Efficacious CO2 Photoconversion to C2 and C3 Hydrocarbons on Upright SnS-SnS2 Heterojunction Nanosheet Frameworks.
In this work, SnS-SnS2 heterostructured upright nanosheet frameworks are constructed on FTO substrates, which demonstrate promising photocatalytic performances for the conversion of CO2 and water to C2 (acetaldehyde) and C3 (acetone) hydrocarbons without H2 formation. With post annealing in designated atmospheres, the photocatalytic activity of the SnS-SnS2 heterostructured nanosheet framework is critically enhanced by increasing the fraction of crystalline SnS in nanosheets through partial transformation of the SnS2 matrix to SnS but not obviously influenced by improving the crystallinity of the SnS2 matrix. DFT calculations indicate that transformed SnS possesses the CO2 adsorption sites with significantly lower activation energy for the rate-determining step to drive efficient CO2 conversion catalysis. The experimental results and DFT calculations suggest that the SnS-SnS2 heterojunction nanosheet framework photocatalyst experiences Z-scheme charge transfer dynamic to allow the water oxidation and CO2 reduction reactions occurring on the surfaces of SnS2 and SnS, respectively. The Z-scheme SnS-SnS2 heterostructured nanosheet framework photocatalyst exhibits not only efficient charge separation but also highly catalytic active sites to boost the photocatalytic activity for CO2 conversion to C2 and C3 hydrocarbons.


Genetics of inflammatory bowel diseases--past, present, and future.
In this review, the evidence to support the multifactorial and polygenic nature of the disease is briefly described. The past of genetics of inflammatory bowel disease (IBD) is characterized by unfulfilled promises and is now closed with a new vision and a new promise coming from a genetic epidemiology approach. The genome-wide screening has led to the first gene of IBD and has given a new insight into the regulation of chronic inflammation. The future of IBD will be under scrutiny of the visionaries, but also the skeptics and the enthusiasts.


Ineffectiveness of cognitive forcing strategies to reduce biases in diagnostic reasoning: a controlled trial.
Cognitive forcing strategies (CFS) may reduce error arising from cognitive biases. This is the first experimental test to determine the effect of CFS training in medical students. Students were allocated to CFS training or control during a 4-week emergency medicine rotation (n = 191). At the end of the rotation examination, students were tested using computer-based cases. Application of CFS could enable reduction of diagnostic error, as evidenced by identifying multiple correct diagnoses for the two cases prone to search satisficing bias (SSB) and uncommon diagnoses for the two cases prone to availability bias (AB). Two "false positive" cases were included to test for possible "oversearching." There were 145 students in the intervention and 46 in the control group. For the SSB cases, 52% of students with CFS training and 48% in the control group initiated a search for the second diagnosis (χ2 = 0.13, df = 1, p = 0.91). More than half (54%) correctly identified the second diagnosis in the CFS group, and 48% identified it in the control group. The difference was not significant (χ2 = 2.25, df = 1, p = 0.13). For the second diagnosis in the false positive cases, 64% of the CFS group and 77% of the control group incorrectly identified it. There were no significant differences between groups (χ2 = 2.38, df = 1, p = 0.12). In the AB cases, only 45% in each group identified the uncommon correct diagnosis (χ2 = 0.001, df = 1, p = 0.98). The educational interventions suggested by experts in clinical reasoning and employed in our study to teach CFS failed to show any reduction in diagnostic error by novices.


Effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients.
To determine the effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients with heart valve replacement. The study was conducted in 170 patients on therapy with acenocoumarol following heart valve replacement surgery. Single nucleotide polymorphisms (SNP) namely CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), and VKORC1 (rs9923231) were identified by quantitative Real-Time Polymerase Chain Reaction (RT-PCR) method. Patients with at least one variant allele of CYP2C9 (*1*2 or *1*3) required 44% and 28.2% lower daily maintenance dose of acenocoumarol (2.0mg and 2.5mg, respectively) than the normal CYP2C9*1*1 genotype group (3.4mg) (p<0.05). Patients with VKORC1 GG genotype required higher dose (3.3mg) as compared to those with genotype VKORC1 GA (2.3mg) and VKORC1 AA (1.0mg) (p<0.001). Patients with both CYP2C9*1*2/*1*3 and VKORC1 GA genotype required 38% lower dose (2.46mg) than patients with CYP2C9*1*1 and VKORC1 GG genotype (3.52mg) (p<0.0001). The clinical (age, body mass index) and genetic variables (VKORC1-1639 G>A, CYP2C9*2, CYP2C9*3) contribute together to predict 30.4% of the required maintenance dose of acenocoumarol. The genetic polymorphisms of CYP2C9 and VKORC1 results in decreased requirement of daily maintenance dose of acenocoumarol. The polymorphism VKORC1 (-1639 G>A) was found to be the major predictor of acenocoumarol dose requirement in South Indian population.


The beneficial effect of propolis on cerulein-induced experimental acute pancreatitis in rats.
Inflammatory cytokines and oxidative stress have a central role in the pathogenesis of acute pancreatitis. Propolis is a resinous hive product collected by honeybees from various plant sources and has anti-inflammatory and anti-oxidant effects. The present work aimed to investigate the therapeutic role of ethanolic extract of propolis on a cerulein-induced acute pancreatitis model in rats. Seventy male Wistar albino rats were used in the study. Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 microg/kg) four times at one-hour intervals. Ethanolic extract of propolis 300 mg/kg was given subcutaneously at the beginning of the procedure (ethanolic extract of propolis-1 group) or 12 h after the last cerulein injection (ethanolic extract of propolis-2 group). Serum amylase and lipase levels, white blood cell count and serum tumor necrosis factor-alpha levels were measured and pancreatic tissue was evaluated histologically. In the acute pancreatitis group, serum amylase and lipase levels were found to be elevated and the histopathological evaluation of the tissue revealed massive edema and inflammation with less fatty necrosis when compared to the sham and control groups. Serum amylase and lipase levels and edema formation were significantly decreased in the ethanolic extract of propolis-treated groups (p<0.001). In the ethanolic extract of propolis-2 group, in particular, tissue edema was improved markedly (p=0.001). Tissue inflammation and fatty necrosis were decreased with ethanolic extract of propolis treatment; however, the improvement was not statistically significant. Treatment with ethanolic extract of propolis improved the biochemical and histopathological findings in a rat model of experimental pancreatitis. Although our findings suggest that ethanolic extract of propolis might be considered an effective agent for the treatment of acute pancreatitis, this notion should be supported with further experimental and clinical investigations.


Length dependent activation of OAS proteins by dsRNA.
The oligoadenylate synthetase (OAS) family of enzymes are interferon-inducible antiviral proteins, which synthesize the secondary messenger 2'-5'-linked oligoadenosine (2-5A) in response to viral infection. The production of 2-5As induces RNA decay within the infected cells, thereby effectively preventing further viral replication. OAS shares structural similarity as well as the enzymatic mechanism with a different antiviral protein, cyclic GMP-AMP synthase (cGAS), but OAS is activated by dsRNA whereas cGAS is activated by dsDNA. Here, we have studied the structural requirement for the dsRNA activating OAS1 and OAS3, and compared it to recent studies on cGAS. We find that both OAS1 and OAS3, like cGAS, achieve their maximum activity with dsRNA molecules that are substantial longer than what one monomer of the enzyme can interact with. One molecule of OAS1 can cover approximately 18-20 base pairs of dsRNA, which is just short of two turns of a helix. However, RNAs of this length gave a very limited activity and the length dependency was even more pronounced for OAS3. Our data suggest that the OAS enzymes evolved to recognize long dsRNA as virally derived PAMPs, and that the length of the dsRNA is an important factor in discriminating self from non-self. Several structures of OAS1 bound to short dsRNAs exist, but our data show that OAS can only achieve minimal activity with these short activators (approximately 7-8% of maximal activity) and it is thus possible that these structures do not reveal the fully activated state of the OAS enzymes.


Neural networks for visual field analysis: how do they compare with other algorithms?
To compare the performance of a neural network in identifying visual field defects with the performance of other available algorithms. A feed-forward neural network with a single hidden layer was trained to recognize visual field defects previously collected in a longitudinal follow-up glaucoma study, and then tested on fields taken from the same study but not used in the training. The receiver operating characteristics of the network then were compared with the previously determined performance of other algorithms on the same data set. At a specificity greater than 90%, the neural network was more sensitive than any of the available algorithms (although only the global indices were available for comparison, as the cluster and cross-meridional algorithms did not achieve such high specificity at their current settings). At a lower specificity (80-85%), the neural network was unable to attain the high sensitivity of the cluster or cross-meridional algorithms; in fact, the cluster algorithm from the Low-Tension Glaucoma study was significantly more sensitive. The receiver operating characteristics of a feed-forward neural network designed to detect visual field defects were explored. At a very high specificity (90-95%) a neural network performed better than the global indices. However, at a lower specificity (78%-88%), the neural network performed worse than cluster and cross-meridional algorithms.


Reconstructing three-dimensional shape envelopes from time-resolved small-angle X-ray scattering data.
Modern computing power has made it possible to reconstruct low-resolution, three-dimensional shapes from solution small-angle X-ray scattering (SAXS) data on biomolecules without a priori knowledge of the structure. In conjunction with rapid mixing techniques, SAXS has been applied to time resolve conformational changes accompanying important biological processes, such as biomolecular folding. In response to the widespread interest in SAXS reconstructions, their value in conjunction with such time-resolved data has been examined. The group I intron from Tetrahymena thermophila and its P4-P6 subdomain are ideal model systems for investigation owing to extensive previous studies, including crystal structures. The goal of this paper is to assay the quality of reconstructions from time-resolved data given the sacrifice in signal-to-noise required to obtain sharp time resolution.


Combined hyperextension and supination of the elbow joint induces lateral ligament lesions. An experimental study of the pathoanatomy and kinematics in elbow ligament injuries.
An epidemiological study suggested that the injury mechanism of 'handball goalie's elbow' may be hyperextension. The pathomechanics of hyperextension combined with supination was studied in ten macroscopically normal, male, cadaveric elbow joint specimens. The age of the donors was 28.8 years (range 18-45 years). Extension loading of the elbow was performed in an experimental three-dimensional (3D)-kinematic loading apparatus. The degree of extension increased by 16.7 degrees +/- 8.7 degrees after loading. Hyperextension loads induced significant joint laxity in joint flexion (< 50 degrees) during forced valgus, external and internal rotation, respectively, but not during forced varus. The hyperextension trauma produced three lesions: (1) anterior capsule rupture, (2) avulsion of the proximal insertion of both the medial and the lateral collateral ligaments, and (3) occasional single rupture of the lateral collateral ligament. The lesions indicate that combined hyperextension and supination represent a possible mechanism leading to 'handball goalie's elbow'.


