Nanosecond photoreduction of cytochrome p450cam by channel-specific Ru-diimine electron tunneling wires.
We report the synthesis and characterization of Ru-diimine complexes designed to bind to cytochrome p450cam (CYP101). The sensitizer core has the structure [Ru(L(2))L'](2+), where L' is a perfluorinated biphenyl bridge (F(8)bp) connecting 4,4'-dimethylbipyridine to an enzyme substrate (adamantane, F(8)bp-Ad), a heme ligand (imidazole, F(8)bp-Im), or F (F(9)bp). The electron-transfer (ET) driving force (-deltaG degrees ) is varied by replacing the ancillary 2,2'-bipyridine ligands with 4,4',5,5'-tetramethylbipyridine (tmRu). The four complexes all bind p450cam tightly: Ru-F(8)bp-Ad (1, K(d) = 0.077 microM); Ru-F(8)bp-Im (2, K(d) = 3.7 microM); tmRu-F(9)bp (3, K(d) = 2.1 microM); and tmRu-F(8)bp-Im (4, K(d) = 0.48 microM). Binding is predominantly driven by hydrophobic interactions between the Ru-diimine wires and the substrate access channel. With Ru-F(8)bp wires, redox reactions can be triggered on the nanosecond time scale. Ru-wire 2, which ligates the heme iron, shows a small amount of transient heme photoreduction (ca. 30%), whereas the transient photoreduction yield for 4 is 76%. Forward ET with 4 occurs in roughly 40 ns (k(f) = 2.8 x 10(7) s(-)(1)), and back ET (Fe(II) --> Ru(III), k(b) approximately 1.7 x 10(8) s(-)(1)) is near the coupling-limited rate (k(max)). Direct photoreduction was not observed for 1 or 3. The large variation in ET rates among the Ru-diimine:p450 conjugates strongly supports a through-bond model of Ru-heme electronic coupling.


Successful Mechanical Thrombectomy for Isolated Internal Carotid Artery Occlusion in a Patient with Monocular Blindness: A Case Report.
We report a rare case of isolated internal carotid artery occlusion complicated by central retinal artery occlusion that was successfully treated with mechanical thrombectomy for internal carotid artery occlusion. A 59-year-old man visited the emergency room because of right monocular blindness. Magnetic resonance imaging showed multiple acute small embolic infarctions in the right frontal lobe, and magnetic resonance angiography revealed right internal carotid artery occlusion without the associated occlusion of the circle of Willis, which indicates the patency of the anterior and middle cerebral arteries. An electrocardiogram showed atrial fibrillation. Therefore, we performed mechanical thrombectomy with a stent retriever under continuous manual aspiration with a balloon-guiding catheter and confirmed complete recanalization, anterograde flow in the right ophthalmic artery, and retinal brush. The procedure was completed without complications, and the patient noticed an improvement in visual acuity immediately after the procedure. When a patient with atrial fibrillation complains of monocular blindness, it is important to consider internal carotid artery occlusion due to cardioembolism, to perform an examination promptly, and to consider early treatment, including mechanical thrombectomy.


Unlike AML1, CBFbeta gene is not deregulated by point mutations in acute myeloid leukemia and in myelodysplastic syndromes.
The core-binding factor (CBF) complex is a heterodimeric transcription factor composed of 2 subunits, CBFalpha and CBFbeta, that play a major role in hematopoiesis. Both members of the CBF complex are frequently altered in acute myeloid leukemia (AML) by translocation, most commonly t(8;21), t(12;21), and t(3;21) for CBFalpha, located in 21q22, and inv(16)(p13;q22) for CBFbeta, located on 16q22. Recently, a new mechanism of alteration of CBFalpha, by point mutation, has been reported in myeloid malignancies, particularly in M0 AML. In the present study, we found no point mutation of the CBFbeta gene in 30 myelodysplastic syndromes and 100 AMLs, suggesting a limited role, if any, of CBFbeta point mutations in those disorders.


Developmental issues of grandchildren who provide care to grandparents.
This qualitative research examined the perceptions, beliefs, attitudes, and experiences of grandchildren caregivers who ranged in age from 7 to 29 years. Thirty-four caregiving grandchildren participated in face to-face semistructured interviews lasting approximately 35 to 90 minutes. Interviews were audiotaped and transcribed verbatim. Analysis of the data revealed that caregiving grandchildren: a) experienced a wide range of emotions as providers of care to their grandparents; and b) developed specific coping strategies to deal with the stress of providing care. The intensity, type, and range of emotions experienced and the coping strategies used were a reflection of the developmental issues of the grandchildren. Although grandchildren caregivers experienced similar responsibilities, their developmental level and the context in which care was provided played a role on how they were best able to cope with caregiving responsibilities. Practitioners must consider grandchildren caregivers when developing programs and services for family caregivers.


From Hydrogen Bond to van der Waals Force: Molecular Scalpel Strategy to Exfoliate a Two-Dimensional Metal-Organic Nanosheet.
The facile exfoliation of a two-dimensional metal-organic nanosheet of {[Co(HL)(H2O)(Py)3/4]·1/2H2O·DMF}n [1-Py; H3L = 5-(1H-pyrazol-4-yl)isophthalic acid and Py = pyridine] was achieved, via a molecular scalpel strategy, by weakening intermolecular forces between adjacent layers. The resulting 1-Py/KB40 (KB = Ketjen black) shows an increased oxygen evolution reaction (OER) performance with an overpotential of 370 mV at a current density of 10 mA cm-2 and a Tafel slope of 58 mV dec-1. This work sheds light on the structure-morphology-reactivity relationship of such materials in OER.


Surgical Treatment of Calcaneal Avulsion Fracture in Elderly Patients Using Cannulated Cancellous Screws and Titanium Wire.
Avulsion fractures of the calcaneus are relatively uncommon and are seen most frequently in elderly or osteoporotic patients. A surgical method that avoids displacement of the avulsed fragment after fixation has not been developed. We report the cases of 3 patients (a 73-year-old male, an 85-year-old male, and an 81-year-old female) treated by open reduction and internal fixation using titanium wire and cannulated cancellous screws. The posterior approach was used by way of a vertical midline incision. The fracture was fixed with 2 screws, and then a titanium wire was passed through the holes of the cannulated screws. A small incision on the lateral side of planter was added for the exit and return of the wire. The wire knot was bent inside the proximal Achilles tendon bursa in 2 patients and was directed to the plantar side in 1 to avoid irritation. Bony union was achieved without repeat displacement of the fragment in all 3 patients. Normal ankle function was restored, and the patients recovered the activities of daily living almost to the original level. Although an additional plantar incision is required, this surgical technique provides strong internal fixation.


Proton-catalyzed hydroamination and hydroarylation reactions of anilines and alkenes: a dramatic effect of counteranions on reaction efficiency.
The anilinium salt, [PhNH3][B(C6F5)4], has been identified as a catalyst for the hydroamination and hydroarylation of several different types of alkenes with anilines. The weakly coordinating counterion of this acid plays a key role in this transformation. The reaction is facile for styrenes and tolerates norbornene, cyclic alkenes, and cyclohexadiene. Selectivity between hydroamination and hydroarylation products can be tuned using reaction time, temperature, and substrate substitution. Details regarding the substrate scope and selectivity of this hydroamination/hydroarylation reaction are discussed.


Nutritional Assessment of the Children of the Beta Israel Community in Ethiopia: A 2017 Update.
Malnutrition is a common phenomenon worldwide and a major public health problem, particularly in developing poorer countries like Ethiopia. Although malnutrition can affect any age group, children are at a higher risk and it is associated with an increased morbidity and mortality. The aim of this study was to update and assess the nutritional status of children of the Beta Israel community in the Gondar area of Ethiopia. This was a community-based cross-sectional anthropometrical study of all the children of the community age 0-60 months. A structured questionnaire was used to collect sociodemographic data, nutritional history, and clinical parameters. Nutritional indices weight for age, height for age, and weight for height were used to define the nutritional status of the children. The 2006 World Health Organization (WHO) growth curves served as reference parameters. Statistical analysis included binary logistical regression analysis. A total of 489 children, representing over 90% of the community's children were studied with the mean age and standard deviation of 36.5 and 18 months, respectively. The overall prevalence of malnutrition was found to be 39.1% with wasting, underweight, and stunting occurring in 22.1%, 26.2%, and 18.4% of the children, respectively. Severe wasting, severe underweight, and severe stunting occurred in 8.4%, 8.2% and 5.3% of the children, respectively. Multivariate analysis showed that age was significantly associated with the occurrence of malnutrition with younger children being at a higher risk (p = 0.044). Gender of child, family income, maternal education, presence of illness in the month preceding data collection, and household size did not show any association with malnutrition prevalence. The prevalence of malnutrition as measured by stunting, underweight, and wasting has remained high among children younger than 5 years of the Beta Israel community in Gondar. Moreover, younger children were found to be more malnourished than older children.


Environmental fate and metabolic transformation of two non-ionic pesticides in soil: Effect of biochar, moisture, and soil sterilization.
Soil moisture, organic matter, and soil microbes are the key considering factors that control the persistence, degradation, and transformation of applied pesticides under varied soil conditions. In this study, underlying influence of these factors was assessed through the fates and metabolic transformation of two non-ionic pesticides (e.g., Phorate and Terbufos) in soils. Concisely, two distinct experiments including a customized batch equilibrium (sorption study), and a lab incubation trial (degradation study) were performed, following the OECD guidelines. As per study findings, biochar (BC) amendment was found to be the most influential factors during sorption study, particularly, 1% BC amendment contributed to achieve the best results. In addition, the non-linearity of sorption isotherm (1/n < 1.0) was revealed through Freundlich isotherm, indicating the strong adsorption of studied pesticides onto the soils. On the other hand, during degradation study, soil moisture initiates the enhanced degradation of parent pesticides and subsequent metabolism. In the presence of 40% water holding capacity (WHC), 1% BC amendment enhances the metabolic transformation, while H2O2 treatment could hinder the process. Additionally, the half-life degradation (t1/2) of phorate and terbufos was controlled by biochar amendment, moisture, and soil sterilization, respectively. Finally, BC can accelerate the metabolic transformation, whereas, phorate underwent a metabolic change into sulfoxide and sulfone while terbufos turned into solely sulfoxide. This pioneering study gathered crucial data for understanding the persistence and metabolic transition of non-ionic pesticides in soils and their patterns of degradation.


