Ecology and epidemiology of Echinococcus multilocularis in Europe.
Human alveolar echinococcosis (AE), caused by the larval stage of Echinococcus multilocularis has a high mortality rate in untreated patients. The life-cycle of E. multilocularis in Europe predominantly involves foxes as definitive hosts. However, experimental studies demonstrated a comparable biotic potential of E. multilocularis in dogs and raccoon dogs but an insignificant potential in cats. AE occurs in central and eastern Europe at low incidence rates. Recent studies in foxes have shown that E. multilocularis has a wider geographic range (including Italy) than previously thought. In recent years, increases in fox populations have been observed in many European countries, especially in urban areas. As a result, the E. multilocularis cycle is now established in the urban environment. This presents an increased risk of infection for a large human population. Based on these facts and new epidemiological data, possible intervention strategies are presented.


ASA Status, NPPA/NPPB Haplotype and Coronary Artery Disease Have an Impact on BNP/NT-proBNP Plasma Levels.
Plasma concentrations of natriuretic peptides (NP) contribute to risk stratification and management of patients undergoing non-cardiac surgery. However, genetically determined variability in the levels of these biomarkers has been described previously. In the perioperative setting, genetic contribution to NP plasma level variability has not yet been determined. A cohort of 427 patients presenting for non-cardiac surgery was genotyped for single-nucleotide polymorphisms (SNPs) from the NPPA/NPPB locus. Haplotype population frequencies were estimated and adjusted haplotype trait associations for brain natriuretic peptide (BNP) and amino-terminal pro natriuretic peptide (NT-proBNP) were calculated. Five SNPs were included in the analysis. Compared to the reference haplotype TATAT (rs198358, rs5068, rs632793, rs198389, rs6676300), haplotype CACGC, with an estimated frequency of 4%, showed elevated BNP and NT-proBNP plasma concentrations by 44% and 94%, respectively. Haplotype CGCGC, with an estimated frequency of 9%, lowered NT-proBNP concentrations by 28%. ASA classification status III and IV, as well as coronary artery disease, were the strongest predictors of increased NP plasma levels. Inclusion of genetic information might improve perioperative risk stratification of patients based on adjusted thresholds of NP plasma levels.


The Ilizarov external fixator for treatment of deformities in Paget's disease.
Paget's disease of bone may cause progressive bowing of affected femurs and tibiae. Fractures or osteotomies in these patients technically are difficult to treat and may lead to delayed union or nonunion. The authors report their early results with the use of the Ilizarov external fixator to affix 3 corrective closing wedge osteotomies, 1 fracture, and 1 delayed union. Deformities were corrected fully during the surgery, with an option to correct remaining deformation progressively during the rest of treatment. Compression of the healing bone was applied to enhance osseous healing, when necessary. Three-dimensional control is possible, and the stability of the fixation is excellent in this structurally weak bone. Bony union was achieved without complications in all patients within 4 months.


Clinical features in hepatocellular carcinoma and the impact of autopsy on diagnosis. A study of 530 cases from a low-endemicity area.
Hepatocellular carcinoma (HCC) had been one of the malignancies with the highest reported increase of incidence in Sweden, but during the late 20-year period the incidence has been decreasing. The aims of our study were to state the impact of autopsy on diagnosis and to identify clinical characteristics in HCC. This retrospective study was performed in Göteborg, Sweden and included all cases with a diagnosis of liver cancer from a period with a high autopsy frequency (1958-1979). The cases were reevaluated histopathologically and the autopsy records as well as the case files were scrutinized. The majority (63%) of the 530 biopsy verified cases of HCC were diagnosed unexpectedly at autopsy. Cirrhosis of the liver could be established in 71% of the cases, but was diagnosed or at least clinically suspected before the diagnosis of the tumor only in a minority (19%) of all HCC patients. At presentation, malaise (85%), weight loss (78%), anorexia (67%) and hepatomegaly (84%) were common. The median survival time from diagnosis was one month. In most cases (92%) the cause of death was either directly or indirectly related to HCC and/or underlying liver disease such as advanced tumor disease, hepatic failure and gastrointestinal bleeding. Spontaneous rupture of HCC was the cause of death in 17 cases (3%) In an unselected population in a low incidence area of HCC, most patients have clinically unknown cirrhosis of the liver and present with vague general paramalignant symptoms. HCC has an extremely poor prognosis. Since HCC, in a majority of cases, remains undiagnosed before death, the autopsy has great impact on the diagnosis. This should be considered in interpretation of results from epidemiological studies.


Baseline correlates of inconsistent and incorrect condom use among sexually active women in the contraceptive CHOICE Project.
: To provide protection against sexually transmitted infections and pregnancy, condoms must be used consistently and correctly. However, a significant proportion of couples in the United States fail to do so. Our objective was to determine the demographic and behavioral correlates of inconsistent and incorrect condom use among sexually active, condom-using women. : Analysis of baseline data from a prospective cohort of sexually active, condom-using women in the Contraceptive CHOICE Project (n = 2087) using self-reported demographic and behavioral characteristics. Poisson regression was used to determine the relative risk of inconsistent and incorrect condom use after adjusting for variables significant in the univariate analysis. : Inconsistent and incorrect condom use was reported by 41% (n = 847) and 36% (n = 757) of women, respectively. A greater number of unprotected acts was most strongly associated with reporting 10 or more sex acts in the past 30 days, younger age at first intercourse, less perceived partner willingness to use condoms, and lower condom use self-efficacy. Incorrect condom use was associated with reporting 10 or more sex acts in the past 30 days, greater perceived risk for future STIs, and inconsistent condom use. : Inconsistent and incorrect condom use is common among sexually active women. Targeted educational efforts and prevention strategies should be implemented among women at highest risk for STIs and unintended pregnancies to increase consistent and correct condom use.


Pogonophora in the Western Atlantic Ocean.
The occurrence of pogonophoran worms of the genus Siboglinum off the east coast of Florida is reported. Their presence in association with pennatulids is noted, and compared with a similar instance in the Bering Sea. This association is probably due to similar ecological requirements.


Time course of cytokines, hemodynamic and metabolic parameters during hyperthermic intraperitoneal chemotherapy.
Systemic response to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) causes the activation of endocrine, metabolic, hemodynamic and inflammatory processes. The aim of this work is to describe and analyze the time course of the inflammatory markers concentration during CRS+HIPEC in plasma and peritoneal fluids and the association with hemodynamic and metabolic parameters. Pre-, intra- and postoperative data were collected. Tumor necrosis factor (TNF), interleukine 6 (IL-6), pro-calcitonin (PCT), cancer antigen 125 (CA-125) in blood and in peritoneal fluids were evaluated. Thirty-eight patients were included, 29 (76.3%) of them were female. Mean/median PCI was 9.2/5, primary malignancy was 5 colorectal cancer (13.2%), 5 gastric cancer (13.2%), 23 ovarian cancer (60.5%) and 5 other malignancies (13.2%). Combined clinical risk 0-1 was reached in all patients. Cardiac index, heart rate and central venous pressure increased during the procedure, while stroke volume variation showed a decrease. Mean arterial pressure and superior vena cava oxygenation were stable throughout the whole procedure. TNF and CA-125 were steady during the whole procedure; IL-6 had a relevant increase from baseline to start of perfusion (P<0.01); PCT had a steady increase at every time point. Peritoneal sampling showed a statistically significant increase (P<0.01) between start and end of the perfusion phase for all markers but TNF. Serum and peritoneal marker concentration were similar for TNF, PCT and CA-125. IL-6 showed a sharp difference. The most significant variations were in IL-6 and PCT levels. The cytokines level parallels the hemodynamic derangements. Treatment during HIPEC should mimic the established treatment during sepsis and septic shock.


[Seasonal variations of female aggressiveness and population dynamics of Culex quinquefasciatus Say 1823 in Abidjan (Republic of Côte d'Ivoire)].
Seasonal variations of Culex quinquefasciatus aggressiveness were studied in Abidjan where this mosquito is very harmful. Abidjan is crossed from East to West by the Ebrié lagoon, which is a vast expanse of brackish water (about 566 km2). In the North of this expanse of water lay continental plateaux and in the South lay low-plateaux. The city is composed of 10 districts, most of which are situated on the continental plateaux. Culex quinquefasciatus adult populations were caught monthly in 1989 on human bait traps in Abidjan 10 districts, one study place was located in each district. Captures took place outside the houses, in the dusk and during the first part of night, that is to say between 4 p.m. and 1 a.m. In Abidjan, Culex quinquefasciatus population density varies considerably within the city area. In the areas where the species is numerous, a high percentage of it seems to be developing all year through from breeding places which are, in most cases, permanent. Besides, the aggressiveness seasonal cycle which was registered in the above mentioned areas is particularly diversified.


Complex evolution in Aphis gossypii group (Hemiptera: Aphididae), evidence of primary host shift and hybridization between sympatric species.
Aphids provide a good model system to understand the ecological speciation concept, since the majority of the species are host-specific, and they spend their entire lifecycle on certain groups of host plants. Aphid species that apparently have wide host plant ranges have often turned out to be complexes of host-specialized biotypes. Here we investigated the various host-associated populations of the two recently diverged species, Aphis gossypii and A. rhamnicola, having multiple primary hosts, to understand the complex evolution with host-associated speciation. Using mitochondrial DNA marker and nine microsatellite loci, we reconstructed the haplotype network, and analyzed the genetic structure and relationships. Approximate Bayesian computation was also used to infer the ancestral primary host and host-associated divergence, which resulted in Rhamnus being the most ancestral host for A. gossypii and A. rhamnicola. As a result, Aphis gossypii and A. rhamnicola do not randomly use their primary and secondary host plants; rather, certain biotypes use only some secondary and specific primary hosts. Some biotypes are possibly in a diverging state through specialization to specific primary hosts. Our results also indicate that a new heteroecious race can commonly be derived from the heteroecious ancestor, showing strong evidence of ecological specialization through a primary host shift in both A. gossypii and A. rhamnicola. Interestingly, A. gossypii and A. rhamnicola shared COI haplotypes with each other, thus there is a possibility of introgression by hybridization between them by cross-sharing same primary hosts. Our results contribute to a new perspective in the study of aphid evolution by identifying complex evolutionary trends in the gossypii sensu lato complex.


