Validation of Group-wise Registration for Surface-based Functional MRI Analysis.
Resting-state functional MRI (rsfMRI) provides important information for studying and mapping the activities and functions of the brain. Conventionally, rsfMRIs are often registered to structural images in the Euclidean space without considering cortical surface geometry. Meanwhile, a surface-based representation offers a relaxed coordinate chart, but this still requires surface registration for group-wise data analysis. In this work, we investigate the performance of two existing surface registration methods in a surface-based rsfMRI analysis framework: FreeSurfer and Hierarchical Spherical Deformation (HSD). To minimize registration bias, we establish shape correspondence using both methods in a group-wise manner that estimates the unbiased average of a given cohort. To evaluate their performance, we focus on neuroanatomical alignment as well as the amount of distortion that can potentially bias surface tessellation for secondary level rsfMRI data analyses. In the pilot analysis, we examine a single timepoint of imaging data from 100 subjects out of an aging cohort. Overall, HSD establishes improved shape correspondence with reduced mean curvature deviation (10.94% less on average per subject, paired t-test: p <10-10) and reduced registration distortion (FreeSurfer: average 41.91% distortion per subject, HSD: 18.63%, paired t-test: p <10-10). Furthermore, HSD introduces less distortion than FreeSurfer in the areas identified in the individual components that were extracted by surface-based independent component analysis (ICA) after spatial smoothing and time series normalization. Consequently, we show that FreeSurfer capture individual components with globally similar but locally different patterns in ICA in visual inspection.


Signal antonymy unique to myelodysplastic marrows correlates with altered expression of E2F1.
Myelodysplastic syndromes (MDS) have previously been reported to show competitively high rates of apoptosis and proliferation in the bone marrow (BM). Using a double-labelling technique in the present study, we demonstrated that a significantly high number of S-phase cells were simultaneously apoptotic (signal antonymy; SA) in MDS (mean +/- s.e.m. 53.5 +/- 6.7%, n = 24, P < 0.001). In contrast, SA was negligible in all other specimens studied, including normal control BM (n = 13) from non-Hodgkin's lymphoma (NHL) patients, BM from patients with de novo acute myelogenous leukaemia (1'AML; n = 5), or secondary AML that had transformed from MDS (2'AML; n = 10), or the solid tumours from patients with NHL (n = 9) or head and neck squamous cell carcinoma (HNSCC; n = 10). Subsequently, the expression of a transcription factor, E2F1, was studied in density-separated BM aspirate mononuclear cells from MDS patients (n = 9) and a normal control. Two separate sets of primers were used that recognized the regulatory retinoblastoma (Rb) protein-binding region and the functional DNA-binding region of E2F1. Interestingly, although the latter manifested the expected band (280 bp) in all samples, the Rb-specific primers showed the expected band (380 bp) in the normal and in 4/9 MDS specimens. Two other MDS specimens also showed a smaller band ( approximately 325 bp), whereas 3/9 MDS patients showed exclusively the smaller band. The levels of SA were significantly higher in those MDS cases that showed the smaller Rb-specific band either alone or in addition to the expected band (median 19.5%, n = 4, P = 0.037) than in those showing exclusively the expected band (median 0.4%, n = 3). Our present studies show SA as a characteristic feature of MDS and, importantly, demonstrate its link with an altered expression of E2F1 in some MDS patients.


Passive leg raising test induced changes in plethysmographic variability index to assess fluid responsiveness in critically ill mechanically ventilated patients with acute circulatory failure.
Passive leg raising (PLR) reliably predicts fluid responsiveness but requires a real-time cardiac index (CI) measurement or the presence of an invasive arterial line to achieve this effect. The plethysmographic variability index (PVI), an automatic measurement of the respiratory variation of the perfusion index, is non-invasive and continuously displayed on the pulse oximeter device. We tested whether PLR-induced changes in PVI (ΔPVIPLR) could accurately predict fluid responsiveness in mechanically ventilated patients with acute circulatory failure. This was a secondary analysis of an observational prospective study. We included 29 mechanically ventilated patients with acute circulatory failure in this study. We measured PVI (Radical-7 device; Masimo Corp., Irvine, CA) and CI (Echocardiography) before and during a PLR test and before and after volume expansion of 500 mL of crystalloid solution. A volume expansion-induced increase in CI of >15% defined fluid responsiveness. To investigate whether ΔPVIPLR can predict fluid responsiveness, we determined areas under the receiver operating characteristic curves (AUROCs) and gray zones for ΔPVIPLR. Of the 29 patients, 27 (93.1%) received norepinephrine. The median tidal volume was 7.0 [IQR: 6.6-7.6] mL/kg ideal body weight. Nineteen patients (65.5%) were classified as fluid responders (increase in CI > 15% after volume expansion). Relative ΔPVIPLR accurately predicted fluid responsiveness with an AUROC of 0.89 (95%CI: 0.72-0.98, p < 0.001). A decrease in PVI ≤ -24.1% induced by PLR detected fluid responsiveness with a sensitivity of 95% (95%CI: 74-100%) and a specificity of 80% (95%CI: 44-97%). Gray zone was acceptable, including 13.8% of patients. The correlations between the relative ΔPVIPLR and changes in CI induced by PLR and by volume expansion were significant (r = -0.58, p < 0.001, and r = -0.65, p < 0.001; respectively). In sedated and mechanically ventilated ICU patients with acute circulatory failure, PLR-induced changes in PVI accurately predict fluid responsiveness with an acceptable gray zone. ClinicalTrials.govNCT03225378.


Protocol for DEprescribing and Care to reduce Antipsychotics in Dementia (DECADE)-A hybrid effectiveness-implementation pilot study.
Behavioural and psychological symptoms of dementia (BPSD) should only rarely and briefly be treated with antipsychotics. Despite recommendations to the contrary, the use of antipsychotics in nursing home residents with dementia is widespread and followed by serious adverse effects. Intervention studies on methods to reduce the use of antipsychotics in persons with dementia are few and needed. The aim of this protocol is to describe the rationale and content of the intervention DEprescribing and Care to reduce Antipsychotics in DEmentia (DECADE)-a hybrid effectiveness-implementation pilot study. This is a protocol of a prospective hybrid effectiveness-implementation pilot study. The primary aim of DECADE is to reduce the use of antipsychotic drugs by 50% in 50% of nursing home residents with dementia while maintaining or improving BPSD. The intervention is implemented in six nursing homes including approximately 190 residents with dementia and consists of Academic Detailing, medication review, education of nursing home staff, and care plans. The evaluation of feasibility and potential effectiveness is an overall assessment of all clinical and process outcomes. Logistic regression analyses will be used to investigate factors characterizing situations with prescription of antipsychotics. BPSD is analysed with a before- and after design using self-controlled case series methods and the use of antipsychotics is analysed as interrupted time series. This protocol describes a study that will provide an indication of DECADE effectiveness and a model for upscaling and further evaluation in a controlled design.


[Results and complications of expanded polytetrafluoroethylene in frontalis suspension ptosis surgery. Study of 59 cases].
To evaluate the functional results and complications of the use of expanded polytetrafluoroethylene (ePTFE) in frontalis suspension surgery for the treatment of moderate-severe palpebral ptosis (> 3 mm) with poor or absent levator muscle function. Retrospective study of 59 frontalis suspension procedures performed between 1992 and 2003 on 38 patients with palpebral ptosis (21 bilateral). Seventeen (44.7%) cases were women and 21 (55.3%) men. The mean age was 51.7 S.D. 27.6 years (range, 2 to 87). The surgical techniques used were performed by a Wright fascia needle. The etiology, ptosis grade, levator function, Bell's phenomenon and frontalis compensation were studied. After a median follow-up time of 35.9 S.D. 18.5 months (range, 6 to 72), we observed that the functional results were good in 55 cases (93.2%). Infection with preseptal cellulitis appeared in 1 case (1.7%) and required removal of the material, and in 2 cases (3.4%) there were foreign body granulomas that were resolved by excision. Two cases (3.4%) had to be reoperated due to recurrence. The ePTFE, in our experience, is a good material with excellent functional results and relatively few complications in the surgical treatment of eyelid ptosis for frontalis suspension. Other synthetic materials or fascia lata may be used, but all carry the risk of potential infection, extrusion, granuloma formation or recurrence.


Probing myosin structural conformation in vivo by second-harmonic generation microscopy.
Understanding of complex biological processes requires knowledge of molecular structures and measurement of their dynamics in vivo. The collective chemomechanical action of myosin molecules (the molecular motors) in the muscle sarcomere represents a paradigmatic example in this respect. Here, we describe a label-free imaging method sensitive to protein conformation in vivo. We employed the order-based contrast enhancement by second-harmonic generation (SHG) for the functional imaging of muscle cells. We found that SHG polarization anisotropy (SPA) measurements report on the structural state of the actomyosin motors, with significant sensitivity to the conformation of myosin. In fact, each physiological/biochemical state we probed (relaxed, rigor, isometric contraction) produced a distinct value of polarization anisotropy. Employing a full reconstruction of the contributing elementary SHG emitters in the actomyosin motor array at atomic scale, we provide a molecular interpretation of the SPA measurements in terms of myosin conformations. We applied this method to the discrimination between attached and detached myosin heads in an isometrically contracting intact fiber. Our observations indicate that isometrically contracting muscle sustains its tetanic force by steady-state commitment of 30% of myosin heads. Applying SPA and molecular structure modeling to the imaging of unstained living tissues provides the basis for a generation of imaging and diagnostic tools capable of probing molecular structures and dynamics in vivo.


TeenEARS: development of a pilot assessment battery for cochlear implanted adolescents.
Changes in selection criteria have led to the inclusion of pre-lingually deafened adolescents as potential cochlear implant candidates, depending on their degree of residual hearing, access to and use of acoustic amplification, use of oral communication, and other factors such as motivation and support. Outcomes results in adolescents vary widely, and it has become evident that there is a need for a test battery that can assess a wide range of skills over time. This article presents the development and validation of one such test battery: TeenEARS. Eleven tests were assessed for inclusion in the test battery. Consideration was given to the ability of the test to measure improvement over time; the fact that there needed to be easier and more difficult tests in terms of language, communication and listening; the need for closed and open-set assessments; and a range of listening tasks: from sounds to conversational language. Data on 23 adolescents assessed and judgment based on clinical experience resulted in eight tests being included in the TeenEARS test battery.


