Scar Remodeling with the Association of Monopolar Capacitive Radiofrequency, Electric Stimulation, and Negative Pressure.
A study was established to objectively assess the effects of low-intensity electromagnetic and electric stimulation plus negative pressure on mature scars. Radiofrequency plus negative pressure therapy demonstrated a favorable reorganization and regeneration of the collagen and elastic fibers and was proposed for the treatment of cellulitis and skin stretch marks. Twenty-six mature scars in 20 Caucasian patients (15 females and 5 males) were enrolled in the study. The treatments were carried out with a Class I, BF-type electromedical device equipped with a radiofrequency generator, an electric pulse generator, and a vacuum pump twice a week for 3 months. Corneometry, transepidermal water loss, elastometry, colorimetry, and three-dimensional skin surface pattern were objectively assessed with Multi Probe Adapter System MPA and PRIMOS pico. A subjective assessment was carried out with the VAS and PSAS scales. Each scar was compared before and after the treatment and with the skin in the corresponding healthy contralateral anatomical area at the same times. Reduction of the scar surface wrinkling and overall scar flattening were demonstrated after the treatment. The scar slightly tended to approach the color and elasticity of healthy skin too. The combined local treatment of mature scars with low-intensity electromagnetic and electric stimulation in association with negative pressure might suggest a favorable synergic effect on the scar collagen and elastic fiber remodeling.


A Phase I-II, Open-Label, Multicenter Trial to Determine the Dosimetry and Safety of 99mTc-Sestamibi in Pediatric Subjects.
Myocardial perfusion imaging has long been used off label by practitioners attending for children with cardiac aliments. To provide clinicians with evidence-based dosage recommendation, a phase I-II, open-label, nonrandomized, multicenter trial was therefore designed using (99m)Tc-sestamibi in pediatric subjects (registered under www.clinicaltrials.gov identifier no. NCT00162045). Safety and pharmacokinetic data were collected from 78 subjects using either a 1-d imaging protocol (3.7-7.4 MBq/kg, followed by 11.1 MBq/kg) or a 2-d protocol (7.4 MBq/kg for both rest and stress). Anterior and posterior planar images were collected at 15 min, 1.5 h, 4 h, and 8 h. Blood and urine samples were collected at predetermined times. Subjects included 39 children (mean age ± SD, 8.5 ± 2.04 y) and 39 adolescents (mean age ± SD, 13.6 ± 1.39 y). Mean estimated organ-absorbed doses to the upper large intestine, small intestine, gallbladder wall, and lower large intestines were 0.082, 0.043, 0.042, and 0.035 mSv/MBq, respectively. All patients tolerated the radiotracer without serious adverse effects. Significant differences were observed in the liver, upper large intestine contents, and small intestine contents between rest and stress imaging. The effective dose equivalent and effective dose averages were lower in adolescents than younger children (0.011 and 0.019 mSv/MBq, respectively; P < 0.0001). Percentage injected doses (%IDs) corrected for radioactive decay in all dosimetry-evaluable subjects at 15 min and 4 h were 1.9% and 1.2% in the myocardium. Similarly in the lungs, the %ID for all dosimetry-evaluable subjects was 4.9% at 15 min after injection. At rest, the %ID in the liver decreased from a maximum of about 26% at 15 min to less than 9% at 90 min. With stress, values decreased from 15% to 7%, respectively. The estimates of radiation dosimetry, pharmacokinetic parameters, and safety profile in this study population are similar to published studies based on body-mass extrapolations from studies in adults. As such, applying current (99m)Tc-sestamibi dosing regimens for 1- and 2-d protocols based on those extrapolations will result in the expected radiation dose in children and adolescents.


Structure and function of human Vps20 and Snf7 proteins.
Snf7p (sucrose non-fermenting) and Vps20p (vacuolar protein-sorting) are small coil-coiled proteins involved in yeast MVB (multivesicular body) structure, formation and function. In the present study, we report the identification of three human homologues of yeast Snf7p, designated hSnf7-1, hSnf7-2 and hSnf7-3, and a single human Vps20p homologue, designated hVps20, that may have similar roles in humans. Immunofluorescence studies showed that hSnf7-1 and hSnf7-3 localized in large vesicular structures that also co-localized with late endosomal/lysosomal structures induced by overexpressing an ATPase-defective Vps4-A mutant. In contrast, overexpressed hVps20 showed a typical endosomal membrane-staining pattern, and co-expression of hVps20 with Snf7-1 dispersed the large Snf7-staining vesicles. Interestingly, overexpression of both hSnf7 and hVps20 proteins induced a post-endosomal defect in cholesterol sorting. To explore possible protein-protein interactions involving hSnf7 proteins, we used information from yeast genomic studies showing that yeast Snf7p can interact with proteins involved in MVB function. Using a glutathione S-transferase-capture approach with several mammalian homologues of such yeast Snf7p-interacting proteins, we found that all three hSnf7s interacted with mouse AIP1 [ALG-2 (apoptosis-linked gene 2) interacting protein 1], a mammalian Bro1p [BCK1 (bypass of C kinase)-like resistance to osmotic shock]-containing protein involved in cellular vacuolization and apoptosis. Whereas mapping experiments showed that the N-terminus of AIP1 containing both a Bro1 and an alpha-helical domain were required for interaction with hSnf7-1, Snf7-1 did not interact with another human Bro1-containing molecule, rhophilin-2. Co-immunoprecipitation experiments confirmed the in vivo interaction of hSnf7-1 and AIP1. Additional immunofluorescence experiments showed that hSnf7-1 recruited cytosolic AIP1 to the Snf7-induced vacuolar-like structures. Together these results suggest that mammalian Vps20, AIP1 and Snf7 proteins, like their yeast counterparts, play roles in MVB function.


Carbamazepine in the treatment of phantom limb pain.
The successful use of carbamazepine in treating a case of severe phantom limb pain prompted me to review this condition and its experiential treatment with carbamazepine, as well as the drug's possible mechanism of action on phantom limb pain. Experience to date indicates the need for controlled double-blind crossover studies to test the therapeutic validity of carbamazepine.


Establishment of community mental health systems in a postdeinstitutional era: a study of organizational structures and service provision in Sweden.
This article analyzes the state of community mental health services for people with psychiatric disabilities and the interplay between different organizational levels. The study is based on document analysis and interviews with stakeholders in 10 Swedish municipalities. The results show how systems are slow to change and are linked to local traditions. The services are often delivered in closed settings, and the organizations struggle to meet the needs of a new generation of users. There is a gap between local systems and national policies because the latter pays attention to the attributes of a recovery approach.


Disaster preparation and the functioning of a hospital social work department during the Gulf War.
The nature of the Gulf War and its consequences for the public at the personal and community levels, called for considerable alterations in organization and management at the Chaim Sheba Medical Center, the largest government general hospital in Israel, with constant adaptation to the changing situation. The preparations and exercises preceding the state of emergency, combined with the knowledge and experience gained in similar situations in the past, equipped the staff of the Social Work Department to function adequately and to make appropriate decisions and changes in the face of moral and ethical dilemmas, as well as immediate physical threat. This article presents the rationale for the model of intervention that guided the hospital during the Gulf War in offering services to casualty victims and their families. Also discussed are the process of developing an organizational framework and its content that meets wartime demands, and the implications for social work practice in dealing with a war crisis.


Assessing the impacts of phosphate mining on coral reef communities and reef development.
Phosphate mining activities on Christmas Island began in the late 1800's providing a unique, long-term case study in which to assess the impacts of mining on coral reef development. Watershed modelling was used to identify potential "hotspots" of mining runoff on to adjacent reefs. Pollution hotspots were also confirmed by analysis of reef sediment. Phosphate rich mining runoff flowed from local watersheds onto nearshore coral reefs with levels of up to 54,000 mg/kg of total phosphate recorded in reef sediment at the Dryers reef site adjacent to the main phosphate storage facility. Using this combination of watershed modelling and in-situ sediment contamination data we identified six coral reef sites along an environmental impact gradient. In-situ benthic transects were paired with a new rubble-encruster method enabling the analysis to combine large scale transect information alongside fine-scale data on epibenthic and encruster assemblages. Results demonstrate that phosphate rich sediment loading negatively impacted coral reef building communities, in particular, branching corals and calcareous encrusting organisms, critical to the future survival of coral reef ecosystems. These findings highlight the importance of curtailing runoff and pollution from catchment based mining activities and protecting reefs for the future.


Drug Extravasation in a Large General Hospital in Hunan, China: A Retrospective Survey.
Drug extravasation is one of the most common complications of intravenous therapy, which can lead to severe tissue injury if inappropriately treated. This study analyzes the current situation of extravasation and the risk factors affecting the severity of extravasation to provide a theoretical basis for carrying out prospective research, reducing the severity of drug extravasation, and strengthening the management of drug extravasation. We retrieved the data on extravasation from January 2016 to December 2020 from the hospital's safe infusion management system. We used nonparametric tests to assess the differences in the severity of drug extravasation among each variable and performed a multivariate analysis using multivariate ordered logistic regression. Extravasation occurred in 0.038% (263/694,043) of patients, including 203 cases of mild extravasation (77.2%), 57 cases of moderate extravasation (21.7%), and 3 cases of severe extravasation (1.1%). The main diseases of the patients with extravasation were cancer (24.7%), neurological-related diseases (19.4%), circulatory-related diseases (14.8%), and digestive-related diseases (14.1%); the main extravasated drugs were hypotonic or hypertonic drugs (31.9%) and contrast media (27.8%); the infusion tools of extravasation were indwelling needles (92.0%) and steel needles (8.0%). The multi-factor analysis showed that close to joints, patients' age ≤6 or age >65, cancer, neurological-related diseases, circulatory-related diseases, antineoplastic agents, hypotonic or hypertonic drugs and strong acid or alkali drugs were independent risk factors for more severe extravasation. The nurses' age and first identified by nurse were nurse-related factors that influenced the severity of drug extravasation. To prevent the occurrence of drug extravasation and reduce its severity, the nurses should strengthen the learning of emergency plans related drug extravasation, strengthen inspections of high-risk patients. Besides, the managers should strengthen the risk warning management of high-risk extravasated drugs.


