[Morphometrical and immunohistochemical analysis of cortical and medullary thymoma: its correlation with invasiveness and association with myasthenia gravis].
Forty-seven thymomas were histologically classified to 28 cases of cortical type, 13 cases of medullary type, and 6 cases of mixed type. They were analyzed morphometrically and immuno-histochemically, and the results were examined with their invasiveness and association with myasthenia gravis (MG). Thirty-seven resected thymic tissues were used as controls. Cortical thymomas were more often invasive ones and associated with MG than the medullary type, with significant difference. Epithelial cell nuclei of the cortical thymomas were significantly larger than those of the medullary ones. Epithelial cell nuclei of cortical and medullary thymomas were significantly larger than those of thymic cortex and medulla, respectively. Morphometrical results showed that the cortical thymomas were more malignant than the medullary ones. Immunohistochemically, all cases of thymomas were positive for Leu7 and keratin, but stainability of them were variable among each subtype. In thymic tissues epithelial cells in outer cortex were positive for Leu7 and keratin, whereas those in inner cortex and medulla were negative for Leu7 and positive for keratin.


Glucose uptake and glycogen synthesis in muscles from immobilized limbs.
The purposes of this study were to determine whether the defects in glucose metabolism in muscles of immobilized limbs of mice were related to alterations in insulin binding, insulin responsiveness, glucose supply, and insulin activation of glycogen synthase. These were tested by in vitro methodology. A significant lessening in the insulin-induced maximal response of 2-deoxyglucose uptake into the mouse soleus muscle occurred between the 3rd and 8th h of limb immobilization, suggesting a decreased insulin responsiveness. Lack of change in the specific binding of insulin to muscles of 24-h immobilized limbs indicates that a change in insulin receptor number did not play a role in the failure of insulin to stimulate glucose metabolism. It's inability to stimulate glycogen synthesis in muscle from immobilized limbs is due, in part, to a lack of glucose supply to glycogen synthesis and also to the ineffectiveness of insulin to increase the percentage of glycogen synthase in its active form in muscles from 24-h immobilized limbs.


Diffuse left ventricular hypokinesis in cardiogenic shock--its cause or consequence?
Five patients in cardiogenic shock due to acute myocardial infarction were examined by two-dimensional echocardiography. In one patient, cardiogenic shock developed only after rupture of the interventricular septum, four subjects had "primary" cardiogenic shock. In these four persons there were found extensive disturbances of left ventricular wall motion (the mean extent of the akinetic or dyskinetic zone amounted to 41% of the left ventricle (LV). However, equally extensive (and even larger) disturbances of LV kinetics were found in another 11 patients with acute MI, in whom there did not develop cardiogenic shock. The basic difference between the two groups consisted in the fact that in patients in cardiogenic shock the remaining part of the left ventricle exhibited severe hypokinesis, whereas in other infarcts it was normokinetic or hyperkinetic. Autopsy findings in all patients revealed severe diffuse involvement of all coronary arteries. In the discussion, it is pointed out that the above-mentioned phenomenon (hypokinesis of the "intact" part of the left ventricle) may be both one of the causes of shock as well as merely its consequence.


The Spectrum of Genetic Testing.
To introduce genetic testing as it relates to oncology and nursing. Peer-reviewed journals, government web sites and resources, published recommendations, and professional experience as a genetic counselor. Genetic testing is a major component of oncology health care and with the continued expansion of the application of genetic testing, many patients will have genetic testing throughout their cancer journey. To provide supportive care for patients with cancer or at risk for cancer, oncology nurses need to appreciate the many and varied genetic testing platforms and testing strategies. Oncology nurses can be a resource for patients and family members regarding testing options, insurance coverage, and understanding medical management decisions.


Chemical-Fuel-Driven Assembly in Macromolecular Science: Recent Advances and Challenges.
In the past decade, chemical-fuel-driven processes have been integrated with synthetic self-assembled systems, in which both the formation and properties can be carefully controlled. This strategy can drive systems far away from equilibrium, tailor the lifetime window of transient self-assembled systems, thus holding promise for future smart, adaptive, self-regulated, and life-like systems. By judging whether the building blocks or transient self-assembled systems participate in the fuel-to-waste conversion, the reported systems can be divided into two classes: dissipative self-assembly and self-assembly under dissipative conditions. Among these systems, the utilization of macromolecular building blocks to design non-equilibrium self-assemblied systems is becoming common. Macromolecular systems capable of dissipating energy with a programmed time domain have found widespread application, and have therefore been an active field of scientific inquiry. This Minireview aims to highlight the recent progress and opportunities of chemical-fuel-driven assembly in macromolecules. We envision that chemical-fuel-driven approach will play an increasingly important role in polymer science in the near future.


Are Canadian women achieving a fit pregnancy? A pilot study.
Canadian recommendations exist for energy intake (EI), physical activity (PA) and gestational weight gain (GWG) to help pregnant women avoid excessive GWG and attain "fit pregnancies". Our objectives were: 1) to measure daily EI, PA and GWG to observe whether pregnant women were meeting recommendations, 2) to explore the impact of health care provider advice on PA and GWG, and 3) to determine behaviours associated with recommended weekly GWG. Women (n = 81) were recruited from prenatal classes. Current weight and self-reported pre-pregnancy weight were documented. Current PA levels and provider advice for PA and GWG were surveyed using questionnaires. Dietary recalls and pedometer steps were recorded for three and seven days respectively. The majority of our women were classified as having average pre-pregnancy body mass indices (BMI) of 23.3 +/- 4 kg/m2, average EI of 2237 kcal/d and energy expenditure (EE) of 2328 kcal/d, but with weekly rates of GWG in excess of current recommendations despite having received advice about GWG (74%) and PA (73%). Most were classified as sedentary (< 5000 steps/day (d)) and 36% as low active (< 7500 steps/d). Women were most likely to achieve appropriate GWG if their total PA was > 8.5 MET-hr/wk. Health care providers need to provide appropriate PA and GWG guidelines to pregnant women. Development of pregnancy step and MET-hr/wk recommendations are warranted in order to promote greater PA during pregnancy.


Mitomycin C and vinblastine in anthracycline-resistant metastatic breast cancer: a phase II study.
The purpose of this phase II study was to evaluate the clinical efficacy of mitomycin C and vinblastine in patients with anthracycline-resistant metastatic breast cancer. This single-center, non-randomized trial enrolled 39 patients. Eligible patients must have received at least three chemotherapy regimens with epirubicin or CAF and had treatment failure while on chemotherapy or within 6 months of completing therapy. Treatment consisted of mitomycin C at a starting dose of 8 mg/m2 on day 1 and vinblastine (8 mg/m2, days 1 and 28). The regimen was repeated every 6 weeks with a 20% dose escalation of both drugs after the first cycle in the absence of grade III hematologic or other toxicity. On an intent-to-treat basis, 38 patients were eligible for assessment; 9 (23.7%, 95% confidence interval 1.92-2.45%) achieved a partial response and 13 (34.2%) had stable disease. The median time to disease progression was 6.21+/-4.26 months (range, 1-15; 95% confidence interval, 4.81-7.61), and the median survival was 10.76+/-7.6 (range, 1-29; 95% confidence interval 8.0-13.1%). Responsive patients had a significantly better survival than those with stable and progressive disease. Treatment was well tolerated. Anemia and neutropenia (grade I-III) developed in 28.9% and 26.3% of the patients, respectively. One patient with grade III granulocytopenia developed fever and infection that required hospitalization. Moderate neurotoxicity, myalgia, constipation, diarrhea and alopecia were observed. No toxic death occurred. Mitomycin C plus vinblastine is an effective and well-tolerated regimen for anthracycline resistant cancer.


Atypical Melissococcus plutonius strains: their characteristics, virulence, epidemiology, and mysteries.
Melissococcus plutonius is a Gram-positive lanceolate coccus that is the causative agent of European foulbrood, an important bacterial disease of honey bee brood. Although this bacterium was originally described in the early 20th century, a culture method for this bacterium was not established until more than 40 years after its discovery due to its fastidious characteristics, including the requirement for high potassium and anaerobic/microaerophilic conditions. These characteristics were considered to be common to the majority of M. plutonius strains isolated worldwide, and M. plutonius was also thought to be genetically homologous or clonal for years. However, non-fastidious variants of this species (designated as atypical M. plutonius) were very recently identified in Japan. Although the morphology of these unusual strains was similar to that of traditionally well-known M. plutonius strains, atypical strains were genetically very different from most of the M. plutonius strains previously isolated and were highly virulent to individual bee larva. These atypical variants were initially considered to be unique to Japan, but were subsequently found worldwide; however, the frequency of isolation varied from country to country. The background of the discovery of atypical M. plutonius in Japan and current knowledge on atypical strains, including their biochemical and culture characteristics, virulence, detection methods, and global distribution, are described in this review. Remaining mysteries related to atypical M. plutonius and directions for future research are also discussed.


Cerebellar hemorrhage after spinal surgery: report of two cases and literature review.
Cerebellar hemorrhage remote from the site of surgery may complicate neurosurgical procedures. We describe our experience with two cases of cerebellar hemorrhage after spinal surgery and review the three cases previously reported in the literature to determine whether these cases provide insight regarding the pathogenesis of remote cerebellar hemorrhage. One of our patients developed cerebellar hemorrhage in the vermis and right hemisphere after transpedicular removal of a partially intradural T9-T10 herniated disc with the patient in the prone position. The other patient developed cerebellar hemorrhage in the vermis and bilateral hemispheres after L3-S1 decompression and instrumentation with the patient in the prone position, during which the dura was inadvertently opened. The first patient was treated conservatively and had mild residual dysarthria and gait ataxia 2 months after surgery. The second patient underwent exploration and revision of the lumbar wound with primary dural repair. The cerebellar hemorrhage was treated conservatively, and the patient had mild dysarthria and ataxia 1 month after surgery. Cerebellar hemorrhage must be considered in patients with unexplained neurological deterioration after spinal surgery. Dural opening with loss of cerebrospinal fluid has occurred in every reported case of cerebellar hemorrhage complicating a spinal procedure, supporting the hypothesis that loss of cerebrospinal fluid is central to the pathogenesis of this condition. Because remote cerebellar hemorrhage can occur after procedures with the patient in the supine, sitting, and prone positions, patient positioning seems unlikely to play a causative role in its occurrence.