Photoimmunotherapy targeting prostate-specific membrane antigen: are antibody fragments as effective as antibodies?
Photoimmunotherapy is a highly cell-selective cancer therapy based on an armed antibody conjugate with a phthalocyanine-based photosensitizer, IR700. Photoimmunotherapy induces rapid and highly specific necrosis in targeted cancer cells after exposure to near-infrared (NIR) light. Cells not expressing the antigen are not affected. To date, photoimmunotherapy has been demonstrated only with full antibody-IR700 conjugates. In this study, small and bivalent antibody fragments, including anti-prostate-specific membrane antigen (PSMA) diabody (Db) and minibody (Mb), were compared with intact IgG for their effectiveness as photoimmunotherapy agents. Radioiodinated antibody and antibody fragments with (125)I were used to determine the timing of maximum binding of each anti-PSMA antibody fragment on the cell surface in vivo in mice bearing either PSMA-positive or -negative PC3 tumors. Then therapeutic efficacy of photoimmunotherapy was examined by exposing mice to NIR light at 2 time points based on the time of maximum cell surface binding at 6 h after injection for Db-IR700 and 24 h after injection for Mb-IR700 and IgG-IR700 as well as 24 h after the peak uptake times. Photoimmunotherapy with the same molar concentration of PSMA-Db-IR700, PSMA-Mb-IR700, and PSMA-IgG-IR700 conjugate showed similar therapeutic effects in vitro and in vivo on PSMA-positive PC3 tumor xenografts in cytotoxicity and survival curves (P > 0.05). The use of PSMA-Db-IR700 conjugate results in the shortest time interval between injection and NIR exposure without compromising therapeutic effects of photoimmunotherapy.


Is India overurbanised?
This paper questions the frequently posed thesis of India being overurbanized. The diverse connotations of the term "overurbanization" have been taken into account and tested against the Indian reality. It is concluded that on a net balance of positive and negative effects emanating from urbanization, there is no reason to believe that India is urbanized to an extravagant degree. Any continued adherence to the "overurbanization" thesis is likely to distort our perceptions about the vital role which Indian urbanization is playing in economic growth.


Are cytochrome b gene mutations the only cause of atovaquone resistance in Pneumocystis?
There is evidence that exposure of the opportunistic pathogen Pneumocystis to atovaquone enhances the development of resistance to the drug. Atovaquone is a structural analog of ubiquinone, which binds to the mitochondrial cytochrome bc(1) complex and inhibits electron transport. Like the parasites Plasmodium and Toxoplasma, atovaquone resistance can result from mutations in the cytochrome b gene of Pneumocystis. However, atovaquone resistance cannot be explained by cytochrome b gene mutations in all cases. The discovery that atovaquone also inhibits biosynthesis of ubiquinone in P. carinii may unfold other mechanisms by which drug resistance develops.


Are you really smiling? Display rules for emojis and the relationship between emotion management and psychological well-being.
Display rules specify socially appropriate facial expressions in a given situation. However, managing emotions for such a social adaption sometimes leads to deleterious psychological outcomes. Given that people nowadays rely on emojis to express emotions online, the present study investigated (1) whether display rules exist in emoji communications and (2) how emotion management using emojis is associated with psychological well-being. Prior studies have demonstrated the effects of context on the frequency of emoji use. However, the intensity and type of expression may differ, even if emojis are used at the same frequency. The current study thus investigated whether emotional expressions and the types of emojis used are adjusted to contexts similar to facial displays. As many as 1,289 Japanese participants typed emojis in response to Internet chats and reported the intensity of their emotional expressions. The contexts of the chats varied depending on the target of use, the emotional value of contexts, and private or public settings. The results showed that, similar to facial displays, individuals expressed emotions through emojis more with those closely related, more in positive contexts than in negative contexts, and more in private than in public contexts. When the expressions were intense, individuals used emojis consistent with the emotional value of the context. Upon attenuating the expressions, this study found that individuals tended to use euphemistic emojis and sent smiling emojis in negative contexts to manage the expressions. Moreover, expressing emotions with emojis was associated with subjective well-being, whereas managing emotions with emojis was weakly associated with depressive symptoms. Together, this study indicates the existence of display rules for emojis, calling for future research on the psychological impact of online emotion norms.


Surgical feasibility of ascending aorta manipulation after transcatheter aortic valve implantation: a computed tomography theoretical analysis.
The expansion of TAVI will involve an increase in the frequency of emergent or late cardiac surgery after THV implantation. This study was designed to investigate the anatomical feasibility of surgical cross-clamp and aortotomy after TAVI through a post-TAVI CT-scan assessment. We retrospectively analysed 117 CTs acquired after TAVI procedures with high stent prostheses in three high-volume centres between October 2008 and May 2017. The mean distance observed between the innominate artery and the top of the transcatheter heart valve was 45±11 mm, being <30 mm in 8/117 (6.8%) patients and <20 mm in none. The mean distance between the sinotubular junction and the first free site for aortotomy was 22±7 mm (>20 mm in 78/117 [66.7%] cases). A total of 56/117 (47.9%) patients showed a complete continuous contact between the anterior aortic wall and the anterior part of the valve stent. Aortic cross-clamp appears not to be an issue when cardiac surgery is needed after TAVI; however, a careful and possibly higher aortotomy may be required. CT should be performed prior to planned cardiac surgery after TAVI to determine a safe positioning for aortic cross-clamp and aortotomy.


Prediction of the hydroxypropyl cellulose-poly(vinyl alcohol) ratio in aqueous solution containing papaverine hydrochloride in terms of drug loaded electrospun fiber formation.
Papaverine hydrochloride loaded electrospun fibers were prepared for buccal drug delivery with the aim of improving the oral bioavailability of the crystalline drug, which can be achieved by the increased solubility and by the circumvention of the intensive first pass metabolism. The water soluble hydroxypropyl cellulose (HPC) was chosen as a mucoadhesive polymer. In order to improve the electrospinnability of HPC, the also mucoadhesive poly(vinyl alcohol) (PVA) was used. During the experiments, the total polymer concentration was kept constantly at 15% (w/w), and only the ratio of the two polymers was changed. Five different HPC:PVA ratios (5:5, 6:4, 7:3, 8:2, 9:1) were examined. Combination of rheological measurements and molar reflectance characterization with scanning electron microscopy was applied for the determination of the optimum composition of the gels for fiber formation. The crystalline-amorphous transition of papaverine hydrochloride was also tracked by Fourier transform infrared spectroscopy. A correlation was found between the macrostructural properties of the polymer solutions and their electrospinnability and the consequent morphology of the resultant samples. Along with the changes of the polymer ratio, the corresponding morphology of the electrospun samples also varied. With decreasing HPC ratio of the system, a transition from the spray-dried film-like structure through fibrous film to fibers was observed. Polymer solutions of the lowest elasticity and smallest intermolecular interactions contributed to the best fiber characteristics of the samples. The results enable the determination of the polymer ratio for the formation of applicable quality of electrospun fibers. According to the results 5:5 and 6:4 polymer ratios enabled the best fiber performance.


Glutamic acid 181 is uncharged in dark-adapted visual rhodopsin.
We have performed a high-level quantum chemical analysis to study the chromophore-protein interaction involving the charged (B) and/or uncharged (C) form of E181 and also a mutant E181Q model in the presence of the primary counterion E113 (A). As the magnitude of the calculated spectral shifts on either side remains within +/-10 nm, we show that the orientation of the dipole moment vector is the key to unlocking the puzzle on this contentious issue. We find that E181 is present in the uncharged (or) protonated form in the dark-adapted visual Rhodopsin, and therefore an electrostatically neutral environment is envisaged.


New Powder Diffraction File (PDF-4) in relational database format: advantages and data-mining capabilities.
The International Centre for Diffraction Data (ICDD) is responding to the changing needs in powder diffraction and materials analysis by developing the Powder Diffraction File (PDF) in a very flexible relational database (RDB) format. The PDF now contains 136,895 powder diffraction patterns. In this paper, an attempt is made to give an overview of the PDF-4, search/match methods and the advantages of having the PDF-4 in RDB format. Some case studies have been carried out to search for crystallization trends, properties, frequencies of space groups and prototype structures. These studies give a good understanding of the basic structural aspects of classes of compounds present in the database. The present paper also reports data-mining techniques and demonstrates the power of a relational database over the traditional (flat-file) database structures.


Expression of complement regulating factors in gastric cancer cells.
To investigate the deposition of complement components, C3d and C5b-9, and the expression of complement regulating factors (S protein, membrane cofactor protein (MCP; CD46), protectin (CD59), decay accelerating factor (DAF; CD55), and type 1 complement receptor (CR1; CD35)) in gastric cancers. Specimens of gastric cancer were examined by immunohistochemistry and immunoelectron microscopy. Four complement regulating factors (S protein, MCP, protectin, and DAF) were expressed on gastric cancer cells, in ultrastructurally localised areas on the cell membrane. CR1 was not expressed. The staining intensity of DAF in both differentiated and undifferentiated adenocarcinomas was significantly higher than in histologically normal gastric epithelium. Furthermore, the staining intensity of DAF in gastric cancers showing a diffusely infiltrating growth pattern was higher than in gastric cancers showing an expanding growth pattern. These data indicate that DAF may play a role in cancer cell infiltration and resistance in tumour cells.


Prevalence of depression and anxiety in irritable bowel syndrome: A clinic based study from India.
Irritable Bowel Syndrome (IBS) is a very common gastrointestinal dysfunction. Despite strong evidence of high prevalence of depression and anxiety in IBS there is very limited research on this in India. Cases of IBS and controls with non-ulcerative dyspepsia were recruited from a gastroenterology clinic in Mumbai, India. Presence of anxiety disorder and depression were assessed by using the Hamilton Anxiety rating scale and Hamilton Depression rating scale respectively. Prevalence rates of anxiety and depression were established and Odds Ratio (OR) was calculated to determine the association of depression and anxiety disorders with IBS. In IBS cases, the prevalence of depression and anxiety disorder was 37.1% and 31.4% respectively. In patients with IBS the OR for depression was 6.3 (95% CI 1.6-24.74, P=0.009) and the OR for anxiety disorder was 7.56 (95% CI 1.53-37.29, P=0.01). The prevalence of depression and anxiety disorder in IBS is very high. Therefore, screening of IBS patients for anxiety and depression would facilitate better interventions and consequently better outcomes.