Cloning and expression of a prion protein (PrP) gene from Korean bovine (Bos taurus coreanae) and production of rabbit anti-bovine PrP antibody.
A PrP gene, from a Korean bovine, exhibiting a nonsense and a missense polymorphism respectively at nucleotides 576 and 652 has been cloned. The latter resulted in Glu to Lys substitution at amino acid residue 218. After expression and purification of the recombinant bovine PrP (recBoPrP) with Glu218Lys substitution, a polyclonal antibody against this protein was raised. ELISA and Western blot analysis suggested that the recBoPrP obtained in this study had a unique conformation not presented in native PrP(C), and the polyclonal antibody recognized PrP in a conformation dependent manner. These reagents will be valuable tools for studying PrP conformation.


Potential application of notochordal cells for intervertebral disc regeneration: an in vitro assessment.
Recent studies suggest that notochordal cells (NCs) might be involved in intervertebral disc homeostasis, a role exploitable to counteract matrix degradation as observed during degeneration. This study aimed to evaluate the potential of NCs to promote matrix production by nucleus pulposus cells (NPCs) and to compare it to the currently proposed addition of bone marrow stromal cells (BMSCs). Using alginate beads, bovine NPCs were exposed for 28 d to porcine NC conditioned medium (NCCM); direct co-culture with porcine NCs or bovine BMSCs; or the combination of BMSCs and NCCM. Effects on cell proliferation, disc matrix production (proteoglycans, collagens) and disc matrix protein expression (aggrecan, collagen 1 and 2, SOX9) were determined and compared to TGFβ stimulation. NCCM strongly promoted NPC proliferation (x 2.2) and matrix production (x 3.9) to levels similar to that with TGFβ, whereas the direct addition of NCs had no effect. Co-culture of NPCs and BMSCs led to proteoglycan synthesis similar to NPCs alone, which was slightly improved by NCCM (x 1.5). Histological analysis confirmed biochemical data. Gene expression of analysed proteins remained stable for all groups and unaffected by medium conditions. NCs could substantially stimulate NPCs through factors secreted into conditioned medium and in levels similar to the addition of BMSCs. This study showed that molecular agents secreted by NCs constitute a promising alternative to the proposed "standard" injection of BMSCs for disc repair: their effects are similar, do not require the injection of a large number of cells and can be further amplified when the factors are identified.


Impact of a short-term educational intervention on adherence to asthma treatment and on asthma control.
To evaluate the effect of a short-term individualized education program on adherence to asthma treatment, inhalation techniques, and asthma control. A prospective study involving patients aged 14 years or older, with a confirmed diagnosis of asthma and recruited from the asthma outpatient clinic of a university hospital in the city of Porto Alegre, Brazil. The study was conducted in two phases (before and after the educational intervention). At a routine medical visit, the participants completed a general questionnaire in order to assess the level of asthma control and inhalation techniques. The participants also underwent pulmonary function testing. Subsequently, they participated in an asthma education program, which consisted of one individualized session. The participants were reevaluated after three months. Of the 174 patients recruited, 115 completed the study. Between the first and second evaluations, there was a significant improvement in the effective use of inhaled corticosteroids (90.4% vs. 93.3%; p = 0.003), the effective use of long-acting β2 agonists (57.4% vs. 63.5%; p < 0.0001), the effective use of a combined regimen with these two medications (57.4% vs. 62.6%; p < 0.0001), and the self-reported adherence to corticosteroid therapy (p = 0.001). There was a significant decrease in the proportion of patients visiting ERs (30.4% vs. 23.5%; p = 0.012). However, the level of asthma control and the inhalation technique did not improve significantly (p = 0.095 and p = 0.512, respectively). This short-term asthma education program resulted in an improvement in the use of medications for asthma control and a decrease in the number of ER visits, although it had no significant effect on the inhalation technique.


[Visual evoked potentials from the viewpoint of test theory].
Retest reliability and objectivity (i.e. interrater agreement) are very important aspects of diagnostic tests. We report on studies concerning the retest reliability and objectivity (interrater agreement) of visual evoked potentials. The reliability and different facets of objectivity had been calculated. The confidence interval of single measurement can be identified, when the retest reliability is known. The confidence interval has to be taken into account for interpretation of measurement. The interrater agreement of measurement and interpretation of visual evoked potentials is high, but special attention has to be paid to the fact, that the interpretation of identical VEP-plots can be influenced by different preinformation.


Facet-Dependent Oxidative Goethite Growth As a Function of Aqueous Solution Conditions.
Nitroaromatic compounds are groundwater pollutants that can be degraded through reactions with Fe(II) adsorbed on iron oxide nanoparticles, although little is known about the evolving reactivity of the minerals with continuous pollutant exposure. In this work, Fe(II)/goethite reactivity toward 4-chloronitrobenzene (4-ClNB) as a function of pH, organic matter presence, and reactant concentrations was explored using sequential-spike batch reactors. Reaction rate constants were smaller with lower pH, introduction of organic matter, and diluted reactant concentrations as compared to a reference condition. Reaction rate constants did not change with the number of 4-ClNB spikes for all reaction conditions. Under all conditions, oxidative goethite growth was demonstrated through X-ray diffraction, magnetic characterization, and transmission electron microscopy. Nonparametric statistics were applied to compare histograms of lengths and widths of goethite nanoparticles as a function of varied solution conditions. The conditions that slowed the reaction also resulted in statistically shorter and wider particles than for the faster reactions. Additionally, added organic matter interfered with particle growth on the favorable {021} faces to a greater extent, with statistically reduced rate of growth on the tip facets and increased rate of growth on the side facets. These data demonstrate that oxidative growth of goethite in aqueous systems is dependent on major groundwater variables, such as pH and the presence of organic matter, which could lead to the evolving reactivity of goethite particles in natural environments.


[Role of the liaison officer in disaster countermeasures implemented by the Japanese Society of Neurology: Hope for the best and prepare for the worst].
Disaster countermeasures have been implemented by the Japanese Society of Neurology based on the experience of support to the areas affected by the Great East Japan Earthquake on March 11, 2011. The countermeasures activity began at the end of 2011. We, the Committee for Measures Against Disaster, officially started work in 2014. We developed a support network to urgently deal with patients with intractable neurological disease at the time of disaster and strengthen disaster measures, including effective disaster countermeasure training. During the 2016 Kumamoto earthquake, we realized the need to prepare for natural disasters, leading to a state of emergency, at normal times. A list of vulnerable people should be prepared and the individual support plan for disaster should be confirmed during normal times. Furthermore, during disaster, livelihood support is required for patients with intractable neurological disease living in evacuation centers in affected areas. Therefore, we compiled and published the book, titled "The manual of disaster countermeasures," in 2017. The Committee for Measures Against Disaster in the Japanese Society of Neurology has appointed a liaison officer for patients with intractable neurological disease in each prefecture. The liaison's role of is gathering and disseminating information on the disaster-hit areas, arranging medical support, and coordinating health activities, when natural disasters occur. It is hoped that the liaison officer will play an active role both at normal times and during disaster, even unforeseen ones. Although we hope for the best, we aim to be prepared for the worst.


Co-producing an inclusive-care model for young people transitioning from adolescent eating disorder services to adult care: A qualitative study protocol for Transition for Eating Disorder Youth intervention.
Eating disorders (EDs) present a chronic issue to child paediatric mental health services due to their high mortality and relapse rates. The transition from Child and Adolescent Mental Health Services to Adult Mental Health Services is a particularly high-risk period for young people with EDs given their high vulnerability to change, which can negatively impact treatment outcomes. However, there is lack of evidence on the feasibility of inclusive and youth-specific interventions that address the multiple and complex needs of this group during their transition to adult care. This proposed study aims to develop a newly introduced model of care called Transition for Eating Disorder Youth intervention (TEDYi) for young people aged 16-18 years with EDs transitioning from adolescent ED services to adult care. TEDYi will be co-produced with young people, carers, and staff targeting interpersonal and psychosocial needs during the transition process. The first phase of the study involves interviews with young people (N = 15) and carers (N = 15) as well as focus groups with mental health professionals (N = 15) across four ED adolescent and adult specialist services to explore their transition experiences. The second phase, consists of four Experience-Based Co-Design workshops, aimed at collaboratively developing and refining TEDYi.


The value of different washout parameters in the evaluation of renal transplants by technetium-99m-ethylene- l-l-dicysteine.
Technetium-99m-ethylene-l-l-dicysteine ((99m)Tc-EC) is an agent with a potential for renal imaging. It is reported that EC uses the same tubular transporter system as ortho-hippurate (OIH) and mercaptoacetyltriglycine (MAG3) and that this agent has good imaging properties and higher renal clearance than MAG3. In this study we used (99m)Tc-EC to compare different washout parameters in renal transplanted patients. Sixty nine scans in 55 patients (38 males, 17 females) were performed with (99m)Tc-EC during the follow-up period after kidney transplantation. After bolus injection of 280MBq (99m)Tc-EC, 60x1sec and 29x1min images were taken in anterior position. Perfusions of transplanted kidneys were examined visually and perfusion indices (PI) were calculated according to Hilson's method. The semiquantitative washout parameters such as 20 and 30min to peak activity ratios and 20 and 30min to 3min activity ratios were calculated. The patients were clinically evaluated by nephrologists experienced in renal transplantation cases and followed-up by serum creatinine and blood urea nitrogen determinants which were checked every postoperative day until stabilized to a optimal level for each patient. Two standard deviations above the mean values derived from all cases with normal functioning transplanted kidneys were calculated for each method. Then, these values served as the threshold to differentiate the pathological cases respectively. Of the 69 total studies performed, we found 34 normal kidneys, 14 rejections, 19 acute tubular necrosis (ATN) and 2 cyclosporin A toxicity cases. The number of abnormal cases detected with 30/3min, 30/max, 20/3min and 20/max indices were 27, 26, 24, and 18, respectively. In conclusion, we strongly recommend in studying renal transplants to consider the activity at the 3(rd) min post injection as a reference point instead of the time to maximum activity for washout index calculation. If, for any reason the time to maximum counts using (99m)Tc-(peak activity) is prefered, then the period of study should not be performed for less than 30min to achieve reliable results.