Role of Toll-like receptors in pathogen recognition.
The innate immune system relies on a vast array of non-clonally expressed pattern recognition receptors for the detection of pathogens. Pattern recognition receptors bind conserved molecular structures shared by large groups of pathogens, termed pathogen-associated molecular patterns. The Toll-like receptors (TLRs) are a recently discovered family of pattern recognition receptors which show homology with the Drosophila Toll protein and the human interleukin-1 receptor family. Engagement of different TLRs can induce overlapping yet distinct patterns of gene expression that contribute to an inflammatory response. The TLR family is characterized by the presence of leucine-rich repeats and a Toll/interleukin-1 receptor-like domain, which mediate ligand binding and interaction with intracellular signaling proteins, respectively. Most TLR ligands identified so far are conserved microbial products which signal the presence of an infection, but evidence for some endogenous ligands that might signal other danger conditions has also been obtained. Molecular mechanisms for pathogen-associated molecular pattern recognition still remain elusive but seem to be more complicated than initially anticipated. In most cases, direct binding of microbial ligands to TLRs still has to be demonstrated. Moreover, Drosophila TLRs bind endogenous ligands, generated through a proteolytic cascade in response to an infection. In the case of endotoxin, recognition involves a complex of TLR4 and a number of other proteins. Moreover, TLR heterodimerization further extends the spectrum of ligands and modulates the response towards specific ligands. The fact that TLR expression is regulated in both a cell type- and stimulus-dependent fashion further contributes to the complexity.


Giardia infection in Auckland and New Zealand: trends and international comparison.
To describe the epidemiological pattern of Giardia infection in the Auckland region and compare it with national and international patterns of Giardia infection. Anonymised giardiasis notification data from the Auckland District Health Board for the period July 1996 to June 2000 were analysed by person, place and time. Infection rates and relative risks were calculated and compared with national and international information. Auckland had a significantly higher rate of Giardia infection than New Zealand as a whole. Infection rates, which peaked during February-May, were significantly higher in Pakeha/Europeans and Asian/others, compared with Maori/Pacificans. Adjusted notification rates were higher for residents of North Shore and Auckland cities than for other areas of Auckland. The crude regional and national notification rates were almost six times the rate of laboratory identification of positive isolates in the UK and four times US reported rates. The higher rates of giardiasis observed in Auckland and New Zealand, in comparison with other developed countries, may be related to environmental or social factors. Missing ethnicity information precludes clear interpretation of variations in notification rate by ethnic group and suggests a need for improvement in data collection. There are opportunities to investigate the influence of risk factors on seasonal changes in notification rates both locally and nationally.


Expression of melanocortin-5 receptor in secretory epithelia supports a functional role in exocrine and endocrine glands.
Melanocortins (alphaMSH and ACTH-related peptides) influence the physiological functions of certain peripheral organs, including exocrine and endocrine glands. This study was designed to determine the identity and anatomical localization of the melanocortin receptors (MC-R) expressed in these organs in the rat. MC5-R messenger RNA was found in exocrine glands, including lacrimal, Harderian, preputial, and prostate glands and pancreas, as well as in adrenal gland, esophagus, and thymus, as demonstrated by ribonuclease protection assays. In exocrine glands, MC5-R messenger RNA expression was restricted to secretory epithelia. MC-R protein was likewise present in secretory epithelia of exocrine glands, as determined by 125I-labeled [Nle4,D-Phe7]alphaMSH ([125I]NDP-MSH) binding and autoradiography in tissue sections. Specific [125I]NDP-MSH binding was also observed in adrenal cortex, thymus, spleen, and esophageal and trachealis muscle. MC receptors in these sites are accessible to circulating MC-R agonists in vivo, as specific binding of [125I]NDP-MSH was observed in exocrine and adrenal glands after systemic injection in vivo. Taken together, these findings show that the MC5 receptor is commonly and selectively expressed in exocrine glands and other peripheral organs. Based on these findings and compelling evidence from other studies, a functional coherence is suggested between central and peripheral actions of melanocortins and melanocortin receptors in physiological functions, including thermoregulation, immunomodulation, and sexual behavior.


Insertion of an immunodominant T helper cell epitope within the Group A Streptococcus M protein promotes an IFN-γ-dependent shift from a non-protective to a protective immune response.
The common pathogen Group A Streptococcus (GAS, Streptococcus pyogenes) is an extracellular bacterium that is associated with a multitude of infectious syndromes spanning a wide range of severity. The surface-exposed M protein is a major GAS virulence factor that is also target for protective antibody responses. In this study, we use a murine immunization model to investigate aspects of the cellular and molecular foundation for protective adaptive immune responses generated against GAS. We show that a wild type M1 GAS strain induces a non-protective antibody response, while an isogenic strain carrying the immunodominant 2W T helper cell epitope within the M protein elicits an immune response that is protective against the parental non-recombinant M1 GAS strain. Although the two strains induce total anti-GAS IgG levels of similar magnitude, only the 2W-carrying strain promotes elevated titers of the complement-fixing IgG2c subclass. Protection is dependent on IFN-γ, and IFN-γ-deficient mice show a specific reduction in IgG2c levels. Our findings suggest that inclusion of the 2W T cell epitope in the M protein confers essential qualitative alterations in the adaptive immune response against GAS, and that sparsity in IFN-γ-promoting Th cell epitopes in the M protein may constitute an immune evasion mechanism, evolved to allow the pathogen to avoid attack by complement-fixing antibodies.


An audit of patients investigated by Hysterosalpingo-Contrast-Sonography (HyCoSy) for infertility.
We reviewed 171 case notes of patients investigated by HyCoSy for sub-fertility in South Manchester University Hospital to assess HyCoSy as a screening test for tubal occlusion, in low risk infertile women and to evaluate the performance of HyCoSy in our unit by confirming its results with the results of laparoscopy & dye test in those patients who had both procedures. We also assessed the prognostic significance of HyCoSy, for fertility outcome over a follow-up period ranging from 12 to 63 months. An audit proforma was designed to collect data on maternal age, type of infertility (primary or secondary), duration of infertility and parity. History suggestive of ovulatory factors (PCO), pelvic inflammatory disease and endometriosis was noted. Findings of standard trans-vaginal scan, hysterosalpingography and HyCoSy were recorded. In total 333 tubes were examined in 171 patients. There were 121/171 diagnoses of bilateral patent tubes, 24/171 bilateral blocked tubes and 26/171 findings of one patent tube. In 15 (8.8%) women, laparoscopy and dye test was performed after HyCoSy and 19 patients had laparoscopy and dye test before HyCoSy. The findings in both investigations were similar. 70 additional uterine and adnexal pathologies were detected. Out of 171 40.9% (n=70) women conceived, 62 of these women had both tubes patent and 8 had one patent tube. In conclusion we have found that HyCoSy is a valuable cost effective screening test for low risk couples. Its results in our hands are as good as demonstrated by other studies. HyCoSy can be offered as a screening test for low risk infertile women as it is an effective alternative for laparoscopy and dye test.


Adding carotid total plaque area to the Framingham risk score improves cardiovascular risk classification.
Cardiovascular events (CE) due to atherosclerosis are preventable. Identification of high-risk patients helps to focus resources on those most likely to benefit from expensive therapy. Atherosclerosis is not considered for patient risk categorization, even though a fraction of CE are predicted by Framingham risk factors. Our objective was to assess the incremental value of combining total plaque area (TPA) with the Framingham risk score (FramSc) using post-test probability (Ptp) in order to categorize risk in patients without CE and identify those at high risk and requiring intensive treatment. A descriptive cross-sectional study was performed in the primary care setting in an Argentine population aged 22-90 years without CE. Both FramSc based on body mass index and Ptp-TPA were employed in 2035 patients for risk stratification and the resulting reclassification was compared. Total plaque area was measured with a high-resolution duplex ultrasound scanner. 57% male, 35% hypertensive, 27% hypercholesterolemia, 14% diabetes. 20.1% were low, 28.5% moderate, and 51.5% high risk. When patients were reclassified, 36% of them changed status; 24.1% migrated to a higher and 13.6% to a lower risk level (κ index = 0.360, SE κ = 0.16, p < 0.05, FramSc vs. Ptp-TPA). With this reclassification, 19.3% were low, 18.9% moderate and 61.8% high risk. Quantification of Ptp-TPA leads to higher risk estimation than FramSc, suggesting that Ptp-TPA may be more sensitive than FramSc as a screening tool. If our observation is confirmed with a prospective study, this reclassification would improve the long-term benefits related to CE prevention.


Narrating positive versus negative memories of illness: does narrating influence the emotional tone of memories?
Psychoncological studies have recognised a reduced autobiographical memory in cancer patients, furthermore cognitive studies have found that narrative is an effective instrument to re-elaborate memories. However, it is still unclear whether narrating positive versus negative events can have a different impact on autobiographical memory. The present study aims to explore the emotional experience of autobiographical memory before and after having narrated negative or positive events related to the illness. Of 63 oncological patients, 35 were selected for the present study. Participants completed a Memory Fluency Task twice, before and after having selected and narrated a positive (PN group) or a negative (NN group) memory of illness. They also had to attribute one or more emotions to each memory and to the narrative. The number of emotions and the percentage of emotional tones in both narrated and non-narrated memories were assessed. Narrated memories were more emotionally re-elaborated than non-narrated ones. Negative group participants, more than positive group ones, decreased negative emotions and increased complex ones. Authors discuss these results claiming that narrating works as a rehearsal of autobiographical memories in oncological patients and narrating negative memories eases the emotional re-elaboration of illness.


