Detecting Salient Objects via Color and Texture Compactness Hypotheses.
In recent years, the object-level saliency detection has attracted much research attention, due to its usefulness in many high-level tasks. Existing methods are mostly based on the contrast hypothesis, which regards the regions with high contrast in a certain context as salient objects. Although the contrast hypothesis is effective in many scenarios, it cannot handle some difficult cases. As a remedy to address the weakness of contrast hypothesis, we propose a novel compactness hypothesis, which assumes salient regions are more compact than background from the perspectives of both color layout and texture layout. Based on the compactness hypotheses, we implement an effective object-level saliency detection method. In the proposed method, we first construct a weak saliency map based on the compact hypotheses, then collect samples from the weak saliency map to train a dedicated classifier. This classifier is applied on each individual pixel of the input image to produce a confidence score. Finally, the confidence scores are used to form a saliency map. This process is carried out at different scales, and the corresponding results are integrated into the formation of the final saliency map. The proposed approach is evaluated on eight benchmark data sets, where it delivers the competitive performance compared with the state-of-the-art methods.


Leaving the meristem behind: the genetic and molecular control of leaf patterning and morphogenesis.
Leaves, which play an essential role in plant photosynthesis, share common features such as being flat structures, but also show an impressive variability in their sizes and shapes. Following its initiation in the meristems, leaf development is patterned along three polarization axes to establish its basic architecture. This process is further complicated in the case of compound leaves with the formation of new growth axes. Growth and differentiation must be properly coordinated to regulate the size and the flatness of the leaf. This review provides an overview of the genetic and molecular regulatory networks underlying leaf development, with an emphasis on leaf polarity and the comparison of simple and compound leaves.


The seven countries study: 2,289 deaths in 15 years.
Among 11,579 men ages 40-59 without evidence of cardiovascular disease, 2,289 died in 15 years, 618 from coronary heart disease. The 15 cohorts in seven countries (four regions) differed in all-causes death rate, mainly reflecting great differences in coronary mortality. Among characteristics of entry, only mean blood pressure helped to explain cohort differences in all-causes death rate. Three-quarters of the variance in coronary death rate was accounted for by differences in mean serum cholesterol and blood pressure of the cohorts. The mortality risk for individuals was examined in each of the regions. For coronary death, age, serum cholesterol, blood pressure, and smoking were highly significant in all regions except Japan, where coronary deaths were too few for evaluation. Relative weight was not significant anywhere. Physical activity was significant only in southern Europe, where differences are associated with socioeconomic status. For all-causes death, age and blood pressure were highly significant risk factors in all regions as was smoking habit, except in Japan. Relative body weight tended to be a negative risk factor everywhere, significantly so in southern Europe. Expectations for coronary death from the experience in the United States and northern Europe greatly exceeded observed deaths in southern Europe for men of their age, serum cholesterol, blood pressure, smoking habits, physical activity, and relative weight. The reverse, prediction of coronary deaths in America and in northern Europe from the southern European experience, greatly underestimated the deaths observed. Similar cross-predictions between the United States and northern Europe were good for all-causes deaths, excellent for coronary deaths. Analysis of time trends in relationships of mortality to entry characteristics showed continued importance of age, blood pressure, and smoking and a tendency for the importance of cholesterol to fall in the last 5 years of follow-up.


The level of viral antigen presented by hepatocytes influences CD8 T-cell function.
CD8 T cells exert their antiviral function through cytokines and lysis of infected cells. Because hepatocytes are susceptible to noncytolytic mechanisms of viral clearance, CD8 T-cell antiviral efficiency against hepatotropic viruses has been linked to their capacity to produce gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). On the other hand, intrahepatic cytokine production triggers the recruitment of mononuclear cells, which sustain acute and chronic liver damage. Using virus-specific CD8 T cells and human hepatocytes, we analyzed the modulation of virus-specific CD8 T-cell function after recognition peptide-pulsed or virally infected hepatocytes. We observed that hepatocyte antigen presentation was generally inefficient, and the quantity of viral antigen strongly influenced CD8 T-cell antiviral function. High levels of hepatitis B virus production induced robust IFN-gamma and TNF-alpha production in virus-specific CD8 T cells, while limiting amounts of viral antigen, both in hepatocyte-like cells and naturally infected human hepatocytes, preferentially stimulated CD8 T-cell degranulation. Our data document a mechanism where virus-specific CD8 T-cell function is influenced by the quantity of virus produced within hepatocytes.


Finding Small Root Canals.
One of the main reasons for failure of teeth that have been root treated is the inability to locate and clean canals that are very small or not identified by the clinician. In contemporary practice the use of dyes, such as methylene blue, or magnificatin, such as the microscope are used rotinely in these situations to find the canal orifice in the pulp chamber. Prior to this, other more aggressive methods have been used, such as that identified in 1920.


Microwave-assisted functionalization of the Aurivillius phase Bi2SrTa2O9: diol grafting and amine insertion vs. alcohol grafting.
Microwave-assisted functionalization of the layered Aurivillius phase Bi2SrTa2O9 by alcohols is thoroughly investigated. The grafting of linear aliphatic and bulky alcohols is studied as a function of the starting material, underlining the importance of the prefunctionalization of the layered perovskite, for instance by butylamine. In addition, the functionalization by α,ω-alkanediols is explored. α,ω-alkanediols bearing long alkyl chains (n C > 3) adopt an unprecedented pillaring arrangement, whereas 1,3-propanediol and ethyleneglycol adopt a bilayer arrangement, only one out of the two hydroxyl groups being coordinated. Finally, the reactivities of alcohols and amines towards insertion are compared: the preferential reactivity of the two functional groups appears to be strongly dependent of the reaction conditions, and especially of the water content. This study is further extended to the case of amino-alcohol insertion. In this case, the amine group is preferentially bound, but it is possible to control the grafting of the alcohol moiety, thus going from a bilayer arrangement to a pillaring one. This work is of particular importance to be able to functionalize easily and rapidly layered oxides with elaborated molecules, bearing several different potentially reactive groups.


Idiopathic Small Bowel Intussusception in Adults: Conservative Versus Surgical Management.
Intussusception is a rare diagnosis in adults and generally has a pathological cause. In this case report, we highlight an adult, male patient who presented with typical signs and symptoms of intussusception, and a diagnosis was subsequently confirmed with imaging. After 24 hours of no clinical improvement, the intussusception was resolved through a laparoscopic approach. No lead point or other pathological cause was identified that may have contributed to the development of intussusception. The idiopathic presentation of intussusception in adults is scarcely represented in the scientific literature, making its best management practices vague and leaving room for studies regarding best surgical management. We conducted a brief literature review of adult idiopathic intussusception cases and found fewer than 25 cases documented since 2010. Our analysis revealed that the majority of cases were resolved through a laparoscopic method and only about a quarter were conservatively managed with supportive measures. More research is needed in this subject matter to more accurately determine the need for surgical management in cases of adult idiopathic intussusception.


Role of CYP3A in ethanol-mediated increases in acetaminophen hepatotoxicity.
CYP2E is considered the only form of cytochrome P450 responsible for ethanol-mediated increases in acetaminophen hepatotoxicity. However, in experimental systems used for investigating ethanol-mediated increases in acetaminophen hepatotoxicity, animals are withdrawn from ethanol for 16 to 24 hr before the administration of acetaminophen to ensure the clearance of ethanol from the circulation. In rats, CYP2E has been shown to decrease to control levels after this time period of withdrawal from ethanol. We have previously shown in cultured human and rat hepatocytes, and in intact rats, that ethanol induces CYP3A in addition to CYP2E. To determine if there might be a role for CYP3A in ethanol-mediated APAP hepatotoxicity in addition to the recognized role for CYP2E, we investigated the effect of triacetyloleandomycin (TAO) on acetaminophen hepatotoxicity in ethanol-pretreated rats, as well as the effect of 11 hr withdrawal from ethanol on hepatic levels of CYP3A and CYP2E. TAO was dissolved in saline instead of dimethylsulfoxide, the solvent most usually employed, since dimethylsulfoxide inhibits CYP2E. Rats were administered 6.3% ethanol as part of the Lieber-DeCarli diet for 7 days, followed by replacement of the liquid diet with water for 11 hr. This 11-hr withdrawal from ethanol resulted in a decrease in hepatic levels of ethanol-induced CYP2E; however, considerable induction was still evident. There was no significant decrease in CYP3A. TAO completely prevented the histologically observed liver damage from acetaminophen in ethanol-pretreated rats, but did not prevent the increase in serum levels of AST. In ethanol-pretreated rats, exposure to APAP in the absence of TAO was associated with a 75% decrease in CYP3A, compared to animals exposed to APAP in the presence of TAO. These results suggest that CYP3A may have been suicidally inactivated by acetaminophen in the absence of TAO. Our findings suggest that CYP3A has a major role in ethanol-mediated increases in acetaminophen hepatotoxicity.


T-cell lymphoma presenting as painful ophthalmoplegia.
To present a case of peripheral T-cell lymphoma presenting as painful ophthalmoplegia. A 61-year-old woman presented with a 2-week history of headache and eyeball pain. Examination showed mild exophthalmos, complete ophthalmoplegia, and ptosis of the left eye. Under the impression of nonspecific orbital inflammation, she was treated with oral prednisone with initial response. Two months later, she revisited the clinic with exacerbated symptoms. Anterior orbitotomy and incisional biopsy was performed for the inferior rectus muscle lesion. Histopathologic examination revealed an infiltrate of atypical lymphoid cells between degenerative muscle bundles. It was consistent with peripheral T-cell lymphoma. A metastatic workup was performed without any evidence of extraorbital tumor. The patient was recommended to be treated with chemotherapy, however, refused to take the treatment. The patient died of progression of the disease in a month. T-cell lymphoma in the orbit can present as painful ophthalmoplegia and take a rapid clinical course. The disease should be regarded as one of the differential diagnosis for painful ophthalmoplegia refractory to corticosteroid therapy.


Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study.
This randomized, double-blind, placebo-controlled, ascending-dose study was conducted in healthy volunteers to evaluate the safety of the investigational cyanide antidote hydroxocobalamin. Four ascending dosing groups received intravenous doses of 2.5, 5, 7.5 or 10 g hydroxocobalamin over 7.5 to 30 minutes at a constant infusion rate. Volunteers (n = 136) randomized 3:1 to receive hydroxocobalamin or placebo underwent a 4-day in-house observation after infusion on Day 1 and follow-up visits on Days 8, 15, and 28. The most common drug-related adverse events were asymptomatic and self-limiting chromaturia and reddening of the skin, which are attributed to the red color of hydroxocobalamin. Other adverse events included pustular/papular rash, headache, erythema at the injection site, decrease in lymphocyte percentage, nausea, pruritus, chest discomfort, and dysphagia. Hydroxocobalamin was associated with an increase in blood pressure in some volunteers. Blood pressure changes peaked toward the end of hydroxocobalamin infusion and typically returned to baseline levels by 4 hours postinfusion. Maximum mean changes from baseline in systolic blood pressure ranged from 22.6 to 27.0 mmHg across hydroxocobalamin doses compared with 0.2 to 6.7 mmHg in the corresponding placebo groups. Maximum mean change from baseline in diastolic blood pressure ranged from 14.3 to 25.4 mmHg across hydroxocobalamin doses compared with -3.0 to 3.8 mmHg in the corresponding placebo groups. Two allergic reactions that occurred within minutes after start of the 5- and 10-g hydroxocobalamin infusions were successfully managed with dexamethasone and/or dimethindene maleate. Timely intervention for acute cyanide poisoning could entail administration of an antidote in the prehospital setting based on a presumptive diagnosis. Results of this placebo-controlled study in healthy volunteers corroborate previous studies and French postmarketing experience in cyanide-exposed patients in suggesting that the safety profile of hydroxocobalamin is consistent with prehospital or hospital use.


From globally coupled maps to complex-systems biology.
Studies of globally coupled maps, introduced as a network of chaotic dynamics, are briefly reviewed with an emphasis on novel concepts therein, which are universal in high-dimensional dynamical systems. They include clustering of synchronized oscillations, hierarchical clustering, chimera of synchronization and desynchronization, partition complexity, prevalence of Milnor attractors, chaotic itinerancy, and collective chaos. The degrees of freedom necessary for high dimensionality are proposed to equal the number in which the combinatorial exceeds the exponential. Future analysis of high-dimensional dynamical systems with regard to complex-systems biology is briefly discussed.


Proton nuclear magnetic resonance spectroscopy of human transferrin N-terminal half-molecule: titration and hydrogen-deuterium exchange.
The binding of Ga(III) to the proteolytically derived N-terminal half-molecule of human transferrin (HTF/2N) was studied by proton nuclear magnetic resonance spectroscopy. The pH-dependent titration curves of the histidinyl C(2) proton chemical shifts were altered upon formation of the GaIIIHTF/2N(C2O4) ternary complex. Two high-pK'a histidines failed to titrate when the metal and synergistic anion formed a complex with the protein. These results implicated two histidinyl residues as direct ligands to the metal. The rates of hydrogen-deuterium exchange for the C(2) protons of certain histidinyl residues were substantially decreased by metal ion binding. The two ligand histidines were protected from exchange, and a third, low-pK'a, histidinyl residue was protected. We propose that this third histidinyl residue is involved in anion binding and may serve as the base in the putative proton-relay scheme proposed for complex formation.


Poly[diimidazole-μ(4)-oxalato-μ(2)-oxalato-dicopper(II)].
The title compound, [Cu(2)(C(2)O(4))(2)(C(3)H(4)N(2))(2)](n), was obtained as an unexpected product under hydro-thermal conditions. The Cu(II) atom is in a Jahn-Teller-distorted octa-hedral environment formed by one imidazole N atom and five O atoms from three oxalate anions. The two independent oxalate anions are situated on centres of inversion and coordinate to the Cu(II) atom in two different modes, viz. bidentate and monodentate. The bidentate anions bridge two Cu(II) atoms, whereas the monodentate anions bridge four Cu(II) atoms, leading to a layered arrangement parallel to (100). These layers are further linked into a final three-dimensional network structure via inter-molecular N-H⋯O hydrogen bonds. The title compound is isotypic with the Zn analogue.


Double quantization of the regressor space for long-term time series prediction: method and proof of stability.
The Kohonen self-organization map is usually considered as a classification or clustering tool, with only a few applications in time series prediction. In this paper, a particular time series forecasting method based on Kohonen maps is described. This method has been specifically designed for the prediction of long-term trends. The proof of the stability of the method for long-term forecasting is given, as well as illustrations of the utilization of the method both in the scalar and vectorial cases.


Is the prescription of amphetamine justified as a harm reduction measure?
Although amphetamine is the most widely illicitly used drug in the United Kingdom after cannabis, relatively few problematic users present to treatment agencies. Injecting amphetamine users are a high risk group as far as HIV transmission is concerned. This paper reviews the first 3 years' operation of an oral amphetamine prescribing programme for injecting users. Over half the subjects ceased injecting, and there was a considerable reduction in injecting by the remainder. 85% had not used or shared injecting equipment during the programme. However, subjects reported still using street amphetamine and offending, although at a lower rate than previously. There was little change in sexual practices. There was an increase in primary amphetamine users presenting for treatment. There is a case to be made that closely controlled and monitored programmes such as this can be justified on harm reduction grounds. A number of issues concerned with amphetamine prescribing are discussed.


Three-dimensional cobalt oxide microstructures with brush-like morphology via surfactant-dependent assembly.
In this study, three-dimensional cobalt oxide microstructures were developed. Cobalt oxide microdumbbells and microspheres, assembled by nanowires and primary particles, were successfully synthesized by a multistep hydrothermal method. Of all of the structures, the cobalt oxide microdumbbell electrode possesses the largest surface area of 70.8 m(2) g(-1) and the highest specific capacitance of 407.5 F g(-1). The as-prepared electrode also demonstrates excellent electrochemical stability and retains 97.5% of the initial capacitance after 2000 charge-discharge cycles. This performance is attributed to the desirable morphology, uniform microarchitecture stability, and high surface area. The results show that the as-fabricated Co3O4 is a promising electrode material for supercapacitor applications.


Characterization of Chitosan-Hybridized Diatomite as Potential Delivery Systems of Oxaliplatin and 5-Fluorouracil Drugs: Equilibrium and Release Kinetics.
The current work involves the modification of diatomite's biosiliceous frustules employing chitosan polymer chains (CS/Di) to serve as low-cost, biocompatible, multifunctional, and enhanced pharmaceutical delivery systems for 5-fluorouracil (5-Fu) together with oxaliplatin (OXPL). The CS/Di carrier displayed strong loading characteristics, notably at saturation (249.17 mg/g (OXPL) and 267.6 mg/g (5-Fu)), demonstrating a substantial 5-Fu affinity. The loading of the two types of medications onto CS/Di was conducted based on the kinetic behaviors of the conventional pseudo-first-order theory (R2 > 0.90). However, while the loading of OXPL follows the isotherm assumptions of the classic Langmuir model (R2 = 0.99), the loading of 5-Fu displays Fruendlich isotherm properties. Therefore, the 5-Fu loading displayed physical, heterogeneous, and multilayer loading properties, whereas the loading of OXPL occurred in homogeneous and monolayer form. The densities of occupied active sites of CS/Di were 37.19 and 32.8 mg/g for the sequestrations of OXPL and 5-Fu, respectively. Furthermore, by means of multimolecular processes, each loading site of CS/Di can bind up to 8 molecules of OXPL and 9 molecules of 5-Fu in a vertical orientation. This observation explains the higher loading capacities of 5-Fu in comparison to OXPL. The loading energies, which exhibit values <40 kJ/mol, provide confirmation of the dominant and significant consequences of physical processes as the regulating mechanisms. The release patterns of OXPL and 5-Fu demonstrate prolonged features over a duration of up to 120 h. The release kinetic simulation and diffusion exponents which are more than 0.45 provide evidence of the release of OXP and 5-Fu via non-Fickian transportation characteristics and the erosion/diffusion mechanism. The CS/Di carrier exhibited a substantial enhancement in the cytotoxicity of OXPL and 5-Fu against HCT-116 carcinoma cell lines, resulting in a reduction in cell viability by 4.61 and 2.26% respectively.


Influence of quality of sleep in the first trimester on blood pressure in the third trimester in primipara women.
Purpose: The purpose of this study was to clarify the relationship between decreased sleep quality during the first trimester and a rise in blood pressure during an otherwise normal course of pregnancy in primipara women. Materials and methods: We recruited 128 pregnant women (primipara) who visited the obstetrics and gynecology clinic for medical examination, of which 89 were longitudinally investigated from the first to the third trimester after obtaining informed consent. A survey was conducted in the first, second, and third trimesters to evaluate sleep quality using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J). Patients were assigned to either a good sleep quality group (PSQI-J ≤ 5) or a poor sleep quality group (PSQI-J ≥ 6). Blood pressure was measured using a home blood pressure measurement method. We analyzed the relationship between sleep quality in the first trimester and blood pressure during pregnancy. Results: The increase in morning systolic blood pressure from first to third trimester was larger in the poor sleep quality group than in the good sleep quality group (7.1 ± 7.0 vs. 3.0 ± 5.6 mmHg, p < .01). Sleep latency (r = 0.38, β = 0.43, p = .02) and sleep disturbances (r = 0.24, β = 0.33, p = .04) in the first trimester affected the increase in systolic blood pressure during pregnancy. Conclusions: Understanding sleep quality at the beginning of pregnancy can help predict a rise in systolic blood pressure in the third trimester. This emphasizes the importance of sleep education during pregnancy.


Electrophoretic Separation of Hemoglobins from the Chicken.
The filter paper strips used in V. L. Johnson and J. S. Dunlap "Electrophoretic separation of hemoglobins from the chicken" [Science 122, 1186 (1955)] should be listed as follows: S. and S. No. 2043 B.


Patents, commercialization and the Canadian stem cell research community.
There has been a great deal of discussion in relevant literature on the adverse impact of commercialization agendas and the patenting regime on research in emerging fields. We sought to assess the perceived impact of these factors on the stem cell research community in Canada. We surveyed 283 researchers from Canada's Stem Cell Network using a survey instrument informed by relevant literature and systematic consultations with Canadian and international regulators, stem cell researchers and research ethics experts designed to identify pressing ethical, legal and social issues relevant to stem cell research. A total of 108 researchers responded to the survey. Results indicate that although many researchers believe that patents may have adverse effects on research, very few have encountered any such effects in practice. The researchers admitted to withholding data to protect patenting opportunities, while also maintaining that patents did not contribute to publication delays. The pressure to commercialize their research was largely held to be reasonable by researchers.