The atomic orbitals of the topological atom.
The effective atomic orbitals have been realized in the framework of Bader's atoms in molecules theory for a general wavefunction. This formalism can be used to retrieve from any type of calculation a proper set of orthonormalized numerical atomic orbitals, with occupation numbers that sum up to the respective Quantum Theory of Atoms in Molecules (QTAIM) atomic populations. Experience shows that only a limited number of effective atomic orbitals exhibit significant occupation numbers. These correspond to atomic hybrids that closely resemble the core and valence shells of the atom. The occupation numbers of the remaining effective orbitals are almost negligible, except for atoms with hypervalent character. In addition, the molecular orbitals of a calculation can be exactly expressed as a linear combination of this orthonormalized set of numerical atomic orbitals, and the Mulliken population analysis carried out on this basis set exactly reproduces the original QTAIM atomic populations of the atoms. Approximate expansion of the molecular orbitals over a much reduced set of orthogonal atomic basis functions can also be accomplished to a very good accuracy with a singular value decomposition procedure.


In memoriam of David P. Rall.
As a scientist, administrator, and diplomat, David P. Rall pioneered the effort to identify and understand the elements that make up the human environment and their consequences for human health. As an intellectual and aggressive activist, he educated scientists, governments, and the world community to the critical need to address the existence of environmental agents and their consequences for human health. As a leader he marshalled some of the best minds and hearts of his time to the cause of world health through a safe and clean environment. And as a visionary he provided the goals of environmental health science and the direction to guide both current and future generations. His death on September 28 brought to a close a chapter in the evolution of our understanding of the interconnectedness of human health and the environment, a chapter he was largely responsible for writing.


A phospho-signaling pathway controls the localization and activity of a protease complex critical for bacterial cell cycle progression.
Temporally and spatially controlled master regulators drive the Caulobacter cell cycle by regulating the expression of >200 genes. Rapid clearance of the master regulator, CtrA, by the ClpXP protease is a critical event that enables the initiation of chromosome replication at specific times in the cell cycle. We show here that a previously unidentified single domain-response regulator, CpdR, when in the unphosphorylated state, binds to ClpXP and, thereby, causes its localization to the cell pole. We further show that ClpXP localization is required for CtrA proteolysis. When CpdR is phosphorylated, ClpXP is delocalized, and CtrA is not degraded. Both CtrA and CpdR are phosphorylated via the same CckA histidine kinase phospho-signaling pathway, providing a reinforcing mechanism that simultaneously activates CtrA and prevents its degradation by delocalizing the CpdR/ClpXP complex. In swarmer cells, CpdR is in the phosphorylated state, thus preventing ClpXP localization and CtrA degradation. As swarmer cells differentiate into stalked cells (G1/S transition), unphosphorylated CpdR accumulates and is localized to the stalked cell pole, where it enables ClpXP localization and CtrA proteolysis, allowing the initiation of DNA replication. Dynamic protease localization mediated by a phospho-signaling pathway is a novel mechanism to integrate spatial and temporal control of bacterial cell cycle progression.


Digestibility of phosphorus and calcium in meat and bone meal fed to growing pigs.
Seventy-two growing pigs (initial BW: 18.0 ± 1.6 kg) were used to determine the apparent total tract digestibility (ATTD) of P and Ca and the standardized total tract digestibility (STTD) of P in 8 different sources of meat and bone meal (MBM) and to develop equations to predict digestibility of P and Ca in MBM. Pigs were housed individually in metabolism cages and were randomly allotted to 9 diets with 8 replicate pigs per diet. Eight diets were formulated by mixing cornstarch, sucrose, soybean oil, sodium chloride, vitamin-mineral premix, and 8% of each source of MBM, and MBM was the sole source of P and Ca in each diet. A P-free diet was used to measure basal endogenous P losses (EPL) by the pigs. Feces were collected for 5 d based on the marker to marker approach after a 5-d adaptation period. On an as-fed basis, the concentration of P in the MBM sources ranged from 2.6 to 5.3% with an average of 4.3 ± 0.8% whereas Ca concentration ranged from 5.1 to 11.0% with an average of 9.2 ± 2.0%. The variation among MBM samples in Ca and P concentrations was calculated (CV = 22.1 and 20.0%, respectively) as was the variation in the concentration of other chemical components (CV = 6.2, 10.5, and 13.8% for CP, acid-hydrolyzed ether extract, and ash, respectively). The ATTD of P (52.1 to 80.1%, average = 65.9 ± 8.8%) and Ca (53.0 to 81.0%, average = 63.9 ± 9.4%) differed (P < 0.05) among MBM sources. The basal EPL was measured at 106 ± 51 mg/kg DMI in pigs fed the P-free diet. The STTD of P was different (54.8 to 84.4%; average = 68.8 ± 9.3%; P < 0.05) among MBM sources. The ATTD of Ca and the STTD of P decreased (P < 0.01) as ash, Ca, and P concentration in MBM increased, and the ATTD of Ca was positively related (R(2) = 0.99, P < 0.001) with the STTD of P. The STTD of P (%) in MBM may be predicted as 107.857 - 8.8 × total P [R(2) = 0.68, root mean square error (RMSE) = 5.73, P < 0.01] whereas ATTD of Ca (%) may be predicted as 105.375 - 9.327 × total P (R(2) = 0.75, RMSE = 4.70, P < 0.01). In conclusion, P and Ca digestibility varies among sources of MBM, but prediction equations using the concentration of total P in MBM may be used to estimate P and Ca digestibility in MBM fed to growing pigs.


Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans.
1. Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia. 2. Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-alpha-methoxy-9,10-dihydrolysergol (MMDL), which is further N-demethylated to form 10-alpha-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms. 3. After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes. 4. The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL Cmax 59 nmol l-1 and AUC (0, th) 144 nmol l-1h, mean MDL Cmax 183 nmol l-1 and AUC 2627 nmol l-1h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL Cmax 356 nmol l-1 and AUC 10512 nmol l-1h, MDL concentrations below limit of quantitation). 5. We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism.


[Tight suturing of the abdominal cavity after cholecystectomy].
A comparative analysis of two series of operations for acute and chronic cholecystitis was made. In the first series of operations (289) the abdominal cavity was drained with gauze napkins, in the second series (256 operations) a drainage tube was used or the abdominal cavity was sutured tightly. The authors came to a conclusion that in planned and postponed cholecystectomies tight suture of the abdominal cavity is the method of choice.


Early Experiences Engaging Patients Through Patient and Family Advisory Councils.
Primary care practices are increasingly asked to engage patients in improving care delivery. We report early experiences with Patient and Family Advisory Councils (PFACs) from interviews of patients and practice staff in the Comprehensive Primary Care initiative, and identify ways to improve PFACs. Patients and practice staff report PFACs help practices elicit patient feedback and, in response, improve care delivery. Nonetheless, there are areas for refinement, including recruiting more diverse patients, providing an orientation to members, overcoming reticence of some patients to raise issues, and increasing transparency by sharing progress with PFAC members and patients in the practice more generally.


High-dispersive mirrors for femtosecond lasers.
We report on the development of highly dispersive mirrors for chirped-pulse oscillators (CPO) and amplifiers (CPA). In this proof-of-concept study, we demonstrate the usability of highly dispersive multilayer mirrors for high-energy femtosecond oscillators, namely for i) a chirped-pulse Ti:Sa oscillator and ii) an Yb:YAG disk oscillator. In both cases a group delay dispersion (GDD) of the order of 2x10(4) fs(2) was introduced, accompanied with an overall transmission loss as low as approximately 2 per cent. This unprecedented combination of high dispersion and low loss over a sizeable bandwidth with multilayer structures opens the prospects for femtosecond CPA systems equipped with a compact, alignment-insensitive all-mirror compressors providing compensation of GDD as well as higher-order dispersion.


Exploring the relationship between online buyers and sellers of image and performance enhancing drugs (IPEDs): Quality issues, trust and self-regulation.
Online drug markets are expanding the boundaries of drug supply including the sale and purchase of image and performance enhancing drugs (IPEDs). However, the role of the internet in IPED markets, and in particular the ways in which these substances are supplied via the surface web, has rarely been considered. This article examines the online IPED market in order to inform drug policy and to provide a nuanced understanding of retailers involved, particularly exploring the relationship between buyers and sellers. This paper is based on two extensive research projects conducted in the Netherlands and Belgium. The first project focuses on muscle drugs and is based on 64 IPED dealing cases, semi-structured interviews with authorities (N=32), and dealers (N=15), along with an analysis of 10 steroid-selling websites. The second research project primarily focuses on weight loss drugs and sexual enhancers in the Netherlands, and relies on interviews with authorities (N=38), suppliers (N=30), and consumers (N=10), analysis of 69 criminal case files, and an online analysis. In the literature, the illicit online sale of IPEDs is generally associated with illegal online pharmacies that try to mislead buyers. While confirmed in our research, we also illustrate that there are online suppliers who invest in customer relationships and services, and that users are aware of the illegal nature of their business. These e-vendors incorporate a 'social supply business model' by providing the best possible service to their customers and attempting to minimise risks in order to attract, satisfy and maintain customers. As it is likely that users will continue to make use of the internet to order IPEDs, regardless of closing down selling websites, it is first of all important to counteract these online sources by educating all types of consumers and providing harm reduction services.


Biogeography of cryoconite bacterial communities on glaciers of the Tibetan Plateau.
Cryoconite holes, water-filled pockets containing biological and mineralogical deposits that form on glacier surfaces, play important roles in glacier mass balance, glacial geochemistry and carbon cycling. The presence of cryoconite material decreases surface albedo and accelerates glacier mass loss, a problem of particular importance in the rapidly melting Tibetan Plateau. No studies have addressed the microbial community composition of cryoconite holes and their associated ecosystem processes on Tibetan glaciers. To further enhance our understanding of these glacial ecosystems on the Tibetan Plateau and to examine their role in carbon cycling as the glaciers respond to climate change, we explored the bacterial communities within cryoconite holes associated with three climatically distinct Tibetan Plateau glaciers using Illumina sequencing of the V4 region of the 16S rRNA gene. Cryoconite bacterial communities were dominated by Cyanobacteria, Chloroflexi, Betaproteobacteria, Bacteroidetes and Actinobacteria. Cryoconite bacterial community composition varied according to their geographical locations, exhibiting significant differences among glaciers studied. Regional beta diversity was driven by the interaction between geographic distance and environmental variables; the latter contributed more than geographic distance to the variation in cryoconite microbial communities. Our study is the first to describe the regional-scale spatial variability and to identify the factors that drive regional variability of cryoconite bacterial communities on the Tibetan Plateau.


