Surgical decision-making strategies in tuberculum sellae meningioma resection.
Although the transcranial route (TCR) has been the traditional approach for removing tuberculum sellae meningiomas (TSMs), the use of the microscopic and/or more recently the endoscopic transsphenoidal approach (ETSA) has gained acceptance for selected cases. In this study, the authors present their experience with the ETSA and the TCR and examine the criteria most important for deciding the optimal approach in a particular case. The authors retrospectively reviewed recent cases of TSMs treated surgically by the senior author via either the TCR or the ETSA or both. Demographic information, clinical presentation, and clinical and radiological outcomes of the patients were evaluated. Twenty-seven patients underwent removal of a TSM during a recent period. Gross-total or near-total resection was achieved in 20 (91%) of 22 patients who underwent resection via the TCR and in 3 (60%) of 5 patients who underwent the ETSA. Among the patients in whom gross- or near-total resection was achieved, recurrence was observed in only 1 patient, whose tumor was removed via the ETSA. In the majority of patients, the TCR provided complete resection of the tumor without compromising the safety of the procedure. In select cases of tumors with a reasonable size and location (midline and/or extending into the sphenoid sinus) as well as no involvement of inaccessible neurovascular and bony elements via this approach, the ETSA could also be a viable option.


Antitumor effects of Newcastle Disease Virus in vivo: local versus systemic effects.
Newcastle Disease Virus (NDV) has interesting anti-neoplastic and pleiotropic immune stimulatory properties. The virus preferentially replicates in and kills tumor cells and appears to be safe and to varying degrees effective in phase II-clinical studies in the US and in Europe. Here we have compared various lytic and non-lytic strains of NDV with regard to their antitumor effects after local or systemic application. As tumor models we used human metastatic melanoma xenotransplants in nude mice and murine metastatic colon carcinoma (CT26), renal carcinoma (Renca) and lymphoma (ESb) cell lines. Intra or peri-tumoral application of NDV or NDV infected tumor cells showed more pronounced antitumor activity than systemic application even when in the latter case much higher dose ranges were used. In the CT26 colon carcinoma model the non-lytic strain Ulster showed stronger antitumor activity than the lytic strain 73T. In the human MeWo melanoma xentransplant model strong antitumor bystander effects were observed by 20% admixture of melanoma cells pre-infected in vitro with NDV (either strain Ulster or Italien). Virus therapy of pre-established human melanomas by intra-tumoral injection of NDV was effective with the lytic strain Italien but not with the non-lytic strain Ulster. Systemic anti-metastatic effects were never observed with NDV alone in contrast to previous results obtained with NDV modified tumor vaccines.


Pathophysiology and pathogenesis of contractile failure in stunned myocardium.
To investigate excitation-contraction coupling in stunned myocardium, intracellular free calcium concentration [( Ca2+]i) was measured before and after ischemia in perfused hearts using gated 19F NMR and the Ca2+ indicator 5F-BAPTA. Maximal Ca(2+)-activated force was also measured in parallel experiments. Stunned myocardium was created by reperfusion after 15 min global ischemia at 37 degrees C in isolated ferret hearts. In stunned myocardium, peak [Ca2+]i was paradoxically higher than that in control, but maximal Ca(2+)-activated pressure was lower in stunned hearts. These results indicate that contractile failure in stunned myocardium is due to a decrease in the myofilament sensitivity to Ca2+ as well as to a decrease in maximal Ca(2+)-activated force; failure of activator Ca2+ delivery cannot be implicated. The role of intracellular calcium overload in the pathogenesis of stunned myocardium was also investigated. Time-averaged 19F NMR measurements directly revealed the increase in [Ca2+]i during ischemia and in the early phase of reperfusion. The strategies to prevent Ca overload during reperfusion with modified reperfusate succeeded in preserving contractile function. Transient Ca overload without ischemia induced by different causes, i.e., high [Ca]0 perfusion, ventricular fibrillation or treatment with adriamycin, also produced contractile dysfunction that outlasted the interventions themselves. Thus, we propose that transient Ca overload during ischemia and early reperfusion initiates long-lasting contractile dysfunction in stunned myocardium.


Corifollitropin alfa followed by highly purified HMG versus recombinant FSH in young poor ovarian responders: a multicentre randomized controlled clinical trial.
Does administration of corifollitropin alfa followed by highly purified (hp) HMG result in higher ongoing pregnancy rates compared with daily recombinant FSH (rFSH) in young poor responders? Corifollitropin alfa followed by hp-HMG does not increase ongoing pregnancy rates compared with rFSH in young poor responders, although more supernumerary cryopreserved embryos were obtained with corifollitropin alfa and hp-HMG. Poor ovarian response remains one of the main therapeutic challenges in women undergoing ovarian stimulation, given that very low live birth rates of 6% have been reported in this particular group of infertile patients. Nevertheless, concerns have been raised that a degree of heterogeneity remains, as the prognostic effect of individual factors is still unclear, particularly for the young poor responder group. The rationale for conducting the current randomized trial was based on the results of a previous pilot study demonstrating promising results with the administration of hp-HMG following corifollitropin alpha in women younger than 40 years of age, fulfilling the 'Bologna' criteria. A multicenter, phase III, superiority, randomized trial was conducted using a parallel two-arm design. The study included 152 patients younger than 40 years old and fulfilling the 'Bologna' criteria for poor ovarian response, from one tertiary referral centre in Europe and one tertiary referral centre in Asia. Enrolment was performed from March 2013 to May 2016. Eligible patients were randomized to either administration of 150 μg corifollitropin alfa followed by 300 IU hp-HMG (Group A) or to 300 IU of daily recombinant FSH (Group B) in a fixed GnRH antagonist protocol. The randomization sequence was created using a computer generated randomization list stratified by centre, using 1:1 allocation. The primary outcome was ongoing pregnancy rate (defined as the presence of an intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 9-10 weeks of gestation). Secondary outcomes included embryo cryopreservation rates, clinical and biochemical pregnancy rates and number of oocytes retrieved. Overall, 152 poor ovarian responders defined by the 'Bologna' criteria were included in the study. Using an intention-to treat analysis, the ongoing pregnancy rates did not differ significantly between Group A 11/77 (14.3%) and Group B 11/70 (15.7%), absolute difference: -0.4 (-11.5 to 10.8), OR = 0.9 (0.4-2.4). Biochemical and clinical pregnancy rates, live birth rates and the number of oocytes retrieved were also comparable between the two groups. Nevertheless, more patients in the corifollitropin alfa group had cryopreserved embryos compared to the rFSH group [22 (28.6%) versus 10 (14.3%), OR = 2.4 (1.01-5.5)]. Incidentally, Asian patients had significantly lower cancellation rates compared to European poor responders [2/64 (3.1%) versus 17/83 (20.4%), OR = 0.12 (0.03-0.5)]. This discrepancy could be explained by the fact that Asian women were better prognosis patients than European patients, with significantly lower FSH [9.8 (5.3) versus 11.5 (5.4), P = 0.017] and significantly higher AMH [1.1 (0.9) versus 0.4 (0.3), P-value <0.001] levels. Ongoing pregnancy rates close to 14% for both treatment groups differ significantly from the hypothesized primary outcome rates used in the power calculation. Therefore, our randomized trial might have been underpowered to detect smaller differences. The use of multiple secondary outcomes and multiple comparisons could have increased a Type 1 error. Finally, although the chance of selection biases remains low given the nature of the infertile population, the open-label design could have been a limitation. Poor ovarian response represents a challenge and although a specific protocol may have increased the number of cryopreserved embryos, no difference was observed in ongoing pregnancy rates. Our study, being one of the largest RCTs in 'Bologna' criteria poor responders, highlights that baseline characteristics may play a crucial role in clinical prognosis of this population. Given that ovarian stimulation using novel protocols does not seem to significantly increase pregnancy rates even in young women, we suggest that future clinical research should focus on increasing the number of recruitable follicles and on oocyte quality rather than evaluating different stimulation protocols. No external funding was used for this study. P.D., N.L.V., N.A.V.H., A.V., M.T.H., M.C., A.T.L. and A.V.V. have no conflict of interest to report. C.B. has received unrestricted research grants from MSD and Ferring as well as honoraria for lectures from Abbott, MSD, Merck and Ferring. P.H has received unrestricted research grants from MSD, Merck and Ferring as well as honoraria for lectures from Merck, MSD and IBSA. H.T. has received unrestricted research grants from MSD, Merck, Ferring, Cook, Roche Diagnostics, Besins International and Goodlife as well as consultation fees for research project in female infertility from Merck Finox, Abbott and ObsEva. N.P.P. has received unrestricted research grants from MSD, Ferring, Roche Diagnostics and Besins International as well as honoraria for lectures from MSD, Merck and Ferring. The EUDRACT number of the trial was 2013-000583-29 and the study was registered at clinicaltrials.gov (NCT01816321). 19 February 2013. 28 February 2013.


Determination of DNA sequences required for regulated Mycobacterium tuberculosis RecA expression in response to DNA-damaging agents suggests that two modes of regulation exist.
The recA gene of Mycobacterium tuberculosis has previously been cloned and sequenced (E. O. Davis, S. G. Sedgwick, and M. J. Colston, J. Bacteriol. 173:5653-5662, 1991). In this study, the expression of this gene was shown to be inducible in response to various DNA-damaging agents by using a transcriptional fusion to the reporter gene encoding chloramphenicol acetyltransferase. A segment of DNA around 300 bp upstream of the coding region was shown to be required for expression. However, primer extension analysis indicated that the transcriptional start sites were 47 and 93 bp upstream of the translation initiation codon. Sequence motifs with homology to two families of Escherichia coli promoters but also with significant differences were located near these proposed transcription start sites. The differences from the E. coli consensus patterns would explain the previously described lack of expression of the M. tuberculosis recA gene from its own promoter in E. coli. In addition, the M. tuberculosis LexA protein was shown to bind specifically to a sequence, GAAC-N4-GTTC, overlapping one of these putative promoters and homologous to the Bacillus subtilis Cheo box involved in the regulation of SOS genes. The region of DNA 300 bp upstream of the recA gene was shown not to contain a promoter, suggesting that it functions as an upstream activator sequence.