Leaf Age, Canopy Position, and Habitat Affect the Carbon Isotope Discrimination and Water-Use Efficiency in Three C3 Leguminous Prosopis Species from a Hyper-Arid Climate.
The present study involved measurements of the stable carbon isotope composition (δ13C) and intrinsic water-use efficiency (iWUE) of three C3 leguminous Prosopis spp. (P. juliflora, P. cineraria, and P. pallida) foliage at different canopy positions (east and west) from saline (SLH) and non-saline habitats (NSH). Integrated measurements of the stable carbon isotope composition (δ13C) of plant tissue were broadly used to study iWUE, taking into consideration the effect of leaf age and canopy position on C isotope discrimination. Mature foliage of P. pallida from an SLH with a west canopy position had significantly higher δ13C (less negative) than that from NSH. On the west side, Δ13C values ranged from 17.8‱ (P. pallida) to 22.31‱ (P. juliflora) for a west canopy position, while they varied from 18.05‱ (P. pallida) to 22.4‱ (P. cineraria) on the east canopy side. Because the patterns are similar for the three Prosopis species, the difference in carbon isotope discrimination (Δ13C) between the canopy position (west and east) is relatively consistent among species and sites, ranging between 17.8 ± 4.43‱ for the young foliage in the west and 18.05 ± 4.35‱ for the east canopy position. The iWUE of P. pallida was twice that of P. cineraria. The iWUE of P. juliflora was higher from NSH than SLH. Mature leaves possessed a higher iWUE than the young leaves. We concluded that exotic P. juliflora and P. pallida have higher iWUE values than the native P. cineraria, which might be due to the rapid below-ground development of plant roots in the Arabian deserts of the United Arab Emirates (UAE). This could enable the alien species access to deeper humid soil layers or water resources.


Atypical cells in pregnancy and postpartum smears.
The cytologic changes of pregnancy and the postpartum period are presented. Atypical cells were identified in 12% of smears; the majority of these atypical cells were related to degenerating decidual cells. Cells thought to represent changes due to folic acid deficiency are also described, and the features that help separate decidual cells from other cell types in the genital tract are illustrated. True neoplasia, when present, tended to persist after delivery, and these cells should not be confused with pregnancy-associated atypia.


Monolingual and bilingual children's use of the mutual exclusivity constraint.
The use of the mutual exclusivity constraint was examined in three-year-old and six-year-old children who were either monolingual in English (N = 32) or bilingual in English/Urdu (N = 32) or in English/Greek (N = 32). Three tests of the constraint were used: disambiguation rejection, and restriction. On the disambiguation test, the mutual exclusivity bias was significantly more evident in five- and six-year-old monolingual children than in their same-age bilingual peers. Monolingual children were also more likely than bilingual children to reject a new name for a familiar object. However, using a restriction test, neither monolingual nor bilingual children readily accepted and restricted typical names for hybrid objects. Developmental differences were also found, as older (five- to six-year-old) monolingual children's responses on the tests were generally more consistent with the constraint than younger (three- to four-year-old) children's responses. Nevertheless, bilingual children did use the constraint, but not to the extent of monolingual children.


Feasibility and Tolerability of Daily Pulse Consumption in Individuals with Peripheral Artery Disease.
The present study investigated the feasibility, tolerability, and adherence of daily consumption of whole pulses (dried beans, peas, lentils, chickpeas) by individuals with peripheral artery disease participating in an 8-week study. Study questionnaires and semi-structured interviews for 26 participants were used to determine prestudy pulse consumption and participants' experiences with respect to adherence, positive and negative effects, bowel routine, satiety, and enjoyment of the foods. Although the majority of participants rarely consumed pulses prior to the study, there was a high rate of adherence to daily consumption of the study foods for 8 weeks despite comments regarding study fatigue during the latter part of the study. Participants had no gastrointestinal side effects (42%) or experienced flatulence that resolved by week 4 (23%), whereas 62% reported improvements in their bowel pattern. By week 8 greater satiety was noted by some participants (19%), with the categories "less afternoon snacking" and "not snacking" receiving more responses. The key finding of this study was that consumption of pulses is a viable approach for this population; however, the frequency of consumption that is tolerable in the long term should be integrated with the dose and timeframe required to achieve and maintain health benefits.


Diagnostic yield of nondiagnostic thyroid nodules is not altered by timing of repeat biopsy.
Guidelines from the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference recommend a repeat fine-needle aspiration biopsy (FNAB) after 3 months for thyroid nodules with a nondiagnostic (ND) result. Our aims were to assess which factors influenced their clinical management and to determine if the timing of the repeat FNAB affects the diagnostic yield. A retrospective institutional review of 298 patients from 1/2006 to 12/2007 with an ND FNAB was performed. The factors influencing the next step in management, including age, gender, history of radiation, presence of Hashimoto's thyroiditis, thyroid-stimulating hormone levels, and ultrasound characteristics, were evaluated. The effect of the time of the repeat FNABs on their diagnostic yield was assessed. Of the 298 patients in our cohort, 9% were referred directly for surgery, 76% had a repeat FNAB, and 15% were observed. Tumor size was the only independent variable correlated with treatment strategy after a ND FNAB. There was not a significant difference in diagnostic yields between repeat FNABs performed earlier than 3 months compared to those preformed later (p=0.58). The timing of repeat FNAB for an initial ND FNAB does not affect diagnostic yield of the repeat FNAB.


Spatio-Temporal Analysis of Suicide-Related Emergency Calls.
Considerable effort has been devoted to incorporate temporal trends in disease mapping. In this line, this work describes the importance of including the effect of the seasonality in a particular setting related with suicides. In particular, the number of suicide-related emergency calls is modeled by means of an autoregressive approach to spatio-temporal disease mapping that allows for incorporating the possible interaction between both temporal and spatial effects. Results show the importance of including seasonality effect, as there are differences between the number of suicide-related emergency calls between the four seasons of each year.


Fear facilitates utilitarian moral judgments: Evidence from a moral judgment task.
Previous research on moral judgment (MJ) has focused on understanding the cognitive processes and emotional factors that influence different types of moral judgment tasks, such as personal and impersonal dilemmas. However, few studies have distinguished between the emotions related to cognition and the complex emotions specifically caused by MJ tasks. This gap in knowledge is important to address to have a better understanding of how emotions influence moral judgment. The aim of this study was to investigate the influence of fear and the role of moral emotions on MJ. Data were collected from 145 participants through jsPsych and analyzed using mixed-model analysis of variance (ANOVA) and correlation analysis. The study found that individuals who were triggered by the fear increased the number of utilitarian moral judgments in personal moral scenarios and lengthened the cognitive process, but not in impersonal moral dilemmas. Hence, we speculate that fear may play a cognitive role in personal moral dilemmas and an emotional role in impersonal moral dilemmas. Another finding is that the complex moral emotions arising from the moral decision-making process may affect the effectiveness of fear and potentially influence moral judgments. However, this study adopts a cautious attitude toward these discoveries, and further verification of this hypothesis should be conducted in the future.


Impaired endothelial release of tissue-type plasminogen activator in patients with chronic kidney disease and hypertension.
We have shown that the capacity for local release of tissue-type plasminogen activator (tPA) from the vascular endothelium is impaired in patients with primary hypertension. Because this response is an important protective mechanism against intravascular clotting, we investigated whether this system is also defective in patients with advanced chronic kidney disease and hypertension. Nine nondiabetic nonsmoking men with chronic kidney disease (glomerular filtration rate 11 to 28 mL/min x 1.73 m2; aged 33 to 75 years) were compared with age-matched healthy controls. Intraarterial infusions of desmopressin, methacholine, and sodium nitroprusside were given locally in the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography and blood collected repeatedly during the desmopressin infusion for determination of stimulated net and total cumulated release of tPA. The maximal release rate of active tPA (P<0.05) and the capacity for acute tPA release were markedly impaired in the renal patients as compared with healthy subjects (ANOVA, P=0.013). Accordingly, the accumulated release of tPA was 1905 (SEM 366) and 3387 (718) ng/L tissue, respectively (P<0.05). However, there were no significant differences in vasodilator responses between the groups. Thus, patients with advanced chronic kidney disease and hypertension have a markedly impaired capacity for acute release of tissue plasminogen activator, despite preserved endothelium-dependent vasodilation. This defect may contribute to a defective local defense against arterial thrombosis.


Adaptive response of lysine and threonine degrading enzymes in adult rats.
The mechanism of variation inlysine and threonine conservation was investigated by measuring the activity of the enzyme initiating the amino acid catabolism in adult rats adapted to different diets. Both liver threonine dehydratase and lysine-ketoglutarate reductase activities were increased by high protein intake. Supplementation with 2% L-lysine HCI to a 5% lactalbumin diet increased liver lysine-ketoglutarate reductase activity three-fold. Feeding a lysine-free diet or a 10% wheat gluten diet significantly decreased the activity below the level obtained by feeding a protein-free diet. In contrast, dietary threonine in either excess or deficiency did not change the liver threonine dehydratase activity. At the same level of lysine intake, an excess of dietary wheat gluten seemed to increase the liver lysine-ketoglutarate reductase activity much more than dietary lactalbumin. These data suggest that the activity of lysine-ketoglutarate reductase in rat liver might be influenced by dietary lysine as well as excesses of other amino acids in wheat gluten. The different response of these two catabolic enzymes to their substrate might explain the variation of lysine and threonine conservation during amino acid deficiency.


High CD34 cell doses do not worsen regimen-related toxicity or early mortality after autologous blood stem cell transplantation for breast cancer.
Some transplant-related complications, such as the engraftment syndrome, are thought to be mediated by cytokines released during expansion of hematopoietic progenitors at the time of neutrophil recovery. Since there is an inverse correlation between CD34(+) cell dose and time to neutrophil recovery, we sought to determine if peritransplant toxicity and early mortality were adversely affected by high CD34(+) cell doses. The study group included 186 women with breast cancer who received high-dose cyclophosphamide, carmustine, thiotepa and an autologous PBSC transplant. The median CD34(+) cell dose was 5.9 x 10(6)/kg (1.0-154.7 x 10(6)/kg). Patients were categorized by CD34(+) cell dose (1.0-3.5, 3.6-5.9, 6.0-19.9, and 20.0-154.7 x 10(6)/kg) for assessment of outcomes. Grades 2-4 mucositis occurred in 49%, cardiac toxicity in 7%, pulmonary toxicity in 5%, cystitis in 4%, diarrhea in 3%, renal toxicity in 1%, and central nervous system toxicity in 1%. A Grade 2-4 regimen-related toxicity occurred in 109 patients (59%) and Grade 3-4 in eight patients (4%). Overall survival was 100% at Day 30, 96% at Day 90, and 89% at 1 year. Treatment-related mortality was 3.8%. In multivariate analyses that included prior chemotherapy, disease status, visceral metastases, prior chest radiation and age, CD34(+) cell dose group was not an independent risk factor for Grade 2-4 mucositis, Grade 2-4 maximum toxicity, Grade > or =3 cumulative toxicity, 90 day survival or 1 year survival. We conclude that CD34(+) cell doses >20 x 10(6)/kg do not affect transplant outcome in a negative or positive fashion.