Identification of regions in HIV-1 Nef required for efficient downregulation of cell surface CD4.
Downregulation of cell surface CD4 is a characteristic property of all lentiviral Nef proteins. We have used mutational analysis to define regions within HIV-1 Nef that are critical for this biological activity. Two discontinuous regions in Nef, extending approximately from residues 96 to 144 and from residues 175 to 186, are reported to be essential for efficient CD4 downregulation. Interestingly, these sequences coincide with two conserved regions of the Nef protein that are juxtaposed to form a single surface on the known structure of Nef. A third, more amino terminal conserved region in Nef, previously reported to be important for Nef enhancement of virion infectivity, was found to be largely dispensable for CD4 downregulation. These data raise the possibility that Nef may contain two structurally distinct functional domains, only one of which contributes to the CD4 downregulation phenotype.


Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teriparatide in Postmenopausal Women With Low Bone Mass.
Romosozumab is a monoclonal antibody that inhibits sclerostin and has been shown to reduce the risk of fractures within 12 months. In a phase II, randomized, placebo-controlled clinical trial of treatment-naïve postmenopausal women with low bone mass, romosozumab increased bone mineral density (BMD) at the hip and spine by the dual effect of increasing bone formation and decreasing bone resorption. In a substudy of that trial, which included placebo and teriparatide arms, here we investigated whether those observed increases in BMD also resulted in improvements in estimated strength, as assessed by finite element analysis. Participants received blinded romosozumab s.c. (210 mg monthly) or placebo, or open-label teriparatide (20 μg daily) for 12 months. CT scans, obtained at the lumbar spine (n = 82) and proximal femur (n = 46) at baseline and month 12, were analyzed with finite element software (VirtuOst, O.N. Diagnostics) to estimate strength for a simulated compression overload for the spine (L1 vertebral body) and a sideways fall for the proximal femur, all blinded to treatment assignment. We found that, at month 12, vertebral strength increased more for romosozumab compared with both teriparatide (27.3% versus 18.5%; p = 0.005) and placebo (27.3% versus -3.9%; p < 0.0001); changes in femoral strength for romosozumab showed similar but smaller changes, increasing more with romosozumab versus teriparatide (3.6% versus -0.7%; p = 0.027), and trending higher versus placebo (3.6% versus -0.1%; p = 0.059). Compartmental analysis revealed that the bone-strengthening effects for romosozumab were associated with positive contributions from both the cortical and trabecular bone compartments at both the lumbar spine and hip. Taken together, these findings suggest that romosozumab may offer patients with osteoporosis a new bone-forming therapeutic option that increases both vertebral and femoral strength within 12 months. © 2017 American Society for Bone and Mineral Research.


The pharmacologic effects of PGE1 on murine lymphocytes.
Although PGE1, in pharmacologic quantities, possesses significant in vivo immune-modulating activities, its effects on different lymphoid populations have not been defined. In the present study, lymphocyte numbers, turnover rates, and functional activities were assessed in Swiss-Webster mice receiving PGE1, 200 microgram twice daily, for up to 14 days. The most pronounced cellular alterations were observed in the thymus. After 2 wk, the number of theta-positive cells decreased by 81%. Total splenic cellularity was concomitantly reduced by 28%. This was primarily due to a loss of B lymphocytes; the number of these cells decreased by 40%. Bone marrow lymphocytes were also decreased by PGE1 administration. By contrast, peripheral blood lymphocytes and splenic T cells were not significantly altered. Similar changes in lymphocyte numbers were observed in adrenalectomized mice, indicating that depletion was not due to a corticosteroid effect. In normal mice, PGE1 reduced the in vivo incorporation of 3HTdr in both the thymus and the spleen by approximately 50%; this finding, in conjunction with histologic and cytologic observations, suggests a decrease in intrinsic rates of lymphopoiesis. Residual splenocytes were not impaired in their in vitro responses to three polyclonal mitogens: PHA, Con-A, and endotoxin. Studies in cortisol-treated mice showed that PGE1 caused a decrease in both steroid-sensitive and steroid-resistant thymocytes and splenocytes.


Budding behaviors: Growth of the limb as a model of morphogenesis.
Questions regarding morphogenesis have played second fiddle to those pertaining to pattern formation among the limb development set for some time. A recent series of publications has reinvigorated the search for mechanisms by which the limb bud arises, elongates and acquires its peculiar shape. While there are stage-specific variations, the theme that resonates across these studies is that mesoderm and cartilage cells in the limb bud exhibit polarity that drives directional movement and oriented division. Noncanonical Wnt signalling is important for these cell behaviors at all stages of limb development. While the emerging morphogenetic mechanisms underlying limb bud outgrowth are partly analogous to those of other developing structures, insights from the limb have the potential to reveal intriguing new mechanisms by which three dimensional mesoderm changes shape.


Antioxidant defenses in the peripheral cell layers of legume root nodules.
Ascorbate peroxidase (AP) is a key enzyme that scavenges potentially harmful H2O2 and thus prevents oxidative damage in plants, especially in N2-fixing legume root nodules. The present study demonstrates that the nodule endodermis of alfalfa (Medicago sativa) root nodules contains elevated levels of AP protein, as well as the corresponding mRNA transcript and substrate (ascorbate). Enhanced AP protein levels were also found in cells immediately peripheral to the infected region of soybean (Glycine max), pea (Pisum sativum), clover (Trifolium pratense), and common bean (Phaseolus vulgaris) nodules. Regeneration of ascorbate was achieved by (homo)glutathione and associated enzymes of the ascorbate-glutathione pathway, which were present at high levels. The presence of high levels of antioxidants suggests that respiratory consumption of O2 in the endodermis or nodule parenchyma may be an essential component of the O2-diffusion barrier that regulates the entry of O2 into the central region of nodules and ensures optimal functioning of nitrogenase.


Influence of the microporous substratum and hydrodynamics on resistances to drug transport in cell culture systems: calculation of intrinsic transport parameters.
Although cell culture models are increasingly used to study drug transport and metabolism, the influence of the substratum on the transport properties of the cell monolayer has not been studied in great detail. Furthermore, the use of effective (or apparent) permeabilities (Peff) assumes that the contribution of the microporous filter substratum and the aqueous boundary layer (ABL) to transport are negligible or are at least constant for a series of drugs. In the present study, the permeabilities of the substratum, ABL, and monolayer were obtained for a series of compounds at variable flow rates in side-by-side diffusion chambers. Comparisons of transport properties were made between cell monolayers grown on substrata made of polycarbonate (PC) and polyester (PE). All paracellular markers demonstrated a reduction in permeability and a corresponding increase in transepithelial electrical resistance (TEER) through PE-grown monolayers. The permeabilities of two carrier-mediated compounds, phenylalanine and proline, were 55% higher and 48% lower through PE-grown monolayers than through the PC-grown monolayers, respectively. The resistance to progesterone transport attributed to the PE and PC filters was large (71% and 27% of total resistance, respectively) at a flow rate of 20 mL/min, indicating that the monolayer was not the rate-limiting transport barrier. Therefore, for highly permeable compounds, reporting Peff has limited value since it is an indicator of the transport properties of the substratum rather than of the monolayer. These results demonstrate that substratum properties (e.g., membrane composition, pore size, etc.) significantly affect the barrier properties of the Caco-2 cell monolayer. The most probable mechanism is by the modulation of the functional expression of nutrient and ion transporters resulting in variable transcellular and paracellular transport properties. These results further demonstrate the importance of calculating intrinsic membrane transport parameters if the monolayer is not maintained as the rate-determining barrier in the transport experiment. Using higher flow rates and higher porosity substrata supports may help maintain the monolayer as the rate-limiting transport barrier.


IFN-α-Induced Downregulation of miR-221 in Dendritic Cells: Implications for HCV Pathogenesis and Treatment.
Although interferon (IFN)-α is known to exert immunomodulatory and antiproliferative effects on dendritic cells (DCs) through induction of protein-coding IFN-stimulated genes (ISGs), little is known about IFN-α-regulated miRNAs in DCs. Since several miRNAs are involved in regulating DC functions, it is important to investigate whether IFN-α's effects on DCs are mediated through miRNAs as well. In this study, we examined miRNA expression patterns in myeloid DCs (mDCs) and plasmacytoid DCs after exposing them to IFN-α. We report that IFN-α downregulates miR-221 in both DC subsets via inhibition of STAT3. We validated proapoptotic proteins BCL2L11 and CDKN1C as miR-221 targets suggesting that IFN-α can induce DC apoptosis via miR-221 downregulation. In addition, we validated another miR-221 target, SOCS1, which is known to be a negative regulator of JAK/STAT signaling. Consistent with this, miR-221 overexpression in mDCs enhanced the secretion of proinflammatory cytokines IL-6 and TNF-α. In peripheral blood mononuclear cells (PBMCs) of HIV-1/HCV co-infected individuals undergoing IFN-α-based treatment the baseline miR-221 expression was lower in non-responders compared with responders; and miR-221 expression directly correlated with DC frequency and IL-6/TNF-α secretion. In addition to PBMCs, we isolated total liver cells and kupffer cells from HCV-infected individuals and individuals with alcoholic cirrhosis. We found that both total liver cells and kupffer cells from HCV-infected individuals had significantly higher miR-221 levels compared with individuals with cirrhosis. Overall, we demonstrate that IFN-α exerts both antiproliferative and immunomodulatory effects on mDCs via miR-221 downregulation; and IFN-miR-221 axis can play important role in HCV pathogenesis and treatment.