Immunoregulatory molecules of trophoblast and decidual suppressor cell origin at the maternofetal interface.
The mammalian fetus expresses a variety of paternal histocompatible, oncofetal, and trophoblast antigens against which the mother can mount an immune response. Survival of the "fetal graft" appears to depend upon local immunosuppressive mechanisms in lymph nodes draining the uterus and at the intrauterine implanation site itself. Nonspecific not-T-Fc-receptor-bearing small lymphocytes containing cytoplasmic granules present in successfully allopregnant mice can suppress both the generation of maternal-antipaternal killer T cells and the infiltration of cytotoxic T lymphocytes into sponge-matrix allografts during the effector phase of the immune response. These suppressor cells are deficient at the implantation sites of xenogeneic and allogeneic mouse embryos that are susceptible to maternal immunity and are destined to resorb. A soluble suppressor factor of approximately 100,000 daltons in size can be obtained from the suppressor cells and acts to block the response of T cells to interleukin-2 by interfering with IL-2 receptors. The development of the suppressor cells in the decidua requires certain hormonal signals as well as signals provided by trophoblast cells. Freshly explanted or cultured murine trophoblast cell lines elaborate soluble factor(s) that are active in recruitment or activation of suppressor cells. Since suppressor cells may be isolated from decidua of successfully allopregnant humans, the suppressor cell mechanism and its regulation may represent a key factor in the protection of the "fetal allograft" from rejection by maternal immunity.


Hydroxyurea-induced amyopathic dermatomyositis presenting with heliotrope erythema.
Hydroxyurea (HU) is a chemotherapeutic agent used for the treatment of myeloproliferative disorders such as chronic myeloid leukemia, polycythemia vera, and essential thrombocytosis. We describe a 69-year-old man who had essential thrombocytosis and developed amyopathic dermatomyositis after long-term HU therapy. He presented with Gottron papules and heliotrope erythema. The former has been described in all cases of HU-induced dermatomyositis; the latter has been seen in a few cases of that disorder.


Citrus aurantium L. Dry Extracts Ameliorate Adipocyte Differentiation of 3T3-L1 Cells Exposed to TNFα by Down-Regulating miR-155 Expression.
Citrus aurantium L. dry extracts (CAde) improve adipogenesis in vitro. These effects are dependent from an early modulation of CCAAT/enhancer-binding protein beta (C/Ebpβ) expression and cyclic Adenosine Monophosphate (cAMP) response element-binding protein (CREB) activation. C/Ebpβ and Creb are also targets of miR-155. This study investigated whether CAde regulates miR-155 expression in the early stages of adipogenesis and whether it ameliorates adipocyte differentiation of cells exposed to tumor necrosis factor-alpha (TNFα). Adipogenic stimuli (AS) were performed in 3T3-L1 pre-adipocytes treated with CAde, TNFα, or both. Gene and miRNA expression were determined by quantitative real-time PCR. Adipogenesis was evaluated by Oil-Red O staining. CAde treatment enhanced AS effects during the early adipogenesis phases by further down-regulating miR-155 expression and increasing both C/Ebpβ and Creb mRNA and protein levels. At variance, TNFα inhibited 3T3-L1 adipogenesis and abolished AS effects on miR-155, C/Ebpβ, and Creb expression. However, in cells exposed to TNFα, CAde improved adipocyte differentiation and restored the AS effects on miRNA and gene expression at early time points. In conclusion, this study identified miR-155 down-regulation as part of the mechanism through which CAde enhances adipogenesis of pre-adipocytes in vitro. Furthermore, it provides evidence of CAde efficacy against TNFα negative effects on adipogenesis.


The formation energy, phase transition, and negative thermal expansion of Fe2-xScxW3O12.
Tungstates with a molecular formula A2W3O12 exhibits a wider negative thermal expansion (NTE) temperature range than molybdates but are challenging to synthesize, especially when A = Fe or Cr with metastable structures. To enhance the structural stability of Fe2W3O12, Sc with lower electronegativity is adopted to substitute Fe according to Fe2-xScxW3O12, considering the thermodynamic stability of Sc2W3O12. It is shown that the solid solutions can be easily synthesized and the phase transition temperature (PTT) can be tuned to well below room temperature (RT). Theoretical calculations and experimental results show that the formation energy decreases and the W-O bond in Fe-O-W gradually strengthens as the substitution of Sc in Fe2-xScxW3O12 increases, indicating an increase in structural stability. NTE is enhanced after phase transition with an increase in the Sc content. The reduction in PTT and the enhancement in NTE properties of Fe2W3O12 could result in a decrease in the effective electronegativity of the Fe-site elements, resulting in a low formation energy and strengthened W-O bond in Fe-O-W, which corresponds to a more stable structure.


The Oticon Medical Neuro Zti cochlear implant and the Neuro 2 sound processor: multicentric evaluation of outcomes in adults and children.
Objective: This study evaluated the outcomes of the Oticon Medical Neuro Zti cochlear implant and the Neuro 2 sound processor.Design: Neuro One users were upgraded to Neuro 2. Monosyllabic word identification was evaluated in adults with Neuro One after ≥5 months, with Neuro 2 at upgrade, and with Neuro 2 after 3 months. Self-reported listening ability, satisfaction, and usability were measured in adults and children.Study sample: Participants were 44 adults and 26 children.Results: Speech identification scores in quiet and noise were 58% and 45% with Neuro One and 67% and 55% with Neuro 2 after 3 months, respectively. Hearing impairment duration and number of active electrodes significantly predicted speech identification in noise with Neuro 2. Significantly higher questionnaire ratings were obtained for Neuro 2 than Neuro One regarding listening ability in complex listening situations, comfort and music, as well as nine aspects of satisfaction and usability.Conclusion: This study demonstrates the clinical superiority of the Neuro 2 sound processor over Neuro One in terms of speech identification in quiet and in noise and reported patient benefit and satisfaction. Given the study design, sources of improvement may include factors unrelated to the sound processor itself.


Inhibition of postmenopausal atherosclerosis progression: a comparison of the effects of conjugated equine estrogens and soy phytoestrogens.
Experimental evidence was sought concerning whether soy phytoestrogens (SPEs) inhibit postmenopausal atherosclerosis progression/extent and, if so, their effectiveness relative to traditional estrogen replacement therapy. Premenopausal cynomolgus monkeys were fed a moderately atherogenic diet (26 months) to induce atherosclerosis. After ovariectomy, the moderately atherogenic diet was continued, and they were treated (36 months) with a control diet (soy protein depleted of SPEs), a diet containing SPEs in soy protein isolate, or a diet containing SPE-depleted soy protein with conjugated equine estrogens (CEE; Premarin) added. SPE effects on plasma lipids were better than those of CEE (higher high density lipoprotein cholesterol and no increase in triglyceride). Relative to the control group, CEE treatment inhibited (P = 0.0001), and SPE treatment partially inhibited (P = 0.10) the progression of atherosclerosis (common iliac artery atherosclerosis before and after treatment). CEE-treated monkeys had much less coronary artery atherosclerosis than the controls (P = 0.0002), whereas SPE-treated monkeys were intermediate in lesion extent between the controls and the CEE-treated animals (P = 0.02). Both CEE and SPE significantly reduced the extent of common carotid and internal carotid artery atherosclerosis, and the two treatment groups were not significantly different.


OKT3 incubation of donor marrow for prophylaxis of acute graft-vs.-host disease (GvHD) in allogeneic bone marrow transplantation.
Following allogeneic (matched or minor mismatched) bone marrow transplantation with marrow incubated with OKT3, 17 patients have been observed for at least 60 days for the development of acute graft-vs.-host disease. One milligram of the monoclonal (murine) antibody OKT3 was incubated with the donor marrow for one hr at room temperature prior to infusion. It was anticipated that coated/opsonized immune competent T lymphocytes would subsequently be phagocytosed by the recipient reticulo-endothelial system. Three of 17 patients developed Grade II or greater acute graft-vs.-host disease. In two, this proved fatal when complicated by cytomegalovirus infection. Eleven patients showed no evidence of acute graft-vs.-host disease and three had transient limited skin rashes (Grade I graft-vs.-host disease). Opsonization of T lymphocytes has reduced the incidence of severe acute graft-vs.-host disease in this unit from 79% (historical group) to 18% when added to prophylactic methotrexate given according to the Seattle protocol.


Certification, empowerment, and intent to leave current position and the profession among critical care nurses.
This study was based on the American Association of Critical-Care Nurses' (AACNs') interest in determining the value and influence of specialty certification. To examine relationships between AACN specialty certification and empowerment, and, secondarily, to examine these variables as related to intent to leave the current position and the nursing profession. AACN members were asked to participate in a Web-based survey; 6589 AACN members completed the surveys. Perceptions of empowerment differed significantly among nurses certified by AACN and nurses without such certification. Additional analyses revealed significant differences in empowerment related to position, education, salary, ethnicity, sex, intent to leave the current position, and intent to leave the profession. Forty-one percent of the participants indicated intent to leave their current position in the next year; only 6.9% indicated their intent to leave the profession in the next year. Intent to leave current position differed significantly according to age, sex, years of experience, ethnicity, educational level, and certification. The value of specialty certification and the importance of empowerment among critical care nurses are affirmed. The next step in the continued journey toward increasing retention of critical care nurses, and thereby improving patient care, is to evaluate existing programs focused on retention and identify needed enhancements.