Differential diagnosis of agitation following brain injury.
Posttraumatic agitation is perhaps the most dramatic behavioral consequence of severe traumatic brain injury. The mechanism for this behavior remains to be determined. The development of effective management strategies has been hampered at least in part by the lack of a consensus definition for posttraumatic agitation. The diagnosis of posttraumatic agitation is a diagnosis of exclusion. Concurrent neurologic or medical decline during the recovery from an acute traumatic brain injury may precipitate delirium, which has many clinical features that overlap with posttraumatic agitation. Hence, the differential diagnosis of posttraumatic agitation includes all medical and neurologic etiologies for transient declines in consciousness and cognition.


Characterization of particulate matter in carbon-graphite/epoxy advanced composite material smoke.
The physical and chemical properties of the particulate fraction of carbon-graphite/epoxy advanced composite material (cgeACM) smoke were measured to address concerns regarding potential health hazards posed by the release of fibers during pyrolysis of this material. Filter, low-pressure cascade impactor, and electrostatic precipitator samples were collected from cgeACM smoke in which the aerosol concentration ranged from 0.20 to 5.39 g/m3. Fibers were found in the smoke among individual, spherical, or nearly spherical particles and chain aggregates. The fibers had a mean count diameter of 0.54 micron and an average length of 2.84 microns. However, fibers accounted for approximately 0.3% of the particles counted. The smoke aerosols (including fibers) had mass median aerodynamic diameters (MMAD) ranging from 1.4 to 1.9 microns with standard geometric deviations ranging from 1.6 to 1.8, and hence more than 88% of the particles were in the thoracic size range (MMAD < or = 4.0 microns). All particles were composed primarily of carbon, silicon, sulfur, and oxygen with traces of other metals. By comparison fibers were composed almost exclusively of silicon.


Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus.
Gestational diabetes mellitus (GDM) and type 2 diabetes share a common pathophysiological background, including beta cell dysfunction and insulin resistance. In addition, women with GDM are at increased risk of developing type 2 diabetes later in life. Our aim was to investigate whether, like type 2 diabetes, GDM has a genetic predisposition by studying five common polymorphisms in four candidate genes that have previously been associated with type 2 diabetes. We studied 1,777 unrelated Scandinavian women (588 with GDM and 1,189 pregnant non-diabetic controls) for polymorphisms in the genes encoding potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11 E23K), insulin receptor substrate 1 (IRS1 G972R), uncoupling protein 2 (UCP2 -866G-->A) and calpain 10 (CAPN10 SNP43 and SNP44). The EE, EK and KK genotype frequencies of the KCNJ11 E23K polymorphism differed significantly between GDM and control women (31.5, 52.7 and 15.8% vs 37.3, 48.8 and 13.9%, respectively; p=0.050). In addition, the frequency of the K allele was increased in women with GDM (odds ratio [OR]=1.17, 95% CI 1.02-1.35; p=0.027), and this effect was greater under a dominant model (KK/EK vs EE) (OR=1.3, 95% CI 1.05-1.60; p=0.016). Analysis of the IRS1 G972R polymorphism showed that RR homozygosity was found exclusively in women with GDM (91.0, 8.3 and 0.7% vs 90.7, 9.3 and 0.0% for GG, GR and RR genotypes, respectively; p=0.014). The genotype and allele frequencies of the other polymorphisms studied were not statistically different between the GDM and control women. The E23K polymorphism of KCNJ11 seems to predispose to GDM in Scandinavian women.


p53, a pivotal effector of a functional cross-talk linking presenilins and Pen-2.
The γ-secretase is a multiprotein complex responsible for the ultimate cut yielding amyloid-β peptides and their N-terminal truncated species. This complex is composed of at least four distinct entities, namely presenilin-1 (PS1) or PS2, anterior pharynx defective-1, presenilin enhancer-2 (Pen-2) and nicastrin. Very few studies examined the transcriptional regulation of this complex, and more precisely, whether some of the members functionally interact. Here, we summarize our previous data documenting the fact that Pen-2 controls cell death in a p53-dependent manner and our recent demonstration of a pivotal role of p53 as a regulator of Pen-2 transcription. As PS trigger amyloid precursor protein intracellular domain-dependent regulation of p53, our studies delineate a feedback control mechanism by which PS and Pen-2 functionally interact in a p53-dependent manner.


Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States.
Endothelial nitric oxide synthase (eNOS) plays a critical role in regulating and maintaining a healthy cardiovascular system. The importance of eNOS can be emphasized from the genetic polymorphisms of the eNOS gene, uncoupling of eNOS dimerization, and its numerous signaling regulations. The activity of eNOS on the cardiac myocytes, vasculature, and the central nervous system are discussed. The effects of eNOS on the sympathetic autonomic nervous system (SANS) and the parasympathetic autonomic nervous system (PANS), both of which profoundly influence the cardiovascular system, will be elaborated. The relationship between the eNOS protein with cardiovascular autonomic reflexes such as the baroreflex and the Exercise Pressor Reflex will be discussed. For example, the effects of endogenous nitric oxide (NO) are shown to be mediated by the eNOS protein and that eNOS-derived endothelial NO is most effective in regulating blood pressure oscillations via modulating the baroreflex mechanisms. The protective action of eNOS on the CVS is emphasized here because dysfunction of the eNOS enzyme is intricately correlated with the pathogenesis of several cardiovascular diseases such as hypertension, arteriosclerosis, myocardial infarction, and stroke. Overall, our current understanding of the eNOS protein with a focus on its role in the modulation, regulation, and control of the cardiovascular system in a normal physiological state and in cardiovascular diseases are discussed.


Study of the nervous tissue development in rainbow trout (Oncorhynchus mykiss) embryos treated with oxytetracycline.
The purpose of this study was to discover whether the use of different doses of oxytetracycline causes any alteration in the development of nervous tissue in rainbow trout embryos. Five thousands eggs of females rainbow trout were divided into five groups. One group acted as control and the other four were administered with one of four doses of oxytetracycline, 0.025, 0.050, 0.100, or 0.201 microM, at the moment of fertilization. The eggs were incubated under pisciculture conditions to just before being ready to spring off. From the 10th day, 10-egg samples were taken regularly and fixed. Five were processed for histological techniques and stained with haematoxylin and eosin, cresyl fast violet and silver, the other five were homogenized for antibiotic detection. Histological alterations appeared in 37-day-old embryos, with an abnormal migration of the neuroblasts to the marginal layer of the neural cord, and alterations in the development of the lens and eye layers. Some embryos showed abnormal curvature of the spinal cord but these changes were not statistically significant.


[Tobacco smoking and cardiovascular risk].
Cigarette smoking is firmly established as a risk factor for coronary heart disease, stroke and peripheral vascular disease, and is associated with increased cardiovascular mortality. A possible explanation for this relation is that smoking increases the development of atherosclerosis. Indeed, tobacco smoking has been associated with modified lipids levels, decreased fibrinolysis, increased fibrinogen levels and changes in endothelial and platelet functions for instance, which are themselves either known risk factors for or early features of atherosclerosis. Passive smoking, defined as the the involuntary exposure of non-smokers to tobacco combustion products in the indoor environment is now convincingly linked to heart disease mortality and morbidity. Stopping smoking works, decreasing cardiovascular mortality and morbidity within 5 years, whatever the age and sex of the previous smoker.


Case Report: Single-Cell Transcriptomic Analysis of an Anaplastic Oligodendroglioma Post Immunotherapy.
Glioma is the most common primary malignant brain tumor with a poor prognosis. Immune checkpoint inhibitors have been of great interest in investigation of glioma treatments. Here, we report single-cell transcriptomic analyses of two tumor areas from an oligodendroglioma taken from a patient who had multiple tumor recurrences, following several chemotherapies and radiation treatments. The patient subsequently received nivolumab and was considered have disease progression based on conventional diagnostic imaging after two cycles of treatment. He underwent a debulking surgical resection and pathological diagnosis was recurrent disease. During the surgery, tumor tissues were also collected from the enhancing and non-enhancing areas for a scRNAseq analysis to investigate the tumor microenvironment of these radiographically divergent areas. The scRNAseq analysis reveals a plethora of immune cells, suggesting that the increased mass observed on MRI may be partially a result of immune cell infiltration. The patient continued to receive immunotherapy after a short course of palliative radiation and remained free of disease progression for at least 12 months after the last surgery, suggesting a sustained response to immunotherapy. The scRNAseq analysis indicated that the radiological progression was in large part due to immune cell infiltrate and continued immunotherapy led to a positive clinical outcome in a patient who would have otherwise been admitted to hospice care with halting of immunotherapy. Our study demonstrates the potential of scRNAseq analyses in understanding the tumor microenvironment, which may assist the clinical decision-making process for challenging glioma cases following immunotherapy.


eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5'-Untranslated Regions.
Translation initiation in eukaryotes is a multi-step pathway and the most regulated phase of translation. Eukaryotic initiation factor 3 (eIF3) is the largest and most complex of the translation initiation factors, and it contributes to events throughout the initiation pathway. In particular, eIF3 appears to play critical roles in mRNA recruitment. More recently, eIF3 has been implicated in driving the selective translation of specific classes of mRNAs. However, unraveling the mechanism of these diverse contributions-and disentangling the roles of the individual subunits of the eIF3 complex-remains challenging. We employed ribosome profiling of budding yeast cells expressing two distinct mutations targeting the eIF3 complex. These mutations either disrupt the entire complex or subunits positioned near the mRNA-entry channel of the ribosome and which appear to relocate during or in response to mRNA binding and start-codon recognition. Disruption of either the entire eIF3 complex or specific targeting of these subunits affects mRNAs with long 5'-untranslated regions and whose translation is more dependent on eIF4A, eIF4B, and Ded1 but less dependent on eIF4G, eIF4E, and PABP. Disruption of the entire eIF3 complex further affects mRNAs involved in mitochondrial processes and with structured 5'-untranslated regions. Comparison of the suite of mRNAs most sensitive to both mutations with those uniquely sensitive to disruption of the entire complex sheds new light on the specific roles of individual subunits of the eIF3 complex.