A large-deformation phase transition electrothermal actuator based on carbon nanotube-elastomer composites.
An electrothermal phase transition actuator based on a superaligned carbon nanotube film and elastomers has been designed and fabricated. Compared with a conventional electrothermal bimorph actuator using cantilever structures, this new-type actuator introduces a novel concept of phase transition large-deformation actuation. The actuator consists of an enclosed cavity made up of highly elastic elastomers and an embedded carbon nanotube based electrical heater. A low-boiling liquid was injected into the cavity and it can vaporize rapidly to make the elastic cavity expand significantly when electrically heated. The size and speed of the expansion can be easily controlled by the applied voltage (electrical power). The expanded elastomer membrane can lift more than 1000 times of its own weight. The cyclic actuation test shows the excellent durability of the actuator. A heart-shaped closed liquid circulation system based on the phase transition pump-type actuators has been made, which can work like a real heart. Owing to the advantages of low driving voltage, large deformation, simple fabrication, easy operation, lightweight and durability, we think that the phase transition actuator will have great potential usage in various areas, such as artificial muscles, soft robots, sensors, and especially in the biomedical field.


Demographic, epidemiological and nutritional profile of elders using home enteral nutritional therapy in Distrito Federal, Brazil.
According to statistical projections of the World Health Organization, during the period between 1950 and 2025, the group of elderly in Brazil will have increased 15 times. Chronic-degenerative diseases are the illnesses that most affect the elderly population, directly related to the growing demand for Enteral Nutrition Therapy. The objective of this study was to analyze the demographic, epidemiological and nutritional profile of elderly patients assisted at the public hospitals in the Home Enteral Nutrition Therapy Program, of the State Health Department of Distrito Federal. This is a retroprospective, cross-sectional and analytical study, based on primary data, which enrolled 141 elderly patients who were prescribed home enteral nutrition. The collected variables corresponded to age, gender, clinical diagnosis, enteral route and nutritional status at the beginning of Home Enteral Nutrition Therapy. The association between variables was analyzed through the t-Student and chi-square tests, with a significance level of 0.05 and a Confidence Interval (CI) of 95%. There was a higher number of female patients (53.9%) when compared to male (46.1%), average age 75.82 years old for both groups. The most prevalent diseases were cerebro-vascular accident sequels and cancer (42.6% and 22.7% respectively). It was observed a prevalence of malnutrition equal to 69.7%, independent of age and gender. The most used enteral route was the nasal. Though Brazilian policies concerning assistance to the elderly have advanced during the last few years, the need for public policies for nutritional recovery of such patients persists, to promote a better quality of life for them.


The critical role of germinal center-associated nuclear protein in cell biology, immunohematology, and hematolymphoid oncogenesis.
Germinal center-associated nuclear protein (GANP) is a unique and multifunctional protein that plays a critical role in cell biology, neurodegenerative disorders, immunohematology, and oncogenesis. GANP is an orthologue of Saccharomyces Sac3, one of the components of the transcription export 2 (TREX-2) complex and a messenger RNA (mRNA) nuclear export factor. GANP is widely conserved in all mammals, including humans. Although GANP was originally discovered as a molecule upregulated in the germinal centers of secondary lymphoid follicles in peripheral lymphoid organs, it is expressed ubiquitously in many tissues. It serves numerous functions, including making up part of the mammalian TREX-2 complex; mRNA nuclear export via nuclear pores; prevention of R-loop formation, genomic instability, and hyper-recombination; and B-cell affinity maturation. In this review, we first overview the extensive analyses that have revealed the basic functions of GANP and its ancestor molecule Sac3, including mRNA nuclear export and regulation of R-loop formation. We then describe how aberrant expression of GANP is significantly associated with cancer development. Moreover, we discuss a crucial role for GANP in B-cell development, especially affinity maturation in germinal centers. Finally, we illustrate that overexpression of GANP in B cells leads to lymphomagenesis resembling Hodgkin lymphoma derived from germinal center B cells, and that GANP may be involved in transdifferentiation of B cells to macrophages, which strongly affects Hodgkin lymphomagenesis.


Circadian rhythms in Neurospora: a new measurement, the reset zone.
The authors define a new feature of a circadian rhythm, the reset zone, and point out its usefulness for predictions concerning oscillator behavior. The reset zone measures the responses of a circadian system to resetting pulses. It can be easily determined from a phase transition curve (PTC), which is simply a phase response curve (PRC) replotted as new phase versus old phase (Winfree's format). The reset zone is the range of new phases seen in such a plot and has two potentially useful characteristics: its size and its midpoint. A series of experiments with Neurospora involving temperature pulses indicated that the size of the reset zone changed in a nonlinear way in response to both the duration of 40 degrees C pulses and to the magnitude of temperature change for 3-h pulses. Other existing data are replotted to show how the reset zone size varies with growth temperature and with the period of different clock mutants. Employing exclusively reset zone data within the framework of a limit cycle displacement model, an equation is formulated that predicts the relative changes in the values of state variables of the oscillator for changes in any given environmental condition, such as temperature. Examples are also drawn from other organisms, such as hamsters, Gonyalaux, Kalanchoe, and Drosophila, illustrating the usefulness of the reset zone measurement. It can be used as a numerical scale for assessing the strength of a pulse, for comparing the relative effects of a given pulse applied to different organisms or mutants, for determining the directionality of the changes in state variables produced by various types of pulses, and possibly for measuring clock amplitude.


[Efficiency of a package of therapeutic and preventive measures in the Republic of Tajikistan in the malaria postepidemic period (2000-2007)].
In 2005, Tajikistan joined the Move of Elimination of Tropical Malaria in 2010 and Tertian Malaria to 2015 (Tashkent Declaration, WHO European Office for European). To achieve the targets and goals, it is necessary to evaluate the efficiency of therapeutic and preventive measures in 2000-2007, i.e. in the postepidemic period preceding elimination (pre-elimination according to the WHO terminology). Investigations were conducted in the Gorno-Badakhstan Autonomous Region, Khatlon and Sogdiysk Regions, in the districts under the Republic's jurisdiction, and in the city of Dushanbe. The results of the investigations has shown that a small proportion of the population has red blood cell glucose-6-phosphate dehydrogenase deficiency, which does not preclude mass preventive treatment with primaquine that is responsible for a 2.5-fold reduction in the number of foci (783 foci of different types). Foci should be typified for the rational use of a package of therapeutic and preventive measures in the endemic areas. Differentiated packages of therapeutic and preventive measures correspondingly to the National Malaria Strategy of the Republic of Tajikistan should be implemented depending on the type of a focus.


Factors influencing emergency department preference for access to healthcare.
African-Americans are more likely than Caucasians to access healthcare through the emergency department (ED); however, the reasons behind this pattern are unclear. The objective is to investigate the effect of race, insurance, socioeconomic status, and perceived health on the preference for ED use. This is a prospective study at a tertiary care ED from June to July 2009. Patients were surveyed to capture demographics, healthcare utilization, and baseline health status. The primary outcome of interest was patient-reported routine place of healthcare. Other outcomes included frequency of ED visits in the previous 6 months, barriers to primary care and patient perception of health using select questions from the Medical Outcomes Study Short Form 36 (SF-36). Two hundred and ninety-two patients completed the survey of whom 58% were African-American and 44% were uninsured. African-Americans were equally likely to report 3 or more visits to the ED, but more likely to state a preference for the ED for their usual place of care (24% vs. 13%, p < 0.01). No significant differences between groups were found for barriers to primary care, including insurance. African-Americans less often reported comorbidities or hospitalization within the previous 6 months (23% vs. 34%, p = 0.04). On logistic regression modeling, African-Americans were more than 2 times as likely to select the ED as their usual place of healthcare (OR 2.24, 95% CI 1.22 - 4.08). African-Americans, independent of health insurance, are more likely than Caucasians to designate the ED as their routine place of healthcare.


Blocking two-component signalling enhances Candida albicans virulence and reveals adaptive mechanisms that counteract sustained SAPK activation.
The Ypd1 phosphorelay protein is a central constituent of fungal two-component signal transduction pathways. Inhibition of Ypd1 in Saccharomyces cerevisiae and Cryptococcus neoformans is lethal due to the sustained activation of the 'p38-related' Hog1 stress-activated protein kinase (SAPK). As two-component signalling proteins are not found in animals, Ypd1 is considered to be a prime antifungal target. However, a major fungal pathogen of humans, Candida albicans, can survive the concomitant sustained activation of Hog1 that occurs in cells lacking YPD1. Here we show that the sustained activation of Hog1 upon Ypd1 loss is mediated through the Ssk1 response regulator. Moreover, we present evidence that C. albicans survives SAPK activation in the short-term, following Ypd1 loss, by triggering the induction of protein tyrosine phosphatase-encoding genes which prevent the accumulation of lethal levels of phosphorylated Hog1. In addition, our studies reveal an unpredicted, reversible, mechanism that acts to substantially reduce the levels of phosphorylated Hog1 in ypd1Δ cells following long-term sustained SAPK activation. Indeed, over time, ypd1Δ cells become phenotypically indistinguishable from wild-type cells. Importantly, we also find that drug-induced down-regulation of YPD1 expression actually enhances the virulence of C. albicans in two distinct animal infection models. Investigating the underlying causes of this increased virulence, revealed that drug-mediated repression of YPD1 expression promotes hyphal growth both within murine kidneys, and following phagocytosis, thus increasing the efficacy by which C. albicans kills macrophages. Taken together, these findings challenge the targeting of Ypd1 proteins as a general antifungal strategy and reveal novel cellular adaptation mechanisms to sustained SAPK activation.


Histological patterns of gastritis in H. pylori-infected individuals with a family history of gastric cancer.
Different types of chronic gastritis, including antral predominant, corpus predominant, and multifocal pangastritis, are associated with Helicobacter pylori infection. Specific patterns of H. pylori gastritis that might characterize individuals with family histories of noncardia gastric cancer (GC) were investigated. Histopathological changes associated with H. pylori gastritis were assessed in 111 individuals with family histories of GC and in 77 without from a region with high prevalence of H. pylori infection and GC. Gastric biopsies were taken from 12 sites (antrum, five; corpus, six; and cardia, one). Individuals (age < 36 yr) with family histories of GC developed pangastritis and had higher H. pylori bacterial scores (p < 0.05) in the gastric corpus, whereas those without family histories of GC typically had antral predominant gastritis. The correlation between density of polymorphonuclear leukocytes and density of H. pylori at each biopsy site was statistically significant (p < 0.01). Pangastritis was associated with a higher density of lymphoid aggregates and follicles (p < 0.05) in the corpus of younger individuals (age < 36) and in the antrum of older individuals (age > or = 48) with positive family histories of GC. Pangastritis and high lymphoid follicle density associated with H. pylori infection were found in patients with family histories of GC. Because a family history of gastric carcinoma is associated with increased risk of gastric cancer development, characterization of histological patterns of gastritis may be applicable to gastric cancer screening and surveillance, especially in relatively young at-risk populations.


