Myosin Va and kinesin II motor proteins are concentrated in ribosomal domains (periaxoplasmic ribosomal plaques) of myelinated axons.
Periaxoplasmic ribosomal plaques (PARPs) are discrete ribosome-containing domains distributed intermittently along the periphery of axoplasm in myelinated fibers. Thus, they are structural formations in which translational machinery is spatially organized to serve as centers of protein synthesis for local metabolic requirements and perhaps repair as well. Because of evidence that RNA is transported to putative PARP domains, involving both microtubule- and actin-based mechanisms, it was of interest to investigate whether cytoskeletal motor proteins exhibit a nonrandom localization within PARP domains. Axoplasm, from large Mauthner fibers and rat or rabbit spinal ventral nerve root fibers, removed from the myelin sheath in the form of an "axoplasmic whole-mount" was used for this analysis. PARP domains were identified either by specific immunofluorescence of rRNA, ribosomal P antigen, or by nonspecific RNA fluorescence using RNA binding dyes YOYO-1 or POPO-1. A polyclonal antibody (pAb) against the motor domain of myosin Va showed prominent nonrandom immunofluorescence labeling in PARP domains. Similarly, monoclonal antibodies (mAb) against kinesin KIF3A and a pan-specific antikinesin (mAb IBII) also showed a preponderant immunofluorescence in PARP domains. On the other hand, H2, a mAb antikinesin KIF5A, exhibited only random immunofluorescence labeling in axoplasm, as was also the case with pAb antidynein heavy chain immunofluorescence. Several possible explanations for these findings are considered, primary among which is targeted trafficking of translational machinery that results in local accumulation of motor proteins. Additional possibilities are trafficking functions intrinsic to the domain, and/or functions that govern dynamic organizational properties of PARPs.


Loading and release mechanisms of a biocide in polystyrene-block-poly(acrylic acid) block copolymer micelles.
The kinetics of loading of polystyrene197-block-poly(acrylic acid)47 (PS197-b-PAA47) micelles, suspended in water, with thiocyanomethylthiobenzothiazole biocide and its subsequent release were investigated. Loading of the micelles was found to be a two-step process. First, the surface of the PS core of the micelles is saturated with biocide, with a rate determined by the transfer of solid biocide to micelles during transient micelle-biocide contacts. Next, the biocide penetrates as a front into the micelles, lowering the Tg in the process (non-Fickian case II diffusion). The slow rate of release is governed by the height of the energy barrier that a biocide molecule must overcome to pass from PS into water, resulting in a uniform biocide concentration within the micelle, until Tg is increased to the point that diffusion inside the micelles becomes very slow. Maximum loading of biocide into micelles is approximately 30% (w/w) and is achieved in 1 h. From partition experiments, it can be concluded that the biocide has a similar preference for polystyrene as for ethylbenzene over water, implying that the maximum loading is governed by thermodynamics.


A Fractional Bipolar Radiofrequency Device Combined with a Bipolar Radiofrequency and Infrared Light Treatment for Improvement in Facial Wrinkles and Overall Skin Tone and Texture.
A variety of techniques and energy-based technologies are currently utilized for the treatment of facial wrinkles. Fractional bipolar radiofrequency treatment and treatment with bipolar radiofrequency combined with infrared light have both been reported to be safe and effective for the non-invasive treatment of wrinkles and overall facial rejuvenation. A multicenter, prospective clinical trial evaluated a protocol of treatment with a device incorporating bipolar radiofrequency and infrared light followed by treatment with a fractional bipolar radiofrequency device for facial wrinkle reduction and improvement in the overall appearance of aged facial skin. Fifty-six patients with mild to moderate facial wrinkles received three full-face treatments (forehead, nose, cheeks, periorbital, and perioral areas) at 4 to 6 week intervals and were evaluated at 12 and 24 weeks after the last treatment. Clinical photographs at baseline and follow-ups were assessed by both the investigators and patients using the Global Aesthetic Improvement scale. Treatment safety was evaluated. Study participants also completed a satisfaction and improvement questionnaire. Fitzpatrick Wrinkling and Elastosis Score was decreased significantly at three months (P < .01; paired t test) and at six months (P < .001; paired t test) after the final treatment. Investigators' assessments of overall improvement in facial appearance, demonstrated 88% improvement at 12 weeks and 82% at 24 weeks after the final treatment. Subject evaluations were similar, consistently reporting improvement in wrinkles and overall facial skin appearance throughout the study, and high a degree of satisfaction with their final results. Subjects tolerated the procedures well, with only transient mild to moderate erythema and edema occurring in most patients, and without complications. A combined protocol of bipolar radiofrequency and infrared light treatment followed by fractionated bipolar radiofrequency treatment results in safe, well tolerated, and effective improvement in overall skin tone and texture and reduction of facial wrinkles. 4 Therapeutic.


[Acute flaccid paralysis].
Acute flaccid paralysis, a common paediatric disorder, is fundamentally caused by disorders involving neuromuscular diseases of acute onset. It generally presents as an acute or extremely acute motor disorder which is progressive or extremely progressive. Successful management depends on a rapid, accurate differential diagnosis, based on the patient s history of muscular weakness.


[Synthesis and antiinflammatory activity of 2-(E)-(4-hydroxy-3-methoxybenzylidene)-5-(N-substituted aminomethyl) cyclopentanones].
In search for new antiinflammatory agents, a series of 2-(E)-(4-hydroxy-3-methoxybenzylidene)-5-(N-substituted aminomethyl) cyclopentanones was synthesized via Stork reaction, Mannich reaction and amine exchange reaction. All of the fifteen target compounds were characterized by spectral analysis and elemental analysis. Preliminary pharmacological tests showed that several target compounds exerted appreciable effect on xylene-induced ear edema in mice and that alteration of the substituents of anilines showed significant influence on antiinflammatory potency.


Diverse novel mesorhizobia nodulate New Zealand native Sophora species.
Forty eight rhizobial isolates from New Zealand (NZ) native Sophora spp. growing in natural ecosystems were characterised. Thirty eight isolates across five groups showed greatest similarity to Mesorhizobium ciceri LMG 14989(T) with respect to their 16S rRNA and concatenated recA, glnll and rpoB sequences. Seven isolates had a 16S rRNA sequence identical to M. amorphae ATCC 19665(T) but showed greatest similarity to M. septentrionale LMG 23930(T) on their concatenated recA, glnll and rpoB sequences. All isolates grouped closely together for their nifH, nodA and nodC sequences, clearly separate from all other rhizobia in the GenBank database. None of the type strains closest to the Sophora isolates based on 16S rRNA sequence similarity nodulated Sophora microphylla but they all nodulated their original host. Twenty one Sophora isolates selected from the different 16S rRNA groupings produced N2-fixing nodules on three Sophora spp. but none nodulated any host of the type strains for the related species. DNA hybridisations indicated that these isolates belong to novel Mesorhizobium spp. that nodulate NZ native Sophora species.


[Toxicity and efficacy of chemotherapy dependent on circadian time of cytostatic drug administration].
A prospective, controlled study was carried out in order to evaluate efficacy and toxicity of chemotherapy based on cisplatin in dependence on the circadian rhythm of drugs administration in patients with testicular and ovarian cancer. The study included 80 patients (40 with testicular cancer and 40 with ovarian cancer), divided into two groups (A and B). The cytostatics were administered in the evening in the group A and in the morning in the group B. The response rates and the 3-years survival rates were comparable in both groups. However the patients in the group A presented less haematological and renal side effects, while nausea and vomiting were milder. Chronotherapy may appear to be a method improving the tolerance of chemotherapy based on cisplatin.


Successful use of amphotericin B lipid complex in the treatment of cryptococcosis.
The efficacy and renal safety of amphotericin B lipid complex (ABLC) injection were assessed in 106 patients with cryptococcal infection. Eighty-three patients (78%) had a central nervous system (CNS) infection. Of these patients, 20 initiated azole therapy concomitantly with ABLC therapy, and 7 had received prior azole therapy, which continued during administration of ABLC. Clinical response (cured or improved) was achieved in 67 (66%) of 101 patients whose results could be evaluated. Response rates were 65% (51/78) for patients with a CNS infection and 70% (16/23) for patients without a CNS infection. The response rate for patients with HIV infection was 58% (30/52). Response rates were 56% (19/34) for patients who were refractory to prior antifungal therapy, 65% (11/17) for patients who were intolerant of prior antifungal therapy, 60% (3/5) for patients with underlying renal disease who received prior antifungal therapy, 76% (25/33) for patients with underlying renal disease who did not receive prior antifungal therapy, and 73% (8/11) for patients with no renal disease who did not receive prior antifungal therapy. A mean serum creatinine level decrease of 0.02 mg/dL occurred. ABLC was an effective treatment for cryptococcal infection in immunocompromised patients.


Implementation of a relational patient record with integration of educational and reference information.
The clinician must identify pertinent diagnostic information and develop appropriate medical management plans in the context of rapidly changing research information, new therapeutic options and expanding diagnostic modalities. To assist in recognition of patterns relevant to diagnostic or therapeutic interventions, the medical record must be presented in a format that emphasizes important data interrelationships. Reference and educational information specifically pertinent to the case being reviewed must be immediately accessible. A system that presents point of care patient centered clinical information, a summarized patient record, in a relational format with linked reference information has been developed. Data is acquired from the VA patient information database and provided over a PC network. At the time of data transfer, preliminary analysis and reorganization of data is performed such that interrelationships between laboratory, pharmacy and diagnostic information can be rapidly recognized. During data compilation reference and educational information is linked with patient data such that it can be accessed with a mouse click ("hotspot") when the record is subsequently reviewed. The medical record and CD-ROM based reference databases are then made available to users on a PC network in a Windows (tm) environment. Initial experience with the system is very favorable and suggests that evaluation of patient data may be significantly enhanced.


[Review of the extratransference intervention practice in the psychoanalytic psychotherapy].
The transference analysis takes the central position of the work in psychoanalytic psychotherapy. The work in extratransference sphere and experience in practical work with extratransference interventions are not often reported in expert literature. Extratransference sphere includes less transferring relation to the psychotherapist, transference on the other objects, or may refer to the external reality rather than the psychic reality or fantasy. In our illustration, we gave emphasis to extratransference interventions. Application of genetic interpretation and reconstruction were demonstrated as well, which can restore and establish connections between past and present, in order to understand influences of the past and current reality, and helping us to resolve infantile conflicts. Interpretation of extratransference situations is an important part of the analytical work and it is the essential category of interpretation. Analytic understanding should include transference and extratransference spheres, fantasy and reality, past and present. Working with neurotic patterns and character resistance needs an optimal choice of intervention in a given moment of analytic process. Extratransference interventions are the essential category of intervention, irreplaceable for their effectiveness in analytic process.