Involving students in experimental design: three approaches.
Many faculty want to involve students more actively in laboratories and in experimental design. However, just "turning them loose in the lab" is time-consuming and can be frustrating for both students and faculty. We describe three different ways of providing structures for labs that require students to design their own experiments but guide the choices. One approach emphasizes invertebrate preparations and classic techniques that students can learn fairly easily. Students must read relevant primary literature and learn each technique in one week, and then design and carry out their own experiments in the next week. Another approach provides a "design framework" for the experiments so that all students are using the same technique and the same statistical comparisons, whereas their experimental questions differ widely. The third approach involves assigning the questions or problems but challenging students to design good protocols to answer these questions. In each case, there is a mixture of structure and freedom that works for the level of the students, the resources available, and our particular aims.


Exploring emotional face processing in 5-month-olds: The relation with quality of parent-child interaction and spatial frequencies.
It is unclear whether infants differentially process emotional faces in the brain at 5 months of age. Contradictory findings of previous research indicate that additional factors play a role in this process. The current study investigated whether five-month-old infants show differential brain activity between emotional faces. Furthermore, we explored the relation between emotional face processing and (I) stimulus characteristics, specifically the spatial frequency content, and (II) parent, child, and dyadic qualities of interaction characteristics. Face-sensitive components (i.e., N290, P400, Nc) in response to neutral and fearful faces that contained only lower or higher spatial frequencies were assessed. Quality of parent-child interaction was assessed with the Manchester Assessment of Caregiver Infant Interaction (MACI). The results show that, as a full group, none of the components differed between emotional expressions. However, when splitting the group based on median MACI scores, infants who showed high quality of interaction (i.e., more attentiveness to caregiver, positive and negative affect, and liveliness) processed emotions differently, whereas infants who showed low quality did not. These results indicate that a sub-group of infants show differential emotional face processing at 5 months of age, which seem to relate to quality of their behavior during the parent-child interaction.


Three-dimensional endosonography of the pelvic floor: an additional diagnostic tool in surgery for continence problems in children.
Three-dimensional endorectal sonography with a specially developed system is able to produce an image of the entire pelvic floor including the sphincter muscles and the rectal wall even in small children. This special system is based on conventional endorectal ultrasound and allows recording of a controlled withdrawal of the axially rotating transducer, creating an image sequence resembling that of a spiral CT-scan; this sequence is digitized off-line and evaluated in a three-dimensional form by a workstation computer. This evaluation has several advantages compared with conventional examination, for example, the complete recording of organs with the possibility of volumetry, construction of arbitrary sections, volume-rendering procedures and the interactive segmentation of organ borders and their three-dimensional visualization. Based on images from this 3D endorectal sonography, the normal anatomy of the pelvic floor that is visible using ultrasound is described, followed by some pathological findings concerning continence surgery. Finally we discuss the advantages and restrictions compared to other examination procedures and the possibilities of technical development.


Evaluation of Patient Migration Patterns and Related Health Care Costs Within a National Medicare Advantage Prescription Drug Plan After Implementation of an Oxycodone HCl Extended-Release Access Restriction.
Health plans use formulary restrictions (e.g., prior authorization, step therapy, tier change, nonformulary status) in an effort to control cost and promote quality, safety, and appropriate prescription utilization. Some Medicare payers perceive that the inclusion of certain agents, such as branded oxycodone HCl extended-release tablets (OERs), on their formularies is associated with attracting high-cost members to the plan. To evaluate disenrollment rates, patient migration, and subsequent health care costs among OER users who disenrolled from a national Medicare Advantage Prescription Drug plan (study-MAPD) in the plan year following OER nonformulary restriction. A retrospective, longitudinal cohort study using IMS pharmacy and medical claims data between July 1, 2011, and December 31, 2014, was conducted. In the study-MAPD, adults aged ≥ 18 years who were chronic OER users with ≥ 2 OER claims 6 months before the nonformulary restriction date on January 1, 2013 (index date) and with continuous activity in pharmacy and medical claims for 6 months pre- and post-index were included in the study. Comparison years of 2012 and 2014 prerestriction/postrestriction were selected. All groups were followed for 6 months postindex. Year-to-year disenrollment rates of OER patients and the overall plan, as well as patient characteristics and costs of those who disenrolled from and those who remained with the plan, were measured. Costs were compared using a difference-in-differences approach. This study identified 2,935 eligible OER users from the study-MAPD population after imposing nonformulary restrictions on OERs on January 1, 2013. Mean age was 62.1 years, and 59.8% were female. The mean Charlson Comorbidity Index score was 1.83 for those 1,001 patients with medical claims data. For comparison years 2012 (prerestriction) and 2014 (postrestriction), 2,248 and 2,222 OER patients were identified, respectively. Patient characteristics were similar across patient cohorts in all 3 study years. Disenrollment rates for OER users (12.9%, 5.5%, and 14.3% for years 2012, 2013, and 2014, respectively) were lower or similar to those of the overall plan (18.3%, 7.6%, and 14.1%, respectively, for the same 3 years). Approximately 40% of OER users who disenrolled from the study-MAPD migrated to plans also imposing a nonformulary restriction on OERs, while about 25% moved to plans with less restrictive OER coverage. The majority (59.9%) of patients continued OER use irrespective of their disenrollment from the study-MAPD in 2013. Although a nonsignificant decrease ($117; P = 0.340) in per patient per month (PPPM) cost was observed among OER patients postrestriction (from 2012 to 2013), the difference-in-difference analysis indicated a net postrestriction increase of $124 (P = 0.461) in PPPM for OER patients. This study found little evidence to support any consistent directional effect on patient enrollment behavior as a result of an OER non-formulary restriction. Implementation of an OER nonformulary restriction did not lead to higher OER patient disenrollment or lower patient costs in the study-MAPD. Funding for this study was provided by Purdue Pharma. De, Chen, and Wade are employees of QuintilesIMS, a for-profit company that was contracted by Purdue Pharma to undertake this research. Sweet was a paid consultant for Purdue Pharma at the time of this study. Study concept and design were contributed by Chen, Wade, and De. Chen, De, and Wade collected the data, which were interpreted by all the authors. The manuscript was written by Chen and De, along with Sweet and Wade, and revised by all the authors.


Placental growth factor-1 and epithelial haemato-retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy.
Disruption of the retinal pigment epithelial (RPE) barrier contributes to sub-retinal fluid and retinal oedema as observed in diabetic retinopathy. High placental growth factor (PLGF) vitreous levels have been found in diabetic patients. This work aimed to elucidate the influence of PLGF-1 on a human RPE cell line (ARPE-19) barrier in vitro and on normal rat eyes in vivo. ARPE-19 permeability was measured using transepithelial resistance and inulin flux under stimulation of PLGF-1, vascular endothelial growth factor (VEGF)-E and VEGF 165. Using RT-PCR, we evaluated the effect of hypoxic conditions or insulin on transepithelial resistance and on PLGF-1 and VEGF receptors. The involvement of mitogen-activated protein kinase (MEK, also known as MAPK)/extracellular signal-regulated kinase (ERK, also known as EPHB2) signalling pathways under PLGF-1 stimulation was evaluated by western blot analysis and specific inhibitors. The effect of PLGF-1 on the external haemato-retinal barrier was evaluated after intravitreous injection of PLGF-1 in the rat eye; evaluation was by semi-thin analysis and zonula occludens-1 immunolocalisation on flat-mounted RPE. In vitro, PLGF-1 induced a reversible decrease of transepithelial resistance and enhanced tritiated inulin flux. These effects were specifically abolished by an antisense oligonucleotide directed at VEGF receptor 1. Exposure of ARPE-19 cells to hypoxic conditions or to insulin induced an upregulation of PLGF-1 expression along with increased transcellular permeability. The PLGF-1-induced RPE cell permeability involved the MEK signalling pathway. Injection of PLGF-1 in the rat eye vitreous induced an opening of the RPE tight junctions with subsequent sub-retinal fluid accumulation, retinal oedema and cytoplasm translocation of junction proteins. Our results indicate that PLGF-1 may be a potential regulation target for the control of diabetic retinal and macular oedema.


Chondroitin 4-O-sulfotransferases are required for cell adhesion and morphogenesis in the Ciona intestinalis embryo.
Chondroitin sulfate (CS) is a carbohydrate component of proteoglycans. Several types of sulfotransferases determine the pattern of CS sulfation, and thus regulate the biological functions of proteoglycans. The protochordate ascidians are the closest relatives of vertebrates, but the functions of their sulfotransferases have not been investigated. Here, we show that two chondroitin 4-O-sulfotransferases (C4STs) play important roles in the embryonic morphogenesis of the ascidian Ciona intestinalis. Ci-C4ST-like1 is predominantly expressed in the epidermis and muscle. Epidermal and muscle cells became spherical upon the injection of a Ci-C4ST-like1-specific morpholino oligo (MO), thus suggesting weakened cell adhesion. Co-injection of a Ci-C4ST-like1-expressing transgene rescued the phenotype, suggesting that the effects of the MO were specific. Ci-C4ST-like3 was expressed in the central nervous system, muscle, and mesenchyme. A specific MO appeared to affect cell adhesion in the epidermis and muscle. Convergent extension movement of notochordal cells was also impaired. Forced expression of Ci-C4ST-like3 restored normal morphogenesis, suggesting that the effects of the MO were specific. The present study suggests that Ci-C4ST-like1 and Ci-C4ST-like3 are required for cell adhesion mainly in the epidermis and muscle.


