FAQs about the GOLD 2011 assessment proposal of COPD: a comparative analysis of four different cohorts.
Since the publication of the new Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposal for the assessment of chronic obstructive lung disease (COPD), four studies have used existing cohorts to explore the characteristics, temporal variability and/or relationship with outcomes of the four resulting patient categories (A, B, C and D). Here, we compare their results and address a number of frequently asked questions (FAQs) on the topic. The most salient findings were that: 1) the prevalence of these four groups depends on the specific population studied, C being the least prevalent; 2) comorbidities are particularly prevalent in the two "high-symptom" groups (B and D); 3) patients classifiedZ as A or D tend to remain in the same group over time, whereas those classified as B or C change substantially during follow-up; 4) mortality at 3 years was lowest in A and worst in D but surprisingly similar (and intermediate) in B and C; and 5) the incidence of exacerbations during follow-up increases progressively from A to D but that of hospitalisations behave similarly to mortality. These results identify several strengths and shortcomings of the new GOLD assessment proposal, particularly that group B is associated with more morbidity and high mortality.


Evaluation of cross-linking procedures of collagen tubes used in peripheral nerve repair.
Three different cross-linking methods were compared to prepare collagen tubes, namely irradiation by ultraviolet (UV), heating and immersing in glutaraldehyde (GA). Bridge grafting of 15 mm was carried out with these tubes, as well as with non-cross-linked collagen tubes for comparison, in a defect of rat sciatic nerves (N = 21 in each group). As a control, isografting was carried out (N = 6). The specimens were taken from the grafted site in each experimental group for histological observation after, respectively 1, 2, 4, 6 and 8 weeks (N = 3 each). Evoked muscle action potentials were recorded on the calf muscle in the experimental and control groups after 12 weeks, and the grafted material and tibial nerve were harvested for histological analysis (N = 6). The inner space of UV-irradiated tubes was preserved with almost no cell infiltration and nerve regeneration matching for isograft was obtained. Rapid degradation of the heat-treated tubes occurred and many macrophages were mobilized to remove the collagen debris. The non-treated tube swelled and the regenerated nerve tissue in the tube was constricted with time. The GA-immersed tubes showed less cellular activity and poor regenerated nerve tissue compared with the other cross-linking methods. Therefore, UV irradiation to collagen tubes is recommended as a cross-linking method for nerve conduit.


The Development and Implementation of a New Graduate Registered Nurse Nephrology Nurse Residency Program in Acute Hemodialysis.
New graduate registered nurses (NGRNs) can become competent in providing acute care hemodialysis for complex medical and critically ill patients. As the renal patient population grows, nephrology nursing will need RNs prepared to provide high-quality, patient-centered care through evidence-based practice. This article describes the successful development and implementation of a comprehensive Nephrology Nurse Residency Program at Emory University Hospital. Utilizing Benner's Novice to Expert theory, this project evaluated providing NGRNs with the essential residency experiences to become nephrology nurses who are competent in the provision of acute care hemodialysis, with the ability to care for medically complex and critically ill patients. It is recommended that this program be offered at health care institutions that provide acute dialysis services.


Purification and characterization of multiple forms of rat liver xanthine oxidoreductase expressed in baculovirus-insect cell system.
cDNA of rat liver xanthine oxidoreductase (XOR), a molybdenum-containing iron-sulfur flavoprotein, was expressed in a baculovirus-insect cell system. The expressed XOR consisted of a heterogeneous mixture of native dimeric, demolybdo-dimeric, and monomeric forms, each of which was separated and purified to homogeneity. All the expressed forms contained flavin, of which the semiquinone form was stable during dithionite titration after dithiothreitol treatment, indicating that the flavin domains of all the expressed molecules have the intact conformations interconvertible between NAD(+)-dependent dehydrogenase (XDH) and O(2)-dependent oxidase (XO) types. The absorption spectrum and metal analyses showed that the monomeric form lacks not only molybdopterin but also one of the iron-sulfur centers. The reductive titration of the monomer with dithionite showed that the monomeric form required only three electrons for complete reduction, and the redox potential of the iron-sulfur center in the monomeric form is a lower value than that of FAD. In contrast to native or demolybdo-dimeric XDHs, the monomer showed a very slow reductive process with NADH under anaerobic conditions, although the conformation around FAD is a dehydrogenase form, suggesting the important role of the iron-sulfur center in the reductive process of FAD with the reduced pyridine nucleotide.


Implementation of a service for physicians' consultation and information in euthanasia requests in Belgium.
To study the implementation of LEIF, the consultation service which provides access to specially trained physicians to act as the legally required second physician in requests for euthanasia in Flanders and Brussels, Belgium, the use of which has been to shown to be beneficial to the careful practice of euthanasia. A representative sample of 3006 Belgian physicians from the area where LEIF is active received a questionnaire investigating their attitude and practice regarding euthanasia, asking about their knowledge of LEIF, their attitude towards the service, their use of the service and their intentions regarding its future use. Seventy-eight per cent of physicians knew about the existence of the organization, 90% felt supported by the idea of being able to consult a LEIF physician and 90% intended to use LEIF in the future. Only 35% of those who had received a euthanasia request since LEIF became active had made use of LEIF. Awareness, use and intended use of LEIF were lower among specific groups of physicians (e.g. specialists). Positive attitudes towards consultation and training were positively associated with future use of LEIF. Implementation can be considered successful but LEIF should continue promoting its services as widely as possible, with specific attention paid to specialists.


Contemporary role of palliative cystoprostatectomy or pelvic exenteration in advanced symptomatic prostate cancer.
To access the feasibility of palliative cystoprostatectomy/pelvic exenteration in patients with bladder/rectal invasion due to prostate cancer (PC). Twenty-five men with cT4 PC were retrospectively identified in the institutional databases of six tertiary referral centers in the last decade. Local invasion was documented by CT or MRI scans and was confirmed by urethrocystoscopy. Oncological therapies, local symptoms, previous local treatments, time from diagnosis to intervention and type of surgical procedure were recorded. Patients were divided into groups: ADT group (12 pts) and 13 pts without any history of previous local/systemic treatments for PCa (nonADT groups). Perioperative complications were classified using the Clavien-Dindo system. Overall survival (OS) was defined as the time from surgery to death from any cause. A Cox regression analysis, stratified for ISUP score and previous hormonal treatment (ADT) was also performed for survival analysis. Ileal conduit was the main urinary diversion in both cohorts. For the entire cohort, complication rate was 44%. No significant differences regarding perioperative complications and complication severity between both subgroups were observed (p = 0.2). Median follow-up was 15 months (range 3-41) for the entire cohort with a median survival of 15 months (95% CI 10.1-19.9). In Cox regression analysis stratified for ISUP score, no statistically significant differences in OS in patients with and without previous ADT before cystectomy or exenteration were observed (HR 3.26, 95% CI 0.62-17.23, p = 0.164). Palliative cystoprostatectomy and pelvic exenteration represent viable treatment options associated with acceptable morbidity and good short-term survival outcome.


An ecological basis for managing giant sequoia ecosystems.
A strategy for management of giant sequoia groves is formulated using a conceptual framework for ecosystem management recently developed by Region Five of the USDA Forest Service. The framework includes physical, biological, and social dimensions. Environmental indicators and reference variability for key ecosystem elements are discussed in this paper. The selected ecosystem elements include: 1) attitudes, beliefs, and values; 2) economics and subsistence; 3) stream channel morphology; 4) sediment; 5) water; 6) fire; 7) organic debris; and 8) vegetation mosaic. Recommendations are made for the attributes of environmental indicators that characterize these elements. These elements and associated indicators will define and control management activities for the protection, preservation, and restoration of national forest giant sequoia ecosystems.


Electronic binding energy and thermal relaxation of Li and LiNa atomic alloying clusters.
We examined the effects of atomic hetero- and under-coordination on the relaxation of the interatomic bonding and electronic binding energy of Li and LiNa cluster alloying using a combination of the bond-order-length-strength correlation and density functional theory calculations. We found that bond nature alteration by heterocoordination, bond relaxation by thermal excitation and atomic coordination contribute intrinsically to the core-level energy shifts with resolution of the binding energy at the atomic sites of terrace edges, facets, and bulk of the LiNa alloy nanoclusters. Our strategies may simplify the complexity of core electron binding energies in analyzing the experimental data of the irregularly coordinating atoms.


Developing an effective community conservation program for cotton-top tamarins (Saguinus oedipus) in Colombia.
Developing effective conservation programs that positively impact the survival of a species while considering the needs of local communities is challenging. Here we present an overview of the conservation program developed by Proyecto Tití to integrate local communities in the conservation of Colombia's critically endangered primate, the cotton-top tamarin (Saguinus oedipus). Our comprehensive assessment of the threats effecting the long-term survival of the cotton-top tamarin allowed us to establish the primary components of our program. Proyecto Tití has three areas of emphasis: (1) scientific studies detailing the biology and long-term survival of the cotton-top tamarin, (2) conservation education programs to increase public awareness and conservation knowledge, and (3) community empowerment programs that demonstrate a valuable economic incentive to protecting wildlife and forested areas in Colombia. This integrated approach to conservation that involves local communities in activities that benefit individuals, as well as wildlife, has proven to be remarkably effective in protecting cotton-top tamarins and their forested habitat. Our bindes program, which uses small cook stoves made from clay, has demonstrated a marked reduction in the number of trees that have been harvested for firewood. Developing environmental entrepreneurs, who create products made from recycled plastic for sale in national and international markets, has had a significant impact in reducing the amount of plastic that has been littering the environment and threatening the health of wildlife, while creating a stable economic income for rural communities. Proyecto Tití has provided economic alternatives to local communities that have dramatically reduced the illegal capture of cotton-top tamarins and forest destruction in the region that has positively impacted the long-term survival of this critically endangered primate.