The potential allergenicity of two 2S albumins from soybean (Glycine max): a protein microarray approach.
The 2S albumins are a group of storage proteins that occur widely in seeds of dicotyledonous plants. The widespread distribution and stability to digestion of allergenic 2S albumins raise the question of why some members of this family present in important food sources, such as soybean, are not regarded as major allergens. The pepsinolytic stability of two 2S albumins from soybean seed was determined using simulated gastric fluid. Using a new protein microarray system, IgE binding to these soybean 2S albumins was studied with the sera from 23 European individuals allergic to soybean. In order to validate the microarray result, two of the sera were selected and further tested using the micro-ELISA and UniCAP system. Both albumins exhibited high stability to digestion similar to other allergenic members of the 2S albumin, trypsin/amylase inhibitor and lipid transfer protein superfamily. None of the patients was found to have IgE specific to soybean 2S albumins by the microarray system, and this result was in agreement with the results from the micro-ELISA and UniCAP system. The results from microarray, micro-ELISA and UniCAP system suggested that the 2S albumins from soybean are not major allergens within the patient population analyzed.


Modeling solvent evaporation during thin film formation in phase separating polymer mixtures.
Preparation of thin films by dissolving polymers in a common solvent followed by evaporation of the solvent has become a routine processing procedure. However, modeling of thin film formation in an evaporating solvent has been challenging due to a need to simulate processes at multiple length and time scales. In this work, we present a methodology based on the principles of linear non-equilibrium thermodynamics, which allows systematic study of various effects such as the changes in the solvent properties due to phase transformation from liquid to vapor and polymer thermodynamics resulting from such solvent transformations. The methodology allows for the derivation of evaporative flux and boundary conditions near each surface for simulations of systems close to the equilibrium. We apply it to study thin film microstructural evolution in phase segregating polymer blends dissolved in a common volatile solvent and deposited on a planar substrate. Effects of the evaporation rates, interactions of the polymers with the underlying substrate and concentration dependent mobilities on the kinetics of thin film formation are studied.


Improving HIV pre-exposure prophylaxis persistence among adolescent girls and young women: Insights from a mixed-methods evaluation of community, hybrid, and facility service delivery models in Namibia.
Despite the potential for community-based approaches to increase access to pre-exposure prophylaxis (PrEP) for adolescent girls and young women (AGYW), there is limited evidence of whether and how they improve PrEP persistence. We compared PrEP persistence among AGYW receiving services through community and hybrid models in Namibia to facility-based services. We subsequently identify potential mechanisms to explain how and why community and hybrid models achieved (or not) improved persistence to inform further service delivery innovation. Data were collected from PrEP service delivery to AGYW over two-years in Namibia's Khomas Region. We used Kaplan-Meier analysis to estimate survival curves for PrEP persistence beyond three-months after initiation and report the cumulative probability of persistence at one- and three-months. Persistence was defined as any PrEP use within three months after initiation followed by a PrEP refill or previously prescribed supply of at least 30 days at the three-month visit. Interviews were conducted with 28 AGYW and 19 providers and analyzed using a deductive-inductive thematic approach. From October 2017 through September 2019, 372 (18.7%) AGYW received services through a facility model, 302 (15.1%) through a community model, and 1,320 (66.2%) through a hybrid model. PrEP persistence at one- and three-months was 41.2% and 34.9% in the community model and 6.2% and 4.8% in the hybrid model compared to 36.8% and 26.7% in the facility model. Within the community and hybrid models, we identified three potential mechanisms related to PrEP persistence. Individualized service delivery offered convenience and simplicity which enabled AGYW to overcome barriers to obtaining refills but did not work as well for highly mobile AGYW. Consistent interactions and shared experiences fostered social connectedness with providers and with peers, building social networks and support systems for PrEP use. PrEP and HIV-related stigma, however, was widely experienced outside of these networks. Community-to-facility referral for PrEP refill triggered apprehension towards unfamiliar PrEP services and providers in AGYW, which discouraged persistence. Service delivery approaches that offer convenience and simplicity and foster social connectedness may reduce access barriers and increase social support enabling AGYW to self-manage their PrEP use and achieve improved PrEP persistence.


Congenital scoliosis - presentation of three severe cases treated conservatively.
In view of the very limited data about conservative treatment of patients with congenital scoliosis (CS) available, early surgery is suggested already in mild cases with formation failures in the first three years of life. It is common sense that patients with failures of segmentation will not benefit from conservative treatment at all and the same applies to failures of formation with curves of >50 degrees in infancy. Two patients with rib synostosis denied surgery before entering the pubertal growth spurt. These patients have been treated conservatively with braces and Scoliosis In-Patient Rehabilitation (SIR) and now are beyond the pubertal growth spurt. One patient with a formation failure and a curve of >50 degrees lumbar has been treated with the help of braces and physiotherapy from 1.6 years on and is still under treatment now at the age of 15 years. Severe decompensation was prevented in the two patients with failure of segmentation, however a severe thoracic deformity is evident with underdeveloped lung function and severe restrictive ventilation disorder. The patient with failure of formation is well developed, now without cosmetic or physical complaints although his curve progressed at the end of the growth spurt due to final mal-compliance. Failures of segmentation should be advised to have surgery before entering the pubertal growth spurt. In case they deny, conservative treatment can at least in part be beneficial. For patients with failures of formation conservative treatment should be suggested in the first place because long-term outcomes of early surgery beyond pubertal growth spurt are not yet revealed.


In vitro activities of eight macrolide antibiotics and RP-59500 (quinupristin-dalfopristin) against viridans group streptococci isolated from blood of neutropenic cancer patients.
From January 1988 to December 1994, 66 consecutive blood culture isolates of viridans group streptococci collected from febrile neutropenic cancer patients were tested for antimicrobial susceptibilities by the agar dilution method. The antibiotics studied were erythromycin, clarithromycin, roxithromycin, dirithromycin, azithromycin, josamycin, diacetyl-midecamycin, spiramycin, and quinupristin-dalfopristin. A total of 26 (39.4%) strains were resistant to erythromycin with an MIC range of 0.5 to > 128 micrograms/ml. The strains were classified into three groups according to their penicillin susceptibility: 42 (63.6%) were susceptible, 8 (12.1%) were intermediately resistant, and 16 (24.3%) were highly resistant. The percentages of erythromycin-resistant strains in each group were 23.8, 62.5, and 68.8%, respectively. Streptococcus mitis was the species most frequently isolated (83.3%) and showed the highest rates of penicillin (40%) and erythromycin (43.6%) resistance. MICs of all macrolide antibiotics tested and of quinupristin-dalfopristin were higher for penicillin-resistant strains than for penicillin-susceptible strains. All macrolide antibiotics tested had cross-resistance to erythromycin, which was not observed with quinupristin-dalfopristin. Our study shows a high rate of macrolide resistance among viridans group streptococci isolated from blood samples of neutropenic cancer patients, especially those infected with penicillin-resistant strains. These findings make macrolides unsuitable prophylactic agents against viridans group streptococcal bacteremia in this patient population.


Nuclear Receptors in Skeletal Homeostasis.
Nuclear receptors are a family of transcription factors that can be activated by lipophilic ligands. They are fundamental regulators of development, reproduction, and energy metabolism. In bone, nuclear receptors enable bone cells, including osteoblasts, osteoclasts, and osteocytes, to sense their dynamic microenvironment and maintain normal bone development and remodeling. Our views of the molecular mechanisms in this process have advanced greatly in the past decade. Drugs targeting nuclear receptors are widely used in the clinic for treating patients with bone disorders such as osteoporosis by modulating bone formation and resorption rates. Deficiency in the natural ligands of certain nuclear receptors can cause bone loss; for example, estrogen loss in postmenopausal women leads to osteoporosis and increases bone fracture risk. In contrast, excessive ligands of other nuclear receptors, such as glucocorticoids, can also be detrimental to bone health. Nonetheless, the ligand-induced osteoprotective effects of many other nuclear receptors, e.g., vitamin D receptor, are still in debate and require further characterizations. This review summarizes previous studies on the roles of nuclear receptors in bone homeostasis and incorporates the most recent findings. The advancement of our understanding in this field will help researchers improve the applications of agonists, antagonists, and selective modulators of nuclear receptors for therapeutic purposes; in particular, determining optimal pharmacological drug doses, preventing side effects, and designing new drugs that are more potent and specific.


Characterization of transgenic mouse models targeting neuromodulatory systems reveals organizational principles of the dorsal raphe.
The dorsal raphe (DR) is a heterogeneous nucleus containing dopamine (DA), serotonin (5HT), γ-aminobutyric acid (GABA) and glutamate neurons. Consequently, investigations of DR circuitry require Cre-driver lines that restrict transgene expression to precisely defined cell populations. Here, we present a systematic evaluation of mouse lines targeting neuromodulatory cells in the DR. We find substantial differences in specificity between lines targeting DA neurons, and in penetrance between lines targeting 5HT neurons. Using these tools to map DR circuits, we show that populations of neurochemically distinct DR neurons are arranged in a stereotyped topographical pattern, send divergent projections to amygdala subnuclei, and differ in their presynaptic inputs. Importantly, targeting DR DA neurons using different mouse lines yielded both structural and functional differences in the neural circuits accessed. These results provide a refined model of DR organization and support a comparative, case-by-case evaluation of the suitability of transgenic tools for any experimental application.


Control of cell type proportions by a secreted factor in Dictyostelium discoideum.
It has been shown that, in Dictyostelium discoideum, conversion of prestalk cells to prespore cells in suspension cultures is inhibited by coexisting prespore cells. To examine whether the inhibition of conversion requires direct cell contact or is mediated by substances secreted by the cells, prestalk cells and prespore cells were incubated in shaken suspension, separated from each other by a dialysis membrane, and conversion of the prestalk cells to prespore cells scored after 24 h. Prestalk-to-prespore conversion was significantly inhibited if the density of the prespore cells was sufficiently high. In contrast, prestalk cells had little influence on prestalk-to-prespore conversion. Media conditioned by prespore cells, but not by prestalk cells, also inhibited the conversion of prestalk cells. Adenosine, propionate, diethylstilboestrol and differentiation inducing factor (DIF), all of which are known to influence the prestalk/prespore differentiation, were examined for their effects on prestalk-to-prespore conversion. Among these, all except adenosine significantly inhibited the conversion. Based on these results, possible mechanisms for maintenance of the constant cell-type ratio in D. discoideum slugs were discussed.