Inequalities, the arts and public health: Towards an international conversation.
This paper considers how participatory arts informed by thinking in public health can play a significant part internationally in addressing inequalities in health. It looks beyond national overviews of arts and health to consider what would make for meaningful international practice, citing recent initiatives of national networks in English-speaking countries and examples of influential developments in South America and the European Union. In the context of public health thinking on inequalities and social justice, the paper posits what would make for good practice and appropriate research that impacts on policy. As the arts and health movement gathers momentum, the paper urges the arts to describe their potency in the policy-making arena in the most compelling ways to articulate their social, economic and cultural values. In the process, it identifies the reflexive consideration of participatory practice - involving people routinely marginalised from decision-making processes - as a possible avenue into this work.


Familial aggregation of abdominal visceral fat level: results from the Quebec family study.
The purpose of this study was to investigate the importance of familial aggregation in abdominal visceral fat (AVF) level as assessed by computed tomography (CT). Four measures of abdominal adipose tissue, obtained from an abdominal scan between the fourth and fifth Lumbar vertebrae (L4-L5) taken in 366 adult subjects from 100 French-Canadian nuclear families, were considered in this study. Total abdominal fat, AVF, subcutaneous abdominal fat, obtained by computing the difference between total and AVF tissue areas, and the visceral to total abdominal fat ratio were measured. Spouses, parent-offspring, and sibling correlations were computed by maximum likelihood methods after adjustment of the four phenotypes for age and for age and total fat mass (FM) derived from underwater weighing. Significant familial aggregation was found for all phenotypes, whether adjusted or not for body FM. However, after adjustment of data for body FM, in addition to age, all spouse correlations became nonsignificant, suggesting that the familial aggregation of abdominal fat is primarily genetic. Heritability estimates reached 42% and 56% for subcutaneous fat and AVF, respectively. These results suggest that genetic factors are major determinants of the familial aggregation observed in the amount of abdominal fat, irrespective of total body fat content, and that AVF seems more influenced by genetic factors than abdominal subcutaneous adipose tissue. These findings imply that some individuals are more at risk than others to exhibit the various metabolic complications associated with upper-body obesity because of their inherited tendency to store abdominal fat in the visceral depot rather than in the subcutaneous depot.


Anti-SARS-CoV-2 antibody kinetics up to 6 months of follow-up: Result from a nation-wide population-based, age stratified sero-epidemiological prospective cohort study in India.
Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.


Living labs for patient engagement and knowledge exchange: an exploratory sequential mixed methods study to develop a living lab in paediatric rehabilitation.
Despite recognition of the importance of patient engagement in research and knowledge translation, systematic approaches to engagement and co-ideation remain limited. Living labs are collaborative knowledge sharing systems that use multimethod, user-centred approaches that hold potential to catalyse these aims. However, their use in healthcare is limited, and no living lab has been developed in paediatric rehabilitation. In response to this gap and to propel innovative knowledge exchange, we propose a mixed methods study to co-develop a living lab prototype (ie, preliminary infrastructure with opportunity for scale up) in paediatric rehabilitation, with relevance to other healthcare contexts. An exploratory sequential mixed methods study will be undertaken to determine research and knowledge exchange priorities and to inform the development of the living lab prototype. Stage 1: we will use a multipronged approach to sample 18-21 youth with developmental differences or rehabilitation needs, their youth siblings and parents/guardians from a provincial paediatric rehabilitation centre, to participate in qualitative and arts-based data collection. Data will provide insight into desirable features of the living lab. Stage 2: E-surveys to youth, siblings, parents/guardians and clinicians who receive or provide services at this same centre will expand on priorities and living lab features. Stage 3: integrated analysis will inform the living lab prototype development. Inductive thematic analysis using interpretive description, integrated analysis of visual data and descriptive and content analysis of e-survey data will be undertaken. Joint displays will facilitate data integration. Priorities will be identified using a modified rank-order method for each key living lab domain. Institutional ethics and site approval have been granted. A parent advisory group and rehabilitation engineering partners will confer on data and inform the development of the living lab prototype. User engagement with the prototype will occur during an online or in-person event, and findings shared through non-technical research summaries, journal articles and academic presentations.


Arachidonic acid-induced LH release is ATP-independent and insensitive to N-ethyl maleimide.
The mechanism of arachidonic acid (AA)-induced LH release was characterized using sheep pituitary cells in primary culture permeabilized with Staphylococcal alpha-toxin. In intact cells, exogenous AA evoked release of LH in a manner which was partially dependent on extracellular Ca2+. At similar concentrations, AA also caused cell permeabilization as monitored by efflux of [3H]2-deoxyglucose metabolites. In alpha-toxin-permeabilized cells where cytosolic Ca2+ was clamped at resting levels, AA retained its ability to cause LH release. Unlike the stimulation of exocytosis produced by Ca2+, phorbol ester or cyclic AMP, AA-evoked release was independent of ATP and was not inhibited by pretreatment with N-ethyl maleimide. These findings indicated that exogenous AA does not cause LH release by Ca2+ influx or mobilization or by activating protein kinase C. The results suggest that LH release induced by exogenous AA is probably due to its detergent-like properties, and does not represent true exocytosis.


Manganese-Based Immunomodulatory Nanocomposite with Catalase-Like Activity and Microwave-Enhanced ROS Elimination Ability for Efficient Rheumatoid Arthritis Therapy.
Rheumatoid arthritis (RA) is a chronic autoimmune disease commonly associated with the accumulation of hyperactive immune cells (HICs), particularly macrophages of pro-inflammatory (M1) phenotype, accompanied by the elevated level of reactive oxygen species (ROS), decreased pH and O2 content in joint synovium. In this work, an immunomodulatory nanosystem (IMN) is developed for RA therapy by modulating and restoring the function of HICs in inflamed tissues. Manganese tetraoxide nanoparticles (Mn3 O4 ) nanoparticles anchored on UiO-66-NH2 are designed, and then the hybrid is coated with Mn-EGCG film, further wrapped with HA to obtain the final nanocomposite of UiO-66-NH2 @Mn3 O4 /Mn-EGCG@HA (termed as UMnEH). When UMnEH diffuses to the inflammatory site of RA synovium, the stimulation of microwave (MW) irradiation and low pH trigger the slow dissociation of Mn-EGCG film. Then the endogenously overexpressed hydrogen peroxide (H2 O2 ) disintegrates the exposed Mn3 O4 NPs to promote ROS scavenging and O2 generation. Assisted by MW irradiation, the elevated O2 content in the RA microenvironment down-regulates the expression of hypoxia-inducible factor-1α (HIF-1α). Coupled with the clearance of ROS, it promotes the re-polarization of M1 phenotype macrophages into anti-inflammatory (M2) phenotype macrophages. Therefore, the multifunctional UMnEH nanoplatform, as the IMN, exhibits a promising potential to modulate and restore the function of HICs and has an exciting prospect in the treatment of RA.


Predictive Model for Neoplastic Potential of Gallbladder Polyp.
To provide the statistical predictive model for neoplastic potential of gallbladder polyp (GBP). Many studies have attempted to define the risk factors for neoplastic potential of GBP. It remains difficult to precisely adapt the reported risk factors for the decision of surgery. Estimating the probability for neoplastic potential of GBP using a combination of several risk factors before surgical resection would be useful in patient consultation. We collected data of patients confirmed as GBP through cholecystectomy at Samsung Medical Center between January 1997 and March 2015. Those with a definite evidence for malignancy, such as adjacent organ invasion, metastasis on preoperative imaging studies, polyp >15 mm, and absence of proper preoperative ultrasonographic imaging were excluded. A total of 1976 patients were enrolled. To make and validate the predictive model, we divided the cohort into the modeling group (n=979) and validation group (n=997). Clinical information, ultrasonographic findings, and blood tests were retrospectively analyzed. Clinical factors of older age, single lesion, sessile shape, and polyp size showed statistical significance for neoplastic potential of GBP in the modeling group. A predictive model for neoplastic potential of GBP was constructed utilizing the statistical outcome of the modeling group. Statistical validation was performed with the validation group to determine the optimal clinical sensitivity and specificity of the predictive model. Optimal cut-off value for neoplastic probability was 7.4%. The predictive model for neoplastic potential of GBP may support clinical decisions before cholecystectomy.


Liver transplantation.
The field of liver transplantation continues to evolve. This review discusses the major themes of controversy and investigation over the past 12 months. Organ allocation remains a major area of investigation and controversy in liver transplantation. The MELD system, which has been implemented since 2002, appears to adequately predict both death on the waiting list and short-term survival after OLT. However, regional variations in allocation remain despite this system. In an attempt to further increase available organs, living donor adult transplantation has gained interest. However, with continued high rates of reported complications and additional reports of donor deaths, interest has been tempered and more diligent evaluation of the ethics and techniques for this procedure have been sought. As more patients continue to survive for longer periods after OLT, medical complications from medications are now seen and require skillful management in these individuals. Recurrent viral disease after transplant remains a significant challenge as will the increasing need for retransplantation in these patients. The review of the literature in liver transplantation continues to raise more issues than answer questions. It is likely that going into the future the key themes reviewed here will remain as further studies of larger patient populations will be required to more specifically identify "best practice" for care of these individuals.


Photoreceptor layer assessed in tissue layer image using spectral-domain optical coherence tomography after surgical closure of macular hole.
To investigate changes in the photoreceptor layer in tissue layer images using spectral-domain optical coherence tomography after macular hole surgery. Visual acuity and spectral-domain optical coherence tomography scans were obtained in 24 eyes with surgically closed macular holes prospectively at 1, 2, 4, and 6 months after surgery. The scanned data were processed to generate tissue layer images of the photoreceptor layer, namely, photoreceptor layer map. Hyporeflective area and reflectivity at the fovea were analyzed to find a correlation with visual acuity. Mean visual acuity improved from 48.1 letters preoperatively to 62.5 letters at 1 month and to 73.8 letters at 6 months. Hyporeflective area in the photoreceptor layer map corresponded to attenuated signals from the junction of the inner and outer segments of the photoreceptors. Hyporeflective area decreased from 1.54 mm at 1 month to 0.60 mm at 6 months. Foveal reflectivity increased from 0.77 to 0.85. Visual acuity correlated with the hyporeflective area (r = 0.43-0.63) and foveal reflectivity (r = 0.35-0.61). After macular hole closure, attenuated signal from the junction of the inner and outer segments of the photoreceptors representing disorganization of the photoreceptor layer was shown in the photoreceptor layer map as a hyporeflective area, which correlated with the postoperative visual acuity. Hyporeflectivity decreased gradually with concurrent improvement in visual acuity.


