First-trimester assessment of the nasal bones using the retronasal triangle view: a 3-dimensional sonographic study.
The purpose of this study was to evaluate a new sonographic technique for identifying the nasal bones using the retronasal triangle view, ie, the coronal plane at which the palate and frontal processes of the maxilla are simultaneously visualized. Three-dimensional (3D) volumes were acquired from women undergoing first-trimester sonographic screening for aneuploidy by 2 accredited operators. Those data sets in which the fetal face was clearly identified were selected for offline analysis by 2 other observers who were unaware of the sonographic or clinical findings. The nasal bones were classified as both present, only 1 present (right or left), or absent according to the presence or absence of 2 small paired echogenic linear structures at the upper tip of the retronasal triangle as determined by 3D navigation in the coronal plane and compared to those findings obtained by 3D navigation in the sagittal plane. Additional 3D data sets involving a subset of 4 first-trimester fetuses with trisomy 21 and absent nasal bones were also analyzed retrospectively and included randomly in the study group. A total of 110 3D data sets were analyzed, of which 86% were obtained transabdominally and 14% transvaginally. The quality of nasal bone identification was classified subjectively by the observers as good in 67% of cases, fair in 29%, and poor in 4%. The nasal bones were classified as at least 1 present in 106 of the cases (96%) and absent in 4 (4%), with complete agreement between observers in both the sagittal and coronal planes (κ = 1). Discrimination between the right and left nasal bones was possible in 89% and 93% for observer A and in 96% and 96% for observer B by assessing the sagittal and coronal views, respectively (right nasal bone: κ = 0.90 [95% confidence interval (CI), 0.79-1]; left nasal bone: κ = 0.85 [95% CI, 0.60-0.99]). The nasal bones were not identified at the level of the retronasal triangle view in any of the fetuses with trisomy 21 and absent nasal bones. This study shows that the nasal bones can be confidently identified as paired echogenic structures located at the upper tip of the retronasal triangle. This coronal view of the fetal face offers the possibility of screening for the presence or absence of the nasal bones in the first trimester, especially when the standard midsagittal views of the fetal face are suboptimal because of fetal or maternal factors. Because both nasal bones can be evaluated simultaneously in the coronal plane, the retronasal triangle view may be advantageous over the conventional midsagittal view assessment, in which only 1 of the 2 nasal bones is evaluated.


Periodic nonsinusoidal vibration: effects in matched filtering for detection of signals buried in noise of uniform spectral density.
In the present paper, the effects of periodic nonsinusoidal vibrations of spatial filters in signal detection experiments are considered. Performance degradation of such an optical information processing system is shown graphically, assuming that the signal is buried in noise of uniform spectral density. Results are compared with those in the presence of pure sinusoidal vibrations of the spatial filter. It is observed that the performance of the system decreases with the increase in departure from the pure sinusoidal case.


Gut REG3γ-Associated Lactobacillus Induces Anti-inflammatory Macrophages to Maintain Adipose Tissue Homeostasis.
Gut microbiota may not only affect composition of local immune cells but also affect systemic immune cells. However, it is not completely clear how gut microbiota modulate these immune systems. Here, we found that there exist expanded macrophage pools in huREG3γ tgIEC mice. REG3γ-associated Lactobacillus, which is homology to Lactobacillus Taiwanese, could enlarge macrophage pools not only in the small intestinal lamina propria but also in the spleen and adipose tissues. STAT3-mediated signal(s) was a critical factor in the Lactobacillus-mediated anti-inflammatory macrophages. We also offered evidence for critical cellular links among REG3γ-associated Lactobacillus, tissue macrophages, and obesity diseases. Anti-inflammatory macrophages in the lamina propria, which are induced by REG3γ-associated Lactobacillus, may migrate into adipose tissues and are involved in resistance against high-fat diet-mediated obesity. Thus, REG3γ-associated Lactobacillus-induced anti-inflammatory macrophages in gut tissues may play a role in adipose tissue homeostasis.


Advances in the bioanalytical study of drug delivery across the skin.
The study of a drug's dermal penetration profile provides important pharmaceutical data for the rational development of topical and transdermal delivery systems because the skin is a broadly used delivery route for local and systemic drugs and a potential route for gene therapy and vaccines. Monitoring drug penetration across the skin and quantifying its levels in different skin layers have been constant challenges due to the detection limitations of the available techniques, as well as the inherent interference in this tissue. This review explores and discusses several bionalytical methods that are indispensable tools to study drugs across the skin. In addressing the main topic, we structure the review highlighting the skin as an important route of drug administration and its structure, skin membrane models most used and its properties, in vitro and in vivo assays most used in the study of drug delivery to the skin, the techniques for processing the skin for subsequent analysis by bioanalytical methods that have a theoretical and practical approach showing its applicability, limitations and also including examples of its use. This review has a comprehensive approach in order to help researchers design their experiments and update the applicability and advances in this area of expertise.


[Depression status of elderly patients with metabolic syndrome in three provinces of China].
Objective: To understand the depression status and its influencing factors in elderly patients with MS in China and to explore the correlation between various components of elderly MS and depression. Methods: This study is based on the "Prevention and Intervention of Key Diseases in Elderly" project. We used a multi-stage stratified cluster random sampling method to complete 16 199 elderly aged 60 years and above in 16 counties (districts) in Liaoning, Henan, and Guangdong Provinces in 2019, excluding 1 001 missing variables. Finally, 15 198 valid samples were included for analysis. The respondents' MS disease was obtained through questionnaires and physical examinations, and the respondents' depression status within the past half month was assessed using the PHQ-9 Depression Screening Scale. The correlation between elderly MS and its components and depression and its influencing factors were analyzed by logistic regression. Results: A total of 15 198 elderly aged 60 years and above were included in this study, with the prevalence of MS at 10.84% and the detection rate of depressive symptoms in MS patients at 25.49%. The detection rates of depressive symptoms in patients with 0, 1, 2, 3, and 4 MS abnormal group scores were 14.56%, 15.17%, 18.01%, 25.21%, and 26.65%, respectively. The number of abnormal components of MS was positively correlated with the detection rate of depressive symptoms, and the difference between groups was statistically significant (P<0.05). The risk of depression symptoms in patients with MS, overweight/obesity, hypertension, diabetes, and dyslipidemia was 1.73 times (OR=1.73, 95%CI:1.51-1.97), 1.13 times (OR=1.13, 95%CI:1.03-1.24), 1.25 times (OR=1.25, 95%CI:1.14-1.38), 1.41 times (OR=1.41, 95%CI:1.24-1.60), 1.81 times (OR=1.81,95%CI:1.61-2.04), respectively, more than those without the disease. Multivariate logistic regression analysis showed that the detection rate of depressive symptoms in patients with sleep disorders was higher than that with normal sleep (OR=4.89, 95%CI: 3.79-6.32). The detection rate of depressive symptoms in patients with cognitive dysfunction was 2.12 times higher than that in the average population (OR=2.12, 95%CI: 1.56-2.89). The detection rate of depressive symptoms in patients with impaired instrumental activities of daily living (IADL) was 2.31 times (OR=2.31, 95%CI: 1.64-3.26) higher than that in the average population. Tea drinking (OR=0.73, 95%CI: 0.54-0.98) and physical exercise (OR=0.67, 95%CI: 0.49-0.90) seemed to be protective factors for depression in elderly MS patients (P<0.05). Conclusions: Older patients with MS and its component abnormalities have a higher risk of depression than the average population. Sleep disorders, cognitive impairment, and IADL impairment are important influencing factors for depression in elderly MS patients, while tea drinking and physical exercise may help to reduce the risk of the disease.


Basal and postprandial metabolic rates in lactating and nonlactating women.
Basal and postprandial metabolic rates were determined by indirect calorimetry in lactating, nonlactating postpartum, and nulliparous women who received a controlled diet of protein at 1.0 g.kg-1.d-1 and energy that approximated usual intake levels on the basis of diet records. Milk production was measured by the test-weighing procedure and by milk expression. Basal metabolic rates (BMRs) were similar among all groups of women. No relationships were detected between BMRs and postpartum time in lactating women. In contrast, postprandial metabolic rates (PMRs) increased (P less than 0.01) in lactating compared with nonlactating women. Milk nitrogen concentrations but not energy showed a linear relationship with PMR (r = 0.86, P less than 0.001). The energy cost of milk production was estimated to be 125% of the energy output in milk. Thus, increased energy needs during lactation are associated not only with milk production but also with elevated PMRs. This increase was met by an increase in dietary energy intakes of 50% above the intakes of nonlactating counterparts.


Development and evaluation of a novel fluorescent chiral derivatization reagent DBD-S-M-Pro: first observation of four chiral amino acids in human hair.
This study reports a novel fluorescent chiral derivatization reagent, 4-(N,N-dmethylaminosulfonyl)-2,1,3-benzoxadiazole-(2-succinimidoxy)-trans-2-methyl-L-proline (DBD-S-M-Pro), with a benzoxadiazole structure containing an N-hydroxysuccinimide activation group. DBD-S-M-Pro targets chiral amino-functional compounds under alkaline conditions without a condensation agent. Gradient elution was performed on a BEH C18 (100 × 2.1 mm, 1.7 μm) column with a mobile phase of 0.05% formic acid (FA) in 10 mM ammonium acetate (CH3COONH4) and 0.1% FA in acetonitrile or methanol. The efficiency of the chiral resolution was evaluated under excitation and emission wavelengths of 450 nm and 560 nm, respectively. The 19 chiral amino acids were separated in the range of 1.45-14.84. The resolutions of almost all DL-amino acids exceeded 1.5; the exceptions were serine (Ser) and lysine (Lys), with resolutions of 1.45 and 1.46, respectively. In addition, a new approach was devised for the simultaneous analysis of four chiral amino acids (DL-Glu, DL-Ala, DL-Val, and DL-Phe) in human hair. These amino acids were analyzed in the range of 12.5-400 pmol, with R2 ≥ 0.9990, limits of detection (S/N = 3) of 4-10 pmol, and intraday and interday precisions of 0.57-6.23%. The average spikes in the hair recoveries were 89.76-111.54%, and the matrix effects were 92.47-102.40%. Next, the contents of free chiral amino acids in the hair samples of 10 healthy volunteers (five males and five females) were analyzed with this method, and the differences were compared. The developed DBD-S-M-Pro provides a novel strategy for the sensitive determination of free chiral amino acids in living organisms.