Physicochemical characterization of complex drug substances: evaluation of structural similarities and differences of protamine sulfate from various sources.
The purpose of this study was to characterize and evaluate differences of protamine sulfate, a highly basic peptide drug, obtained from five different sources, using orthogonal thermal and spectroscopic analytical methods. Thermogravimetric analysis and modulated differential scanning calorimetry showed that all five protamine sulfate samples had different moisture contents and glass transition and melting temperatures when temperature was modulated from 25 to 270°C. Protamine sulfate from source III had the highest residual moisture content (4.7 ± 0.2%) at 105°C, resulting in the lowest glass transition (109.7°C) and melting (184.2°C) temperatures compared with the other four sources. By Fourier-transform infrared (FTIR) spectroscopy, the five sources of protamine sulfate had indistinguishable spectra, and the spectra were consistent with a predominantly random coil conformation in solution and a minor population in a β-sheet conformation (~12%). Circular dichroism spectropolarimetry confirmed the FTIR results with prominent minima at 206 nm observed for all five sources. Finally, proton ((1)H) nuclear magnetic resonance spectroscopy showed that all five protamine sulfate sources had identical spectra with backbone amide chemical shifts between 8.20 and 8.80 ppm, consistent with proteins with predominantly random coil conformation. In conclusion, thermal analyses showed differences in the thermal behavior of the five sources of protamine sulfate, while spectroscopic analyses showed the samples had a predominantly random coil conformation with a small amount of β-sheet present.


Nickel-catalyzed Negishi arylations of propargylic bromides: a mechanistic investigation.
Although nickel-catalyzed stereoconvergent couplings of racemic alkyl electrophiles are emerging as a powerful tool in organic chemistry, to date there have been no systematic mechanistic studies of such processes. Herein, we examine the pathway for enantioselective Negishi arylations of secondary propargylic bromides, and we provide evidence for an unanticipated radical chain pathway wherein oxidative addition of the C-Br bond occurs through a bimetallic mechanism. In particular, we have crystallographically characterized a diamagnetic arylnickel(II) complex, [(i-Pr-pybox)Ni(II)Ph]BAr(F)4, and furnished support for [(i-Pr-pybox)Ni(II)Ph](+) being the predominant nickel-containing species formed under the catalyzed conditions as well as a key player in the cross-coupling mechanism. On the other hand, our observations do not require a role for an organonickel(I) intermediate (e.g., (i-Pr-pybox)Ni(I)Ph), which has previously been suggested to be an intermediate in nickel-catalyzed cross-couplings, oxidatively adding alkyl electrophiles through a monometallic pathway.


Phosphate binding by a novel Zn(II) complex featuring a trans-1,2-diaminocyclohexane ligand. Effective anion recognition in water.
In this work we have investigated the binding properties of a new synthetic receptor for phosphate anions that combines metal ion coordination with electrostatic and H-bonding interactions. The described receptor is obtained by assembling an iminodiacetic (IDA) fragment, as a Zn(II) binding site, with a polyamine macrocyclic portion containing two trans-1,2-diaminocyclohexane (DAC) units and a pyrrole ring, as a cationic binding site, into an adaptive structure appropriately spanning the length of di- and tridentate phosphates. Potentiometric measurements together with (1)H and (31)P NMR investigation showed that, in a wide pH range including values of physiological interest, the Zn(II) complex of the receptor binds di- and triphosphates, such as ADP, ATP, pyrophosphate (PP) and triphosphate (TP), far better than monophosphate (MP), and that TP is poorly bound by methyliminodiacetate (MIDA) as a model for the Zn(II) binding site. Besides the excellent selectivity over other phosphates, the affinity for TP is the largest reported to date for Zn(II) complexes in water.


Erythropoietin in chronic heart failure.
In patients with chronic heart failure (CHF), anemia is common and is associated with adverse outcome. Correction of anemia by erythropoiesis-stimulating proteins would thus seem attractive. Endogenous erythropoietin (Epo) levels are increased in CHF and are associated with severity of the disease and with increased mortality. Furthermore, Epo levels poorly correlate with hemoglobin levels, suggesting that elevated Epo levels are not only driven by anemia, but by the condition of CHF as well. Several experimental studies have demonstrated ancillary cardioprotective effects of the recombinant form of Epo, including reduced apoptosis and increased neovascularization. Three early, small studies and 3 subsequent phase 2 trials found that erythropoiesis-stimulating proteins in anemic CHF patients were safe overall and potentially beneficial. Currently, a large phase 3, randomized, clinical trial is ongoing that evaluates the effects of darbepoetin alpha on morbidity and mortality in CHF.


Surgery and perioperative management for post-intubation tracheoesophageal fistula: case series analysis.
Post-intubation tracheoesophageal fistula (PITEF) is an often mistreated, severe condition. This case series reviewed for both the choice and timing of surgical technique and outcome PITEF patients. This case series reviewed ten consecutive patients who had undergone esophageal defect repair and airway resection/reconstruction between 2000 and 2014. All cases were examined for patients: general condition, medical history, preparation to surgery, diagnostic work-up, timing of surgery and procedure, fistula size and site, ventilation type, nutrition, post-operative course and complications. All patients were treated according to Grillo's technique. Overall, 6/10 patients had undergone a preliminary period of medical preparation. Additionally, 3 patients had already had a tracheostomy, one had had a gastrostomy and 4 had both. One patient had a Dumon stent with enlargement of the fistula. Concomitant tracheal stenosis had been found in 7 patients. The mean length of the fistulas was 20.5 mm (median 17.5 mm; range, 8-45 mm), at a median distance from the glottis of 43 mm (range, 20-68 mm). Tracheal resection was performed in all ten cases. The fistula was included in the resection in 6 patients, while it was excluded in the remaining 4 due to their distance. Post-repair tracheotomy was performed in 3 patients. The procedure was performed in 2 ventilated patients. Morbidity related to fistula and anastomosis was recorded in 3 patients (30%), with one postoperative death (10%); T-Tube placement was necessary in 3 patients, with 2/3 decannulations after long-stenting. Definitive PITEF closure was obtained for all patients. At 5-year follow-up, the 9 surviving patients had no fistula-related morbidity. Primary esophageal closure with tracheal resection/reconstruction seemed to be effective treatment both short and long-term. Systemic conditions, mechanical ventilation, detailed preoperative assessment and appropriate preparation were associated with outcome. Indeed, the 3 patients who had received T-Tube recovered from anastomotic complications.


[Significance of coronary risk factors and coronary arteriosclerosis for coronary vasospasm].
The clinical significance of coronary arteriosclerosis and coronary risk factors was investigated in patients with coronary spasm. Coronary spasm induction test with acetylcholine was performed in 140 consecutive patients (85 males and 55 females) with chest pain in our hospital. The patients were divided into positive, borderline, and negative groups according to the results of the test. The positive and borderline groups were categorized as the coronary contractive group. The coronary sclerosis index was used to evaluate the degree of coronary arteriosclerosis. Coronary risk factors were evaluated in terms of hypertension, diabetes mellitus, hyperlipidemia, obesity, history of smoking and drinking, and family history of cardiovascular events. Patients could be divided into 34.3% in the positive group and 23.6% in the borderline group, i.e. 57.9% in the coronary contractive group, and 42.1% in the negative group. There were more males than females in both positive and coronary contractive groups. The proportion of males in the coronary contractive group was higher in patients over 60 years of age than in patients under 60. In contrast, the proportion of females was higher in patients under 60 than in patients over 60. In male patients, the coronary sclerosis indices in the positive, borderline, and coronary contractive groups were higher than those in the negative group. The indices in female patients in the positive and coronary contractive groups were higher than the index in the negative group. There were no differences in terms of the presence or absence, or the degree of organic stenosis between spastic sites and nonspastic branches in the positive group. The history of smoking in male patients was significantly more common in the positive group than in the negative group. The family history was more relevant in female patients in the positive or coronary contractive group compared to the negative group. Moreover, the history of smoking in the coronary contractive group was significantly more common than that in the negative group. The development of coronary spasm may be determined, at least in part, by the degree of coronary sclerosis as well as by gender and age. Smoking habits in both sexes and family history in females are proposed as the most important risk factors for coronary spasm.


Controlling aromatic helix dimerization in water by tuning charge repulsions.
Several helically folded aromatic oligoamides were designed and synthesized. The sequences were all water-soluble thanks to the charged side chains borne by the monomers. Replacing a few, sometimes only two, charged side chains by neutral methoxy groups was shown to trigger the formation of various aggregates which could be tentatively assigned to head-to-head stacked dimers of single helices, double helical duplexes and a quadruplex, none of which would form in organic solvent with organic-soluble analogues. The nature of the aggregates was supported by concentration and solvent dependent NMR studies, 1H DOSY experiments, mass spectrometry, and X-ray crystallography or energy-minimized models, as well as analogies with earlier studies. The hydrophobic effect appears to be the main driving force for aggregation but it can be finely modulated by the presence or absence of a small number of charges to an extent that had no precedent in aromatic foldamer architectures. These results will serve as a benchmark for future foldamer design in water.


Glutathione S-transferase Polymorphisms in Head and Neck Squamous Cell Carcinoma Treated with Chemotherapy and/or Radiotherapy.
The Glutathione S-transferases (GSTs) are important carcinogen-metabolizing enzymes. Polymorphisms involved in these enzymes can modulate the development and treatment of head and neck cancer. To investigate the association of GSTs polymorphisms with head and neck cancer and risk factors, clinical-pathological features, and survival time of the patients treated with chemotherapy and/or radiotherapy. The GST gene polymorphisms were evaluated in 197 cases and 514 controls by PCR-RFLP-Polymerase Chain Reaction Restriction Fragment Length Polymorphism. The GSTP-313 was associated with a decreased risk for HNSCC (p=0.050). The GSTP1 haplotype analysis revealed a higher frequency of the AC and AT haplotypes in the case group than in the control group (p=0.013 and p=0.019, respectively), and the opposite for G-C haplotype (p = 0.015). Yet, the different combinations between the genotypes were associated with an increased risk of cancer. The study showed no association between the polymorphisms and primary tumor site, clinical-pathological characteristics, treatment (chemotherapy and/or radiotherapy) and survival time of the patients. The GST polymorphisms combination showed an increased risk for carcinogenesis, and studies with larger casuistry can contribute to the clarification of the role in individual patient differences for the response to chemotherapy and/or radiotherapy and identify biomarkers of susceptibility.


Multicentre study of a new test for TSH-screening in blood spots.
A multicentre study for the detection of congenital hypothyroidism by enzyme-immunoassay of thyrotropin in filter paper blood spots is described. The method is accurate, with good precision and adequate sensitivity. No interference due to common blood constituents has been observed. Moreover, the TSH determination can easily be performed by photometric measurement of enzyme activity. Large series of samples can be processed by automation using common laboratory analysers. Values show good agreement with those obtained by RIA methods. We present a method for screening for congenital hypothyroidism which can be performed in all clinical laboratories.


