A Comparative Study of Intravenous Dexmedetomidine and Intravenous Clonidine for Postspinal Shivering in Patients Undergoing Lower Limb Orthopedic Surgeries.
Dexmedetomidine and clonidine have been used for the prevention and treatment of shivering following spinal blockade. A prospective randomized, double-blinded study was conducted to compare the efficacy and safety of dexmedetomidine and clonidine in controlling postspinal shivering. A total of sixty participants of equal sex, aged between 18 and 60 years of American Society of Anesthesiologists (ASA) I/II Class, who underwent orthopedic lower limb surgeries under spinal anesthesia with ≥Grade III shivering were randomly divided into two groups, Group D (n = 30) received injection dexmedetomidine 0.5 μg/kg and Group C (n = 30) received injection clonidine 1 μg/kg when they experienced shivering. Time taken to control shivering, response rate, recurrence rate, and side effects such as nausea, vomiting, dry mouth, respiratory depression, and deep sedation were observed. The demographic profile, ASA Class, duration of surgery, duration of anesthesia, temperature, onset and grade of shivering were all comparable between the two groups. Time taken to control shivering and recurrence rate were significantly lower in Group D when compared with Group C. Level of sedation was adequate with Group D, and the incidence of hypotension and bradycardia were significantly higher in Group C. The other side effects profiles were comparable between the two groups. Dexmedetomidine 0.5 μg/kg is more efficient than clonidine 1 μg/kg in controlling postspinal blockade shivering. Dexmedetomidine has early onset of effect, high response rate, and less recurrence rate with added advantage of good sedation and stable cardiorespiratory parameters.


Rapid screening of marketed paracetamol tablets: use of thin-layer chromatography and a semiquantitative spot test.
Evaluated is the use of thin-layer chromatography (TLC) to determine the quality of paracetamol tablets marketed in Bangladesh. The procedure was carried out using a cheap and rapid TLC method developed by the U.S. Food and Drug Administration. Reported also is a semiquantitative specific spot test for screening paracetamol tablets. The results obtained indicate that, of the 38 brands tested, three were spurious, while 11 were of borderline quality. In some cases, the results were also verified using the British Pharmacopoeia method. The simplified tests described in this article cannot replace the British Pharmacopoeia or U.S. Pharmacopoeia methods but can be employed as initial screening tests.


Geometrical risk factors for atherosclerosis in the femoral artery: a longitudinal angiographic study.
In order to study the evolution of atherosclerosis in the superficial femoral artery in relation to local factors of vascular geometry, image processing of digitized angiograms was carried out in 237 hyperlipidemic patients before and after a three-year period of lipid-lowering treatment. The degree of atherosclerosis was measured as edge roughness, which was calculated separately for inner curves, outer curves, and straight segments and, in a subgroup of 110 patients, for segments with and without branches on either side of the artery. Initially, inner curves had significantly higher roughness values than outer curves, and outer curves higher than straight segments. After three years, there was an increase of borderline significance in the outer curves, and the difference between inner and outer curves was no longer significant. In several subpopulations, the increase in outer curve roughness was clearly significant. When branched and nonbranched segments were compared, the only significant difference was at the second examination where segments with a lateral branch had higher roughness of the medial edge than those without such a branch. It is concluded that curves are more likely than bifurcations to constitute a geometric risk factor for atherosclerosis, but it remains to explain the causal mechanism for this factor.


Optical waveguide sensor based on a porous anodic alumina/aluminum multilayer film.
An optical waveguide sensor was fabricated by forming a multilayer film made by porous anodic alumina (PAA) and Al layers on a glass substrate. The fabricated sensor system was based on the monitoring of a waveguide coupling mode, which is sensitive to the change in the refractive index of the PAA layer caused by collection of target molecules into the pores of the PAA layer. The PAA/Al multilayer film was formed by partial anodization of an Al film deposited on the glass substrate, and the waveguide coupling mode was examined by measuring angular spectra (reflectivity dependence on the incident angle of monitoring light; green He-Ne laser, 534.5 nm). A deep and sharp waveguide coupling dip was obtained for the PAA/Al multilayer system where the thicknesses of the PAA and Al layers were 200 and 17 nm, respectively. The optical sensor response of the PAA/Al multilayer system was compared to the responses of a surface plasmon resonance (SPR) sensor made by a Au thin film on a SF10 glass substrate. It was inferred that the optical waveguide sensor made by the PAA/Al multilayer could detect a smaller change in the refractive index of a solution, and it provided higher resolution than the SPR sensor. The sensor response for a change in the complex refractive index of the PAA layer was examined next, and it was found that the optical waveguide sensor was sensitive to the change in the imaginary part of the complex refractive index rather than the change in the real part. This result indicated that the sensitivity of the optical waveguide sensor could be improved by using the light absorption of a target compound.


Chondrocyte Polarity During Endochondral Ossification Requires Protein-Protein Interactions Between Prickle1 and Dishevelled2/3.
The expansion and growth of the endochondral skeleton requires organized cell behaviors that control chondrocyte maturation and oriented division. In other organs, these processes are accomplished through Wnt/planar cell polarity (Wnt/PCP) signaling pathway and require the protein-protein interactions of core components including Prickle1 (PK1) and Dishevelled (DVL). To determine the function of Wnt/PCP signaling in endochondral ossification of the cranial base and limb, we utilized the Prickle1Beetlejuice (Pk1Bj ) mouse line. The Pk1Bj allele has a missense mutation in the PK1 LIM1 domain that results in a hypomorphic protein. Similar to human patients with Robinow syndrome, the Prickle1Bj/Bj mouse mutants lack growth plate expansion resulting in shorter limbs and midfacial hypoplasia. Within the Prickle1Bj/Bj limb and cranial base growth plates we observe precocious maturation of chondrocytes and stalling of terminal differentiation. Intriguingly, we observed that the growth plate chondrocytes have randomized polarity based on the location of the primary cilia and the location of PRICKLE1, DVL2, and DVL3 localization. Importantly, mutant PK1Bj protein has decreased protein-protein interactions with both DVL2 and DVL3 in chondrocytes as revealed by in vivo co-immunoprecipitation and proximity ligation assays. Finally, we propose a model where the interaction between the Prickle1 LIM1 domain and DVL2 and DVL3 contributes to chondrocyte polarity and contributes to proximal-distal outgrowth of endochondral elements. © 2021 American Society for Bone and Mineral Research (ASBMR).


Regulation of autoreactive CD4 T cells by FoxO1 signaling in CNS autoimmunity.
Myelin-specific CD4 T effector cells (Teffs), Th1 and Th17 cells, are encephalitogenic in experimental autoimmune encephalomyelitis (EAE), a well-defined murine model of multiple sclerosis (MS) and implicated in MS pathogenesis. Forkhead box O 1 (FoxO1) is a conserved effector molecule in PI3K/Akt signaling and critical in the differentiation of CD4 T cells into T helper subsets. However, it is unclear whether FoxO1 may be a target for redirecting CD4 T cell differentiation and benefit CNS autoimmunity. Using a selective FoxO1 inhibitor AS1842856, we show that inhibition of FoxO1 suppressed the differentiation and expansion of Th1 cells. The transdifferentiation of Th17 cells into encephalitogenic Th1-like cells was suppressed by FoxO1 inhibition upon reactivation of myelin-specific CD4 T cells from EAE mice. The transcriptional balance skewed from the Th1 transcription factor T-bet toward the Treg transcription factor Foxp3. Myelin-specific CD4 T cells treated with the FoxO1 inhibitor were less encephalitogenic in adoptive transfer EAE studies. Inhibition of FoxO1 in T cells from MS patients significantly suppressed the expansion of Th1 cells. Furthermore, FoxO1 inhibition with AS1842856 promoted the development of functional iTreg cells. The immune checkpoint programmed cell death protein-1 (PD-1)-induced Foxp3 expression in CD4 T cells was impaired by FoxO1 inhibition. These data illustrate an important role of FoxO1 signaling in CNS autoimmunity via regulating autoreactive Teff and Treg balance.


Biodegradable vs Nonbiodegradable Cardiac Support Device for Treating Ischemic Cardiomyopathy in a Canine Heart.
Clinical studies of the efficacy of the nonbiodegradable CorCap device have shown inconsistent findings, at least in part, because of device-related impairment of diastolic cardiac function. We hypothesized that use of biodegradable material for the cardiac support device could contribute to an improvement in the diastolic function of the failing heart. Polyglycolic acid and polyethylene terephthalate were used to prepare biodegradable and nonbiodegradable cardiac support devices, respectively. Twelve-month-old beagles underwent anterior coronary artery ligation. One week after, the beagles were randomly assigned for implantation of a biodegradable cardiac support device (n = 7), nonbiodegradable cardiac support device (n = 8), or sham operation (n = 8). Twelve weeks after coronary artery ligation, the biodegradable group showed a significantly greater recovery of echocardiographical ejection fraction than the nonbiodegradable and the sham groups (40% ± 3.3%, 32% ± 2.5%, and 29 ± 2.6%, respectively). Of note, diastolic function, as assessed by Tau, -dp/dt min, and end-diastolic pressure-volume relationship in the cardiac catheter, was significantly better in both left and right ventricles in the biodegradable group than in the nonbiodegradable group. Moreover, global end-systolic wall stress was significantly lower in the 2 device groups than in the sham group (P < 0.03). Furthermore, global end-diastolic wall stress was significantly less in the biodegradable device group than in the nonbiodegradable group (P < 0.02). The cardiac support devices made of biodegradable material were more effective in improving systolic function, with preservation of diastolic function in the canine infarct heart, than devices made of nonbiodegradable material.


Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments.
Pathogenic strains of Helicobacter pylori cause progressive vacuolation and death of epithelial cells. To identify the nature of vacuoles, the distribution of markers of various membrane traffic compartments was studied. Vacuoles derive from the endocytic pathway since they include the fluid-phase marker Lucifer yellow. Early endosome markers such as rab5, transferrin, and transferrin receptor, as well as the lysosomal hydrolase cathepsin D, are excluded from these structures. In contrast, the vacuolar membrane is specifically stained by affinity-purified antibodies against rab7, a small GTPase, localized to late endosomal compartments. The labeling of rab7 on vacuolar membranes increases as vacuolation progresses, without a concomitant increase of cellular rab7. Cell vacuolation is inhibited by the microtubule-depolymerizing agents nocodazole and colchicine. Taken together, these findings indicate that the vacuoles specifically originate from late endosomal compartments.