The recent colonization of south Brazil by the Azores chromis Chromis limbata.
The damselfish Chromis limbata is native to the Macaronesian Archipelagos (Azores, Madeira and Canaries) and the western coast of Africa between Senegal and Angola. During the austral summers of 2008 and 2009 the species was recorded for the first time in the south-western Atlantic Ocean around Campeche and Xavier Islands, in Florianópolis, Santa Catarina State, Brazil. Here, the progression of C. limbata in southern Brazilian waters is described using visual counts and genetic surveys and changes in the density of the native congener Chromis multilineata were also investigated. Underwater visual censuses of both Chromis species were carried out from 2009 to 2014. Chromis limbata tissue samples were collected and the mtDNA control region was sequenced and compared with mtDNA haplotypes from the natural range to confirm species identity, compare genetic diversity and to infer connectivity between newly established Brazilian populations. The Brazilian population of C. limbata increased significantly over the past 5 years and the effect on C. multilineata is still an open question, longer time-series data will be necessary to clarify possible interactions. The molecular analyses confirmed species identity, revealed strong haplotype connectivity among Brazilian study sites and showed a low genetic diversity in Brazil when compared with the native populations, suggesting few individuals started the invasion. Four hypotheses could explain this colonizing event: C. limbata was released by aquarium fish keepers; larvae or juveniles were transported via ship ballast water; the species has rafted alongside oil rigs; they crossed the Atlantic Ocean through normal larval dispersal or naturally rafting alongside drifting objects. The rafting hypotheses are favoured, but all four possibilities are plausible and could have happened in combination.


An immunosuppressive lipoprotein fraction from TEPC-183 bearing mice.
Lipoprotein (LP) fractions prepared from sera of normal and plasmacytoma (TEPC-183) bearing mice, were compared with respect to their effect on the in vitro anti-2,4,6-trinitrophenyl plaque forming cell response. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions of sera from the plasmacytoma bearing mice contained immunosuppressive activity that was absent in VLDL and LDL fractions of normal serum LP fractions. The suppressive activity did not correlate with cholesterol or triglyceride content. Crossed-immunoelectrophoresis and polyacrylamide gel electrophoresis revealed components of the suppressive VLDL and LDL fractions which were not present in normal serum LP fractions, suggesting a modification of serum LPs by the plasmacytoma.


Studies of the active site of cytochrome P-450scc with a high-affinity spin-labeled inhibitor.
The intramolecular site of P-450scc for conversion of cholesterol to pregnenolone involves a substrate site, an active site, and a site for transmission of electrons. The substrate site was studied with a high-affinity, high-potency nitroxide spin-labeled inhibitor of cholesterol side-chain cleavage. This substance, 17 alpha-hydroxy-11-deoxycorticosterone nitroxide (SL-V), has an affinity comparable to that of the most active substrate inhibitors ever reported and 2-50 times greater than that of the natural substrate cholesterol. Competition experiments with cholesterol and its analogues confirmed that SL-V binds reversibly to the substrate site. Titration experiments showed a single binding site on the P-450 molecule. The substrate site is on the apoprotein and has little or no direct interaction with the heme. Spin-spin interactions between the Fe3+ and side-chain or A-ring spin-labeled groups could not be demonstrated, which is consistent with carbons 22 and 20 being closest to the heme iron. We postulate that substrate disrupts a histidine nitrogen coordination with the heme iron and induces conformational changes in the apoprotein. These changes lead to increased affinity for iron-sulfur protein.


Cellular mechanisms underlying the formation of circulating microparticles.
Microparticles (MPs) derived from platelets, monocytes, endothelial cells, red blood cells, and granulocytes may be detected in low concentrations in normal plasma and at increased levels in atherothrombotic cardiovascular diseases. The elucidation of the cellular mechanisms underlying the generation of circulating MPs is crucial for improving our understanding of their pathophysiological role in health and disease. The flopping of phosphatidylserine (PS) to the outer leaflet of the plasma membrane is the key event that will ultimately lead to the shedding of procoagulant MPs from activated or apoptotic cells. Research over the last few years has revealed important roles for calcium-, mitochondrial-, and caspase-dependent mechanisms leading to PS exposure. The study of Scott cells has unraveled different molecular mechanisms that may contribute to fine-tuning of PS exposure and MP release in response to a variety of specific stimuli. The pharmacological modulation of MP release may have a substantial therapeutic impact in the management of atherothrombotic vascular disorders. Because PS exposure is a key feature in pathological processes different from hemostasis and thrombosis, the most important obstacle in the field of MP-modulating drugs seems to be carefully targeting MP release to relevant cell types at an optimal level, so as to achieve a beneficial action and limit possible adverse effects.


Risk factors for latent tuberculosis infection in children in South Korea.
In South Korea, latent tuberculosis infection (LTBI) screening is a critical strategy associated with efforts to reduce the incidence of tuberculosis (TB). Currently, only children with a known history of TB contact are considered as pediatric high-risk groups for LTBI, and consequently, LTBI screening is only provided to these children. However, to reduce the incidence of TB, the high-risk groups that undergo LTBI screening should be expanded. This study aimed to assess the risk factors for LTBI among children living in South Korea with no known history of TB contact for the identification of additional high-risk groups. We investigated the risk factors for LTBI among US visa applicant children, who undergo LTBI screening regardless of their TB contact history. We obtained data on demographic characteristics, medical history, Bacillus Calmette-Guerin (BCG) vaccination history, and results of LTBI screening for children aged 2-14 years. A tuberculin skin test was used for the diagnosis of LTBI, and an induration of 10 mm or greater was used to define a positive test. Adjusted odds ratios and 95% confidence intervals were calculated to determine the association between clinical and demographic variables and LTBI. Of the 1,664 study participants, 91 (5.5%) had LTBI. The binary logistic regression analysis showed that children born in high TB burden foreign countries had the highest odds of LTBI when considering all the risk factors investigated. Increasing age, absence of BCG vaccination, and a previous diagnosis of asthma were also significant risk factors for LTBI. These results indicate that children born in high TB burden foreign countries should be considered a high-risk group for LTBI in South Korea; the inclusion of these children in LTBI screening should be considered.


FITNESS VARIATION ACROSS A SUBDIVIDED POPULATION OF THE ANNUAL PLANT IMPATIENS CAPENSIS.
The evolution of a subdivided population depends on whether subpopulations with high mean fitness make a greater per capita contribution to the next generation than subpopulations with lower mean fitness. I distinguish two different models of ecological population structure, denoted local compensation and global compensation. Local compensation restricts the differential contribution of subpopulations, whereas global compensation allows subpopulations to contribute in direct proportion to their mean fitness. I describe a simple regression-based method that distinguishes these alternatives as points on a continuum of possible population structures. The method is applied to field measurements of local abundance and reproduction in a subdivided population of the annual plant Impatiens capensis. These data suggest that the global compensation model is a more accurate description of the population studied. This result is surprising because local density effects on growth and reproduction occur in I. capensis. The implications of ecological population structure for both geographical variation in selection and kin selection are discussed.


Spatiotemporal regulation of cAMP signaling controls the human trophoblast fusion.
During human placentation, mononuclear cytotrophoblasts fuse to form multinucleated syncytia ensuring hormonal production and nutrient exchanges between the maternal and fetal circulation. Syncytial formation is essential for the maintenance of pregnancy and for fetal growth. The cAMP signaling pathway is the major route to trigger trophoblast fusion and its activation results in phosphorylation of specific intracellular target proteins, in transcription of fusogenic genes and assembly of macromolecular protein complexes constituting the fusogenic machinery at the plasma membrane. Specificity in cAMP signaling is ensured by generation of localized pools of cAMP controlled by cAMP phosphodiesterases (PDEs) and by discrete spatial and temporal activation of protein kinase A (PKA) in supramolecular signaling clusters inside the cell organized by A-kinase-anchoring proteins (AKAPs) and by organization of signal termination by protein phosphatases (PPs). Here we present original observations on the available components of the cAMP signaling pathway in the human placenta including PKA, PDE, and PP isoforms as well as AKAPs. We continue to discuss the current knowledge of the spatiotemporal regulation of cAMP signaling triggering trophoblast fusion.


Eosinophil accumulation in rats injected with Sephadex particles.
Intravenous injection of Sephadex G200 particles into rats on days 0, 2 and 5 caused an increase in eosinophil numbers in blood and lung tissues. Peak numbers were obtained on days 3-12 and thereafter declined to approach control values by day 21. The rise in eosinophil numbers was paralleled by an increase in lung cell fragility as measured by a transient reduction in the number of viable cells isolated from parenchymatous tissue following the digestion of lung fragments in vitro. This decrease in lung cell viability was not seen in rats given a single injection of Sephadex. Dexamethasone, dapsone and isoprenaline given before each injection of Sephadex reduced lung and blood eosinophil numbers and prevented lung cell death. Aspirin and indomethacin were without effect. Incubation of normal lung tissues with disrupted peritoneal eosinophils reduced the numbers of viable cells recovered. No such effects were seen using intact eosinophils and disrupted or intact neutrophils and mononuclear cells. This system provides a model of lung cell damage associated with eosinophil infiltration in vivo.


