggest that the survival of neuroblastoma cells might be promoted by bcl-2 expression and that bcl-2 might be associated with the tumorigenesis of neuroblastomas.


Membrane-plate transition in leaves as an influence on dietary selectivity and tooth form.
Primates need accurate sensory signals about food quality to forage efficiently. Current evidence suggests that they target leaf foods based on color at long-range, reinforcing this with post-ingestive sensations relating to leaf toughness evoked during chewing. Selection against tough leaves effectively selects against high fiber content, which in turn gives a greater opportunity of acquiring protein. Here we consider a novel intermediate mechanical factor that could aid a folivore: leaves may transform mechanically from membranes (sheets that cannot maintain their shape under gravitational loads and thus 'flop') early on in development into plates (that can maintain their shape) as they mature. This transformation can be detected visually. Mechanical tests on two species of leaf eaten by southern muriqui monkeys (Brachyteles arachnoides) in Southern Atlantic Forest, Brazil, support a membrane-to-plate shift in turgid leaves during their development. A measure of this mechanical transition, termed lambda (λ), was found to correlate with both leaf color and toughness, thus supporting a potential role in leaf selection. Muriquis appear to select membranous leaves, but they also eat leaves that are plate-like. We attribute this to the degree of cresting of their molar teeth. A dietary choice restricted to membranous leaves might typify the type of 'fallback' leaf that even frugivorous primates will target because membranes of low toughness are relatively easily chewed. This may be relevant to the diets of hominins because these lack the bladed postcanine teeth seen in mammals with a specialized folivorous diet. We suggest that mammals with such dental adaptations can consume tougher leaf 'plates' than others.


Role of cations in stability of acidic protein Desulfovibrio desulfuricans apoflavodoxin.
Apoflavodoxin from the sulfate reducing bacteria Desulfovibrio desulfuricans is a small, acidic protein with a net charge of -19 at neutral pH. Here, we show that monovalent cations in biologically relevant amounts have dramatic effects on apoflavodoxin stability. The effect is largest for Gdm(+) and decreases as a function of increased cation charge density (Gdm(+)>NH(4)(+)K(+) approximately Cs(+) approximately Na(+)>Li(+)). A linear correlation of stabilizing effects with cation hydration properties suggests an important role of dehydration in efficient cation interaction with the protein. The effects on stability are due to preferential binding of one cation to native apoflavodoxin and results in an increase in thermal midpoint of 20 degrees C and the free energy of unfolding (at 20 degrees C) increases fivefold. Tuning of biophysical properties (such as folding and ligand/cofactor binding) of acidic proteins by cation binding may be important in vivo.


The promoter -1031(T/C) polymorphism in tumor necrosis factor-alpha associated with polycystic ovary syndrome.
A tumor necrosis factor-alpha is a multifunctional pro-inflammation cytokine, which has been considered as one of pathogenic factors for various diseases. The promoter -1031(T/C) polymorphism in the tumor necrosis factor-alpha gene was reported that it plays a part in reproduction-related diseases. Among these, polycystic ovary syndrome (PCOS) is known to be a common gynecological disease of women in reproductive age women. Here, we performed a comparative study of -1031(T/C) polymorphism of TNF-alpha gene with PCOS in a Korean population. The -1031(T/C) polymorphism of TNF-alpha gene was analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in a total of 217 PCOS patients and 144 matched female controls of healthy women. And statistical analysis was performed using HapAnalyzer. X2 test and logistic regression were utilized analyze the association between two groups. A p-value under 0.05 was considered statistically significant. The genotype and allelic frequencies were in Hardy-Weinberg equilibrium (HWE). There was strong association between the -1031(T/C) polymorphism in the promoter region of TNF-alpha gene and PCOS (p-value = 0.0003, odd ratio (OR) = 2.53). In addition, the frequency of C allele was significantly higher in PCOS patients compared with controls. Sequence analyses also showed the -1031(T/C) polymorphism of TNF-alpha gene. This is the first study on the -1031(T/C) polymorphism of TNF-alpha gene in PCOS. We concluded that the -1031(T/C) polymorphism of TNF-alpha gene is associated with PCOS in a Korean population. Therefore, it is possible that it may be considered as a clinical biomarker to diagnose for PCOS, and is helpful in understanding the etiology for the pathogenesis of PCOS.


Antifilarial efficacy of andrographolide: Ex vivo studies on bovine filarial parasite Setaria cervi.
Lymphatic filariasis caused by filarial nematode is an important disease leading to considerable morbidity throughout tropical countries. Even after specific elimination programs, the disease continue to spread in endemic countries. Thus newer therapeutic interventions are urgently needed to control the spread. In the present study, we have seen the effect of andrographolide (andro), a diterpenoid lactone from the leaves of Andrographis paniculata on filarial parasite Setaria cervi. There was time and concentration dependent decrease in motility and viability leading to death of parasite after 6 h of the exposure of andro. Andro showed potential antifilarial activity with an IC50 value of 24.80 μM assessed through MTT assay. There was concentration dependent decrease in the antioxidant enzymes activity and increase in proapoptotic markers after 5 h exposure of andro. Further, molecular docking analysis revealed that andro binds with filarial glutathione-S-transferase at glutathione (GSH) binding site and inhibiting enzyme activity competitively. Andro induced oxidative stress mediated apoptosis in parasites as evidenced by increase in the intracellular reactive oxygen species (ROS) and apoptotic markers.Therefore this study suggested that andro could be further explored as a new antifilarial drug.


Changes in the antigenic specificity of influenza hemagglutinin in the course of adaptation to mice.
Influenza virus strains A/USSR/90/77 (H1N1) and A/USSR/92/77 (H1N1) have been adapted to mice by successive intranasal passages. In the course of adaptation a loss (for A/USSR/90/77) or a reduction (for A/USSR/92/77) of the reactivity toward two monoclonal antibodies in a panel of seven monoclones has been registered. The changes emerged after two or three passages, long before the acquisition of the lethal effect for mice. Possible significance of the phenomenon for the antigenic variation of influenza A virus is discussed.