Principles of thromboprophylaxis in surgical patients.
Thromboprophylactic treatment during surgery reduces mortality and morbidity. The type of prophylaxis may be individualized according to type of operation and presence of major risk factors, such as prior thromboembolism, malignancy, long duration of immobilization, and medical conditions. All patients over the age of 40, or even younger, who have major risk factors, and whose operations will last for more than 1 hour, may benefit from thromboprophylaxis. Available prophylactic methods allow for treatment with an acceptably low level of side effects and economic cost, when compared with the cost of diagnostics and treatment of thromboembolism.


Computational investigation of the increased virulence and pathogenesis of SARS-CoV-2 lineage B.1.1.7.
New variants of SARS-CoV-2 are being reported worldwide. The World Health Organization has reported Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529) as the variants of concern. There are speculations that the variants might evade the host immune responses induced by currently available vaccines and develop resistance to drugs under consideration. The first step of viral infection in COVID-19 occurs through the interaction of the spike protein's receptor-binding domain (RBD) with the peptidase domain of the human ACE-2 (hACE-2) receptor. This study aims to get a molecular-level understanding of the mechanism behind the increased infection rate in the alpha variant. We have computationally studied the spike protein interaction in both the wild-type and B.1.1.7 variant with the hACE-2 receptor using molecular dynamics and MM-GBSA based binding free energy calculations. The binding free energy difference shows that the mutant variant of the spike protein has increased binding affinity for the hACE-2 receptor (i.e. ΔG(N501Y,A570D) is in the range -7.2 to -7.6 kcal mol-1) and the results were validated using Density functional theory. We demonstrate that with the use of state-of-the-art computational approaches, we can, in advance, predict the virulent nature of variants of SARS-CoV-2 and alert the world healthcare system.


The role of the Escherichia coli lambda receptor in the transport of maltose and maltodextrins.
The lambda receptor is a peptidoglycan-associated integral protein that spans the outer membrane. Beside its function in phage lambda adsorption it participates in transport. The latter function can be summarized as follows: 1) Receptor allows the nonspecific permeation of small molecules other than maltose and maltodextrins (in close analogy to a molecular sieve). Here the only criterion for selectivity is size and it has the properties of an unspecific pore. In this respect, it is similar to the outer membrane proteins Ia, Ib, and Ic, the porins. 2) It is a binding protein for maltodextrins. Binding affinity is low but increases by a factor of 500 as the chain length of the maltodextrins increases. In contrast, the affinity of the periplasmic maltose-binding protein for maltose and maltodextrins is similarly high (in the microM range). 3) In the in vitro system of liposomes, the lambda receptor facilitates specifically the diffusion of maltodextrins that exceed the size limit given by its porin function. This clearly demonstrates that the lambda receptor alone is able to specifically overcome the permeability barrier of the outer membrane for maltodextrins. 4) From the genetic and kinetic analysis of maltose and maltodextrin transport, it can be concluded that the lambda receptor interacts with the periplasmic maltose-binding protein. 5) Electron microscopic studies indicate a location for the maltose-binding protein in the outer cell envelope. This location is dependent on the presence of the lambda receptor.


Modulation by immunosuppressive agents of peripheral blood mononuclear cell responses to influenza A virus.
The response to influenza A virus of peripheral blood mononuclear cells (PBMC) isolated from normal healthy adults was studied by measuring antigen-specific lymphocyte proliferation and interferon and interleukin-2 production by these cells in vitro. Under various experimental conditions, methylprednisolone, doxorubicin, vincristine, and vinblastine each reduced lymphocyte proliferation of the PBMC exposed to influenza A virus antigen. Treatment of cells with these drugs did not reduce expression of influenza A virus antigens by PBMC as detected by flow cytometry and did not reduce cell viability. In vitro treatment of the cells with methylprednisolone and doxorubicin reduced interferon and interleukin-2 yields. Experimental conditions necessary to reduce lymphokine yields varied with the immunosuppressive drug tested. Vincristine and vinblastine treatment of the cells did not reduce interferon or interleukin-2 yields. We conclude that methylprednisolone and doxorubicin at clinically achievable concentrations significantly affected the response of PBMC to influenza A virus in vitro. The effects of these immunosuppressive agents on lymphokine production were different from those reported in previous studies in which mitogens and Newcastle disease virus were used as inducers. The sensitivity of PBMC to these immunosuppressive agents is clearly related to the inducing agent used.


The vasoactive properties of ascitic fluid in acute pancreatitis in a porcine model.
The hemodynamic effect of pancreatic ascitic fluid was studied in a porcine model. Pancreatitis was induced by a low-pressure infusion of trypsin and taurocholate sodium into the pancreatic duct. The ascitic fluid that accumulated was then injected into the inferior vena cava of five pigs, with each pig receiving five infusions at 40-minute intervals. Mean arterial blood pressure and peripheral vascular resistance fell with each infusion, while pulmonary artery pressure increased. The magnitude of the drop in arterial blood pressure decreased with subsequent infusions, suggesting tachyphylaxis. The rise in pulmonary artery pressure increased with successive infusions. Anesthesia artifact and decay of the pancreatic ascitic fluid were ruled out as causes of the tachyphylaxis. Filtration separated the substances producing pulmonary effects and systemic blood pressure effects (0.2 to 11 microns vs 10,000 daltons to 0.2 micron). These data suggest that two mediators may produce the hemodynamic effects of pancreatic ascitic fluid.


Immature teratoma of the nose and paranasal sinuses masquerading as bilateral nasal polyposis: a unique presentation.
Teratomas are tumors of multipotent cells derived from all three germ cell layers and recapitulate normal organogenesis. Teratomas are hypothesized to arise by misplacement of multipotent germ cells. Teratoma is usually developmental and sometimes congenital neoplasm which displays both solid and cystic components with gross and microscopic differentiation into a wide variety of tissues representative of all three germ layers--ectoderm, mesoderm and endoderm. We are describing a case which was initially diagnosed as bilateral nasal polyposis clinically but histopathology report came out to be immature teratoma. This case is being reported to make aware all ENT surgeons of such unique presentation of sinonasal teratomas as such presentation of these tumors has not been reported in literature previously, and hence teratomas should be considered in the differential diagnosis of nasal polyposis in future.


Ki-67 staining is an independent correlate of biochemical failure in prostate cancer treated with radiotherapy.
To determine the significance of Ki-67/MIB1 staining as a marker of patient outcome for prostate cancer patients treated with radiotherapy. Pretreatment archival prostate biopsy tumor tissue was available from 106 stage T1-T4 prostate cancer patients treated with external beam radiotherapy between 1987 and 1993 at M. D. Anderson Cancer Center. Diagnosis was made from prostate needle biopsy in 64 cases and from transurethral resection of the prostate (TURP) in 42 cases. All patients had a pretreatment prostate-specific antigen (PSA), and no patient had evidence of metastasis. Immunohistochemical staining for MIB1 was used to determine the percentage of Ki-67-positive tumor cells, the Ki-67 labeling index (Ki67-LI). Biochemical failure after radiotherapy was defined as three rises in PSA on follow-up. Median follow-up was 62 months. The mean and median Ki67-LI for the entire cohort was 3.2 and 2.3. The mean and median Ki67-LIs for those diagnosed by needle biopsy were 3.2 and 2.3, and by TURP were 3.1 and 2.4. For all patients, mean Ki67-LI levels were significantly higher with stage T3/T4 disease, Gleason 7-10 disease, and in those that developed treatment failure. Similar relationships were observed when the Ki67-LI was dichotomized into low (< or =3.5%) and high (>3.5%) groups. Actuarial freedom from biochemical failure (bNED) when Ki67-LI was low and high was 76 and 33% at 5 years (P < 0.0001, log rank). Similar statistically significant differences were observed when the TURP and needle biopsy groups were analyzed separately. Cox proportional hazards regression showed that dichotomized Ki67-LI was an independent correlate of bNED, along with pretreatment PSA, Gleason score, and clinical stage. The Ki67-LI obtained from pretreatment prostate cancer tissue is a strong independent predictor of failure after radiotherapy using biochemical criteria. This prognostic factor was equally valuable for patients diagnosed by TURP or needle biopsy.


Fabrication of a Monolithic Lab-on-a-Chip Platform with Integrated Hydrogel Waveguides for Chemical Sensing.
Hydrogel waveguides have found increased use for variety of applications where biocompatibility and flexibility are important. In this work, we demonstrate the use of polyethylene glycol diacrylate (PEGDA) waveguides to realize a monolithic lab-on-a-chip device. We performed a comprehensive study on the swelling and optical properties for different chain lengths and concentrations in order to realize an integrated biocompatible waveguide in a microfluidic device for chemical sensing. Waveguiding properties of PEGDA hydrogel were used to guide excitation light into a microfluidic channel to measure the fluorescence emission profile of rhodamine 6G as well as collect the fluorescence signal from the same device. Overall, this work shows the potential of hydrogel waveguides to facilitate delivery and collection of optical signals for potential use in wearable and implantable lab-on-a-chip devices.


The haploinsufficient tumor suppressor, CUX1, acts as an analog transcriptional regulator that controls target genes through distal enhancers that loop to target promoters.
One third of tumor suppressors are haploinsufficient transcriptional regulators, yet it remains unknown how a 50% reduction of a transcription factor is translated at the cis-regulatory level into a malignant transcriptional program. We studied CUX1, a haploinsufficient transcription factor that is recurrently mutated in hematopoietic and solid tumors. We determined CUX1 DNA-binding and target gene regulation in the wildtype and haploinsufficient states. CUX1 binds with transcriptional activators and cohesin at distal enhancers across three different human cell types. Haploinsufficiency of CUX1 altered the expression of a large number of genes, including cell cycle regulators, with concomitant increased cellular proliferation. Surprisingly, CUX1 occupancy decreased genome-wide in the haploinsufficient state, and binding site affinity did not correlate with differential gene expression. Instead, differentially expressed genes had multiple, low-affinity CUX1 binding sites, features of analog gene regulation. A machine-learning algorithm determined that chromatin accessibility, enhancer activity, and distance to the transcription start site are features of dose-sensitive CUX1 transcriptional regulation. Moreover, CUX1 is enriched at sites of DNA looping, as determined by Hi-C analysis, and these loops connect CUX1 to the promoters of regulated genes. We propose an analog model for haploinsufficient transcriptional deregulation mediated by higher order genome architecture.