Cross-sectional description of nursing and midwifery pre-service education accreditation in east, central, and southern Africa in 2013.
In 2013, the World Health Organization issued guidelines, Transforming and Scaling Up Health Professional Education and Training, to improve the quality and relevance of health professional pre-service education. Central to these guidelines was establishing and strengthening education accreditation systems. To establish what current accreditation systems were for nursing and midwifery education and highlight areas for strengthening these systems, a study was undertaken to document the pre-service accreditation policies, approaches, and practices in 16 African countries relative to the 2013 WHO guidelines. This study utilized a cross-sectional group survey with a standardized questionnaire administered to a convenience sample of approximately 70 nursing and midwifery leaders from 16 countries in east, central, and southern Africa. Each national delegation completed one survey together, representing the responses for their country. Almost all countries in this study (15; 94%) mandated pre-service nursing education accreditation However, there was wide variation in who was responsible for accrediting programs. The percent of active programs accredited decreased by program level from 80% for doctorate programs to 62% for masters nursing to 50% for degree nursing to 35% for diploma nursing programs. The majority of countries indicated that accreditation processes were transparent (i.e., included stakeholder engagement (81%), self-assessment (100%), evaluation feedback (94%), and public disclosure (63%)) and that the processes were evaluated on a routine basis (69%). Over half of the countries (nine; 56%) reported limited financial resources as a barrier to increasing accreditation activities, and seven countries (44%) noted limited materials and technical expertise. In line with the 2013 WHO guidelines, there was a strong legal mandate for nursing education accreditation as compared to the global average of 50%. Accreditation levels were low in the programs that produce the majority of the nurses in this region and were higher in public programs than non-public programs. WHO guidelines for transparency and routine review were met more so than standards-based and independent accreditation processes. The new global strategy, Workforce 2030, has renewed the focus on accreditation and provides an opportunity to strengthen pre-service accreditation and ensure the production of a qualified and relevant nursing workforce.


Pain Experiences of Children and Adolescents With Osteogenesis Imperfecta: An Integrative Review.
Pain is a commonly experienced symptom for children and adolescents diagnosed with osteogenesis imperfecta (OI). The purpose of this integrative review was to describe the pain experience of children and adolescents with OI as well as critically appraise the content and methods of studies assessing OI pain. Five electronic bibliographic databases were searched. Published quantitative, qualitative, and/or mixed-method studies assessing pain in children and adolescents with OI were included and appraised. Constant comparison of the extracted data was used to synthesize themes. A total of 783 titles were identified, and 19 studies that met the inclusion criteria were included in this review. Study appraisal scores ranged from 25.0% to 83.3% using the Quality Assessment Tool. The majority of studies included assessed pain as a secondary outcome (63%) and less than half used moderately established or well-established tools (42%). Two themes were uncovered: "Pain is Present and Problematic" and "Issues with Pain Assessment." Key findings under each theme include: (1) the negative impacts of pain and the substandard use of pain management strategies; and (2) the lack of multidimensional and consistent pain assessments, as well as difficulties in assessing pain in younger children. Research on OI has focused very little on pain experience in children and adolescents, and there is no standard method of assessing pain. To better describe the pain experience of these patients, future research should focus on better characterizing OI pain with the use of age-appropriate valid, reliable, and multidimensional pain assessment tools.


Endometrial gene expression profile of pregnant sows with extreme phenotypes for reproductive efficiency.
Prolificacy can directly impact porcine profitability, but large genetic variation and low heritability have been found regarding litter size among porcine breeds. To identify key differences in gene expression associated to swine reproductive efficiency, we performed a transcriptome analysis of sows' endometrium from an Iberian x Meishan F2 population at day 30-32 of gestation, classified according to their estimated breeding value (EBV) as high (H, EBV > 0) and low (L, EBV < 0) prolificacy phenotypes. For each sample, mRNA and small RNA libraries were RNA-sequenced, identifying 141 genes and 10 miRNAs differentially expressed between H and L groups. We selected four miRNAs based on their role in reproduction, and five genes displaying the highest differences and a positive mapping into known reproductive QTLs for RT-qPCR validation on the whole extreme population. Significant differences were validated for genes: PTGS2 (p = 0.03; H/L ratio = 3.50), PTHLH (p = 0.03; H/L ratio = 3.69), MMP8 (p = 0.01; H/L ratio =4.41) and SCNN1G (p = 0.04; H/L ratio = 3.42). Although selected miRNAs showed similar expression levels between H and L groups, significant correlation was found between the expression level of ssc-miR-133a (p < 0.01) and ssc-miR-92a (p < 0.01) and validated genes. These results provide a better understanding of the genetic architecture of prolificacy-related traits and embryo implantation failure in pigs.


Coastal Water Quality Modelling Using E. coli, Meteorological Parameters and Machine Learning Algorithms.
In this study, machine learning models were implemented to predict the classification of coastal waters in the region of Eastern Macedonia and Thrace (EMT) concerning Escherichia coli (E. coli) concentration and weather variables in the framework of the Directive 2006/7/EC. Six sampling stations of EMT, located on beaches of the regional units of Kavala, Xanthi, Rhodopi, Evros, Thasos and Samothraki, were selected. All 1039 samples were collected from May to September within a 14-year follow-up period (2009-2021). The weather parameters were acquired from nearby meteorological stations. The samples were analysed according to the ISO 9308-1 for the detection and the enumeration of E. coli. The vast majority of the samples fall into category 1 (Excellent), which is a mark of the high quality of the coastal waters of EMT. The experimental results disclose, additionally, that two-class classifiers, namely Decision Forest, Decision Jungle and Boosted Decision Tree, achieved high Accuracy scores over 99%. In addition, comparing our performance metrics with those of other researchers, diversity is observed in using algorithms for water quality prediction, with algorithms such as Decision Tree, Artificial Neural Networks and Bayesian Belief Networks demonstrating satisfactory results. Machine learning approaches can provide critical information about the dynamic of E. coli contamination and, concurrently, consider the meteorological parameters for coastal waters classification.


Association between osteonecrosis of the jaws and chronic high-dosage intravenous bisphosphonates therapy.
Bisphosphonates (BPs) are used to inhibit bone resorption. Recently, they have been used in cancer patients to prevent bone loss due to bone metastasis. Fourteen consecutive patients, undergoing BPs monthly IV infusion due to neoplastic bone diseases, were diagnosed with osteonecrosis of the jaws. None of the patients had been previously undergoing radiotherapy of the head and neck region. Eight patients showed maxillary involvement, and nine patients had had a recent tooth extraction in the osteonecrosis areas. Biopsies and surgical debridment were performed. Histologically, none of the patients showed signs of bone metastasis. As high-dosage long-term BP therapy appears to be associated with osteonecrosis of the jaws, dental practitioners should exercise caution in the treatment of such patients.


Effects of diethylcarbamazine and cromolyn sodium on hypoxic pulmonary vasoconstriction in dogs.
Evidence has recently been accumulated that leukotrienes might be involved in the still unknown biochemical mechanism of hypoxic pulmonary vasoconstriction. We therefore investigated the effects of i.v. cromolyn sodium, which prevents the release of leukotrienes from mast cells by a membrane stabilizing effect, and of i.v. diethylcarbamazine citrate (DEC), a leukotriene synthesis inhibitor, in 13 dogs challenged with the inhalation of 10% O2 in nitrogen (FIO2 0.1) during 10 min. The dogs were anaesthetized with pentobarbital, paralysed with pancuronium, ventilated with a FIO2 of 0.4 and equipped with catheters for the purpose of pulmonary and systemic vascular pressure measurements and thermodilution cardiac output determinations. Thirty minute infusions of DEC at respectively 100 mg, 400 mg, 2 g, 5 g, 10 g and 15 g (one dosage per dog) did not alter the hypoxic pulmonary pressor response. Dosages of 10 g and 15 g DEC were associated with systemic hypotension, and one additional dog given 20 g died in refractory shock. A continuous infusion of cromolyn sodium inhibited hypoxic pulmonary vasoconstriction, partially at 3 and 4.5 mg X kg-1 X min-1 (2 dogs) and completely at 6 mg X kg-1 X min-1 (3 dogs). A lower dosage of 1 mg X kg-1 X min-1 cromolyn sodium (one dog) had no circulatory effect. These results do not support the hypothesis that hypoxic pulmonary vasoconstriction is mediated by vasoconstricting leukotrienes in the dog. The mechanisms accounting for the inhibition of the pulmonary hypoxic pressor response by cromolyn sodium are uncertain.


A strong reconstruction option for tissue loss on hand and wrist due to firearm injury in the Syrian war: Reverse posterior interosseous flap.
All of the injuries were the open injuries with bone or tendon structures in the hand and wrist region as a result of the firearm injury (FI) in the Syria. In the study, we assessed the outcomes of the posterior interosseous flap (PIF) on hand and wrist that we used for the Syrian injured people including civilians and soldiers in this War. PIF was applied to 77 patients who composed of 43 female and 34 male that all patients were evaluated for tissue loss resulting from gunshot wounds and injured in the War between 2014 and 2020 years with tissue loss in hand and wrist as a result of FI. The flap survival rate was 100% for all the patients. The dimensions of flaps ranged from 4.1 cm × 2.2 cm to 9cm × 5.4 cm with 0.51 ± 0.12 cm thickness. The mean pedicle length was 6.33 ± 1.08 cm. The surgery for PIF took 68.8 ± 22.1 minutes, while blood loss was 60 ± 24 mL. We observed no palsy conditions including the posterior interosseous nerve. The donor sites were treated by primary intention in the patients. We found the superiority of PIF with the postoperative follow-up comfort, ease of fracture healing, easy and fast, easy-to-apply method and no second additional session requirement in FI patients. We did not detect flap necrosis in any patient or observe a flap-related complication. As a result of the present study, it strongly supports the thesis that PIF is the best option in these cases.


Clinical profile of patients presenting with breast cancer in Nepal.
Breast cancer is the second most common cancer in women in Nepal. Even though the evaluation and treatment of patients is done as per western guidelines, there are considerable variations in risk factors, presenting stage and prognostic factors such as receptor status. To evaluate the clinical profile of patients presenting with breast cancer in Nepal. The study was conducted at Department of Radiotherapy and Oncology, Bir Hospital and Department of Radiation Oncology, BP Koirala Memorial Cancer Hospital, Bharatpur from 16th July 2007 to 15th June 2008 for a period of one year and 114 patients were enrolled. Detailed history, clinical examination and necessary investigations performed. Histological features including receptor status were recorded. Tumor Node Metastasis (TNM) staging system was as per American Joint Committee on Cancer (AJCC), fifth edition. Data was collected in preformed case report form and was managed using SPSS version 13. The incidence was high (34.2%) among perimenopausal women age ranging from 41 to 50. The majority of women presented with lump (98.2%) and others with pain (21.9%), nipple retraction (16.7%), ulceration (7.9%), discharge (7%), or symptoms of metastasis (6.1%). Regarding receptor status, the majority (64.0%) were Estrogen receptor (ER) and Progesterone receptor (PR) negative with 21.9 percent. ER+PR+, Younger women were more likely to be both ER and PR negative. Where available, Her- 2 immunohistochemistry showed that 45.0 % of post menopausal women were Her-2 neative, compared to 64.0 % of premenopausal women. Incidence of Triple negative disease was 41.3 %. The most common stage at presentation was stage III (26.3%). Majority of patients were perimenopausal, presenting with locally advanced disease (Stage III and Stage II) and with average tumor size two to five cm and were hormonal receptor negative. These findings are similar to other South Asian population but is inverse than profile reported in Western populations.