A finite-size dynamic-scaling approach for the diffusion front of particles.
The scaling behavior of the diffusion front, originated by the random motion of particles under a concentration gradient, is studied by means of the Monte Carlo method and solving the diffusion equation. Simulations are performed on the square lattice using confined geometries of size MxL, where the gradient is established along the M direction while periodic boundary conditions are set along the L direction. A dynamic scaling Ansatz is proposed such as the width of the front [w(M,t)] scales as w(M,t) approximately M(alpha)f(t/M(alpha/beta)), where alpha and beta are the roughness and growing exponents, respectively. This proposal is based on the fact that the development of w is constrained by the gradient, that decays as M(-1), in contrast to the standard Family-Vicsek scaling Ansatz where correlations are constrained by the lateral dimension of the sample. It is found that the roughness exponent exhibits a systematic dependence on the sample size that can be rationalized in terms of a finite-size correction. Extrapolation to the thermodynamic limit gives alpha=4/7, in excellent agreement with theoretical predictions linking the diffusion system to the percolation problem. The evaluation of the growing exponent gives beta=0.30+/-0.02, leading us to the conjecture beta=2/7 for the exact value.


Management of infected total knee arthroplasties.
In a prospective study of 14 consecutive infected total knee arthroplasties ( TKAs ) treated through 1979, the management consisted of: (1) 11 delayed exchange arthroplasties, with 2 failures requiring above-knee amputation; (2) 2 in situ debridements; and (3) 1 arthrodesis. The final outcome of the delayed exchange arthroplasty group regarding joint pain, patient function, and joint performance was (a) inferior to that of primary TKA (before infection), (b) better than that of resection arthroplasty, and (c) worse than that of a control group of non-infected TKAs respectively. Debridement without prosthesis resection was successful only in cases of immediate postoperative infection (2 successes in 4 TKAs ) and uniformly unsuccessful in infections occurring beyond the perioperative period (4 failures in 4 TKAs ). The study indicates that delayed exchange total knee arthroplasty is a reasonable alternative to arthrodesis following resection of an infected TKA and can be performed without undue risk of recurrent infection.


Functional and structural biomarkers to monitor heavy metal pollution of one of the most contaminated freshwater sites in Southern Europe.
This study evaluated the biological effects of highly polluted freshwater environment (Regi Lagni channels, S Italy) on the aquatic moss Leptodictyum riparium, exposed in bags at three sites representative of different environmental conditions and characterized by different heavy metal burdens. Bioaccumulation, ultrastructural alterations, Reactive Oxygen Species (ROS) production, antioxidant enzymes activity and DNA damage were assessed. To better evaluate the biological response of the moss species to heavy metals, the same biological parameters were assessed also in L. riparium samples cultured in vitro using metal mixtures at the same concentrations as measured at the 3 field exposure sites. Heavy metals were accumulated into the moss tissues causing severe ultra-structural damages at higher concentration case studies, and the ROS production as well as the activity of the enzyme followed a concentration-dependent increase. However, the DNA damage trend suggested a threshold effect that changed between field and in vitro experiment. The enrichment factor suggests that the concentration in the most polluted site is close to the upper limit of L. riparium to accumulate metals. Overall, combining measures of the morpho-functional traits at different level contribute to improving the knowledge about the tolerance of L. riparium to heavy metal stress, suggesting that this moss could be suitable for biomonitoring activity in field conditions.


Sulfinate Based Selective Labeling of 5-Hydroxymethylcytosine: Application to Biotin Pull Down Assay.
We developed an enzyme-free, chemical method to selectively label the epigenetic base, 5-hydroxymethylcytosine (hmC) with versatile sulfinate reagents in aqueous solvent under mild reaction conditions. This method allows efficient single step conjugation of biotin to hmC site in DNA for enrichment and pull down assays.


Prevalence of Accessory Branches and Other Anatomical Variations in the Radial Artery Encountered during Radial Forearm Flap Harvest: A Systematic Review and Meta-analysis.
Harvest of the radial forearm flap (RFF) for reconstructive surgery is proceeded by the Allen test to assess for adequate contralateral perfusion of the hand, yet the Allen test may fail to detect anatomical variations in the radial artery such as aberrant branching. Therefore, the goal of this study was to systematically review the literature regarding anatomical abnormalities of the radial artery that can affect flap harvest and to perform a meta-analysis to estimate the prevalence of such abnormalities. A systematic review of the literature was conducted using five online databases to identify all instances of radial artery anatomical variations. Abstracts were reviewed and categorized into either (1) large cohort studies of anatomical variations identified by angiogram or (2) case reports specifically mentioning anomalous or accessory branches of the radial artery. Data from the large cohort studies were included in a random effect meta-analysis to estimate the prevalence of such variations. Eighteen angiogram cohort studies containing a total of 18,115 patients were included in the meta-analysis. Accessory branches were the least common anatomical variant reported, with an estimated average prevalence of 0.5%. Prevalence estimates for more common anatomical variants, including radial artery loops (0.9%), stenosis (1.3%), hypoplasia (1.9%), tortuosity (4.3%), and abnormal origin (5.6%), were also calculated. Thirteen case reports detailing anomalous branches of the radial artery were identified, seven of which involved accessory branches encountered during RFF harvest with no incidence of flap loss. Radial artery accessory branches are exceedingly rare, but the prevalence of other anatomical variations that can affect harvest of the RFF warrants consideration. We recommend surgeons consider comprehensive screening prior to RFF harvest to avoid intraoperative discovery of anatomical variants and suggest a low threshold for repeat perfusion testing intraoperatively if radial artery accessory branches are encountered.


True and quasi-long-range order in the generalized q-state clock model.
From consideration of the order-parameter distribution, we propose an observable which makes a clear distinction between true and quasi-long-range orders in the two-dimensional generalized q-state clock model. Measuring this quantity by Monte Carlo simulations for q=8, we construct a phase diagram and identify critical properties across the phase-separation lines among the true long-range order, quasi-long-range order, and disorder. Our result supports the theoretical prediction that there appears a discontinuous order-disorder transition as soon as the two phase-separation lines merge.


Diflomotecan, a promising homocamptothecin for cancer therapy.
Diflomotecan, a 10,11-difluoro-homocamptothecin, represents a new promising class of topoisomerase I inhibitors with enhanced plasma stability and superior preclinical anti-tumour activity as compared to the established camptothecins, irinotecan and topotecan. Diflomotecan was the first homocamptothecin to enter clinical studies. Phase I data are summarized for both the intravenous and oral schedules. The toxicity is primarily haematological while no severe gastrointestinal toxicity has been observed in contrast to other topoisomerase I inhibitors. Diflomotecan has a high oral bioavailability (72 - 95%) and the oral day 1 - 5 every 3 weeks regimen is recommended for Phase II testing because it is relatively well tolerated, convenient and mimics protracted exposure. This review summarizes the developments and innovations in the topoisomerase I inhibitor field with an emphasis on diflomotecan.


[A case of Sjögren's syndrome accompanied by lymphadenopathy and IgG4 hypergammaglobulinemia].
A 78-year-old male patient suffered from slight dryness of his mouth and eyes, which was followed by swelling of the parotid and submandibular glands on both sides. Subsequently, he developed generalized lymphadenopathy accompanied by hypergammaglobulinemia IgG 7740 mg/dl, main subclass: IgG4, 5800 mg/dl. Histopathological examination of lymph nodes from his left neck showed follicular proliferation of plasma cells containing cytoplasmic kappa and lambda chains of IgG4, without destruction of the lymph node structure. His serum showed very low levels of complement: 0 U/ml of CH 50, 14 mg/ml of C3 and less than 11 mg/ml of C4. During treatment with prednisolone at 30 mg/day, the swelling of the salivary glands and lymph nodes reduced the IgG and IgG4 decreased and the complement increased. Finally, all lymph nodes, IgG and complement abnormalities were normalized. Anticomplementariness of IgG4 was demonstrated in this patient.


Bax mitochondrial relocation is linked to its phosphorylation and its interaction with Bcl-xL.
The heterologous expression of Bax, and other Bcl-2 family members, in the yeast Saccharomyces cerevisiae, has proved to be a valuable reporter system to investigate the molecular mechanisms underlying their interaction with mitochondria. By combining the co-expression of Bax and Bcl-xL mutants with analyzes of their localization and interaction in mitochondria and post-mitochondrial supernatants, we showed that the ability of Bax and Bcl-xL to interact is dependent both on Bax phosphorylation - mimicked by a substitution S184D - and by Bax and Bcl-xL localization. This, and previous data, provide the molecular basis for a model of dynamic equilibrium for Bax localization and activation, regulated both by phosphorylation and Bcl-xL.


Effect of adding ethylene glycol dimethacrylate to resin cements: durability against thermal stress of adhesion to titanium.
The present study was conducted to examine the effect of the addition of a dimethacrylate to resin cements on bond strength between titanium and resin after thermocycling. Titanium disks, polished and treated with a phosphate monomer, were bonded to acrylic rods using two types of experimental resin cements. The cements were composed of methyl methacrylate (MMA) containing a tributylborane initiator and 0-10 wt% of ethylene glycol dimethacrylate (EGDMA) and two types of polymer component of hard poly (MMA) or soft fluoropolymer (2-6F). The bonded specimens were subjected to a thermocycling test in water and then to tensile strength testing. The addition of 5% or more dimethacrylate monomer to the two MMA-based resin cements caused a drastic decrease in bond strength to the metal after the thermocycling test. The resin prepared with soft 2-6F as a polymer component was significantly more durable than the rigid type resin based on PMMA. However, even a 1% addition of ECDMA to the 2-6F resin resulted in a significant decrease in durability.


