Quantum verification of NP problems with single photons and linear optics.
Quantum computing is seeking to realize hardware-optimized algorithms for application-related computational tasks. NP (nondeterministic-polynomial-time) is a complexity class containing many important but intractable problems like the satisfiability of potentially conflict constraints (SAT). According to the well-founded exponential time hypothesis, verifying an SAT instance of size n requires generally the complete solution in an O(n)-bit proof. In contrast, quantum verification algorithms, which encode the solution into quantum bits rather than classical bit strings, can perform the verification task with quadratically reduced information about the solution in [Formula: see text] qubits. Here we realize the quantum verification machine of SAT with single photons and linear optics. By using tunable optical setups, we efficiently verify satisfiable and unsatisfiable SAT instances and achieve a clear completeness-soundness gap even in the presence of experimental imperfections. The protocol requires only unentangled photons, linear operations on multiple modes and at most two-photon joint measurements. These features make the protocol suitable for photonic realization and scalable to large problem sizes with the advances in high-dimensional quantum information manipulation and large scale linear-optical systems. Our results open an essentially new route toward quantum advantages and extend the computational capability of optical quantum computing.


Locomotor and learning deficits in adult rats exposed to monosodium-L-glutamate during early life.
Neonatal administration of neurotoxic doses of monosodium-L-glutamate (MSG) to rats causes neuronal necrosis of the hypothalamus along with behavioral abnormalities. In the present study the behavioral effects in rats treated with subneurotoxic doses of MSG (2 mg/g, p.o., for 10 days) at the weaned stage were investigated at day 90 post-dosing. The MSG-treated rats did not show significant changes in any of the components of spontaneous locomotor activity but, after apomorphine challenge, marked decreases in the distance travelled, ambulatory and stereotypic times, and the number of stereotypic movements with an increase in the resting time were observed. Significant decrease in the active avoidance learning performance was observed in the MSG-treated rats in the learning (acquisition) phase without any changes in the extinction and relearning phases. The results indicate that exposure to MSG in early life in rats could lead to subtle behavioral aberrations in late adulthood.


Late and very late initial probing for congenital nasolacrimal duct obstruction: what is the cause of failure?
To find the cure rate of late (second year of age) and very late (3-5 years of age) initial probing for congenital nasolacrimal duct obstruction (CNLDO) and to identify the factors contributing to the failure rate of the probing in older children. In a prospective interventional case series study, 169 eyes of 125 consecutive patients (1-5 years old) with CNLDO underwent probing under general anaesthesia. Cure was defined as absence of tearing and discharge in the affected eye. 138 eyes of 101 patients aged 13-60 months (mean 23.4 (SD 10.2)) were included. Of 15 eyes (10.8%) with complex CNLDO, 80% presented after 24 months of age (p<0.0001). The cure rate was 89% in patients 13-24 months of age and 72% after the age of 24 months (p = 0.01). It was 90.2% in the membranous and 33.3% in the complex CNLDO in both late and very late probing (p<0.0001). There was a high correlation (r = 0.97) and no significant difference between the cure rate at 1 week and final follow up. Accumulation of the complex CNLDO is the main risk factor for failure of probing in the older children. The outcome of the nasolacrimal duct probing at 1 week follow up is highly indicative of the final outcome.


A prospective randomized study to evaluate the effect of leukodepletion on the rate of alveolar production of exhaled nitric oxide during cardiopulmonary bypass.
Cardiopulmonary bypass is associated with a whole body inflammatory reaction. Exhaled nitric oxide increases in inflammatory lung conditions (eg, asthma) in proportion to the severity of inflammation, and has been proposed as a marker of pulmonary inflammation during cardiopulmonary bypass. This study evaluated the effect of arterial line leukocyte depletion during cardiopulmonary bypass on the rate of alveolar production of exhaled nitric oxide. One hundred and ten patients with normal respiratory function, undergoing first time coronary artery bypass grafting, were randomized to two groups. Fifty-five patients had an arterial line leukocyte-depleting filter and 55 controls had a standard arterial line filter. Nitric oxide was sampled through an endotracheal Teflon tube after median sternotomy, but before cardiopulmonary bypass and 30 minutes after cardiopulmonary bypass, using a real time chemiluminescence analyzer, during the phase of the alveolar plateau. There were no significant differences in the precardiopulmonary bypass values of exhaled nitric oxide between the control (2.92 +/- 1.51 ppb/s) and the leukodepletion group (3.11 +/- 1.53 ppb/s) (p = 0.4). After cardiopulmonary bypass, the rate of alveolar production of exhaled nitric oxide increased in both groups, being, however, significantly higher in the control group (4.68 +/- 1.89 vs 3.72 +/- 1.33 ppb/s) (p = 0.02). Continuous arterial line leukocyte-depletion significantly reduces the rate of alveolar production of exhaled nitric oxide after cardiopulmonary bypass. Changes in the rate of alveolar production of exhaled nitric oxide may be used as a marker of pulmonary inflammation in coronary artery surgery.


Isolation, characterization, and localization of a capsule-associated gene, CAP10, of Cryptococcus neoformans.
Cryptococcus neoformans is a pathogenic fungus which most commonly affects the central nervous system and causes fatal meningoencephalitis primarily in patients with AIDS. This fungus produces a thick extracellular polysaccharide capsule which is well recognized as a virulence factor. Here, we describe the isolation and characterization of a novel gene, CAP10, which is required for capsule formation. Complementation of the acapsular cap10 mutant produced an encapsulated strain and the deletion of CAP10 from a wild strain resulted in an acapsular phenotype. The molecular mass of the hemagglutinin epitope-tagged Cap10p is about 73 kDa, which is similar to the size predicted from sequence analysis. When CAP10 was fused with a hybrid green fluorescent protein construct, the fluorescence signals appeared as patches in the cytoplasm. Using a reporter gene construct, we found that CAP10 was expressed at high levels in late-stationary-phase cells. In addition, we found that the expression levels of CAP10 are modulated by the transcriptional factor STE12alpha. Deletion of STE12alpha downregulated the expression levels of CAP10 while overexpression of STE12alpha upregulated the expression levels of CAP10. Animal model studies indicate that deletion of the CAP10 gene results in the loss of virulence, and complementation of the acapsular phenotype of cap10 restores virulence. Thus, CAP10 is required for capsule formation and virulence.


Molecular characterization of p16-immunopositive but HPV DNA-negative oropharyngeal carcinomas.
Recent studies have reported that p16 protein overexpression qualifies as a surrogate marker identifying an oncogenic human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC). However, there is still a percentage of OPSCCs that are positive for p16 immunohistochemistry (p16 IHC) but lack HPV DNA. The objective of this study was to characterize this group at the molecular level by performing sensitive HPV DNA- and RNA-based PCR methods and genetic profiling. All patients diagnosed with an OPSCC in the period 2000-2006 in two Dutch university medical centers were included (n = 841). The presence of HPV in a tumor sample was tested by p16 IHC followed by an HPV DNA GP5+/6+ PCR. p16 IHC scored positive in 195 samples, of which 161 were HPV DNA-positive and 34 (17%) HPV DNA-negative. In the latter group, a SPF10-LiPA25 assay, an HPV16 type-specific E7 PCR and an E6 mRNA RT-PCR were performed. Next, ten of these cases were further analyzed for loss of heterozygosity (LOH) of 15 microsatellite markers at chromosome arms 3p, 9p and 17p. Of the 34 p16-positive but PCR-negative OPSCCs, two samples tested positive by SPF10 assay, HPV16 E7 PCR and HPV16 E6 mRNA RT-PCR. Three samples tested positive by SPF10 assay but negative by the HPV16-specific assays. Nine of ten cases that were tested for LOH showed a genetic pattern comparable to that of HPV-negative tumors. This study categorizes p16-positive but HPV DNA-negative OPSCCs as HPV-negative tumors based on genetic profiling. This study highlights the importance of performing HPV testing in addition to p16 IHC for proper identification of HPV-associated OPSCCs.


Bionanotechnology. Colloidal nanoparticles as advanced biological sensors.
Colloidal nanoparticle biosensors have received intense scientific attention and offer promising applications in both research and medicine. We review the state of the art in nanoparticle development, surface chemistry, and biosensing mechanisms, discussing how a range of technologies are contributing toward commercial and clinical translation. Recent examples of success include the ultrasensitive detection of cancer biomarkers in human serum and in vivo sensing of methyl mercury. We identify five key materials challenges, including the development of robust mass-scale nanoparticle synthesis methods, and five broader challenges, including the use of simulations and bioinformatics-driven experimental approaches for predictive modeling of biosensor performance. The resultant generation of nanoparticle biosensors will form the basis of high-performance analytical assays, effective multiplexed intracellular sensors, and sophisticated in vivo probes.


Anticipatory modulation of digit placement for grasp control is affected by Parkinson's disease.
Successful object manipulation relies on the ability to form and retrieve sensorimotor memories of digit forces and positions used in previous object lifts. Past studies of patients affected by Parkinson's disease (PD) have revealed that the basal ganglia play a crucial role in the acquisition and/or retrieval of sensorimotor memories for grasp control. Whereas it is known that PD impairs anticipatory control of digit forces during grasp, learning deficits associated with the planning of digit placement have yet to be explored. This question is motivated by recent work in healthy subjects revealing that anticipatory control of digit placement plays a crucial role for successful manipulation. We asked ten PD patients off medication and ten age-matched controls to reach, grasp and lift an object whose center of mass (CM) was on the left, right or center. The only task requirement was to minimize object roll during lift. The CM remained the same across consecutive trials (blocked condition) or was altered from trial to trial (random condition). We hypothesized that impairment of the basal ganglia-thalamo-cortical circuits in PD patients would reduce their ability to anticipate digit placement appropriate to the CM location. Consequently, we predicted that PD patients would exhibit similar digit placement in the blocked vs. random conditions and produce larger peak object rolls than that of control subjects. In the blocked condition, PD patients exhibited significantly weaker modulation of fingertip contact points to CM location and larger object roll than controls (p<0.05 and p<0.01, respectively). Nevertheless, both controls and PD patients minimized object roll more in the blocked than in the random condition (p<0.01). Our findings indicate that, even though PD patients may have a residual ability of anticipatory control of digit contact points and forces, they fail to implement a motor plan with the same degree of effectiveness as controls. We conclude that intact basal ganglia-thalamo-cortical circuits are necessary for successful sensorimotor learning of both grasp kinematics and kinetics required for dexterous hand-object interactions.