Correlation of quantitative light-induced fluorescence and optical coherence tomography applied for detection and quantification of early dental caries.
Fluorescence loss in enamel following demineralization has been correlated with the amount of mineral lost during the demineralization. The correlation between fluorescence loss measured by quantitative light-induced fluorescence (QLF) and the reflectivity loss measured by a versatile en face optical coherence tomography (OCT) system was investigated in a demineralization process to produce artificial dental caries. We used an OCT system that can collect A-scans (reflectivity versus depth), B-scans (longitudinal images), and C-scans (en face images). The power to the sample was 250 microW, the wavelength lambda = 850 nm, and the depth resolution in air 16 microm. A-scans, which show the profile of the reflectivity versus the depth of penetration into the tooth tissue, were used for quantitative analysis of the reflectivity loss. The results have shown that both the fluorescence radiance and reflectivity of the enamel decrease with increasing de- mineralization time. A linear correlation was observed between the percentage of fluorescence loss measured by QLF and the percentage of reflectivity loss measured by OCT. It was concluded that the decrease in reflectivity of the enamel during demineralization, measured by OCT, could be related to the amount of mineral lost during the de- mineralization process.


Framework to Advance Oncology-Related Telehealth.
As telehealth is increasingly used across the clinical care spectrum to provide patient-centered care, it is important to have robust measures to assess its impact on patient outcomes and care processes. The National Quality Forum (NQF) developed a Telehealth Framework to organize measures and inform target areas for measure development that includes the following four domains: access to care, financial impact or cost, experience, and effectiveness. Our goal is to identify and categorize within the NQF domains currently existing measures of telehealth applicable to oncology to detect priority areas for future research and measure development. We reviewed telehealth-related measures applied to oncology care reported in systematic reviews and identified NQF-endorsed quality measures related to oncology care potentially amenable to telehealth. We organized identified measures by the NQF domains to inform suggestions for advancing the care of patients with cancer through telehealth. We identified 12 systematic reviews representing 183 studies reporting telehealth-related oncology research. Most studied outcomes related to diagnosis and treatment or user experience and symptom monitoring. Clinical effectiveness measures were most frequently reported (38%), and most were psychosocial. Patient, family, and/or caregiver experience was the next most frequently reported measure. There were only a few other cancer-related clinical effectiveness measures (eg, morbidity). Most NQF-endorsed oncology measures amenable to telehealth applied to the domains of access to care and effectiveness, with a lack of measures informing financial impact or cost and experience. Overall, there has been a lack of quality measures to assess use of telehealth for the care of oncology patients. Future work should focus on developing measures within each of the NQF-identified domains, with special attention to the financial impact or cost domain.


Enabling Analysis of Big, Thick, Long, and Wide Data: Data Management for the Analysis of a Large Longitudinal and Cross-National Narrative Data Set.
Distinctive longitudinal narrative data, collected during a critical 18-year period in the history of the HIV epidemic, offer a unique opportunity to examine how young Africans are making sense of evolving developments in HIV prevention and treatment. More than 200,000 young people from across sub-Saharan Africa took part in HIV-themed scriptwriting contests held at eight discrete time points between 1997 and 2014, creating more than 75,000 narratives. This article describes the data reduction and management strategies developed for our cross-national and longitudinal study of these qualitative data. The study aims to inform HIV communication practice by identifying cultural meanings and contextual factors that inform sexual behaviors and social practices, and also to help increase understanding of processes of sociocultural change. We describe our sampling strategies and our triangulating methodologies, combining in-depth narrative analysis, thematic qualitative analysis, and quantitative analysis, which are designed to enable systematic comparison without sacrificing ethnographic richness.


Responding to summer emergencies.
Summer's arrival ushers in health hazards ranging from bee stings to lightning strikes. This article discusses preventive measures and provides first aid and ongoing care instructions for common summertime emergencies.


Direct measurement of transition frequencies in isolated pHe+ atoms, and new CPT-violation limits on the antiproton charge and mass.
A radio frequency quadrupole decelerator and achromatic momentum analyzer were used to decelerate antiprotons and produce p4He+ and p3He+ atoms in ultra-low-density targets, where collision-induced shifts of the atomic transition frequencies were negligible. The frequencies at near-vacuo conditions were measured by laser spectroscopy to fractional precisions of (6-19) x 10(-8). By comparing these with QED calculations and the antiproton cyclotron frequency, we set a new limit of 1 x 10(-8) on possible differences between the antiproton and proton charges and masses.


Association of HOTAIR expression with PI3K/Akt pathway activation in adenocarcinoma of esophagogastric junction.
Although the Hox transcript antisense intergenic RNA (HOTAIR), a vital long non-coding RNA, is known to participate in the development and progression of a wide range of carcinomas, there are still no published reports regarding its expression in adenocarcinoma of esophagogastric junction (AEJ). The aims of this study were to investigate the expression of HOTAIR, and to analyze the association of its expression with PI3K/Akt pathway activation in clinical AEJ patients. Nine normal epithelial tissues and 41 samples of AEJ were studied comparably. The expression of HOTAIR was detected by real-time PCR according to the different tumor grades in these AEJ tissues. Western blot was performed to reveal the Ser473-phosphorylated Akt and total Akt levels. Results: HOTAIR was found to be up-regulated in higher grades of AEJ tissues compared to low grades and/or noncancerous tissues. pAkt expression was also found to be up-regulated in tissues of higher tumor stages. We found that the overexpression of HOTAIR finely correlated with elevated Ser473-phosphorylated Akt levels. Conclusion: Upregulated HOTAIR was associated with abnormal activated PI3K/Akt pathway, which might serve as a promising therapeutic strategy for AEJ treatment.


Studies of fibronectin-binding proteins of Streptococcus equi.
Streptococcus equi subsp. equi is the causative agent of strangles, a disease of the upper respiratory tract in horses. The initiation of S. equi subsp. equi infection is likely to involve cell surface-anchored molecules mediating bacterial adhesion to the epithelium of the host. The present study describes the cloning and characterization of FNEB, a fibronectin-binding protein with cell wall-anchoring motifs. FNEB can thus be predicted as cell surface located, contrary to the two previously characterized fibronectin-binding proteins in S. equi subsp. equi, FNE and SFS. Assays of antibody titers in horses and in experimentally infected mice indicate that the protein is immunogenic and expressed in vivo during S. equi subsp. equi infection. Using Western ligand blotting, it was shown that FNEB binds to the N-terminal 29-kDa fragment of fibronectin, while SFS and FNE both bind to the adjacent 40-kDa fragment. S. equi subsp. equi is known to bind fibronectin to a much lower degree than the closely related S. equi subsp. zooepidemicus, but the binding is primarily directed to the 29-kDa fragment. Inhibition studies using S. equi subsp. equi cells indicate that FNEB mediates cellular binding to fibronectin in this species.


Prognostic value of tripartite motif containing 29 expression in patients with gastric cancer following surgical resection.
Tripartite motif containing 29 (TRIM29) dysregulation serves an important function in the progression of numerous types of cancer, but its function in the prognosis of patients with gastric cancer remains unknown. The present study assessed the prognostic value of TRIM29 in patients with gastric cancer following surgical resection. A total of 243 fresh gastric adenocarcinoma and adjacent normal tissues were continuously retrieved from patients who underwent curative surgery for gastric cancer at the Cancer Hospital of Henan Province (Zhengzhou, China) between January 2005 and December 2011. The reverse transcription-quantitative polymerase chain reaction was performed to assess TRIM29 expression. The association between TRIM29 expression and clinicopathological features and prognosis was subsequently evaluated. The results of the present study revealed that the expression of TRIM29 was increased in the gastric cancer tissues compared with the normal adjacent tissues, and that upregulated expression of TRIM29 was associated with tumor cell differentiation, tumor stage, lymph node metastasis, and tumor-node-metastasis (TNM) stage. In the training and validation data, high TRIM29 expression was associated with poor overall survival in patients with gastric cancer. Furthermore, multivariate analysis identified that TRIM29 expression was an independent prognostic factor for overall survival, in addition to TNM stage and Lauren classification. Combining TRIM29 expression with the TNM staging system generated a novel predictive model that exhibited improved prognostic accuracy for overall survival in patients with gastric cancer. The present study revealed that TRIM29 was an independent adverse prognostic factor in patients with gastric cancer. Incorporating TRIM29 expression level into the TNM staging system may improve risk stratification and render prognosis more accurate in patients with gastric cancer.


A case report of an atypical presentation of pyogenic iliopsoas abscess.
Iliopsoas abscess is a collection of pus in the iliopsoas muscle compartment. It can be primary or secondary in origin. Primary iliopsoas abscess occurs as a result of hematogenous or lymphatic seeding from a distant site. This is commonly associated with a chronic immunocompromised state and tends to occur in children and young adults. Secondary iliopsoas abscess occurs as a result of the direct spread of infection to the psoas muscle from an adjacent structure, and this may be associated with trauma and instrumentation in the inguinal region, lumbar spine, or hip region. The incidence of iliopsoas abscess is rare and often the diagnosis is delayed because of non-specific presenting symptoms. We describe a patient with iliopsoas abscess who presented to the Emergency Department at X Hospital on three separate occasions with non-specific symptoms of thigh pain and fever before finally being admitted for treatment. This case illustrates how the diagnosis can be delayed due to its atypical presentation. Hence, highlighting the need for clinicians to have a high index of clinical suspicion for iliopsoas abscess in patients presenting with thigh pain and fever. The classic triad of fever, flank pain, and hip movement limitation is presented in only 30% of patients with iliopsoas abscess. Clinicians should consider iliopsoas abscess as a differential diagnosis in patients presenting with fever and thigh pain. The rare condition with the varied clinical presentation means that cross-sectional imaging should be considered early to reduce the risk of fulminant sepsis.