Long-term issues and supportive care needs of adolescent and young adult childhood brain tumour survivors and their caregivers: A systematic review.
Long-term issues following diagnosis and treatment of a childhood brain tumour often become apparent as the survivor enters adolescence and young adulthood. Their caregivers may additionally face long-term impacts on their emotional and psychological functioning. This review synthesised evidence on the issues and supportive care needs of adolescent and young adult (AYA) survivors of a brain tumour diagnosed in childhood and their caregivers. Electronic databases were searched up until September 2017. All studies reporting on issues or needs of childhood brain tumour survivors (aged 14-39) and their caregivers were included. Narrative synthesis methods were used to summarise, integrate, and interpret findings. Fifty-six articles (49 studies) met the inclusion criteria. Social issues (ie, isolation and impaired daily functioning) were most commonly reported by survivors, followed by cognitive (ie, impaired memory and attention) and physical issues (ie, endocrine dysfunctions and fatigue). Survivors experienced poorer social functioning and sexual functioning and were less likely to be employed or have children, when compared with other AYA cancer survivors. Caregivers experienced reduced support as the survivor moved into young adulthood. Caregivers reported uncertainty, increased responsibilities, and problems maintaining their own self-well-being and family relationships. Few studies reported on supportive care needs. Survivors expressed a need for better educational support and age-specific psychosocial services. Surviving a childhood brain tumour can be particularly challenging for AYA survivors and their caregivers. Robust structured research is needed to identify specific support needs of both survivors and their caregivers and how these can be optimally addressed.


A Hemispherical Image Sensor Array Fabricated with Organic Photomemory Transistors.
Hemispherical image sensors simplify lens designs, reduce optical aberrations, and improve image resolution for compact wide-field-of-view cameras. To achieve hemispherical image sensors, organic materials are promising candidates due to the following advantages: tunability of optoelectronic/spectral response and low-temperature low-cost processes. Here, a photolithographic process is developed to prepare a hemispherical image sensor array using organic thin film photomemory transistors with a density of 308 pixels per square centimeter. This design includes only one photomemory transistor as a single active pixel, in contrast to the conventional pixel architecture, consisting of select/readout/reset transistors and a photodiode. The organic photomemory transistor, comprising light-sensitive organic semiconductor and charge-trapping dielectric, is able to achieve a linear photoresponse (light intensity range, from 1 to 50 W m-2 ), along with a responsivity as high as 1.6 A W-1 (wavelength = 465 nm) for a dark current of 0.24 A m-2 (drain voltage = -1.5 V). These observed values represent the best responsivity for similar dark currents among all the reported hemispherical image sensor arrays to date. A transfer method was further developed that does not damage organic materials for hemispherical organic photomemory transistor arrays. These developed techniques are scalable and are amenable for other high-resolution 3D organic semiconductor devices.


Pediatric computed tomography practice in Japanese university hospitals from 2008-2010: did it differ from German practice?
Computed tomography (CT) is an essential tool in modern medicine and is frequently used to diagnose a wide range of conditions, particularly in industrial countries, such as Japan and Germany. However, markedly higher doses of ionizing radiation are delivered during CT imaging than during conventional X-ray examinations. To assess pediatric CT practice patterns, data from three university hospital databases (two in Japan and one in Germany) were analyzed. Anonymized data for patients aged 0 to 14 years who had undergone CT examinations between 2008 and 2010 were extracted. To assess CT practice, an interdisciplinary classification scheme for CT indications, which incorporated the most common examination types and radiosensitive tissues, was developed. The frequency of CT examinations was determined according to sex, age at examination, and indications. A total of 5182 CT examinations were performed in 2955 children. Overall, the frequency of CT examinations at the Japanese university hospitals did not differ significantly from that at the German hospital. However, differences were detected in the age distribution of the patients who underwent CT examinations (the proportion of patients <5 years of age was significantly higher in Japan than in Germany) and in the indications for CT. Substantial practice differences regarding the use of CT in pediatric health care were detected between the three hospitals. The results of this study point towards a need for approaches such as clinical guidelines to reduce unwarranted medical radiation exposures, particularly abdominal and head CT, in the Japanese health system.


Increasing occupational therapy research: is it time to try something new?
Lack of substantial occupational therapy research is a recognized and persistent problem; which is often discussed throughout the literature but not truly addressed. Action must be taken to involve clinicians in the effort to substantiate the efficacy of treatments through outcome studies. We offered several proactive recommendations that could be implemented on a national level to encourage hesitant practitioners to conduct research. Past recommendations have not tapped the expertise of a large segment of our profession. Our recommendations will enhance the accessibility of research to a greater percentage of occupational therapy professionals by specifically targeting problems related to money, education, and time.


Inhibition of glycogen synthase kinase-3β by lithium chloride suppresses 6-hydroxydopamine-induced inflammatory response in primary cultured astrocytes.
An increasing amount of evidence has emerged to suggest that neuroinflammatory process is involved in the pathogenesis of Parkinson's disease (PD). Activated microglia and astrocytes are found in the substantia nigra (SN) of Parkinson's disease brains as well as in animal models of Parkinson's disease. Although reactive astrocytes are involved in the progression of PD, the role of reactive astrocytes in neuroinflammation of PD has received limited attention to date. Recently, Glycogen synthase kinase-3β (GSK-3β) was identified as a crucial regulator of the inflammatory response. The purpose of this study was to explore the mechanism by which 6-hydroxydopamine (6-OHDA) induces inflammatory response in astrocytes and observe the anti-inflammatory effect of lithium chloride (LiCl) on 6-OHDA-treated astrocytes. In the present study, we found that glial fibrillary acidic protein (GFAP) was markedly upregulated in the presence of 6-OHDA. Moreover, our results revealed that proinflammatory molecules including inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2(COX-2), prostaglandins E2 (PGE2), and tumor necrosis factor-α (TNF-α) were obviously increased in astrocytes exposed to 6-OHDA. Western blot analysis revealed that 6-OHDA significantly increased dephosphorylation/activation of GSK-3β as well as the nuclear translocation of nuclear factor-κB (NF-κB) p65. Besides, GSK-3β inhibitor LiCl and SB415286 inhibited the GSK-3β/NF-κB signaling pathway, leading to the reduction of proinflammatory molecules in 6-OHDA-activated astrocytes. These results confirmed that GSK-3β inhibitor LiCl and SB415286 provide protection against neuroinflammation in 6-OHDA-treated astrocytes. Therefore, GSK-3β may be a potential therapeutic target for the treatment of PD.


Perioperative evaluation of primary hemostasis in patients undergoing mitral valve repair.
No data exist on the prevalence of primary hemostatic defects and acquired von Willebrand disease in mitral valve prolapse with severe regurgitation. Primary hemostasis was evaluated by PFA-100, von Willebrand Factor Antigen (vWF:Ag) and Ristocetin cofactor (vWF:RiCof) assays in a prospective observational trial. Sixty-five consecutive patients with mitral regurgitation (study group) or aortic stenosis (control group) who were operated for mitral valve repair or aortic valve replacement were enrolled in the study. There were no differences in Closure Time in the two groups at all time points. The concentration of plasma vWF: Ag was within normal limits in all patients preoperatively; after surgery, a significant increase was observed in both groups from baseline (199 +/- 144 mcg/dL vs. 295 +/-141 mcg/dL in the study group, p=0.002; 243 +/- 141 mcg/dLl vs 338 +/- 154 mcg/dL in the control group, p=0.009). The ratio of vWF:RiCof to vWF:Ag was slightly decreased preoperatively in both groups (ratio= 0.91) and showed a marked increase in the postoperative period (ratio=0.22) as, probably, new hemostatically effective large multimeric forms of vWF were released. Patients who present for surgery with a valvular pathology with high shear stress have some degree of primary hemostasis defect; nevertheless, the potent stimulus of surgery and the correction of the underlying disease allow quick restoration of vWF activity and normalization of PFA-100.


Supramolecular hydrogen-bonding patterns in 1:1 cocrystals of 5-fluorouracil with 4-methylbenzoic acid and 3-nitrobenzoic acid.
The design of a pharmaceutical cocrystal is based on the identification of specific hydrogen-bond donor and acceptor groups in active pharmaceutical ingredients (APIs) in order to choose a `complementary interacting' molecule that can act as an efficient coformer. 5-Fluorouracil (5FU) is a pyrimidine derivative with two N-H donors and C=O acceptors and shows a diversity of hydrogen-bonding motifs. Two 1:1 cocrystals of 5-fluorouracil (5FU), namely 5-fluorouracil-4-methylbenzoic acid (5FU-MBA), C4H3FN2O2·C8H8O2, (I), and 5-fluorouracil-3-nitrobenzoic acid (5FU-NBA), C4H3FN2O2·C7H5NO4, (II), have been prepared and characterized by single-crystal X-ray diffraction. In (I), the MBA molecules form carboxylic acid dimers [R22(8) homosynthon]. Similarly, the 5FU molecules form two types of base pair via a pair of N-H...O hydrogen bonds [R22(8) homosynthon]. In (II), 5FU interacts with the carboxylic acid group of NBA via N-H...O and O-H...O hydrogen bonds, generating an R22(8) ring motif (heterosynthon). Furthermore, the 5FU molecules form base pairs [R22(8) homosynthon] via N-H...O hydrogen bonds. Both of the crystal structures are stabilized by C-H...F interactions.


Reduction of insulin secretion in the insulinoma cell line INS-1 by overexpression of a Ca(v)2.3 (alpha1E) calcium channel antisense cassette.
Multiple types of voltage-activated Ca(2+) channels (T, L, N, P, Q and R type) coordinate a variety of Ca(2+)-dependent processes in neurons and neuroendocrine cells. In insulinoma cell lines as well as in endocrine tissues, the non-L-type alpha1E (Ca(v)2.3) subunit is expressed as the tissue-specific splice variant alpha1Ee. To understand the functional role of alpha1E-containing Ca(2+) channels, antisense alpha1E mRNA was overexpressed in INS-1 cells by stable transfection of an antisense alpha1E cassette cDNA. As controls, either a sense alpha1E cassette or a control vector containing enhanced green fluorescent protein as an unrelated gene was stably transfected. The overexpression of each transfected cassette cDNA was recorded by RT-PCR. In three independent antisense alpha1E INS-1 clones, the glucose-induced insulin release was significantly reduced as compared with wild-type INS-1 cells and with a sense alpha1E INS-1 clone. However, in the antisense INS-1 clones, the KCl-induced insulin release was less impaired by overexpressing the antisense alpha1E cassette than the glucose-induced insulin release, leading to the assumption that glucose (15 mmol/l) and KCl (25 mmol/l) finally depolarize the membrane potential to a different extent. alpha1E is involved in glucose-induced insulin secretion probably by influencing the excitability of INS-1 cells.