Dual presence of Anaplasma phagocytophilum and its closely related Anaplasma sp. in ixodid ticks in Hokkaido, Japan, and their specific molecular detection.
Anaplasma phagocytophilum causes human granulocytic anaplasmosis (HGA) and tick-borne fever in ruminants. A closely related and potentially novel Anaplasma sp. in Japan was recently characterized. The aims of the study were to provide molecular evidence for the presence of these 2 species in Japan, and to develop a reliable PCR method based on the nucleotide differences within the citrate synthase (gltA) gene. DNA samples from 182 ixodid ticks (134 Ixodes persulcatus, 35 Haemaphysalis douglasii and 13 I. ovatus) collected from 2 sites in Hokkaido, Japan, were screened for A. phagocytophilum and its closely related Anaplasma sp. (herein designated as Anaplasma sp. Japan) using 16S rRNA PCR, revealing a combined prevalence rate of 27.5% (50 samples). The positive samples were then used to evaluate a newly developed gltA-based nested PCR method. Selected positive samples were further characterized using the groEL gene for confirmation and phylogenetic analyses. Two groups of sequence results were obtained: those that had closer identities with (1) A. phagocytophilum (99.5-99.6% for 16S rRNA, 97.5% for gltA and 98.4% for groEL), and those that had closer identities with (2) Anaplasma sp. closely related to A. phagocytophilum in Japan (99.3% for 16S rRNA, 96.4-98.7% for gltA and 97.5-97.9% for groEL). The present study confirmed the distinct presence of A. phagocytophilum and its closely related Anaplasma sp. in Japan, and developed a new PCR detection method based on gltA that can distinguish the 2 organisms.


Mannose binding lectin (MBL) gene mutation is not a risk factor for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Japanese.
Mannose binding lectin (MBL) deficiency may be associated with increased susceptibility to infection and autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In the present study, we performed for the first systematic search for mutations in all the four exons of the MBL gene using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis. Of 49 healthy Japanese individuals studied, only the previously reported mutation at the codon 54 (substitution from Gly to Asp; G54D) was identified. The allele frequencies of G54D in 105 healthy Japanese individuals, 95 SLE patients and 59 RA patients, were 0.233, 0.226 and 0.178, respectively, which were not significantly different. In addition, two polymorphisms at positions of -550 and -221 in the promoter region were not associated with SLE and RA. It is unlikely that MBL deficiency plays a major role in the pathogenesis of SLE and RA in Japanese.


New insights into interactions between the human PTH/PTHrP receptor and agonist/antagonist binding.
We prepared a polyclonal antiserum [Ab-(88-97)] against residues 8-97 of the NH2-terminal tail of the human (h) parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor. Ab-(88-97) bound specifically to the receptor, as assessed by fluorescence-activated cell sorter analysis of HEK C21 cells, which stably express approximately 400,000 hPTH/PTHrP receptors per cell. Unlike PTH, Ab-(88-97) binding did not elicit either adenosine 3',5'-cyclic monophosphate or intracellular calcium concentration signaling responses in these cells. Incubation of C21 cells for 90 min at 4 degrees C with hPTH-(1-34) plus antiserum reduced the Ab-(88-97) binding to the cells by up to 40-50% of control values in a PTH concentration-dependent fashion with a half-maximal effective concentration of approximately 5 nM. The decrease in Ab-(88-97) binding caused by hPTH-(1-34) was completely reversed by coincubation with hPTHrP-(7-34). We conclude that residues 88-97 of the hPTH/PTHrPR are involved, either directly or indirectly, in agonist but not antagonist binding to the receptor.


Reclaiming the social in community movements: perspectives from the USA and Brazil/South America: 25 years after Ottawa.
Since the Ottawa Charter 25 years ago, community participation has been adopted worldwide by nation states and communities as a core health promotion strategy. Rising inequities since that time, however, have been largely unchecked in the Americas and globally, and have presented us with an acutely paradoxical time for community participation and action. On the one hand, transnational globalized markets and accompanying economic and environmental devastation have challenged the effectiveness of community action to create health. On the other hand, hopeful signs of local through national and international activism and of new mechanisms for community engagement continue to surface as meaningful and effective democratic acts. This article presents a dialogue on these issues between colleagues in the United States and Brazil, and considers the broader applicability to Latin America and worldwide. We begin by discussing how community participation and community organizing grew out of our respective histories. We consider the catalytic role of the Ottawa Charter in spurring a reorientation of health promotion and the genesis of healthy city and community initiatives, as well as other current community organizing strategies and the growth of participatory research/CBPR. We unpack the potential for co-optation of both community and social participation and end with recommendations for what we can do to maintain our integrity of belief in democratic social participation to promote improved health and health equity.


Disk Area Is a More Reliable Measurement Than Anteroposterior Length in the Assessment of Lumbar Disk Herniations: A Validation Study.
Retrospective study. The goal of this study is to identify and validate the reliability and accuracy of 2 methods used to assess lumbar disk herniations (LDHs): anteroposterior length and cross-sectional area. Many clinicians characterize LDHs through the measurement of the anteroposterior length in the axial plane. Radiologists, on the other hand, have utilized software to measure the disk and canal areas to define the injury. In this study, the authors consider the reliability and accuracy of anteroposterior length in comparison with the area. Using International Classification of Diseases, 10th Revision (ICD-10) code M51.26, patients at a single academic medical center who received a diagnosis of primary lumbar radicular pain with subsequent magnetic resonance imaging documentation of a single-level disk herniation in 2015 and 2016 were identified. AGFA-IMPACS software was utilized to make the following measurements: anterior-posterior canal length; anterior-posterior disk length; mid-canal width; mid-disk width; total canal area; total disk area. Data analysis was conducted in SPSS and a 2-tailed reliability analysis using Cronbach alpha as a measure of reliability was obtained. A total of 408 patients met the inclusion and exclusion criteria for this study. Sixteen (3.9%) had L3-L4 herniation, 208 had L4-L5 herniation (51.0%), and 184 had L5-S1 herniation (47.5%). The least reliable interobserver metrics, with respective Cronbach alpha values of 0.381 and 0.659, were the linear measurements of mid-disk width and anterior-posterior canal length. Area measurements of the disk and canal areas generated Cronbach alpha values of 0.707 and 0.863. Intraobserver Cronbach alpha values for all measurements, including all areas and lengths, met or exceeded 0.982. The cross-sectional area provides a more reliable measurement modality for diskLDHs in comparison to linear measurements. Unlike anteroposterior length, cross-sectional area incorporates the shape of a herniation or canal in its measurement. Thus, it is superior in its characterization LDH particularly in light of its stronger reproducibility. Level III-retrospective study.


Ultrasonographic detection of portal branches and hepatic vein gas associated with mesenteric artery occlusion: a new finding correlated with patient prognosis?
The diagnosis of bowel infarction is still a challenge. In some cases, portal venous gas is an associated feature and in these patients, the prognosis is very poor. We report on our experience with two consecutive cases in which ultrasonography showed gas in the portal venous branches, and also in the hepatic veins in one of them. At laparotomy, advanced bowel necrosis was found, and both patients died within 24 hours. Other cases of portal venous gas associated with bowel infarction have been reported, but this is the first report of gas also being found in the hepatic veins. There may be a relationship between the amount of gas in the intrahepatic veins and the stage of bowel ischemia. Confirmation of this might improve the selection of patients and eliminate unnecessary procedures.


Characterization of the fecal microbiota of sows and their offspring from German commercial pig farms.
Strategies to combat microbiota-associated health problems are of high interest in pig production. Successful intervention strategies with beneficial long-term effects are still missing. Most studies on pig microbiota have been conducted under standardized experimental conditions, but the situation in commercial farms differs dramatically. This study describes the fecal microbiota in German commercial pig farms under practical conditions. The study is part of the larger project "Optibiom" that aims to use bacterial composition and farm metadata to formulate tailor-made solutions for farm-specific health maintenance strategies. Special consideration is given to the sow-piglet relationship. Fecal samples from sows and their piglets were collected at two time points each in 20 different farms (sows ante- and postpartum and piglets before and after weaning). The extracted DNA was sequenced with Illumina 16S rDNA sequencing. For data analysis and visualization, differential abundance analyses, as well as hierarchical clustering and nonmetric multidimensional scaling (NMDS) were performed. A new "family unit" was implemented to compare farms based on the association between the microbiota in sows and their offspring. There are distinct changes in the microbial communities in sows before and after birth as well as in suckling and post-weaning piglets. The suckling pig microbiota is particularly different from all other groups and shows a lower bacterial diversity. While dominant genera in antepartum sows further displace the abundance of non-dominant genera postpartum, the opposite was true for piglets, where non-dominant bacteria in the suckling phase became dominant after weaning. The family unit for sows and their piglets led to separate cluster formation for some farms. The results indicate that the sow-piglet relationship is one driving force for the observed differences of the pig farms. The next step in the analysis will be the combination of metadata (feeding, housing and management practices) to find farm-specific differences that can be exploited to formulate a farm-specific health maintenance strategy.