Site-specific phosphorylation by protein kinase C inhibits assembly-promoting activity of microtubule-associated protein 4.
We have examined the phosphorylation of bovine microtubule-associated protein 4 (MAP4), formerly named MAP-U, by protein kinase C (PKC). When MAP4 was incubated with PKC, about 1 mol of phosphate was incorporated/mol of MAP4. Phosphorylation of MAP4 caused a remarkable decrease in the ability of the MAP to stimulate microtubule assembly. MAP4 consists of an amino-terminal projection domain and a carboxyl-terminal microtubule-binding domain. The carboxyl-terminal domain is subdivided into a Pro-rich region and an assembly-promoting (AP) sequence region containing four tandem repeats of AP sequence that is conserved in MAP4, MAP2, and tau [Aizawa et al. (1990) J. Biol. Chem. 265, 13849-13855]. In order to identify the site of MAP4 phosphorylated by PKC, a series of expressed MAP4 fragments was prepared and treated with the kinase. A fragment corresponding to the Pro-rich region (P fragment) was phosphorylated, while fragments corresponding to the projection domain and the AP sequence region were not. In addition, chymotryptic digestion of an authentic MAP4 prephosphorylated by PKC revealed that phosphate was incorporated almost exclusively into a 27-kDa fragment containing the carboxyl-terminal half of the Pro-rich region. We investigated the phosphorylation site in MAP4 using the P fragment and found that Ser815 was phosphorylated almost exclusively. We conclude that the phosphorylation of a single Ser residue in the Pro-rich region negatively regulates the assembly-promoting activity of MAP4.


Improved long-term bonding performance of an experimental all-in-one adhesive.
The aim of this study was to determine the performance of an experimental all-in-one adhesive. The adhesive, named MTB-200 (Kuraray Medical), contained components to enhance both bond strength and hydrophobicity. The performance of the adhesive was compared with that of CLEARFIL TRI-S BOND (Kuraray Medical) and BeautiBond (SHOFU) using micro-tensile bond strength test and ultramicroscopic observations. The study revealed that the new adhesive had the highest tensile strength value among the three adhesives over time, although transmission electron microscopic images showed the phenomenon of filler de-bonding in the adhesive resin layer. In spite of modification in the experimental adhesive, the adhesive was suspected to degrade bond performance. However, revision of the composition of adhesives would be one of the solutions to enhance durability of interface.


Alertness management: strategic naps in operational settings.
Managing fatigue in complex operational settings requires attention to multiple factors, including hours of service, scheduling, education and training, counter-measures, technology, and research. Alertness-management strategies can be used to promote safety, performance, and productivity in operational settings. These strategies can involve both preventive (used prior to duty/shift) and operational (used during duty/shift) approaches. Studies have demonstrated the effectiveness of naps to improve subsequent performance and alertness. Strategic naps can be used effectively to promote performance and alertness in operational settings. Two potential negative effects of naps, sleep inertia and effects on subsequent sleep periods, are discussed. Sleep inertia can involve sleepiness and decreased performance immediately upon awakening from a nap. It should be a consideration prior to implementing nap strategies in work environments. A study of planned rest periods in long-haul flight operations demonstrated the effectiveness of in-flight naps to promote performance and alertness during subsequent critical phases of flight (descent and landing). Empirical evaluation of alertness-management strategies during regular operations will be critical to their implementation. Combining strategies may be the most effective approach to managing fatigue engendered by 24-h operational demands. Other considerations prior to implementing alertness-management strategies in operational environments are discussed.


N-heterocyclic carbene (NHC)-stabilized silanechalcogenones: NHC-->Si(R2)=E (E=O, S, Se, Te).
A series of N-heterocyclic carbene-stabilized silanechalcogenones 2 a,b (Si=O), 3 a,b (Si=S), 4 a,b (Si=Se), and 5 a,b (Si=Te) are described. The silanone complexes 2 a,b were prepared by facile oxygenation of the carbene-silylene adducts 1 a,b with N(2)O, whereas their heavier congeners were synthesized by gentle chalcogenation of 1 a,b with equimolar amounts of elemental sulfur, selenium, and tellurium, respectively. These novel compounds have been isolated in a crystalline form in high yields and have been fully characterized by a variety of techniques including IR spectroscopy, ESIMS, and multinuclear NMR spectroscopy. The structures of 2 b, 3 a, 4 a, 4 b, and 5 b have been confirmed by single-crystal X-ray crystallography. Due to the NHC-->Si donor-acceptor electronic interaction, the Si=E (E=O, S, Se, Te) moieties within these compounds are well stabilized and thus the compounds possess several ylide-like resonance structures. Nevertheless, these species also exhibit considerable Si=E double-bond character, presumably through a nonclassical Si=E pi-bonding interaction between the chalcogen lone-pair electrons and two antibonding Si-N sigma* orbitals, as evidenced by their high stretching vibration modes and the shortening of the Si-E distances (between 5.4 and 6.3%) compared with the corresponding Si-E single-bond lengths.


Alterations in Membrane Protein-Profile during Cold Treatment of Alfalfa.
Changes in pattern of membrane proteins during cold acclimation of alfalfa have been examined. Cold acclimation for 2 to 3 days increases membrane protein content. Labeling of membrane proteins in vivo with [(35)S]methionine indicates increases in the rate of incorporation as acclimation progresses. Cold acclimation induces the synthesis of about 10 new polypeptides as shown by SDS-PAGE and fluorography of membrane proteins labeled in vivo.


Renal cortical necrosis and Purtscher's retinopathy in hemorrhagic pancreatitis.
A patient presented with acute hemorrhagic pancreatitis complicated by both renal cortical necrosis and Purtscher's retinopathy. Either of these two complications is rare and never before have both been reported in the same patient. The patient's renal insufficiency required hemodialysis; it gradually improved over two years when dialysis could be discontinued. The patient's retinopathy included bilateral hemorrhages and cotton wool spots; visual fields and acuity remained normal. Funduscopic lesions disappeared by three months after the acute event. These two rare vasculo-occlusive complications of pancreatitis simultaneously occurring in one individual might suggest complement-mediated leukostatic mechanisms.


Effect of methionine sulfoximine on asparaginase activity and ammonium levels in pea leaves.
In developing leaves of Pisum sativum the levels of ammonium did not change during the light-dark photoperiod even though asparaginase (EC 22.214.171.124) did; asparaginase activity in detached leaves doubled during the first 2.5 hours in the light. When these leaves were supplied with 1 millimolar methionine sulfoximine (MSX, an inhibitor of glutamine synthetase, GS, activity) at the beginning of the photoperiod, levels of ammonium increased 8-to 10-fold, GS activity was inhibited 95%, and the light-stimulated increase in asparaginase activity was completely prevented, and declined to less than initial levels. When high concentrations of ammonium were supplied to leaves, the light-stimulated increase of asparaginase was partially prevented. However, it was also possible to prevent asparaginase increase, in the absence of ammonium accumulation, by the addition of MSX together with aminooxyacetate (AOA, which inhibits transamination and some other reactions of photorespiratory nitrogen cycling). AOA alone did not prevent light-stimulated asparaginase increase; neither MSX, AOA, or elevated ammonium levels inhibited the activity of asparaginase in vitro. These results suggest that the effect of MSX on asparaginase increase is not due solely to interference with photorespiratory cycling (since AOA also prevents cycling, but has no effect alone), nor to the production of high ammonium concentration or its subsequent effect on photosynthetic mechanisms. MSX must have further inhibitory effects on metabolism. It is concluded that accumulation of ammonium in the presence of MSX may underestimate rates of ammonium turnover, since liberation of ammonium from systems such as asparaginase is reduced by the effects of MSX.


Effect of ageing and hypertension on endothelial modulation of ouabain-induced contraction and sodium pump activity in the rat aorta.
To investigate the endothelial modulation of the rat thoracic aorta sodium-potassium ATPase activity and its possible alteration by ageing and hypertension. Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) aged 5 weeks, 3, 6, 12 and 18 months were anaesthetized. Their aortae were dissected and divided into cylindrical segments and vasomotor responses obtained in segments with or without endothelium were recorded on a polygraph. Endothelium removal increased ouabain responses in young (aged 3 and 6 months) WKY rat aortic segments, but reduced those obtained in old (aged 18 months) WKY rat segments and in segments from SHR aged 3, 6 and 12 months. An enhancement of contractions in response to ouabain with age was observed in both strains, but it occurred at earlier ages in vessels from SHR. At ages 3 and 6 months, responses to ouabain were higher in intact vessels from SHR than they were in those from WKY, but were lower in endothelium-denuded vessels. In aortic segments from 6-month-old WKY rats and SHR, ouabain reduced or abolished potassium-induced relaxations in segments with or without endothelium, respectively. In vessels from SHR and WKY rats aged 18 months, ouabain abolished potassium-induced relaxations both in intact and in endothelium-denuded vessels. Endothelium of WKY rat aorta might release a factor in response to ouabain that modulates its contraction negatively. Endothelium of SHR and old WKY rat aorta releases a contracting factor that modulates ouabain contractions positively. Thus, the inhibitory effect of endothelium on contractions induced by ouabain might be lost as a consequence both of hypertension and of age, being replaced by an endothelium-dependent contracting factor that facilitates ouabain responses.


Focusing geometries for constant fluence in infrared multiple-photon dissociation.
Generalized mathematical expressions are presented that describe the fluence distribution of a laser beam focused properly into an optically thick gas medium so that the axial fluence distribution is made nearly constant. The laser-beam focusing parameters are optimized such that they compensate for the decrease in pulse energy along the beam axis. Two cases are taken into account for optical absorption. These cases are linear and nonlinear absorption, of which the latter is often met in infrared multiple-photon dissociation and applied widely to laser-isotope separation. It is demonstrated that an optimized focusing is effective in achieving almost constant axial fluence distribution, thereby maximizing reaction yields of a target isotopic component without the loss of isotopic selectivities in laser-isotope separation.


Description of the imago of Neocapritermes utiariti (Isoptera: Termitidae: Termitinae).
The neotropical termite genus Neocapritermes Holmgren (1912) was revised by Krishna & Araujo (1968), who recognized 14 valid species. Two additional species were described by Constantino (1991), and another one by Bandeira & Cancello (1992). However, the imago of most species of Neocapritermes remain unknown. In this paper we describe for the first time the imago of Neocapritermes utiariti based on specimens from the State of Rondônia, Brazil. The examined material will be deposited in the Invertebrate Collection of the Instituto Nacional de Pesquisas da Amazônia, in Manaus, Amazonas, Brazil (INPA). Comparisons with other imagoes of Neocapritermes were made based on descriptions and figures from Krishna & Araújo (1968). The measurements were taken with an ocular micrometer following Roonwal's (1970) system of morphometric characters.


