The relationship of climate variables in the prevalence of acute respiratory infection in children under two years old in Rondonópolis-MT, Brazil.
It is estimated that approximately 30% of childhood diseases can be attributed to environmental factors and 40% involve children under the age of five years old, representing about 10% of world population. This study aimed to analyze the relationship of climate variables in the prevalence of acute respiratory infection (ARI) in children under two years old, in Rondonopolis-MT, from 1999 to 2014. It was used a cross-sectional study with a quantitative and a descriptive approach with meteorological teaching and research data from the database from the health information system. For statistical analysis, it adjusted the negative binomial model belonging to the class of generalized linear models, adopting a significance level of 5%, based on the statistical platform R. The average number of cases of ARI decreases at approximately by 7.9% per degree centigrade increase above the average air temperature and decrease about 1.65% per 1% increase over the average air relative humidity. Already, the rainfall not associated with these cases. It is the interdisciplinary team refocus practical actions to assist in the control and reduction of ARI significant numbers in primary health care, related climate issues in children.


Enhancing economic models for the analysis of animal disease.
This paper discusses how economic tools can be targeted and combined to enhance their usefulness in analyses of animal disease problems. It briefly reviews the most commonly used economic modelling techniques to clarify the applicability of specific economic methods to different problems in animal health analysis. The paper then reviews applications of these methods in the literature and suggests how further research could integrate and improve different economic approaches and link epidemiological and economic methods to address a wider range of issues at different scales of analysis.


Improved Fluoroquinolone-Resistant and Extensively Drug-Resistant Tuberculosis Treatment Outcomes.
Treatment outcomes of multidrug-resistant tuberculosis (MDR TB) remain poor, particularly for fluoroquinolone-resistant (FQ-R) MDR TB. The aim of this study was to determine treatment outcomes and factors associated with failure of MDR TB treatment, focusing on FQ resistance. Medical records were retrospectively reviewed of patients diagnosed and treated for MDR TB from January 2005 through December 2017 at Severance Hospital, South Korea. Of a total of 129 patients with MDR TB, 90 (69.8%) cases were FQ-sensitive (FQ-S) and 39 (30.2%) were FQ-R. FQ-R MDR TB was associated with more severe clinical symptoms, including cavitary lesions and bilateral disease, and tended to require treatment with a greater number of drugs for a longer period of time than FQ-S MDR TB. Linezolid (51.3% vs 7.8%, P < .001), bedaquiline (20.5% vs 8.9%, P = .083), and delamanid (10.3% vs 5.6%, P = .452) were more frequently used in FQ-R cases. Overall, 95/124 patients (76.6%) had favorable treatment outcomes, and we did not detect a significant difference between FQ-R and FQ-S (FQ-S 65/87, 74.7%, vs FQ-R 30/37, 81.1%; P = .443). Old age, low body mass index, smoking, and malignancy-but not FQ resistance or extensively drug-resistant (XDR) TB-were associated with poor clinical outcomes. Overall, 76.6% of MDR TB patients had successful treatment outcomes. Effective drug combinations and appropriate use of new drugs may improve treatment outcomes of FQ-R MDR and XDR TB. Poor clinical outcomes were more related to the patients' general condition rather than FQ resistance or XDR.


Using Yield Response Curves to Measure Variation in the Tolerance and Resistance of Wheat Cultivars to Fusarium Crown Rot.
The disease crown rot, caused predominantly by the fungal pathogen Fusarium pseudograminearum, is a major disease of winter cereals in many regions of the world, including Australia. A methodology is proposed, using response curves, to robustly estimate the relationship between grain yield and increasing crown rot pathogen burdens. Using data from a field experiment conducted in northern New South Wales, Australia in 2016, response curves were derived for five commercial wheat cultivars exposed to six increasing rates of crown rot inoculum, where the rates served to establish a range of crown rot pathogen burdens. In this way, the response curve methodology is fundamentally different from alternate approaches that rely on genetic or environmental variation to establish a range in pathogen burdens over which yield loss relationships are estimated. By manipulating only the rates of crown rot inoculum and, thus, pathogen burden directly, the number of additional confounding factors and interactions are minimized, enabling the robust estimation of the rate of change in yield due to increasing crown rot pathogen burdens for each cultivar. The methodology revealed variation in the rate of change in yield between cultivars, along with the extent of crown rot symptoms expressed by the cultivars. Variation in the rate of change in yield between cultivars provides definitive evidence of differences in the tolerance of commercial Australian wheat cultivars to crown rot caused by F. pseudograminearum, while variation in the extent of crown rot symptoms signifies differences in the resistance of the cultivars to this disease. The response curve methodology also revealed variation in how the different mechanisms of tolerance and resistance act to limit yield losses due to crown rot for different cultivars.


Decision aid for patients considering total knee arthroplasty with preference report for surgeons: a pilot randomized controlled trial.
To evaluate feasibility and potential effectiveness of a patient decision aid (PtDA) for patients and a preference report for surgeons to reduce wait times and improve decision quality in patients with osteoarthritis considering total knee replacement. A prospective two-arm pilot randomized controlled trial. Patients with osteoarthritis were eligible if they understood English and were referred for surgical consultation about an initial total knee arthroplasty at a Canadian orthopaedic joint assessment clinic. Patients were randomized to the PtDA intervention or usual education. The intervention was an osteoarthritis PtDA for patients and a one-page preference report summarizing patients' clinical and decisional data for their surgeon. The main feasibility outcomes were rates of recruitment and questionnaire completion; the preliminary effectiveness outcomes were wait times and decision quality. Of 180 patients eligible for surgical consultation, 142 (79%) were recruited and randomized to the PtDA intervention (n = 71) or usual education (n = 71). Data collection yielded a 93% questionnaire completion rate with less than 1% missing items. After one year, 13% of patients remained on the surgical wait list. The median time from referral to being off the wait list (censored using survival analysis techniques) was 33.4 weeks for the PtDA group (n = 69, 95% CI: 26.0, 41.4) and 33.0 weeks for usual education (n = 71, 95% CI: 26.1, 39.9). Patients exposed to the PtDA had higher decision quality based on knowledge (71% versus 47%; p < 0.0001) and quality decision being an informed choice that is consistent with their values for option outcomes (56.4% versus 25.0%; p < 0.001). Recruitment of patients with osteoarthritis considering surgery and data collection were feasible. As some patients remained on the surgical waiting list after one year, follow-up should be extended to two years. Patients exposed to the PtDA achieved higher decision quality compared to those receiving usual education but there was no difference in wait for surgery. ClinicalTrials.Gov NCT00743951.


Role of hydroxycinnamic acids in the infection of maize silks by Fusarium graminearum Schwabe.
In the current study, the hydroxycinnamic acids in silks of diverse maize inbred lines differing in Fusarium resistance were determined at several times after inoculation with Fusarium graminearum or sterile water as control. The main objective was to determine the possible relationship between the hydroxycinnamic acid changes in silks and ear rot resistance. Several changes in the cell-wall-bound hydroxycinnamic acid concentrations were observed after inoculation with F. graminearum, although these changes were not directly correlated with genotypic resistance to this fungus. Ester-bound ferulic acid decreased, probably due to degradation of hemicellulose by hydrolytic enzymes produced by Fusarium spp., while p-coumaric acid and diferulates showed slight increases that, in conjunction, did not result in delayed F. graminearum progression through the silks. It is important to note that the decrease of ferulic acid in the F. graminearum treatment was faster in susceptible than in resistant genotypes, suggesting a differential hemicellulose degradation in silk tissues. Therefore, the ability of the maize genotypes to slow down that process through hemicellulose structural features or xylanase inhibitors needs to be addressed in future studies.


Effects of sex hormones on the pineal response to isoproterenol and on pineal beta-adrenergic receptors.
Several studies have shown sex hormone effects on pineal function. In order to clarify the role of adrenergic mechanisms in these effects, we investigated the pineal response to adrenergic stimulation and pineal beta-adrenergic receptors following castration and/or sex hormone treatment in 2-month-old male and female Sprague-Dawley rats. The urinary 6-sulphatoxymelatonin (aMT6s) response to isoproterenol (ISO) was compared in castrated and sham-operated animals. Ovariectomy caused an increase and orchiectomy a decrease in ISO-induced urinary aMT6s excretion. The melatonin response to ISO was examined in pineal glands and serum samples obtained from castrated, sex-hormone-treated castrated and sham-operated rats. Consistently, ovariectomy increased pineal and serum melatonin responses to ISO, while orchiectomy decreased the responses; oestradiol and testosterone treatments, respectively, reversed these effects. 3H-dihydroalprenolol binding was measured in single pineal glands from castrated, sex-hormone-treated castrated and sham-operated rats. Ovariectomy increased the density of beta-adrenoceptors, whereas orchiectomy decreased the density; oestradiol and testosterone replacement, respectively, blocked these effects. No significant effect on receptor Kd values was found. These data suggest that sex hormones regulate pineal melatonin production by modifying beta-adrenergic mechanisms.


Long-term breeding phenology shift in royal penguins.
The Earth's climate is undergoing rapid warming, unprecedented in recent times, which is driving shifts in the distribution and phenology of many plants and animals. Quantifying changes in breeding phenology is important for understanding how populations respond to these changes. While data on shifts in phenology are common for Northern Hemisphere species (especially birds), there is a dearth of evidence from the Southern Hemisphere, and even fewer data available from the marine environment. Surface air temperatures at Macquarie Island have increased by 0.62°C during the 30-year study period (0.21°C decade(-1)) and royal penguins (Eudyptes schlegeli) commenced egg laying on average three days earlier in the 1990s than during the 1960s. This contrasts with other studies of Southern Ocean seabirds; five of nine species are now breeding on average 2.1 days later than during the 1950s. Despite the different direction of these trends, they can be explained by a single underlying mechanism: resource availability. There was a negative relationship between the Southern Annular Mode (SAM) and median laying date of royal penguins, such that low-productivity (low SAM) years delayed laying date. This accords with the observations of other seabird species from the Antarctic, where later laying dates were associated with lower sea ice and lower spring productivity. The unifying factor underpinning phenological trends in eastern Antarctica is therefore resource availability; as food becomes scarcer, birds breed later. These changes are not uniform across the region, however, with resource increases in the subantarctic and decreases in eastern Antarctica.