Female Psychopathy and Mortality.
The mortality of female psychopaths has scarcely been investigated. To estimate the association between psychopathy and mortality, data from subjects having been in forensic psychiatric assessments at Niuvanniemi Hospital during 1984-1993 were linked to the data from the National Death Registry. Sixteen psychopathic females scoring 25 points or higher in the PCL-R scale (psychopaths) were followed up for a median (IQR) 21 (17-25) years and 41 offenders scoring <25 on the PCL-R (non-psychopathic offenders) for 22 (17-25) years. In both psychopath and non-psychopath offender groups, the mortality was significantly higher (p < 0.01) than in the general population, being over 12-fold among psychopathic and over 6-fold among the non-psychopathic offenders.


Secretion of total solids (solutes) in the saliva of long-term tobacco users.
It is generally believed that repeated exposure of a receptor to a stimulus results in inactivation (suppression or adaptation) of the receptor. Most of the methods of tobacco use are linked to the oral cavity where the taste receptors, a primary site for stimulation of salivary secretion, are constantly exposed to tobacco for long time. The present study was designed to document changes in salivary concentration of total solids in response to this effect in chronic tobacco users, if any. Subjects of the study were divided into smokers, pan (tobacco-betel-lime quid) chewers, niswar (moist oral snuff) dippers and non tobacco users as controls. The saliva of each subject was collected under resting condition and following application of crude nicotine and citric acid solutions to the tip of his tongue. After stimulation with nicotine all groups showed a decrease in the total solids concentration but the decrease was not significant in any group. After stimulation with citric acid, further decrease was seen in all groups but it was also insignificant statistically. We conclude that the total solids concentration decreases with the increase in salivary flow rates (and vice versa) in long-term tobacco users, salivary reflex is not adversely affected by long-term use of tobacco and this observation is not much different from that in non users.


The MLL gene and translocations involving chromosomal band 11q23 in acute leukemia.
Reciprocal chromosomal translocations are recurrent features of many hematological malignancies. The cloning of the genes located at the breakpoints of chromosomal translocations in leukemia and lymphoma has led to the identification of new genes involved in carcinogenesis. Molecular studies of the breakpoint of several translocations involving chromosomal band 11q23 led to the cloning of a gene that was named MLL. Based on 7969 cases of acute myeloblastic leukemia (AML) and 1252 cases of acute lymphoblastic leukemia (ALL) taken from the literature, band 11q23 and/or the MLL gene was involved in 5.2% of AML and 22% of ALL. Differences in the frequency and the distribution of translocations were noted according to the type of acute leukemia and age of the patients. Seventy-five different rearrangements involving band 1 q23 have so far been identified, 39 MLL partner genes having been cloned. The fusion of MLL and its partner gene leads to a gain of function of the MLL gene. The accumulating data suggests that the fusion protein affects the differentiation of the hematopoietic pluripotent stem cells or the lymphoid or myeloid committed stem cells by deregulating the HOX gene expression patterns.


Low-dose mitomycin C as a prophylaxis for corneal haze in myopic surface ablation.
To evaluate the efficacy of low-dose (0.002%) mitomycin C (MMC) vs no prophylactic MMC (control) in reducing corneal haze after surface laser ablation. Two-year retrospective follow-up study performed in Jaipur, India. Ninety-two eyes with no MMC application and 83 eyes with 0.002% MMC application during laser epithelial keratomileusis (LASEK) were analyzed in a retrospective chart review with one month, two months, three months, six months, one year, and two years of postoperative follow-up. Postoperative haze, visual acuity, and efficacy ratio (EFFR) then were analyzed statistically. The no-dose MMC and low-dose MMC groups were statistically similar except for a thinner corneal pachymetry (P < .001), higher spherical equivalent error (P = .006), and smaller ablation zone (P = .009) in eyes not treated with MMC when subjected to univariate analysis. Multivariate analysis was used to overcome the preoperative statistical differences among the two groups. Eyes treated with low-dose MMC (0.002%) demonstrated statistically less haze at all postoperative time points and in each myopic subgroup (P < .001). The postoperative uncorrected visual acuity (UCVA) and EFFR, however, showed no difference between the groups, except for better EFFR with MMC at one month (P < .001) and two months (P = .034). Low-dose MMC (0.002%) in eyes after LASEK results in less corneal haze than in eyes not receiving this agent. Concerns regarding the potential toxicity of MMC make a 10-fold less concentration more desirable in refractive surgery. Further comparative study of low- vs higher-dose MMC is recommended to characterize its clinical benefit fully.


Acute and transient psychotic disorders: A review of Indian research.
Acute and transient psychotic disorder (ATPD) was recognized as separate from other psychotic disorders and described in the International Classification of Diseases (ICD) tenth revision for the first time. A lot of research on ATPD has been conducted in India over the last six decades, but a review focusing exclusively on Indian research on ATPD is not available. This paper aims to review the literature on ATPD emerging from India. A combination of search terms "Acute and Transient Psychosis," "acute psychosis," "non-affective psychosis," "non-affective psychotic disorder," "reactive psychosis," "first-episode psychosis," and "India" were searched on various search engines like PUBMED, Medknow, Hinari, and Google Scholar. We also did a hand search for additional relevant articles, including published abstracts of the Indian Journal of Psychiatry from 2007 to 2023. Relevant papers were selected. The prevalence of ATPD varies across different study settings, and it tends to have an abrupt to acute onset, and is primarily associated with stress. Few studies have assessed the subtypes of ATPD, and symptom profile has been inconsistently reported. There is a lack of trials on the effectiveness or efficacy of antipsychotics in ATPD patients. In a large proportion of patients initially diagnosed with ATPD, the diagnosis remains stable, with recurrence varying from 10% to 46.6% based on the duration of follow-up. There is a need for more multicentric studies, studies with larger sample sizes, and consistency in data about risk factors. There is a need to evaluate symptom profile, course, outcome, and treatment outcomes in patients with ATPD using validated instruments to improve our understanding. Further, there is a need for comparative studies to evaluate the risk factors for ATPD.


Liquid-chromatographic determination of indomethacin in blood from newborns with patent ductus arteriosus.
This rapid, accurate "high-performance" liquid-chromatographic procedure is intended for measuring indomethacin in serum from neonates who are receiving indomethacin for symptomatic patent ductus arteriosus. Indomethacin and an internal standard (flufenamic acid) are extracted from serum or plasma with chloroform or diethyl ether at pH 5.0. For the chromatography we used a Waters' Radial Compression Separation System (Radial-NOVA PAK C18 reversed-phase column) and a mobile phase of methanol/sodium acetate buffer (10 mmol/L, pH 3.6), 70/30 by vol. The column effluent is monitored at 254 nm. Both indomethacin and flufenamic acid are eluted within 7 min. Indomethacin can be detected in concentrations as low as 50 micrograms/L, in 100-microL samples. Response varies linearly with indomethacin concentration to at least 2 mg/L. Analytical recovery is 75%; relative recovery is 100%. Precision is excellent. Using this method, we were able to improve the success rate for pharmacological management of symptomatic patent ductus arteriosus, especially in neonates with fast clearance rates for the drug.


Intermunicipal health care consortia in Brazil: strategic behavior, incentives and sustainability.
This article studies strategic behavior in municipal health care consortia where neighboring municipalities form a partnership to supply high-complexity health care. Each municipality partially funds the organization. Depending on the partnership contract, a free rider problem may jeopardize the organization. A municipality will default its payments if it can still benefit from the services, especially when political pressures for competing expenditure arise. The main result is that the partnership sustainability depends on punishment mechanisms to a defaulting member, the gains from joint provision of services and the overall economic environment. Possible solutions to the incentive problem are discussed.


Study on Fabrication of ZnO Waveguide Layer for Love Wave Humidity Sensor Based on Magnetron Sputtering.
The ZnO waveguide layer for the Love wave humidity sensor was fabricated by radio frequency (RF) magnetron sputtering technique using ZnO as the target material. To investigate the effect of RF magnetron sputtering temperature on the ZnO waveguide layer and Love wave device, a series of Love wave devices with ZnO waveguide layer were fabricated at different sputtering temperatures. The crystal orientation and microstructure of ZnO waveguide was characterized and analyzed, and the response characteristics of the Love wave device were analyzed by network analyzer. Furthermore, a humidity measurement system is designed, and the performance of the Love wave humidity sensor was measured and analyzed. The research results illustrate that the performance of the ZnO waveguide layer is improved when the sputtering temperature changes from 25 °C to 150 °C. However, when the sputtering temperature increases from 150 °C to 200 °C, the performance of the ZnO waveguide layer is degraded. Compared with the other sputtering temperatures, the ZnO waveguide layer fabricated at 150 °C has the best c-axis orientation and the largest average grain size (53.36 nm). The Love wave device has the lowest insertion loss at 150 °C. In addition, when the temperature of the measurement chamber is 25 °C and the relative humidity is in the range of 10% to 80%, the fabricated Love wave humidity sensor with ZnO waveguide layer has good reproducibility and long-term stability. Moreover, the Love wave humidity sensor has high sensitivity of 6.43 kHz/RH and the largest hysteresis error of the sensor is 6%.


Prognostic Analysis for Cardiogenic Shock in Patients with Acute Myocardial Infarction Receiving Percutaneous Coronary Intervention.
Cardiogenic shock (CS) is uncommon in patients suffering from acute myocardial infarction (AMI). Long-term outcome and adverse predictors for outcomes in AMI patients with CS receiving percutaneous coronary interventions (PCI) are unclear. A total of 482 AMI patients who received PCI were collected, including 53 CS and 429 non-CS. Predictors for AMI patients with CS including recurrent MI, cardiovascular (CV) mortality, all-cause mortality, and repeated-PCI were analyzed. The CS group had a lower central systolic pressure and central diastolic pressure (both P < 0.001). AMI patients with hypertension history were less prone to develop CS (P < 0.001). Calcium channel blockers and statins were less frequently used by the CS group than the non-CS group (both P < 0.05) after discharge. Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score, CV mortality, and all-cause mortality were higher in the CS group than the non-CS group (all P < 0.005). For patients with CS, stroke history was a predictor of recurrent MI (P = 0.036). CS, age, SYNTAX score, and diabetes were predictors of CV mortality (all P < 0.05). CS, age, SYNTAX score, and stroke history were predictors for all-cause mortality (all P < 0.05). CS, age, and current smoking were predictors for repeated-PCI (all P < 0.05).