Fibrillogenesis in continuously spun synthetic collagen fiber.
The universal structural role of collagen fiber networks has motivated the development of collagen gels, films, coatings, injectables, and other formulations. However, reported synthetic collagen fiber fabrication schemes have either culminated in short, discontinuous fiber segments at unsuitably low production rates, or have incompletely replicated the internal fibrillar structure that dictates fiber mechanical and biological properties. We report a continuous extrusion system with an off-line phosphate buffer incubation step for the manufacture of synthetic collagen fiber. Fiber with a cross-section of 53+ or - 14 by 21 + or - 3 microm and an ultimate tensile strength of 94 + or - 19 MPa was continuously produced at 60 m/hr from an ultrafiltered monomeric collagen solution. The effect of collagen solution concentration, flow rate, and spinneret size on fiber size was investigated. The fiber was further characterized by microdifferential scanning calorimetry, transmission electron microscopy (TEM), second harmonic generation (SHG) analysis, and in a subcutaneous murine implant model. Calorimetry demonstrated stabilization of the collagen triple helical structure, while TEM and SHG revealed a dense, axially aligned D-periodic fibril structure throughout the fiber cross-section. Implantation of glutaraldehyde crosslinked and noncrosslinked fiber in the subcutaneous tissue of mice demonstrated limited inflammatory response and biodegradation after a 6-week implant period.


Advanced Therapy Medicinal Products: A Guide for Bone Marrow-derived MSC Application in Bone and Cartilage Tissue Engineering.
Millions of people worldwide suffer from trauma- or age-related orthopedic diseases such as osteoarthritis, osteoporosis, or cancer. Tissue Engineering (TE) and Regenerative Medicine are multidisciplinary fields focusing on the development of artificial organs, biomimetic engineered tissues, and cells to restore or maintain tissue and organ function. While allogenic and future autologous transplantations are nowadays the gold standards for both cartilage and bone defect repair, they are both subject to important limitations such as availability of healthy tissue, donor site morbidity, and graft rejection. Tissue engineered bone and cartilage products represent a promising and alternative approach with the potential to overcome these limitations. Since the development of Advanced Therapy Medicinal Products (ATMPs) such as TE products requires the knowledge of diverse regulation and an extensive communication with the national/international authorities, the aim of this review is therefore to summarize the state of the art on the clinical applications of human bone marrow-derived stromal cells for cartilage and bone TE. In addition, this review provides an overview of the European legislation to facilitate the development and commercialization of new ATMPs.


Eicosapentaenoic acid and rosiglitazone increase adiponectin in an additive and PPARγ-dependent manner in human adipocytes.
Adiponectin, an anti-inflammatory and insulin-sensitizing protein secreted from adipose tissue, may be modulated by dietary fatty acids, although the mechanism is not fully known. Our objective was to investigate the effect of long-chain n-3 polyunsaturated fatty acids (PUFAs) on adiponectin in cultured human adipocytes, and to elucidate the role of peroxisome proliferator-activated receptor-γ (PPARγ) in this regulation. Isolated human adipocytes were cultured for 48 h with 100 µmol/l eicosapentaenoic acid (C20:5n-3, EPA), docosahexaenoic acid (C22:6n-3, DHA), palmitic acid (C16:0), 100 µmol/l EPA plus 100 µmol/l DHA, or bovine serum albumin (control). Additionally, adipocytes were treated for 48 h with a PPARγ antagonist (BADGE) or agonist (rosiglitazone) in isolation or in conjunction with either EPA or DHA. At 48 h, EPA and DHA increased (P < 0.05) adiponectin secretion by 88 and 47%, respectively, while EPA, but not DHA, also increased (136%, P < 0.001) cellular adiponectin protein. Interestingly, PPARγ antagonism completely abolished the DHA-mediated increase in secreted adiponectin, but only partially attenuated the EPA-mediated response. Thus, EPA's effects on adiponectin do not appear to be entirely PPARγ mediated. Rosiglitazone increased (P < 0.001) the secreted and cellular adiponectin protein (90 and 582%, respectively). Finally, the effects of EPA and rosiglitazone on adiponectin secretion were additive (+230% at 48 h combined, compared to 121 and 124% by EPA or rosiglitazone alone, respectively). Overall, our findings emphasize the therapeutic importance of long-chain n-3 PUFA alone, or in combination with a PPARγ agonist, as a stimulator of adiponectin, a key adipokine involved in obesity and related diseases.


Implications of Blanc's Law for Use in Trapped Ion Mobility Spectrometry.
Blanc's Law has served as a way to predict the mobilities of ions in mixed drift gases for over 100 years yet has remained largely unexplored using newer ion mobility spectrometry (IMS) configurations, including traveling wave and trapped IMS (TIMS) systems. Here, we evaluate a drift-tube IMS (DTIMS) and compare it to a similar set of experiments performed in TIMS. We found that Blanc's Law can be applied in a DTIMS to determine the mobility of an analyte in the minor gas component of a ternary mixed drift gas system within 2% error. Additionally, the calibration procedure for TIMS to convert elution voltages into a mobility value corrects for significant deviations (>4%) from Blanc's Law in the elution voltage domain. For the range of gas identities probed in this effort, up to an 11% error in calibrated mobilities was observed when using a gas mixture in the TIMS that differed from the gas used for the reference mobility. However, when the gas mixture within the TIMS was the same as the respective calibrant mobilities, calibration errors within the TIMS were as low as 0.01%. Interestingly, when probing the behavior of ions with argon-containing mixtures within the TIMS, the current accepted paradigm of elution voltage being proportional to inverse mobilities in TIMS calibrations procedures was shown to deviate substantially from the trends observed with DTIMS measurements. With this initial effort, foundations for future mixed drift gas measurements in TIMS are set for expanded analyte classes and larger molecules.


Lateral pelvic lymph node dissection can be omitted in lower rectal cancer in which the longest lateral pelvic and perirectal lymph node is less than 5 mm on MRI.
The goal of the study was to examine the use of magnetic resonance imaging (MRI) for identification of patients with lower rectal cancer who may benefit from lateral pelvic lymph node dissection (LPLD). Diagnoses and oncological outcomes were examined in 160 cases. Patients in whom the long-axis diameter of the longest detected lymph node was < 5 mm or ≥ 5 mm were classified as LPLN(-) (n = 102) and LPLN(+) (n = 58), respectively. Diagnostic results gave a 21.6% positive predictive value (PPV) and a 95.0% negative predictive value (NPV) for the LPLN. These values were 59.6% and 91.5%, respectively, for the perirectal lymph node (PRLN). Multivariate analysis showed that a pathologic PRLN (pPRLN)(+) status was an independent prognostic factor for relapse-free survival (RFS) (P = 0.0424) in the LPLN(-) group. The 5-year RFS did not differ significantly between cases that did not and did undergo LPLD (90.0% vs. 83.8%) in the LPLN(-) and pPRLN(-) groups. The low PPV and high NPV indicate that it is difficult to identify patients who may benefit from LPLD. However, the results show that LPLD has no benefit in LPLN(-) and PRLN(-) cases and that these cases can be identified based on MRI findings.


Planning the American Future: Daniel Bell, Future Research, and the Commission on the Year 2000.
This article examines the sociologist Daniel Bell's interest in future research. Future research, to Bell, had as its particular purpose to ensure forms of coordination and steering acceptable to a liberal society. By examining Bell's interest in future research and the activities of the Commission on the Year 2000, the essay proposes that future research played a role in Cold War intellectual history as a particular form of planning for the liberal polity. This idea of planning a liberal society changed decisively, however, between 1965 and 1975.


Myocardial protection by pre- and post-anesthetic conditioning.
Perioperative myocardial ischemia is commonly observed, and it can increase significantly postoperative morbidity and mortality. The cardioprotective properties of volatile anesthetics and opioids have been studied during several decades and currently constitute powerful tools in the management of patients with ischemic coronariopathy. The objective of this review was to provide the fundaments of myocardial protection by preconditioning. The concepts of cellular damage secondary to ischemia and reperfusion, ischemic preconditioning (IPC), and anesthetic preconditioning (APC), as well as the mechanisms of myocardial protection, are discussed. Recent studies in cardiac surgery demonstrated that the use of short periods of ischemia during reperfusion can reduce the area of myocardial infarction. Volatile anesthetic can also have a protective effect in myocardial reperfusion. Independently of the signaling pathway that leads to preconditioning, both anesthetic and ischemic, mitochondrial dependent KATP channels are considered the final mediators of cardioprotection by controlling the mitochondrial influx of calcium and, therefore, preventing the induction of necrosis and apoptosis. Although IPC and APC effectively reduce the area of myocardial infarction and improve postoperative ventricular function, it is important to stress that those treatments should be instituted before ischemic events to justify their clinical applicability. Phenomena known as myocardial ischemic preconditioning and anesthetic preconditioning are well known, and the mechanism of protection is similar in both situations; however, not every step that leads to this protection has been fully explained. Further studies are necessary to increase the clinical applicability of the cardioprotective properties of anesthetics.


Effect of Yttria Content on the Translucency and Masking Ability of Yttria-Stabilized Tetragonal Zirconia Polycrystal.
Translucent zirconia, manufactured by increasing the yttria content, offers improved translucency, but may have a negative effect on esthetic outcomes under clinical conditions such as discolored abutment because of the reflection of the underlying color. The purpose of this in vitro study was to compare the translucency parameter and masking ability of 3 mol % yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP (Katana HT)), 4Y-ZP (Katana STML), and 5Y-ZP (Katana UTML) with those of lithium disilicate (Rosetta SM). Zirconia and lithium disilicate specimens of 10 mm diameters and 0.8 and 1.5 mm thicknesses were fabricated. Their CIE L*a*b* values (L*, brightness; a*, red-green value; b*, yellow-blue value) were measured at the center of the specimens against black and white backgrounds using a spectrophotometer, and translucency parameter (TP) values were determined. The microstructure of the specimens was observed using scanning electron microscopy. Four cylindrical backgrounds of different shades were prepared. The zirconia and lithium disilicate specimens were placed on the backgrounds without any intervening medium. CIE L*a*b* values were obtained, and the color difference value (ΔE) was calculated. Thresholds for acceptability and perceptibility were assumed as ΔE = 5.5 and ΔE = 2.6, respectively, to evaluate masking ability. Data were compared using one-way analysis of variance and post-hoc was performed using Scheffe's test (α = 0.05). In zirconia specimens, the TP value increased as the yttria content increased from 3 mol %, through 4 mol % to 5 mol %, and all zirconia specimens showed lower TP values than lithium disilicate specimens did. All zirconia specimens showed optimal masking ability against a normal dentin shade (ND3) and acceptable masking ability against titanium at a minimum thickness of 1.5 mm. However, no zirconia specimen could mask severely discolored dentin (ND9), regardless of thickness. The decrease in zirconia thickness from 1.5 to 0.8 mm significantly increased translucency. Monolithic Y-TZP ceramics could mask a normal dentin background but could not mask severely discolored dentin at either 0.8 or 1.5 mm thicknesses.