Effects of intravaginal administration of prostaglandin F2α on luteolysis and subsequent estrus in Shiba goats (Capra hircus).
This study examined the effects of intravaginal administration of prostaglandin F2α (PGF2α ) on luteolysis and subsequent estrus in cycling goats. Goats with functional corpus lutea received one of five treatments: 2 mg of PG intramuscularly (IM2 × 1; n = 6), 2 mg of PGF2α intravaginally (IVG2 × 1; n = 7), 4 mg of PGF2α intravaginally (IVG4 × 1; n = 7), and 1 or 2 mg of PGF2α intravaginally 8 h apart (IVG1 × 2 group; n = 6 and IVG2 × 2; n = 8). Blood samples were collected at 24-h intervals from 0 to 7 days after PGF2α administration. Estrus was checked twice daily during the experiment. The proportion of goats with complete luteolysis (reduction of progesterone concentrations to <1 ng/mL until 48 h after treatment) in the IVG2 × 1 group (28.6%) was significantly lower than in the other groups (IM2 × 1; 100%, IVG4 × 1; 57.1%, IVG1 × 2; 87.5%, IVG2 × 2; 100%, respectively). For goats completing luteolysis, there was no significant difference in the onset and duration of estrus among the groups. These results suggest that intravaginal administration of PGF2α can be applied as an alternative to intramuscular administration.


Kinase Substrate Profiling Using a Proteome-wide Serine-Oriented Human Peptide Library.
The human proteome encodes >500 protein kinases and hundreds of thousands of potential phosphorylation sites. However, the identification of kinase-substrate pairs remains an active area of research because the relationships between individual kinases and these phosphorylation sites remain largely unknown. Many techniques have been established to discover kinase substrates but are often technically challenging to perform. Moreover, these methods frequently rely on substrate reagent pools that do not reflect human protein sequences or are biased by human cell line protein expression profiles. Here, we describe a new approach called SERIOHL-KILR (serine-oriented human library-kinase library reactions) to profile kinase substrate specificity and to identify candidate substrates for serine kinases. Using a purified library of >100000 serine-oriented human peptides expressed heterologously in Escherichia coli, we perform in vitro kinase reactions to identify phosphorylated human peptide sequences by liquid chromatography and tandem mass spectrometry. We compare our results for protein kinase A to those of a well-established positional scanning peptide library method, certifying that SERIOHL-KILR can identify the same predominant motif elements as traditional techniques. We then interrogate a small panel of cancer-associated PKCβ mutants using our profiling protocol and observe a shift in substrate specificity likely attributable to the loss of key polar contacts between the kinase and its substrates. Overall, we demonstrate that SERIOHL-KILR can rapidly identify candidate kinase substrates that can be directly mapped to human sequences for pathway analysis. Because this technique can be adapted for various kinase studies, we believe that SERIOHL-KILR will have many new victims in the future.


Intraepidermal free nerve fiber endings in the hairless skin of the rat as revealed by the zinc iodide-osmium tetroxide technique.
The nerve fiber distribution in the epidermis of the hairless rat skin was studied light microscopically by means of zinc iodide-osmium tetroxide staining. Two different morphological types of free nerve fiber endings could be detected: clusters of relatively thick nerve fibers stretched up through the spinous layer up to the granular layer sending off terminal branches. In addition, many solitary thin varicose nerve fibers were seen within the epidermis. The observed discrepancies in nerve fiber diameters appeared to be larger than those reported for human intraepidermal nerve fibers in recent immunohistochemical studies. Moreover, dendritic cells, most probably representing Langerhans cells, could be selectively stained. These cells appeared to be in a close location to thin varicose nerve fibers. Both types of demonstrated free nerve endings have to be functionally connected with different sensoric functions. Possibly, a subpopulation of the thin nerve fibers might possess primarily a nociceptive task, whereas the thick ones have most probably to be regarded as mechanoreceptive. The nerve fibers innervating dendritic cells appear to be identical to the peptidergic ones which may regulate the antigen-presenting capacity of these cells. Due to its selectivity for intraepidermal nerve fibers, the used method might supplement immunohistochemical procedures in a helpful manner.


Four-Year Analyses of Renal Graft Biopsies: A Single-Center Pathology Experience.
Kidney transplant is the best treatment for patients with end-stage renal disease. Long-term graft survival depends on the protection of renal allograft function. Renal allograft biopsy is the most important method for examining an allograft function. Biopsy provides critical information, enabling diagnosis and grading of pathologic changes, prediction of response to therapy, and long-term graft prognosis. We reviewed the medical records of patients who underwent renal transplant from living and deceased donors at Baskent University Adana Teaching and Research Hospital between 2010 and 2014 and who had an indication for biopsy. Clinical characteristics and laboratory results of patients were recorded. Patient biopsy samples were examined according to the Banff 2009 classification. Between 2010 and 2014, there were 175 renal transplants performed at our hospital, with 134 recipients (76.6%) having living-donor and 41 recipients (23.4%) having deceased-donor transplants. Fifty-one patients (29.1%) were children, and 124 patients (70.9%) were adults. We found that there were 123 biopsies made from 75 transplant patients over a 4-year period. When examined according to Banff 2009 criteria, the biopsy samples revealed acute T-cell-mediated rejection alone in 14.1% of the samples, acute antibody-mediated rejection in 4%, and a combination of the 2 rejections in 5.7%. Specific infections were detected in 12 patients. The graft nephrectomy rate was 5.1%. This study investigated biopsy results, their relation with patient clinical status and 4-year survival rates, and our pathology experience and found that rejection and infection rates were similar to the literature. Our future studies with a longer follow-up and a larger sample size will likely provide more accurate information about graft survival and biopsy results.


Ureteral injury during left colectomy for cancer: Laparoscopic management. A case report.
Iatrogenic ureteral lesions may occur after any abdominal and pelvic surgery. They are severe and can affect renal function and even vital prognosis. This study aimed to determine the clinical aspects and the therapeutic approaches of a lower third injury of the ureter during a laparoscopic left colectomy. An 81 year-old-man with left-sided colon cancer underwent laparoscopic left colectomy. During surgery there was a continuous full-thickness solution of the left ureter for which an end-to-end ureteral anastomosis was performed. In the postoperative period the patient underwent multiple urological and radiological interventional procedures due to the aforementioned injury. Ureteral injury was defined as any laceration, transection or ligation of the ureter that required an unexpected procedure for repair, stent or drainage. It can be managed with several procedures. An appropriate repair should be chosen according to length and position of ureteral injuries. The lower third of the ureter, as the lesion of our patient, has a profuse blood supply resulting in this way less susceptible to ischemia. In the last decade urological surgery, laparoscopy, ureteroscopic procedures and gynecological surgery are the main causes of iatrogenic ureteral lesions. Prognosis is conditioned by early diagnosis and the anatomic condition of the ureter. Laparoscopic end-to-end ureteral anastomosis could be considered a good option in the case of intraoperative iatrogenic lower ureteral injuries.


[Kidney sorbitol dehydrogenase: kinetic mechanism].
Properties of sorbitol dehydrogenase isolated from rat kidney were studied. Sorbitol dehydrogenase reactions followed the consecutive irregular order as shown in studies of kinetic patterns, inhibition by end products and thermoinactivation of the enzyme in the presence of substrates.


S100A10 Is a Critical Mediator of GAS6/AXL-Induced Angiogenesis in Renal Cell Carcinoma.
Angiogenesis is a hallmark of cancer that promotes tumor progression and metastasis. However, antiangiogenic agents have limited efficacy in cancer therapy due to the development of resistance. In clear cell renal cell carcinoma (ccRCC), AXL expression is associated with antiangiogenic resistance and poor survival. Here, we establish a role for GAS6/AXL signaling in promoting the angiogenic potential of ccRCC cells through the regulation of the plasminogen receptor S100A10. Genetic and therapeutic inhibition of AXL signaling in ccRCC tumor xenografts reduced tumor vessel density and growth under the renal capsule. GAS6/AXL signaling activated the expression of S100A10 through SRC to promote plasmin production, endothelial cell invasion, and angiogenesis. Importantly, treatment with the small molecule AXL inhibitor cabozantinib or an ultra-high affinity soluble AXL Fc fusion decoy receptor (sAXL) reduced the growth of a pazopanib-resistant ccRCC patient-derived xenograft. Moreover, the combination of sAXL synergized with pazopanib and axitinib to reduce ccRCC patient-derived xenograft growth and vessel density. These findings highlight a role for AXL/S100A10 signaling in mediating the angiogenic potential of ccRCC cells and support the combination of AXL inhibitors with antiangiogenic agents for advanced ccRCC. SIGNIFICANCE: These findings show that angiogenesis in renal cell carcinoma (RCC) is regulated through AXL/S100A10 signaling and support the combination of AXL inhibitors with antiangiogenic agents for the treatment of RCC.


Dystrophic epidermolysis bullosa. A new variant characterized by progressive symmetrical centripetal involvement with scarring.
A patient is reported with a form of epidermolysis bullosa, hitherto undescribed to the best of our knowledge, characterized by the slow centripetal progression of symmetrical blister formation, milia, scarring, atrophy, and nail dystrophy. Electron microscopy, immunofluorescence mapping, and KF-1 monoclonal antibody studies confirm this disease to be a form of dystrophic epidermolysis bullosa, probably of autosomal recessive transmission despite the absence of acral deformities, contractures, mucosal involvement, and growth retardation.


Hydrocarbon gases produced during in vitro peroxidation of polyunsaturated fatty acids and decomposition of preformed hydroperoxides.
Hydrocarbon gases have been used previously as an index of lipid peroxidation in vivo and in vitro. In vitro experiments are reported on the formation of hydrocarbon gases from peroxidizing omega-3 and omega-6 fatty acids. Hydrocarbon gases were not released during a 20-hr peroxidation phase but were released following the decomposition of hydroperoxides by addition of excess ascorbic acid. The major hydrocarbon gas products in iron, copper, or hematin catalyzed peroxidation systems were ethane or ethylene from linolenic acid, and pentane from linoleic acid and arachidonic acid. Calculations of the ratios of hydrocarbon gases formed were based on fatty acid decrease and/or change in diene conjugation and peroxide values. Depending on the fatty acid, catalyst, and calculation basis used, pentane formation was as high as 1.3 mol %, ethane 4.3 mol %, and ethylene 10.6 mol %.