Severity of parkinsonism associated with environmental manganese exposure.
Exposure to occupational manganese (Mn) is associated with neurotoxic brain injury, manifesting primarily as parkinsonism. The association between environmental Mn exposure and parkinsonism is unclear. To characterize the association between environmental Mn exposure and parkinsonism, we performed population-based sampling of residents older than 40 in Meyerton, South Africa (N = 621) in residential settlements adjacent to a large Mn smelter and in a comparable non-exposed settlement in Ethembalethu, South Africa (N = 95) in 2016-2020. A movement disorders specialist examined all participants using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3). Participants also completed an accelerometry-based kinematic test and a grooved pegboard test. We compared performance on the UPDRS3, grooved pegboard, and the accelerometry-based kinematic test between the settlements using linear regression, adjusting for covariates. We also measured airborne PM2.5-Mn in the study settlements. Mean PM2.5-Mn concentration at a long-term fixed site in Meyerton was 203 ng/m3 in 2016-2017 - approximately double that measured at two other neighborhoods in Meyerton. The mean Mn concentration in Ethembalethu was ~ 20 times lower than that of the long-term Meyerton site. UPDRS3 scores were 6.6 (CI 5.2, 7.9) points higher in Meyerton than Ethembalethu residents. Mean angular velocity for finger-tapping on the accelerometry-based kinematic test was slower in Meyerton than Ethembalethu residents [dominant hand 74.9 (CI 48.7, 101.2) and non-dominant hand 82.6 (CI 55.2, 110.1) degrees/second slower]. Similarly, Meyerton residents took longer to complete the grooved pegboard, especially for the non-dominant hand (6.9, CI -2.6, 16.3 s longer). Environmental airborne Mn exposures at levels substantially lower than current occupational exposure thresholds in the United States may be associated with clinical parkinsonism.


Epitope specificity of Th0/Th2 CD4+ T-lymphocyte clones induced by vaccination with rHBsAg vaccine.
Different amino acid sequences of hepatitis B virus surface antigen (HBsAg) are involved in the activation of CD4+ lymphocytes needed to induce an optimal antiviral function. The aim of this study was to characterize the CD4-mediated response to immunodominant HBsAg epitopes in hepatitis B virus (HBV) vaccine recipients by defining minimal sequences recognized by T cells, cytokine profiles, and HLA restriction of peptide recognition. T-lymphocyte lines and clones specific for HBsAg were isolated from the peripheral blood of subjects immunized with recombinant HBsAg and stimulated in vitro with synthetic peptides spanning the whole HBsAg sequence. Four immunodominant epitopes (sequences 21-40, 136-155, 156-175, and 211-226) were identified. Using panels of truncated peptides of different length, sequences 21-28, 165-172, and 215-223 were shown to correspond to the minimal epitopes recognized by T cells. The antigen-specific T-lymphocyte proliferation was HLA class II restricted, and each peptide could be presented in association with different HLA class II determinants. Th0/Th2 cytokine patterns were induced on peptide stimulation. These results indicate the presence of at least four immunodominant epitopes within HBsAg that represent potential candidates for the design of anti-HBV synthetic vaccines.


[Dust and gas factors in extraction of polymetallic ore in Arctic conditions and their hygienic assessment].
Studies of drilling and blasting method of copper and nickel ores extraction at underground Transpolar mines proved that the highest concentrations of dust appeared during dry drilling of vertical blast holes, work of scraper windlass, fragmentation of out-size blocks, preparation of concrete mixture. Presence of aggressive metals, especially nickel, in the ore dust is a main base for planned thorough investigations of fibrogenic, toxic and carcinogenic effects of copper and nickel ore dust, for more precise assessment of its MAC in the air of workplace. Two-step purification of exhaust gases appearing due to mining diesel machines is not quite efficient, as the concentrations of nitrogen oxides (assessed through nitrogen dioxide) continually exceeded the MAC.


Lymphoid enhancer factor-1 links two hereditary leukemia syndromes through core-binding factor alpha regulation of ELA2.
Two hereditary human leukemia syndromes are severe congenital neutropenia (SCN), caused by mutations in the gene ELA2, encoding the protease neutrophil elastase, and familial platelet disorder with acute myelogenous leukemia (AML), caused by mutations in the gene AML1, encoding the transcription factor core-binding factor alpha (CBFalpha). In mice, CBFalpha regulates the expression of ELA2, suggesting a common link for both diseases. However, gene-targeted mouse models have failed to reproduce either human disease, thus prohibiting further in vivo studies in mice. Here we investigate CBFalpha regulation of the human ELA2 promoter, taking advantage of bone marrow obtained from patients with either illness. In particular, we have identified novel ELA2 promoter substitutions (-199 C to A) within a potential motif for lymphoid enhancer factor-1 (LEF-1), a transcriptional mediator of Wnt/beta-catenin signaling, in SCN patients. The LEF-1 motif lies adjacent to a potential CBFalpha binding site that is in a different position in human compared with mouse ELA2. We find that LEF-1 and CBFalpha co-activate ELA2 expression. In vitro, the high mobility group domain of LEF-1 interacts with the runt DNA binding and proline-, serine-, threonine-rich activation domains of CBFalpha. ELA2 transcript levels are up-regulated in bone marrow of an SCN patient with the -199 C to A substitution. Conversely, a mutation of the CBFalpha activation domain, found in a patient with familial platelet disorder with AML, fails to stimulate the ELA2 promoter in vitro, and bone marrow correspondingly demonstrates reduced ELA2 transcript. Observations in these complementary patients indicate that LEF-1 cooperates with CBFalpha to activate ELA2 in vivo and also suggest the possibility that up-regulating promoter mutations can contribute to SCN. Two hereditary AML predisposition syndromes may therefore intersect via LEF-1, potentially linking them to more generalized cancer mechanisms.


Conditionally immortalized cell lines as a new in vitro model for the study of barrier functions.
Conditionally immortalized brain and retinal capillary endothelial and choroid plexus epithelial cell lines were established from a transgenic rat (Tg rat) and mouse (Tg mouse) harboring the temperature-sensitive simian virus 40 (ts SV 40) large T-antigen. These cell lines exhibit temperature-sensitive cell growth due to the expression of ts SV 40 large T-antigen. Mouse brain (TM-BBB) and rat brain (TR-BBB) and rat retinal (TR-iBRB) capillary endothelial cell lines appear to have a spindle-fiber shaped morphology and exhibit the typical endothelial markers, such as von Willebrand factor and acetylated low-density lipoprotein uptake. These cell lines express in vivo influx and efflux transporters, such as P-glycoprotein (P-gp) and GLUT1, which is capable of 3-O-methyl-D-glucose transport. TM-BBB cells are able to undergo efflux transport of cyclosporin A, which is a substrate for P-gp transport activity. They may also express oatp2 and exhibit dehydroepiandrosterone sulfate and digoxin uptake activity. TR-BBB cells express the mRNA of multidrug resistance associated protein 1 (MRP1) and a large neutral amino acid transporter, which consists of LAT1 and 4F2hc. TR-iBRB cells exhibit pH-dependent L-lactic acid transport activity and express the mRNA of monocarboxylate transporter (MCT) 1 and 2. The choroid plexus epithelial cell line (TR-CSFB) has polygonal cell morphology, expresses the typical choroid plexus epithelial cell marker, transthyretin, and has Na+, K+-ATPase located on the apical side. TR-CSFB cells also exhibit amino acid transport activity which has been observed in vivo. These barrier cell lines established from the Tg rat and Tg mouse have in vivo transport functions and are good in vitro models for drug transport to the brain and retina and as a screen for drugs which might be capable of delivery to the brain and retina.


THE EFFECT OF DIABETES SYMPTOMS ON QUALITY OF LIFE IN INDIVIDUALS WITH TYPE 2 DIABETES.
This study aimed to investigate the effect of symptoms of diabetes on the quality of life of individuals with Type 2 diabetes. The study used a cross-sectional design. No sampling procedure was employed in the study; instead, 410 individuals presenting to the Balikesir Atatürk City Hospital Endocrinology and Internal Medicine Polyclinics between December 2016 and July 2017, diagnosed with Type 2 diabetes, and meeting the inclusion criteria were enrolled in the study sample. The study data were collected with a "Socio-demographic Characteristics Questionnaire", the "Diabetes Symptom Checklist", and the "SF-36 Quality of Life Questionnaire". The participants obtained the highest mean scores from the hyperglycemia subscale of the Diabetes Symptoms Checklist (3.35±0.60) and the mental health subscale of the SF-36 Quality of Life Questionnaire (50.65±8.10). The hypoglycemia, cardiology, psychology, and neurology variables included in the model were statistically significant and predicted 35% of the mental subscale score of the SF 36 questionnaire. SF 36 physical subscale score increased as the hypoglycemia, cardiology, psychology, and neurology scores decreased (p<0.05). The participants obtained high scores from the hyperglycemia subscale of the diabetes symptom checklist and mental health subscale of the quality of life questionnaire. Diabetes symptoms were found to affect the quality of life of individuals with diabetes.


Neural predictors of evaluative attitudes toward celebrities.
Our attitudes toward others influence a wide range of everyday behaviors and have been the most extensively studied concept in the history of social psychology. Yet they remain difficult to measure reliably and objectively, since both explicit and implicit measures are typically confounded by other psychological processes. We here address the feasibility of decoding incidental attitudes based on brain activations. Participants were presented with pictures of members of a Japanese idol group inside an functional magnetic resonance imaging scanner while performing an unrelated detection task, and subsequently (outside the scanner) performed an incentive-compatible choice task that revealed their attitude toward each celebrity. We used a real-world election scheme that exists for this idol group, which confirmed both strongly negative and strongly positive attitudes toward specific individuals. Whole-brain multivariate analyses (searchlight-based support vector regression) showed that activation patterns in the anterior striatum predicted each participant's revealed attitudes (choice behavior) using leave-one-out (as well as 4-fold) cross-validation across participants. In contrast, attitude extremity (unsigned magnitude) could be decoded from a distinct region in the posterior striatum. The findings demonstrate dissociable striatal representations of valenced attitude and attitude extremity and constitute a first step toward an objective and process-pure neural measure of attitudes.