Synthesis of homoveratric acid-imprinted polymers and their evaluation as selective separation materials.
A bulk polymerization method was used to easily and efficiently prepare homoveratric acid (3,4-dimethoxyphenylacetic acid)-imprinted polymers from eight basic monomers: 2-vinylpyridine, 4-vinylpyridine, 1-vinylimidazole, N-allylaniline, N-allylpiperazine, allylurea, allylthiourea, and allylamine, in the presence of homoveratric acid as a template in N,N-dimethylformamide as a porogen. The imprinted polymer prepared from allylamine had the highest affinity to the template, showing an imprinting factor of 3.43, and allylamine polymers MIP8/NIP8 were selected for further studies. Their binding properties were analyzed using the Scatchard method. The results showed that the imprinted polymers have two classes of heterogeneous binding sites characterized by two pairs of K(d), B(max) values: K(d)(1) = 0.060 μmol/mL, B(max)(1) = 0.093 μmol/mg for the higher affinity binding sites, and K(d)(2) = 0.455 μmol/mL, B(max)(2) = 0.248 μmol/mg for the lower affinity binding sites. Non-imprinted polymer has only one class of binding site, with K(d) = 0.417 μmol/mL and B(max) = 0.184 μmol/mg. A computational analysis of the energies of the prepolymerization complexes was in agreement with the experimental results. It showed that the selective binding interactions arose from cooperative three point interactions between the carboxylic acid and the two methoxy groups in the template and amino groups in the polymer cavities. Those results were confirmed by the recognition studies performed with the set of structurally related compounds. Allylamine polymer MIP8 had no affinity towards biogenic amines. The obtained imprinted polymer could be used for selective separation of homoveratric acid.


Daily proactive problem-solving and next day stress appraisals: the moderating role of behavioral activation.
Background and objectives: Drawing upon transactional theory, this study examined the interactive effects of daily problem-prevention behaviors and an aspect of personality relevant to stress responses (i.e., behavioral activation) on next-day stress appraisals of problem-solving demands. Design and methods: Data were collected from 188 employees across a range of industries using an initial survey to collect information on personality, followed by twice-daily surveys over five consecutive work days to measure daily problem-prevention, stress appraisals and problem-solving demands. Results: Multilevel analyses revealed that behavioral activation system (BAS) affected stress appraisals in unique ways. As hypothesized, BAS had a positive direct effect on challenge appraisal. It also moderated the effects of problem-prevention on next-day hindrance appraisals, such that the relationship was more strongly positive for individuals with low levels of BAS. Conclusions: The results demonstrate the BAS has implications not just for promoting positive challenge appraisals, but also for alleviating detrimental effects on stress appraisal. Overall, the findings emphasize the value of exploring the interactive effects of day- and person-level factors on stress appraisals, thereby offering a platform for future research.


Adsorption behavior of multicomponent protein mixtures containing alpha 1-proteinase inhibitor with the anion exchanger, 2-(diethylamino)ethyl-Spherodex.
The equilibrium binding behavior of alpha 1-proteinase inhibitor (alpha 1-PI) in the presence of human serum albumin (HSA) has been determined in packed bed systems with the anion exchanger, 2-(diethylamino)ethyl (DEAE)-Spherodex. Experimental data derived for the individual proteins were compared with the corresponding data obtained from batch adsorption studies as well as studies in which mixtures of these two proteins were loaded at different concentration ratios onto columns of the same anion exchange adsorbent. The results confirm that alpha 1-PI has a greater affinity for the anion exchanger, although competitive adsorption was observed as the inlet concentration of HSA was increased. Under these conditions, decreased binding capacities and lower dynamic adsorption rates were observed for alpha 1-PI with the DEAE-Spherodex anion exchange adsorbent. The results are discussed in terms of the influence which various contaminants that occur in multicomponent mixtures of proteins from human plasma can have on the equilibrium binding characteristics of a target protein with weak or strong ion exchange adsorbents under conditions approaching concentration overload in preparative chromatographic systems. These investigations have also addressed, as the first part of an iterative approach for the simulation of the adsorption behavior of multicomponent mixtures of human plasma proteins with ion exchange and affinity chromatographic adsorbents, the ability of noncompetitive and competitive Langmuirean models to simulate the adsorption of alpha 1-PI in the presence of different concentrations of HSA to DEAE-Spherodex.


Absolute frequency of cesium 6S-8S 822 nm two-photon transition by a high-resolution scheme.
We present an alternative scheme for determining the frequencies of cesium (Cs) atom 6S-8S Doppler-free transitions. With the use of a single electro-optical crystal, we simultaneously narrow the laser linewidth, lock the laser frequency, and resolve a narrow spectrum point by point. The error budget for this scheme is presented, and we prove that the transition frequency obtained from the Cs cell at room temperature and with one-layer μ-metal shielding is already very near that for the condition of zero collision and zero magnetic field. We point out that a sophisticated linewidth measurement could be a good guidance for choosing a suitable Cs cell for better frequency accuracy.


Human epithelial cell death caused by Actinobacillus actinomycetemcomitans infection.
The gingival sulcus is the shallow crevice around the tooth, and its epithelium is a gateway for initial bacterial infection in periodontal disease. Recent studies have shown that Actinobacillus actinomycetemcomitans invades an epithelial cell line, KB cells, in vitro. The aim of the present study was to clarify the changes in KB cells after A. actinomycetemcomitans infection. The cytotoxic effects of A. actinomycetemcomitans on KB cells were determined at 72, 96 and 120 h after infection by an MTT assay. Nuclear morphological changes were observed by staining with Hoechst 33258. Cytoplasmic histone-associated DNA fragmentation in the infected KB cells was determined by ELISA. A. actinomycetemcomitans was cytotoxic on KB cells, and condensation and degradation of the nuclei were observed. DNA fragmentation was increased after the infection. In addition, A. actinomycetemcomitans showed similar cytotoxic effects on human gingival epithelial cells. The present study demonstrated that A. actinomycetemcomitans induces apoptotic cell death of oral epithelial cells in an in-vitro culture system. This induced apoptosis might be involved in the initiation and progression of periodontitis.


1-stage urethral reconstruction using colonic mucosa graft for the treatment of a long complex urethral stricture.
We investigated the possibility of urethroplasty with a free graft of colonic mucosa for long, complex urethral strictures. We report our initial experience with colonic mucosa graft urethroplasty for such urethral strictures in 16 patients. Between September 2000 and December 2002, 16 patients with a long, complex urethral stricture were treated with colonic mucosal graft urethroplasty. Patients had undergone an average of 2.5 previous unsuccessful repairs. Urethral reconstruction was done with a 10 to 17 cm (median 13) graft of colonic mucosa Patients were followed 6 to 33 months postoperatively. Meatal stenosis that developed in 1 patient 3 months postoperatively needed reoperation. The patient was voiding well with a urinary peak flow of 28.7 ml per second during 9-month followup after reoperation. Hyperplasia of the verumontanum was observed during urethroscopy and transurethral colliculectomy was performed in 1 patient more than 14 months postoperatively. Uroflowmetry showed a urinary peak flow of 46.5 ml per second postoperatively. The other patients were voiding well with a urinary peak flow of greater than 15 ml per second. Urethrogram revealed a patent urethra with an adequate lumen and no significant graft sacculation. This initial experience in 16 patients indicates that colonic mucosa graft urethroplasty is a feasible procedure for long, complex anterior urethral strictures. The technique may be considered for urethral reconstruction when more conventional procedures have failed.


Strategies to grow your practice in a struggling economy.
Creating a successful aesthetic medicine practice in times of economic uncertainty is a daunting challenge. This article introduces the concept of Retailicine, combining inherent edicts of medicine with the best practices in business, so today's aesthetic physician can develop strategies for success in any economy. Through the efficient use of marketing strategies catered to aesthetic medicine, aesthetic practices can thrive. Emphasizing the patient's experience, effectively using the Internet, and an ego-devoid introspective analysis of the flaws of one's practice are essential for any successful aesthetic physician to grow and be prosperous despite any shortfalls in the economy.


[Topiramate treatment for decreasing alcohol consumption in alcoholics: a comparative study of responders and nonresponders].
The present study investigated the effectiveness of topiramate (TPM) treatment for decreasing alcohol consumption in alcoholics. Alcoholics of outpatients, relapsed repeatedly, were included in this study. The study was conducted over 24 weeks. Subject characteristics (e.g., gender) and medical variables (e.g., age of onset) were recorded. Autistic features were determined using the Autism - Spectrum Quotient (>or=27 points). The average daily alcohol consumption was assessed at the start of the study and at 4, 12, and 24 weeks after its start. The five-step alcohol consumption scale of the Obsessive-Compulsive Drinking Scale (OCDS) was used. The extent of the change between the first assessment and subsequent assessment was considered the primary evaluation point. Responders were defined as subjects showing an improvement of at least two steps in the score. Patients not treated with TPM were retrospectively selected according to the same criteria on the basis of their medical records and were used as controls. The TPM group was further subdivided into responders and nonresponders. Of the 31 subjects who consented to TPM therapy, 11 stopped or discontinued TPM, and they were considered nonresponders. The average TPM maintenance dosage (standard deviation) was 62.9 (38.1) mg. Alcohol consumption scores significantly decreased at each assessment point in the study. The percentage of responders in the TPM group (n = 31) was significantly higher than that in the control group (n = 41) at the 24-week assessment point (45.2% vs. 19.5%, p=0.0193). A significant difference was observed between responders (n = 14) and nonresponders (n = 17) only in well-educated and autistic subjects (50% vs. 5.9%, p = 0.0109). TPM decreased the amount of alcohol consumption in alcoholics. In addition, a correlation between autistic features and TPM treatment response was suggested.


Eustachian Tube dysfunction in chronic rhinosinusitis: pre and post-operative results following endoscopic sinus surgery, a prospective study.
Prospective study investigating the incidence of concurrent Eustachian Tube dysfunction (ETD) in patients with CRS refractory to medical therapy, and the effect of Endoscopic Sinus Surgery (ESS) on ETD in this patient group. Prospective study of 57 CRS patients. Outcome measures were SNOT-22 and ETDQ-7 questionnaires, tympanometry and Valsalva manoeuvre recorded pre-operatively and at 3 and 9 months post ESS. There was a moderate positive correlation between pre-operative ETDQ-7 and SNOT 22 scores (r equals 0.5715, p less than 0.0001). 68% of patients recorded positive ETDQ-7 scores pre-operatively, mean equals 20.6 (SD plus or minus 10.34). Mean ETDQ-7 scores were significantly lower at 3 months; mean equals 11.4 (SD plus or minus 5.65) (P less than 0.0001) and 9 months mean equals 11.4 (SD plus or minus 6.15) (P less than 0.0001) following ESS. Type A tympanograms increased form 76.6% pre-operatively, to 94.5% at 3 months and 96% at 9 months. Reported positive Valsalva increased from 38% pre-operatively to 96% at 3 and 9 months. Mean ETDQ-7 scores were higher in the CRSwNP group; 24.34 (SD plus or minus 9.2) compared to the CRSsNP group; 18.11 (SD plus or minus 10.3), (p equals 0.6101). 16 patients in the cohort had existing diagnoses of asthma, of which 4 had documented aspirin sensitivity. The mean pre-operative SNOT-22 score in this overall subgroup was 64.81 (SD equals plus or mins 20.13) compared with 49.07 (SD equals plus or minus 21.37) in non-asthmatic patients (p equals 0.0168). We found a high incidence of concurrent ETD symptoms in patients with severe CRS, which improve following ESS. Further research is required to better understand the association between CRS and ETD in order to provide effective treatments.