[Predictive criteria of early recurrence of atrial arrhythmia after reduction by electrical cardioversion].
The management of atrial arrhythmias aims not only to restore sinus rhythm but also to maintain it. Ten to thirty per cent of patients have early recurrence of atrial arrhythmias, the treatment of which remains empiric. The aim of this study was to define factors predictive of early recurrence of atrial arrhythmias and the consequences on the length of hospital stay. A series of 131 patients who underwent reduction of atrial arrhythmias by electrical cardioversion was studied retrospectively. A recurrence within 24 hours was observed in 12.2% of the patients. These recurrences significantly increased the length of hospital stay (6.8+/-6.3 versus 3.6+/-3.8 days, p=0.005). This study confirms two previously reported results with respect to more long-term recurrences. In the "early recurrence" group, the duration of the atrial arrhythmia was longer (p=0.003) and there were fewer treatments with amiodarone (p=0.03). In addition, original results were obtained. In the "early recurrence" group, the patients were more often treated with furosemide (p=0.02), class Ic antiarrhythmics (p=0.007) or anaesthetised with thiopental (p=0.002) than patients without early recurrences. Experimental data explain these results. However, they require confirmation by a prospective randomised trial.


Separation and analysis of triazine herbcide residues by capillary electrophoresis.
Triazines are widely used in agriculture around the world as selective pre- and post-emergence herbicides for the control of broad leaf and grassy weeds. With high toxicity and persistence, triazines can contaminate the environment and crops, so the development of rapid and sensitive methods for the determination of different triazines is necessary. Capillary electrophoresis comprises a group of techniques used to separate chemical mixtures. Analytical separation is based on different electrophoretic mobilities. This review focuses on the analysis of triazine herbicides with different modes of capillary electrophoresis, including capillary zone electrophoresis, micellar electrokinetic capillary electrophoresis, capillary electrochromatography and nonaqueous capillary electrophoresis. Determinations of triazines in various matrices such as surface water, groundwater, vegetables, soil and grains are emphasized.


Application of one-step inner-recycling counter-current chromatography for the preparative separation and purification of chemical constituents from the rhizome of Bergenia ciliate (haw.) Sternb.
Bergenia ciliata (haw.) Sternb, the renowned pharmaceutical plant in Jammu and Kashmir of Pakistan, is widely applied in treating different illnesses including diabetes, diarrhea, and vomiting. This work employed an efficient one-step inner-recycling counter-current chromatography for preparative separating and purifying compounds with similar partition coefficients from the rhizome of Bergenia ciliate (haw.). Five compounds, including quercetin rhamnodiglucoside (1), quercetin-3-O-rutinoside (2), bergenine (3), kaempferol (4), and palmatic acid (5), were successfully separated using the optimized biphasic solvent system that contained ter-butylmetylether/n-butanol/acetonitrile/water (2:2:1:5, v/v) with the purities over 98%. Mass spectrometry and nuclear magnetic resonance were conducted for structural identification. As a result, our proposed strategy might be applied in separating compounds with similar partition coefficients, which was advantageous with regard to the less solvent and time consumption, and the increased number of theoretical plates.


Combination Treatment of Perioperative Rehabilitation and Psychoeducation Undergoing Thoracic Surgery.
Postoperative pulmonary complications are a risk associated with thoracic surgery. However, there have been few reports on cases at high risk of postoperative complications. Cancer patients often have negative automatic thoughts about illness, and these negative automatic thoughts are associated with reduced health behavior and physical activity. This case series demonstrates the successful combination treatment of perioperative rehabilitation and psychoeducation for negative automatic thoughts in two cancer patients who underwent thoracic surgery. One patient underwent pneumonectomy with laryngeal recurrent nerve paralysis; the other patient, who had a history of recurrent hepatic encephalopathy and dialysis, underwent S6 segmentectomy. Both patients had negative automatic thoughts about cancer-related stress and postoperative pain. The physical therapists conducted a perioperative rehabilitation program in which the patients were educated to replace their maladaptive thoughts with more adaptive thoughts. After rehabilitation, the patients had improved adaptive thoughts, increased physical activity, and favorable recovery without pulmonary complications. This indicates that the combination treatment of perioperative rehabilitation and psychoeducation was useful in two thoracic cancer surgery patients. The psychoeducational approach should be expanded to perioperative rehabilitation of patients with cancer.


High-sensitivity hybridization assay for quantitation of residual E. coli DNA.
Impurity assays for recombinant protein therapeutics are essential to ensure batch-to-batch consistency and to meet the FDA's criteria for a well-characterized biopharmaceutical. For determination of residual host cell DNA, membrane hybridization assays utilizing radiolabeled DNA probes prepared from the host cell's genomic DNA have traditionally been used for products derivedfrom bacterial expression systems to obtain the required low picogram sensitivity. Nonradioactive methods, while desirable to eliminate radioactive waste disposal and safety issues, typically suffer from poor sensitivity and high backgrounds. We report the development of a suitably sensitive, nonradioactive assay to quantitate residual E. coli DNA levels in purified protein drugs by means of a slot-blot hybridization method. The assay utilizes digoxigenin-labeled E. coli DNA probes and SuperSignal chemiluminescent substrate. The optimized chemiluminescent hybridization assay has both low background and high sensitivity, allowing routine detection of 2.5 pg E. coli DNA. The method can be tailored for detection/quantitation of DNA contamination in recombinant protein products expressed in E. coli or other bacterial expression systems.


Novel IRAK Degraders for Treating Cancer.
Provided herein are novel compounds used as IRAK4 degraders, their pharmaceutical compositions, the use of such compounds in treating cancer, and processes for preparing such compounds.


Low-power ultrasounds as a tool to culture human osteoblasts inside cancellous hydroxyapatite.
Bone graft substitutes and cancellous biomaterials have been widely used to heal critical-size long bone defects due to trauma, tumor resection, and tissue degeneration. In particular, porous hydroxyapatite is widely used in reconstructive bone surgery owing to its biocompatibility. In addition, the in vitro modification of cancellous hydroxyapatite with osteogenic signals enhances the tissue regeneration in vivo, suggesting that the biomaterial modification could play an important role in tissue engineering. In this study, we have followed a tissue-engineering strategy where ultrasonically stimulated SAOS-2 human osteoblasts proliferated and built their extracellular matrix inside a porous hydroxyapatite scaffold. The ultrasonic stimulus had the following parameters: average power equal to 149 mW and frequency of 1.5 MHz. In comparison with control conditions, the ultrasonic stimulus increased the cell proliferation and the surface coating with bone proteins (decorin, osteocalcin, osteopontin, type-I collagen, and type-III collagen). The mechanical stimulus aimed at obtaining a better modification of the biomaterial internal surface in terms of cell colonization and coating with bone matrix. The modified biomaterial could be used, in clinical applications, as an implant for bone repair.


Mucosal plication (Gant-Miwa procedure) with anal encircling for rectal prolapse--a review of the Japanese experience.
Although mucosal plication for rectal prolapse, known as the Gant-Miwa procedure, is described in some English textbooks, it has been infrequently performed in the West. However, this procedure has been used and developed in conjunction with anal encircling in Japan since the 1960s and is still considered to play a major role in the treatment of rectal prolapse. Certain technical details have been found necessary to ensure the success of the procedure, especially in the technique of anal encircling. For example, the use of Teflon tape and routing relatively deeply and outside the external anal sphincter are necessary. Clinical results show a recurrence rate of 0 to 31 percent with no mortality and almost never any serious complications such as significant bleeding or severe sepsis, which are occasionally encountered in other perineal procedures. Most patients report improved continence after this procedure, and worsening of evacuation is rarely encountered based on our experience. Some physiologic studies have shown improved resting pressure and rectal sensation, which can have a positive influence on the defecatory function. We believe that the Gant-Miwa procedure with anal encircling should be considered as a treatment of choice among perineal procedures for rectal prolapse.


Strain-induced substitutional lability in a Ru(II) complex of a hypodentate polypyridine ligand.
The ruthenium(II) complex of heptadentate N,N,N',N'-tetrakis(2-pyridylmethyl)-2,6-bis(aminomethyl)pyridine (tpap) was isolated as the hexafluorophosphate complex Ru(tpap)(PF6)2. The crystal structure has been determined for the triflate salt Ru(tpap)(CF3SO3)2.2H2O, which crystallizes in the monoclinic space group P2(1)/n. The structure was refined to a final R value of 0.0549 for 5894 observed reflections. The heptadentate ligand coordinates with six nitrogens, i.e. with two tertiary nitrogens and four pyridine nitrogens, one of the pyridines remaining un-coordinated. The resulting structure is significantly distorted from octahedral geometry with an equatorial Nsp3-Ru-Npyridine angle of 120 degrees. The consequence of the above steric strain is a labilization of the system and fluxional behaviour involving exchange between equatorially coordinated and non-coordinated pyridines has been observed by 1H NMR for Ru(tpap)(PF6)2 in d6-acetone solution. The activation parameters of DeltaG(not equal to 298) = 53 kJ mol(-1), DeltaH(not equal) = 56 +/- 1 kJ mol(-1) and DeltaS(not equal) = -10 +/- 3 J mol(-1) K(-1) were determined on the basis of NMR experiments. In addition electronic structure calculations applying density functional theory (DFT) have been performed in order to identify a transition state and to estimate the activation barrier. On the basis of NMR and DFT results the mechanism of isoexchange involving a hepta-coordinated intermediate has been proposed.


Isolation and analysis of plant RNA-dependent RNA polymerases.
RNA-dependent RNA polymerases (RDRPs) are encoded by RNA viruses as well as eukaryotic organisms such as plants. The function of these cellular RDRPs has been associated with the synthesis of short interfering RNAs (siRNAs), which are essential regulators of genomic integrity and plant viral defense. The multiple gene copies, and functional diversities, of the plant RDRPs raise the question of whether their intrinsic properties differ. This chapter describes protocols to extract and test in vitro, the activity of plant RDRPs.


The Francis Crick Institute.
The Francis Crick Institute Laboratory, opened in 2016, is supported by the Medical Research Council, Cancer Research UK, the Wellcome Trust, and University College London, King's College London and Imperial College London. The emphasis on research training and early independence of gifted scientists in a multidisciplinary environment provides unique opportunities for UK medical science, including clinical and translational research.