Glycosylated DOTA-alpha-melanocyte-stimulating hormone analogues for melanoma targeting: influence of the site of glycosylation on in vivo biodistribution.
alpha-Melanocyte-stimulating hormone (alpha-MSH) is known to bind to the melanocortin receptor 1 (MC1R) which is overexpressed on melanotic and amelanotic melanoma cells. alpha-MSH analogues are potential candidates for specific targeting of melanoma metastases. Several linear and cyclic radiolabeled MSH peptides have been designed and tested in the past, showing both high affinity for the MC1R in vitro and good incorporation in tumor xenografts in vivo. However, considerable kidney reabsorption of the radiopeptides could not be avoided. With the aim to increase the tumor-to-kidney ratio, we synthesized six glycosylated derivatives of NAPamide, an alpha-MSH octapeptide analogue with high tumor selectivity and coupled them to the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The peptides were evaluated in vitro for MC1R binding and bioactivity and, after labeling with (111)In, for in vitro cellular uptake and in vivo tissue distribution in mice carrying B16F1 melanoma tumors. The glycopeptides showed excellent binding affinities in the low nanomolar to subnanomolar range using both murine and human melanoma cell lines. However, five glycopeptides displayed lower selectivity in vivo than the parent DOTA-NAPamide, because of either a lower tumor uptake or a higher kidney uptake. In particular C-terminal extension of the amide group by a galactosyl moiety increased the kidney retention dramatically. By contrast, an N-terminally positioned galactose residue in DOTA-Gal-NAPamide improved the tumor-to-kidney ratio (4-48 h AUC of 1.34) by a factor of about 1.2 as compared to the parent DOTA-NAPamide (4-48 h AUC of 1.11), thus serving as new lead compound for MC1R-targeting molecules.


Ideological Differences in Anchoring and Adjustment During Social Inferences.
Recent research has demonstrated that conservatives perceive greater similarity to political ingroup members than do liberals. In two studies, we draw from a framework of "anchoring and adjustment" to understand why liberals and conservatives differ in their perceptions of ingroup similarity. Results indicate that when participants made judgments under time pressure, liberals and conservatives did not differ in assuming ingroup similarity. However, when participants were given sufficient time to make judgments, liberals assumed less similarity than conservatives did, suggesting that liberals adjusted their judgments to a greater extent than conservatives did (Studies 1 and 2). In examining an underlying motivational process, we found that when conservatives' desire to affiliate with others was attenuated, they adjusted their initial judgments of ingroup similarity to a similar extent as liberals did (Study 2). We discuss implications for research on ideology and social judgment.


Do we need to overcome barriers to learning in the workplace for foundation trainees rotating in neurosurgery in order to improve training satisfaction?
Junior doctors go through a challenging transition upon qualification; this repeats every time they start a rotation in a new department. Foundation level doctors (first 2 years postqualification) in neurosurgery are often new to the specialty and face various challenges that may result in significant workplace dissatisfaction. The neurosurgical environment is a clinically demanding area with a high volume of unwell patients and frequent emergencies - this poses various barriers to learning in the workplace for junior doctors. We identify a number of key barriers and review ideas that can be trialed in the department to overcome them. Through an evaluation of current suggestions in the literature, we propose that learning opportunities need to be made explicit to junior doctors in order to encourage them to participate as a member of the team. We consider ideas for adjustments to the induction program and the postgraduate medical curriculum to shift the focus from medical knowledge to improving confidence and clinical skills in newly qualified doctors. Despite being a powerful window for opportunistic learning, the daily ward round is unfortunately not maximized and needs to be more learner focused while maintaining efficiency and time consumption. Finally, we put forward the idea of an open forum where trainees can talk about their learning experiences, identify subjective barriers, and suggest solutions to senior doctors. This would be achieved through departmental faculty development. These interventions are presented within the context of the neurosurgical ward; however, they are transferable and can be adapted in other specialties and departments.


Symphalangism in children. Case report and review of the literature.
Symphalangism is an uncommon syndrome characterized by fusion of the interphalangeal joints of the hands and feet. The fusion can involve the proximal or the distal joints; however, involvement of the proximal interphalangeal joints is more common. Symphalangism often is associated with several other skeletal and nonskeletal abnormalities. Analysis of the pedigrees of affected families reveals this trait to be autosomal dominant. The authors present the case of a 9-year-old boy with bilateral symphalangism of the proximal interphalangeal joints in the fingers and toes. His father is affected similarly. A comparison of these cases with those published in the literature indicates that although the radiologic appearance of symphalangism appears disabling, the fused phalanges seldom cause disability or loss of function of the hand. Surgical intervention is not required in most patients. The father and son reported also had capitellar hypoplasia and subluxation of the radial head associated with limitation of elbow flexion and extension.


Development of Receptor Binding Domain (RBD)-Conjugated Nanoparticle Vaccines with Broad Neutralization against SARS-CoV-2 Delta and Other Variants.
The SARS-CoV-2 Delta (B.1.617.2) strain is a variant of concern (VOC) that has become the dominant strain worldwide in 2021. Its transmission capacity is approximately twice that of the original strain, with a shorter incubation period and higher viral load during infection. Importantly, the breakthrough infections of the Delta variant have continued to emerge in the first-generation vaccine recipients. There is thus an urgent need to develop a novel vaccine with SARS-CoV-2 variants as the major target. Here, receptor binding domain (RBD)-conjugated nanoparticle vaccines targeting the Delta variant, as well as the early and Beta/Gamma strains, are developed. Under both a single-dose and a prime-boost strategy, these RBD-conjugated nanoparticle vaccines induce the abundant neutralizing antibodies (NAbs) and significantly protect hACE2 mice from infection by the authentic SARS-CoV-2 Delta strain, as well as the early and Beta strains. Furthermore, the elicitation of the robust production of broader cross-protective NAbs against almost all the notable SARS-CoV-2 variants including the Omicron variant in rhesus macaques by the third re-boost with trivalent vaccines is found. These results suggest that RBD-based monovalent or multivalent nanoparticle vaccines provide a promising second-generation vaccine strategy for SARS-CoV-2 variants.


Cervical Angina: A Literature Review on Its Diagnosis, Mechanism, and Management.
Cervical angina has been defined as chest pain that resembles true cardiac angina but originates from the disorders of the cervical spine. Thus, physicians and spine surgeons alike should raise awareness of this unusual condition for diagnosis and treatment. Particularly when neurologic signs and symptoms are present, there should be a strong suspicion for cervical angina in any patient with inadequately explained noncardiac chest pain. Cervical angina can be diagnosed according to negative cardiac workups, positive neurologic examination, and cervical radiographic findings (herniated disk, spinal cord compression, or foraminal encroachment). However, the mechanisms of pain production in cervical angina remain unclear. Previous studies attributed the pain to cervical nerve root compression, cervical sympathetic afferent fibers, referred pain, or lesions of the posterior horn of the spinal cord. Conservative treatments, which include neck collar fixation, head traction, and nonsteroidal anti-inflammatory drugs, have been determined to be successful in most patients with cervical angina. But when conservative treatment fails, anterior cervical surgery with complete decompression of the spinal cord and/or nerve root has been identified to effectively relieve cervical angina symptoms.


Ternary Monolithic ZnS/CdS/rGO Photomembrane with Desirable Charge Separation/Transfer Routes for Effective Photocatalytic and Photoelectrochemical Hydrogen Generation.
Highly efficient and easy recyclable monolithic photocatalysts with ideal separation/transport route for photogenerated charge carriers are much desired. In this work, a ZnO seed-induced growth approach is developed to fabricate a ternary monolithic photomembrane, that is, ZnS/CdS heterojunction nanorods in situ grow into the interspaces of multilayer reduced graphene oxide (rGO) sheets (denoted as ZnS/CdS/rGO). The monolithic ZnS/CdS/rGO photomembrane can serve as an efficient visible-light photoactive membrane for photocatalytic (PC) or photoelectrochemical (PEC) hydrogen generation. The fast electron transport of 1D CdS nanorods, the excellent electronic conductivity of multilayer stacked rGO sheets, the intense visible-light absorption of CdS, the unique hierarchical structure, and double heterojunctions (ZnS/CdS and CdS/rGO) efficiently boost the photogenerated electron-hole pairs separation and transfer across the interfacial domain of the photomembrane under visible-light irradiation. Furthermore, the superior stability and reusability of the photomembrane is achieved by the ideal process of photogenerated electron-hole pair separation/transfer, i.e., holes transfer to ZnS and electrons transfer to rGO to inhibit CdS from photocorrosion.


Results of pancreaticoduodenectomy for pancreatic cancer: extended versus standard procedure.
In Western experience, the long-term survival benefit after extended pancreaticoduodenectomy (EPD) in patients with pancreatic ductal adenocarcinoma is still controversial. The aim of this work was to evaluate weather EPD for pancreatic ductal adenocarcinoma prolongs long-term survival compared to standard pancreaticoduodenectomy (SPD). From November 1992 to September 1996, we performed pancreatic resections in 30 patients affected by stage I-III pancreatic ductal adenocarcinoma: 13 patients underwent SPD and 17 patients underwent EPD, consecutively. The two groups of patients were similar for all the demographic, clinical, and pathological characteristics, and all the intraoperative factors considered except the number of resected lymph nodes (mean number per case = 34.2 +/- 15.5 in the EPD group versus 12.8 +/- 3.6 in the SPD group, p <0.001) and the operative time (median time per case = 375 minutes in the EPD group versus 270 minutes in the SPD group, p = 0.009). Patients in the two groups experienced a similar postoperative course. The estimated survival probability at 1 and 3 years after operation was 0.76 (95% confidence interval [CI]: 0.49 to 0.90) and 0.24 (95% CI: 0.07 to 0.45) in the EPD group; 0.31 (95% CI: 0.09 to 0.55) and 0.08 (95% CI: 0.00 to 0.29) in the SPD group (p = 0.014). According to a Cox model, the treatment was associated with R0 patients' long-term survival (SPD versus EPD: hazard ratio (HR) = 4.82, 95% CI: 1.66 to 14.00, p = 0.004). Grading of tumor differentiation was confirmed to be a relevant prognostic factor (poor versus moderate: HR = 4.33, 95% CI: 1.49 to 12.61, p = 0.007), whereas type of resection had no significant effect (pylorus-preserving versus hemigastrectomy: HR = 1.49, 95% CI: 0.56 to 3.95, p = 0.42). The proportion of R0 patients with local recurrence was lower in the EPD group (20.0% versus 70.0%, p = 0.034).