Position of the American Dietetic Association: benchmarks for nutrition in child care.
It is the position of the American Dietetic Association that child-care programs should achieve recommended benchmarks for meeting children's nutrition needs in a safe, sanitary, and supportive environment that promotes optimal growth and development. Use of child care has become increasingly common and is now the norm for the majority of families in the United States. Therefore, it is essential that registered dietitians; dietetic technicians, registered; and other food and nutrition practitioners work in partnership with child-care providers and families of children in child care to meet children's nutrition needs and provide them with models of healthful eating and active lifestyles. This Position Paper provides guidance for food and nutrition practitioners, health professionals, and child-care providers regarding recommendations for nutritional quality of foods and beverages served; menus, meal patterns, and portion sizes; food preparation and service; physical and social environment; nutrition training; nutrition consultation; physical activity and active play; and working with families. This Position Paper targets children aged 2 to 5 years attending child-care programs and highlights opportunities for food and nutrition practitioners to promote healthful eating in child care through both intervention and policy-based initiatives.


Non-invasive investigation of Spironucleus vortens transmission in freshwater angelfish Pterophyllum scalare.
Spironucleus vortens is a protozoan fish parasite of veterinary and economic importance in the ornamental aquaculture industry. Despite this, key aspects of the life cycle of this organism, including its mode of transmission, have not been fully elucidated. We developed a non-invasive method for quantifying S. vortens in freshwater angelfish, which was then used to investigate parasite transmission and aggregation within host populations. As previously observed for S. meleagridis and S. salmonis, motile S. vortens trophozoites were detected in host faeces using light microscopy. Species-level identification of these flagellates was confirmed using 16S rDNA PCR. Faecal trophozoite counts were significantly correlated with trophozoite counts from the posterior intestine, the primary habitat of the parasite. This novel finding allowed effective prediction of intestinal parasite load from faecal counts. Overall, faecal count data revealed that 20% of hosts harbour 83% of parasites, conforming to the Pareto Principle (80/20 rule) of parasite aggregation with implications for parasite transmission. Trophozoites survived for ≥36 d outside the host within faeces and remained motile at low pH (comparable with that of angelfish stomach). No putative S. vortens cysts were observed in cultures or faecal samples. This calls into question the commonly accepted hypothesis that a protective cyst is required in the life cycle of S. vortens to facilitate transmission to a new host.


Postoperative B-type natriuretic peptide for prediction of major cardiac events in patients undergoing noncardiac surgery: systematic review and individual patient meta-analysis.
It is unclear whether postoperative B-type natriuretic peptides (i.e., BNP and N-terminal proBNP) can predict cardiovascular complications in noncardiac surgery. The authors undertook a systematic review and individual patient data meta-analysis to determine whether postoperative BNPs predict postoperative cardiovascular complications at 30 and 180 days or more. The authors identified 18 eligible studies (n = 2,051). For the primary outcome of 30-day mortality or nonfatal myocardial infarction, BNP of 245 pg/ml had an area under the curve of 0.71 (95% CI, 0.64-0.78), and N-terminal proBNP of 718 pg/ml had an area under the curve of 0.80 (95% CI, 0.77-0.84). These thresholds independently predicted 30-day mortality or nonfatal myocardial infarction (adjusted odds ratio [AOR] 4.5; 95% CI, 2.74-7.4; P < 0.001), mortality (AOR, 4.2; 95% CI, 2.29-7.69; P < 0.001), cardiac mortality (AOR, 9.4; 95% CI, 0.32-254.34; P < 0.001), and cardiac failure (AOR, 18.5; 95% CI, 4.55-75.29; P < 0.001). For greater than or equal to 180-day outcomes, natriuretic peptides independently predicted mortality or nonfatal myocardial infarction (AOR, 3.3; 95% CI, 2.58-4.3; P < 0.001), mortality (AOR, 2.2; 95% CI, 1.67-86; P < 0.001), cardiac mortality (AOR, 2.1; 95% CI, 0.05-1,385.17; P < 0.001), and cardiac failure (AOR, 3.5; 95% CI, 1.0-9.34; P = 0.022). Patients with BNP values of 0-250, greater than 250-400, and greater than 400 pg/ml suffered the primary outcome at a rate of 6.6, 15.7, and 29.5%, respectively. Patients with N-terminal proBNP values of 0-300, greater than 300-900, and greater than 900 pg/ml suffered the primary outcome at a rate of 1.8, 8.7, and 27%, respectively. Increased postoperative BNPs are independently associated with adverse cardiac events after noncardiac surgery.


A systematic review to identify challenges of demonstrating efficacy of HIV behavioral interventions for gay, bisexual, and other men who have sex with men (MSM).
Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV but few MSM-specific evidence-based interventions (EBIs) have been identified for this vulnerable group. We conducted a systematic review to identify reasons for the small number of EBIs for MSM. We also compared study, intervention and sample characteristics of EBIs versus non-EBIs to better understand the challenges of demonstrating efficacy evidence. Thirty-three MSM-specific studies were evaluated: Nine (27 %) were considered EBIs while 24 (73 %) were non-EBIs. Non-EBIs had multiple methodological limitations; the most common was not finding a significant positive effect. Compared to EBIs, non-EBIs were less likely to use peer intervention deliverers, include sexual communication in their interventions, and intervene at the community level. Incorporating characteristics associated with EBIs may strengthen behavioral interventions for MSM. More EBIs are needed for substance-using MSM, MSM of color, MSM residing in the south and MSM in couples.


The retinoblastoma tumor suppressor and stem cell biology.
Stem cells play a critical role during embryonic development and in the maintenance of homeostasis in adult individuals. A better understanding of stem cell biology, including embryonic and adult stem cells, will allow the scientific community to better comprehend a number of pathologies and possibly design novel approaches to treat patients with a variety of diseases. The retinoblastoma tumor suppressor RB controls the proliferation, differentiation, and survival of cells, and accumulating evidence points to a central role for RB activity in the biology of stem and progenitor cells. In some contexts, loss of RB function in stem or progenitor cells is a key event in the initiation of cancer and determines the subtype of cancer arising from these pluripotent cells by altering their fate. In other cases, RB inactivation is often not sufficient to initiate cancer but may still lead to some stem cell expansion, raising the possibility that strategies aimed at transiently inactivating RB might provide a novel way to expand functional stem cell populations. Future experiments dedicated to better understanding how RB and the RB pathway control a stem cell's decisions to divide, self-renew, or give rise to differentiated progeny may eventually increase our capacity to control these decisions to enhance regeneration or help prevent cancer development.


Précis of How children learn the meanings of words.
Normal children learn tens of thousands of words, and do so quickly and efficiently, often in highly impoverished environments. In How Children Learn the Meanings of Words, I argue that word learning is the product of certain cognitive and linguistic abilities that include the ability to acquire concepts, an appreciation of syntactic cues to meaning, and a rich understanding of the mental states of other people. These capacities are powerful, early emerging, and to some extent uniquely human, but they are not special to word learning. This proposal is an alternative to the view that word learning is the result of simple associative learning mechanisms, and it rejects as well the notion that children possess constraints, either innate or learned, that are specifically earmarked for word learning. This theory is extended to account for how children learn names for objects, substances, and abstract entities, pronouns and proper names, verbs, determiners, prepositions, and number words. Several related topics are also discussed, including naïve essentialism, children's understanding of representational art, the nature of numerical and spatial reasoning, and the role of words in the shaping of mental life.


Stereotactic radiosurgery for trigeminal neuralgia: a multiinstitutional study using the gamma unit.
A multiinstitutional study was conducted to evaluate the technique, dose-selection parameters, and results of gamma knife stereotactic radiosurgery in the management of trigeminal neuralgia. Fifty patients at five centers underwent radio-surgery performed with a single 4-mm isocenter targeted at the nerve root entry zone. Thirty-two patients had undergone prior surgery, and the mean number of procedures that had been performed was 2.8 (range 1-7). The target dose of the radiosurgery used in the current study varied from 60 to 90 Gy. The median follow-up period after radiosurgery was 18 months (range 11-36 months). Twenty-nine patients (58%) responded with excellent control (pain free), 18 (36%) obtained good control (50%-90% relief), and three (6%) experienced treatment failure. The median time to pain relief was 1 month (range 1 day-6.7 months). Responses remained consistent for up to 3 years postradiosurgery in all cases except three (6%) in which the patients had pain recurrence at 5, 7, and 10 months. At 2 years, 54% of patients were pain free and 88% had 50% to 100% relief. A maximum radiosurgical dose of 70 Gy or greater was associated with a significantly greater chance of complete pain relief (72% vs. 9%, p = 0.0003). Three patients (6%) developed increased facial paresthesia after radiosurgery, which resolved totally in one case and improved in another. No patient developed other deficits or deafferentation pain. The proximal trigeminal nerve and root entry zone, which is well defined on magnetic resonance imaging, is an appropriate anatomical target for radiosurgery. Radiosurgery using the gamma unit is an additional effective surgical approach for the management of medically or surgically refractory trigeminal neuralgia. A longer-term follow-up review is warranted.