Good Reporting Practice for Thermophysical and Thermochemical Property Measurements (IUPAC Technical Report).
Scientific projects frequently involve measurements of thermophysical, thermochemical, and other related properties of chemical compounds and materials. These measured property data have significant potential value for the scientific community, but incomplete and inaccurate reporting often hampers their utilization. The present IUPAC Technical Report summarizes the needs of chemical engineers and researchers as consumers of these data and shows how publishing practices can improve information transfer. In the Report, general principles of Good Reporting Practice are developed together with examples illustrating typical cases of reporting issues. Adoption of these principles will improve the quality, reproducibility, and usefulness of experimental data, bring a better level of consistency to results, and increase the efficiency and impact of research. Closely related to Good Reporting Practice, basic elements of Good Research Practice are also introduced with a goal to reduce the number of ambiguities and unresolved problems within the thermophysical property data domain.


Single-fiber diffuse optical time-of-flight spectroscopy.
We demonstrate interstitial diffuse optical time-of-fight spectroscopy based on a single fiber for both light delivery and detection. Detector saturation due to the massive short-time reflection is avoided by ultrafast gating of a single photon avalanche diode. We show that the effects of scattering and absorption are separable and that absorption can be assessed independently of scattering. Measurements on calibrated liquid phantoms and subsequent Monte Carlo-based evaluation illustrate that absorption coefficients can be accurately assessed over a wide range of medically relevant optical properties. Our findings pave the way to simplified and less invasive interstitial in vivo spectroscopy.


Examining the media portrayal of obesity through the lens of the Common Sense Model of Illness Representations.
This study examined the Irish media discourse on obesity by employing the Common Sense Model of Illness Representations. A media sample of 368 transcripts was compiled from newspaper articles (n = 346), radio discussions (n = 5), and online news articles (n = 17) on overweight and obesity from the years 2005, 2007, and 2009. Using the Common Sense Model and framing theory to guide the investigation, a thematic analysis was conducted on the media sample. Analysis revealed that the behavioral dimensions of diet and activity levels were the most commonly cited causes of and interventions in obesity. The advertising industry was blamed for obesity, and there were calls for increased government action to tackle the issue. Physical illness and psychological consequences of obesity were prevalent in the sample, and analysis revealed that the economy, regardless of its state, was blamed for obesity. These results are discussed in terms of expectations of audience understandings of the issue and the implications of these dominant portrayals and framings on public support for interventions. The article also outlines the value of a qualitative analytical framework that combines the Common Sense Model and framing theory in the investigation of illness narratives.


Phorbol ester-induced human cytomegalovirus major immediate-early (MIE) enhancer activation through PKC-delta, CREB, and NF-kappaB desilences MIE gene expression in quiescently infected human pluripotent NTera2 cells.
The ways in which human cytomegalovirus (HCMV) major immediate-early (MIE) gene expression breaks silence from latency to initiate the viral replicative cycle are poorly understood. A delineation of the signaling cascades that desilence the HCMV MIE genes during viral quiescence in the human pluripotent N-Tera2 (NT2) cell model provides insight into the molecular mechanisms underlying HCMV reactivation. In this model, we show that phorbol 12-myristate 13-acetate (PMA) immediately activates the expression of HCMV MIE RNA and protein and greatly increases the MIE-positive (MIE(+)) NT2 cell population density; levels of Oct4 (pluripotent cell marker) and HCMV genome penetration are unchanged. Decreasing PKC-delta activity (pharmacological, dominant-negative, or RNA interference [RNAi] method) attenuates PMA-activated MIE gene expression. MIE gene activation coincides with PKC-delta Thr505 phosphorylation. Mutations in MIE enhancer binding sites for either CREB (cyclic AMP [cAMP] response element [CRE]) or NF-kappaB (kappaB) partially block PMA-activated MIE gene expression; the ETS binding site is negligibly involved, and kappaB does not confer MIE gene activation by vasoactive intestinal peptide (VIP). The PMA response is also partially attenuated by the RNAi-mediated depletion of the CREB or NF-kappaB subunit RelA or p50; it is not diminished by TORC2 knockdown or accompanied by TORC2 dephosphorylation. Mutations in both CRE and kappaB fully abolish PMA-activated MIE gene expression. Thus, PMA stimulates a PKC-delta-dependent, TORC2-independent signaling cascade that acts through cellular CREB and NF-kappaB, as well as their cognate binding sites in the MIE enhancer, to immediately desilence HCMV MIE genes. This signaling cascade is distinctly different from that elicited by VIP.


[The Mood Disorder Questionnaire (MDQ-NL), an instrument to improve recognition of bipolar disorder].
Bipolar disorderis underdiagnosed. On average there is a delay of about 12 years between the onset of symptoms and a correct diagnosis of the disorder. This delay may lead to inadequate treatment. The Mood Disorder Questionnaire (MDQ) is a screening instrument to improve the detection ofbipolar disorder. Research has shown that the English version of this self-administered questionnaire has sufficient reliability and validity. A Dutch version of the MDQ (MDQ-NL) is now available. The MDQ-NL is not time-consuming for both patient and investigator and is well suited for screening. A positive test should be followed by assessment of the patient by a psychiatrist. Application of the MDQ-NL will lead to better recognition and treatment of bipolar disorder in the Netherlands.


Inequities in utilization of maternal health interventions in Namibia: implications for progress towards MDG 5 targets.
Inequities in the utilization of maternal health services impede progress towards the MDG 5 target of reducing the maternal mortality ratio by three quarters, between 1990 and 2015. In Namibia, despite increasing investments in the health sector, the maternal mortality ratio has increased from 271 per 100,000 live births in the period 1991-2000 to 449 per 100,000 live births in 1998-2007. Monitoring equity in the use of maternal health services is important to target scarce resources to those with more need and expedite the progress towards the MDG 5 target. The objective of this study is to measure socio-economic inequalities in access to maternal health services and propose recommendations relevant for policy and planning. Data from the Namibia Demographic and Health Survey 2006-07 are analyzed for inequities in the utilization of maternal health. In measuring the inequities, rate-ratios, concentration curves and concentration indices are used. Regions with relatively high human development index have the highest rates of delivery by skilled health service providers. The rate of caesarean section in women with post secondary education is about seven times that of women with no education. Women in urban areas are delivered by skilled providers 30% more than their rural counterparts. The rich use the public health facilities 30% more than the poor for child delivery. Most of the indicators such as delivery by trained health providers, delivery by caesarean section and postnatal care show inequities favoring the most educated, urban areas, regions with high human development indices and the wealthy. In the presence of inequities, it is difficult to achieve a significant reduction in the maternal mortality ratio needed to realize the MDG 5 targets so long as a large segment of society has inadequate access to essential maternal health services and other basic social services. Addressing inequities in access to maternal health services should not only be seen as a health systems issue. The social determinants of health have to be tackled through multi-sectoral approaches in line with the principles of Primary Health Care and the recommendations of the Commission on Social Determinants of Health.


Mindful Coping Power Effects on Children's Autonomic Nervous System Functioning and Long-Term Behavioral Outcomes.
Mindful Coping Power (MCP) was developed to enhance the effects of the Coping Power (CP) preventive intervention on children's reactive aggression by integrating mindfulness training into CP. In prior pre-post analyses in a randomized trial of 102 children, MCP improved children's self-reported anger modulation, self-regulation, and embodied awareness relative to CP but had fewer comparative effects on parent- and teacher-reported observable behavioral outcomes, including reactive aggression. It was hypothesized that MCP-produced improvements in children's internal awareness and self-regulation, if maintained or strengthened over time with ongoing mindfulness practice, would yield improvements in children's observable prosocial and reactive aggressive behavior at later time points. To appraise this hypothesis, the current study examined teacher-reported child behavioral outcomes at a one-year follow-up. In the current subsample of 80 children with one-year follow-up data, MCP produced a significant improvement in children's social skills and a statistical trend for a reduction in reactive aggression compared with CP. Further, MCP produced improvements in children's autonomic nervous system functioning compared with CP from pre- to post-intervention, with a significant effect on children's skin conductance reactivity during an arousal task. Mediation analyses found that MCP-produced improvements in inhibitory control at post-intervention mediated program effects on reactive aggression at the one-year follow-up. Within-person analyses with the full sample (MCP and CP) found that improvements in respiratory sinus arrhythmia reactivity were associated with improvements in reactive aggression at the one-year follow-up. Together, these findings indicate that MCP is an important new preventive tool to improve embodied awareness, self-regulation, stress physiology, and observable long-term behavioral outcomes in at-risk youth. Further, children's inhibitory control and autonomic nervous system functioning emerged as key targets for preventive intervention.