Associations between insulin-like growth factors and their binding proteins and other prognostic indicators in breast cancer.
Recent studies have suggested that insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) may be implicated in the development and progression of breast cancer. Prostate-specific antigen (PSA), a serine protease, may play a role in the regulation of IGFs' function through cleavage of IGFBP-3, resulting in release of active IGFs from IGFBP-3. As IGFs, IGFBPs and PSA are all present in breast cancer, possible associations among these proteins were speculated. In this study, we have measured PSA, IGF-I, IGF-II, IGFBP-1 and IGFBP-3 in tumour tissue cytosols from 200 women with primary breast cancer, and have examined relationships between IGFs or IGFBPs and PSA along with other markers, including p53 protein, steroid hormone receptors (oestrogen and progesterone), cathepsin-D, epidermal growth factor receptor, Her-2/neu protein, S-phase fraction and DNA ploidy. Correlations or associations between PSA and IGF-I, IGF-II, IGFBP-1 or IGFBP-3 were not observed. IGF-II was positively correlated with both IGFBP-3 and IGFBP-1. IGF-I was not associated with either of the two binding proteins, nor with IGF-II. Both IGF-II and IGFBP-3 were inversely associated with the oestrogen receptor, and IGFBP-3 was also positively associated with S-phase fraction. Our finding of IGF-II and IGFBP-3 in association with unfavourable prognostic indicators of breast cancer suggests that IGFs may be involved in the progression of breast cancer.


[Informed consent: opinions of health care personnel from a teaching hospital].
To conduct a descriptive analysis of the opinions of health care personnel regarding different aspects related with the informed consent, and mainly the information given on informed consent forms. All health care professionals (physicians, nurses and nursing auxiliaries) of a teaching hospital were invited to fill out an anonymous, 20-item questionnaire based on legal health guidelines. Degree of knowledge was assessed by age, professional and seniority status, speciality or position and bioethical background. The questionnaire was filled out by 277 participants, with a hospital participation of 67%. A total of 45.1% of the health care professionals believed they had insufficient information on what the informed consent consists of and when it should be completed by patients; 81.2% considered that informed consent is an instrument of professional protection against demands by the user; 62.8% thought that the information provided is not sufficiently clear to the patient; 76.2% that the reading and understanding are difficult for the average person and 37.9% considered that there is excessive information. Regarding the basic elements that should be included in the informed consent form, 96.7% advocate information, 93.5% comprehension, 84.1% willingness and 74% competence. A total of 98.9% of participants believed that side effects of a diagnostic or therapeutic intervention should be specified in the document, 57% the likelihood of success and 70.8% alternatives. Furthermore, 59.6% are not in favor of using numerical percentages to express procedure risks. Half of health-care professionals were unaware of what an informed consent consists of, its different sections, the law that regulates it and the philosophy underlying its development.


Integrated multi-omics reveals the roles of cecal microbiota and its derived bacterial consortium in promoting chicken growth.
The improvement of chicken growth performance is one of the major concerns for the poultry industry. Gut microbes are increasingly evidenced to be associated with chicken physiology and metabolism, thereby influencing chicken growth and development. Here, through integrated multi-omics analyses, we showed that chickens from the same line differing in their body weight were very different in their gut microbiota structure and host-microbiota crosstalk; microbes in high body weight (HBW) chickens contributed to chicken growth by regulating the gut function and homeostasis. We also verified that a specific bacterial consortium consisting of isolates from the HBW chickens has the potential to be used as chicken growth promoters. These findings provide new insights into the potential links between gut microbiota and chicken phenotypes, shedding light on future manipulation of chicken gut microbiota to improve chicken growth performance.


[Plastic surgery to correct deformities of the ear].
For the plastic-surgical correction of mild deformities of the ears, well-proven incisional and suturing techniques are available. Only in exceptional cases is skin grafting or the use of cartilage ersatz material required. In the plastic surgical treatment of moderate to severe ear deformities, in contrast, not only incisional and suturing techniques, but also free skin grafts and ersatz materials are needed. At the ENT Department of the Ludwig-Maximilian University in Munich, plastic reconstruction of moderate to severe deformities of the external ear using porous polyethylene implants instead of rib cartilage grafts has been practiced with success for the past two years or so. Porous polyethylene implants provide good results and may help to avoid pre- and postoperative morbidity at donor site defects.


The Caenorhabditis briggsae genome contains active CbmaT1 and Tcb1 transposons.
The maT clade of transposons is a group of transposable elements intermediate in sequence and predicted protein structure to mariner and Tc transposons, with a distribution thus far limited to a few invertebrate species. We present evidence, based on searches of publicly available databases, that the nematode Caenorhabditis briggsae has several maT-like transposons, which we have designated as CbmaT elements, dispersed throughout its genome. We also describe two additional transposon sequences that probably share their evolutionary history with the CbmaT transposons. One resembles a fold back variant of a CbmaT element, with long (380-bp) inverted terminal repeats (ITRs) that show a high degree (71%) of identity to CbmaT1. The other, which shares only the 26-bp ITR sequences with one of the CbmaT variants, is present in eight nearly identical copies, but does not have a transposase gene and may therefore be cross mobilised by a CbmaT transposase. Using PCR-based mobility assays, we show that CbmaT1 transposons are capable of excising from the C. briggsae genome. CbmaT1 excised approximately 500 times less frequently than Tcb1 in the reference strain AF16, but both CbmaT1 and Tcb1 excised at extremely high frequencies in the HK105 strain. The HK105 strain also exhibited a high frequency of spontaneous induction of unc-22 mutants, suggesting that it may be a mutator strain of C. briggsae.


N-acetyltransferase polymorphisms are associated with risk of lymphoma subtypes.
Genes encoding for arylamine N-acetyltransferase 1 and 2 (NAT1 and NAT2) have been investigated with alternate findings in relation to risk of non-Hodgkin lymphoma (NHL). We tested functional haplotype-based NAT1 and NAT2 gene polymorphisms in relation to risk of lymphoma overall and its major B cell subtypes, diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). We used allele specific primers and multiplex PCR to detect NAT1 and NAT2 haplotypes in 248 patients with incident lymphoma and 208 population controls. We inferred the NAT1 rapid and slow acetylator and the NAT2 rapid, intermediate or slow acetylator phenotype, based on published functional data on the respective genotypes. Odds ratios and 95% confidence intervals (95% CIs) for lymphoma, B-NHL, DLBCL, FL, CLL, and other B-NHL combined associated with the inferred rapid NAT1 acetylator and with the intermediate and slow NAT2 acetylator phenotypes were estimated with unconditional and polytomous logistic regression analysis, adjusting for age, gender and education. NAT1 rapid acetylators showed a 2.8-fold excess risk (95% CI 1.5-5.2) for lymphoma (all subtypes combined). Risk was highest for CLL and FL, with significant heterogeneity detected across subtypes. Risk also increased with decreasing NAT2 acetylating capacity with no heterogeneity detected across B cell lymphoma subtypes. Risks did not vary by gender. Although poor statistical power was a major limitation in our study, larger studies and pooled analyses are warranted to test whether NAT1 and NAT2 gene polymorphisms might modulate risk of specific lymphoma subtypes through the varying metabolic activity of their products. Copyright © 2015 John Wiley & Sons, Ltd.


Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations.
Recent studies have done much to reveal the biological and genetic underpinnings of gastrointestinal stromal tumors (GISTs). Constitutive activation of the KIT receptor tyrosine kinase is a central pathogenetic event in most GISTs and generally results from oncogenic point mutations which can involve either extracellular or cytoplasmic domains of the receptor. Oncogenic mutations enable the KIT receptor to phosphorylate various substrate proteins, leading to activation of signal transduction cascades which regulate cell proliferation, apoptosis, chemotaxis, and adhesion. KIT mutations can be broadly assigned to 2 groups, those that involve the "regulatory" regions responsible for modulating KIT enzymatic activity and those that involve the enzymatic region itself. In vitro studies suggest that GISTs with regulatory-region KIT mutations are more likely to respond to STI-571 than are GISTs with enzymatic-region mutations. A minority of GISTs lack demonstrable KIT mutations, but KIT is nonetheless strongly activated. Such GISTs might contain KIT mutations which are not readily detected by conventional screening methods, or alternately, KIT might be activated by nonmutational mechanisms. Most GISTs have noncomplex cytogenetic profiles, often featuring deletions of chromosomes 14 and 22. Additional chromosomal aberrations are acquired as the GISTs progress to higher histologic grade. These cytogenetic aberrations are undoubtedly important in GIST pathogenesis, but currently they do not play a key role as diagnostic adjuncts.


Twenty-three-gauge pars plana vitrectomy, Densiron-68, and 360° endolaser versus combined 20-gauge pars plana vitrectomy, scleral buckle, and SF6 for pseudophakic retinal detachment with inferior retinal breaks.
To compare the anatomical and functional outcomes of 23-gauge pars plana vitrectomy (PPV) with Densiron-68 tamponade and 360° endolaser versus 20-gauge PPV with encircling scleral buckling (ESB) and an SF6 gas tamponade for the repair of primary pseudophakic retinal detachment with inferior retinal breaks. Prospective, randomized, comparative, interventional study. Eighty-two eyes of 82 consecutive patients were randomly assigned to 1 of the 2 treatment groups: 23-gauge PPV/Densiron-68 (44 eyes, 54%) or 20-gauge PPV/ESB/SF6 (20%) (38 eyes, 46%). The inclusion criterion was the presence of primary pseudophakic retinal detachment with at least 1 retinal break between the 4- and 8-o'clock positions. The study protocol involved a minimum of 7 visits: baseline, day of surgery, 1 week, and 1, 3, 6, and 9 months postoperation. Densiron-68 removal was performed within 12 weeks of the initial surgery. Two surgical procedures were required in the Densiron group to remove the oil. After the primary procedure, the retina was reattached in 90% (40 of 44) of cases in the 23-gauge PPV/Densiron group and in 92% (35 of 38) of cases in the 20-gauge PPV/ESB/SF6 group (P = 0.2, Fisher's exact test). After resolution of redetachments, final anatomical success rate rose to 97% (43 of 44) in the 23-gauge PPV/Densiron group and 94% (36 of 38) in the 20-gauge PPV/SB/SF6 group (P = 0.32, Fisher's exact test). Mean final best-corrected visual acuity (logarithm of the minimum angle of resolution) was 0.40 in the 23-gauge PPV/Densiron group and 0.48 in the 20-gauge PPV/ESB/SF6 group (P = 0.31, t-test). Operative time was significantly less in the 23-gauge PPV/Densiron group (P = 0.002, t-test). No statistically significant difference in the complication rate between the two groups was recorded. Twenty-three-gauge PPV combined with Densiron-68 and 360° endolaser and 20-gauge PPV combined with ESB/SF6 seemed to have similar efficacy in the repair of primary pseudophakic retinal detachment. Supplementary scleral buckling can be avoided using a Densiron-68 tamponade for retinal detachment with inferior retinal breaks.