Comparison of the mRNA expression of factors related to drug resistance in lung tumors and adjacent normal tissue.
Drug resistance related proteins P-glycoprotein (P170), multidrug resistance associated protein (MRP), glutathione S-transferase-pi (GST-pi), glutathione peroxidase (GPX), topoisomerase II (Topo II), thymidylate synthase (TS), O-6-methylguanine-DNA-methyltransferase (MGMT), the heat shock proteins HSP27 and HSP70 and the protooncogenes Fos, Jun and EGFR were investigated in human lung carcinomas and matched normal tissues. We found that the mRNA expression of Topo II and TS were elevated in tumor tissue versus corresponding normal tissue. Additionally Topo II and TS correlated with the proliferating activity determined by expression of histone 3. P170, MRP, HSP70 and also EGFR mRNA were elevated in some tumor probes, but not GST-pi, GPX, MGMT and HSP27 mRNA. Additionally, we determined various values of Fos and Jun mRNA expression but there was no uniform pattern. The finding that some proteins were abnormally expressed in lung tumors compared to the adjacent normal tissue is an important finding for further investigations on the development of individualized chemotherapy but more samples should be examined to extend these observations.


Corneal Edema in Inducible Slc4a11 Knockout Is Initiated by Mitochondrial Superoxide Induced Src Kinase Activation.
Inducible Slc4a11 KO leads to corneal edema by disruption of the pump and barrier functions of the corneal endothelium (CE). The loss of Slc4a11 NH3-activated mitochondrial uncoupling leads to mitochondrial membrane potential hyperpolarization-induced oxidative stress. The goal of this study was to investigate the link between oxidative stress and the failure of pump and barrier functions and to test different approaches to revert the process. Mice which were homozygous for Slc4a11 Flox and Estrogen receptor -Cre Recombinase fusion protein alleles at 8 weeks of age were fed Tamoxifen (Tm)-enriched chow (0.4 g/Kg) for 2 weeks, and controls were fed normal chow. During the initial 14 days, Slc4a11 expression, corneal thickness (CT), stromal [lactate], Na+-K+ ATPase activity, mitochondrial superoxide levels, expression of lactate transporters, and activity of key kinases were assessed. In addition, barrier function was assessed by fluorescein permeability, ZO-1 tight junction integrity, and cortical cytoskeleton F-actin morphology. Tm induced a rapid decay in Slc4a11 expression that was 84% complete at 7 days and 96% complete at 14 days of treatment. Superoxide levels increased significantly by day 7; CT and fluorescein permeability by day 14. Tight junction ZO-1 distribution and the cortical cytoskeleton were disrupted at day 14, concomitant with decreased expression of Cldn1, yet with increased tyrosine phosphorylation. Stromal lactate increased by 60%, Na+-K+ ATPase activity decreased by 40%, and expression of lactate transporters MCT2 and MCT4 significantly decreased, but MCT1 was unchanged at 14 days. Src kinase was activated, but not Rock, PKCα, JNK, or P38Mapk. Mitochondrial antioxidant Visomitin (SkQ1, mitochondrial targeted antioxidant) and Src kinase inhibitor eCF506 significantly slowed the increase in CT, with concomitant decreased stromal lactate retention, improved barrier function, reduced Src activation and Cldn1 phosphorylation, and rescued MCT2 and MCT4 expression. Slc4a11 KO-induced CE oxidative stress triggered increased Src kinase activity that resulted in perturbation of the pump components and barrier function of the CE.


Selective preoperative evaluation for possible N2 disease in carcinoma of the lung.
The efficacy of computed tomography and surgical mediastinal exploration in determining tumor resectability were retrospectively evaluated in 92 consecutive patients with non-small cell lung carcinoma. Status of mediastinal nodes was ultimately determined by surgical mediastinal exploration or thoracotomy. Patients were divided into three groups on the basis of chest roentgenography: Group I comprised 30 patients with peripheral T1 or T2 lesions with normal hilar and mediastinal shadows. Only one patient was found to have an involved node. Chest roentgenography had an accuracy rate of 96% and computed tomography, 93%. Thoracotomy is recommended without either computed tomography or surgical mediastinal exploration in this group. Group II comprised 47 patients with T1 or T2 lesions with an abnormal hilus, an abnormal mediastinal shadow, or either the hilus or mediastinum obscured by overlying parenchymal disease. Computed tomography revealed mediastinal nodes 1 cm or greater in size (abnormal node group) in 21 patients (45%) and smaller than 1 cm (normal node group) in 26 patients (55%). Surgical mediastinal exploration was performed in the abnormal node group and involved nodes were found in 17 of 21 patients (81%). In the normal node group, thoracotomy only was performed and no involved nodes were found. Computed tomography is recommended in all patients in Group II. Patients in the normal node group may be subjected to thoracotomy only and those in the abnormal node group should undergo surgical mediastinal exploration as the next diagnostic step before thoracotomy. Group III comprised 15 patients with grossly abnormal mediastinal shadows. Findings from computed tomography were abnormal in all 10 patients in whom it was done. Surgical mediastinal exploration was done in all 15 and yielded abnormal results in 14. It is recommended in this group that computed tomography is unnecessary and surgical mediastinal exploration should be the only diagnostic procedure. Thus, in potentially resectable non-small cell lung carcinoma, the use of computed tomography and surgical mediastinal exploration should be selective and should be determined by appropriate initial interpretation of the chest roentgenogram.


[Analysis of resistance phenotype and homology of Klebsiella pneumoniae in burn patients].
To study the resistance phenotype and homology of Klebsiella pneumoniae (KPN) in burn patients with infection. Fifty-four strains of KPN were isolated from wound excretion, blood, sputum, venous catheter, feces, and oral cavity of patients hospitalized in Institute of Burn Research of Southwest Hospital (briefly called our institute) from January 2007 to June 2011. Drug resistance of the 54 strains of KPN to 18 antibiotics commonly used in clinic, including ampicillin, ticarcillin, etc, was tested by K-B paper disk diffusion method after being identified. Extended-spectrum β-lactamase (ESBL)-producing KPN was screened based on the drug resistance result. The positive rates of drug-resistant genes SHV, TEM, and CTX-M of the ESBL-producing KPN were detected by polymerase chain reaction. The homology of the ESBL-producing KPN was analyzed by pulse field gel electrophoresis and clustering methodology. The homology of ESBL-producing KPN isolated in each year was analyzed too. (1) The sensitive rate of the 54 strains of KPN to imipenem, meropenem, and ertapenem was respectively 96.30%, 92.59%, and 81.48%, that of these strains to cefotetan and cefoxitin was respectively 70.37% and 64.81%, and that of these strains to ceftazidime was 57.41%. The sensitive rates of the 54 strains of KPN to the other antibiotics were all lower than 40.00%. (2) Twenty-six ESBL-producing KPN strains were screened and the positive rate of SHV, TEM, and CTX-M was 96.15% (25/26), 76.92% (20/26), and 57.69% (15/26), respectively. Detection rate of ESBL-producing KPN strains carrying three genes at the same time was 42.31% (11/26), that of these strains carrying both SHV and TEM was 34.62% (9/26), and those of these strains carrying only a single gene were all less than 10.00%. (3) The twenty-six ESBL-producing KPN were classified into 9 gene types, with 30.77% (8/26) in type A, 19.23% (5/26) in type B, 15.38% (4/26) in type C, 11.54% (3/26) in type D, 7.69% (2/26) in type E, and the rest four strains respectively in type F, G, H, I [3.85% (1/26)]. (4) The major gene type of ESBL-producing KPN in the year of 2007 and 2010 was type A, respectively accounting for 2/3 and 1/2, while that in the year of 2009 was type B, accounting for 1/2. The three strains in 2008 was respectively in type C, E, and F. The four strains in 2011 was respectively in type A, D, H, I. KPN in burn patients with infection in our institute are highly resistant to commonly used antibiotics in clinic, but carbapenems antibiotics can be used for the treatment. Most of the ESBL-producing KPN strains carry two or three drug-resistant genes, and the main gene type of them is type A.


Nanotechnology to advance CRISPR-Cas genetic engineering of plants.
CRISPR-Cas genetic engineering of plants holds tremendous potential for providing food security, battling biotic and abiotic crop stresses caused by climate change, and for environmental remediation and sustainability. Since the discovery of CRISPR-Cas technology, its usefulness has been demonstrated widely, including for genome editing in plants. Despite the revolutionary nature of genome-editing tools and the notable progress that these tools have enabled in plant genetic engineering, there remain many challenges for CRISPR applications in plant biotechnology. Nanomaterials could address some of the most critical challenges of CRISPR genome editing in plants through improvements in cargo delivery, species independence, germline transformation and gene editing efficiency. This Perspective identifies major barriers preventing CRISPR-mediated plant genetic engineering from reaching its full potential, and discusses ways that nanoparticle technologies can lower or eliminate these barriers. We also describe advances that are needed in nanotechnology to facilitate and accelerate plant genome editing. Timely advancement of the application of CRISPR technologies in plant engineering is crucial for our ability to feed and sustain the growing human population under a changing global climate.


[A case of monozygotic twins with Crohn's disease].
Although the incidence and prevalence rates of IBD in Korea are still lower than Western populations, they have been increasing rapidly during the past decades. Crohn's disease (CD) tends to run in families because it is thought to be related to genetic susceptibility coupled with environmental factors. A large number of monozygotic and dizygotic twin pairs with inflammatory bowel disease have been reported in western countries. The population relative risk in first-degree relatives is considered to be about equal in both Koreans and westerners. To our best knowledge, there is no report in monozygotic twins with CD in Korea. This case report is the first documented occurrence of concordant CD occurring in monozygotic twins in Korea.


Emamectin-sodium alginate nano-formulation based on charge attraction with highly improved systemic translocation and photolysis resistance.
Nano pesticides offer an effective means of improving the bioavailability of pesticide due to their excellent solubility and wettability, superior foliar adhesion, and permeability to target insects. By using high-speed homogenization and ultrasonic dispersion technology, an emamectin-sodium alginate nano-formulation (EB@SA) with a particle size ranging from 30 to 50 nm was successfully fabricated using electrostatic self-assembly. The microscopic morphology and structure of EB@SA were further analyzed through transmission electron microscopy, dynamic light scattering, infrared spectroscopy, and 1H NMR. The photolysis resistance behavior of EB@SA demonstrated an improved anti-photolysis ability more than double that of conventional formulations while also exhibiting good sustained-release properties. Not only does EB@SA maintain the inherent insecticidal toxicity of emamectin benzoate (EB), but it also significantly prolongs its insecticidal duration. At a concentration of 20 mg/L, the lethality rate against Armyworms remains above 70 % over a period of 16 days compared to <50 % for general emamectin emulsifiable concentrate. Furthermore, EB@SA greatly enhances the systemic translocation of EB in corn plants by exhibiting favorable bidirectional systemic translocation characteristics. This research presents an efficient and environmentally friendly pesticide nano-formulation that can be effectively utilized for field pest control.