Multiple intestinal lymphangiomas with episodic hemorrhage requiring partial laparoscopic resection: a case report.
Lymphangioma is a non-epithelial tumor marked by aggregates of abnormally dilated lymphatics. Mesenteric occurrences account for < 1% of all cases, and < 0.05% involve the gastrointestinal tract. Most are confined to children, rarely affecting adults. Herein, we describe an elderly Japanese woman with anemia, hypoalbuminemia, and episodic bleeding due to multiple intestinal lymphangiomas. Abdominal computed tomography revealed multiple low-density defects of mesentery, with areas of intermediate (T1 images) or high (T2 images) signal intensity similarly dispersed in magnetic resonance scanning sequences. Single-balloon enteroscopy was undertaken, enabling identification and tattooing of a small intestinal bleeding source. Laparoscopy-assisted resection at this site served to control related hemorrhage, removing a histologically confirmed hemolymphangioma. Having recovered uneventfully, the patient remained stable 2 months postoperatively. Although rare in adults, mesenteric or gastrointestinal lymphangiomas must be considered in a setting of anemia and hypoalbuminemia. Complete resection is advantageous to improve patient symptoms, but limited resection of multiple lesions may be equally effective.


Evaluation of effectiveness of connective tissue graft as a barrier with bioresorbable collagen membrane in the treatment of mandibular Class II furcation defects in humans: 4-year clinical results.
Connective tissue grafts (CTGs) have been used as a barrier for closing mandibular Class II furcation defects. The present study compared long-term (48 months) effectiveness of CTG as a barrier with bioresorbable collagen membrane in the treatment of mandibular Class II furcation defects in humans. Twenty chronic periodontitis patients with a single Class II furcation defect on the buccal surface of mandibular teeth were included in the study. Vertical probing pocket depth (V-PPD), vertical relative attachment level (V-RAL), and relative gingival margin level (RGML) were recorded at baseline, 6 months, 12 months, and 48 months post-surgery. The mean V-PPD reductions observed in the test group and control group were statistically significant at all time intervals when compared with the baseline. Similarly, the mean V-RAL gain at 6 months, 12 months, and 48 months were statistically significant, compared with the baseline data in both the groups. At 48 months the difference in V-RAL gain between the groups was found to be statistically significant, with greater improvements in test group. Complete closure of furcation and improvement in horizontal classification were better in the test group than in the control group. It can be concluded that both treatment modalities result in improvement in clinical parameters. However, the results obtained with CTG appeared to be more stable.


Mutation of YMYL in the Nipah virus matrix protein abrogates budding and alters subcellular localization.
Matrix (M) proteins reportedly direct the budding of paramyxoviruses from infected cells. In order to begin to characterize the assembly process for the highly lethal, emerging paramyxovirus Nipah virus (NiV), we have examined the budding of NiV M. We demonstrated that expression of the NiV M protein is sufficient to produce budding virus-like particles (VLPs) that are physically and morphologically similar to NiV. We identified in NiV M a sequence, YMYL, with similarity to the YPDL late domain found in the equine infectious anemia virus Gag protein. When the YMYL within NiV M was mutated, VLP release was abolished and M was relocalized to the nucleus, but the mutant M proteins retained oligomerization activity. When YMYL was fused to a late-domain mutant of the Ebola virus VP40 matrix protein, VP40 budding was restored. These results suggest that the YMYL sequence may act as a trafficking signal and a late domain for NiV M.


CA125 level as a predictor of progression-free survival and overall survival in ovarian cancer patients with surgically defined disease status prior to the initiation of intraperitoneal consolidation therapy.
Recent data suggest that differences in CA125 levels within the normal range may predict progression-free survival (PFS), but limited information is available regarding the value of these differences in predicting overall survival (OS) in patients with epithelial ovarian cancer. The objective of this study was to determine whether CA125 is an independent predictor of OS in patients with surgically defined disease status at the end of primary therapy prior to intraperitoneal (IP) consolidation chemotherapy. A secondary objective was to assess the relationship of CA125 level to PFS. Using data from a retrospective cohort of 433 patients who received intraperitoneal (IP) therapy following primary treatment for ovarian cancer between 1984 and 1998, we identified 241 patients with a complete clinical response and CA125 data at the time of second-look surgery prior to IP chemotherapy. Patient demographics and updated follow-up status were abstracted from medical records. Kaplan-Meier survival curves were compared using the log-rank test, and Cox regression models were used for multivariate analysis. The majority of patients had advanced stage III or IV disease (n=201, 83%) and high-grade histology (n=163, 68%). Taxane was used as part of primary platinum-based therapy in 56% (n=134) of patients, and subsequent IP chemotherapy was platinum-based in 85% (n=206). When considered as a continuous variable, CA125 was a predictor of OS (P=0.029). Using the median CA125 level in our study group as a cut-off, OS was increased in patients with CA125 < or =12 U/ml (median 5.8 years) compared with >12 (3.7 years) (P=0.0027). CA125 level was an independent predictor of OS (HR: 1.410; 95% CI, 1.044, 1.904, P=0.0248) in a multivariate model that included stage (P=0.0166), grade (P=0.0001), and findings at second-look surgery (P=0.0003). CA125 level was also a predictor of clinical PFS (radiographic or CA125 elevation criteria alone) in a subset of 161 patients as a continuous variable (P=0.0036), and when divided at the median (< or = or >12; median 2.8 years vs. 1.7 years; P=0.0017). In our study population, CA125 level at the end of primary therapy was a predictor of OS and PFS when considered as a continuous variable, or when divided at the median (< or = or >12 U/ml). Further prospective study is required to optimize clinically significant cut-off values within the normal range of CA125 levels for both OS and PFS endpoints.


Nanoantenna-Enhanced Infrared Spectroscopic Chemical Imaging.
Spectroscopic infrared chemical imaging is ideally suited for label-free and spatially resolved characterization of molecular species, but often suffers from low infrared absorption cross sections. Here, we overcome this limitation by utilizing confined electromagnetic near-fields of resonantly excited plasmonic nanoantennas, which enhance the molecular absorption by orders of magnitude. In the experiments, we evaporate microstructured chemical patterns of C60 and pentacene with nanometer thickness on top of homogeneous arrays of tailored nanoantennas. Broadband mid-infrared spectra containing plasmonic and vibrational information were acquired with diffraction-limited resolution using a two-dimensional focal plane array detector. Evaluating the enhanced infrared absorption at the respective frequencies, spatially resolved chemical images were obtained. In these chemical images, the microstructured chemical patterns are only visible if nanoantennas are used. This confirms the superior performance of our approach over conventional spectroscopic infrared imaging. In addition to the improved sensitivity, our technique provides chemical selectivity, which would not be available with plasmonic imaging that is based on refractive index sensing. To extend the accessible spectral bandwidth of nanoantenna-enhanced spectroscopic imaging, we employed nanostructures with dual-band resonances, providing broadband plasmonic enhancement and sensitivity. Our results demonstrate the potential of nanoantenna-enhanced spectroscopic infrared chemical imaging for spatially resolved characterization of organic layers with thicknesses of several nanometers. This is of potential interest for medical applications which are currently hampered by state-of-art infrared techniques, e.g., for distinguishing cancerous from healthy tissues.


A continuum of InsP3-mediated elementary Ca2+ signalling events in Xenopus oocytes.
1. The elementary release events underlying inositol 1,4, 5-trisphosphate (InsP3)-mediated calcium signalling were investigated in Xenopus oocytes by means of high-resolution confocal linescan imaging together with flash photolysis of caged InsP3. 2. Weak photolysis flashes evoked localized, transient calcium signals that arose at specific sites following random latencies of up to several seconds. The duration, spatial spread and amplitude of these elementary events varied widely. Event durations (at half-maximal amplitude) were distributed exponentially between about 100 and 600 ms. Fluorescence magnitudes (F/F0 of Oregon Green 488 BAPTA-1) showed a skewed distribution with a peak at about 1.5 and a tail extending as high as 3.5. 3. Individual release sites exhibited both small events (blips) and large events (puffs). The spatiotemporal distribution of calcium signals during puffs was consistent with calcium diffusion from a point source (< a few hundred nanometres), rather than with propagation of a microscopic calcium wave. 4. Estimates of the calcium flux associated with individual events were made by integrating fluorescence profiles along the scan line in three dimensions to derive the 'signal mass' at each time point. The smallest resolved events corresponded to liberation of < 2 x 10-20 mol Ca2+, and large events to about 2 x 10-18 mol Ca2+. The rise of signal mass was more prolonged than that of the fluorescence intensity, suggesting that calcium liberation persists even while the fluorescence begins to decline. Rates of rise of signal mass corresponded to Ca2+ currents of 0.4-2.5 pA. 5. Measurements of signal mass from different events showed a continuous, exponential distribution, arising through variability in magnitude and duration of calcium flux. 6. We conclude that localized calcium transients in the oocyte represent a continuum of events involving widely varying amounts of calcium liberation, rather than falling into separate populations of 'fundamental' and 'elementary' events (blips and puffs) involving, respectively, single and multiple InsP3 receptor channels. This variability probably arises through stochastic variation in both the number of channels recruited and the duration of channel opening.


Schumannella luteola gen. nov., sp. nov., a novel genus of the family Microbacteriaceae.
An actinobacterial strain KHIA(T), isolated from lichen in Tokyo, was taxonomically characterized using a polyphasic approach. The isolate is a Gram-positive, anaerobic, non-motile and rodshaped bacterium. Phylogenetic analyses based on 16S rRNA gene sequences revealed that the isolate is represented as an independent lineage distinctive from the Microbacteriaceae genera. The G + C content of DNA was 58.7 mol%. The chemotaxonomic characteristics of the isolate are cell wall peptidoglycan type (2,4-diaminobutyric acid), major cellular fatty acids (anteiso-C(15:0) and iso-C(16:0)) and quinone type (MK-11 and MK-10). On the basis of the phenotypic and phylogenetic distinctness, it is proposed that strain KHIA(T )represents a novel species in a new genus of the family Microbacteriaceae, Schumannella luteola gen. nov., sp. nov. The type strain is KHIA(T )(=JCM 23215(T)=TISTR 1824(T)).