Protein CutA undergoes an unusual transfer into the secretory pathway and affects the folding, oligomerization, and secretion of acetylcholinesterase.
The mammalian protein CutA was first discovered in a search for the membrane anchor of mammalian brain acetylcholinesterase (AChE). It was co-purified with AChE, but it is distinct from the real transmembrane anchor protein, PRiMA. CutA is a ubiquitous trimeric protein, homologous to the bacterial CutA1 protein that belongs to an operon involved in resistance to divalent ions ("copper tolerance A"). The function of this protein in plants and animals is unknown, and several hypotheses concerning its subcellular localization have been proposed. We analyzed the expression and the subcellular localization of mouse CutA variants, starting at three in-frame ATG codons, in transfected COS cells. We show that CutA produces 20-kDa (H) and 15-kDa (L) components. The H component is transferred into the secretory pathway and secreted, without cleavage of a signal peptide, whereas the L component is mostly cytosolic. We show that expression of the longer CutA variant reduces the level of AChE, that this effect depends on the AChE C-terminal peptides, and probably results from misfolding. Surprisingly, CutA increased the secretion of a mutant possessing a KDEL motif at its C terminus; it also increased the formation of AChE homotetramers. We found no evidence for a direct interaction between CutA and AChE. The longer CutA variant seems to affect the processing and trafficking of secretory proteins, whereas the shorter one may have a distinct function in the cytoplasm.


Lymphotoxin production by subsets of T cells.
Lymphotoxin is produced by T cells sensitized to antigen upon re-exposure in vitro. It is also elicited by mitogen treatment. Its production has been correlated with delayed-type hypersensitivity and it may be a mediator of that phenomenon. We have examined the Ly phenotype of the subset(s) of T cells that produce lymphotoxin in order to investigate the relationship of lymphotokin killing to allo-killing mediated by Ly2+ T cells. We have found that Ly1 T cells sensitized to ovalbumin secrete more lymphotoxin than Ly2 cells. The ovalbumin-sensitized T cells do not lyse their target in a short term 51Cr-release assay even when "glued" to the target with Con A. Thus, lymphotoxin-producing cells differ phenotypically from the previously defined cytotoxic T cells that bear the Ly2 differentiation marker.


Homeobox genes in mouse development.
Following the discovery of the homeobox as a conserved sequence in developmentally important genes of Drosophila, a plethora of such sequences have been identified in evolutionarily distant organisms. Among mammals, the mouse homeobox genes have been studied most intensively with a hope of deciphering basic mechanisms of embryonic development. The genomic arrangement of many mouse homeobox genes is similar to the organization of the Drosophila genes, suggesting that they arose as a consequence of gene duplication and divergence from a primordial cluster during evolution. Homeobox genes encode proteins that may form a part of the autoregulatory and transregulatory network specifying positional value in the embryo. Supporting this view, the more diverged members of this growing family function as transcription factors, some of which regulate the expression of tissue-specific genes. Mouse homeobox genes are expressed during embryonic development in a spatially restricted manner and alterations in their expression pattern can disrupt embryonic development. The implications of these findings will be discussed in the context of the role of homeobox genes in the embryonic development of Drosophila and other organisms.


Cardiac arrest as a major complication of bilateral cervico-dorsal sympathectomy.
Severe palmar and/or axillary hyperhidrosis can be socially and psychologically very disturbing. We present a case of a patient who suffered from a 43 s asystolic cardiac arrest the night following a second contralateral thoracoscopic T(2)-T(3) sympathectomy for severe axillary and truncal hyperhidrosis. The cardiovascular effects of cervico-dorsal sympathectomy will be reviewed. Evaluation required to prevent such a serious cardiac complication will also be discussed.


Oscillatory synchrony between head direction cells recorded bilaterally in the anterodorsal thalamic nuclei.
The head direction (HD) circuit is a complex interconnected network of brain regions ranging from the brain stem to the cortex. Recent work found that HD cells corecorded ipsilaterally in the anterodorsal nucleus (ADN) of the thalamus displayed coordinated firing patterns. A high-frequency oscillation pattern (130-160 Hz) was visible in the cross-correlograms of these HD cell pairs. Spectral analysis further found that the power of this oscillation was greatest at 0 ms and decreased at greater lags, and demonstrated that there was greater synchrony between HD cells with similar preferred firing directions. Here, we demonstrate that the same high-frequency synchrony exists in HD cell pairs recorded contralaterally from one another in the bilateral ADN. When we examined the cross-correlograms of HD cells that were corecorded bilaterally, we observed the same high-frequency (~150- to 200-Hz) oscillatory relationship. The strength of this synchrony was similar to the synchrony seen in ipsilateral HD cell pairs, and the degree of synchrony in each cross-correlogram was dependent on the difference in tuning between the two cells. Additionally, the frequency rate of this oscillation appeared to be independent of the firing rates of the two cross-correlated cells. Taken together, these results imply that the left and right thalamic HD network are functionally related despite an absence of direct anatomical projections. However, anatomical tracing has found that each of the lateral mammillary nuclei (LMN) project bilaterally to both of the ADN, suggesting the LMN may be responsible for the functional connectivity observed between the two ADN.NEW & NOTEWORTHY This study used bilateral recording electrodes to examine whether head direction cells recorded simultaneously in both the left and right thalamus show coordinated firing. Cross-correlations of the cells' spike trains revealed a high-frequency oscillatory pattern similar to that seen in cross-correlations between pairs of ipsilateral head direction cells, demonstrating that the bilateral thalamic head direction signals may be part of a single unified network.


Outcome of phacoemulsification in previously vitrectomized myopic eyes with axial length greater than 26 mm.
To determine the outcome, including the intraoperative and postoperative complications, of phacoemulsification with intraocular lens (IOL) implantation in myopic eyes with axial length of 26 mm or more that had undergone previous pars plana vitrectomy (PPV). This prospective study comprised 37 highly myopic eyes (axial length over 26 mm) with previous vitrectomy that underwent phacoemulsification and were reviewed at a mean postoperative follow-up of 3-6 weeks. The main outcome measures were preoperative and postoperative spherical equivalent, preoperative and postoperative visual acuity, difference between intended and achieved refraction, and any complications during cataract surgery. The mean age for cataract surgery was 61.5 years. Nuclear sclerosis was present in 91.89% of patients. The mean axial length was 27.53 mm (range 26.03-30.52 mm). The most common indication for vitrectomy in our study was retinal detachment surgery (35 out of 37). Postoperatively, 34 patients (91.89%) had a visual acuity improvement of 2 or more Snellen lines and the best-corrected visual acuity at final refraction was 6/9 (0.2 logMAR) or better in 30 patients (81.08%). Two patients had perioperative complications (5.4%). Cataract surgery with IOL implantation can be performed safely in highly myopic eyes after PPV and the final visual acuity outcomes appear to be dependent on the preoperative status of the retina. Our study suggests that the incidence of intraoperative and postoperative complications can be reduced to a minimum with proper planning and meticulous attention to detail during cataract surgery.


Non-Alcoholic Fatty Liver Disease.
Non-alcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic and it is the most common cause of liver diseases. The development of hepatic steatosis in majority of patients is linked to dietary fat ingestion. NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol, fatty acyl CoA or ceramides. Lipotoxicity-related mechanism of NAFLD could be explained still best by the "double-hit" hypothesis. Insulin resistance is the major mechanism in the development and progression of NAFLD/Non-alcoholic steatohepatitis (NASH). Metabolic oxidative stress, autophagy, and inflammation induce NASH progression. In the "first hit" the hepatic concentrations of diacylglycerol increase with rising saturated liver fat content in human NAFLD. Activities of mitochondrial respiratory chain complexes are decreased in liver tissue of patients with NASH. Furthermore, hepatocyte lipoapoptosis is a critical feature of NASH. In "second hit" reduced glutathione levels due to oxidative stress lead to overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling that induces cell death in the steatotic liver. Accumulation of toxic levels of reactive oxygen species (ROS) is caused by the ineffectual cycling of the endoplasmic reticulum (ER) oxidoreductin (Ero1)-protein disulfide isomerase oxidation cycle through the downstream of the inner membrane mitochondrial oxidative metabolism and Kelch like-ECH-associated protein 1 (Keap1)- Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway.


Multiple imaging findings in SAPHO syndrome.
SAPHO syndrome is an acronym for a clinical entity characterized by synovitis, acne, palmoplantar pustulosis, hyperostosis, and osteitis. The association of sterile inflammatory bone lesions and neutrophilic skin eruptions is indicative of this syndrome, even though not all components always coexist. We report a case of a 62-year-old female presenting with a lytic manubrial lesion. Diagnoses of metastasis or infection were initially entertained but excluded on open biopsy, and SAPHO syndrome was confirmed on additional investigation and follow-up. Striking imaging findings included intense uptake on bone scintigraphy, photopenia on white blood cell imaging, and dramatically elevated lumbar spine bone density on dual energy x-ray absorptiometry (DXA).


Evidence-based medicine designed to save physicians time, energy, FPS told.
Although not all physicians welcome the current move toward evidence-based medicine, Dr. Warren McIsaac, a member of the Institute for Clinical Evaluative Sciences in Ontario, says it is designed to save them time and energy. He made the comments during a meeting of family physicians in Ontario.


Nuclear magnetic resonance and molecular modeling analysis of the interaction of the antimalarial drugs artelinic acid and artesunic acid with beta-cyclodextrin.
The artemisinin derivatives artelinic acid and artesunic acid are members of a class of compounds that have shown promise for the treatment of multidrug resistant strains of Plasmodium falciparum. Unfortunately, these compounds exhibit poor solubility and stability in aqueous solution. The research presented herein was conducted to determine whether complexation of artelinic acid or artesunic acid with beta-cyclodextrin would result in complexes with increased aqueous solubility while retaining the potent antimalarial activity of these compounds. Preliminary complexation studies with natural beta-cyclodextrins were conducted as a proof of concept, with a primary focus on understanding the electrostatic interactions that stabilize the resulting complexes. Complex formation was monitored using UV spectroscopy. The structures of the resulting complexes were determined using multidimensional nuclear magnetic resonance spectroscopy (NMR) and molecular modeling. NMR results are most consistent for artelinic acid and beta-cyclodextrin forming complexes in a ratio of 2:1; however, the presence of 1:1, 2:2, and 3:1 complexes in solution cannot be excluded based on the experimental data collected. The NMR data also indicate selective insertion of artelinic acid into the hydrophobic cavity of the beta-cyclodextrin via the primary face. NMR results indicate artesunic acid forms a similar complex with beta-cyclodextrin in a ratio of 1:1; again however, the presence of 1:1, 2:2, and 3:1 complexes in solution cannot be ruled out.