The Effect of 0.01% Atropine Eye Drops on the Ocular Surface in Children for the Control of Myopia-The Primary Results from a Six-Month Prospective Study.
To evaluate the effect of 0.01% atropine eye drops on the ocular surface in children for the control of myopia. A total of 72 participants were recruited for this prospective study. Prior to and after 1, 3, and 6 months of 0.01% atropine administration, an ocular surface disease index (OSDI) questionnaire was obtained, Keratograph 5M was used for the measurement of the tear meniscus height (TMH), noninvasive keratographic tear film break-up time (NK-BUT, the first keratographic break-up time, [NK-BUTfirst] and the average keratographic break-up time, [NK-BUTave]), bulbar redness (BR), meiboscore (MS), and anterior segment optical coherence tomography (AS-OCT) was used to calculate the inferior tear meniscus area (TMA). After using the 0.01% atropine eye drops for 1 month, 9 subjects complained of discomfort immediately after administration, but this quickly subsided, and 1 subject was temporarily dazzled. All the ocular surface symptoms were mild and occurred rarely. After 3 months, these complaints no longer occurred. Compared with the baseline values, the OSDI scores (0.08 ± 0.28), values of TMH (0.23 ± 0.04 mm), TMA (0.0420 ± 0.0444 mm2), NK-BUTfirst (9.39 ± 5.25 s), NK-BUTave (10.49 ± 4.94 s), BR (0.63 ± 0.37), and MS (0.89 ± 0.70) did not change significantly after 6 months of 0.01% atropine eye drop administration (P > 0.05). In this 6-month prospective study, no side effects were observed on the ocular surface after using 0.01% atropine in children.


Russian electrical stimulation: the early experiments.
Russian forms of electrical stimulation became popular to a large extent as a result of the activities of Kots, who claimed force gains of up to 40% in elite athletes as a result of what was then a new form of stimulation. He did not provide details of his published work, nor did he give references. Russian electrical stimulation became popular despite the lack of research in the English-language literature. No studies published in English examined whether the "10/50/10" treatment regimen (10 seconds of stimulation followed by 50 seconds rest, repeated for 10 minutes) advocated by Kots is optimal, and only one study addressed whether maximum muscle torque was produced at an alternating current frequency of 2.5 kHz. The few studies that compared low-frequency monophasic pulsed current and Russian electrical stimulation are inconclusive. This article reviews and provides details of the original studies by Kots and co-workers. The authors contend that these studies laid the foundations for the use of Russian forms of electrical stimulation in physical therapy. The authors conclude that there are data in the Russian-language literature that support the use of Russian electrical stimulation but that some questions remain unanswered.


Endothelial membrane potential regulates production of both nitric oxide and superoxide--a fundamental determinant of vascular health.
There is recent evidence that the membrane potential of vascular endothelium regulates not only nitric oxide (NO) synthesis, but also superoxide generation, such that hyperpolarization stimulates NO production while suppressing that of superoxide. Given that NO works in a variety of ways to inhibit atherothrombotic disease and hypertension, whereas superoxide not only vetoes the benefits of NO but also disrupts endothelial metabolism and promotes LDL oxidation through its oxidant activity, it is thus evident that endothelium membrane potential is a crucial determinant of cardiovascular risk. Membrane polarization can be enhanced by measures which increase the synthesis or availability of the Na+-K+-ATPase, moderately enhance serum K+ and increase the conductance of membrane K+ channels. Such measures may include high-K+/low-Na+ natural diets, insulin sensitizing modalities, 'euthyroid replacement therapy' and ACE inhibitors. Epidemiological correlations of insulin resistance with hypertension and cardiovascular risk may reflect the low membrane potential of insulin-resistant vascular endothelium. Adjunctive measures for suppressing the generation or half-life of endothelial superoxide are suggested.


Laparoscopic hepatic cryotherapy: a study of safety in rabbits.
Hepatic cryotherapy is used to treat unresectable liver tumors and could potentially be undertaken laparoscopically; however, the risk of gas embolism during laparoscopic hepatic cryotherapy has not been studied. Eight New Zealand White rabbits underwent laparoscopic hepatic cryotherapy with continuous precordial ultrasound monitoring for gas embolism. No episodes of gas embolism were detected, and at postmortem no intracardiac gas was found in any rabbit. In conclusion, this study found no evidence that gas embolism is any more likely to occur during laparoscopic than in open hepatic cryotherapy.


Progression in Moyamoya Disease: Clinical Features, Neuroimaging Evaluation, and Treatment.
Moyamoya disease (MMD) is a chronic cerebrovascular disease characterized by progressive stenosis of the arteries of the circle of Willis, with the formation of collateral vascular network at the base of the brain. Its clinical manifestations are complicated. Numerous studies have attempted to clarify the clinical features of MMD, including its epidemiology, genetic characteristics, and pathophysiology. With the development of neuroimaging techniques, various neuroimaging modalities with different advantages have deepened the understanding of MMD in terms of structural, functional, spatial, and temporal dimensions. At present, the main treatment for MMD focuses on neurological protection, cerebral blood flow reconstruction, and neurological rehabilitation, such as pharmacological treatment, surgical revascularization, and cognitive rehabilitation. In this review, we discuss recent progress in understanding the clinical features, in the neuroimaging evaluation and treatment of MMD.


Truncated type II receptor for BMP-4 induces secondary axial structures in Xenopus embryos.
BRK-3 is a vertebrate type II receptor for BMP-4 distantly related to invertebrate type II receptors for BMP-2/BMP-4/dpp, such as daf-4 and punt. BRK-3 has a long carboxy-terminal sequence following intracellular kinase domain and is capable of forming a high-affinity complex with a type I receptor, BRK-2. To examine the role of BRK-2 + BRK-3 receptor complex in BMP signaling during early embryogenesis, the dominant-negative form of BRK-3 was ectopically expressed in the Xenopus embryos. A secondary body axis expressing the Sonic hedgehog and N-CAM genes is induced by injecting mRNA encoding truncated form of BRK-3 into ventral marginal region, implicating the BMP signaling in axial mesoderm induction. Formation of the secondary axis depends on whether the deletion extends into the kinase domain, not into the carboxy-terminal tail, suggesting that the kinase domain, but not the tail region, is essential for BMP signaling.


Classifying osteosarcoma patients using machine learning approaches.
Metabolomic data analysis presents a unique opportunity to advance our understanding of osteosarcoma, a common bone malignancy for which genomic and proteomic studies have enjoyed limited success. One of the major goals of metabolomic studies is to classify osteosarcoma in early stages, which is required for metastasectomy treatment. In this paper we subject our metabolomic data on osteosarcoma patients collected by the SJTU team to three classification methods: logistic regression, support vector machine (SVM) and random forest (RF). The performances are evaluated and compared using receiver operating characteristic curves. All three classifiers are successful in distinguishing between healthy control and tumor cases, with random forest outperforming the other two for cross-validation in training set (accuracy rate for logistic regression, support vector machine and random forest are 88%, 90% and 97% respectively). Random forest achieved overall accuracy rate of 95% with 0.99 AUC on testing set.


Validity and reliability of adult recall of past sun exposure in a case-control study of multiple sclerosis.
Measurement of past sun exposure through recall by adults has the potential for measurement error. We aimed to investigate aspects of validity and reliability of self-reported past sun exposure. A population-based case-control study was conducted in Tasmania on 136 cases with multiple sclerosis and 272 age- and sex-matched community controls. Repeat interviews on 52 cases and 52 controls were done on average 11 weeks after the initial interview. Sun exposure was assessed by questionnaire and lifetime calendar. Other measurements included serum 25-hydroxyvitamin D, actinic damage, and skin phenotype. There was an association between recent sun exposure and serum vitamin D (time in the sun: r = 0.22, P < 0.01; activities outside: r = 0.31, P < 0.01 for controls) and between lifetime sun exposure and actinic damage [correlation between 0.34 (P < 0.01) and 0.17 (P = 0.01) for controls]. The test-retest weighted kappa statistic of self-reported sun exposure ranged from 0.43 to 0.74. Recall of childhood/adolescent sun exposure by standardized questioning was no less reproducible than recall of recent adult sun exposure and no less reliable when made with the calendar method. Comparing the questionnaire and calendar method, the measures of childhood/adolescent sun exposure had a similar predictive validity for multiple sclerosis. The results of this study provide further evidence that adults are able to recall past sun exposure with shown validity and reliability and present information about the possible reasons for the good reliability of recalled sun exposure measures.


Estimating the scene illumination chromaticity by using a neural network.
A neural network can learn color constancy, defined here as the ability to estimate the chromaticity of a scene's overall illumination. We describe a multilayer neural network that is able to recover the illumination chromaticity given only an image of the scene. The network is previously trained by being presented with a set of images of scenes and the chromaticities of the corresponding scene illuminants. Experiments with real images show that the network performs better than previous color constancy methods. In particular, the performance is better for images with a relatively small number of distinct colors. The method has application to machine vision problems such as object recognition, where illumination-independent color descriptors are required, and in digital photography, where uncontrolled scene illumination can create an unwanted color cast in a photograph.


Real-time electrical measurement of L929 cellular spontaneous and synchronous oscillation.
Nonexcitable cell types, fibroblasts of heart muscle or astrocytes, are well known for their spontaneous Ca(2+) oscillations. On the other hand, murine fibroblast (L929) cells are known to be deficient in cell-cell adhesive proteins and therefore lack gap junctions for cellular communication. However, these cells exhibit a unique property of collectively synchronized and spontaneous oscillation, as revealed by real-time monitoring of cells cultured on a 250-μm diameter microelectrode for more than 3 days using an electrical cell-substrate impedance-sensing system (ECIS). Live-cell imaging is a widely used technique for oscillation detection, but it has limitations relating to cellular physiological environment maintenance for microscopic analysis and for prolonged periods of study. The present research emphasizes an electrical-sensing technique (ECIS) capable of overcoming the most important issues inherent in live-cell imaging systems for the detection of L929 cellular spontaneous and synchronized oscillation in real-time for longer periods. Possible mechanisms involved in L929 oscillation were elucidated to be periodic extension/contraction of lamellipodia continued as blebbing, which is produced by signals from the actomyosin complex initiated by connexin hemichannel opening and adenosine triphosphate (ATP) release. By applying the connexin hemichannel inhibitor, flufenamic acid, the hindrance of ATP release and calcium transients were analyzed to elucidate this hypothesis.


Tagless extraction-retentate chromatography: a new global protein digestion strategy for monitoring differential protein expression.
A new global protein digestion and selective peptide extraction strategy for the purpose of monitoring differential protein expression, coined as tagless extraction-retentate chromatography, is introduced. Target protein populations are firstly digested under reduced and alkylated conditions, and resultant peptides selectively extracted via covalent attachment to methionine residues by bromoacetyl reactive groups tethered to the surface of glass beads packed in small reaction vessels. After conjugation, reactive beads are stringently washed to remove nonspecifically bound peptides and then later treated with beta-mercaptoethanol to release captured methionine peptides in their nascent state, without complicating affinity tags. Recovered methionine containing peptides are profiled using the surface-enhanced laser desorption/ionization (SELDI) retentate chromatography mass spectrometry (RCMS) method. Selected peptides are further studied employing ProteinChip tandem mass spectrometry (MS/MS) analysis to identify their parent proteins. This approach has been applied to an Escherichia coli lysate model system and has demonstrated facility in reducing global digest complexity, sensitivity to low protein expression levels, and significant quantitative capability. It is envisioned that tagless extraction-RCMS will evolve to be a valuable approach for both basic research and clinical proteomics endeavors.