Evidence for the neoplastic transformation of Von-Meyenburg complexes.
Von-Meyenburg complexes (VMC) are seen frequently in the liver and are largely considered to be innocuous, with only 11 cases reported in the literature of neoplastic transformation of VMCs. The authors report three cases of cholangiocarcinoma, each occurring in a background of fibrosis and nodularity that was reported initially as micronodular cirrhosis. Although the livers showed cirrhosis, the central veins were often preserved, and regenerative activity was patchy and focal. Histologic examination revealed many VMCs, and a gradual transition from VMCs to hyperplastic or adenomatous lesions and cholangiocarcinoma. The adenomatous lesions consisted of extensive replacement of the parenchyma by tumor-like nodules of ductular proliferations without obvious features of malignancy. All three patients were older than 60 years of age and had portal hypertension. Computed tomographic scans showed multiple, small renal cysts in one patient. Immunohistochemical staining showed positivity for epithelial membrane antigen, carcinoembryonic antigen, and keratins (AE1/AE3 and CAM5.2) in tumor cells, consistent with cholangiocarcinoma. The pattern of fibrosis and nodularity in these cases is not typical of either congenital hepatic fibrosis or usual cirrhosis. The authors propose that these patients represent another aspect in the spectrum of ductal plate malformations that may be modified by other factors such as alcohol, drugs, or infection. To their knowledge, neoplastic transformation of VMCs in the background of such changes has never been reported before.


Three-Dimensional Imaging Anatomic Study and Clinical Application of the Third Ventricle Transcallosal-Transforniceal Approach.
The third ventricle is a narrow, funnel-shaped, unilocular, midline cavity located between the 2 thalami, under the body of the lateral ventricle, in the center of the head. Damaging of brain tissue in the third ventricle when conducting operation under the microscope will lead to serious consequence. The study aimed to precisely detect the relative location of specific structures on the approach to the third ventricle. The authors rebuilt a 3-dimensional reconstruction of the brain and selected specific sections and then measured several crucial distance, angle to precisely assure the approaching pathway and localize the hypothalamic sulcus, interthalamic adhesion, anterior commissure, optic chiasm, and pineal body. In the study, canthomeatal line was used as base line to measure angle. Parameters were obtained from 58 samples (22 males and 36 females) between 21 and 76 years old. Means and standard deviation were calculated as well as the 95% confidence interval for the mean value of the measured data. The data were analyzed by SPSS, statistical software with the comparison between sexes and sides. The results could be reference for clinical and anatomic utilities.


[Beer-Fick criteria and generic drugs in Brazil].
Determine, according to the Beer-Fick criteria, the prevalence of drugs potentially inappropriate for the elderly available as generic medication in Brazil. Analysis of the list of generic medications issued by " Diário Oficial da União" on July/12/2004 and of the page of the National Agency for Sanitary Surveillance (ANVISA) - www.anvisa.gov.br, using the Beers-Fick criteria. From the list of 299 products 20 (6.7% of the total) included in the Beers-Fick criteria were analyzed, mainly in the categories of anxiolytics, platelet antiaggregants, antiallergics, anti-angina and vasodilators, antiarrythmics, antidepressants, antispasmodics, anti-hypertensive's, non steroid antinflammatories, antiulceratives and cardiac glycosides. These criteria do not include drugs such as cough suppressants, cinnarizine, diltiazem, piracetam, quinolones, xanthines, creams, ointments and ophthalmic solutions which are also present in the list of generic medication. The Beers-Fick criteria may prevent use of drugs potentially inappropriate for the elderly, however, it should be stressed that these criteria are not complete for Brazilian generic medications.


Regimens of vitamin D supplementation for women during pregnancy.
Vitamin D deficiency during pregnancy increases the risk of pre-eclampsia, gestational diabetes, preterm birth, and low birthweight. In a previous Cochrane Review we found that supplementing pregnant women with vitamin D alone compared to no vitamin D supplementation may reduce the risk of pre-eclampsia, gestational diabetes, and low birthweight and may increase the risk of preterm births if it is combined with calcium. However the effects of different vitamin D regimens are not yet clear. To assess the effects and safety of different regimens of vitamin D supplementation alone or in combination with calcium or other vitamins, minerals or nutrients during pregnancy, specifically doses of 601 international units per day (IU/d) or more versus 600 IU/d or less; and 4000 IU/d or more versus 3999 IU/d or less. We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2018), and the reference lists of retrieved studies. Randomised trials evaluating the effect of different vitamin D regimens (dose, frequency, duration, and time of commencement of supplementation during pregnancy), alone or in combination with other nutrients on pregnancy and neonatal health outcomes. We only included trials that compared 601 IU/d or more versus 600 IU/d or less and 4000 IU/d or more versus 3999 IU/d or less. We did not include in the analysis groups that received no vitamin D, as that comparison is assessed in another Cochrane Review. Two review authors independently: i) assessed the eligibility of studies against the inclusion criteria; ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Our primary maternal outcomes were: pre-eclampsia, gestational diabetes, and any adverse effects; our primary infant outcomes were preterm birth and low birthweight. Data were checked for accuracy. The certainty of the evidence was assessed using the GRADE approach. In this review, we included data from 30 trials involving 7289 women. We excluded 11 trials, identified 16 ongoing/unpublished trials and two trials are awaiting classification. Overall risk of bias for the trials was mixed.Comparison 1. 601 IU/d or more versus 600 IU/d or less of vitamin D alone or with any other nutrient (19 trials; 5214 participants)Supplementation with 601 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of pre-eclampsia (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.65 to 1.42); 5 trials; 1553 participants,low-certainty evidence), may reduce the risk of gestational diabetes (RR 0.54, 95% CI 0.34 to 0.86; 5 trials; 1846 participants; moderate-certainty evidence), may make little or no difference to the risk of preterm birth (RR 1.25, 95% CI 0.92 to 1.69; 4 trials; 2294 participants; low-certainty evidence); and may make little or no difference to the risk of low birthweight (RR 0.90, 95% CI 0.66 to 1.24; 4 trials; 1550 participants; very low-certainty evidence) compared to women receiving 600 IU/d or less.Comparison 2. 4000 IU or more versus 3999 IU or less of vitamin D alone (15 trials; 4763 participants)Supplementation with 4000 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of: pre-eclampsia (RR 0.87, 95% CI 0.62 to 1.22; 4 trials, 1903 participants, low-certainty evidence); gestational diabetes (RR 0.89, 95% CI 0.56 to 1.42; 5 trials, 2276 participants; low-certainty evidence); preterm birth (RR 0.85, 95% CI 0.64 to 1.12; 6 trials, 2948 participants, low-certainty evidence); and low birthweight (RR 0.92, 95% CI 0.49 to 1.70; 2 trials; 1099 participants; low-certainty evidence) compared to women receiving 3999 IU/d or less.Adverse events (such as hypercalcaemia, hypocalcaemia, hypercalciuria, and hypovitaminosis D) were reported differently in most trials; however, in general, there was little to no side effects reported or similar cases between groups. Supplementing pregnant women with more than the current vitamin D recommendation may reduce the risk of gestational diabetes; however, it may make little or no difference to the risk of pre-eclampsia, preterm birth and low birthweight. Supplementing pregnant women with more than the current upper limit for vitamin D seems not to increase the risk of the outcomes evaluated. In general, the GRADE was considered low certainty for most of the primary outcomes due to serious risk of bias and imprecision of results. With respect to safety, it appears that vitamin D supplementation is a safe intervention during pregnancy, although the parameters used to determine this were either not reported or not consistent between trials. Future trials should be consistent in their reports of adverse events. There are 16 ongoing trials that when published, will increase the body of knowledge.


Immunoelectron microscopic study of the location of group-specific and type-specific polysaccharide antigens on isolated walls of group B streptococci.
The ultrastructural locations of the group-specific polysaccharide and the type-specific polysaccharides Ia, Ib, II and III of group B streptococci (Streptococcus agalactiae) were studied on isolated walls by the direct immunoferritin technique. The type polysaccharides were located exclusively on the outer side of the wall on which they formed a distinct capsule. Except for strain 58/59 (type Ia) the thickness of the capsule was characteristic of each strain investigated. In all strains the type-specific ferritin labelling was confined to the outer surface of the capsule. The group-specific polysaccharide could be demonstrated on the inner surface in all strains tested. It could also be demonstrated on the outer surface in strains 59/59 (type Ib) and 8/66 (group B variant) and on most of the walls of strain 58/59 (type Ia). The failure to detect this antigen on the outer side of the walls of strains 60/59 (type II) and 13/63 (type III) and on some walls of strain 58/59 was probably due to the thickness of the type polysaccharide capsule.


Biodegradable Extremely-Small-Diameter Vascular Graft Made of Silk Fibroin can be Implanted in Mice.
Synthetic vascular grafts are widely used in surgical revascularization, mainly for medium- to large-sized vessels. However, synthetic grafts smaller than 6 mm in diameter are associated with a high incidence of thrombosis. In this study, we evaluated silk fibroin, a major protein of silk, with high biocompatibility and biodegradability, as a useful material for extremely-small-diameter vascular grafts. A small-sized (0.9 mm inner diameter) graft was braided from a silk fibroin thread. The right carotid arteries of 8- to 14-week-old male C57BL/6 mice were cut at the midpoint, and fibroin grafts (5- to 7-mm in length) were transplanted using a cuff technique with polyimide cuffs. The grafts were harvested at different time points and analyzed histologically. CD31+ endothelial cells had already started to proliferate at 2 weeks after implantation. At 4 weeks, neointima had formed with α-smooth muscle actin+ cells, and the luminal surface was covered with CD31+endothelial cells. Mac3+ macrophages were accumulated in the grafts. Graft patency was confirmed at up to 6 months after implantation. This mouse model of arterial graft implantation enables us to analyze the remodeling process and biocompatibility of extremely-small-diameter vascular grafts. Biodegradable silk fibroin might be applicable for further researches using genetically modified mice.


