In vitro stability of B-type natriuretic peptide (BNP) in plasma stored under different conditions when measured with the Lumipulse® assay.
Natriuretic peptides are a laboratory tool with significant implications for the diagnosis and prognosis of heart failure (HF). The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommended that assays must be examined for sample stability because there appears to be assay dependent. We aimed to evaluate the in vitro stability of B-type natriuretic peptide (BNP) under different handling conditions and using a BNP assay from Fujirebio Diagnostics (Tokyo, Japan). BNP concentrations were measured in plasma EDTA samples from 11 subjects to evaluate the in vitro stability at room temperature and at 4 °C and in 10 subjects to check the in vitro stability of samples stored at -20 °C during 1 and 3 months. Stability limit was defined according to Spanish Society of Laboratory Medicine (SEQC-ML) recommendations. At room temperature and 4 °C, BNP concentrations decreased progressively in samples collected in both groups, remaining stable within four hours from collection. BNP concentrations also were stable within four hours from collection in whole blood at room temperature. Finally, at -20 °C, BNP concentrations remained stable in both groups at 1 and 3 months, respectively. According to our results, BNP, stored at room temperature or at 4 °C, should be assayed in the first four hours after collection. Besides, BNP was shown to be stable in whole blood for at least four hours at room temperature. If the testing cannot be performed within the first four hours, the plasma should be frozen and kept at -20 °C for up to 3 months.


Design, synthesis, and biological evaluation of cosalane, a novel anti-HIV agent which inhibits multiple features of virus reproduction.
Cosalane (3), a novel anti-HIV agent having a disalicylmethane unit linked to C-3 of cholestane by a three-carbon linker, was synthesized from commercially available starting materials by a convergent route. Cosalane proved to be a potent inhibitor of HIV with a broad range of activity against a variety of laboratory, drug-resistant, and clinical HIV-1 isolates, HIV-2, and Rauscher murine leukemia virus. The cytotoxicity of cosalane is relatively low as reflected by an in vitro therapeutic index of > 100. Although cosalane inhibits HIV-1 reverse transcriptase and protease, time of addition experiments indicate that it prevents the cytopathic effect of HIV by acting earlier than reverse transcription in the viral replication cycle. The available evidence indicates that the primary mechanism of action of cosalane involves inhibition of gp120-CD4 binding as well as inhibition of a postattachment event prior to reverse transcription.


By land or by sea: the role of perceptual similarity in infants' categorization of animals.
In 3 experiments, the authors used an object-examining task to investigate the role of perceptual similarity in infants' categorization. In Experiment 1, infants were familiarized with a set of either perceptually similar or perceptually variable exemplars from 1 category and tested with novel exemplars from both categories. Ten-month-olds did not respond to the category in either condition, and 13-month-olds responded categorically in both conditions but somewhat differently in the 2 conditions. Experiment 2 showed that when 10-month-olds were familiarized with similar exemplars but not with variable exemplars, they responded to the categorical distinction when given tests with typical exemplars. Experiment 3 established that 10-month-olds could differentiate among the exemplars. These results suggest that the perceptual similarity of the exemplars influences infants' recognition of categorical distinctions.


Renal cell carcinoma with venous neoplastic thrombosis: a ten years review.
To review the 10-year experience of our urological unit in the surgical management of renal cell carcinoma (RCC) with neoplastic tumor thrombosis focusing on postoperative survival. We underwent a retrospective analysis of the patients treated for this pathology during the last decade 2002-2012, stratifying them by tumor thrombus level and histological subtype. Kaplan-Meyer curves were used to assess survival. Overall, 67 patients underwent surgery for RCC with neoplastic tumoral thrombosis in the period under review. 60 were clear cell RCC, 4 were urothelial papillary tumors of the renal pelvis and 3 were rare histotypes, as a nefroblastoma, a spinocellular tumor of the renal pelvis and an unclassifiable renal carcinoma. Thrombus level was I in 40 cases, II in 17, III in 2 and IV in 8 patients. We report the main postoperative complications and our survival data, with mean follow up of 36 months. Tumor stage is the most important variable in predicting survival. Patients with N0M0 disease had 70% survival at 36 months, instead of 20% for those with primitive metastatic tumor. Our survival results fit with the main reports in literature and our surgical management was completely in keeping with international guidelines. We did not observe relevany post-operative complications, except of hemorrhagic ones that occurred in 6 patients (9% of total) and were always successfully managed. Eighteen patients (26.87% of total) underwent caval filter positioning, without evidence of complications during its positioning or removal. Life expectancy was particularly low for the cases of RCC without clear cell histotype (7 cases in our series, 10.4% of total) that always was less than one year from surgery.


[Primary structure of hemoglobins of the musk rat (Ondatra zibethica, Rodentia)].
The amino-acid sequence for the hemoglobin of the musk-rat (Ondatra zibethica) was determined. The sequence of both chains was established by automatic Edman-Begg degradation of the tryptic peptides and, in the case of the beta-chains additionally of the prolyl-peptide. The complete primary structure of the alpha-chains differs at 22, that of the beta-chains at 36 positions from the adult human hemoglobin. There are no changes in the heme-binding residues, the alpha 1--beta 2 contact positions and the allosteric regulator sites. In the heme-pocket we found beta 44 Ser leads to His and 8 positions changed within the alpha 1--beta 1 contact regions. These changes are discussed with respect to the function of the respective regions.


Nitric oxide (NO) pathway and locomotor hyperactivity towards dopaminomimetics in rats.
The effects of the NO donor molsidomine and the inhibitors of the NO synthase (NOS) 7-nitroindazole (7-NI) and NG-nitro-L-arginine methyl ester (L-NAME) on the motor hyperactivity induced by indirect (amphetamine and cocaine) or direct (SKF 38393 and bromocriptine) dopamine (DA) agonists were studied in rats. The hyperactivity induced by 0.5 mg/kg of amphetamine or 5 mg/kg of cocaine was potentiated in a dose-dependent manner by molsidomine (30-100 mg/kg), but attenuated by 7-NI (3-30 mg/kg) or L-NAME (3-30 mg/kg). The NOS inhibitors also inhibited the locomotor hyperactivity evoked by 15 mg/kg of SKF 38393 (a DA D1 agonist) or 5 mg/kg of bromocriptine (a DA D2 agonist). On the other hand, the hyperactivity induced by those direct DA receptor agonists was potentiated by molsidomine. The present findings provide further evidence for an interaction at the behavioral level between NO and the DA-mediated effects of amphetamine and cocaine; moreover, they seem to indicate that both DA D1 and DA D2 receptor subtypes are under such influence.


Forecasting distributions of an aquatic invasive species (Nitellopsis obtusa) under future climate scenarios.
Starry stonewort (Nitellopsis obtusa) is an alga that has emerged as an aquatic invasive species of concern in the United States. Where established, starry stonewort can interfere with recreational uses of water bodies and potentially have ecological impacts. Incipient invasion of starry stonewort in Minnesota provides an opportunity to predict future expansion in order to target early detection and strategic management. We used ecological niche models to identify suitable areas for starry stonewort in Minnesota based on global occurrence records and present-day and future climate conditions. We assessed sensitivity of forecasts to different parameters, using four emission scenarios (i.e., RCP 2.6, RCP 4.5, RCP 6, and RCP 8.5) from five future climate models (i.e., CCSM, GISS, IPSL, MIROC, and MRI). From our niche model analyses, we found that (i) occurrences from the entire range, instead of occurrences restricted to the invaded range, provide more informed models; (ii) default settings in Maxent did not provide the best model; (iii) the model calibration area and its background samples impact model performance; (iv) model projections to future climate conditions should be restricted to analogous environments; and (v) forecasts in future climate conditions should include different future climate models and model calibration areas to better capture uncertainty in forecasts. Under present climate, the most suitable areas for starry stonewort are predicted to be found in central and southeastern Minnesota. In the future, suitable areas for starry stonewort are predicted to shift in geographic range under some future climate models and to shrink under others, with most permutations indicating a net decrease of the species' suitable range. Our suitability maps can serve to design short-term plans for surveillance and education, while future climate models suggest a plausible reduction of starry stonewort spread in the long-term if the trends in climate warming remain.


[Evaluation of blood eosinophil in the diagnosis of eosinophilic chronic rhinosinusitis].
To evaluate the practice of peripheral blood eosinophil in the diagnosis of eosinophilic chronic rhinosinusitis(ECRS). The correlation between eosinophil count and percentage in peripheral blood and that in topic tissue in 787 patients (the first affiliated hospital of Wenzhou medical university, from Jan. 2013 to Jun. 2016) with chronic rhinosinusitis (CRS) were retrospectively analysed. The optimal cutoff value of blood eosinophil count and percentage as predictors for ECRS was determined by receiver operating characteristic curves (ROC) and their diagnostic ability was compared. The positive correlation between eosinophil count and percentage in blood and that in tissue was found respectively in 787 patients with CRS (r=0.450, 0.499, 0.463, 0.465, P<0.01). Although the significant correlation between blood eosinophil count and its count and percentage in tissue was not found after blood leukocyte and tissue eosinophilic inflammation was controlled respectively (r=0.041, P=0.380; r=0.046, P=0.329 and r=0.023, P=0.618; r=0.032, P=0.499), blood eosinophil percentage still showed significant correlation with tissue eosinophil count and percentage, but reduced unequally after that(r=0.383, 0.436 and r=0.153, 0.169, P<0.01). With ROC analysis, the diagnostic ability of optimal cut off values of eosinophil count and percentage varied as the histological criteria for ECRS differed. Eosinophil in peripheral blood showed significant positive correlation with its tissue infiltration, which may be not strong and easily effected by individual factors.Theoretically, blood eosinophil may have a diagnostic significance as a predictor for ECRS but not practically.