The effect of an HIV-1 viral protease inhibitor on staurosporine-induced apoptosis in immortalized mesangial cells.
Progressive glomerular sclerosis is a condition characterized by the accumulation of glomerular extracellular matrix and a decrease in the number of glomerular cells. The mechanisms involved in the progressive loss of glomerular cells are not well understood but may involve the process of apoptosis. The principal mediators for the apoptotic pathway are a class of protease enzymes called caspases. It is not known how other therapeutic protease inhibitors affect the caspase cascade and therefore whether they would be effective in preventing excessive apoptosis in the late stages of progressive glomerular sclerosis. To evaluate whether an inhibitor of the HIV-1 viral protease Ac-Leu-Val-phenylalanine (PI) could inhibit apoptosis in immortalized mesangial cells. Experimental. Nephrology Division, Universidade Federal de São Paulo/Escola Paulista de Medicina. Immortalized mesangial cells. Cell culture. Viability and rate of apoptosis. Immortalized mesangial cells were treated with staurosporine (at concentrations of 10-100 nM for 8-28 hours) to induce apoptosis. Staurosporine at 10 nM for 8 hours had no effect on viability, but did cause a significant increase in the rate of apoptosis (p = 0.0411, n = 6). Increasing the incubation time elicited a greater increase in the rate of apoptosis (p = 0.0001, n = 6), although there was also a significant decrease in viability (p=0.0002). Increasing the concentration of staurosporine to 100 nM resulted in a marked increase in apoptosis (p <0.0001) but resulted in unacceptable viability (<40%, p <0.0001, n = 6). Incubation of immortalized mesangial cells with PI (900 nM) alone for 2-24 hours had no effect on cell viability or the rate of apoptosis when compared with vehicle (methanol) controls. Co-incubation of the cells with staurosporine (10 nM) and PI for 24 hours had no significant effect on the rate of apoptosis. Therefore, in immortalized mesangial cells, staurosporine-induced apoptosis was not significantly affected by the HIV-1 viral protease inhibitor Ac-Leu-Val-phenylalanine.


Neck muscle spindle noise biases reaches in a multisensory integration task.
Reference frame transformations (RFTs) are crucial components of sensorimotor transformations in the brain. Stochasticity in RFTs has been suggested to add noise to the transformed signal due to variability in transformation parameter estimates (e.g., angle) as well as the stochastic nature of computations in spiking networks of neurons. Here, we varied the RFT angle together with the associated variability and evaluated the behavioral impact in a reaching task that required variability-dependent visual-proprioceptive multisensory integration. Crucially, reaches were performed with the head either straight or rolled 30° to either shoulder, and we also applied neck loads of 0 or 1.8 kg (left or right) in a 3 × 3 design, resulting in different combinations of estimated head roll angle magnitude and variance required in RFTs. A novel three-dimensional stochastic model of multisensory integration across reference frames was fitted to the data and captured our main behavioral findings: 1) neck load biased head angle estimation across all head roll orientations, resulting in systematic shifts in reach errors; 2) increased neck muscle tone led to increased reach variability due to signal-dependent noise; and 3) both head roll and neck load created larger angular errors in reaches to visual targets away from the body compared with reaches toward the body. These results show that noise in muscle spindles and stochasticity in general have a tangible effect on RFTs underlying reach planning. Since RFTs are omnipresent in the brain, our results could have implications for processes as diverse as motor control, decision making, posture/balance control, and perception. NEW & NOTEWORTHY We show that increasing neck muscle tone systematically biases reach movements. A novel three-dimensional multisensory integration across reference frames model captures the data well and provides evidence that the brain must have online knowledge of full-body geometry together with the associated variability to plan reach movements accurately.


Impact of novel human immunodeficiency virus type 1 reverse transcriptase mutations P119S and T165A on 4'-ethynylthymidine analog resistance profile.
2',3'-Didehydro-3'-deoxy-4'-ethynylthymidine (4'-Ed4T), a derivative of stavudine (d4T), has potent activity against human immunodeficiency virus and is much less inhibitory to mitochondrial DNA synthesis and cell growth than its progenitor, d4T. 4'-Ed4T triphosphate was a better reverse transcriptase (RT) inhibitor than d4T triphosphate, due to the additional binding of the 4'-ethynyl group at a presumed hydrophobic pocket in the RT active site. Previous in vitro selection for 4'-Ed4T-resistant viral strains revealed M184V and P119S/T165A/M184V mutations on days 26 and 81, respectively; M184V and P119S/T165A/M184V conferred 3- and 130-fold resistance to 4'-Ed4T, respectively. We investigated the relative contributions of these mutations, engineered into the strain NL4-3 background, to drug resistance, RT activity, and viral growth. Viral variants with single RT mutations (P119S or T165A) did not show resistance to 4'-Ed4T; however, M184V and P119S/T165A/M184V conferred three- and fivefold resistance, respectively, compared with that of the wild-type virus. The P119S/M184V and T165A/M184V variants showed about fourfold resistance to 4'-Ed4T. The differences in the growth kinetics of the variants were not more than threefold. The purified RT of mutants with the P119S/M184V and T165A/M184V mutations were inhibited by 4'-Ed4TTP with 8- to 13-fold less efficiency than wild-type RT. M184V may be the primary resistance-associated mutation of 4'-Ed4T, and P119S and T165A are secondary mutations. On the basis of our findings and the results of structural modeling, a virus with a high degree of resistance to 4'-Ed4T (e.g., more than 50-fold resistance) will be difficult to develop. The previously observed 130-fold resistance of the virus with P119S/T165A/M184V to 4'-Ed4T may be partly due to mutations both in the RT sequence and outside the RT sequence.


Determination of bone mineral density of the hip and spine in human pedigrees by genetic and life-style factors.
In 40 human pedigrees with 563 subjects, we evaluated the contribution of genetic and life-style factors (exercise, smoking, and alcohol consumption) and the interactions between non-genetic factors in determining bone mineral density (BMD) of the hip and spine. In our analysis, we adjusted for age, weight, height, menopausal status in females, life-style factors, and the significant interactions among these factors. For the spine and hip BMD, heritabilities (h(2)) (+/- SE) were, respectively, 0.68 (0.21) and 0.86 (0.28) in males and 0.64 (0.13) and 0.67 (0.14) in females. Exercise had significant beneficial effects for male spine BMD and female hip BMD. Alcohol consumption experienced in our sample had significant beneficial effects on hip BMD in both sexes. Although the main effect of smoking was not significant, there were significant interaction effects between smoking and other important factors (e.g., exercise, weight, alcohol consumption). For example, for female spine BMD, exercise had significant beneficial effects in smokers; however, its effect in non-smokers was non-significant. This result indicates that exercise may reduce deleterious effects of smoking (if any) on BMD, but may have minor effects in increasing BMD in non-smokers. The various interaction effects among risk factors explicitly revealed here for the first time indicate that the detailed effects and direction of individual risk factors may depend on the presence and magnitude of other factors. Weight invariably affected BMD of the hip and spine in both sexes. Age effects were significant for hip BMD, but not for male spine BMD.


Involvement of RNA-binding protein Hfq in the osmotic-response regulation of invE gene expression in Shigella sonnei.
The expression of Type III secretion system (TTSS) in Shigella is regulated in response to changes in environmental osmolarity and temperature. Temperature-dependent regulation of virF, the master regulator of TTSS synthesis, is believed to occur at the transcriptional level. We recently demonstrated, however, that TTSS synthesis also involves post-transcriptional regulation of the synthesis of InvE, a target of virF and key regulator of TTSS synthesis. The mRNA levels of invE (virB) are stable at 37 degrees C, but mRNA stability markedly decreases at low temperatures where the TTSS synthesis is tightly repressed. Deletion of hfq, which encodes an RNA chaperone in Gram-negative bacteria, results in the restoration of expression of invE and other TTSS genes at low temperature due to an increase in the stability of invE mRNA. To date, the molecular details of the regulation of TTSS expression in response to osmotic pressure are not known. In the current study, we investigated the mechanism of regulation of TTSS by osmotic pressure. Transcription of virF, which encodes the master regulator of TTSS expression, was partially repressed under low osmotic conditions. Several lines of evidence indicated that osmolarity-dependent changes in TTSS synthesis are controlled at the post-transcriptional level, through the regulation of InvE synthesis. First, the expression InvE protein was tightly repressed under low osmotic growth conditions, even though invE mRNA transcripts were readily detectable. Second, under low osmotic conditions, invE mRNA was rapidly degraded, whereas deletion of hfq, which encodes an RNA chaperone, resulted in increased invE mRNA stability and the production of InvE protein. Third, the binding of purified Hfq in vitro to invE RNA was stronger in low-salt buffer, as assessed by gel-shift analysis and surface plasmon resonance (Biacore analysis). Osmolarity-dependent changes in TTSS synthesis in Shigella involve the post-transcriptional regulation of InvE expression, in addition to partial transcriptional activation by virF. The stability of invE mRNA is reduced under low osmotic conditions, similar to the effect of temperature. Deletion of an RNA chaperone gene (hfq) abolished the repression of TTSS synthesis at low osmolarity through a mechanism that involved increased stability of invE mRNA. We propose that the expression of Shigella virulence genes in response to both osmolarity and temperature involves the post-transcriptional regulation of expression of InvE, a critical regulator of TTSS synthesis.


Autofocusing in optical scanning holography.
We present autofocusing in optical scanning holography (OSH) with experimental results. We first record the complex hologram of an object using OSH and then create the Fresnel zone plate (FZP) that codes the object constant within the depth range of the object using Gaussian low-pass filtering. We subsequently synthesize a real-only spectrum hologram in which its phase term contains information about a distance parameter. Finally, we extract the distance parameter from the real-only spectrum hologram using fringe-adjusted filtering and the Wigner distribution. Using the extracted distance parameter, we reconstruct a three-dimensional image of the object from the complex hologram using digital convolution, which bypasses the conventional blind convolution to reconstruct a hologram. To the best of our knowledge, this is the first report with experimental results that autofocusing in OSH is possible without any searching algorithm or tracking process.


An analysis of the abstracts presented at the annual meetings of the Society for Neuroscience from 2001 to 2006.
Annual meeting abstracts published by scientific societies often contain rich arrays of information that can be computationally mined and distilled to elucidate the state and dynamics of the subject field. We extracted and processed abstract data from the Society for Neuroscience (SFN) annual meeting abstracts during the period 2001-2006 in order to gain an objective view of contemporary neuroscience. An important first step in the process was the application of data cleaning and disambiguation methods to construct a unified database, since the data were too noisy to be of full utility in the raw form initially available. Using natural language processing, text mining, and other data analysis techniques, we then examined the demographics and structure of the scientific collaboration network, the dynamics of the field over time, major research trends, and the structure of the sources of research funding. Some interesting findings include a high geographical concentration of neuroscience research in the north eastern United States, a surprisingly large transient population (66% of the authors appear in only one out of the six studied years), the central role played by the study of neurodegenerative disorders in the neuroscience community, and an apparent growth of behavioral/systems neuroscience with a corresponding shrinkage of cellular/molecular neuroscience over the six year period. The results from this work will prove useful for scientists, policy makers, and funding agencies seeking to gain a complete and unbiased picture of the community structure and body of knowledge encapsulated by a specific scientific domain.