Diffraction of a one-dimensional phase grating in the deep Fresnel field.
We analyze theoretically the diffraction of phase gratings in the deep Fresnel field on the basis of the theory of scalar diffraction and Green's theorem and present the general formula for the diffraction intensity of a one-dimensional sinusoidal phase grating. The numerical calculations show that in the deep Fresnel region the diffraction distribution can be described by designating three characteristic regions that are influenced by the parameters of the grating. The microlensing effect of the interface of the phase grating provides the corresponding explanation. Moreover, according to the viewpoint that the diffraction intensity distribution is the result of the interference of the diffraction orders of the grating, we find that the diffraction patterns, depending on the carved depth of the phase grating, are determined by the contributing diffraction orders, their relative power, and the quasi-Talbot effect of the phase grating, which results from the second meeting of the diffraction orders carrying most of the power of the total field, as in the case of the amplitude grating.


Sexually transmitted diseases in homosexual males in Seville, Spain.
The absence of any official statistics on the prevalence of STD in homosexual men in Spain induced us to carry out a prospective study of new homosexual patients who consulted the STD Clinic of the School of Medicine in Seville, between January 1988 and December 1989. The aim of the study was to determine the prevalence of symptomatic and asymptomatic infections in this group of patients. 1805 patients were seen during the study period; 318 patients were homosexual of whom 309 agreed to participate in the study. Of the 309 homosexual men, 108 (35%) had symptoms and the remaining 201 (65%) were asymptomatic. In the symptomatic group the diagnoses were: syphilis 28 (25.9%); urethritis 40 (37%) (of these 40, 11 had Neisseria gonorrhoeae, five had Chlamydia trachomatis, five had Ureaplasma urealyticum, one had Herpes simplex virus and in 18 no pathogen was detected); genital herpes seven (6.4%). Eleven (10%) had concomitant infections. The following infections were found in the asymptomatic group: syphilis 23 (11.4%), N gonorrhoeae six (3%), C trachomatis two (1%), Herpes simplex virus one (0.5%). Antibodies against HIV were detected in 30 (9.6%) of the total group. Sexually transmitted diseases are common amongst homosexual men in Seville and many of these are asymptomatic.


Microbiological and real-time mechanical analysis of Bacillus licheniformis and Pseudomonas fluorescens dual-species biofilm.
In natural habitats, bacterial species often coexist in biofilms. They interact in synergetic or antagonistic ways and their interactions can influence the biofilm development and properties. Still, very little is known about how the coexistence of multiple organisms impact the multispecies biofilm properties. In this study, we examined the behaviour of a dual-species biofilm at the air-liquid interface composed by two environmental bacteria: Bacillus licheniformis and a phenazine mutant of Pseudomonas fluorescens. Study of the planktonic and biofilm growths for each species revealed that P. fluorescens grew faster than B. licheniformis and no bactericidal effect from P. fluorescens was detected, suggesting that the growth kinetics could be the main factor in the dual-species biofilm composition. To validate this hypothesis, the single- and dual-species biofilm were characterized by biomass quantification, microscopy and rheology. Bacterial counts and microscale architecture analysis showed that both bacterial populations coexist in the mature pellicle, with a dominance of P. fluorescens. Real-time measurement of the dual-species biofilms' viscoelastic (i.e. mechanical) properties using interfacial rheology confirmed that P. fluorescens was the main contributor of the biofilm properties. Evaluation of the dual-species pellicle viscoelasticity at longer time revealed that the biofilm, after reaching a first equilibrium, created a stronger and more cohesive network. Interfacial rheology proves to be a unique quantitative technique, which combined with microscale imaging, contributes to the understanding of the time-dependent properties within a polymicrobial community at various stages of biofilm development. This work demonstrates the importance of growth kinetics in the bacteria competition for the interface in a model dual-species biofilm.


Bifurcated drum occluder endograft for treatment of abdominal aortic aneurysm: an experimental study in dogs.
To evaluate a new, low profile, home-made, bifurcated drum occluder endograft (BDOEG), designed for percutaneous, transcatheter treatment of abdominal aortic aneurysm (AAA). AAA was created in 10 dogs with over-dilated Palmaz stents. To prevent back filling, the lumbar arteries, inferior mesenteric artery, and common internal iliac arteries were embolized. The BDOEG was constructed of a drum occluder device and two PTFE endografts. The drum device consisted of a modified Z stent with Dacron stretched across and held within the ends of the stent, each with two 8 x 6-mm slits through which PTFE endografts were delivered. The PTFE endografts were 8 mm in diameter and 9.5 cm in length. Preloaded, the BDOEG was delivered through a 10-F sheath from both femoral arteries in a three-step procedure. All 10 animals were treated with BDOEG. Aortography was performed immediately, 6 weeks, and 12 weeks after stent-graft placement. Five animals were killed at 6 weeks and five were killed at 3 months. Gross and histologic evaluation was performed. The infrarenal aortic diameters and both external iliac arteries ranged from 8.0 mm to 10.3 mm (mean, 9.4 mm +/- 0.6) and from 5.2 mm to 6.8 mm (mean, 5.8 mm +/- 0.5), respectively. Creation of the AAA was successful in all 10 dogs. AAA diameters ranged from 13.7 mm to 15.9 mm (mean, 14.9 mm +/- 0.7). Complete exclusion of the AAA was achieved immediately after BDOEG placement and aneurysms remained excluded without perigraft leak to the time of killing in all 10 animals. There was a high incidence of aortoiliac limb occlusion. Occlusion of 12 aortoiliac limbs (60%) caused by intimal hyperplasia at the distal end of the endografts in iliac arteries developed in nine animals (90%). In six animals (60%), one limb occluded and, in three animals (30%), there was occlusion of both limbs. This study suggests a new approach for treatment of AAA. BDOEG use reduces sheath size for endograft delivery and may eliminate the need for a surgical cut down on femoral arteries. Tapering of the iliac ends of endografts to the size of the artery will be needed to prevent distal intimal hyperplasia.


Sensitive and specific monoclonal antibody recognition of human lung cancer antigen on preserved sputum cells: a new approach to early lung cancer detection.
Murine monoclonal antibodies (Mabs) to a glycolipid antigen of small-cell (SCC) and a protein antigen of non-small-cell lung cancer (NSCC) were applied to preserved sputum specimens from individuals who participated in The Johns Hopkins Lung Project (JHLP). In that study, undertaken in 1973 to evaluate the efficacy of sputum cytology screening, half of the high-risk participants (5,226 men, greater than or equal to 45 years of age, currently smoking greater than or equal to 1 pack of cigarettes per day) were randomly assigned to produce specimens for cytopathological analysis. During regular screenings over the next 5 to 8 years, 626 (12%) showed moderate (or greater) atypia. Sixty-nine of these (26 who progressed to cancer, 43 who did not) were randomly selected for a blinded improved Mab immunostaining protocol in the present study. Satisfactory specimens with morphologic atypia immunostained positively in 14 of the 22 patients who eventually progressed to cancer (sensitivity 64%), and were nonreactive in 35 of the 40 patients who did not progress to lung cancer (specificity 88%). Review of the true positive specimens (14/22 atypias) showed that they were collected 24 months in advance of diagnosis. In contrast, the 8/22 false negative atypias (failure to stain) showed that they were collected for an average of 57 months preceding the diagnosis of cancer. Subsequent specimens (average, 26 months before cancer) from participants who were originally considered "false negative" did stain positively improving sensitivity to 91% among specimens collected for an average of 2 years in advance of the clinical appearance of lung cancer. Specificity remained at 88%. Recognition of neoplastic antigen expression 2 years in advance of clinical cancer may be a valuable intermediate end point in studies of lung cancer prevention, detection, and therapy.


One-year outcomes of community-acquired and healthcare-associated pneumonia in the Veterans Affairs Healthcare System.
While studies have demonstrated higher medium-term mortality for community-acquired pneumonia (CAP), mortality and costs have not been characterized for healthcare-associated pneumonia (HCAP) over a 1-year period. We conducted a retrospective cohort study to evaluate mortality rates and health system costs for patients with CAP or HCAP during initial hospitalization and for 1 year after hospital discharge. We selected 50 758 patients admitted to the Veterans Affairs (VA) healthcare system between October 2003 and May 2007. Main outcome measures included hospital, post-discharge, and cumulative mortality rates and cost during initial hospitalization and at 12 months following discharge. Hospital and 1-year HCAP mortality were nearly twice that of CAP. HCAP was an independent predictor for hospital mortality (odds ratio (OR) 1.62, 95% confidence interval (CI) 1.49-1.76) and 1-year mortality (OR 1.99, 95% CI 1.87-2.11) when controlling for demographics, comorbidities, pneumonia severity, and factors associated with multidrug-resistant infection, including immune suppression, previous antibiotic treatment, and aspiration pneumonia. HCAP patients consistently had higher mortality in each stratum of the Charlson-Deyo-Quan comorbidity index. HCAP patients incurred significantly greater cost during the initial hospital stay and in the following 12 months. Demographics and comorbid conditions, particularly aspiration pneumonia, accounted for 19-33% of this difference. HCAP represents a distinct category of pneumonia with particularly poor survival up to 1 year after hospital discharge. While comorbidities, pneumonia severity, and risk factors for multidrug-resistant infection may interact to produce even higher mortality compared to CAP, they alone do not explain the observed differences.