Delayed-onset posttraumatic stress disorder: a prospective evaluation.
Delayed onset posttraumatic stress disorder (PTSD) refers to PTSD that develops at least 6 months after the traumatic event. This study aimed to index the features of patients who develop delayed-onset PTSD. This study investigated delayed onset PTSD by prospectively assessing 103 motor vehicle accident survivors within 1 month of the motor vehicle accident for acute stress disorder, and subsequently assessing them for PTSD 6 months post-accident, and 2 years post-accident. Patients were initially assessed for symptoms of traumatic stress, anxiety, depression, and resting heart rate. Five patients displayed PTSD 2 years post-trauma without meeting PTSD criteria 6 months posttrauma. Delayed onset cases were characterized by elevated psycho-pathology scores and resting heart rate levels within the initial month and elevated psychopathology 6 months posttrauma. These findings suggest that cases of delayed onset PTSD suffer subsyndromal levels of posttraumatic stress prior to the diagnosis of PTSD. These findings challenge the notion of PTSD developing after a period without symptoms.


Frequency of ABO blood groups and RhD factor in the female population of District Peshawar.
To determine the frequency of ABO blood group and Rhesus (Rh) D antigen in the females of "District" Peshawar, Khyber Pakhtunkhwa Province, Pakistan. This cross-sectional study was conducted on 429 women having pregnancy induced hypertension, admitted in the three teaching hospitals of Peshawar, over a period of one year. Blood sample was collected from each subject after taking informed consent. The antigen antibody agglutination slide test for "blood grouping (ABO)" and RhD factors was done by using IgM and IgG monoclonal reagents. The antisera used were from Biolaboratory, USA. Data was analyzed for percentage calculation. The blood group distribution was 134 (31.2%), 43 (10.1%), 116 (27%), 136 (31.7%) for blood groups A, AB, O and B, respectively. Subjects having blood group B was slightly more dominant, followed by A and O, while blood group AB was rare in these females. Blood group A Rh negative is more in female 12 (37.5%) followed by group O 10 (31.3%), group B 09 (28.1%) and group AB 01 (3.1%). Frequency of "Rh-positive blood group" is B, A, O and AB, whereas the frequency of the most common Rh-negative blood group are A, O, B and AB respectively. The determination of the frequency of blood groups in the region would not only help in blood transfusion services, but also reduce the risk of erythroblastosis foetalis in the neonates.


Effect of organic amendments on the retention and mobility of imazaquin in soils.
The influence of two organic amendments consisting of an urban waste compost (SUW) and a commercial amendment from olive mill wastes (OW) was assessed on the sorption properties and leaching of the ionizable herbicide imazaquin on four soils with different physicochemical characteristics. A loamy sand soil (CR), a loam soil (P44), a silt loam soil (AL), and a clay soil (TM), with low-medium organic matter contents, were chosen. Sorption-desorption experiments were performed on the original soils and on a mixture of these soils with the organic amendments at a rate of 6.25% (w/w). These mixtures were used just after preparation and after aging for 3 months. Imazaquin adsorption was higher on AL soil because of its high content of amorphous iron oxides, whereas it was related to the soils' organic matter (OM) contents on TM and CR soils and to acid pH on P44 soil. Addition of exogenous OM to soils caused a decrease in the adsorption of the herbicide with the only exception of CR soil, due to blocking of adsorptive surfaces and/or equilibrium pH rise. The extent of this decrease was dependent only on the nature of the added amendment on AL soil. The adsorbed amounts of imazaquin on aged organic fertilized soils were usually fairly close to that on original soils. Results of soil column experiments indicate that addition of exogenous organic matter cannot be considered as a regular practice for retarded movement of imazaquin.


[Treatment of typical trigeminus neuralgias. Overview of the current state of drug and surgical therapy].
Carbamazepine continues to be the most useful drug in the treatment of trigeminal neuralgia. Diphenylhydantoin may be given in addition to or instead of Carbamazepine. Refractory cases may benefit from combination with Baclofen or Chlorphenesin. In cases of persistent pain the concomitant use of tricyclic antidepressant drugs is recommended. If pain continues in spite of multiple medical therapies or if serious side effects develop, then surgical procedures such as percutaneous controlled thermocoagulation or microvascular decompression are indicated. Percutaneous thermocoagulation is associated with the lowest mortality and morbidity rate and can easily be repeated. Microvascular decompression should especially be offered to young patients, who want to avoid any sensory disturbance of the face, and recommended for other patients for whom all other forms of therapy including percutaneous thermocoagulation have failed.


Advances and Breakthroughs in IRES-Directed Translation and Replication of Picornaviruses.
Viruses lack the properties to replicate independently due to the limited resources encoded in their genome; therefore, they hijack the host cell machinery to replicate and survive. Picornaviruses get the prerequisite for effective protein synthesis through specific sequences known as internal ribosome entry sites (IRESs). In the past 2 decades, significant progress has been made in identifying different types of IRESs in picornaviruses. This review will discuss the past and current findings related to the five different types of IRESs and various internal ribosome entry site trans-acting factors (ITAFs) that either promote or suppress picornavirus translation and replication. Some IRESs are inefficient and thus require ITAFs. To achieve their full efficiency, they recruit various ITAFs, which enable them to translate more effectively and efficiently, except type IV IRES, which does not require any ITAFs. Although there are two kinds of ITAFs, one promotes viral IRES-dependent translation, and the second type restricts. Picornaviruses IRESs are classified into five types based on their use of sequence, ITAFs, and initiation factors. Some ITAFs regulate IRES activity by localizing to the viral replication factories in the cytoplasm. Also, some drugs, chemicals, and herbal extracts also regulate viral IRES-dependent translation and replication. Altogether, this review will elaborate on our understanding of the past and recent advancements in the IRES-dependent translation and replication of picornaviruses. IMPORTANCE The family Picornaviridae is divided into 68 genera and 158 species. The viruses belonging to this family range from public health importance, such as poliovirus, enterovirus A71, and hepatitis A virus, to animal viruses of great economic importance, such as foot-and-mouth disease virus. The genomes of picornaviruses contain 5' untranslated regions (5' UTRs), which possess crucial and highly structured stem-loops known as IRESs. IRES assemble the ribosomes and facilitate the cap-independent translation. Virus-host interaction is a hot spot for researchers, which warrants deep insight into understanding viral pathogenesis better and discovering new tools and ways for viral restriction to improve human and animal health. The cap-independent translation in the majority of picornaviruses is modulated by ITAFs, which bind to various IRES regions to initiate the translation. The discoveries of ITAFs substantially contributed to understanding viral replication behavior and enhanced our knowledge about virus-host interaction more effectively than ever before. This review discussed the various types of IRESs found in Picornaviridae, past and present discoveries regarding ITAFs, and their mechanism of action. The herbal extracts, drugs, and chemicals, which indicated their importance in controlling viruses, were also summarized. In addition, we discussed the movement of ITAFs from the nucleus to viral replication factories. We believe this review will stimulate researchers to search for more novel ITAFs, drugs, herbal extracts, and chemicals, enhancing the understanding of virus-host interaction.


Human genetic factors in tuberculosis: an update.
Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB.


[PART-KESSLER TECHNIQUE WITH SUTURE ANCHOR IN REPAIR OF SPONTANEOUS Achilles TENDON RUPTURE].
To summarize the application and experience of repairing spontaneous Achilles tendon rupture by part-Kessler technique with suture anchor. Between January 2011 and December 2013, 31 patients with spontaneous Achilles tendon rupture were treated by part-Kessler technique with suture anchor. Of 31 cases, 23 were male and 8 were female, aged 16-53 years (mean, 38 years). The left side was involved in 15 cases and the right side in 16 cases. The causes of injury included sudden heel pain and walking weakness during sports in 22 cases; no surefooted down-stairs, slip, and carrying heavy loads in 9 cases. The distance from broken site to the calcaneus adhension of Achilles tendon was 3-6 cm (mean, 4.2 cm). The time from injury to operation was 7 hours to 4 days (mean, 36.8 hours). All incisions healed by first intention without nerve injury or adhering with skin. The patients were followed up 6-24 months (mean, 15 months). All patients could complete 25 times heel raising without difficulty at 6 months after operation. No Achilles tendon rupture occurred again during follow-up. At 6 months after operation, the range of motion of the ankle joint in dorsiflexion and plantar flexion showed no significant difference between normal and affected sides (t=0.648, P=0.525; t=0.524, P=0.605). The circumference of the affected leg was significantly smaller than that of normal leg at 6 months after operation (t=2.074, P=0.041), but no significant difference was found between affected and normal sides at 12 months after operation (t=0.905, P=0.426). The American Orthopedic Foot and Ankle Society (AOFAS) scores at 6, 12, 18, and 24 months after operation were significantly higher than preoperative score (P<0.05); the score at 6 months after operation was significantly lower than that at other time points (P<0.05), but no significant difference was shown between the other time points (P>0.05). Repairing spontaneous Achilles tendon rupture by part-Kessler technique with suture anchor can supply strong strain and decrease the shear forces of suture. So part-Kessler technique with suture anchor is successful in repairing spontaneous Achilles tendon rupture.


Effects of low-dose radiation on tumor growth, erythrocyte immune function and SOD activity in tumor-bearing mice.
Activating on mammalian and human body LDR is thought to induce adaptive response, enhance immune function and increase anti-tumor ability. This study was designed to assess the effect of low-dose radiation on tumor growth and on erythrocyte immune function and superoxide dismutase (SOD) activity in tumor-bearing mice. Male Kunming mice were subcutaneously implanted with S180 sarcoma cells in the right inguen to create an experimental in situ animal model. Six hours before implantation, the mice were given 75 mGy X-ray radiation, over the body. Tumor size was observed 5 days later while tumor volume was calculated every other day, allowing for the creation of a graph depicting tumor growth. Fifteen days after implantation, the mice were killed to measure tumor weight and observe the necrotic areas and the location of tumor-infiltrating lymphocytes (TILs). Erythrocyte immune function and SOD activity were also determined. Mice pre-exposed to low-dose radiation had a lower tumor formation rate than did those receiving no radiation (P < 0.05). Tumor growth was significantly lower in the mice pre-exposed to low-dose radiation; after 15 days, the average tumor weight in the mice pre-exposed to low-dose radiation was also lower (P < 0.05). Areas of tumor necrosis and infiltration of TILs were larger in the low-dose radiation group than in the non-radiation group. Erythrocyte immune function and SOD activity were higher in the low-dose radiation group than in the non-radiation group (P < 0.05). Low-dose radiation can markedly increase the anti-tumor ability of an organism and improve erythrocyte immune function and red blood cell SOD activity as well, suggesting that low-dose radiation might be useful in the clinical treatment of cancer.