Body temperature and thermal environment in a generalized arboreal anthropoid, wild mantled howling monkeys (Alouatta palliata).
Free-ranging primates are confronted with the challenge of maintaining an optimal range of body temperatures within a thermally dynamic environment that changes daily, seasonally, and annually. While many laboratory studies have been conducted on primate thermoregulation, we know comparatively little about the thermal pressures primates face in their natural, evolutionarily relevant environment. Such knowledge is critical to understanding the evolution of thermal adaptations in primates and for comparative evaluation of humans' unique thermal adaptations. We examined temperature and thermal environment in free-ranging, mantled howling monkeys (Alouatta palliata) in a tropical dry forest in Guanacaste, Costa Rica. We recorded subcutaneous (Tsc ) and near-animal ambient temperatures (Ta ) from 11 animals over 1586.5 sample hours during wet and dry seasons. Howlers displayed considerable variation in Tsc , which was largely attributable to circadian effects. Despite significant seasonal changes in the ambient thermal environment, howlers showed relatively little evidence for seasonal changes in Tsc . Howlers experienced warm thermal conditions which led to body cooling relative to the environment, and plateaus in Tsc at increasingly warm Ta . They also frequently faced cool thermal conditions (Ta < Tsc ) in which Tsc was markedly elevated compared with Ta . These data add to a growing body of evidence that non-human primates have more labile body temperatures than humans. Our data additionally support a hypothesis that, despite inhabiting a dry tropical environment, howling monkeys experience both warm and cool thermal pressures. This suggests that thermal challenges may be more prevalent for primates than previously thought, even for species living in nonextreme thermal environments.


Early Results from the Flexibility in Surgical Training Research Consortium: Resident and Program Director Attitudes Toward Flexible Rotations in Senior Residency.
To assess the attitudes of residents and program directors (PDs) involved in flexible training to gauge satisfaction with this training paradigm and elicit limitations. Anonymous surveys were sent to residents and PDs in participant programs. Respondents were asked to rate responses on a 5-point Likert scale (1 = strongly disagree and 5 = strongly agree). A total of 9 residency programs that are collaborating to prospectively study the effect of flexible tracks on resident performance and outcome. A total of 138 residents who were in clinical years 4 and 5 and 10 PDs. Of the 138 possible residents, 100 responded to the resident survey (72.5% response rate). Among resident respondents, 33% were participating in a flexible track option. The most frequently listed specialties of focus were cardiothoracic surgery (19%), vascular surgery (13%), acute care surgery (11%), colorectal surgery (8%), surgical oncology (7%), and pediatric surgery (7%). Participants in flexible tracks tended to strongly agree that their career would be enhanced by flexible rotations; interestingly, of those not in flexible tracks, most tended to also agree that flexible rotations would enhance their future careers. Flexible track participants report receiving greater autonomy on flexible rotations and believe they would be better prepared for fellowship and career. They express overall very high satisfaction with the flexible experience. Limitations expressed by residents (in flexible tracks or not) include uncertainty for how this paradigm serves those interested in comprehensive general surgery, concern about scheduling difficulties, and some displeasure in missing high-volume general surgery rotations in lieu of specialty-focused rotations. The PD survey was completed by 8 of 9 PDs for a response rate of 89%. All the respondents agreed or strongly agreed that careers of residents are enhanced by flexible rotations and that important operative and clinical experiences are gained. Overall, 87.5% of PD respondents agreed or strongly agreed that those in flexible tracks have greater opportunities for mentorship in their chosen field. PDs also expressed high levels of satisfaction with flexible rotations. Limitations include concerns that the flexibility option presents scheduling difficulties and does not go far enough in reforming postgraduate education. This survey of 9 residency programs participating in flexible tracks indicates satisfaction with this training option. The role of comprehensive general surgery as a training end point and scheduling difficulties remain as major challenges. Outcomes of graduates in these tracks and control peers are being prospectively evaluated.


Range clusters based time-of-flight 3D imaging obstacle detection in manifold space.
A new obstacle detection method using time-of-flight 3D imaging sensor based on range clusters is proposed. To effectively reduce the influence of outlier and noise in range images, we utilize intensity images to estimate noise deviation of the range images and a weighted local linear smoothing is used to project the data into a new manifold surface. The proposed method divides the 3D imaging data into range clusters with different shapes and sizes according to the distance ambient relation between the pixels, and some regulation criterions are set to adjust the range clusters into optimal shape and size. Experiments on the SwissRanger sensor data show that, compared to the traditional obstacle detection methods based on regular data patches, the proposed method can give more precious detection results.


Quantifying effects of seedborne inoculum on virus spread, yield losses, and seed infection in the pea seed-borne mosaic virus-field pea pathosystem.
Field experiments examined the effects of sowing field pea seed with different amounts of infection with Pea seed-borne mosaic virus (PSbMV) on virus spread, seed yield, and infection levels in harvested seed. Plots were sown with seed with actual or simulated seed transmission rates of 0.3 to 6.5% (2005) or 0.1 to 8% (2006), and spread was by naturally occurring migrant aphids. Plants with symptoms and incidence increased with the amount of primary inoculum present. When final incidence reached 97 to 98% (2005) and 36% (2006) in plots sown with 6.5 to 8% infected seed, yield losses of 18 to 25% (2005) and 13% (2006) resulted. When incidence reached 48 to 76% in plots sown with 1.1-2 to 2% initial infection, seed yield losses were 15 to 21% (2005). Diminished seed weight and seed number both contributed to the yield losses. When the 2005 data for the relationships between percent incidence and yield or yield gaps were plotted, 81 to 84% of the variation was explained by final incidence and, for each 1% increase, there was a yield decline of 7.7 to 8.2 kg/ha. Seed transmission rates in harvested seed were mostly greater than those in the seed sown when climatic conditions favored early virus spread (1 to 17% in 2005) but smaller when they did not (0.2 to 2% in 2006). In 2007, sowing infected seed at high seeding rate with straw mulch and regular insecticide application resulted in slower spread and smaller seed infection than sowing at standard seeding rate without straw mulch or insecticide. When data for the relationship between final percent incidence and seed transmission in harvested seed were plotted (all experiments), 95 to 99% of the variation was explained by PSbMV incidence. A threshold value of <0.5% seed infection was established for sowing in high-risk zones.


Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.
Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (P<0.02; log-rank Mantel-Cox test). There was no correlation of protective MHC contributing to infection control. The RM without detectable circulating SIV, now hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform.


Artificial Cell Membrane Polymersome-Based Intranasal Beta Spike Formulation as a Second Generation Covid-19 Vaccine.
Current parenteral coronavirus disease 2019 (Covid-19) vaccines inadequately protect against infection of the upper respiratory tract. Additionally, antibodies generated by wild type (WT) spike-based vaccines poorly neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. To address the need for a second-generation vaccine, we have initiated a preclinical program to produce and evaluate a potential candidate. Our vaccine consists of recombinant Beta spike protein coadministered with synthetic CpG adjuvant. Both components are encapsulated within artificial cell membrane (ACM) polymersomes, synthetic nanovesicles efficiently internalized by antigen presenting cells, including dendritic cells, enabling targeted delivery of cargo for enhanced immune responses. ACM vaccine is immunogenic in C57BL/6 mice and Golden Syrian hamsters, evoking high serum IgG and neutralizing responses. Compared to an ACM-WT spike vaccine that generates predominantly WT-neutralizing antibodies, the ACM-Beta spike vaccine induces antibodies that neutralize WT and Beta viruses equally. Intramuscular (IM)-immunized hamsters are strongly protected from weight loss and other clinical symptoms after the Beta challenge but show delayed viral clearance in the upper airway. With intranasal (IN) immunization, however, neutralizing antibodies are generated in the upper airway concomitant with rapid and potent reduction of viral load. Moreover, antibodies are cross-neutralizing and show good activity against Omicron. Safety is evaluated in New Zealand white rabbits in a repeated dose toxicological study under Good Laboratory Practice (GLP) conditions. Three doses, IM or IN, at two-week intervals do not induce an adverse effect or systemic toxicity. Cumulatively, these results support the application for a Phase 1 clinical trial of ACM-polymersome-based Covid-19 vaccine (ClinicalTrials.gov identifier: NCT05385991).


Pulmonary immune cells in health and disease: lymphocytes.
Immunological defence mechanisms of the lung are provided by several different types of immunocompetent cell. Among these, the most important are lymphocytes, alveolar macrophages and neutrophils. This review focuses mainly on the pattern of physiological activities of pulmonary lymphocytes in the local host defences. The article provides an overview of the events leading to the recruitment, homing and activity of lymphocytes in the lower respiratory tract. The pathways through which the pulmonary lymphoid system recognizes, destroys and contributes to removing potentially harmful inhaled antigenic materials are also briefly discussed. The final section of the article highlights the pathogenetic role envisaged for lymphoid cells in disease states, in the context of the known biology of these cells.


Application of the Zürich biofilm model to problems of cariology.
The term biofilm is increasingly replacing 'plaque' in the literature, but concepts and existing paradigms are changing much more slowly. There is little doubt that biofilm research will lead to more realistic perception and interpretation of the physiology and pathogenicity of microorganisms colonizing plaques in the oral cavity. There is clear evidence that the genotypic and phenotypic expression profiles of biofilm and planktonic bacteria are different. Several techniques are available today to study multispecies biofilms of oral bacteria, each having its particular advantages and weaknesses. We describe a biofilm model developed in Zürich and demonstrate a number of applications with direct or indirect impact on prophylactic dentistry: spatial arrangement and associative behavior of various species in biofilms; multiplex fluorescent in situ hybridization analysis of oral bacteria in biofilms; use of the biofilm model to predict in vivo efficacy of antimicrobials reliably; mass transport in biofilms; de- and remineralization of enamel exposed to biofilms in vitro. The potential of biofilm experimentation in oral biology has certainly not yet been fully exploited and dozens of possible interesting applications could be investigated. The overall physiological parameters of multispecies biofilms can be measured quite accurately, but it is still impossible to assess in toto the multitude of interactions taking place in such complex systems. What can and should be done is to test hypotheses stemming from experiments with planktonic cells in monospecies cultures. In particular, it will be interesting to investigate the relevance to biofilm composition and metabolism of specific gene products by using appropriate bacterial mutants.