In Vitro Fertilization and Early Pregnancy Outcomes After Coronavirus Disease 2019 (COVID-19) Vaccination.
To assess whether coronavirus disease 2019 (COVID-19) mRNA vaccination is associated with controlled ovarian hyperstimulation or early pregnancy outcomes. This retrospective cohort study included patients who underwent controlled ovarian hyperstimulation or single euploid frozen-thawed embryo transfer at a single academic center. Patients fully vaccinated with a COVID-19 mRNA vaccine were compared with unvaccinated patients who cycled during the same time period. The primary outcome was the fertilization rate for controlled ovarian hyperstimulation and the clinical pregnancy rate for frozen-thawed embryo transfer. Secondary outcomes for controlled ovarian hyperstimulation included eggs retrieved, mature oocytes retrieved, mature oocytes ratio, blastulation rate, and euploid rate. Secondary outcomes for frozen-thawed embryo transfer included pregnancy rate, ongoing pregnancy rate, biochemical pregnancy loss rate, and clinical pregnancy loss rate. Among 222 vaccinated patients and 983 unvaccinated patients who underwent controlled ovarian hyperstimulation cycles between February and September 2021, there was no association on adjusted analysis between COVID-19 vaccination and fertilization rate (β=0.02±0.02, P=.20) or any of the secondary outcomes assessed: eggs retrieved (β=0.01±0.57, P=.99), mature oocytes retrieved (β=0.26±0.47, P=.58), mature oocytes ratio (β=0.02±0.01, P=.12), blastulation rate (β=0.02±0.02, P=.27), or euploid rate (β=0.05±0.03, P=.08). Among 214 vaccinated patients and 733 unvaccinated patients undergoing single euploid frozen-thawed embryo transfer, adjusted analysis demonstrated no significant association between vaccination and clinical pregnancy (adjusted odds ratio [aOR] 0.79, 95% CI 0.54-1.16) or any of the secondary outcomes: pregnancy (aOR 0.88, 95% CI 0.58-1.33), ongoing pregnancy (aOR 0.90, 95% CI 0.61-1.31), biochemical pregnancy loss (aOR 1.21, 95% CI 0.69-2.14), or clinical pregnancy loss (aOR 1.02, 95% CI 0.51-2.06). Administration of COVID-19 mRNA vaccines was not associated with an adverse effect on stimulation or early pregnancy outcomes after IVF. Our findings contribute to the growing body of evidence regarding the safety of COVID-19 vaccination in women who are trying to conceive.


Numerical Analysis of the Influence of Low Frequency Vibration on Bubble Growth.
Numerical simulation of bubble growth during pool boiling under the influence of low frequency vibration was performed to understand the influence of common vibrations such as those induced by wind, highway transportation, and nearby mechanical devices on the performance of thermal systems that rely on boiling. The simulations were done for saturated R123 boiling at 277.6 K with a 15 K wall superheat. The numerical volume-of-fluid method (fixed grid) was used to define the liquid-vapor interface. The basic bubble growth characteristics including the bubble departure diameter and the bubble departure time were determined as a function of the bubble contact angle (20°-80°), the vibration displacement (10 µm-50 µm), the vibration frequency (5 Hz-25 Hz), and the initial vibration direction (positive or negative). The bubble parameters were shown to be strongly dependent on the bubble contact angle at the surface. For example, both the bubble departure diameter and the bubble departure time increased with the contact angle. At the same vibration frequency and the initial vibration direction, the bubble departure diameter and the bubble departure time both decreased with increasing vibration displacement. In addition, the vibration frequency had a greater effect on the bubble growth characteristics than did the vibration displacement. The vibration frequency effect was strongly influenced by the initial vibration direction. The pressure contour, the volume fraction of vapor phase, the temperature profile, and the velocity vector were investigated to understand these dynamic bubble behaviors. The limitation of the computational fluid dynamics approach was also described.


Epithelial Na+ channels and stomatin are expressed in rat trigeminal mechanosensory neurons.
Caenorhabditis elegans MEC-4 and MEC-10 are subunits of the degenerin/epithelial Na+ channel (DEG/ENaC) ion channel superfamily thought to be associated with MEC-2 (a stomatin-like protein) in a mechanotransducing molecular complex in specialized touch sensory neurons. A key question is whether analogous molecular complexes in higher organisms transduce mechanical signals. To address this question, we selected mechanoreceptors of the rat vibrissal follicle-sinus complex in the mystacial pad and the trigeminal ganglia for an immunocytochemical and molecular biological study. RT-PCR of poly(A+) mRNA of rat trigeminal ganglia indicated that alpha-, beta-, and gamma-ENaC and stomatin mRNA are expressed in rat trigeminal ganglia. Using immunocytochemistry, we found that alpha-, beta-, and gamma-ENaC subunits and stomatin are localized in the perikarya of the trigeminal neurons and in a minor fraction of their termination site in the vibrissal follicle-sinus complex, where longitudinal lanceolate endings are immunopositive. We conclude that alpha-, beta-, and gamma-ENaC subunits as well as the candidate interacting protein stomatin are coexpressed in a mammalian mechanoreceptor, a location consistent with a possible role in mechanotransduction.


Assessing the use of diagnostic laboratory accession data to support national bovine viral diarrhoea control in New Zealand.
Aims: To assess the suitability of using existing national diagnostic laboratory testing data to support national bovine viral diarrhoea (BVD) research, surveillance, and control in New Zealand. Methods: Data on laboratory accessions for BVD diagnostic testing in New Zealand from 1 January 2015 to 31 December 2017 were provided by four commercial veterinary diagnostic companies. The data were integrated into a single dataset containing the unique accession number, sample submission date, farm location (territorial authority level), test type (bulk milk antibody-ELISA, bulk milk PCR, serum antibody-ELISA, blood/serum/tissue antigen-ELISA, or blood/serum/tissue PCR), and test results. Estimates for the number of registered cattle farms in each territorial authority were generated from the National Animal Identification and Tracing database. Results were summarised for July 2015 to June 2016 and July 2016 to June 2017. Results: There was a total of 59,007 unique BVD diagnostic test accessions including 39,920 (67.6%) for bulk milk antibody-ELISA, 27,832 (47.2%) for bulk milk PCR, 3,229 (5.5%) for serum antibody-ELISA, 9,132 (15.5%) for blood/serum/tissue antigen-ELISA, and 7,122 (12.1%) for blood/serum/tissue PCR. Of the 17,946 accessions for blood/serum/tissue samples, 4,316 (24.0%) were missing the herd production type and 6,678 (37.2%) were missing the animals age. Approximately 7,000/10,958 (65%) dairy herds and 1,600/43,611 (4%) beef herds were conducting annual BVD screening tests. In 2016/2017, the prevalence of accessions with ≥1 BVD-positive result was 40.6% for bulk milk antibody, 6.4% for bulk milk PCR, 45.6% for serum antibody, and 9.8% for blood/serum/tissue antigen-ELISA or PCR tests. There was substantial regional variation in both the percentage of herds testing for BVD and the prevalence of positive accessions. Following pooled serum antibody-ELISA, only 175/604 (29.0%) beef herds and 177/566 (31.3%) dairy herds had recorded follow-up testing. Conclusions and Clinical Relevance: Laboratory diagnostic accession data has the potential to provide valuable insights about BVD epidemiology in New Zealand, but there are significant limitations in the data collected and discrepancies in the different systems that each laboratory uses to measure, interpret, and record diagnostic data. There is a strong need to develop a more consistent national system for recording and sharing BVD test results to support BVD management at farm and industry levels. Abbreviations: BVD: Bovine viral diarrhoea; Ct: Cycle threshold; NAIT: National Animal Identification and Tracing; NZVP: New Zealand Veterinary Pathology; PI: Persistently infected; S/P: Sample to positive control.


How Do Physical Therapists in the United Kingdom Manage Patients With Hip Osteoarthritis? Results of a Cross-Sectional Survey.
Hip osteoarthritis (OA) is common, painful, and disabling. Physical therapists have an important role in managing patients with hip OA; however, little is known about their current management approach and whether it aligns with clinical guideline recommendations. The objective of this study is to describe United Kingdom (UK) physical therapists' current management of patients with hip OA and to determine whether it aligns with clinical guidelines. The design is a cross-section questionnaire. A questionnaire was mailed to 3126 physical therapists in the UK that explored physical therapists' self-reported management of a patient with hip OA using a case vignette and clinical management questions. The response rate was 52.7% (n = 1646). In total, 1148 (69.7%) physical therapists had treated a patient with hip OA in the last 6 months and were included in the analyses. A treatment package was commonly provided incorporating advice, exercise (strength training 95.9%; general physical activity 85.4%), and other nonpharmacological modalities, predominantly manual therapy (69.6%), and gait retraining (66.4%). There were some differences in reported management between physical therapists based in the National Health Service (NHS) and non-NHS-based physical therapists, including fewer treatment sessions being provided by NHS-based therapists. Limitations include the potential for nonresponder bias and, in clinical practice, physical therapists may manage patients with hip OA differently. UK-based physical therapists commonly provide a package of care for patients with hip OA that is broadly in line with current clinical guidelines, including advice, exercise, and other nonpharmacological treatments. There were some differences in clinical practice between NHS and non-NHS-based physical therapists, but whether these differences impact on clinical outcomes remains unknown.


Preparedness for threat of chikungunya in the pacific.
Chikungunya virus (CHIKV) caused significant outbreaks of illness during 2005-2007 in the Indian Ocean region. Chikungunya outbreaks have also occurred in the Pacific region, including in Papua New Guinea in 2012; New Caledonia in April 2013; and Yap State, Federated States of Micronesia, in August 2013. CHIKV is a threat in the Pacific, and the risk for further spread is high, given several similarities between the Pacific and Indian Ocean chikungunya outbreaks. Island health care systems have difficulties coping with high caseloads, which highlights the need for early multidisciplinary preparedness. The Pacific Public Health Surveillance Network has developed several strategies focusing on surveillance, case management, vector control, laboratory confirmation, and communication. The management of this CHIKV threat will likely have broad implications for global public health.