Protein tyrosine phosphatase expression profile of rheumatoid arthritis fibroblast-like synoviocytes: a novel role of SH2 domain-containing phosphatase 2 as a modulator of invasion and survival.
The fibroblast-like synoviocytes (FLS) in the synovial intimal lining of the joint are key mediators of inflammation and joint destruction in rheumatoid arthritis (RA). In RA, these cells aggressively invade the extracellular matrix, producing cartilage-degrading proteases and inflammatory cytokines. The behavior of FLS is controlled by multiple interconnected signal transduction pathways involving reversible phosphorylation of proteins on tyrosine residues. However, little is known about the role of the protein tyrosine phosphatases (PTPs) in FLS function. This study was undertaken to explore the expression of all of the PTP genes (the PTPome) in FLS. A comparative screening of the expression of the PTPome in FLS from patients with RA and patients with osteoarthritis (OA) was conducted. The functional effect on RA FLS of SH2 domain-containing phosphatase 2 (SHP-2), a PTP that was up-regulated in RA, was then analyzed by knockdown using cell-permeable antisense oligonucleotides. PTPN11 was overexpressed in RA FLS compared to OA FLS. Knockdown of PTPN11, which encodes SHP-2, reduced the invasion, migration, adhesion, spreading, and survival of RA FLS. Additionally, signaling in response to growth factors and inflammatory cytokines was impaired by SHP-2 knockdown. RA FLS that were deficient in SHP-2 exhibited decreased activation of focal adhesion kinase and mitogen-activated protein kinases. These findings indicate that SHP-2 has a novel role in mediating human FLS function and suggest that it promotes the invasiveness and survival of RA FLS. Further investigation may reveal SHP-2 to be a candidate therapeutic target for RA.


Pulmonary hypertension and vasculopathy in incontinentia pigmenti: a case report.
Incontinentia pigmenti (IP; Bloch-Sulzberger syndrome) is a rare, genetic syndrome inherited as an X-linked dominant trait. It primarily affects female infants and is lethal in the majority of males during fetal life. The clinical findings include skin lesions, developmental defects, and defects of the eyes, teeth, skeletal system, and central nervous system. Cardiovascular complications of this disease in general, and pulmonary hypertension in particular, are extremely rare. This report describes the case of a 3-year-old girl with IP complicated by pulmonary arterial hypertension. Extensive cardiology workup done to the patient indicates underlying vasculopathy. This report sheds light on the relationship between IP and pulmonary hypertension, reviews the previously reported cases, and compares them with the reported case.


Measurement of NO(x) fluxes from a tall tower in Central London, UK and comparison with emissions inventories.
Direct measurements of NOx concentration and flux were made from a tall tower in central London, UK as part of the Clean Air for London (ClearfLo) project. Fast time resolution (10 Hz) NO and NO2 concentrations were measured and combined with fast vertical wind measurements to provide top-down flux estimates using the eddy covariance technique. Measured NOx fluxes were usually positive and ranged from close to zero at night to 2000-8000 ng m(-2) s(-1) during the day. Peak fluxes were usually observed in the morning, coincident with the maximum traffic flow. Measurements of the NOx flux have been scaled and compared to the UK National Atmospheric Emissions Inventory (NAEI) estimate of NOx emission for the measurement footprint. The measurements are on average 80% higher than the NAEI emission inventory for all of London. Observations made in westerly airflow (from parts of London where traffic is a smaller fraction of the NOx source) showed a better agreement on average with the inventory. The observations suggest that the emissions inventory is poorest at estimating NOx when traffic is the dominant source, in this case from an easterly direction from the BT Tower. Agreement between the measurements and the London Atmospheric Emissions Inventory (LAEI) are better, due to the more explicit treatment of traffic flow by this more detailed inventory. The flux observations support previous tailpipe observations of higher NOx emitted from the London vehicle diesel fleet than is represented in the NAEI or predicted for several EURO emission control technologies. Higher-than-anticipated vehicle NOx is likely responsible for the significant discrepancies that exist in London between observed NOx and long-term NOx projections.


Characteristics and anaerobic treatability of municipal and industrial estate wastewaters.
Centralised treatment of domestic sewage coming from A Coruña city (250000 inhabitants) and several medium and small size villages (up to 15000 inhabitants) together with industrial estate effluents was planned. The area population is about 380000 inhabitants and the overall effluent will reach about 600000 equivalent inhabitants. The characteristics of different streams will determine the treatment alternatives and pre-treatment requirements for individual streams. Domestic sewage from A Coruña showed medium to high organic content (741 mg l(-1) of COD), while domestic sewage from small villages (Lorbé, Oleiros) and industrial estates (Sabón, A Grela) showed a high variability in organic content, with COD concentration ranging from 100 to 4000 mg L(-1) or more. About 50-65% COD corresponded to suspended solids, although some industrial effluents showed lower values. Characterized industrial effluents had lower concentration of nutrients (nitrogen and phosphorus) and higher concentration of sulphate and alkalinity than domestic sewage. Anaerobic biodegradability was about 80% for domestic sewage, and ranged from 20 to 100% for industrial estate effluents. Furthermore, some industrial streams showed high microbial toxicity. The results indicate that anaerobic treatment of these effluents is of interest. However, specific pre-treatment for some individual streams or the adoption of minimisation and prevention measures in order to reach total or partial detoxification is suggested.


Eotaxin receptor (CCR3) antagonism in asthma and allergic disease.
A range of low molecular weight chemicals have been developed to antagonise the eotaxin receptor, cysteine-cysteine chemokine receptor-3 (CCR3), with the aim of selectively inhibiting eosinophil recruitment into tissue sites. However, the results of recent clinical trials with monoclonal antibodies directed against interleukin-5 (IL-5) question the role of eosinophils in mediating the symptoms of asthma and allergic disease. For this reason, the plans for clinical development of certain CCR3 antagonists have been halted. However, eotaxin 1-3 and a variety of other chemokines interact with CCR3; and this receptor is expressed not only on eosinophils but also on basophils, mast cell subpopulations, activated Th2 cells, macrophages, and airway epithelial cells. Hence, CCR3 is closely associated with asthma and allergy and blockade of this receptor may have pronounced beneficial effects in these diseases. We consider the chemical structures of CCR3 antagonist molecules from a range of pharmaceutical companies, and present an early clinical development plan for a hypothetical CCR3 antagonist. CCR3 antagonists are likely to be safe and effective therapies for allergic diseases, and their clinical pharmacology can readily be defined within phase I/II studies in patients with allergy and asthma.


Correlation between BTG3, CASP9 and LRP4 single-nucleotide polymorphisms and susceptibility to papillary thyroid carcinoma.
Objective: To study the association of BTG3, CASP9 and LRP4 single-nucleotide polymorphisms with susceptibility to papillary thyroid carcinoma (PTC). Methods: The BTG3 rs9977638, CASP9 rs884363 and LRP4 rs898604 genotypes of 175 PTC patients and 175 controls were analyzed. Results: Rs9977638 TC genotype and CC genotype, rs884363 CC genotype and rs898604 GG genotype were related to a lower PTC susceptibility risk (p < 0.01). The risk of PTC susceptibility was higher when carrying BTG3 rs9977638 CC, CASP9 rs884363 AC and LRP4 rs898604 AG at the same time (p < 0.01). Conclusion: Combined BTG3, CASP9 and LRP4 genotype analysis has a certain application value in the diagnosis of PTC.


Adjuvant hormonal therapy for stage I endometrial cancer.
What is the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer? There is little consensus on the role of adjuvant treatment for patients with stage i endometrial cancer. Although the use of hormonal therapy has been established in advanced disease, less agreement has emerged concerning the benefits of adjuvant hormonal therapy for patients with early-stage disease. The objective of the present evidence series was to review the existing literature on the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer. REPORTS WERE SOUGHT THAT INCLUDED AT LEAST ONE OF THE FOLLOWING OUTCOMES: overall survival, disease-free survival, recurrence (local, or distant, or both), adverse effects, and quality of life. Because of the potential for long-term adverse effects with adjuvant hormonal treatment in this patient population, especially with regard to thromboembolic or cardiovascular events, the rates of non-cancer-related death were also of interest. The medline, embase, and Cochrane Library databases were systematically searched for randomized controlled trials, practice guidelines, systematic reviews, and meta-analyses. The resulting evidence informed the development of the clinical practice guideline. The systematic review with meta-analyses and practice guideline were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (DSG). Nine randomized trials and one published meta-analysis comparing adjuvant hormonal therapy with no adjuvant therapy in women with stage i endometrial cancer constituted the evidence base. One trial reported a statistically significant survival benefit with adjuvant progestogen as compared with no further treatment (97% vs. 69%, p < 0.001). In that trial, the treatment group had a higher number of patients with less myometrial invasion, and a lower number of patients with advanced-stage disease. These differences in baseline characteristics between the randomized groups were considered to be clinically important. In addition, the results of that trial were not consistent with those of other trials, and the trial was a source of statistical heterogeneity when data were pooled across trials. In two of the nine randomized trials, statistically significant recurrence-free benefits were detected with adjuvant hormonal therapy as compared with no further therapy. In one trial, the difference between the rates of recurrence was 16%; however, the methodologic concerns related to that that trial limited its relevance. In the other trial, the difference between the rates of recurrence was 5%. In that trial, patients were at a high risk of recurrence. None of the remaining seven randomized trials reported any significant difference in recurrence rates between treatment groups. The meta-analysis identified in the literature detected no statistically significant recurrence-free or overall survival benefit associated with adjuvant hormonal therapy as compared with no adjuvant therapy [odds ratio (or): 1.05; 95% confidence interval (ci): 0.88 to 1.24). Those results are consistent with the results of the meta-analysis in the present report, which included an additional two trials (or: 1.10; 95% ci: 0.91 to 1.34). This clinical recommendation applies to women with newly diagnosed stage i endometrial cancer. The available evidence does not demonstrate any benefit for adjuvant hormonal therapy. The use of hormonal therapy is not recommended as adjuvant treatment for patients with stage i endometrial cancer.