[Efficacy of tigecycline in treating severe infections of patients with hematological diseases].
To evaluate the efficacy and safety of tigecycline in treating secondary infections of patients with hematological diseases. A total of 85 cases of hematological patients with secondary infections were classified into empirical and targeted therapy groups. Empirical therapy group was composed of patients receiving tigecycline as an alternative due to ineffective anti-infection treatment for 3-5 days in the absence of microbiological evidence while those taking tigecycline based on microbiological evidence belonged to targeted therapy group. Dosage regimen of tigecycline: loading dose 100 mg, 50 mg every 12 hours as maintenance therapy for 2-4 weeks. Among them, except for 11 cases of bloodstream infections and 2 cases of fever for unknown reasons, the most common site for infection was lower respiratory tract. Among 45 isolated bacterial strains, Stenotrophomonas maltophilia (40%) was the most commonly seen while extended spectrum beta-lactamases (ESBLS)+ multidrug resistant gram negative bacilli 15.6%. Among 5 bacterial strains, there were 3 methicillin-resistant Staphylococcus aureus+golden staphylococci strains and 2 excrement enterococci. The total effective rate of tigecycline was 72.9%. And the bacterial clearance rates of acinetobacter baumannii, ESBLS+ gram-negative bacillus and stenotrophomonas maltophilia were 85%, 70% and 55% respectively. The effect of tigecycline was equivalent for two groups. Pneumonia patients obtained an effective rate of 71%, compared to those with bloodstream infections (54.5%). For patients whose absolute neutrophil counts were less than 0.2 × 10⁹/L, the effective rate decreased obviously (45% vs 81.5%, P = 0.003). Adverse reaction was mild due to mostly gastrointestinal symptoms. Tigecycline is a new treatment choice in treating secondary multidrug resistant infections of patients with hematological diseases. Empirical therapy of tigecycline may improve the therapeutic efficacy of patients non-responding favorably to conventional anti-infectives.


The equal environments assumption of classical twin studies may not hold.
The classical twin method - comprising comparisons of monozygotic (MZ) and dizygotic (DZ) twins - in the domain of cognitive abilities and attainments has led to wide acceptance of results suggesting a large amount of additive genetic variance, with far-reaching implications both for the nature of future studies on the causes of cognitive variance and for intervention policies, as in education. However, this interpretation is only valid if the method observes a number of conditions, which have to hold. Here, we show that the most crucial of these, namely, the equal environments assumption (EEA), may not hold. Consequently, differences in twin correlations might be at least partly explained by treatment effects from parents, teachers, peers, and so on. In addition, well-known interactions at various levels confound the model of simple additive effects on which the classical twin method is predicated and results are interpreted. For example, at a socio-cognitive level, DZ twins may respond to treatments differently from MZ twins. This interaction may further explain MZ-DZ correlation differences. There is abundant evidence for such interactive effects in published twin data. We suggest that there is a need for a more thorough examination of these problems.


Airway and Transpulmonary Driving Pressure by End-Inspiratory Holds During Pressure Support Ventilation.
The precision of quasi-static airway driving pressure (ΔP) assessed in pressure support ventilation (PSV) as a surrogate of tidal lung stress is debatable because persistent muscular activity frequently alters the readability of end-inspiratory holds. In this study, we used strict criteria to discard excessive muscular activity during holds and assessed the accuracy of ΔP in predicting global lung stress in PSV. Additionally, we explored whether the physiological effects of high PEEP differed according to the response of respiratory system compliance (CRS). Adults with ARDS undergoing PSV were enrolled. An esophageal catheter was inserted to calculate lung stress through transpulmonary driving pressure (ΔPL). ΔP and ΔPL were assessed in PSV at PEEP 5, 10, and 15 cm H2O by end-inspiratory holds. CRS was calculated as tidal volume (VT)/ΔP. We analyzed the effects of high PEEP on pressure-time product per minute (PTPmin), airway pressure at 100 ms (P0.1), and VT over PTP per breath (VT/PTPbr) in subjects with increased versus decreased CRS at high PEEP. Eighteen subjects and 162 end-inspiratory holds were analyzed; 51/162 (31.5%) of the holds had ΔPL ≥ 12 cm H2O. Significant association between ΔP and ΔPL was found at all PEEP levels (P < .001). ΔP had excellent precision to predict ΔPL, with 15 cm H2O being identified as the best threshold for detecting ΔPL ≥ 12 cm H2O (area under the receiver operating characteristics 0.99 [95% CI 0.98-1.00]). CRS changes from low to high PEEP corresponded well with lung compliance changes (R2 0.91, P < .001) When CRS increased, a significant improvement of PTPmin and VT/PTPbr was found, without changes in P0.1. No benefits were observed when CRS decreased. In subjects with ARDS undergoing PSV, high ΔP assessed by readable end-inspiratory holds accurately detected potentially dangerous thresholds of ΔPL. Using ΔP to assess changes in CRS induced by PEEP during assisted ventilation may inform whether higher PEEP could be beneficial.


Effects of selective beta 2-adrenoceptor blockade on serum potassium and exercise performance in normal men.
1. The differential effects of beta-adrenoceptor subtypes on potassium fluxes and exercise capacity were compared in eight healthy young men using single oral doses of the selective beta 2-adrenoceptor antagonist ICI-118551, the selective beta 1-adrenoceptor antagonist atenolol or the non-selective beta-adrenoceptor antagonist propranolol. The study was randomized, double-blind and placebo controlled. 2. Potassium in the venous effluent from the exercising muscles increased progressively with increasing exercise intensity. This response was augmented by propranolol, whereas neither atenolol nor ICI-118551 modified the response. After exercise potassium concentration fell exponentially with no difference between the treatment regimens. 3. Cumulative work was significantly reduced by ICI-118551 (6.4%, P = 0.04) and by propranolol (12.4%, P less than 0.01), whereas the reduction with atenolol (5.6%) did not reach statistical significance. 4. Atenolol and propranolol reduced peak heart rate by 23% and 29%, and peak systolic blood pressure by 9% and 11% respectively during maximal exercise. ICI-118551 caused a non-significant reduction in heart rate during submaximal exercise, with a significant reduction at maximum exercise (6% reduction), whereas systolic blood pressure was not different from placebo. Diastolic blood pressures were similar across all treatment regimens. 5. Similar glucose concentrations were obtained at baseline and at exhaustion during all treatment regimens. Lactate concentrations were comparable for any given exercise intensity irrespective of treatment regimens. Propranolol reduced lactate concentrations from the exercising muscles at maximum exercise in proportion to the reduction of maximal exercise capacity. 6. The subjective perception of fatigue was not affected by either beta 1- or beta 2-adrenoceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)


Photoperiodic Flowering Response of Essential Oil, Grain, and Fiber Hemp (Cannabis sativa L.) Cultivars.
Cultivation of hemp (Cannabis sativa L.) in tropical and subtropical regions can be challenging if the flowering behavior of a given cultivar is unknown, poorly understood, or not accurately selected for the photoperiod. Identifying cultivars adapted to local environmental conditions is key to optimizing hemp vegetative and flowering performance. We investigated the effects of varying light cycles in regulating extension growth and flowering response of 15 essential oil and 12 fiber/grain hemp cultivars both indoors and outdoors. Plants were subjected to 11 photoperiods in the controlled rooms ranging from 12 to 18 h, and natural day length in the field. The critical photoperiod threshold was identified for seven essential oil cultivars and two fiber/grain cultivars. "Cherry Wine-CC," "PUMA-3," and "PUMA-4" had the shortest critical day length between 13 h 45 min and 14 h. The flowering of essential oil cultivars was generally delayed by 1-2 days when the photoperiod exceeded 13 h compared with 12 h, and flowering was further delayed by 7-8 days when the photoperiod exceeded 14 h. In fiber/grain cultivars, flowering was generally delayed by 1-3 days when the day length exceeded 14 h. Flowering for most essential oil cultivars was delayed by 5-13 days under a 14-h photoperiod compared with 13 h 45 min, suggesting a photoperiod difference as little as 15 min can significantly influence the floral initiation of some essential oil cultivars. Cultivars represented by the same name but acquired from different sources can perform differently under the same environmental conditions, suggesting genetic variation among cultivars with the same name. Average days to flower of fiber/grain cultivars was correlated with reported cultivar origin, with faster flowering occurring among northern cultivars when compared with southern cultivars. Plant height generally increased as the day length increased in essential oil cultivars but was not affected in fiber/grain cultivars. In addition, civil twilight of ~2 μmol·m-2·s-1 was discovered to be biologically effective in regulating hemp flowering. Collectively, we conclude that most of the essential oil cultivars and some southern fiber/grain cultivars tested express suitable photoperiods for tropical and sub-tropical region cultivation.


Alternative Medicine: Contagion and Cure in Karel Čapek's The White Plague.
Though written amid an atmosphere of unprecedented medical advance in both diagnosis and therapeutics, Karel Čapek's The White Plague takes a starkly critical stance against overconfidence in medical science and its dubious ethical orbit. This article explores Čapek's censure of those who would privilege scientific interest in disease over the holistic plight of the sufferer. Provocatively, Čapek achieves this not only via the play's content, but also-prefiguring aspects of contemporary live art practice by several decades-by placing audience members in worrying proximity to abject ill bodies. Čapek proposes a sort of theatrical homeopathy, suggesting that limited exposure to the threat of disease might spur spectators toward empathy for those who suffer and promote a healthier, more compassionate society.