Optimal Location of Wells for Storage and Recovery of Surplus Desalinated Water in Coastal Aquifers.
Storage of water in aquifers using injection wells is an efficient way for utilizing excess desalinated water in arid regions. In this investigation we estimate the benefits of optimally recharging seasonal surplus desalinated water into a strategic coastal aquifer already benefitting from natural recharge of flash-floods water by a recharge dam. Since, usually the buyers of desalinated water commit to purchase surplus desalinated water under take-or-pay contracts, any attempt in utilizing the paid water is beneficial. Coastal cities are observing an increased urbanization leaving limited space for aquifer recharge infrastructure. In order to determine the optimal location of wells and maximize the use of surplus desalinated water available in winter period, a decision tool combining a numerical groundwater flow simulation model (MODFLOW) with an optimization model is developed. The results of this study show that increasing the number of wells from the existing 45 wells to 173 would allow storing 31.4 million cubic meter per year of excess desalinated water into the aquifer that can be used during later during summer months. The net benefit would reach US$55 million/year while the cost of drilling the new wells is US$5.11 million.


Oncogenic and tumor suppressive roles of polo-like kinases in human hepatocellular carcinoma.
Polo-like kinase (PLK) proteins play critical roles in the control of cell cycle progression, either favoring or inhibiting cell proliferation, and in DNA damage response. Although either overexpression or down-regulation of PLK proteins occurs frequently in various cancer types, no comprehensive analysis on their function in human hepatocellular carcinoma (HCC) has been performed to date. In the present study, we define roles for PLK1, PLK2, PLK3, and PLK4 during hepatocarcinogenesis. Levels of PLK1, as assessed by means of real-time reverse-transcription PCR and western blot analysis, were progressively increased from nonneoplastic surrounding liver tissues to HCC, reaching the highest expression in tumors with poorer outcome (as defined by the length of patients' survival) compared with normal livers. In sharp contrast, PLK2, PLK3, and PLK4 messenger RNA and protein expression gradually declined from nontumorous liver to HCC, with the lowest levels being detected in HCC with shorter survival. In liver tumors, PLK2-4 down-regulation was paralleled by promoter hypermethylation and/or loss of heterozygosity at the PLK2-4 loci. Subsequent functional studies revealed that PLK1 inhibition led to suppression of cell growth in vitro, whereas opposite effects followed PLK2-4 silencing in HCC cell lines. In particular, suppression of PLK1 resulted in a block in the G2/M phase of the cell cycle and in massive apoptosis of HCC cells in vitro regardless of p53 status. PLK1-4 proteins are aberrantly regulated and possess different roles in human HCC, with PLK1 acting as an oncogene and PLK2-4 being presumably tumor suppressor genes. Thus, therapeutic approaches aimed at inactivating PLK1 and/or reactivating PLK2-4 might be highly useful in the treatment of human liver cancer.


Prevalence of workplace violence in Chinese obstetric nurses under the new situation and its correlation with violence prevention knowledge-attitude-practice and climate perception: a cross-sectional study.
Workplace violence severely impacts individual nurses. With the three-child opening policy of China and the impact of the COVID-19 epidemic in the recently years, obstetric nurses face the double attack of heavy workload and staffing shortage. This study aimed to evaluate the current situation of workplace violence among Chinese obstetric nurses under the new situation, assess the level of violence prevention knowledge-attitude-practice and climate perception in Chinese obstetric nurses and explore the correlation between workplace violence and the level of violence prevention knowledge-attitude-practice and climate perception. A cross-sectional survey on the workplace violence for Chinese obstetric nurses was conducted from August to February 2023. All the questionnaires came from 10 provinces and 3 autonomous regions in China. The basic characteristics of obstetric nurse's workplace violence, workplace violence prevention knowledge-attitude-practice scale and workplace violence climate perception scale were collected. Totally, 522 Chinese obstetric nurses were included. 55.0% of obstetric nurses (287) had experienced workplace violence in the past 12 months, including verbal assault (40.4%), physical assault (34.1%), and sexual assault (31.0%). The overall level of obstetric nurses' workplace violence prevention knowledge-attitude-practice and climate perception of workplace violence was low. Multiple linear regression analysis showed that the violence prevention knowledge dimension significantly influenced obstetric nurses' workplace violence (B = -0.278, P < .001), attitude dimension (B = -0.241, P < .001), behavior dimension (B = -0.216, P < .001) and the violence climate perception's organizational management (B = -0.177, P < .001), organizational training (B = -0.175, P < .001), organizational support (B = -0.143, p < .001) and the violence handling (B = -0.165, P < .001). The incidence of workplace violence among obstetric nurses in the new situation is high. However, the overall violence prevention knowledge-attitude-practice and climate perception levels are low. Therefore, nursing managers should take targeted measures according to the relevant influencing factors and the characteristics of obstetrics to improve the level of obstetric nurses' violence prevention knowledge-attitude-practice and climate perception to reduce workplace violence among obstetric nurses.


Comparing two identically protocolized, multicentre, randomized controlled trials on caregiver-mediated exercises poststroke: Any differences across countries?
The evidence for rehabilitation interventions poststroke lack sufficient robustness. However, variation in treatment effects across countries have been given little attention. To compare two identically protocolized trials conducted in different western countries in order to identify factors that may have caused variation in secondary trial outcomes. Comparative study based on individual patient data (N = 129) from two randomized controlled trials, conducted in hospitals and rehabilitation facilities in the Netherlands (N = 66) and Australia (N = 63). Patients with stroke and their caregivers were randomly allocated to an 8-week caregiver-mediated exercises intervention (N = 63; 31 Australian and 32 Dutch) or to a control group (N = 66; 32 Australian and 34 Dutch). Patient characteristics, compliance, usual care and process measures were compared across countries. We examined if study setting significantly moderated the trial outcomes: Hospital Anxiety and Depression Scale, Fatigue Severity Scale and General Self-Efficacy Scale, measured at 8- and 12 weeks follow-up. In addition, we explored if factors that were significantly different across countries caused variation in these trial outcomes. Most patients suffered an ischemic stroke, were in the subacute phase and participated with their partner. Dutch patients were younger (P = 0.005) and had a lower functional status (P = 0.001). Australian patients were recruited earlier poststroke (P<0.001), spent less time in exercise therapy (P<0.001) and had a shorter length of stay (P<0.001). The level of contamination was higher (P = 0.040) among Dutch controls. No effect modification was observed and trial outcomes did not change after controlling for cross-country differences. The present study highlighted important clinical differences across countries whilst using an identical study protocol. The observed differences could result in a different potential for recovery and variation in treatment effects across trials. We argue that we can proceed faster to evaluating interventions within international pragmatic trials.


Screening for lung cancer.
This is an updated version of the original review published in The Cochrane Library in 1999 and updated in 2004 and 2010. Population-based screening for lung cancer has not been adopted in the majority of countries. However it is not clear whether sputum examinations, chest radiography or newer methods such as computed tomography (CT) are effective in reducing mortality from lung cancer. To determine whether screening for lung cancer, using regular sputum examinations, chest radiography or CT scanning of the chest, reduces lung cancer mortality. We searched electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5), MEDLINE (1966 to 2012), PREMEDLINE and EMBASE (to 2012) and bibliographies. We handsearched the journal Lung Cancer (to 2000) and contacted experts in the field to identify published and unpublished trials. Controlled trials of screening for lung cancer using sputum examinations, chest radiography or chest CT. We performed an intention-to-screen analysis. Where there was significant statistical heterogeneity, we reported risk ratios (RRs) using the random-effects model. For other outcomes we used the fixed-effect model. We included nine trials in the review (eight randomised controlled studies and one controlled trial) with a total of 453,965 subjects. In one large study that included both smokers and non-smokers comparing annual chest x-ray screening with usual care there was no reduction in lung cancer mortality (RR 0.99, 95% CI 0.91 to 1.07). In a meta-analysis of studies comparing different frequencies of chest x-ray screening, frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, 95% CI 1.00 to 1.23); however several of the trials included in this meta-analysis had potential methodological weaknesses. We observed a non-statistically significant trend to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, 95% CI 0.74 to 1.03). There was one large methodologically rigorous trial in high-risk smokers and ex-smokers (those aged 55 to 74 years with ≥ 30 pack-years of smoking and who quit ≤ 15 years prior to entry if ex-smokers) comparing annual low-dose CT screening with annual chest x-ray screening; in this study the relative risk of death from lung cancer was significantly reduced in the low-dose CT group (RR 0.80, 95% CI 0.70 to 0.92). The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Annual low-dose CT screening is associated with a reduction in lung cancer mortality in high-risk smokers but further data are required on the cost effectiveness of screening and the relative harms and benefits of screening across a range of different risk groups and settings.


Bilateral iridocyclitis with retinal capillaritis in juveniles.
The authors present clinical features of 18 juvenile patients with a new type of uveitis termed bilateral iridocyclitis with retinal capillaritis (BIRC). The authors reviewed medical records of 18 consecutive patients who showed bilateral iridocyclitis with retinal capillary leakage but no systemic manifestations during an 11-year period from January 1985 to December 1995. Twelve of the 18 patients were female and the age at onset ranged from 9 to 17 years old. All patients had many cells in the anterior chamber and anterior vitreous, together with mutton fat keratic precipitates. Fluorescein angiography showed leakage from the optic disc and retinal capillaries, mainly in the midperiphery, which corresponded to retinal cloudiness. Macular edema was minimal, and all patients maintained good vision. The inflammation responded well topical, oral, and intravenous administration of corticosteroids, the choice of which was based on the extent of retinal inflammation. Human leukocyte antigen (HLA)-DR6 and HLA-Cw7 were associated significantly with the presence of BIRC (chi square test, P < 0.0001). Bilateral retinal capillaritis affecting capillaries in various areas of the retina and overlying retinal cloudiness with no distinct lesions are unique to these patients. Fluorescein angiography is essential for diagnosis of BIRC.