Discrimination among rhinovirus serotypes for a variant ICAM-1 receptor molecule.
Intercellular adhesion molecule 1 (ICAM-1) is the cellular receptor for the major group of human rhinovirus serotypes, including human rhinovirus 14 (HRV14) and HRV16. A naturally occurring variant of ICAM-1, ICAM-1Kilifi, has altered binding characteristics with respect to different HRV serotypes. HRV14 binds to ICAM-1 only transiently at physiological temperatures but forms a stable complex with ICAM-1Kilifi. Conversely, HRV16 forms a stable complex with ICAM-1 but does not bind to ICAM-1Kilifi. The three-dimensional structures of HRV14 and HRV16, complexed with ICAM-1, and the structure of HRV14, complexed with ICAM-1Kilifi, have been determined by cryoelectron microscopy (cryoEM) image reconstruction to a resolution of approximately 10 angstroms. Structures determined by X-ray crystallography of both viruses and of ICAM-1 were fitted into the cryoEM density maps. The interfaces between the viruses and receptors contain extensive ionic networks. However, the interactions between the viruses and ICAM-1Kilifi contain one less salt bridge than between the viruses and ICAM-1. As HRV16 has fewer overall interactions with ICAM-1 than HRV14, the absence of this charge interaction has a greater impact on the binding of ICAM-1Kilifi to HRV16 than to HRV14.


Reproducibility study of whole-brain 1H spectroscopic imaging with automated quantification.
A reproducibility study of proton MR spectroscopic imaging ((1)H-MRSI) of the human brain was conducted to evaluate the reliability of an automated 3D in vivo spectroscopic imaging acquisition and associated quantification algorithm. A PRESS-based pulse sequence was implemented using dualband spectral-spatial RF pulses designed to fully excite the singlet resonances of choline (Cho), creatine (Cre), and N-acetyl aspartate (NAA) while simultaneously suppressing water and lipids; 1% of the water signal was left to be used as a reference signal for robust data processing, and additional lipid suppression was obtained using adiabatic inversion recovery. Spiral k-space trajectories were used for fast spectral and spatial encoding yielding high-quality spectra from 1 cc voxels throughout the brain with a 13-min acquisition time. Data were acquired with an 8-channel phased-array coil and optimal signal-to-noise ratio (SNR) for the combined signals was achieved using a weighting based on the residual water signal. Automated quantification of the spectrum of each voxel was performed using LCModel. The complete study consisted of eight healthy adult subjects to assess intersubject variations and two subjects scanned six times each to assess intrasubject variations. The results demonstrate that reproducible whole-brain (1)H-MRSI data can be robustly obtained with the proposed methods.


[Swedish white paper on donation can give more donors without compromising ethics].
Swedish white paper on donation can give more donors without compromising ethics The White Paper on organ donation (SOU 2015:84) proposes new regulations for organ donation. In particular it spells out that it is permissible to take medical steps to preserve organs while the patient is still alive. It is proposed that this should be allowed after the medical team has declared that the continuation of life sustaining treatment is futile. The white paper opens up for donation after cardiac death. There has been some critique of the white paper for lack of deeper ethical discussions. The ethical issues pertaining to the proposals are discussed in this paper. It is concluded that the proposals are ethically acceptable. The human dignity principle will however demand that the decision to end life sustaining treatment is taken regardless of whether the patient is a possible organ donor or not.


Senile entropion - cure rate by retractor tightening and horizontal shortening.
In order to clarify the efficiency of two operations aimed at curing the principal causes of senile entropion, a consecutive series of patients were examined. In 19 lids, the lower lid retractors were tightened transcutaneously and in 45 a simultaneous horizontal lid shortening was performed. Surgery was uneventful in all cases. The patients were reexamined 7-53 months after surgery. In the group with mere retractor surgery were five recurrences; all lids that also had a horizontal shortening were satisfactorily cured. Lower eyelid retractor tightening with simultaneous horizontal shortening of the lid is recommended to correct senile operation with a lasting result.


In Situ fuel processing in a microbial fuel cell.
A microbial fuel cell (MFC) was designed in which fuel is generated in the cell by the enzyme glucoamylase, which is displayed on the surface of yeast. The enzyme digests starch specifically into monomeric glucose units and as a consequence enables further glucose oxidation by microorganisms present in the MFC anode. The oxidative enzyme glucose oxidase was coupled to the glucoamylase digestive enzyme. When both enzymes were displayed on the surface of yeast cells in a mixed culture, superior fuel-cell performance was observed in comparison with other combinations of yeast cells, unmodified yeast, or pure enzymes. The feasibility of the use of the green macroalgae Ulva lactuca in such a genetically modified MFC was also demonstrated. Herein, we report the performance of such fuel cells as a proof of concept for the enzymatic digestion of complex organic fuels in the anode of MFCs to render the fuel more available to microorganisms.


[Differences and similarities in approach of integrated strategy for dengue prevention and control between Colombia and Peru].
We analyzed and compared two Integrated Management Strategies for Dengue Prevention and Control (IMS-dengue Colombia and IMS-dengue Peru), through a narrative review of available literature, in order to identify common and dissimilar patterns in two Andean countries with epidemiological differences in the context of dengue disease. We were able to identify differences related to: formal assessment of problem, formation of groups of actors, and quantitative information provided by performance indicators. These limitations identified in IMS-dengue Colombia 2006-2010 were overcome in a new version of the strategy (IMS-dengue Colombia 2012-2021). We were able to document an epidemiological impact of implementation of IMS-dengue Colombia 2006-2010. Additionally, a gradual increase was observed in incidence rates of dengue cases that could be related to the strengthening of surveillance system of IMS- dengue Peru.


Prevalence and determinants of frailty and associated comorbidities among older Gurkha welfare pensioners in Nepal.
Population aging is increasing in low-income countries. Despite this, there is distinct lack of knowledge about the prevalence of comorbidities and determinants of frailty among older people in these countries. We examined data from "Health and Social Care Needs Assessment Survey of the Gurkha Welfare Pensioners" carried out in 2014. Participants were aged ≥60 years from the Gorakha, Lamjung and Tanahu districts of Nepal. Face-to-face interviews were carried out using validated questionnaires. Demographic data, socioeconomic status, and self-reported symptoms and illnesses were collected. Frailty was assessed using the Canadian Study of Health and Aging scale. Univariable and multivariable regression models were constructed to identify the determinants of frailty defined as Canadian Study of Health and Aging scale ≥4. A total of 253 participants (32.0% men) were included in the present study. Most (82.2%) participants were from the Janajati ethnic background. Men who were ex-servicemen had higher educational attainment than women, most of whom (95.3%) were widows of ex-servicemen (P < 0.01). A total of 48.5% of women lived with their sons, whereas 43% of the male participants lived with their wives. Women reported a higher prevalence of mental health issues, such as anxiety and insomnia, compared with men. The prevalence of frailty was 46.2% (46.3% in men and 46.1% in women). In this population, frailty was significantly associated with older age, smoking, living with son, breathing problems, unspecified pain and fatigue, poor dental health, and history of falls and fracture (P < 0.001 for all) after controlling for potential confounders. The present study highlights the growing nature of the comorbidity burden, and frailty and its determinants in a low-income setting. Concerted efforts should be made with regard to how best to tackle this globally. Geriatr Gerontol Int 2017; 17: 2493-2499.


Functional correction of dystrophin actin binding domain mutations by genome editing.
Dystrophin maintains the integrity of striated muscles by linking the actin cytoskeleton with the cell membrane. Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD) that result in progressive, debilitating muscle weakness, cardiomyopathy, and a shortened lifespan. Mutations of dystrophin that disrupt the amino-terminal actin-binding domain 1 (ABD-1), encoded by exons 2-8, represent the second-most common cause of DMD. In the present study, we compared three different strategies for CRISPR/Cas9 genome editing to correct mutations in the ABD-1 region of the DMD gene by deleting exons 3-9, 6-9, or 7-11 in human induced pluripotent stem cells (iPSCs) and by assessing the function of iPSC-derived cardiomyocytes. All three exon deletion strategies enabled the expression of truncated dystrophin protein and restoration of cardiomyocyte contractility and calcium transients to varying degrees. We show that deletion of exons 3-9 by genomic editing provides an especially effective means of correcting disease-causing ABD-1 mutations. These findings represent an important step toward eventual correction of common DMD mutations and provide a means of rapidly assessing the expression and function of internally truncated forms of dystrophin-lacking portions of ABD-1.


Aerobic biotransformation of 6:2 fluorotelomer sulfonate in soils from two aqueous film-forming foam (AFFF)-impacted sites.
Although 6:2 fluorotelomer sulfonate (6:2 FTS) is a common ingredient in aqueous film-forming foam (AFFF) formulations, its environmental fate at AFFF-impacted sites remains poorly understood. This study investigated the biotransformation of 6:2 FTS in microcosms prepared with soils collected from two AFFF-impacted sites; the former Loring Air Force Base (AFB) and Robins AFB. The half-life of 6:2 FTS in Loring soil was 43.3 days; while >60 mol% of initially spiked 6:2 FTS remained in Robins soil microcosms after a 224-day incubation. Differences in initial sulfate concentrations and the depletion of sulfate over the incubation likely contributed to the different 6:2 FTS biotransformation rates between the two soils. At day 224, stable transformation products, i.e., C4C7 perfluoroalkyl carboxylates, were formed with combined molar yields of 13.8 mol% and 1.2 mol% in Loring and Robins soils, respectively. Based on all detected transformation products, the biotransformation pathways of 6:2 FTS in the two soils were proposed. Microbial community analysis suggests that Desulfobacterota microorganisms may promote 6:2 FTS biotransformation via more efficient desulfonation. In addition, species from the genus Sphingomonas, which exhibited higher tolerance to elevated concentrations of 6:2 FTS and its biotransformation products, are likely to have contributed to 6:2 FTS biotransformation. This study demonstrates the potential role of biotransformation processes on the fate of 6:2 FTS at AFFF-impacted sites and highlights the need to characterize site biogeochemical properties for improved assessment of 6:2 FTS biotransformation behavior.