Impact of sex, age and BMI on depth and diameter of the infraclavicular axillary vein when measured by ultrasonography.
The axillary vein is another option for central venous catheterisation, with less chance of accidental arterial puncture as there is a greater distance between artery and vein, and from vein to rib cage, compared with other sites. Better success, lower complication rates and faster access can be achieved with ultrasound guidance which is becoming the established technique for central venous catheterisation. We measured two key factors for successful infraclavicular axillary venous catheterisation: depth and diameter of the infraclavicular axillary vein in its medial part using ultrasound. We recruited 98 patients, classified according to sex, age and BMI. Groups were divided according to BMI as follows: group 1 (≤20 kg m⁻²), group 2 (20.01-25.00 kg m⁻²) and group 3 (>25 kg m⁻²); and these were further subdivided according to age: 20-39 years, 40-59 years and 60-80 years. The depth and diameter of the infraclavicular axillary vein was measured at a point between the medial third and midpoint of the clavicle. Vein diameter was significantly different between men and women (P = 0.005), whereas depth showed no significant difference. In the BMI subgroups, there was a significant difference in depth (P < 0.001), and a trend to significant difference in diameter (P = 0.056). However, age-specific differences in depth and diameter were not observed. During catheterisation of infraclavicular axillary vein, real-time visualisation of the needle tip when using ultrasound to gauge vein depth and diameter may diminish major complications such as pneumothorax and artery puncture.


An examination of the relationship between foot length, foot breath, ball girth, height and weight of Turkish university students aged between 17 and 25.
In this study the relationship between foot length, foot breadth, ball girth or foot circumference, height and weight of Turkish students aged between 17 and 25 was examined. It was noted that in both sexes the correlation between foot length and height was more significant than the correlation between foot length and weight. When the percentage ratio of foot breadth and ball girth to foot length is calculated in both sexes, the percentage ratio in students with longer feet turned out to be smaller. However, it was found that foot breadth and ball girth of the male students in the same foot length category were greater than in the female students. The comparison of right foot length and ball girth in the same foot length category in Turkish, French and Japanese indicated that there was a similarity between Turkish and French with regard to foot breadth. The ball girth of the individuals from these three different populations were quite different from each other. It was observed that the average foot length of the Turkish was larger than that of both French and Japanese. The following conclusions can be drawn from this study: 1. Foot breath, ball girth and foot length can be regarded as three separate elements. 2. These three elements are to be precisely known for the optimal manufacturing of shoe lasts. 3. Apart from the above mentioned three elements, both individual and racial differences must also be considered concerning an optimal manufacturing of shoe lasts.


Going back to Donald: how comparisons shape judgmental priming effects.
The authors examine how judgmental priming effects are shaped by comparisons. Specifically, they suggest that concept priming involves spontaneous activation of concept-consistent standards, which are then spontaneously compared to the judgmental target. In 6 studies, they used a variety of priming methods (contextual cue, subliminal priming, indirect priming) to test these notions of spontaneous standard activation and spontaneous comparison. Study 1 demonstrates that priming a trait concept activates concept-consistent standards. Study 2 suggests that these activated standards contribute to priming effects. If alternative standards that are not particularly consistent with the primed concept are activated, priming effects diminish. Studies 3-6 show that the magnitude and direction of priming effects depend on the intensity and the type of the engaged comparison. Specifically, Study 3 demonstrates that the magnitude of a priming effect depends on the intensity of comparative processing. Studies 4 through 6 show that the direction of a priming effect (assimilation vs. contrast) depends on whether judges engage in a similarity or dissimilarity testing comparison mechanism--a factor which has been found to shape comparison consequences in other domains. (PsycINFO Database Record (c) 2008 APA, all rights reserved).


Building a neuroinfectious disease consensus curriculum.
To delineate a comprehensive curriculum for fellowship training in neuroinfectious diseases, we conducted a modified Delphi approach to reach consensus among 11 experts in the field. The authors invited a diverse range of experts from the American Academy of Neurology Neuro-Infectious Diseases (AAN Neuro-ID) Section to participate in a consensus process using a modified Delphi technique. A comprehensive list of topics was generated with 101 initial items. Through 3 rounds of voting and discussion, a curriculum with 83 items reached consensus. The modified Delphi technique provides an efficient and rigorous means to reach consensus on topics requiring expert opinion. The AAN Neuro-ID section provided the pool of diverse experts, the infrastructure, and the community through which to accomplish the consensus project successfully. This process could be applied to other subspecialties and sections at the AAN.


A method to remove odd harmonic interferences in square wave reference digital lock-in amplifier.
Digital lock-in amplifier using square wave reference is much easier to be implemented compared to digital lock-in amplifier using sinusoidal wave reference. However, because of the odd harmonics containing in the square wave reference, the interferences at the odd harmonics of the reference cannot be removed with conventional algorithm. A new square wave digital lock-in algorithm is presented in this paper. It cannot only be capable of removing the interferences of the odd harmonics in the signal, but also can detect the amplitudes and the phases of the interferences. The real and imaginary parts of the frequency component of interest and those of the odd harmonic interferences are calculated simultaneously. The results of simulation experiments show the feasibility of the proposed algorithm. The algorithm is computationally efficient and thus suitable for weak signal detection implemented in the general microprocessor.


The role of postoperative radiation and coordination of care in patients with metastatic bone disease of the appendicular skeleton.
Metastatic bone disease affects approximately 300,000 people in the United States, and the burden is rising. These patients experience significant morbidity and decreased survival. The management of these patients requires coordinated care among a multidisciplinary team of physicians, including orthopaedic surgeons. This article reviews the role of radiation therapy after orthopaedic stabilization of impending or realized pathologic extremity fractures. Orthopaedic surgeons have an opportunity to benefit patients with metastatic bone disease by referring them for consideration of post-operative radiation therapy. Further research into rates of referral and the effect on clinical outcomes in this population is needed.


Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway.
Macrophages are a major component of the leukocyte infiltrate of tumors and play a pivotal role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which macrophages promote HCC invasion are poorly understood. The present study was undertaken to investigate the relationship between macrophages and epithelial-mesenchymal transition (EMT) of HCC. Double-staining immunohistochemistry was used to observe the association between macrophages and EMT markers in clinical HCC samples and it showed that EMT primarily occurred at the edge of the tumor nest, in which infiltrating macrophages were always observed. This indicated that CD68 which is a marker of macrophages, was correlated with EMT marker levels. In addition, after being cultured with macrophages for 24 h, the ability of HCC cells to migrate and invade increased, Snail and N-Cadherin expression was upregulated, and E-Cadherin was downregulated. An antibody array assay was applied to analyze the supernatant of these cultures and it demonstrated IL-8 increased significantly in the macrophage co-culture system. Finally, the role of macrophage-derived IL-8 in the invasion of HCC cells was assayed, and downstream signaling pathways were also investigated. We found that IL-8: i) may induce EMT and promote HCC cell migration and invasion and ii) is associated with the JAK2/STAT3/Snail signaling pathway. Taking together, these findings revealed that macrophages that have infiltrated tumors may induce epithelial-mesenchymal transition of HCC cells via the IL-8 activated JAK2/STAT3/Snail pathway. Thus, this may offer a potential target for developing new HCC therapies.


Interstitial nephritis associated with perianeurysmal retroperitoneal fibrosis.
Renal failure in retroperitoneal fibrosis is usually secondary to ureteric obstruction. We report a patient whose renal failure did not improve following relief of obstruction. Renal biopsy showed an interstitial nephritis, and function improved with steroid therapy. We suggest that renal biopsy should be considered in cases of renal failure associated with retroperitoneal fibrosis that do not respond to the relief of ureteric obstruction.


Dietary peppermint (Mentha piperita) powder affects growth performance, hematological indices, skin mucosal immune parameters, and expression of growth and stress-related genes in Caspian roach (Rutilus caspicus).
Peppermint is a popular herbal medicine due to its several pharmaceutical applications. In this study, peppermint powder was used as a feed additive to evaluate growth performance, hematological parameters, protein profile of skin mucus, and immune parameters, as well as growth hormone (GH), insulin-like growth factor (IGF), and 70 kDa heat shock protein (HSP70) gene expression in Caspian roach (Rutilus caspicus). The fingerlings (average weight of 2.40 ± 0.12 g) were fed with diet containing 0 (control), 2, 3, and 4 g/kg peppermint for 8 weeks. The addition of peppermint significantly enhanced the growth parameters and decreased the food conversion ratio. Hematological indices of fish fed with peppermint-supplemented diets were significantly different from the control group (P < 0.05). Soluble protein, alkaline phosphatase, and lysozyme enzyme activity in mucus samples showed an incremental trend by increasing the peppermint levels in the diet. Evaluation of mucosal immunity indicated a remarkable difference between the protein profile in treatments fed with peppermint-supplemented diets and the control group. A new protein band (approximately 27 kDa) was also found in the skin mucus of fish fed with the diet containing 4 g/kg peppermint, and the highest band density was observed in this treatment. The highest IGF and GH gene expression were observed in 4 g/kg peppermint treatment. There was a significant difference in HSP70 expression between the fish fed with peppermint powder and the control group (P < 0.05). Overall, the results showed that dietary oral administration of peppermint at 4 g/kg of feed can act as a growth promoter and immunostimulant.


Photoinduced Photosensitizer-Antibody Conjugates Kill HIV Env-Expressing Cells, Also Inactivating HIV.
HIV-infected cells persist for decades in patients administered with antiretroviral therapy (ART). Meanwhile, an alarming surge in drug-resistant HIV viruses has been occurring. Addressing these issues, we propose the application of photoimmunotherapy (PIT) against not only HIV Env-expressing cells but also HIV. Previously, we showed that a human anti-gp41 antibody (7B2) conjugated to cationic or anionic photosensitizers (PSs) could specifically target and kill the HIV Env-expressing cells. Here, our photolysis studies revealed that the binding of photoimmunoconjugates (PICs) on the membrane of HIV Env-expressing cells is sufficient to induce necrotic cell death due to physical damage to the membrane by singlet oxygen, which is independent of the type of PSs. This finding persuaded us to study the virus photoinactivation of PICs using two HIV-1 strains, X4 HIV-1 NL4-3 and JR-CSF virus. We observed that the PICs could destroy the viral strains, probably via physical damage on the HIV envelope. In conclusion, we report the application of PIT as a possible dual-tool for HIV immunotherapy and ART by killing HIV-expressing cells and cell-free HIV, respectively.