Folate deficiency induces cell-specific changes in the steady-state transcript levels of genes involved in folate metabolism and 1-carbon transfer reactions in human colonic epithelial cells.
Intracellular folate homeostasis is essential for the 1-carbon transfer reactions necessary for DNA synthesis and biological methylation reactions in colonic epithelial cells. Perturbed 1-carbon transfer reactions resulting from folate depletion predispose normal colonic epithelial cells to neoplastic transformation while inhibiting the growth of colon cancer cells. Using an in vitro model of folate deficiency, we determined the effects of folate deficiency on the steady-state transcript levels of genes involved in intracellular folate metabolism and 1-carbon transfer reactions in HCT116 and Caco2 human colon adenocarcinoma cells. In HCT116 cells, folate depletion was associated with changes in transcript levels of genes favoring increased folate uptake and intracellular folate retention, the provision of metabolically more effective substrates for folate-dependent enzymes, and reduced folate hydrolysis and efflux. In HCT116 cells, folate depletion was associated with changes in transcript levels of genes favoring the preferential shuttling of the flux of 1-carbon units to the methionine cycle over the nucleotide synthesis pathway. In Caco2 cells, some adaptive responses in response to folate depletion were not as apparent as in HCT116 cells, and in some cases, the direction of change was counterintuitive. In Caco2 cells, the metabolic priority in response to folate depletion was to shuttle the available folate pools to the nucleotide biosynthesis pathway at the expense of biological methylation reactions. In both HCT116 and Caco2 cells, folate depletion was associated with the conservation of the existing pattern and extent of DNA methylation.


The role of thiamine in cancer: possible genetic and cellular signaling mechanisms.
The relationship between supplemental vitamins and various types of cancer has been the focus of recent investigation, and supplemental vitamins have been reported to modulate cancer rates. A significant association has been demonstrated between cancer and low levels of thiamine in the serum. Genetic studies have helped identify a number of factors that link thiamine to cancer, including the solute carrier transporter (SLC19) gene, transketolase, transcription factor p53, poly(ADP-ribose) polymerase-1 gene, and the reduced form of nicotinamide adenine dinucleotide phosphate. Thiamine supplementation may contribute to a high rate of tumor cell survival, proliferation and chemotherapy resistance. Thiamine has also been implicated in cancer through its effects on matrix metalloproteinases, prostaglandins, cyclooxygenase-2, reactive oxygen species, and nitric oxide synthase. However, some studies have suggested that thiamine may exhibit some antitumor effects. The role of thiamine in cancer is controversial. However, thiamine deficiency may occur in patients with cancer and cause serious disorders, including Wernicke's encephalopathy, that require parenteral thiamine supplementation. A very high dose of thiamine produces a growth-inhibitory effect in cancer. Therefore, further investigations of thiamine in cancer are needed to clarify this relationship.


Oral health-related quality of life of children with craniofacial conditions.
Evaluation of the Dutch Child Oral Health Impact Profile (COHIP), assessing the level of concordance between parents and children. The internal consistency and the predictive validity of the COHIP for self-reported general health were examined. Sample size was 35 pairs of parents and children age 11 to 14 with craniofacial conditions. Cronbach alphas were calculated and the level of concordance between parents and children was studied using t tests and intraclass correlations. Predictive validity was assessed using Pearson correlations and linear regression analyses. The COHIP and its subscales, except for one, had satisfactory to high Cronbach alphas (.59 to .94). Parents and children did not differ significantly. Correlations between parents and children were high (.62 to .91). Only "Oral symptoms" proved to be a significant predictor of general health, but only in the parent sample. In spite of the high level of concordance found, proxy reports have to be considered complementary to the reports of the children themselves. The Dutch version of the COHIP performs adequately, but could use some further psychometric evaluation and revision. It does not seem advisable to use the subscales separately as predictors in the same regression model, since they are strongly intercorrelated. For use in craniofacial patients, further validation is needed on a larger sample and some items need to be revised or removed. Finally, given the small number of cases, conclusions must be drawn with caution.


Effect of band and knife castration of beef calves on welfare indicators of pain at three relevant industry ages: II. Chronic pain.
Three experiments were conducted to evaluate the effects of band and knife castration on behavioral and physiological indicators of chronic pain in beef calves at 3 different ages (36 calves/age group): 1 wk of age (Exp. 1, 4 ± 1.1 d of age, 43 ± 1.1 kg BW), 2 mo of age (Exp. 2, 63 ± 2.3 d of age, 92 ± 1.7 kg BW), and 4 mo of age (Exp. 3, 125 ± 4.6 d of age, 160 ± 3.4 kg BW). In each experiment calves were randomly assigned to either sham (CT), band (BA) or knife (KN) castration. Experiments 1, 2, and 3 ended when the testicles of banded calves had sloughed off (68, 49, and 42 d, respectively). Animal BW and rectal temperature were recorded weekly over the experimental period. Salivary cortisol, substance P, haptoglobin, scrotal area temperature using infrared thermography, visual evaluation of swelling (5-point scale), and gait stride length were collected on d -1 and immediately before castration and weekly thereafter until the end of the study. Hair samples were collected 1 d prior to and 28 d after castration and at the end of the study for cortisol concentration. Standing and lying behaviors were recorded over a 28-d period immediately after castration. No differences ( > 0.10) were observed in salivary cortisol, substance P, haptoglobin, or hair cortisol among castration methods for any of the 3 ages. No changes in behavior were observed in calves castrated at 1 wk or 2 mo of age. In 4 mo-old-calves, BA spent less time lying ( < 0.01) than CT and KN calves. Also, the average duration of lying time for BA calves was greater ( < 0.05) than for CT calves. Both, 1-wk- and 2-mo-old calves had inflammation in the scrotal area lasting 7 d after KN castration, whereas inflammation was observed for up to 14 d in 4-mo-old calves. Swelling in BA calves lasted for 21 to 28 d in the 2 younger groups of calves, whereas in 4-mo-old calves swelling was observed until d 35 postcastration. Knife- and band-castrated calves did not exhibit indicators of chronic pain or distress when the procedures were performed in calves younger than 2 mo of age. Therefore, pain mitigation should be used when castrating to improve animal welfare, especially when castrations are performed in calves older than 2 mo of age independent of the method of castration.


Refining Measurement of Substance Use Disorders Among Women of Child-Bearing Age Using Hospital Records: The Development of the Explicit-Mention Substance Abuse Need for Treatment in Women (EMSANT-W) Algorithm.
Substance use disorder (SUD) in women of reproductive age is associated with adverse health consequences for both women and their offspring. US states need a feasible population-based, case-identification tool to generate better approximations of SUD prevalence, treatment use, and treatment outcomes among women. This article presents the development of the Explicit Mention Substance Abuse Need for Treatment in Women (EMSANT-W), a gender-tailored tool based upon existing International Classification of Diseases, 9th Edition, Clinical Modification diagnostic code-based groupers that can be applied to hospital administrative data. Gender-tailoring entailed the addition of codes related to infants, pregnancy, and prescription drug abuse, as well as the creation of inclusion/exclusion rules based on other conditions present in the diagnostic record. Among 1,728,027 women and associated infants who accessed hospital care from January 1, 2002 to December 31, 2008 in Massachusetts, EMSANT-W identified 103,059 women with probable SUD. EMSANT-W identified 4,116 women who were not identified by the widely used Clinical Classifications Software for Mental Health and Substance Abuse (CCS-MHSA) and did not capture 853 women identified by CCS-MHSA. Content and approach innovations in EMSANT-W address potential limitations of the Clinical Classifications Software, and create a methodologically sound, gender-tailored and feasible population-based tool for identifying women of reproductive age in need of further evaluation for SUD treatment. Rapid changes in health care service infrastructure, delivery systems and policies require tools such as the EMSANT-W that provide more precise identification methods for sub-populations and can serve as the foundation for analyses of treatment use and outcomes.


Cell-based meniscal tissue engineering: a case for synoviocytes.
Avascular meniscal injuries are largely incapable of healing; the most common treatment remains partial meniscectomy despite the risk of subsequent osteoarthritis. Meniscal responses to injury are partially mediated through synovial activity and strategies have been investigated to encourage healing through stimulating or transplanting adjacent synovial lining. However, with their potential for chondrogenesis, synovial fibroblast-like stem cells hold promise for meniscal cartilage tissue engineering. Thus, specific purposes of this review were to (1) examine how the synovial intima and synoviomeniscal junction affect current meniscal treatment modalities; and (2) examine the components of tissue engineering (cells, scaffolds, bioactive agents, and bioreactors) in the specific context of how cells of synovial origin may be used for meniscal healing or regeneration. An online bibliographic search through PubMed was performed in March 2010. Studies were subjectively evaluated and reviewed if they addressed the question posed. Fifty-four resources were initially retrieved, which offered information on the chondrogenic potential of synovial-based cells that could prove valuable for meniscal fibrocartilage engineering. Based on the positive effects of adjoining synovium on meniscal healing as used in some current treatment modalities, the chondrogenic potential of fibroblast-like stem cells of synovial origin make this cell source a promising candidate for cell-based tissue engineering strategies. The abundance of autologous synovial lining, its ability to regenerate, and the potential of synovial-derived stem cells to produce a wide spectrum of chondral matrix components make it an ideal candidate for future meniscal engineering investigations.


Proliferation of donor marrow and thymus cells in the myeloid and lymphoid organs of irradiated syngeneic host mice.
CBA/HT(6)T(6) bone marrow cells (1 x 10(7)) or CBA/H bone marrow cells (1 x 10(7)) plus CBA/HT(6)T(6) thymus cells (5 x 10(7)) were injected intravenously into lethally (800 R) irradiated CBA/H mice. Chromosome analyses of dividing cells in the host lymphoid and myeloid organs were performed at intervals after irradiation. Donor marrow cells settled and proliferated in the host bone marrow, spleen, and lymph nodes soon after injection, but donor marrow cells did not proliferate in the host thymus until day 10; then host-type cells were quickly replaced by donor-type cells in the thymus by day 20. On the other hand, donor thymus cells settled and proliferated in the host thymus and lymph nodes soon after injection but they gradually disappeared from these organs. On day 20, a few donor-type dividing cells (of thymus origin) were found in the host lymphoid and myeloid organs.