Electrophysiological correlates of visual singleton detection.
Identifying a fixed-feature singleton that pops out from an otherwise uniform array of distractors elicits an ERP component called the N2pc over the posterior scalp. The N2pc has been used to track attention with millisecond accuracy, inform theories of visual selection, and test for specific attention deficits in clinical populations, yet it is still unclear what neuro-cognitive process gives rise to the component. One hypothesis is that the N2pc reflects a spatial filtering process that suppresses irrelevant distractors. In support of this hypothesis, Luck and Hillyard (1994a) showed that the N2pc is eliminated when the features of the target and distractors switch unpredictably across trials (so that participants cannot prepare to filter out irrelevant items). The present study aimed to replicate Luck and Hillyard's singleton detection experiment but with modifications to enhance the N2pc signal and to gain statistical power. We show that orientation singletons do, in fact, elicit the N2pc as well as an earlier-onset and longer-lasting singleton detection positivity over the occipital scalp when the target and distractor orientations swap randomly across trials. We conclude that spatial filtering might not play a major role in the generation of the N2pc and that the selection processes required to search for fixed-feature targets (in feature-search mode) are also engaged in the detection of variable-feature singletons (in singleton detection mode).


Prognosis of patients with unilateral extracranial occlusion of the internal carotid artery.
One hundred fifty-five patients (121 men and 34 women) had an angiographically verified unilateral internal carotid artery (ICA) occlusion immediately after carotid bifurcation. The median follow-up period was 53 months. Forty-five percent of the patients were fully independent in the activities of daily living (ADL), 22% required assistance in ADL, 11% were disabled, and 22% died within the follow-up period. The mortality rate was exceptionally low compared with previous series. A life-table analysis of the material gave a 94% probability of surviving the first year, 84% the third year, and 78% the fifth year. Young age was favorable in regard to functional recovery, but it had no influence on mortality. The condition at the acute stage was the most important clinical sign in predicting the prognosis. The prognosis of mortality and functional recovery was poorer for smokers than for nonsmokers, and hypertension had no effect on prognosis. Cerebrovascular disease and coronary heart disease were found to be the cause of death with equal frequency in this study.


Financial fragility and demographic factors predict pet owners' perceptions of access to veterinary care in the United States.
Access to veterinary care is critical for pet, human, and community health. However, inequities in how easily pet owners can access veterinary care may exacerbate health disparities in vulnerable populations. This research analyzed pet owners' perceptions of access to veterinary care in order to understand how demographic characteristics and financial fragility predict perceived access to veterinary services. This study utilized survey data (n = 750) from a larger cross-sectional survey of adults in the US conducted by the Tufts University Equity Research Group. Survey data were collected in May and June of 2020 from a nationally representative group of pet owners via an online panel. Descriptive statistics, ANOVAs, and a sequential linear regression model were conducted in order to predict perceived access to veterinary care. Results of a sequential linear regression model indicated that race or ethnicity, education, and financial fragility significantly predicted perceived ease of access to veterinary care (F[7,617] = 19.80; P < .001). Additionally, financial fragility was prevalent among most pet owners of almost all income brackets, highlighting the need for more research into the cost burden of veterinary care. Future studies should focus on diverse sampling strategies that capture the experiences of minority pet owners in order to further understand issues of access in veterinary medicine.


Endosymbiosis undone by stepwise elimination of the plastid in a parasitic dinoflagellate.
Organelle gain through endosymbiosis has been integral to the origin and diversification of eukaryotes, and, once gained, plastids and mitochondria seem seldom lost. Indeed, discovery of nonphotosynthetic plastids in many eukaryotes--notably, the apicoplast in apicomplexan parasites such as the malaria pathogen Plasmodium--highlights the essential metabolic functions performed by plastids beyond photosynthesis. Once a cell becomes reliant on these ancillary functions, organelle dependence is apparently difficult to overcome. Previous examples of endosymbiotic organelle loss (either mitochondria or plastids), which have been invoked to explain the origin of eukaryotic diversity, have subsequently been recognized as organelle reduction to cryptic forms, such as mitosomes and apicoplasts. Integration of these ancient symbionts with their hosts has been too well developed to reverse. Here, we provide evidence that the dinoflagellate Hematodinium sp., a marine parasite of crustaceans, represents a rare case of endosymbiotic organelle loss by the elimination of the plastid. Extensive RNA and genomic sequencing data provide no evidence for a plastid organelle, but, rather, reveal a metabolic decoupling from known plastid functions that typically impede organelle loss. This independence has been achieved through retention of ancestral anabolic pathways, enzyme relocation from the plastid to the cytosol, and metabolic scavenging from the parasite's host. Hematodinium sp. thus represents a further dimension of endosymbiosis--life after the organelle.


Exploring the use of five color flow cytometry to examine the effect of acute tai chi practice on pro inflammatory monocyte subtypes - biomed 2013.
The purpose of this study was to determine whether five-color flow cytometry could be used to examine the effect of acute Tai Chi (TC) practice on pro-inflammatory monocyte subtypes within the total monocyte population in peripheral blood. A pilot pre- post- intervention design was our experimental model: pre-intervention measurements acted as the control for the post- intervention measurements. The research was conducted at Landsbaum Center for Health Education in a Midwestern community. Healthy subjects were asked to perform their style of TC for one hour. Four milliliter of peripheral blood was collected in the BD Vacutainer CPT tubes immediately prior and after one hour of TC practice. Peripheral blood mononuclear cells (PBMCs) were isolated following the manufacturer's protocol. PBMCs were then assessed for CD14, CD16, TLR2, TLR4, and HLA-DR expressions using five-color flow cytometry measurement. FlowJo and Graphpad Prism software were used to analyze the results. The proportion of pro-inflammatory CD14+CD16+ monocytes decreased immediately after one hour of TC practice (p<0.01). The results indicate that the five-color flow cytometric process was sufficiently sensitive to be used to explore changes in peripheral blood pro-inflammatory monocytes following one hour of TC practice.


Cellular fatty acyl and alkenyl residues in Megasphaera and Pectinatus species: contrasting profiles and detection of beer spoilage.
SUMMARYThe strictly anaerobic Gram-negative beer spoilage bacteria Megasphaera cerevisiae, Pectinatus cerevisiiphilus and P. frisingensis were subjected to cellular fatty acid analysis, employing acid- and base-catalysed cleavage, gas chromatography and mass spectrometry. M. cerevisiae contained 12:0, 16:0, 16:1, 18:1, 17:cyc, 19:cyc, 12:0(3OH), 14:0(3OH) as the main fatty acids, and alk-1-enyl chains instead of acyl chains were detected to a considerable extent (14% of total fatty acids), indicating the presence of plasmalogens. The fatty acid pattern of M. cerevisiae was almost identical to that of M. elsdenii, the only species previously assigned to this genus. P. cerevisiiphilus and P. frisingensis yielded fatty acids that were heavily dominated by odd-numbered chains; 11:0, 15:0, 17:1, 18:cyc and 13:0(3OH) were the main fatty acids detected in both species. Alk-1-enyl chains with similar chain lengths were also found. Both Pectinatus species contained six different 3-hydroxy fatty acids with chain lengths between 11 and 15 carbons, 13:0(3OH) being dominant and the others accounting for generally less than 1% of total fatty acids. Among the minor components, an unsaturated 3-hydroxy fatty acid was detected which was shown to be 13:1(30H). In addition, fatty acid analysis was shown to be applicable to detection of bacterial contamination of beer.


Stretchable graphene transistors with printed dielectrics and gate electrodes.
With the emergence of human interface technology, the development of new applications based on stretchable electronics such as conformal biosensors and rollable displays are required. However, the difficulty in developing semiconducting materials with high stretchability required for such applications has restricted the range of applications of stretchable electronics. Here, we present stretchable, printable, and transparent transistors composed of monolithically patterned graphene films. This material offers excellent mechanical, electrical, and optical properties, capable of use as semiconducting channels as well as the source/drain electrodes. Such monolithic graphene transistors show hole and electron mobilities of 1188 ± 136 and 422 ± 52 cm(2)/(V s), respectively, with stable operation at stretching up to 5% even after 1000 or more cycles.


Synergism between plant extract and antimicrobial drugs used on Staphylococcus aureus diseases.
Searches for substances with antimicrobial activity are frequent, and medicinal plants have been considered interesting by some researchers since they are frequently used in popular medicine as remedies for many infectious diseases. The aim of this study was to verify the synergism between 13 antimicrobial drugs and 8 plant extracts--"guaco" (Mikania glomerata), guava (Psidium guajava), clove (Syzygium aromaticum), garlic (Allium sativum), lemongrass (Cymbopogon citratus), ginger (Zingiber officinale), "carqueja" (Baccharis trimera), and mint (Mentha piperita)--against Staphylococcus aureus strains, and for this purpose, the disk method was the antimicrobial susceptibility test performed. Petri dishes were prepared with or without dilution of plant extracts at sub-inhibitory concentrations in Mueller-Hinton Agar (MHA), and the inhibitory zones were recorded in millimeters. In vitro anti-Staphylococcus aureus activities of the extracts were confirmed, and synergism was verified for all the extracts; clove, guava, and lemongrass presented the highest synergism rate with antimicrobial drugs, while ginger and garlic showed limited synergistic capacity.