Presence of peptide synthetase gene transcripts and accumulation of ergopeptines in Claviceps purpurea and Neotyphodium coenophialum.
The production of toxic ergopeptine alkaloids by the fungi Claviceps purpurea and Neotyphodium coenophialum involves the activity of one or more nonribosomal peptide synthetases. Claviceps purpurea and N. coenophialum each have several different peptide synthetase genes, fragments of which have been cloned previously. An additional Claviceps purpurea peptide synthetase gene was cloned by hydridization with one of the N. coenophialum peptide synthetase gene fragments. We detected the presence of mRNA from the peptide synthetase genes in cultures of different ages grown under conditions favorable or unfavorable for ergopeptine production. All four peptide synthetase genes from Claviceps purpurea were transcribed under at least some of the experimental conditions. Transcripts from three of the four genes were detected under conditions consistent with their potential involvement in ergopeptine biosynthesis. All three peptide synthetase genes previously identified in N. coenophialum were transcribed during symbiotic growth of this fungus with tall fescue, as well as ergopeptine-producing cultures. The data show that all of the peptide synthetase genes are transcribed, that one of the peptide synthetase genes is dissociated from ergopeptine biosynthesis, and, as a result, prioritize the remaining genes for functional analyses by transformation-mediated gene disruption.


Osmotic stress response: quantification of cell maintenance and metabolic fluxes in a lysine-overproducing strain of Corynebacterium glutamicum.
Osmotic stress diminishes cell productivity and may cause cell inactivation in industrial fermentations. The quantification of metabolic changes under such conditions is fundamental for understanding and describing microbial behavior during bioprocesses. We quantified the gradual changes that take place when a lysine-overproducing strain of Corynebacterium glutamicum is grown in continuous culture with saline gradients at different dilution rates. The use of compatible solutes depended on environmental conditions; certain osmolites predominated at different dilution rates and extracellular osmolalities. A metabolic flux analysis showed that at high dilution rates C. glutamicum redistributed its metabolic fluxes, favoring energy formation over growth. At low dilution rates, cell metabolism accelerated as the osmolality was steadily increased. Flexibility in the oxaloacetate node proved to be key for the energetic redistribution that occurred when cells were grown at high dilution rates. Substrate and ATP maintenance coefficients increased 30- and 5-fold, respectively, when the osmolality increased, which demonstrates that energy pool management is fundamental for sustaining viability.


Gaucher Disease Presenting in an Adult with Intracerebral Bleed.
Gaucher disease (GD) is the most common lysosomal storage disorder, caused by deficiency of acid beta glucosidase. GD usually presents in children but occasional cases can present in adulthood. Here we report a case of type I GD in a 37 year old female who presented with intracerebral bleed due to long standing thrombocytopenia. She underwent splenectomy in view of limited resources for enzyme replacement therapy. With splenectomy her platelet counts normalised and neurological status also improved.


β2-Glycoprotein I/IgA Immune Complexes: A Marker to Predict Thrombosis After Renal Transplantation in Patients With Antiphospholipid Antibodies.
Antiphospholipid syndrome is characterized by recurrent thrombosis and gestational morbidity in patients with antiphospholipid autoantibodies (aPLs). Predictive value of the presence of aPLs is low, and new markers are necessary to identify aPL carriers at higher risk and take preventive measures on them. The presence of circulating immune complexes of IgA bound to β2-glycoprotein I (B2A-CIC) has been associated with occurrence of acute thrombotic events. In this work we study its possible predictive value for the appearance of acute thrombotic events in patients who are going to undergo transplant surgery, a well-known trigger of acute thrombotic events in aPL carriers. We performed a follow-up study based on the Magnum 12+12 Cohort of patients who received a kidney transplant (n=1339). Three groups were established: group 1 patients who were positive for IgA anti-β2-glycoprotein I (aB2GP1) and B2A-CIC (n=125); group 2 patients who were positive only for IgA aB2GP1 (n=240); and control group, patients who were negative for IgA aB2GP1 (n=974). Levels of autoantibodies and B2A-CIC were quantified immediately before the transplant surgery and patients were followed up for 6 months. In group 1, 46.4% of patients experienced any type of thrombosis versus 10.4% in group 2 (P<0.001) and 8.6% in the control group (P<0.001). The incidence of graft thrombosis in group 1 (31.2%) was significantly higher than that observed in group 2 (3.3%, P<0.001) and the control group (2.6%, P<0.001). In a multivariate analysis, the presence of B2A-CIC was an independent variable to experience any type of posttransplant thrombosis (hazard ratio, 6.72; 95% confidence interval, 4.81-9.37) and, prominently, for graft thrombosis (hazard ratio, 14.75; 95% confidence interval, 9.11-23.89). No significant differences were found between B2A-CIC-negative and control group patients. The presence of B2A-CIC is a predictor of acute thrombotic events. Patients who were positive for IgA aB2GP1 only are at risk of experiencing thrombosis if they are B2A-CIC positive. If they are B2A-CIC-negative patients, they have the same risk as the control group. Treatments to prevent acute thrombotic events should focus on B2A-CIC-positive patients.


Management of critically ill patients with diabetes.
Disorders of glucose homeostasis, such as stress-induced hypoglycemia and hyperglycemia, are common complications in patients in the intensive care unit. Patients with preexisting diabetes mellitus (DM) are more susceptible to hyperglycemia, as well as a higher risk from glucose overcorrection, that may results in severe hypoglycemia. In critically ill patients with DM, it is recommended to maintain a blood glucose range between 140-180 mg/dL. In neurological patients and surgical patients, tighter glycemic control (i.e., 110-140 mg/d) is recommended if hypoglycemia can be properly avoided. There is limited evidence that shows that critically ill diabetic patients with a glycosylated hemoglobin levels above 7% may benefit from looser glycemic control, in order to reduce the risk of hypoglycemia and significant glycemic variability.


Implications of repair models for LET effects and other radiobiological phenomena.
Repair models account for shoulders to survival curves by the postulate of a mode of repair which is depleted ("saturated") as dose increases, and which should therefore be distinguished, conceptually and linguistically, from what is commonly known as "repair of potentially lethal damage". Acceptance of repair models entails new interpretations of some radiobiological phenomena. "Recovery" of cells between dose fractions would be attributable to reconstitution or resynthesis of the putative agent of repair, so elucidation of the mechanism of such "recovery" requires a different approach from any that have been used in attempts to discover the nature of "sub-lethal lesions" or the mechanism of their repair--attempts that have not been attended by success. Even mammalian cells can yield exponential survival curves; but this fact has been ignored in some proposals for mechanisms of radiation-induced cell killing, and in "theories of RBE" based on multi-sublethal lesion models for shouldered survival curves. According to repair models, however, cells in general are basically single-hit detectors. Comparisons between the responses of repair-proficient cells and their deficient mutants to change in radiation quality support the hypothesis that increases in RBE are attributable to reduced capacity for some mode(s) of repair as LET increases; but there is evidence that some capacity remains, even at very high values of LET.


Hybrid CNN-LSTM for Predicting Diabetes: A Review.
Diabetes is a common and deadly chronic disease caused by high blood glucose levels that can cause heart problems, neurological damage, and other illnesses. Through the early detection of diabetes, patients can live healthier lives. Many machine learning and deep learning techniques have been applied for noninvasive diabetes prediction. The results of some studies have shown that the CNN-LSTM method, a combination of CNN and LSTM, has good performance for predicting diabetes compared to other deep learning methods. This paper reviews CNN-LSTM-based studies for diabetes prediction. In the CNNLSTM model, the CNN includes convolution and max pooling layers and is applied for feature extraction. The output of the max-pooling layer was fed into the LSTM layer for classification. The CNN-LSTM model performed well in extracting hidden features and correlations between physiological variables. Thus, it can be used to predict diabetes. The CNNLSTM model, like other deep neural network architectures, faces challenges such as training on large datasets and biological factors. Using large datasets can further improve the accuracy of detection. The CNN-LSTM model is a promising method for diabetes prediction, and compared with other deep-learning models, it is a reliable method.


Horizontal and Vertical Distribution of Heavy Metals in Farm Produce and Livestock around Lead-Contaminated Goldmine in Dareta and Abare, Zamfara State, Northern Nigeria.
Background. Hitherto studies in response to the June 2010 lead poisoning, Zamfara State, Nigeria, have focused on clinical interventions without information on livestock and other metals. Objective. This study has investigated the distribution of heavy metals in farm produce and livestock around lead-contaminated goldmine in Dareta and Abare, Zamfara State, Nigeria. Methods. Vegetables, soil, water, blood, and different meat samples were harvested from goat, sheep, cattle, and chicken from Dareta, Abare, and Gusau communities. The samples were digested with 10 mL of a mix of nitric and perchloric acids; the mixture was then heated to dryness. Lead, cadmium, zinc, chromium, copper, magnesium, and nickel were analysed using flame Atomic Absorption Spectrophotometer. The daily intake, bioaccumulation factor, and target hazard quotient (THQ) were calculated. Results. Chicken bone-muscles from Dareta had the highest concentrations of lead, zinc, and nickel (28.2750, 16.1650, and 4.2700 mg/kg, resp.), while chicken brain had the highest levels of cadmium, magnesium (0.3800 and 67.5400 mg/kg), and chromium (6.1650 mg/kg, kidney tissue inclusive). Conclusion. In addition to lead, cadmium may also be of concern in the contaminated mining communities of Zamfara State, Nigeria, given the high levels of cadmium in meat and vegetables samples from these areas.


Thermal characteristics of a transparent film heater using single-walled carbon nanotubes.
This article presents thermal characteristics of a transparent thin-film heater made of single-walled carbon nanotubes on a glass substrate. A simplified analysis model is developed for predicting the thermal behaviors of the heater and its validity is verified by numerical and experimental results. The analytic solution discloses that the key factors controlling steady thermal performance and transient thermal adjustment. For a thin heater of which the Biot number is very small, the temperature of the heater is determined by the applied gradient of electric potential, the sheet resistance of the nanotube film, and the surface heat transfer coefficient. The time scale required for transient heat-up is a function of the thermal mass of glass substrate and the surface heat transfer coefficient.