Imaging findings in pancreatic lymphoma: differential aspects.
When the radiologist is faced with a well-circumscribed tumoral mass in the pancreas, knowing when to direct the patient toward nonsurgical biopsy instead of surgical biopsy and staging is critical. Lymphoma does not require surgical staging or a palliative Whipple's procedure before chemotherapy or radiation therapy. A better overall prognosis with nonsurgical treatment is additional impetus to search for secondary signs of primary pancreatic lymphoma. In patients with primary pancreatic lymphoma, no marked pancreatic ductal dilatation is present even with ductal invasion. Adenocarcinoma commonly dilates the more distal pancreatic duct when more proximal ductal invasion has taken place. Lymph node involvement below the level of the renal veins was another finding not seen with adenocarcinoma. Clinical and imaging findings are otherwise not specific in the differentiation of pancreatic lymphoma and pancreatic cancer, but a bulky homogeneous tumoral mass without alteration of Wirsung's duct or the peripancreatic vessels should suggest the diagnosis. In patients with diffuse infiltration of the pancreatic gland without clinical signs of pancreatitis, the radiologist should be alert to the possibility of pancreatic lymphoma.


Genetic features of mitochondrial respiratory chain disorders.
Oxidative phosphorylation, i.e., ATP synthesis by the oxygen-consuming respiratory chain (RC), supplies most organs and tissues with a readily usable energy source, being functional before birth. Consequently, RC deficiencies can theoretically give rise to any symptom, in any organ or tissue, at any age and with any mode of inheritance, because of the twofold genetic origin of RC components (nuclear DNA and mitochondrial DNA). It was long wrongly considered that RC disorders originate from mutations of mitochondrial DNA, because for a long time only mutations or deletions of mitochondrial DNA were identified. However, the number of known disease-causing mutations in nuclear genes is steadily growing. These genes encode the various subunits of each complex, ancillary proteins functioning at different stages of holoenzyme biogenesis, including transcription, translation, chaperoning, addition of prosthetic groups, and protein assembly, and various enzymes involved in mitochondrial DNA metabolism.


Depression and anxiety among postpartum and adoptive mothers.
Similar to biological mothers during the postpartum period, women who adopt children experience increased stress and life changes that may put them at risk for developing depression and anxiety. The purpose of the current study was to compare levels of depression and anxiety symptoms between postpartum and adoptive women and, among adoptive women, to examine associations between specific stressors and depressive symptoms. Data from adoptive mothers (n = 147), recruited from Holt International, were compared to existing data from postpartum women (n = 147). Differences in the level of depression and anxiety symptoms as measured by the Inventory of Depression and Anxiety Symptoms among postpartum and adoptive women were examined. Associations between specific stressors and depressive symptoms were examined among adoptive mothers. Postpartum and adoptive women had comparable levels of depressive symptoms, but adoptive women reported greater well-being and less anxiety than postpartum women. Stressors (e.g., sleep deprivation, history of infertility, past psychological disorder, and less marital satisfaction) were all significantly associated with depressive symptoms among adoptive women. The level of depressive symptoms was not significantly different between the two groups. In contrast, adoptive women experienced significantly fewer symptoms of anxiety and experienced greater well-being. Additionally, adoptive mothers experienced more depressive symptoms during the year following adoption when the stressors were present. Thus, women with these characteristics should be routinely screened for depression and anxiety.


NMDA-mediated increase in renal sympathetic nerve discharge within the PVN: role of nitric oxide.
The paraventricular nucleus (PVN) of the hypothalamus is an important site of integration in the central nervous system for sympathetic outflow. Both glutamate and nitric oxide (NO) play an important role in the regulation of sympathetic nerve activity. The purpose of the present study was to examine the interaction of NO and glutamate within the PVN in the regulation of renal sympathetic nerve activity in rats. Renal sympathetic nerve discharge (RSND), arterial blood pressure (BP), and heart rate (HR) were measured in response to administration of N-methyl-D-aspartic acid (NMDA) and N(G)-monomethyl-L-arginine (L-NMMA) into the PVN. We found that microinjection of NMDA (25, 50, and 100 pmol) into the PVN increased RSND, BP, and HR in a dose-dependent manner, reaching 53 +/- 9%, 19 +/- 3 mmHg, and 32 +/- 12 beats/min, respectively, at the highest dose. These responses were significantly enhanced by prior microinjection of L-NMMA. On the other hand, inhibition of NO within the PVN by microinjection of L-NMMA also induced increases in RSND, BP, and HR in a dose-dependent manner, reaching 48 +/- 6.5%, 11 +/- 4 mmHg, and 55 +/- 16 beats/min, respectively, at the highest dose. This sympathoexcitatory response was eliminated by prior microinjection of DL-2-amino-5-phosphonovaleric acid, an antagonist of the NMDA receptor. Furthermore, with the use of the push-pull technique, perfusion of glutamate (0.5 micromol) or NMDA (0.1 nmol) into the PVN induced an increase in NO release. In conclusion, our data indicate that NMDA receptors within the PVN mediate an excitatory effect on renal sympathetic nerve activity, arterial BP, and HR. NO in the PVN, which is released by activation of the NMDA receptor, also inhibits NMDA-mediated increases in sympathetic nerve activity. This negative feedback of NO on the glutamate system within the PVN may play an important role in maintaining the overall balance and tone of sympathetic outflow in normal and pathophysiological conditions known to have increased sympathetic tone.


Second amorphous-to-crystalline phase transformation in Cu(60)Ti(20)Zr(20) bulk metallic glass.
The second amorphous-to-crystalline phase transformation in Cu(60)Ti(20)Zr(20) bulk metallic glass was investigated by differential scanning calorimetry and x-ray diffractometry. The difference of the Gibbs free energies between the amorphous phase and the crystalline products during the transformation is estimated to be about 2.46 kJ mol(-1) at 753 K, much smaller than the 61 kJ mol(-1) obtained assuming that it is a polymorphic transformation. It was revealed that the phase transformation occurs through a eutectic crystallization of Cu(51)Zr(14) and Cu(2)TiZr, having an effective activation energy of the order of 400 kJ mol(-1). The average Avrami exponent n is about 2.0, indicating that the crystallization is diffusion controlled.


A Systematic Review on Healthcare Artificial Intelligent Conversational Agents for Chronic Conditions.
This paper reviews different types of conversational agents used in health care for chronic conditions, examining their underlying communication technology, evaluation measures, and AI methods. A systematic search was performed in February 2021 on PubMed Medline, EMBASE, PsycINFO, CINAHL, Web of Science, and ACM Digital Library. Studies were included if they focused on consumers, caregivers, or healthcare professionals in the prevention, treatment, or rehabilitation of chronic diseases, involved conversational agents, and tested the system with human users. The search retrieved 1087 articles. Twenty-six studies met the inclusion criteria. Out of 26 conversational agents (CAs), 16 were chatbots, seven were embodied conversational agents (ECA), one was a conversational agent in a robot, and another was a relational agent. One agent was not specified. Based on this review, the overall acceptance of CAs by users for the self-management of their chronic conditions is promising. Users' feedback shows helpfulness, satisfaction, and ease of use in more than half of included studies. Although many users in the studies appear to feel more comfortable with CAs, there is still a lack of reliable and comparable evidence to determine the efficacy of AI-enabled CAs for chronic health conditions due to the insufficient reporting of technical implementation details.


Taking inspiration from climbing plants: methodologies and benchmarks-a review.
One of the major challenges in robotics and engineering is to develop efficient technological solutions that are able to cope with complex environments and unpredictable constraints. Taking inspiration from natural organisms is a well-known approach to tackling these issues. Climbing plants are an important, yet innovative, source of inspiration due to their ability to adapt to diverse habitats, and can be used as a model for developing robots and smart devices for exploration and monitoring, as well as for search and rescue operations. This review reports the main methodologies and approaches used by scientists to investigate and extract the features of climbing plants that are relevant to the artificial world in terms of adaptation, movement, and behaviour, and it summarizes the current available climbing plant-inspired engineering solutions.


Variations of the Bender-Gestalt Test: implications for training and practice.
Although the Bender-Gestalt Visual Motor Test has been a popular and influential clinical assessment instrument for the last half century, authoritative opinion and a substantial research literature are often inconsistent or contradictory. This paper documents variations in designs, administration procedures, forms, and applications to particular populations. A careful review of scoring systems indicates the current status of objective approaches as contrasted with interpretation that is global, intuitive, and subjective. Some implications of these variations and interpretive procedures for training and assessment practice are discussed. The major conclusions of the review are summarized in seven points.


Coronavirus disease 2019 (COVID-19) associated bacterial coinfection: Incidence, diagnosis and treatment.
Coronavirus disease 2019 (COVID-19) emerged as a pandemic that spread rapidly around the world, causing nearly 500 billion infections and more than 6 million deaths to date. During the first wave of the pandemic, empirical antibiotics was prescribed in over 70% of hospitalized COVID-19 patients. However, research now shows a low incidence rate of bacterial coinfection in hospitalized COVID-19 patients, between 2.5% and 5.1%. The rate of secondary infections was 3.7% in overall, but can be as high as 41.9% in the intensive care units. Over-prescription of antibiotics to treat COVID-19 patients fueled the ongoing antimicrobial resistance globally. Diagnosis of bacterial coinfection is challenging due to indistinguishable clinical presentations with overlapping lower respiratory tract symptoms such as fever, cough and dyspnea. Other diagnostic methods include conventional culture, diagnostic syndromic testing, serology test and biomarkers. COVID-19 patients with bacterial coinfection or secondary infection have a higher in-hospital mortality and longer length of stay, timely and appropriate antibiotic use aided by accurate diagnosis is crucial to improve patient outcome and prevent antimicrobial resistance.


Quality and education.
Juxtaposing quality with education in emergency medicine (EM) generates two distinct issues: 1) the quality of education in EM, and 2) educating about quality in EM. There is considerable overlap between the two, and neither should be considered without the other. This paper focuses on education about quality in EM, with some discussion of the quality of EM education. Despite its apparent importance, there is a relative paucity of research on this topic.