Schwartz Jampel syndrome responding positively to carbamazepine therapy: a case report and a novel mutation.
Gürbüz G, Mutlu Albayrak H. Schwartz Jampel syndrome responding positively to carbamazepine therapy: a case report and a novel mutation. Turk J Pediatr 2019; 61: 967-970. Schwartz Jampel syndrome was first described in 1962. It is an autosomal recessive disease with generalized myotonic myopathy and skeletal dysplasia. A mutation in the HSPG2 gene occurs. Approximately 150 cases have been reported in literature. A 4-year-old girl presented to the pediatric neurology clinic due to difficulty in walking. The patient had difficulty opening her mouth and swallowing. She was unable to eat solid foods and was bottle fed. She was able to stand leaning forward, with her legs open and with one hand supported. Bilateral blepharospasm, posterior cleft palate, microstomia, pursed lips, kyphoscoliosis, contracture in the elbows, long thin fingers and campodactyly in the bilateral 5th fingers were present. Myotonic contraction with thenar percussion was observed. Previously undescribed mutation was determined in HSPG2 gene in the genetic study. Oral carbamazepine therapy was initiated and 1.5 months later the patient`s muscle rigidity had decreased and her motor skills had improved. This report contributes to the literature by defining a new mutation in HSPG2 gene and showing the importance of early diagnosis of the disease.


Use of the laparoscopic knot introducer in urethrovesical anastomosis following radical prostatectomy.
One of the most delicate stages of retropubic radical prostatectomy intervention is urethrovesical anastomosis, especially if it is performed in a deep bony pelvis with a short urethral stump. Correct knot tying is essential to avoid the risk of postoperative anastomotic leakage. In such conditions, the urethrovesical anastomosis is performed with six 4-0 Monocril sutures and the knots are tied under vision using the laparoscopic knot introducer. In a 2-year period we performed 106 retropubic radical prostatectomies in our urology department. In four cases (3.8%) we performed urethrovesical anastomosis with the aid of the described technique. Two weeks after catheter placement, the radiologic control showed no leakage or contracture of the anastomosis. Mean follow-up is 14.8 months (range 8 to 20); all of the patients are continent. A second radiologic study 6 months after the intervention documented in all cases a correct new anatomical repair without stenoses or contracture. This technique is a minor modification of the direct urethrovesical anastomosis that facilitates the anastomosis between the urethral stump and the bladder neck and reduces the risk of anastomotic leakage due to incorrect suture knot positioning and tying.


Neuronal Avalanches Across the Rat Somatosensory Barrel Cortex and the Effect of Single Whisker Stimulation.
Since its first experimental signatures, the so called "critical brain hypothesis" has been extensively studied. Yet, its actual foundations remain elusive. According to a widely accepted teleological reasoning, the brain would be poised to a critical state to optimize the mapping of the noisy and ever changing real-world inputs, thus suggesting that primary sensory cortical areas should be critical. We investigated whether a single barrel column of the somatosensory cortex of the anesthetized rat displays a critical behavior. Neuronal avalanches were recorded across all cortical layers in terms of both multi-unit activities and population local field potentials, and their behavior during spontaneous activity compared to the one evoked by a controlled single whisker deflection. By applying a maximum likelihood statistical method based on timeseries undersampling to fit the avalanches distributions, we show that neuronal avalanches are power law distributed for both multi-unit activities and local field potentials during spontaneous activity, with exponents that are spread along a scaling line. Instead, after the tactile stimulus, activity switches to a transient across-layers synchronization mode that appears to dominate the cortical representation of the single sensory input.


Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations.
Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor.


A Clinical Decision Support System for Assessing the Risk of Cardiovascular Diseases in Diabetic Hemodialysis Patients.
One of the greatest challenges in the field of medicine is the increasing burden of chronic diseases, such as diabetes. Diabetes may cause several complications, such as kidney failure which is followed by hemodialysis and an increasing risk of cardiovascular diseases. The purpose of this research was to develop a clinical decision support system for assessing the risk of cardiovascular diseases in diabetic patients undergoing hemodialysis by using a fuzzy logic approach. This study was conducted in 2018. Initially, the views of physicians on the importance of assessment parameters were determined by using a questionnaire. The face and content validity of the questionnaire was approved by the experts in the field of medicine. The reliability of the questionnaire was calculated by using the test-retest method (r = 0.89). This system was designed and implemented by using MATLAB software. Then, it was evaluated by using the medical records of diabetic patients undergoing hemodialysis (n=208). According to the physicians' point of view, the most important parameters for assessing the risk of cardiovascular diseases were glomerular filtration, duration of diabetes, age, blood pressure, type of diabetes, body mass index, smoking, and C reactive protein. The system was designed and the evaluation results showed that the values of sensitivity, accuracy, and validity were 85%, 92% and 90%, respectively. The K-value was 0.62. The results of the system were largely similar to the patients' records and showed that the designed system can be used to help physicians to assess the risk of cardiovascular diseases and to improve the quality of care services for diabetic patients undergoing hemodialysis. By predicting the risk of the disease and classifying patients in different risk groups, it is possible to provide them with better care plans.


Vagal nerve activity and the high frequency peak of the heart rate variability.
For the Quality of life (QOL) of patients with an artificial heart system, monitoring an information of the cardiovascular control system may be important. We have been evaluating the autonomic nervous system for that purpose. Recently, fluctuations in hemodynamic parameters including heart rate variability (HRV) were evaluated by means of spectral analysis and nonlinear mathematical analysis. Respiratory wavers in HRV were thought to reflect ongoing information of the parasympathetic nerve activity. Is it true? In order to confirm this hypothesis, we recorded vagal nerve activity directly in the chronic animal experiments. Six healthy adult goats were anesthetized with Halothene inhalation and thoracotomy were performed by the fourth lib resection during mechanical ventilation. Arterial blood pressure, right and left atrial pressures were continuously monitored with the catheter insertion. Cardiac output was measured by the electromagnetic flowmeter attached to the ascending aorta. After the chest was closed, incision was made to the left neck and left vagal nerve was separated. Stainless steel electrodes were inserted into the vagal nerve and fixed by the plasticizer. After the incision was closed, the goats were transferred to the cage and extubated after waking. Hemodynamic parameters and vagal nerve activity were measured in the awake condition. The results showed that clear observation of the autonomic nerve discharges were embodied by this experimental system. The vagal nerve discharges were synchronized with heart beat and respiration. The vagal nerve tonus was significantly influenced by the hemodynamic alteration. However in some condition, the respiratory wave was not always consistent with tonus of the vagal nerve activity, thus suggesting that we should check another information to evaluate the parasympathetic tone. We must continue this study to evaluate an autonomic nerve during artificial heart circulation.


Manipulation of skyrmion motion by magnetic field gradients.
Magnetic skyrmions are particle-like, topologically protected magnetisation entities that are promising candidates as information carriers in racetrack memory. The transport of skyrmions in a shift-register-like fashion is crucial for their embodiment in practical devices. Here, we demonstrate that chiral skyrmions in Cu2OSeO3 can be effectively manipulated under the influence of a magnetic field gradient. In a radial field gradient, skyrmions were found to rotate collectively, following a given velocity-radius relationship. As a result of this relationship, and in competition with the elastic properties of the skyrmion lattice, the rotating ensemble disintegrates into a shell-like structure of discrete circular racetracks. Upon reversing the field direction, the rotation sense reverses. Field gradients therefore offer an effective handle for the fine control of skyrmion motion, which is inherently driven by magnon currents. In this scheme, no local electric currents are needed, thus presenting a different approach to shift-register-type operations based on spin transfer torque.


Pharmacokinetics and pharmacodynamics of intra-graft iloprost in femorodistal bypass surgery.
Intra-graft injection of the prostacyclin analogue, iloprost, was performed at the end of femorodistal bypass procedures in 12 patients with severe peripheral arterial occlusive disease. Iloprost plasma levels were measured and compared with changes in haemodynamics. There was a high initial iloprost plasma level (mean 625 pg/ml) which dropped to a mean of 50 pg/ml after 15 min. This correlated with an immediate reduction in systolic blood pressure which had returned to pretreatment levels after 15 min. In contrast, the vascular resistance distal to the graft showed a reduction after 5 min which was maintained for at least 20 min after iloprost injection and the mean blood flow through the graft increased steadily throughout the same period of measurement. The study showed an effect of iloprost on blood pressure which correlated with plasma levels, but the time course of the changes in distal vascular resistance and graft blood flow demonstrated an effect more prolonged than the half-life of iloprost.


Perception about the importance and use of therapeutic massage as a treatment modality among physical therapists working in Saudi Arabia.
[Purpose] To report perceptions about the importance and use of therapeutic massage as a treatment modality among physical therapists working in Saudi Arabia. [Subjects and Methods] A 21-item structured questionnaire was used to assess various domains including the demographic and professional characteristics of physical therapists and their perceptions about the importance and use of therapeutic massage in their daily practice. The questionnaire was uploaded online and the web link was sent to 140 members of the Saudi Physical Therapy Association (SPTA). [Results] The overall response rate was 86%. Among the respondents, 31% reported occasional use of therapeutic massage in their clinical practice, and 55% reported to have received formal training for therapeutic massage. Use of therapeutic massage was more common among female physical therapists. [Conclusion] Many physical therapists working in Saudi Arabia consider therapeutic massage to be an important treatment modality, but its use is relatively limited, either due to the time and effort required to dispense it, or the lack of scientific evidence for its efficacy.


Ongoing sexually transmitted disease acquisition and risk-taking behavior among US HIV-infected patients in primary care: implications for prevention interventions.
To better understand the factors associated with HIV- and sexually transmitted disease (STD)-transmitting behavior among HIV-infected persons, we estimated STD prevalence and incidence and associated risk factors among a diverse sample of HIV-infected patients in primary care. We analyzed data from 557 participants in the SUN Study, a prospective observational cohort of HIV-infected adults in primary care in 4 US cities. At enrollment and 6 months thereafter, participants completed an audio computer-assisted self-interview about their sexual behavior, and were screened for genitourinary, rectal, and pharyngeal Neisseria gonorrhoeae and Chlamydia trachomatis infections by nucleic acid amplification testing, and for serologic evidence of syphilis. Women provided cervicovaginal samples and men provided urine to screen for Trichomonas vaginalis by polymerase chain reaction. Thirteen percent of participants had a prevalent STD at enrollment and 7% an incident STD 6 months later. The most commonly diagnosed infections were rectal chlamydia, oropharyngeal gonorrhea, and chlamydial urethritis among the men and trichomoniasis among the women. Other than trichomoniasis, 94% of incident STDs were identified in men who have sex with men. Polysubstance abuse other than marijuana, and having ≥4 sex partners in the 6 months before testing were associated with diagnosis of an incident STD. STDs were commonly diagnosed among contemporary HIV-infected patients receiving routine outpatient care, particularly among sexually active men who have sex with men who used recreational drugs. These findings underscore the need for frequent STD screening, prevention counseling, and substance abuse treatment for HIV-infected persons in care.