Nursing considered as moral practice: a philosophical-ethical interpretation of nursing.
Discussions of ethical approaches in nursing have been much enlivened in recent years, for instance by new developments in the theory of care. Nevertheless, many ethical concepts in nursing still need to be clarified. The purpose of this contribution is to develop a fundamental ethical view on nursing care considered as moral practice. Three main components are analyzed more deeply -- i.e., the caring relationship, caring behavior as the integration of virtue and expert activity, and "good care" as the ultimate goal of nursing practice. For the development of this philosophical-ethical interpretation of nursing, we have mainly drawn on the pioneering work of Anne Bishop and John Scudder, Alasdair MacIntyre, Lawrence Blum, and Louis Janssens. We will also show that the European philosophical background offers some original ideas for this endeavor.


Control of rubella and congenital rubella syndrome (CRS) in developing countries, Part 2: Vaccination against rubella.
In 1995-96 we conducted a review of rubella immunization strategies. Worldwide, 78 countries (more than one-third) reported a national policy of using rubella vaccine. This was closely related to country economic status. Based on the United Nations country classification, rubella vaccine is used in 92% of industrialized countries, 36% of those with economies-in-transition, and 28% of developing countries. Cases of congenital rubella syndrome (CRS) may be prevented as follows: by providing direct protection to women and/or schoolgirls (a selective vaccination strategy); by vaccinating boys and girls to provide indirect protection by reducing the transmission of rubella virus (a childhood vaccination strategy); or by a combination of these approaches (a combined strategy). A combined strategy was most commonly reported (60% of countries); seven countries (9%) reported a selective strategy; and 24 countries (31%) reported only childhood immunization. Experience has shown that it is essential to include vaccination of women of childbearing age in any rubella control strategy. Childhood vaccination alone may pose a risk of an increase in CRS cases. Although many countries have introduced rubella vaccine, few report any data on the impact of vaccination. Countries using rubella vaccine need to establish surveillance for rubella and CRS and monitor coverage in each of the target groups.


Three-phase interlines electrochemically driven into insulator compounds: a penetration model and its verification by electroreduction of solid AgCl.
A dynamic three-phase interline model has been developed for the reduction of a solid insulating metal compound to the metal in a suitable electrolyte, focusing on the electrochemically driven penetration of the process (or the three-phase interlines) into the insulator. Consideration is given to the effects of electrochemical, concentration and ohmic polarizations in the reduction-generated porous metal layer on top of the solid compound. Under potentiostatic conditions, reduction in the depth direction (penetration) becomes progressively slower as a result of the rising ohmic and concentration polarizations, whilst the electrochemical polarization exerts a declining effect. The quantitative equations established here also provide simple methods for the determination of some kinetic parameters of the reduction process, including rho (total resistivity) and D(R) (diffusion coefficient). The model has been experimentally verified by electrochemical reduction of solid AgCl with two novel metal|AgCl cylinder electrodes in aqueous solutions.


The Posterior Condylar Offset Ratio.
Posterior Condylar Offset is an area of interest in knee arthroplasty research and clinical outcome. The aim of the study is to define a quantifiable Posterior Condylar Offset Ratio, a normal value for this ratio and to confirm its reproducibility on pre-operative radiographs. We propose a new Posterior Condylar Offset Ratio which is defined as the maximal thickness of the posterior condyle projecting posteriorly to a straight line drawn as the extension of the posterior femoral shaft cortex, divided by the maximal thickness of the posterior condyle projecting posterior to a straight line drawn as the extension of the anterior femoral shaft cortex on a true lateral radiograph of the distal quarter of the femur. We have measured this on 100 true lateral radiographs (50 females, 50 males, and mean age 65 years). The mean ratio was 0.44 (SD 0.02) and was shown to have good reproducibility (intra-observer error 0.899 and inter-observer error 0.882. The ratio was also very consistent between male and female patients (0.44 (SD 0.02) for the males and 0.45 (SD 0.02) for the females). Adjusting the ratio for reported posterior condyle articular cartilage thickness increased the ratio to 0.47 (SD 0.02). We suggest our Posterior Condylar Offset Ratio is a useful tool to aid further research in this area of knee arthroplasty and propose a normal value of 0.44 on radiographs and 0.47 on post-operative knee arthroplasty radiographs.


Comparison of the chlorine inactivation of Yersinia enterocolitica in chlorine demand and demand-free systems.
Inactivation of Yersinia enterocolitica by chlorine (0.6 to 20 ppm) was investigated in distilled water and in tryptic soy broth (TSB, 0.015%) at different temperatures (4, 20, and 40 degrees C). In distilled water, chlorine inactivation of Y. enterocolitica was enhanced by increasing the temperature from 4 to 20 degrees C, and survival curves were described by a model that assumed first-order kinetics followed by tailing in which the microbial concentration remained constant. The presence of TSB increased chlorine resistance of Y. enterocolitica, and survival curves were concave downward. These survival curves were described by a model based on the Weibull distribution. Chlorine decay in distilled water was independent of temperature and of the initial concentration of available chlorine and was modeled by first-order reaction kinetics. Chlorine decay in TSB was independent of the initial chlorine concentration but depended on the treatment temperature and was modeled by the addition of two first-order decay equations. The increased resistance of Y. enterocolitica to chlorine in TSB was not due only to the chlorine demand by the TSB components. These components protected Y. enterocolitica cells from the antimicrobial effect of chlorine.


Effect of an intervention in storm drains to prevent Aedes aegypti reproduction in Salvador, Brazil.
Aedes aegypti, the principal vector for dengue, chikungunya and Zika viruses, is a synanthropic species that uses stagnant water to complete its reproductive cycle. In urban settings, rainfall water draining structures, such as storm drains, may retain water and serve as a larval development site for Aedes spp. reproduction. Herein, we describe the effect of a community-based intervention on preventing standing water accumulation in storm drains and their consequent infestation by adult and immature Ae. aegypti and other mosquitoes. Between April and May of 2016, local residents association of Salvador, Brazil, after being informed of water accumulation and Ae. aegypti infestation in the storm drains in their area, performed an intervention on 52 storm drains. The intervention consisted of placing concrete at the bottom of the storm drains to elevate their base to the level of the outflow tube, avoiding water accumulation, and placement of a metal mesh covering the outflow tube to avoid its clogging with debris. To determine the impact of the intervention, we compared the frequency at which the 52 storm drains contained water, as well as adult and immature mosquitoes using data from two surveys performed before and two surveys performed after the intervention. During the pre-intervention period, water accumulated in 48 (92.3%) of the storm drains, and immature Ae. aegypti were found in 11 (21.2%) and adults in 10 (19.2%). After the intervention, water accumulated in 5 (9.6%) of the storm drains (P < 0.001), none (0.0%) had immatures (P < 0.001), and 3 (5.8%) contained adults (P = 0.039). The total number of Ae. aegypti immatures collected decreased from 109 to 0 (P < 0.001) and adults decreased from 37 to 8 (P = 0.011) after the intervention. Collection of immature and adult non-Aedes mosquitoes (mainly Culex spp.) in the storm drains also decreased after the intervention. This study exemplifies how a simple intervention targeting storm drains can result in a major reduction of water retention, and, consequently, impact Ae. aegypti larval populations. Larger and multi-center evaluations are needed to confirm the potential of citywide structural modifications of storm drains to reduce Aedes spp. infestation level.


AMPA receptors control fear extinction through an Arc-dependent mechanism.
Activity-regulated cytoskeleton-associated protein (Arc) supports fear memory through synaptic plasticity events requiring actin cytoskeleton rearrangements. We have previously shown that reducing hippocampal Arc levels through antisense knockdown leads to the premature extinction of contextual fear. Here we show that the AMPA receptor antagonist CNQX elevates hippocampal Arc levels during extinction and blocks extinction that can be rescued by reducing Arc. Increasing Arc levels with CNQX also overcomes the actin-destabilizing properties of cytochalasin D and promotes extinction. Therefore, extinction is dependent on AMPA-mediated reductions of Arc via a mechanism consistent with a role for Arc in stabilizing the actin cytoskeleton to constrain extinction.


A Volterra series-based method for extracting target echoes in the seafloor mining environment.
The purpose of this research was to evaluate the applicability of the Volterra adaptive method to predict the target echo of an ultrasonic signal in an underwater seafloor mining environment. There is growing interest in mining of seafloor minerals because they offer an alternative source of rare metals. Mining the minerals cause the seafloor sediments to be stirred up and suspended in sea water. In such an environment, the target signals used for seafloor mapping are unable to be detected because of the unavoidable presence of volume reverberation induced by the suspended sediments. The detection of target signals in reverberation is currently performed using a stochastic model (for example, the autoregressive (AR) model) based on the statistical characterisation of reverberation. However, we examined a new method of signal detection in volume reverberation based on the Volterra series by confirming that the reverberation is a chaotic signal and generated by a deterministic process. The advantage of this method over the stochastic model is that attributions of the specific physical process are considered in the signal detection problem. To test the Volterra series based method and its applicability to target signal detection in the volume reverberation environment derived from the seafloor mining process, we simulated the real-life conditions of seafloor mining in a water filled tank of dimensions of 5×3×1.8m. The bottom of the tank was covered with 10cm of an irregular sand layer under which 5cm of an irregular cobalt-rich crusts layer was placed. The bottom was interrogated by an acoustic wave generated as 16μs pulses of 500kHz frequency. This frequency is demonstrated to ensure a resolution on the order of one centimetre, which is adequate in exploration practice. Echo signals were collected with a data acquisition card (PCI 1714 UL, 12-bit). Detection of the target echo in these signals was performed by both the Volterra series based model and the AR model. The results obtained confirm that the Volterra series based method is more efficient in the detection of the signal in reverberation than the conventional AR model (the accuracy is 80% for the PIM-Volterra prediction model versus 40% for the AR model).


Deep-tissue photoacoustic tomography of Förster resonance energy transfer.
Förster resonance energy transfer (FRET) is a distance-dependent process that transfers excited state energy from a donor molecule to an acceptor molecule without the emission of a photon. The FRET rate is determined by the proximity between the donor and the acceptor molecules; it becomes significant only when the proximity is within several nanometers. Therefore, FRET has been applied to visualize interactions and conformational changes of biomolecules, such as proteins, lipids, and nucleic acids that cannot be resolved by optical microscopy. Here, we report photoacoustic tomography of FRET efficiency at a 1-cm depth in chicken breast tissue, whereas conventional high-resolution fluorescence imaging is limited to <0.1 cm. Photoacoustic tomography is expected to facilitate the examination of FRET phenomena in living organisms.