Positive modulation of the adipoconversion of adipoblasts derived from genetically obese rats by sodium butyrate.
Using a new serum-free primary culture system, we have previously reported genotypic differences between adipoblasts derived from the epididymal adipose deposit of lean and obese 8-week-old Zucker and Wistar Diabetic Fatty (WDF) rats (15). In these strictly controlled culture conditions, obese-derived adipoblasts expressed low levels of the late markers of differentiation (lipid accumulation, GPDH). In order to further characterize obese-derived adipoblasts and analyze the critical relationship between growth and differentiation, growth arrest was induced in lean- and obese-derived cultures using sodium butyrate treatment. Addition of 2.5 mM sodium butyrate to the serum-free medium from day 1 reduced markedly the growth of lean as well as obese-derived cells. Adipoconversion of lean-derived adipoblasts was not altered, similar levels of LPL and GPDH activities being obtained in control and butyrate-treated groups. By contrast, a marked increase in both activities was observed in obese-derived cultures, restoring the level of both markers of differentiation to the lean level. Similar results were obtained with adipoblasts derived from subcutaneous inguinal (ING) fat pad of obese Zucker as well as adipoblasts derived from ING and EPI fat deposits from obese WDF rats. Taken together, these results suggest that adipose deposits of these genetically obese rats contain a specific adipoblast population which differs from lean-derived adipoblasts in respect to its adipoconversion capacity and/or its stage of commitment to differentiation.


[Combination of three cutaneous diseases in Mayotte].
This report describes the case of a young woman from Mayotte (Comoros Islands) who presented a combination of three cutaneous diseases, i.e. pityriasis versicolor, scabies, and multibacillary leprosy. Symptoms of leprosy were concealed by those of the other two diseases. After multidrug therapy for leprosy, the patient developed erythema nodosum leprosum that was successfully treated using pentoxifylline. Combination of cutaneous diseases can alter usual presentations and lead to misdiagnosis. It is important to take into account possible disease combination to establish proper diagnosis and prescribe effective treatment.


Roller coasters, g forces, and brain trauma: on the wrong track?
There has been enormous attention in the general press on the possibility that high G force roller coasters are inducing brain injury in riders. Armed with a handful of anecdotal case reports of brain injuries, the U.S. Congress has recently proposed legislation to regulate the level of G forces of roller coasters. However, high G forces are well tolerated during many activities and, therefore, are a poor measure for the risk of brain injury. Rather, accelerations of the head that can be caused by G forces are the key to producing injury. To determine the extent of head accelerations during roller coaster rides, we acquired G force data from three popular high G roller coasters. We used the highest recorded G forces in a simple mathematical model of head rotational acceleration, with the head rigidly pivoting from the base of the skull at a radius representing typical men and women. With this model, we calculated peak head rotational accelerations in three directions. Even for a conservative worst-case scenario, we found that the highest estimated peak head accelerations induced by roller coasters were far below conventional levels that are predicted for head injuries. Accordingly, our findings do not support the contention that current roller coaster rides produce high enough forces to mechanically deform and injure the brain.


LKB1-Dependent Regulation of TPI1 Creates a Divergent Metabolic Liability between Human and Mouse Lung Adenocarcinoma.
KRAS is the most frequently mutated oncogene in human lung adenocarcinomas (hLUAD), and activating mutations frequently co-occur with loss-of-function mutations in TP53 or STK11/LKB1. However, mutation of all three genes is rarely observed in hLUAD, even though engineered comutation is highly aggressive in mouse lung adenocarcinoma (mLUAD). Here, we provide a mechanistic explanation for this difference by uncovering an evolutionary divergence in the regulation of triosephosphate isomerase (TPI1). In hLUAD, TPI1 activity is regulated via phosphorylation at Ser21 by the salt inducible kinases (SIK) in an LKB1-dependent manner, modulating flux between the completion of glycolysis and production of glycerol lipids. In mice, Ser21 of TPI1 is a Cys residue that can be oxidized to alter TPI1 activity without a need for SIKs or LKB1. Our findings suggest this metabolic flexibility is critical in rapidly growing cells with KRAS and TP53 mutations, explaining why the loss of LKB1 creates a liability in these tumors. Utilizing phosphoproteomics and metabolomics in genetically engineered human cell lines and genetically engineered mouse models (GEMM), we uncover an evolutionary divergence in metabolic regulation within a clinically relevant genotype of human LUAD with therapeutic implications. Our data provide a cautionary example of the limits of GEMMs as tools to study human diseases such as cancers. This article is highlighted in the In This Issue feature, p. 799.


Postoperative surveillance, registration and classification of wound infection in cardiac surgery--experiences from Great Britain.
Wound infection in cardiac surgery is a continuing problem despite improvements in surgical technique. The risk factors for, and appearance of, the infected wound differ from operations in other specialties. A robust definition is required for successful surveillance but many are open to different interpretations. At UCLH, comparison between UK and US definitions shows marked differences in patients defined as infected. Surveillance with feedback is effective if conducted over several years, but a high proportion of infected wounds are only identified during post-discharge follow-up. Deteriorating performance of an individual surgeon can be detected and interventions focused on improving faults identified during data collection. Often highlighting the problem is sufficient to reverse the trend, but the process of audit and control is becoming more important as accountability and performance is demanded by primary care providers and patients.


Ectopic expression of RASSF2 and its prognostic role for gastric adenocarcinoma patients.
RASSF2 has recently been identified as a potential tumor suppressor that serves as a Ras effector in various types of human cancers. However, there have been few reports detailing this in gastric cancer. Samples of gastric adenocarcinoma from 276 Chinese patients with follow-up were analyzed for RASSF2 protein expression by immunohistochemistry. RASSF2 was expressed in up to 31.2% (86/276) of this group of gastric carcinoma. The expression of RASSF2 was significantly lower in carcinomas than in normal mucosas (P<0.05). RASSF2 corresponded positively with patient age, histological differentiation, depth of tumor invasion, regional lymph node and distant metastasis, and TNM stage (all P<0.05). Further multivariate analysis revealed that patient gender, depth of tumor invasion, distant metastasis, TNM stage and the expression of RASSF2 were independent prognostic factors for patients with gastric cancer. The Kaplan-Meier plot showed that the overall mean survival time of the patients with RASSF2-negative expression was shorter than that of patients with positive expression (χ(2)=156.874, P<0.0001). Moreover, RASSF2-negative expression had a much more significant effect on the survival of those patients with early stage tumors (χ(2)=127.167, P<0.0001), highlighted by a >50.9% reduction in 3-year survival compared to that of patients with RASSF2-positive expression. In late stages, the difference was also significant (χ(2)=6.246, P=0.019), with a 35.5% reduction in 3-year survival. It is suggested that RASSF2 plays an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for its prognosis.


Soil persistence of triasulfuron herbicide as affected by biotic and abiotic factors.
Persistence of triasulfuron [3-(6-methoxy-4methyl-1,3,5-triazin-2-yl)-1-{2-(2-chloroethoxy)-phenylsulfonyl}-urea] in soil was studied under wheat crop and laboratory conditions. Field experiment was conducted in the farms of Agronomy Division, Indian Agricultural Research Institute (IARI), New Delhi. Randomized block design (RBD) was followed with four replicates and two rates of treatments along with control and weedy check. Triasulfuron was applied as post-emergent application to wheat crop at two rates of application viz., 15 g and 20 g a.i. ha-1. Soil samples at 0 (3 h), 1, 3, 5, 7, 10, 15, 20, and 30-day intervals after application were drawn, extracted, cleaned up, and analyzed for herbicide residues by high performance liquid chromatography (HPLC) using C18 column and methanol: water (8:2) as mobile phase at 242 nm wave length. Effect of microbial activity and soil pH was studied under laboratory conditions. Dissipation of triasulfuron followed a first-order-rate kinetics. Residues dissipated from field soil with half-life of 5.8 and 5.9 days at two rates of application. The study indicated biphasic degradation with faster rate initially (t1/2 = 3.7 days), followed by a slower dissipation rate at the end (t1/2 = 9.4 days). Similar trend was observed with non-sterile soil in laboratory with a longer half-life. Acidic pH and microbial activity contributed toward the degradation of triasulfuron in soil.


Using J-coupling constants for force field validation: application to hepta-alanine.
A computational solution to the protein folding problem is the holy grail of biomolecular simulation and of the corresponding force fields. The complexity of the systems used for folding simulations precludes a direct feedback between the simulations and the force fields, thus necessitating the study of simpler systems with sufficient experimental data to allow force field optimization and validation. Recent studies on short polyalanine peptides of increasing length (up to penta-alanine) indicated the presence of a systematic deviation between the experimental (NMR-derived) J-couplings and the great majority of biomolecular force fields, with the χ(2) values for even the best-performing force fields being in the 1.4-1.8 range. Here we show that by increasing the number of residues to seven and by achieving convergence through an increase of the simulation time to 2 μs, we can identify one force field (the AMBER99SB force field, out of the three force fields studied) which when compared with the experimental J-coupling data (and for a specific set of Karplus equation parameters and estimated J-coupling errors previously used in the literature) gave a value of χ(2) = 0.99, indicating that full statistical consistency between experiment and simulation is feasible. However, and as a detailed analysis of the effects of estimated errors shows, the χ(2) values may be unsuitable as indicators of the goodness of fit of the various biomolecular force fields.


Enhancement of monoclonal antibody uptake in human colon tumor xenografts following irradiation.
Indium-111-labeled AUA1 tumor-associated monoclonal antibody raised against an antigen of colon adenocarcinoma was used to evaluate the effect of ionizing radiation on antibody uptake by the LoVo adenocarcinoma cell line grown as a xenograft in nude mice. Tumors were exposed to single doses of external X-irradiation of between 400 and 1600 cGy followed, 24 h later, by administration of specific or nonspecific antibody. Animals were sacrificed 3 days after antibody administration. At doses higher than 400 cGy, tumor uptake with both specific and nonspecific antibody was significantly increased. No difference in changes in tumor volume was observed between the groups receiving irradiation and the controls. Specific antibody uptake by tumors was always significantly higher than nonspecific having an approximate 4-fold binding advantage. Vascular permeability and the vascular volume of irradiated and control tumors was measured 24 and 72 h after irradiation, using iodine-125-labeled nonspecific antibody and labelling of the red blood cells in vivo with 99mTcO4. At doses higher than 400 cGy, vascular permeability in the tumor 24 h after irradiation was significantly increased (P less than 0.05), while the vascular volume decreased (P less than 0.001) compared to control values. However at 72 h after irradiation there was no difference between treated and control groups. The results obtained in this study suggest a potential value of external irradiation to increase monoclonal antibody uptake by tumors governed mainly by the increased vascular permeability of the tumor vasculature soon after the irradiation exposure.