DNA polymerase III of Escherichia coli. Purification and identification of subunits.
DNA polymerase III, the core of the DNA polymerase III holoenzyme, has been purified 28,000-fold to 97% homogeneity from Escherichia coli HMS-83. The enzyme contains subunits: alpha, epsilon, and theta of 140,000, 25,000, and 10,000 daltons, respectively. The alpha subunit has been previously shown to be a component of both DNA polymerase III and the more complex DNA polymerase III holoenzyme (Livingston, D.M., Hinkle, D., and Richardson, C. (1975) J. Biol. Chem. 250, 461-469; McHenry, C., and Kornberg, A. (1977) J. Biol. Chem. 252, 6478-6484). It is demonstrated here that the epsilon and theta subunits are also subunits of the DNA polymerase III holoenzyme. Thus, the DNA polymerase III holoenzyme contains at least six different subunits. Our preparation has both the 3' leads to 5' and 5' leads to 3' exonuclease activities previously assigned to DNA polymerase III (Livingston, D., and Richardson, C. (1975) J. Biol. Chem. 250, 470-478).


Human exposure to trace metals and possible public health risks via consumption of mussels Mytilus galloprovincialis from the Adriatic coastal area.
Considering the growing concern due to different levels of anthropogenic loadings, the main purpose of this study was to identify the levels of trace metals (Fe, Mn, Cu, Zn, Co, Ni, Cd, Pb and Hg) in the mussels Mytilus galloprovincialis sampled along the marine coast of Boka Kotorska Bay, Montenegro. In comparison with the permissible limits set by the EU and the US FDA, all trace metal concentrations found in the mussels from the coastal area of Boka Kotorska Bay were lower than the prescribed limits. Generally, the trace metal concentrations found in Montenegrin mussels are within the range of trace metal concentrations determined in low to moderately polluted Adriatic areas. Based on these and other available literature data published by other authors for Adriatic region, the public health risks associated with the consumption of mussels in relation to reported trace metal concentrations were evaluated. In terms of the obtained trace metals concentrations in mussels and the provisional tolerable weekly intake prescribed by the JECFA and oral reference doses by the US EPA, the Pb and Cd concentrations and the Co and Cd concentrations were recognized as the limiting factor for the consumption of mussels from some Adriatic areas, respectively.


Morphological control enables nanometer-scale dissection of cell-cell signaling complexes.
Protein micropatterning enables robust control of cell positioning on electron-microscopy substrates for cryogenic electron tomography (cryo-ET). However, the combination of regulated cell boundaries and the underlying electron-microscopy substrate (EM-grids) provides a poorly understood microenvironment for cell biology. Because substrate stiffness and morphology affect cellular behavior, we devised protocols to characterize the nanometer-scale details of the protein micropatterns on EM-grids by combining cryo-ET, atomic force microscopy, and scanning electron microscopy. Measuring force displacement characteristics of holey carbon EM-grids, we found that their effective spring constant is similar to physiological values expected from skin tissues. Despite their apparent smoothness at light-microscopy resolution, spatial boundaries of the protein micropatterns are irregular at nanometer scale. Our protein micropatterning workflow provides the means to steer both positioning and morphology of cell doublets to determine nanometer details of punctate adherens junctions. Our workflow serves as the foundation for studying the fundamental structural changes governing cell-cell signaling.


Phosphonate fertilizers suppressed root knot nematodes Meloidogyne javanica and M. incognita.
The efficacy of the phosphonate fertilizers, Calphos(®) (a.i. calcium phosphonate), Magphos(®) (a.i. magnesium phosphonate and potassium phosphonate) and Phosphoros(®) (a.i. potassium phosphonate) against two species of root knot nematodes (RKN), Meloidogyne javanica and M. incognita is evaluated. Laboratory experiments showed that Calphos(®), Magphos(®) and their main components inhibited egg hatching and caused 100% mortality of the second stage juveniles (J2s) of the two RKN species; the hatching inhibition effects persisted after transferring the egg masses of both species to water. However, Phosphoros(®) (0.5%) did not suppress egg hatching or the survival of J2s of both RKN species. No hatching occurred when egg masses were treated for one week with the nematicide Vydate L(®) (2 ml/l), however, J2s hatched when the Vydate L(®) treated egg masses were moved to water. The glasshouse study indicated that Magphos(®), Calphos(®) and Phosphoros(®) reduced root galling caused by M. javanica by 98, 66 and 47%, respectively, in comparison to the untreated controls. Magphos(®) resulted in the lowest number of root galls formed by M. incognita, the reduction was 84%. In contrast, Calphos(®) and Phosphoros(®) reduced galling by 47 and 39%, respectively. The Magphos(®) treatment resulted in the lowest numbers of egg masses and the lowest reproductive factor (RF) of both nematode species. However, plants treated with Phosphoros(®) resulted in higher foliage weights compared with the application of the other two fertilizers and the untreated plants.


Pesticide detection in air samples from contrasted houses and in their inhabitants' hair.
In order to identify associations between indoor air contamination and human exposure to pesticides, hair samples from 14 persons (9 adults and 5 children below 12 years) were collected simultaneously with the air of their 5 contrasted houses. Three houses were situated in Alsace (France), one in Lorraine (France) and one in Luxembourg (Luxembourg). Houses were located in urban (n=3), semi-urban (n=1) and rural areas (n=1). Twenty five (25) pesticides were detected at least once in indoor air samples and 20 pesticides were detected at least once in hair samples. The comparison between hair and air samples for the same sampling periods shows that pesticides detected in the two matrices were not necessarily associated. Exposure profiles varied from one home to another but also between inhabitants of the same home, suggesting that exposure can be different between inhabitants of the same home. This study demonstrated the usefulness and the complementarity of hair analysis, for the personalized biomonitoring of people exposure to pesticides, and air analysis, for the identification of airborne exposure and house contamination.


Periodontal disease in a Portuguese identified skeletal sample from the late nineteenth and early twentieth centuries.
Periodontal status was investigated in 600 adult dentitions belonging to the identified osteological collections curated at the University of Coimbra, Portugal. These collections date to a point temporally intermediate between the large epidemiological studies of the 20th century and archaeological collections that antedate the 19th century. The aim of this study is to compare periodontal data derived from contemporary samples with statistics compiled from epidemiological studies to determine if factors such as age-at-death, sex, and tooth type are essential or not to account for in future archaeological studies of periodontitis. Periodontal disease status was assessed based on the textural and architectural variations of the interdental septum and the extent of bone loss. Overall, the frequency of periodontitis within the Coimbra collections is 73.8%. Men were more susceptible to periodontal disease than women. Gingivitis was widespread in the younger age groups. Destructive periodontitis was observed early in adulthood, rising steadily with age. The most susceptible sites to periodontal breakdown were located in the posterior region of the upper jaw. Some variation in reported frequencies of periodontitis was found in epidemiological reports, which might result from variation in methods for identifying the pathology, differences in the age composition of the samples examined, variation in oral hygiene and/or diet, or some other factors. Regarding the pattern of distribution of periodontal disease, Coimbra results were similar to comparable modern epidemiological surveys, making clear the importance of considering sex, age, and oral distribution of periodontitis in future archaeological studies.


Tetrahydrocannabinol (Delta 9-THC) Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey.
Central neuropathic pain is difficult to treat, but delta 9-Tetrahydrocannabinol (delta 9-THC) may be a promising therapeutic agent. We administered in 172 patients on average 7.5 mg delta 9-THC over 7 months. Of these, 48 patients prematurely withdrew due to side effects, insufficient analgesia, or expense of therapy. Thus, 124 patients were assessed retrospectively in a multicenter telephone survey. Reported changes in pain intensity, recorded on a numeric rating scale (NRS), Pain Disability Index (PDI), Medical Outcomes Short-Form (SF-12), Quality of Life Impairment by Pain (QLIP), Hospital Anxiety Depression Scale (HADS), and amount of concomitant pain medication were recorded. Psychometric parameters (PDI, SF-12, QLIP, HADS) and pain intensity improved significantly during delta 9-THC treatment. Opioid doses were reduced and patients perceived THC therapy as effective with tolerable side effects. About 25% of the patients, however, did not tolerate the treatment. Therapy success and tolerance can be assessed by a transient delta 9-THC titration and its maintained administration for several weeks. The present survey demonstrates its ameliorating potential for the treatment of chronic pain in central neuropathy and fibromyalgia. A supplemental delta 9-THC treatment as part of a broader pain management plan therefore may represent a promising coanalgesic therapeutic option.


Spatio-temporal analysis of the progression of Aujeszky's disease virus infection in wild boar of Saxony-Anhalt, Germany.
Aujeszky's disease (AD, pseudorabies) is a notifiable disease caused by Suid herpesvirus 1 (SuHV-1), also named pseudorabies virus (PrV). The study aimed at determining the occurrence and spatio-temporal trend of specific antibodies to AD virus (ADV) among wild boar of Saxony-Anhalt, a landlocked federal state situated in the western part of eastern Germany. To this end, a total of 7,209 blood samples were collected and tested from 2000 to 2011. An average seroprevalence of 6.8% was found for the entire observation period, whilst seroprevalence increased significantly between time periods January 2000-March 2009 (n = 3,605; prevalence = 4.5%) and March 2009-December 2011 (n = 3,604; prevalence = 9.1%). Spatial analysis revealed an extremely heterogenous distribution of seropositive samples with cluster formation [relative risk (RR) up to 41, P = 0.001] in the east. A comparison of spatial clusters between the aforementioned time intervals showed an expansion of the disease in the north to north-westerly direction. A test for spatial shift involving the entire territory of Saxony-Anhalt detected a spread of ADV infection in the latter direction (P = 0.079) at the average speed of 3.3 km/year. Detailed study of the distribution and spread of the disease among wild boar, including assessment of the speed of spatial spread, has not been done in the region before. Saxony-Anhalt has been officially recognised as being free of AD in domestic pigs since 1996. Despite increasing ADV seroprevalences in the wild boar population of Saxony-Anhalt and other federal states in the east of Germany, no spill-over to domestic pigs have been reported. The currently implemented monitoring will be continued in conjunction with surveillance of classical swine fever (CSF) to further trace ADV infections in the wild boar population of Saxony-Anhalt.