Synthesis of novel compounds containing morpholine and 5(4H)-oxazolone rings as potent tyrosinase inhibitors.
In this study, six new compounds containing morpholine and 5(4H)-oxazolone rings were synthesized. Structures of the new compounds using IR, (1)H NMR, mass spectroscopy and elemental analysis were characterized. All new compounds (4a-4f) have a strong inhibitory effect against mushroom tyrosinase. And the inhibitory effects of these compounds were compared with Kojic acid as standard.


Iridoids from Teucrium yemense.
The aerial parts of Teucrium yemense yielded two iridoid glycosides. Their structures were elucidated by spectral means as teucardosid and 8-O-acetylharpagid.


Global warming and cyanobacterial harmful algal blooms.
The Earth and the oceans have warmed significantly over the past four decades, providing evidence that the Earth is undergoing long-term climate change. Increasing temperatures and changing rainfall patterns have been documented. Cyanobacteria have a long evolutionary history, with their first occurrence dating back at least 2.7 billion years ago. Cyanobacteria often dominated the oceans after past mass extinction events. They evolved under anoxic conditions and are well adapted to environmental stress including exposure to UV, high solar radiation and temperatures, scarce and abundant nutrients. These environmental conditions favor the dominance of cyanobacteria in many aquatic habitats, from freshwater to marine ecosystems. A few studies have examined the ecological consequences of global warming on cyanobacteria and other phytoplankton over the past decades in freshwater, estuarine, and marine environments, with varying results. The responses of cyanobacteria to changing environmental patterns associated with global climate change are important subjects for future research. Results of this research will have ecological and biogeochemical significance as well as management implications.


Effects and mechanisms of crude astragalosides fraction on liver fibrosis in rats.
Astragalosides is the major active constituent of Radix Astragali. The present study was carried out to investigate the effect of crude astragalosides fraction (CAF) on rats liver fibrosis and its possible mechanisms. Hepatic fibrosis was induced by subcutaneous injection with 50% CCl(4) in Sprague-Dawley rats. The amount of CCl(4) administered was 1 mg kg(-1). The alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in culture supernatants of Kupffer cells (KCs) were determined with ELISA. Liver samples collected after 8 weeks of CCl(4) treatment were stained with hematoxylin-eosin (HE) and massion, and scored. Intragastric administration of CAF (10, 20 and 40 mg kg(-1)) significantly decreased indices of liver and spleen, the serum transaminase activities, HA and PC III levels, and Hyp and MDA contents in liver tissue in rats of hepatic fibrosis. Decreased SOD and GSH-px levels were reversed after administration of CAF. Histopathological scores showed CAF had inhibitory effect on the progression of hepatic fibrosis. In the in vitro experiments, CAF significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs. The results showed CAF significantly inhibited the progression of hepatic fibrosis induced by CCl(4), and the inhibitory effect of CAF on hepatic fibrosis might be associated with its ability to scavenge free radical and inhibit the production of TNF-alpha and TGF-beta1 from activated KCs.


Motor function improvement following intrathecal baclofen pump placement in a patient with locked-in syndrome.
We describe a patient with locked-in syndrome who had minimal volitional motor function and severe spasticity in all four extremities. The patient showed a significant improvement in volitional motor function following intrathecal baclofen pump therapy to control spasticity. This case study suggests that intrathecal baclofen pump therapy might improve motor function in select patients with locked-in syndrome.


Thoracic bilateral sympathectomy attenuates oxidative stress and prevents ventricular remodelling in experimental pulmonary hypertension.
Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease that affects the pulmonary vasculature, leading to increased afterload and eventually right ventricular (RV) remodelling and failure. Bilateral sympathectomy (BS) has shown promising results in dampening cardiac remodelling and dysfunction in several heart failure models. In the present study, we investigated whether BS reduces pulmonary arterial remodelling and mitigates RV remodelling and failure. PAH was induced in male Wistar rats by intraperitoneal injection of monocrotaline. Rats were divided into 3 groups, involving untreated PAH (n = 15), BS-treated PAH (n = 13) and non-manipulated control rats (n = 13). Three weeks after PAH induction, the rats were anaesthetized and RV function was assessed via the pressure-volume loop catheter approach. Upon completion of the experiment, the lungs and heart were harvested for further analyses. BS was found to prevent pulmonary artery remodelling, with a clear reduction in α-smooth muscle actin and endothelin-1 expression. RV end-systolic pressure was reduced in the BS group, and preload recruitable stroke work was preserved. BS, therefore, mitigated RV remodelling and cardiomyocyte hypertrophy and diminished oxidative stress. We showed that thoracic BS may be an important treatment option for PAH patients. Blockade of the sympathetic pathway can prevent pulmonary remodelling and protect the RV from oxidative stress, myocardial remodelling and function decay.


Maternal behavior in normal and androgenized female rats: effect of age and experience.
The aim of the experiments presented here was to evaluate the influence of age and of previous maternal experience on care of pups in normal virgin and androgenized Wistar female rats. When sensitization occurred before they were 60 days old, androgenized females failed to develop consistent retrieving, probably because of excessive timidity (Experiments 1 and 2) whereas they were able to keep pups warm in their nests. During pup-toy choice tests (Experiment 2) young androgenized females displayed only erratic carrying of toys. On the other hand, 60-, 80- or 100-day-old androgenized females developed full maternal behavior like cyclic controls. In the third experiment, control and androgenized females exposed to pups when 60 days old, were reexposed when 95 days old. Androgenized females proved to be more sensitive to earlier exposure to pups than control females and showed significant reductions in latencies of emergence of maternal responses.


Huaiqihuang Granules () reduce proteinuria by enhancing nephrin expression and regulating necrosis factor κB signaling pathway in adriamycin-induced nephropathy.
To investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms. Rats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers. HQH ameliorated the rat's general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis. HQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.