Expectant management compared with elective delivery at 37 weeks for gastroschisis.
To estimate obstetric and neonatal outcomes after induction of labor at 37 weeks of gestation compared with expectant management in pregnancies complicated by fetal gastroschisis. The management of 296 pregnancies involving fetal gastroschisis (1980-2011) was reviewed from a single perinatal center. Ultrasound surveillance and nonstress testing were performed every 2 weeks from 30 weeks of gestation, weekly from 34 weeks of gestation, and twice weekly after 35 weeks of gestation until delivery. Labor was induced if fetal well-being testing was abnormal and, since 1994, labor was routinely induced at 37 weeks of gestation. Of 153 pregnancies reaching 37 weeks of gestation, labor was induced in 77 (26%) and 76 (25.7%) were allowed to labor spontaneously. There were no significant differences in mean maternal age (22 years in both), parity (56% compared with 66% nulliparous), presence of other fetal anomalies (12% compared with 9%), cesarean delivery rate (20% in both), 5-minute Apgar score less than 7 (10% compared with 12%), meconium at birth (36% compared with 49%), or respiratory distress syndrome (16% compared with 7%) between the induced and expectantly managed groups. However, neonatal sepsis (25% compared with 42%; P=.02) and a composite outcome of neonatal death and bowel damage (necrosis, atresia, perforation, adhesion; 8% compared with 21%; P=.02) were more common in expectantly managed pregnancies. Moreover, time to oral feeds (-3.4 days), time on total parenteral nutrition (-6.2 days), and hospital stay (-6.7 days) were reduced when labor was induced. In fetuses with gastroschisis, induction of labor at 37 weeks of gestation was associated with reduced risks of sepsis, bowel damage, and neonatal death compared with pregnancies managed expectantly beyond 37 weeks of gestation. II.


Healthy Life Expectancy in 2010 for Native Hawaiian, White, Filipino, Japanese, and Chinese Americans Living in Hawai'i.
Healthy life expectancy (HALE) varies substantially among countries, regions, and race/ethnicities. Utilizing the Sullivan method, this article examines HALE for Native Hawaiian, White, Filipino, Japanese, and Chinese Americans living in Hawai'i, the United States. HALE varies by sex and race/ethnicity. The HALE at birth in 2010 for females was 78.3, 77.8, 74.2, 73.7, and 62.6 years in contrast to life expectancy of 90, 88, 88.1, 83.4, and 79.4 for Chinese, Japanese, Filipino Americans, White, and Native Hawaiians, respectively. In the same order, HALE at birth for males was 73.0, 71.6, 72.3 70.7, and 60.7 years, compared with life expectancy of 85.3, 81.2, 80.8, 78.3, and 73.9. The gaps in HALE between Native Hawaiians and the longest living Chinese Americans were 15.7 years for females and 12.3 years for males. Our results highlight sex and racial/ethnic disparities in HALE, which can inform program and policy development.


Ozone oxidation of oestrogenic active substances in wastewater and drinking water.
Ozone oxidation is proven to be an effective solution for the degradation of selected oestrogenic active substances detected in secondary wastewaters such as beta-oestradiol, oestrone, oestriol, 17-alpha-ethinyloestradiol, mestranol, daidzeine, beta-sitosterol, bisphenol A, norethisterone, 4-tert-octylphenol and 4-iso-nonylphenol, up to their limit of detection. The matrix-effect of wastewater was investigated performing ozone experiments under batch mode and continuous mode using drinking water and a wastewater issued from a local plant both spiked with the non-detected substances. The results obtained indicate that the wastewater matrix greatly affects the kinetics of ozone reaction with these substances but does not really change the related reactivity scale. The ozone dose corresponding to the full conversion of target EDCs consequently increases as their oxidation takes place competing with reactions of background pollutants represented by the COD and DOC content. However, a usual dose close to 12 mg/L was found sufficient to provide high degradation yields for all substances studied while 35% of COD was removed. This is a contribution to the numerous current works focused on technologies able to improve the quality of water discharged from wastewater treatment plants, both considering conventional parameters and emerging contaminants.


Understanding the Economic Value and Impacts on Informal Carers of People Living with Mental Health Conditions.
Informal carers play a vital role in supporting people living with mental health conditions, but comparatively little is known about the economic value of caring. This study undertook an online survey of adult informal carers supporting adults with mental health conditions to better understand the impacts of caring on carer quality of life, levels of loneliness, finances and employment, as well as estimate the economic value of time spent caring. In total, 712 carers participated in the multi-national survey between August 2019 and April 2020. A total of 17% were male, with a mean age of 53, and 68% supported a child living with a mental health condition. A total of 56% of care recipients were male, with a mean age of 37. Adverse impacts on quality of life, loneliness and personal finances were greatest in carers living with care recipients. Overall mean weekly hours of care were 43.42, rising to 65.41 for carers living with care recipients. Mean weekly costs of care per carer ranged from €660 to €2223 depending on living arrangements. Annual costs ranged between €34,960 and €125,412, depending on living arrangements and valuation method. Informal care costs are substantial, and policy makers should consider investing more in carer support, especially for carers living with care recipients.


Explicitly solvated ligand contribution to continuum solvation models for binding free energies: selectivity of theophylline binding to an RNA aptamer.
To provide more accurate computational estimates of binding free energies in solution from molecular dynamics (MD) simulations, a separate solvation contribution for the binding ligand is determined from a linear response treatment. We use explicit water coordinates for this term and combine with MM-PBSA (molecular mechanics, Poisson-Boltzmann, and surface area contributions) in a new approach (MM-PB/LRA-SA). To assess this method, application to the binding between theophylline and its derivatives to an RNA aptamer was performed and compared with experimental binding affinities. Explicitly solvated MD trajectories were generated with the same parameter set used in the previous work by Gouda et al., who compared the relative binding of these molecules by both the MM-PBSA and thermodynamic integration methods. Substituting the linear response term for the ligand in the MM-PB/LRA-SA approach led to an improvement upon MM-PBSA when compared with experimental and thermodynamic integration results at approximately twice the computational cost. The balance between accuracy and computational expense achieved using this method suggests potential advantages in applying it in the virtual drug-screening process.


Detection of circulating tumor cells in patients with breast cancer using the conditionally reprogrammed cell culture method and reverse transcription-PCR of hTERT and MAGE A1-6.
The present study aimed to verify the efficacy of the conditionally reprogrammed cell (CRC) culture method for the detection of circulating tumor cells (CTCs) in breast cancer. CTCs were isolated from the peripheral blood of patients with breast cancer, and culture of the collected CTCs was performed according to the conditional reprogramming protocol. Total RNA was extracted from cultured CTCs, and the hTERT and MAGE A1-6 genes were amplified using reverse transcription-PCR (RT-PCR). In addition, RNA extraction from another blood sample was performed and the expression of the two genes was analyzed by RT-PCR only. Following CRC culture, grown CTCs were observed in 7 samples (23.3%). The CTC detection rates by RT-PCR for the hTERT and MAGE A1-6 genes in CTCs grown using the CRC culture method were 26.7 and 10.0%, respectively. The positive expression rates for the hTERT and MAGE genes in CTCs assessed by RT-PCR only were 44.1 and 23.5%, respectively. When combining the positive expression rates of RT-PCR only and CRC culture for the hTERT and MAGE A1-6 genes, CTC detection rates increased to 53.3 and 23.3%, respectively. Additionally, when combining the positive expression rates of the two genes by either method, the CTC detection rate was the highest value observed. In conclusion, the present study revealed the potential of CRC culture in the detection of CTCs in breast cancer. Furthermore, a combination of CRC culture and RT-PCR for the hTERT and MAGE A1-6 genes is useful in enhancing the detection rate of CTCs in the blood.


Multiple sequence alignment by conformational space annealing.
We present a new method for multiple sequence alignment (MSA), which we call MSACSA. The method is based on the direct application of a global optimization method called the conformational space annealing (CSA) to a consistency-based score function constructed from pairwise sequence alignments between constituting sequences. We applied MSACSA to two MSA databases, the 82 families from the BAliBASE reference set 1 and the 366 families from the HOMSTRAD set. In all 450 cases, we obtained well optimized alignments satisfying more pairwise constraints producing, in consequence, more accurate alignments on average compared with a recent alignment method SPEM. One of the advantages of MSACSA is that it provides not just the global minimum alignment but also many distinct low-lying suboptimal alignments for a given objective function. This is due to the fact that conformational space annealing can maintain conformational diversity while searching for the conformations with low energies. This characteristics can help us to alleviate the problem arising from using an inaccurate score function. The method was the key factor for our success in the recent blind protein structure prediction experiment.


Operative lengthening of the femur.
Femoral lengthening with the aid of the apparatus described in this article can be accomplished safely and predictably. However, it is not without considerations and problems which must be fully understood and appreciated. The healing process requires months to years; with a cooperative patient and a diligent attentive orthopedist, the equalization of leg lengths is more than justified.