Electrotonic current spread in colonic smooth muscle.
Current-induced changes in the membrane potential (electrotonic potentials) were measured intracellularly. The electrotonic potentials were seen to decay exponentially over many cells, suggesting electrotonic current spread. The characteristics of the electrotonic current spread were used to determine passive membrane properties of both circular and longitudinal muscle cells of human and dog colon. Electrotonic current spread was first determined along the long axes of the cells. The space constant of the circular muscle of human colon was 2.14 mm and that of the longitudinal muscle was 1.63 mm. The space constants for the dog colon were similar. The value for the time constant of dog colon circular muscle was 160 ms, whereas much higher time constants, averaging between 500 and 800 ms, were recorded from dog longitudinal muscle and both human colon muscle layers. These data suggest good electrotonic coupling in all tissues studied, along the long axes of the cells. They further suggest a relatively high membrane resistance and junctional resistance in the longitudinal muscle. Electrotonic coupling along the short axes of circular muscle cells, along the long axis of the colon, was studied in the dog. The space constant was 0.43 mm, suggesting a relatively high resistance to current flow along the short axes of the cells. In addition, along the short axes of the cells from the submucosa to the myenteric plexus side (i.e., in radial direction) a gradient was observed in resting membrane potential, slow-wave amplitude, and rate of rise of the slow-wave upstroke.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of patients with clinically suspected melanoma recurrence: current practice patterns of plastic surgeons.
The optimal extent-of-disease evaluation for patients with clinically suspected melanoma recurrence is not known. The available modalities are numerous and many are expensive. We documented the extent of work-up carried out by plastic surgeons when their patients with melanoma develop clinical recurrence. A custom-designed questionnaire was mailed to a random sample (n=3,032) of the 4,320 members of the American Society of Plastic and Reconstructive Surgeons (ASPRS). Subjects were asked which specific laboratory tests and imaging studies they would order for a patient with initial T2N0M0 disease treated with curative intent who later presented with either regional nodal metastases or pulmonary metastases. We measured the variability in practice patterns among surgeons and estimated the effects of physician age, U.S. census region, health maintenance organization (HMO) penetration rates, and type of recurrence (regional versus systemic) on work-up intensity. Of the 1,142 questionnaires completed (38%), 395 (35%) were evaluable. Non-evaluability was usually due to lack of melanoma patient follow-up in surgeons' practices. Lesion biopsy, chest X-ray, complete blood count, liver function tests, and computed tomography were frequently used, but there was no consensus for most modalities. More tests, particularly computed tomography, were utilized for evaluating systemic recurrence than for regional recurrence (p<0.05). The intensity of work-up differed significantly (p<0.05) by surgeon age for three diagnostic tests but not by U.S. census region or HMO penetration rate. This is the first empirical data on this subject from a large sample of an international society of highly credentialed experts. The lack of consensus for most tests in current practice is presumably due to multiple factors, including the lack of evidence supporting any particular strategy.


Zebrafish yolk lipid processing: a tractable tool for the study of vertebrate lipid transport and metabolism.
Dyslipidemias are a major cause of morbidity and mortality in the world, particularly in developed nations. Investigating lipid and lipoprotein metabolism in experimentally tractable animal models is a crucial step towards understanding and treating human dyslipidemias. The zebrafish, a well-established embryological model, is emerging as a notable system for studies of lipid metabolism. Here, we describe the value of the lecithotrophic, or yolk-metabolizing, stages of the zebrafish as a model for studying lipid metabolism and lipoprotein transport. We demonstrate methods to assay yolk lipid metabolism in embryonic and larval zebrafish. Injection of labeled fatty acids into the zebrafish yolk promotes efficient uptake into the circulation and rapid metabolism. Using a genetic model for abetalipoproteinemia, we show that the uptake of labeled fatty acids into the circulation is dependent on lipoprotein production. Furthermore, we examine the metabolic fate of exogenously delivered fatty acids by assaying their incorporation into complex lipids. Moreover, we demonstrate that this technique is amenable to genetic and pharmacologic studies.


CO2 Capture from Ambient Air by Crystallization with a Guanidine Sorbent.
Carbon capture and storage is an important strategy for stabilizing the increasing concentration of atmospheric CO2 and the global temperature. A possible approach toward reversing this trend and decreasing the atmospheric CO2 concentration is to remove the CO2 directly from air (direct air capture). Herein we report a simple aqueous guanidine sorbent that captures CO2 from ambient air and binds it as a crystalline carbonate salt by guanidinium hydrogen bonding. The resulting solid has very low aqueous solubility (Ksp =1.0(4)×10-8 ), which facilitates its separation from solution by filtration. The bound CO2 can be released by relatively mild heating of the crystals at 80-120 °C, which regenerates the guanidine sorbent quantitatively. Thus, this crystallization-based approach to CO2 separation from air requires minimal energy and chemical input, and offers the prospect for low-cost direct air capture technologies.


Catalytic Depolymerization of Lignin and Woody Biomass in Supercritical Ethanol: Influence of Reaction Temperature and Feedstock.
The one-step ethanolysis approach to upgrade lignin to monomeric aromatics using a CuMgAl mixed oxide catalyst is studied in detail. The influence of reaction temperature (200-420 °C) on the product distribution is investigated. At low temperature (200-250 °C), recondensation is dominant, while char-forming reactions become significant at high reaction temperature (>380 °C). At preferred intermediate temperatures (300-340 °C), char-forming reactions are effectively suppressed by alkylation and Guerbet and esterification reactions. This shifts the reaction toward depolymerization, explaining high monomeric aromatics yield. Carbon-14 dating analysis of the lignin residue revealed that a substantial amount of the carbon in the lignin residue originates from reactions of lignin with ethanol. Recycling tests show that the activity of the regenerated catalyst was strongly decreased due to a loss of basic sites due to hydrolysis of the MgO function and a loss of surface area due to spinel oxide formation of the Cu and Al components. The utility of this one-step approach for upgrading woody biomass was also demonstrated. An important observation is that conversion of the native lignin contained in the lignocellulosic matrix is much easier than the conversion of technical lignin.


Reduction of spherical aberration with the nidek NAVEX customized ablation system.
Spherical aberration is the most frequent optical aberration induced by refractive surgery, reducing visual acuity and causing halos. We present preliminary results of Custom Ablation Transition Zone (CATz), which we developed for Nidek's Final Fit software, part of the Nidek NAVEX customized ablation system. We studied 55 eyes of 51 patients (31 males, 20 females) who underwent refractive surgery. Mean preoperative spherical equivalent refraction was -5.50 +/- 3.30 D (range -12.00 to +4.50 D). Mean age was 35 years (range 23 to 47 yr). All patients underwent complete preoperative ophthalmologic examination, including aberrometry and topography, then surgery with laser epithelial keratomileusis, and OPD-based refractive treatment with the Nidek EC-5000 excimer laser. The Nidek Final Fit software with the CATz feature was always used. Postoperatively, all patients repeated the ophthalmologic examination inclusive of aberrometry at day 30, 60, and 90. The 3-month follow-up rate was 21.8%. Mean postoperative spherical equivalent refraction was -0.33 +/- 0.91 D (range -0.75 to +0.75 D), with a mean sphere of -0.23 +/- 0.78 D (range -2.50 to +0.75 D) and a mean cylinder of -0.21 +/- 0.33 (range -1.00 to 0 D). At 3 months, 43% of eyes achieved 20/15 or better UCVA, and 43% achieved 20/20 or better UCVA; 63% achieved 20/15 or better BSCVA and 25% achieved 20/20 or better BSCVA. Postoperative spherical aberration was unchanged for a 3-mm pupil. Customized ablation with the Nidek NAVEX system provided excellent refractive results. The CATz algorithm of the Nidek Final Fit software appeared to prevent induction of spherical aberration.


The relative compliance of energy-storing tendons may be due to the helical fibril arrangement of their fascicles.
A nonlinear elastic microstructural model is used to investigate the relationship between structure and function in energy-storing and positional tendons. The model is used to fit mechanical tension test data from the equine common digital extensor tendon (CDET) and superficial digital flexor tendon (SDFT), which are used as archetypes of positional and energy-storing tendons, respectively. The fibril crimp and fascicle helix angles of the two tendon types are used as fitting parameters in the mathematical model to predict their values. The outer fibril crimp angles were predicted to be 15.1° ± 2.3° in the CDET and 15.8° ± 4.1° in the SDFT, and the average crimp angles were predicted to be 10.0° ± 1.5° in the CDET and 10.5° ± 2.7° in the SDFT. The crimp angles were not found to be statistically significantly different between the two tendon types (p = 0.572). By contrast, the fascicle helix angles were predicted to be 7.9° ± 9.3° in the CDET and 29.1° ± 10.3° in the SDFT and were found to be statistically highly significantly different between the two tendon types (p < 0.001). This supports previous qualitative observations that helical substructures are more likely to be found in energy-storing tendons than in positional tendons and suggests that the relative compliance of energy-storing tendons may be directly caused by these helical substructures.


Inhibition of hybrid- and complex-type glycosylation reveals the presence of the GlcNAc transferase I-independent fucosylation pathway.
A mammalian N-acetylglucosamine (GlcNAc) transferase I (GnT I)-independent fucosylation pathway is revealed by the use of matrix-assisted laser desorption/ionization (MALDI) and negative-ion nano-electrospray ionization (ESI) mass spectrometry of N-linked glycans from natively folded recombinant glycoproteins, expressed in both human embryonic kidney (HEK) 293S and Chinese hamster ovary (CHO) Lec18.104.22.168 cells deficient in GnT I activity. The biosynthesis of core fucosylated Man5GlcNAc2 glycans was enhanced in CHO Lec126.96.36.199 cells by the alpha-glucosidase inhibitor, N-butyldeoxynojirimycin (NB-DNJ), leading to the increase in core fucosylated Man5GlcNAc2 glycans and the biosynthesis of a novel core fucosylated monoglucosylated oligomannose glycan, Glc1Man7GlcNAc2Fuc. Furthermore, no fucosylated Man9GlcNAc2 glycans were detected following inhibition of alpha-mannosidase I with kifunensine. Thus, core fucosylation is prevented by the presence of terminal alpha1-2 mannoses on the 6-antennae but not the 3-antennae of the trimannosyl core. Fucosylated Man5GlcNAc2 glycans were also detected on recombinant glycoprotein from HEK 293T cells following inhibition of Golgi alpha-mannosidase II with swainsonine. The paucity of fucosylated oligomannose glycans in wild-type mammalian cells is suggested to be due to kinetic properties of the pathway rather than the absence of the appropriate catalytic activity. The presence of the GnT I-independent fucosylation pathway is an important consideration when engineering mammalian glycosylation.