Enhancing hydrogen storage performances of MgH2 by Ni nano-particles over mesoporous carbon CMK-3.
Nano-dispersed Ni particles over mesoporous carbon material CMK-3 (Ni/CMK-3) was fabricated by means of impregnation-reduction strategy using precursor NiCl2 · 6H2O, which is beneficial to improving the de/rehydrogenation performances of MgH2. The dehydrogenation onset temperature of MgH2-Ni/CMK-3 is significantly lowered by 170 K from that of pristine MgH2 (around 603 K). Totally 5.9 wt% of hydrogen absorption capacity is liberated within 1 h at a temperature of 423 K under a pressure of 3 MPa. This composite can absorb 3.9 wt% hydrogen even at a temperature of 328 K under 3 MPa H2. Activation energy values of both dehydrogenation (43.4 kJ mol-1) and rehydrogenation (37.4 kJ mol-1) for MgH2-Ni/CMK-3 are greatly enhanced from those of as-milled MgH2. Ni/CMK-3 also slightly destabilizes the dehydrogenation of MgH2 by 1.5 kJ mol [Formula: see text] The enhanced performances can be attributed to the synergistic effects of both destabilization and activation from nano-dispersed Ni particles.


Patterns and predictors of personal exposure to indoor air pollution from biomass combustion among women and children in rural China.
Indoor air pollution (IAP) from domestic biomass combustion is an important health risk factor, yet direct measurements of personal IAP exposure are scarce. We measured 24-h integrated gravimetric exposure to particles < 2.5 μm in aerodynamic diameter (particulate matter, PM₂.₅) in 280 adult women and 240 children in rural Yunnan, China. We also measured indoor PM₂.₅ concentrations in a random sample of 44 kitchens. The geometric mean winter PM₂.₅ exposure among adult women was twice that of summer exposure [117 μg/m³ (95% CI: 107, 128) vs. 55 μg/m³ (95% CI: 49, 62)]. Children's geometric mean exposure in summer was 53 μg/m³ (95% CI: 46, 61). Indoor PM₂.₅ concentrations were moderately correlated with women's personal exposure (r=0.58), but not for children. Ventilation during cooking, cookstove maintenance, and kitchen structure were significant predictors of personal PM₂.₅ exposure among women primarily cooking with biomass. These findings can be used to develop exposure assessment models for future epidemiologic research and inform interventions and policies aimed at reducing IAP exposure. Our results suggest that reducing overall PM pollution exposure in this population may be best achieved by reducing winter exposure. Behavioral interventions such as increasing ventilation during cooking or encouraging stove cleaning and maintenance may help achieve these reductions.


On the origin of species specificity of fibronectin. Immunological identification of a species-specific domain of human fibronectin.
We have investigated whether species-specific epitopes of human fibronectin are localized at a specific domain of fibronectin using rabbit polyclonal antibodies. Tryptic fragments of human fibronectin were tested for reactivity with anti-human fibronectin antibody, which had been previously absorbed with other animal fibronectin to establish species specificity. Human-specific epitopes were found to be present on 75,000, 65,000, and 42,000 dalton fragments. The 42,000-dalton fragment shares almost all the epitopes with the 75,000 and 65,000 dalton fragments. It does not promote BHK cell spreading, whereas the 75,000 and 65,000 dalton fragments do. The amino acid sequence from the amino terminus of the 42,000-dalton fragment is Asp/Gly-Gln/Val-?-Ile-Val-, which is almost identical to the sequence Asp-Gln-Cys-Ile-Val- located in the carboxyl terminal 1/3 of the collagen-binding domain of human fibronectin (Kornblihtt et al. (1985) EMBO J. 4, 1755-1759). These results suggest that human fibronectin bears human-specific epitopes mainly on the amino-terminal half of domain 4 (Hayashi & Yamada (1983) J. Biol. Chem. 258, 3332-3340) located between the collagen and cell binding domains almost at the center of the fibronectin polypeptide. The domain specific for human fibronectin may be a general species-specific domain of animal fibronectins.


Hydroxychloroquine for subglottic stenosis: a novel therapy in the battle for air.
Upper airway obstruction due to subglottic edema and granulation tissue proliferation may cause severe morbidity and may be life threatening. Hydroxychloroquine interferes with antigen processing by means of raising lysosomal pH and immune response modulation. Herein, we present the outcome of a steroid-sparing treatment using hydroxychloroquine in an 80-year-old man with acquired subglottic stenosis and steroid dependency. Twice daily oral hydroxychloroquine at 2 mg/kg/day allowed cessation of systemic steroids without recurrence of the stenosis. Successful weaning of the hydroxychloroquine took place over a 5-month period.


RCAS1 increases cell morphological changes in murine fibroblasts by reducing p38 phosphorylation.
Receptor‑binding cancer antigen expressed on SiSo cells (RCAS1) is a tumor‑associated antigen that is expressed in a number of human malignancies. RCAS1 acts as a ligand for a putative RCAS1 receptor that is present on various human cells including T and B lymphocytes and natural killer cells, in which it induces cell growth inhibition and apoptosis. It has been suggested that RCAS1 might serve an important role in tumor cell evasion from the host immune system. In fact, RCAS1 expression is related to malignant characteristics including tumor size, invasion depth, clinical stage and poor overall survival. The authors previously established doxycycline‑induced RCAS1 overexpression murine fibroblast L cells to analyze the biological functions of RCAS1 and reported that its expression inhibited cell cycle progression via the downregulation of cyclin D3, which subsequently induced apoptosis. Additionally, it was found that RCAS1 expression induced cell morphological changes prior to caspase‑mediated apoptosis. Thus, the present study examined signaling pathways associated with changes in cell morphology that were induced by RCAS1 expression. The data showed that increased RCAS1 expression caused a reduction in actin stress fibers and decreased cofilin phosphorylation. Recent studies have shown that p38 signaling regulates actin polymerization. The data the present study showed that increased RCAS1 expression significantly decreased p38 phosphorylation.


Principal component analysis coupled with artificial neural networks--a combined technique classifying small molecular structures using a concatenated spectral database.
In this paper we present several expert systems that predict the class identity of the modeled compounds, based on a preprocessed spectral database. The expert systems were built using Artificial Neural Networks (ANN) and are designed to predict if an unknown compound has the toxicological activity of amphetamines (stimulant and hallucinogen), or whether it is a nonamphetamine. In attempts to circumvent the laws controlling drugs of abuse, new chemical structures are very frequently introduced on the black market. They are obtained by slightly modifying the controlled molecular structures by adding or changing substituents at various positions on the banned molecules. As a result, no substance similar to those forming a prohibited class may be used nowadays, even if it has not been specifically listed. Therefore, reliable, fast and accessible systems capable of modeling and then identifying similarities at molecular level, are highly needed for epidemiological, clinical, and forensic purposes. In order to obtain the expert systems, we have preprocessed a concatenated spectral database, representing the GC-FTIR (gas chromatography-Fourier transform infrared spectrometry) and GC-MS (gas chromatography-mass spectrometry) spectra of 103 forensic compounds. The database was used as input for a Principal Component Analysis (PCA). The scores of the forensic compounds on the main principal components (PCs) were then used as inputs for the ANN systems. We have built eight PC-ANN systems (principal component analysis coupled with artificial neural network) with a different number of input variables: 15 PCs, 16 PCs, 17 PCs, 18 PCs, 19 PCs, 20 PCs, 21 PCs and 22 PCs. The best expert system was found to be the ANN network built with 18 PCs, which accounts for an explained variance of 77%. This expert system has the best sensitivity (a rate of classification C = 100% and a rate of true positives TP = 100%), as well as a good selectivity (a rate of true negatives TN = 92.77%). A comparative analysis of the validation results of all expert systems is presented, and the input variables with the highest discrimination power are discussed.


Rhythmic Interventions, Musical Returns: The Health Benefits of Music as an Embodied, Everyday Practice.
In this essay, I explore the intermodal nature of well-being by considering the health benefits of music as an embodied, everyday practice in the unrelenting tempo of contemporary society. I draw from Henri Lefebvre's concept of rhythmanalysis to perform an embodied appraisal of neoliberal ideology as I experience it within the everyday spaces of higher education, and to promote an appreciation for, and utilization of musical and rhythmic interventions that restore balance and well-being amid the compressing agenda of the doctoral-degree chase. I weave together autoethnographic accounts of my own experience as I alternate between the challenges of graduate school and my involvement in various musical projects. My oscillations between these differently rhythmed worlds prompts the imagining of new possibilities for wellness and social relations through their coalescence.


Scaffold-attached regions from the human interferon beta domain can be used to enhance the stable expression of genes under the control of various promoters.
We have transfected DNA corresponding to the complete chromatin domain of human interferon beta (huIFN-beta) gene into mouse L cells. In this construct, which is flanked by scaffold-attached regions (SARs), the gene's transcription was enhanced 20-30-fold with respect to DNAs containing only the immediate regulatory elements. To elucidate the role of SAR elements in the transcriptional enhancement, their position was varied relative to several artificial promoter-gene combinations. It was found that SARs enhance general promoter functions in an orientation- and partially distance-independent manner; their effect is restricted to the integrated state of transfected templates. During the phase of transient expression, SAR elements were generally found to have an antagonizing effect.


Use of laser photocoagulation for treatment of cutaneous angiomatosis in one dog and two cats.
One dog and 2 cats were evaluated because of multiple progressively enlarging cutaneous vascular plaques. Biopsies were performed and revealed small well-circumscribed dermal nodules of dilated fully enclosed blood-filled spaces lined by single layers of endothelial cells aligned on thin fibrous walls, with minimal mitotic activity. A diagnosis of cutaneous angiomatosis was made in all 3 animals. Cutaneous angiomatosis is a progressive proliferative lesion of vascular tissue involving the dermis and subcutaneous tissues of dogs and cats. Lasers of selected wavelengths have been used to induce photothermal coagulation of hemoglobin-containing cutaneous lesions in humans; argon-pumped dye and neodymium:yttrium-aluminum-garnet lasers were used to treat the cutaneous lesions in the animals of this report. Laser treatment may provide an alternative to wide surgical resection or limb amputation for management of this condition in veterinary patients.