Use of different primer directed sequence amplification by polymerase chain reaction for identification of Pneumocystis jirovecii in clinical samples.
Pneumocystis carinii pneumonia (PCP), caused by opportunistic agent Pneumocystis jirovecii (formerly, Pneumocystis carinii is one of the most serious respiratory infection in immunocompromised patients. The present study was conducted to compare polymerase chain reaction (PCR) assays targetting three different genes of Pneumocystis to study their application in its diagnosis. One hundred and eighty (n = 180) clinical samples from 145 immunocompromised patients with clinical suspicion of PCP and 35 samples from control group of 30 immunocompetent individuals with respiratory infections other than PCP were prospectively examined for the presence of Pneumocystis jirovecii (P. jirovecii). All the samples were subjected to microscopic examination, one single [major surface glycoprotein, (MSG)] and two nested [mitochondrial large subunit ribosomal ribonucelic acid, (mtLSU rRNA) and internal transcribed spacer (ITS) region], polymerase chain reaction assays. Microscopic examination was positive in only six (n = 6) patients, whereas single round MSG PCR detected P. jirovecii deoxyribonucleic acid (DNA) in 16 cases. When the clinical samples were tested by mtLSU rRNA and ITS nested PCR assays, it was possible to detect seven additional cases of PCP, making it to a total of 23 cases. None of the clinical specimens in control group (n = 30) were positive by any of the above-mentioned techniques. Amongst the 81 bronchoalveolar lavage (BAL) samples tested, 16 were positive by MSG PCR, while 20 were positive by both nested, i.e., mtLSU rRNA and ITS PCR assays. Similarly, out of 50 sputum samples, only three were positive by MSG, seven by mtLSU rRNA and six by ITS nested PCR assays. It has been observed that MSG is relatively more sensitive when single round PCR assay is used for detection of human Pneumocystosis compared to the first (single) rounds of either ITS or mtLSU rRNA nested PCRs. However, the two nested PCRs using ITS and mtLSU rRNA have been found to be more sensitive. On comparison of two nested PCR assays, the results have been more or less comparable.


Expression of CR2 (the C3dg/EBV receptor, CD21) on normal human peripheral blood T lymphocytes.
The expression of CR2 (the C3dg/EBV receptor, CD21) on normal human T lymphocytes was investigated using purified peripheral blood T cells and indirect immunofluorescence with biotinylated anti-CR2 mAb and streptavidin-phycoerythrin. Thirty to 40% of normal peripheral blood T lymphocytes expressed CR2 Ag. The cells expressed three nonoverlapping epitopes of CR2. The specificity of the staining for CR2 epitopes was demonstrated by the ability of unlabeled anti-CR2 mAb but not of anti-CR1 mAb of the same isotype to compete for the binding of biotinylated anti-CR2 mAb to T cells. The intensity of staining of T lymphocytes with anti-CR2 mAb was approximately 10-fold lower than that of peripheral blood B cells. CR2 was immunoprecipitated from purified T lymphocytes as a single protein of apparent Mr 145,000. The presence of CR2 on normal human T lymphocytes suggests that the receptor may modulate the function of T cells in the immune response and the susceptibility of the cells to infection by lymphocytotropic viruses.


Intentional Closing/Opening of "Hole-in-Cube" Fullerene Crystals with Microscopic Recognition Properties.
We report production of highly crystalline fullerene C70 cubes possessing an open-hole structure at the center of each of their faces using a solution-based self-assembly strategy. The holes are isolated with a solid core at the interiors of the cubes. The open-hole structure of the cubes can be intentionally closed by introducing additional C70 and reopened by applying electron beam irradiation. The open-hole cubes exhibit preferential recognition of graphitic carbon particles over polymeric resin particles of similar dimensions due to the cubes' sp2-rich carboniferous nature.


[Evaluation of the immediate transfusion reaction incident reporting system at the Brest University Hospital Center].
The Haemovigilance Unit of Brest University Hospital has had a reporting system of transfusion reactions since october 1994. Reporting "any unexpected or undesirable effect due or likely to be due to the administering of blood cell components" must be done on an answering machine immediately or in the next eight hours. The main goal of the evaluation of this epidemiological surveillance system was to assess its sensitivity, its positive predictive value, its acceptability, its timeliness and its simplicity, according to the Centers for Disease Control criteria. An exhaustive monitoring of the immediate transfusion reactions (ITR) occurring within the 24 hours following the procedure was conducted from April 1, to June 30, 1998. Two sources of information were used, the spontaneous notification to the Haemovigilance Unit using the answering machine, and a telephone survey of the nurse responsible for the transfusion or post-transfusion follow-up. During the survey, 19 ITR, among which 12 were reported to the Haemovigilance Unit on the answering machine, were recorded. The incidence rate of the I.T.R. was estimated at 5@1000 transfused blood cell components. The sensitivity of the notification system was estimated at 63% (95% confidence interval: 41-85) and the positive predictive value at 70% (95% confidence interval: 48-92). This notification system is operational. The function of sanitary alert is ensured at the primary level of the system surveillance. The undernotification of the ITR (37% of false negative) must be corrected by specific recommendations.


Metabolic and kinematic effects of self-selected Q Factor during bike fit.
Correct bicycle fit is important, and kinematic instability must be addressed to reduce the risk of knee injury. A change in Q Factor (horizontal distance between crank arms) has been shown to decrease metabolic cost. The combined effect upon gross mechanical efficiency (GME) and knee variability is unclear, however; there is no known simple method to predict self-selected Q Factor (SSQ). The SSQ was hypothesized to provide the greatest GME and least variability at the knee. Ten trained cyclists completed bouts of submaximal cycling at a range of Q Factors. The effectiveness of hanging and stepping tasks as predictors of SSQ was also tested. Measured SSQ (142 mm) provided the best combination of GME and knee stability compared with other Q Factors, and could be accurately predicted using a simple hanging task. The SSQ has the potential to lower the risk of knee injury and provide increased efficiency whilst cycling.


Pyogenic liver abscess with two normal ultrasound scans.
I report a case of a large liver abscess causing a severe debilitating condition in which the diagnosis was delayed by several weeks following two normal ultrasound scans at days 5 and 19 of the illness. Up to one in four cases of liver abscess can be missed on ultrasound. A high degree of clinical suspicion must be maintained and repeated or alternative imaging methods used if the diagnosis of this rare, curable but often fatal condition is not to be missed.


Capacity of Pneumococci to Activate Macrophage Nuclear Factor κB: Influence on Necroptosis and Pneumonia Severity.
During pneumococcal pneumonia, antibacterial defense requires the orchestrated expression of innate immunity mediators, initiated by alveolar macrophages and dependent on transcription driven by nuclear factor κB (NF-κB). Such immune pressure may select for pneumococci, which avoid or subvert macrophage NF-κB activation. Analyzing pneumococci collected from children in Massachusetts, we found that the activation of macrophage NF-κB by Streptococcus pneumoniae is highly diverse, with a preponderance of low NF-κB activators that associate particularly with complicated pneumonia. Low NF-κB activators cause more severe lung infections in mice, and they drive macrophages toward an alternate and detrimental cell fate of necroptosis. Both outcomes can be reversed by activation of macrophages with pneumococci that are high NF-κB activators. These results suggest that low NF-κB activation is a virulence property of pneumococci and that the appropriate activation of macrophages, including NF-κB, may hold promise as an adjunct therapeutic avenue for pneumococcal pneumonia.


A Severe Case of Cutaneous Adverse Drug Reaction Secondary to a Novice Drug: Idelalisib.
Phosphatidylinositol 3-kinase δ (PIK3δ) is a tyrosine kinase essential for B cell survival, making it an important target in the treatment of chronic lymphocytic leukemia. Idelalisib is an inhibitor of PIK3δ demonstrating initial success in disease response, but is now shown to have a decreased overall survival and life-threatening serious adverse events. The following is an unfortunate case of a grade III adverse skin reaction secondary to idelalisib with the likely complication of methicillin-resistant Staphylococcus aureus bacteremia.


Postoperative Medial Cuneiform Position Correlation With Patient-Reported Outcomes Following Cotton Osteotomy for Reconstruction of the Stage II Adult-Acquired Flatfoot Deformity.
Residual supination of the midfoot during reconstruction of the stage II adult-acquired flatfoot deformity (AAFD) is often addressed with a medial cuneiform (Cotton) osteotomy after adequate correction of the hindfoot valgus deformity. The purpose of this study was to determine if there was a correlation between postoperative alignment of the medial cuneiform and patient-reported outcomes. Sixty-three feet in 61 patients with stage II AAFD who underwent a Cotton osteotomy as part of a flatfoot reconstruction were included in the study. Radiographic angles were measured on weightbearing lateral radiographs at a minimum of 40 weeks postoperatively. Pearson's correlation analysis was used to determine if there was an association between postoperative radiographic angles and Foot and Ankle Outcome Score (FAOS) at a minimum of 24 months postoperatively. Patients were also divided into mild plantarflexion (cuneiform articular angle [CAA] ≥-2 degrees) and moderate plantarflexion (CAA <-2 degrees) groups to evaluate for differences in clinical outcomes. Postoperative CAA was significantly positively correlated with the postoperative FAOS symptoms ( r = .27, P = .03), daily activities ( r = .29, P = .02), sports activities ( r = .26, P = .048), and quality of life ( r = .28, P = .02) subscales. Patients in the mild plantarflexion group had statistically and clinically better outcomes compared with the moderate plantarflexion group in the FAOS symptoms ( P = .04), daily activities ( P = .04), and sports activities ( P = .01) subscales. Our study suggests that the surgeon should avoid excessive plantarflexion of the medial cuneiform and use the Cotton osteotomy judiciously as part of a flatfoot reconstruction for stage II AAFD. Level III, comparative series.