Aligned poly(L-lactic-co-e-caprolactone) electrospun microfibers and knitted structure: a novel composite scaffold for ligament tissue engineering.
We developed a novel technique involving knitting and electrospinning to fabricate a composite scaffold for ligament tissue engineering. Knitted structures were coated with poly(L-lactic-co-e-caprolactone) (PLCL) and then placed onto a rotating cylinder and a PLCL solution was electrospun onto the structure. Highly aligned 2-microm-diameter microfibers covered the space between the stitches and adhered to the knitted scaffolds. The stress-strain tensile curves exhibited an initial toe region similar to the tensile behavior of ligaments. Composite scaffolds had an elastic modulus (150 +/- 14 MPa) similar to the modulus of human ligaments. Biological evaluation showed that cells proliferated on the composite scaffolds and they spontaneously orientated along the direction of microfiber alignment. The microfiber architecture also induced a high level of extracellular matrix secretion, which was characterized by immunostaining. We found that cells produced collagen type I and type III, two main components found in ligaments. After 14 days of culture, collagen type III started to form a fibrous network. We fabricated a composite scaffold having the mechanical properties of the knitted structure and the morphological properties of the aligned microfibers. It is difficult to seed a highly macroporous structure with cells, however the technique we developed enabled an easy cell seeding due to presence of the microfiber layer. Therefore, these scaffolds presented attractive properties for a future use in bioreactors for ligament tissue engineering.


Block coherence: a method for measuring the interdependence between two blocks of neurobiological time series.
Multisensor recordings are becoming commonplace. When studying functional connectivity between different brain areas using such recordings, one defines regions of interest, and each region of interest is often characterized by a set (block) of time series. Presently, for two such regions, the interdependence is typically computed by estimating the ordinary coherence for each pair of individual time series and then summing or averaging the results over all such pairs of channels (one from block 1 and other from block 2). The aim of this paper is to generalize the concept of coherence so that it can be computed for two blocks of non-overlapping time series. This quantity, called block coherence, is first shown mathematically to have properties similar to that of ordinary coherence, and then applied to analyze local field potential recordings from a monkey performing a visuomotor task. It is found that an increase in block coherence between the channels from V4 region and the channels from prefrontal region in beta band leads to a decrease in response time.


Evaluation of Tween 80 incorporated media to increase pathogen isolation from peritoneal fluid of CAPD patients at Hospital Kuala Lumpur.
Continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis remains a major complication in patients on CAPD leading to increased morbidity and mortality. Successful therapy of peritonitis is highly dependent on a positive microbiological culture because narrow spectrum antibiotics are essential to efficiently combat infection. Therefore, this study evaluated the performance of Tween 80 containing media at three different concentrations (0.1%, 1.0% and 2.0%) to increase the pathogen yield from peritoneal fluid in comparison with the standard culture media. Peritoneal fluid samples (n=121) obtained from CAPD patients suspected of peritonitis at Hospital Kuala Lumpur were analysed macroscopically and microscopically prior to culture. All samples were cultured on seven different culture media, including sheep blood agar, MacConkey agar, Sabouraud dextrose agar, brain heart infusion agar and Tween 80 incorporated blood agar. All plates were incubated at an optimum temperature up to 48 hours. Among all the culture media investigated, 0.1% to 2.0% Tween 80 incorporated blood agar yielded the highest positive culture (23/121) in comparison with all other standard media, thus lowering the negative culture rate among CAPD patients. Statistical analysis by Chi Square revealed significant differences (p <0.001) between the three concentrations of Tween 80 tested in this study. Among the three different concentrations of Tween 80 optimised in this study, blood agar containing 0.1% Tween 80 generated the best results, achieved by optimum growth of all Gram-positive organisms, Gram-negative organisms and yeast cells simultaneously. Using a small amount of detergent at low cost significantly increased the pathogen yield during CAPD-associated peritonitis.


Protein engineering study of β-mannosidase to set up a potential chemically efficient biocatalyst.
This study is focused on the analysis and mutagenesis of β-mannosidase from Bacteroides thetaiotaomicron with the aim of broadening its substrate specificity to 2-acetamido-2-deoxy-β-d-mannopyranosyl (β-ManNAc) derivatives. Various conformations ((4)C1, (4)H5 and (1)S5) of native and modified ligands were docked to the binding site of the protein to determine the most suitable conformation of sugars for further hydrolysis. Key amino acid residues were mutated in silico focusing on stabilizing the acetamido group of β-ManNAc as well as forming the oxazoline intermediate needed for hydrolysis. The results of large set of 5 ns molecular dynamic simulations showed that the majority of the active site residues are involved in substrate interaction and do not exhibit a higher flexibility except for Asn178. Mutations of Asn178 to alanine and Asp199 to serine could lead to a stabilization of the acetamido group in the binding site. So far, in vitro mutagenesis and the screen of a large variety of biological sources were unable to extend β-mannosidase's activity to include β-ManNAc derivatives.


Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment.
Pyridox(am)ine phosphate oxidase (PNPO) deficiency causes severe early infantile epileptic encephalopathy and has been characterized as responding to pyridoxal-5'-phosphate but not to pyridoxine. Two males with PNPO deficiency and novel PNPO mutations are reported and their clinical, metabolic, and video-electroencephalographic (EEG) findings described. The first child showed electro-clinical responses to pyridoxine and deterioration when pyridoxine was withheld. At last review, he has well-controlled epilepsy with pyridoxal-5'-phosphate monotherapy and an autism spectrum disorder. The second child had a perinatal middle cerebral artery infarct and a myoclonic encephalopathy. He failed to respond to pyridoxine but responded well to pyridoxal-5'-phosphate. At the age of 21 months he has global developmental delay and hemiparesis but is seizure-free with pyridoxal-5'-phosphate monotherapy. Plasma and cerebrospinal fluid pyridoxamine levels were increased in both children during treatment with pyridoxine or pyridoxal-5'-phosphate. These observations indicate that differential responses to pyridoxine and pyridoxal-5'-phosphate treatment cannot be relied upon to diagnose PNPO deficiency.


Biological markers of oxidative stress in mitochondrial myopathies with progressive external ophthalmoplegia.
According to experimental models suggesting that overproduction of oxygen free-radicals may occur when the electron transport in the respiratory chain is impaired, we searched for in vivo biological markers of oxidative stress in 11 patients affected by histologically proven mitochondrial myopathy with progressive external ophthalmoplegia (PEO) and partial cytochrome c oxidase deficiency in muscle fibres. Six of the patients carried large-scale deletions of mitochondrial DNA. Biochemical assays included the determination of plasma and erythrocyte reduced glutathione (GSH) concentration, plasma malondialdehyde, fluorescent adducts of aldehydes with plasma proteins, and serum level of lipid peroxides. In patients with PEO the mean values of lipid peroxides and of the fluorescent adducts of aldehydes with plasma proteins were significantly higher with respect to normal controls, while the mean values of plasma and erythrocyte GSH concentration were significantly lower. The reported data indicate an increase of lipid peroxidation indexes along with the reduction of one of the most important antioxidant systems and suggest the hypothesis that overproduction of reduced oxygen species might be an adjunctive cause of cell damage in mitochondrial myopathies and encephalomyopathies associated with defects of oxidative phosphorylation.


Tobacco Control and Socioeconomic Inequalities in Adolescent Smoking in Europe.
The strength of national tobacco control varies by country, but it is unclear how this relates to smoking in adolescents of high and low SES. This study examined the association between tobacco control policies and adolescent smoking and investigated the differences in this association between adolescents of high and low SES. Data of 90,351 adolescents aged 15-16 years from 13 European countries were obtained from the 2003, 2007, and 2011 European Survey Project on Alcohol and other Drugs databases. Logistic regression analyses were performed in 2014 with a random intercept at the country level and with daily smoking as the outcome. The Tobacco Control Scale was the score for national tobacco control policy. SES was based on parental education. In all studied countries, except Portugal, adolescent smoking prevalence rates were highest among low-SES respondents. Stronger tobacco control policies were associated with lower smoking rates in all three survey waves (2003, OR=0.75, 95% CI=0.55, 1.01; 2007, OR=0.84, 95% CI=0.73, 0.98; 2011, OR=0.85, 95% CI=0.74, 0.98). The association was consistently stronger in high-SES than in low-SES individuals, but the difference was not statistically significant. Countries with stronger tobacco control policies tend to have lower smoking rates. We are unable to demonstrate significant socioeconomic inequalities in the effect of tobacco control policies on adolescent smoking.


Life at low water activity.
Two major types of environment provide habitats for the most xerophilic organisms known: foods preserved by some form of dehydration or enhanced sugar levels, and hypersaline sites where water availability is limited by a high concentration of salts (usually NaCl). These environments are essentially microbial habitats, with high-sugar foods being dominated by xerophilic (sometimes called osmophilic) filamentous fungi and yeasts, some of which are capable of growth at a water activity (a(w)) of 0.61, the lowest a(w) value for growth recorded to date. By contrast, high-salt environments are almost exclusively populated by prokaryotes, notably the haloarchaea, capable of growing in saturated NaCl (a(w) 0.75). Different strategies are employed for combating the osmotic stress imposed by high levels of solutes in the environment. Eukaryotes and most prokaryotes synthesize or accumulate organic so-called 'compatible solutes' (osmolytes) that have counterbalancing osmotic potential. A restricted range of bacteria and the haloarchaea counterbalance osmotic stress imposed by NaCl by accumulating equivalent amounts of KCl. Haloarchaea become entrapped and survive for long periods inside halite (NaCl) crystals. They are also found in ancient subterranean halite (NaCl) deposits, leading to speculation about survival over geological time periods.