Effect of an E461G mutation of beta-galactosidase (Escherichia coli, lac Z) on pL rate profiles and solvent deuterium isotope effects.
An E461G mutation of beta-galactosidase results in the disappearance of the high pL (L = H, D) downward break in the rate profiles for k(cat)/K(m) for wild-type enzyme-catalyzed hydrolysis of 4-nitrophenyl beta-D-galactopyranoside (Gal-OPNP) and a decrease from (k(cat))(HOH)/(k(cat))(DOD) = 1.7 to (k(cat))(HOH)/(k(cat))(DOD) = 1.2 in the solvent deuterium isotope effect. These observations provide evidence that the propionic acid side chain of Glu 461 is protonated at catalytically active free beta-galactosidase and they are consistent with a role for this residue in Brønsted acid catalysis at the leaving group. The earlier observation that this same E461G mutation results in the loss of a downward break at high pH in the rate profile for k(s) for transfer of the beta-D-galactopyranosyl group from beta-galactosidase to water cannot be simply explained by a mechanism in which the single side chain of Glu 461 functions to provide general acid catalysis in the rate limiting step for formation of the beta-D-galactopyranosyl intermediate and general base catalysis of breakdown of this intermediate. Evidence is presented that there may be different catalytic mechanisms, with different roles for the side chain for Glu-461, for nucleophilic addition of water and of small alkyl alcohols to the beta-D-galactopyranosyl reaction intermediate.


[Drinking habits and characteristics of urban male residents with high alcohol intake--analysis of temporary housing residents after the Great Hanshin Earthquake].
In December 1996, a health survey was conducted of 49,033 temporary housing residents of Kobe City, who were victims of the Great Hanshin Earthquake on Tuesday, January 17, 1995. A total of 33,414 residents (68.1% of those requested) filled in self-administered questionnaires. This study focused on males over 20 years old and examined factors related to increase in alcohol intake. A total of 14,179 men were analyzed, 67.4% of whom reported habitual drinking, and 32.1% an increase in their alcohol intake. The factors related to elevated alcohol intake were a low Breslow's health practice index, a high nervous complaint score and a low living score. In addition, the health practice index demonstrated an inverse link. There are many drinkers among urban residents and drinking related problems are easily evoked when living conditions worsen, as in the case of a natural disaster. Logistic regression analyses were used to predict which persons are likely to increase their alcohol intake. Significant predictors identified were the smoking habit, sleep disturbance, nervous complaints and the health practice index. It is important to ensure that this latter remains high to prevent the alcohol-related problems in urban residents.


Surgery of the Achilles' tendon.
Without question, injury to the Achilles' tendon is one of the commonest running injuries involving the lower extremity. Repair of acute and delayed ruptures is discussed. Tendonitis is by far commoner than ruptures. The pathology and conservative and surgical treatments are discussed.


Niobium(v)-catalyzed defluorinative triallylation of α,α,α-trifluorotoluene derivatives by triple C-F bond activation.
The catalytic defluorinative triallylation of α,α,α-trifluorotoluene derivatives via C-F bond activation has been achieved by the use of the NbCl5 catalyst and allyltrimethylsilane as a nucleophile. Several control experiments have suggested the importance of the conjugation between the fluorine atoms and the carbocation center in this reaction.


Teriparatide therapy enhances devitalized femoral allograft osseointegration and biomechanics in a murine model.
Despite the remarkable healing potential of long bone fractures, traumatic injuries that result in critical defects require challenging reconstructive limb sparing surgery. While devitalized allografts are the gold standard for these procedures, they are prone to failure due to their limited osseointegration with the host. Thus, the quest for adjuvants to enhance allograft healing remains a priority for this unmet clinical need. To address this, we investigated the effects of daily systemic injections of 40 μg/kg teriparatide (recombinant human parathyroid hormone) on the healing of devitalized allografts used to reconstruct critical femoral defects (4mm) in C57Bl/6 mice. The femurs were evaluated at 4 and 6 weeks using micro CT, histology, and torsion testing. Our findings demonstrated that teriparatide induced prolonged cartilage formation at the graft-host junction at 4 weeks, which led to enhanced trabeculated bone callus formation and remarkable graft-host integration at 6-weeks. Moreover, we observed a significant 2-fold increase in normalized callus volume (1.04 ± 0.3 vs. 0.54 ± 0.14 mm³/mm; p < 0.005), and Union Ratio (0.28 ± 0.07 vs. 0.13 ± 0.09; p < 0.005), compared to saline treated controls at 6-weeks. Teriparatide treatment significantly increased the torsional rigidity (1175 ± 311 versus 585 ± 408 N.mm²) and yield torque (10.5 ± 4.2 versus 6.8 ± 5.5 N.mm) compared to controls. Interestingly, the Union Ratio correlated significantly with the yield torque and torsional rigidity (R²=0.59 and R²=0.77, p < 0.001, respectively). These results illustrate the remarkable potential of teriparatide as an adjuvant therapy for allograft repair in a mouse model of massive femoral defect reconstruction, and warrant further investigation in a larger animal model at longer time intervals to justify future clinical trials for PTH therapy in limb sparing reconstructive procedures.


Subunit interactions in hemoglobin probed by fluorescence and high-pressure techniques.
The dissociation of the subunits of human adult oxyhemoglobin has been investigated by using steady-state fluorescence anisotropy, multifrequency phase fluorometry, and high hydrostatic pressure. Human hemoglobin obtained by using two purification procedures (bulk preparation by centrifugation or further fractionation using anion-exchange chromatography) was labeled with an extrinsic fluorescent probe, 5-(dimethylamino)naphthalene-1-sulfonyl chloride (DNS-Cl). The long fluorescence lifetime of this probe allows for the observation of the macromolecular tumbling, and thus provides a method for observing changes in the size of the complex upon subunit dissociation under differing solution conditions of proton and organic phosphate concentration. At pH 7, the dansylated preparations of bulk and fractionated hemoglobin showed a concentration-dependent decrease in the anisotropy which though not identical can only arise from the tetramer to dimer dissociation. We observed primarily the dimer at pH 9 and a small destabilization of the tetramer in the presence of saturating inositol hexaphosphate (IHP). High-pressure experiments allowed for the observation of the dissociation of the hemoglobin dimer into monomers. From these measurements, we estimate the dimer dissociation constant to be between 0.1 and 1 nM. We compare the present results on the subunit affinities in hemoglobin obtained from steady-state and time-resolved fluorescence data with those obtained previously by using gel filtration, sedimentation, and kinetic techniques. These comparisons are indicative of a certain degree of conformational heterogeneity in the hemoglobin preparations.


Giant cell fibroblastoma: a report of three cases.
Three cases of giant cell fibroblastoma are presented. All three patients were boys younger than four years of age. The neoplasms involved the subcutaneous tissue of the back, perineum, and shoulder, respectively. The tumors were characterized histologically by a mixture of spindle cells and multinucleated giant cells in a myxoid or collagenous background and by the presence of irregular, sinusoidal spaces. All three patients had local recurrence, but all were tumor-free at latest follow-up.


Improved in vitro fertilization and development by use of modified human tubal fluid and applicability of pronucleate embryos for cryopreservation by rapid freezing in inbred mice.
We examined in vitro fertilizability and development of 10 inbred mouse strains (C57BL/6J, C57BL/10, C57BL/10.D2/newSn, C57BL/10-Thy1.1, C57BL/10.Br/Sn, C3H/He, RFM/Ms, STS/A, BALB/c-nu and C.B-17/Icr), and the viability of frozen-thawed in vitro fertilized (IVF) embryos after embryo transfer (ET). In seven strains, fertilizability was significantly greater in modified human tubal fluid (mHTF) compared with modified Krebs-Ringer's bicarbonate solution (TYH medium). The TYH medium supported almost no fertilization in four strains. More than 80% of IVF embryos developed to the blastocyst stage by 120 h in potassium-enhanced simplex optimization medium (KSOM). Reciprocal fertilization between C57BL/6J and BALB/c-nu gametes in TYH medium yielded poor fertilization o f BALB/c-nu due to spermatozoal deficiencies. Increased concentrations of bovine serum albumin and spermatozoa during capacitation and Percoll washing did not drastically affect fertilization. The mHTF, but not TYH medium, supported BALB/c-nu spermatozoa penetration into the zona pellucida irrespective of capacitation media. In vitro fertilized embryos frozen-thawed rapidly were transferred to surrogate mothers at the two-cell stage. Compared with that of unfrozen controls, rapid freezing had no significant effect on fetus development except in C57BL/10.D2/newSn mice. These results suggest that mHTF medium is superior with respect to IVF of inbred mice, and that KSOM adequately supports in vitro fertilized embryo development in inbred mice. The data also indicate that rapid freezing of pronucleate embryos following IVF is suitable for cryopreservation and embryo banking of inbred mice and for the production of genetically modified mice.


Inhibition of the dimorphic transition of Candida albicans by the ornithine decarboxylase inhibitor 1,4-diaminobutanone: alterations in the glycoprotein composition of the cell wall.
Hyphal development in Candida albicans was selectively blocked by the ornithine decarboxylase competitive inhibitor 1,4-diaminobutanone (DAB). Inhibition of hyphal development required DAB during both yeast inoculum growth and subsequent incubation at 37 degrees C to induce mycelial growth. This effect was not due to general growth inhibition since DAB did not inhibit yeast growth, and reduced protein synthesis by 30% at most. Moreover, protein synthesis was unaffected by DAB when cells were pre-grown in drug-containing media. Since DAB inhibited dimorphic transition at 37 degrees C, morphology- and temperature-dependent protein synthesis could be distinguished. DAB stimulated the synthesis of several yeast wall-proteins, irrespective of morphology or growth temperature, and two at 37 degrees C only, but it inhibited the synthesis of a single mycelial-specific glycoprotein species.