The genetic basis for individual differences in mRNA splicing and APOBEC1 editing activity in murine macrophages.
Alternative splicing and mRNA editing are known to contribute to transcriptome diversity. Although alternative splicing is pervasive and contributes to a variety of pathologies, including cancer, the genetic context for individual differences in isoform usage is still evolving. Similarly, although mRNA editing is ubiquitous and associated with important biological processes such as intracellular viral replication and cancer development, individual variations in mRNA editing and the genetic transmissibility of mRNA editing are equivocal. Here, we have used linkage analysis to show that both mRNA editing and alternative splicing are regulated by the macrophage genetic background and environmental cues. We show that distinct loci, potentially harboring variable splice factors, regulate the splicing of multiple transcripts. Additionally, we show that individual genetic variability at the Apobec1 locus results in differential rates of C-to-U(T) editing in murine macrophages; with mouse strains expressing mostly a truncated alternative transcript isoform of Apobec1 exhibiting lower rates of editing. As a proof of concept, we have used linkage analysis to identify 36 high-confidence novel edited sites. These results provide a novel and complementary method that can be used to identify C-to-U editing sites in individuals segregating at specific loci and show that, beyond DNA sequence and structural changes, differential isoform usage and mRNA editing can contribute to intra-species genomic and phenotypic diversity.


Antioxidant activities of rosemary, sage, and sumac extracts and their combinations on stability of natural peanut oil.
The antioxidant efficacy of rosemary (Rosmarinus officinalis L.), sage (Salvia fruticosa L.), and sumac (Rhus coriaria L.) extracts and combinations at 4% concentrations (wt/vol, extract/oil) were investigated. Methanolic extracts of rosemary, sage, sumac, and their combinations were applied to peanut oil stored at 80 degrees C for 24 h. The antioxidant effect was determined by measuring the peroxide value. All extracts showed antioxidant effects compared with control. But the antioxidant effect of all extracts was low compared with that of butylated hydroxytoluene. Rosemary extract (except for 3 and 4 h) exhibited the most antioxidant effect compared with other individual extracts. Of blends, the most effective ones were sage plus sumac combinations. Sumac extract is also promising as a source of natural antioxidants.


Antiseizure Medications Withdrawal Seizures in Patients with Juvenile Myoclonic Epilepsy.
Patients with juvenile myoclonic epilepsy (JME) are especially prone to having antiseizure medications (ASMs) withdrawal seizures (WS). To clarify whether WS in JME patients are caused by a high tendency of non-adherence from seizure-free patients or by a constitutive increased sensitivity to drug withdrawal. Epilepsy patients followed in a tertiary epilepsy clinic between 2010 and 2013 were included in the study. WS prevalence was compared between drug-responsive and drug-resistant JME patients and patients with other types of epilepsy. The study included 23 JME patients (16 drug-responsive and 7 drug-resistant) and 138 patients with other epilepsies (74 drug-responsive and 64 drug-resistant). JME patients were younger and included more women than non-JME patients. Significantly more WS were seen in JME than in non-JME patients (P = 0.01) and in the drug-resistant fraction of JME patients in comparison to drug-resistant non-JME patients (P = 0.02). On logistic regression, the type of epilepsy, but not the patient's sex, was found to significantly predict WS. No significant difference was found in the prevalence of WS between drug-responsive and drug-resistant JME patients. The main ASM discontinued in JME was valproic acid (VPA), especially in women. Our findings suggest a higher sensitivity of JME patients to withdrawal of medications. It is important to educate JME patients about treatment adherence and to explain to their physicians how to carefully reduce or replace ASMs to mitigate the morbidity and mortality related to ASM withdrawal.


The elaboration of personal construct psychology.
More than half a century has passed since the publication of George Kelly's (1955/1991) The Psychology of Personal Constructs. This review considers the elaboration of personal construct psychology (PCP) during this time, both by Kelly and by others who developed his ideas. Advances to the theory have principally concerned implicative relationships between constructs, construing of the self, social relationships, emotions, links with other approaches, and supporting research. With regard to methods of assessment of construing, major developments have occurred in both repertory grid and nongrid techniques, such as laddering. The principal advances in the applications of PCP have been in the clinical, educational, and organizational fields, but have by no means been limited to these areas. It can be concluded that PCP has met Kelly's own design specifications for a useful theory and that PCP can perhaps anticipate at least another half-century of elaboration.


Synthesis, purification, properties and characterization of sorted single-walled carbon nanotubes.
Single-walled carbon nanotubes (SWCNTs) have attracted significant attention due to their outstanding mechanical, chemical and optoelectronic properties, which makes them promising candidates for use in a wide range of applications. However, as-produced SWCNTs have a wide distribution of various chiral species with different properties (i.e. electronic structures). In order to take full advantage of SWCNT properties, highly purified and well-separated SWCNTs are of great importance. Recent advances have focused on developing new strategies to effectively separate nanotubes into single-chirality and/or semiconducting/metallic species and integrating them into different applications. This review highlights recent progress in this cutting-edge research area alongside the enormous development of their identification and structural characterization techniques. A comprehensive review of advances in both controlled synthesis and post-synthesis separation methods of SWCNTs are presented. The relationship between the unique structure of SWCNTs and their intrinsic properties is also discussed. Finally, important future directions for the development of sorting and purification protocols for SWCNTs are provided.


Lesions of the alar ligaments. In vivo and in vitro studies with magnetic resonance imaging.
This study analyzed anatomic characteristics of the alar ligaments and the possibility of imaging them with magnetic resonance imaging. Also determined was whether artificial ruptures of the alar ligament can be recognized experimentally. To determine the ability of magnetic resonance imaging to visualize normal, torn, resected alar ligaments. There are no studies about computed tomography or magnetic resonance imaging findings of alar ligaments and after anatomic sections. Direct visualization of the complete ligament is not possible for computed tomography. No precise diagnostic method for showing a ruptured alar ligaments has been described. Magnetic resonance imaging seems to be the method of choice for distinguishing between normal and pathologic soft tissue. Fifteen specimens from accident victims underwent anatomic dissection. In addition, ligaments from three groups were examined: 1) eight volunteers, 2) seven patients, and 3) 17 fresh cadaveric specimen before anatomic exploratory dissection. In seven of these specimens, one ligament was cut to simulate an artificial disruption and magnetic resonance imaging was repeated. Lesions of the alar ligaments were found in four of 15 prepared specimens. Using magnetic resonance imaging, the alar ligaments could be identified in all volunteers, patients, and specimen except one. No ruptures were found in the 17 specimens. Of the seven resected specimens, all cuts could be demonstrated by magnetic resonance imaging. Magnetic resonance imaging is useful for showing lesions of the alar ligaments because of a high soft tissue contrast, plane independence imaging, possibility of functional scans, and secondary reconstruction from three-dimensional data sets.


Predicting One-Year Non-Cancer-Related Adverse Events After Lung Resection.
Assessing the risk for non-cancer-related outcomes following lung cancer surgery is crucial for high-risk patients. This study examined non-cancer-related adverse events within one year after lung resection, emphasizing the role of resected lung volume and postoperative atrial fibrillation. We conducted a retrospective analysis of 460 patients who underwent anatomical lung resection for malignant lung tumours. We assessed perioperative factors, such as the number of resected subsegments and postoperative atrial fibrillation, as potential predictors of one-year non-cancer-related adverse events. Additionally, we validated a previously published nomogram for predicting postoperative atrial fibrillation. One-year non-cancer-related adverse events occurred in 20% of patients. Multivariable analysis identified higher age, lower percentage-predicted forced expiratory volume in 1 s, greater number of resected subsegments, and postoperative atrial fibrillation as independent predictors of these adverse events. The incidence of postoperative atrial fibrillation was 8.5%, with higher age, history of atrial fibrillation, and open thoracotomy as independent predictors. A temporal link between postoperative atrial fibrillation and other severe postoperative complications was observed, as 71% of postoperative atrial fibrillation cases preceded other complications. The nomogram's predicted risk for postoperative atrial fibrillation was associated well with the actual incidence. Resected lung volume and postoperative atrial fibrillation are statistically significant factors associated with non-cancer-related outcomes after lung resection. Minimizing resected lung volume when oncologically and technically feasible, along with identifying patients at risk for postoperative atrial fibrillation, may contribute to improved postoperative outcomes. Our results have implications for risk stratification and preoperative decision-making in lung cancer surgery.


Vitamin D status and physical function in nursing home residents: a 1-year observational study.
Low vitamin D blood levels are highly prevalent in elderly people, particularly in nursing home residents (NHR). A relation between vitamin D levels and physical function (PF) is described in several studies in older adults; however, data on NHR are scarce and there is presently no information on the time course of vitamin D levels and PF in this population. The aim of the present study was to describe the 25-hydroxyvitamin D [25(OH)D] status of NHR at baseline (t1) and after 1 year (t2) to examine whether 25(OH)D blood levels are related to PF at t1 and at t2, and whether changes in 25(OH)D levels over 1 year are related to changes in PF. All NHR (≥ 65 years) without tube-feeding and severe acute or end-stage disease were asked to participate. At t1 and t2 fasting blood samples were taken for the analysis of 25(OH)D serum levels and PF was estimated by activities of daily living (Barthel ADL) and measured by handgrip strength (HGS) and timed 'up and go' test (TUG). In total, 115 residents, aged 87 (82-93) years (all data in median and 1st-3rd quartile), showed the following values for PF: ADL 50 (20-65) points, HGS 40 (30-50) kPa and TUG 26 (18-31) s. Vitamin D deficiency (< 50 nmol/l) was present in 93.9 % (70.4 % < 25 nmol/l) at t1 and in 71.2 % (57.3 % < 25 nmol/l) at t2. At t1 and at t2 a weak correlation between vitamin D level and PF (Spearman's correlation coefficient t1: ADL r = 0.367, HGS r = 0.313; t2: ADL: r = 0.247; all p < 0.01) was observed. There was no correlation between changes in vitamin D levels over 1 year and changes in PF. Almost all NHR included in the study showed vitamin D deficiency. 25(OH)D levels were weakly correlated to PF at baseline and at follow-up, and an increase in vitamin D levels was not associated with positive effects on PF in this study.