Mumefural, citric acid derivative improving blood fluidity from fruit-juice concentrate of Japanese apricot (Prunus mume Sieb. et Zucc).
The effects of food components on blood fluidity were studied by in vitro assay using a dedicated microchannel instrument for model capillaries. We found that the fruit-juice concentrate of the Japanese apricot (Prunus mume Sieb. et Zucc), a traditional Japanese food, markedly improved the fluidity of human blood. Using HPLC, we isolated the active compounds and characterized them using UV, MS, IR, and NMR. They included a novel compound, 1-[5-(2-formylfuryl)methyl] dihydrogen 2-hydroxypropane-1,2, 3-tricarboxylate (mumefural), and a related compound, 5-hydroxymethyl-2-furfural (HMF). Mumefural markedly improved blood fluidity in all subjects, while HMF worked differently in different individuals. The flow rate of blood spiked with mumefural or HMF was compared to that of the two predominant organic acids in the fruit. Citric acid, malic acid, and furfuryl alcohol also improved fluidity in all subjects. The activity of P. mume is derived from not only artifacts produced during thermal processing, such as mumefural, but also from endogenous organic acids.


Genetic characterization of circulating seasonal Influenza A viruses (2005-2009) revealed introduction of oseltamivir resistant H1N1 strains during 2009 in eastern India.
Influenza surveillance was implemented in Kolkata, eastern India in 2005 to identify the circulating subtypes and characterize their genetic diversity. Throat and nasal swabs were collected from outpatients with influenza-like illness (ILI). Of 2844 ILI cases identified at two referral hospitals during October 2005-September 2009, 309 (10.86%) were positive for Influenza A by real time RT-PCR, of which 110 (35.60%) were subtyped as H1N1 and 199 (64.40%) as H3N2. Comparison of the nucleotide (nt) and amino acid (aa) sequences of the HA1 gene for H1N1 and H3N2 strains showed that a subset of strains precede WHO recommended contemporary strains by 1-2 years. The Kolkata H1N1 strains clustered in Clade II, subgroup 2B with A/Brisbane/59/2007 but were distant from the corresponding vaccine strains (New Caledonia/20/99 and A/Solomon Island/3/06). The 2005-06 and 2007 H3N2 strains (15/17) clustered either A/Brisbane/10/2007-like (n=8) or A/Nepal/921/2006 like (n=7) strains, whereas 2008 strains (8/12) and 2009 strains (4/4) were similar to the 2010-11 vaccine strain A/Perth/16/2009. More aa substitutions were found in HA or NA genes of H3N2 than in H1N1 strains. No mutation conferring neuraminidase resistance was observed in any of the strain during 2005-08, however in 2009, drug resistant marker (H275Y) was present in seasonal H1N1, but not in co-circulating H3N2 strains. This is the first report of genetic characterization of circulating Influenza A strains from India. The results also highlight the importance of continuing Influenza surveillance in developing countries of Asia for monitoring unusual strains with pandemic potential and mutations conferring antiviral resistance.


An apparent association between glycosylphosphatidylinositol-anchored proteins and a sphingolipid in Tetrahymena mimbres.
Sphingolipids are thought to stabilize glycosylphosphatidylinositol (GPI)-anchored protein-rich membrane domains of yeast and polarized higher animal cells during the processing and targeting of these proteins to the plasma membrane. A widely used criterion for identifying the stable sphingolipid- and GPI-anchored protein-enriched membrane domains is the resistance of these lipid-modified proteins to solubilization by the detergent Triton X-100 (TX-100) at low temperature. Surprisingly, there have been no reports of sphingolipid/GPI-anchored protein association in protozoans, despite the fact that these cells contain considerably higher levels of GPI-anchored proteins than does any other organism. We report here the presence in Tetrahymena mimbres of a significant pool of GPI-anchored proteins which resisted extraction by 1% TX-100 at 4 degrees C but not at 37 degrees C. Of the total cellular complement of GPI-anchored proteins, which together accounted for more than 2% of whole-cell protein and were especially enriched in surface membranes, 10% of the major 63kDa component (gpi63) and 23% of a somewhat less abundant component (gpi23) were insoluble in TX-100 at 4 degrees C. A substantial proportion of the cell's only abundant sphingolipid, ceramideaminoethylphosphonate (CAEP), was also insoluble in 1% TX-100 at 4 degrees C. Radiolabelling studies involving [3H]leucine incorporation into proteins and [3H]palmitic acid incorporation into lipids revealed that the TX-100-resistant gpi63, gpi23 and CAEP molecules were all metabolically distinct from their TX-100-soluble counterparts in other compartments of the cell. The presence of detergent-resistant sphingolipid/GPI-anchored protein domains in non-polarized ciliate and trypanosomatid cells was probably obscured in previous studies by the profusion of accompanying detergent-soluble molecules.


Coupling heat waves and wildfires occurrence across multiple ecoregions within a Eurasia longitudinal gradient.
Understanding the relationship between heat waves occurrence and wildfires spread represents a key priority in global change studies due to the significant threats posed on natural ecosystems and society. Previous studies have not explored the spatial and temporal mechanism underlying the relationship between heat waves and wildfires occurrence, especially over large geographical regions. This study seeks to investigate such a relationship with a focus on 37 ecoregions within a Eurasia longitudinal gradient. The analysis is based on the wildfire dataset provided by the GlobFire Final Fire Event Detection and the meteorological dataset ERA5-land from Copernicus Climate service. In both cases we focused on the 2001-2019 timeframe. By means of a 12 km square grid, three wildfire metrics, i.e., density, seasonality, and severity of wildfires, were computed as proxy of fire regime. Heat waves were also characterized in terms of periods, duration, and intensity for the same period. Statistical tests were performed to evaluate the different patterns of heat waves and wildfires occurrence in the 37 ecoregions within the study area. By using Geographically Weighted Regression (GWR) we modeled the spatial varying relationships between heat waves characteristics and wildfires metrics. As expected, our results suggest that the 37 ecoregions identified within the Eurasia longitudinal gradient differ in terms of fire regimes. However, the occurrence of heat waves did not show significant differences among ecoregions, but a more evident variability in terms of relationship between fire regime metrics and heat waves within the study area. The outcome of the GWR analysis allowed us to identify the spatial locations (i.e., hotspot areas) where the relationship between heat waves and wildfires is positive and significant. Hence, in hotspots the presence of heat waves can be seen as a driver of wildfire occurrence in forest and steppe ecosystems. The findings from this study could contribute to a more comprehensive assessment of wildfire patterns in this geographical region, thus supporting cross-regional prevention strategies for disaster risk mitigation.


Microbial quality of raw aquacultured fish fillets procured from Internet and local retail markets.
The microbial quality of raw fillets of aquacultured catfish, salmon, tilapia, and trout was evaluated. A total of 272 fillets from nine local and nine Internet retail markets were tested. Mean values were 5.7 log CFU/g for total aerobic mesophiles, 6.3 log CFU/g for psychrotrophs, and 1.9 log most probable number (MPN) per gram for coliforms. Differences in these microbial levels between the two kinds of markets and among the four types of fish were not significant (P > 0.05), except that Internet trout fillets had about 0.8-log higher aerobic mesophiles than did trout fillets purchased locally. Although Escherichia coli was detected in 1.4, 1.5, and 5.9% of trout, salmon, and tilapia, respectively, no sample had > or = 1.0 log MPN/g. However, E. coli was found in 13.2% of catfish, with an average of 1.7 log MPN/g. About 27% of all fillets had Listeria spp., and a positive correlation between the prevalence of Listeria spp. and Listeria monocytogenes was observed. Internet fillets had a higher prevalence of both Listeria spp. and L. monocytogenes than did those fillets purchased locally. L. monocytogenes was present in 23.5% of catfish but in only 5.7, 10.3, and 10.6% of trout, tilapia, and salmon, respectively. Salmonella and E. coli O157 were not found in any sample. A follow-up investigation using catfish operation as a model revealed that gut waste exposed during evisceration is a potential source of coliforms and Listeria spp.


Immunotype epitopes of Neisseria meningitidis lipooligosaccharide types 1 through 8.
Lipooligosaccharides (LOS) of the eight immunotypes found in serogroup B Neisseria meningitidis were purified from their prototype strains grown in tryptic soy broth. Rabbit antisera to these LOS were prepared. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining revealed that most of the LOS antigens contained two major components; the larger components had apparent molecular weights (Mrs) in the range of 4,800 +/- 300, and the smaller components had an apparent Mr of 4,300. Immunoblot analysis showed that the larger major component of an LOS, in general, was much more immunogenic because the rabbits produced antibodies exclusively or primarily to this component even though the LOS immunogen contained both large and small major components. Antibodies to the smaller 4,300-Mr components were infrequently observed but, when present, were cross-reactive with the same-size components of all heterologous LOS. Hence, the immunotype epitopes reside in the larger major components of all immunotypes except type 5, in which a smaller major component having an apparent Mr of 4,400 carries the epitope. Rabbit antisera to types 1, 5, and 6 were immunotype specific. Antisera to other types had cross-reactivities with some heterologous LOS, and the larger components, but not the 4,300-Mr components, of the LOS were primarily responsible for the cross-reactivities. This finding suggests that the larger components of cross-reactive LOS have a similar structure in addition to their type-specific sugar moieties. The LOS of N. meningitidis M986, a strain used for the production of a serotype 2a vaccine, was found to contain the immunotype 7 epitope.


Association between antiseizure medications and quality of life in epilepsy: A mediation analysis.
The relationship between antiseizure medications (ASMs), which improve health outcomes by controlling seizures, and health-related quality of life (HRQOL) is poorly understood and may involve intermediate variables. We evaluated the potential mediators of the association between ASMs and HRQOL. Data are from an outpatient registry of adult patients with epilepsy seen at the Foothills Medical Center, Calgary, Alberta, Canada. Quality of life was measured using the 10-item Quality of Life in Epilepsy, and depression was measured using the Neurological Disorders Depression Inventory for Epilepsy. Propensity score matching was used to adjust for covariate imbalance between patients who received a single ASM (monotherapy) and those who received two or more ASMs (polytherapy) due to confounding. Mediation analysis was used to estimate the mediating effects of depression and ASM side effects on the association between patients' ASM polytherapy and HRQOL. Of 778 patients included in this analysis, 274 (35.2%) were on two or more ASMs. Patient-reported depression and ASM side effects jointly mediated the association between ASMs and HRQOL; these mediators accounted for 42% of the total average effect of ASM polytherapy ( β = -13.6, 95% confidence interval = -18.2 to -8.6) on HRQOL. These findings highlight the importance of managing depression and ASM side effects for improving health outcomes of patients requiring treatment with ASMs. Intervention programs aimed at improving HRQOL of patients with epilepsy need to target these potential mediators.