Histological Classification and Invasion Prediction of Thymoma by Machine Learning-Based Computed Tomography Imaging.
The values of machine learning-based computed tomography (CT) imaging in histological classification and invasion prediction of thymoma were investigated. 181 patients diagnosed with thymoma by surgery or biopsy in Shantou Central Hospital between February 2017 and March 2022 were selected. According to the concept of simplified histological classification and the latest histological classification by the WHO, thymoma was divided into two groups, including low-risk (types A, AB, B1, and metaplastic type) and high-risk groups (types B2 and B3). CT images were reconstructed by filtering back projection (FBP) algorithm. CT image features were collected for statistical analysis. The main symptoms of patients diagnosed with thymoma included respiratory tract infection, chest distress and shortness of breath, and chest pain. 35.91% of them suffered from complicated myasthenia gravis. Tumor size and position in low-risk and high-risk groups showed no statistical significance (P > 0.05). Tumor morphology and boundary between the two groups suggested statistical difference (P < 0.05). Whether tumor invaded adjacent tissues was apparently correlated with simplified histological classification (P < 0.01). The sensitivity and specificity of CT images for the invasion of mediastinal pleura or pericardium were around 90% and negative predictive values both reached above 95%. Those of the CT images for lung invasion were over 80%. The negative and positive predictive values were 93.54% and 63.82%, respectively. Those of the CT images for blood vessel invasion were 67.32% and 97.93%. The negative and positive predictive values were 98.21% and 83%, respectively. The machine learning-based CT image had significant values in the prediction of different histological classification and even invasion level.


[Effects of the improved FUS-invest investment for zirconium-oxide titanium crown and bridge on the reaction layer].
To investigate the effects of the improved FUS-invest investment for zirconium-oxide titanium crown and bridge on the reaction layer. 10 mm x 10 mm x 1 mm titanium castings were invested. Spectrum analysis was done to its reaction layer, the metallographic examination was observed and Vickers hardness was measured. The reaction layer was not obvious by the metallographic examination. The layer with plenty of Si was hardly detectable. The needle crystal layer diffused distribution on the surface of the titanium matrix. The depth was about 55 microm. Spectrum analysis showed that the contents of Si and Zr decreased as the depth increased. The microhardness, which obviously decreased from the surface to the matrix, tended to be equal with the hardness of the matrix after the depth reached 75 microm from the surface. The thickness of the reaction layer of the improved FUS-invest investment for zirconium-oxide titanium crown and bridge was decreased to 55 microm from 85 microm, which was the thickness before improvement.


Principles and features of single-scan two-dimensional NMR spectroscopy.
Two-dimensional nuclear magnetic resonance (2D NMR) provides one of the foremost contemporary tools available for the elucidation of molecular structure, function, and dynamics. Execution of a 2D NMR experiment generally involves scanning a series of time-domain signals S(t(2)), as a function of a t(1) time variable which undergoes parametric incrementation throughout independent experiments. Very recently, we proposed and demonstrated a general approach whereby this serial mode of data acquisition is parallelized, enabling the acquisition of complete bidimensional NMR data sets via the recording of a single transient. The present paper discusses in more detail various conceptual and experimental aspects of this novel 2D NMR methodology. The basic principles of the approach are reviewed, various homo- and heteronuclear NMR applications are illustrated, and the main features and artifacts affecting the method are derived. Extensions to higher-dimensional experiments are also briefly noted.


SOSPES: SPIRIVA® observational study measuring SGRQ score in routine medical practice in Central and Eastern Europe.
The long-acting inhaled anticholinergic agent, tiotropium, is recommended as first-line maintenance therapy for moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) to improve symptoms, exercise tolerance, health status, and to reduce exacerbations. Few studies have evaluated the therapeutic efficacy of tiotropium in patients in routine clinical conditions. The current study was designed to investigate the therapeutic efficacy of tiotropium delivered via the HandiHaler® device on the health status of patients with COPD with Global initiative for chronic Obstructive Lung Disease (GOLD) disease classification 2-4 in six central and eastern European countries in a real-life clinical setting. The study was an open-label, prospective, uncontrolled, and single-arm surveillance study with three clinic visits during a 6-month observation period (baseline, and months 3 and 6). Health status was measured using the disease-specific St George's Respiratory Questionnaire (SGRQ). The primary efficacy endpoint was the mean change from baseline in SGRQ total score at the end of the 6-month observational period. Patients treated with tiotropium 18 μg once daily showed statistically significant and clinically meaningful reduction (improvement) of 21.7 units in the SGRQ total score, regardless of smoking status or cardiac comorbidities at enrollment (P < 0.0001). The analysis also showed that age, treatment compliance, and GOLD disease classification were significant factors that impact the health status of patients with COPD differently. These results provide further support for the use of the tiotropium HandiHaler® as first-line maintenance treatment of patients with COPD with a clinician-assessed disease.


Food-grade antioxidants and antimicrobials to control growth and ochratoxin a production by Aspergillus section Nigri on peanut kernels.
Each year, a significant portion of the peanuts produced cannot be marketed because of fungal disease at the postharvest stage and mycotoxin contamination. Antioxidants could be used as an alternative to fungicides to control ochratoxigenic fungi in peanuts during storage. This study was carried out to determine the effect of the antioxidant butylated hydroxyanisole (BHA) and the antimicrobial propyl paraben (PP) on the lag phase before growth, growth rate, and ochratoxin A (OTA) production by Aspergillus section Nigri strains in peanut kernels under different conditions of water activity (aw) and temperature. At 20 mM/g BHA, 18 degrees C, and 0.93 aw, complete inhibition of growth occurred. For PP, there was no growth at 20 mM/g, 18 degrees C, and 0.93, 0.95, and 0.98 aw. BHA at 20 mM/g inhibited OTA production in peanuts by Aspergillus carbonarius and Aspergillus niger aggregate strains at 0.93 aw and 18 degrees C. PP at 20 mM/g completely inhibited OTA production at 18 degrees C. The results of this work suggest that PP is more appropriate than BHA for controlling growth and OTA production by Aspergillus section Nigri species in peanut kernels.


Cerebellar theta burst stimulation impairs eyeblink classical conditioning.
Theta burst stimulation (TBS) protocols of repetitive transcranial magnetic stimulation (rTMS) have after-effects on excitability of motor areas thought to be due to LTP- and LTD-like processes at cortical synapses. The present experiments ask whether, despite the low intensities of stimulation used and the anatomy of the posterior fossa, TBS can also influence the cerebellum. Acquisition and retention of eyeblink classical conditioning (EBCC) was examined in 30 healthy volunteers after continuous theta burst stimulation (cTBS) over the right cerebellar hemisphere. In subjects who received cerebellar cTBS, conditioned responses were fewer and their onsets were earlier (in the last half of the acquisition blocks) than those from control subjects. There was, however, no effect of cerebellar cTBS on the re-acquisition of EBCC in another session of EBCC 7–10 days later. There was also no effect of cerebellar cTBS on the re-acquisition of EBCC in subjects not naïve to EBCC when the stimulation was delivered immediately before a re-acquisition session. Control experiments verified that suppressive effects of cTBS on EBCC were not due to changes in motor cortical excitability or sensory disturbance caused by cTBS. Based on previous EBCC studies in various cerebellar pathologies, our data are compatible with the hypothesis that cerebellar cTBS has a focal cerebellar cortical effect, and are broadly in line with data from studies of EBCC in various animal models. These results confirm that cerebellar TBS has measurable effects on the function of the cerebellum, and indicate it is a useful non-invasive technique with which to explore cerebellar physiology and function in humans.


All-optical ultrafast XOR/XNOR logic gates, binary counter, and double-bit comparator with silicon microring resonators.
We present designs of all-optical ultrafast YES/NOT, XOR/XNOR logic gates, binary counter, and double-bit comparator based on all-optical switching by two-photon absorption induced free-carrier injection in silicon 2 × 2 add-drop microring resonators. The proposed circuits have been theoretically analyzed using time-domain coupled-mode theory based on reported experimental values to realize low power (∼ 28 mW) ultrafast (∼ 22 ps) operation with high modulation (80%) and bit rate (45 Gb/s). The designs are complementary metal-oxide semiconductor compatible and provide advantages of high Q-factor, tunability, compactness, cascadibility, scalability, reconfigurability, simplicity, and minimal number of switches and inputs for realization of the desired logic. Although a two-bit counter has been shown, the scheme can easily be extended to N-bit counter through cascading.


Pondering the Potential of Hyaline Cartilage-Derived Chondroprogenitors for Tissue Regeneration: A Systematic Review.
Chondroprogenitors have recently gained prominence due to promising results seen in in vitro and animal studies as a potential contender in cell-based therapy for cartilage repair. Lack of consensus regarding nomenclature, isolation techniques, and expansion protocols create substantial limitations for translational research, especially given the absence of distinct markers of identification. The objective of this systematic review was to identify and collate information pertaining to hyaline cartilage-derived chondroprogenitors, with regard to their isolation, culture, and outcome measures. As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a web-based search of Scopus and PubMed databases was performed from January 2000 to May 2020, which yielded 509 studies. A total of 65 studies were identified that met the standardized inclusion criteria which comprised of, but was not limited to, progenitors derived from fibronectin adhesion, migrated subpopulation from explant cultures, and single-cell sorting. Literature search revealed that progenitors demonstrated inherent chondrogenesis and minimal tendency for hypertrophy. Multiple sources also demonstrated significantly better outcomes that bone marrow-derived mesenchymal stem cells and comparable results to chondrocytes. With regard to progenitor subgroups, collated evidence points to better and consistent outcomes with the use of migratory progenitors when compared to fibronectin adhesion assay-derived progenitors, although a direct comparison between the two cell populations is warranted. Since chondroprogenitors exhibit favorable properties for cartilage repair, efficient characterization of progenitors is imperative, to complete their phenotypic profile, so as to optimize their use in translational research for neocartilage formation.