Compartment analysis of T cell receptor gamma--and immunoglobulin V(H) rearrangements by microdissection in patients with malt lymphoma and chronic gastritis with lymphatic hyperplasia.
The interpretation of clonality within H. pylori-associated gastritis and low-grade MALT lymphoma remains controversial. Due to the observation of MALT lymphoma regression after H. pylori eradication, new definitions concerning the border between benign reactive lesions and malignant gastric lymphoma are needed. Gene rearrangements for immunoglobulin heavy-chain in low-grade MALT lymphoma (N= 12) and H. pylori-associated chronic gastritis with lymphatic hyperplasia (N= 13) were analyzed by microdissection and polymerase chain reaction. Furthermore, T cell receptor-gamma chain rearrangements were analyzed by gene scan analysis. In 11 of 12 cases with initial low-grade MALT lymphoma, intraepithelial and subepithelial B cell rearrangements showed a restricted usage of the immunoglobulin heavy-chain 3. In H. pylori-associated chronic gastritis, the intraepithelial B cell compartment showed an oligoclonal the immunoglobulin heavy-chain rearrangement pattern with a predominance of VH3. The subepithelial compartment did not show any restrictive immunoglobulin heavy-chain gene usage. Additionally a mono- to oligoclonal rearrangement pattern of the T cell receptor-y chain was observed in low-grade MALT lymphoma, whereas an oligoclonal pattem was observed in chronic gastritis. Our data provide evidence that low-grade MALT lymphoma may start within the epithelium and subsequently infiltrate the subepithelial compartment. The observation of a mono- to oligoclonal TCR-gamma rearrangement suggests that an antigen selecting process also takes place within reactive T cells. Combining TCR-gamma gene scan analysis with IgH chain rearrangement analysis might help in discriminating between chronic gastritis and initial MALT lymphoma in questionable cases.


Cost-effectiveness of adding novel or group 5 interventions to a background regimen for the treatment of multidrug-resistant tuberculosis in Germany.
Treatment of multidrug-resistant tuberculosis (MDR-TB) is complex, lengthy, and involves a minimum of four drugs termed a background regimen (BR), that have not previously been prescribed or that have proven susceptible to patient sputum culture isolates. In recent years, promising new treatment options have emerged as add-on therapies to a BR. The aim of this study was to evaluate the long-term costs and effectiveness of adding the novel or group 5 interventions bedaquiline, delamanid, and linezolid to a background regimen (BR) of drugs for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis (MDR-TB), within their marketing authorisations, from a German healthcare cost-effectiveness perspective. A cohort-based Markov model was developed to simulate the incremental cost-effectiveness ratio of bedaquiline plus BR, delamanid plus BR, or linezolid plus BR versus BR alone in the treatment of MDR-TB, over a 10-year time horizon. Effectiveness of treatment was evaluated in Quality-Adjusted Life-Years (QALYs) and Life-Years Gained (LYG), using inputs from clinical trials for bedaquiline and delamanid and from a German observational study for linezolid. Cost data were obtained from German Drug Directory costs (€/2015), published literature, and expert opinion. A 3% yearly discount rate was applied. Probabilistic and deterministic sensitivity analyses were conducted. The total discounted costs per-patient were €85,575 for bedaquiline plus BR, €81,079 for delamanid plus BR, and €80,460 for linezolid plus BR, compared with a cost of €60,962 for BR alone. The total discounted QALYs per-patient were 5.95 for bedaquiline plus BR, 5.36 for delamanid plus BR, and 3.91 for linezolid plus BR, compared with 3.68 for BR alone. All interventions were therefore associated with higher QALYs and higher costs than BR alone, with incremental costs per QALY gained of €22,238 for bedaquiline, €38,703 for delamanid, and €87,484 for linezolid, versus BR alone. In a fully incremental analysis, bedaquiline plus BR was the most cost-effective treatment option at thresholds greater than €22,000 per QALY gained. In probabilistic analyses, the probability that bedaquiline plus BR was the most cost-effective treatment strategy at a willingness-to-pay threshold of €30,000 was 54.5%, compared with 22.9% for BR alone, 18.2% for delamanid plus BR, and 4.4% for linezolid. In Germany, the addition of bedaquiline, delamanid, or linezolid to a BR would result in QALY gains over BR alone. Based on this analysis, bedaquiline is likely to be the most cost-effective intervention for the treatment of MDR-TB, when added to a BR regimen at thresholds greater than €22,000 per QALY.


Histology of testicular biopsies taken at operation for bilateral maldescended testes in relation to fertility in adulthood.
A total of 91 boys underwent bilateral orchiopexy with testicular biopsy. The percentage of tubular transverse sections containing spermatogonia, the fertility index (FI) and the number of spermatogonia per tubular transverse section (S/T) were measured and expressed as a percentage of the minimum normal value (FI% and S/T%, respectively). The maximum and mean of the 2 FI% and S/T% values were noted for each patient. At follow-up, testicular volume was measured in 73 men; 71 of these gave a blood sample for FSH and 67 provided specimens of semen for analysis. The maximum and the mean FI% and S/T% values of the patients were positively correlated to maximal sperm density and to volume of pair of testes and negatively correlated to serum FSH. It seems reasonable to use these histological parameters as prognostic indices of fertility potential. In adulthood only 11 patients had sperm density greater than or equal to 20 million/ml, 37 had normal serum FSH and 29 had bilateral testicular volume greater than or equal to 15 ml. Patients with both testes originally placed in the superficial inguinal pouch at surgical exploration had a higher maximal sperm density than the rest of the study group.


Assessment of renal function and prevalence of acute kidney injury following coronary artery bypass graft surgery and associated risk factors: A retrospective cohort study at a tertiary care hospital in Islamabad, Pakistan.
Acute kidney injury (AKI) is a sudden decline in renal function after cardiac surgery. It is characterized by a significant reduction in glomerular filtration rate, alterations in serum creatinine (S.Cr) levels, and urine output. This study aimed to retrospectively analyze a cohort of 704 patients selected using stringent inclusion and exclusion criteria. AKI was defined by an increase of 0.3 mg/dL in S.Cr levels compared to baseline. Data were collected from the hospital and analyzed using SPSS 16.0. Data analysis revealed that 22% (n = 155) of the patients developed AKI on the second post-operative day, accompanied by a substantial increase in S.Cr levels (from 1.064 ± 0.2504 to 1.255 ± 0.2673, P < .000). Age and cardiopulmonary bypass duration were identified as risk factors along with ejection fraction and days of hospital stay, contributing to the development of AKI. Early renal replacement therapy can be planned when the diagnosis of AKI is established early after surgery.


Primary Thyroid NUT Carcinoma With High PD-L1 Expression and Novel Massive IGKV Gene Fusions: A Case Report With Treatment Implications and Literature Review.
Nuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive undifferentiated carcinoma that typically arises from midline supradiaphragmatic structures. It is uniquely driven by a NUT gene rearrangement on chromosome 15q14. Few thyroid NCs have been reported and there are no established treatment guidelines for NUT carcinoma. Ultrasound-guided fine needle aspiration smear was performed for the preoperative diagnosis of thyroid lesions. Cytopathology, histology, and immunochemical staining all indicated NC. Fluorescence in situ hybridization (FISH), qRT-PCR, and next-generation sequencing (NGS) were used to analyze the genetic characteristics of NC. We describe a rare case of thyrogenic NC in a 38-year-old male with cytological, histological, immunohistochemical, and genetic features. Cytological smears and histopathological specimens showed typical features of NC. Immunohistochemistry confirmed strong immunoreactivity with NUT, EMA, P63, TTF-1, and c-myc. CK19 was positive exclusively in sudden keratosis. No immunoreactivity was found for neuroendocrine markers. FISH was applied to isolate the NUT gene on chromosome 15q14. The NGS results revealed a BRD4-NUT gene fusion, which was further confirmed by RT-qPCR. Structural variation (SV) of NUTM1 occurred in the exon region, and the mutation site was 15q14. Moreover, BRD4 single-nucleotide variation (SNV) occurs in the 3' UTR at mutation site 19p13.12. The PD-L1 combined predictive score was over 30%. The patient received chemotherapy, followed by programmed cell death 1 (PD-1) inhibition with camrelizumab, and died 10 months after surgery. Thyroid NC is an extremely rare and fatal malignant tumor. It is necessary to consider NC when squamous differentiation is observed cytologically or histologically. NGS is an effective tool for obtaining the final diagnosis and obtaining a better understanding of tumor pathogenesis. A large number of IGKV gene fusions in addition to the BRD4-NUT fusion may play a role in the pathogenesis and immunotherapy response of NC. Immunotherapy for NC remains to be explored due to the rarity of this aggressive malignancy.


Two familial cases of Olmsted-like syndrome with a G573V mutation of the TRPV3 gene.
Olmsted syndrome (OS) is a rare disease, characterized by symmetrical, sharply defined, hyperkeratotic, mutilating plaques on the palms and soles, which are associated with periorificial keratotic plaques. Other clinical manifestations of OS include diffuse alopecia, leucokeratosis of the oral mucosa, onychodystrophy, hyperkeratotic linear streaks, follicular hyperkeratosis and constriction of the digits. A recent study identified de novo mutations in the gene for transient receptor potential vanilloid 3 (TRPV3), causing constitutive activation of the TRPV3 channel, as a cause of OS. We report familial inheritance of OS in a family from Mongolia, which was caused by a previously undescribed G573V point mutation in TRPV3. To date, mutations in the G573 residue of TRPV3 have been reported in seven cases of OS: G573S in five cases, and G573C and G573A mutations in one case each. We present a Mongolian familial case of G573V point mutation in TRPV3.


QGQS Granule in SHR Serum Metabonomics Study Based on Tools of UPLC-Q-TOF and Renin-Angiotensin-Aldosterone System Form Protein Profilin-1.
QGQS granule is effective for the therapeutic of hypertension in clinic. The aim of this research is to observe the antihypertension effect of QGQS granule on SHR and explain the mechanism of its lowering blood pressure. 30 SHR were selected as model group, captopril group, and QGQS group, 10 WKYr were used as control group, and RBP were measured on tail artery consciously. And all the serum sample analysis was carried out on UPLC-TOF-MS system to determine endogenous metabolites and to find the metabonomics pathways. Meanwhile, ELISA kits for the determination pharmacological indexes of PRA, AngI, AngII, and ALD were used for pathway confirmatory; WB for determination of profilin-1 protein expression was conducted for Ang II pathway analysis as well. It is demonstrated that QGQS granule has an excellent therapeutic effect on antihypertension, which exerts effect mainly on metabonomics pathway by regulating glycerophospholipid, sphingolipid, and arachidonic acid metabolism, and it could inhibit the overexpression of the profilin-1 protein. We can come to a conclusion that RAAS should be responsible mainly for the metabonomics pathway of QGQS granule on antihypertension, and it plays a very important role in protein of profilin-1 inhibition.