Relation of a common variant of the adiponectin gene to serum adiponectin concentration and metabolic traits in an aged Japanese population.
Adiponectin is an adipocyte-derived protein that is down-regulated in obesity-linked disorders. Variants of the adiponectin gene (ADIPOQ) have been shown to affect adiponectin level. We have now examined the relation of polymorphisms of ADIPOQ to adiponectin concentration and to metabolic disorders in the Kita-Nagoya Genomic Epidemiology study, a population-based study of elderly Japanese. The genomic region including ADIPOQ was genotyped for 30 single nucleotide polymorphisms in 500 subjects of a screening population with the use of a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Four polymorphisms were then selected for genotyping in an additional 2797 subjects. Serum adiponectin level was negatively associated with metabolic abnormalities after adjustment for age and sex. The minor alleles of the rs1656930, Ile164Thr, and rs9882205 polymorphisms were associated with a low serum adiponectin level. Whereas the minor alleles of rs1656930 and rs9882205 were common (minor allele frequency of 6.2 and 38.5%, respectively), that of Ile164Thr was rare (0.9%). The minor allele of rs1656930 was positively associated with systolic blood pressure and the prevalence of hypertension. The association of rs1656930 with adiponectin level was replicated in an independent population. A subject with the 164Thr/Thr genotype had an extremely low serum adiponectin level (0.6 μg/ml) and the phenotype of metabolic syndrome. Our results suggest that a common variant of ADIPOQ, the minor allele of rs1656930, is associated with hypoadiponectinemia and hypertension. Screening for a common genetic background underlying low adiponectin levels might provide important information for assessment and management of metabolic disorders.


The Far Nasal Part of the Field of Vision - Part II. Contribution to the Timely Diagnosis of Glaucoma.
The aim of this study was to examine possible changes in the conventionally undiagnosed nasal visual field in patients diagnosed with early primary open angle glaucoma. Examination of the far nasal part of the visual field was performed in 30 patients (60 eyes) with early stage of primary open angle glaucoma (preperimetric stage of changes). The cohort consisted of 16 women (mean age 46.5 years) and 14 men (mean age 44.7 years). In all eyes, the glaucoma program (rapid threshold program of 50 degrees nasally and 22 degrees temporally) was performed with the Medmont M700 instrument to determine the physiological visual field. Visual acuity was 1.0 with a possible correction less than or equal to ±3 diopters and they had no other ocular defect except glaucoma disease. The visual field was subsequently examined with the same instrument by moving the fixation point 40 degrees temporally (spatially adaptive program) and simultaneously turning the head 10 degrees nasally. A total of 89 examination points were included using flicker stimuli and a range of 0-120 degrees nasally. The far nasal limit of the visual field reached 100° in 13.33% of eyes, 105° in 20% of eyes and up to 110° in 66.67% of eyes. In all eyes, depression of the distal periphery of the nasal part of the visual field was found to range from 50 to 95 degrees, with a normal visual field examined by the glaucoma program.


Fatal poorly differentiated angiosarcoma of the scalp.
Cutaneous angiosarcoma is a very rare but aggressive tumor. Angiosarcoma of the scalp is very rare, and a review of the world literature revealed less than 60 cases. Here, the author reports a case of poorly differentiated angiosarcoma of the scalp. The pathological diagnosis was very difficult. A 70-year-old Japanase man was admitted to our hospital complaining of red mass of the scalp. An excisional biopsy was done. The biopsy showed proliferation of malignant spindle cells in the dermis. Apparent differentiation was not recognized. Invasion into the lateral dermis and subcutis was recognized. There were many mitotic figures and a few foci of necrosis. The size was 2 x 2 x 3 cm. Intracytoplasmic vacuoles were recognized in the malignant tumor cells in some places. A few vague vasoformative features were recognized in one very small area. Immunohistochemically, the malignant spindle cells were positive for factor VIII-related antigen (F-VIII-RA), Ulex lectin, CD31, CD34, vimentin, p53 protein. The Ki-67 labeling was 76%. In contrast, the tumor cells were negative for cytokeratins, epithelial membrane antigen, desmin, S100 protein, alpha-smooth muscle antigen, bcl-2, melanosome, and myoglobin. The intracytoplasmic vacuoles were strongly positive for F-VIII-RA, Ulex lectin, CD31, and CD34, The abortive vasoformative channels were moderately positive for these endothelial markers. A pathologic diagnosis of angiosarcoma of the scalp was made. Chemoradiation and immunotherapy were performed. However, the tumor recurred several times, and ultimately metastasized to the systemic bones and lungs. The patient died of systemic carcinomatosis 33 months after the first manifestation.


Combined treatments of facial contour deformities resulting from Parry-Romberg syndrome.
Parry-Romberg syndrome is characterized by a progressive hemifacial atrophy involving the skin, subcutaneous tissue, and underlying bone structures. The aim of plastic surgical treatment is to restore a harmonious and symmetrical appearance to facial deficits. The authors report that 17 patients with Parry-Romberg syndrome were treated with combined techniques in multiple stages. Revascularized free flaps, including 12 anteriolateral thigh adipofascial flaps and two latissimus dorsi flaps, were used for soft tissue augmentations in the first stage. Additional procedures, including dermis grafting, lipoinjection, placement of Medpor implant, and plastic techniques, such as genioplasty, liposuction revision, and others, were used for bone augmentations or corrections of minor deficits in the second or third stage. Generally, it took an average of 3.5 procedures to obtain satisfying results. Postoperative courses were smooth in 15 patients except for two hematoma complications in two cases. Transferred tissues had partial fat liquefying and subcutaneous indurations 6 months postoperatively in two cases. All patients received good or improved aesthetic outcomes. Combined treatments are needed to correct facial contour deformities resulting from Parry-Romberg syndrome.


High-Intensity Events in International Women's Team Handball Matches.
International women's team handball is a physically demanding sport and is intermittent in nature. The aim of the study was to profile high-intensity events (HIEs) in international women's team handball matches with regard to playing positions. Twenty female national-team handball players were equipped with inertial movement units (OptimEye S5, Catapult Sports, Australia) in 9 official international matches. Players were categorized in 4 different playing positions: backs, wings, pivots, and goalkeepers (GKs). PlayerLoad™, accelerations (Acc), changes of direction (CoD), decelerations (Dec), and the sum of the latter 3, HIEs, were extracted from raw-data files using the manufacturer's software. All Acc, Dec, CoD, and HIEs >2.5 m/s were included. Data were log-transformed and differences were standardized for interpretation of magnitudes and reported with effect-size statistics. Mean numbers of events were 0.7 ± 0.4 Acc/min, 2.3 ± 0.9 Dec/min, and 1.0 ± 0.4 CoD/min. Substantial differences between playing positions, ranging from small to very large, were found in the 3 parameters. Backs showed a most likely greater frequency for HIE/min (5.0 ± 1.1 HIE/min) than all other playing positions. Differences between playing positions were also apparent in PlayerLoad/min. HIEs in international women's team handball are position specific, and the overall intensity depends on the positional role within a team. Specific HIE and intensity profiles from match play provide useful information for a better understanding of the overall game demands and for each playing position.


Identification and characterization of novel immunomodulatory bursal-derived pentapeptide-II (BPP-II).
The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement.


Insights on the functional dualism of nitric oxide in the hallmarks of cancer.
Nitric oxide (NO), a gaseous radical, governs a variety of physiological and pathological processes, including cancer, pro-inflammatory signalling, and vasodilation. The family of nitric oxide synthases (NOS), which comprises the constitutive forms, nNOS and eNOS, and the inducible form, iNOS, produces NO enzymatically. Additionally, NO can be generated non-enzymatically from the nitrate-nitrite-NO pathway. The anti- and pro-oxidant properties of NO and its functional dualism in cancer is due to its highly reactive nature. Numerous malignancies have NOS expression, which interferes with the tumour microenvironment to modulate the tumour's growth in both favourable and unfavourable ways. NO regulates a number of mechanisms in the tumour microenvironment, including metabolism, cell cycle, DNA repair, angiogenesis, and apoptosis/necrosis, depending on its concentration and spatiotemporal profile. This review focuses on the bi-modal impact of nitric oxide on the alteration of a few cancer hallmarks.


Improvement of L(+)-lactic acid production from cassava wastewater by Lactobacillus rhamnosus B 103.
L(+)-Lactic acid is used in the pharmaceutical, textile and food industries as well as in the synthesis of biodegradable plastics. The aim of this study was to investigate the effects of different medium components added in cassava wastewater for the production of L(+)-lactic acid by Lactobacillus rhamnosus B 103. The use of cassava wastewater (50 g L(-1) of reducing sugar) with Tween 80 and corn steep liquor, at concentrations (v/v) of 1.27 mL L(-1) and 65.4 mL L(-1) respectively led to a lactic acid concentration of 41.65 g L(-1) after 48 h of fermentation. The maximum lactic acid concentration produced in the reactor after 36 h of fermentation was 39.00 g L(-1) using the same medium, but the pH was controlled by addition of 10 mol L(-1) NaOH. The use of cassava wastewater for cultivation of L. rhamnosus is feasible, with a considerable production of lactic acid. Furthermore, it is an innovative proposal, as no references were found in the scientific literature on the use of this substrate for lactic acid production.


Gene expression and epigenetic responses of the marine Cladoceran, Evadne nordmanni, and the copepod, Acartia clausi, to elevated CO2.
Characterizing the capacity of marine organisms to adapt to climate change related drivers (e.g., pCO2 and temperature), and the possible rate of this adaptation, is required to assess their resilience (or lack thereof) to these drivers. Several studies have hypothesized that epigenetic markers such as DNA methylation, histone modifications and noncoding RNAs, act as drivers of adaptation in marine organisms, especially corals. However, this hypothesis has not been tested in zooplankton, a keystone organism in marine food webs. The objective of this study is to test the hypothesis that acute ocean acidification (OA) exposure alters DNA methylation in two zooplanktonic species-copepods (Acartia clausii) and cladocerans (Evadne nordmanii). We exposed these two species to near-future OA conditions (400 and 900 ppm pCO2) for 24 h and assessed transcriptional and DNA methylation patterns using RNA sequencing and Reduced Representation Bisulfite Sequencing (RRBS). OA exposure caused differential expression of genes associated with energy metabolism, cytoskeletal and extracellular matrix functions, hypoxia and one-carbon metabolism. Similarly, OA exposure also caused altered DNA methylation patterns in both species but the effect of these changes on gene expression and physiological effects remains to be determined. The results from this study form the basis for studies investigating the potential role of epigenetic mechanisms in OA induced phenotypic plasticity and/or adaptive responses in zooplanktonic organisms.