Draft Genome Sequences of Porphyromonas crevioricanis JCM 15906T and Porphyromonas cansulci JCM 13913T Isolated from a Canine Oral Cavity.
Here, we report the draft genome sequences of Porphyromonas crevioricanis JCM 15906(T) and Porphyromonas cansulci JCM 13913(T), which were isolated from a canine oral cavity and were recently united under the single species P. crevioricanis. These two genome sequences are very similar, and yet a high degree of genome rearrangements is observed.


[Differential expression of HSU17714 gene in colorectal cancer and normal colonic mucosa].
HSU17714 is a new gene discovered by subtractive hybridization. Its cDNA is 2,932 bp long and the gene is located at human chromosome 22 as defined by fluorescence in- situ hybridization combined fluorescence R-banding technique. Northern blot and RNA dot blot analyses showed that the expression level of HSU17714 gene was significantly lower in 15 cases of colorectal cancer than that in adjacent normal colonic mucosa. The defective expression of HSU17714 in colorectal cancer suggests that it is a new candidate tumor suppressor gene.


Direct evidence for a geometrically constrained "entatic state" effect on copper(II/I) electron-transfer kinetics as manifested in metastable intermediates.
The absolute magnitude of an "entatic" (constrained) state effect has never been quantitatively demonstrated. In the current study, we have examined the electron-transfer kinetics for five closely related copper(II/I) complexes formed with all possible diastereomers of [14]aneS(4) (1,4,8,11-tetrathiacyclotetradecane) in which both ethylene bridges have been replaced by cis- or trans-1,2-cyclohexane. The crystal structures of all five Cu(II) complexes and a representative Cu(I) complex have been established by X-ray diffraction. For each complex, the cross-reaction rate constants have been determined with six different oxidants and reductants in aqueous solution at 25 degrees C, mu = 0.10 M. The value of the electron self-exchange rate constant (k(11)) has then been calculated from each cross reaction rate constant using the Marcus cross relation. All five Cu(II/I) systems show evidence of a dual-pathway square scheme mechanism for which the two individual k(11) values have been evaluated. In combination with similar values previously determined for the parent complex, Cu(II/I)([14]aneS(4)), and corresponding complexes with the two related monocyclohexanediyl derivatives, we now have evaluated a total of 16 self-exchange rate constants which span nearly 6 orders of magnitude for these 8 closely related Cu(II/I) systems. Application of the stability constants for the formation of the corresponding 16 metastable intermediates--as previously determined by rapid-scan cyclic voltammetry--makes it possible to calculate the specific electron self-exchange rate constants representing the reaction of each of the strained intermediate species exchanging electrons with their stable redox partners--the first time that calculations of this type have been possible. All but three of these 16 specific self-exchange rate constants fall within--or very close to--the range of 10(5)-10(6) M(-1) s(-1), values which are characteristic of the most labile Cu(II/I) systems previously reported, including the blue copper proteins. The results of the current investigation provide the first unequivocal demonstration of the efficacy of the entatic state concept as applied to Cu(II/I) systems.


Combining Nitrogen-Doped Graphene Sheets and MoS2 : A Unique Film-Foam-Film Structure for Enhanced Lithium Storage.
With a notable advantage in terms of capacity, molybdenum disulfide has been considered a promising anode material for building high-energy-density lithium-ion batteries. However, its intrinsically low electronic conductivity and unstable electrochemistry lead to poor cycling stability and inferior rate performance. We herein describe the scalable assembly of free-standing MoS2 -graphene composite films consisting of nitrogen-doped graphene and ultrathin honeycomb-like MoS2 nanosheets. The composite has a unique film-foam-film hierarchical top-down architecture from the macroscopic to the microscopic and the nanoscopic scale, which helps rendering the composite material highly compact and leads to rapid ionic/electronic access to the active material, while also accommodating the volume variation of the sulfide upon intercalation/deintercalation of Li. The unique structural merits of the composite lead to enhanced lithium storage.


Joint efficacy of the three biomarkers SNCA, GYPB and HBG1 for atrial fibrillation and stroke: Analysis via the support vector machine neural network.
Atrial fibrillation (AF) is the most common type of persistent arrhythmia. Although its incidence has been increasing, the pathogenesis of AF in stroke remains unclear. In this study, a total of 30 participants were recruited, including 10 controls, 10 patients with AF and 10 patients with AF and stroke (AF + STROKE). Differentially expressed genes (DEGs) were identified, and functional annotation of DEGs, comparative toxicogenomic database analysis associated with cardiovascular diseases, and predictions of miRNAs of hub genes were performed. Using RT-qPCR, biological process and support vector machine neural networks, numerous DEGs were found to be related to AF. HBG1, SNCA and GYPB were found to be upregulated in the AF group. Higher expression of hub genes in AF and AF + STROKE groups was detected via RT-PCR. Upon training the biological process neural network of SNCA and GYPB for HBG1, only small differences were detected. Based on the support vector machine, the predicted value of SNCA and GYPB for HBG1 was 0.9893. Expression of the hub genes of HBG1, SNCA and GYPB might therefore be significantly correlated to AF. These genes are involved in the incidence of AF complicated by stroke, and may serve as targets for early diagnosis and treatment.


Porous Curdlan-Based Hydrogels Modified with Copper Ions as Potential Dressings for Prevention and Management of Bacterial Wound Infection-An In Vitro Assessment.
Bacterial infections at the wound site still remain a huge problem for current medicine, as they may lead to development of chronic wounds. In order to prevent such infections, there is a need to use wound dressings that possess ability to inhibit bacterial colonization. In this study, three new curdlan-based biomaterials modified with copper ions were fabricated via simple and inexpensive procedure, and their structural, physicochemical, and biological properties in vitro were evaluated. Received biomaterials possessed porous structure, had ability to absorb high amount of simulated wound fluid, and importantly, they exhibited satisfactory antibacterial properties. Nevertheless, taking into account all evaluated properties of new curdlan-based biomaterials, it seems that Cur_Cu_8% is the most promising biomaterial for management of wounds accompanied with bacterial infections. This biomaterial exhibited the best ability to reduce Escherichia coli and Staphylococcus aureus growth and moreover, it absorbed the highest amount of simulated wound fluid as well as enabled optimal water vapor transmission. Furthermore, Cur_Cu_8% biomaterial possessed the best values of selective indexes, which determine its potential safety in vitro. Thus, Cur_Cu_8% hydrogel may be considered as a promising candidate for management of infected wounds as well as it may constitute a good platform for further modifications.


Diagnosis by metagenomic next-generation sequencing of a Talaromyces marneffei bloodstream infection in an HIV-negative child: A case report.
Talaromyces marneffei (TM) bloodstream infections are life- threatening in immunocompromised individuals. The lack of specific clinical features for these infections and poor sensitivity associated with routine examination procedures make diagnosis challenging. Untimely diagnosis and delayed antifungal treatment threatens the life of such patients. We report a case of a TM bloodstream infection, confirmed by the results of blood culture, of a child who was HIV negative and possessed a CD40LG gene mutation. A diagnosis of TM was established by blood metagenomic next-generation sequencing (mNGS) of the patient's blood, which was confirmed by microbiological culture of blood. On admission, this previously healthy male patient was 8-months of age, who presented with recurrent fever and a cough of 6-days in duration. His condition did not improve after antibacterial treatment for 5-days, with significant and recurrent fever and worsening spirit. He was referred to the Department of Pediatrics in our tertiary medical institution with a white blood cell count of 21.5*10∧9/L, C-reactive protein of 47.98 mg/L, and procalcitonin of 0.28 ng/mL. A bloodstream infection was not excluded and blood was collected for microbial culture. The patient received a 1-day treatment of cefoperazone sulbactam and 6-days of imipenem cilastatin. Symptoms did not improve and fever persisted. Blood was submitted for mNGS analysis and within 14-h, 14,352 TM reads were detected with a relative abundance of 98.09%. Antibiotic treatment was immediately changed to intravenous amphotericin B combined with oral itraconazole. The condition of the child gradually improved. Blood culture showed TM on the 7th day after hospitalization, confirming bloodstream infection. After the 13th day of hospital admission, the patient's body temperature dropped close to 38°C and was discharged on the 30th day of hospitalization. Oral itraconazole was prescribed with follow up at the outpatient clinic. HIV-negative patients with CD40LG mutations may be potential hosts for TM. TM infections are rare in children and their detection by conventional microbial culture methods are inadequate for an early diagnosis. mNGS is a rapid detection method that permits early diagnosis of uncommon infectious agents, such as TM, allowing for improved patient outcomes.


Biomass generation and biodiesel production from macroalgae grown in the irrigation canal wastewater.
The wastewater concentration is commonly acceptable for macroalgae growth; this process consumes water and is applicable for bioremediation. This study evaluated biodiesel's potential production from freshwater macroalga, Nitella sp., using batch experiment. Algae were collected from wastewater saturated from irrigation canals. Water quality and algae growth environment characteristics were monitored and analyzed. COD and BOD values were 18.67 ± 4.62 mg/L and 5.40 ± 0.30 mg/L, respectively. The chemical composition contents were high, demonstrating that water quality and sufficient nutrients could support algae growth. Oil extraction was estimated by the room temperature and heat extraction methods. The biodiesel in room temperature treatment was 0.0383 ± 0.014%, and in heat, extraction treatment was 0.0723 ± 0.029%. Results confirmed that the heat extraction treatment gave a high amount of oil and biodiesel yield. Gas chromatography/mass spectrometry (GC/MS) was used to analyze fatty acid methyl esters (FAME). Results revealed that 9-octadecane was a major portion of the substance. The obtained results confirmed that the wastewater contains many elements that can be utilized for dual-mode, like bioremediation and enhanced macroalgae growth for biodiesel production. Therefore, macroalgae grown in canal wastewater were highly feasible for use in sustainable biodiesel production.


Sensitive enzyme-linked immunosorbent assay (ELISA) to measure parasite-specific antibodies of Indian soft-furred rats, Millardia meltada.
Immunoglobulin G (IgG) of Indian soft-furred rat, Millardia meltada, was purified by an immunoaffinity chromatography and antibodies against it was raised in rabbit. Using this rabbit anti-M. meltada IgG antibody, sensitivity of enzyme-linked immunosorbent assay (ELISA) to measure parasite-specific antibodies in the sera of M. meltada was markedly enhanced than the previous method using rabbit anti-mouse IgG and rabbit anti-rat IgG antibodies, which could cross-react to M. meltada IgG. Since M. meltada could effectively produce circulating antibodies against two intestinal helminths, Strongyloides venezuelensis and Nippostrongylus brasiliensis, the high susceptibility of this animal to an array of parasites seems to be not due to general immunological deficiency.