Protective effects of ascorbic acid against lead-induced apoptotic neurodegeneration in the developing rat hippocampus in vivo.
Lead is a neurotoxin that affects the developing central nervous system and may potentially induce apoptotic cell death. We investigated the effect of ascorbic acid against lead-induced neurotoxicity in the developing rat hippocampus. Female Sprague-Dawley rats were divided into three groups: control group, lead-treated group and lead plus ascorbic acid-treated group. Lead (0.2% lead acetate) was administered to female rats during pregnancy and lactation, in their drinking water. During this period, rats in the lead plus ascorbic acid-treated group received 100 mg/kg/day ascorbic acid, orally. At the end of the treatment, neuronal damage, apoptosis and blood lead levels were determined and the levels of Bax and Bcl-2 were immunodetected in the hippocampus of 21-day-old male pups. Histopathological evaluation demonstrated that ascorbic acid significantly attenuates apoptosis in the developing hippocampus and also spares hippocampal CA1, CA3 and dentate gyrus (DG) neurons. Simultaneous administration of ascorbic acid and lead lowered the level of Bax protein and increased Bcl-2 in pup hippocampus and reduced lead level in blood of dams compared with lead-treated only. Based on these results, it seems that ascorbic acid may potentially be beneficial in treating lead-induced brain injury in the developing rat brain.


Delayed transfers of older people from hospital: Causes and policy implications.
Health and social care agencies in the UK. have been under pressure for some time to reduce delayed transfers of older people from hospital because they absorb scarce health service resources and incur a human cost through inappropriate placement. A local study based on an analysis of records and interviews with managers showed that delays reflect the complex needs of older people, and arise from financing and organisational problems at both the planning and implementation stages of a discharge. Family resistance may also be a factor. Budgetary constraints result in delays in confirming public support for some clients. Shortages of professional staff and care assistants limit the provision of domiciliary packages. The contraction of the residential sector has reduced the availability of beds and increased the cost of care home placements. Scope exists for expediting administrative aspects of transfers by coordinating health and social services. More recent legislation that imposes fines on social service departments for delayed transfers does not address underlying causes.


Bronchodilatory, antitussive and anti-inflammatory effect of morin in the setting of experimentally induced allergic asthma.
Using an experimental model of allergic asthma, we evaluated the anti-asthmatic potential of polyphenol flavonol derivate morin after either acute or long-term treatment of male OVA-sensitised guinea pigs. The following methods were used in experiments: the in-vitro tracheal smooth muscle contraction induced by histamine; the changes in specific airway resistance (sRaw) to histamine and the sensitivity of a chemically induced cough reflex both via an in-vivo method; the serum and BALF concentrations' analysis of the inflammatory cytokines interleukin IL-4, IL-5, IL-13; and lung tissue infiltration by eosinophils and mastocytes. Our data show that acute morin (30 mg/kg) and chronic 21-day morin (30 mg/kg/day) administration had a comparable antitussive efficiency with opioid antitussive codeine. Acute morin bronchodilatory activity defined by in-vivo sRaw decline did not reach SABA salbutamol effect. However, bronchodilatory efficiency of morin after long-term administration was by 34% higher as effect of LABA salmeterol. The 21-day morin treatment of OVA-sensitised guinea pigs reduced the serum, BALF levels of IL-4 and IL-13, lung tissue eosinophil and mastocyte infiltration comparable with corticosteroid budesonide. In summary, morin represents very rational target for additional studies as potential substance for control as well as prevention of asthma inflammation and symptoms.


Interaction of the mouse and bovine myelin basic proteins and two cleavage fragments with anionic detergents.
The binding of deoxycholate and dodecyl sulfate to the mouse and bovine myelin basic proteins and two peptide fragments, obtained by cleavage of the bovine basic protein at its single tryptophan residue, was examined. Complete equilibrium binding isotherms for both detergents were obtained by examining their binding to each of the polypeptides immobilized on agarose. The bulk of the binding of dodecyl sulfate was found to be highly cooperative, and at saturation all four polypeptides bound far more detergent than globular, water-soluble proteins. The sum of the dodecyl sulfate bound by each of the two bovine basic protein cleavage fragments was almost twice that bound by the intact protein at saturation, suggesting that cleavage of the bovine basic protein exposes sites for additional binding of dodecyl sulfate. At pH values below pH 8.0, an additional cooperative transition was observed below the critical micelle concentration of sodium dodecyl sulfate in the binding isotherms of all four polypeptides. The midpoint of this transition corresponded to an apparent pK of approximately 5.5; however, the destruction of 90% of the histidine residues in the bovine basic protein had no effect on this transition. At pH 9.2 and moderate ionic strength (I = 0.1), the bulk of the binding of deoxycholate to the mouse and bovine basic proteins occurred at and above the critical micelle concentration of the detergent; and saturation values of deoxycholate binding to these two proteins were considerably higher than that reported for globular, water-soluble proteins. In marked contrast to the results with dodecyl sulfate, neither cleavage fragment was observed to bind deoxycholate. The results suggest that the higher ordered structure of the bovine basic protein may play an important role in the binding of anionic amphiphiles to the protein.


Direction of gaze and emergence of speech in the second year.
Orienting to the right member of a pair of identical pictures increased monotonically with age in a longitudinal sample of 14 infants seen monthly from 13 to 22 months. The magnitude of the correlation between this orientation bias and a measure of language development also rose with age reaching a peak at 20 months and then declining. It was suggested that the acceleration of vocabulary and maturational changes in the central nervous system that occur between 16 and 22 months are associated with a special excitatory state in the temporal cortex of the left hemisphere.


De novo development of a cavernous malformation of the brain: significance of factors with paracrine and endocrine activity: case report.
De novo development of cavernous malformations is poorly documented in the literature. We report the case of a 37-year old woman with de novo growth of a cavernous malformation of the brain. The patient presented with a 12-month history of nonspecific headaches and paresthesias after two pregnancies. After computed tomographic scanning of the cranium, a cavernous malformation located parieto-occipitally within the right brain hemisphere was diagnosed. Control magnetic resonance imaging scans obtained 12 years earlier did not reveal a similar lesion. Surgery was performed, and the specimen was analyzed histopathologically. Immunohistochemistry demonstrated lack of expression of pituitary hormones as well as of androgen, estrogen, and progesterone hormone receptors. However, strong expression of both basic fibroblast growth factor and CD44 was detected in surrounding tissue, and expression of CD44 was noted within the matrix of the cavernous malformation.