Molecular Screening for Cancer Treatment Optimization (MOSCATO-01) in Pediatric Patients: A Single-Institutional Prospective Molecular Stratification Trial.
Purpose: This single-institutional feasibility study prospectively characterized genomic alterations in recurrent or refractory solid tumors of pediatric patients to select a targeted therapy.Experimental Design: Following treatment failure, patients with signed consent and ages above 6 months, underwent tumor biopsy or surgical resection of primary or metastatic tumor site. These newly acquired samples were analyzed by comparative genomic hybridization array, next-generation sequencing for 75 target genes, whole-exome and RNA sequencing. Biological significance of the alterations and suggestion of most relevant targeted therapies available were discussed in a multidisciplinary tumor board.Results: From December 2012 to January 2016, 75 patients were included, 73 patients underwent 79 interventions, 56 of which were research biopsies with a low complication rate. All patients were pretreated, 37.0% had a brain tumor, and 63.0% had an extra-cranial solid tumor. Median tumor cell content was 70% (range, 0%-100%). Successful molecular analysis in 69 patients detected in 60.9% of patients an actionable alteration in various oncogenic pathways (42.4% with copy-number change, 33.3% with mutation, 2.1% with fusion), and change in diagnosis in three patients. Fourteen patients received 17 targeted therapies; two had received a matched treatment before inclusion.Conclusions: Research biopsies are feasible in advanced pediatric malignancies that exhibit a considerable amount of potentially actionable alterations. Genetic events affecting different cancer hallmarks and limited access to targeted agents within pediatric clinical trials remain the main obstacles that are addressed in our two subsequent precision medicine studies MAPPYACTS and AcSé-ESMART. Clin Cancer Res; 23(20); 6101-12. ©2017 AACR.


Virus encoded cytokines and cytokine receptors.
In order to replicate efficiently within the host, viruses have evolved multiple strategies to evade the host's immune system. In many cases viruses have actually hijacked various components of the host's immune system to ensure their own survival. One such strategy is the expression of virus encoded cytokines and cytokine receptors. Members of the poxvirus and herpesvirus families have been particularly successful with this strategy. The study of virus survival strategies provides important information regarding both virus biology as well as information about the immune system itself.


Free carnitine levels in respiratory distress syndrome during the first week of life.
Antenatal carnitine administration has been shown to induce fetal lung maturity by increasing pulmonary surfactant in animal and human studies. The aim of this study was to investigate serum free carnitine (FC) levels in preterm infants with respiratory distress syndrome (RDS) and controls during the first week of postnatal life. The study groups consisted of 76 preterm infants with gestational ages ranging from 28 to 36 weeks, and birthweights ranging from 1046 to 2352 g. Serum FC levels were measured in preterm infants (group A, 37 with RDS; group B, 39 controls without RDS) within the first 6 hours after birth, on days 3 and 7. For specific analyses, serum FC levels were determined for gestational ages 28 to 31 weeks and 32 to 36 weeks in both groups. Initial FC levels were decreased insignificantly in group A (22.5 +/- 7.3 micromol/L) compared with group B (23.5 +/- 6.8 micromol/L; P > 0.05). On days 3 and 7 of life, serum FC levels were significantly lower in group A (18.3 +/- 6.1 and 10.2 +/- 3.3 micromol/L, respectively) than in group B (23.4 +/- 7.1 and 22.8 +/- 3.7 micromol/L, respectively; P < 0.05 and P < 0.05, respectively) on days 3 and 7 of life, respectively. Serum FC level remained stable in the non-RDS group ( P > 0.05), but it decreased significantly in the RDS group during the first week of postnatal life ( P < 0.05). No differences were seen between the corresponding gestational age groups. Serum FC levels in RDS infants decreased from days 1 to 7. Decreased neonatal serum carnitine levels in preterm infants with RDS during the first week of life might be caused by increasing consumption of carnitine in lung tissue for surfactant synthesis.


Quality assessment of controlled clinical trials published in Orthopaedics and Traumatology journals in Spanish: An observational study through handsearching and evidence mapping.
Few Orthopaedics and Traumatology journals from Latin America and Spain are indexed in major databases; controlled clinical trials published in these journals cannot be exhaustively retrieved using electronic literature searches. We aimed to identify, describe and assess the quality of controlled clinical trials published in Orthopaedics and Traumatology journals from Latin America and Spain through handsearching and evidence mapping methods. We identified controlled clinical trials published in eligible Orthopaedics/Traumatology journals in Spanish until July 2017 by handsearching. Data were extracted for controlled clinical trials main characteristics and the Cochrane risk of bias tool was used to assess the controlled clinical trials methodological quality. In addition, we mapped the main findings of these trials. As a result, we assessed 5631 references in 29 eligible journals of which 57 were controlled clinical trials (1.0%). Controlled clinical trials were published between 1995 and 2017 at a rate of 2.5 per year. Journals from Spain and Mexico published around 63% of the controlled clinical trials identified. The median sample size of patients enrolled was 60 (range = 30-300 participants). About conditions assessed, 38.5% of controlled clinical trials assessed issues related to knee conditions, 15.7% about hip and 10.5% about trauma or spine. The risk of bias domains most affected was selective reporting bias and random sequence generation. In addition, only two and seven trials had low risk of bias in all items related to participant/personnel and outcome assessment blindings, respectively. More than 40% of studies did not report differences on benefits/harms between the interventions assessed. As a conclusion, the number of controlled clinical trials published in Orthopaedics/Traumatology journals from Latin America and Spain is low. These controlled clinical trials had important methodological shortcomings and were judged as unclear or high risk of bias. These trials are now available in CENTRAL for their potential inclusion in systematic reviews and other documents of synthesis.


An application of kappa-type analyses to interobserver variation in classifying chest radiographs for pneumoconiosis.
We investigated interobserver variation between three physician readers in the independent classification of chest radiographs from 1771 taconite workers for pneumoconiosis. We analysed variation with a general methodology for the analysis of categorical data, and quantified interobserver agreement in terms of kappa-type statistics. The results revealed considerable variation in the profusion of opacities reported by each observer. This was especially so for the earliest radiographic changes, but variation also occurred with the small number of films in the series showing category 2 pneumoconiosis or over. Variation in the classification of profusion of small opacities was greater in films of poor quality, and also increased with the length of time between taking and reading the film (film age). We could not account for the effect of film age by controlling for film quality, as subjectively assessed by the readers.


The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells.
Gene therapy of cancer using adenovirus as a single treatment modality has met limited success and efforts to enhance therapeutic outcomes have included combination of gene therapy with chemotherapy. The goal of this study was to investigate which chemotherapeutic agents may be suitable for combination with gene therapy of prostate cancer. Using an adenovirus expressing green fluorescent protein (GFP), we determined the effect of cisplatin, gemcitabine, doxorubicin, depsipeptide and MS-275 on adenoviral infectivity and transgene expression in LNCaP cells. We found that the two histone deacetylase inhibitors (HDACi), depsipeptide and MS-275, and to a lesser extent doxorubicin, increased infectivity and transgene expression. However, only the HDACi selectively increased infectivity in LNCaP cells while doxorubicin increased infectivity to a greater extent in normal prostate epithelial cells (PrEC). The increase in infectivity but not transgene expression correlated to increased surface expression of coxsackie and adenovirus receptor (CAR). Increased transgene expression following infection with an adenovirus expressing tumor necrosis factor-related apoptosis inducing ligand (TRAIL) was observed only in LNCaP cells treated with depsipeptide or MS-275. Combination of TRAIL gene therapy with HDACi but not doxorubicin resulted in increased induction of apoptosis in LNCaP cells. In contrast, apoptosis was not enhanced by HDACi in normal PrEC. These results suggest that combination of HDACi with adenoviral TRAIL gene therapy may be a new therapeutic approach for the treatment of prostate cancer that warrants further investigation.


Intracellular response properties of units in the dorsal cochlear nucleus of unanesthetized decerebrate gerbil.
Intracellular recording experiments on the dorsal cochlear nuclei of unanesthetized decerebrate gerbils were conducted. Acceptable recordings were those in which resting potentials were -50 mV or less and action potentials (APs) were > or = 40 mV. Responses to short-duration tones and noise, and to current pulses delivered via recording electrodes, were acquired. Units were classified according to the response map scheme (types I-IV). Ninety-two acceptable recordings were made. Most units had simple APs (simple-spiking units); nine units had both simple and complex APs, which are bursts of spikes embedded on slow, transient depolarizations (complex-spiking units). Of 83 simple-spiking units, 46 were classified as follows: type I/III (9 units), type II (9 units), type III (25 units), type IV (2 units), and type IV-T (1 unit). One complex-spiking unit was classifiable (a type III unit); six were unclassifiable because of weak acoustic responses. Classifying 39 other simple-spiking units and 2 complex-spiking units was impossible, because they were either injured or lost before sufficient data were acquired. Many simple-spiking units showed depolarization or hyperpolarization (approximately 5-10 mV) during acoustic stimulation; some were hyperpolarized during the stimulus-off period. Type I/III units were not hyperpolarized during off-best-frequency (off-BF) stimulation. In contrast, many type II units were hyperpolarized by off-BF frequencies, suggesting that they received strong inhibitory sideband inputs. When inhibited, some type III units were hyperpolarized. Type IV units were hyperpolarized during inhibition even at low levels (<60 dB SPL); sustained depolarizations occurred only at higher levels, suggesting that they receive strong inhibitory and weak excitatory inputs. Several intracellular response properties were statistically different from those of extracellularly recorded units. Intracellularly recorded type II units had higher thresholds and lower maximum BF-driven and noise-driven rates than their extracellularly recorded counterparts. Type I/III units recorded intracellularly had lower maximum BF-driven rates. Type III units recorded intracellularly had higher maximum noise rates compared with those recorded extracellularly. Weaker acoustic responses most likely result from membrane disruption, but heightened responses may be related to weakened chloride-channel-dependent inhibition due to altered driving forces resulting from KCl leakage. Firing rates of simple-spiking units increased monotonically with increasing levels of depolarizing current pulses. In contrast, many complex-spiking units responded nonmonotonically to depolarizing current injection. The monotonic rate-versus-current curves and the nonmonotonic rate-versus-sound level curves of type IV and III units suggest that the acoustic behavior is the result of extrinsic inhibitory inputs and not due solely to intrinsic membrane properties.