Seasonal relationships between dopamine D1 and D2 receptor and equine FSH receptor mRNA in equine ovarian epithelium.
Dopamine (DA) blockade during anestrus or early spring transition can facilitate ovarian recrudescence and advance the timing of the first ovulation of the season. Some laboratories have reported variable results using DA antagonists to stimulate follicular growth during the mid-portion of the anestrual period. Differences in DA antagonist efficacy may be due to the FSH secretory status of the anestrous mare and the presence or absence of functional ovarian FSH receptors. We hypothesize that direct ovarian dopaminergic input can affect follicular growth through regulation of FSH receptor (FSHr) populations. To investigate this, the amount of DA D1 and D2 receptor (D1r, D2r) and FSHr mRNA was quantified in ovarian tissues in anestrous and mares expressing estrus at typical intervals that are detected during the breeding season. Ovaries (n=26) were collected from 10 anestrous mares and 13 mares that had initiated estrous cycles (n=8 luteal; n=5 follicular phase). The quantity of D1r and D2r mRNA and FSHr mRNA was determined in cortex of both groups and granulosa/theca (those having initiated estrous cycles) tissues by semi-quantitative polymerase chain reaction using the comparative cycle time method. The reference gene was glyceraldehyde-3-phosphate dehydrogenase. The fold-change for each sample was calculated based on a calibrator sample. Fold-change values for D1r and D2r were the dependent variable and tissue was the independent variable in a one-way ANOVA. Results of fold-change in FSHr were compared by ANCOVA due to unequal sample sizes from each mare. Correlations between receptors within each tissue type were determined. For each receptor type and tissue, correlations between follicular and luteal phases were determined. The fold-change of D1r mRNA was less than D2r mRNA in all tissue types and between seasons. The quantity of D2r message in ovarian cortex was greater (p<0.05) during anestrus than after estrous cycles had been initiated. Fold-change in D2r in granulosa/theca was not different dependant on estrous cycle phase or follicle size. Quantity of FSHr mRNA was less in anestrous ovarian cortex and greater after estrous cycles had been initiated. FSHr mRNA fold-change in the ovarian cortex after estrous cycle initiation was not different between estrous cycle phases, but was greater in smaller (<30mm) follicles compared with larger (> or =30mm) follicles. We have demonstrated an inverse temporal relation between ovarian D2r and FSHr in mares dependant upon season. The functional significance of this relationship deserves further study.


A smoothing gradient-based neural network strategy for solving semidefinite programming problems.
Linear semidefinite programming problems have received a lot of attentions because of large variety of applications. This paper deals with a smooth gradient neural network scheme for solving semidefinite programming problems. According to some properties of convex analysis and using a merit function in matrix form, a neural network model is constructed. It is shown that the proposed neural network is asymptotically stable and converges to an exact optimal solution of the semidefinite programming problem. Numerical simulations are given to show that the numerical behaviours are in good agreement with the theoretical results.


[Informal sellers' health status and working conditions in the Bazurto market in Cartagena].
Determining informal sellers' health status and working conditions in the Bazurto market in Cartagena. The target population consisted of informal sellers working in the Bazurto market; sample size consisted of 584 sellers. A check-list was used to describe their working conditions. A "health disorders" test and neurotoxic symptoms scale (Q16) were used to determine health status and the body mass index (BMI) for determining nutritional status. 583 sellers participated in the study, having an average age of 39 years (38-40 95 %CI). 87.8 % (512) of the participants were exposed to constant noise, 84.9 % (495) worked in places having high temperatures, 74.1 % (432) were exposed to dust, and 69.8 % (407) did not use personal protective equipment. They were working 10 hours a day on average. 71 % (414) suffered from physical exhaustion, 72.4 % (422) had headaches, 63.7 % (371) had back pain and 62.7 % (365) suffered from pains in their legs. The target population's physical environment was inadequate, they worked for too many hours and some workplaces were dangerous. The informal sellers' symptoms included back pain, headaches, leg pain, eye strain and physical fatigue.


Design Concepts for Solution and Solid-State Emitters - A Modern Viewpoint on Classical and Non-Classical Approaches.
For a long time, luminescence phenomena were strictly distinguished between the emission of isolated molecules in dilute solutions or close-packed structures such as in powders or aggregates. This changed with the breakthrough observation of dual-state efficient materials, which led to a rapid boost of publications examining the influence of structural features to achieve balanced emission with disregarded molecular surroundings. Some first general structural design concepts have already been proposed based on reoccurring patterns and pivotal motifs. However, we have found another way to classify these solution and solid-state emitters (SSSEs). Hence, this minireview aims to present an overview of published structural features of SSSEs while shining light on design concepts from a more generalized perspective. Since SSSEs are believed to bridge the gap of hitherto known aggregation-sensitive compound classes, we hope to give future scientists a versatile tool in hand to efficiently design novel luminescent materials.


Diagnostic testing patterns for Streptococcus equi subsp. equi in Ontario horses during the years 2008 to 2018.
This retrospective study describes testing patterns and the incidence of Streptococcus equi subsp. equi in Ontario to assess the utility of laboratory data for surveillance purposes. Laboratory records for equine infectious disease test submissions were extracted from the Animal Health Laboratory (AHL) at the University of Guelph for the years 2008 to 2018. Yearly and seasonal trends in S. equi testing and the proportion of tests that returned positive results were assessed. The number of samples submitted for S. equi testing decreased over the 11-year period (odds ratio = 0.96, 95% confidence interval: 0.92 to 0.999; P = 0.04). A generalized linear model identified a significant seasonal effect for animals recognized as clinically ill, with the highest test positivity noted in the winter. Although this study identified important trends in the incidence of S. equi in Ontario, the variability in information accompanying test submissions made the data challenging to interpret, highlighting the need for more complete diagnostic submission data for S. equi.


Stem cell differentiation trajectories in Hydra resolved at single-cell resolution.
The adult Hydra polyp continually renews all of its cells using three separate stem cell populations, but the genetic pathways enabling this homeostatic tissue maintenance are not well understood. We sequenced 24,985 Hydra single-cell transcriptomes and identified the molecular signatures of a broad spectrum of cell states, from stem cells to terminally differentiated cells. We constructed differentiation trajectories for each cell lineage and identified gene modules and putative regulators expressed along these trajectories, thus creating a comprehensive molecular map of all developmental lineages in the adult animal. In addition, we built a gene expression map of the Hydra nervous system. Our work constitutes a resource for addressing questions regarding the evolution of metazoan developmental processes and nervous system function.


Report of two siblings with APECED in Serbia: is there a founder effect of c.769C>T AIRE genotype?
Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) or autoimmune polyglandular syndrome Type 1 is a rare autosomal recessive syndrome. The disorder is caused by mutations in the AIRE (AutoImmune Regulator) gene. According to the classic criteria, clinical diagnosis requires the presence of at least two of three main components: chronic mucocutaneous candidiasis, hypoparathyroidism and primary adrenal insufficiency. Furthermore, patients are often affected by other endocrine or non-endocrine associated autoimmune conditions. The enrichment of the non-classical triad seems to occur differently in different cohorts. Screenings of the population revealed that homozygous AIRE mutations c.769C > T, c.415C > T and c.254A > G have a founder effect in Finnish, Sardinian and Iranian Jew populations respectively. We report here the clinical and genetic characteristics of two new Serbian APECED siblings, one male and one female, actual age of 27 and 24 respectively, born from non-consanguineous parents. Addison's disease was diagnosed in the male at the age of 3.5 and hypoparathyroidism at the age of 4. The female developed hypoparathyroidism at 4 years of age. She presented diffuse alopecia, madarosis, onychomycosis, teeth enamel dysplasia. She further developed Addison's disease at the age of 11 and Hashimoto's thyroiditis at the age of 13.5. She had menarche at the age of 14 but developed autoimmune oophoritis and premature ovarian failure at the age of 16. A treatment with hydrocortisone, fludrocortisone and alfacalcidiol was established for both siblings; L-T4 (levo-thyroxine) for thyroid dysfunction and levonorgestrel and etinilestradiol for POF were also administered to the female. Genetic screening revealed a homozygous c.769C > T (R257X (p.Arg257X)) AIRE mutation. We additionally reviewed the literature on 11 previously published Serbian patients and evaluated the frequency of their main diseases in comparison to Finnish, Sardinian, Turkish, Indian and North/South American cohorts. A founder effect was discovered for the R257X genotype detected in the DNA of 10 homozygous and 2 heterozygous patients. Of note, all Serbian APECED patients were affected by adrenal insufficiency and 10 out of 13 patients presented CMC.


A Systematic Review and Meta-Analysis of the Brief Cognitive Assessment for Multiple Sclerosis (BICAMS).
Multiple sclerosis (MS) is a neurological disease of the central nervous system which can lead to a range of severe physical disabilities. A large proportion of those affected will experience cognitive impairment, which is associated with a worse prognosis. Effective assessment of cognition in MS has been problematic due to a lack of suitable scales. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) was developed in 2010 as part of an international endeavour to facilitate cognitive assessment. The aim of this systematic review and meta-analysis was to synthesise the available literature published as part of the BICAMS international validation protocol. A literature search conducted using PubMed, PsycINFO and Google Scholar identified 16 studies for inclusion in the systematic review, 14 of which could be included in a meta-analysis. BICAMS has been widely validated across 11 languages and 14 individual cultures and locations. The meta-analysis demonstrated that BICAMS identified significantly reduced cognitive functioning in adults with MS compared to healthy controls. This was true for all three cognitive domains assessed by BICAMS: information processing speed (g = 0.943, 95% CI 0.839, 1.046, g < 0.001), immediate verbal recall memory (g = 0.688, 95% CI 0.554, 0.822, p < 0.001) and immediate visual recall memory (g = 0.635, 95% CI 0.534, 0.736, p < 0.001). BICAMS has been widely applied across cultures and languages to assess cognition in MS. BICAMS offers a feasible, cost-effective means of assessing cognition in MS worldwide. Further validation studies are underway to support this project.


Release of nitrite from the antitubercular nitroimidazole drug PA-824 and analogues upon one-electron reduction in protic, non-aqueous solvent.
The one-electron reduction chemistry of the antituberculosis drug PA-824, together with a series of closely related compounds, has been investigated in irradiated anaerobic propan-2-ol solution. The protic solvent, of low dielectric constant, was chosen to mimic the environment of a water-restricting active site of a model protein, which is capable of reducing the compounds. Radiolytic reduction of the compounds containing electron donating substituents in the 2-position of the imidazole ring released nitrite, with compounds that are highly active against Mycobacterium tuberculosis exhibiting high yields of nitrite. The release of cytotoxic reactive nitrogen species through a one-electron pathway, by as yet unidentified proteins, may play a role in the activity of this class of compounds against TB. The described radiolytic quantification of nitrite release may have utility as a preliminary screening test for nitroaromatic candidate drugs against the disease.