[Changes in bone mineral density of postmenopausal women in relation to the menstrual cycle length].
There is a strong relationship between the age of menarche, the length of the menstrual cycle and menstrual bleeding and fracture risk in the postmenopausal period. Evaluation of the menstrual cycle length and lumbar bone mineral density in postmenopausal women. We investigated three groups of postmenopausal women (each - n = 50). The first group included women with menstrual duration of 27 days during reproductive age, the second group included postmenopausal women with menstrual duration of 28 days during the reproductive age, and the third group consisted of postmenopausal women with menstrual duration of 30 days during reproductive age. The average age of women was 58.80 +/- 0.94 y. in the first group, 60.36 +/- 5.12 y. in the second group and -61.84 +/- 0.80 y. in the third group. Age, age of menarche, number of childbirths, length of the menstrual cycle and menstrual bleeding, and lumbar bone density were assessed and registered for each woman. We used DXA in a anterior-posterior projection to assess the bone density of the lumbar spine; the obtained results are shown in gram/cm2. The women from the third group, with average menstrual cycle length of 30 days, reach menopause at a significantly later age, have longer menstrual cycle and shorter menstrual bleeding, and higher lumbar spine bone density, compared to the other two groups. The data from our research show that women with anamnesis for average normal menstrual cycle length of 30 days reach menopausal period at a significantly later age, have shorter menstrual bleeding, and higher lumbar spine bone density compared to those with shorter menstrual cycle duration (27 and 28 days).


Isolation, sequencing, and structure-activity relationships of cyclotides.
Cyclotides are a topologically fascinating family of miniproteins discovered over the past decade that have expanded the diversity of plant-derived natural products. They are approximately 30 amino acids in size and occur in plants of the Violaceae, Rubiaceae, and Cucurbitaceae families. Despite their proteinaceous composition, cyclotides behave in much the same way as many nonpeptidic natural products in that they are resistant to degradation by enzymes or heat and can be extracted from plants using methanol. Their stability arises, in large part, due to their characteristic cyclic cystine knot (CCK) structural motif. Cystine knots are present in a variety of proteins of insect, plant, and animal origin, comprising a ring formed by two disulfide bonds and their connecting backbone segments that is threaded by a third disulfide bond. In cyclotides, the cystine knot is uniquely embedded within a head-to-tail cyclized peptide backbone, leading to the ultrastable CCK structural motif. Apart from the six absolutely conserved cysteine residues, the majority of amino acids in the six backbone loops of cyclotides are tolerant to variation. It has been predicted that the family might include up to 50,000 members; although, so far, sequences for only 140 have been reported. Cyclotides exhibit a variety of biological activities, including insecticidal, nematocidal, molluscicidal, antimicrobial, antibarnacle, anti-HIV, and antitumor activities. Due to their diverse activities and common structural core from which variable loops protrude, cyclotides can be thought of as combinatorial peptide templates capable of displaying a variety of amino acid sequences. They have thus attracted interest in drug design as well as in crop protection applications.


Incidence and morphology of the accessory head of the flexor pollicis longus muscle (Gantzer`s muscle) in a Turkish population.
To present the incidence, morphology, and the relationships of the accessory head of the flexor pollicis longus (Gantzer`s) muscle (AHFPL) in a recent Turkish population. The study was performed on 52 upper extremities of 26 adult Turkish cadavers in the Department of Anatomy, Ege University Faculty of Medicine, Izmir, Turkey in 2005. In our dissections, the prevalence and anatomical morphology of the AHFPL including muscle shape, origin and insertion point, and its relation to the anterior interosseous nerve (AIN) was examined. The AHFPL muscle was found in 27 upper extremities (51.9%). It was bilateral in 10 cadavers (74%), and unilateral in 7 cadavers (26%). The muscle shape was spindle in 19 (70.4%), and papillary in 8 (29.6%). The AHFPL originated from the coronoid process of the ulna in 22 upper extremities (81.5%), and the medial epicondyle of the humerus in 5 cases (18.5%). The AIN passed anterior to the AHFPL in one case (3.7%), lateral in 3 (11.1%), posterolateral in 8 (29.6%) and posterior in 15 (55.6%) cases. The knowledge of the morphology and the topography of the AIN and AHFPL is important for understanding the mechanism of the AIN syndrome. The results of this study show the mechanical compression due to the AHFPL may be a cause of the pronator and AIN syndromes.


What Can SCORE Web Portal Usage Analytics Tell Us About How Surgical Residents Learn?
The Surgical Council on Resident Education (SCORE) was established in 2004 with 2 goals: to develop a standardized, competency-based curriculum for general surgery residency training; and to develop a web portal to deliver this content. By 2012, 96% of general surgery residency programs subscribed to the SCORE web portal. Surgical educators have previously described the myriad ways they have incorporated SCORE into their curricula. The aim of this study was to analyze user data to describe how and when residents use SCORE. Using analytic software, we measured SCORE usage from July, 2013 to June, 2016. Data such as IP addresses, geo-tagging coordinates, and operating system platforms were collected. The primary outcome was the median duration of SCORE use. Secondary outcomes were the time of day and the operating system used when accessing SCORE. Descriptive statistics were performed, and a p < 0.05 was deemed statistically significant. There were 42,743 total SCORE subscribers during the study period (75% resident and 25% faculty) with a mean of 14,248 subscribers per year. The overall median duration of SCORE use was 11.9minute/session (interquartile range [IQR]: 6.8). Additionally, there was a significant increase in session length over the 3 academic years; 10.1 (IQR: 6.4), 11.9 (IQR: 7.2), and 13.2minute/session (IQR: 5.4) in 2013 to 2014, 2014 to 2015, and 2015 to 2016, respectively (p < 0.001). SCORE usage was highest in November to February at 21.0minute/session (14.2) compared to July to October and March to June (12.3 [IQR: 3.2] and 9.6minute/session [IQR: 2.2]), respectively (p < 0.001). This seasonal trend continued for all 3 years. We observed an increased number of sessions per day over the 3 years: median of 1500 sessions/d (IQR: 1115) vs 1706 (IQR: 1334) vs 1728 (IQR: 1352), p < 0.001. (Fig.). Most SCORE sessions occurred at night: 38,011 (IQR: 4532) vs 17,529 (IQR: 19,850) during the day (p < 0.001). Windows was the most frequently used operating system at 48.9% (p < 0.001 vs others). SCORE usage has increased significantly over the last 3 years, when measured by number of sessions per day and length of time per session. There are predictable daily, diurnal, and seasonal variations in SCORE usage. The annual in-training examination is a prominent factor stimulating SCORE usage.


A three-dimensional finite-element stress analysis of an endodontically prepared maxillary central incisor.
This study is an application of a three-dimensional Finite-Element Method to investigate the changes in stress characteristics of a prepared maxillary central incisor. The purpose of this study was to analyze stress distributions in this tooth after simulated canal preparation and static loading. A maxillary central incisor was embedded in acrylic, sectioned, photographed, and digitized. A three-dimensional finite-element model was generated by a computer and appropriately modified to simulate canal preparation. Data identified the highest stress magnitudes to be located between the middle and coronal thirds of the root; an area clinically observed to be prone to fracture during treatment. In addition, the magnitude of generated stresses was directly correlated with the simulated prepared canal diameter. The development of a validated three-dimensional finite-element method could identify areas that may predispose a tooth to structural failure during condensation loads.


Fused Deposition Modeling (FDM), the new asset for the production of tailored medicines.
Over the last few years, conventional medicine has been increasingly moving towards precision medicine. Today, the production of oral pharmaceutical forms tailored to patients is not achievable by traditional industrial means. A promising solution to customize oral drug delivery has been found in the utilization of 3D Printing and in particular Fused Deposition Modeling (FDM). Thus, the aim of this systematic literature review is to provide a synthesis on the production of pharmaceutical solid oral forms using FDM technology. In total, 72 relevant articles have been identified via two well-known scientific databases (PubMed and ScienceDirect). Overall, three different FDM methods have been reported: "Impregnation-FDM", "Hot Melt Extrusion coupled with FDM" and "Print-fill", which yielded to the formulation of thermoplastic polymers used as main component, five families of other excipients playing different functional roles and 47 active ingredients. Solutions are underway to overcome the high printing temperatures, which was the initial brake on to use thermosensitive ingredients with this technology. Also, the moisture sensitivity shown by a large number of prints in preliminary storage studies is highlighted. FDM seems to be especially fitted for the treatment of rare diseases, and particular populations requiring tailored doses or release kinetics. For future use of FDM in clinical trials, an implication of health regulatory agencies would be necessary. Hence, further efforts would likely be oriented to the use of a quality approach such as "Quality by Design" which could facilitate its approval by the authorities, and also be an aid to the development of this technology for manufacturers.


Whole-exome sequencing diagnosis of two autosomal recessive disorders in one family.
Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous disorder for which subtyping through molecular analysis can help determine the eventual phenotype and prognosis. We used whole-exome sequencing to identify a new homozygous splice-site mutation in ST14 (IVS5+1G>A), encoding matriptase, in a 4-year-old girl with ARCI from a consanguineous Kuwaiti family. Clinically, she also had hypotrichosis, which supported a diagnosis of ARCI type 11. Only four previous examples of pathogenic mutations in ST14 have been reported, and our findings expand the genotype-phenotype correlation for this subtype of ARCI. Our patient was the second child born to these parents; the first (deceased) and third children had congenital brain and eye abnormalities, of uncertain aetiology and with no precise diagnosis. Further analysis of our patient's exome dataset revealed heterozygosity for a splice-site mutation in POMT1 (IVS4+1G>T), encoding the protein O-mannosyltransferase, a gene implicated in Walker-Warburg syndrome. DNA sequencing in the third child showed homozygosity for this mutation in POMT1. The first-cousin parents were both heterozygous for the splice-site mutations in ST14 and POMT1. In this family, whole-exome sequencing provided accurate subtyping of a form of ARCI in one child and provide an explanation for an undiagnosed developmental disorder in two other children, findings that improve the prospects for diagnostic accuracy and genetic counselling, and demonstrate the impact of next-generation sequencing technologies on clinical genetics.


Glycosylated seryl residues in wall protein of elongating pea stems.
The protein content of salt-washed cell walls isolated from etiolated stems of Pisum sativum L. approximately doubled during elongation. In the same period the concentration in the wall of hydroxyproline, hydrazine-labile (= presumably glycosylated) serine, valine, tyrosine, lysine, and histidine increased markedly in comparison with other amino acids. After elongation was completed both the amino acid composition and the protein content of the cell wall changed only slightly. The ratio for the wall of hydrazine-labile seryl residues to hydroxyprolyl residues remained constant during and after elongation and was found to be 0.20. A linear relationship was established between the rate of elongation and the concentration in the wall of the hydroxyproline-rich glycoprotein both in vivo and in cut sections incubated in buffer.