Political representation of medical doctors in Switzerland's executive and legislative branches in 2023.
Background: Healthcare policy is an important societal concern in Switzerland, often dominating the national agenda. In other countries, studies have explored the influence of physicians in public office on healthcare policies, but little is known about the representation of medical doctors in Switzerland's political structures, despite ongoing health-related debates. Methods: In January 2023, we examined the proportion of registered doctors currently serving in Swiss governmental branches: the executive (the Federal Council) and the legislative (the Council of States and the National Council, together the United Federal Assembly). We used publicly available information to demarcate Federal, State, and National Councillors with professional medical backgrounds. We subsequently verified physician registrations using the Federal Office of Public Health's "Register of Medical Professionals" (MedReg) Results: Six physicians registered in MedReg were identified across the Federal Council and the United Federal Assembly in 2023, equivalent to 2.37% of the total number of Councillors in these chambers. This corresponds to 14.20% of members in the Federal Council (the executive chamber) and 2.03% of members in the United Federal Assembly (the legislative chamber). Conclusions: Rates of physicians sitting in Switzerland's Federal Council and United Federal Assembly are higher than general population trends for doctors per person. Nonetheless, physicians in Swiss legislative positions are proportionally lower than comparative data from the United States. We highlight how existing professional frameworks may already ensure medical doctors are sufficiently participating in Swiss healthcare debates outside of formal roles. We also suggest that more international evidence is needed to determine the benefits of physicians serving in public office.


Cardiac pacemakers and implantable cardioverter defibrillators: in vitro magnetic resonance imaging evaluation at 1.5-tesla.
To evaluate the effect of Magnetic Resonance Imaging (MRI) performed at 1.5-Tesla on current generation pacemakers and ICDs to identify safe parameters for MRI examinations. Pacemakers (Identity ADx XL DR+ 5386 and Identity ADx DR + 5380 generators; 1688T/52-cm atrial and ventricular leads) and ICDs (Atlas + V-243, Epic + V-236, and Epic + HF V-350 generators; Riata 1581/65-cm and QuickSite 1056K/75-cm leads; St. Jude Medical, Sylmar, California, USA) were evaluated for magnetic field interactions. MRI-related heating was assessed using various levels of RF power (SARs) and conditions that included scans on different body regions. Functional aspects of the devices were evaluated immediately before and after MRI procedures utilizing nine different pulse sequences. Induced currents were measured using a custom built system. Magnetic field interactions will not create a hazard for these pacemakers and ICDs. All scans of the "head" and "lumbar" regions resulted in temperature changes < or =0.5 degrees C at SARs ranging from 2.0 to 3.0-W/kg. For the "chest" area, temperature increases ranged from 0.4 degrees C to 3.6 degrees C at an SAR of 2.0-W/kg. No memory corruption, hardware changes, or changes in device parameters were seen. Magnetic field gradients have a low likelihood of inducing currents that would stimulate the heart. No hazardous magnetic field interactions or physiologically significant heating occurred for certain conditions. There was no permanent effect on device function. By following specific conditions, these pacemakers and ICDs may be safe for patients scanned at 1.5-Tesla.


Risk-stratified versus Non-Risk-stratified Diagnostic Testing for Management of Suspected Acute Biliary Obstruction: Comparative Effectiveness, Costs, and the Role of MR Cholangiopancreatography.
Purpose To analyze the cost-effectiveness of the American Society for Gastrointestinal Endoscopy (ASGE) risk stratification guidelines versus magnetic resonance (MR) cholangiopancreatography-based treatment of patients with possible choledocholithiasis. Materials and Methods A decision-analytic model was constructed to compare cost and effectiveness of three diagnostic strategies for gallstone disease with possible choledocholithiasis: noncontrast MR cholangiopancreatography, contrast material-enhanced MR imaging/MR cholangiopancreatography, and ASGE risk stratification guidelines for diagnostic evaluation recommending endoscopy (high risk), MR cholangiopancreatography (intermediate risk), or no test (low risk). Analysis was performed from a U.S. health system perspective over 1-year and lifetime horizons. The model accounted for benign and malignant causes of biliary obstruction and procedural complications. Cost information was based on Medicare reimbursements. Sensitivity analysis assessed the impact of parameter variability on model results. Results Noncontrast MR cholangiopancreatography was most cost-effective in 45-55-year-old patients (less than $100 000 per quality-adjusted life-year [QALY] gained), while contrast-enhanced MR imaging was favored in younger adults. Risk-stratified testing was less costly than MR cholangiopancreatography, with long-term savings of $1870 and $2068 versus noncontrast and contrast-enhanced MR cholangiopancreatography, respectively, but was also less effective (-0.1814, -0.1831 QALY, respectively). The lifetime incremental cost per QALY for noncontrast MR cholangiopancreatography was $10 311. Contrast-enhanced MR imaging was favored with pretest probabilities of biliary stricture or malignancy 0%-73% for patients aged 20-44 years. For patients older than 55 years, ASGE guidelines maximized QALYs at the lowest cost. Conclusion Although adults older than 55 years of age are optimally evaluated by using ASGE guidelines, younger patients suspected of having acute biliary obstruction likely benefit from MR cholangiopancreatography rather than risk-stratified diagnostic imaging because of improved detection of choledocholithiasis and alternative causes of biliary obstruction. © RSNA, 2017 Online supplemental material is available for this article.


Prevention of Chemotherapy-Induced Nausea and Vomiting in Cancer Patients.
The supportive care of patients receiving antineoplastic treatment has dramatically improved over the past few years and development of effective measures to prevent nausea and vomiting after chemotherapy serves as one of the most important examples of this progress. A patient who starts cancer treatment with chemotherapy lists chemotherapy-induced nausea and vomiting as among their greatest fears. Inadequately controlled emesis impairs functional activity and quality of life, increases the use of health care resources, and may occasionally compromise adherence to treatment. New insights into the pathophysiology of chemotherapy-induced nausea and vomiting, a better understanding of the risk factors for these effects, and the availability of new antiemetic agents have all contributed to substantial improvements in emetic control. This review focuses on current understanding of chemotherapy-induced nausea and vomiting and the status of pharmacological interventions for their prevention and treatment.


Applications of brachytherapy in head and neck cancer.
Brachytherapy offers the radiation oncologist the opportunity to deliver high doses of radiation to the tumor, with minimal doses to the surrounding normal tissue. This combination enhances the therapeutic ratio. It allows for enhanced tumor control, with minimal toxicity. When utilized, it often allows for tumor control without the need for resection. This is especially important in the head and neck. Resection of organs such as the lip, oral tongue, base-of-tongue, and other sites can cause significant functional and cosmetic morbidity. The ability to save these structures, using radiation therapy instead of surgery, can provide excellent tumor control and optimal quality-of-life outcome. In situations of recurrent disease, especially when prior radiation has been given, brachytherapy is often the only way to re-irradiate certain areas. This can be done alone, or in combination with surgery. Therefore, brachytherapy becomes an important component of the treatment of recurrent disease. This broad overview of the use of brachytherapy in head and neck cancer will include applications in the primary as well as the recurrent disease setting.


Comparison of pharmacy services at critical access hospitals and other rural and small hospitals in Illinois.
The results of a survey evaluating pharmacy services and technology use at critical access hospitals (CAHs) and other small and rural hospitals in Illinois are reported. A mail survey was sent to pharmacy directors at 86 CAHs and other rural and small hospitals in Illinois not designated as CAHs. Independent sample t tests and chi-square statistics were used to compare CAHs and non-CAHs in areas such as pharmacy services, staffing, use of technology, and sterile compounding practices. The survey response rate was 46.5%, with usable data received from 40 hospitals. Analysis of the survey data indicated that hospitals designated as CAHs were significantly less likely than non-CAHs to have automatic therapeutic interchange policies (p = 0.012) and more likely to conduct pharmacist-provided educational programs on medication costs for physicians and other health care personnel (p = 0.037). Relative to non-CAHs, CAHs were significantly less likely to have automated dispensing cabinets (p = 0.016) and to out-source the preparation of sterile products to offsite vendors (p = 0.012); pharmacy directors at CAHs were less likely to report the use of technology for remote medication order entry or review (p = 0.038). At both types of facilities, pharmacists typically have both distributive and clinical responsibilities, and patient-specific clinical pharmacy services (e.g., patient education or counseling, other drug therapy monitoring, medication reconciliation, pharmacokinetic consultations) are offered at similar frequencies. A survey of pharmacy departments at small and rural hospitals in Illinois determined that there were more similarities than differences between CAHs and non-CAHs. The survey indicated significant differences in dispensing processes, the use of technology and drug policy tools, and outsourcing of sterile product preparation.


Mapping the Mechanical and Immunological Profiles of Polymeric Microneedles to Enable Vaccine and Immunotherapy Applications.
Biomaterials hold great promise for vaccines and immunotherapy. One emerging biomaterials technology is microneedle (MNs) delivery. MNs are arrays of micrometer-sized needles that are painless and efficiently deliver cargo to the specialized immunological niche of the skin. MNs typically do not require cold storage and eliminate medical sharps. Nearly all materials exhibit intrinsic properties that can bias immune responses toward either pro-immune or inhibitory effects. Thus, because MNs are fabricated from degradable polymers to enable cargo loading and release, understanding the immunological profiles of these matrices is essential to enable new MN vaccines and immunotherapies. Additionally, understanding the mechanical properties is important because MNs must penetrate the skin and conform to a variety of skin or tissue geometries. Here we fabricated MNs from important polymer classes - including extracellular matrix biopolymers, naturally-derived polymers, and synthetic polymers - with both high- and low-molecular-weights (MW). We then characterized the mechanical properties and intrinsic immunological properties of these designs. The library of polymer MNs exhibited diverse mechanical properties, while causing only modest changes in innate signaling and antigen-specific T cell proliferation. These data help inform the selection of MN substrates based on the mechanical and immunological requirements needed for a specific vaccine or immunotherapy application.


Phacotrabeculectomy: comparison of results from 3.5- and 5.2-mm incisions.
To compare the intraocular pressure control, visual results, and astigmatic results of 3.5-mm and 5.2-mm incisions following phacotrabeculectomy with 12 months of follow-up. Fifty eyes underwent clear cornea punch trabeculectomy under a 5.0 x 2.5-mm scleral flap, closed with two 10-0 polyglactin sutures. The first 25 eyes underwent wound extension to 5.2 mm for insertion of a single-piece polymethylmethacrylate (PMMA) lens. The next 25 eyes underwent wound extension to 3.5 mm for insertion of a folded silicone lens. The mean intraocular pressure decrease from the preoperative level was 7.6 mm Hg in the 3.5-mm incision group and 7.8 mm Hg in the 5.2-mm incision group. One patient required continued medication. The best-corrected visual acuity was 20/40 or better in 86% of the patients, with no significant difference between the groups. The mean "with the wound" induced astigmatism showed no statistical difference between the two groups. The use of 10-0 polyglactin appears to aid filtration, yet minimizes hypotony or the need for antimetabolites. For surgeons who wish to reduce costs without compromising results during phacotrabeculectomy, there is merit in considering a 5.2-mm incision; moreover, the more rigid single-piece PMMA lens appears to be associated with fewer complications in the immediate postoperative period.