Metal-free synthesis of aminomethylated imidazoheterocycles: dual role of tert-butyl hydroperoxide as both an oxidant and a methylene source.
A novel and efficient aminomethylation approach has been developed for the regioselective functionalization of imidazoheterocycles under metal-free conditions. A wide range of imidazoheterocycles and 2/4-aminoazaheterocycles successfully provided corresponding aminomethylated imidazoheterocycles in moderate to excellent (33-80%) yields. The isotopic labelling study suggested that TBHP played a dual role as both an oxidant and a methylene source in this transformation. The developed protocol follows a radical pathway which is supported by radical trapping experiments.


Getting to the Heart of Alzheimer Disease.
In a somewhat narrow diagnostic lens, Alzheimer disease (AD) has been considered a brain-specific disease characterized by the presence of Aβ (β-amyloid) plaques and tau neural fibrillary tangles and neural inflammation; these pathologies lead to neuronal death and consequently clinical symptoms, such as memory loss, confusion, and impaired cognitive function. However, for decades, researchers have noticed a link between various cardiovascular abnormalities and AD-such as heart failure, coronary artery disease, atrial fibrillation, and vasculopathy. A considerable volume of work has pointed at this head to heart connection, focusing mainly on associations between cerebral hypoperfusion and neuronal degradation. However, new evidence of a possible systemic or metastatic profile to AD calls for further analysis of this connection. Aβ aggregations-biochemically and structurally akin to those found in the typical AD pathology-are now known to be present in the hearts of individuals with idiopathic dilated cardiomyopathy, as well as the hearts of patients with AD. These findings suggest a potential systemic profile of proteinopathies and a new hypothesis for the link between peripheral and central symptoms of heart failure and AD. Herein, we provide an overview of the cardiovascular links to Alzheimer disease.


3D reconstruction and comparison of shapes of DNA minicircles observed by cryo-electron microscopy.
We use cryo-electron microscopy to compare 3D shapes of 158 bp long DNA minicircles that differ only in the sequence within an 18 bp block containing either a TATA box or a catabolite activator protein binding site. We present a sorting algorithm that correlates the reconstructed shapes and groups them into distinct categories. We conclude that the presence of the TATA box sequence, which is believed to be easily bent, does not significantly affect the observed shapes.


Evaluation of Myocardial Injury using Standard Diagnostic Tools and Tissue Doppler Imaging in Blunt Trauma Chest.
Myocardial contusion is an entity in chest trauma which is difficult to diagnose. Current practice relies more on cardiac-specific biochemical markers and standard echocardiography, but no gold standard test exists. The application of Tissue Doppler imaging is yet unexplored. The present study was designed to evaluate cardiac injury in patients with blunt trauma chest using conventional trans-thoracic echocardiography parameters and Tissue Doppler imaging. After ethical approval was taken from the Hospital and University and a written informed consent from all patients/attendants, this prospective study was conducted on a total of 30 patients in range of 15-60 years of age with blunt trauma chest. Patients with positive Trop-T and raised CPK (> 308 IU/L), raised CK-MB (> 24 IU/L) levels were suspected to have myocardial injury and were enrolled in the study. All patients fulfilling the inclusion criteria then underwent 2D-Echo and Tissue Doppler Imaging. Results of the observations were analysed using chi-square test. Out of the total of 30 patients, 63.3% showed ECG changes suggestive of cardiac injury. A 76.7% patients suffered systolic dysfunction and 36.6% patients suffered diastolic dysfunction irrespective of ECG changes. On comparison of early filling velocity wave i.e., E wave (measured by transthoracic echocardiography) and tricuspid annular velocity Em wave (measured by tissue Doppler echocardiography) at tricuspid valve, we found statistically significant difference among two techniques. (p = 0.04). Echocardiography is very sensitive parameter for evaluation of myocardial contusion. Tissue Doppler imaging provides additional and reliable information.


The essential health reform in Chile; a reflection on the 1952 process.
The authors claim that the critical health reform in Chilean history was the establishment of the National Health Service (NHS) in 1952. The development of modern Chilean health care since the end of the 19th century is discussed both in terms of the prevailing health situation and the subsequent evolution of institutions and policies, with an emphasis on the social and political conditions that led to the creation of the NHS in 1952. From this analysis and from a comparison of infant mortality rates among Latin American countries during the same period, the authors infer that the 1952 health reform was the social and political benchmark that allowed Chile to exhibit the relatively favorable health situation it still enjoys. Using Cavanaugh's scheme, it is clear that the "first-generation reform" was the reform imposed by the military regime in the early 1980s, which aimed to change the orientation of the health system. Similarly, the "second-generation reform" was that implemented by the democratic administrations of the early 1990s to reverse the harm done by their military predecessors. The rapid aging of the population and the advent of new technologies pose a challenge to the insurance system's coverage capacity and threaten the sustainability of all health systems. The implementation of universal, comprehensive, collective health systems, managed under the most integrated authority political conditions will allow, is emphasized as an appropriate solution for developed and developing countries alike.


Unintentional Pediatric Exposures to Marijuana in Colorado, 2009-2015.
As of 2015, almost half of US states allow medical marijuana, and 4 states allow recreational marijuana. To our knowledge, the effect of recreational marijuana on the pediatric population has not been evaluated. To compare the incidence of pediatric marijuana exposures evaluated at a children's hospital and regional poison center (RPC) in Colorado before and after recreational marijuana legalization and to compare population rate trends of RPC cases for marijuana exposures with the rest of the United States. Retrospective cohort study of hospital admissions and RPC cases between January 1, 2009, and December 31, 2015, at Children's Hospital Colorado, Aurora, a tertiary care children's hospital. Participants included patients 0 to 9 years of age evaluated at the hospital's emergency department, urgent care centers, or inpatient unit and RPC cases from Colorado for single-substance marijuana exposures. Marijuana. Marijuana exposure visits and RPC cases, marijuana source and type, clinical effects, scenarios, disposition, and length of stay. Eighty-one patients were evaluated at the children's hospital, and Colorado's RPC received 163 marijuana exposure cases between January 1, 2009, and December 31, 2015, for children younger than 10 years of age. The median age of children's hospital visits was 2.4 years (IQR, 1.4-3.4); 25 were girls (40%) . The median age of RPC marijuana exposures was 2 years (IQR, 1.3-4.0), and 85 patients were girls (52%). The mean rate of marijuana-related visits to the children's hospital increased from 1.2 per 100 000 population 2 years prior to legalization to 2.3 per 100,000 population 2 years after legalization (P = .02). Known marijuana products involved in the exposure included 30 infused edibles (48%). Median length of stay was 11 hours (interquartile range [IQR], 6-19) and 26 hours (IQR, 19-38) for admitted patients. Annual RPC pediatric marijuana cases increased more than 5-fold from 2009 (9) to 2015 (47). Colorado had an average increase in RPC cases of 34% (P < .001) per year while the remainder of the United States had an increase of 19% (P < .001). For 10 exposure scenarios (9%), the product was not in a child-resistant container; for an additional 40 scenarios (34%), poor child supervision or product storage was reported. Edible products were responsible for 51 exposures (52%). Colorado RPC cases for pediatric marijuana increased significantly and at a higher rate than the rest of the United States. The number of children's hospital visits and RPC case rates for marijuana exposures increased between the 2 years prior to and the 2 years after legalization. Almost half of the patients seen in the children's hospital in the 2 years after legalization had exposures from recreational marijuana, suggesting that legalization did affect the incidence of exposures.


Higher Dietary Magnesium Intake and Higher Magnesium Status Are Associated with Lower Prevalence of Coronary Heart Disease in Patients with Type 2 Diabetes.
In type 2 diabetes mellitus (T2D), the handling of magnesium is disturbed. Magnesium deficiency may be associated with a higher risk of coronary heart disease (CHD). We investigated the associations between (1) dietary magnesium intake; (2) 24 h urinary magnesium excretion; and (3) plasma magnesium concentration with prevalent CHD in T2D patients. This cross-sectional analysis was performed on baseline data from the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1, n = 450, age 63 ± 9 years, 57% men, and diabetes duration of 11 (7-18) years). Prevalence ratios (95% CI) of CHD by sex-specific quartiles of magnesium indicators, as well as by magnesium intake per dietary source, were determined using multivariable Cox proportional hazard models. CHD was present in 100 (22%) subjects. Adjusted CHD prevalence ratios for the highest compared to the lowest quartiles were 0.40 (0.20, 0.79) for magnesium intake, 0.63 (0.32, 1.26) for 24 h urinary magnesium excretion, and 0.62 (0.32, 1.20) for plasma magnesium concentration. For every 10 mg increase of magnesium intake from vegetables, the prevalence of CHD was, statistically non-significantly, lower (0.75 (0.52, 1.08)). In this T2D cohort, higher magnesium intake, higher 24 h urinary magnesium excretion, and higher plasma magnesium concentration are associated with a lower prevalence of CHD.


Defining interdisciplinary research: conclusions from a critical review of the literature.
To summarize findings from a systematic exploration of existing literature and views regarding interdisciplinarity, to discuss themes and components of such work, and to propose a theoretically based definition of interdisciplinary research. Two major data sources were used: interviews with researchers from various disciplines, and a systematic review of the education, business, and health care literature from January 1980 through January 2005. Systematic review of literature, one-on-one interviews, field test (survey). We reviewed 14 definitions of interdisciplinarity, the characteristics of 42 interdisciplinary research publications from multiple fields of study, and 14 researcher interviews to arrive at a preliminary definition of interdisciplinary research. That definition was then field tested by 12 individuals with interdisciplinary research experience, and their responses incorporated into the definition of interdisciplinary research proposed in this paper. Three key definitional characteristics were identified: the qualitative mode of research (and its theoretical underpinnings), existence of a continuum of synthesis among disciplines, and the desired outcome of the interdisciplinary research. Existing literature from several fields did not provide a definition for interdisciplinary research of sufficient specificity to facilitate activities such as identification of the competencies, structure, and resources needed for health care and health policy research. This analysis led to the proposed definition, which is designed to aid decision makers in funding agencies/program committees and researchers to identify and take full advantage the interdisciplinary approach, and to serve as a basis for competency-based formalized training to provide researchers with interdisciplinary skills.