A pragmatic intervention to promote condom use by female sex workers in Thailand.
An overview is presented of a multifaceted intervention to promote consistent condom use by female commercial sex workers in Thailand, in the context of the government's 100% condom use policy for preventing spread of human immunodeficiency virus (HIV) infection. The project is described with reference to a succession of stages including pre-programme needs assessment, intervention design, implementation and evaluation. The key elements of the intervention were video scenarios and discussions coordinated by health personnel, and video-depicted open-ended narratives aimed at helping sex workers to explore their personal and work-related dilemmas and concerns. A core objective was to enhance sex workers' self-esteem and perceived future with a view to strengthening their motivation to take preventive action against HIV infection. The intervention was evaluated using a combination of qualitative (process evaluation) and quantitative (outcome) methods. The outcome evaluation was undertaken using a pretest, post-test intervention and control group quasi-experimental design. There were significant increases in consistent condom use among the intervention groups but not among the controls. Pragmatic stability is advocated for the Thai sex industry and recommendations are offered for good quality HIV prevention activities.


ROCK inhibition enhances microRNA function by promoting deadenylation of targeted mRNAs via increasing PAIP2 expression.
The reduced expression levels and functional impairment of global miRNAs are related to various human diseases, including cancers. However, relatively little is known about how global miRNA function may be upregulated. Here, we report that global miRNA function can be enhanced by Rho-associated, coiled-coil-containing protein kinase (ROCK) inhibitors. The regulation of miRNA function by ROCK inhibitors is mediated, at least in part, by poly(A)-binding protein-interacting protein 2 (PAIP2), which enhances poly(A)-shortening of miRNA-targeted mRNAs and leads to global upregulation of miRNA function. In the presence of a ROCK inhibitor, PAIP2 expression is enhanced by the transcription factor hepatocyte nuclear factor 4 alpha (HNF4A) through increased ROCK1 nuclear localization and enhanced ROCK1 association with HNF4A. Our data reveal an unexpected role of ROCK1 as a cofactor of HNF4A in enhancing PAIP2 transcription. ROCK inhibitors may be useful for the various pathologies associated with the impairment of global miRNA function.


Cytotoxic effects of children's faeces: relation to diarrhoea due to Clostridium difficile and other enteric pathogens.
Cytotoxicity of faecal extracts was demonstrated in 47 of 88 children (54%) referred for microbiological investigation of stools. Cytotoxic Clostridium difficile and vertotoxigenic Escherichia coli (VTEC) were the pathogens identified most commonly but cytotoxicity was also found in association with Campylobacter jejuni, Salmonella spp, Shigella sonnei, Giardia lamblia, rotavirus, adenovirus and poliovirus type 1 which had been acquired by oral immunization. In two patients, one of whom had cystic fibrosis, cytotoxicity of faecal extracts was associated with isolation of Pseudomonas aeruginosa. In five of 13 patients with diarrhoea and cytotoxic C. difficile, other pathogens were also present, in agreement with the view that C. difficile are more readily recovered when the intestinal flora have been altered by colonization with other micro-organisms. There was no correlation between previous treatment with antibiotics and isolation of C. difficile. Cytotoxicity neutralized by antitoxin, usually to C. sordellii, is used to detect cytotoxic C. difficile. We suggest that cytotoxicity not neutralized in this way should be an indication for further investigation of stools for the presence of other pathogens such as VTEC or viruses.


cDNA cloning and sequence analysis of Musca domestica antifungal peptide-1 (MAF-1).
To clone the cDNA sequence of Musca domestica antifungal peptide-1 (MAF-1) and analyze the amino acid sequence of MAF-1 by bioinformatics method. Based on the primer designed according to the N-terminal amino acid sequence of MAF-1, the cDNA and amino sequence of MAF-1 were obtained by the methods of RACE and NestPCR. The accuracy of the experiment was confirmed by RT-PCR The characteristic of the sequence was analyzed by bioinformatics software. The length of the cDNA sequence of MAF-1 was 568 bp by 3'RACE, including an open reading frame (ORF) of 441 bp length and 3'UTR of 127 bp. It was a novel sequence with the submission number of HM178948 in GenBank since none homology was found when compared with other sequences by Blast. Added with the 9 amino acids that were not used to design primer, the whole sequence of MAF-1 was 156 amino acids conferred from its cDNA. 139 bp cDNA sequence was obtained by 5'RACE and the result was consistent to 3'RACE. The result of RT-PCR showed the cDNA of MAF-1 mature peptide was accurate. The bioinformatics analysis deduced that the theoretic molecular weight and isoelectric point of the whole protein sequence of MAF-1 gene were similar to those detected. The ExPASy illustrated that the MAF-1 gene had a signal peptide. There were abundant a-helix in it, the domain located between the 128 and 153 amino acid residuals. Subcellular analysis showed MAF-1 was almost in the nucleus. Predict Protein found two protein kinase C phosphorylation sites and one N-myristoylation site, and predicted that it was not a globular protein. In the end, the three dimension image of MAF-1 was set up with 3D-pssm of ExPASy. The cDNA sequence and the amino acid sequence of MAF-1 have been obtained and analyzed successfully.


Mildly Impaired Foot Control in Long-Term Treated Patients with Wilson's Disease.
Abnormal gait is a common initial symptom of Wilson's disease, which responds well to therapy, but has not been analyzed in detail so far. In a pilot study, a mild gait disturbance could be detected in long-term treated Wilson patients. The question still is what the underlying functional deficit of this gait disturbance is and how this functional deficit correlates with further clinical and laboratory findings. In 30 long-term treated Wilson patients, the vertical component of foot ground reaction forces (GRF-curves) was analyzed during free walking without aid at the preferred gait speed over a distance of 40 m. An Infotronic® gait analysis system, consisting of soft tissue shoes with solid, but flexible plates containing eight force transducers, was used to record the pressure of the feet on the floor. Parameters of the GRF-curves were correlated with clinical scores as well as laboratory findings. The results of Wilson patients were compared to those of an age- and sex-matched control group. In 24 out of 30 Wilson patients and all controls, two peaks could be distinguished: the first "heel-on" and the second "push-off" peak. The heights of these peaks above the midstance valley were significantly reduced in the patients (p < 0.05). The time differences between peaks 1 or 2 and midstance valley were significantly negatively correlated with the total impairment score (p < 0.05). Gait speed was significantly correlated with the height of the "push-off" peak above the midstance valley (p < 0.045). The GRF-curves of free walking, long-term treated patients with Wilson's disease showed a reduced "push-off" peak as an underlying deficit to push the center of mass of the body to the contralateral side with the forefoot, explaining the reduction in gait speed during walking.


Comparative analysis of intraluteal steroidogenic enzymes emphasises the functionality of fresh and persistent corpora lutea during pro--and metoestrus in the lynx.
European lynx species demonstrate an atypical ovarian cycle compared to other felids. The physiological persistence of corpora lutea (CLs), reflected in constantly elevated progesterone (P4) concentrations in serum, is thought to ensure a seasonal monooestrus. Moreover, the coexistence of CLs from a recent ovulation (freshCLs) and persistent CLs from previous years (perCLs) on the same ovary has been proven. We assume that perCLs in lynxes occur due to fundamentally different mechanisms of luteal regression. Our study presents a detailed analysis of steroidogenic enzymes and steroids in fresh and perCLs obtained from Iberian lynxes during metoestrus, and in perCLs obtained from Eurasian lynxes during prooestrus. By quantitative PCR we measured relative mRNA amounts of steroidogenic acute regulatory protein (STAR), cytochrome P450 oxidases (CYPs), hydroxysteroid dehydrogenases (HSDs) and a steroid reductase (SRD). Protein expression in CLs was investigated for CYP11A1, CYP17A1, CYP19A1 and HSD3B. Additionally, the intraluteal and serum steroid content was determined. During metoestrus, mRNA amounts of STAR, CYP11A1, CYP19A1, HSD17B7 and SRD5A1 were significantly higher in perCLs compared to freshCLs. Protein of CYP11A1 was detected independently of the CL age in metoestrus, but expression was less evident in prooestrous perCLs. The protein signal of CYP17A1 was strong in freshCLs and perCLs of metoestrus, but weak at prooestrus. The presence of CYP19A1 protein was confirmed in each stage of the CL. These findings contribute to the hypothesis that CLs from previous years might support freshly developed CLs for pregnancy maintenance. However, initiation of ovulation might require a functional down-regulation of perCLs prior to breeding. It is noteworthy that the HSD3B1 mRNA amount was significantly elevated in fresh compared to perCLs (metoestrus). Accordingly, HSD3B protein was substantially present in freshCLs, whereas signals were literally absent in all perCLs. Elevated expression of HSD3B coincided with high intraluteal oestrogen concentrations in freshCLs; however, the enzyme pattern was less concordant with intraluteal P4 and androgen concentrations. Serum P4 concentrations of Iberian lynxes were constant between prooestrus and prolonged dioestrus. Moreover, constantly high serum oestrogen concentrations were measured during pro-, met- and prolonged dioestrus. The physiology of exceptionally high serum oestrogen concentrations outside the breeding season of lynxes merits further investigation. In conclusion our study supports the concept that the unique reproductive strategy of lynxes is directly linked to sustained intraluteal steroid biogenesis in persistent CLs.


Adriamycin (doxorubicin), vinblastine, and mitomycin C combination chemotherapy in refractory breast carcinoma.
Twenty-seven evaluable patients with refractory, metastatic breast carcinoma were treated with Adriamycin (doxorubicin) 30 mg/m2 and vinblastine 6 mg/m2 intravenously on days 1 and 28 every 8 weeks, and mitomycin C 10 mg/m2 intravenously on day 1 every 8 weeks (AVM). There were three complete and six partial responses for a total response rate of 33%. In addition, 2 patients had minimal responses, and 10 patients achieved disease stabilization. Median time to disease progression for responders was 116 days (range, 49-812+ days). Drug toxicity was tolerable: 12 patients (44%) experienced significant bone marrow suppression. There were no drug-related deaths. Although AVM appears to be an active drug combination in heavily pretreated patients with metastatic breast carcinoma, the contribution of vinblastine and mitomycin C to single agent Adriamycin in previously treated patients is not clear from this study.