Obstructor-A is required for epithelial extracellular matrix dynamics, exoskeleton function, and tubulogenesis.
The epidermis and internal tubular organs, such as gut and lungs, are exposed to a hostile environment. They form an extracellular matrix to provide epithelial integrity and to prevent contact with pathogens and toxins. In arthropods, the cuticle protects, shapes, and enables the functioning of organs. During development, cuticle matrix is shielded from premature degradation; however, underlying molecular mechanisms are poorly understood. Previously, we identified the conserved obstructor multigene-family, which encodes chitin-binding proteins. Here we show that Obstructor-A is required for extracellular matrix dynamics in cuticle forming organs. Loss of obstructor-A causes severe defects during cuticle molting, wound protection, tube expansion and larval growth control. We found that Obstructor-A interacts and forms a core complex with the polysaccharide chitin, the cuticle modifier Knickkopf and the chitin deacetylase Serpentine. Knickkopf protects chitin from chitinase-dependent degradation and deacetylase enzymes ensure extracellular matrix maturation. We provide evidence that Obstructor-A is required to control the presence of Knickkopf and Serpentine in the extracellular matrix. We propose a model suggesting that Obstructor-A coordinates the core complex for extracellular matrix protection from premature degradation. This mechanism enables exoskeletal molting, tube expansion, and epithelial integrity. The evolutionary conservation suggests a common role of Obstructor-A and homologs in coordinating extracellular matrix protection in epithelial tissues of chitinous invertebrates.


Size coding of alternative responses is sufficient to induce a potentiation effect with manipulable objects.
The mere perception of manipulable objects usually grasped with a power-grip (e.g., an apple) or a precision-grip (e.g., a cherry) potentiate power-grip- and precision-grip-responses, respectively. This effect is seen as to be driven by automatic access of the representation of manipulable objects that includes a motor representation of usually performed grasping behaviors (i.e., the embodied view). Nevertheless, a competing account argues that this effect could be due to an overlapping of size codes used to represent both manipulable objects and response options. Indeed, objects usually grasped with a power- and a precision-grip (e.g., an apple vs. a cherry) could be coded as large- and small-objects, respectively; and power- and precision-grip responses as large- and small-responses, respectively. We conducted 4 experiments to test this hypothesis. In Experiment 1, the response device usually used in studies reporting a potentiation effect is fixed horizontally (the grasping component of responses was removed). We instructed participants to press the small-switch with their index-digit and the large-switch with their palm-hand. In line with the size-coding-hypothesis, responses on the small-switch performed with the index-digit led to shorter RTs when objects usually associated with a precision-grip (e.g., a cherry) were presented compared to objects usually associated with a power-grip (e.g., an apple). A reverse pattern was obtained for responses on the large-switch performed with the palm-hand. In Experiments 2, 3 and 4, we went further by investigating which factors of Experiment 1 allow the size coding of responses: the size of switch and/or the size of the effector part used. Data confirmed the critical involvement of the size of switches and the possible involvement of the size of the effector part used. Thus, data support the possibility that the potentiation of grasping is due to a compatibility/incompatibility between size codes rather than involving motor representations of usually performed grasping behaviors as advocated in several embodied views. Moreover, data support the possibility that responses are coded thanks to a size code that extends the Theory of Event Coding.


A critical period in the development of tectal neurons in the chick, as revealed by early enucleation.
To further study the existence of a critical trophic period in the development of the chick optic tectum, during which the presence of retinal synapses is essential to the continued growth of tectal neurons, we have unilaterally enucleated embryos between stages 14--20 and allowed survival until stages 35--43. If the critical trophic period is between stages 40--44, as previously reported, then we reasoned that early removal of the eye might not have any effect on tectal development until the critical period. We assessed tectal neuron survival by staining for degeneration in the efferent projections of tectal neurons. In early enucleates, degeneration was present from stages 37--43, and the severity of the degeneration was much reduced in comparison to animals enucleated during the critical period. These findings substantiate the proposition that there is a critical period late in chick tectal development. However, because the degeneration in tectal projections is less intense than in animals enucleated during the critical period, we suggest that the early enucleation has permitted axons from the remaining eye to be routed to the deafferented tectum, where they may help to sustain a portion of the tectal neurons through the critical period. Moreover, the somewhat earlier appearance of degeneration in tectal efferent pathways of early enucleates suggests that a subtle trophic relationship between retina and tectum may exist prior to stage 40, even though this relationship is not revealed when enucleations are performed later, as between stages 35--40 (ref. 17).


Statistical analysis of changes of pediatric nasal patency with growth.
The purpose of this study was to further investigate the changes of pediatric nasal patency with growth. The nasal patency of Japanese children aged 6 to 14 years was measured by active anterior mask rhinomanometry in terms of effective cross-sectional area (ECSA). The total nasal ECSA of the boys studied was larger than that of the girls of the same age groups. Total nasal ECSA was significantly correlated to age and height, as not transformed, and to weight as logarithmically transformed. Moreover, our study suggests that pediatric nasal resistance is inversely proportional to the second power of age, of height, and of body weight; however, it was concluded that the parameter of height was in itself sufficient to permit an approximate calculation of the total nasal ECSA in normal subjects.