Cone biopsy in premenopausal women: why was outpatient management abandoned?
In a 2-year retrospective study, I reviewed the records of 180 premenopausal patients who had had cone biopsy. The purpose of this study was to determine the indications for the procedure in the view of the practicing clinician and to determine whether these young women might have received better treatment as outpatients. In this series, positive findings on endocervical curettage (ECC) in patients with otherwise satisfactory results of colposcopy was by far the leading reason for cone biopsy, and positive findings on ECC did not correlate with occult disease in the canal when the cone specimen was examined. Also, a significant number of women had cone biopsy solely for severe dysplasia, though the literature clearly shows the effectiveness of outpatient management in these cases (eg, using proper cryotherapeutic methods). If ECC is done routinely despite satisfactory results of colposcopic examination and unexpectedly positive results are obtained, I recommend repeat colposcopy with aggressive use of an endocervical speculum and a careful, adequate ECC before abandoning outpatient management. Proper histologic interpretation of ECC in light of all clinical data is essential to avoid unnecessary morbidity.


Outcome measures in pediatric neurology: why do we need them?
Outcome measures should include the patient's values and preferences (from the patient's perspective) in addition to performance ratings and physiologic states. Outcome measures can assess relationships between services and interventions and their end results, can clarify which therapies are worth providing and which therapies need more evidence about their effectiveness, and can measure the burdens of different disorders and interventions. Researchers recently have shown the feasibility of creating and using outcome measures for children with neurodevelopmental disorders. Clinicians may wish to familiarize themselves with the concepts of outcome measures and health-related quality of life in order to understand the rationale, utility, properties, and various types of outcome measures in order to select the most appropriate instruments that will best serve their patient populations. Ongoing research efforts are currently using such measures in children with central nervous system tumors, with neural tube defects, and of extremely low birthweight; in childhood and adolescent epilepsy; and in adolescents with headaches.


Intercultural health care as reflective negotiated practice.
This interpretive study sought to understand how intercultural health care to immigrants can be practically conceptualized in multicultural populations. Interviews were conducted with 20 Canadian health service informants, and 12 interviews were staged during 31 months with a multicultural coordinator in an Australian teaching hospital. Transcripts of 11 previously conducted group discussions with 34 staff members from this same Australian hospital were also included. Interpretation was based on these data as well as on the literature and the author's own experience. It was concluded that intercultural health care can be practically conceptualized as reflective health worker practice. Through this practice, responsive care can be situationally negotiated between the health worker and the client in a framework of jointly considered needs. For implementation, the barriers to negotiation must be addressed.


Two-year follow-up study of primary and transitional progressive multiple sclerosis.
This study documents changes in clinical and magnetic resonance imaging (MRI) characteristics in a large cohort of patients with primary and transitional progressive multiple sclerosis (PP and TPMS) over 2 years. Patients with PPMS and TPMS were recruited from six European centres and underwent clinical and MRI examination at three time points: baseline, year one and year two. Of the 190 patients recruited clinical data were available on 125 patients (66%, five centres) and MRI data were available on 113 patients (59%, four centres) at 2 years. Significant increases were seen in T2 load and T1 hypointensity, while brain and cord volume decreased. In PPMS significantly higher lesion loads were found in those who presented with non-cord syndromes when compared to cord presentation and there was a trend to greater brain atrophy in those who deteriorated clinically over the course of the study compared to those who remained stable. Significant cord atrophy was only seen in those with a cord presentation. Measurable changes in MRI parameters can be detected in PPMS patients over a relatively short period of time. MRI quantification is likely to be useful in elucidating disease mechanisms in PPMS and in the execution of clinical trials.


An update on combination therapies for multiple sclerosis: where are we now?
In theory, combination of two agents, which are suboptimal when given individually, may result in a significant increase in therapeutic effect. Combination therapies have proven particularly effective against infections such as HIV, cancer, and also chronic autoimmune diseases such as rheumatoid arthritis. The authors review the literature, searching for randomized placebo-controlled or comparative, double-blind or investigator-blinded clinical trials, not including open label clinical trials, of treatment of multiple sclerosis (MS) with combination therapy or add-on therapy, including trials of induction therapy, trials for prevention of disease activity or worsening, amelioration of adverse effects, and treatment of relapses, and trials to increase remyelination. Combination of two platform therapies (Interferon-beta or glatiramer acetate) was without additional effect. Clinical trials with add-on, often applying repurposed drugs (e.g. simvastatin, atorvastatin, minocycline, estriol, cyclophosphamide, azathioprine, albuterol, vitamin D), have been negative, apart from monthly methylprednisolone that, however, had low tolerability. Combination therapy for neuroprotection/remyelination showed some interesting results, though we are still awaiting results of phase III trials. The results of combination of anti-inflammatory therapies have in general been disappointing. In the future, combination of new effective neuroprotective/remyelinating drugs and highly effective anti-inflammatory treatments may benefit people with MS.


[A randomized controlled study on warming needle moxibustion for treatment of knee osteoarthritis].
To assess the short-term and long-term therapeutic effect of warming needle moxibustion for treatment of knee osteoarthritis. Ninety cases were randomly divided into a warming needle moxibustion group, a western medicine group and a waiting group, 30 cases in each group. The warming needle moxibustion group was treated with warming needle moxibustion on Xuehai (SP 10), Dubi (ST 35) and Zusanli (ST 36), etc.; the western medicine group was treated with oral administration of Ibuprofen sustained release capsule; the waiting group did not receive any treatment. Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Chinese version of SF-16 were used to assess the therapeutic effect before treatment, after treatment and 10 weeks after treatment. After treatment for 2 weeks, the total effective rate was 86.7% in the warming needle moxibustion group, 90.0% in the western medicine group, and 60.0% in the waiting group, both the warming needle moxibustion group and the western medicine group being significantly better than the waiting group (both P<0.05) and with no significant difference between the warming needle moxibustion group and the western medicine group (P>0.05); 10 weeks after treatment, the total effective rate of 83.3% in the warming needle moxibustion group was better than that of 60.0% in the western medicine group (P<0.05). There were no significant differences in comparison of WOMAC and SF-16 scores after treatment between the warming needle moxibustion group and the western medicine group, and the warming needle moxibustion group in improvement of these scores was superior to the western medicine group (P<0.01, P<0.05). The therapy of warming needle moxibustion is effective for treatment of knee osteoarthritis, and the short-term therapeutic effect is same as that of oral administration of Ibuprofen and the long-term therapeutic effect is better than that of Ibuprofen.


Medical device related pressure ulcers in hospitalized patients.
Most pressure ulcers occur over bony prominences such as heels and the sacrum. However, the National Pressure Ulcer Advisory Panel recognises that pressure ulcers can also occur on any tissue under pressure and thereby can develop beneath medical devices. This article reports on results from a secondary analysis of existing data collected by The Nebraska Medical Center on pressure ulcer quality improvement initiatives and outcomes. The purpose of this study was to quantify the extent of the problem and identify risk factors for medical device related (MDR) pressure ulcer development in hospitalised patients. A subset of data collected during eight quarterly pressure ulcer incidence and prevalence studies (N = 2178) was created and analysed. The overall rate of hospital-acquired pressure ulcers was 5·4% (113 of 2079). The proportion of patients with hospital-acquired ulcers related to medical devices was 34·5% (39 of 113). Findings indicate that if a patient had a medical device, they were 2·4 times more likely to develop a pressure ulcer of any kind. Numerous risk factors for pressure ulcer development were identified; however, none differentiated between those with MDR and traditional pressure ulcers.


CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer.
In this study, we used a bioinformatic approach to identify genes whose expression is dysregulated in human prostate cancers. One of the most dramatically downregulated genes identified encodes CYP27A1, an enzyme involved in regulating cellular cholesterol homeostasis. Importantly, lower CYP27A1 transcript levels were associated with shorter disease-free survival and higher tumor grade. Loss of CYP27A1 in prostate cancer was confirmed at the protein level by immunostaining for CYP27A1 in annotated tissue microarrays. Restoration of CYP27A1 expression in cells where its gene was silenced attenuated their growth in vitro and in tumor xenografts. Studies performed in vitro revealed that treatment of prostate cancer cells with 27-hydroxycholesterol (27HC), an enzymatic product of CYP27A1, reduced cellular cholesterol content in prostate cancer cell lines by inhibiting the activation of sterol regulatory-element binding protein 2 and downregulating low-density lipoprotein receptor expression. Our findings suggest that CYP27A1 is a critical cellular cholesterol sensor in prostate cells and that dysregulation of the CYP27A1/27HC axis contributes significantly to prostate cancer pathogenesis. Cancer Res; 77(7); 1662-73. ©2017 AACR.


Person-centered support and athletes' motivation for performance.
The purpose of the study was to examine the effect of person-centered intervention on motivation for athletic performance. 74 volleyball players, 24 boys and 50 girls (M age = 13 yr., SD = 1.0), completed a motivation questionnaire, the Leistungs Motivations Test für Jugendlichen prior to and after an 8-mo. group treatment that included the application of Roger's person-centered method to the participants of the experimental group (1 boys' team n = 12; 1 girls' team n = 11), at a frequency of at least one session per week. In the control group (1 boys' team n = 12; 3 girls' teams n = 39), no particular method was used apart from the pedagogical methods that coaches selected. Results revealed a statistically significant decrease in boys' scores on desire for performance and success between the pre- and posttest measurements. No significant change in girls' scores was observed. Thus, the 8-mo. treatment using the person-centered method did not improve volleyball players' motivation for performance.