Integrated PPI- and WGCNA-retrieval of hub gene signatures for soft substrates inhibition of human fibroblasts proliferation and differentiation.
Fibroblasts (FBs) are the most important functional cells in the process of wound repair, and their functions can be activated by different signals at the pathological site. Although wound repair is associated with microenvironmental stiffness, the effect of matrix stiffness on FBs remains elusive. In this study, TGF-β1 was used to mimic the fibrotic environment under pathological conditions. We found that the soft substrates made FBs slender compared with tissue culture plastic, and the main altered biological function was the inhibition of proliferation and differentiation ability. Through PPI and WGCNA analysis, 63 hub genes were found, including GADD45A, CDKN3, HIST2H3PS2, ACTB, etc., which may be the main targets of soft substrates affecting the proliferation and differentiation of FBs. Our findings not only provide a more detailed report on the effect of matrix stiffness on the function of human skin FBs, but also may provide new intervention ideas for improving scars and other diseases caused by excessive cell proliferation, with potential clinical application prospects.


The effect of transcutaneous vagus nerve stimulation on fear generalization and subsequent fear extinction.
Fear overgeneralization is thought to be one of the cardinal processes underlying anxiety disorders, and a determinant of the onset, maintenance and recurrence of these disorders. Animal studies have shown that stimulating the vagus nerve (VNS) affects neuronal pathways implicated in pattern separation and completion, suggesting it may reduce the generalization of a fear memory to novel situations. In a one-day study, 58 healthy students were subjected to a fear conditioning, fear generalization, and fear extinction paradigm. Participants were randomly assigned to receive either transcutaneous auricular VNS (tVNS; final N = 29) or sham stimulation (final N = 29) during the generalization and extinction phases. tVNS did not affect fear generalization, as reflected by US expectancy ratings and fear potentiated startle responses. However, participants who received tVNS reported lower US expectancy ratings to the CS+ during the extinction phase, possibly reflecting a stronger declarative extinction of fear. No effects of tVNS on fear potentiated startle responses during extinction were found. The pattern of findings regarding extinction of declarative fear suggest a facilitating effect of tVNS.


Use of infrared thermal imaging to isolate Arabidopsis mutants defective in stomatal regulation.
In response to drought, plants synthesise the hormone abscisic acid (ABA), which triggers closure of the stomatal pores. This process is vital for plants to conserve water by reducing transpirational water loss. Moreover, recent studies have demonstrated the advantages of the Arabidopsis stomatal guard cell for combining genetic, molecular and biophysical approaches to characterise ABA action. However, genetic dissection of stomatal regulation has been limited by the difficulty of identifying a reliable phenotype for mutant screening. Leaf temperature can be used as an indicator to detect mutants with altered stomatal control, since transpiration causes leaf cooling. In this study, we optimised experimental conditions under which individual Arabidopsis plants with altered stomatal responses to drought can be identified by infrared thermography. These conditions were then used to perform a pilot screen for mutants that displayed a reduced ability to close their stomata and hence appeared colder than the wild type. Some of the mutants recovered were deficient in ABA accumulation, and corresponded to alleles of the ABA biosynthesis loci ABA1, ABA2 and ABA3. Interestingly, two of these novel aba2 alleles were able to intragenically complement the aba2-1 mutation. The remaining mutants showed reduced ABA responsiveness in guard cells. In addition to the previously known abi1-1 mutation, we isolated mutations at two novel loci designated as OST1 (OPEN STOMATA 1) and OST2. Remarkably, ost1 and ost2 represent, to our knowledge, the first Arabidopsis mutations altering ABA responsiveness in stomata and not in seeds.


Cycling vrille expression is required for a functional Drosophila clock.
We identified a novel regulatory loop within Drosophila's circadian clock. A screen for clock-controlled genes recovered vrille (vri), a transcription factor essential for embryonic development. vri is expressed in circadian pacemaker cells in larval and adult brains. vri RNA levels oscillate with a circadian rhythm. Cycling is directly regulated by the transcription factors dCLOCK and CYCLE, which are also required for oscillations of period and timeless RNA. Eliminating the normal vri cycle suppresses period and timeless expression and causes long-period behavioral rhythms and arrhythmicity, indicating that cycling vri is required for a functional Drosophila clock. We also show that dCLOCK and VRI independently regulate levels of a neuropeptide, pigment dispersing factor, which appears to regulate overt behavior.


Virtual endoscopy.
Virtual endoscopy is a new-generation technique which combines the features of endoscopic viewing and cross-sectional volumetric imaging. In the evaluation of gastrointestinal cancers, virtual endoscopy has been most commonly used in colorectal carcinomas and to a much lesser extent in gastric carcinomas. In this review, the current status of virtual colonoscopy was reviewed together with a brief discussion of virtual gastroscopy.


Ameloblastoma in the Hong Kong Chinese. Part 2: systematic review and radiological presentation.
The aim of this part of the study was to determine the radiological presentation on conventional radiographs of central ameloblastomas in the Hong Kong Chinese and compare them with other reported series by a systematic review (SR). The study had two elements, that of a complete series of all ameloblastomas presenting at a major Chinese maxillofacial surgical unit and a SR. The files of the Department of Oral and Maxillofacial Surgery of the University of Hong Kong between 1989 and 2000 were reviewed for ameloblastoma cases. The relevant literature was identified by electronic databases, review of citation lists and handsearching of key journals. The principal selection criterion was that the study should represent a complete collection of cases. Only 13 reports gave any radiological details. The present study of the Hong Kong Chinese contained 61 cases. With the exception of radiodensity and shape of radiolucency, the majority of the 13 other reports did not record the other radiological features that could be important in the diagnosis. The present study agreed with the synthesis of the 13 reports with regards to complete radiolucency and cortication of ameloblastomas, but disagreed with regards to other important features. The present study had a significantly higher proportion of unilocular lesions, better marginal definition, and more frequent perforation of the cortex and buccolingual expansion. Nine of the ten maxillary lesions straddled both anterior and posterior sextants with four crossing the midline, whereas only 13 of the 51 mandibular cases affected both sextants, of which eight crossed the midline. The unicystic form, which was most prevalent, appeared significantly more frequently as unilocular radiolucencies in comparison with the non-unicystic forms. The frequencies of unicystic forms and unilocular presentations were significantly greater in the young. The lesions in the young were significantly sited solely in the posterior sextant. The lower border of the mandible was reached and affected by ameloblastoma in 36 cases in the present report. It was displaced and thinned in 15 cases whereas in just five it was at least partially undisplaced with the lesion expanding down past it either buccally or lingually to it. The unicystic form was significantly more associated with root resorption, tooth displacement and crowns of unerupted teeth. Radiologically, ameloblastomas in the Hong Kong Chinese differ significantly with regards to many features. This can be in part explained by the higher proportion of the unicystic form.


Efficacy of whole lung lavage in pulmonary alveolar proteinosis: a 20-year experience at a reference center in Thailand.
Pulmonary alveolar proteinosis (PAP) is a rare lung syndrome. The current standard treatment is whole lung lavage (WLL). We reviewed PAP cases treated with WLL during a 243-month period. The primary objective was to describe the efficacy of WLL. We compared chest imaging resolution and pulmonary function tests (PaO2 and DLCO) before the first and after the last WLL. The secondary objectives were to compare mMRC dyspnea scores, other lung function parameters, and complications of WLL. We retrospectively reviewed PAP patients from 1 January 2000 to 31 March 2020. Demographic data, pulmonary function tests, and the efficacy of WLL were collected from the electronic medical database and analyzed by descriptive analysis. Differences in data used the student t-test to compare parameters pre- and post-WLL. A total of 19 PAP patients and 50 WLL procedures were included. Eleven patients (57.9%) were females and the mean age was 51.5±11.7 years. Dyspnea (100%) and cough (94.7%) were the two leading symptoms. The most common indication for WLL was progressive dyspnea. There were significant improvements in SpO2 from 86% to 94% (P<0.001), PaO2 from 49.3 to 66.1 (P<0.001), DLCO from 31.8% to 52.5% predicted (P=0.013), and the mMRC dyspnea score from 3 to 2 (P<0.001) without major complications. WLL is an effective standard treatment for PAP cases. It is safe and can be used as a primary treatment in case of inhaled anti GM-CSF is not available.


Symposium: The potential impact of diagnosis-related groups on long term care.
On April 29, 1983, a group of 33 individuals in the field of long term care convened to discuss the potential impact on long term care of federal regulations that mandate prospective reimbursement to hospitals by the Government of a fixed amount for all cases in the same category, or diagnosis-related group (DRG). The following is an edited text of that symposium, sponsored by the PRIDE Institute, Department of Community Medicine, St. Vincent's Hospital and Medical Center of New York.


[School escorts in inclusive education- the current situation in the state of Baden-Wurttemberg].
In the context of inclusive education, so-called «Schulbegleiter» (school escorts) have been installed to assist children with special needs. However, adequate conceptions of their role are lacking, and no provisions exist describing the exact tasks and duties of these school escorts. This article presents data on a statewide empirical study and provides information on the professional background, qualifications, and assignments of such escorts as well as the nature of the assisted children in the German state of Baden-Württemberg. The data were collected in nearly 50 % of all schools providing general education in Baden-Württemberg, and a total of 526 school escorts completed a questionnaire on their work. Children with special needs who received such assistance were aged 6 to 19 years (M = 10.4) and had a mental disorder in nearly three-fourths of all cases, with autism spectrum disorders being most common (59.4 %). The most frequent assignments of the escorts were providing practical assistance during classes and mobilizing the child as well as providing direct support in emotionally challenging situations. Such escorts can make a significant contribution to the inclusive education of disabled children. They do, however, need an adequate qualification and practical competences to meet the diverse challenges of children with special needs. Child and adolescent psychiatrists are supposed to stay involved in the process, not only by planning interventions, but also during the course of inclusive education itself. Thus, the emotional situation and adjustment of included children with mental disorders over time must be monitored adequately.