Noise analysis of miniature IPSCs in adult rat brain slices: properties and modulation of synaptic GABAA receptor channels.
1. The properties of synaptic gamma-aminobutyric acid (GABA)A receptor channels were resolved by using tight-seal, whole-cell recordings from granule cells of the dentate gyrus in adult rat hippocampal slices and by applying the technique of nonstationary noise analysis to study miniature inhibitory postsynaptic currents (mIPSCs) recorded in the presence of tetrodotoxin (TTX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and D-2-amino-5-phosphonovaleric acid (D-AP5). This technique allowed us to extract information about the conductance, the number, and the kinetics of ligand gated channels underlying elementary synaptic currents. 2. To ascertain the validity of the nonstationary noise analysis method we have first tested it on computer simulated mIPSCs with different channel activation, lifetime kinetics, and opening probabilities. Using intraburst mean open times, shorter than the time to the first opening following activation, caused a large variance at the peak due to the stochastic channel properties. This resulted in a skewed mean current-variance relationship, which precluded proper estimation of unit conductance and especially the number of channels open at the peak of mIPSCs. Regardless of the probability of channel opening, accurate estimates of the unit conductance and the number of channels underlying each simulated mIPSC were obtained when channels had mean open times longer than the time to first opening. 3. Once the validity of the nonstationary analysis had been ascertained, it was used on mIPSCs recorded at 35 degrees C. The unit conductance of the synaptic GABAA channels was 28 +/- 1 (SE) pS and the average number of channels underlying mIPSCs was 46 +/- 4. The mean current-variance relationship was not skewed at higher amplitudes, suggesting that the intrinsic variance at the peak of the GABAA mIPSCs is low and that the open time of the channels is longer than the time to first opening. The estimated unit conductance of the channels was constant over a wide range of holding potentials. 4. The amplitude distribution of mIPSCs with rapid 10-90% rise times (290 +/- 20 microseconds) was clearly skewed towards low values. This skew was not due to filtering of electrotonically distant currents. Current-variance analysis revealed that the skewness resulted from differences in the number of GABAA receptor channels and not from the heterogeneity of unitary conductances at various synapses. Selection of mIPSCs with slower rise times yielded smaller unit conductance estimates.(ABSTRACT TRUNCATED AT 400 WORDS)


Distribution of very late activation integrins in the human cornea. An immunohistochemical study using monoclonal antibodies.
There is growing evidence that cellular adhesion mechanisms characterized by cell-cell and cell-matrix interactions are a fundamental process in the immunobiology of the cornea. Interactions with various extracellular matrix components are mediated by the very late activation (VLA) subgroup of the integrin superfamily of adhesion molecules. The six different VLA dimers known thus far consist of a common beta 1 subunit and a variable alpha (1 to 6) subunit. They serve as receptors for laminin (alpha 3 and alpha 6), collagen (alpha 2 and alpha 3), and fibronectin (alpha 4 and alpha 5). Using in situ immunohistochemistry and monoclonal antibodies, the distribution of the common beta 1 and the variable alpha-chains of VLA molecules was studied in normal human cornea and in cases with scarring or subepithelial/retrocorneal fibrous tissue. Epithelial cells were VLA-beta 1 and VLA-alpha 2, -alpha 3, -alpha 4, -alpha 5, and -alpha 6 positive. This is consistent with their intercellular adhesion and may aid in their attachment to the basement membrane which is composed of collagen, laminin, and fibronectin. Keratocytes in normal stroma expressed only the common beta 1-chain and no detectable alpha-chains. In regions of scar or fibrous tissue, however, an upregulated expression of the alpha-chains was detected. The VLA- alpha 1, -alpha 3, -alpha 4, and -alpha 5 were expressed in young fibrous tissue; in older lesions, VLA- alpha 1, -alpha 2, -alpha 3, -alpha 4, and -alpha 5 could be detected. The corneal endothelium showed a strikingly strong positivity for all VLA integrins.(ABSTRACT TRUNCATED AT 250 WORDS)


Fresh stillborn and severely asphyxiated neonates share a common hypoxic-ischemic pathway.
To characterize, among non-breathing flaccid neonates at delivery, immediate heartrate and responses to ventilation in relation to the clinical diagnosis of fresh stillbirth (FSB) or early neonatal death (END) within 24 hours. The present cross-sectional study included all deliveries at Haydom Hospital in rural Tanzania between July 1, 2013, and July 31, 2016. Ventilation parameters and heartrate were recorded by monitors with ventilation and dry-electrocardiography sensors. Perinatal characteristics were recorded on data forms by trained research assistants. Among 12 789 neonates delivered, 915 were ventilated; among ventilated neonates, there were 53 (6%) FSBs and 64 (7%) ENDs. Electrocardiography was used in 46 FSBs and 55 ENDs, and these neonates were included in a subanalysis. Initial heartrate was detected in 27 (59%) of 46 FSBs and 52 (95%) of 55 ENDs, and was lower in FSBs (52 ± 19 vs 76 ± 37 bpm; P=0.003). More ENDs responded to ventilation (53% vs 9%; P<0.001), with heartrate increasing above 100 bpm. Heartrate at ventilation discontinuation was higher among ENDs (115 ± 49 vs 52 ± 33 bpm; P<0.001). Progression to FSB or END after intrapartum hypoxia/anoxia is probably part of the same circulatory end-process. Distinguishing FSB from severely asphyxiated newborns is clinically difficult and probably influences estimated global perinatal mortality rates.


Influence of barometric pressure on interleukin-1 beta secretion.
Monocytes and macrophages are activated by various environmental challenges, including microorganisms, radiation, and pollutants. These cells release cytokines, such as interleukin (IL)-1 beta, that mediate physiological adaptations to stress. This study sought to define further the role of IL-1 beta in general adaptation to environmental stress by testing the hypothesis that high altitude (20,000 ft, 6,096 m) would stimulate IL-1 beta secretion from isolated human blood mononuclear cells. Cells from six young men (aged 22--26 yr) were divided into separate cultures incubated in either standard ambient conditions or in one of three test conditions, hypobaric hypoxia (simulating 20,000 ft), hypobaric normoxia (20,000 ft, O(2) supplemented), and normobaric hypoxia (10% O(2)). This design allowed differentiation between pressure-related vs. oxygen-related effects. Each subject made multiple blood donations in order that cells from all subjects were tested in all conditions. Contrary to the hypothesis, IL-1 beta secretion was not induced at simulated altitude in basal cell cultures. In lipopolysaccharide-stimulated cell cultures, exposure to altitude inhibited IL-1 beta secretion by approximately 40%, and the inhibition was due to the change in pressure (P = 0.039) rather than the change in oxygen. Secretion of other factors (IL-1 receptor antagonist and soluble IL-1 receptor type II) was not inhibited. Although these results are in opposition to the original hypothesis, they provide insight regarding adaptations necessary for hematopoiesis in response to high altitude and also provide a cellular rationale for the mountain sanatoriums of the 19th and early 20th centuries.


Phenobarbital-induced fibromyalgia as the cause of bilateral shoulder pain.
A female swimming instructor was seen with chronic bilateral shoulder pain and loss of range of motion. Intensive physical therapy significantly improved the range of motion but did not alleviate the pain. Osteopathic manipulative treatment produced no further improvement in pain or function. Results of laboratory tests were all within normal limits. Four months after the initial consultation, the patient, who was taking medication for tonic/clonic seizures, recalled that her symptoms began after her anticonvulsant medication was switched from hydantoin sodium to phenobarbital. Therefore, phenobarbital-induced fibromyalgia was diagnosed. In 4 months, pain had completely disappeared. The authors discuss several theories regarding the cause of fibromyalgia and the mechanism of action of phenobarbital, including its relationship to sleep disturbance, a probable contributor to pain and dysfunction in the patient described.


Spin-orbit interactions of a Gaussian light propagating in biaxial crystals.
Based on the plane-wave angular spectrum representation, we derive a formal expression for any light fields propagating in biaxial crystals, and particularly, present an effective numerical method to investigate the propagation behavior for a Gaussian light beam. Unlike uniaxial crystals, we observe the intriguing formation, repulsion and disappearance of vortex pairs, as the refractive indices deviate slightly and gradually from the uniaxial limit. In the Minkowski angular momentum picture, we also investigate the orbital angular momentum dynamics for both left- and right-handed circularly polarized components. Of further interest is the revelation of nonconservation of the angular momentum within the light field during the spin-orbit interactions, and the optical torque per photon that the light exerts on the biaxial crystal is quantified. We interpret these interesting phenomena by the weakly broken rotational invariance of biaxial crystals. The self-consistency of our theory is confirmed by the balance equation describing the conservation law of total angular momentum of filed and crystal in the Minkowski picture.


School experiences may be important determinants of mental health problems in middle childhood - a Swedish longitudinal population-based study.
Little is known about the association between school experiences and mental health in young schoolchildren. This study explored the cross-sectional and prospective associations between children's school experiences and mental health in middle childhood. We gathered comprehensive population-based data on the school experiences and mental health of 592 schoolchildren attending grades three and six in Sweden (ages approximately nine and 12 years). The KIDSCREEN questionnaire was used to measure school experiences in both age groups while the Child Behavior Checklist and the Strengths and Difficulties Questionnaire measured mental health in grades three and six, respectively. Children with problematic school experiences in grade three had an approximately two times higher odds for concurrent total, internalised, externalised, attention-hyperactivity and social problems. They also had a 1.5-2.5 higher odds for these mental health problems three years later. Likewise, there was an association between problematic school experiences in grade three and lower levels of prosocial behaviour three years later. These associations were shown in both boys and girls, but were particularly pronounced in girls. This study indicated that school experiences in young schoolchildren may be important determinants of concurrent and later mental health problems.