Pharmacophore-Model-Based Virtual-Screening Approaches Identified Novel Natural Molecular Candidates for Treating Human Neuroblastoma.
The mortality of cancer patients with neuroblastoma is increasing due to the limited availability of specific treatment options. Few drug candidates for combating neuroblastoma have been developed, and identifying novel therapeutic candidates against the disease is an urgent issue. It has been found that muc-N protein is amplified in one-third of human neuroblastomas and expressed as an attractive drug target against the disease. The myc-N protein interferes with the bromodomain and extraterminal (BET) family proteins. Pharmacologically inhibition of the protein potently depletes MYCN in neuroblastoma cells. BET inhibitors target MYCN transcription and show therapeutic efficacy against neuroblastoma. Therefore, the study aimed to identify potential inhibitors against the BET family protein, specifically Brd4 (brodamine-containing protein 4), to hinder the activity of neuroblastoma cells. To identify effective molecular candidates against the disease, a structure-based pharmacophore model was created for the binding site of the Brd4 protein. The pharmacophore model generated from the protein Brd4 was validated to screen potential natural active compounds. The compounds identified through the pharmacophore-model-based virtual-screening process were further screened through molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, and molecular dynamics (MD) simulation approach. The pharmacophore-model-based screening process initially identified 136 compounds, further evaluated based on molecular docking, ADME analysis, and toxicity approaches, identifying four compounds with good binding affinity and lower side effects. The stability of the selected compounds was also confirmed by dynamic simulation and molecular mechanics with generalized Born and surface area solvation (MM-GBSA) methods. Finally, the study identified four natural lead compounds, ZINC2509501, ZINC2566088, ZINC1615112, and ZINC4104882, that will potentially inhibit the activity of the desired protein and help to fight against neuroblastoma and related diseases. However, further evaluations through in vitro and in vivo assays are suggested to identify their efficacy against the desired protein and disease.


Reflections on Democratic Deliberation in Bioethics.
Over the course of six years and more than two dozen meetings, members of the Presidential Commission for the Study of Bioethical Issues learned so many things: about emerging science; technological challenges; citizen engagement; the public's, experts', and our own understandings and misperceptions; and even the nature of our own most cherished values. Our commission's commitment to democratic deliberation began deliberatively, when we decided (in the summer of 2010) upon basic principles to guide our first report. At the time, Craig Venter had just announced that he had used techniques of synthetic biology to "create life," albeit the most elementary form of life, from nonliving building blocks. Headlines alternated between applauding Venter for creating life and accusing him of playing God. It was one of those all-too-frequent instances where sound-bite democracy was headed toward shedding more heat and fear than light and understanding. The commission was asked to take synthetic biology under review and make recommendations to President Obama on how to proceed. We saw the need to question the most salient facts of the matter: what were the fundamental values at stake in this kind of discovery?


[Leiomyosarcoma of the prostate treated with neoadjuvant intra-arterial chemotherapy and pelvic excenteration ; a case report].
A 34-year-old man presented with left inguinal discomfort. Digital rectal examination revealed an enlarged nodular prostate. Computed tomography showed an enlarged prostate invading the bladder and rectum. A histological examination of transrectal prostatic needle biopsy specimens revealed sarcoma of the prostate. He received three courses of neoadjuvant arterial injection chemotherapy consisting of adriamycin (30 mg/m2) and cisplatin (70 mg/m2). Total pelvic excenteration was perfomed. Histopathological examination of the tumor revealed leiomyosarcoma of the prostate. He remains alive 11 months after the operation without recurrence.


Numerical Simulation of Coalescence-Induced Jumping of Multidroplets on Superhydrophobic Surfaces: Initial Droplet Arrangement Effect.
The coalescence-induced droplet jumping on superhydrophobic surfaces (SHSs) has attracted considerable attention over the past several years. Most of the studies on droplet jumping mainly focus on two-droplet coalescence events whereas the coalescence of three or more droplets is actually more frequent and still remains poorly understood. In this work, a 3D lattice Boltzmann simulation is carried out to investigate the effect of initial droplet arrangements on the coalescence-induced jumping of three equally sized droplets. Depending on the initial position of droplets on the surface, the droplet coalescence behaviors can be generally classified into two types: one is that all droplets coalesce together instantaneously (concentrated configuration), and the other is that the initial coalesced droplet sweeps up the third droplet in its moving path (spaced configuration). The critical Ohnesorge number, Oh, for the transition of inertial-capillary-dominated coalescence to inertially limited-viscous coalescence is found to be 0.10 for droplet coalescence on SHSs with a contact angle of 160°. The jumping droplet velocity for concentrated multidroplet coalescence at Oh ⩽ 0.10 still follows the inertial-capillary scaling with an increased prefactor, which indicates a viable jumping droplet velocity enhancement scheme. However, the droplet jumping velocity is drastically reduced for the spaced configuration compared to that for the aforementioned concentrated configuration. Because Oh exceeds 0.10, the effects of initial droplet arrangements on multidroplet jumping become weaker as viscosity plays a key role in the merging process. This work will provide effective guidelines for the design of functional SHSs with enhanced droplet jumping for a wide range of industrial applications.


Rhodium-Catalyzed Enantioselective Defluorinative α-Arylation of Secondary Amides.
We exploited the reactivity of an electronically biased Michael acceptor to perform a defluorinative α-arylation reaction using a chiral diene(L*)-rhodium catalyst. Through this methodology, we are able to obtain various secondary amides, containing a tertiary α-stereocenter and a β,γ-unsaturated gem-difluoro olefin, with excellent enantioselectivities. This methodology addresses the limitations of the previously described α-arylation methods to construct stereo-labile tertiary α-stereocenters. Further investigation of the reaction via in situ 19 F NMR monitoring suggests that the formation of the product leads to the inhibition of the active rhodium catalyst.


Vulnerability and impacts of climate change on forest and freshwater wetland ecosystems in Nepal: A review.
Climate change (CC) threatens ecosystems in both developed and developing countries. As the impacts of CC are pervasive, global, and mostly irreversible, it is gaining worldwide attention. Here we review vulnerability and impacts of CC on forest and freshwater wetland ecosystems. We particularly look at investigations undertaken at different geographic regions in order to identify existing knowledge gaps and possible implications from such vulnerability in the context of Nepal along with available adaptation programs and national-level policy supports. Different categories of impacts which are attributed to disrupting structure, function, and habitat of both forest and wetland ecosystems are identified and discussed. We show that though still unaccounted, many facets of forest and freshwater wetland ecosystems of Nepal are vulnerable and likely to be impacted by CC in the near future. Provisioning ecosystem services and landscape-level ecosystem conservation are anticipated to be highly threatened with future CC. Finally, the need for prioritizing CC research in Nepal is highlighted to close the existing knowledge gap along with the implementation of adaptation measures based on existing location specific traditional socio-ecological system.


Comparative effectiveness of Roux-en-Y gastric bypass and sleeve gastrectomy in super obese patients.
The disproportionate increase in the super obese (SO) is a hidden component of the current obesity pandemic. Data on the safety and efficacy of bariatric procedures in this specific patient population are limited. Our aim is to assess the comparative effectiveness of the two most common bariatric procedures in the SO. Using the Bariatric Outcomes Longitudinal Database from 2007 to 2012, we compared SO patients (BMI ≥ 50) undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Stepwise logistic regression modeling was used to calculate a propensity score to adjust for patient demographics and comorbidities. We identified 50,987 SO patients who underwent RYGB (N = 42,119) or SG (N = 8868). There was no difference in adjusted overall 30-day complication rate comparing RYGB and SG patients (11.5 vs. 11.1 %, p = 0.250). RYGB patients had higher adjusted rates of 30-day mortality (0.3 vs. 0.2 %, p = 0.042), reoperation (4.0 vs. 2.4 %, p < 0.001), and readmission (6.9 vs. 5.5 %, p < 0.001) compared to SG patients. The percent of total weight loss (%TWL) was significantly higher for RYGB patients compared to SG at 3 months (14.1 vs. 13.1 %, p < 0.001), 6 months (25.2 vs. 22.4 %, p < 0.001), and 12 months (34.5 vs. 29.7 %, p < 0.001). RYGB patients had increased resolution of all measured comorbidities: diabetes mellitus (61.6 vs. 50.8 %, p < 0.001), hypertension (43.1 vs. 34.5 %, p < 0.001), gastroesophageal reflux disease (53.9 vs. 32.5 %, p < 0.001), hyperlipidemia (39.7 vs. 32.5 %, p < 0.001), and obstructive sleep apnea (42.8 vs. 40.6 %, p = 0.058) at 12 months compared to SG patients. There are significant differences in comorbidity improvement and resolution as well as weight loss between RYGB and SG in the SO population. There was no difference in overall 30-day complications, but more RYGB patients required readmission and reoperation. However, RYGB was considerably more effective in controlling obesity-related comorbidities. Our results favor performance of RYGB in SO patients of appropriate risk.


Porous membranes for reconstitution of ion channels.
Functional biological synthetic composite (BSC) membranes were made using phospholipids, biological membrane proteins and permeable synthetic supports or membranes. Lipid bilayers were formed on porous polycarbonate (PC), polyethylene terephthalate (PETE) and poly (l-lactic acid) (PLLA) membranes and in 10-100 microm laser-drilled pores in a 96-well plastic plate as measured by increased resistance or decreased currents. Bilayers in 50 microm and smaller pores were stable for up to 4 h as measured by resistance changes or a current after gramicidin D reconstitution. Biological membrane transport reconstitution was then carried out. Using vesicles containing Kv1.5 K(+) channels, K(+) currents and decreased resistance were measured across bilayers in 50 microm pores in the plastic plate and PLLA membranes, respectively, which were inhibited by compound B, a Kv1.5 K(+) channel inhibitor. Functional reconstitution of Kv1.5 K(+) channels was successful. Incorporation of membrane proteins in functional form in stable permeable membrane-supported lipid bilayers is a simple technology to create BSC membranes that mimic biological function which is readily adaptable for high throughput screening.


Jejunal adenocarcinoma with cutaneous metastasis.
Small bowel adenocarcinoma (SBA) is a rare primary gastrointestinal malignancy. We present a 60-year old man who developed a cutaneous metastasis of jejunal adenocarcinoma to his neck. This case highlights the clinicopathologic and immunophenotypic features of this uncommon cutaneous metastasis.