Yolk sac fatty acid composition, yolk absorption, embryo development, and chick quality during incubation in eggs from young and old broiler breeders.
The objective of the present study was to examine the changes in yolk and yolk sac fatty acid composition and also to investigate egg content, yolk absorption, embryo development during incubation, and chick quality at hatch in eggs from 36- and 52-wk-old broiler breeders. The fatty acid profiles of the yolk, the yolk sac of embryos, and the residual yolk sac of chicks were analyzed before incubation, on d 18, and at hatch, respectively. Yolk sac weight, and embryo weight and length were measured on d 18, and chick weight and length were measured at hatch. Egg weight, yolk and albumen weight, yolk percentage, and yolk:albumen ratio increased as breeder age increased, but the albumen percentage decreased. Yolk absorption in absolute value (g) was higher in embryos from the old flock on d 18 and at hatch. Relative yolk absorption was similar between age groups on d 18, whereas it was higher in the young flock at hatch. Breeder age affected the yolk sac weight and was higher in the old flock during incubation. Embryo or chick weight and length, and yolk-free BW were affected by breeder age during incubation. These parameters were higher in the old flock with a difference of 3.7 g, 0.8 cm, and 2.6 g, respectively, on d 18 and 7.4 g, 1.4 cm, and 6.3 g, respectively, at hatch compared with the young flock. The effect of breeder age on fatty acid composition differed significantly by sampling day. Palmitic, stearic, oleic, and linoleic acids were major fatty acids in the fresh yolk, ranging from 13.02 to 29.24%. These were followed by palmitoleic and arachidonic acids ranging from 1.24 to 7.04%, with the remaining fatty acids below 1%. Higher concentrations of myristic, palmitoleic, and oleic acids and lower concentrations of heptadeconoic, stearic, linoleic, and arachidonic acids were found in the residual yolk sac of the young flock than the old flock. The results showed preferentially selective absorption of some fatty acids by the embryo during incubation.


Inactivation determinant in the I-II loop of the Ca2+ channel alpha1-subunit and beta-subunit interaction affect sensitivity for the phenylalkylamine (-)gallopamil.
1. The role of calcium (Ca2+) channel inactivation in the molecular mechanism of channel block by phenylalkylamines (PAAs) was analysed in a PAA-sensitive rabbit brain class A Ca2+ channel mutant (alpha1A-PAA). Use-dependent barium current (IBa) inhibition of alpha1A-PAA by (-)gallopamil and Ca2+ channel recovery from inactivation and block were studied with two-microlectrode voltage clamp after expression of alpha1A-PAA and auxiliary alpha2-delta- and beta1a- or beta2a-subunits in Xenopus oocytes. 2. Mutation Arg387Glu (alpha1A numbering) in the intracellular loop connecting domains I and II of alpha1A-PAA slowed the inactivation kinetics and reduced use-dependent inhibition (100 ms test pulses at 0.2 Hz from -80 to 20 mV) of the resulting mutant alpha1A-PAA/R-E/beta1a channels by 100 microM (-)gallopamil (53 +/- 2 %, alpha1A-PAA/beta1a vs. 31 +/- 2 %, alpha1A-PAA/R-E/beta1a, n >= 4). This amino acid substitution simultaneously accelerated the recovery of channels from inactivation and from block by (-)gallopamil. 3. Coexpression of alpha1A-PAA with the beta2a-subunit reduced fast IBa inactivation and induced a substantial reduction in use-dependent IBa inhibition by (-)gallopamil (25 +/- 4 %, alpha1A-PAA/beta2a; 13 +/- 1 %, alpha1A-PAA/R-E/beta2a). The time constant of recovery from block at rest was not significantly affected. 4. These results demonstrate that changes in channel inactivation induced by Arg387Glu or beta2a-alpha1-subunit interaction affect the drug-channel interaction.


Health and health-related quality of life in pig farmers carrying livestock-associated methicillin-resistant Staphylococcus aureus.
There is limited knowledge about the effect of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) carriage on health-related quality of life (QoL). With this study, we explored whether LA-MRSA causes infections or affects health-related QoL in pig farmers. This prospective cohort study surveyed persons working on 49 farrowing pig farms in The Netherlands for 1 year (2010-2011). On six sampling moments, nasal swabs, environmental samples and questionnaires on activities and infections were collected. At the end of the study year, persons were asked about their QoL using the validated SF-36 and EQ-5D questionnaires. Of 120 persons, 44 (37%) were persistent MRSA carriers. MRSA carriage was not associated with infections, use of antimicrobials, healthcare contact and health-related QoL items in univariate or multivariate analysis, most likely due to the 'healthy worker effect'. Despite high carriage rates, the impact of LA-MRSA carriage in this population of relatively healthy pig farmers on health and health-related QoL appears limited; more research is needed for confirmation.


Enteral feeding in the critically ill: the role of the gastroenterologist.
Expertise in enteral nutrition (EN) is an important aspect of the skill set of the clinical gastroenterologist. Delivery of adequate EN in critically ill patients is an active therapy that attenuates the metabolic response to stress and favorably modulates the immune system. EN is less expensive than parenteral nutrition and is favored in most cases because of improvement in patient outcomes, including infections and length of stay. Newer endoscopic techniques for placing nasoenteric feeding tubes have been developed, which improve placement success and efficiency. It appears that there is an ideal window period of 24-48 h when enteral feeding should be started in critically ill patients. Most patients can be fed into the stomach, but certain groups may benefit from small bowel feeding. Protocols on how to start and monitor enteral feeding have been developed. Immune-modulating feeding formulations also appear to be beneficial in specific patient populations. The gastroenterologist is a crucial member of the multidisciplinary team for nutritional support in the intensive care unit patient, with his knowledge of gastrointestinal pathophysiology, nutrition, and endoscopic feeding-tube placement.


The implications of stochastic synthesis for the conjugation of functional groups to nanoparticles.
Stochastic synthesis of a ligand coupled to a nanoparticle results in a distribution of populations with different numbers of ligands per nanoparticle. This distribution was resolved and quantified using HPLC and is in excellent agreement with the ligand/nanoparticle average measured by 1H NMR, gel permeation chromatography (GPC), and potentiometric titration, and yet significantly more disperse than commonly held perceptions of monodispersity. Two statistical models were employed to confirm that the observed heterogeneity is consistent with theoretical expectations.


Prion protein gene (PrP) polymorphisms in healthy sheep in Turkey.
Scrapie, a transmissible spongiform encephalopathy (TSE) or prion disease, is a fatal, neurodegenerative disease in sheep and goats. This disease has been known in Europe for more than 250 years. Susceptibility to scrapie is associated with polymorphisms in the sheep prion protein gene (PrP) gene. In sheep, polymorphism in the PrP gene has been identified at a number of codons, and polymorphisms at codons 136, 154 and 171 have reported linkage with susceptibility to scrapie. Polymorphisms at the PrP locus were studied in 413 animals representing three native sheep breeds (Imroz, Chios and Kıvırcık) in Turkey. Genomic DNA was obtained from blood, and genotypes were screened using PCR and direct DNA sequencing. We report 17 genotypes derived from seven different alleles. The most frequent genotype in the Kıvırcık sheep is ARQ/ARQ, whereas the ARR/ARQ genotype is predominant in the Chios and Imroz breeds. In general, the ARQ haplotype was the predominant haplotype. ARQ haplotype was also predominant in the Kıvırcık and Chios sheep breeds, whereas the Imroz sheep predominantly had the ARR haplotype. The susceptibility-associated VRQ haplotype was found in 2.38%, 0.35% and 0.81% of the Imroz, Kıvırcık and Chios sheep, respectively. Moreover, seven additional polymorphisms have been detected at codons G127S, G127V, H143R, G145S, Y172D, N174Y and Q189L. Among these polymorphisms, the N174Y allele is a novel polymorphism, and the G145S allele is a novel allele for a known polymorphic locus.


Radiation-induced versus endogenous DNA damage and assays that measure parameters reflecting DNA damage on cell by cell basis: comments on the article by Pollycove and Feinendegen.
The article by Pollycove and Feinendegen raises important issues regarding the relative contributions of endogenous and radiation-induced DNA damage to the overall DNA damage burden following low level radiation exposures. Clearly, resolution of the issues raised in their article will have important implications regarding regulatory philosophy. Dose-limiting studies of DNA damage measured on a cell-by-cell basis was used to analyze available data in the context of the proposed model. If one proposes that significant numbers of oxidative DNA lesions are present in cells at a steady state level at any give time, then such damage will be included in the background measure of any DNA damage dependent parameter that is sensitive to these classes of DNA damage. Then the expected number of lesions per cell was compared, prior to X- or gamma-ray exposure, at the dose that gives the minimum statistically significant difference from background, at the dose where the DNA damage dependent parameter is twice background (i.e., the doubling dose). The lesion frequencies predicted from the model by Pollycove and Feinendegen are reasonable for the micronucleus assay and the inhibition of DNA supercoil rewinding, but appear to be inconsistent with results from the comet assay. Possible explanations for the inconsistency between the comet assay dose-response data and the predicted levels of DNA damage predicted by the model are discussed, suggesting that the estimates of the radiation induced damage are too low and those for endogenous damage are too high. The goal in introducing these issues is not to be negative to the article but to present a basis for future discussions and more importantly future experimental work, by which the important issues raised can be resolved.


'Children awaken by playing': a qualitative exploration of caregivers' norms, beliefs and practices related to young children's learning and early childhood development in rural Burkina Faso.
Evidence suggests that responsive caregiving and early learning activities positively impact developmental outcomes, with positive effects throughout the life course. Early childhood development interventions should align with local values, beliefs and resources but there has been little research of caregiver beliefs and perspectives on development and learning, especially in sub-Saharan Africa. This qualitative study explored norms, beliefs, practices and aspirations around child development of caregivers of young children in rural Burkina Faso. We conducted 32 in-depth interviews with mothers and fathers of young children and 24 focus group discussions with mothers, fathers and grandmothers, which included trying behaviours and reporting on experiences. The research informed the development of Scaling Up Nurturing Care, a Radio Intervention to Stimulate Early Childhood Development (SUNRISE), an early child development radio intervention. Caregivers described a process of 'awakening', through which children become aware of themselves and the world around them.Perceptions of the timing of awakening varied, but the ability to learn was thought to increase as children became older and more awake. Consequently, talking and playing with babies and younger children were perceived to have little developmental impact. Caregivers said children's interactions with them, alongside God-given intelligence, was believed to impact later behaviour and development. Caregivers felt their role in helping their children achieve later in life was to pay for education, save money, provide advice and be good role models. Interaction and learning activities were not specifically mentioned. Caregivers who trialled interaction and learning activities reported positive experiences for themselves and their child, but interactions were often caregiver led and directive and play was often physical. Key barriers to carrying out the behaviours were poverty and a lack of time. Exploring early childhood beliefs and practices can reveal important sociocultural beliefs which, if incorporated into programme planning and implementation, could help achieve more impactful, acceptable and equitable programmes. NCT05335395.