Barriers to provision of dental care in long-term care facilities: the confrontation with ageing and death.
The aim of the study was to reveal barriers to providing dental care for residents in long-term care (LTC) facilities. Participants were selected randomly from the dentist register in Berlin and Saxony, Germany. The sample consisted of 60 self-employed and 60 employed dentists, a further 60 dentists worked in their own dental practice but also part-time in an LTC facility. In semi-structured interviews a questionnaire with 36 statements concerning working conditions, administration and cost, insecurity concerning treatment decisions as well as confrontation with ageing and death was employed. Subsequently, the study participants were asked to rank the four dimensions concerning their impact on the decision against providing dental care in an LTC facility. The random sample was representative in age and gender for the dental register in Berlin and Saxony. Fifty-six per cent of the participants (63% of the men and 51% of the women; 52% of the self-employed, 60% of the employed and 56% of the consultant dentists) indicated unfavourable working conditions as biggest obstacle in providing dental care in an LTC-facility. Thirty-two per cent of participants rated administration and cost, 7% the insecurity in treatment decisions as major hindrance. Only 5% of the participants rated the confrontation with age and death as substantial barrier. There were no age and gender differences. Dentists in Berlin seemed more concerned about administration and cost of a consultancy activity and less secure in their therapy decisions than the colleagues from Saxony (p < 0.001). Dentists who work partly in LTC facilities were the least concerned about the confrontation with ageing and death (not significant), employed dentist showed the least secure in their treatment decisions (p > 0.001). It can be concluded that the awareness of infra-structural and financial aspects in providing dental care in LTC facilities should be raised with health politicians and that these aspects should be considered when inaugurating or re-structuring the consultancy services to LTC facilities. Further it would be desirable to establish more postgraduate training programmes to increase clinical and ethical competence in the area of gerodontology.


Comparison of success rates using video laryngoscopy versus direct laryngoscopy by residents during a simulated pediatric emergency.
Emergency airway situations are relatively rare events in pediatrics with most graduating residents having little exposure to intubate. Newer video technology offers the promise of reducing complications associated with intubation. This study proposes that video laryngoscopy (VL) should aid less skilled residents to intubate an infant mannequin with greater success and speed as compared with traditional direct laryngoscopy (DL). Pediatric (PED) and emergency medicine (EM) residents were randomized in a prospective controlled study. A standard respiratory failure scenario was conducted using SimBaby with an uncomplicated airway. Residents who inadvertently performed esophageal intubation were made aware as part of the scenario and allowed to reattempt until successful. Sixty-nine residents voluntarily participated, 49% EM and 51% PED. Seven subjects in the DL group required multiple attempts (21%), compared with 6 subjects in the VL group (17%) (P = 0.718). Median time to intubation was 30 seconds (95% confidence interval [CI], 19-41 seconds) for DL and 39 seconds (95% CI, 36-42 seconds) for VL (P = 0.111). Comparison of programs revealed a 77% PED success rate versus 85% EM success rate (P = 0.578) and median time to intubation of 38 seconds (95% CI, 31-45 seconds) for PED compared with 32 seconds (95% CI, 23-41 seconds) for EM residents (P = 0.316). In a subanalysis, subjects successful at first attempt revealed a 13-second median difference (DL, 23 seconds [95% CI, 18-28 seconds] vs. VL, 36 seconds [95% CI, 29-43 seconds; P = 0.01). In a simulated respiratory failure scenario involving residents, VL provided no additional success over DL with slightly longer time to intubation.


Multiple-family group treatment of outpatients with schizophrenia: impact on service utilization.
The impact of multiple-family group treatment (MFGT) on outpatient and inpatient mental health service utilization of 97 persons with schizophrenia was investigated. Participants were randomly assigned to standard care (n = 44) or standard care plus MFGT (n = 53). Service use for a year prior to randomization, the 2-year study period, and a 1-year follow-up were examined. Relative to standard care participants, the MFGT group had reduced community hospitalization during year 1 of the intervention and reduced state hospitalization at follow-up. During the intervention period, MFGT participants demonstrated a significant increase in outpatient utilization as a direct consequence of the intervention. However, when service use was summed across 3 years post-randomization, no group differences were observed. Results suggest that implementation of MFGT in a community mental health setting reduces inpatient service at specific time periods, without significantly increasing outpatient service utilization. These findings add to other outcomes from this study that demonstrate decreased psychiatric symptoms and caregiver distress.


Laboratory evaluation of a potential diesel fuel interference in the determination of polycyclic aromatic compounds on dermal samplers.
Road pavers are exposed to asphalt fumes through dermal contact, inhalation, or ingestion. These fumes contain polycyclic aromatic compounds (PACs), a class of compounds including polycyclic aromatic hydrocarbons (PAHs). The PAHs include compounds such as pyrene and benzo(a)pyrene and a large number of other compounds of known or suspected carcinogenicity. To estimate dermal deposition of asphalt fume particulate matter, polypropylene sampling patches can be worn on a worker's inside wrist. Diesel fuel used for cleaning can splash onto the dermal sampler. Exposed dermal patches were solvent extracted and PACs estimated in the extract using a modification of NIOSH Method 5800. The final solution was analyzed by high pressure liquid chromatography (HPLC) with a fluorescence detector using an excitation wavelength of 270 nanometers and an emission wavelength of 415 nanometers. The PACs were concentrated on a C-18 reverse phase guard column but not separated so that they could be measured expediently as a group. In this study we examined whether deposited diesel fuel interferes with the HPLC determination of PACs. We characterized the effect of diesel fuel contamination over broad ranges of both analyte and interferent. Two drops, or approximately 100 microL, of diesel fuel on the dermal samplers caused an overestimation of the concentration of polycyclic aromatic compounds (PACs). In the range of PACs determined in our field study (0 to 54 microg per sample), these errors could have exceeded 100%. Because 100 microL of deposited diesel fuel produced a clear visual "wetness," this observation can serve as one of the criteria for sample rejection. Sampling media must be examined carefully for visible contamination to prevent bias in the measurement of PACs deposited from asphalt fume.


Clinical and Radiographic Assessment of Three-Implant-Supported Fixed-Prosthesis Rehabilitation of the Edentulous Mandible: Immediate Versus Delayed Loading.
To evaluate and compare the clinical and radiographic outcomes of mandibular rehabilitation with fixed prostheses on three implants with immediate versus delayed loading. The sample comprised 21 patients who underwent treatment with immediate loading and 23 who received delayed loading. All had worn their prostheses for at least 18 months. Radiographic evaluation of bone loss was carried out in Adobe Photoshop CS5 by a single calibrated examiner using digitized panoramic radiographs. Clinical examination of the technical conditions of the prosthetic device assessed the condition of the acrylic resin base, dental occlusion, metal framework, presence of cover screws, screw fixation of the prosthesis and abutments, length of cantilever (effort) and resistance arms, presence of plaque on prosthetic abutments, and hygiene of the prosthesis. One implant failed in each group, resulting in a 95.23% treatment success rate with immediate loading and 95.65% with delayed loading (no statistically significant between-group difference). In the immediate-loading group, the mean bone loss was 1.96 ± 0.73 mm around central implants and 1.64 ± 0.84 mm at distal implants. In the delayed-loading group, the mean bone loss was 1.85 ± 0.67 mm around central implants and 1.70 ± 0.77 mm at distal implants. According to Student t test, there was no significant within-group difference in bone loss and no difference between the immediate-loading and delayed-loading groups. The only prosthesis-related complications that differed significantly between groups were "condition of the acrylic base," "occlusion," and "presence of right cover screw." There was no statistically significant association of lever arm ratio with peri-implant bone loss or bone loss on the mesial surfaces compared to the distal surfaces of the distal implants. The three-implant-supported fixed prosthesis protocol tested in this study proved to be a viable therapeutic strategy for mandibular edentulous patients with maxillary complete dentures, regardless of whether loading was immediate or delayed, with no difference in peri-implant bone loss.


Single-step Marker Switching in Schizosaccharomyces pombe Using a Lithium Acetate Transformation Protocol.
The ability to utilize different selectable markers for tagging or mutating multiple genes in Schizosaccharomyces pombe is hampered by the historical use of only two selectable markers, ura4+ and kanMX6; the latter conferring resistance to the antibiotic G418 (geneticin). More markers have been described recently, but introducing these into yeast cells often requires strain construction from scratch. To overcome this problem we and other groups have created transformation cassettes with flanking homologies to ura4+ and kanMX6 which enable an efficient and time-saving way to exchange markers in existing mutated or tagged fission yeast strains. Here, we present a protocol for single-step marker switching by lithium acetate transformation in fission yeast, Schizosaccharomyces pombe. In the following we describe how to swap the ura4+ marker to a kanMX6, natMX4, or hphMX4 marker, which provide resistance against the antibiotics G418, nourseothricin (clonNAT) or hygromycin B, respectively. We also detail how to exchange any of the MX markers for nutritional markers, such as arg3+, his3+, leu1+ and ura4+ .


Human infection patterns and heterogeneous exposure in river blindness.
Here we analyze patterns of human infection with Onchocerca volvulus (the cause of river blindness) in different continents and ecologies. In contrast with some geohelminths and schistosome parasites whose worm burdens typically exhibit a humped pattern with host age, patterns of O. volvulus infection vary markedly with locality. To test the hypothesis that such differences are partly due to heterogeneity in exposure to vector bites, we develop an age- and sex-structured model for intensity of infection, with parasite regulation within humans and vectors. The model is fitted to microfilarial data from savannah villages of northern Cameroon, coffee fincas of central Guatemala, and forest-dwelling communities of southern Venezuela that were recorded before introducing ivermectin treatment. Estimates of transmission and infection loads are compared with entomological and epidemiological field data. Host age- and sex-heterogeneous exposure largely explains locale-specific infection patterns in onchocerciasis (whereas acquired protective immunity has been invoked for other helminth infections). The basic reproductive number, R0, ranges from 5 to 8, which is slightly above estimates for other helminth parasites but well below previously presented values.