Population intervention causal effects based on stochastic interventions.
Estimating the causal effect of an intervention on a population typically involves defining parameters in a nonparametric structural equation model (Pearl, 2000, Causality: Models, Reasoning, and Inference) in which the treatment or exposure is deterministically assigned in a static or dynamic way. We define a new causal parameter that takes into account the fact that intervention policies can result in stochastically assigned exposures. The statistical parameter that identifies the causal parameter of interest is established. Inverse probability of treatment weighting (IPTW), augmented IPTW (A-IPTW), and targeted maximum likelihood estimators (TMLE) are developed. A simulation study is performed to demonstrate the properties of these estimators, which include the double robustness of the A-IPTW and the TMLE. An application example using physical activity data is presented.


[Effects of two different types of whole body vibration on neuromuscular performance and body composition in postmenopausal women].
The effects of different types of whole body vibration (WBV) training on neuromuscular performance and body composition were determined in postmenopausal women. In the Erlangen Longitudinal Vibration Study II (ELVIS-II-Study) 108 postmenopausal women between 60 and 75 years of age (average 65.8 ± 3.5 years) were randomly assigned to one of three groups: two WBV training-groups (n = 36 each), each performing an identical program thrice a week for 15 min on two different types of vibration plates for one year: 1. vertical vibrating, 35 Hz, 1.7 mm (VG); 2. rotational vibrating 12.5 Hz, 12 mm (RG). A control group (n = 36) conducted a low intensity gymnastic and relaxation program. Muscular strength and power were assessed, body composition was determined by Dual-energy X-ray absorptiometry (DXA), and pain intensity was assessed by a questionnaire. Maximum leg strength (VG: 24.4 %; RG: 26.6 %; KG: 6.2 %; p < 0.001) and maximum trunk flexion strength (VG: 12.2 %; RG: 11.5 %; KG: -5.5 %; p = 0.01) significantly increased in both vibration groups. No changes were found for body composition parameters (lean body mass, appendicular muscle mass, fat mass). Pain intensity in the big joints (p < 0.05) decreased in both vibration groups, in the lumbar spine region this was not significant. There was no difference between vibration types. No vibration-related side effects were observed. The study results suggest that WBV might be an alternative to classic training contents to increase maximum strength and reduce pain.


[Sleep apnea and fibromyalgia: the absence of correlation does not indicate an exclusive central hypothesis].
Fibromyalgia (FM) is a chronic painful syndrome characterized by widespread aching and points of tenderness, changed perception of pain and reduced brain serotonin. Abnormal EEG patterns have been reported in this condition. A study of FM occurrence in subjects with sleep abnormalities demonstrated by polysomnography was performed. Fifty patients (group 1:29 with sleep apnea and group 2:21 with poor sleep without sleep apnea) and 31 control subjects (without any sleep abnormalities) were submitted to the same clinical research of FM (ACR criteria). There was one 1 FM in group 1 (3.4%), one FM in group 2 (4.7%), and one FM in control group (3.2%). Sleep abnormalities and particularly sleep apnea are not significantly associated with FM. Other pathophysiological factors than central mechanisms are probably involved in the pathogenesis of FM.


Missed opportunities for depression screening in patients with arthritis in the United States.
Arthritis affects 20 % of the adult US population and is associated with comorbid depression. Depression screening guidelines have been endorsed for high-risk groups, including persons with arthritis, in the hopes that screening will increase recognition and use of appropriate interventions. To examine national rates of depression and depression screening for patients with arthritis between 2006 and 2010. We used nationally representative cross-sections of ambulatory visits in the United States from the National Ambulatory Medical Care Survey from 2006 to 2010, which included 18,507 visits with a diagnosis of arthritis. When weighted to the US population, this total represents approximately 644 million visits. Visits where arthritis was listed among diagnoses. Outcomes were survey-weighted estimates of depression and prevalence of depression screening among patients with arthritis across patient and physician characteristics. Of the 644,419,374 visits with arthritis listed, 83,574,127 (13 %) were associated with a comorbid diagnosis of depression. The odds ratio for comorbid depression with arthritis was 1.42 (95 % CI 1.3, 1.5). Depression screening occurred at 3,835,000 (1 %) visits associated with arthritis. When examining the rates of depression screening between ambulatory visits with and without arthritis listed, there was no difference in depression screening rates; both were approximately 1 %. There was no difference in screening rates by provider type. Compared to visits with other common, chronic conditions, the prevalence of depression at arthritis visits was high (13 per 100 visits), although the prevalence of depression screening at arthritis visits was low (0.68 per 100 visits). Despite the high prevalence of depression with arthritis, screening for depression was performed at few arthritis visits, representing missed opportunities to detect a common, serious comorbidity. Improved depression screening by providers would identify affected patients, and may lead to appropriate interventions such as mental health referrals and/or treatment with anti-depressants.


A feature selection method based on multiple kernel learning with expression profiles of different types.
With the development of high-throughput technology, the researchers can acquire large number of expression data with different types from several public databases. Because most of these data have small number of samples and hundreds or thousands features, how to extract informative features from expression data effectively and robustly using feature selection technique is challenging and crucial. So far, a mass of many feature selection approaches have been proposed and applied to analyse expression data of different types. However, most of these methods only are limited to measure the performances on one single type of expression data by accuracy or error rate of classification. In this article, we propose a hybrid feature selection method based on Multiple Kernel Learning (MKL) and evaluate the performance on expression datasets of different types. Firstly, the relevance between features and classifying samples is measured by using the optimizing function of MKL. In this step, an iterative gradient descent process is used to perform the optimization both on the parameters of Support Vector Machine (SVM) and kernel confidence. Then, a set of relevant features is selected by sorting the optimizing function of each feature. Furthermore, we apply an embedded scheme of forward selection to detect the compact feature subsets from the relevant feature set. We not only compare the classification accuracy with other methods, but also compare the stability, similarity and consistency of different algorithms. The proposed method has a satisfactory capability of feature selection for analysing expression datasets of different types using different performance measurements.


Measures of and changes in heart rate variability in pediatric heart transplant recipients.
Heart rate variability is primarily regulated by the autonomic nervous system. Heart transplant recipients undergo surgical denervation of the graft, which results in interruption of autonomic innervation with resultant diminished heart rate variability although some degree of autonomic control may return. This study aimed to characterize heart rate variability in this population. We report a retrospective review of Holter monitor data from transplanted patients between 2005 and 2013. Studies with significant atrial or ventricular arrhythmias were excluded. We evaluated changes over time and compared standard time domain measures to published pediatric normal values. Data were reviewed from 582 monitors in 152 patients. We found that pediatric heart transplant recipients have lower heart rate variability than age-matched controls and higher average heart rate in recipients older than 3 years. There is an increase in measures of variability through the first 3 years post-transplant with plateau after that time. Surgical technique in regard to interruption of the vagus nerve does not affect variability, nor does underlying congenital vs acquired heart disease.


Analysis and Multi-Objective Optimization for Reducing Energy Consumption and Improving Surface Quality during Dry Machining of 304 Stainless Steel.
Cutting quality and production cleanliness are main aspects to be considered in the machining process, and determining the optimal cutting parameters is a significant measure to reduce energy consumption and optimize surface quality. In this paper, 304 stainless steel is adopted as the research objective. The regression models of the specific cutting energy, surface roughness, and microhardness are constructed and the inherent influence mechanism between cutting parameters and output responses are analyzed by analysis of variance (ANOVA). The desirability analysis method is introduced to perform the multi-objective optimization for low energy consumption (LEC) mode and low surface roughness (LSR) mode. Optimal combination of process parameters with composite desirability of 0.925 and 0.899 are obtained in such two modes respectively. As indicated by the results of multi-objective genetic algorithm (MOGA), genetic algorithm (GA) combined with weighted-sum-type objective function and experiment, the relative deviation values are within 10%. Moreover, the results also reveal that the feed rate is the most significant factor affecting the three responses, while the correlation of cutting depth is less noticeable. The effect of low feed rate on microhardness is primarily related to the mechanical load caused by extrusion, and the influence at high feed rate is determined by plastic deformation.


[Is there an association between the sleep apnea syndrome and the circadian peak of myocardial infarction in the morning hours?].
To determine whether there is a relationship between the circadian rhythm of acute myocardial infarction (AMI) in the morning hours and the sleep apnea syndrome (SAS). 203 patients who had sustained an AMI were examined 7-14 days later for sleep-associated breathing disorders using a 5-channel recording system. The diagnostic criterion for SAS was > 10 episodes of apnea and hypopnea per hour (AHI >10). 76 % of all patients were male, mean age 62 years. SAS was diagnosed in 91 of the 203 patients (44.8 %). Compared to the 112 patients without SAS there were significantly more AMI in the morning hours (6:00 am to 12:00 am) in the SAS-group (49.5 %) than in the non-SAS-group (21.4 %). The two groups differed with regard to the symptoms of day-time sleepiness (29.7 % vs 17.0 %), age (mean 64.6 years vs 60.2 years), gender (83.5 % vs 69.9 % male) and smoking (33.0 % vs 51.8 %). There were no significant differences in Body mass index, hypertension, hyperlipoproteinemia, diabetes mellitus, family history, history of cardiovascular disease and taking of sedatives. The strong association between SAS and morning onset of AMI found in this study could be the result of a sympathetic stress reaction to the breathing disorder.


Monitoring of fusion gene transcripts to predict relapse in pediatric acute myeloid leukemia.
In acute myeloid leukemia (AML), accurate detection of minimal residual disease (MRD) enables better risk-stratified therapy. There are few studies, however, on the monitoring of multiple fusion transcripts and evaluation of their accuracy as indicators of MRD at multiple time points. We retrospectively examined RNA obtained from 82 pediatric AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study. The expression of six important fusion transcripts (AML1(RUNX1)-ETO, CBFB-MYH11, MLL(KMT2A)-AF9, MLL-ELL, MLL-AF6, and FUS-ERG) was analyzed at five time points 30-40 days apart following diagnosis. In patients with AML1-ETO (n = 36 at time point 5), all six patients with >3,000 copies and four of 30 patients with ≤3,000 copies relapsed. AML1-ETO transcripts persisted during treatment even in patients without relapse, as well as CBFB-MYH11 transcripts. In contrast, in patients with MLL-AF9 (n = 9 at time point 5), two patients were positive for MLL-AF9 expression (>50 copies) and both relapsed. Only one of seven MLL-AF9-negative patients relapsed. In the AML1-ETO group, MRD-positive patients (>3,000 copies at time point 5) had significantly lower relapse-free survival (RFS; P < 0.0001) and overall survival (OS; P = 0.009) than MRD-negative patients. Similarly, in the MLL-AF9 group, MRD-positive patients (>50 copies at time point 5) had significantly lower RFS (P = 0.002) and OS (P = 0.002) than MRD-negative patients. Detection of MLL-AF9 transcripts on real-time quantitative polymerase chain reaction is a promising marker of relapse in pediatric AML. In contrast, the clinical utility of detecting AML1-ETO and CBFB-MYH11 expression is limited, although higher AML1-ETO expression can be a potential predictor of relapse when assessed according to an optimal threshold.