Leprosy research--setting priorities and facilitating collaborations: a personal perspective.
In recent years, as the prevalence of leprosy has declined and the tuberculosis epidemic has gained increasing attention, leprosy research has generally taken a 'back seat' to research in tuberculosis and other emerging and re-emerging infections. This has resulted as much from perceived differences of scientific opportunities in these fields as from differences of the disease burden. At the United States National Institutes of Health (NIH), research priority setting is typically based on a number of factors. In the case of leprosy research, the technical difficulties associated with this scientific area have clearly lessened enthusiasm for and progress in this field. Today, however, we are confronted by the reality of not having sufficient scientific understanding to explain a stable or increasing number of leprosy cases detected annually in the face of a dramatically decreasing total number of identified cases. We also lack adequate tools for diagnosis and prevention. At the same time, new molecular and cellular approaches and knowledge of the complete sequence of the genome of Mycobacterium leprae render leprosy research significantly more tractable than ever before. The combination of these factors has led a number of groups, including the National Institute of Allergy and Infectious Diseases of the NIH, to review the current state of knowledge in leprosy research and draft recommendations for future leprosy research priorities. It is clear that many of the necessary and exciting research activities can best be addressed through collaborations among investigators, with control programmes, and among countries of high and low endemicity.


Real-world treatment patterns in resectable (stages I-III) non-small-cell lung cancer: a systematic literature review.
Aim: The aim of this systematic literature review was to describe treatment patterns in nonmetastatic non-small-cell lung cancer. Methods: A search was conducted in MEDLINE and EMBASE. Eligible studies were multicentered (>50 patients) and conducted after 2000 in North America, Europe and Asia. Results: Twenty studies met the eligibility criteria. Based on US and Canadian studies in the resectable population, the proportion of patients who received neoadjuvant chemotherapy/chemoradiotherapy and adjuvant chemotherapy/chemoradiotherapy increased with increasing stage (i.e., from <3% in stage I to about 40% in stage III and from 15% in stage I to 30% in stage III, respectively). Within the resectable population, the breakdown between bimodal and trimodal therapy was variable, suggesting that clinical practice is not uniform. Conclusion: Overall, studies were heterogeneous, precluding data extrapolation across regions. Despite heterogeneity and limited evidence, this review suggested an increase in neoadjuvant and adjuvant chemotherapy with increasing stage, generally in line with treatment guidelines.


Vibrational characterization of granulosa cells from patients affected by unilateral ovarian endometriosis: New insights from infrared and Raman microspectroscopy.
Endometriosis is a chronic gynaecological disease characterised by the presence of endometrial cells in extra-uterine regions. One of the main factors impacting on the fertility of women affected by endometriosis is the poor oocyte quality. Granulosa Cells (GCs) regulate oocyte development and maintain the appropriate microenvironment for the acquisition of its competence; hence, the dysregulation of these functions in GCs can lead to severe cellular damages also in oocytes. In this study, luteinized GCs samples were separately collected from both ovaries of women affected by Unilateral Ovarian Endometriosis and analysed by infrared and Raman microspectroscopy. The spectral data were compared with those of GCs from women with diagnosis of tubal, idiopathic or male infertility (taken as control group). The coupling of these two spectroscopic techniques sheds new light on the alteration induced by this pathology on GCs metabolism and biochemical composition. In fact, the study revealed similar biochemical modifications in GCs from both ovaries of women affected by unilateral ovarian endometriosis, such as the alteration of the protein pattern, the induction of oxidative stress mechanisms, and the deregulation of lipid and carbohydrate metabolisms. These evidences suggest that unilateral endometriosis impairs the overall ovarian functions, causing alterations not only in the ovary with endometriotic lesions but also in the contralateral "healthy" one.


Current treatment options for osteoporosis.
The goals of treatment for patients with osteoporosis are to maintain normal bone and to prevent the deterioration of normal bone to osteoporotic bone. Achievement of these goals, combined with a successful approach to prevention of falls, may substantially decrease the incidence and risk of fractures. Strategies for osteoporosis therapy include patient strategies (e.g., administration of calcium, exercise), drug therapy to stimulate bone formation (e.g., fluoride, anabolic steroids), and drugs to inhibit bone resorption (e.g., estrogen replacement therapy, calcitonin, bisphosphonates).


Indocyanine green angiography of well-defined plaque choroidal neovascularization in age-related macular degeneration.
To determine the natural course of well-defined plaque choroidal neovascularization (CNV) using indocyanine green angiography. Two ophthalmologists, experts in macular diseases and indocyanine green angiography, examined 40 eyes with exudative age-related macular degeneration and a well-defined plaque CNV using complete ophthalmoscopic evaluation, fluorescein angiography, and indocyanine green angiography. The increase in the size of the plaques was analyzed using multivariate analysis, in relation to the worsening of visual acuity, with adjustment for age, sex, and length of follow-up. Mean follow-up was 13.5 months (median, 11 months). Initial and final mean visual acuity were 20/46 (median, 20/50) and 20/65 (median, 20/100), respectively. The mean initial size of the plaque was 6.62 mm2 (median, 6.20 mm2), and the mean final size was 10.40 mm2 (median, 9.76 mm2). The enlargement was statistically significant (P<.001). We found that plaque CNV tends to become larger with time, the enlargement reaching about 40% in 1 year of follow-up. The resulting loss of visual acuity, however, is not significant, and is slightly correlated with the extension of the lesion; it also does not appear to be directly related to sex.


Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model.
Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp(-/-)) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murineBcrppromoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP.


Soybean phytophthora resistance gene Rps8 maps closely to the Rps3 region.
Root and stem rot is one of the major diseases of soybean. It is caused by the oomycete pathogen Phytophthora sojae. A series of resistance genes (Rps) have been providing soybean with reasonable protection against this pathogen. Among these genes, Rps8, which confers resistance to most P. sojae isolates, recently has been mapped. However, the most closely linked molecular marker was mapped at about 10 cM from Rps8. In this investigation, we attempted to develop a high-density genetic map of the Rps8 region and identify closely linked SSR markers for marker-assisted selection of this invaluable gene. Bulk segregant analysis was conducted for the identification of SSR markers that are tightly linked to Rps8. Polymorphic SSR markers selected from the Rps8 region failed to show cosegregation with Phytophthora resistance. Subsequently, bulk segregant analysis of the whole soybean genome and mapping experiments revealed that the Rps8 gene maps closely to the disease resistance gene-rich Rps3 region.


Temporal dynamics of genetic variability in a mountain goat (Oreamnos americanus) population.
The association between population dynamics and genetic variability is of fundamental importance for both evolutionary and conservation biology. We combined long-term population monitoring and molecular genetic data from 123 offspring and their parents at 28 microsatellite loci to investigate changes in genetic diversity over 14 cohorts in a small and relatively isolated population of mountain goats (Oreamnos americanus) during a period of demographic increase. Offspring heterozygosity decreased while parental genetic similarity and inbreeding coefficients (F(IS) ) increased over the study period (1995-2008). Immigrants introduced three novel alleles into the population and matings between residents and immigrants produced more heterozygous offspring than local crosses, suggesting that immigration can increase population genetic variability. The population experienced genetic drift over the study period, reflected by a reduced allelic richness over time and an 'isolation-by-time' pattern of genetic structure. The temporal decline of individual genetic diversity despite increasing population size probably resulted from a combination of genetic drift due to small effective population size, inbreeding and insufficient counterbalancing by immigration. This study highlights the importance of long-term genetic monitoring to understand how demographic processes influence temporal changes of genetic diversity in long-lived organisms.


Image registration using the Walsh transform.
This paper presents a new algorithm which can be used to register images of the same or different modalities, e.g., images with multiple channels, such as X-rays, temperature or elevation, or simply images of different spectral bands. In particular, a correlation-based scheme is used, but instead of gray values, it correlates numbers formulated by different combinations of the extracted local Walsh coefficients of the images. Each image patch is expanded in terms of Walsh basis functions. Each Walsh basis function can be thought of as measuring a different aspect of local structure, e.g., horizontal edge, corner, etc. The coefficients of the expansion, therefore, can be thought of as dense local features, estimating at each point the degree of presence of, for example, a horizontal edge, a corner with contrast of a certain type, etc. These coefficients are normalized and used as digits in a chosen number system which allows one to create a unique number for each type of local structure. The choice of the basis of the number system allows one to give different emphasis to different types of local feature (e.g., corners versus edges), and, thus, the method we present forms a unified framework in terms of which several feature matching methods may be interpreted. The algorithm is compared with wavelet and contour based approaches, using simulated and real images. The two images are assumed to differ from each other by a rotation and a translation only.


Continual Learning for Cuffless Blood Pressure Measurement using PPG and ECG Signals.
Although numerous studies have been conducted on cuffless blood pressure (BP) estimation using machine learning methods, most of the data-driven models are static, with model parameters fixed after training is complete. However, BP is dynamic and the performance would degrade for a static model when the to-be predicted BP distribution deviates from the training BP distribution. In this paper, we propose a continual learning (CL) framework in which deep learning models are developed to learn dynamically and continuously for arterial BP (ABP) estimation with photoplethysmography (PPG) and electrocardiogram (ECG) waveforms. The effectiveness of the CL model is validated on UCI Repository and MIMIC-III database with a total of 132 individual samples, and compared with conventional training method. It was found that the CL model improved the ABP estimation accuracy in terms of mean absolute error (MAE) by 17.47% on average compared with conventional training model. Furthermore, the improvement increased with the variability of ABP. These results demonstrate that CL model has potential to estimate dynamic ABP, which has been challenging with conventional training.