Myosin V stepping mechanism.
We observe the myosin V stepping mechanism by traveling wave tracking. This technique, associated with optical tweezers, allows one to follow a scattering particle in a two-dimensional plane, with nanometer accuracy and a temporal resolution in the microsecond range. We have observed that, at the millisecond time scale, the myosin V combines longitudinal and vertical motions during the step. Because at this time scale the steps appear heterogeneous, we deduce their general features by aligning and averaging a large number of them. Our data show that the 36-nm step occurs in three main stages. First, the myosin center of mass moves forward 5 nm; the duration of this short prestep depends on the ATP concentration. Second, the motor performs a fast motion over 23 nm; this motion is associated to a vertical movement of the myosin center of mass, whose distance from the actin filament increases by 6 nm. Third, the myosin head freely diffuses toward the next binding site and the vertical position is recovered. We propose a simple model to describe the step mechanism of the dimeric myosin V.


Effects of the novel NMDA antagonists CP-98,113, CP-101,581 and CP-101,606 on cognitive function and regional cerebral edema following experimental brain injury in the rat.
The present study evaluated the effects of two novel N-methyl-D-aspartate (NMDA) receptor blockers and ifenprodil derivatives, CP-101,606 and CP-101,581, and their racemic mixture CP-98,113, on spatial memory and regional cerebral edema following experimental fluid-percussion (FP) brain injury in the rat (n = 66). Fifteen minutes after brain injury (2.5 atm), animals received either (1) CP-98,113 (5 mg/kg, i.p., n = 11), (2) CP-101,581 (5 mg/kg, i.p., n = 13), (3) CP-101,606 (6.5 mg/kg, i.p., n = 12), or (4) DMSO vehicle (equal volume, n = 12); followed by a continuous 24-h subcutaneous infusion of drug at a rate of 1.5 mg/kg/h by means of miniature osmotic (Alzet) pumps implanted subcutaneously. Control (uninjured) animals were subjected to identical anesthesia and surgery without injury and received DMSO vehicle (n = 8); CP-98,113 (5 mg/kg, i.p., n = 3); CP-101,581 (5 mg/kg, i.p., n = 3); or CP-101,606 (6.5 mg/kg, i.p., n = 3). FP brain injury produced a significant cognitive impairment assessed at 2 days postinjury using a well-characterized testing paradigm of visuospatial memory in the Morris Water Maze (MWM) (p < 0.001). Administration of either CP-98,113, CP-101,581, or CP-101,606 had no effect on sham (uninjured) animals, but significant attenuated spatial memory impairment assessed at 2 days postinjury (p = 0.004, p = 0.02, or p = 0.02, respectively). Administration of CP-89,113 but not CP-101,581 or CP-101,606 significantly reduced the extent of regional cerebral edema in the cortex adjacent to the site of injury (p < 0.05) and in the ipsilateral hippocampus (p < 0.05) and thalamus (p < 0.05). These results suggest that excitatory neurotransmission may play a pivotal role in the pathogenesis of memory dysfunction following traumatic brain injury (TBI) and that blockade of the NMDA receptor may significantly attenuate cognitive deficits associated with TBI.


Towards standardization of echocardiography for the evaluation of left ventricular function in adult rodents: a position paper of the ESC Working Group on Myocardial Function.
Echocardiography is a reliable and reproducible method to assess non-invasively cardiac function in clinical and experimental research. Significant progress in the development of echocardiographic equipment and transducers has led to the successful translation of this methodology from humans to rodents, allowing for the scoring of disease severity and progression, testing of new drugs, and monitoring cardiac function in genetically modified or pharmacologically treated animals. However, as yet, there is no standardization in the procedure to acquire echocardiographic measurements in small animals. This position paper focuses on the appropriate acquisition and analysis of echocardiographic parameters in adult mice and rats, and provides reference values, representative images, and videos for the accurate and reproducible quantification of left ventricular function in healthy and pathological conditions.


Transgenic Cotton-Fed Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) Affects the Parasitoid Encarsia desantisi Viggiani (Hymenoptera: Aphelinidae) Development.
Cotton cultivars expressing Cry proteins are widely used to control lepidopteran pests. The effects of transgenic plants containing insecticidal Cry proteins on non-target species must be comprehended for a better and rational use of this technology for pest management. We investigated the influence of the Bt cotton cultivars NuOPAL and FM 975 on biological parameters of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), a non-target pest of Bt cotton cultivars and on its parasitoid Encarsia desantisi Viggiani (Hymenoptera: Aphelinidae). The experiments were conducted in a climatized room, and the non-transgenic near isolines were used for rearing whiteflies as control hosts. The effects of the Bt cotton cultivars on the period of embryonic and larval development and the percentage of adult emergence of B. tabaci were assessed. The period required for embryonic, larval, and pupal development and the percentage of emergence and longevity of E. desantisi females were determined using Bt cotton-fed and non-Bt cotton-fed B. tabaci as hosts. Both Bt cotton cultivars resulted in a decrease of approximately 20% of adult emergence of B. tabaci. Differently, an increase of approximately 10% of adult emergence of E. desantisi was observed for parasitoids that used hosts fed with both Bt cotton cultivars. However, female parasitoid longevity decreased when their hosts were fed on Bt cotton cultivars. Our data suggest that the use of Bt cotton cultivars in association with the biological control agent E. desantisi could be functional for the management of B. tabaci in Bt cotton crops.


Long-Term Ticagrelor in Patients With Prior Coronary Stenting in the PEGASUS-TIMI 54 Trial.
Background Coronary stent type and risk of stent thrombosis remain important factors affecting recommended duration of dual antiplatelet therapy. We investigated the efficacy and safety of long-term ticagrelor in patients with prior coronary stenting enrolled in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial. Methods and Results Patients in PEGASUS-TIMI 54 had a myocardial infarction 1 to 3 year prior and were randomized 1:1:1 to ticagrelor 60 or 90 mg BID or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events). Stent thrombosis was prospectively adjudicated (Academic Research Consortium definition). Baseline characteristics were compared by most recent stent type (bare metal versus drug-eluting stent and first- versus later-generation drug-eluting stent). Treatment arms were compared using Cox proportional hazards models. Of 21 162 patients randomized, 80% (n=16 891) had prior coronary stenting. Following randomization, myocardial infarction was the most frequent ischemic event in patients with prior stenting in the placebo arm, occurring in 5.2% of patients (Type 1: 4.1%), followed by cardiovascular death (2.3%), stroke (1.7%), and stent thrombosis (0.9%). Ticagrelorpooled reduced major adverse cardiovascular events (7.0% versus 8.0%; hazard ratio [HR], 0.85; 95% CI, 0.75-96) regardless of stent type (bare metal stent versus drug-eluting stent: pinteraction=0.767; first versus later generation: pinteraction=0.940). The rate of any stent thrombosis was numerically lower with ticagrelorpooled (0.7% versus 0.9%; HR, 0.73; 95% CI, 0.50-1.05) and Thrombolysis in Myocardial Infarction major bleeding was increased (HR, 2.65; 95% CI, 1.90-3.68). Conclusions Long-term ticagrelor reduces major adverse cardiovascular events in patients with prior myocardial infarction and coronary stenting regardless of stent type, with the benefit driven predominantly by reduction in de novo events. Nonfatal major bleeding is increased with ticagrelor. Registration Information clinicaltrials.gov. Identifier: NCT01225562.


Electrocatalytic Production of C3-C4 Compounds by Conversion of CO2 on a Chloride-Induced Bi-Phasic Cu2O-Cu Catalyst.
Electrocatalytic conversion of carbon dioxide (CO2) has recently received considerable attention as one of the most feasible CO2 utilization techniques. In particular, copper and copper-derived catalysts have exhibited the ability to produce a number of organic molecules from CO2. Herein, we report a chloride (Cl)-induced bi-phasic cuprous oxide (Cu2O) and metallic copper (Cu) electrode (Cu2OCl) as an efficient catalyst for the formation of high-carbon organic molecules by CO2 conversion, and identify the origin of electroselectivity toward the formation of high-carbon organic compounds. The Cu2OCl electrocatalyst results in the preferential formation of multi-carbon fuels, including n-propanol and n-butane C3-C4 compounds. We propose that the remarkable electrocatalytic conversion behavior is due to the favorable affinity between the reaction intermediates and the catalytic surface.


Identification of the sequence determinants of protein N-terminal acetylation through a decision tree approach.
N-terminal acetylation is one of the most common protein modifications in eukaryotes and occurs co-translationally when the N-terminus of the nascent polypeptide is still attached to the ribosome. This modification has been shown to be involved in a wide range of biological phenomena such as protein half-life regulation, protein-protein and protein-membrane interactions, and protein subcellular localization. Thus, accurately predicting which proteins receive an acetyl group based on their protein sequence is expected to facilitate the functional study of this modification. As the occurrence of N-terminal acetylation strongly depends on the context of protein sequences, attempts to understand the sequence determinants of N-terminal acetylation were conducted initially by simply examining the N-terminal sequences of many acetylated and unacetylated proteins and more recently by machine learning approaches. However, a complete understanding of the sequence determinants of this modification remains to be elucidated. We obtained curated N-terminally acetylated and unacetylated sequences from the UniProt database and employed a decision tree algorithm to identify the sequence determinants of N-terminal acetylation for proteins whose initiator methionine (iMet) residues have been removed. The results suggested that the main determinants of N-terminal acetylation are contained within the first five residues following iMet and that the first and second positions are the most important discriminator for the occurrence of this phenomenon. The results also indicated the existence of position-specific preferred and inhibitory residues that determine the occurrence of N-terminal acetylation. The developed predictor software, termed NT-AcPredictor, accurately predicted the N-terminal acetylation, with an overall performance comparable or superior to those of preceding predictors incorporating machine learning algorithms. Our machine learning approach based on a decision tree algorithm successfully provided several sequence determinants of N-terminal acetylation for proteins lacking iMet, some of which have not previously been described. Although these sequence determinants remain insufficient to comprehensively predict the occurrence of this modification, indicating that further work on this topic is still required, the developed predictor, NT-AcPredictor, can be used to predict N-terminal acetylation with an accuracy of more than 80%.