Synthesis of functionalized tetrahydro-1,3-diazepin-2-ones and 1-carbamoyl-1H-pyrroles via ring expansion and ring expansion/ring contraction of tetrahydropyrimidines.
A general approach to 6-phenylthio-substituted 2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones based on the ring expansion reaction of 1,2,3,4-tetrahydropyrimidin-2-ones under the action of nucleophiles has been developed. The first step of the synthesis was preparation of N-[(2-benzoyloxy-1-tosyl)ethyl]urea by three-component condensation of 2-benzoyloxyethanal, urea and p-toluenesulfinic acid. Nucleophilic substitution of the tosyl group in the obtained sulfone with sodium enolates of α-phenylthioketones followed by cyclization-dehydration, and debenzoylation gave 4-hydroxymethyl-5-phenylthio-1,2,3,4-tetrahydropyrimidin-2-ones which were transformed into the 4-mesyloxymethyl-derivatives. Treatment of the latter with nucleophilic reagents, such as NaCN, sodium diethyl malonate, PhSNa, MeONa, NaBH(4), sodium succinimide, or potassium phthalimide, afforded the target multi-functionalized diazepinones. The obtained 6-phenylthio-diazepinones and their 6-tosyl-substituted analogues were converted into 3-substituted 1-carbamoyl-1H-pyrroles under acidic conditions as a result of ring contraction. Effective one-pot synthesis of the latter from 4-mesyloxymethyl-pyrimidines was realized using a ring expansion/ring contraction sequence.


Initial Response of Human Bone Marrow-Derived Stem Cells after Contact with Ultrahigh-Molecular-Weight Polyethylene (UHMWPE) Material: An In Vitro Study on Cell Viability and Interleukin-6 Expression.
Ultrahigh-molecular-weight polyethylene (UHMWPE) is a thermoplastic polymer useful in biomaterial applications, especially in orthopedic field. Yet, little is known concerning its initial effect on human bone marrow stem cells (hBMSCs) after implantation. A cytotoxicity analysis was performed with a 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium assay after 24, 48, and 72h of incubation of hBMSC culture. Expression of interleukin-6 (IL-6) was measured using enzyme-linked immunosorbent assay. Cell viability was measured with Inhibitory concentration 50% (IC50) formula. All treatment groups showed a cell viability of >50% ranging from 78% to >100%. Lower expression of IL-6 of hBMSC compared to control group was found in 48h of incubation period. hBMSC showed high cell viability after initial contact with UHMWPE material. Modulation of IL-6 expression was present at the initial stage as a response to foreign material.


Cochlear implantation in postlingually hearing-impaired adults: choosing the most appropriate ear.
Choice of the most appropriate ear for CI in postlingually hearing-impaired adults is becoming more relevant as more patients are considered eligible for intervention. The aim of this study is to review factors that influence this choice and to formulate a flowchart. An extensive Medline search was performed. Factors can be divided into surgical, audiological, and patient factors. Surgical factors are anatomic variation and otological medical history. Both are divided in absolute and relative contraindications. Duration of deafness and residual hearing are combined in the audiological factor. Likeliness of improvement of speech perception after CI at different durations of deafness is estimated. This is followed by comparison of between-ear differences in duration of deafness. If there is a large difference, above the presented 5% interval, the ear with the shortest duration is preferred. This review and its flowchart are an aid for decision making in the choice of ear for CI. Being as representative of current knowledge as possible, future refinements may occur as new insights are gained.


Economic burden associated with inadequate antidepressant medication management among patients with depression and known cardiovascular diseases: insights from a United States-based retrospective claims database analysis.
Aims: The current study examined the association between insufficient major depressive disorder (MDD) care and healthcare resource use (HCRU) and costs among patients with prior myocardial infarction (MI) or stroke.Methods: This was a retrospective study conducted using the MarketScan Claims Database (2010-2015). The date of the first MI/stroke diagnosis was defined as the cardiovascular disease (CVD) index date and the first date of a subsequent MDD diagnosis was the index MDD date. Adequacy of MDD care was assessed during the 90 days following the index MDD date (profiling period) using 2 measures: dosage adequacy (average fluoxetine equivalent dose of ≥20 mg/day for nonelderly and ≥10 mg/day for elderly patients) and duration adequacy (measured as the proportion of days covered of 80% or higher for all MDD drugs). Study outcomes included all-cause and CVD-related HCRU and costs which were determined from the end of the profiling period until the end of study follow-up. Propensity-score adjusted generalized linear models (GLMs) were used to compare patients receiving adequate versus inadequate MDD care in terms of study outcomes.Results: Of 1,568 CVD patients who were treated for MDD, 937 (59.8%) were categorized as receiving inadequate MDD care. Results from the GLMs suggested that patients receiving inadequate MDD care had 14% more all-cause hospitalizations, 4% more all-cause outpatient visits, 17% more CVD-related outpatient visits, 13% more CVD-related emergency room (ER) visits, higher per patient per year CVD-related hospitalization costs ($21,485 vs. $17,756), higher all-cause outpatient costs ($2,820 vs. $2,055), and higher CVD-related outpatient costs ($520 vs. $434) compared to patients receiving adequate MDD care.Limitations: Clinical information such as depression severity and frailty, which are potential predictors of adverse CVD outcomes, could not be ascertained using administrative claims data.Conclusions: Among post-MI and post-stroke patients, inadequate MDD care was associated with a significantly higher economic burden.


Addition of Wollastonite Fibers to Calcium Phosphate Cement Increases Cell Viability and Stimulates Differentiation of Osteoblast-Like Cells.
Calcium phosphate cement (CPC) that is based on α-tricalcium phosphate (α-TCP) is considered desirable for bone tissue engineering because of its relatively rapid degradation properties. However, such cement is relatively weak, restricting its use to areas of low mechanical stress. Wollastonite fibers (WF) have been used to improve the mechanical strength of biomaterials. However, the biological properties of WF remain poorly understood. Here, we tested the response of osteoblast-like cells to being cultured on CPC reinforced with 5% of WF (CPC-WF). We found that both types of cement studied achieved an ion balance for calcium and phosphate after 3 days of immersion in culture medium and this allowed subsequent long-term cell culture. CPC-WF increased cell viability and stimulated cell differentiation, compared to nonreinforced CPC. We hypothesize that late silicon release by CPC-WF induces increased cell proliferation and differentiation. Based on our findings, we propose that CPC-WF is a promising material for bone tissue engineering applications.


[Hypervascularization syndrome of the penis following arterialization of the dorsal penile vein for erectile impotence].
A hypervascularization syndrome following arterialization of the deep dorsal vein of the penis to amend venous erectile impotence is a rare cause of penile ulcers that has not previously been described in the dermatological literature. Arterialization is performed by installing a shunt from the inferior epigastric artery or a venous bypass from the femoral artery to the deep dorsal vein of the penis, resulting in a blockage of venous outflow and in retrograde inflow into the corpora cavernosa. Complications arise as a result of persistently elevated blood pressure in the deep venous system and the erectile tissue in 10-20% of cases and are most often linked to dilatation of the shunt: the consequences are enlargement and induration of the glans, hazard of phimosis and paraphimosis, pulsation of the penis, micturation difficulties and, ultimately, ulceration of the glans. Surgical reduction of the arterial inflow ("banding" of the shunt) is the only therapeutic procedure that reduces hypervascularization without compromising the newly gained erectile function.


Reducing the haystack to find the needle: improved protein identification after fast elimination of non-interpretable peptide MS/MS spectra and noise reduction.
Tandem mass spectrometry (MS/MS) has become a standard method for identification of proteins extracted from biological samples but the huge number and the noise contamination of MS/MS spectra obstruct swift and reliable computer-aided interpretation. Typically, a minor fraction of the spectra per sample (most often, only a few %) and about 10% of the peaks per spectrum contribute to the final result if protein identification is not prevented by the noise at all. Two fast preprocessing screens can substantially reduce the haystack of MS/MS data. (1) Simple sequence ladder rules remove spectra non-interpretable in peptide sequences. (2) Modified Fourier-transform-based criteria clear background in the remaining data. In average, only a remainder of 35% of the MS/MS spectra (each reduced in size by about one quarter) has to be handed over to the interpretation software for reliable protein identification essentially without loss of information, with a trend to improved sequence coverage and with proportional decrease of computer resource consumption. The search for sequence ladders in tandem MS/MS spectra with subsequent noise suppression is a promising strategy to reduce the number of MS/MS spectra from electro-spray instruments and to enhance the reliability of protein matches. Supplementary material and the software are available from an accompanying WWW-site with the URL http://mendel.bii.a-star.edu.sg/mass-spectrometry/MSCleaner-2.0/.


Extensor carpi ulnaris tenosynovitis caused by the tip of an oversized ulnar styloid: a case report.
Background Degenerative tendinopathy of the extensor carpi ulnaris (ECU) produced by the tip of an oversized ulnar styloid has not been formerly reported. Case Description We report an uncommon case of an injury to the ECU tendon that was related to a prominent oversized ulnar styloid. The patient's symptoms improved following resection of the styloid process. Literature Review Our case differs from previous reports in that it involves an uninjured oversized ulnar styloid that damaged the overlying ECU tendon with no apparent instability. Clinical Relevance Besides ulnar styloid impaction syndrome, the diagnosis of ECU tenosynovitis should also be considered in patients with ulnar-side pain and an oversized ulnar styloid.


Latent Autoimmune Diabetes in Adults (LADA): From Immunopathogenesis to Immunotherapy.
Latent autoimmune diabetes in adults (LADA) is a type of diabetes characterized by slow autoimmune damage of pancreatic β cells without insulin treatment in the early clinical stage. There are differences between LADA and classical type 1 diabetes (T1D) and type 2 diabetes (T2D) in genetic background, autoimmune response, rate of islet function decline, clinical metabolic characteristics, and so on. The disease progression and drug response of patients with LADA are closely related to the level of islet autoimmunity, thus exploring the pathogenesis of LADA is of great significance for its prevention and treatment. Previous studies reported that adaptive immunity and innate immunity play a critical role in the etiology of LADA. Recent studies have shown that the intestinal microbiota which impacts host immunity hugely, participates in the pathogenesis of LADA. In addition, the progression of autoimmune pancreatic β cell destruction in LADA is slower than in classical T1D, providing a wider window of opportunities for intervention. Therefore, therapies including antidiabetic drugs with immune-regulation effects and immunomodulators could contribute to promising interventions for LADA. We also shed light on potential interventions targeting the gut microbiota and gut-associated immunity, which may be envisaged to halt or delay the process of autoimmunity in LADA.