Extraction, Composition, and Antioxidant Activity of Flavonoids from Xanthoceras sorbifolium Bunge Leaves.
Xanthoceras sorbifolium Bunge leaves (XLs) are valuable resources rich in phytochemicals, especially in flavonoids, but they are rarely exploited and utilized. The purpose of this paper is to reduce the waste of XLs resources (usually used as agricultural waste) and extract the high added value of active ingredients from XLs. The extraction of flavonoids from XLs using ultrasonic-assisted extraction (UAE) was reported. Response surface methodology (RSM) was used to adopt different ultrasonic conditions such as ethanol concentration, liquid:solid ratio, and ultrasonic power. In addition, the chemical structures were identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and HPLC. Response surface analysis indicated the optimal level of ethanol concentration, liquid:solid ratio, and ultrasonic power as 71.49%, 13.87 mL/g, and 157.49 W respectively for the maximum response of total flavonoids (5.52 ± 0.23%), which fitted well with the predicted value (5.68 ± 0.17%). In addition, the extracts from XLs exhibited potent antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt (ABTS). The potent antioxidant activity of flavonoids from XLs is beneficial for their application in the food and drug industry, which will facilitate the rise of the added value of the flavonoids from XLs. Myricetin, rutin, and epicatechin, which may be responsible for the antioxidant activity of the extracts from XLs, were confirmed by UPLC-MS/MS and HPLC analysis. The extracted flavonoids can be used as a natural antioxidant additive to food products.


Mechanisms of neuronal loss in Parkinson's disease: a neuroanatomical-biochemical perspective.
It is shown that the specific inter- and subregional patterns of striatal dopamine loss in idiopathic Parkinson's disease can serve as a criterion for the evaluation of neurotoxic processes suggested to play an etiological role in this disorder. Based on this premise, the possibility is examined that dopamine-based free radicals (oxidative stress), or a MPTP-like mechanism may be the primary cause of the substantia nigra cell death in idiopathic Parkinson's disease. It is concluded that the most likely determinant of the specific patterns of nigral cell loss and striatal dopamine deficit might be the peculiar topomorphological arrangement of the melanin-containing neurones in the human substantia nigra.


Circulating and Exosomal microRNA-33 in Childhood Obesity.
MicroRNA-33 may control a wide range of different metabolic functions. This study aims to assess the miR-33a circulating profile in normal-weight (N = 20) and obese (O = 30) adolescents and to correlate its expression levels to their metabolic parameters. In a subset of subjects, we compared circulating miR-33a with exosomal miR-33a. Metabolic parameters were altered in O, with initial hyperinsulinemia. Circulating miR-33a was significantly higher in O than in N (p = 0.0002). Significant correlations between miR-33a and auxological and metabolic indices (Insulin p = 0.01; Cholesterol p = 0.01; LDL p = 0.01; HbA1c p = 0.01) were found. Splitting our population (O + N) into two groups, according to the median value of mRNA expression miR-33a levels (0.701), irrespective of the presence or absence of obesity, we observed that those having a higher expression of miR-33a were more frequently obese (87.5% vs. 12.5%; p < 0.0001) and had significantly increased values of auxological and metabolic parameters. Exosomes extracted from plasma of N and O carried miR-33a, and its expression was lower in O (p = 0.026). No correlations with metabolic parameters were observed. While exosome miR-33a does not provide any advantage, circulating miR-33a can provide important indications in an initial phase of metabolic dysfunction, stratifying obese adolescents at higher cardiometabolic risk.


Reversal of pulmonary arterial hypertension and neointimal formation by kinin B1 receptor blockade.
This study examined whether BI113823, a novel selective kinin B1 receptor antagonist can reverse established pulmonary arterial hypertension (PAH), prevent right heart failure and death, which is critical for clinical translation. Left pneumonectomized male Wistar rats were injected with monocrotaline to induce PAH. Three weeks later, when PAH was well established, the rats received daily treatment of BI113823 or vehicle for 3 weeks. Treatment with BI113823 from day 21 to day 42 after monocrotaline injection reversed established PAH as shown by normalized values of mean pulmonary arterial pressure (mPAP). BI113823 therapy reversed pulmonary vascular remodeling, pulmonary arterial neointimal formation, and heart and lung fibrosis, reduced right ventricular pressure, right heart hypertrophy, improved cardiac output, and prevented right heart failure and death. Treatment with BI113823 reduced TNF-α and IL-1β, and macrophages recruitment in bronchoalveolar lavage, reduced CD-68 positive macrophages and expression of proliferating cell nuclear antigen (PCNA) in the perivascular areas, and reduced expression of iNOS, B1 receptors, matrix metalloproteinase (MMP)-2 and MMP-9 proteins, and the phosphorylation of ERK1/2 and AKT in lung. Treatment with BI113823 reduced mRNA expression of ANP, BNP, βMHC, CGTF, collange-I and IV in right heart, compared to vehicle treated controls. In human monocytes cultures, BI113823 reduced LPS-induced TNF-α production, MMP-2 and MMP-9 expression, and reduced TNF-α-induced monocyte migration. We conclude that BI113823 reverses preexisting severe experimental pulmonary hypertension via inhibition of macrophage infiltration, cytokine production, as well as down regulation of matrix metalloproteinase proteins.


FRET-based nanoprobes for simultaneous monitoring of multiple mRNAs in living cells using single wavelength excitation.
We demonstrate a novel strategy using FRET-based nanoprobes for the simultaneous detection of multiple mRNAs with single wavelength excitation in living cells.


Changes of mitochondrial lipid molecules, structure, cytochrome c and ROS of beef Longissimus lumborum and Psoas major during postmortem storage and their potential associations with beef quality.
This study investigated changes in mitochondrial lipid molecules and their potential associations with Longissimus lumborum (LL) and Psoas major (PM) quality during storage. A total of 1610 lipid species that matched with 36 lipid classes were identified from isolated mitochondria. PM had more key lipid molecules at storage d-1 including diacylglycerol and triacylglycerol (may play roles in membrane stability), phosphatidylethanolamine, acyl carnitine and cardiolipin (involved in energy metabolism), and cardiolipin and phosphatidylserine (important factors in apoptosis). Correspondingly, with extended storage time, mitochondrial structure, cytochrome c and reactive oxygen species (ROS) were changed, and muscle oxidation intensified. These changes have close associations with shear force and water holding capacity (WHC). Compared with LL, PM had higher content of lipid classes, more mitochondrial ROS, greater muscle oxidation, and lower shear force and WHC. These findings provided new insights into the effects of lipidome on mitochondrial structure, ROS and cytochrome c, and their potential associations with beef quality.