Silylcarborane acrylate nanoimprint lithography resists.
The synthesis of a novel silylcarborane acrylate monomer is reported as well as its application as an etch-resistant component for the formulation of imprint layers for UV nanoimprint lithography (NIL). By introduction of 10% by weight of the silylcarborane acrylate monomer into NIL resist formulations, the oxygen plasma etch rate of the resulting film was reduced by nearly a factor of 2. When used in NIL, the patterned resist layer had excellent oxygen plasma etch resistance, leading to effective image transfer to the underlying poly(hydroxyethyl methacrylate) lift-off layer. The latter allowed for the fabrication of metallic interdigitated electrode patterns via a NIL/lift-off process. This work demonstrates the robustness of silylcarborane-containing resists and paves the way for the investigation of new, high-resolution patterning methods.


[Clinical risk prevention by coordinator nurses, knowledge and organizational tools].
Coordinator nurses have a pivotal role to play in clinical risk prevention. They can and must influence the design of work processes to promote a culture of safety through the use of checklists, protocols, decision support systems, and by improving access to information, standardising tasks, and reducing the number of "hand-overs" and tasks performed relying only on one's memory. In order to evaluate knowledge and use of organisational tools for clinical risk prevention by coordinator nurses, an exploratory questionnaire survey was performed at a university teaching hospital in central Italy. Approximately 100 coordinators were asked to participate in the study. The aims of the survey were to assess the extent to which certain clinical governance tools are being used in individual hospital departments, evaluate knowledge of organisational processes that lead to errors and of measures, pertaining to nursing, that are considered to be effective in reducing adverse events. Wide differences were found among departments in the use of risk management strategies. Results also show that many nurse coordinators are not clearly aware of their organisational and professional responsibilities in clinical risk management. Though many professionals are well qualified and knowledgeable, only few are prepared educationally to manage clinical risk effectively when delivering patient care. For this reason, leadership should be encouraged and sustained, through educational courses and the promotion of a shift towards a culture of safety substantiated by scientific evidence.


Phaeohyphomycosis of brain: granulomatous encephalitis caused by Drechslera spicifera.
Drechslera spicifera is a dematiaceous fungus which occurs widely in nature but only rarely has been implicated in animal and human infections. Previous infections have occurred in superficial and subcutaneous sites or were encountered in immunologically compromised hosts. This report documents a case of granulomatous encephalitis due to Drechslera spicifera in an immunologically competent woman with no known underlying disease, from whom the fungus was isolated. Animal pathogenicity studies in mice reproduced the histopathologic features, and the fungus was reisolated from the animals.


Reducing two-dimensional rearfoot motion variability during walking.
Although three-dimensional movement analysis is the preferred method of assessing rearfoot motion during gait, the high cost of equipment and the time required to use it often make it unreasonable or impractical in a clinical setting. The authors discuss a method of minimizing the variability of rearfoot motion measurements during walking, using two-dimensional analysis when three-dimensional is not available to the clinician.


Chitosan-Coated Alginate Nanoparticles Enhanced Absorption Profile of Insulin Via Oral Administration.
In this study, four nanoparticle formulations (F1 to F4) comprising varying ratios of alginate, Pluronic F-68 and calcium chloride with a constant amount of insulin and chitosan as a coating material were prepared using polyelectrolyte complexation and ionotropic gelation methods to protect insulin against enzymatic degradation. This study describes the formulation design, optimisation, characterisation and evaluation of insulin concentration via oral delivery in rats. A reversed-phase high-performance liquid chromatography (HPLC) method was developed and validated to quantify insulin concentration in rat plasma. The proposed method produced a linear response over the concentration range of 0.39 to 50 µg/ml. In vitro release study showed that dissolution of insulin in simulated gastric juice of pH 1.2 was prevented by alginate core and chitosan coating but rapidly released in simulated intestinal fluid (pH 6.8). Additionally, Formulation 3 (F3) has a particle size of 340.40 ± 2.39 nm with narrow uniformity exhibiting encapsulation efficiency (EE) of 72.78 ± 1.25 % produced highest absorption profile of insulin with a bioavailability of 40.23 ±1.29% and reduced blood glucose after its oral administration in rats. In conclusion, insulin oral delivery system containing alginate and chitosan as a coating material has the ability to protect the insulin from enzymatic degradation thus enhance its absorption in the intestine. However, more work should be done for instance to involve human study to materialise this delivery system for human use.


Rapid Denaturing Organic Digestion Method for Targeted Protein Identification and Characterization.
Bottom-up mass spectrometry-based protein analysis methods employing protease digestion are routinely used to identify and characterize proteins with high specificity and sensitivity. Method performance is generally measured by sequence coverage capability and the total number of characteristic peptides identified, when compared to predicted databases. Limitations to commonly used solvent-based digestion methods currently employed include long digestion times (18-24 h or more), leading to protease autolysis, which also precludes automation, decreases sensitivity, and increases both intra- and inter-day performance variability. This report describes the development and validation of a simple, 5 min tryptic denaturing organic digestion (DOD) method for use with tandem mass spectrometry in bottom-up protein identification and characterization. It has been evaluated across select protein toxins and diagnostic clinical protein targets, substantially improving digestion performance when compared to other solution-based and enzyme-immobilized methods. The method was compared to two currently used bottom-up methods, the 24 h filter-aided sample prep (FASP) and Flash Digest (1 and 4 h) methods. Single proteins used to compare the methods included the ricin light chain, ricin heavy chain, ricin holotoxin, serotype A Clostridium botulinum toxin, Staphylococcus enterotoxin B, ribonuclease A, and thyroglobulin. In tests, across the proteins investigated, the 5 min DOD digestion method resulted in sequence coverages ranging from 55 to 100%, with relatively high reproducibility and precision; results were better than or equal to FASP method results and were greatly enhanced when compared to Flash method results. Importantly, DOD method intra- and inter-day precision was much improved as compared to results for both FASP and Flash digestions. These data indicated that the DOD method, when compared to the FASP and Flash Digest methods, dramatically reduced digestion time, while maintaining or improving the ability to detect and characterize targeted proteins, and reduced analytical variability for tryptic digestion, resulting in markedly faster and more precise analyses.


Estimation of oestrogen and progesterone receptors in chronic rhinitis.
The turbinates of 38 patients with chronic rhinitis were examined biochemically for oestrogen and progesterone receptors. Low levels of oestrogen-receptor-like activity (1-20 fmol/mg protein) were found in 50% of patients of both sexes. Progesterone receptor activity was also weak (1-16 fmol/mg protein) but was present only in 5 female patients. Immunocytochemical assay failed to demonstrate focal areas of oestrogen receptor activity. One juvenile nasopharyngeal angiofibroma was negative for both oestrogen and androgen receptors. Other possible mechanisms of hormonal action are considered.


Proximal femoral replacement in contemporary revision total hip arthroplasty for severe femoral bone loss: a review of outcomes.
Loss or absence of proximal femoral bone in revision total hip arthroplasty (THA) remains a significant challenge. While the main indication for the use of proximal femoral replacements (PFRs) is in the treatment of malignant disease, they have a valuable role in revision THA for loosening, fracture and infection in patients with bone loss. Our aim was to determine the clinical outcomes, implant survivorship, and complications of PFRs used in revision THA for indications other than malignancy. A retrospective review of 44 patients who underwent revision THA using a PFR between 2000 and 2013 was undertaken. Their mean age was 79 years (53 to 97); 31 (70%) were women. The bone loss was classified as Paprosky IIIB or IV in all patients. The mean follow-up was six years (2 to 12), at which time 22 patients had died and five were lost to follow-up. The mean Harris Hip Score improved from 42.8 (25.9 to 82.9) pre-operatively to 68.5 (21.0 to 87.7) post-operatively (p = 0.0009). A total of two PFRs had been revised, one for periprosthetic infection eight years post-operatively and one for aseptic loosening six years post-operatively. The Kaplan-Meier survivorship free of any revision or removal of an implant was 86% at five years and 66% years at ten years. A total of 12 patients (27%) had a complication including six with a dislocation. PFRs provide a useful salvage option for patients, particularly the elderly with massive proximal femoral bone loss who require revision THA, with significant clinical improvement. While the survivorship of the implant is good at five years, dislocation continues to be the most common complication. The judicious use of larger femoral heads, dual-mobility constructs, or constrained liners may help to minimise the risk of dislocation. Cite this article: Bone Joint J 2017;99-B:325-9.


Comparison of ConsExpo estimated exposure levels to glycol ethers during professional cleaning work to existing regulatory occupational exposure limit values.
Objectives. Researchers have shown that cleaning workers have an increased risk of asthma and rhinitis, mainly due to exposure to chemical substances present in the cleaning products they use. Among the important substances are glycol ethers, increasingly used as components in cleaning products. This study aimed to assess exposure levels of glycol ether in professional cleaning products and compare them to existing regulatory exposure limit values. Methods. Information from safety data sheets of the products is used to identify the glycol ethers present in the cleaning products and their respective concentrations. Other sources were used to obtain the relevant data required for use in the tool to generate exposure assessments. Exposure levels for various cleaning work exposure scenarios were estimated using the ConsExpo Web tool. Results. The estimated exposure values are significantly lower than the existing regulatory occupational exposure limit (OEL) values for the different glycol ethers. Conclusions. The study showed that the risk of exposure to glycol ethers by inhalation from professional cleaning products is minimal as exposure estimates were much below the regulatory OEL values.