Analysis of Blimp-1 and PD-1/PD-L1 Immune Checkpoint in an Autoimmune Thyroiditis Animal Model.
B lymphocyte-induced maturation protein 1 (Blimp-1) and programmed cell death protein 1 (PD-1) have opposing roles in the development of T cells; however, the mechanism of autoimmune thyroiditis- (AIT-) associated abortion is unclear. The present study investigated the expression of Blimp-1 and PD-1/PD-ligand 1 (PD-L1) in AIT-associated pregnancy loss and elucidated the related signaling pathway involving in the inflammatory response. An experimental fetal loss model with autoimmune thyroiditis was established after murine thyroglobulin- (mTg-) immunized CBA/J female mice mating with Balb/c males. ELISA was employed to investigate the TgAb level in the serum of CBA/J female mice. The expression of Blimp-1, PD-1/PD-L1, mammalian target protein rapamycin (mTOR), and Foxp3 proteins in the placenta and spleen was detected through immunofluorescence staining and western blotting. ELISA indicated that the serum TgAb level in the mTg group was higher than that in the control group (P < 0.001). Fetal resorption rates increased in the mTg group compared with those in the control group (45.63% vs. 3.1%, P < 0.05). Blimp-1 levels in the placenta and spleen were higher in the AIT-related miscarriage group than in the control group. However, the expression of PD-1/PD-L1 and Foxp3 was significantly decreased in the placenta and spleen in the AIT-related miscarriage group. Blimp-1 participates in the pathogenesis of autoimmune thyroid disease-associated pregnancy loss through the inflammatory immune response, which is potentially mediated through the PD-1/PD-L1 signaling pathway.


[Assessment of influence of dose variation on the effectiveness and toxicity of cytostatic therapy of disseminated breast cancer].
Main indices of efficacy such as objective response and stabilization frequency, objective response median and survival rate were evaluated in 84 patients with disseminated breast cancer receiving different doses of cytostatics: high-dose chemotherapy (HDC) plus transplantation of peripheral blood stem cells, standard-dose (SDC), dose reduced by 20% (RDC20) or by 50% (RDC50). There was an inverse correlation between complete+partial response frequency, on the one hand, and dosage, on the other: highest dose--70% and lowest dose--11.1%. Objective response median in both groups was pretty close--8.5 +/- 5.5 and 5 +/- 0.4% months, respectively. The lowering of dose involved a higher risk of tumor progression from 15% after HDC, 46.6%--SDC and 44.4%--RDC20 to 61.1% after RDC50, with likelihood of objective response decreasing. Nether median nor mean survival rates depended on dosage, nor the difference was significant (p = 0.72). Hence, adequate dose proved to be an important factor, as far as treatment efficacy is concerned. Escalation to high dose was followed by an increase in objective response rates to 70%, SDC - 35.7%, RDC20--33.4% and RDC50--11.1%. Yet, nether dose escalation nor dose reduction involved significant variation in survival (p = 0.72).


Calgary Diversion Program: A Community-based Alternative to Incarceration for Mentally Ill Offenders.
The management of mentally ill people committing minor criminal offences has been a social concern in Canada for more than thirty years. Processing of these individuals through the Justice system results in a well-known 'revolving door' syndrome. One approach to this problem is the diversion of these offenders from the Justice system to the network of health and social services that can address their overall well-being. A lack of empirical evidence on diversion programs has been identified as a main roadblock to their acceptance. To describe outcomes and service utilization of clients using the Calgary Diversion Program, a community-based alternative to incarceration for persons with serious mental disorders who commit minor offences. The study employed mixed quantitative and qualitative methods, and used a quasi-experimental design with the clients serving as their own controls. The Calgary Diversion Program was formed in 2002, with this study spanning client enrollment (n=179) from 2002-2003. Before to after program enrolment comparisons found justice system complaints, charges and court appearances to have been reduced between 84% and 91% in those clients that participated successfully in the program, while at the same time found reductions of between 25% and 48% of acute services. Both quantitative and qualitative results indicated a high degree of satisfaction on the part of both providers and clients. Statistically significant improvement in the Brief Psychiatric Rating Scale values between baseline and three months after program entry were observed, while quality of life measurement showed statistically significant improvements in six of nine indicators. Acute health care and justice system costs were compared for the nine months prior to referral and the nine months following referral, with an average reduction in total costs of CAD 1,721 per client. The findings presented in this paper are the first significant contribution to empirical research on diversion programs in Canada. The study suggests improved outcomes, support from clients and providers, and reduced overall costs. However, the nature of the study design limits firm conclusions to be made. Longer term follow-up is a key area for future research. IMPLICATION FOR HEALTH POLICIES: This results identified through the study, as well as the accompanying information on the Calgary program's implementation and functioning, are an important building block in moving towards a strategy to address a long-standing social concern. In an era of cost-consciousness, policy makers need to consider programs that not only have the opportunity to improve patient outcomes, but as well show promise in reducing health and other social service costs.


Cardiac and vascular changes in mice after exposure to ultrafine particulate matter.
Increased ambient air particulate matter (PM) concentrations are associated with risk for myocardial infarction, stroke, and arrhythmia, and ultrafine PM (UFPM) might be particularly toxic to the cardiovascular system. Recent epidemiological studies are beginning to offer mechanistic insights, yet the rodent model remains a valuable tool to explore potential mechanisms. This article reviews a series of studies from our laboratory demonstrating the promise of mouse models to link health effects to biological mechanisms. Specifically, data from 6- to 10-wk-old male ICR mice exposed to intratracheal instillation of 100 microg of UFPM collected from the Chapel Hill, NC airshed are described. Studies of ischemia/reperfusion, vascular function, and hemostasis are described. In summary, UFPM exposure doubles the size of myocardial infarction attendant to an episode of ischemia and reperfusion while increasing postischemic oxidant stress. UFPM alters endothelial-dependent and -independent regulation of systemic vascular tone; increases platelet number, plasma fibrinogen, and soluble P-selectin levels; and reduces bleeding time, implying enhanced thrombogenic potential. Taking these findings together, this model of acute UFPM exposure in the mouse indicates that UFPM induces a prothrombotic state and decreases vasomotor responsiveness, thereby offering insight into how UFPM could contribute to vascular events associated with thrombosis and ischemia and increasing the extent of infarction.


Opinions of health care professionals and the public after eight years of euthanasia legislation in the Netherlands: a mixed methods approach.
The practice of euthanasia and physician-assisted suicide (PAS) in the Netherlands has been regulated since 2002 by the Euthanasia Act. In the ongoing debate about the interpretation of this Act, comparative information about the opinions of the different stakeholders is needed. To evaluate the opinions of Dutch physicians, nurses and the general public on the legal requirements for euthanasia and PAS. A cross-sectional survey among Dutch physicians and nurses in primary and secondary care and members of the Dutch general public, followed by qualitative interviews among selected respondents. The participants were: 793 physicians, 1243 nurses and 1960 members of the general public who completed the questionnaire; 83 were interviewed. Most respondents agreed with the requirement of a patient request (64-88%) and the absence of a requirement concerning life expectancy (48-71%). PAS was thought acceptable by 24-39% of respondents for patients requesting it because of mental suffering due to loss of control, chronic depression or early dementia. In the case of severe dementia, one third of physicians, 58% of nurses and 77% of the general public agreed with performing euthanasia based on an advance directive. Interviewees illustrated these findings and supported the Act. Health care professionals and the general public mostly support the legal requirements for euthanasia and PAS. The law permits euthanasia or PAS for mental suffering but this possibility is not widely endorsed. The general public is more liberal towards euthanasia for advanced dementia than health care professionals. We conclude that there is ample support for the law after eight years of legal euthanasia.


Prevention of temporal alopecia following rhytidectomy: the prophylactic use of minoxidil. A study of 60 patients.
Temporal hair loss that results from traumatized hair follicles following rhytidectomy is an unsightly complication that can distress both the patient and the operating surgeon. Topical minoxidil is a proven therapy for androgenic alopecia and female senile alopecia. It has also been found to be useful in preventing the hair loss that commonly follows hair transplantation. To analyze through a retrospective study the effect of topical minoxidil on the incidence of temporal hair loss following facelift procedures. To our knowledge this is the first study to investigate the role of minoxidil in preventing post-rhytidectomy temporal alopecia. The charts of 60 women with a mean age of 58 years who underwent primary cervicofacial rhytidectomy were studied. Either a standard SMAS/flap technique or pliation was done in all cases. Each patient received either 2% or 5% topical minoxidil for 2 weeks before surgery and for 4 weeks after surgery, with a 5-day break period beginning on the day of surgery. Patients were monitored for complications immediately postoperatively and in 3-6 months of follow-up. Almost 80% of the patients underwent SMAS/flap procedures. Transient temporal alopecia was noted in only one patient, 6 weeks after discontinuing minoxidil. This resolved within 4 weeks of its reintroduction. The only other complications noted included minor hematomas (3.3%), skin slough/infection (1.7%), minor transient and localized edema (8.3%), minor ecchymosis (1.7%), a unilateral neuropraxia of the buccal nerve lasting 3 months (1.7%), and a minor temporary unilateral skin depression (1.7%). Side effects of minoxidil were not observed. On comparing our findings to results of larger rhytidectomy series in which minoxidil was not used prophylactically, and our experience before using minoxidil, we conclude that minoxidil plays a role in effectively preventing the temporal hair loss that occurs following primary cervicofacial rhytidectomies. We also found that minoxidil did not negatively impact on the risk of hematoma formation, skin necrosis, edema, or ecchymosis. Side effects of minoxidil did not present a problem.


Androgenic status in patients with lepromatous leprosy.
To assess the incidence of testicular atrophy by evaluation of hormonal status, testicular histology and sperm production in chronic lepromatous patients. Forty-one male patients with a mean age of 39.5 years (range 16-57) were studied at the Leprosy Hospital, Istanbul, Turkey, and were compared with 15 age-matched controls with proven fertility. Reduced testicular size was observed in 51% and gynaecomastia in 27%. Of the 31 patients who were married, 15 were primarily or secondarily infertile. Twelve of 16 patients had oligospermia or azoospermia. The mean basal luteinizing hormone (LH), follicle stimulating hormone (FSH) and oestradiol levels were significantly elevated and the level of testosterone significantly reduced when compared with the control group. Whenever leprosy is diagnosed patients should be informed of the need for treatment of an acute attack and the need for routine assessment of FSH, LH, testosterone and oestradiol levels to detect hypogonadism and potential infertility.