[Retinal vein occlusion. III. Arteriolar constriction].
The author assumes that the process of the adjustment of the disproportion between the arterial and the venous volume can be favourably influenced by a decrease in the offered arterial volume to the venous occluded blood path. This can be achieved by a narrowing of the input arteriole with the help of the method of arteriolar constriction using the argon laser. The author is of the opinion that the method of arteriolar constriction finds its application especially in the treatment of severe prognostically unfavourable forms of occlusion of the branch of the retinal vein with presence of extensive hemorrhages in the retina. In such severe forms of occlusion, the author recommends to apply the arteriolar constriction already in the early acute phase of the disease.


In vitro prediction of breast cancer therapy toxicity.
Understanding the basis of clinical radiosensitivity is a key goal of radiation research. In this study, we used the limiting dilution assay (LDA) to analyze in vitro radiosensitivity of cell lines from individuals with breast and other cancers, who had been treated with ionizing radiation, and who either had a non-radiosensitive (RS) radiation response or who were clinically RS. Lymphoblastoid cell lines (LCLs) were created from 29 cancer patients including 19 RS patients, 10 controls who had not developed severe normal tissue reactions, and 1 ataxia telangiectasia RS control cell line. The clinically RS patients had grade 3 or grade 4 reactions; one had a grade 2 reaction. All cells were exposed to graded doses of gamma-radiation in vitro and cell survival assessed via LDA. Cell survival was expressed on non-linear regression analysis-fitted survival curves and also as the surviving fraction at 2 Gray (Gy) (SF2). Our LDA analysis yielded two notable positive results. Firstly, it could distinguish control cells from cells from pooled breast cancer cases with severe reactions of all types (acute reactors, consequential late reactors and late reactors). Secondly, two radiosensitivity outliers were detected on the fitted curves, corresponding clinically to grade 3 and 4 late radiation reactions in breast and head and neck cancer cases respectively. The assay showed considerable cell survival heterogeneity. The LDA as used here may provide unique clinical utility in detecting potential RS breast cancer patients prior to radiotherapy (RT), a form of personalized medicine. The assay may be especially useful in situations where its results can be temporally available prior to therapy initiation (e.g., those patients not undergoing RT until some months after surgery, typically those having adjuvant chemotherapy prior to RT). Two LCLs from RS outliers could potentially yield insight into the cellular and/or genetic basis of radiosensitivity, for example by undertaking genomic analyses on these cell lines.


Ethical issues in pediatric life-threatening illness: dilemmas of consent, assent, and communication.
The treatment of life-threatening illnesses in childhood is replete with ethical issues and with clinical issues that have ethical implications. The central issues are those involved with a child's participation in the decision-making process and with communication of information about the illness and treatments to children. This article examines the questions of patient autonomy and of parental responsibility and prerogative in the context of pediatric oncology. Included in this examination of the ethical dimensions of pediatric life-threatening illness is a discussion of the many related aspects involved, including medical, cultural, psychosocial, legal, and developmental. A multidimensional approach that considers the ways in which these multiple aspects interact with one another, and which focuses on establishing a strong working alliance between the health care team and the pediatric patient's family, can help to avoid or resolve potential ethical and clinical conflicts.


Purification and properties of an iron-sulfur and FAD-containing 4-hydroxybutyryl-CoA dehydratase/vinylacetyl-CoA delta 3-delta 2-isomerase from Clostridium aminobutyricum.
4-Hydroxybutyryl-CoA dehydratase, the key enzyme in the metabolism of gamma-aminobutyrate in Clostridium aminobutyricum, represents approximately 15-25% of the soluble protein. The enzyme was purified to homogeneity under anaerobic conditions to a specific activity of 209 nkat mg-1. The dehydratase catalyses the reversible conversion of 4-hydroxybutyryl-CoA (Km = 50 microM) to crotonyl-CoA and possesses a probably intrinsic vinylacetyl-CoA delta 3-delta 2-isomerase with a specific activity of 223 nkat mg-1. The equilibrium of the reversible dehydration was determined from both sides as K = [crotonyl-CoA]/[4-hydroxybutyryl-CoA] = 4.2 +/- 0.3. Cyclopropylcarboxyl-CoA was not converted to crotonyl-CoA. The native enzyme has an apparent molecular mass of 232 kDa and is composed of four apparently identical subunits (molecular mass = 56 kDa), indicating a homotetrameric structure. Under anaerobic conditions the active enzyme revealed a brown colour and contained 2 +/- 0.2 mol FAD (64 +/- 5% oxidized), 16 +/- 0.8 mol Fe and 14.4 +/- 1.2 mol inorganic sulfur, which probably form iron-sulfur clusters. Exposure to air resulted initially in a slight activation followed by irreversible inactivation. Concomitantly the vinylacetyl-CoA delta-isomerase activity was lost and the colour of the enzyme changed to yellow. Reduction by sodium dithionite yielded inactive enzyme which could be completely reactivated by oxidation with potassium hexacyanoferrate(III). The data indicate that the active enzyme contains oxidized FAD despite its sensitivity towards oxygen. During the dehydration a non activated C-H bond at C-3 of 4-hydroxybutyryl-CoA has to be cleaved. A putative mechanism for 4-hydroxybutyryl-CoA dehydratase is proposed in which this cleavage is achieved by a FAD-dependent oxidation of 4-hydroxybutyryl-CoA to 4-hydroxycrotonyl-CoA. In a second step the hydroxyl group is substituted by a hydride derived from the now reduced FAD in an SN2' reaction leading to vinylacetyl-CoA. Finally isomerisation yields crotonyl-CoA. 4-Hydroxybutyryl-CoA dehydratase is quite distinct from 3-hydroxyacyl-CoA dehydratase (crotonase) and 2-hydroxyacyl-CoA dehydratases. Contrary to the latter enzyme [e.g. (R)-lactyl-CoA dehydratase and (R)-2-hydroxyglutaryl-CoA dehydratase] which are composed of three different subunits and similarly catalyse the cleavage of a non activated C-H bond at C-3, 4-hydroxybutyryl-CoA dehydratase does not require ATP, MgCl2 and Ti(III)citrate for activity. Furthermore 4-hydroxybutyryl-CoA dehydratase is not inactivated by oxidants such as 5 mM 4-nitrophenol, 5 mM chloramphenicol and 5 mM hydroxylamine.


Carotid endarterectomy.
Carotid endarterectomy is a procedure that has withstood the test of time and scientific scrutiny to remain an important technique for the surgical prevention of stroke. Several aspects of this operation are critical for success, i.e., improving on the natural history of carotid artery stenosis. The procedure is described in a stepwise manner, with emphasis on key steps for avoiding thrombotic or embolic complications.


Association between Helicobacter pylori Infection and Cerebral Small Vessel Disease.
Small vessel disease is an important cause of cerebrovascular diseases and cognitive impairment in the elderly. There have been conflicting results regarding the relationship between Helicobacter pylori infection and ischemic stroke. This study aimed to examine the association between H. pylori infection and cerebral small vessel disease. The study included 1,117 patients who underwent brain magnetic resonance imaging and H. pylori identification between 2005 and 2013 at Health Promotion Center, Seoul National University Hospital. Multivariable logistic regression analysis was used to assess the association between H. pylori infection and small vessel disease with adjustment for age, sex, hypertension, diabetes mellitus, dyslipidemia, body mass index, smoking status, problem drinking, and antiplatelet use. The adjusted odds ratios (aORs) for the association between H. pylori infection and silent brain infarction and cerebral microbleeds were 1.03 (95% confidence interval [CI], 0.66-1.61) and 0.70 (95% CI, 0.38-1.28), respectively. The aORs for silent brain infarction and cerebral microbleeds were 0.81 (95% CI, 0.44-1.44) and 0.59 (95% CI, 0.30-1.18) in patients aged <65 years and 1.59 (95% CI, 0.78-3.22) and 1.89 (95% CI, 0.38-9.33) in those aged >65 years, respectively. Moreover, the aORs for silent brain infarction and cerebral microbleeds were 0.96 (95% CI, 0.54-1.71) and 0.74 (95% CI, 0.33-1.69) in H. pylori-infected patients without atrophic gastritis and 0.89 (95% CI, 0.48-1.62) and 0.99 (95% CI, 0.43-2.27) in those with atrophic gastritis, respectively. No association between H. pylori infection and small vessel disease was observed. H. pylori-induced inflammation may not be a risk factor for microcirculatory damage in the brain.


Chitosan Glutamate-Coated Niosomes: A Proposal for Nose-to-Brain Delivery.
The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS), while size and morphology were also studied by atomic force microscopy (AFM). Bilayer properties and mucoadhesive behavior were investigated by fluorescence studies and DLS analyses, respectively. Changes in vesicle size and ζ-potential values were shown after addition of chitosan glutamate to niosomes, and when in contact with mucin solution. In particular, interactions with mucin were observed in both drug free and pentamidine loaded niosomes regardless of the presence of the coating. The characteristics of the proposed systems, such as pentamidine entrapment and mucin interaction, show promising results to deliver pentamidine or other possible drugs to the brain via nasal administration.


Disparate statin prescribing following hospital discharge for stroke or transient ischemic attack: Findings from COMPASS.
Published guidelines recommend high-intensity statins following an ischemic stroke or transient ischemic attack (TIA). The authors examined the potential for disparate patterns of statin prescribing in a cluster randomized trial of transitional care following acute stroke or TIA. Medications taken before hospitalization and statins prescribed at discharge among stroke and TIA patients at 27 participating hospitals were examined. Any statin and intensive statin prescribed at discharge were compared by age (<65, 65-75, >75 years), racial category (White vs. Black), sex (male vs. female), and rurality (urban vs. non-urban) using logistic mixed models. Among 3211 patients (mean age 67 years; 47% female; 29% Black), 90% and 55%, respectively, were prescribed any statin or intensive statin therapy at discharge. White (vs. Black) patients (0.71, 0.51-0.98) less commonly received any statin prescription, while stroke (vs. TIA) patients (1.90, 1.38-2.62) and those residing in urban areas (1.66, 1.07-2.55) more commonly received any statin prescription. Among those prescribed a statin, only 42% of White and 51% of Black patients >75 years. were prescribed an intensive statin; the OR for intensive statin prescribing was 0.44 for patients >75 years and was similar in a subgroup not on a statin previously. Following stroke or TIA, statin prescribing remains lower in White patients, in those with TIA, and in those in non-urban areas. Intensive statin prescribing remains limited, particularly in patients >75 years. These data may inform efforts to improve guideline concordant prescribing for post-stroke patients.