Sex-Specific Population Differences in Resting Metabolism Are Associated with Intraspecific Variation in Sexual Size Dimorphism of Brown Anoles.
AbstractSexual size dimorphism can vary in direction and magnitude across populations, but the extent to which such intraspecific variation is associated with sex and population differences in underlying metabolic processes is unclear. We compared resting metabolic rates (RMRs) of brown anole lizards (Anolis sagrei) from two island populations in the Bahamas (Eleuthera and Great Exuma) that differ in the magnitude of male-biased sexual size dimorphism. Whereas females from each population exhibit similar growth rates and body sizes, males from Great Exuma grow more quickly and attain larger body sizes than males from Eleuthera. We found that these population differences in growth of males persisted in captivity. Therefore, we predicted that males from each population would differ in RMR, whereas females would not. Consistent with this prediction, we found that RMR of males from Eleuthera was higher than that of males from Great Exuma, particularly at higher temperatures. As predicted, RMR of females did not differ between populations. Despite this apparent sex-specific trade-off between growth rate and RMR at the population level, we found a positive relationship between growth rate and RMR at the individual level. The fact that Great Exuma males maintain lower RMR than Eleuthera males, despite their greater absolute growth rates and the positive relationship between RMR and growth rate across individuals, suggests that Great Exuma males may have lower baseline metabolic demands and/or greater growth efficiency than Eleuthera males. Our results call attention to sex-specific divergence in metabolism as a potential mechanism for intraspecific divergence in sexual size dimorphism.


Cobalt-Catalyzed Cross-Benzannulation of Conjugated Enynes and Diynes.
The [4 + 2] cross-benzannulation of conjugated enynes and diynes under cobalt-catalysis led to 1,2,3-trisubstituted benzene derivatives in good yields. The reaction proceeds smoothly in absolute regiospecific control when symmetrical diynes are applied. Moreover, the use of unsymmetrical diynes was investigated, resulting in the formation of the unprecedented regioisomers as major products, which is in contrast to the results obtained in palladium-catalyzed benzannulation reactions. Also, 4-bromophenyl-substituted starting materials could be applied successfully in the cobalt-catalyzed process, which can be problematic in the palladium-catalyzed counterpart.


Experimental design and optimisation (4): Plackett-Burman designs.
Good experimental design is important in many studies of analytical and other chemical processes. Complete factorial designs, which study all the factors (experimental variables) affecting the system response, using at least two levels (values) for each factor, can give rise to an unacceptably large number of trial experiments. This is because even apparently simple processes may be affected by a large number of factors. Moreover these factors may affect the system response interactively, i.e. the effect of one factor may depend on the levels of others. Any interactions must also be distinguished from random measurement errors. So it is more common to use partial factorial designs in which some information, especially about interactions, may be sacrificed in the interests of a manageable number of experiments.


Automated synthesis and composition of taskblocks for control of manufacturing systems.
Automated control synthesis methods for discrete-event systems promise to reduce the time required to develop, debug, and modify control software. Such methods must be able to translate high-level control goals into detailed sequences of actuation and sensing signals. In this paper, we present such a technique. It relies on analysis of a system model, defined as a set of interacting components, each represented as a form of condition system Petri net. Control logic modules, called taskblocks, are synthesized from these individual models. These then interact hierarchically and sequentially to drive the system through specified control goals. The resulting controller is automatically converted to executable control code. The paper concludes with a discussion of a set of software tools developed to demonstrate the techniques on a small manufacturing system.


[Dental awareness among young adults].
Awareness of own dental appearance was studied in 150 18-year old individuals by assessing their ability to identify a photograph of own teeth among 17 alternative photographs. More than two thirds of the subjects identified their picture on first trial, which reflects a high level of dental awareness in the group. Consciousness about dental arrangement was high as 56% reported deviating tooth position as a primary cause for recognition. Other features, such as tooth morphology, discolouration and fractures were stated as reasons for identification by 26% of the individuals. The findings indicate that young adults are able to recognize a good orthodontic treatment result. Therefore, a high standard of the treatment delivered seems to be justified by the level of dental awareness in young adults.


Dual adrenergic control of renin during nonhypotensive hemorrhage in conscious dogs.
These experiments evaluated the contribution of renal alpha-adrenoceptors, renal beta-adrenoceptors, and extrarenal beta-adrenoceptors to increased plasma renin activity (PRA) during nonhypotensive hemorrhage in conscious dogs. Blood withdrawal at a rate of 16 g/kg body wt over 20 min increased PRA to nearly threefold control levels without decreasing mean arterial pressure. The PRA response to hemorrhage was reduced to a greater extent by simultaneous direct renal arterial (ira) infusion of phenoxybenzamine and propranolol than by propranolol alone. Phenoxybenzamine infusion ira did not block alpha-adrenoceptors located outside of the kidney. The PRA and heart rate responses to hemorrhage were both significantly reduced when propranolol was infused either ira or intravenously (iv) at a rate of 2 micrograms.kg-1.min-1 for 20 min followed by 0.5 microgram.kg-1.min-1 continuous infusion. Propranolol infusion at a lower rate (0.5 microgram.kg-1.min-1 for 20 min followed by 0.12 microgram.kg-1.min-1) had little effect on the magnitude of increase in PRA when infused either iv or ira. The calculated renal arterial plasma propranolol concentration was at least fivefold higher or more during ira than during iv propranolol infusion at each rate and was approximately the same during ira infusion at the lower rate (17.5 +/- 0.7 ng/ml) as during iv infusion at the higher rate (16.7 +/- 2.4 ng/ml). These data indicate that the hemorrhage-induced increase in PRA is mediated by renal alpha-adrenoceptors and extrarenal beta-adrenoceptors, whereas renal beta-adrenoceptors appear to play little or no role.


Three-dimensional spinal coupling mechanics: Part I. A review of the literature.
To determine the state of knowledge relative to three-dimensional spinal coupled motion and to check the validity of currently accepted two-dimensional coupling as taught in chiropractic. A hand search of available reference texts and a computer search of literature from Index Medicus were collected with an emphasis on three-dimensional studies of human spinal movements. Most postural movements result in complicated three-dimensional spinal coupling in six degrees of freedom. Previous spinal coupling results based upon two-dimensional radiographic studies are inadequate and inaccurate. It is important that chiropractic colleges and techniques use the three-dimensional spinal kinematics to update their curricula and advance chiropractic treatment procedures. Full three-dimensional investigations of spinal coupling patterns have shown that the vertebrae rotate and translate in all three axes and that previous theories of spinal coupling based upon two-dimensional studies are inaccurate and invalid. Postural rotations and translations, which are the main motions studied in spinal coupling research, and altered configurations of the normal sagittal plane curves are the cause of both normal and abnormal spinal coupling patterns in three dimensions. Chiropractic letter listings (such as PRS, ASRP, etc.) are outdated, incomplete, invalid representations of coupled segmental movements. Mechanical loading of the neuromusculoskeletal tissues plays a vital role in position, dynamics, proper growth, repair and symptoms. Future studies of spinal kinematics should study the postural translations of the skull and thorax for their associated coupling in three dimensions. Combined postural rotations and translations along with altered sagittal curvatures need to be studied for their associated coupling characteristics as well.


The Factor Structure and Measurement Invariance of the Coping Inventory for Stressful Situations in a Sexual Minority Population.
Coping strategies have been studied as protective factors against stress for individuals. However, the psychometric properties of the most widely used coping self-report questionnaires, the Coping Inventory for Stressful Situations (CISS-21), have not been examined in a sexual minority population (men and women that identify as lesbian, gay, or bisexual or LGB). In this study, we conducted exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) simultaneously to assess the factor structure of the CISS-21 questionnaire in LGBs. Also, we tested the measurement invariance of CISS across sex and sexual identity in the LGB sample (N = 2850, 52.00% woman, mean age = 32.46 years). The results show that a four-factor structure consisting of task-oriented coping (TOC), emotion-oriented coping (EOC), distraction-oriented coping (DOC), and social diversion-oriented coping (SOC) explained the data best. The results also show acceptable internal consistency reliability, convergent validity, and discriminant validity. Subsequently, multi-group analyses established measurement invariance across sex and sexual identity. These results indicate that the CISS-21 could be used as a simple, reliable, and valid scale for measuring coping strategies in LGBs, and that it allows valid score comparisons from different sex and sexual identity groups.


Tobacco retailer density and smoking behaviour: how are exposure and outcome measures classified? A systematic review.
To date only a limited number of reviews have focused on how exposure and outcome measures are defined in the existing literature on associations between tobacco retailer density ('density') and smoking behaviour ('smoking'). Therefore this systematic review classified and summarised how both density and smoking variables are operationalised in the existing literature, and provides several methodological recommendations for future density and smoking research. Two literature searches between March and April 2018 and April 2022 were conducted across 10 databases. Inclusion and exclusion criteria were developed and keyword database searches were undertaken. Studies were imported into Covidence. Cross-sectional studies that met the inclusion criteria were extracted and a quality assessment was undertaken. Studies were categorised according to the density measure used, and smoking was re-categorised using a modified classification tool. Large heterogeneity was found in the operationalisation of both measures in the 47 studies included for analysis. Density was most commonly measured directly from geocoded locations using circular buffers at various distances (n = 14). After smoking was reclassified using a smoking classification tool, past-month smoking was the most common smoking type reported (n = 26). It is recommended that density is measured through length-distance and travel time using the street network and weighted (e.g. by the size of an area), or by using Kernel Density Estimates as these methods provide a more accurate measure of geographical to tobacco and e-cigarette retailer density. The consistent application of a smoking measures classification tool, such as the one developed for this systematic review, would enable better comparisons between studies. Future research should measure exposure and outcome measures in a way that makes them comparable with other studies. This systematic review provides a strong case for improving data collection and analysis methodologies in studies assessing tobacco retailer density and smoking behaviour to ensure that both exposure and outcome measures are clearly defined and captured. As large heterogeneity was found in the operationalisation of both density and smoking behaviour measures in the studies included for analysis, there is a need for future studies to capture, measure and classify exposure measures accurately, and to define outcome measures in a manner that makes them comparable with other studies.