Laser-Controlled Torsions: Four-Dimensional Theory and the Validity of Reduced Dimensionality Models.
A multitude of possible applications along with unique coherence, chirality, and symmetry properties makes the control of molecular torsion with moderately strong, nonresonant laser pulses a fascinating subject. A description of combined rotation and torsion requires at least four angular degrees of freedom, which is challenging for the majority of systems. Lower-dimensional models have been proposed but also questioned. Here, we develop a four-dimensional model for the coupled rotational-torsional motions of molecules consisting of two identical moieties. By comparing four-dimensional calculations with a two-dimensional model, we define conditions under which the lower-dimensional model is valid. In particular, we point to the crucial role of coordinate dependence of the polarizability tensor. Our results do not agree with those of previous four-dimensional calculations but support the conclusions of recent experiments.


Hepatitis C and HIV incidence and harm reduction program use in a conflict setting: an observational cohort of injecting drug users in Kabul, Afghanistan.
Armed conflict may increase the risk of HIV and other pathogens among injecting drug users (IDUs); however, there are few prospective studies. This study aimed to measure incidence and potential predictors, including environmental events and needle and syringe distribution and collection program (NSP) use, of hepatitis C virus (HCV) and HIV among IDUs in Kabul, Afghanistan. Consenting adult IDUs completed interviews quarterly in year 1 and semi-annually in year 2 and HCV and HIV antibody testing semi-annually through the cohort period (November 2007-December 2009). Interviews detailed injecting and sexual risk behaviors, NSP service use, and conflict-associated displacement. Quarters with peak conflict or local displacement were identified based on literature review, and key events, including insurgent attacks and deaths, were reported with simple counts. Incidence and predictors of HCV and HIV were measured with Cox proportional hazards models. Of 483 IDUs enrolled, 385 completed one or more follow-up visits (483.8 person-years (p-y)). All participants were male with a median age of 28 years and a median duration of injecting of 2 years. Reported NSP use among the participants ranged from 59.9 to 70.5 % in the first year and was 48.4 and 55.4 % at 18 and 24 months, respectively. There were 41 confirmed deaths, with a crude death rate of 93.4/1000 p-y (95 % confidence interval (CI) 67.9-125) and overdose as the most common cause. HCV and HIV incidence were 35.6/100 p-y (95 % CI 28.3-44.6) and 1.5/100 p-y (95 % CI 0.6-3.3), respectively. Changing from injecting to smoking was protective for HCV acquisition (adjusted hazard ratio (AHR) = 0.53, 95 % CI 0.31-0.92), while duration of injecting (AHR = 1.09, 95 % CI 1.01-1.18/year) and sharing syringes (AHR = 10.09, 95 % CI 1.01-100.3) independently predicted HIV infection. There is high HCV incidence and high numbers of reported deaths among male Kabul IDUs despite relatively consistent levels of harm reduction program use; peak violence periods did not independently predict HCV and HIV risk. Programming should increase awareness of HCV transmission and overdose risks, prepare clients for harm reduction needs during conflict or other causes of displacement, and continue efforts to engage community and police force support.


Cro's role in the CI Cro bistable switch is critical for {lambda}'s transition from lysogeny to lytic development.
CI represses cro; Cro represses cI. This double negative feedback loop is the core of the classical CI-Cro epigenetic switch of bacteriophage lambda. Despite the classical status of this switch, the role in lambda development of Cro repression of the P(RM) promoter for CI has remained unclear. To address this, we created binding site mutations that strongly impaired Cro repression of P(RM) with only minimal effects on CI regulation of P(RM). These mutations had little impact on lambda development after infection but strongly inhibited the transition from lysogeny to the lytic pathway. We demonstrate that following inactivation of CI by ultraviolet treatment of lysogens, repression of P(RM) by Cro is needed to prevent synthesis of new CI that would otherwise significantly impede lytic development. Thus a bistable CI-Cro circuit reinforces the commitment to a developmental transition.


Zygomatico-maxillary Reconstruction with Computer-aided Manufacturing of a Free DCIA Osseous Flap and Intraoral Anastomoses.
Craniomaxillofacial reconstruction using virtual surgical planning, computer-aided manufacturing, and new microsurgical techniques optimizes patient-specific and defect-directed reconstruction. A 3D customized free deep circumflex iliac artery (DCIA) flap with intraoral anastomoses was performed on a 23-year-old man with a posttraumatic right zygomatico-maxillary defect with failure of alloplastic implant reconstruction. An osseous iliac crest flap was sculpted based on a customized 3D model of the mirror image of the patient's unaffected side to allow for perfect fit to the zygomatico-maxillary defect. An intraoral dissection of the facial artery and vein was performed within the right cheek mucosa and allowed for end-to-end microvascular anastomoses. 3D preoperative planning and customized free DCIA osseous flap combined with an intraoral microsurgical technique provided restoration of facial esthetics and function without visible scars. In cases where zygomatico-malar reconstruction by alloplastic material fails, a customized free DCIA osseous flap can be designed by virtual surgical planning to restore facial appearance and function.


Activated carbon load equalization of gas-phase toluene: effect of cycle length and fraction of time in loading.
Fluctuating pollutant concentrations pose challenges in the design and operation of air pollution control devices such as biofilters. Effective load equalization could decrease or eliminate many of these difficulties. In research described here, experiments were conducted to evaluate effects of cycle length and fraction of time contaminants are supplied on the degree of load equalization achieved by passively operated granular activated carbon (GAC) beds. Columns packed with Calgon BPL 4 x 6 mesh GAC were subjected to a variety of cyclic loading conditions in which toluene was supplied at concentrations of 1000 or 250 ppm, during loading intervals, and uncontaminated air flowed through the columns during no-loading intervals. The fraction of time when toluene was supplied ranged from 1/2 to 1/6, and cycle lengths ranged from 6 to 48 h. Results demonstrate that passively operated GAC columns can temporarily accumulate contaminants during intervals of high influent concentration and desorb contaminants during intervals of no loading, resulting in appreciable load equalization without need for external regeneration by heating or other means. Greater load equalization was achieved as the fraction of time toluene was loaded decreased and as the cycle length decreased. A pore and surface diffusion model, able to predict the level of contaminant concentration attenuation in GAC columns with reasonable accuracy, was used to further explore the range of load equalization performance expected from columns of various packed bed depths.


Limitations in Faculty Advancement for Underrepresented Groups in Academic Otolaryngology.
Despite the increasing racial diversity of the United States, representation in academic medicine faculty does not reach concordance with the general population and worsens with higher rank. Few studies have examined this within academic Otolaryngology and surgical subspecialties. This project aims to compare rank equity in academic Otolaryngology on self-reported gender and race/ethnicity between the years 2000 and 2020. Publicly available data were obtained from the Association of American Medical Colleges under the "Data & Reports" section for the years 2000 and 2020. The report comprised of full-time faculty from all U.S. medical schools. To determine parity between faculty ranks across gender and race/ethnicity, rank equity index (REI) was calculated for associate/assistant, professor/associate, and professor/assistant professor comparisons. The percentage of women faculty in Otolaryngology has increased from 21% in 2000 to 37% in 2020; however, they did not achieve parity at all rank comparisons for both years. On the contrary, men were above parity at all rank comparisons. Improvements in rank equity occurred for Black/African American (Black) and Hispanic Latino/Spanish Origin (Latine) faculty between the years 2000 and 2020; however, when accounting for gender, benefits were concentrated among men. Advancement along the academic ladder is limited for women of all racial groups in academic Otolaryngology. While improved rank equity was seen for Black and Latine faculty, these improvements were largely among men. Future directions should aim to identify barriers to recruitment, retention, and promotion for women and underrepresented in medicine (URiM) academic otolaryngologists and create interventions that diversify Otolaryngology faculty at all ranks. N/A Laryngoscope, 2023.


Anti-Tribbles Pseudokinase 2 (TRIB2)-Immunization Modulates Hypocretin/Orexin Neuronal Functions.
Recent findings showed that 16%-26% of narcolepsy patients were positive for anti-tribbles pseudokinase 2 (TRIB2) antibody, and the intracerebroventricular administration of immunoglobulin-G purified from anti-TRIB2 positive narcolepsy patients caused hypocretin/orexin neuron loss. We investigated the pathophysiological role of TRIB2 antibody using TRIB2-immunized rats and hypocretin/ataxin-3 transgenic (ataxin-3) mice. Plasma, cerebrospinal fluid (CSF), and hypothalamic tissues from TRIB2-immunized rats were collected. Anti-TRIB2 titers, hypocretin contents, mRNA expressions, the cell count of hypocretin neurons, and immunoreactivity of anti-TRIB2 antibodies on hypocretin neurons were investigated. The plasma from ataxin-3 mice was also used to determine the anti-TRIB2 antibody titer changes following the loss of hypocretin neurons. TRIB2 antibody titers increased in the plasma and CSF of TRIB2-immunized rats. The hypothalamic tissue immunostained with the sera from TRIB2-immunized rats revealed positive signals in the cytoplasm of hypcretin neurons. While no changes were found regarding hypothalamic hypocretin contents or cell counts, but there were significant decreases of the hypocretin mRNA level and release into the CSF. The plasma from over 26-week-old ataxin-3 mice, at the advanced stage of hypocretin cell destruction, showed positive reactions against TRIB2 antigen, and positive plasma also reacted with murine hypothalamic hypocretin neurons. Our results suggest that the general activation of the immune system modulates the functions of hypocretin neurons. The absence of a change in hypocretin cell populations suggested that factors other than anti-TRIB2 antibody play a part in the loss of hypocretin neurons in narcolepsy. The increased anti-TRIB2 antibody after the destruction of hypocretin neurons suggest that anti-TRIB2 antibody in narcolepsy patients is the consequence rather than the inciting cause of hypocretin cell destruction.


Developing practice guidelines for psychoanalysis.
Consensus-based practice guidelines codify clinical intelligence and the rich oral tradition in medicine. Because they reflect actual practice, they are readily accepted by clinicians as a basis for external review. This article illustrates the development of guidelines for a psychoanalytic approach to the large pool of patients who present with a depression. It suggests an integrated biopsychosocial approach to these individuals that is useful in current practice, and it offers propositions that may be tested in future research undertakings. Eventually, practice guidelines such as these may form the basis of economical systems of health care that avoid arbitrary, clinically untenable limitations on services.