Leg crossing with muscle tensing, a physical counter-manoeuvre to prevent syncope, enhances leg blood flow.
In patients with orthostatic intolerance, the mechanisms to maintain BP (blood pressure) fail. A physical counter-manoeuvre to postpone or even prevent orthostatic intolerance in these patients is leg crossing combined with muscle tensing. Although the central haemodynamic effects of physical counter-manoeuvres are well documented, not much is known about the peripheral haemodynamic events. Therefore the purpose of the present study was to examine the peripheral haemodynamic effects of leg crossing combined with muscle tensing during 70 degrees head-up tilt. Healthy subjects (n=13) were monitored for 10 min in the supine position followed by 10 min in 70 degrees head-up tilt and, finally, for 2 min of leg crossing with muscle tensing in 70 degrees head-up tilt. MAP (mean arterial BP), heart rate, stroke volume, cardiac output and total peripheral resistance were measured continuously by Portapres. Leg blood flow was measured using Doppler ultrasound. Leg vascular conductance was calculated as leg blood flow/MAP. A significant increase in MAP (13 mmHg), stroke volume (27%) and cardiac output (18%), a significant decrease in heart rate (-5 beats/min) and no change in total peripheral resistance during the physical counter-manoeuvre were observed when compared with baseline 70 degrees head-up tilt. A significant increase in leg blood flow (325 ml/min) and leg vascular conductance (2.9 arbitrary units) were seen during the physical counter-manoeuvre when compared with baseline 70 degrees head-up tilt. In conclusion, the present study indicates that the physical counter-manoeuvre of leg crossing combined with muscle tensing clearly enhances leg blood flow and, at the same time, elevates MAP.


Evolution of the Shanghai city region 1978-1998: an analysis of indicators.
Building on a description of the present situation in Shanghai, a series of ten regionally relevant indicators are identified and described. Using data from 1978-1998, relationships between these economic, social and environmental indicators are explored using correlation and regression analysis. The analysis indicated that, in Shanghai, conflict between economy and environment existed throughout the research period and the evolution of the city region system seems to lack regularity. The key elements affecting trends in the development of the Shanghai city region are Gross Domestic Product, Total Investment and Urban Living Area per Head. The city region system seemed more sustainable, indicated by an improvement in environmental quality and relative lower investment growth rate, when the annual change rate of Gross Domestic Product was less than 7-8%.


Hepatitis B vaccine birthdose practices in a country where hepatitis B is endemic - Laos, December 2011-February 2012.
Chronic hepatitis B virus (HBV) infection causes approximately 325,000 deaths from cirrhosis and liver cancer each year in the Western Pacific Region of the World Health Organization (WHO). With an estimated infection prevalence of >8%, HBV is considered highly endemic in Laos and is most commonly transmitted from mother to child during birth and early childhood. A hepatitis B vaccine birth dose (HepB-BD) is needed to prevent mother-to-child HBV transmission. To assess gaps in coverage and identify possible remedies for improvement of coverage, during the 3-month period December 2011-February 2012, the Laos Ministry of Health and WHO staff members surveyed 37 health facilities in five provinces in Laos, inquiring about HepB-BD knowledge and practices among health-care providers and estimating HepB-BD coverage provided by the facilities. For facility-based births, the median HepB-BD coverage was 74% (interquartile range: 39%-97%). Hepatitis B vaccine was not in stock at 18 (49%) of the 37 facilities on the day they were visited. Of the 37 facilities, 17 (46%) assisted with home births, and 23 (62%) conducted postnatal home visits. Of the 17 facilities that assisted with home births, seven (41%) included HepB-BD vaccination as part of the service; of the 23 that conducted postnatal home visits, 15 (65%) provided HepB-BD as part of the visit. However, among those reporting that they provided these outreach services, only 48 births were recorded as attended, and only 81 postnatal visits were recorded as conducted during the 3-month period. Health facilities can help prevent mother-to-child HBV transmission in Laos by ensuring vaccine availability, vaccinating all infants born in the facility, and enhancing outreach services for home births.


Pregnancy and nasopharyngeal carcinoma: a prognostic evaluation of 27 patients.
In order to study the influence of pregnancy on the prognosis of nasopharyngeal carcinoma (NPC), we have retrospectively studied 27 patients who either were discovered to be pregnant during radiotherapy (9 patients, herein abbreviated as concurrent group) or became pregnant after treatment (18 patients, herein abbreviated as subsequent group). This material was collected from the 811 NPC patients treated in our hospital from March 1958 to 1972. The results obtained are presented as follows: Concurrent pregnancy had a disastrous effect on the prognosis of NPC patients giving a five year survival of only 11% (1/9). Of the eight patients who died, six did so within one year of the treatment, five of whom died of distant metastases. This fatal outcome was not altered by any measure we instituted. This adverse influence was not observed in the subsequent group, yet the time of gestation seemed to be relevant to the prognosis. Two of the three patients who became pregnant within one year of the treatment died of disease, those who became pregnant beyond the second year after irradiation had the best prognosis. All seven patients who became pregnant after the second year of treatment survived. The frequency of pregnancy did not influence the prognosis of patients if the conception occurred beyond the second year in the subsequent group. All the five patients who gave birth to two, three or even four children survived for more than five years without any evidence of tumor. A total of 21 children were born to the patients of these two groups. They have been followed regularly for 10 to 20 years. No deformity, or retardation in growth or mentality was discovered, nor was there any evidence of radiation tumor or leukemia observed.


Age at marriage and fertility in Taiwan.
"This study is concerned with the effects of age at marriage on fertility in Taiwan, with the primary objective of understanding the nature and causes of the recent upsurge of the...birth rate." Data are taken from the population register for the period 1975 to 1978 and from two fertility surveys undertaken in 1967 and 1976. It is found that the increase in the birth rate between 1975 and 1978 was primarily due to a large increase in the proportion and number of women aged 25 to 29. It was also due, in part, to an increase in the age at marriage. The effects of shifts in marriage duration, improved fecundability, and increases in premarital pregnancy are also considered. The author suggests that a further decline in fertility is unlikely in the near future unless there are changes in traditional family values, son preference, and number of children desired. (summary in CHI)


Insecticide resistance and malaria vector control: the importance of fitness cost mechanisms in determining economically optimal control trajectories.
The evolutionary dynamics of insecticide resistance in harmful arthropods has economic implications, not only for the control of agricultural pests (as has been well studied), but also for the control of disease vectors, such as malaria-transmitting Anopheles mosquitoes. Previous economic work on insecticide resistance illustrates the policy relevance of knowing whether insecticide resistance mutations involve fitness costs. Using a theoretical model, this article investigates economically optimal strategies for controlling malaria-transmitting mosquitoes when there is the potential for mosquitoes to evolve resistance to insecticides. Consistent with previous literature, we find that fitness costs are a key element in the computation of economically optimal resistance management strategies. Additionally, our models indicate that different biological mechanisms underlying these fitness costs (e.g., increased adult mortality and/or decreased fecundity) can significantly alter economically optimal resistance management strategies.


Observing others: multiple action representation in the frontal lobe.
Observation of actions performed by others activates monkey ventral premotor cortex, where action meaning, but not object identity, is coded. In a functional MRI (fMRI) study, we investigated whether other monkey frontal areas respond to actions performed by others. Observation of a hand grasping objects activated four frontal areas: rostral F5 and areas 45B, 45A, and 46. Observation of an individual grasping an object also activated caudal F5, which indicates different degrees of action abstraction in F5. Observation of shapes activated area 45, but not premotor F5. Convergence of object and action information in area 45 may be important for full comprehension of actions.


Efficacy of Comedy on Health-Related Quality of Life and Oxidative Stress in Cancer Survivors.
Cancer survivors have reduced health-related quality of life (HRQOL) due to impaired daily functioning. In addition, daily stress leads to worsening oxidative stress. The purpose of this study is to investigate the efficacy of laughter therapy on HRQOL and oxidative stress in cancer survivors. This before-and-after study asked cancer survivors to watch a 15-minute or longer comedy video over a four-week period to assess the Functional Assessment of Cancer Therapy-General (FACT-G), EuroQOL 5 dimension 3-level (EQ-5D-3L), Hospital Anxiety and Depression Scale (HADS), biological Antioxidant Potential (BAP), Reactive Oxygen Metabolites-derived compounds (d-ROMs), Oxidative Stress Index (OSI), and the antioxidant/oxidative stress ratio. The nonparametric Friedman test showed significant increases from baseline in FACT-G and EQ-VAS scores and significant decreases in HADS-Anxiety and HADS-Depression scores. Post hoc analyses showed that these items commonly differed significantly at baseline versus three and four weeks after Bonferroni correction. T-test results in the biological analysis revealed small and moderate effects with significant differences in BAP (p < 0.01, d = 0.49), OSI (p = 0.03, d = 0.33), and BAP/d-ROMs (p < 0.01, d = 0.51). These results suggest that daily comedy viewing may be an effective intervention to improve quality of life and antioxidant capacity in cancer survivors. Considering its safety, convenience, and low cost, it should be considered a high-value intervention for cancer survivors.


Long-term follow-up analysis after rituximab therapy in children with refractory symptomatic ITP: identification of factors predictive of a sustained response.
We report the long-term follow-up (median 39.5 months) of 49 paediatric patients (33 females and 16 males) with refractory symptomatic immune thrombocytopenic purpura (ITP) treated with rituximab. The overall response rate was 69% (34/49 patients). Twenty-one responders had a platelet count >50 x 10(9)/l at a median 20.2 months from treatment. Kaplan-Meier analysis showed a probability of relapse-free survival (RFS) of 60% at 36 months from the first rituximab infusion. The number of infusions and a previous splenectomy did not influence overall response rate. Patients who achieved complete response were significantly older at diagnosis and first rituximab infusion than partial responders (P = 0.027). Older children displayed a significantly greater probability of sustained response (RFS) at 36 months than younger children (88.9% vs. 56.7%, P = 0.037). Earlier responses (within 20 d from treatment) were significantly associated with both complete (P = 0.004) and sustained response (P = 0.002). Only mild and transient side-effects were observed in 9/49 children; no major infections nor delayed toxicities were recorded during the follow-up.