Nerve growth factor (NGF) in serum: evaluation of serum NGF levels with a sensitive bioassay employing embryonic sensory neurons.
Considerable controversy surrounds the question of whether or not nerve growth factor (NGF) or a related nerve growth-promoting factor is present in serum. Recently, supporting its role as a local neuronotrophic factor, the presence of NGF in glial cells and its production in target tissues of NGF-responsive neurons were demonstrated [Rush: Nature 312:364-367, 1984; Heumann, Korsching, Scott, Thoenen: EMBOJ 3:3183-3189, 1984; Shelton and Reichardt: Proc Natl Acad Sci USA 81:7952-7955, 1984]. At the same time, the concept that NGF may play a role as a humoral factor has been questioned, since careful analyses of serum with specific and sensitive radioimmunoassays [Suda, Barde, Thoenen: Proc Natl Acad Sci USA 75:4042-4046, 1978; Korsching and Thoenen; Proc Natl Acad Sci USA 80:3513-3516, 1983; Furukawa, Kamo, Furukawa, Akazawa, Satoyoshi, Itoh, Hayashi: J Neurochem 40:734-744, 1983] as well as bioassays [Skaper and Varon: Exp Neurol 76:655-665, 1982] have not confirmed earlier reports [Levi-Montalcini and Booker; Proc Natl Acad Sci USA 46:373-391, 1960; Banks, Banthorpe, Charlwood, Pearce, Vernon: Nature 246:503-504, 1973; Hendry: Biochem J 128:1265-1272, 1972] on NGF's representation in serum. In this study serum from mouse, rat, and man was analyzed with an in vitro bioassay system which employs sensory neurons from chicken embyro dorsal root ganglia and which allows the measurement of NGF concentrations as low as 0.8 pM. It was found that sera from all these species contained neuronotrophic activity (S-NGF). The target cell spectrum as well as characteristic parameters of the neuronal growth response of S-NGF and of NGF were identical. S-NGF of mouse serum was completely inhibitable by polyclonal and monoclonal antibodies to mouse submandibular gland beta NGF. On polyacrylamide isoelectric focussing gels mouse and human S-NGF could be recovered from the same position as NGF as well as from the region where alpha 2-macroglobulin and serum albumin focused. In newborn and adult male and female mice basal S-NGF levels were equivalent to 10-50 pM NGF. A fraction of the serum samples of male mice showed elevated S-NGF levels. The incidence of high S-NGF levels was more frequent in NMRI and C57BL/6 males than in BALB/c males. Following sialectomy of male mice only basal S-NGF levels were observed up to 5 weeks after the operation. This indicates that although the submandibular gland may contribute to S-NGF levels in serum under certain conditions that appeared to be stress related, it cannot be the only source of S-NGF.


Experimental characterization and micromechanical modeling of the elastic response of the human humerus under bending impact.
This paper investigates the characterization and numerical modeling of the elastic behavior of the human humerus bone using a recently developed micromechanical approach coupled to nanoindentation measurements. At first, standard three-point bending experiments were conducted under low static loading, using several humerus diaphysis in order to identify the apparent elastic modulus of the bone in static regime. Then, a drop tower impact experiment was used on the same set of humerus diaphysis specimens, in order to assess the elastic modulus in dynamic regime. These measurements will be used as reference bases for comparison purpose. The originality of this work, lies in the coupling between a two-phase micromechanical approach based on Mori-Tanaka homogenization scheme for cylindrical voids and nanoindentation measurements of the elastic modulus of the bone matrix phase. This model has been implemented using a user defined material subroutine VMAT in ABAQUS© Explicit code. The bone mechanical response prediction using the proposed methodology was validated against previous standard experimental data. Finally, it was shown that the numerical predictions are consistent with the physical measurements obtained on human humerus via the good estimation of the ultimate impact load.


Bone turnover markers are correlated with quantitative ultrasound of the calcaneus: 5-year longitudinal data.
Associations between bone turnover markers and calcaneal ultrasound (quantitative ultrasound, QUS) were studied in a population-based sample of 810 elderly women. Baseline bone turnover markers correlated with baseline QUS as well as with 5-year prospective changes in QUS. Bone turnover markers are associated with areal bone mineral density, but the knowledge on the association with QUS is limited. Eight hundred ten women, all 75 years old, were investigated at baseline. Five hundred six completed a 5-year follow-up. Bone turnover markers and calcaneal QUS [speed of sound (SoS), broadband ultrasound attenuation (BUA), stiffness] were investigated at baseline. QUS was investigated at follow-up. All bone turnover markers were correlated with baseline QUS [standardized regression (Beta(std)) values from -0.07, p < 0.05 to -0.23, p < 0.001], with the exception of bone-specific alkaline phosphatase (S-Bone ALP) which was not correlated with BUA and stiffness index. When the correlations between baseline bone turnover markers and 5-year changes in QUS were analyzed, three serum osteocalcins were correlated with changes of SoS and stiffness index (Beta(std) = -0.11, p < 0.05 to -0.17, p < 0.001). Also S-CTX-I correlated with changes of SoS and stiffness index (Beta(std) = -0.10 and -0.09, respectively, p < 0.05). S-TRACP5b, urinary deoxypyridinoline/crea, and U-MidOC/crea correlated with changes of SoS (Beta(std) = -0.10 and p < 0.05 for all). S-Bone ALP did not correlate with change of QUS. None of the bone turnover markers correlated with changes of BUA. Bone turnover markers correlate with concomitantly assessed QUS as well as with longitudinal change in QUS.


Coordination of arm and eye movements in tracking of sinusoidally moving targets.
Human subjects tracked sinusoidally moving visual targets with arm and eyes, in absence of visual feedback of the arm. The resulting frequency responses indicated that predictive mechanisms are involved both in arm and in eye tracking, and that the respective upper frequency limits are similar. Most importantly, substantial differences between arm and eye performance were observed: At low frequencies the gain of arm, but not of eye movement was consistently smaller than 0 dB. At higher frequencies arm, but not eye gain exhibited a marked amplitude non-linearity. The intra-trial gain and phase variability of arm movement was not correlated with the respective variability of eye movement. The reaction times to sudden changes of target parameters could be considerably different for arm and eye, and their inter-trial variability was not, or only marginally, correlated. Taken together, these findings strongly suggest that the mechanisms controlling predictive arm and eye movements in our experiment are organized to a major part in independent, parallel channels. The results are discussed with reference to a simple scheme of eye-arm coordination.