Orbital paraganglioma in a dog.
A 10-year-old Rottweiler presented with right-sided moderately painful exophthalmia, blindness, absence of dazzle and pupillary light reflexes, a swollen optic nerve head and ventrolateral indentation of the globe. On magnetic resonance imaging, a 3 x 2 x 2 cm mass with a fluid filled center and contrast-enhancing periphery was noted posteriolateral of the globe. Orbital ultrasound was used for a guided fine needle aspirate of the mass. Cytology revealed moderate numbers of polygonal cells with lightly basophilic cytoplasm. Several cells showed nuclear pseudoinclusions. Histopathology following exenteration of the orbit revealed an infiltrative, extradural neoplasm surrounding the optic nerve. Cells were arranged in packets. Neoplastic cells were immunopositive for neuron specific enolase, synaptophysin and chromogranin A and immunonegative for cytokeratin. Findings were consistent with an extra-adrenal paraganglioma (neuroendocrine tumour). Although complete excision could not be confirmed on histopathology, the owners reported no apparent tumour recurrence 25 months after surgery. In conclusion a paraganglioma should be considered as a differential diagnosis of an orbital mass.


Effect of proper oral hygiene on gingivitis and dental caries in Swedish schoolchildren.
The present paper reports the effect of a 3-year study of regularly repeated professional toothcleaning on oral hygiene status, gingivitis, and dental caries. At the initiation of the study in 1971, the children were 7-8 years old (Group 1), 10-11 (Group 2) or 13-14 (Group 3). The children were divided into test and control groups. Before the study all the children were examined regarding oral hygiene, state of the gingiva and dental caries. Throughout the 3-year period the controls brushed their teeth with a 0.2% sodium fluoride solution once a month under supervision. During the first 2 years of the trial all the children of the test groups were given professional oral prophylaxis once every second week during the school terms. During the third year the interval between consecutive prophylactic sessions was prolonged to 4 weeks in Groups 1 and 2 and to 8 weeks in Group 3. The results demonstrated that regularly repeated professional cleaning of the teeth combined with fluoride applications and toothbrushing instructions, over a 3-year period in schoolchildren resulted in the establishment and maintenance of excellent oral hygiene standards. Inflammation of the marginal gingiva almost entirely disappeared, and practically no new carious lesions developed.


Genetic implication for an interaction between release factor one and ribosomal protein L7/L12 in vivo.
Strains with mutant alleles of the genes encoding release factor one (RF1), prfA, and ribosomal protein L7/L12, rplL, have been analyzed. The prfA1 allele has previously been shown to be associated with temperature sensitivity for growth at 43 degrees C and increased misreading of the nonsense codons UAG and UAA. Here we show that the prfA1 mutation is a nucleotide substitution that results in an arginine to proline change at amino acid position 137 in RF1. This alters the factor in a domain which may be involved in ribosome-binding. The rplL564 allele codes for a mutant form of protein L7/L12 that has a change in its conserved, translation-factor binding, domain. The rplL564 mutation suppresses the temperature sensitive phenotype and the increased translational misreading associated with the prfA1 allele, while other studied rplL mutant alleles do not. These data are consistent with an interaction between L7/L12 and RF1 in vivo.


A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer.
To evaluate the efficacy and toxicity of erlotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway. Thirty-eight patients with MBC were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o. daily) plus bevacizumab, an anti-VEGF antibody (15 mg/kg i.v. every 3 weeks). Patients had one to two prior chemotherapy regimens for metastatic disease. The primary end point was response rate by Response Evaluation Criteria in Solid Tumors criteria using a Simon 2-stage design. Secondary end points included toxicity, time to progression, response duration, and stabilization of disease of > or = 26 weeks. Correlative studies were done on tumor tissue, including EGFR expression and mutation analysis. One patient achieved a partial response for 52+ months. Fifteen patients had stable disease at first evaluation at 9 weeks; 4 of these patients had stable disease beyond 26 weeks. Median time to progression was 11 weeks (95% confidence interval, 8-18 weeks). Diarrhea of any grade was observed in 84% of patients (grade 3 in 3%); 76% experienced grade 1 or 2 skin rash, and 18% developed hypertension (grade 3 in 11%). The level of EGFR expression was not predictive of response to therapy. The combination of erlotinib and bevacizumab was well-tolerated but had limited activity in unselected patients with previously treated MBC. Biomarkers are needed to identify those MBC patients likely to respond to anti-EGFR/HER1 plus anti-VEGF therapy.


[AFP gene expression and antigenic protein localization in the cells of hepatocellular carcinoma and its surrounding tissues].
Using a double immunoenzymatic technique (PAP) and AFPcDNA-RNA in situ hybridization technique, we detected and analyzed the AFP gene expression and antigenic protein localization in hepatocellular carcinoma (HCC) and its surrounding tissues. The results demonstrated that AFP was truly synthesized again by some host liver cells around the cancer nodules. We considered that the cells which showed AFPmRNA positive hybridized signs might be a kind of preneoplastic cells. Their appearance might be related to injury caused by HBV infection and the inactivities of the inhibited gene on the AFP control mechanism. The substances secreted by the involved cancer cells, might be another causative factor for the excessive expression of the AFP in the liver cells near the cancer.


[The development of the red blood picture in growing parrot chicks].
In order to evaluate the development of the erythrogram of growing parrot nestlings, blood samples were taken monthly from birds of six different parrot species at the age of 30-200 days. Values for the packed cell volume (PCV), the total red blood cell count (TRBC) and the hemoglobin content (Hb) were determined directly and served as basic data for the calculation of the red blood cell indices MCV (mean cellular volume), MCH (mean cellular hemoglobin) and MCHC (mean cellular hemoglobin concentration). Additionally, stained blood smears were evaluated microscopically to judge the morphology of the red blood cells. The results of five species confirmed most results from earlier publications. The data from the species Pyrrhura leucotis formed an exception. The birds showed a decrease of the Hb during the investigated period. Simultaneously, an increase of the PCV and the TRBC could be observed. Thus an anemia as possible cause for the development of the hemoglobin content is rather unlikely. Possibly a certain hemoglobin structure compensates for this development and may be of metabolic advantage for the affected species.


Interleukins 1β and 10 expressions in the periimplant crevicular fluid from patients with untreated periimplant disease.
To analyze the interleukin (IL)-1β and IL-10 expressions in periimplant crevicular fluid (PICF) in healthy and diseased regions to elucidate the inflammatory process around implants and its influence on clinical diagnosis. PICF samples from 30 patients were analyzed for IL-1β and IL-10 concentrations by enzyme-linked immunosorbent assay. Patients were divided in Groups A (health), B (mucositis), and C (periimplantitis). Plaque accumulation, periodontal phenotype (PP), depth on probing, and history of periodontitis (HP) were evaluated. IL-1β levels were lower in healthy group compared with Groups B (P < 0.0005) and C (P < 0.001). IL-10 levels were higher in Groups A compared with B (P = 0.033) and C (P = 0.0001). Patients with HP and thin PP had 9 and 4.5 times more chance of presenting disease, respectively. Lower IL-1β and higher IL-10 levels characterized healthy periimplant conditions, which demonstrate the anti-inflammatory predominance in sites without disease signs. IL-10 levels decrease significantly according to increase of disease status. Therefore, its levels can differentiate healthy, mucositis, and periimplantitis. Thin PP and HP are associated with periimplant disease. These findings suggest the use of ILs as a biochemical marker for early diagnosis of periimplant disease.


Induction of differentiation and growth arrest associated with nascent (nonoligosomal) DNA fragmentation and reduced c-myc expression in MCF-7 human breast tumor cells after continuous exposure to a sublethal concentration of doxorubicin.
The effects on DNA integrity of continuous (72-h) exposure of human MCF-7 breast adenocarcinoma cells to 50 nM doxorubicin (a concentration which can be maintained in the plasma by continuous infusion) were characterized by bisbenzimide spectrofluorophotometry, cell flow cytometry, agarose gel electrophoresis, and neutral elution. Spectrofluorophotometry and cell flow cytometry indicated the presence of DNA fragmentation, which was maximal at 24 h. Resolution of these fragments on agarose gels failed to demonstrate "laddered" oligosomal profiles. Neutral elution analysis at 24 h indicated that doxorubicin induced fragmentation of nascent, but not mature, double-stranded DNA. Drug-treated cells exhibited endoreduplication and significant shifts in cell cycle distribution, (i.e., increased G0/G1 and G2/M fractions and a markedly reduced S-phase fraction). These alterations occurred without inhibiting the incorporation of [3H]dThd into cellular DNA; in fact, both the rate and magnitude of [3H]dThd incorporation increased progressively. Doxorubicin also produced a sustained decline in c-myc mRNA levels that paralleled both growth arrest and induction of DNA fragmentation. Ultrastructural examination revealed morphological alterations consistent with the induction of differentiation (e.g., increased lipid content and mitochondrial density, appearance of tight junctions, and secretory ducts) and further suggested the possibility of autocatalysis (e.g., lipofuschin-containing vacuoles). A gradual decline in cell number was observed, with loss of approximately 35% of the cell population after 72 h.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of continuous gonadotropin-releasing hormone (GnRH) agonist treatment on luteinizing hormone and testosterone secretion, the response to GnRH, and the testicular response to human chorionic gonadotropin in male rhesus monkeys.
Five adult male rhesus monkeys were continuously infused for 56 days with 25 micrograms/day of GnRH agonist (Wy-40972; Ag) using an implanted osmotic pump. Bioassayable serum levels of LH were elevated 8-fold on the second day of Ag treatment and then declined precipitously to below pretreatment levels by day 15. Serum levels of testosterone (T) changed similarly during Ag treatment, except that the fall in serum LH levels preceded the decline in serum levels of T by at least 2 days. Ag administration also eliminated the diurnal variation in serum LH and T. GnRH administration (50 micrograms) induced a 13- to 20-fold rise in serum LH and a 3- to 7-fold increase in serum T in control monkeys. After 4 weeks of Ag administration , none of the animals responded to GnRH. Both control and experimental monkeys had a rise in serum T in response to hCG after 7 weeks of Ag treatment. Basal levels of LH and T returned to normal by 12 days posttreatment, and the serum LH and T responses to GnRH were normal 19 days posttreatment. These results indicate that 1) continuous administration of Ag is an effective method of inducing antiferility effects in male rhesus monkeys; 2) pituitary desensitization is a major factor involved in Ag-induced gonadal dysfunction in this species; and 3) the method of administration may be the critical factor in determining the effectiveness of GnRH agonists.