Saccadic Impairments in Patients with the Norrbottnian Form of Gaucher's Disease Type 3.
Chronic neuronopathic Gaucher's disease type 3 (GD3) is relatively frequent in northern Sweden. Besides multiple other neurological symptoms, horizontal gaze palsy or oculomotor apraxia is common in GD3. To characterize the saccades in patients with Norrbottnian GD3 with respect to their neurological and cognitive status using a computer-based eye-tracking technique. Horizontal and vertical reflexive saccades as well as antisaccades of nine GD3 patients [4M/5F; 41.1 ± 11.0 years; modified severity scoring tool (mSST): 9.3 ± 5.4; Montreal Cognitive Assessment (MoCA): 24.0 ± 4.2] and age-matched controls were analyzed using EyeBrain T2, a head-mounted binocular eye tracker. Systematic clinical assessment included the mSST, a valid tool for monitoring the neurological progression in GD3 and MoCA. In Norrbottnian GD3 patients, gain, peak, and average velocity (107.5°/s ± 41.8 vs. 283.9°/s ± 17.0; p = 0.0009) of horizontal saccades were reduced compared to healthy controls (HCs). Regarding vertical saccades, only the average velocity of downward saccades was decreased (128.6°/s ± 63.4 vs. 244.1°/s ± 50.8; p = 0.004). Vertical and horizontal saccadic latencies were increased (294.3 ms ± 37.0 vs. 236.5 ms ± 22.4; p = 0.005) and the latency of horizontal reflexive saccades was correlated with the mSST score (R2 = 0.80; p = 0.003). The latency of antisaccades showed association to MoCA score (R2 = 0.70; p = 0.009). GD3 patients made more errors in the antisaccade task (41.5 ± 27.6% vs. 5.2 ± 5.8%; p = 0.005), and the error rate tended to correlate with the cognitive function measured in MoCA score (p = 0.06). The mean age of 41 years of our GD3 cohort reflects the increased life expectancy of patients in the Norrbottnian area compared to other GD3 cohorts. Marked impairment of horizontal saccades was evident in all patients, whereas vertical saccades showed distinct impairment of downward velocity. Latency of reflexive saccades was associated with the severity of neurological symptoms. Increased latency and error rate in the antisaccade task were linked to cognitive impairment. The assessment of saccades provides markers for neurological and neuropsychological involvement in Norrbottnian GD3.


Remote meta-C-H olefination of phenylacetic acids directed by a versatile U-shaped template.
meta-C-H olefination of phenylacetic acid derivatives has been achieved using a commercially available nitrile-containing template. The identification of N-formyl-protected glycine as the ligand (Formyl-Gly-OH) was crucial for the development of this reaction. Versatility of the template approach in accommodating macrocyclopalladation processes with different ring sizes is demonstrated.


[Clinical research of chronic pelvic cavity pain syndrome treated with acupoint catgut embedding therapy].
To explore the clinical efficacy of acupoint catgut embedding therapy on chronic pelvic cavity pain syndrome differentiated as kidney deficiency and stagnation of damp heat, and explore the impacts on plasma P substance (SP), plasma beta-endorphin (β-EP). One hundred and eighty cases were randomly divided into a catgut embedding group (90 cases) and a western medication group (90 cases). In the western medication group, tamsulosin capsules 0. 2 mg were prescribed for oral administration, once a day; indometacin sustained release tablets, 25 mg, three times a day. Totally, the oral administration for 8 weeks was required. In the catgut embedding group, the acupoint catgut embedding therapy was applied to Qugu (CV 2), Shenshu (BL 23), Zhibian (BL 54), Huiyin (CV 1) and Sanyinjiao (SP 6), once every two weeks; the treatment of 4 weeks made one session, and two sessions were required. Before and after treatment, TCM symptom score, NIH-CPSI (the National Institute of Health Chronic Prostatitis Symptom Index) score, lecithin body numbers in prostatic fluid, score in SAS (self-rating anxiety scale), score in SDS (self-rating depression scale), the levels of SP and β-EP, etc. were observed in the two groups, and the clinical efficacy was assessed in the two groups. (1) Ten cases were dropped in either group. The total effective rate was 91. 25% (73/80) in the catgut embedding group, higher than 78. 75% (63/80) in the western medication group (P<0. 05). (2) After treatment, TCM symptom score, total score in NIH-CPSI, pain score and the scores in SAS and SDS were all reduced as compared with those before treatment in the two groups (all P<0. 05). After treatment, TCM symptom score, total score and pain score in NIH-CPSI, and the scores in SAS and SDS in the catgut embedding group were both lower than those in the western medication group (all P<0. 05). (3) After treatment, the lecithin body numbers were both increased as compared with those before treatment in the two groups (both P<0. 05), and the result in the catgut embedding group was higher than that in the western medication group (P<0. 05). (4)After treatment, the SP level was lower than that before treatment in the two groups (both P<0. 05); the level of p-EP was increased as compared with that before treatment (both P<0. 05). The SP level in the catgut embedding group was lower than that in the western medication group (P<0. 05); the level of β-EP was higher than that in the western medication group (P<0. 05). The acupoint catgut embedding therapy apparently relieves the clinical symptoms of chronic pelvic cavity pain syndrome differentiated as kidney deficiency and stagnation of damp heat as well as the condition of anxiety and depression, increases lecithin body numbers in prostatic fluid and β-EP level and reduces SP level.


Multidisciplinary care of craniosynostosis.
The management of craniosynostosis, especially in the setting of craniofacial syndromes, is ideally done in a multidisciplinary clinic with a team focused toward comprehensive care. Craniosynostosis is a congenital disorder of the cranium, caused by the premature fusion of one or more cranial sutures. This fusion results in abnormal cranial growth due to the inability of the involved sutures to accommodate the growing brain. Skull growth occurs only at the patent sutures, resulting in an abnormal head shape. If cranial growth is severely restricted, as seen in multisuture craniosynostosis, elevation in intracranial pressure can occur. Whereas most patients treated in a multidisciplinary craniofacial clinic have non-syndromic or isolated craniosynostosis, the most challenging patients are those with syndromic craniosynostosis. The purpose of this article was to discuss the multidisciplinary team care required to treat both syndromic and non-syndromic craniosynostosis.


An alternative multipolar expansion for intermolecular potential functions.
We have derived a new multipolar expansion for intermolecular potential-energy functions with applications in molecular physics, theoretical chemistry, and mathematical physics. The new formulation employs a separation of radial and angular terms with a simple index structure that leads to computational efficiency and ease of physical interpretation. For the case of the Coulomb interaction, we compare the present formulation with two conventional multipole expansions: the Cartesian tensor and the irreducible spherical tensor expansions. The new formalism leads to efficient numerical algorithms that are useful for general applications beyond intermolecular potentials. In addition to the electrostatic Coulomb interaction, we illustrate the formalism with applications to special function theory and a bipolar expansion involved in potential theory.


Evolutionary genomics revealed interkingdom distribution of Tcn1-like chromodomain-containing Gypsy LTR retrotransposons among fungi and plants.
Chromodomain-containing Gypsy LTR retrotransposons or chromoviruses are widely distributed among eukaryotes and have been found in plants, fungi and vertebrates. The previous comprehensive survey of chromoviruses from mosses (Bryophyta) suggested that genomes of non-seed plants contain the clade which is closely related to the retrotransposons from fungi. The origin, distribution and evolutionary history of this clade remained unclear mainly due to the absence of information concerning the diversity and distribution of LTR retrotransposons in other groups of non-seed plants as well as in fungal genomes. In present study we preformed in silico analysis of chromodomain-containing LTR retrotransposons in 25 diverse fungi and a number of plant species including spikemoss Selaginella moellendorffii (Lycopodiophyta) coupled with an experimental survey of chromodomain-containing Gypsy LTR retrotransposons from diverse non-seed vascular plants (lycophytes, ferns, and horsetails). Our mining of Gypsy LTR retrotransposons in genomic sequences allowed identification of numerous families which have not been described previously in fungi. Two new well-supported clades, Galahad and Mordred, as well as several other previously unknown lineages of chromodomain-containing Gypsy LTR retrotransposons were described based on the results of PCR-mediated survey of LTR retrotransposon fragments from ferns, horsetails and lycophytes. It appeared that one of the clades, namely Tcn1 clade, was present in basidiomycetes and non-seed plants including mosses (Bryophyta) and lycophytes (genus Selaginella). The interkingdom distribution is not typical for chromodomain-containing LTR retrotransposons clades which are usually very specific for a particular taxonomic group. Tcn1-like LTR retrotransposons from fungi and non-seed plants demonstrated high similarity to each other which can be explained by strong selective constraints and the 'retained' genes theory or by horizontal transmission.


A protocol for the Hearing impairment in Adults: A Longitudinal Outcomes Study (HALOS).
Often considered an "invisible disability", hearing loss is one of the most prevalent chronic diseases and the third leading cause for years lived with disability worldwide. Hearing loss has substantial impacts on communication, psychological wellbeing, social connectedness, cognition, quality of life, and economic independence. The Hearing impairment in Adults: a Longitudinal Outcomes Study (HALOS) aims to evaluate the: (1) impacts of hearing devices (hearing aids and/or cochlear implants), (2) differences in timing of these interventions and in long-term outcomes between hearing aid and cochlear implant users, and (3) cost-effectiveness of early intervention for adult-onset hearing loss among hearing device users. HALOS is a mixed-methods study collecting cross-sectional and longitudinal data on health and social outcomes from 908 hearing aid and/or cochlear implant users aged ≥40 years, recruited from hearing service providers across Australia. The quantitative component will involve an online survey at baseline (time of recruitment), 24-months, and 48-months and will collect audiological, health, psychosocial, functional and employment outcomes using validated instruments. The qualitative component will be conducted in a subset of participants at baseline and involve semi-structured interviews to understand the patient journey and perspectives on the Australian hearing service model. This study has been approved by the Macquarie University Human Research Ethics Committee (ID: 11262) and Southern Adelaide Local Health Network (ID: LNR/22/SAC/88). Dissemination of results: Study findings will be disseminated to participants via a one-page summary, and to the public through publications in peer-reviewed journals and presentations at conferences. Australia New Zealand Clinical Trial Registry (ANZCTR) registration number: ACTRN12622000752763.