Outcome of free gracilis muscle transfer for the restoration of elbow flexion in traumatic brachial plexus palsy.
The aim of this study was to evaluate the functional outcomes of patients with free gracilis muscle transfer (FGMT) for the restoration of elbow flexion. Between January 2012 and January 2019, a total of 16 patients (13 males, 3 females; mean age: 27.3±11.7 years; range: 18 to 53 years) who underwent FGMF to achieve elbow flexion after traumatic brachial plexus palsy (TBPP) were retrospectively analyzed. Data including demographic and clinical characteristics of the patients, etiology, affected side, injury level, accompanying injuries, time between injury and surgery, follow-up time, complications, whether nerve reconstruction and artery repair were performed previously, and details of the procedure were recorded. The outcome measures were elbow range of motion in degrees, muscle strength, and Disabilities of the Arm, Shoulder and Hand (DASH) and Short Form-36 (SF-36) scores. The mean follow-up was 30±11.5 (range, 24 to 42) months. Two patients had C5-C8 injuries, two patients had C6-T1 injuries, and all other patients had injuries to the C5-T1 roots. Muscle strength was M3/M4 in 11 (68.8%) patients, M2 in two (12.5%) patients, and M0 in one (6.2%) patient. The median active range of motion of the elbow joint in patients with successful results (M3 and above) was measured as 75 (range, 30 to 100) degrees. A statistically significant improvement was observed in the pre- and postoperative DASH scores and in some SF-36 subscale scores of patients with successful results. Free gracilis muscle flap is a reliable option in the restoration of elbow flexion in patients with TBPP. Although there is an improvement in functional results, disability, and quality of life, there may be no change in patients' mental status and pain.


Wnt9a Is Required for the Aortic Amplification of Nascent Hematopoietic Stem Cells.
All mature blood cell types in the adult animal arise from hematopoietic stem and progenitor cells (HSPCs). However, the developmental cues regulating HSPC ontogeny are incompletely understood. In particular, the details surrounding a requirement for Wnt/β-catenin signaling in the development of mature HSPCs are controversial and difficult to consolidate. Using zebrafish, we demonstrate that Wnt signaling is required to direct an amplification of HSPCs in the aorta. Wnt9a is specifically required for this process and cannot be replaced by Wnt9b or Wnt3a. This proliferative event occurs independently of initial HSPC fate specification, and the Wnt9a input is required prior to aorta formation. HSPC arterial amplification occurs prior to seeding of secondary hematopoietic tissues and proceeds, in part, through the cell cycle regulator myca (c-myc). Our results support a general paradigm, in which early signaling events, including Wnt, direct later HSPC developmental processes.


A pharmacological analysis of the cholinergic regulation of urokinase-type plasminogen activator secretion in the human colon cancer cell line, HT-29.
Urokinase-type plasminogen activator (uPA) is an important factor for tumour cell invasion and metastasis. We recently showed that acetylcholine is an autocrine/paracrine growth factor for the human colon cancer cell line, HT-29, in part via the α7 subtype of the nicotinic acetylcholine receptors. In the current study, we investigated whether acetylcholine participates in the regulation of the protein expressions of also uPA and its receptor (uPAR) in the HT-29 cell line. Such were investigated by immunocytochemistry and Western blotting, and quantitation of uPA secretion was undertaken by ELISA. Stimulation of the cells for 24h with nicotine caused increased uPA secretion with peak effect (78% above the control) occurring at a nicotine concentration of 10nM. This effect was markedly inhibited by α-Bungarotoxin, thus showing the involvement of α7 nicotinic acetylcholine receptors. Basal uPA secretion was found to be partly dependent on ongoing activation of nicotinic receptors, suggesting tonic production of acetylcholine. Conversely, there was no cholinergic influence on the expression of uPAR. The current findings demonstrate novel aspects of receptor-mediated regulation of tumour metastatic potential via uPA secretion. This may suggest future pharmaceutical strategies in treatment of colorectal cancer.


Fully delocalized (ethynyl)(vinyl)phenylene bridged triruthenium complexes in up to five different oxidation states.
Triruthenium [(dppe)(2)Ru{-C≡C-1,4-C(6)H(2)-2,5-R(2)-CH═CH-RuCl(CO)(P(i)Pr(3))(2)}(2)](n+) (4a, R = H; 4b, R = OMe) containing unsymmetrical (ethynyl)(vinyl)phenylene bridging ligands and displaying five well-separated redox states (n = 0-4) are compared to their bis(alkynyl)ruthenium precursors (dppe)(2)Ru{-C≡C-1,4-C(6)H(2)-2,5-R(2)-C≡CR'} (2a,b: R' = TMS; 3a,b: R' = H) and their symmetrically substituted bimetallic congeners, complexes {Cl(dppe)(2)Ru}(2){μ-C≡C-1,4-C(6)H(2)-2,5-R(2)-C≡C} (A(a), R = H; A(b), R = OMe) and {RuCl(CO)(P(i)Pr(3))(2)}(2){μ-CH═CH-1,4-C(6)H(2)-2,5-R(2)-CH═CH} (V(a), R = H; V(b), R = OMe) as well as the mixed (ethynyl)(vinyl)phenylene bridged [Cl(dppe)(2)Ru-C≡C-1,4-C(6)H(4)-CH═CH-RuCl(CO)(P(i)Pr(3))(2)] (M(a)). Successive one-electron transfer steps were studied by means of cyclic voltammetry, EPR and UV-vis-NIR-IR spectroelectrochemistry. These studies show that the first oxidation mainly involves the central bis(alkynyl) ruthenium moiety with only limited effects on the appended vinyl ruthenium moieties. The second to fourth oxidations (n = 2, 3, 4) involve the entire carbon-rich conjugated path of the molecule with an increased charge uniformly distributed between the two arms of the molecules, including the terminal vinyl ruthenium sites. In order to assess the charge distribution, we judiciously use (13)CO labeled analogues to distinguish stretching vibrations due to the acetylide triple bonds and the intense and charge-sensitive Ru(CO) IR probe in different oxidation states. The comparison between complex pairs 4a,b(n+) (n = 0-3), A(a,b)(n+) and V(a,b)(n+) (n = 0-2) serves to elucidate the effect of the methoxy donor substituents on the redox and spectroscopic properties of these systems in their various oxidation states and on the metal/ligand contributions to their frontier orbitals.


Probing the mechanisms of the biological intermolecular transfer of reduced flavin.
NAD(P)H-flavin oxidoreductases [flavin reductases (FR)] are a class of enzymes capable of producing reduced flavin for bacterial bioluminescence and other biological processes. Bacterial luciferase utilizes oxygen, reduced FMN (FMNH2) and a long-chain aliphatic aldehyde as substrates for light emission. The Vibrio harveyi luciferase and FRP (for which we have cloned the gene and determined the crystal structure) is a model for the elucidation of the reduced flavin transfer mechanism using both a flavin reductase single-enzyme assay monitoring the NADPH oxidation and a flavin reductase-luciferase coupled assay measuring bioluminescence intensity or quantum output. The FRP exhibits a ping-pong kinetic pattern in the single-enzyme assay but changes to a sequential pattern in the coupled assay. Furthermore, FMN at >2x10(-6) mol/L reduced both the light intensity and quantum yield of the coupled reaction by noncompetitively inhibiting NADPH and competitively inhibiting luciferase. These results support a scheme in which the luciferase forms specific complex(es) with FRP. Indeed, such complexes were shown by fluorescence anisotropy to exist between luciferase and monomeric FRP either in the holo- or apoenzyme form. Furthermore, the reduced flavin cofactor of FRP is transferred directly to luciferase for bioluminescence, whereas the reduced flavin product of FRP is inefficient in supporting the luminescence reaction. The mechanism of reduced flavin transfer is apparently flavin and flavin reductase specific.


UO(2) 2+ speciation determines uranium toxicity and bioaccumulation in an environmental Pseudomonas sp. isolate.
In the present study, experiments were performed to investigate how representative cellulosic breakdown products, when serving as growth substrates under aerobic conditions, affect hexavalent uranyl cation (UO(2) (2+)) toxicity and bioaccumulation within a Pseudomonas sp. isolate (designated isolate A). Isolate A taken from the Cold Test Pit South (CTPS) region of the Idaho National Laboratory (INL), Idaho Falls, ID, USA. The INL houses low-level uranium-contaminated cellulosic material and understanding how this material, and specifically its breakdown products, affect U-bacterial interactions is important for understanding UO(2) (2+) fate and mobility. Toxicity was modeled using a generalized Monod expression. Butyrate, dextrose, ethanol, and lactate served as growth substrates. The potential contribution of bicarbonate species present in high concentrations was also investigated and compared with toxicity and bioaccumulation patterns seen in low-bicarbonate conditions. Isolate A was significantly more sensitive to UO(2) (2+) and accumulated significantly more UO(2) (2+) in low-bicarbonate concentrations. In addition, UO(2) (2+) growth inhibition and bioaccumulation varied depending on the growth substrate. In the presence of high bicarbonate concentrations, sensitivity to UO(2) (2+) inhibition was greatly mitigated, and did not vary between the four substrates tested. The extent of UO(2) (2+) accumulation was also diminished. The observed patterns were related to UO(2) (2+) aqueous complexation, as predicted by MINTEQ (ver. 2.52) (Easton, PA, USA). In the low- bicarbonate medium, the presence of positively charged and unstable UO(2) (2+)-hydroxide complexes explained both the greater sensitivity of isolate A to UO(2) (2+), and the ability of isolate A to accumulate significant amounts of UO(2) (2+). The exclusive presence of negatively charged and stable UO(2) (2+)-carbonate complexes in the high bi-carbonate medium explained the diminished sensitivity of isolate A to UO(2) (2+) toxicity, and limited ability of isolate A to accumulate UO(2) (2+).