RETROSPECTIVE STUDY OF EVALUATION OF PATIENTS WITH ST ELEVATION MYOCARDIAL INFARCTION AND INTACT CORONARY ARTERIES. EVALUATION OF TREATMENT APPROACHES; OUTCOME AND PROGNOSIS.
Myocardial infarction with normal coronary arteries is a well known pathology. It may or may not be associated with left ventricle wall motion abnormalities. Data was reviewed retrospectively for patients with ST elevation myocardial infarction who underwent cardiac catheterization. From the total number of patients evaluated 10.3% (17) patients had Myocardial Infarction with normal coronary arteries. Females were more likely to present with MINCA then males. Coronary flow was normal in 11 from 17 patients with MINCA. In 6 cases slow coronary flow was detected. Myocardial segments with slow coronary flow did not correlate with wall motion abnormalities detected by echocardiography and ventriculography. In 8 females, Takotsubo cardiomyopathy was suspected. Data were analyzed retrospectively and we were not able to obtain full coagulation panel for all evaluated patients. Myocardial biopsy was not performed in either of patients under observation. Spontaneous thrombolysis was suspected in number of cases. Most angiography investigations were done within three hours after symptoms start. Prognosis of patients with ST-elevation Myocardial Infarction (STEMI) and normal coronary arteries was good. No fatal or non-fatal complications during hospitalization. During 6 month, follow up one male patient was re-hospitalized due to Acute Coronary Syndrome (ACS) in 5.5 month after initial event. Repeated coronary angiography did not reveal the abnormalities. Our study is first attempt for collecting retrospectively different data for patients with STEMI and NCA. Important is that no correlation was found between wall motion abnormalities and coronary flow limitations (if present). Compared to other studies we found higher incidences of wall motion abnormalities detected by echocardiography and/or ventriculography. Future prospective design studies in STEMI and NCA are warranted to understand the pathophysiology and define right treatment approaches. Stress may be considered as prominent factor, but future studies are needed with psychological evaluation; autonomous nerves system testing and catecholamine levels determination to verify its role in this pathology.


Neurofilaments can undergo axonal transport and cytoskeletal incorporation in a discontinuous manner.
Neurofilaments (NFs) are thought to provide structural support for axons. Some NFs exhibit an extended residence time along axons, the nature of which remains unclear. In prior studies in NB2a/d1 cells, hypophosphorylated NFs were demonstrated to be dispersed throughout the axon and to undergo relatively rapid axonal transport, while extensively phosphorylated NFs organized into a "bundle" localized along the center of the axon. It was not conclusively determined whether bundled NFs underwent transport or instead underwent turnover via exchange with transporting individual NFs. Herein, using transfection with multiple constructs and regional photobleaching, we demonstrate that bundled NFs undergo relatively slow transport as well as exchange with surrounding individual NFs. We also demonstrate that newly synthesized NFs disperse nonhomogenously throughout axonal neurites and perikarya. These findings provide a mechanism by which some NFs exhibit extended residence time within axons, which lessens the metabolic burden of cytoskeletal turnover.


Primary care nursing role and care coordination: an observational study of nursing work in a community health center.
Care coordination is a core element of the Patient-Centered Medical Home and requires an effective, well educated nursing staff. A greater understanding of roles and tasks currently being carried out by nurses in primary care is needed to help practices determine how best to implement care coordination and transform into PCMHs. We conducted an observational study of primary care nursing in a Community Health Center by creating a classification schema for nursing responsibilities, directly observing and tracking nurses' work, and categorizing their activities. Ten nurses in eight different practice sites were observed for a total of 61 hours. The vast majority of nursing time was spent in vaccine and medication administration; telephone work; and charting and paper work, while only 15% of their time was spent in activity that was classified broadly as care coordination. Care coordination work appeared to be subsumed by other daily tasks, many of which could have been accomplished by other, lesser trained members of the health care team. Practices looking to implement care coordination need a detailed look at work flow, task assignments, and a critical assessment of staffing, adhering to the principal of each team member working to the highest level of his or her education and license. Care coordination represents a distinct responsibility that requires dedicated nursing time, separate from the day to day tasks in a busy practice. To fully support these new functions, reimbursement models are needed that support such non visit-based work and provide incentives to coordinate and manage complex cases, achieve improved clinical outcomes and enhance efficiency of the health system. This article describes our study methods, data collection, and analysis, results, and discussion about reorganizing nursing roles to promote care coordination.


Reevaluation of the effects of growth hormone and prolactin on anuran tadpole growth and development.
The effects of ovine prolactin (oPRL) and ovine (o) or porcine (p) growth hormone (GH) on growth of anuran larvae were compared. In grass frog tadpoles (Rana pipiens), injections of oPRL (10 micrograms/gm/day) increased tail growth and body weight but had no effect on hindlimb growth or development. The same dose of oGH did not significantly affect the tail or body weight but it caused a striking increase in limb length and development. In bullfrog tadpoles (Rana catesbeiana) given an ergot drug (bromocriptine) to induce metamorphic changes, significant tail regression and loss of body weight occurred. Treatment with oPRL reversed these effects but had no effect on hindlimb growth or development. The pGH was much less effective than the oPRL in blocking tail regression and body weight loss but it significantly increased limb growth and development. These results show that GH and PRL can differentially regulate growth and development of structures in larval anurans. The effects of GH on limb growth and development can not be explained simply by a thyrotropic effect.


PET imaging of hepatocellular carcinoma with 2-deoxy-2[18F]fluoro-D-glucose, 6-deoxy-6[18F] fluoro-D-glucose, [1-11C]-acetate and [N-methyl-11C]-choline.
This study was designed to investigate the performance of positron emission tomography (PET) imaging for hepatocellular carcinoma (HCC) on a hepatitis viral infection-induced woodchuck model using existing tracers such as 2-deoxy-2[(18)F]fluoro-D-glucose (2FDG), 6-deoxy-6[(18)F]fluoro-D-glucose (6FDG), [1(-11)C]acetate (acetate) and [N-methyl(-11)C]choline (choline). Fourteen woodchucks with HCC were imaged with different radiotracers: 13 (10 with HCC and 3 controls) with 2FDG; 4 (3 with HCC and 1 control) with 6FDG; 13 (10 with HCC and 3 controls) with acetate; 4 (2 with HCC and 2 controls) with choline. The woodchucks were euthanized after imaging experiments and liver tissues were harvested for histology, for enzymatic activities including hexokinase (HK), glucose-6-phosphatase, acetyl-CoA synthetase (ACAS) and choline kinase (CK), and for differential gene expressions between the HCCs and the surrounding hepatic tissues. 2FDG detected 7/13 tumors with a tumor-to-liver uptake ratio (T/L) of 1.36+/-0.13. Five of these HCCs were moderately- or poorly-differentiated. The HK/glucose-6-phosphatase ratio was significantly higher in HCCs compared to the surrounding liver tissues (P=0.05). None of the HCCs imaged with 6FDG were detected by PET (T/L=1.01+/-0.11). Acetate detected 16/17 HCCs (T/L=2.02+/-0.7). ACAS activity was significantly higher in HCCs (P=0.01) and lipids-related genes were found up-regulated. Choline imaging detected all HCCs (T/L=1.63+/-0.34). CK activity was significantly higher in HCCs (P=0.001). Well-differentiated and some moderately-differentiated HCCs do not uptake 2FDG more than the surrounding liver tissues, but display increased acetate uptake. There is no contrast between HCCs and the surrounding liver tissues on the 6FDG PET images. Despite elevated background signal from the liver, choline uptake seems to be detectable in the HCCs scanned in this study.


Dalbavancin as chronic antibiotic suppression therapy for left ventricular assist device driveline infection due to methicillin-resistant Staphylococcus aureus: a case report.
Left Ventricular Assist Devices (LVADs) represent an important therapeutic option in the management of advanced heart failure. We report a case of 74 years-old male with a Jarvik 2000® (Jarvik Heart, New York, USA) LVAD who presented with an infection of the LVAD driveline due to methicillin-resistant Staphylococcus aureus (MRSA) that was treated with dalbavancin as chronic antimicrobial suppression therapy without adverse events and maintaining a good quality of life for more than 37 weeks. Dalbavancin could represent a valid option for the treatment of LVAD infections because of its efficacy, pharmacokinetic/pharmacodynamic proprieties, safety and tolerability.


Serum ferritin, insulin resistance, and metabolic syndrome: clinical and laboratory associations in 769 non-hispanic whites without diabetes mellitus in the HEIRS study.
In some reports, serum ferritin (SF) has been associated with insulin resistance and metabolic syndrome. We studied non-Hispanic whites without diabetes mellitus in a postscreening examination. Participants included cases [HFE C282Y homozygosity; and transferrin saturation (TS) >50% and SF >300 μg/L (males) and TS >45% and SF >200 μg/dL (females), regardless of HFE genotype] and controls [HFE wild-type (wt/wt) and TS/SF 25th-75th percentiles]. We excluded participants with overnight fasts <8 hr, cirrhosis, hepatitis B or C, pregnancy, or missing data. Observations were age, sex, C282Y homozygosity, body mass index (BMI), systolic and diastolic blood pressures (SBP, DBP), lymphocytes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), TS, SF, and glucose/insulin. Insulin resistance was defined as homeostasis model assessment of insulin resistance (HOMA-IR) 4th quartile (≥2.70). A total of 407 women and 362 men (mean age 54 years) included 188 C282Y homozygotes and 371 wt/wt. Significant trends across HOMA-IR quartiles included age, male sex, BMI, SBP, DBP, lymphocytes, ALT, CRP >0.5 mg/dL (positive), and TS (negative). Multiple regression on HOMA-IR revealed significant associations with male sex, BMI, SBP, lymphocytes, ALT, CRP>0.5 mg/dL (positive), and DBP and SF (negative). Logistic regression on HOMA-IR 4th quartile revealed significant positive associations with age, male sex, BMI, and lymphocytes. Metabolic syndrome occurred in 53 participants (6.9%). Logistic regression on metabolic syndrome revealed these odds ratios: HOMA-IR 4th quartile [9.1 (4.8, 17.3)] and CRP >0.5 mg/dL [2.9 (1.6, 5.4)]. Age, male sex, BMI, and lymphocytes were positively associated with HOMA-IR after correction for other factors. HOMA-IR 4th quartile and CRP >0.5 mg/dL predicted metabolic syndrome.