Evidence for existence of an apoptosis-inducing BH3-only protein, sayonara, in Drosophila.
Cells need to sense stresses to initiate the execution of the dormant cell death program. Since the discovery of the first BH3-only protein Bad, BH3-only proteins have been recognized as indispensable stress sensors that induce apoptosis. BH3-only proteins have so far not been identified in Drosophila despite their importance in other organisms. Here, we identify the first Drosophila BH3-only protein and name it sayonara. Sayonara induces apoptosis in a BH3 motif-dependent manner and interacts genetically and biochemically with the BCL-2 homologous proteins, Buffy and Debcl. There is a positive feedback loop between Sayonara-mediated caspase activation and autophagy. The BH3 motif of sayonara phylogenetically appeared at the time of the ancestral gene duplication that led to the formation of Buffy and Debcl in the dipteran lineage. To our knowledge, this is the first identification of a bona fide BH3-only protein in Drosophila, thus providing a unique example of how cell death mechanisms can evolve both through time and across taxa.


Astrocytic responses in the lateral geniculate nucleus of monkeys with experimental glaucoma.
To investigate the responses of lateral geniculate nucleus (LGN) astrocytes to experimental glaucoma in monkeys. Rhesus monkeys (Macaca mulatta). Unilateral chronic elevation of intraocular pressure (IOP) was induced in six rhesus monkeys by laser photocoagulation of the trabecular meshwork. Four normal monkeys were used as controls. Immunohistochemistry with antibodies to glial fibrillary acidic protein (GFAP), S100β and parvalbumin was used to specifically label astrocytes and neurons in the LGN. The relative immunointensity (RI) of GFAP was defined as the ratio of intensity between each region of interest to a reference field and compared between the experimental and control groups as a function of percentage optic nerve fiber loss. Ultrastructural changes of LGN astrocytes were examined by transmission electron microscopy. An increase in GFAP and S100β immunoreactivity was observed in the LGN layers receiving projections from the experimental glaucoma eyes. Quantitative analysis revealed that the RI of GFAP in both the magnocellular and parvocellular layers connected to the glaucomatous eyes increased in a linear fashion with increasing optic nerve fiber loss. Compared to controls, the RI of GFAP was also moderately elevated in LGN layers connected to the fellow nonglaucomatous eyes. Ultrastructurally, accumulation of glial filaments that occurred throughout the perikaryon and extended into the process in reactive astrocytes was observed in LGN layers of glaucomatous monkeys. Reactive astrogliosis occurs in the magnocellular and parvocellular LGN layers of monkeys with unilateral glaucoma. Astrocytes may play an important role in the regulation of LGN microenvironment in glaucoma.


Maintaining activity engagement: individual differences in the process of self-regulating motivation.
Typically, models of self-regulation include motivation in terms of goals. Motivation is proposed to differ among individuals as a consequence of the goals they hold as well as how much they value those goals and expect to attain them. We suggest that goal-defined motivation is only one source of motivation critical for sustained engagement. A second source is the motivation that arises from the degree of interest experienced in the process of goal pursuit. Our model integrates both sources of motivation within the goal-striving process and suggests that individuals may actively monitor and regulate them. Conceptualizing motivation in terms of a self-regulatory process provides an organizing framework for understanding how individuals might differ in whether they experience interest while working toward goals, whether they persist without interest, and whether and how they try to create interest. We first present the self-regulation of motivation model and then review research illustrating how the consideration of individual differences at different points in the process allows a better understanding of variability in people's choices, efforts, and persistence over time.


Virtual 2D map of cyanobacterial proteomes.
Cyanobacteria are prokaryotic Gram-negative organisms prevalent in nearly all habitats. A detailed proteomics study of Cyanobacteria has not been conducted despite extensive study of their genome sequences. Therefore, we conducted a proteome-wide analysis of the Cyanobacteria proteome and found Calothrix desertica as the largest (680331.825 kDa) and Candidatus synechococcus spongiarum as the smallest (42726.77 kDa) proteome of the cyanobacterial kingdom. A Cyanobacterial proteome encodes 312.018 amino acids per protein, with a molecular weight of 182173.1324 kDa per proteome. The isoelectric point (pI) of the Cyanobacterial proteome ranges from 2.13 to 13.32. It was found that the Cyanobacterial proteome encodes a greater number of acidic-pI proteins, and their average pI is 6.437. The proteins with higher pI are likely to contain repetitive amino acids. A virtual 2D map of Cyanobacterial proteome showed a bimodal distribution of molecular weight and pI. Several proteins within the Cyanobacterial proteome were found to encode Selenocysteine (Sec) amino acid, while Pyrrolysine amino acids were not detected. The study can enable us to generate a high-resolution cell map to monitor proteomic dynamics. Through this computational analysis, we can gain a better understanding of the bias in codon usage by analyzing the amino acid composition of the Cyanobacterial proteome.


Depletion of phosphatidylinositol 4-phosphate at the Golgi translocates K-Ras to mitochondria.
Ras proteins are small GTPases localized to the plasma membrane (PM), which regulate cellular proliferation, apoptosis and differentiation. After a series of post-translational modifications, H-Ras and N-Ras traffic to the PM from the Golgi via the classical exocytic pathway, but the exact mechanism of K-Ras trafficking to the PM from the ER is not fully characterized. ATP5G1 (also known as ATP5MC1) is one of the three proteins that comprise subunit c of the F0 complex of the mitochondrial ATP synthase. In this study, we show that overexpression of the mitochondrial targeting sequence of ATP5G1 perturbs glucose metabolism, inhibits oncogenic K-Ras signaling, and redistributes phosphatidylserine (PtdSer) to mitochondria and other endomembranes, resulting in K-Ras translocation to mitochondria. Also, it depletes phosphatidylinositol 4-phosphate (PI4P) at the Golgi. Glucose supplementation restores PtdSer and K-Ras PM localization and PI4P at the Golgi. We further show that inhibition of the Golgi-localized PI4-kinases (PI4Ks) translocates K-Ras, and PtdSer to mitochondria and endomembranes, respectively. We conclude that PI4P at the Golgi regulates the PM localization of PtdSer and K-Ras.This article has an associated First Person interview with the first author of the paper.


Membrane-encapsulated camouflaged nanomedicines in drug delivery.
Owing to the limitations of conventional therapies, there has been an increasing need for nanomedicines for real-time diagnosis and effective treatment of life-threatening diseases. Despite the conceptual and technological success achieved by researchers worldwide, the complexities of biological systems, efficient engineering and formulation of monodispersed nanomedicines, inadequate information on bio-nano interactions, issues on health hazards, clinical trials and commercialization have set new challenges in biomedical research. This review highlights how the biological membrane improves the performance of nanomedicines in drug delivery. With the list of nanomedicines getting longer gradually to overcome the drawbacks of conventional therapeutics, it is important to concentrate on the interactions between nanostructures and living systems in order to improve the biocompatibility and therapeutic efficacy of functional nanomedicines.


Temporal trends in cardiogenic shock treatment and outcomes among ontario patients with myocardial infarction between 1992 and 2008.
Clinical trials have demonstrated that emergent revascularization improves survival of patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). However, rates of uptake and impact on outcomes remain uncertain. We identified 9750 patients (3.1%) with CS among 311 183 AMI patients in the Ontario Myocardial Infarction Database between 1992 and 2008 (55.8% men; mean age, 73 years). CS incidence, mortality, revascularization, and transfers from nonrevascularization sites were studied over 3 periods: period 1, before the 1999 American College of Cardiology/American Heart Association AMI guidelines recommending urgent revascularization for patients <75 years; period 2 (1999 to 2004); and period 3, after 2004 guideline revisions suggesting revascularization for patients ≥75 years. Compared with period 1, period 3 was marked by significantly lower CS incidence (3.4% versus 2.6%), increase in transfers from nonrevascularization sites (10.6% versus 23.9%), and adjusted 1-year mortality rates (81.9% versus 71.5%; all comparisons statistically significant). Admission to nonrevascularization sites was associated with lower revascularization rates (8.6% versus 46.6%, P<0.001) and higher adjusted 1-year mortality rates (78.8% [95% confidence interval, 77.4 to 80.2] versus 71.9% [95% confidence interval, 69.8 to 74.1]). Patients ≥75 years of age were less likely to be revascularized or transferred. The greatest increase in transfers from nonrevascularization sites occurred between periods 1 and 2 for patients <75 years (16.5% to 31.4%; P<0.001) and between periods 2 and 3 for patients ≥75 years (6.7% to 12.8%; P<0.001). Publication of American College of Cardiology/American Heart Association guidelines was followed by increased revascularization and transfer rates, along with declining mortality rates among Ontario AMI patients with CS. These results highlight possibilities for further improvement, particularly among patients eligible for transfer from nonrevascularization sites.


Extraction of entity relations from Chinese medical literature based on multi-scale CRNN.
Entity relation extraction technology can be used to extract entities and relations from medical literature, and automatically establish professional mapping knowledge domains. The classical text classification model, convolutional neural networks for sentence classification (TEXTCNN), has been shown to have good classification performance, but also has a long-distance dependency problem, which is a common problem of convolutional neural networks (CNNs). Recurrent neural networks (RNN) address the long-distance dependency problem but cannot capture text features at a specific scale in the text. To solve these problems, this study sought to establish a model with a multi-scale convolutional recurrent neural network for Sentence Classification (TEXTCRNN) to address the deficiencies in the 2 neural network structures. In entity relation extraction, the entity pair is generally composed of a subject and an object, but as the subject in the entity pair of medical literature is always omitted, it is difficult to use this coding method to obtain general entity position information. Thus, we proposed a new coding method to obtain entity position information to re-establish the relationship between subject and object and complete the entity relation extraction. By comparing the benchmark neural network model and 2 typical multi-scale TEXTCRNN models, the TEXTCRNN [bidirectional long- and short-term memory (BiLSTM)] and TEXTCRNN [double-layer stacking gated recurrent unit (GRU)], the results showed that the multi-scale CRNN model had the best F1 value performance, and the TEXTCRNN (double-layer stacking GRU) was more capable of entity relation classification when the same entity word did not belong to the same entity relation. The experimental results of the entity relation extraction from Pharmacopoeia of the People's Republic of China-Guidelines for Clinical Drug Use-Volume of Chemical Drugs and Biological Products showed that entity relation extraction could effectively proceed using the new labeling method. Additionally, compared to typical neural network models, including the TEXTCNN, GRU, and BiLSTM, the multi-scale convolutional recurrent neural network structure had advantages across several evaluation indicators.