The microbiome of the middle meatus in healthy adults.
Rhinitis and rhinosinusitis are multifactorial disease processes in which bacteria may play a role either in infection or stimulation of the inflammatory process. Rhinosinusitis has been historically studied with culture-based techniques, which have implicated several common pathogens in disease states. More recently, the NIH Human Microbiome Project has examined the microbiome at a number of accessible body sites, and demonstrated differences among healthy and diseased patients. Recent DNA-based sinus studies have suggested that healthy sinuses are not sterile, as was previously believed, but the normal sinonasal microbiome has yet to be thoroughly examined. Middle meatus swab specimens were collected from 28 consecutive patients presenting with no signs or symptoms of rhinosinusitis. Bacterial colonization was assessed in these specimens using quantitative PCR and 16S rRNA pyrosequencing. All subjects were positive for bacterial colonization of the middle meatus. Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes were the most prevalent and abundant microorganisms detected. Rich and diverse bacterial assemblages are present in the sinonasal cavity in the normal state, including opportunistic pathogens typically found in the nasopharynx. This work helps establish a baseline for understanding how the sinonasal microbiome may impact diseases of the upper airways.


Unique presence of a manganese catalase in a hyperthermophilic archaeon, Pyrobaculum calidifontis VA1.
We had previously isolated a facultatively anaerobic hyperthermophilic archaeon, Pyrobaculum calidifontis strain VA1. Here, we found that strain VA1, when grown under aerobic conditions, harbors high catalase activity. The catalase was purified 91-fold from crude extracts and displayed a specific activity of 23,500 U/mg at 70 degrees C. The enzyme exhibited a K(m) value of 170 mM toward H(2)O(2) and a k(cat) value of 2.9 x 10(4) s(-1).subunit(-1) at 25 degrees C. Gel filtration chromatography indicated that the enzyme was a homotetramer with a subunit molecular mass of 33,450 Da. The purified catalase did not display the Soret band, which is an absorption band particular to heme enzymes. In contrast to typical heme catalases, the catalase was not strongly inhibited by sodium azide. Furthermore, with plasma emission spectroscopy, we found that the catalase did not contain iron but instead contained manganese. Our biochemical results indicated that the purified catalase was not a heme catalase but a manganese (nonheme) catalase, the first example in archaea. Intracellular catalase activity decreased when cells were grown anaerobically, while under aerobic conditions, an increase in activity was observed with the removal of thiosulfate from the medium, or addition of manganese. Based on the N-terminal amino acid sequence of the purified protein, we cloned and sequenced the catalase gene (kat(Pc)). The deduced amino acid sequence showed similarity with that of the manganese catalase from a thermophilic bacterium, Thermus sp. YS 8-13. Interestingly, in the complete archaeal genome sequences, no open reading frame has been assigned as a manganese catalase gene. Moreover, a homology search with the sequence of kat(Pc) revealed that no orthologue genes were present on the archaeal genomes, including those from the "aerobic" (hyper)thermophilic archaea Aeropyrum pernix, Sulfolobus solfataricus, and Sulfolobus tokodaii. Therefore, Kat(Pc) can be considered a rare example of a manganese catalase from archaea.


Manganese(III) acetate mediated oxidative radical cyclizations. Toward vicinal all-carbon quaternary stereocenters.
Manganese(III) acetate mediated oxidative radical cyclizations have been used to synthesize a range of densely functionalized and sterically congested cyclopentane-lactones. A number of the resulting lactones contain vicinal all-carbon quaternary stereocenters adjacent to a tertiary benzylic stereocenter and are formed with high levels of stereocontrol.


Childbearing in radiology training and early career: Challenges, opportunities, and finding the best time for you.
For many women, radiology residency occurs during the childbearing years and they often question when is the best time to have children. Anxiety regarding fertility and pregnancy-related complications contribute to early career burnout in women physicians and many have fertility regrets. Supporting radiologists in training and early in their career as they navigate pregnancy and childbearing is critical to achieving a diverse workforce and leadership. Herein, we explore career-related challenges of childbearing and highlight opportunities for radiologists in residency, fellowship, and early in their career, so that they can make an informed childbearing decision.


Analysis of nonlinear gain-induced effects on short-pulse amplification in doped fibers by use of an extended power equation.
Optical pulse amplification in doped fibers is studied using an extended power transport equation for the coupled pulse spectral components. This equation includes the effects of gain saturation, gain dispersion, fiber dispersion, fiber nonlinearity, and amplified spontaneous emission. The new model is employed to study nonlinear gain-induced effects on the spectrotemporal characteristics of amplified subpicosecond pulses, in both the anomalous and the normal dispersion regimes.


Small computer algorithms for comparing therapeutic performances of single-plane iridium implants.
We present a uniform method for selecting an optimum implant geometry by presenting techniques for evaluating the therapeutically significant maximum dose rate (herein referred to as the "maximum dose rate"), the reference isodose (85% of the maximum dose rate), and the area enclosed by the reference isodose contour. The therapeutic performances of planar iridium implants may be compared by evaluating their respective maximum dose rates, reference isodoses , and areas within the reference isodose contours. Because these parameters are mathematically defined, they reproducibly describe each implant geometry. We chose a small microcomputer to develop these comparison algorithms so that the radiotherapist need not have large, expensive computer facilities available to conduct his own studies. The development of these algorithms led to some significant conclusions and recommendations regarding the placement of interstitial implants. Using seeds that are centrally located in the array to evaluate the maximum dose contour avoids underestimating the array's maximum dose rate. This could occur if edge or corner seeds were used. Underestimating the maximum dose rate (and hence the reference isodose contour area) may have a serious therapeutic outcome, because the actual total treatment dosage may be excessive. As ribbon spacing is increased, there is a point beyond which the reference isodose contours become decoupled. At this point, a single relatively uniform reference isodose contour separates into several contours. This effect not only complicates the planimetry calculations, but it also adversely affects the therapeutic efficacy of the implant by producing therapeutically "cold" regions.


The acute retroviral syndrome and the pathogenesis of HIV-1 infection.
The acute retroviral syndrome associated with primary HIV-1 infection is characterized by clinical signs of immune activation, multi-system dysfunction, and high levels of cell-associated and plasma viremia, p24 antigenemia, and proviral burden. Clinical abnormalities associated with acute HIV-1 infection and measures of viral burden and replication generally decline in concert with seroconversion. Despite clearance of virus, patients experiencing severe forms of the acute retroviral syndrome appear to have a poorer prognosis than patients with asymptomatic primary infection. This accelerated natural history may be due to the virulence of strains causing symptomatic infection, sequelae of initial high-titer viremia and consequent high viral burden, or immune depletion through immunopathologic mechanisms accelerated by strong antigenic stimulus in primary infection. Early intervention with anti-retroviral and immune modulatory agents has the potential to alter the natural history of patients with this syndrome.


Circulated activated platelets and increased platelet reactivity in patients with Behçet's disease.
Behçet's disease (BD) is a multisystem disorder. Venous as well as arterial thrombosis is a common complication of BD but exact pathogenetic mechanism of the thrombotic tendency is not well known. This study aimed to evaluate circulating activated platelets and platelet reactivity in Behçet's patients. Twenty-two Behçet's patients (4 female, 18 male; mean age 38.6 +/- 10.9 years) and 20 control subjects (8 female, 12 male; mean age 38.8 +/- 9.4 years) were included. Those patients who had hypertension, hyperlipidemia, peripheral or coronary artery disease, hepatic or renal function abnormality, and who were using aspirin and other platelet-active drugs were excluded. Platelet activity and reactivity to adenosine diphosphate (ADP) were measured by whole blood flow cytometry. We assessed markers of platelet degranulation (P-selectin; CD62P) and the activated glycoprotein IIb/IIIa receptor (PAC1 binding to fibrinogen binding site) before and after stimulation with ADP. Platelet P-selectin expression was not significantly different between patients and control subjects both at baseline (p=0.420) and after stimulation (p=0.56). Baseline (p=0.001) and ADP-stimulated (p=0.003) PAC1 binding was significantly higher in Behçet's patients than in the control group. Clinical activity has no effect on P-selectin expression and PAC1 binding. There is evidence of platelet activity and hyperreactivity in patients with BD and this may contribute to a prothrombotic state. In addition to aspirin, other antiplatelet drugs may be useful in the prevention and treatment of thrombosis in Behçet's patients.


[Treatment strategies and research progress of acute ilio-femoral deep vein thrombosis].
In the past,treatment of acute ilio-femoral deep vein thrombosis (IFDVT) was mainly based on anticoagulation alone,but 30%-50% of patients will develop post-thrombotic syndrome,causing a serious medical burden.Thrombus removal technology such as catheter-directed thrombolysis and percutaneous mechanical thrombectomy can effectively remove blood clots and compensate for the deficiencies of simple anticoagulation,which is expected to improve the prognosis of such disease,but the current evidence is insufficient,and other treatments such as filter implantation and compression therapy are also controversial.This article summarizes the treatment strategies and the latest progress of acute IFDVT,hoping to help the treatment of this type of disease.


A resonant single-wing bionic piezoelectric motor based on a biasing self-clamping mechanism.
In this study, a resonant single-wing bionic piezoelectric motor based on a biasing self-clamping mechanism inspired by dragonfly flight was designed, assembled, and tested. The main mechanism of the designed piezoelectric motor includes a mover (including a vibrator, clamping foot, bionic pedestal, etc.), a stator, and other auxiliary components. The clamping foot of the mover contacts the side of the stator to form a biasing self-clamping mechanism, which can achieve a clamping effect within half a cycle of the vibrator's resonant vibration. The piezoelectric plate on the vibrator receives a single harmonic excitation from the signal generator, causing the base plate to bend and distort. The base plate drives the clamping foot to move regularly, causing the mover to perform a linear motion. Moreover, repeated single harmonic excitations can realize the continuous movement of the mover. The structure of the piezoelectric motor was optimized using COMSOL6.0, which is a finite element analysis software. The first-order bending vibration of the vibrator was chosen as the working mode through finite element simulation, and an experimental platform was built. The performance of the prototype piezoelectric motor was tested and verified on the experimental platform. The final experimental data show that under the conditions of 300 Vp-p excitation voltage and 109 Hz driving frequency, the maximum no-load speed of the prototype reaches 6.184 mm/s, and the maximum load of the motor is 4 g.