Relationship between circulating E-selectin, DD genotype of angiotensin-converting-enzyme, and cardiovascular damage in central obese subjects.
Fifty-six young central obese patients were investigated to evaluate relationships between soluble E-selectin (sE-S), angiotensin-converting enzyme (ACE) gene polymorphism, left ventricular function and structure, and carotid morphology by determination of sE-S and ACE genotypes. Our results indicated that central obese subjects with concomitant higher levels of sE-S and ACE DD genotype may be characterized by early cardiovascular alterations and then considered a particular subset of subjects at higher risk of cardiovascular disease.


Characterization of omega-3 tablets.
Omega-3 nutraceuticals are extensively used as health supplements worldwide. Various administration forms for delivery of omega-3 are available. However, the niche omega-3 tablets have so far remained unexplored. In this work tablets containing 25-40% (w/w) omega-3 oil as triglycerides or ethyl esters were prepared utilizing a direct compaction grade powder with β-cyclodextrin as encapsulating agent. It was found that powders with up to 35% (w/w) triglyceride oil and 30% (w/w) ethyl ester oil, respectively, can be directly compressed into tablets of excellent quality. Physical properties of omega-3 containing powders and tablets are described. The powder X-ray diffractograms of the powders and crushed tablets show evidence of the formation of new crystalline phases not present in β-cyclodextrin. In addition, (1)H NMR data suggest that the ethyl esters form inclusion complexes with β-cyclodextrin. Compaction of other, commercially available, omega-3 powders was performed as a comparison and deemed unsuccessful.


Precocious loss of cortical granules during mouse oocyte meiotic maturation and correlation with an egg-induced modification of the zona pellucida.
Fertilization results in cortical granule exocytosis, which is thought to be involved in modifications of the zona pellucida that constitute the zona pellucida block to polyspermy. A previous report demonstrated that a decrease in the number of Lens culinaris agglutinin-staining granules, which are likely to be cortical granules, occurred during in vivo mouse oocyte maturation with arrest at metaphase II, as well as the formation of a cortical granule-free domain in the area of the metaphase II spindle (T. Ducibella, E. Anderson, D.F. Albertini, J. Aalberg, and S. Rangarajan, 1988, Dev. Biol. 130, 184-197). We extend these observations by reporting here that germinal vesicle-intact oocytes matured in vitro to metaphase II in either the absence or the presence of serum develop a cortical granule-free domain and have reduced numbers of cortical granules when compared to germinal vesicle-intact oocytes; these changes are similar to those of oocytes matured in vivo. The reduction in the number of cortical granules requires germinal vesicle breakdown, since it is prevented by dibutyryl cAMP, which inhibits germinal vesicle breakdown in vitro. The ability of oocytes to respond to the calcium ionophore A23187 with a reduction in the number of cortical granules is also associated with meiotic maturation and develops between 7 and 12 hr after initiation of maturation. The maturation-associated reduction in the number of cortical granules is likely to represent cortical granule exocytosis, since this reduction is accompanied by the formation of a cortical granule-free domain and a conversion of ZP2 to ZP2f when the oocytes are matured in vitro in serum-free medium; this zona pellucida modification occurs following fertilization and is thought to be due to cortical granule exocytosis. In contrast, the loss of cortical granules and development of the cortical granule-free domain of oocytes matured in vitro in the presence of serum is not accompanied by the modification of ZP2. The inhibitory effect of serum on the ZP2 modification may afford in vivo a physiological mechanism to prevent a precocious modification of the zona pellucida that could result in a premature block to polyspermy and hence inhibit fertilization.


Investigation of 3D dynamic and quasistatic models for spinal moments during combined manual material handling tasks.
Digital human modeling software uses biomechanical models to compute workers' risk of injury during industrial work processes. In many cases, the biomechanics are calculated using quasistatic models, which neglect the body's dynamics and therefore might be erroneous. This study investigated the differential effect of using a dynamic vs. a quasistatic model on spinal loading during combined manual material handling tasks that are prevalent in industry. An experiment was conducted involving nine male and nine female participants performing a total of 3402 cycles of a box-conveying task (removing, carrying and depositing) for different box masses and shelf heights. Using motion capture data, the peak and cumulative moments acting on the L5/S1 joint were calculated using 3D dynamic and quasistatic models. This revealed that neglecting the dynamic movements (i.e., using a quasistatic model) results in an on average underestimation of 19.7% in the peak spinal moment and 3.6% in the cumulative moment that in some cases exceeds the maximal limit for the compression forces acting on the lower back.


Power-law behavior of heart rate variability in Chagas' disease.
Beta slope is a nonlinear index derived from the power-law analysis of 24-hour heart rate variability (HRV); in healthy subjects, the beta index is typically near -1, suggesting a fractal behavior of HRV. There is scarce data on HRV in Chagas' disease. This transversal study intends to describe power-law and linear HRV patterns in different forms of Chagas' disease. Patients and healthy controls (n = 26) without other diseases were submitted to a standardized protocol, including electrocardiography, echocardiography, and 24-hour Holter monitoring. Patients with Chagas' disease were divided into groups according to their left ventricular (LV) systolic function: normal (group 1, n = 85), segmental abnormalities (group 2, n = 49), and reduced ejection fraction (group 3, n = 26). The temporal series were carefully processed to obtain the HRV indexes and beta slope. Despite the differences in the LV systolic function, the 3 groups were comparable in terms of long-term HRV index values. After adjustment for covariates, short-term HRV index values were consistently reduced in the Chagas' disease groups. The beta-index values were also diminished in Chagas' disease groups (group 1: -1.09 +/- 0.03, group 2: -1.11 +/- 0.06; group 3: -1.14 +/- 0.03; and controls: 0.95 +/- 0.03, p <0.001). This breakdown of fractal long-range correlation of RR interval dynamics, a strong predictor of mortality in other cardiomyopathies, may reflect cardiac dysautonomia that may have gone undetected in long-term time-domain analysis. This abnormality may explain the increased risk for arrhythmic sudden death found in Chagas' disease even in the absence of signs of LV dysfunction.