Synthesis and Biological Activity of New 4-tert-Butylcyclohexanone Derivatives.
In the synthesis performed in this study, derivatives of 4-tert-butylcyclohexanone 1 were obtained using typical reactions of organic synthesis. The bioactivity of the selected compounds was evaluated. 1-(Bromomethyl)-8-tert-butyl-2-oxaspiro[4.5]decan-3-one (5) was characterized by attractant properties against larvae and a weak feeding deterrent activity against adults of Alphitobius diaperinus Panzer. This bromolactone was a moderate antifeedant towards Myzus persicae Sulzer. In addition, ethyl (4-tert-butylcyclohexylidene)acetate (2) and bromolactone 5 displayed antibacterial activity. The strongest bacteriostatic effect was observed against Gram-positive strains: Bacillus subtilis and Staphylococcus aureus. The bromolactone 5 also limited the growth of Escherichia coli strain.


[Intracerebral radiation-induced cavernous angiomas].
We present four cases of cerebral cavernous angioma that developed after radiatherapy for brain tumor in three cases and for cavernous angioma in one case. The time interval between irradiation and the detection of the cavernous angioma varied from three to nine years and the doses from 24 to 60 Grays. Brain hemorrhage appeared in two cases. Explanation for the formation of cavernous malformations is unclear but is probably related to proliferation and dilatation of the vascular endothelium with formation of capillary telangiectasis with evolution to cavernous angiomas. The pediatric brain appears particularly vulnerable to radiation injury. The risk of hemorrhage appears higher than with spontaneous cavernous malformations.


GB virus C/hepatitis G virus infection in dialysis patients and kidney transplant recipients in Central Brazil.
In order to investigate the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) infection in dialysis patients and kidney transplant recipients in Central Brazil and also to analyze the virus genotypes distribution, a total of 123 patients including 98 on hemodialysis, 13 on continuous ambulatory peritoneal dialysis treatment, and 12 who received kidney transplantation were interviewed in one unit of dialysis treatment in Goiania city. Blood samples were collected and serum samples tested for GBV-C/HGV RNA by polymerase chain reaction. Genotypes were determined by restriction fragment length polymorphism (RFLP) analysis. Eighteen samples were GBV-C/HGV RNA-positive, resulting in an overall prevalence of 14.6% (95% CI: 9.2-21.7). A high positivity for GBV-C/HGV RNA was observed in patients who had received kidney transplant (16.7%), followed by those on hemodialysis (15.3%), and peritoneal dialysis (7.7%). RFLP analysis revealed the presence of genotypes 1, 2, and 3 of GBV-C/HGV; more precisely, 9 (50%) samples were found belonging to the 2b subtype, 4 (22%) to the 2a subtype, 3 (17%) to genotype 1, and 2 (11%) to genotype 3. The present data indicate an intermediate prevalence of GBV-C/HGV infection among dialysis patients and kidney transplant recipients in Central Brazil. Genotype 2 (subtype 2b) seems to be the most prevalent GBV-C/HGV genotype in our region.


Conventional versus accelerated collagen cross-linking for keratoconus.
: Collagen cross-linking (CXL) is a procedure that primarily aims to increase corneal stiffness. Although used for a variety of conditions, it is most commonly applied to the treatment of keratoconus. Collagen cross-linking involves irradiation of the cornea with ultraviolet A (UVA) irradiation after it has been soaked with riboflavin (vitamin B), a photosensitizer. In conventional treatment, based on the Dresden protocol, a minimum corneal thickness threshold of 400 μm is recommended and UVA (370 nm) irradiation of 3 mW/cm irradiance is applied for 30 min, resulting in a cumulative dose of 5.4 J/cm. Evidence presented in this review shows that conventional CXL stabilizes the vision and corneal topographic parameters in the majority of treated patients, with only a small failure rate. It has a good safety profile with no endothelial cell loss and a small risk of corneal infiltration and infection. To reduce the treatment duration, accelerated protocols of similar efficacy have been sought. In accelerated protocols, UVA irradiation of higher irradiance, typically 9 mW/cm, is applied for a shorter time, typically 10 min. The evidence, limited to small studies with short follow-up, shows that they may also stabilize the vision and the ectasia, with no additional safety concerns highlighted. Randomized controlled studies are, however, required to confirm the encouraging results and noninferiority to conventional treatment.


Ethics, empathy, and gender in health care.
The changes that have taken place in medicine over the past few decades have challenged our views about the responsibilities and obligations of those providing health care and about their relationships with their patients. The demands brought by technologic advances and economic concerns have tested our ability to practice humane, empathic, and ethical medicine. This paper addresses the connection between ethics and empathy in the context of our current health care system. The author reviews the concept of empathy and argues that ethical medicine is empathic medicine. Since gender differences in health care needs and disparities in treatment have been identified, gender serves to focus some of the issues and exemplify some concerns about empathic and ethical practice.


Optimising verbal fluency analysis in neurological patients with dysarthria: examples from Parkinson's disease and hereditary ataxia.
Verbal fluency tests (VFTs) are widely used to assess cognitive-linguistic performance in neurological diseases. However, the influence of dysarthria on performance in tests requiring oral responses is unclear in ataxia and Parkinson's disease. To determine the impact of dysarthria on VFT performance and evaluate the validity and reliability of alternative methods for analyzing VFT data. Trained raters evaluated dysarthria using VFT recordings in people with ataxia (N = 61) or Parkinson's disease (PD; N = 69). Total Correct Items scores and qualitative parameters (intrusions, ambiguous verbalizations, perseverations, and interjections) were compared across semantic, phonemic, and alternating fluency tasks. Disease severity was considered as a covariate in the regression model. VFT dysarthria ratings correlated with the benchmark (ground truth) dysarthria scores derived from a monologue. Ambiguous responses resulting from unclear speech impeded the rater's ability to determine if a response was correct. Regression analysis indicated that more severe dysarthria ratings predicted diminished scores in all three tasks (semantic fluency, phonemic fluency and alternating fluency) in the ataxia group. The contribution of disease severity to semantic, phonemic and alternating fluency was reduced substantially in the ataxia group after accounting for dysarthria severity in the model in both groups. Dysarthria severity can be estimated based on speech samples derived from VFT. Dysarthria can lead to lower total correct items and is associated with more ambiguous verbalizations in VFT. Dysarthria severity should be considered when interpreting VFT performance in common movement disorders.


Preparation and characterization of light-switchable polymer networks attached to solid substrates.
Surface-attached polymer networks that carry light-responsive nitrospiropyran groups in a hydrophilic PDMAA matrix were prepared on planar silicon and glass surfaces and were characterized with respect to their switching behavior under the influence of an external light trigger. Functional polymers bearing light-responsive units as well as photo-cross-linkable benzophenone groups were first synthesized using free radical copolymerization. The number of spiropyran groups in the copolymer was controlled by adjusting the concentration of the respective monomer in the copolymerization feed. The polymer films were prepared by spin-coating the functional polymers from solution and by ultraviolet light (UV)-induced cross-linking utilizing benzophenone photochemistry. On substrates with immobilized benzophenone groups, the complete polymer network is linked to the surface. The dry thickness of the films can be controlled over a wide range from a few nanometers up to more than 1 μm. The integration of such light-switchable organic moieties into a surface-attached polymer network allows one to increase the overall number of light-responsive groups per surface area by adjusting the amount of surface-attached polymer networks. The spiropyran's function in dry (solvent-free) and swollen polymer films can be reversibly switched by UV and visible irradiation. In addition, the switching in water is faster than in the dry state. Therefore, implementing light-responsive spiropyran functions in polymer films linked to solid surfaces could allow for switching of the chemical and optical surface properties in a fast and spatially controlled fashion.


Mentoring Top Leadership Promotes Organizational Innovativeness through Psychological Safety and Is Moderated by Cognitive Adaptability.
Mentoring continues to build momentum among startups and established enterprises due to its positive impact on individuals and organizations. Unlike previous studies, this research focuses on mentoring higher level leadership, such as the CEO, and demonstrates its unique relationship to organizational innovativeness. Our sample included 200 mentored executives and entrepreneurs who personally identify and exploit opportunities. Our findings confirm that mentoring top leaders positively relates to their perceived innovativeness of the organization and that the relationship is mediated by these leaders' perception of psychological safety within the organization. Our findings also confirm that the relationship is negatively moderated by these leaders' cognitive adaptability. The reliability and validity of the results have been proved by using confirmatory factor analysis and advanced regression analytics. As a result, this work demonstrates the value of mentoring top leadership and advocates the importance of establishing a psychologically safe environment to inspire not only top leadership to try new avenues but also for all those within the organization to speak up and speak out. Additionally, our findings encourage organizations to proactively and selectively prioritize mentoring among top leadership, taking into account their differing levels of cognitive adaptability. Finally, further research could focus on how to provide greater support for mentors of higher level leaders.


[Effect of RNAi-mediated STAT3 gene inhibition on metastasis of human pancreatic cancer cells].
To investigate the effect of RNAi-mediated STAT3 gene inhibition on metastasis of human pancreatic cancer cells and its underlying mechanism. STAT3 shRNA expression vector was constructed and transfected into SW1990 cells. STAT3 mRNA and STAT3 DNA-binding activity were examined using reverse transcription polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA), respectively. The metastasis ability of SW1990 cells in vivo was determined in acute hematogenous metastasis model using nude mice. RT-PCR was performed to detect the mRNA expression of the MMP-2 and VEGF. The mRNA expression of STAT3 and STAT3 DNA-binding activity were inhibited significantly by stable transfection of STAT3 shRNA expressing vectors. RNAi inhibition of STAT3 significantly suppressed the metastasis ability of SW1990 cells in vivo, and also markedly reduced the mRNA expression of MMP-2 and VEGF in SW1990 cells. Inhibition of STAT3 by RNAi significantly inhibits the metastasis ability of pancreatic cancer cells through down-regulation of MMP-2 and VEGF, and may provide a novel strategy for preventing the metastasis of pancreatic cancer.