Bmi‑1‑targeting suppresses osteosarcoma aggressiveness through the NF‑κB signaling pathway.
Bone cancer is one of the most lethal malignancies and the specific causes of tumor initiation are not well understood. B‑cell‑specific Moloney murine leukemia virus integration site 1 protein (Bmi‑1) has been reported to be associated with the initiation and progression of osteosarcoma, and as a prognostic indicator in the clinic. In the current study, a full‑length antibody targeting Bmi‑1 (AbBmi‑1) was produced and the preclinical value of Bmi‑1‑targeted therapy was evaluated in bone carcinoma cells and tumor xenograft mice. The results indicated that the Bmi‑1 expression level was markedly upregulated in bone cancer cell lines, and inhibition of Bmi‑1 by AbBmi‑1 reduced the invasiveness and migration of osteosarcoma cells. Overexpression of Bmi‑1 promoted proliferation and angiogenesis, and increased apoptosis resistance induced by cisplatin via the nuclear factor‑κB (NF‑κB) signal pathway. In addition, AbBmi‑1 treatment inhibited the tumorigenicity of osteosarcoma cells in vivo. Furthermore, AbBmi‑1 blocked NF‑κB signaling and reduced MMP‑9 expression. Furthermore, Bmi‑1 promoted osteosarcoma tumor growth, whereas AbBmi‑1 significantly inhibited osteosarcoma tumor growth in vitro and in vivo. Notably, AbBmi‑1 decreased the percentages of Ki67‑positive cells and terminal deoxynucleotidyl transferase dUTP nick end labeling‑positive cells in tumors compared with Bmi‑1‑treated and PBS controls. Notably, MMP‑9 and NF‑κB expression were downregulated by treatment with AbBmi‑1 in MG‑63 osteosarcoma cells. In conclusion, the data provides evidence that AbBmi‑1 inhibited the progression of osteosarcoma, suggesting that AbBmi‑1 may be a novel anti‑cancer agent through the inhibition of Bmi‑1 via activating the NF‑κB pathway in osteosarcoma.


Methods of adolescent suicide prevention.
This article reviews a series of studies developed to address the public health problem of adolescent suicide. The clinical predictors of adolescent suicide are presented, and several related prevention strategies are offered and critiqued. The method of suicide prevention found to be most effective is a systematic, direct-screening procedure that has a high potential for institutionalization.


Adalimumab Therapy Has a Beneficial Effect on Bone Metabolism in Patients with Crohn's Disease.
Infliximab has been shown to have beneficial effects on bone metabolism in patients with Crohn's disease (CD) although as yet the exact mechanisms have not been fully elucidated. To evaluate the impact of adalimumab therapy on bone metabolism using a combined in vivo and in vitro model. Parathyroid hormone, vitamin D, bone formation markers, bone resorption marker, pro-inflammatory cytokines, anti-inflammatory cytokines, osteoprotegerin, and sRANKL were measured in control patients and pre- and post-treatment with adalimumab in CD patients. The effect of control patients' and pre- and post-treatment CD patients' sera on human osteoblasts (hFOB 1.19) in vitro cell viability and differentiation was also analyzed. There was a significant increase in bone formation markers osteocalcin (P < 0.05) and procollagen type 1 N-terminal propeptide (P < 0.01) at 1 and 3 months post-treatment. Moreover, there was a sustained but not significant fall in serum CTx, a bone resorption marker. No significant change was seen over time with other parameters measured. Serum from CD patients pre-treated with adalimumab showed increased osteoblast viability compared with that of post-treated patients at 6 months (P = 0.002) and controls. However, post-adalimumab treatment sera at 6 months appeared to increase osteoblast differentiation (P = 0.001), which is likely to be important in new bone formation. This first study evaluating the role of adalimumab as a possible bone protector in Crohn's disease patients has shown that similar to infliximab, adalimumab has complex and potentially beneficial effects on bone metabolism.


Successful treatment of non-Hodgkin's lymphoma using R-CHOP in a patient with Wiskott-Aldrich syndrome followed by a reduced-intensity stem cell transplant.
WAS is an X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and increased incidence of autoimmunity and malignancy. HSCT is the only curative treatment for WAS. Herein, we report the case of a 17-yr-old boy with WAS who received an unrelated HSCT while in complete remission of diffuse large B-cell lymphoma after chemotherapy. Pretransplant conditioning consisted of fludarabine, busulfan, and total body irradiation (4 Gy). GvHD prophylaxis consisted of tacrolimus and short-course methotrexate. Following HSCT, rapid and stable engraftment was observed. Platelet count gradually increased, and the generalized eczema improved. The patient developed grade II acute GvHD and limited chronic GvHD on days 30 and 210, respectively, which resolved with immunosuppressive treatment. Symptoms caused by the reactivation of human herpes virus-6, BK virus, and VZV were observed from days 21, 60, and 96, respectively; they were resolved after conservative treatment and acyclovir administration. No other regimen-related toxicity was observed. Complete donor bone marrow chimerism was achieved one month after transplantation. RIST is an effective therapeutic option for older children with WAS accompanied by malignant lymphoma.


Complexity of weighted graph: A new technique to investigate structural complexity of brain activities with applications to aging and autism.
In recent years complexity of the brain structure in healthy and disordered subjects has been studied increasingly. But to the best of the authors' knowledge, researchers so far have investigated the structural complexity only in the context of two restricted networks known as Small-World and Scale-free networks; whereas other aspects of the structural complexity of brain activities may be affected by aging and neurodegenerative disorders such as the Alzheimer's disease and autism spectrum disorder. In this study, two general complexity metrics of graphs, Graph Index Complexity and Offdiagonal Complexity are proposed as general measures of complexity, not restricted to SWN only. They are adopted to measure the structural complexity of the weighted graphs instead of the common binary graphs. Fuzzy Synchronization Likelihood is applied to the EEGs and their sub-bands, as a functional connectivity metric of the brain, to construct the functional connectivity graphs. Two applications are used to evaluate the efficacy of the complexity measures: diagnosis of autism and aging, both based on EEG. It was discovered that the Graph Index Complexity of gamma band is discriminative in distinguishing autistic children from non-autistic children. Also, Offdiagonal Complexity of theta band in young subjects was observed to be significantly different than old subjects. This study shows that changes in the structure of functional connectivity of brain in disorders and different healthy states can be revealed by unrestricted metrics of graph complexity. While the applications presented in this paper are based on EEG, the approach is general and can be used with other modalities such as fMRI, MEG, etc. Further, it can be used to study every other neurological and psychiatric disorder.


Helping hemiparetics to help themselves. Sensory feedback therapy.
Despite the presence of some voluntary movement, the loss of discrete control impairs functioning of the arm and hand in most hemiparetics. Seventy hemiparetic patients, aged 12 to 78 years, were treated and followed up for six months to three years. Electromyographic activity monitored from dysfunctional primary movers during attempted movement was displayed to the patients as a continuous oscilloscopic trace, reflecting generated muscle activity and allowing its quantification. Coupled with operant conditioning techniques, these displays were modified gradually by reinforcing the patient's effort with auditory feedback during successive approximations to a desired level. Such therapeutic use of electromyographic displays often resulted in a progressive improvement of voluntary movement. More than half the patients acquired and retained purposive movements that meaningfully improved their functional capabilities.


[The neurobiological bases of epileptogenesis in the developing brain].
The basics of neurophysiological, neurochemical and molecular mechanisms of epileptogenesis in early ontogeny are discussed. The role of developmental neuropathology, synaptogenesis; the role of glutamatergic and GABA-ergic transmitter systems are summarized. The candidates of genes in the childhood epilepsies, developmental changes in the expression of genes of voltage-gated ionic channels and receptor genes are reviewed.


Micropatterned surfaces: techniques and applications in cell biology.
Engineering of cell culture substrates provides a unique opportunity for precise control of the cellular microenvironment with both spatial as well as temporal resolutions. This greatly enhances studies of cell-cell, cell-matrix and cell-factor interaction studies in vitro. The technologies used for micropatterning in the biological field over the last decade and new applications in the last few years for dynamic control of surfaces, tissue engineering, drug discovery, cell-cell interactions and stem cell studies are presented. The reader will gain knowledge on the state of the art in micropatterning and its wide ranging applications in cell patterning, with new pathways to control the cell environment. Micropatterning of cells has been studied and developed enough to be widely applied ranging from single cell assays to tissue engineering. Techniques have evolved from many-step processes to direct writing of biologically selective patterns.


Changes in lysosomal enzymes in acute experimental liver injury.
1. An investigation has been made of the changes occurring in lysosomal enzyme activities during the early development of experimentally produced liver injury in the rat. Three enzymes have been studied: acid phosphatase, acid ribonuclease and beta-glucuronidase. Four different methods of inducing liver injury have been used: administration of carbon tetrachloride, thioacetamide, dimethylnitrosamine and the fungal toxin sporidesmin. 2. The majority of the data presented concern alterations produced by carbon tetrachloride. Despite the extensive central necrosis and accompanying fat accumulation which this poison produced in the liver, only small changes in the activity and latency of lysosomal enzymes could be detected. In the early (pre-necrotic) period of injury these changes were insignificant. At a late stage of injury, when extensive centrilobular necrosis was present, there were indications of lysosomal rupture. 3. The results obtained with the other three hepatotoxins were similar to those described for carbon tetrachloride in that no evidence of early lysosomal rupture was obtained during the pre-necrotic period. It is concluded that lysosomes probably play no role in the early development of the four types of liver injury studied but, instead, are involved in later scavenging processes.