Distribution of neurofilament-positive nerve fibres and sensory endings in the human anterior cruciate ligament.
The present immunocytochemical study describes the distribution of neurofilament-containing nerve fibres and corpuscular-like endings in the human anterior cruciate ligament. The entire anterior cruciate ligament of a non-injured knee joint from a child was cut into serial 15-microns-thick frozen sections, which were processed for immunofluorescence staining with a monoclonal antibody against the 68-kDa neurofilament subunit. Numerous neurofilament-positive fibres were found in bundles. These bundles were mostly located near blood vessels in the subsynovial layer and in interfascicular gaps. Only a few single nerve fibres were found independent of blood vessels in interfascicular gaps and between collagen bundles. Neurofilament-containing nerve fibres were preferentially located near the bony attachments of the anterior cruciate ligament. Two types of corpuscular-like endings were found, i.e. "spiral-like" (type I) and "spray-like" (type II) endings. Similarly to nerve fibres, both types of corpuscular-like endings were found mainly near the tibial and femoral attachment sites (15 of 17), whereas only two were found in the middle third of the ligament. Most likely, the type I and type II corpuscular-like endings serve a mechanoreceptive function involved in the sensory control of normal movements and in stress protection.


[Studies on the effects of rhTNF-alpha anti-replication against EHFV and HAV in vitro].
It was demonstrated in this study that rhTNF-alpha can inhibit the replication of epidemic hemorrhagic fever virus and hepatitis A virus in tissue culture. EHFV infection produced strong fluorescence ( - +) on Vero-E6 cells after 9 days. In the rhTNF-alpha treated group, however the fluorescence was very weak (- or +/-). rhTNF-alpha also showed anti-HAV effects on 2BS cells. The fluorescence intensity on 2BS cells infected by HAV was - +, but in the rhTNF-alpha treated group, the fluorescence was negative. We observed that rhTNF-alpha inhibited EHFV antigen expression on Vero-E6 at different times (-2h, 0h, +2h). Dr. Old had recently suggested that the physiological role of rhTNF-alpha is that of a protective agent against infectious diseases, and this view is supported by our findings.


A European perspective on testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys.
What clinical practices, patient management strategies and experimental methods are currently being used to preserve and restore the fertility of prepubertal boys and adolescent males? Based on a review of the clinical literature and research evidence for sperm freezing and testicular tissue cryopreservation, and after consideration of the relevant ethical and legal challenges, an algorithm for the cryopreservation of sperm and testicular tissue is proposed for prepubertal boys and adolescent males at high risk of fertility loss. A known late effect of the chemotherapy agents and radiation exposure regimes used to treat childhood cancers and other non-malignant conditions in males is the damage and/or loss of the proliferating spermatogonial stem cells in the testis. Cryopreservation of spermatozoa is the first line treatment for fertility preservation in adolescent males. Where sperm retrieval is impossible, such as in prepubertal boys, or it is unfeasible in adolescents prior to the onset of ablative therapies, alternative experimental treatments such as testicular tissue cryopreservation and the harvesting and banking of isolated spermatogonial stem cells can now be proposed as viable means of preserving fertility. Advances in clinical treatments, patient management strategies and the research methods used to preserve sperm and testicular tissue for prepubertal boys and adolescents were reviewed. A snapshot of the up-take of testis cryopreservation as a means to preserve the fertility of young males prior to December 2012 was provided using a questionnaire. A comprehensive literature review was conducted. In addition, survey results of testis freezing practices in young patients were collated from 24 European centres and Israeli University Hospitals. There is increasing evidence of the use of testicular tissue cryopreservation as a means to preserve the fertility of pre- and peri-pubertal boys of up to 16 year-old. The survey results indicate that of the 14 respondents, half of the centres were actively offering testis tissue cryobanking as a means of safeguarding the future fertility of boys and adolescents as more than 260 young patients (age range less than 1 year old to 16 years of age), had already undergone testicular tissue retrieval and storage for fertility preservation. The remaining centres were considering the implementation of a tissue-based fertility preservation programme for boys undergoing oncological treatments. The data collected were limited by the scope of the questionnaire, the geographical range of the survey area, and the small number of respondents. The clinical and research questions identified and the ethical and legal issues raised are highly relevant to the multi-disciplinary teams developing treatment strategies to preserve the fertility of prepubertal and adolescent boys who have a high risk of fertility loss due to ablative interventions, trauma or genetic pre-disposition.


The evolution of the ileal segment bladder substitution operation.
The historical background and events leading to the development of ileal conduit bladder substitution are reviewed. The reported results of twenty-five years experience with the operation are discussed with special reference to the early and long-term complications and risk to renal function. The importance of continued efforts to minimize these risks, especially when the operation is done in children and for benign disease, is emphasized. It is suggested that some of the more promising variations in the operation should be set up as prospective studies in order that meaningful comparisons may be possible in the future.


EZH2 phosphorylation regulates Tat-induced HIV-1 transactivation via ROS/Akt signaling pathway.
EZH2 plays a major role in HIV-1 latency, however, the molecular linkage between Tat-induced HIV-1 transactivation and EZH2 activity is not fully understood. It was shown Tat induced HIV-1 transactivation through inhibiting EZH2 activity. Tat decreased the levels of H3K27me3 and EZH2 occupy at the long terminal repeat (LTR) of HIV-1. We further showed for the first time that transfected with Tat construct resulted in an increase in phosphorylated EZH2 (p-EZH2), mediated by active Akt. ROS/Akt-dependent p-EZH2 was correlated with Tat-induced transactivation. Our study reveals that novel mechanisms allow Tat-induced HIV-1 transactivation by ROS/Akt-dependent downregulating the EZH2 epigenetic silencing machinery.