Human nasal blood vessels after permanent tracheostomy. Electron-microscopic study.
Biopsy specimens from the inferior turbimate of 13 permanently tracheostomized patients were examined by the electron microscope. Variations from the normal were recorded, as proliferation of capillaries, venous congestion and arteriolar contraction. The relation of shunting air away to these changes is discussed.


Aphasia and accent in identifying medical sentences.
The objective of this quasi-experimental pilot study was to assess the effect that the presence of aphasia in participants and the presence of an accent in speakers had on the accurate identification of 30 medical sentences. 20 participants, 10 with aphasia and 10 age- and sex-matched adults without aphasia, pointed to printed medical sentences matching utterances produced in English by native and nonnative English speakers. Analysis showed participants with aphasia had significantly lower identification scores than participants without aphasia. Across speakers' languages, scores for sentences produced by the native English speaker were significantly higher than scores for the nonnative English speakers. No interaction effects occurred. Investigations should continue to explore the effect of acquired language disorders on the understanding of accented speech.


In-plane heterostructures of Sb/Bi with high carrier mobility.
In-plane two-dimensional (2D) heterostructures have been attracting public attention due to their distinctive properties. However, the pristine materials that can form in-plane heterostructures are reported only for graphene, hexagonal BN, transition-metal dichalcogenides. It will be of great significance to explore more suitable 2D materials for constructing such ingenious heterostructures. Here, we demonstrate two types of novel seamless in-plane heterostructures combined by pristine Sb and Bi monolayers by means of first-principle approach based on density functional theory. Our results indicate that external strain can serve as an effective strategy for bandgap engineering, and the transition from semiconductor to metal occurs when a compressive strain of -8% is applied. In addition, the designed heterostructures possess direct band gaps with high carrier mobility (∼4000 cm2 V-1 s-1). And the mobility of electrons and holes have huge disparity along the direction perpendicular to the interface of Sb/Bi in-plane heterostructures. It is favorable for carriers to separate spatially. Finally, we find that the band edge positions of Sb/Bi in-plane heterostructures can meet the reduction potential of hydrogen generation in photocatalysis. Our results not only offer alternative materials to construct versatile in-plane heterostructures, but also highlight the applications of 2D in-plane heterostructures in diverse nanodevices and photocatalysis.


Metabolic syndrome and the risk for recurrent pre-eclampsia: a retrospective cohort study.
To compare the prevalence of recurrent pre-eclampsia between women who have and do not have metabolic syndrome when non-pregnant. Retrospective cohort study. Three tertiary referral hospitals in the Netherlands. Formerly pre-eclamptic women. The presence or absence of metabolic syndrome was assessed in 480 women at least 6 months after their first pre-eclamptic pregnancy using World Health Organization criteria. We compared the prevalence of recurrent pre-eclampsia in the subsequent pregnancy, calculating odds ratios (OR), adjusted for confounders. Recurrence of pre-eclampsia in the subsequent pregnancy. Subsequent pregnancy outcome data were available for 197 women. Forty women had metabolic syndrome after previous pregnancy (20%). The prevalence of recurrent pre-eclampsia was 18/40 (45%) in women with metabolic syndrome versus 27/157 (17%) in women without metabolic syndrome; OR 3.94 (95% confidence interval [CI] 1.86-8.33, adjusted OR 3.77 (95% CI 1.61-8.81). The risk of recurrent pre-eclampsia increased with each extra component of the metabolic syndrome from 11.8% for absent components up to 43.9% for three or more (P for trend < 0.001). Interpregnancy metabolic syndrome predisposes to recurrent pre-eclampsia.


Endotoxin causes neutrophil-independent oxidative stress in rats.
Endotoxin-induced oxidative stress is investigated in rats by measuring changes in plasma and lung tissue levels of glutathione disulfide (GSSG) using a modified enzymatic assay that allows simultaneous measurement of up to 80 samples. Salmonella enteritidis endotoxin (2 and 20 mg/kg) acutely increased both plasma reduced glutathione and GSSG with a rise in the ratio of GSSG to total glutathione. This increase in GSSG was enhanced by pretreatment with 1,3-bis(2-chloroethyl)1-nitrosourea (BCNU), an inhibitor of the glutathione reductase enzyme. However, there was no significant arteriovenous difference in plasma GSSG across the lung, and lung tissue GSSG did not increase after endotoxin treatment. The increase in plasma GSSG was not blocked by vinblastine-induced neutropenia and could not be reproduced by incubating rat blood in vitro with endotoxin. Receptor antagonists of platelet-activating factor (PAF), at a dose that previously inhibited endotoxin-induced lung injury, attenuated the endotoxin-induced increase in plasma GSSG. We conclude that endotoxin causes neutrophil-independent oxidative stress in rats, which may be enhanced by the action of platelet-activating factor.


Identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse hepatocyte growth factor gene.
Hepatocyte growth factor (HGF), a cytokine with multiple functions, exhibits cell-type-specific as well as cytokine- and steroid hormone-regulated expression. The HGF gene is known to be expressed predominately in mesenchymal but not in epithelial cells. In this study, we report the identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse HGF gene, which is evidently responsible for the suppression of HGF expression in epithelial cells. Gel mobility shift assays and DNase I footprinting studies revealed that a 27-bp element (-16 to +11) around the transcription initiation site is responsible for the binding of a nuclear protein which is present in epithelial but not in mesenchymally derived cells. Further analysis of the binding activity of the DNA region with nuclear protein revealed that an approximately 19-bp sequence containing a unique palindromic structure (5'-AACCGACCGGTT-3') overlapped by a CAP box is essential for binding. Substitution of a single base (the contact site) within this region by site-directed mutagenesis resulted in total abrogation of the binding of the nuclear protein and a concomitant increase in the transcriptional activity of various lengths of HGF-chloramphenicol acetyltransferase fused genes when transfected into the epithelial cell line RL95-2 but not the mesenchymal cell line NIH 3T3. Southwestern (DNA-protein) analyses revealed that the nuclear protein which binds to this repressor element is a single polypeptide of approximately 70 kDa. Analysis of the nuclear extract prepared from regenerating mouse liver at various times after two-thirds partial hepatectomy by gel mobility shift assay revealed a substantial reduction (more than 75% within 3 h) in the binding of the repressor to its cognate binding site. Our results suggest that a cis-acting transcriptional repressor in the promoter region of the mouse HGF gene is involved in cell-type-specific regulation through binding to its cognate trans-acting protein which exists in epithelial cells but is absent in fibroblast cells.


Activation of liver X receptors and retinoid X receptors induces growth arrest and apoptosis in insulin-secreting cells.
Liver X receptors (LXRs) form functional heterodimers with the retinoid X receptors (RXRs) and regulate cholesterol, lipid, and glucose metabolism. We demonstrated previously that activation of LXR modulates insulin secretion in MIN6 cells and pancreatic islets. In this study we investigated the effects of the LXR agonist T0901317 and the RXR agonist 9-cis-retinoic acid (9cRA) on cell proliferation and apoptosis in MIN6 cells. Whereas T0901317 showed no effect on proliferation of MIN6 cells, combination of T0901317 with 9cRA inhibited cell proliferation. Flow cytometry analysis of cell cycle demonstrated that activation of LXR/RXR prevented MIN6 cells from G1 to G2 phase progression. Combination of T0901317 and 9cRA increased apoptosis rate and caspase-3/7 activity in MIN6 cells. Moreover, T0901317 or its combination with 9cRA significantly increased the cell susceptibility to free fatty acid- and cytokine-induced apoptosis. Treatment of MIN6 cells with LXR and RXR agonists produced a strong increase in expression of mothers against decapentaplegic homolog 3, a protein known to inhibit cell cycle G1/S phase progression and induce apoptosis. In isolated rat islets, the effect of palmitic acid on caspase-3/7 activity was increased with T0901317 alone and even more with the combination of T0901317 and 9cRA. Thus, activation of LXR/RXR signaling inhibits cell proliferation and induces apoptosis in pancreatic beta-cells.


Studies on the reactivity of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone: reactions with indole derivatives and other C-nucleophiles.
[reaction: see text] Thermal decomposition of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone) in the presence of indole derivatives affords 3-acylated indoles existing in their enol forms, through a ring contraction and alpha,alpha'-dioxoketene formation reaction. The same reactants afford 3-(3-indolyl)-2-hydroxy-1,4-naphthoquinones in a copper-catalyzed reaction. Enamines, among other C-nucleophiles tested, give analogous results.


Micro-decompression for lumbar spinal stenosis: the early outcome using a modified surgical technique.
We describe a modified technique of micro-decompression of the lumbar spine involving the use of an operating microscope, a malleable retractor and a high-speed burr, which allows decompression to be performed on both sides of the spine through a unilateral, hemi-laminectomy approach. The first 100 patients to be treated with this technique have been evaluated prospectively using a visual analogue score for sciatica and back pain, the MacNab criteria for patient satisfaction, and functional assessment with the Oswestry Disability Index. After a period of follow-up from 12 months to six years and four months, sciatica had improved in 90 patients and back pain in 84 patients. Their result was graded as good or excellent by 82 patients according to the MacNab criteria, and 75 patients had subjective improvement in their walking distance. Late instability developed in four patients. Lumbar micro-decompression has proved to be safe, with few complications. Postoperative instability requiring fusion was uncommon, and less than using traditional approaches in published series.