The biomechanical efficacy of dressings in preventing heel ulcers.
The heels are the most common site for facility-acquired pressure ulcers (PUs), and are also the most susceptible location for deep tissue injuries. The use of multilayer prophylactic dressings to prevent heel PUs is a relatively new prevention concept, generally aimed at minimizing the risk for heel ulcers (HUs) through mechanical cushioning and reduction of friction at the dressing-support interface. We used 9 finite element model variants of the posterior heel in order to evaluate the biomechanical performance of a multilayer dressing in prevention of HUs during supine lying. We compared volumetric exposures of the loaded soft tissues to effective and maximal shear strains, as well as peak stresses in the Achilles tendon, without any dressing and with a single-layer or a multilayer dressing (Mepilex(®) Border Heel-type), on supports with different stiffnesses. The use of the multilayer dressing consistently and considerably reduced soft tissue exposures to elevated strains at the posterior heel, on all of the tested support surfaces and when loaded with either pure compression or combined compression and shear. The aforementioned multilayer design showed (i) clear benefit over a single-layer dressing in terms of dissipating tissue strains, by promoting internal shear in the dressing which diverts loads from tissues; (ii) a protective effect that was consistent on supports with different stiffnesses. Recent randomized controlled trials confirmed the efficacy of the simulated multilayer dressing, and so, taken together with this modeling work, the use of a prophylactic multilayer dressing indicates a great promise in taking this route for prevention.


Landscaping biostatistics education in India.
Biostatistics plays an important role in measuring, understanding, and describing the overall health and well-being of a population. Biostatistics as a subject evolved from the application of statistics in various research aspects of biology, biomedical care, and public health. However, with a recent increase in number of health and pharmacy related research, the demand for trained biostatisticians is also increasing. The present paper is an attempt to undertake a situational analysis of biostatistics education in India. A systematic, predefined approach, with three parallel strategies was used to collect and assemble the data regarding training in biostatistics in India. Our study results show that there is paucity of programs providing specialized training in biostatistics in India. Only about 19 institutions in India are offering various courses in biostatistics/medical statistics/health statistics/biometry. It is important to look into the current capacity building initiatives in this domain. Some other means for giving importance to biostatistics could be by making it a separate branch/specialization in a majority of the institutions, particularly in medical colleges.


Screening for cystic fibrosis carrier state.
Carrier screening for cystic fibrosis as part of reproductive health care, including prenatal care, is not the standard of practice at this time. However, a recent National Institutes of Health Consensus Development Conference recommended that cystic fibrosis carrier screening should be offered to adults with a family history of cystic fibrosis, partners of individuals with cystic fibrosis, couples planning a pregnancy, and couples seeking prenatal testing. A workshop convened to discuss the implementation of these recommendations concluded that several issues must be resolved before these recommendations can be implemented. This commentary reviews the discussions that occurred and the conclusions that were reached at this workshop. Some of the subjects considered by the workshop participants were: the goals and outcomes of carrier screening; the continuum from making a test available to offering that test; to whom, when, and how cystic fibrosis testing should be offered; laboratory practice and quality assurance; provider and patient education; and insurance issues. The workshop participants concluded that those populations to whom carrier screening should be offered might include individuals and couples in high-risk groups who seek preconception counseling, infertility care, or prenatal care. High-risk groups include individuals of white northern European or of Ashkenazi-Jewish descent, those whose partners have cystic fibrosis, and those with a family history of cystic fibrosis. Before screening can be offered systematically to these individuals or couples, practice guidelines, educational materials for providers and patients, informed-consent protocols, and laboratory standards for testing must be developed.


von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends.
To understand the placement of a certain protein in a physiological system and the pathogenesis of related disorders, it is not only of interest to determine its function but also important to describe the sequential steps in its life cycle, from synthesis to secretion and ultimately its clearance. von Willebrand factor (VWF) is a particularly intriguing case in this regard because of its important auxiliary roles (both intra- and extracellular) that implicate a wide range of other proteins: its presence is required for the formation and regulated release of endothelial storage organelles, the Weibel-Palade bodies (WPBs), whereas VWF is also a key determinant in the clearance of coagulation factor VIII. Thus, understanding the molecular and cellular basis of the VWF life cycle will help us gain insight into the pathogenesis of von Willebrand disease, design alternative treatment options to prolong the factor VIII half-life, and delineate the role of VWF and coresidents of the WPBs in the prothrombotic and proinflammatory response of endothelial cells. In this review, an update on our current knowledge on VWF biosynthesis, secretion, and clearance is provided and we will discuss how they can be affected by the presence of protein defects.


Natural photoreceptors as a source of fluorescent proteins, biosensors, and optogenetic tools.
Genetically encoded optical tools have revolutionized modern biology by allowing detection and control of biological processes with exceptional spatiotemporal precision and sensitivity. Natural photoreceptors provide researchers with a vast source of molecular templates for engineering of fluorescent proteins, biosensors, and optogenetic tools. Here, we give a brief overview of natural photoreceptors and their mechanisms of action. We then discuss fluorescent proteins and biosensors developed from light-oxygen-voltage-sensing (LOV) domains and phytochromes, as well as their properties and applications. These fluorescent tools possess unique characteristics not achievable with green fluorescent protein-like probes, including near-infrared fluorescence, independence of oxygen, small size, and photosensitizer activity. We next provide an overview of available optogenetic tools of various origins, such as LOV and BLUF (blue-light-utilizing flavin adenine dinucleotide) domains, cryptochromes, and phytochromes, enabling control of versatile cellular processes. We analyze the principles of their function and practical requirements for use. We focus mainly on optical tools with demonstrated use beyond bacteria, with a specific emphasis on their applications in mammalian cells.


Cholinergic activity correlates with reserve proxies in Alzheimer's disease.
The clinical expression of Alzheimer's disease (AD) occurs as neuropathology exceeds the brain "reserve capacity." A possible association between the cholinergic system and reserve is suggested by preclinical observations that the cholinergic system allows cortical plasticity and by clinical observations of variable responses to cholinergic treatments depending on the patient's educational level. The aim of this study was to investigate the association of reserve proxies, that is, education and occupation, with acetylcholinesterase (AChE) activity, measured voxelwise by [(11)C]-MP4A and positron emission tomography (PET), in 9 healthy controls (HC), 7 patients with early probable AD, and 9 subjects with mild cognitive impairment (MCI) at the time of PET imaging, who progressed to AD at follow-up (prodromal AD). The analysis of prodromal and early AD showed positive correlations between education and AChE activity in the hippocampus, bilaterally, and between occupation and AChE activity in the right posterior cingulate gyrus. The significant correlation between AChE activity in structures belonging to the memory network and reserve proxies suggests that the brain reserve in AD is associated with a preserved/stimulated cholinergic neurotransmission.


Bronchiolitis obliterans in chronic graft-versus-host disease: analysis of risk factors and treatment outcomes.
Bronchiolitis obliterans (BrOb), a late complication of bone marrow transplantation (BMT), is associated with chronic graft-versus-host disease (GVHD) and is frequently fatal. To identify the risk factors associated with BrOb, the factors affecting survival, treatment outcomes, and causes of death of patients with BrOb, we retrospectively analyzed 2859 BMT recipients. No cases of BrOb occurred among 1070 autologous BMT recipients. Among 1789 allogeneic BMT recipients, we identified 47 patients with BrOb. In multivariate analysis, older recipients or donors and acute GVHD were significantly associated with the development of BrOb. Among patients with BrOb, 5-year survival from the time of transplantation was only 10%, versus 40% among allogeneic BMT recipients without BrOb. The clinical course of BrOb had a significant effect on survival: 79% survived 5 years from the time of BrOb diagnosis if BrOb improved versus 13% if there was no improvement after the first-line therapy. Predictors of response included older donors and recipients, a previous diagnosis of chronic GVHD, and diagnosis of BrOb 6 months after transplantation; each of these significantly increased the likelihood of a favorable response to treatment. BrOb had high mortality rate of 55%, and pulmonary failure was the leading cause of death. More effective BrOb therapy is needed, especially for patients with unfavorable presentation.


Costs associated with changes in antidepressant treatment in a managed care population with major depressive disorder.
This study determined whether persons with major depressive disorder who switch or augment antidepressant therapy have higher health care costs and productivity losses than those who do not. Data from July 1, 2002, through June 30, 2006, were taken from a national employment-based medical and pharmacy claims database. Participants were required to have filled an antidepressant prescription, be treatment naïve six months before the index prescription, be continuously enrolled in the benefits plan at least six months before and 12 months after the index prescription, and have at least one outpatient-based medical claim for major depressive disorder. Participants were categorized according to whether they switched, augmented, or maintained (that is, neither switched nor augmented) their antidepressant therapy in the 12 months after the index prescription. Productivity losses were defined as days absent from work for medical visits multiplied by average daily wage. Multivariate analyses (generalized linear models) were used to compare costs per person in the year after the index prescription, and univariate analyses (Wilcoxon tests) were used to compare productivity losses per person. Of the 7,273 individuals who met study criteria, 40.3% switched, 1.5% augmented, and 58.2% maintained the index antidepressant therapy. After the analyses controlled for baseline characteristics, mean total and depression-related health care costs, respectively, in the year after the index prescription were significantly greater for switchers ($9,288 and $1,388 per person) and for augmenters ($9,350 and $1,027) than for maintainers ($6,151 and $723). Mean total and depression-related productivity losses, respectively, were significantly greater for switchers ($2,081 and $680) and augmenters ($2,010 and $587) than for maintainers ($1,424 and $437). Persons with major depressive disorder who switched or augmented antidepressant therapy within 12 months of treatment initiation had higher resource costs and productivity losses than those who did not.