Mechanisms causing rapid and parallel losses of ribose catabolism in evolving populations of Escherichia coli B.
Twelve populations of Escherichia coli B all lost D-ribose catabolic function during 2,000 generations of evolution in glucose minimal medium. We sought to identify the population genetic processes and molecular genetic events that caused these rapid and parallel losses. Seven independent Rbs(-) mutants were isolated, and their competitive fitnesses were measured relative to that of their Rbs(+) progenitor. These Rbs(-) mutants were all about 1 to 2% more fit than the progenitor. A fluctuation test revealed an unusually high rate, about 5 x 10(-5) per cell generation, of mutation from Rbs(+) to Rbs(-), which contributed to rapid fixation. At the molecular level, the loss of ribose catabolic function involved the deletion of part or all of the ribose operon (rbs genes). The physical extent of the deletion varied between mutants, but each deletion was associated with an IS150 element located immediately upstream of the rbs operon. The deletions apparently involved transposition into various locations within the rbs operon; recombination between the new IS150 copy and the one upstream of the rbs operon then led to the deletion of the intervening sequence. To confirm that the beneficial fitness effect was caused by deletion of the rbs operon (and not some undetected mutation elsewhere), we used P1 transduction to restore the functional rbs operon to two Rbs(-) mutants, and we constructed another Rbs(-) strain by gene replacement with a deletion not involving IS150. All three of these new constructs confirmed that Rbs(-) mutants have a competitive advantage relative to their Rbs(+) counterparts in glucose minimal medium. The rapid and parallel evolutionary losses of ribose catabolic function thus involved both (i) an unusually high mutation rate, such that Rbs(-) mutants appeared repeatedly in all populations, and (ii) a selective advantage in glucose minimal medium that drove these mutants to fixation.


Changes of optical coherence tomographic hyperreflective foci in rhegmatogenous retinal detachment patients after successful surgery.
To assess the changes of hyperreflective foci (HRF) in rhegmatogenous retinal detachment (RRD) patients after successful reattachment surgery. Twenty-nine macula-off RRD eyes with successful reattachment surgery were retrospectively analyzed. Optical coherence tomography (OCT) was used to image macular regions and measure HRF in outer retina and inner retina at 0.5, 1, 3, 6, 12 months after surgery. The relationships between HRF and photoreceptor layer status, visual outcomes were evaluated. After retinal reattachment, HRF mainly distributed at the location where external limiting membrane (ELM) or inner and outer segment (IS/OS) line was disrupted. The HRF numbers in outer and inner retina were greater in eyes with discontinuous IS/OS line than eyes with continuous IS/OS line (all p<0.05). In the outer retina, HRF increased in the initial three months after retinal reattachment, and then decreased gradually after 3 months (p<0.05). The HRF number in the outer retina at postoperative 0.5 months was associated with favorable visual outcomes at 6 and 12 months (r=-0.487, p =0.025; r=-0.626, p=0.005, respectively), nevertheless, the HRF number at 3 months was correlated with poor visual results at 6 and 12 months (r=0.441, p =0.017; r=0.477, p=0.019, respectively). HRF mainly occurred near the site where ELM or IS/OS line was injured after retinal reattachment. In the outer retina, the number of HRF gradually increased in the first 3 months and then gradually decreased. The early appearance of HRF in the outer retina was associated with a good visual prognosis, while the late appearance may suggest a less favorable visual outcome.


Physical Activity- and Alcohol-dependent Association Between Air Pollution Exposure and Elevated Liver Enzyme Levels: An Elderly Panel Study.
The deleterious effects of air pollution on various health outcomes have been demonstrated. However, few studies have examined the effects of air pollution on liver enzyme levels. Blood samples were drawn up to three times between 2008 and 2010 from 545 elderly individuals who regularly visited a community welfare center in Seoul, Korea. Data regarding ambient air pollutants (particulate matter ≤2.5 μm [PM2.5], nitrogen dioxide [NO2], ozone [O3], carbon monoxide, and sulfur dioxide) from monitoring stations were used to estimate air pollution exposure. The effects of the air pollutants on the concentrations of three liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and γ-glutamyltranspeptidase [γ-GTP)]) were evaluated using generalized additive and linear mixed models. Interquartile range increases in the concentrations of the pollutants showed significant associations of PM2.5 with AST (3.0% increase, p=0.0052), ALT (3.2% increase, p=0.0313), and γ-GTP (5.0% increase, p=0.0051) levels; NO2 with AST (3.5% increase, p=0.0060) and ALT (3.8% increase, p=0.0179) levels; and O3 with γ-GTP (5.3% increase, p=0.0324) levels. Significant modification of these effects by exercise and alcohol consumption was found (p for interaction <0.05). The effects of air pollutants were greater in non-exercisers and heavy drinkers. Short-term exposure to air pollutants such as PM2.5, NO2, and O3 is associated with increased liver enzyme levels in the elderly. These adverse effects can be reduced by exercising regularly and abstinence from alcohol.


Endoscopic middle ear exploration in pediatric patients with conductive hearing loss.
To describe our indications, findings, and outcomes for transcanal endoscopic middle ear exploration in pediatric patients with conductive hearing loss of unknown etiology, without effusions. Prospective case series for all pediatric patients undergoing totally endoscopic transcanal middle ear exploration between April 2012 and October 2015 at a pediatric tertiary care referral hospital. Demographic data, operative findings, and hearing results were reviewed. 21 cases were performed in 20 ears (1 revision). Average age at surgery was 7.98 years and average follow up was 2.1 years. Middle ear pathology identified on CT imaging was confirmed in 55% of cases while identified in 45% of cases where pre-operative imaging was non-diagnostic. 6/20 patients (30%) had an ossicular deformity. 8/20(40%) had bony ossicular fixation. 5/20(25%) had ossicular discontinuity. 2/20(10%) had facial nerve dehiscence impinging on the stapes. 15% had adhesive myringosclerosis or severe granulation causing hearing loss. Prosthetic ossiculoplasty was done in 7/21 (33.3%) of the cases, with 1 TORP, 3 PORPs, and 3 IS joint replacements. Imaging was predictive of intra-operative findings in 13/20 cases (55%). Trainees assisted in 16/21(76%) of cases. The average improvement of PTA was 11.65 dB (range -10 to 36.25), and the average ABG improved 10.19 (range -11.25 to 28.75). There were no perioperative complications or adverse events. The endoscopic transcanal approach for middle ear exploration offers excellent visualization and is one of the best applications for the endoscopes in pediatric otology cases. This is particularly helpful for "unexplained" conductive hearing loss where ossicular deformity/fixation/discontinuity is suspected. The etiology of the conductive hearing loss was definitively found in 100% of cases, and can be repaired in the same sitting when applicable.


Are urologists fairly reimbursed for complex procedures: failure of 22 modifier?
The 22 modifier was designed to provide surgeons with additional reimbursement for performing complex procedures. We evaluated whether urologists at a tertiary referral center are reimbursed when using the 22 modifier. We evaluated the charts and billing data of all adult urology noncharity cases using the 22 modifier from January 2006 and September 2007. The 22 modifier was used in 317 of 7494 (4.2%) unique procedures performed. Of these 317 procedures, 99 (31%) were reimbursed at a greater rate than the contract level, with a mean increase greater than the contract of $388 (median $260, range $62-$3524), for a mean of 28% greater than the contract. Of the 317 cases, 114 were within $50 of the contract level and 104 were reimbursed at less than the contract level. Additionally, 56 cases were paid at the initial request and < or = 4 appeals were sent in 228 cases, with a successful result in 57 (25%). When analyzed by payor (n = 289), private insurance paid 81 of 187 (43.3%), Medicare paid 23 of 95 (24.2%), and Medicaid paid 1 of 7 (14.3%). Most payments took > 2 months to be paid. The reasons for using the 22 modifier code included extensive surgery, previous surgery, staghorn calculus, extended lymphadenectomy for bladder cancer, adhesions, difficult anatomy, complex dissection, morbid obesity, previous chemotherapy, scarring, previous radiotherapy, difficult debulking, and pregnancy. Of the 317 cases, > 121 had several confounding factors. The 22 modifier does not provide consistent reimbursement for urologists performing complex procedures. The long-term implications of financial disincentives to performing difficult surgeries need to be further evaluated.


Burden of Herpes Zoster in Individuals with Immunocompromised Conditions and Autoimmune Diseases in the Republic of Korea: A Nationwide Population-Based Database Study.
To estimate herpes zoster (HZ) incidence rate (IR) and economic burden in individuals with immunocompromised conditions and autoimmune diseases (IC/AID) in the Republic of Korea (ROK). The nationwide Health Insurance Review and Assessment Service database was used to identify HZ cases from 2016 to 2020 in ROK. HZ and non-HZ IC/AID cases were matched 1:3 using age, sex, institution, Charlson comorbidity index, IC/AID, and index date. Annual HZ IRs/1000 persons and 1-year HZ-associated all-cause direct medical costs for IC/AID cases were calculated. Among 65,976 individuals with IC/AID (mean age 57.14 years [standard deviation 14.1]; 64.94% female), annual HZ IR (95% confidence interval) fluctuated from 2016 to 2020, averaging 23.41/1000 persons (22.21-24.62) and was higher in women (26.85 [25.40-28.31]) than men (18.96 [18.03-19.89]). IRs were highest in individuals aged ≥ 50 years, and in those with transplants (including solid organ and hematopoietic stem cell transplants; 37.12 [35.45-38.79]) and hemato-oncology conditions (35.5 [31.6-39.3]). Mean 12-month all-cause direct medical costs were higher in individuals with IC/AID and HZ (4,759,671 Korean Republic won [KRW]; approximately 4046 United States dollar [USD; according to the 2020 conversion rate from UNCTAD; 1 KRW = 0.00085 USD]) than those without HZ (3,786,658 KRW; 3219 USD). Individuals with IC/AID have a substantial disease and economic burden from HZ in ROK, highlighting the need for appropriate HZ prevention measures in the IC/AID population.


A review of advance care planning programs in long-term care homes: are they dementia friendly?
Background. Persons living with dementia in the long-term care home (LTCH) setting have a number of unique needs, including those related to planning for their futures. It is therefore important to understand the advance care planning (ACP) programs that have been developed and their impact in order for LTCH settings to select a program that best suits residents' needs. Methods. Four electronic databases were searched from 1990 to 2013, for studies that evaluated the impact of advance care planning programs implemented in the LTCH setting. Studies were critically reviewed according to rigour, impact, and the consideration of the values of residents with dementia and their family members according to the Dementia Policy Lens Toolkit. Results and Conclusion. Six ACP programs were included in the review, five of which could be considered more "dementia friendly." The programs indicated a variety of positive impacts in the planning and provision of end-of-life care for residents and their family members, most notably, increased ACP discussion and documentation. In moving forward, it will be important to evaluate the incorporation of residents with dementia's values when designing or implementing ACP interventions in the LTCH settings.