Impaired Tubular Secretion of Organic Solutes in Advanced Chronic Kidney Disease.
The clearance of solutes removed by tubular secretion may be altered out of proportion to the GFR in CKD. Recent studies have described considerable variability in the secretory clearance of waste solutes relative to the GFR in patients with CKD. To test the hypothesis that secretory clearance relative to GFR is reduced in patients approaching dialysis, we used metabolomic analysis to identify solutes in simultaneous urine and plasma samples from 16 patients with CKD and an eGFR of 7±2 ml/min per 1.73 m2 and 16 control participants. Fractional clearances were calculated as the ratios of urine to plasma levels of each solute relative to those of creatinine and urea in patients with CKD and to those of creatinine in controls. Metabolomic analysis identified 39 secreted solutes with fractional clearance >3.0 in control participants. Fractional clearance values in patients with CKD were reduced on average to 65%±27% of those in controls. These values were significantly lower for 18 of 39 individual solutes and significantly higher for only one. Assays of the secreted anions phenylacetyl glutamine, p-cresol sulfate, indoxyl sulfate, and hippurate confirmed variable impairment of secretory clearances in advanced CKD. Fractional clearances were markedly reduced for phenylacetylglutamine (4.2±0.6 for controls versus 2.3±0.6 for patients with CKD; P<0.001), p-cresol sulfate (8.6±2.6 for controls versus 4.1±1.5 for patients with CKD; P<0.001), and indoxyl sulfate (23.0±7.3 versus 7.5±2.8; P<0.001) but not for hippurate (10.2±3.8 versus 8.4±2.6; P=0.13). Secretory clearances for many solutes are reduced more than the GFR in advanced CKD. Impaired secretion of these solutes might contribute to uremic symptoms as patients approach dialysis.


Evaluation of Staphylococcus aureus Bacteremia: Academic and Community-Based Management Within the Same Health System.
A nonrandomized, retrospective comparison of Staphylococcus aureus bacteremia between an academic hospital setting (n=53) and a community hospital setting (n=245) within a single healthcare system was performed. Despite infectious disease consultations, S. aureus bacteremia management recommendations based on Infectious Diseases Society of America (IDSA) guidelines were not followed as closely in the community hospital setting. The community hospital setting requires management standardization for patients with S. aureus bacteremia. Infect Control Hosp Epidemiol 2017;38:740-742.


Identifying the role of excess electrons and holes for initiating the photocatalytic dissociation of methanol on a TiO2(110) surface.
As a prototype for the catalytic oxidation of organic contaminants, photocatalytic methanol dissociation on rutile TiO2(110) has drawn much attention, but its reaction mechanism remains elusive. While polarons are ubiquitous in photovoltaics and heterogeneous catalysis, how surface polarons influence adsorption remains unclear. In this paper, density functional theory is used to study the effect of excess electrons and holes on methanol dissociation on rutile TiO2(110). The effect of excess carriers for three types of methanol dissociation on the metal oxides are compared. The results show that the excess electron and hole play different roles in the dissociation reactions even though they present similar adsorption behaviors. The excess electron is easily trapped in the lattice Ti atom, and it decreases the dissociation barrier of methanol to 0.13 eV. Furthermore, the excess hole prefers to stick with the hydroxyl radical, which increases the energy barrier of methanol dissociation up to 0.43 eV. It was found that the height of the dissociation barrier is dependent on the orientation of the methanol molecules, not on the distance to the modified electron. This study identifies the essential roles of excess electrons and holes for promoting O-H dissociation. Our findings contribute considerably to broadening the understanding of photocatalytic chemistry.


Relationships between postural balance, aiming technique and performance in elite rifle shooters.
The aim of the present study was to examine the relationships between postural balance, aiming technique and shooting score among elite rifle shooters at an intra- and inter-individual level. Twelve elite athletes belonging to China national team performed 60 shots under test conditions. Shooting score was used to indicate performance and footscan1.0 force platform was used to measure postural balance variables, while a SCATT MX-02 optoelectronic training device was used to measure aiming technique parameters. Inter-individual analyses indicated that postural balance was negatively correlated with shooting score (r = -0.697, P < 0.05) and aiming accuracy (r = -0.810, P < 0.01). Postural balance showed a positive correlation with the stability of hold (r = 0.923, P < 0.01) and stability of triggering (r = 0.564, P < 0.05). Intra-individual analyses indicated that there was a significant correlation between postural balance and performance, aiming accuracy and stability of hold for all shooters. Postural balance was related to the stability of triggering for six shooters. Postural balance was not statistically significant with aiming time on an intra- and inter-individual basis (P > 0.05). Our data indicated that postural balance was very important in aiming technique and shooting performance among elite rifle shooters. Additional balance programmes should be encouraged to improve a shooter's postural balance.


Overexpression of Heme Oxygenase-1 in Mesenchymal Stem Cells Augments Their Protection on Retinal Cells In Vitro and Attenuates Retinal Ischemia/Reperfusion Injury In Vivo against Oxidative Stress.
Retinal ischemia/reperfusion (I/R) injury, involving several ocular diseases, seriously threatens human ocular health, mainly treated by attenuating I/R-induced oxidative stress. Currently, mesenchymal stem cells (MSCs) could restore I/R-injured retina through paracrine secretion. Additionally, heme oxygenase-1 (HO-1) could ameliorate oxidative stress and thus retinal apoptosis, but the expression of HO-1 in MSC is limited. Here, we hypothesized that overexpression of HO-1 in MSC (MSC-HO-1) may significantly improve their retina-protective potentials. The overexpression of HO-1 in MSC was achieved by lentivirus transduction. Then, MSC or MSC-HO-1 was cocultured with retinal ganglion cells (RGC-5) in H2O2-simulated oxidative condition and their protection on RGC-5 was systemically valuated in vitro. Compared with MSC, MSC-HO-1 significantly attenuated H2O2-induced injury of RGC-5, including decrease in cellular ROS level and apoptosis, activation of antiapoptotic proteins p-Akt and Bcl-2, and blockage of proapoptotic proteins cleaved caspase 3 and Bax. In retinal I/R rats model, compared with control MSC, MSC-HO-1-treated retina significantly retrieved its structural thickness, reduced cell apoptosis, markedly attenuated retinal oxidative stress level, and largely regained the activities of typical antioxidant enzymes, SOD and CAT. Therefore, it could be concluded that overexpression of HO-1 provides a promising strategy to enhance the MSC-based therapy for I/R-related retinal injury.


Determinants of psychological functioning in patients undergoing radiotherapy: a descriptive study.
This study sought to confirm the literature reports on psychological well-being during radiotherapy treatment using a population across multiple clinical sites, resulting in a larger population (N = 156) than has typically been followed in quality of life descriptive studies of radiotherapy, and a more varied one in terms of diagnosis. This study is unique in its individual differences perspective, whereby it aimed to identify those demographic variables that predict baseline levels of psychological distress as well as changes in distress during treatment. The data used were the control data from a previous study assessing the effectiveness of a stress management intervention. Participants completed the SF-36, STAI-S, and CES-D scales at baseline and after Weeks 1, 2, and 3 of treatment. Consistent with prior studies, this study found that, on average, patients began with a low level of psychological distress, as indicated by the scale norms. However, this study found considerable variation in anxiety levels, with some patients beginning treatment with a relatively high level of anxiety. For those with relatively high levels of baseline anxiety, anxiety decreased during treatment. A patient's baseline psychological distress level was predicted by marital status, diagnosis, gender, education level, and income range. In addition, cancer type, income level, and education level predicted changes in distress levels over treatment.


Glucose deprivation enhances resistance to paclitaxel via ELAVL2/4-mediated modification of glycolysis in ovarian cancer cells.
The dysregulation of glycolysis regardless of oxygen availability is one of the major characteristics of cancer cells. While the drug resistance of ovarian cancer cells has been extensively studied, the molecular mechanism of anticancer drug resistance under low-glucose conditions remains unknown. In this study, we investigated the pathway mediating drug resistance under low-glucose conditions by examining the relationship between embryonic lethal abnormal vision Drosophila homolog-like (ELAVL) protein and glycolysis-related enzymes. Ovarian cancer cells resistant to 2.5 nM paclitaxel were exposed to low-glucose media for 2 weeks, and the expression levels of ELAVL2, ELAVL4, glycolytic enzymes, and drug resistance-related proteins were elevated to levels comparable to those in cells resistant to 100 nM paclitaxel. Gene silencing of ELAVL2/4 using small interfering RNA prevented the upregulation of glycolysis-related enzymes, reduced lactate production, and sensitized 2.5 nM paclitaxel-resistant ovarian cancer cells to anticancer agents under hypoglycemic conditions. Furthermore, pharmacological inhibition of glycolytic enzymes with 2-deoxyglucose, a specific inhibitor of glycolysis, triggered caspase-dependent apoptosis, reduced lactate generation, and blocked the expression of drug resistance-related proteins under low-glucose conditions. These results suggest that the level of ELAVL2/4 is responsible for the development of chemoresistance through activation of the glycolysis pathway under glucose deprivation conditions.


Human mesenchymal stem cells differentiate to epithelial cells when cultured on thick collagen gel.
The stem cell niche is crucial to the control of stem cell fate determination in vitro as well as in vivo, and an understanding of these niches is required for the progression of stem cell and tissue engineering. The goal of our study was to commit human mesenchymal stem cells (hMSCs) to the epithelial lineage. To do this, we cultured bone marrow-derived mesenchymal stem cells (MSCs) on plates coated with type I collagen gel with or without 10 μM all-trans retinoic acid (ATRA).We found depth-dependent differentiation of hMSCs to the epithelial lineage, with the thick collagen gel (1900 μm) generating more than 80% cytokeratin-18 (CK-18)-positive cells, whereas the thin collagen gel (100 μm) generated significantly fewer CK-18-positive cells. In addition, we found that supplementation of 10 μM ATRA enhanced CK-18 expression and induced cluster-formation in cells grown on the thick collagen gel. The effect of gel depth on hMSC differentiation appears to be caused by partial cytoskeletal disruption.These results suggest that ATRA and a collagen extracellular matrix may have a synergistic effect on differentiation of human mesenchymal stem cells to epithelial lineage.


Dopamine D1 receptor gene polymorphism and schizophrenia in Japan.
We studied the relationship between schizophrenia and the DdeI polymorphism in the 5' untranslated region (5'UTR) of the dopamine D1 receptor (DRD1) gene. This polymorphism is an A (A1 allele) to G (A2 allele) transition in the 5' UTR of exon 2 at bp -48 (A-48G). One hundred forty-eight schizophrenics and 148 control subjects were investigated. No significant differences in genotypic counts and allele frequencies between schizophrenics and controls were found. Although a significant difference between the patients classified as disorganized type and the controls was discovered both in genotypic counts and allele frequencies, neither association proved significant when a Bonferroni correction was used. Moreover, there were no differences in scores of main symptoms of schizophrenia based on the Manchester Scale between patients with A1/A1 genotype and those with A1/A2 genotype. These findings suggest that this gene may not be involved in the pathogenesis of schizophrenia.