Human ribophorins I and II: the primary structure and membrane topology of two highly conserved rough endoplasmic reticulum-specific glycoproteins.
Ribophorins I and II represent proteins that are postulated to be involved in ribosome binding. They are abundant, highly-conserved glycoproteins located exclusively in the membranes of the rough endoplasmic reticulum. As the first step in the further characterization of the structure and function of these proteins, we have isolated and sequenced full-length human cDNA clones encoding ribophorins I and II using probes derived from a human liver expression library cloned into pEX1. The authenticity of the clones was verified by overlaps in the protein sequence of N-terminal and several internal fragments of canine pancreatic ribophorins I and II. The cDNA clones hybridize to mRNA species of 2.5 kb in length, and encode polypeptides of 68.5 and 69.3 kd, respectively. Primary sequence analysis, coupled with biochemical studies on the topology, indicates that both ribophorins are largely luminally disposed, spanning the membrane once and having 150 and 70 amino acid long cytoplasmically disposed C termini, respectively. Both are synthesized as precursors having cleavable signal sequences of 23 (ribophorin I) and 22 (ribophorin II) amino acids. The topology suggested by the primary structure has been confirmed biochemically using proteolytic enzymes and anti-ribophorin antibodies. Proteolysis of intact microsomes with a variety of enzymes resulted in a reduction in the apparent mol. wt of ribophorin I that would correspond to a loss of its 150-amino acid cytoplasmic tail. In the case of ribophorin II, it is completely resistant to such proteolysis which is consistent with its luminal disposition and fairly hydrophobic C terminus.(ABSTRACT TRUNCATED AT 250 WORDS)


Distinct Cytokine and Chemokine Dysregulation in Hospitalized Children With Acute Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome With Similar Levels of Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 Shedding.
Multisystem inflammatory syndrome in children (MIS-C) is a severe clinical phenotype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that remains poorly understood. Hospitalized children <18 years of age with suspected coronavirus disease 2019 (COVID-19) (N = 53) were recruited into a prospective cohort study; 32 had confirmed COVID-19, with 16 meeting the US Centers for Disease Control criteria for MIS-C. Differences in nasopharyngeal viral ribonucleic acid (RNA) levels, SARS-CoV-2 seropositivity, and cytokine/chemokine profiles were examined, including after adjustments for age and sex. The median ages for those with and without MIS-C were 8.7 years (interquartile range [IQR], 5.5-13.9) and 2.2 years (IQR, 1.1-10.5), respectively (P = .18), and nasopharyngeal levels of SARS-CoV-2 RNA did not differ significantly between the 2 groups (median 63 848.25 copies/mL versus 307.1 copies/mL, P = .66); 75% of those with MIS-C were antibody positive compared with 44% without (P = .026). Levels of 14 of 37 cytokines/chemokines (interleukin [IL]-1RA, IL-2RA, IL-6, IL-8, tumor necrosis factor-α, IL-10, IL-15, IL-18, monocyte chemoattractant protein [MCP]-1, IP-10, macrophage-inflammatory protein [MIP]-1α, MCP-2, MIP-1β, eotaxin) were significantly higher in children with MIS-C compared to those without, irrespective of age or sex (false discovery rate <0.05; P < .05). The distinct pattern of heightened cytokine/chemokine dysregulation observed with MIS-C, compared with acute COVID-19, occurs across the pediatric age spectrum and with similar levels of nasopharyngeal SARS-CoV-2 RNA.


Inhaled sildenafil nanocomposites: lung accumulation and pulmonary pharmacokinetics.
Administration of sildenafil citrate (SC) is considered as a strategy in the treatment of pulmonary hypertension. This study reports production of the inhalable microparticles containing SC-loaded poly(lactide-co-glycolic acid)-nanoparticles. SC-nanoparticles were prepared by the double emulsion solvent evaporation method. Next, free SC and SC-loaded nanoparticles were spray dried in the presence of appropriate excipients (lactose, maltose and trehalose). Physicochemical properties and aerodynamic behavior of prepared powders were evaluated. In addition, drug accumulation from selected formulations in the rat lung tissue was compared with oral and IV administration. Size and fine particle fraction of selected nanocomposites and free SC microparticles were 7 and 4.5 µm, and 60.2% and 68.2%, respectively. Following oral and IV administration, the drug was not detectable in the lung after 4 and 6 h, respectively, but in SC-loaded nanoparticles, the drug was detectable in the lung even after 12 h of inhalation. Respirable particles containing free SC provided high concentration at first that was detectable up to 6 after insufflation. In vivo study demonstrated that pulmonary administration of sildenafil and sildenafil nanoparticles produced longer half-life and higher concentration of the drug in the lung tissue as compared to oral and IV administration. So, these formulations could be more effective than oral and IV administration of this drug.


Parental Perceptions, Experiences, and Desires of Music Therapy.
Music therapy (MT) is a therapeutic practice where a therapist uses music to enhance the life quality for their patients. Children have an innate enjoyment of music, making music an effective medium for exploring their potential. In this study, we explore the parental perception of MT through an online survey. Contrary to the public perception that MT only addresses emotional needs, 47 out of 59 parents reported seeing improvements in other areas including behavioral, cognitive, linguistic, and social changes. All but one parent indicated that they would recommend MT to others. The survey results further revealed that even parents of children participating in MT had misconceptions regarding MT, which we describe in the paper. Parents reported inaccessibility and cost as other major limitations surrounding MT adoption. We conclude by discussing how technology solutions could mitigate issues with definition, distance, and cost, while maintaining the benefits of MT.


Mitral mechanical valve without long-term anticoagulation. Eight-year follow-up.
In 12 patients with sinus rhythm (including 5 children and 6 young women), mitral valve replacement was performed with a microporous-surfaced valve similar to the Björk-Shiley Monostrut. After the first 3 months, permitting endothelialization of the suture ring to continue over the groove and adjacent metal valve ring, no long-term anticoagulant treatment was given. There was no thromboembolic complication in this group during follow-up for 6-8 years, during which four women gave birth to a total of seven children. In eight other cases, one mitral case with atrial fibrillation, anti-coagulant was not discontinued, and in the remaining aortic cases it was reinstituted. One of them (with atrial fibrillation) had hematuria during inadequate anticoagulant medication, but no thromboembolism. Of five patients with only aortic valve replacement, two had thromboembolic complications, one without residual symptoms and one with slight hand weakness. Another had a transient ischemic attack while on anticoagulant and acetylsalicylic acid was added. Two patients with aortic and mitral valve replacement died, one from heart tamponade and the other from venous thrombosis with pulmonary embolism.


A fish a day, keeps the cardiologist away! - A review of the effect of omega-3 fatty acids in the cardiovascular system.
Dyslipidemia and its consequences are emerging as epidemics with deleterious consequences on cardiovascular (CV) health. The beneficial effects of omega-3-fatty acids on cardiac and extra cardiac organs have been extensively studied in the last two decades, and continue to show great promise in the primary and secondary prevention of cardiovascular diseases (CVDs). Omega-3-fatty acid supplementation has been proven to have beneficial action on lipid profile, cytokine cascade, oxidant-anti-oxidant balance, parasympathetic and sympathetic tone and nitric oxide synthesis. This review summarizes the current knowledge on the basis of its cardiac and non-cardiac benefits, present results from clinical trials and the recommendations for its use in cardiac diseases and dyslipidemias.


The role of low-grade infection in the pathogenesis of apparently aseptic tibial shaft nonunion.
Aim of this study was to determine the rate of low-grade infection in patients with primarily as aseptic categorized tibial shaft nonunion and lack of clinical signs of infection. In a retrospective study between 2006 and 2013, all patients who underwent revision surgery for treatment of tibial shaft nonunion without clinical evidence of infection were assessed. Bacterial cultures harvested during nonunion revision, C-reactive protein (CRP) and/or white blood cell (WBC) values at hospital admission, outcome, and epidemiological data were analyzed. In 88 patients with tibial shaft nonunion without any clinical signs of infection, bacterial samples remained negative in 51 patients. In 37 patients, microbiological diagnostic studies after long-term culturing demonstrated positive bacterial cultures whereas after short-term culturing for 2 days only 17 positive cultures were observed. In 12 cases a mixed culture with 2.3 different bacteria on average was detected. Among patients with negative bacterial cultures bone healing was achieved after 13.2 months. Nonunion with positive bacterial cultures required 19 (range 2-42) months until osseous healing (p = 0.009). Furthermore, nonunion with positive bacterial cultures require statistically more surgical revisions to achieve healing (2.9 ± 0.5 vs. 1.3 ± 0.1 additional procedure; (p = 0.003). Hematological studies carried out before surgical intervention did not demonstrate significant differences in CRP values (negative vs. positive cultures: 0.3 (range 0.3-2.8) mg/dl vs. 0.5 (range 0.3-5.7) mg/dl (p = 0.181) and in WBC values (negative vs. positive cultures: 7.4 (range 3.5-11.9) /nl vs. 7.3 (range 3.7-11.1) /nl (p = 0.723). Limitations of this study may include the varying amount of the at least four samples for microbiological diagnostics as well as the circumstance that for diagnosing low-grade infection swabs and tissue samples were included in this evaluation as being equivalent. The pathogenesis of nonunion may originate from low-grade infection even in patients without clinical signs of infection. In addition, nonunion with positive bacterial cultures require statistically more surgical revisions to achieve healing. Therefore, during any revision surgery, multiple bacterial samples are intended to be harvested for long-term culturing. Particularly, in tibial shaft nonunion following Gustilo-Anderson type III open fractures, low-grade infection should be suspected. DRKS00014657. 04/26/2018 retrospectively registered.


Alteration of neuronal activity in response to cyclic nucleotide agents in Aplysia.
Responsiveness of Aplysia neurons to agents that affect cyclic nucleotide levels was not limited to neurons exhibiting a spontaneous bursting activity pattern. Analyses of the I-V relationship elicited by triangular current ramps within cells exposed to different agents presumably causing elevated cyclic nucleotide levels showed qualitatively similar alterations. These included an increased slope conductance at more negative potentials, possibly related to anomalous rectification, and the induction of a hysteresis in response to a triangular ramp. The paired metacerebral giant cells showed induction of synchronous bursting when exposed to phosphodiesterase inhibitors, and we examined this phenomenon more closely. Classical methods to inactivate a presynaptic source did not eliminate the induction of synchronous bursting. Intracellular injection of a phosphodiesterase inhibitor into a metacerebral giant cell caused changes in the current-voltage relationship similar to those described above for other cells. Subsequent perfusion with the inhibitor caused an enhancement of these effects and the induction of bursting. The alteration of the current-voltage plot in the metacerebral cells and abdominal ganglion cells is qualitatively similar to that induced in the similarly treated bursting neuron R15, suggesting a similar mechanism of action in both burster and nonburster neurons. The implications of these results for cyclic nucleotide mediation of neuronal events are discussed.