Single-Cell, Time-Resolved Antimicrobial Effects of a Highly Cationic, Random Nylon-3 Copolymer on Live Escherichia coli.
Synthetic random copolymers based on the nylon-3 (β-peptide) backbone show promise as inexpensive antimicrobial agents resistant to proteolysis. We present a time-resolved observational study of the attack of a particular copolymer MM63:CHx37 on single, live Escherichia coli cells. The composition and chain length of MM63:CHx37 (63% cationic subunits, 37% hydrophobic subunits, 35-subunit average length) were optimized to enhance antibacterial activity while minimizing lysis of human red blood cells. For E. coli cells that export GFP to the periplasm, we obtain alternating phase-contrast and green fluorescence images with a time resolution of 12 s over 60 min following initiation of copolymer flow. Within seconds, cells shrink and exhibit the same plasmolysis spaces that occur following abrupt external osmotic upshift. The osmoprotection machinery attempts to replenish cytoplasmic water, but recovery is interrupted by permeabilization of the cytoplasmic membrane (CM) to GFP. Evidently, the highly cationic copolymer and its counterions rapidly translocate across the outer membrane without permeabilizing it to GFP. The CM permeabilization event is spatially localized. Cells whose CM has been permeabilized never recover growth. The minimum inhibitory concentration (MIC) for cells lacking the osmolyte importer ProP is 4-fold smaller than for normal cells, suggesting that osmoprotection is an important survival strategy. In addition, at the time of CM permeabilization, we observe evidence of oxidative stress. The MIC under anaerobic conditions is at least 8-fold larger than under aerobic conditions, further implicating oxidative damage as an important bacteriostatic effect. Once the copolymer reaches the periplasm, multiple growth-halting mechanisms proceed in parallel.


Inhibition of phosphodiesterase-5 suppresses calcineurin/NFAT- mediated TRPC6 expression in pulmonary artery smooth muscle cells.
The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus. Further study indicated that inhibition of calcineurin by cyclosporine A or knockdown of NFATc4 using small interfering RNA suppressed ET-1-induced TRPC6 up-regulation. In addition, luciferase reporter assay showed that NFATc4 directly regulated the expression of TRPC6 in PASMCs. Inhibition of PDE5 by sildenafil suppressed ET-1-induced activation of calcineurin/NFATc4 signaling pathway and consequent TRPC6 up-regulation in PASMCs, while these inhibitory effects of sildenafil were abolished by PKG inhibitor Rp-8Br-cGMPs. Taken together, our study indicates that ET-1 stimulates TRPC6 expression by activation of calcineurin/NFATc4 signaling pathway, and inhibition of PDE5 suppresses calcineurin/NFATc4- mediated TRPC6 expression in PASMCs in a cGMP-PKG-dependent manner.


Managing health expenditure inflation under a single-payer system: Taiwan's National Health Insurance.
As nations strive to achieve and sustain universal health coverage (UHC), they seek answers as to what health system structures are more effective in managing health expenditure inflation. A fundamental macro-level choice a nation has to make is whether to adopt a single- or a multiple-payer health system. Using Taiwan's National Health Insurance (NHI) as a case, this paper examines how a single-payer system manages its health expenditure growth and draws lessons for other countries whose socioeconomic development is similar to Taiwan's. Our analyses show that as a single payer, Taiwan's NHI is able to exercise its monopsony power to manage its health expenditure growth. This is achieved primarily through the adoption of a system-wide global budget. The global budget sets a hard aggregate budget cap to limit NHI's total spending to its expected revenue, with the annual budget growth rate established by a process of negotiation among key stakeholders. The global budget system is complemented by comprehensive and continuous monitoring and review of encounter records of all providers and patients, enabled by the NHI's advanced information technology. However, by paying its providers using a point-based fee schedule, Taiwan's NHI suffers from inefficient service provision. In particular, providers have incentives to increase use of services and drugs with positive profit margins. Furthermore, Taiwan demonstrates that its control of NHI expenditure growth might be leading it to inadequately meet the changing needs of the population, resulting in the rapid growth of private insurance to cover services excluded or not fully covered by the NHI. If this trend persists and results in a two-tier system, Taiwan's NHI may risk compromising the equity it has achieved in the past two decades.


Role of (H2O)(n) (n = 2-3) Clusters on the HO2 + O3 Reaction: A Theoretical Study.
We report a theoretical investigation on the role of the water dimer and trimer in the reaction between the hydroperoxyl radical and ozone. This study is part of an ongoing series of research endeavors that intend to deliver a comprehensive understanding on the role of water on this reaction. Due to the complexity of the potential energy surface, and to be able to make comparisons with our previous works, our calculations have employed model chemistries based on the Kohn-Sham DFT formalism. It is found that the calculated reaction paths share a common scheme, not only in the context of this work, but also in consideration of our previous studies. Also, oxygen-abstraction barriers are always submerged, with the relative energy between the hydrogen- and oxygen-abstraction saddle-points increasing with the number of water molecules, which maintain an apparent spectator role. Finally, we report novel HO2···(H2O)3 and HO3···(H2O)n complexes originating from our reaction schemes.


[Pain in humans: experimental facts and hypotheses].
The description of painful phenomena in humans has to take into account its different components: sensory component (relevant to nociception), affective and emotional components. Nociceptor's (physiology is best understood with electrophysiological and neurochemical methods allowing a clear description of hyperalgesia, with its peripheral and spinal mechanisms. A functional model is partly available to explain allodynia, spontaneous burning pain and lightning pain, the three main consequences following deafferentation. At the thalamo-cortical level, one can describe nociceptive pathways and other pathways or neuronal networks involved in the affective and emotional components of pain.


Performance Analysis of Scattering-Level Multiplexing (SLMux) in Distributed Fiber-Optic Backscatter Reflectometry Physical Sensors.
Optical backscatter reflectometry (OBR) is a method for the interrogation of Rayleigh scattering occurring in each section of an optical fiber, resulting in a single-fiber-distributed sensor with sub-millimeter spatial resolution. The use of high-scattering fibers, doped with MgO-based nanoparticles in the core section, provides a scattering increase which can overcome 40 dB. Using a configuration-labeled Scattering-Level Multiplexing (SLMux), we can arrange a network of high-scattering fibers to perform a simultaneous scan of multiple fiber sections, therefore extending the OBR method from a single fiber to multiple fibers. In this work, we analyze the performance and boundary limits of SLMux, drawing the limits of detection of N-channel SLMux, and evaluating the performance of scattering-enhancement methods in optical fibers.


Lethal cardiac arrhythmia during central venous catheterization in a uremic patient: a case report and review of the literature.
Double-lumen central venous catheter (CVC) is a rapid access technique for hemodialysis (HD) when an arteriovenous fistula or graft is not available. A variety of procedure-related complications have been reported, such as infection and pneumothorax, but serious cardiac complications are relatively less mentioned. We report a uremic woman with preexisting left bundle branch block who required emergent HD and received jugular double-lumen CVC insertion, which was complicated by short-duration ventricular tachycardia followed by complete atrio-ventricular block and bradycardia. Pharmacological management did not reverse heart rate and rhythm. External pacing was not applied because she remained hemodynamically stable in the course of HD. Heart rate returned to sinus rhythm with left bundle branch block 4 hours later and did not recur through the whole admission period. We speculate that the transient arrhythmia might have been induced by mechanical contact with the ventricular wall during the procedure with the guided metallic wire. In conclusion, physicians responsible for CVC catheterization should pay more attention to patients with preexisting cardiac arrhythmia to prevent such technical mistakes from transpiring.


Beyond the operating room: a simulator for sacroiliac screw insertion.
Current teaching techniques for orthopedic screw insertions involve "learning by doing" in the operating room. Minimally invasive insertion of sacroilliac (SI) screws is a relatively uncommon operation, providing scant opportunity for training outside of a few major centers. As such, SI screw insertion is a prime candidate for simulator-based training. This work describes the development and implementation of a simulator for minimally invasive SI screw insertion using accurate 3-dimensional (3D) computed tomography (CT)-based visualization of the pelvic and upper sacral anatomy. The simulator was designed in Tool Command Language atop the Amira 3D visualization package. CT images of pelvic regions were automatically segmented to generate 3D surfaces. Using inlet and outlet 3D views, guidewire insertion can be performed followed by an appropriately sized SI screw. The simulator was found to provide a realistic representation of the pelvis, and test users reported increased understanding of the procedure of SI screw insertion following use. The 3D reconstructions of the pelvis allowed for visual correlations between CT slices and inlet and outlet x-ray views. Pilot work with surgical trainees suggests the tool's value in increasing the familiarity of surgical trainees to visualize the pelvis in 3D and perform SI screw insertion.


Similarities and Differences in Decision-Making Impairments between Autism Spectrum Disorder and Schizophrenia.
Although individuals with autism spectrum disorders (ASD) and schizophrenia (SCH) share overlapping characteristics and may perform similarly on many cognitive tasks, cognitive dysfunctions common to both disorders do not necessarily share the same underlying mechanisms. Decision-making is currently a major research interest for both ASD and SCH. The aim of the present study was to make direct comparisons of decision-making and disorder-specific underlying neuropsychological mechanisms between the two disorders. Thirty-seven participants with ASD, 46 patients with SCH, and 80 healthy controls (HC) were assessed with the Iowa Gambling Task (IGT), which measures decision-making under ambiguity, and the Game of Dice Task (GDT), which measures decision-making under risk. The results revealed that both the ASD and SCH groups had deficits for both the IGT and the GDT compared with the HC. More importantly, in the IGT, participants with ASD displayed a preference for deck A, indicating that they had more sensitivity to the magnitude of loss than to the frequency of loss, whereas patients with SCH displayed a preference for deck B, indicating that they showed more sensitivity to the frequency of loss than to the magnitude of loss. In the GDT, the impaired performance might be due to the deficits in executive functions in patients with SCH, whereas the impaired performance might be due to the deficits in feedback processing in participants with ASD. These findings demonstrate that there are similar impairments in decision-making tasks between ASD and SCH; however, these two disorders may have different impairment mechanisms.


Neurologic problems in renal transplant recipients.
Renal transplant recipients are at an increased risk of developing certain neurologic problems. These problems differ from those encountered in recipients of other organs. Development of atherosclerosis is accelerated in renal transplant patients and results in an increased incidence of thromboembolic events. Immunosuppressive therapy predisposes to infection with opportunistic organisms, including reactivation of latent viruses and also is associated with an increased incidence of de novo neoplasia. The transplantation procedure may be complicated by a neuropathy and occasionally by distal spinal cord infarction. Some immunosuppressive agents have a direct adverse effect on the nervous system, particularly when toxic levels accumulate in the body. Uremia prior to, and if present after transplantation, has a toxic effect on the nervous system as well. The reasons for these problems are discussed. Awareness of these special problems in renal transplant patients will facilitate their prevention and diagnosis. A recommended diagnostic approach has been outlined. After the etiology has been established, treatment can be tailored to the individual patient.