The π Configuration of the WWW Motif of a Short Trp-Rich Peptide Is Critical for Targeting Bacterial Membranes, Disrupting Preformed Biofilms, and Killing Methicillin-Resistant Staphylococcus aureus.
Tryptophan-rich peptides, being short and suitable for large-scale chemical synthesis, are attractive candidates for developing a new generation of antimicrobials to combat antibiotic-resistant bacteria (superbugs). Although there are numerous pictures of the membrane-bound structure of a single tryptophan (W), how multiple Trp amino acids assemble themselves and interact with bacterial membranes is poorly understood. This communication presents the three-dimensional structure of an eight-residue Trp-rich peptide (WWWLRKIW-NH2 with 50% W) determined by the improved two-dimensional nuclear magnetic resonance method, which includes the measurements of 13C and 15N chemical shifts at natural abundance. This peptide forms the shortest two-turn helix with a distinct amphipathic feature. A unique structural arrangement is identified for the Trp triplet, WWW, that forms a π configuration with W2 as the horizontal bar and W1/W3 forming the two legs. An arginine scan reveals that the WWW motif is essential for killing methicillin-resistant Staphylococcus aureus USA300 and disrupting preformed bacterial biofilms. This unique π configuration for the WWW motif is stabilized by aromatic-aromatic interactions as evidenced by ring current shifts as well as nuclear Overhauser effects. Because the WWW motif is maintained, a change of I7 to R led to a potent antimicrobial and antibiofilm peptide with 4-fold improvement in cell selectivity. Collectively, this study elucidated the structural basis of antibiofilm activity of the peptide, identified a better peptide candidate via structure-activity relationship studies, and laid the foundation for engineering future antibiotics based on the WWW motif.


Posterior Cortical Atrophy: Does Complaint Match the Impairment? A Neuropsychological and FDG-PET Study.
Objective: Posterior Cortical Atrophy (PCA) is a neurodegenerative disease characterized predominantly by visual impairment. However, diagnosis of PCA remains complicated with an interval of several years between initial reporting of symptoms and diagnosis. The aim of the present study is to define if patients' visual and gestural complaints are consistent with their clinical profile. Method: An evaluation of daily visual problems as well as a full neuropsychological assessment and FDG-PET were performed in 15 PCA patients. We compared glucose metabolism between these PCA patients and 18 healthy controls. Correlation analyses were conducted in PCA patients between visual and gestural complaint, clinical impairments, and brain glucose metabolism. Results: Major impairment of cognitive functions was detected in PCA patients specifically in visual domains. Positive correlations were found between visual impairments and hypometabolism in the right temporo-parieto-occipital cortices. However, no correlation was found between complaint and visual impairment in PCA patients. Discussion: Our main results suggest a consistent relationship between clinical impairment and brain metabolism. However, the patient's complaint and visual performance are not linked. Combining the literature and our results, it seems that patients are generally aware of difficulties but misinterpret them. This misinterpretation may be responsible for the delayed diagnosis.


The posterior cerebellum supports the explicit sequence learning linked to trait attribution.
Recent research has indicated that the cerebellum is responsible for social judgments, such as making trait attributions. The present study investigated the function of the posterior cerebellum in supporting sequence learning linked to trait inferences about persons. We conducted a memory paradigm that required participants to learn a given temporal order of six behavioral sentences that all implied the same personality trait of the protagonist. We then asked participants to infer the trait of the person and to recall the correct order of the sentences and to rate their confidence in their trait judgments and retrieval accuracy. Two control conditions were created: a nonsocial comparison control, involving six nonsocial sentences implying a feature of an object, and a nonsocial nonsequential reading baseline condition. While learning the specific sequence of the sentences, the posterior cerebellum (Crus 2) was more activated for social trait-related sequencing than nonsocial object-related sequencing. Also, given a longer duration to learn the sequences, the precuneus and posterior cingulate cortex were more activated when participants attempted to retrieve the sequences linked to social traits. In addition, confidence in retrieving the correct order of the social sequences modulated the posterior cerebellum (Crus 1) given a longer duration to learn. Our findings highlight the important function of the posterior cerebellum in supporting an active process of sequencing trait-implying actions.


Sensitivity of photonic crystal fiber modes to temperature, strain and external refractive index.
Several strong narrowband resonances are observed in the transmission spectra of fiber Bragg gratings photo-written in photonic crystal fiber that has a refractive index-neutral germanium/fluorine co-doped core. Experimental results for the strain, temperature and refractive index sensitivities of these mode resonances are reported and compared to those of conventional single mode fiber. In particular, we identify three kinds of resonances whose relative sensitivities to strain, temperature and refractive index are markedly different and present numerical simulations to explain these properties. Potential multiparameter optical sensor applications of these mode resonances are briefly discussed.


Trunk muscle activity increases with unstable squat movements.
The objective of this study was to determine differences in electromyographic (EMG) activity of the soleus (SOL), vastus lateralis (VL), biceps femoris (BF), abdominal stabilizers (AS), upper lumbar erector spinae (ULES), and lumbo-sacral erector spinae (LSES) muscles while performing squats of varied stability and resistance. Stability was altered by doing the squat movement on a Smith machine, a free squat, and while standing on two balance discs. Fourteen male subjects performed the movements. Activities of the SOL, AS, ULES, and LSES were highest during the unstable squat and lowest with the Smith machine protocol (p < 0.05). Increased EMG activity of these muscles may be attributed to their postural and stabilization role. Furthermore, EMG activity was higher during concentric contractions compared to eccentric contractions. Performing squats on unstable surfaces may permit a training adaptation of the trunk muscles responsible for supporting the spinal column (i.e., erector spinae) as well as the muscles most responsible for maintaining posture (i.e., SOL).


Biodegradation of aliphatic and aromatic hydrocarbons at high temperatures.
In this paper, the high temperature (65-75 degrees C) biodegradation of aliphatic and aromatic hydrocarbons is investigated and kinetic parameters are derived. The shift of the physico-chemical system properties with rising temperature will be discussed in detail. For example, the solubility of naphthalene is increased by a factor of about ten if the temperature is increased from 20 to 75 degrees C. This effect is essential to increase the bioavailability of sparingly soluble hydrocarbons. It is also demonstrated in experiments that very high oxygen transfer rates can be obtained at high temperatures in the presence of hydrocarbons. It is shown that efficient phenol biodegradation is essential for high temperature hydrocarbon degradation because some microorganisms tend to transform phenols into polyphenols which are very inhibitory for microbial growth. A defined mixed culture adapted to phenol converted more than 90% of a mixture of phenol, hexadecane and pyreno and a very high maximal growth rate of 0.19 h(-1) was determined. A yield coefficient Y(X/S) of about 0.8 g (biomass)/g (hydrocarbons) was calculated in this experiment. In a separate experiment the influence of the hydrocarbon droplet size on the biodegradation is investigated at 70 degrees C using a newly isolated Thermus sp. In this case, the growth on a hexadecane/pyrene mixture was described by a model based on the Monod equation and the corresponding kinetic parameters are derived. A mixed culture was used for the bioremediation of soil in a slurry reactor. The initial contamination of 11 g/kg was lowered to about 2 g in a reactor inoculated by an immobilized culture of extreme thermophilic microorganisms, while 9 g/kg remained in a sterile control.


Intraobserver variability in the MR determination of tumor volume in squamous cell carcinoma of the pharynx.
If tumor volumes are to be used for evaluating responses to treatment and long-term outcomes of patients with primary pharyngeal carcinomas, the reproducibility of these measurements must be established. We determined the intraobserver variability of MR imaging-based volume measurements of these cancers and their regional metastases. We used an interactive computer program (IDL) that enables the extraction of tumor volumes from 3D MR data to obtain 202 volume measurements in 17 patients with pharyngeal carcinoma (two to five time points each). The primary cancer and largest nodal mass were manually outlined on every T2-weighted image of each MR study. The same neuroradiologist reanalyzed this MR dataset 2-41 weeks later. Measurement error and percentage measurement error (intraobserver variability) were determined. Differences in intraobserver variability between primary lesions and nodes, as well as between stages of treatment were tested with a Wilcoxon rank sum test. The mean and median percentage measurement errors, respectively, were 13% and 12% (range, 0-53%; 95% CI: 10%, 16%) for primary tumors and 9% and 7% (range, 0-37%; 95% CI: 7%, 12%) for nodal metastases. The difference in the percentage measurement error between primary lesions and cervical nodes approached statistical significance (P =.07). Differences in the variation of volume measurements based on the stage of therapy were significant (P =.01). Our results suggest that MR imaging-based tumor volumes are reliably reproducible. Such measurements may be important in predicting patient outcome, determining appropriate therapy, and conducting patient follow-up.


A genome-wide RNAi screen identifies novel targets of neratinib sensitivity leading to neratinib and paclitaxel combination drug treatments.
ErbB2 is frequently activated in tumors, and influences a wide array of cellular functions, including proliferation, apoptosis, cell motility and adhesion. HKI-272 (neratinib) is a small molecule pan-kinase inhibitor of the ErbB family of receptor tyrosine kinases, and shows strong antiproliferative activity in ErbB2-overexpressing breast cancer cells. We undertook a genome-wide pooled lentiviral RNAi screen to identify synthetic lethal or enhancer (synthetic modulator screen) genes that interact with neratinib in a human breast cancer cell line (SKBR-3). These genes upon knockdown would modulate cell viability in the presence of subeffective concentrations of neratinib. We discovered a diverse set of genes whose depletion selectively impaired or enhanced the viability of SKBR-3 cells in the presence of neratinib. We observed diverse pathways including EGFR, hypoxia, cAMP, and protein ubiquitination that, when co-treated with RNAi and neratinib, resulted in arrest of cell proliferation. Examining the changes of these genes and their protein products also led to a rationale for clinically relevant drug combination treatments. Treatment of cells with either paclitaxel or cytarabine in combination with neratinib resulted in a strong antiproliferative effect. The identification of novel mediators of cellular response to neratinib and the development of potential drug combination treatments have expanded our understanding of neratinib's mode-of-action for the development of more effective therapeutic regimens. Notably, our findings support a paclitaxel and neratinib phase III clinical trial in breast cancer patients.


Membrane properties of neuroglia in the optic nerve of Necturus.
The optic nerve of Necturus has proved a useful preparation for the study of glial cell membranes in vivo and in vitro with anatomical relations to axons intact and isolated following axon degeneration. The glial membrane potential behaves as a selective potassium diffusion potential; there is no evidence of a significant permeability to other naturally occurring ions. The specific membrane resistance of the glial cells is high compared to that of neurones; there are low-resistance intercellular connexions among the cells which permit the passage of both ions and the dye Lucifer Yellow. The cells are readily and reversibly uncoupled by procedures which decrease the intracellular pH. There is no evidence for voltage-sensitive sodium channels in the membrane. Following sodium gain and potassium loss the membrane displays a potassium-dependent strophanthidin-sensitive electrogenic sodium pump. The glial membrane is depolarized by potassium released from active axons as well as by glutamate. The glial depolarization contributes to potentials recorded with surface electrodes. Depolarization by K+ plays a role in the redistribution of K+ which locally accumulates around active neurones and also affects glial metabolism and glucose uptake.