Information theoretic approaches for inference of biological networks from continuous-valued data.
Characterising programs of gene regulation by studying individual protein-DNA and protein-protein interactions would require a large volume of high-resolution proteomics data, and such data are not yet available. Instead, many gene regulatory network (GRN) techniques have been developed, which leverage the wealth of transcriptomic data generated by recent consortia to study indirect, gene-level relationships between transcriptional regulators. Despite the popularity of such methods, previous methods of GRN inference exhibit limitations that we highlight and address through the lens of information theory. We introduce new model-free and non-linear information theoretic measures for the inference of GRNs and other biological networks from continuous-valued data. Although previous tools have implemented mutual information as a means of inferring pairwise associations, they either introduce statistical bias through discretisation or are limited to modelling undirected relationships. Our approach overcomes both of these limitations, as demonstrated by a substantial improvement in empirical performance for a set of 160 GRNs of varying size and topology. The information theoretic measures described in this study yield substantial improvements over previous approaches (e.g. ARACNE) and have been implemented in the latest release of NAIL (Network Analysis and Inference Library). However, despite the theoretical and empirical advantages of these new measures, they do not circumvent the fundamental limitation of indeterminacy exhibited across this class of biological networks. These methods have presently found value in computational neurobiology, and will likely gain traction for GRN analysis as the volume and quality of temporal transcriptomics data continues to improve.


Recent Progress in the Chemistry of Daphniphyllum Alkaloids †.
Daphniphyllum is an evergreen species known since 1826. After initial systematic investigations, more than 320 members of this family have been isolated, which comprise complex and fascinating structures. Unique azapolycyclic architectures containing one or more quaternary stereocenters render these alkaloids synthetically challenging. This review covers efforts toward the synthesis of Daphniphyllum alkaloids spanning the period from 2005 to the beginning of 2016, including reported biological activities as well as the isolation of new members of this genus.


The molecular mechanisms that control thrombopoiesis.
Our understanding of thrombopoiesis--the formation of blood platelets--has improved greatly in the last decade, with the cloning and characterization of thrombopoietin, the primary regulator of this process. Thrombopoietin affects nearly all aspects of platelet production, from self-renewal and expansion of HSCs, through stimulation of the proliferation of megakaryocyte progenitor cells, to support of the maturation of these cells into platelet-producing cells. The molecular and cellular mechanisms through which thrombopoietin affects platelet production provide new insights into the interplay between intrinsic and extrinsic influences on hematopoiesis and highlight new opportunities to translate basic biology into clinical advances.


[A case of aminophylline hypersensitivity reaction due to ethylenediamine].
We present a case of aminophylline hypersensitivity reaction due to ethylenediamine. A thirty-year-old Japanese female admitted to our hospital to evaluate generalized urticarial reaction immediately after intravenous administration of aminophylline. Skin intradermal testing was positive with ethylenediamine. A positive intravenous test was found with aminophylline and negative with diprophylline which does not contain ethylenediamine. There are some reports of aminophylline hypersensitivity reaction and the most cases were delayed type reaction in English literatures. However, most of Japanese cases were immediate type. Acetylation is a main metabolic pathway of ethylenediamine. Most of Japanese have a rapid or intermediate acetylators on the other hand. Caucasian have a 50% likelihood of being slow acetylators. This difference suggest the different incidences of immediate and delayed reaction of aminophylline hypersensitivity reaction in Japanese and Caucasian respectively.


A national survey of attitudes and practices of primary-care physicians relating to nutrition: strategies for enhancing the use of clinical nutrition in medical practice.
A nationwide mail survey was used to determine the degree to which primary-care physicians indicated that they practice the "core competencies" in clinical nutrition identified by Young et al (Am J Clin Nutr 1983;38:800-10). We also surveyed the nutrition-related attitudes of these physicians. Although the 3416 physicians who responded to the survey tended to report favorable attitudes toward using nutrition in their practice, these favorable attitudes were not consistent with their own reports of clinical performance. Neither the positive- or negative-attitude score correlated highly with the reported behavior-practice score. The clinical practices reported by those surveyed are well below the minimum level defined by the Young et al essential core competencies in clinical nutrition. The attitudes, practices, and demographic characteristics associated with the clinical performance variables suggest educational strategies for improving the competence of primary-care physicians and medical students in clinical nutrition.


Evidence for (lipo) oligosaccharides in Borrelia burgdorferi and their serological specificity.
SDS-PAGE and Western immunoblot profiles have been determined for different strains of Borrelia burgdorferi. Major proteins of 60 kDa, 41 kDa corresponding to flagellin, 34-36 kDa and 30-31 kDa corresponding to OspB and OspA respectively, and 18-20 kDa corresponding to 'pC' fractions were detected. A "rough" lipopolysaccharide which we called lipooligosaccharide (LOS) of 8-11 kDa appeared to be present, being detected by specific silver staining, as in crude Borrelia lysates as in proteinase K digested Borrelia strains, quite similar in shape among the different strains examined. The LOS reacted in Western blotting with immune anti-B. burgdorferi rabbit serum and also with sera collected from humans affected by Lyme borreliosis. The LOS did not react with sera positive for syphilis or leptospirosis, and their immunological specificity is discussed.


Electric field driven multi-state magnetization switching in triangular nanomagnets on piezoelectric substrate.
Electric field control of magnetic state switching mediated by magneto-elastic coupling in multiferroic heterostructures consisting of shape anisotropic magnetostrictive nanomagnets elastically coupled with a piezoelectric substrate has a promising potential for next generation magneto-elastic memory and logic devices. In this work, by using micromagnetic simulation, we showed that localized strain-induced magnetic anisotropy caused by the electric field-induced piezostrain combined with strong multifold shape anisotropy effect can be used for achieving a multistate switching of magnetization in a triangular soft magnetic nano-island on a piezoelectric substrate. A piezostrain-induced uniaxial magnetic anisotropy pulse applied in specific directions switches the magnetization within the triangular nanomagnet by an angle of 60° from the initial state. The relation between critical magnitude of the strain pulse for the switching of the magnetization states and geometric parameters (thickness and lateral size) within the triangular nanomagnets has been worked out. Complete cycles of clockwise as well as counter-clockwise switching of the magnetization states of the triangular nanomagnet have been achieved by a series of sequential switching with different directions of applied strain-induced magnetic anisotropy. This local gating scheme-based multistate switching can be used for electric field-induced ultra-fast, deterministic and reversible magnetization switching which are the key challenges in designing of the magnetoelastic and/or magnetoelectric memory and logic devices.


Dynamical facilitation governs glassy dynamics in suspensions of colloidal ellipsoids.
One of the greatest challenges in contemporary condensed matter physics is to ascertain whether the formation of glasses from liquids is fundamentally thermodynamic or dynamic in origin. Although the thermodynamic paradigm has dominated theoretical research for decades, the purely kinetic perspective of the dynamical facilitation (DF) theory has attained prominence in recent times. In particular, recent experiments and simulations have highlighted the importance of facilitation using simple model systems composed of spherical particles. However, an overwhelming majority of liquids possess anisotropy in particle shape and interactions, and it is therefore imperative to examine facilitation in complex glass formers. Here, we apply the DF theory to systems with orientational degrees of freedom as well as anisotropic attractive interactions. By analyzing data from experiments on colloidal ellipsoids, we show that facilitation plays a pivotal role in translational as well as orientational relaxation. Furthermore, we demonstrate that the introduction of attractive interactions leads to spatial decoupling of translational and rotational facilitation, which subsequently results in the decoupling of dynamical heterogeneities. Most strikingly, the DF theory can predict the existence of reentrant glass transitions based on the statistics of localized dynamical events, called excitations, whose duration is substantially smaller than the structural relaxation time. Our findings pave the way for systematically testing the DF approach in complex glass formers and also establish the significance of facilitation in governing structural relaxation in supercooled liquids.


Effect of the duration of protease inhibitor therapy in HIV-infected individuals on the severity of obstructive sleep apnea.
Protease inhibitors (PIs) are a vital part of the antiretroviral therapy. Long-term use of PIs may cause lipodystrophy, a clinical syndrome characterized by peripheral lipoatrophy and central fat accumulation, which may increase the risk of developing obstructive sleep apnea (OSA) in HIV-infected patients. We hypothesize that a longer duration of PIs' use might be associated with increasing severity of OSA in HIV-infected patients. This was a retrospective cohort study of HIV-infected patients who were treated with PIs, who presented with symptoms suggestive of OSA, and underwent nocturnal polysomnography. The primary objective of the study is to evaluate the association between the duration of PIs' use and the severity of OSA. The duration of PIs' use measured in months was recorded for each patient. The primary outcome of interest was the apnea-hypopnea index (AHI) obtained at the time of the sleep study. Data were analyzed using univariate and multivariate linear regression between AHIs with PIs' use as well as other predictors. A total of 54 patients diagnosed with HIV and OSA were included in the study cohort for the analysis. Sleep study body mass index (BMI; P = 0.042) and change in BMI (ΔBMI; P = 0.027) were the only statistically significant independent predictors of AHI. The association between AHI and PIs' use duration was found to be nonlinear and nonsignificant. Gender differences evaluation suggested possible duration-related effect relationship between PIs and OSA severity among HIV-infected men exposed to PIs within a 66-month duration. We did not observe a significant association between PIs' use duration and the severity of OSA.


Image-guided radiotherapy using surgical clips as fiducial markers after prostatectomy: a report of total setup error, required PTV expansion, and dosimetric implications.
To determine the total setup error and the required planning target volume (PTV) margin for prostate bed without image guided radiotherapy (IGRT), and to demonstrate the feasibility and dosimetric benefit of IGRT post prostatectomy using surgical clips. Seventeen patients were treated with intensity modulated radiotherapy (IMRT) to the prostate bed with a 1cm PTV margin. Three-dimensional shifts of the surgical clips inside the prostate bed were measured with respect to the isocenter from 364 orthogonal kV image pairs, and the total setup error was calculated to determine the required PTV margin. Alternative IMRT plans using 5mm or 1cm PTV expansion were generated and compared for rectal and bladder sparing. Surgical clips were reproducibly and reliably identified. The mean (standard deviation) shifts in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP), axes were: -0.1 mm (1.7 mm), 0.6 mm (2.4 mm), and -2.1 mm (2.6 mm), respectively. The required PTV margins were calculated to be 6, 8, and 9 mm in the LR, AP, and SI axis, respectively. A PTV expansion of 5mm, compared to 1cm, significantly reduced V65 Gy to the rectum by 10%. In the absence of IGRT, a non-uniform PTV margin of 6mm LR, 8mm AP, and 9 mm SI should be considered. Use of clips as fiducial markers can decrease the total setup error, enable a smaller PTV margin, and improve rectal sparing.